Journal articles
Merriel S, Hamilton W, Ball S, Hyde C (In Press). A prospective evaluation of the fourth be Clear on Cancer ‘Blood in Pee’ campaign in England. European Journal of Cancer Care
Ball S, Hyde C, Hamilton W, Bright C, Gildea C, Wong K, Paley L, Hill H, Mak V, Moffat J, et al (In Press). An evaluation of a national mass media campaign to raise public awareness of possible lung cancer symptoms in England in 2016 and 2017. British Journal of Cancer
Jones OT, Calanzani N, Saji S, Duffy SW, Emery J, Hamilton W, Singh H, de Wit NJ, Walter FM (In Press). Artificial Intelligence Techniques That May be Applied to Primary Care Data to Facilitate Earlier Diagnosis of Cancer: Systematic Review (Preprint).
Abstract:
Artificial Intelligence Techniques That May be Applied to Primary Care Data to Facilitate Earlier Diagnosis of Cancer: Systematic Review (Preprint)
. BACKGROUND
. More than 17 million people worldwide, including 360,000 people in the United Kingdom, were diagnosed with cancer in 2018. Cancer prognosis and disease burden are highly dependent on the disease stage at diagnosis. Most people diagnosed with cancer first present in primary care settings, where improved assessment of the (often vague) presenting symptoms of cancer could lead to earlier detection and improved outcomes for patients. There is accumulating evidence that artificial intelligence (AI) can assist clinicians in making better clinical decisions in some areas of health care.
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. OBJECTIVE
. This study aimed to systematically review AI techniques that may facilitate earlier diagnosis of cancer and could be applied to primary care electronic health record (EHR) data. The quality of the evidence, the phase of development the AI techniques have reached, the gaps that exist in the evidence, and the potential for use in primary care were evaluated.
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. METHODS
. We searched MEDLINE, Embase, SCOPUS, and Web of Science databases from January 01, 2000, to June 11, 2019, and included all studies providing evidence for the accuracy or effectiveness of applying AI techniques for the early detection of cancer, which may be applicable to primary care EHRs. We included all study designs in all settings and languages. These searches were extended through a scoping review of AI-based commercial technologies. The main outcomes assessed were measures of diagnostic accuracy for cancer.
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. RESULTS
. We identified 10,456 studies; 16 studies met the inclusion criteria, representing the data of 3,862,910 patients. A total of 13 studies described the initial development and testing of AI algorithms, and 3 studies described the validation of an AI algorithm in independent data sets. One study was based on prospectively collected data; only 3 studies were based on primary care data. We found no data on implementation barriers or cost-effectiveness. Risk of bias assessment highlighted a wide range of study quality. The additional scoping review of commercial AI technologies identified 21 technologies, only 1 meeting our inclusion criteria. Meta-analysis was not undertaken because of the heterogeneity of AI modalities, data set characteristics, and outcome measures.
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. CONCLUSIONS
. AI techniques have been applied to EHR-type data to facilitate early diagnosis of cancer, but their use in primary care settings is still at an early stage of maturity. Further evidence is needed on their performance using primary care data, implementation barriers, and cost-effectiveness before widespread adoption into routine primary care clinical practice can be recommended.
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. CLINICALTRIAL
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Abstract.
Hall R, Medina-Lara A, Hamilton W, Spencer A (In Press). Attributes used for cancer screening discrete choice experiments: a systematic review. The Patient: Patient Centered Outcomes Research
Price SJ, Spencer A, Medina-Lara A, Hamilton W (In Press). Availability of cancer decision-support tools: a cross-sectional survey of UK primary care. British Journal of General Practice
Bailey S, Mounce L, Hamilton W (In Press). Cancer incidence following a high-normal platelet count: cohort study using electronic healthcare records from English primary care. British Journal of General Practice
Chowienczyk S, Price S, Hamilton W (In Press). Changes in the presenting symptoms of lung cancer between 2000 and 2017. British Journal of General Practice, 1-22.
Bailey SER, Abel GA, Atkins A, Byford R, Davies S-J, Mays J, McDonald TJ, Miller J, Neck C, Renninson J, et al (In Press). Diagnostic performance of the faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: a service evaluation in the South West of England.
Abstract:
Diagnostic performance of the faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: a service evaluation in the South West of England
AbstractObjectivesTo evaluate the faecal immunochemical test (FIT) for primary care clinicians to triage patients with low-risk symptoms of possible colorectal cancer, and to estimate its diagnostic performance.DesignService delivery evaluation.SettingAll primary and secondary care providers in the South West of England, approximate population 4 million.Participants3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer, following NICE NG12 and DG30, with a FIT (HM-JACKarc assay) analysed from 01/06/2018 to 31/12/2018.Main outcome measuresDiagnosis of colorectal cancer.Results618 (15.9%) patients tested positive at a threshold of 10μg Hb/g faeces (median 36μg Hb/g faeces (IQR 17 to 149)); 458 (74.1%) of these had an urgent referral to specialist lower gastrointestinal (GI) services within three months. 43 were diagnosed with colorectal cancer within 12 months. 3272 patients tested negative; 324 (9.9%) were referred on an urgent lower GI pathway in secondary care within three months. 8 were diagnosed with colorectal cancer within 12 months. The positive predictive value of FIT for colorectal cancer in the low-risk symptomatic population was 7.0% (95% CI 5.1% to 9.3%) and the negative predictive value was 99.8% (CI 99.5% to 99.9%). Sensitivity was 84.3% (CI 71.4% to 93.0%),and specificity 85.0% (CI 83.8% to 86.1%). The area under the ROC curve was 0.92 (CI 0.86 to 0.96). A threshold of 37μg Hb/g faeces would identify patients with an individual 3% risk of cancer.ConclusionsFIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care. The threshold value of 10μg Hb/g faeces represents a risk of cancer below 3% used in current NICE guidance; however, this lower value may be appropriate to meet the national aspiration of improving cancer diagnostics.
Abstract.
Price S, Mounce L, Shephard E, Hamilton W (In Press). Effect of pre-existing conditions on stage of bladder cancer at diagnosis: a cohort study using electronic primary care records. British Journal of General Practice, 1-22.
Ukoumunne OC, Moore H, Nixon C, Tariq A, Hamilton W, Hoare Z, Kershenbaum A, Neal RD, Usher-Smith J, Walter FM, et al (In Press). Evaluating a computer aid for assessing stomach symptoms (ECASS): study protocol for a multi-site phase II exploratory cluster randomised controlled trial.
TrialsAbstract:
Evaluating a computer aid for assessing stomach symptoms (ECASS): study protocol for a multi-site phase II exploratory cluster randomised controlled trial
Background
For most cancers, only a minority of patients have symptoms meeting the National Institute for Health and Clinical Excellence guidance for urgent referral. For gastro-oesophageal cancers, the ‘alarm’ symptoms of dysphagia and weight loss are reported by only 32% and 8% of patients respectively and their presence correlates with advanced stage disease. Electronic clinical decision support tools which integrate with clinical computer systems have been developed for general practice, although there is uncertainty about their effectiveness. The objectives of this trial are to optimise the intervention and establish acceptability of both the intervention and randomisation; confirm the suitability and selection of outcome measures; finalise design for the phase III definitive trial; and obtain preliminary estimates of the intervention effect.
Methods/Design
This is a two-arm, multi-centre, cluster randomised controlled phase II trial design, over a 16-month period, across 60 general practices within the North East & North Cumbria and Eastern Local Clinical Research Network areas. Practices will be randomised to receive either the intervention (electronic clinical decision support tool) or to act as control (usual care). From these practices, we will recruit 3000 adults who meet the trial eligibility criteria and present to their GP with symptoms potentially of gastro-oesophageal cancer. The main measures are process data, to include practitioner outcomes, service outcomes, diagnostic intervals, health economic outcomes and patient outcomes. 1:1 interviews in a sub-sample of 30 patient-GP dyads, will be undertaken to understand the impact of the use or non-use of the electronic clinical decision support tool in the consultation. A further 10-15 GPs will be interviewed to identify and gain an understanding of the facilitators and constraints influencing implementation of the electronic clinical decision support tool in practice.
Discussion
We aim to generate new knowledge on the process measures regarding use of electronic clinical decision support tools in primary care in general and to inform a subsequent definitive phase III trial. Preliminary data on the impact on resource utilisation and health care costs of the support tool will also be collected.
Abstract.
Walter F, Thompson MJ, Wellwood I, Abel G, Hamilton W, Johnson M, Lyratzopoulos G, Messenger M, Neal R, Greg R, et al (In Press). Evaluating diagnostic strategies for early detection of cancer: the CanTest Framework. BMC Cancer
Merriel S, Hamilton W (In Press). Experiences of ‘traditional’ and ‘one-stop’ MRI-based prostate cancer diagnostic pathways in England: a qualitative study with patients and GPs. BMJ Open
Hardwick RJL, Heaton J, Griffiths G, Vaidya B, Child S, Fleming S, Hamilton WT, Tomlinson J, Zhelev Z, Patterson A, et al (In Press). Exploring reasons for variation in ordering thyroid function tests in primary care: a qualitative study.
Quality in Primary Care,
22, 256-261.
Abstract:
Exploring reasons for variation in ordering thyroid function tests in primary care: a qualitative study
Background: the ordering of thyroid function tests (TFTs) is increasing but there is not a similar increase in thyroid disorders in the general population, leading some to query whether inappropriate testing is taking place. Inconsistent clinical practice is thought to be a cause of this, but there is little evidence of the views of general practitioners, practice nurses or practice managers on the reasons for variation in the ordering of TFTs.Aim: to find out the reasons for variation in ordering of TFTs from the perspective of primary healthcare professionals Methods: Fifteen semi-structured interviews were carried out with primary healthcare professionals (general practitioners, practice nurses, practice managers) that used one laboratory of a general hospital in South West England for TFTs. Framework Analysis was used to analyse views on test ordering variation at the societal, practice, individual practitioner and patient level.Results: a number of reasons for variation in ordering across practices were suggested. These related to: primary healthcare professionals awareness of and adherence to national policy changes; practices having different protocols on TFTs ordering; the set-up and use of computer systems in practices; the range of practice healthcare professionals able to order TFTs; greater risk-aversion amongst general practitioners and changes in their training and finally how primary healthcare staff responded to patients who were perceived to seek help more readily than in the past.Conclusion: the reasons for variation in TFTs ordering are complex and interdependent. Interventions to reduce variation in TFTs ordering need to consider multiple behavioural and contextual factors to be most effective.
Abstract.
Bailey S, Hamilton W (In Press). Faecal immunochemical test (FIT) to triage patients with abdominal symptoms for suspected colorectal cancer in primary care: review of international use and guidelines. Family Practice
Merriel S, Hamilton W (In Press). Improving early cancer diagnosis in primary care. Prescriber
Hopkins R, Bailey SER, Hamilton W, Shephard E (In Press). Microcytosis as a risk marker of cancer in primary care: a cohort study using electronic patient records. British Journal of General Practice
Newlove-Delgado TV, Hamilton W, Ford T, Stein K, Ukoumunne O (In Press). Prescribing for young people with Attention Deficit Hyperactivity Disorder in UK primary care: analysis of data from the Clinical Practice Research Datalink. ADHD Attention Deficit and Hyperactivity Disorders
Zirk-Sadowski J, Masoli J, Strain WD, Delgado J, Henley W, Hamilton W, Melzer D, Ble A (In Press). Proton-Pump Inhibitors and Fragility Fractures in Vulnerable Older Patients. The American Journal of Gastroenterology (Elsevier)
Streeter A, Rodgers LR, Hamilton F, Masoli JAH, Ble A, Hamilton WT, Henley W (In Press). Real-world effectiveness of pneumococcal vaccination in older adults: cohort study using the UK Clinical Practice Research Datalink. PLoS ONE
Newlove-Delgado TV, Ukoumunne O, Stein K, Ford T, Hamilton W, Janssens A (In Press). Resumption of Attention Deficit Hyperactivity Disorder medication in early adulthood: findings from a UK primary care prescribing study. European Child and Adolescent Psychiatry
Dennis J, Henley W, Weedon M, Lonergan M, Rodgers L, Jones A, Hamilton W, Sattar N, Janmohamed S, Holman R, et al (In Press). Sex and BMI alter the benefits and risks of sulfonylureas and thiazolidinediones in type 2 diabetes: a framework for evaluating stratification using routine clinical and individual trial data. Diabetes Care
walter F, Emery JD, Mendonce S, Hall N, Morris HC, Mills K, Dobson C, Bankhead C, Johnson M, Abel GA, et al (In Press). Symptoms and patient factors associated with longer time to diagnosis for colorectal cancer: results from a prospective cohort study. British Journal of Cancer
Merriel SWD, Pocock L, Gilbert E, Creavin S, Walter FM, Spencer A, Hamilton W (In Press). Systematic Review & Meta-Analysis of the Diagnostic Accuracy of Prostate Specific Antigen (PSA) for the Detection of Prostate Cancer in Symptomatic Patients.
Abstract:
Systematic Review & Meta-Analysis of the Diagnostic Accuracy of Prostate Specific Antigen (PSA) for the Detection of Prostate Cancer in Symptomatic Patients
Abstract
. BackgroundProstate Specific Antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.MethodsA systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.Results563 search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. 19 studies met the inclusion criteria, 18 of which were conducted in secondary care settings (one from a screening study cohort). All studies used histology obtained by Transrectal Ultrasound guided biopsy (TRUS) as a reference test, usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the receiving-operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.ConclusionsCurrently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.
Abstract.
Merriel S, Hamilton W (In Press). Systemic anticancer therapies and the role of primary care. Prescriber
Barlow M, Hamilton W, Ukoumunne OC, Bailey SER (In Press). The association between thrombocytosis and subtype of lung cancer: a systematic review and meta-analysis.
Abstract:
The association between thrombocytosis and subtype of lung cancer: a systematic review and meta-analysis
ABSTRACTBackgroundThrombocytosis is associated with poor lung cancer prognosis and has recently been identified as having a high predictive value in lung cancer detection. Lung cancer has multiple histological and genetic subtypes and it is not known whether platelet levels differ across subtypes.MethodsPubMed and Embase were systematically searched for studies that reported pre-treatment platelet count, as either averages or proportion of patients with thrombocytosis, by histological subtype of lung cancer. Suitable studies were synthesised in meta-analyses; subgroup analyses examined for differences across subtypes.ResultsThe prevalence of pre-treatment thrombocytosis across all lung cancer patients was 27% (95% CI: 17 to 37%). By subtype, this was 22% (95% CI: 7 to 41%) for adenocarcinoma (ADC), 28% (95% CI: 15 to 43%) for squamous cell carcinoma (SCC), 36% (95% CI: 13 to 62%) for large cell carcinoma, and 30% (95% CI: 8 to 58%) for small cell lung cancer (SCLC). The pooled mean platelet count for lung cancer patients was 289×109 /L (95% CI: 268 to 311). By subtype, this was 282×109 /L (95% CI: 259 to 306) for ADC, 297×109 /L (95% CI: 238 to 356) for SCC, 290×109 /L (95% CI: 176 to 404) for LCC, and 293×109 /L (95% CI: 244 to 342) for SCLC. There was no difference in thrombocytosis prevalence (p=0.76) or mean platelet count (p=0.96) across the subtypes.ConclusionWe report no evidence of differences in platelet levels across the major subtypes of lung cancer. A high platelet level is likely to be generic across all lung cancer subtypes.KEY MESSAGESWhat is the key question?Which (if any) subtype(s) of lung cancer are more associated with thrombocytosis?What is the bottom line?This can facilitate lung cancer diagnostics and provide insights into the biological mechanism between lung cancer and thrombocytosis.Why read on?This is the first systematic review to compare platelet count across different subtypes of lung cancer, combining data from 9,891 patients across 38 studies.
Abstract.
Hamilton WT, Hollinghurst S, Banks J, Bigwood L, Walter F, Peters TJ (In Press). Using willingness-to-pay to establish patient preferences for cancer testing in primary care. BMC Medical Informatics and Decision Making
Laake J-P, Vulkan D, Quaife SL, Hamilton WT, Martins T, Waller J, Parmar D, Sasieni P, Duffy SW (In Press). WELCOME-GP: a randomised controlled trial of the effectiveness of a targeted postal cancer awareness intervention for increasing attendance at general practice.
Abstract:
WELCOME-GP: a randomised controlled trial of the effectiveness of a targeted postal cancer awareness intervention for increasing attendance at general practice
ABSTRACTObjectiveTo assess the effectiveness of a targeted postal promotion for improving cancer symptom awareness and increasing help-seeking in general practice, on subsequent general practitioner (GP) consultation rates in a population which has made infrequent use of consultations at their local practice.Setting23 general practices in England.DesignRandomised controlled trial comparing a mailed leaflet providing information on six key cancer symptoms plus a covering letter signed by their general practitioner designed to reduce barriers to primary care help-seeking (intervention arm), with usual care (control arm).Participants1,513 adults aged 50-84 years (783 individually randomised to the intervention arm and 730 individually randomised to the control arm) who had not consulted their GP in the last 12 months and had at least two other risk factors for late presentation with cancer, identified by practice staff between November 2016 and May 2017. 749 individuals in the intervention arm and 705 in the control arm were included in the intention to treat analyses.Outcome measureThe primary outcome was number of GP consultations in the six months subsequent to mailing of the intervention.ResultsThere was a significantly higher rate of consultation in the intervention arm: 436 consultations compared to 335 in the control arm (RR = 1.40, 95% CI 1.11-1.77, p=0.004). However, there was no difference in the numbers of persons consulting their GP, with 165 in each group.ConclusionsTargeted interventions of this nature can change behaviour. This intervention stimulated a greater number of consultations but not a greater number of patients consulting. There is a need to develop interventions which can be more effective on the broader less engaged population.Trial registrationThe trial was registered prospectively on the International Standard Randomised Controlled Trial Number (ISRCTN) registry (ISRCTN95610478).FundingThis research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis, 106/0001. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Additional support, including NHS service support costs, were provided by the National Institute for Health Research Clinical Research Network (NIHR CRN) (UKCRN ID 31163).
Abstract.
McGovern A, Shields B, Hattersley A, Pearson E, Jones AG (In Press). What to do with diabetes therapies when HbA1c lowering is inadequate: add, switch, or continue? a MASTERMIND study. BMC Medicine
White P, Abbey S, Angus B, Ball HA, Buchwald DS, Burness C, Carson AJ, Chalder T, Clauw DJ, Coebergh J, et al (2023). Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.
J Neurol Neurosurg PsychiatryAbstract:
Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.
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Martins T, Ukoumunne OC, Lyratzopoulos G, Hamilton W, Abel G (2023). Are There Ethnic Differences in Recorded Features among Patients Subsequently Diagnosed with Cancer? an English Longitudinal Data-Linked Study.
Cancers,
15(12), 3100-3100.
Abstract:
Are There Ethnic Differences in Recorded Features among Patients Subsequently Diagnosed with Cancer? an English Longitudinal Data-Linked Study
We investigated ethnic differences in the presenting features recorded in primary care before cancer diagnosis. Methods: English population-based cancer-registry-linked primary care data were analysed. We identified the coded features of six cancers (breast, lung, prostate, colorectal, oesophagogastric, and myeloma) in the year pre-diagnosis. Logistic regression models investigated ethnic differences in first-incident cancer features, adjusted for age, sex, smoking status, deprivation, and comorbidity. Results: of 130,944 patients, 92% were White. In total, 188,487 incident features were recorded in the year pre-diagnosis, with 48% (89,531) as sole features. Compared with White patients, Asian and Black patients with breast, colorectal, and prostate cancer were more likely than White patients to have multiple features; the opposite was seen for the Black and Other ethnic groups with lung or prostate cancer. The proportion with relevant recorded features was broadly similar by ethnicity, with notable cancer-specific exceptions. Asian and Black patients were more likely to have low-risk features (e.g. cough, upper abdominal pain) recorded. Non-White patients were less likely to have alarm features. Conclusion: the degree to which these differences reflect disease, patient or healthcare factors is unclear. Further research examining the predictive value of cancer features in ethnic minority groups and their association with cancer outcomes is needed.
Abstract.
Rees CJ, Hamilton W (2023). BSG guidelines on faecal immunochemical testing: are they 'FIT' for purpose?. Gut, 72(10), 1805-1806.
Nankervis H, Huntley A, Whiting P, Hamilton W, Singh H, Dawson S, Sprackman J, Ferguson-Montague A, Watson J (2023). Blood test result communication in primary care: mixed methods systematic review protocol.
BJGP OpenAbstract:
Blood test result communication in primary care: mixed methods systematic review protocol.
BACKGROUND: After testing, ensuring test results are communicated and actioned is important for patient safety, with failure or delay in diagnosis the commonest cause of malpractice claims in primary care worldwide. Identifying interventions to improve test communication from the decision to test through to sharing of results has important implications for patient safety, GP workload and patient engagement. AIM: to assess the factors around communication of blood test results between primary care providers (eg, GPs, nurses, reception staff) and their patients and carers. DESIGN & SETTING: a mixed methods systematic review including primary studies involving communication of blood test results in primary care. METHOD: the review will use a segregated convergent synthesis method. Qualitative information will be synthesised using a meta-aggregative approach and quantitative data will be meta-analysed or synthesised if pooling of studies is appropriate and data is available. If not data will be presented in tabular and descriptive summary form. CONCLUSION: This review has the potential to provide conclusions about blood test result communication interventions and factors important to stakeholders including barriers and facilitators to improved communication.
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Snudden CM, Calanzani N, Archer S, Honey S, Pannebakker MM, Faher A, Chang A, Hamilton W, Walter FM (2023). Can we do better? a qualitative study in the East of England investigating patient experience and acceptability of using the faecal immunochemical test in primary care.
BMJ Open,
13(6).
Abstract:
Can we do better? a qualitative study in the East of England investigating patient experience and acceptability of using the faecal immunochemical test in primary care.
OBJECTIVES: the faecal immunochemical test (FIT) is increasingly used in UK primary care to triage patients presenting with symptoms and at different levels of colorectal cancer risk. Evidence is scarce on patients' views of using FIT in this context. We aimed to explore patients' care experience and acceptability of using FIT in primary care. DESIGN: a qualitative semi-structured interview study. Interviews were conducted via Zoom between April and October 2020. Transcribed recordings were analysed using framework analysis. SETTING: East of England general practices. PARTICIPANTS: Consenting patients (aged ≥40 years) who presented in primary care with possible symptoms of colorectal cancer, and for whom a FIT was requested, were recruited to the FIT-East study. Participants were purposively sampled for this qualitative substudy based on age, gender and FIT result. RESULTS: 44 participants were interviewed with a mean age 61 years, and 25 (57%) being men: 8 (18%) received a positive FIT result. Three themes and seven subthemes were identified. Participants' familiarity with similar tests and perceived risk of cancer influenced test experience and acceptability. All participants were happy to do the FIT themselves and to recommend it to others. Most participants reported that the test was straightforward, although some considered it may be a challenge to others. However, test explanation by healthcare professionals was often limited. Furthermore, while some participants received their results quickly, many did not receive them at all with the common assumption that 'no news is good news'. For those with a negative result and persisting symptoms, there was uncertainty about any next steps. CONCLUSIONS: While FIT is acceptable to patients, elements of communication with patients by the healthcare system show potential for improvement. We suggest possible ways to improve the FIT experience, particularly regarding communication about the test and its results.
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Hamilton W, Turabi N, Harrison S (2023). Cancer care has not caused waiting lists to mushroom.
BMJ,
382 Author URL.
Hamilton W, Bailey SER (2023). Colorectal cancer in symptomatic patients: How to improve the diagnostic pathway. Best Practice & Research Clinical Gastroenterology, 101842-101842.
Richards MA, Hiom S, Hamilton W (2023). Diagnosing cancer earlier: what progress is being made?.
Br J Cancer,
128(3), 441-442.
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Logan RPH, Hamilton W (2023). Editorial: Less is more for colorectal cancer diagnosis - FIT leads the way.
Aliment Pharmacol Ther,
58(7), 725-726.
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Hamilton FW, Abeysekera K, Hamilton W, Timpson NJ (2023). Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations.
BMJ Med,
2(1).
Abstract:
Effect of bilirubin and Gilbert syndrome on health: cohort analysis of observational, genetic, and Mendelian randomisation associations.
OBJECTIVES: to compare associations between the Gilbert syndrome genotype in European populations, measured bilirubin concentrations, genetically predicted bilirubin using this genotype, and a wide range of health outcomes in a large cohort. DESIGN: Cohort study including observational, genetic, and Mendelian randomisation analyses. SETTING: 22 centres across England, Scotland, and Wales in UK Biobank (2006-10), with replication in a national Finnish cohort (FinnGen). PARTICIPANTS: 463 060 participants in the UK Biobank were successfully genotyped for a genetic variant (rs887829) that is strongly associated with Gilbert syndrome and 438 056 participants had measured bilirubin concentrations with linked electronic health record data coded using the tenth edition of the International Classification of Diseases. Replication analyses were performed in FinnGen (n=429 209) with linked electronic health record data. MAIN OUTCOME MEASURES: Odds ratios for the association between serum bilirubin concentrations, rs887829-T homozygosity (the risk genotype for Gilbert syndrome), genetically predicted bilirubin using rs887829-T allele carriage alone, and a wide range of health outcomes recorded in primary and secondary care. RESULTS: 46 189 participants in UK Biobank (about 10%) were homozygous for rs887829-T defining them as having the genotype characterising Gilbert syndrome. However, only 1701 (3%) of this group had a coded diagnosis of Gilbert syndrome. Variation at this locus explained 37.1% of all variation in measured serum bilirubin. In the observational analyses, higher bilirubin concentrations had strong inverse associations with a wide range of outcomes including overall health status, chronic obstructive pulmonary disease, myocardial infarction, and cholesterol measures. These associations were not identified in people with the Gilbert genotype. We identified associations with genetically predicted bilirubin concentrations and biliary and liver pathology (eg, odds ratio for cholelithiasis 1.16 (95% confidence interval 1.12 to 1.20); P=5.7×10-16) and a novel association with pityriasis rosea (1.47 (1.27 to 1.69), P=1.28×10-7). CONCLUSIONS: Only 3% of participants who are homozygous for rs887829-T have a recorded diagnosis of Gilbert syndrome. Carriers of this genotype have modest increases in the odds of developing biliary pathology and pityriasis rosea. Evidence from the analyses of genetic data suggests that bilirubin has no likely causal role in protection from cardiovascular disease, chronic obstructive pulmonary disease, or other key healthcare outcomes and therefore represents a poor target for therapeutic intervention for these outcomes.
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Price S, Wiering B, Mounce LTA, Hamilton W, Abel G (2023). Examining methodology to identify patterns of consulting in primary care for different groups of patients before a diagnosis of cancer: an exemplar applied to oesophagogastric cancer. Cancer Epidemiology, 82, 102310-102310.
Zhou Y, Singh H, Hamilton W, Archer S, Tan S, Brimicombe J, Lyratzopoulos G, Walter FM (2023). Improving the diagnostic process for patients with possible bladder and kidney cancer: a mixed-methods study to identify potential missed diagnostic opportunities.
Br J Gen Pract,
73(733), e575-e585.
Abstract:
Improving the diagnostic process for patients with possible bladder and kidney cancer: a mixed-methods study to identify potential missed diagnostic opportunities.
BACKGROUND: Patients with bladder and kidney cancer may experience diagnostic delays. AIM: to identify patterns of suboptimal care and contributors of potential missed diagnostic opportunities (MDOs). DESIGN AND SETTING: Prospective, mixed-methods study recruiting participants from nine general practices in Eastern England between June 2018 and October 2019. METHOD: Patients with possible bladder and kidney cancer were identified using eligibility criteria based on National Institute for Health and Care Excellence (NICE) guidelines for suspected cancer. Primary care records were reviewed at recruitment and at 1 year for data on symptoms, tests, referrals, and diagnosis. Referral predictors were examined using logistic regression. Semi-structured interviews were undertaken with 15 patients to explore their experiences of the diagnostic process, and these were analysed thematically. RESULTS: Participants (n = 940) were mostly female (n = 657, 69.9%), with a median age of 71 years (interquartile range 64-77 years). In total, 268 (28.5%) received a referral and 465 (48.5%) had a final diagnosis of urinary tract infection (UTI). There were 33 (3.5%) patients who were diagnosed with cancer, including prostate (n = 17), bladder (n = 7), and upper urothelial tract (n = 1) cancers. Among referred patients, those who had a final diagnosis of UTI had the longest time to referral (median 81.5 days). Only one-third of patients with recurrent UTIs were referred despite meeting NICE referral guidelines. Qualitative findings revealed barriers during the diagnostic process, including inadequate clinical examination, female patients given repeated antibiotics without clinical reviews, and suboptimal communication of test results to patients. CONCLUSION: Older females with UTIs might be at increased risk of MDOs for cancer. Targeting barriers during the initial diagnostic assessment and follow-up might improve quality of diagnosis.
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Moore SF, Price SJ, Bostock J, Neal RD, Hamilton W (2023). Incidence of ‘Low-Risk but Not No-Risk’ Features of Cancer Prior to High-Risk Feature Occurrence: an Observational Cohort Study in Primary Care.
Cancers,
15(15), 3936-3936.
Abstract:
Incidence of ‘Low-Risk but Not No-Risk’ Features of Cancer Prior to High-Risk Feature Occurrence: an Observational Cohort Study in Primary Care
Diagnosing cancer may be expedited by decreasing referral risk threshold. Clinical Practice Research Datalink participants (≥40 years) had a positive predictive value (PPV) ≥3% feature for breast, lung, colorectal, oesophagogastric, pancreatic, renal, bladder, prostatic, ovarian, endometrial or laryngeal cancer in 2016. The numbers of participants with features representing a 1–1.99% or 2–2.99% PPV for same cancer in the previous year were reported, alongside the time difference between meeting the ≥3% criteria and the lower threshold criteria. A total of 8616 participants had a PPV ≥3% feature, of whom 365 (4.2%) and 1147 (13.3%), respectively, met 2–2.99% and 1–1.99% criteria in the preceding year. The median time difference was 131 days (Interquartile Range (IQR) 27 to 256) for the 2–2.99% band and 179 days (IQR 58 to 289) for the 1–1.99% band. Results were heterogeneous across cancer sites. For some cancers, participants may progress from presenting lower- to higher-risk features before meeting urgent referral criteria; however, this was not usually the case. The details of specific features across multiple cancer sites will allow for a tailored approach to future reductions in referral thresholds, potentially improving the efficiency of urgent cancer referrals for the benefit both of individuals and the National Health Service (NHS).
Abstract.
Shaw B, Walter FM, Hamilton W, Martins T (2023). Symptom appraisal and help seeking in males with symptoms of possible prostate cancer: a qualitative study with an ethnically diverse sample in London.
British Journal of General Practice,
73(732), e502-e510.
Abstract:
Symptom appraisal and help seeking in males with symptoms of possible prostate cancer: a qualitative study with an ethnically diverse sample in London
BackgroundProstate cancer mortality in Black males is disproportionately high. This problem may be overcome by reducing delays in the pathway to diagnosis, particularly those occurring before initial medical help seeking. A greater understanding of symptom appraisal and help seeking could support the development of targeted interventions for improving early presentation among Black males.AimTo provide an in-depth understanding of males' pre-consultation experiences following the onset of symptoms of possible prostate cancer, identifying both general trends as well as potential differences that may exist between Black and White males.Design and settingQualitative study of 18 males (nine Black, nine White) in London, UK, who had recently seen their GP with urinary symptoms, erectile dysfunction, or haematuria.MethodSemi-structured interviews from a previous multi-methods study of primary care use by males with symptoms of possible prostate cancer were analysed using thematic framework analysis.ResultsSymptoms were often interpreted by patients as unimportant. Most delays occurred due to the absence of reasons to seek help, which, in Black males, often stemmed from poor awareness of prostate cancer. This lack of awareness could have been a consequence of their reluctance to seek health information and discuss health issues with others in their social network. Friends and relatives played an important role in symptom appraisal and help seeking.ConclusionCognitive biases, cultural stigmas, and everyday interpersonal interactions should be important areas at which to target strategies seeking to reduce delays and improve early presentation in males with possible prostate cancer, particularly Black males.
Abstract.
Shaw B, Walter FM, Hamilton W, Martins T (2023). Symptom appraisal and help-seeking in men with symptoms of possible prostate cancer: a qualitative study with an ethnically diverse sample in London.
British Journal of General PracticeAbstract:
Symptom appraisal and help-seeking in men with symptoms of possible prostate cancer: a qualitative study with an ethnically diverse sample in London
Background: Prostate cancer mortality in Black men is disproportionately high. This problem may be overcome by reducing delays in the pathway to diagnosis, particularly those occurring before initial medical help-seeking. A greater understanding of symptom appraisal and help-seeking could support the development of targeted interventions for improving early presentation among Black men. Aim: to provide an in-depth understanding of men’s pre-consultation experiences following the onset of possible prostate cancer symptoms, identifying both general trends as well as potential differences which may exist between Black and White men. Design and Setting: Qualitative study of 18 Black and White men in London who had recently seen their general practitioner (GP) with urinary symptoms, erectile dysfunction or haematuria. Method: Semi-structured interviews from a previous multi-methods study of primary care use by men with symptoms of possible prostate cancer were analysed using thematic framework analysis. Results: Symptoms were often interpreted as being unimportant. Most delays occurred due to the absence of reasons to seek help which, in Black men, often stemmed from poor prostate cancer awareness. This was possibly a consequence of their reluctance to seek health information and discuss health issues with others within their social network. Friends and relatives played an important role in symptom appraisal and help-seeking which may link with these differences. Conclusion: Cognitive biases, cultural stigmas and everyday interpersonal interactions should be important targets for strategies seeking to reduce delays and improve early presentation in Black men.
Abstract.
Shaw B, Walter FM, Hamilton W, Martins T (2023). Symptom appraisal and help-seeking in men with symptoms of possible prostate cancer: a qualitative study with an ethnically diverse sample in London. British Journal of General Practice, 73(732).
Merriel SWD, Hall R, Walter FM, Hamilton W, Spencer AE (2023). Systematic Review and Narrative Synthesis of Economic Evaluations of Prostate Cancer Diagnostic Pathways Incorporating Prebiopsy Magnetic Resonance Imaging.
European Urology Open Science,
52, 123-134.
Abstract:
Systematic Review and Narrative Synthesis of Economic Evaluations of Prostate Cancer Diagnostic Pathways Incorporating Prebiopsy Magnetic Resonance Imaging
Context: Prebiopsy magnetic resonance imaging (MRI) of the prostate has been shown to increase the accuracy of the diagnosis of clinically significant prostate cancer. However, evidence is still evolving about how best to integrate prebiopsy MRI into the diagnostic pathway and for which patients, and whether MRI-based pathways are cost effective. Objective: This systematic review aimed to assess the evidence for the cost effectiveness of prebiopsy MRI-based prostate cancer diagnostic pathways. Evidence acquisition: INTERTASC search strategies were adapted and combined with terms for prostate cancer and MRI, and used to search a wide range of databases and registries covering medicine, allied health, clinical trials, and health economics. No limits were set on country, setting, or publication year. Included studies were full economic evaluations of prostate cancer diagnostic pathways with at least one strategy including prebiopsy MRI. Model-based studies were assessed using the Philips framework, and trial-based studies were assessed using the Critical Appraisal Skills Programme checklist. Evidence synthesis: a total of 6593 records were screened after removing duplicates, and eight full-text papers, reporting on seven studies (two model based) were included in this review. Included studies were judged to have a low-to-moderate risk of bias. All studies reported cost-effectiveness analyses based in high-income countries but had significant heterogeneity in diagnostic strategies, patient populations, treatment strategies, and model characteristics. Prebiopsy MRI-based pathways were cost effective compared with pathways relying on ultrasound-guided biopsy in all eight studies. Conclusions: Incorporation of prebiopsy MRI into prostate cancer diagnostic pathways is likely to be more cost effective in than that into pathways relying on prostate-specific antigen and ultrasound-guided biopsy. The optimal prostate cancer diagnostic pathway design and method of integrating prebiopsy MRI are not yet known. Variations between health care systems and diagnostic approaches necessitate further evaluation for a particular country or setting to know how best to apply prebiopsy MRI. Patient summary: in this report, we looked at studies that measured the health care costs and benefits and harms to patients of using prostate magnetic resonance imaging (MRI), to decide whether men need a prostate biopsy for possible prostate cancer. We found that using prostate MRI before biopsy is likely to be less costly for health care services and probably has better outcomes for patients being investigated for prostate cancer. It is still unclear what the best way to use prostate MRI is.
Abstract.
Hamilton W, Price S (2023). Targeting diagnostic interventions for oesophageal cancer. The Lancet Regional Health - Europe, 32, 100716-100716.
Fletcher E, Burns A, Wiering B, Lavu D, Shephard E, Hamilton W, Campbell JL, Abel G (2023). Workload and workflow implications associated with the use of electronic clinical decision support tools used by health professionals in general practice: a scoping review.
BMC Primary Care,
24(1).
Abstract:
Workload and workflow implications associated with the use of electronic clinical decision support tools used by health professionals in general practice: a scoping review
Abstract
. Background
. Electronic clinical decision support tools (eCDS) are increasingly available to assist General Practitioners (GP) with the diagnosis and management of a range of health conditions. It is unclear whether the use of eCDS tools has an impact on GP workload. This scoping review aimed to identify the available evidence on the use of eCDS tools by health professionals in general practice in relation to their impact on workload and workflow.
.
. Methods
. A scoping review was carried out using the Arksey and O’Malley methodological framework. The search strategy was developed iteratively, with three main aspects: general practice/primary care contexts, risk assessment/decision support tools, and workload-related factors. Three databases were searched in 2019, and updated in 2021, covering articles published since 2009: Medline (Ovid), HMIC (Ovid) and Web of Science (TR). Double screening was completed by two reviewers, and data extracted from included articles were analysed.
.
. Results
. The search resulted in 5,594 references, leading to 95 full articles, referring to 87 studies, after screening. of these, 36 studies were based in the USA, 21 in the UK and 11 in Australia. A further 18 originated from Canada or Europe, with the remaining studies conducted in New Zealand, South Africa and Malaysia. Studies examined the use of eCDS tools and reported some findings related to their impact on workload, including on consultation duration. Most studies were qualitative and exploratory in nature, reporting health professionals’ subjective perceptions of consultation duration as opposed to objectively-measured time spent using tools or consultation durations. Other workload-related findings included impacts on cognitive workload, “workflow” and dialogue with patients, and clinicians’ experience of “alert fatigue”.
.
. Conclusions
. The published literature on the impact of eCDS tools in general practice showed that limited efforts have focused on investigating the impact of such tools on workload and workflow. To gain an understanding of this area, further research, including quantitative measurement of consultation durations, would be useful to inform the future design and implementation of eCDS tools.
.
Abstract.
Watson J, Salisbury C, Whiting PF, Hamilton WT, Banks J (2022). 'I guess I'll wait to hear'- communication of blood test results in primary care a qualitative study.
Br J Gen Pract,
72(723), e747-e754.
Abstract:
'I guess I'll wait to hear'- communication of blood test results in primary care a qualitative study.
BACKGROUND: Rates of blood testing in primary care are rising. Communicating blood test results generates significant workload for patients, GPs, and practice staff. AIM: to explore GPs' and patients' experience of systems of blood test communication. DESIGN AND SETTING: Qualitative interviews with patients and GPs in UK primary care in both urban and rural practices in the West of England. METHOD: a total of 28 patients and 19 GPs from six practices were recruited, with a range of socioeconomic and demographic characteristics. Patients were interviewed at two time points: a) at or soon after their blood test and b) after they had received their test results. The GPs who requested the tests were also interviewed (they could complete a maximum of two interviews about different patients). Eighty qualitative interviews were undertaken; 54 patient interviews and 26 GP interviews. RESULTS: Methods of test result communication varied between doctors and were based on habits, unwritten heuristics, and personal preferences rather than protocols. Doctors expected patients to know how to access their test results. In contrast, patients were often uncertain and used guesswork to decide when and how to access their tests. Patients and doctors generally assumed that the other party would make contact, with potential implications for patient safety. Text messaging and online methods of communication have benefits, but were perceived by some patients as 'flippant' or 'confusing'. Delays and difficulties obtaining and interpreting test results can lead to anxiety and frustration for patients. CONCLUSION: Current systems of test result communication are complex and confusing, and mostly based on habits and routines rather than clear protocols. This has important implications for patient-centred care and patient safety.
Abstract.
Author URL.
Martins T, Abel G, Ukoumunne OC, Price S, Lyratzopoulos G, Chinegwundoh F, Hamilton W (2022). Assessing Ethnic Inequalities in Diagnostic Interval of Common Cancers: a Population-Based UK Cohort Study.
Cancers,
14(13), 3085-3085.
Abstract:
Assessing Ethnic Inequalities in Diagnostic Interval of Common Cancers: a Population-Based UK Cohort Study
Background: This study investigated ethnic differences in diagnostic interval (DI)—the period between initial primary care presentation and diagnosis. Methods: We analysed the primary care-linked data of patients who reported features of seven cancers (breast, lung, prostate, colorectal, oesophagogastric, myeloma, and ovarian) one year before diagnosis. Accelerated failure time (AFT) models investigated the association between DI and ethnicity, adjusting for age, sex, deprivation, and morbidity. Results: of 126,627 eligible participants, 92.1% were White, 1.99% Black, 1.71% Asian, 1.83% Mixed, and 2.36% were of Other ethnic backgrounds. Considering all cancer sites combined, the median (interquartile range) DI was 55 (20–175) days, longest in lung [127, (42–265) days], and shortest in breast cancer [13 (13, 8–18) days]. DI for the Black and Asian groups was 10% (AFT ratio, 95%CI 1.10, 1.05–1.14) and 16% (1.16, 1.10–1.22), respectively, longer than for the White group. Site-specific analyses revealed evidence of longer DI in Asian and Black patients with prostate, colorectal, and oesophagogastric cancer, plus Black patients with breast cancer and myeloma, and the Mixed group with lung cancer compared with White patients. DI was shorter for the Other group with lung, prostate, myeloma, and oesophagogastric cancer than the White group. Conclusion: We found limited and inconsistent evidence of ethnic differences in DI among patients who reported cancer features in primary care before diagnosis. Our findings suggest that inequalities in diagnostic intervals, where present, are unlikely to be the sole explanation for ethnic variations in cancer outcomes.
Abstract.
Watson J, Whiting PF, Salisbury C, Hamilton WT, Banks J (2022). Blood tests in primary care: a qualitative study of communication and decision-making between doctors and patients.
Health Expect,
25(5), 2453-2461.
Abstract:
Blood tests in primary care: a qualitative study of communication and decision-making between doctors and patients.
OBJECTIVE: Blood tests are commonly used in primary care as a tool to aid diagnosis, and to offer reassurance and validation for patients. If doctors and patients do not have a shared understanding of the reasons for testing and the meaning of results, these aims may not be fulfilled. Shared decision-making is widely advocated; yet, most research focusses on treatment decisions rather than diagnostic decisions. The aim of this study was to explore communication and decision-making around diagnostic blood tests in primary care. METHODS: Qualitative interviews were undertaken with patients and clinicians in UK primary care. Patients were interviewed at the time of blood testing, with a follow-up interview after they received test results. Interviews with clinicians who requested the tests provided paired data to compare clinicians' and patients' expectations, experiences and understandings of tests. Interviews were analysed thematically using inductive and deductive coding. RESULTS: a total of 80 interviews with 28 patients and 19 doctors were completed. We identified a mismatch in expectations and understanding of tests, which led to downstream consequences including frustration, anxiety and uncertainty for patients. There was no evidence of shared decision-making in consultations preceding the decision to test. Doctors adopted a paternalistic approach, believing that they were protecting patients from anxiety. CONCLUSION: Patients were not able to develop informed preferences and did not perceive that choice is possible in decisions about testing, because they did not have sufficient information and a shared understanding of tests. A lack of shared understanding at the point of decision-making led to downstream consequences when test results did not fulfil patients' expectations. Although shared decision-making is recommended as best practice, it does not reflect the reality of doctors' and patients' accounts of testing; a broader model of shared understanding seems to be more relevant to the complexity of primary care diagnosis. PATIENT OR PUBLIC CONTRIBUTION: a patient and public involvement group comprising five participants with lived experience of blood testing in primary care met regularly during the study. They contributed to the development of the research objectives, planning recruitment methods, reviewing patient information leaflets and topic guides and also contributed to discussion of emerging themes at an early stage in the analysis process.
Abstract.
Author URL.
Hall R, Medina-Lara A, Hamilton W, Spencer AE (2022). Correction to: Attributes Used for Cancer Screening Discrete Choice Experiments: a Systematic Review.
Patient,
15(3), 379-381.
Author URL.
Black GB, van Os S, Renzi C, Walter FM, Hamilton W, Whitaker KL (2022). Correction: How does safety netting for lung cancer symptoms help patients to reconsult appropriately? a qualitative study. BMC Primary Care, 23(1).
Hopewell S, Keene DJ, Heine P, Marian IR, Dritsaki M, Cureton L, Dutton SJ, Dakin H, Carr A, Hamilton W, et al (2022). Corrigendum: Progressive exercise compared with best-practice advice, with or without corticosteroid injection, for rotator cuff disorders: the GRASP factorial RCT.
Health Technology Assessment,
25(48), 159-160.
Abstract:
Corrigendum: Progressive exercise compared with best-practice advice, with or without corticosteroid injection, for rotator cuff disorders: the GRASP factorial RCT
Abstract
. Corrections to Table 15.
Abstract.
Funston G, Crosbie EJ, Hamilton W, Walter FM (2022). Detecting ovarian cancer in primary care: can we do better?.
Br J Gen Pract,
72(720), 312-313.
Author URL.
Sullivan SA, Kounali D, Morris R, Kessler D, Hamilton W, Lewis G, Lilford P, Nazareth I (2022). Developing and internally validating a prognostic model (P Risk) to improve the prediction of psychosis in a primary care population using electronic health records: the MAPPED study.
Schizophr Res,
246, 241-249.
Abstract:
Developing and internally validating a prognostic model (P Risk) to improve the prediction of psychosis in a primary care population using electronic health records: the MAPPED study.
BACKGROUND: an accurate risk prediction algorithm could improve psychosis outcomes by reducing duration of untreated psychosis. OBJECTIVE: to develop and validate a risk prediction model for psychosis, for use by family doctors, using linked electronic health records. METHODS: a prospective prediction study. Records from family practices were used between 1/1/2010 to 31/12/2017 of 300,000 patients who had consulted their family doctor for any nonpsychotic mental health problem. Records were selected from Clinical Practice Research Datalink Gold, a routine database of UK family doctor records linked to Hospital Episode Statistics, a routine database of UK secondary care records. Each patient had 5-8 years of follow up data. Study predictors were consultations, diagnoses and/or prescribed medications, during the study period or historically, for 13 nonpsychotic mental health problems and behaviours, age, gender, number of mental health consultations, social deprivation, geographical location, and ethnicity. The outcome was time to an ICD10 psychosis diagnosis. FINDINGS: 830 diagnoses of psychosis were made. Patients were from 216 family practices; mean age was 45.3 years and 43.5 % were male. Median follow-up was 6.5 years (IQR 5.6, 7.8). Overall 8-year psychosis incidence was 45.8 (95 % CI 42.8, 49.0)/100,000 person years at risk. A risk prediction model including age, sex, ethnicity, social deprivation, consultations for suicidal behaviour, depression/anxiety, substance abuse, history of consultations for suicidal behaviour, smoking history and prescribed medications for depression/anxiety/PTSD/OCD and total number of consultations had good discrimination (Harrell's C = 0.774). Identifying patients aged 17-100 years with predicted risk exceeding 1.0 % over 6 years had sensitivity of 71 % and specificity of 84 %. FUNDING: NIHR, School for Primary Care Research, Biomedical Research Centre.
Abstract.
Author URL.
Price SJ, Gibson N, Hamilton WT, Bostock J, Shephard EA (2022). Diagnoses after newly-recorded abdominal pain in primary care: observational cohort study. British Journal of General Practice, 72(721).
Martins T, Abel G, Ukoumunne OC, Mounce LTA, Price S, Lyratzopoulos G, Chinegwundoh F, Hamilton W (2022). Ethnic inequalities in routes to diagnosis of cancer: a population-based UK cohort study.
Br J Cancer,
127(5), 863-871.
Abstract:
Ethnic inequalities in routes to diagnosis of cancer: a population-based UK cohort study.
BACKGROUND: UK Asian and Black ethnic groups have poorer outcomes for some cancers and are less likely to report a positive care experience than their White counterparts. This study investigated ethnic differences in the route to diagnosis (RTD) to identify areas in patients' cancer journeys where inequalities lie, and targeted intervention might have optimum impact. METHODS: We analysed data of 243,825 patients with 10 cancers (2006-2016) from the RTD project linked to primary care data. Crude and adjusted proportions of patients diagnosed via six routes (emergency, elective GP referral, two-week wait (2WW), screen-detected, hospital, and Other routes) were calculated by ethnicity. Adjusted odds ratios (including two-way interactions between cancer and age, sex, IMD, and ethnicity) determined cancer-specific differences in RTD by ethnicity. RESULTS: Across the 10 cancers studied, most patients were diagnosed via 2WW (36.4%), elective GP referral (23.2%), emergency (18.2%), hospital routes (10.3%), and screening (8.61%). Patients of Other ethnic group had the highest proportion of diagnosis via the emergency route, followed by White patients. Asian and Black group were more likely to be GP-referred, with the Black and Mixed groups also more likely to follow the 2WW route. However, there were notable cancer-specific differences in the RTD by ethnicity. CONCLUSION: Our findings suggest that, where inequalities exist, the adverse cancer outcomes among Asian and Black patients are unlikely to be arising solely from a poorer diagnostic process.
Abstract.
Author URL.
Black GB, van Os S, Renzi C, Walter FM, Hamilton W, Whitaker KL (2022). How does safety netting for lung cancer symptoms help patients to reconsult appropriately? a qualitative study.
BMC Prim Care,
23(1).
Abstract:
How does safety netting for lung cancer symptoms help patients to reconsult appropriately? a qualitative study.
BACKGROUND: Safety netting in primary care is considered an important intervention for managing diagnostic uncertainty. This is the first study to examine how patients understand and interpret safety netting advice around low-risk potential lung cancer symptoms, and how this affects reconsultation behaviours. METHODS: Qualitative interview study in UK primary care. Pre-covid-19, five patients were interviewed in person within 2-3 weeks of a primary care consultation for potential lung cancer symptom(s), and again 2-5 months later. The general practitioner (GP) they last saw was interviewed face-to-face once. During the covid-19 pandemic, an additional 15 patients were interviewed only once via telephone, and their GPs were not interviewed or contacted in any way. Audio-recorded interviews were transcribed verbatim and analysed using inductive thematic analysis. RESULTS: the findings from our thematic analysis suggest that patients prefer active safety netting, as part of thorough and logical diagnostic uncertainty management. Passive or ambiguous safety netting may be perceived as dismissive and cause delayed reconsultation. GP safety netting strategies are not always understood, potentially causing patient worry and dissatisfaction. Telephone consultations and the diagnostic overshadowing of COVID-19 on respiratory symptoms impacted GPs' safety netting strategies and patients' appetite for active follow up measures. CONCLUSIONS: Safety netting guidelines do not yet offer solutions that have been proven to promote symptom vigilance and timely reconsultation for low-risk lung cancer symptoms. This may have been affected by primary care practices during the COVID-19 pandemic. Patients prefer active or pre-planned safety netting coupled with thorough consultation techniques and a comprehensible diagnostic strategy, and may respond adversely to passive safety netting advice.
Abstract.
Author URL.
Offman J, Pesola F, Fitzgerald RC, Hamilton W, Sasieni P (2022). Impact of Barrett oesophagus diagnoses and endoscopies on oesophageal cancer survival in the UK: a cohort study.
Cancer Med,
11(4), 1160-1171.
Abstract:
Impact of Barrett oesophagus diagnoses and endoscopies on oesophageal cancer survival in the UK: a cohort study.
BACKGROUND: Current guidelines recommend endoscopic surveillance for Barrett oesophagus (BE), but the value of surveillance is still debated. Using a combination of primary care, secondary care and cancer registry datasets, we examined the impact of a prior BE diagnosis, clinical and risk factors on survival from oesophageal cancer and adenocarcinoma. METHODS: Retrospective cohort study of patients aged 50 and above diagnosed with malignant oesophageal cancer between 1993 and 2014 using Clinical Practice Research Datalink (CPRD). All prior BE diagnoses and endoscopies were identified from CPRD and Hospital Episode Statistics. Histology information was obtained from linked cancer registry data. We used flexible parametric models to estimate excess hazard ratios (EHRs) for relative survival. We simulated the potential impact of lead-time by adding random lead-times from a variety of distributions to all those with prior BE. RESULTS: Among our oesophageal cancer (n = 7503) and adenocarcinoma (n = 1476) cohorts only small percentages, 3.4% and 5.3%, respectively, had a prior BE diagnosis. Two-year relative survival was better among patients with BE: 48.0% (95% CI 41.9-54.9) compared to 25.2% (24.3-26.2) without. Patients with BE had a better prognosis (EHR = 0.53, 0.41-0.68). Survival was higher even if patients with BE had fewer than two endoscopies (50.0%; 43.6-57.3). A survival benefit was still observed after lead-time adjustment, with a 20% absolute difference in 2-year survival using a 5 year mean sojourn time. CONCLUSIONS: Patients with a prior BE diagnosis had a survival advantage. This was not fully explained by surveillance endoscopies.
Abstract.
Author URL.
Streeter AJ, Rodgers LR, Hamilton F, Masoli JAH, Blé A, Hamilton WT, Henley WE (2022). Influenza vaccination reduced myocardial infarctions in United Kingdom older adults: a prior event rate ratio study. Journal of Clinical Epidemiology, 151, 122-131.
Price SJ, Gibson N, Hamilton WT, King A, Shephard EA (2022). Intra-abdominal cancer risk with abdominal pain: a prospective cohort primary care study.
British Journal of General Practice,
72(718), e361-e368.
Abstract:
Intra-abdominal cancer risk with abdominal pain: a prospective cohort primary care study
BackgroundQuantifying cancer risk in primary care patients with abdominal pain informs diagnostic strategies.AimTo quantify oesophagogastric, colorectal, liver, pancreatic, ovarian, uterine, kidney, and bladder cancer risks associated with newly reported abdominal pain with or without other symptoms, signs, or abnormal blood tests (that is, features) indicative of possible cancer.Design and settingThis was an observational prospective cohort study using Clinical Practice Research Datalink records with English cancer registry linkage.MethodThe authors studied 125 793 patients aged ≥40 years with newly reported abdominal pain in primary care between 1 January 2009 and 31 December 2013. The 1-year cumulative incidence of cancer, and the composite 1-year cumulative incidence of cancers with shared additional features, stratified by age and sex are reported.ResultsWith abdominal pain, overall risk was greater in men and increased with age, reaching 3.4% (95% confidence interval [CI] = 3.0 to 3.7, predominantly colorectal cancer 1.9%, 95% CI = 1.6 to 2.1) in men ≥70 years, compared with their expected incidence of 0.88% (95% CI = 0.87 to 0.89). Additional features increased cancer risk; for example, for men, colorectal or pancreatic cancer risk with abdominal pain plus diarrhoea at 60–69 years of age was 3.1% (95% CI = 1.9 to 4.9) predominantly colorectal cancer (2.2%, 95% CI = 1.2 to 3.8).ConclusionAbdominal pain increases intra-abdominal cancer risk nearly fourfold in men aged ≥70 years, exceeding the 3% threshold warranting investigation. This threshold is surpassed for the >60 years age group only with additional features. These results will help direct appropriate referral and testing strategies for patients based on their demographic profile and reporting features. The authors suggest non-invasive strategies first, such as faecal immunochemical testing, with safety-netting in a shared decision-making framework.
Abstract.
Briggs E, de Kamps M, Hamilton W, Johnson O, McInerney CD, Neal RD (2022). Machine Learning for Risk Prediction of Oesophago-Gastric Cancer in Primary Care: Comparison with Existing Risk-Assessment Tools.
Cancers,
14(20), 5023-5023.
Abstract:
Machine Learning for Risk Prediction of Oesophago-Gastric Cancer in Primary Care: Comparison with Existing Risk-Assessment Tools
Oesophago-gastric cancer is difficult to diagnose in the early stages given its typical non-specific initial manifestation. We hypothesise that machine learning can improve upon the diagnostic performance of current primary care risk-assessment tools by using advanced analytical techniques to exploit the wealth of evidence available in the electronic health record. We used a primary care electronic health record dataset derived from the UK General Practice Research Database (7471 cases; 32,877 controls) and developed five probabilistic machine learning classifiers: Support Vector Machine, Random Forest, Logistic Regression, Naïve Bayes, and Extreme Gradient Boosted Decision Trees. Features included basic demographics, symptoms, and lab test results. The Logistic Regression, Support Vector Machine, and Extreme Gradient Boosted Decision Tree models achieved the highest performance in terms of accuracy and AUROC (0.89 accuracy, 0.87 AUROC), outperforming a current UK oesophago-gastric cancer risk-assessment tool (ogRAT). Machine learning also identified more cancer patients than the ogRAT: 11.0% more with little to no effect on false positives, or up to 25.0% more with a slight increase in false positives (for Logistic Regression, results threshold-dependent). Feature contribution estimates and individual prediction explanations indicated clinical relevance. We conclude that machine learning could improve primary care cancer risk-assessment tools, potentially helping clinicians to identify additional cancer cases earlier. This could, in turn, improve survival outcomes.
Abstract.
Dave RV, Bromley H, Taxiarchi VP, Camacho E, Chatterjee S, Barnes N, Hutchison G, Bishop P, Hamilton W, Kirwan CC, et al (2022). No association between breast pain and breast cancer: a prospective cohort study of 10 830 symptomatic women presenting to a breast cancer diagnostic clinic.
Br J Gen Pract,
72(717), e234-e243.
Abstract:
No association between breast pain and breast cancer: a prospective cohort study of 10 830 symptomatic women presenting to a breast cancer diagnostic clinic.
BACKGROUND: Women with breast pain constitute >20% of breast clinic attendees. AIM: to investigate breast cancer incidence in women presenting with breast pain and establish the health economics of referring women with breast pain to secondary care. DESIGN AND SETTING: a prospective cohort study of all consecutive women referred to a breast diagnostic clinic over 12 months. METHOD: Women were categorised by presentation into four distinct clinical groups and cancer incidence investigated. RESULTS: of 10 830 women, 1972 (18%) were referred with breast pain, 6708 (62%) with lumps, 480 (4%) with nipple symptoms, 1670 (15%) with 'other' symptoms. Mammography, performed in 1112 women with breast pain, identified cancer in eight (0.7%). of the 1972 women with breast pain, breast cancer incidence was 0.4% compared with ∼5% in each of the three other clinical groups. Using 'breast lump' as reference, the odds ratio (OR) of women referred with breast pain having breast cancer was 0.05 (95% confidence interval = 0.02 to 0.09, P
Abstract.
Author URL.
Khan T, El-Sockary Y, Hamilton WT, Shephard EA (2022). Recognizing sinonasal cancer in primary care: a matched case-control study using electronic records.
Fam Pract,
39(3), 354-359.
Abstract:
Recognizing sinonasal cancer in primary care: a matched case-control study using electronic records.
BACKGROUND: Cancers of the nasopharynx, nasal cavity, and accessory sinuses ("sinonasal") are rare in England, with around 750 patients diagnosed annually. There are no specific National Institute for Health and Care Excellence (NICE) referral guidelines for these cancers and no primary care research published. OBJECTIVE: to identify and quantify clinical features of sinonasal cancer in UK primary care patients. METHODS: This matched case-control study used UK Clinical Practice Research Datalink (CPRD) data. Patients were aged ≥40 years with a diagnosis of sinonasal cancer between January 1, 2000 and December 31, 2009 and had consulted their GP in the year before diagnosis. Clinical features of sinonasal cancer were analysed using conditional logistic regression. Positive predictive values (PPVs) for single and combined features were calculated. RESULTS: in total, 155 cases and 697 controls were studied. Nine symptoms and one abnormal investigation were significantly associated with the cancer: nasal mass; odds ratio, 95 (95% confidence interval 7.0, 1315, P = 0.001); head and neck lumps, 68 (12, 387, P < 0.001); epistaxis, 17 (3.9, 70, P < 0.001); rhinorrhoea, 14 (4.6, 44, P < 0.001); visual disturbance, 12 (2.2, 67, P = 0.004); sinusitis, 7.3 (2.2, 25, P = 0.001); sore throat, 6.0 (2.0, 18, P = 0.001); otalgia, 5.4 (1.6, 18, P = 0.007); headache, 3.6 (1.4, 9.5, P = 0.01); raised white cell count, 8.5 (2.8, 27, P < 0.001). Combined PPVs for epistaxis/rhinorrhoea, epistaxis/sinusitis, and rhinorrhoea/sinusitis were 0.62%. CONCLUSION: This is the first primary care study identifying epistaxis, sinusitis, and rhinorrhoea as part of the clinical prodrome of sinonasal cancer. Although no PPVs meet the 3% NICE referral threshold, these results may help clinicians identify who warrants safety-netting and possible specialist referral, potentially reducing the number of advanced-stage diagnoses of sinonasal cancer.
Abstract.
Author URL.
Price S, Spencer A, Hamilton W (2022). Revising the Suspected-Cancer Guidelines: Impacts on Patients’ Primary Care Contacts and Costs. Value in Health
White B, Rafiq M, Gonzalez-Izquierdo A, Hamilton W, Price S, Lyratzopoulos G (2022). Risk of cancer following primary care presentation with fatigue: a population-based cohort study of a quarter of a million patients.
British Journal of Cancer,
126(11), 1627-1636.
Abstract:
Risk of cancer following primary care presentation with fatigue: a population-based cohort study of a quarter of a million patients
Abstract
. Background
. The management of adults presenting with fatigue presents a diagnostic challenge, particularly regarding possible underlying cancer.
.
. Methods
. Using electronic health records, we examined cancer risk in patients presenting to primary care with new-onset fatigue in England during 2007–2013, compared to general population estimates. We examined variation by age, sex, deprivation, and time following presentation.
.
. Findings
. of 250,606 patients presenting with fatigue, 12-month cancer risk exceeded 3% in men aged 65 and over and women aged 80 and over, and 6% in men aged 80 and over. Nearly half (47%) of cancers were diagnosed within 3 months from first fatigue presentation. Site-specific cancer risk was higher than the general population for most cancers studied, with greatest relative increases for leukaemia, pancreatic and brain cancers.
.
. Conclusions
. In older patients, new-onset fatigue is associated with cancer risk exceeding current thresholds for urgent specialist referral. Future research should consider how risk is modified by the presence or absence of other signs and symptoms. Excess cancer risk wanes rapidly after 3 months, which could inform the duration of a ‘safety-netting’ period. Fatigue presentation is not strongly predictive of any single cancer, although certain cancers are over-represented; this knowledge can help prioritise diagnostic strategies.
.
Abstract.
O'Dowd EL, Ten Haaf K, Kaur J, Duffy SW, Hamilton W, Hubbard RB, Field JK, Callister ME, Janes SM, de Koning HJ, et al (2022). Selection of eligible participants for screening for lung cancer using primary care data.
Thorax,
77(9), 882-890.
Abstract:
Selection of eligible participants for screening for lung cancer using primary care data.
UNLABELLED: Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown. METHOD: the Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the Liverpool Lung Project V.2 (LLPv2) and Prostate Lung Colorectal and Ovarian (modified 2012) (PLCOm2012) models. Lung cancer occurrence over 5-6 years was measured in ever-smokers aged 50-80 years and compared with 5-year (LLPv2) and 6-year (PLCOm2012) predicted risk. RESULTS: over 5 and 6 years, 7123 and 7876 lung cancers occurred, respectively, from a cohort of 842 109 ever-smokers. After recalibration, LLPV2 produced a c-statistic of 0.700 (0.694-0.710), but mean predicted risk was over-estimated (predicted: 4.61%, actual: 0.9%). PLCOm2012 showed similar performance (c-statistic: 0.679 (0.673-0.685), predicted risk: 3.76%. Applying risk-thresholds of 1% (LLPv2) and 0.15% (PLCOm2012), would avoid contacting 42.7% and 27.4% of ever-smokers who did not develop lung cancer for screening eligibility assessment, at the cost of missing 15.6% and 11.4% of lung cancers. CONCLUSION: Risk-prediction models showed only moderate discrimination when applied to routinely collected primary care data, which may be explained by quality and completeness of data. However, they may substantially reduce the number of people for initial evaluation of screening eligibility, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data.
Abstract.
Author URL.
Merriel SWD, Pocock L, Gilbert E, Creavin S, Walter FM, Spencer A, Hamilton W (2022). Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients.
BMC Medicine,
20(1).
Abstract:
Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients
Abstract
. Background
. Prostate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.
.
. Methods
. A systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.
.
. Results
. Five hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.
.
. Conclusions
. Currently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.
.
Abstract.
Smith L, Sansom N, Hemphill S, Bradley SH, Shinkins B, Wheatstone P, Hamilton W, Neal RD (2022). Trends and variation in urgent referrals for suspected cancer 2009/2010-2019/2020.
Br J Gen Pract,
72(714), 34-37.
Author URL.
Zienius K, Ozawa M, Hamilton W, Hollingworth W, Weller D, Porteous L, Ben-Shlomo Y, Grant R, Brennan PM (2022). Verbal fluency as a quick and simple tool to help in deciding when to refer patients with a possible brain tumour.
BMC NEUROLOGY,
22(1).
Author URL.
Calanzani N, Pannebakker MM, Tagg MJ, Walford H, Holloway P, de Wit N, Hamilton W, Walter FM (2022). Who are the patients being offered the faecal immunochemical test in routine English general practice, and for what symptoms? a prospective descriptive study.
BMJ open,
12(9).
Abstract:
Who are the patients being offered the faecal immunochemical test in routine English general practice, and for what symptoms? a prospective descriptive study.
ObjectivesThe faecal immunochemical test (FIT) was introduced to triage patients with lower-risk symptoms of colorectal cancer (CRC) in English primary care in 2018. While there is growing evidence on its utility to triage patients in this setting, evidence is still limited on how official FIT guidance is being used, for which patients and for what symptoms. We aimed to investigate the use of FIT in primary care practice for lower-risk patients who did not immediately meet criteria for urgent referral.DesignA prospective, descriptive study of symptomatic patients offered a FIT in primary care between January and June 2020.SettingEast of England general practices.ParticipantsConsenting patients (aged ≥40 years) who were seen by their general practitioners (GPs) with symptoms of possible CRC for whom a FIT was requested. We excluded patients receiving a FIT for asymptomatic screening purposes, or patients deemed by GPs as lacking capacity for informed consent. Data were obtained via patient questionnaire, medical and laboratory records.Primary and secondary outcome measuresFIT results (10 µg Hb/g faeces defined a positive result); patient sociodemographic and clinical characteristics; patient-reported and GP-recorded symptoms, symptom severity and symptom agreement between patient and GP (% and kappa statistics).ResultsComplete data were available for 310 patients, median age 70 (IQR 61-77) years, 53% female and 23% FIT positive. Patients most commonly reported change in bowel habit (69%) and fatigue (57%), while GPs most commonly recorded abdominal pain (25%) and change in bowel habit (24%). Symptom agreement ranged from 44% (fatigue) to 80% (unexplained weight loss). Kappa agreement was universally low across symptoms.ConclusionAlmost a quarter of this primary care cohort of symptomatic patients with FIT testing were found to be positive. However, there was low agreement between patient-reported and GP-recorded symptoms. This may impact cancer risk assessment and optimal patient management in primary care.
Abstract.
Hall R, Medina-Lara A, Hamilton W, Spencer A (2022). Women’s priorities towards ovarian cancer testing: a best–worst scaling study.
BMJ Open,
12(9), e061625-e061625.
Abstract:
Women’s priorities towards ovarian cancer testing: a best–worst scaling study
ObjectiveTo investigate the importance of key characteristics relating to diagnostic testing for ovarian cancer and to understand how previous test experience influences priorities.DesignCase 1 best–worst scaling embedded in an online survey.SettingPrimary care diagnostic testing in England and Wales.Participants150 women with ovaries over 40 years old living in England and Wales.MethodsWe used best–worst scaling, a preference-based survey method, to elicit the relative importance of 25 characteristics relating to ovarian cancer testing following a systematic review. Responses were modelled using conditional logit regression. Subgroup analysis investigated variations based on testing history.Main outcome measuresRelative importance scores.Results‘Chance of dying from ovarian cancer’ (0.380, 95% CI 0.26 to 0.49) was the most important factor to respondents, closely followed by ‘test sensitivity’ (0.308, 95% CI 0.21 to 0.40). In contrast, ‘time away from usual activities’ (−0.244, 95% CI −0.33 to −0.15) and ‘gender of healthcare provider’ (−0.243, 95% CI −0.35 to −0.14) were least important to respondents overall. Women who had previously undergone testing placed higher importance on certain characteristics including ‘openness of healthcare providers’ and ‘chance of diagnosing another condition’ at the expense of reduced emphasis on characteristics such as ‘pain and discomfort’ and ‘time away from usual activities’.ConclusionsThe results clearly demonstrated items at the extreme, which were most and least important to women considering ovarian cancer testing. Differences in priorities by testing history demonstrate an experience effect, whereby preferences adapt over time based on evidence and experience. Acknowledging these differences helps to identify underlying barriers and facilitators for women with no test experience as well as shortcomings of current service based on women with experience.
Abstract.
Bhartia BSK, Hatton NLF, Aslam R, Bradley SH, Darby M, Hamilton WT, Hurst E, Kennedy MPT, Mounce LTA, Neal RD, et al (2021). A prospective cohort evaluation of the sensitivity and specificity of the chest X-ray for the detection of lung cancer in symptomatic adults.
European Journal of Radiology,
144Abstract:
A prospective cohort evaluation of the sensitivity and specificity of the chest X-ray for the detection of lung cancer in symptomatic adults
Background: the accuracy of the chest x-ray (CXR) in the identification of lung cancer amongst symptomatic individuals is uncertain. Purpose: to determine the diagnostic accuracy of the CXR for the detection of non-small cell carcinomas (NSCLC) and all primary intrathoracic malignancies. Methods: a prospective cohort study of consecutive CXR reports obtained within a primary care open access initiative. Eligibility criteria were symptoms specified by National Institute for Clinical Excellence as indicative of possible lung cancer and age over 50-yrs. A positive test was a CXR which led directly or indirectly to investigation with CT. The reference standards were malignancies observed within a one- or two-year post-test period. Results: 8,948 CXR outcomes were evaluated. 496 positive studies led to a diagnosis of 101 patients with primary intrathoracic malignancy including 80 with NSCLC. Within two-years, a cumulative total of 168 patients with primary intrathoracic malignancies including 133 NSCLC were observed. The sensitivity and specificity for NSCLC were 76% (95 %CI 68–84) and 95% (95 %CI 95–96) within 1-year and 60% (95 %CI 52–69) and 95% (95 %CI 95–96) within 2-years. The 2-yr positive and negative likelihood ratios were 12.8 and 0.4. The results did not differ for NSCLC compared to all primary malignancies. Within this symptomatic population a negative test reduced the 2-year risk of lung cancer to 0.8%. Conclusions: a positive test strongly increases the probability of malignancy whereas a negative test does not conclusively exclude the disease. The findings allow the risk of malignancy following a negative test to be estimated.
Abstract.
Jones OT, Calanzani N, Saji S, Duffy SW, Emery J, Hamilton W, Singh H, de Wit NJ, Walter FM (2021). Artificial Intelligence Techniques That May be Applied to Primary Care Data to Facilitate Earlier Diagnosis of Cancer: Systematic Review.
Journal of Medical Internet Research,
23(3), e23483-e23483.
Abstract:
Artificial Intelligence Techniques That May be Applied to Primary Care Data to Facilitate Earlier Diagnosis of Cancer: Systematic Review
. Background
. More than 17 million people worldwide, including 360,000 people in the United Kingdom, were diagnosed with cancer in 2018. Cancer prognosis and disease burden are highly dependent on the disease stage at diagnosis. Most people diagnosed with cancer first present in primary care settings, where improved assessment of the (often vague) presenting symptoms of cancer could lead to earlier detection and improved outcomes for patients. There is accumulating evidence that artificial intelligence (AI) can assist clinicians in making better clinical decisions in some areas of health care.
.
.
. Objective
. This study aimed to systematically review AI techniques that may facilitate earlier diagnosis of cancer and could be applied to primary care electronic health record (EHR) data. The quality of the evidence, the phase of development the AI techniques have reached, the gaps that exist in the evidence, and the potential for use in primary care were evaluated.
.
.
. Methods
. We searched MEDLINE, Embase, SCOPUS, and Web of Science databases from January 01, 2000, to June 11, 2019, and included all studies providing evidence for the accuracy or effectiveness of applying AI techniques for the early detection of cancer, which may be applicable to primary care EHRs. We included all study designs in all settings and languages. These searches were extended through a scoping review of AI-based commercial technologies. The main outcomes assessed were measures of diagnostic accuracy for cancer.
.
.
. Results
. We identified 10,456 studies; 16 studies met the inclusion criteria, representing the data of 3,862,910 patients. A total of 13 studies described the initial development and testing of AI algorithms, and 3 studies described the validation of an AI algorithm in independent data sets. One study was based on prospectively collected data; only 3 studies were based on primary care data. We found no data on implementation barriers or cost-effectiveness. Risk of bias assessment highlighted a wide range of study quality. The additional scoping review of commercial AI technologies identified 21 technologies, only 1 meeting our inclusion criteria. Meta-analysis was not undertaken because of the heterogeneity of AI modalities, data set characteristics, and outcome measures.
.
.
. Conclusions
. AI techniques have been applied to EHR-type data to facilitate early diagnosis of cancer, but their use in primary care settings is still at an early stage of maturity. Further evidence is needed on their performance using primary care data, implementation barriers, and cost-effectiveness before widespread adoption into routine primary care clinical practice can be recommended.
.
Abstract.
Funston G, Mounce LTA, Price S, Rous B, Crosbie EJ, Hamilton W, Walter FM (2021). CA125 test result, test-to-diagnosis interval, and stage in ovarian cancer at diagnosis: a retrospective cohort study using electronic health records.
British Journal of General Practice,
71(707), e465-e472.
Abstract:
CA125 test result, test-to-diagnosis interval, and stage in ovarian cancer at diagnosis: a retrospective cohort study using electronic health records
BackgroundIn the UK, the cancer antigen 125 (CA125) test is recommended as a first-line investigation in women with symptoms of possible ovarian cancer.AimTo compare time between initial primary care CA125 test and diagnosis, tumour morphology, and stage in women with normal (<35 U/ml) and abnormal (≥35 U/ml) CA125 levels prior to ovarian cancer diagnosis.Design and settingRetrospective cohort study using English primary care and cancer registry data.MethodAssociations between CA125 test results and test-to-diagnosis interval, stage, and ovarian cancer morphology were examined.ResultsIn total, 456 women were diagnosed with ovarian cancer in the 12 months after having a CA125 test. of these, 351 (77%) had an abnormal, and 105 (23%) had a normal, CA125 test result. The median test-to-diagnosis interval was 35 days (interquartile range [IQR] 21–53) for those with abnormal CA125 levels, and 64 days (IQR 42–127) for normal CA125 levels. Tumour morphology differed by CA125 result: indolent borderline tumours were less common in those with abnormal CA125 levels (n = 47, 13%) than those with normal CA125 levels (n = 51, 49%) (P<0.001). Staging data were available for 304 women with abnormal, and 77 with normal, CA125 levels. of those with abnormal CA125 levels, 35% (n = 106) were diagnosed at an early stage, compared to 86% (n = 66) of women with normal levels. The odds of being diagnosed with early-stage disease were higher in women with normal as opposed to abnormal CA125 levels (odds ratio 12.2, 95% confidence interval = 5.8 to 25.1, P<0.001).ConclusionDespite longer intervals between testing and diagnosis, women with normal, compared with abnormal, CA125 levels more frequently had indolent tumours and were more commonly diagnosed at an early stage in the course of the disease. Although testing approaches that have greater sensitivity might expedite diagnosis for some women, it is not known if this would translate to earlier-stage diagnosis.
Abstract.
Bradley SH, Bhartia BS, Callister ME, Hamilton WT, Hatton NLF, Kennedy MP, Mounce LT, Shinkins B, Wheatstone P, Neal RD, et al (2021). Chest X-ray sensitivity and lung cancer outcomes: a retrospective observational study.
Br J Gen Pract,
71(712), e862-e868.
Abstract:
Chest X-ray sensitivity and lung cancer outcomes: a retrospective observational study.
BACKGROUND: Chest X-ray (CXR) is the first-line investigation for lung cancer in many healthcare systems. An understanding of the consequences of false-negative CXRs on time to diagnosis, stage, and survival is limited. AIM: to determine the sensitivity of CXR for lung cancer and to compare stage at diagnosis, time to diagnosis, and survival between those with CXR that detected, or did not detect, lung cancer. DESIGN AND SETTING: Retrospective observational study using routinely collected healthcare data. METHOD: all patients diagnosed with lung cancer in Leeds Teaching Hospitals NHS Trust during 2008-2015 who had a GP-requested CXR in the year before diagnosis were categorised based on the result of the earliest CXR performed in that period. The sensitivity of CXR was calculated and analyses were performed with respect to time to diagnosis, survival, and stage at diagnosis. RESULTS: CXR was negative for 17.7% of patients (n = 376/2129). Median time from initial CXR to diagnosis was 43 days for those with a positive CXR and 204 days for those with a negative CXR. of those with a positive CXR, 29.8% (95% confidence interval [CI] = 27.9% to 31.8%) were diagnosed at stage I or II, compared with 33.5% (95% CI = 28.8% to 38.6%) with a negative CXR. CONCLUSION: GPs should consider lung cancer in patients with persistent symptoms even when CXR is negative. Despite longer duration to diagnosis for those with false-negative CXRs, there was no evidence of an adverse impact on stage at diagnosis or survival; however, this comparison is likely to be affected by confounding variables.
Abstract.
Author URL.
Nicholson BD, Aveyard P, Koshiaris C, Perera R, Hamilton W, Oke J, Hobbs FDR (2021). Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.
PLOS Medicine,
18(8), e1003728-e1003728.
Abstract:
Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis
Background
Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer.
Methods and findings
We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors.
Conclusions
Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.
Abstract.
Wiering B, Lyratzopoulos G, Hamilton W, Campbell J, Abel G (2021). Concordance with urgent referral guidelines in patients presenting with any of six ‘alarm’ features of possible cancer: a retrospective cohort study using linked primary care records.
BMJ Quality & Safety,
31(8), 579-589.
Abstract:
Concordance with urgent referral guidelines in patients presenting with any of six ‘alarm’ features of possible cancer: a retrospective cohort study using linked primary care records
BackgroundClinical guidelines advise GPs in England which patients warrant an urgent referral for suspected cancer. This study assessed how often GPs follow the guidelines, whether certain patients are less likely to be referred, and how many patients were diagnosed with cancer within 1 year of non-referral.MethodsWe used linked primary care (Clinical Practice Research Datalink), secondary care (Hospital Episode Statistics) and cancer registration data. Patients presenting with haematuria, breast lump, dysphagia, iron-deficiency anaemia, post-menopausal or rectal bleeding for the first time during 2014–2015 were included (for ages where guidelines recommend urgent referral). Logistic regression was used to investigate whether receiving a referral was associated with feature type and patient characteristics. Cancer incidence (based on recorded diagnoses in cancer registry data within 1 year of presentation) was compared between those receiving and those not receiving referrals.Results48 715 patients were included, of which 40% (n=19 670) received an urgent referral within 14 days of presentation, varying by feature from 17% (dysphagia) to 68% (breast lump). Young patients (18–24 vs 55–64 years; adjusted OR 0.20, 95% CI 0.10 to 0.42, p<0.001) and those with comorbidities (4 vs 0 comorbidities; adjusted OR 0.87, 95% CI 0.80 to 0.94, p<0.001) were less likely to receive a referral. Associations between patient characteristics and referrals differed across features: among patients presenting with anaemia, breast lump or haematuria, those with multi-morbidity, and additionally for breast lump, more deprived patients were less likely to receive a referral. of 29 045 patients not receiving a referral, 3.6% (1047) were diagnosed with cancer within 1 year, ranging from 2.8% for rectal bleeding to 9.5% for anaemia.ConclusionsGuideline recommendations for action are not followed for the majority of patients presenting with common possible cancer features. A significant number of these patients developed cancer within 1 year of their consultation, indicating scope for improvement in the diagnostic process.
Abstract.
Funston G, Abel G, Crosbie EJ, Hamilton W, Walter FM (2021). Could ovarian cancer prediction models improve the triage of symptomatic women in primary care? a modelling study using routinely collected data.
Cancers,
13(12).
Abstract:
Could ovarian cancer prediction models improve the triage of symptomatic women in primary care? a modelling study using routinely collected data
CA125 is widely used as an initial investigation in women presenting with symptoms of possible ovarian cancer. We sought to develop CA125-based diagnostic prediction models and to explore potential implications of implementing model-based thresholds for further investigation in primary care. This retrospective cohort study used routinely collected primary care and cancer registry data from symptomatic, CA125-tested women in England (2011–2014). A total of 29,962 women were included, of whom 279 were diagnosed with ovarian cancer. Logistic regression was used to develop two models to estimate ovarian cancer probability: Model 1 consisted of age and CA125 level; Model 2 incorporated further risk factors. Model discrimination (AUC) was evaluated using 10-fold cross-validation. The sensitivity and specificity of various model risk thresholds (≥1% to ≥3%) were compared with that of the current CA125 cut-off (≥35 U/mL). Model 1 exhibited excellent discrimination (AUC: 0.94) on cross-validation. The inclusion of additional variables (Model 2) did not improve performance. At a risk threshold of ≥1%, Model 1 exhibited greater sensitivity (86.4% vs. 78.5%) but lower specificity (89.1% vs. 94.5%) than CA125 (≥35 U/mL). Applying the ≥1% model threshold to the cohort in place of the current CA125 cut-off, 1 in every 74 additional women identified had ovarian cancer. Following external validation, Model 1 could be used as part of a ‘risk-based triage’ system in which women at high risk of undiagnosed ovarian cancer are selected for urgent specialist investigation, while women at ‘low risk but not no risk’ are offered non-urgent investigation or interval CA125 re-testing. Such an approach has the potential to expedite ovarian cancer diagnosis, but further research is needed to evaluate the clinical impact and health–economic implications.
Abstract.
Hamilton W, Pascoe J, John J, Coats T, Davies S (2021). Diagnosing groin lumps.
BMJ,
372 Author URL.
Bailey SER, Abel GA, Atkins A, Byford R, Davies S-J, Mays J, McDonald TJ, Miller J, Neck C, Renninson J, et al (2021). Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England.
Br J Cancer,
124(7), 1231-1236.
Abstract:
Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England.
BACKGROUND: the faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence. METHODS: all healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 μg Hb/g faeces defined a positive test. RESULTS: Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1-9.3%). Negative predictive value was 99.8% (CI 99.5-99.9%). Sensitivity was 84.3% (CI 71.4-93.0%), specificity 85.0% (CI 83.8-86.1%). The area under the ROC curve was 0.92 (CI 0.86-0.96). A threshold of 37 μg Hb/g faeces would identify patients with an individual 3% risk of cancer. CONCLUSIONS: FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.
Abstract.
Author URL.
Ladegaard Baun M-L, Dueholm M, Heje HN, Hamilton W, Petersen LK, Vedsted P (2021). Direct access from general practice to transvaginal ultrasound for early detection of ovarian cancer: a feasibility study.
Scand J Prim Health Care,
39(2), 230-239.
Abstract:
Direct access from general practice to transvaginal ultrasound for early detection of ovarian cancer: a feasibility study.
OBJECTIVE: to investigate the feasibility of providing general practitioners (GPs) direct and fast referral access to transvaginal ultrasound (TVUS). DESIGN: a prospective cohort study. SETTING: a total of 232 Danish general practices in parts of the Central Denmark Region. SUBJECTS: Women aged ≥40 years who consulted their GP for vague and non-specific symptoms (n = 479). MAIN OUTCOME MEASURES: the feasibility assessment included the GPs' referral rate, indications for referral, management of test results, and findings from TVUS. RESULTS: a total of 479 women were referred to TVUS. The examinations revealed abnormalities in 104 (21.7%) women. Additional investigations were needed in 68 (14.2%) women of whom seven (1.5%) underwent major surgery. No case of ovarian cancer was diagnosed during the study period or the 6-month follow-up. However, three (0.6%) women with an abnormal transvaginal ultrasound were diagnosed with urogynecological cancer; this yielded a PPV of 4.4% (95% confidence interval: 1.5-12.2) and an NPV of 100.0% (95% confidence interval: 96.7-100.0) for urogynecological cancer. CONCLUSION: Providing GPs with direct access to transvaginal ultrasound was feasible; 80% of the investigated women were referred back to the GP, 14% were further investigated, 0.6% were diagnosed with urogynecological cancer, and 1.5% had major procedures performed without complications. IMPLICATIONS: Direct access to TVUS could be an important pathway to ensure fast evaluation of women presenting with vague non-specific symptoms of potential ovarian cancer. Future studies should explore the patient experience, cancer outcomes, and health economics issues.KEY POINTS Current awareness • GPs have no fast referral option for women presenting with vague non-specific symptoms that could indicate underlying ovarian cancer. Key findings • We offered GPs direct and fast referral access to TVUS; 51.7% of practices used the opportunity. • The GPs referred 479 women to TVUS; 104 had an abnormal TVUS and 68 needed additional investigations. • Seven women underwent major surgery, leading to three cases of urogynecological cancer. No woman had a false negative TVUS result.
Abstract.
Author URL.
Rubin G, Walter FM, Emery J, Hamilton W, Hoare Z, Howse J, Nixon C, Srivastava T, Thomas C, Ukoumunne OC, et al (2021). Electronic clinical decision support tool for assessing stomach symptoms in primary care (ECASS): a feasibility study.
BMJ Open,
11(3), e041795-e041795.
Abstract:
Electronic clinical decision support tool for assessing stomach symptoms in primary care (ECASS): a feasibility study
ObjectiveTo determine the feasibility of a definitive trial in primary care of electronic clinical decision support (eCDS) for possible oesophago-gastric (O-G) cancer.Design and settingFeasibility study in 42 general practices in two regions of England, cluster randomised controlled trial design without blinding, nested qualitative and health economic evaluation.ParticipantsPatients aged 55 years or older, presenting to their general practitioner (GP) with symptoms associated with O-G cancer. 530 patients (mean age 68 years, 58% female) participated.InterventionPractices randomised 1:1 to usual care (control) or to receive a previously piloted eCDS tool for suspected cancer (intervention), for use at the discretion of the GPs, supported by a theory-based implementation package and ongoing support. We conducted semistructured interviews with GPs in intervention practices. Recruitment lasted 22 months.OutcomesPatient participation rate, use of eCDS, referrals and route to diagnosis, O-G cancer diagnoses; acceptability to GPs; cost-effectiveness. Participants followed up 6 months after index encounter.ResultsFrom control and intervention practices, we screened 3841 and 1303 patients, respectively; 1189 and 434 were eligible, 392 and 138 consented to participate. Ten patients (1.9%) had O-G cancer. eCDS was used eight times in total by five unique users. GPs experienced interoperability problems between the eCDS tool and their clinical system and also found it did not fit with their workflow. Unexpected restrictions on software installation caused major problems with implementation.ConclusionsThe conduct of this study was hampered by technical limitations not evident during an earlier pilot of the eCDS tool, and by regulatory controls on software installation introduced by primary care trusts early in the study. This eCDS tool needed to integrate better with clinical workflow; even then, its use for suspected cancer may be infrequent. Any definitive trial of eCDS for cancer diagnosis should only proceed after addressing these constraints.Trial registration numberISRCTN125595588.
Abstract.
Bradley SH, Hatton NLF, Aslam R, Bhartia B, Callister ME, Kennedy MP, Mounce LT, Shinkins B, Hamilton WT, Neal RD, et al (2021). Estimating lung cancer risk from chest X-ray and symptoms: a prospective cohort study.
Br J Gen Pract,
71(705), e280-e286.
Abstract:
Estimating lung cancer risk from chest X-ray and symptoms: a prospective cohort study.
BACKGROUND: Chest X-ray (CXR) is the first-line investigation for lung cancer in many countries but previous research has suggested that the disease is not detected by CXR in approximately 20% of patients. The risk of lung cancer, with particular symptoms, following a negative CXR is not known. AIM: to establish the sensitivity and specificity of CXR requested by patients who are symptomatic; determine the positive predictive values (PPVs) of each presenting symptom of lung cancer following a negative CXR; and determine whether symptoms associated with lung cancer are different in those who had a positive CXR result compared with those who had a negative CXR result. DESIGN AND SETTING: a prospective cohort study was conducted in Leeds, UK, based on routinely collected data from a service that allowed patients with symptoms of lung cancer to request CXR. METHOD: Symptom data were combined with a diagnostic category (positive or negative) for each CXR, and the sensitivity and specificity of CXR for lung cancer were calculated. The PPV of lung cancer associated with each symptom or combination of symptoms was estimated for those patients with a negative CXR. RESULTS: in total, 114 (1.3%) of 8996 patients who requested a CXR were diagnosed with lung cancer within 1 year. Sensitivity was 75.4% and specificity was 90.2%. The PPV of all symptoms for a diagnosis of lung cancer within 1 year of CXR was
Abstract.
Author URL.
Price S, Abel GA, Hamilton W (2021). Guideline interval: a new time interval in the diagnostic pathway for symptomatic cancer.
Cancer Epidemiol,
73Abstract:
Guideline interval: a new time interval in the diagnostic pathway for symptomatic cancer.
BACKGROUND: a standard measure of the cancer diagnostic pathway, diagnostic interval, is the time from "first presentation of cancer" to diagnosis. Cancer presentation may be unclear in patients with multimorbidity or non-specific symptoms, signs or test results ("features"). We propose an alternative, guideline interval, with a more certain start date; namely, when the patient first meets suspected-cancer criteria for investigation or referral. METHODS: This retrospective cohort study used Clinical Practice Research Datalink (CPRD) and English cancer registry data. Participants, aged ≥55 years, had diagnostic codes for oesophagogastric cancers in 1/1/12-31/12/17. Features of oesophagogastric cancer in the year before diagnosis were identified from CPRD codes for dysphagia, haematemesis, upper-abdominal mass or pain, low haemoglobin, reflux, dyspepsia, nausea, vomiting, weight loss or thrombocytosis. Diagnostic interval was the time from first feature to diagnosis; guidance interval, the time from first meeting criteria in NICE suspected-cancer guidance to diagnosis. Multimorbidity burden was quantified using Adjusted Clinical Groups®. Accelerated failure-time models explored associations between multimorbidity burden and length of both diagnostic and guideline interval. RESULTS: There were 3,793 eligible participants (69.0 % male), mean age 74.1 years (SD 10.5). 3,097 (81.7 %) presented with ≥1 feature in the year before diagnosis, and 1,990 (52.5 %) met NICE suspected-cancer criteria. The median for both intervals was 11 days in healthy users, and rose with increasing morbidity burden. At very high multimorbidity burden, diagnostic interval was 5.47 (95%CI 3.25-9.20) times longer and guideline interval was 3.91 (2.63-5.80) times longer than for healthy users. CONCLUSIONS: Guideline interval is proposed as a new measure of the cancer diagnostic pathway. It has a more certain start date than diagnostic interval, and is lengthened less than diagnostic interval in people with a very high multimorbidity burden. Guideline interval has potential for assessing the implementation of suspected-cancer policies.
Abstract.
Author URL.
Zhou Y, Walter FM, Mounce L, Abel GA, Singh H, Hamilton W, Stewart GD, Lyratzopoulos G (2021). Identifying opportunities for timely diagnosis through patterns of primary care tests in patients with bladder and renal cancer: a longitudinal linked data study. British Journal of General Practice, 72(714).
Rodgers LR, Streeter AJ, Lin N, Hamilton W, Henley WE (2021). Impact of influenza vaccination on amoxicillin prescriptions in older adults: a retrospective cohort study using primary care data.
PLOS ONE,
16(1), e0246156-e0246156.
Abstract:
Impact of influenza vaccination on amoxicillin prescriptions in older adults: a retrospective cohort study using primary care data
Background
Bacterial infections of the upper and lower respiratory tract are a frequent complication of influenza and contribute to the widespread use of antibiotics. Influenza vaccination may help reduce both appropriate and inappropriate prescribing of antibiotics. Electronic health records provide a rich source of information for assessing secondary effects of influenza vaccination.
Methods
We conducted a retrospective study to estimate effects of influenza vaccine on antibiotic (amoxicillin) prescription in the elderly based on data from the Clinical Practice Research Datalink. The introduction of UK policy to recommend the influenza vaccine to older adults in 2000 led to a substantial increase in uptake, creating a natural experiment. of 259,753 eligible patients that were unvaccinated in 1999 and aged≥65y by January 2000, 88,519 patients received influenza vaccination in 2000. These were propensity score matched 1:1 to unvaccinated patients. Time-to-amoxicillin was analysed using the Prior Event Rate Ratio (PERR) Pairwise method to address bias from time-invariant measured and unmeasured confounders. A simulation study and negative control outcome were used to help strengthen the validity of results.
Results
Compared to unvaccinated patients, those from the vaccinated group were more likely to be prescribed amoxicillin in the year prior to vaccination: hazard ratio (HR) 1.90 (95% confidence interval 1.83, 1.98). Following vaccination, the vaccinated group were again more likely to be prescribed amoxicillin, HR 1.64 (1.58,1.71). After adjusting for prior differences between the two groups using PERR Pairwise, overall vaccine effectiveness was 0.86 (0.81, 0.92). Additional analyses suggested that provided data meet the PERR assumptions, these estimates were robust.
Conclusions
Once differences between groups were taken into account, influenza vaccine had a beneficial effect, lowering the frequency of amoxicillin prescribing in the vaccinated group. Ensuring successful implementation of national programmes of vaccinating older adults against influenza may help contribute to reducing antibiotic resistance.
Abstract.
Nicholson BD, Oke JL, Aveyard P, Hamilton WT, Hobbs FDR (2021). Individual inflammatory marker abnormalities or inflammatory marker scores to identify primary care patients with unexpected weight loss for cancer investigation?.
Br J Cancer,
124(9), 1540-1542.
Abstract:
Individual inflammatory marker abnormalities or inflammatory marker scores to identify primary care patients with unexpected weight loss for cancer investigation?
BACKGROUND: Combinations of inflammatory markers are used as prognostic scores in cancer patients with cachexia. We investigated whether they could also be used to prioritise patients attending primary care with unexpected weight loss for cancer investigation. METHODS: We used English primary care electronic health records data linked to cancer registry data from 12,024 patients with coded unexpected weight loss. For each individual inflammatory marker and score we estimated the sensitivity, specificity, likelihood ratios, positive predictive value (PPV) and the area under the curve along with 95% confidence intervals for a cancer diagnosis within six months. RESULTS: the risk of cancer associated with two abnormal inflammatory markers combined in a score was higher than the risk associated with individual inflammatory marker abnormalities. However, the risk of cancer in weight loss associated with individual abnormalities, notably a raised C-reactive protein, was sufficient to trigger further investigation for cancer under current NICE guidelines. CONCLUSIONS: If scores including pairs of inflammatory marker abnormalities were to be used, in preference to individual abnormalities, fewer people would be investigated to diagnose one cancer with fewer false positives, but fewer people with cancer would be diagnosed overall.
Abstract.
Author URL.
Chapman D, Poirier V, Fitzgerald K, Nicholson BD, Hamilton W, Accelerate Coordinate Evaluate Multidisciplinary Diagnostic Centre projects (2021). Non-specific symptoms-based pathways for diagnosing less common cancers in primary care: a service evaluation.
Br J Gen Pract,
71(712), e846-e853.
Abstract:
Non-specific symptoms-based pathways for diagnosing less common cancers in primary care: a service evaluation.
BACKGROUND: Although less common cancers account for almost half of all cancer diagnoses in England, their relative scarcity and complex presentation, often with non-specific symptoms, means that patients often experience multiple primary care consultations, long times to diagnosis, and poor clinical outcomes. An urgent referral pathway for non-specific symptoms, the Multidisciplinary Diagnostic Centre (MDC), may address this problem. AIM: to examine the less common cancers identified during the MDC pilots and consider whether such an approach improves the diagnosis of these cancers. DESIGN AND SETTING: a service evaluation of five MDC pilot projects in England from December 2016 to March 2019. METHOD: Data items were collected by pilot sites in near-real time, based mainly on the English cancer outcomes and services dataset, with additional project-specific items. Simple descriptive and comparative statistics were used, including χ2 tests for proportions and t-tests for means where appropriate. RESULTS: from 5134 referrals, 378 cancers were diagnosed, of which 218 (58%) were less common. More than 30 different less common tumour types were diagnosed in this cohort. of the MDC patients with less common cancers, 23% (n = 50) had ≥3 GP consultations before referral and, at programme level, a median time of 57 days was recorded from GP urgent referral to treatment for these tumour types. CONCLUSION: a non-specific symptomatic referral route diagnoses a broad range of less common cancers, and can support primary care case management for patients with symptoms of possible cancer that do not qualify for a site-specific urgent referral.
Abstract.
Author URL.
Hatton N, Bhartia B, Aslam R, Bradley S, Darby M, Hamilton W, Hurst E, Kennedy M, Mounce L, Neil R, et al (2021). P62.09 a Prospective Cohort Evaluation of the Sensitivity and Specificity of the Chest X-Ray for the Detection of Lung Cancer in Symptomatic Adults. Journal of Thoracic Oncology, 16(10), s1180-s1181.
Herbert A, Rafiq M, Pham TM, Renzi C, Abel GA, Price S, Hamilton W, Petersen I, Lyratzopoulos G (2021). Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: a cohort study.
PLOS Medicine,
18(8), e1003708-e1003708.
Abstract:
Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: a cohort study
Background
The diagnostic assessment of abdominal symptoms in primary care presents a challenge. Evidence is needed about the positive predictive values (PPVs) of abdominal symptoms for different cancers and inflammatory bowel disease (IBD).
Methods and findings
Using data from the Health Improvement Network (THIN) in the United Kingdom (2000–2017), we estimated the PPVs for diagnosis of (i) cancer (overall and for different cancer sites); (ii) IBD; and (iii) either cancer or IBD in the year post-consultation with each of 6 abdominal symptoms: dysphagia (n = 86,193 patients), abdominal bloating/distension (n = 100,856), change in bowel habit (n = 106,715), rectal bleeding (n = 235,094), dyspepsia (n = 517,326), and abdominal pain (n = 890,490). The median age ranged from 54 (abdominal pain) to 63 years (dysphagia and change in bowel habit); the ratio of women/men ranged from 50%:50% (rectal bleeding) to 73%:27% (abdominal bloating/distension). Across all studied symptoms, the risk of diagnosis of cancer and the risk of diagnosis of IBD were of similar magnitude, particularly in women, and younger men. Estimated PPVs were greatest for change in bowel habit in men (4.64% cancer and 2.82% IBD) and for rectal bleeding in women (2.39% cancer and 2.57% IBD) and lowest for dyspepsia (for cancer: 1.41% men and 1.03% women; for IBD: 0.89% men and 1.00% women). Considering PPVs for specific cancers, change in bowel habit and rectal bleeding had the highest PPVs for colon and rectal cancer; dysphagia for esophageal cancer; and abdominal bloating/distension (in women) for ovarian cancer. The highest PPVs of abdominal pain (either sex) and abdominal bloating/distension (men only) were for non-abdominal cancer sites. For the composite outcome of diagnosis of either cancer or IBD, PPVs of rectal bleeding exceeded the National Institute of Health and Care Excellence (NICE)-recommended specialist referral threshold of 3% in all age–sex strata, as did PPVs of abdominal pain, change in bowel habit, and dyspepsia, in those aged 60 years and over. Study limitations include reliance on accuracy and completeness of coding of symptoms and disease outcomes.
Conclusions
Based on evidence from more than 1.9 million patients presenting in primary care, the findings provide estimated PPVs that could be used to guide specialist referral decisions, considering the PPVs of common abdominal symptoms for cancer alongside that for IBD and their composite outcome (cancer or IBD), taking into account the variable PPVs of different abdominal symptoms for different cancers sites. Jointly assessing the risk of cancer or IBD can better support decision-making and prompt diagnosis of both conditions, optimising specialist referrals or investigations, particularly in women.
Abstract.
Martins T, Walter FM, Penfold C, Abel G, Hamilton W (2021). Primary care use by men with symptoms of possible prostate cancer: a multi-method study with an ethnically diverse sample in London.
Eur J Cancer Care (Engl),
30(6).
Abstract:
Primary care use by men with symptoms of possible prostate cancer: a multi-method study with an ethnically diverse sample in London.
OBJECTIVE: the objective of this study is to investigate primary care use by men with recent onset of lower urinary tract symptoms (LUTS) to identify differences in presentation and investigation that may explain ethnic inequality in prostate cancer outcomes. METHODS: This is a multi-method study of men presenting LUTS to primary care. Two hundred seventy-four men completed a self-administered questionnaire, and 23 participated in face-to-face interviews. Regression analyses investigated ethnic differences in (a) the period between symptom onset and first primary care presentation (patient interval) and (b) the interval between first primary care presentation and investigation with prostate-specific antigen (PSA) and digital rectal examination (DRE). Interview data were analysed using thematic analysis. RESULTS: Half (144, 53%) reported a solitary first symptom, although multiple first symptoms were also common, particularly in Asian and Black men. There was no difference between ethnicities in patient interval or time from presentation to investigation. However, Asian men were offered less PSA testing (odds ratio 0.39; 95% confidence interval 0.17-0.92; p = 0.03). Qualitative data revealed ethnic differences in general practitioners' offer of DRE and PSA testing and highlighted limitations in doctor-patient communication and safety netting. CONCLUSION: Our study showed only small differences in primary care experiences, insufficient to explain ethnic inequalities in prostate cancer outcomes.
Abstract.
Author URL.
Hopewell S, Keene DJ, Marian IR, Dritsaki M, Heine P, Cureton L, Dutton SJ, Dakin H, Carr A, Hamilton W, et al (2021). Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of patients with rotator cuff disorders (GRASP): a multicentre, pragmatic, 2 × 2 factorial, randomised controlled trial.
Lancet,
398(10298), 416-428.
Abstract:
Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of patients with rotator cuff disorders (GRASP): a multicentre, pragmatic, 2 × 2 factorial, randomised controlled trial.
BACKGROUND: Corticosteroid injections and physiotherapy exercise programmes are commonly used to treat rotator cuff disorders but the treatments' effectiveness is uncertain. We aimed to compare the clinical effectiveness and cost-effectiveness of a progressive exercise programme with a single session of best practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. METHODS: in this pragmatic, multicentre, superiority, randomised controlled trial (2 × 2 factorial), we recruited patients from 20 UK National Health Service trusts. We included patients aged 18 years or older with a rotator cuff disorder (new episode within the past 6 months). Patients were excluded if they had a history of significant shoulder trauma (eg, dislocation, fracture, or full-thickness tear requiring surgery), neurological disease affecting the shoulder, other shoulder conditions (eg, inflammatory arthritis, frozen shoulder, or glenohumeral joint instability), received corticosteroid injection or physiotherapy for shoulder pain in the past 6 months, or were being considered for surgery. Patients were randomly assigned (centralised computer-generated system, 1:1:1:1) to progressive exercise (≤6 sessions), best practice advice (one session), corticosteroid injection then progressive exercise, or corticosteroid injection then best practice advice. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score over 12 months, analysed on an intention-to-treat basis (statistical significance set at 1%). The trial was registered with the International Standard Randomised Controlled Trial Register, ISRCTN16539266, and EuDRACT, 2016-002991-28. FINDINGS: Between March 10, 2017, and May 2, 2019, we screened 2287 patients. 708 patients were randomly assigned to progressive exercise (n=174), best practice advice (n=174), corticosteroid injection then progressive exercise (n=182), or corticosteroid injection then best practice advice (n=178). Over 12 months, SPADI data were available for 166 (95%) patients in the progressive exercise group, 164 (94%) in the best practice advice group, 177 (97%) in the corticosteroid injection then progressive exercise group, and 175 (98%) in the corticosteroid injection then best practice advice group. We found no evidence of a difference in SPADI score between progressive exercise and best practice advice when analysed over 12 months (adjusted mean difference -0·66 [99% CI -4·52 to 3·20]). We also found no evidence of a difference between corticosteroid injection compared with no injection when analysed over 12 months (-1·11 [-4·47 to 2·26]). No serious adverse events were reported. INTERPRETATION: Progressive exercise was not superior to a best practice advice session with a physiotherapist in improving shoulder pain and function. Subacromial corticosteroid injection provided no long-term benefit in patients with rotator cuff disorders. FUNDING: UK National Institute for Health Research Technology Assessment Programme.
Abstract.
Author URL.
Hopewell S, Keene DJ, Heine P, Marian IR, Dritsaki M, Cureton L, Dutton SJ, Dakin H, Carr A, Hamilton W, et al (2021). Progressive exercise compared with best-practice advice, with or without corticosteroid injection, for rotator cuff disorders: the GRASP factorial RCT.
Health Technology Assessment,
25(48), 1-158.
Abstract:
Progressive exercise compared with best-practice advice, with or without corticosteroid injection, for rotator cuff disorders: the GRASP factorial RCT
. Background
. Rotator cuff-related shoulder pain is very common, but there is uncertainty regarding which modes of exercise delivery are optimal and the long-term benefits of corticosteroid injections.
.
.
. Objectives
. To assess the clinical effectiveness and cost-effectiveness of progressive exercise compared with best-practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder.
.
.
. Design
. This was a pragmatic multicentre superiority randomised controlled trial (with a 2 × 2 factorial design).
.
.
. Setting
. Twenty NHS primary care-based musculoskeletal and related physiotherapy services.
.
.
. Participants
. Adults aged ≥ 18 years with a new episode of rotator cuff-related shoulder pain in the previous 6 months.
.
.
. Interventions
. A total of 708 participants were randomised (March 2017–May 2019) by a centralised computer-generated 1 : 1 : 1 : 1 allocation ratio to one of four interventions: (1) progressive exercise (n = 174) (six or fewer physiotherapy sessions), (2) best-practice advice (n = 174) (one physiotherapy session), (3) corticosteroid injection then progressive exercise (n = 182) (six or fewer physiotherapy sessions) or (4) corticosteroid injection then best-practice advice (n = 178) (one physiotherapy session).
.
.
. Main outcome measures
. The primary outcome was Shoulder Pain and Disability Index (SPADI) score over 12 months. Secondary outcomes included SPADI subdomains, the EuroQol 5 Dimensions, five-level version, sleep disturbance, fear avoidance, pain self-efficacy, return to activity, Global Impression of Treatment and health resource use. Outcomes were collected by postal questionnaires at 8 weeks and at 6 and 12 months. A within-trial economic evaluation was also conducted. The primary analysis was intention to treat.
.
.
. Results
. Participants had a mean age of 55.5 (standard deviation 13.1) years and 49.3% were female. The mean baseline SPADI score was 54.1 (standard deviation 18.5). Follow-up rates were 91% at 8 weeks and 87% at 6 and 12 months. There was an overall improvement in SPADI score from baseline in each group over time. Over 12 months, there was no evidence of a difference in the SPADI scores between the progressive exercise intervention and the best-practice advice intervention in shoulder pain and function (adjusted mean difference between groups over 12 months –0.66, 99% confidence interval –4.52 to 3.20). There was also no difference in SPADI scores between the progressive exercise intervention and best-practice advice intervention when analysed at the 8-week and 6- and 12-month time points. Injection resulted in improvement in shoulder pain and function at 8 weeks compared with no injection (adjusted mean difference –5.64, 99% confidence interval –9.93 to –1.35), but not when analysed over 12 months (adjusted mean difference –1.11, 99% confidence interval –4.47 to 2.26), or at 6 and 12 months. There were no serious adverse events. In the base-case analysis, adding injection to best-practice advice gained 0.021 quality-adjusted life-years (p = 0.184) and increased the cost by £10 per participant (p = 0.747). Progressive exercise alone was £52 (p = 0.247) more expensive per participant than best-practice advice, and gained 0.019 QALYs (p = 0.220). At a ceiling ratio of £20,000 per quality-adjusted life-year, injection plus best-practice advice had a 54.93% probability of being the most cost-effective treatment.
.
.
. Limitations
. Participants and physiotherapists were not blinded to group allocation. Twelve-month follow-up may be insufficient for identifying all safety concerns.
.
.
. Conclusions
. Progressive exercise was not superior to a best-practice advice session with a physiotherapist. Subacromial corticosteroid injection improved shoulder pain and function, but provided only modest short-term benefit. Best-practice advice in combination with corticosteroid injection was expected to be most cost-effective, although there was substantial uncertainty.
.
.
. Future work
. Longer-term follow-up, including any serious adverse effects of corticosteroid injection.
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. Trial registration
. Current Controlled Trials ISRCTN16539266 and EudraCT 2016-002991-28.
.
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. Funding
. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 48. See the NIHR Journals Library website for further project information.
.
Abstract.
Zhou Y, Walter FM, Singh H, Hamilton W, Abel GA, Lyratzopoulos G (2021). Prolonged Diagnostic Intervals as Marker of Missed Diagnostic Opportunities in Bladder and Kidney Cancer Patients with Alarm Features: a Longitudinal Linked Data Study.
Cancers,
13(1), 156-156.
Abstract:
Prolonged Diagnostic Intervals as Marker of Missed Diagnostic Opportunities in Bladder and Kidney Cancer Patients with Alarm Features: a Longitudinal Linked Data Study
Background: in England, patients who meet National Institute for Health and Care Excellence (NICE) guideline criteria for suspected cancer should receive a specialist assessment within 14 days. We examined how quickly bladder and kidney cancer patients who met fast-track referral criteria were actually diagnosed. Methods: We used linked primary care and cancer registration data on bladder and kidney cancer patients who met fast-track referral criteria and examined the time from their first presentation with alarm features to diagnosis. Using logistic regression we examined factors most likely to be associated with non-timely diagnosis (defined as intervals exceeding 90 days), adjusting for age, sex and cancer type, positing that such occurrences represent missed opportunity for timely referral, possibly due to sub-optimal guideline adherence. Results: 28%, 42% and 31% of all urological cancer patients reported no, one or two or more relevant symptoms respectively in the year before diagnosis. of the 2105 patients with alarm features warranting fast-track assessment, 1373 (65%) presented with unexplained haematuria, 382 (18%) with recurrent urinary tract infections (UTIs), 303 (14%) with visible haematuria, and 45 (2%) with an abdominal mass. 27% overall, and 24%, 45%, 18% and 27% of each group respectively, had a non-timely diagnosis. Presentation with recurrent UTI was associated with longest median diagnostic interval (median 83 days, IQR 43–151) and visible haematuria with the shortest (median 50 days, IQR 30–79). After adjustment, presentation with recurrent UTIs, being in the youngest or oldest age group, female sex, and diagnosis of kidney and upper tract urothelial cancer, were associated with greater odds of non-timely diagnosis. Conclusion: More than a quarter of patients presenting with fast-track referral features did not achieve a timely diagnosis, suggesting inadequate guideline adherence for some patients. The findings highlight a substantial number of opportunities for expediting the diagnosis of patients with bladder or kidney cancers.
Abstract.
Laake J-P, Vulkan D, Quaife SL, Hamilton WT, Martins T, Waller J, Parmar D, Sasieni P, Duffy SW (2021). Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial.
Br J Gen Pract,
71(706), e339-e346.
Abstract:
Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial.
BACKGROUND: for some common cancers, survival is lower in the UK than in comparable high-income countries. AIM: to assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates. DESIGN AND SETTING: a two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England. METHOD: Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses. RESULTS: in total, 1513 patients were individually randomised to the intervention (n = 783) and control (n = 730) arms between Nov 2016 - May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, P = 0.004). There was, however, no difference in the numbers of patients consulting. CONCLUSION: Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients.
Abstract.
Author URL.
Barlow M, Hamilton W, Ukoumunne OC, Bailey SER (2021). The association between thrombocytosis and subtype of lung cancer: a systematic review and meta-analysis.
Translational Cancer Research,
10(3), 1249-1260.
Abstract:
The association between thrombocytosis and subtype of lung cancer: a systematic review and meta-analysis
Background: Thrombocytosis is associated with poor lung cancer prognosis and has recently been identified as having a high positive predictive value in lung cancer detection. Lung cancer has multiple histological and genetic subtypes and it is not known whether platelet levels differ across these subtypes, or whether thrombocytosis is predictive of a particular subtype. Methods: PubMed and Embase were systematically searched for studies that reported pre-treatment platelet count, as either averages or proportion of patients with thrombocytosis, by subtype of lung cancer using a prespecified search strategy. The Newcastle-Ottowa scale was used to assess study quality and risk of bias. Suitable studies were synthesised in meta-analyses and subgroup analyses examined for differences across subtypes. Results: the prevalence of pre-treatment thrombocytosis across all lung cancer patients was 27% (95% CI: 17% to 37%). By subtype, this was 22% (95% CI: 7% to 41%) for adenocarcinoma, 28% (95% CI: 15% to 43%) for squamous cell carcinoma (SCC), 36% (95% CI: 13% to 62%) for large cell carcinoma (LCC), and 30% (95% CI: 8% to 58%) for small cell lung cancer (SCLC). The pooled mean platelet count for lung cancer patients was 289×109/L (95% CI: 268 to 311). By subtype, this was 282×109/L (95% CI: 259 to 306) for adenocarcinoma, 297×109/L (95% CI: 238 to 356) for SCC, 290×109/L (95% CI: 176 to 404) for LCC, and 293×109/L (95% CI: 244 to 342) for SCLC. There was no difference in thrombocytosis prevalence (P=0.76) or mean platelet count (P=0.96) across the subtypes. Conclusions: These findings suggest thrombocytosis is no more indicative of one lung cancer subtype over another. We therefore conclude a high platelet count is likely to be generic across all lung cancer subtypes.
Abstract.
Moore SF, Price SJ, Chowienczyk S, Bostock J, Hamilton W (2021). The impact of changing risk thresholds on the number of people in England eligible for urgent investigation for possible cancer: an observational cross-sectional study.
British Journal of Cancer,
125(11), 1593-1597.
Abstract:
The impact of changing risk thresholds on the number of people in England eligible for urgent investigation for possible cancer: an observational cross-sectional study
Abstract
. Background
. Expediting cancer diagnosis may be achieved by targeted decreases in referral thresholds to increase numbers of patients referred for urgent investigation.
.
. Methods
. Clinical Practice Research Datalink data from England for 150,921 adults aged ≥40 were used to identify participants with features of possible cancer equating to risk thresholds ≥1%, ≥2% or ≥3% for breast, lung, colorectal, oesophago-gastric, pancreatic, renal, bladder, prostatic, ovarian, endometrial and laryngeal cancers.
.
. Results
. The mean age of participants was 60 (SD 13) years, with 73,643 males (49%). In 2016, 8576 consultation records contained coded features having a positive predictive value (PPV) of ≥3% for any of the 11 cancers. This equates to a rate of 5682/100,000 patients compared with 4601/100,000 Suspected Cancer NHS referrals for these cancers from April 2016–March 2017. Nine thousands two hundred ninety-one patient-consultation records had coded features equating to a ≥2% PPV, 8% more than met PPV ≥ 3%. Similarly, 19,517 had features with a PPV ≥ 1%, 136% higher than for PPV ≥ 3%.
.
. Conclusions
. This study estimated the number of primary-care patients presenting at lower thresholds of cancer risk. The resource implications of liberalising this threshold to 2% are modest and manageable. The details across individual cancer sites should assist planning of English cancer services.
.
Abstract.
Nakagawa S, Dunn AG, Lagisz M, Bannach-Brown A, Grames EM, Sánchez-Tójar A, O’Dea RE, Noble DWA, Westgate MJ, Arnold PA, et al (2020). A new ecosystem for evidence synthesis. Nature Ecology and Evolution, 4(4), 498-501.
Clarke C, Hamilton W, Price S, Bailey SE (2020). Association of non-malignant diseases with thrombocytosis: a prospective cohort study in general practice.
Br J Gen Pract,
70(701), e852-e857.
Abstract:
Association of non-malignant diseases with thrombocytosis: a prospective cohort study in general practice.
BACKGROUND: Thrombocytosis is an excess of platelets, which is diagnosed as a platelet count >400 × 109/l. An association of thrombocytosis with undiagnosed cancer has recently been established, but the association with non-malignant disease has not been studied in primary care. AIM: to examine, in English primary care, the 1-year incidence of non-malignant diseases in patients with new thrombocytosis and the incidence of pre-existing non-malignant diseases in patients who develop new thrombocytosis. DESIGN AND SETTING: Prospective cohort study using English Clinical Practice Research Datalink data from 2000 to 2013. METHOD: Newly incident and pre-existing rates of non-malignant diseases associated with thrombocytosis were compared between patients with thrombocytosis and age- and sex-matched patients with a normal platelet count. Fifteen candidate non-malignant diseases were identified from literature searches. RESULTS: in the thrombocytosis cohort of 39 850 patients, 4579 (11.5%) were newly diagnosed with any one of the candidate diseases, compared with 443 out of 9684 patients (4.6%) in the normal platelet count cohort (relative risk [RR] 2.5, 95% confidence intervals [CI] = 2.3 to 2.8); iron-deficiency anaemia was the most common new diagnosis (4.5% of patients with thrombocytosis, RR 4.9, 95% CI = 4.0 to 6.1). A total of 22 612 (57.0%) patients with thrombocytosis had a pre-existing non-malignant diagnosis compared with 4846 patients (50%) in the normal platelet count cohort (odds ratio 1.3, 95% CI = 1.2 to 1.4). There was no statistically significant difference in cancer diagnoses between patients with and without pre-existing disease in the thrombocytosis cohort. CONCLUSION: Thrombocytosis is associated with several non-malignant diseases. Clinicians can use these findings as part of their holistic diagnostic approach to help guide further investigations and management of patients with thrombocytosis.
Abstract.
Author URL.
Hamilton W (2020). Cancer diagnostic delay in the COVID-19 era: what happens next?.
Lancet Oncol,
21(8), 1000-1002.
Author URL.
Medina-Lara A, Grigore B, Lewis R, Peters J, Price S, Landa P, Robinson S, Neal R, Hamilton W, Spencer AE, et al (2020). Cancer diagnostic tools to aid decision-making in primary care: mixed-methods systematic reviews and cost-effectiveness analysis.
Health Technology Assessment,
24(66), 1-332.
Abstract:
Cancer diagnostic tools to aid decision-making in primary care: mixed-methods systematic reviews and cost-effectiveness analysis
. Background
. Tools based on diagnostic prediction models are available to help general practitioners diagnose cancer. It is unclear whether or not tools expedite diagnosis or affect patient quality of life and/or survival.
.
.
. Objectives
. The objectives were to evaluate the evidence on the validation, clinical effectiveness, cost-effectiveness, and availability and use of cancer diagnostic tools in primary care.
.
.
. Methods
. Two systematic reviews were conducted to examine the clinical effectiveness (review 1) and the development, validation and accuracy (review 2) of diagnostic prediction models for aiding general practitioners in cancer diagnosis. Bibliographic searches were conducted on MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Library and Web of Science) in May 2017, with updated searches conducted in November 2018. A decision-analytic model explored the tools’ clinical effectiveness and cost-effectiveness in colorectal cancer. The model compared patient outcomes and costs between strategies that included the use of the tools and those that did not, using the NHS perspective. We surveyed 4600 general practitioners in randomly selected UK practices to determine the proportions of general practices and general practitioners with access to, and using, cancer decision support tools. Association between access to these tools and practice-level cancer diagnostic indicators was explored.
.
.
. Results
. Systematic review 1 – five studies, of different design and quality, reporting on three diagnostic tools, were included. We found no evidence that using the tools was associated with better outcomes. Systematic review 2 – 43 studies were included, reporting on prediction models, in various stages of development, for 14 cancer sites (including multiple cancers). Most studies relate to QCancer® (ClinRisk Ltd, Leeds, UK) and risk assessment tools.
.
.
. Decision model
. In the absence of studies reporting their clinical outcomes, QCancer and risk assessment tools were evaluated against faecal immunochemical testing. A linked data approach was used, which translates diagnostic accuracy into time to diagnosis and treatment, and stage at diagnosis. Given the current lack of evidence, the model showed that the cost-effectiveness of diagnostic tools in colorectal cancer relies on demonstrating patient survival benefits. Sensitivity of faecal immunochemical testing and specificity of QCancer and risk assessment tools in a low-risk population were the key uncertain parameters.
.
.
. Survey
. Practitioner- and practice-level response rates were 10.3% (476/4600) and 23.3% (227/975), respectively. Cancer decision support tools were available in 83 out of 227 practices (36.6%, 95% confidence interval 30.3% to 43.1%), and were likely to be used in 38 out of 227 practices (16.7%, 95% confidence interval 12.1% to 22.2%). The mean 2-week-wait referral rate did not differ between practices that do and practices that do not have access to QCancer or risk assessment tools (mean difference of 1.8 referrals per 100,000 referrals, 95% confidence interval –6.7 to 10.3 referrals per 100,000 referrals).
.
.
. Limitations
. There is little good-quality evidence on the clinical effectiveness and cost-effectiveness of diagnostic tools. Many diagnostic prediction models are limited by a lack of external validation. There are limited data on current UK practice and clinical outcomes of diagnostic strategies, and there is no evidence on the quality-of-life outcomes of diagnostic results. The survey was limited by low response rates.
.
.
. Conclusion
. The evidence base on the tools is limited. Research on how general practitioners interact with the tools may help to identify barriers to implementation and uptake, and the potential for clinical effectiveness.
.
.
. Future work
. Continued model validation is recommended, especially for risk assessment tools. Assessment of the tools’ impact on time to diagnosis and treatment, stage at diagnosis, and health outcomes is also recommended, as is further work to understand how tools are used in general practitioner consultations.
.
.
. Study registration
. This study is registered as PROSPERO CRD42017068373 and CRD42017068375.
.
.
. Funding
. This project was funded by the National Institute for Health Research (NIHR) Health Technology programme and will be published in full in Health Technology Assessment; Vol. 24, No. 66. See the NIHR Journals Library website for further project information.
.
Abstract.
Chowienczyk S, Price S, Hamilton W (2020). Changes in the presenting symptoms of lung cancer from 2000-2017: a serial cross-sectional study of observational records in UK primary care.
Br J Gen Pract,
70(692), e193-e199.
Abstract:
Changes in the presenting symptoms of lung cancer from 2000-2017: a serial cross-sectional study of observational records in UK primary care.
BACKGROUND: Most patients diagnosed with lung cancer present with symptoms. It is not known if the proportions of patients presenting with each symptom has changed over time. Identifying trends in lung cancer's presenting symptoms is important for medical education and early-diagnosis initiatives. AIM: to identify the first reported symptom of possible lung cancer (index symptom), and to test whether the percentages of patients with each index symptom changed during 2000-2017. DESIGN AND SETTING: This was a serial, cross-sectional, observational study using UK Clinical Practice Research Datalink (CPRD) data with cancer registry linkage. METHOD: the index symptom was identified for patients with an incident diagnosis of lung cancer in annual cohorts between 1 January 2000 and 31 December 2017. Searches were constrained to symptoms in National Institute for Health and Care Excellence (NICE) suspected-cancer referral guidelines, and to the year before diagnosis. Generalised linear models (with a binomial function) were used to test if the percentages of patients with each index symptom varied during 2000-2017. RESULTS: the percentage of patients with an index symptom of cough (odds ratio [OR] 1.01; 95% confidence interval [CI] = 1.00 to 1.02 per year; P
Abstract.
Author URL.
Pearson C, Poirier V, Fitzgerald K, Rubin G, Hamilton W (2020). Cross-sectional study using primary care and cancer registration data to investigate patients with cancer presenting with non-specific symptoms.
BMJ Open,
10(1).
Abstract:
Cross-sectional study using primary care and cancer registration data to investigate patients with cancer presenting with non-specific symptoms.
INTRODUCTION: Patients presenting to primary care with site-specific alarm symptoms can be referred onto urgent suspected cancer pathways, whereas those with non-specific symptoms currently have no dedicated referral routes leading to delays in cancer diagnosis and poorer outcomes. Pilot Multidisciplinary Diagnostic Centres (MDCs) provide a referral route for such patients in England. OBJECTIVES: This work aimed to use linked primary care and cancer registration data to describe diagnostic pathways for patients similar to those being referred into MDCs and compare them to patients presenting with more specific symptoms. METHODS: This cross-sectional study linked primary care data from the National Cancer Diagnosis Audit (NCDA) to national cancer registration and Route to Diagnosis records. Patient symptoms recorded in the NCDA were used to allocate patients to one of two groups - those presenting with symptoms mirroring referral criteria of MDCs (non-specific but concerning symptoms (NSCS)) and those with at least one site-specific alarm symptom (non-NSCS). Descriptive analyses compared the two groups and regression analysis by group investigated associations with long primary care intervals (PCIs). RESULTS: Patients with NSCS were more likely to be diagnosed at later stage (32% stage 4, compared with 21% in non-NSCS) and via an emergency presentation (34% vs 16%). These patients also had more multiple pre-referral general practitioner consultations (59% vs 43%) and primary care-led diagnostics (blood tests: 57% vs 35%). Patients with NSCS had higher odds of having longer PCIs (adjusted OR: 1.24 (1.11 to 1.36)). Patients with lung and urological cancers also had higher odds of longer PCIs overall and in both groups. CONCLUSIONS: Differences in the diagnostic pathway show that patients with symptoms mirroring the MDC referral criteria could benefit from a new referral pathway.
Abstract.
Author URL.
Logan RPH, Hamilton W (2020). Delivering better value colonoscopy: bridging the gap with FIT. Gut, 70(6), 1006-1007.
Keene DJ, Soutakbar H, Hopewell S, Heine P, Jaggi A, Littlewood C, Hansen Z, Barker K, Hamilton W, Carr AJ, et al (2020). Development and implementation of the physiotherapy-led exercise interventions for the treatment of rotator cuff disorders for the ‘Getting it Right: Addressing Shoulder Pain’ (GRASP) trial.
Physiotherapy (United Kingdom),
107, 252-266.
Abstract:
Development and implementation of the physiotherapy-led exercise interventions for the treatment of rotator cuff disorders for the ‘Getting it Right: Addressing Shoulder Pain’ (GRASP) trial
Objectives: the Getting it Right: Addressing Shoulder Pain (GRASP) trial is a large-scale, multicentre, 2 × 2 factorial randomised controlled trial investigating clinical and cost-effectiveness of a progressive exercise programme versus best-practice advice, with or without corticosteroid injection, for treating people with rotator cuff disorders. Here we describe the development, implementation and details of the physiotherapy-led interventions. Methods: Medical Research Council guidance for developing complex interventions were used, taking into account clinical guidelines, expert and patient opinion, research evidence, current practice variation, and deliverability. A stakeholder meeting of 26 experts, clinicians, researchers, and patient representatives was used to design key components of the interventions. Stakeholders prioritised strengthening posterior rotator cuff muscles and using practical, easy-to-do exercises. The interventions were designed to be deliverable across the UK National Health Service. Results: Progressive exercise consists of up to six sessions with a physiotherapist over 16 weeks. The best-practice advice consists of one face-to-face session with a physiotherapist with substantially greater reliance on self-management. Both interventions include self-management advice, home-exercise instruction, and behaviour-change strategies to target exercise adherence. All participants receive a Participant Information Booklet. The best-practice advice intervention is a self-guided system of progressively challenging exercises, with demonstration videos and written materials. The progressive exercise intervention has a wider range of exercise options, and greater flexibility for tailoring, progression, supervised practice and feedback. Conclusion: GRASP has recruited 708 participants and will provide high quality evidence to inform management of people with shoulder pain due to a rotator cuff disorder. Results are anticipated in 2020. Trial registration number: ISRCTN16539266; EudraCT number:2016-002991-28.
Abstract.
Keeney E, Mohiuddin S, Zienius K, Ben‐Shlomo Y, Ozawa M, Grant R, Hamilton W, Weller D, Brennan PM, Hollingworth W, et al (2020). Economic evaluation of GPs’ direct access to computed tomography for identification of brain tumours. European Journal of Cancer Care, 30(1).
Chapman D, Poirier V, Vulkan D, Fitzgerald K, Rubin G, Hamilton W, Duffy SW, Thomas AH, Gulliford D, Rolfe H, et al (2020). First results from five multidisciplinary diagnostic centre (MDC) projects for non-specific but concerning symptoms, possibly indicative of cancer.
British Journal of Cancer,
123(5), 722-729.
Abstract:
First results from five multidisciplinary diagnostic centre (MDC) projects for non-specific but concerning symptoms, possibly indicative of cancer
Abstract
. Background
. Patients with non-specific symptoms often experience longer times to diagnosis and poorer clinical outcomes than those with site-specific symptoms. This paper reports initial results from five multidisciplinary diagnostic centre (MDC) projects in England, piloting rapid referral for patients with non-specific symptoms.
.
. Methods
. The evaluation covered MDC activity from 1st December 2016 to 31st July 2018, with projects using a common dataset. Logistical regression analyses were conducted, with a diagnosis of any cancer as the dependent variable. Exploratory analysis was conducted on presenting symptoms and diagnoses of cancer, and on comparisons within these groupings.
.
. Results
. In total, 2961 patients were referred into the MDCs and 241 cancers were diagnosed. The pathway detected cancers across a broad range of tumour sites, including several rare and less common cancers. An association between patient age and cancer was identified (p < 0.001). GP ‘clinical suspicion’ was identified as a strong predictor of cancer (p = 0.006), with a reduced association with cancer observed in patients with higher numbers of GP consultation before referral (p = 0.008).
.
. Conclusions
. The MDC model diagnoses cancer in patients with non-specific symptoms, with a conversion rate of 8%, demonstrating the diagnostic potential of a non-site-specific symptomatic referral pathway.
.
Abstract.
Funston G, Hardy V, Abel G, Crosbie EJ, Emery J, Hamilton W, Walter FM (2020). Identifying Ovarian Cancer in Symptomatic Women: a Systematic Review of Clinical Tools.
Cancers,
12(12), 3686-3686.
Abstract:
Identifying Ovarian Cancer in Symptomatic Women: a Systematic Review of Clinical Tools
In the absence of effective ovarian cancer screening programs, most women are diagnosed following the onset of symptoms. Symptom-based tools, including symptom checklists and risk prediction models, have been developed to aid detection. The aim of this systematic review was to identify and compare the diagnostic performance of these tools. We searched MEDLINE, EMBASE and Cochrane CENTRAL, without language restriction, for relevant studies published between 1 January 2000 and 3 March 2020. We identified 1625 unique records and included 16 studies, evaluating 21 distinct tools in a range of settings. Fourteen tools included only symptoms; seven also included risk factors or blood tests. Four tools were externally validated—the Goff Symptom Index (sensitivity: 56.9–83.3%; specificity: 48.3–98.9%), a modified Goff Symptom Index (sensitivity: 71.6%; specificity: 88.5%), the Society of Gynaecologic Oncologists consensus criteria (sensitivity: 65.3–71.5%; specificity: 82.9–93.9%) and the QCancer Ovarian model (10% risk threshold—sensitivity: 64.1%; specificity: 90.1%). Study heterogeneity precluded meta-analysis. Given the moderate accuracy of several tools on external validation, they could be of use in helping to select women for ovarian cancer investigations. However, further research is needed to assess the impact of these tools on the timely detection of ovarian cancer and on patient survival.
Abstract.
Zhou Y, Abel GA, Hamilton W, Singh H, Walter FM, Lyratzopoulos G (2020). Imaging activity possibly signalling missed diagnostic opportunities in bladder and kidney cancer: a longitudinal data-linkage study using primary care electronic health records. Cancer Epidemiology, 66, 101703-101703.
Plackett R, Kassianos AP, Kambouri M, Kay N, Mylan S, Hopwood J, Schartau P, Gray S, Timmis J, Bennett S, et al (2020). Online patient simulation training to improve clinical reasoning: a feasibility randomised controlled trial.
BMC Med Educ,
20(1).
Abstract:
Online patient simulation training to improve clinical reasoning: a feasibility randomised controlled trial.
BACKGROUND: Online patient simulations (OPS) are a novel method for teaching clinical reasoning skills to students and could contribute to reducing diagnostic errors. However, little is known about how best to implement and evaluate OPS in medical curricula. The aim of this study was to assess the feasibility, acceptability and potential effects of eCREST - the electronic Clinical Reasoning Educational Simulation Tool. METHODS: a feasibility randomised controlled trial was conducted with final year undergraduate students from three UK medical schools in academic year 2016/2017 (cohort one) and 2017/2018 (cohort two). Student volunteers were recruited in cohort one via email and on teaching days, and in cohort two eCREST was also integrated into a relevant module in the curriculum. The intervention group received three patient cases and the control group received teaching as usual; allocation ratio was 1:1. Researchers were blind to allocation. Clinical reasoning skills were measured using a survey after 1 week and a patient case after 1 month. RESULTS: Across schools, 264 students participated (18.2% of all eligible). Cohort two had greater uptake (183/833, 22%) than cohort one (81/621, 13%). After 1 week, 99/137 (72%) of the intervention and 86/127 (68%) of the control group remained in the study. eCREST improved students' ability to gather essential information from patients over controls (OR = 1.4; 95% CI 1.1-1.7, n = 148). of the intervention group, most (80/98, 82%) agreed eCREST helped them to learn clinical reasoning skills. CONCLUSIONS: eCREST was highly acceptable and improved data gathering skills that could reduce diagnostic errors. Uptake was low but improved when integrated into course delivery. A summative trial is needed to estimate effectiveness.
Abstract.
Author URL.
Merriel SWD, Hardy V, Thompson MJ, Walter FM, Hamilton W (2020). Patient-Centered Outcomes from Multiparametric MRI and MRI-Guided Biopsy for Prostate Cancer: a Systematic Review.
J Am Coll Radiol,
17(4), 486-495.
Abstract:
Patient-Centered Outcomes from Multiparametric MRI and MRI-Guided Biopsy for Prostate Cancer: a Systematic Review.
OBJECTIVE: to identify and characterize patient-centered outcomes (PCOs) relating to multiparametric MRI (mpMRI) and MRI-guided biopsy as diagnostic tests for possible prostate cancer. METHODS: Medline via OVID, EMBASE, PsycInfo, and the Cochrane Central register of Controlled Trials (CENTRAL) were searched for relevant articles. Hand searching of reference lists and snowballing techniques were performed. Studies of mpMRI and MRI-guided biopsy that measured any PCO were included. There were no restrictions placed on year of publication, language, or country for study inclusion. All database search hits were screened independently by two reviewers, and data were extracted using a standardized form. RESULTS: Overall, 2,762 database search hits were screened based on title and abstract. of these, 222 full-text articles were assessed, and 10 studies met the inclusion criteria. There were 2,192 participants featured in the included studies, all of which were conducted in high-income countries. Nineteen different PCOs were measured, with a median of four PCOs per study (range 1-11). Urethral bleeding, pain, and urinary tract infection were the most common outcomes measured. In the four studies that compared mpMRI or MRI-guided biopsy to transrectal ultrasound biopsy, most adverse outcomes occurred less frequently in MRI-related tests. These four studies were assessed as having a low risk of bias. DISCUSSION: PCOs measured in studies of mpMRI or MRI-guided biopsy thus far have mostly been physical outcomes, with some evidence that MRI tests are associated with less frequent adverse outcomes compared with transrectal ultrasound biopsy. There was very little evidence for the effect of mpMRI and MRI-guided biopsy on emotional, cognitive, social, or behavioral outcomes.
Abstract.
Author URL.
Nicholson BD, Aveyard P, Price SJ, Hobbs FDR, Koshiaris C, Hamilton W (2020). Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study.
BMJ-BRITISH MEDICAL JOURNAL,
370 Author URL.
Au-Yong ITH, Hamilton W, Rawlinson J, Baldwin DR (2020). Pulmonary nodules. The BMJ, 371
Quiroga M, Shephard EA, Mounce LTA, Carney M, Hamilton WT, Price SJ (2020). Quantifying the impact of pre-existing conditions on the stage of oesophagogastric cancer at diagnosis: a primary care cohort study using electronic medical records.
Family Practice,
38(4), 425-431.
Abstract:
Quantifying the impact of pre-existing conditions on the stage of oesophagogastric cancer at diagnosis: a primary care cohort study using electronic medical records
Abstract
.
. Background
. Pre-existing conditions interfere with cancer diagnosis by offering diagnostic alternatives, competing for clinical attention or through patient surveillance.
.
.
. Objective
. To investigate associations between oesophagogastric cancer stage and pre-existing conditions.
.
.
. Methods
. Retrospective cohort study using Clinical Practice Research Datalink (CPRD) data, with English cancer registry linkage. Participants aged ≥40 years had consulted primary care in the year before their incident diagnosis of oesophagogastric cancer in 01/01/2010–31/12/2015. CPRD records pre-diagnosis were searched for codes denoting clinical features of oesophagogastric cancer and for pre-existing conditions, including those providing plausible diagnostic alternatives for those features. Logistic regression analysed associations between stage and multimorbidity (≥2 conditions; reference category: no multimorbidity) and having ‘diagnostic alternative(s)’, controlling for age, sex, deprivation and cancer site.
.
.
. Results
. of 2444 participants provided, 695 (28%) were excluded for missing stage, leaving 1749 for analysis (1265/1749, 72.3% had advanced-stage disease). Multimorbidity was associated with stage [odds ratio 0.63, 95% confidence interval (CI) 0.47–0.85, P = 0.002], with moderate evidence of an interaction term with sex (1.76, 1.08–2.86, P = 0.024). There was no association between alternative explanations and stage (odds ratio 1.18, 95% CI 0.87–1.60, P = 0.278).
.
.
. Conclusions
. In men, multimorbidity is associated with a reduced chance of advanced-stage oesophagogastric cancer, to levels seen collectively for women.
.
Abstract.
Watson J, Whiting P, Salisbury C, Banks J, Hamilton W (2020). Raised inflammatory markers as a predictor of one-year mortality: a cohort study in primary care in the UK using electronic health record data.
BMJ Open,
10(10), e036027-e036027.
Abstract:
Raised inflammatory markers as a predictor of one-year mortality: a cohort study in primary care in the UK using electronic health record data
ObjectivesIdentification of patients at increased mortality risk is important in the context of increasing multimorbidity and an ageing population, to help facilitate the planning and delivery of services. The aim of this study was to examine 1-year all-cause mortality in a cohort of primary care patients in whom inflammatory markers including C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and plasma viscosity (PV), had been tested.DesignObservational cohort study using general practitioner Electronic Health Records from the Clinical Practice Research Datalink, with linkage to Office for National Statistics (ONS) Death Registry.SettingUK Primary Care.Participants159 325 patients with inflammatory marker tests done in 2014 and 39 928 age, sex and practice-matched controls without inflammatory marker testing. ONS Death registry data were available for 109 966 participants.Primary and secondary outcome measuresOne-year mortality in those with raised inflammatory markers compared with normal inflammatory markers and untested controls. Subanalyses stratified 1-year mortality by age group, gender and cause of death.ResultsPatients with a raised inflammatory marker (n=47 797) had an overall 1-year all-cause mortality of 6.89%, compared with 1.41% in those with normal inflammatory markers (p<0.001) and 1.62% in untested controls. A raised CRP is associated with the highest mortality rate at 8.76% compared with 4.99% for ESR and 4.66% for PV. One-year mortality is higher in men with a raised inflammatory marker compared with women (9.78% vs 5.29%). The C-statistic of a simple mortality prediction model containing age, sex and CRP test result is 0.89.ConclusionsInflammatory markers are a strong predictor of all-cause mortality in primary care, with a C-statistic comparable to several previously developed frailty indices. Future research should consider the added value of CRP testing, in combination with other risk factors, to improve prediction of mortality in primary care. Evidence- based interventions for frailty are needed alongside predictive tools.
Abstract.
McGovern AP, Hogg M, Shields BM, Sattar NA, Holman RR, Pearson ER, Hattersley AT, Jones AG, Dennis JM (2020). Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation.
BMJ Open Diabetes Research & Care,
8(1), e001238-e001238.
Abstract:
Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation
IntroductionTo identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i).Research design and methodsWe assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation.ResultsGenital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; <1 year before initiation (HR 4.38; 3.73 to 5.13), 1–5 years (HR 3.04; 2.64 to 3.51), and >5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07).ConclusionsFemale sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i.
Abstract.
Martins T, Merriel SWD, Hamilton W (2020). Routes to diagnosis of symptomatic cancer in sub-Saharan Africa: systematic review.
BMJ Open,
10(11), e038605-e038605.
Abstract:
Routes to diagnosis of symptomatic cancer in sub-Saharan Africa: systematic review
BackgroundMost cancers in sub-Saharan Africa (SSA) are diagnosed at advanced stages, with limited treatment options and poor outcomes. Part of this may be linked to various events occurring in patients’ journey to diagnosis. Using the model of pathways to treatment, we examined the evidence regarding the routes to cancer diagnosis in SSA.Design and settingsA systematic review of available literature was performed.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Between 30 September and 30 November 2019, seven electronic databases were searched using terms relating to SSA countries, cancer and routes to diagnosis comprising the population, exposure and outcomes, respectively. Citation lists of included studies were manually searched to identify relevant studies. Furthermore, ProQuest Dissertations & Theses Global was searched to identify appropriate grey literature on the subject.Results18 of 5083 references identified met the inclusion criteria: eight focused on breast cancer; three focused on cervical cancer; two each focused on lymphoma, Kaposi’s sarcoma and childhood cancers; and one focused on colorectal cancer. With the exception of Kaposi’s sarcoma, definitive diagnoses were made in tertiary healthcare centres, including teaching and regional hospitals. The majority of participants initially consulted within primary care, although a considerable proportion first used complementary medicine before seeking conventional medical help. The quality of included studies was a major concern, but their findings provided important insight into the pathways to cancer diagnosis in the region.ConclusionThe proportion of patients who initially use complementary medicine in their cancer journey may explain a fraction of advanced-stage diagnosis and poor survival of cancer in SSA. However, further research would be necessary to fully understand the exact role (or activities) of primary care and alternative care providers in patient cancer journeys.
Abstract.
Nicholson BD, Hamilton W, Koshiaris C, Oke JL, Hobbs FDR, Aveyard P (2020). The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations.
Br J Cancer,
122(12), 1848-1856.
Abstract:
The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations.
BACKGROUND: We aimed to understand the time period of cancer diagnosis and the cancer types detected in primary care patients with unexpected weight loss (UWL) to inform cancer guidelines. METHODS: This retrospective matched cohort study used cancer registry linked electronic health records from the UK's Clinical Practice Research Datalink from between 2000 and 2014. Univariable and multivariable time-to-event analyses examined the association between UWL, and all cancers combined, cancer site and stage. RESULTS: in all, 63,973 patients had UWL recorded, of whom 1375 (2.2%) were diagnosed with cancer within 2 years (days-to-diagnosis: mean 181; median 80). Men with UWL (HR 3.28 (2.88-3.73)) and women (1.87 (1.68-2.08)) were more likely than comparators to be diagnosed with cancer within 3 months. The association was greatest in men aged ≥50 years and women ≥70 years. The commonest cancers were pancreas, cancer of unknown primary, gastro-oesophageal, lymphoma, hepatobiliary, lung, bowel and renal-tract. The majority were late-stage, but there was some evidence of association with stage II and stage III cancers. In the 3-24 months after presenting with UWL, cancer diagnosis was less likely than in comparators. CONCLUSION: UWL recorded in primary care is associated with a broad range of cancer sites of early and late-stage.
Abstract.
Author URL.
Funston G, Hamilton W, Abel G, Crosbie EJ, Rous B, Walter FM (2020). The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: a population-based cohort study. PLOS Medicine, 17(10), e1003295-e1003295.
Hamilton W (2020). The future of diagnosis in general practice.
Br J Gen Pract,
70(696), 319-320.
Author URL.
Arendse KD, Walter FM, Pilling M, Zhou Y, Hamilton W, Funston G (2020). Time from presentation to pre-diagnostic chest X-ray in patients with symptomatic lung cancer: a cohort study using electronic patient records from English primary care.
British Journal of General Practice,
71(705), e273-e279.
Abstract:
Time from presentation to pre-diagnostic chest X-ray in patients with symptomatic lung cancer: a cohort study using electronic patient records from English primary care
BackgroundNational guidelines in England recommend prompt chest X-ray (within 14 days) in patients presenting in general practice with unexplained symptoms of possible lung cancer, including persistent cough, shortness of breath, or weight loss.AimTo examine time to chest X-ray in symptomatic patients in English general practice before lung cancer diagnosis, and explore demographical variation.Design and settingRetrospective cohort study using routinely collected general practice, cancer registry, and imaging data from England.MethodPatients with lung cancer who presented symptomatically in general practice in the year pre-diagnosis and who had a pre-diagnostic chest X-ray were included. Time from presentation to chest X-ray (presentation–test interval) was determined and intervals classified based on national guideline recommendations as concordant (≤14 days) or non-concordant (>14 days). Variation in intervals was examined by age, sex, smoking status, and deprivation.ResultsIn a cohort of 2102 patients with lung cancer, the median presentation–test interval was 49 (interquartile range [IQR] 5–172) days. of these, 727 (35%) patients had presentation–test intervals of ≤14 days (median 1 [IQR 0–6] day) and 1375 (65%) had presentation–test intervals of >14 days (median 128 [IQR 52–231] days). Intervals were longer among patients who smoke (equivalent to 63% longer than non-smokers; P<0.001), older patients (equivalent to 7% longer for every 10 years from age 27; P = 0.013), and females (equivalent to 12% longer than males; P = 0.016).ConclusionIn symptomatic primary care patients who underwent chest X-ray before lung cancer diagnosis, only 35% were tested within the timeframe recommended by national guidelines. Patients who smoke, older patients, and females experienced longer intervals. These findings could help guide initiatives aimed at improving timely lung cancer diagnosis.
Abstract.
Price S, Spencer A, Zhang X, Ball S, Lyratzopoulos G, Mujica-Mota R, Stapley S, Ukoumunne OC, Hamilton W (2020). Trends in time to cancer diagnosis around the period of changing national guidance on referral of symptomatic patients: a serial cross-sectional study using UK electronic healthcare records from 2006–17. Cancer Epidemiology, 69, 101805-101805.
Scott SE, Penfold C, Saji S, Curtis S, Watts C, Hamilton W, Joannides AJ, Walter FM (2019). 'It was nothing that you would think was anything': Qualitative analysis of appraisal and help seeking preceding brain cancer diagnosis.
PLoS One,
14(3).
Abstract:
'It was nothing that you would think was anything': Qualitative analysis of appraisal and help seeking preceding brain cancer diagnosis.
BACKGROUND: the patient's interpretation of the events and decisions leading up to consultation with a healthcare professional for symptoms of brain cancer is under researched. The aim of this study was to document responses to noticing the changes preceding a diagnosis of brain cancer and living with them, focusing on appraisal of changes and the decision to seek (and re-seek) help, with attention to the psychological processes underpinning the appraisal and help-seeking intervals. METHOD: in this qualitative study set in Eastern and NW England, in-depth interviews with adult patients recently diagnosed with primary brain cancer and their family members were analysed thematically, using the Model of Pathways to Treatment as a conceptual framework. RESULTS: 39 adult patients were interviewed. Regarding the appraisal interval, cognitive heuristics were found to underpin explanations of changes/symptoms. The subtlety and normality of changes often suggested nothing serious was wrong. Common explanations included stress or being busy at work, or age and these did not seem to warrant a visit to a doctor. Explanations and the decision to seek help were made within the social context, with friends, family and work colleagues contributing to appraisal and help-seeking decisions. Regarding the help-seeking interval, barriers to seeking help reflected components of Social Cognitive Theory, and included having other priorities, outcome expectations (e.g. 'feeling silly', not sure much can be done about it, not wanting to waste doctors' time) and accessibility of a preferred healthcare professional. CONCLUSION: Application of psychological theory facilitated understanding of the influences on cognition and behaviour. The study highlights implications for theory, awareness campaigns and potential opportunities promoting more timely help-seeking.
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Watson J, Salisbury C, Whiting P, Banks J, Pyne Y, Hamilton W (2019). Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the Clinical Practice Research Datalink.
Br J Gen Pract,
69(684), e470-e478.
Abstract:
Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the Clinical Practice Research Datalink.
BACKGROUND: Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and plasma viscosity) are commonly used in primary care. Though established for specific diagnostic purposes, there is uncertainty around their utility as a non-specific marker to rule out underlying disease in primary care. AIM: to identify the value of inflammatory marker testing in primary care as a rule-out test, and measure the cascade effects of testing in terms of further blood tests, GP appointments, and referrals. DESIGN AND SETTING: Cohort study of 160 000 patients with inflammatory marker testing in 2014, and 40 000 untested age, sex, and practice-matched controls, using UK primary care data from the Clinical Practice Research Datalink. METHOD: the primary outcome was incidence of relevant disease, including infections, autoimmune conditions, and cancers, among those with raised versus normal inflammatory markers and untested controls. Process outcomes included rates of GP consultations, blood tests, and referrals in the 6 months after testing. RESULTS: the overall incidence of disease following a raised inflammatory marker was 15%: 6.3% infections, 5.6% autoimmune conditions, 3.7% cancers. Inflammatory markers had an overall sensitivity of
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Mendonca SC, Abel GA, Gildea C, McPhail S, Peake MD, Rubin G, Singh H, Hamilton W, Walter FM, Roland MO, et al (2019). Associations between general practice characteristics with use of urgent referrals for suspected cancer and endoscopies: a cross-sectional ecological study.
Fam Pract,
36(5), 573-580.
Abstract:
Associations between general practice characteristics with use of urgent referrals for suspected cancer and endoscopies: a cross-sectional ecological study.
BACKGROUND: Large variation in measures of diagnostic activity has been described previously between English general practices, but related predictors remain understudied. OBJECTIVE: to examine associations between general practice population and characteristics, with the use of urgent referrals for suspected cancer, and use of endoscopy. METHODS: Cross-sectional observational study of English general practices. We examined practice-level use (/1000 patients/year) of urgent referrals for suspected cancer, gastroscopy, flexible sigmoidoscopy and colonoscopy. We used mixed-effects Poisson regression to examine associations with the sociodemographic profile of practice populations and other practice attributes, including the average age, sex and country of qualification of practice doctors. RESULTS: the sociodemographic characteristics of registered patients explained much of the between-practice variance in use of urgent referrals (32%) and endoscopic investigations (18-25%), all being higher in practices with older and more socioeconomically deprived patients. Practice-level attributes explained a substantial amount of between-practice variance in urgent referral (19%) but little of the variance in endoscopy (3%-4%). Adjusted urgent referral rates were higher in training practices and those with younger GPs. Practices with mean doctor ages of 41 and 57 years (at the 10th/90th centiles of the national distribution) would have urgent referral rates of 24.1 and 19.1/1000 registered patients, P < 0.001. CONCLUSION: Most between-practice variation in use of urgent referrals and endoscopies seems to reflect health need. Some practice characteristics, such as the mean age of GPs, are associated with appreciable variation in use of urgent referrals, though these associations do not seem strong enough to justify targeted interventions.
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Author URL.
Watson J, Salisbury C, Banks J, Whiting P, Hamilton W (2019). Authors' response.
Br J Gen Pract,
69(687).
Author URL.
Watson J, Mounce L, Bailey SER, Cooper SL, Hamilton W (2019). Blood markers for cancer. BMJ, l5774-l5774.
Watson J, Bailey S, Hamilton F, Mounce LTA, Hamilton W (2019). Clinical implications of increased testing in primary care. BMJ, 364, l175-l175.
Renzi C, Kaushal A, Emery J, Hamilton W, Neal RD, Rachet B, Rubin G, Singh H, Walter FM, de Wit NJ, et al (2019). Comorbid chronic diseases and cancer diagnosis: disease-specific effects and underlying mechanisms.
Nat Rev Clin Oncol,
16(12), 746-761.
Abstract:
Comorbid chronic diseases and cancer diagnosis: disease-specific effects and underlying mechanisms.
An earlier diagnosis is a key strategy for improving the outcomes of patients with cancer. However, achieving this goal can be challenging, particularly for the growing number of people with one or more chronic conditions (comorbidity/multimorbidity) at the time of diagnosis. Pre-existing chronic diseases might affect patient participation in cancer screening, help-seeking for new and/or changing symptoms and clinicians' decision-making on the use of diagnostic investigations. Evidence suggests, for example, that pre-existing pulmonary, cardiovascular, neurological and psychiatric conditions are all associated with a more advanced stage of cancer at diagnosis. By contrast, hypertension and certain gastrointestinal and musculoskeletal conditions might be associated with a more timely diagnosis. In this Review, we propose a comprehensive framework that encompasses the effects of disease-specific, patient-related and health-care-related factors on the diagnosis of cancer in individuals with pre-existing chronic illnesses. Several previously postulated aetiological mechanisms (including alternative explanations, competing demands and surveillance effects) are integrated with newly identified mechanisms, such as false reassurances, or patient concerns about appearing to be a hypochondriac. By considering specific effects of chronic diseases on diagnostic processes and outcomes, tailored early diagnosis initiatives can be developed to improve the outcomes of the large proportion of patients with cancer who have pre-existing chronic conditions.
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Renzi C, Lyratzopoulos G, Hamilton W, Maringe C, Rachet B (2019). Contrasting effects of comorbidities on emergency colon cancer diagnosis: a longitudinal data-linkage study in England.
BMC Health Serv Res,
19(1).
Abstract:
Contrasting effects of comorbidities on emergency colon cancer diagnosis: a longitudinal data-linkage study in England.
BACKGROUND: One in three colon cancers are diagnosed as an emergency, which is associated with worse cancer outcomes. Chronic conditions (comorbidities) affect large proportions of adults and they might influence the risk of emergency presentations (EP). METHODS: We aimed to evaluate the effect of specific pre-existing comorbidities on the risk of colon cancer being diagnosed following an EP rather than through non-emergency routes. The cohort study included 5745 colon cancer patients diagnosed in England 2005-2010, with individually-linked cancer registry, primary and secondary care data. In addition to multivariable analyses we also used potential-outcomes methods. RESULTS: Colon cancer patients with comorbidities consulted their GP more frequently with cancer symptoms during the pre-diagnostic year, compared with non-comorbid cancer patients. EP occurred more frequently in patients with 'serious' or complex comorbidities (diabetes, cardiac and respiratory diseases) diagnosed/treated in hospital during the years pre-cancer diagnosis (43% EP in comorbid versus 27% in non-comorbid individuals; multivariable analysis Odds Ratio (OR), controlling for socio-demographic factors and symptoms: men OR = 2.40; 95% CI 2.0-2.9 and women OR = 1.98; 95% CI 1.6-2.4. Among women younger than 60, gynaecological (OR = 3.41; 95% CI 1.2-9.9) or recent onset gastro-intestinal conditions (OR = 2.84; 95% CI 1.1-7.7) increased the risk of EP. In contrast, primary care visits for hypertension monitoring decreased EPs for both genders. CONCLUSIONS: Patients with comorbidities have a greater risk of being diagnosed with cancer as an emergency, although they consult more frequently with cancer symptoms during the year pre-cancer diagnosis. This suggests that comorbidities may interfere with diagnostic reasoning or investigations due to 'competing demands' or because they provide 'alternative explanations'. In contrast, the management of chronic risk factors such as hypertension may offer opportunities for earlier diagnosis. Interventions are needed to support the diagnostic process in comorbid patients. Appropriate guidelines and diagnostic services to support the evaluation of new or changing symptoms in comorbid patients may be useful.
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Nicholson BD, Aveyard P, Bankhead CR, Hamilton W, Hobbs FDR, Lay-Flurrie S (2019). Determinants and extent of weight recording in UK primary care: an analysis of 5 million adults' electronic health records from 2000 to 2017.
BMC Medicine,
17(1).
Abstract:
Determinants and extent of weight recording in UK primary care: an analysis of 5 million adults' electronic health records from 2000 to 2017
Background: Excess weight and unexpected weight loss are associated with multiple disease states and increased morbidity and mortality, but weight measurement is not routine in many primary care settings. The aim of this study was to characterise who has had their weight recorded in UK primary care, how frequently, by whom and in relation to which clinical events, symptoms and diagnoses. Methods: a longitudinal analysis of UK primary care electronic health records (EHR) data from 2000 to 2017. Descriptive statistics were used to summarise weight recording in terms of patient sociodemographic characteristics, health professional encounters, clinical events, symptoms and diagnoses. Negative binomial regression was used to model the likelihood of having a weight record each year, and Cox regression to the likelihood of repeated weight recording. Results: a total of 14,049,871 weight records were identified in the EHR of 4,918,746 patients during the study period, representing 26,998,591 person-years of observation. Around a third of patients had a weight record each year. Forty-nine percent of weight records were repeated within a year with an average time to a repeat weight record of 1.92 years. Weight records were most often taken by nursing staff (38-42%) and GPs (37-39%) as part of a routine clinical care, such as chronic disease reviews (16%), medication reviews (6-8%) and health checks (6-7%), or were associated with consultations for contraception (5-8%), respiratory disease (5%) and obesity (1%). Patient characteristics independently associated with an increased likelihood of weight recording were as follows: Female sex, younger and older adults, non-drinkers, ex-smokers, low or high BMI, being more deprived, diagnosed with a greater number of comorbidities and consulting more frequently. The effect of policy-level incentives to record weight did not appear to be sustained after they were removed. Conclusion: Weight recording is not a routine activity in UK primary care. It is recorded for around a third of patients each year and is repeated on average every 2 years for these patients. It is more common in females with higher BMI and in those with comorbidity. Incentive payments and their removal appear to be associated with increases and decreases in weight recording.
Abstract.
Zienius K, Chak-Lam I, Park J, Ozawa M, Hamilton W, Weller D, Summers D, Porteous L, Mohiuddin S, Keeney E, et al (2019). Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.
BMC Fam Pract,
20(1).
Abstract:
Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.
BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.
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Santillo M, Sivyer K, Krusche A, Mowbray F, Jones N, Peto TEA, Walker AS, Llewelyn MJ, Yardley L, Lee A, et al (2019). Intervention planning for Antibiotic Review Kit (ARK): a digital and behavioural intervention to safely review and reduce antibiotic prescriptions in acute and general medicine.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY,
74(11), 3362-3370.
Author URL.
Walter FM, Penfold C, Joannides A, Saji S, Johnson M, Watts C, Brodbelt A, Jenkinson MD, Price SJ, Hamilton W, et al (2019). Missed opportunities for diagnosing brain tumours in primary care: a qualitative study of patient experiences.
Br J Gen Pract,
69(681), e224-e235.
Abstract:
Missed opportunities for diagnosing brain tumours in primary care: a qualitative study of patient experiences.
BACKGROUND: Brain tumours are uncommon, and have extremely poor outcomes. Patients and GPs may find it difficult to recognise early symptoms because they are often non-specific and more likely due to other conditions. AIM: to explore patients' experiences of symptom appraisal, help seeking, and routes to diagnosis. DESIGN AND SETTING: Qualitative study set in the East and North West of England. METHOD: In-depth interviews with adult patients recently diagnosed with a primary brain tumour and their family members were analysed thematically, using the Model of Pathways to Treatment as a conceptual framework. RESULTS: Interviews were carried out with 39 patients. Few participants (n = 7; 18%) presented as an emergency without having had a previous GP consultation; most had had one (n = 15; 38%), two (n = 9; 23%), or more (n = 8; 21%) GP consultations. Participants experienced multiple subtle 'changes' rather than 'symptoms', often noticed by others rather than the patient, which frequently led to loss of interest or less ability to engage with daily living activities. The most common changes were in cognition (speaking, writing, comprehension, memory, concentration, and multitasking), sleep, and other 'head feelings' such as dizziness. Not all patients experienced a seizure, and few seizures were experienced 'out of the blue'. Quality of communication in GP consultations played a key role in patients' subsequent symptom appraisal and the timing of their decision to re-consult. CONCLUSION: Multiple subtle changes and frequent GP visits often precede brain tumour diagnosis, giving possible diagnostic opportunities for GPs. Refined community symptom awareness and GP guidance could enable more direct pathways to diagnosis, and potentially improve patient experiences and outcomes.
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Author URL.
Renzi C, Lyratzopoulos G, Hamilton W, Rachet B (2019). Opportunities for reducing emergency diagnoses of colon cancer in women and men: a data-linkage study on pre-diagnostic symptomatic presentations and benign diagnoses.
Eur J Cancer Care (Engl),
28(2).
Abstract:
Opportunities for reducing emergency diagnoses of colon cancer in women and men: a data-linkage study on pre-diagnostic symptomatic presentations and benign diagnoses.
OBJECTIVES: to identify opportunities for reducing emergency colon cancer diagnoses, we evaluated symptoms and benign diagnoses recorded before emergency presentations (EP). METHODS: Cohort of 5,745 colon cancers diagnosed in England 2005-2010, with individually linked cancer registry and primary care data for the 5-year pre-diagnostic period. RESULTS: Colon cancer was diagnosed following EP in 34% of women and 30% of men. Among emergency presenters, 20% of women and 15% of men (p = 0.002) had alarm symptoms (anaemia/rectal bleeding/change in bowel habit) 2-12 months pre-diagnosis. Women with abdominal symptoms (change in bowel habit/constipation/diarrhoea) received a benign diagnosis (irritable bowel syndrome (IBS)/diverticular disease) more frequently than men in the year before EP: 12% vs. 6% among women and men (p = 0.002). EP was more likely in women (OR = 1.20; 95% CI 1.1-1.4), independently of socio-demographic factors and symptoms. Benign diagnoses in the pre-diagnostic year (OR = 2.01; 95% CI 1.2-3.3) and anaemia 2-5 years pre-diagnosis (OR = 1.91; 95% CI 1.2-3.0) increased the risk of EP in women but not men. The risk was particularly high for women aged 40-59 with a recent benign diagnosis vs. none (OR = 4.41; 95% CI 1.3-14.9). CONCLUSIONS: Women have an increased risk of EP, in part due to less specific symptoms and their more frequent attribution to benign diagnoses. For women aged 40-59 years with new-onset IBS/diverticular disease innovative diagnostic strategies are needed, which might include use of quantitative faecal haemoglobin testing (FIT) or other colorectal cancer investigations. One-fifth of women had alarm symptoms before EP, offering opportunities for earlier diagnosis.
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Watson J, Salisbury C, Banks J, Whiting P, Hamilton W (2019). Predictive value of inflammatory markers for cancer diagnosis in primary care: a prospective cohort study using electronic health records.
British Journal of Cancer,
120(11), 1045-1051.
Abstract:
Predictive value of inflammatory markers for cancer diagnosis in primary care: a prospective cohort study using electronic health records
Background: Early identification of cancer in primary care is important and challenging. This study examined the diagnostic utility of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate and plasma viscosity) for cancer diagnosis in primary care. Methods: Cohort study of 160,000 patients with inflammatory marker testing in 2014, plus 40,000 untested matched controls, using Clinical Practice Research Datalink (CPRD), with Cancer Registry linkage. Primary outcome was one-year cancer incidence. Results: Primary care patients with a raised inflammatory marker have a one-year cancer incidence of 3.53% (95% CI 3.37–3.70), compared to 1.50% (1.43–1.58) in those with normal inflammatory markers, and 0.97% (0.87–1.07) in untested controls. Cancer risk is greater with higher inflammatory marker levels, with older age and in men; risk rises further when a repeat test is abnormal but falls if it normalises. Men over 50 and women over 60 with raised inflammatory markers have a cancer risk which exceeds the 3% NICE threshold for urgent investigation. Sensitivities for cancer were 46.1% for CRP, 43.6% ESR and 49.7% for PV. Conclusion: Cancer should be considered in patients with raised inflammatory markers. However, inflammatory markers have a poor sensitivity for cancer and are therefore not useful as ‘rule-out’ test.
Abstract.
Ranson JM, Kuźma E, Hamilton W, Muniz-Terrera G, Langa KM, Llewellyn DJ (2019). Predictors of dementia misclassification when using brief cognitive assessments.
Neurol Clin Pract,
9(2), 109-117.
Abstract:
Predictors of dementia misclassification when using brief cognitive assessments.
BACKGROUND: Brief cognitive assessments can result in false-positive and false-negative dementia misclassification. We aimed to identify predictors of misclassification by 3 brief cognitive assessments; the Mini-Mental State Examination (MMSE), Memory Impairment Screen (MIS) and animal naming (AN). METHODS: Participants were 824 older adults in the population-based US Aging, Demographics and Memory Study with adjudicated dementia diagnosis (DSM-III-R and DSM-IV criteria) as the reference standard. Predictors of false-negative, false-positive and overall misclassification by the MMSE (cut-point
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Author URL.
Zhou Y, van Melle M, Singh H, Hamilton W, Lyratzopoulos G, Walter FM (2019). Quality of the diagnostic process in patients presenting with symptoms suggestive of bladder or kidney cancer: a systematic review.
BMJ Open,
9(10).
Abstract:
Quality of the diagnostic process in patients presenting with symptoms suggestive of bladder or kidney cancer: a systematic review.
OBJECTIVES: in urological cancers, sex disparity exists for survival, with women doing worse than men. Suboptimal evaluation of presenting symptoms may contribute. DESIGN: We performed a systematic review examining factors affecting the quality of the diagnostic process of patients presenting with symptoms of bladder or kidney cancer. DATA SOURCES: We searched Medline, Embase and the Cochrane Library from 1 January 2000 to 13 June 2019. ELIGIBLE CRITERIA: We focused on one of the six domains of quality of healthcare: timeliness, and examined the quality of the diagnostic process more broadly, by assessing whether guideline-concordant history, examination, tests and referrals were performed. Studies describing the factors that affect the timeliness or quality of the assessment of urinary tract infections, haematuria and lower urinary tract symptoms in the context of bladder or kidney cancer, were included. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment were independently performed by two authors. Due to the heterogeneity of study design and outcomes, the results could not be pooled. A narrative synthesis was performed. RESULTS: 28 studies met review criteria, representing 583 636 people from 9 high-income countries. Studies were based in primary care (n=8), specialty care (n=12), or both (n=8). Up to two-thirds of patients with haematuria received no further evaluation in the 6 months after their initial visit. Urinary tract infections, nephrolithiasis and benign prostatic conditions before cancer diagnosis were associated with diagnostic delay. Women were more likely to experience diagnostic delay than men. Patients who first saw a urologist were less likely to experience delayed evaluation and cancer diagnosis. CONCLUSIONS: Women, and patients with non-cancerous urological diagnoses just prior to their cancer diagnosis, were more likely to experience lower quality diagnostic processes. Risk prediction tools, and improving guideline ambiguity, may improve outcomes and reduce sex disparity in survival for these cancers.
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Shephard EA, Parkinson MA, Hamilton WT (2019). Recognising laryngeal cancer in primary care: a large case-control study using electronic records.
Br J Gen Pract,
69(679), e127-e133.
Abstract:
Recognising laryngeal cancer in primary care: a large case-control study using electronic records.
BACKGROUND: over 1700 people are diagnosed with laryngeal cancer annually in England. Current National Institute for Health and Care Excellence (NICE) guidelines on referral for suspected laryngeal cancer were based on clinical consensus, in the absence of primary care studies. AIM: to identify and quantify the primary care features of laryngeal cancer. DESIGN AND SETTING: Matched case-control study of patients aged ≥40 years using data from the UK's Clinical Practice Research Datalink. METHOD: Clinical features of laryngeal cancer with which patients had presented to their GP in the year before diagnosis were identified and their association with cancer was assessed using conditional logistic regression. Positive predictive values (PPVs) for each clinical feature were calculated for the consulting population aged >60 years. RESULTS: in total, 806 patients diagnosed with laryngeal cancer between 2000 and 2009 were studied, together with 3559 age-, sex-, and practice-matched controls. Ten features were significantly associated with laryngeal cancer: hoarseness odds ratio [OR] 904 (95% confidence interval [CI] = 277 to 2945); sore throat, first attendance OR 6.2 (95% CI = 3.7 to 10); sore throat, re-attendance OR 7.7 (95% CI = 2.6 to 23); dysphagia OR 6.5 (95% CI = 2.7 to 16); otalgia OR 5.0 (95% CI = 1.9 to 13); dyspnoea, re-attendance OR 4.7 (95% CI = 1.9 to 12); mouth symptoms OR 4.7 (95% CI = 1.8 to 12); recurrent chest infection OR 4.5 (95% CI = 2.4 to 8.5); insomnia OR 2.7 (95% CI = 1.3 to 5.6); and raised inflammatory markers OR 2.5 (95% CI = 1.5 to 4.1). All P-values were 5%. CONCLUSION: These results expand current NICE guidance by identifying new symptom combinations that are associated with laryngeal cancer; they may help GPs to select more appropriate patients for referral.
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Author URL.
Bradley SH, Abraham S, Callister ME, Grice A, Hamilton WT, Lopez RR, Shinkins B, Neal RD (2019). Sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms: a systematic review.
Br J Gen Pract,
69(689), e827-e835.
Abstract:
Sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms: a systematic review.
BACKGROUND: Despite increasing use of computed tomography (CT), chest X-ray remains the first-line investigation for suspected lung cancer in primary care in the UK. No systematic review evidence exists as to the sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms. AIM: to estimate the sensitivity of chest X-ray for detecting lung cancer in symptomatic people. DESIGN AND SETTING: a systematic review was conducted to determine the sensitivity of chest X-ray for the detection of lung cancer. METHOD: Databases including MEDLINE, EMBASE, and the Cochrane Library were searched; a grey literature search was also performed. RESULTS: a total of 21 studies met the eligibility criteria. Almost all were of poor quality. Only one study had the diagnostic accuracy of chest X-ray as its primary objective. Most articles were case studies with a high risk of bias. Several were drawn from non-representative groups, for example, specific presentations, histological subtypes, or comorbidities. Only three studies had a low risk of bias. Two primary care studies reported sensitivities of 76.8% (95% confidence interval [CI] = 64.5 to 84.2%) and 79.3% (95% CI = 67.6 to 91.0%). One secondary care study reported a sensitivity of 79.7% (95% CI = 72.7 to 86.8%). CONCLUSION: Though there is a paucity of evidence, the highest-quality studies suggest that the sensitivity of chest X-ray for symptomatic lung cancer is only 77% to 80%. GPs should consider if further investigation is necessary in high-risk patients who have had a negative chest X-ray.
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Author URL.
Nicholson BD, Aveyard P, Hamilton W, Bankhead CR, Koshiaris C, Stevens S, Hobbs FD, Perera R (2019). The internal validation of weight and weight change coding using weight measurement data within the UK primary care Electronic Health Record.
Clin Epidemiol,
11, 145-155.
Abstract:
The internal validation of weight and weight change coding using weight measurement data within the UK primary care Electronic Health Record.
PURPOSE: to use recorded weight values to internally validate weight status and weight change coding in the primary care Electronic Health Record (EHR). PATIENTS AND METHODS: We included adult patients with weight-related Read codes recorded in the UK's Clinical Practice Research Datalink EHR between 2000 and 2017. Weight status codes were compared to weight values recorded on the same day and positive predictive values (PPVs) were calculated for commonly used codes. Weight change codes were validated using three methods: the percentage (%) difference in kilograms at the time of the code and 1) the previous weight measurement, 2) the weight predicted using linear regression, and 3) the historic mean weight. Weight change codes were validated if estimates were consistent across two out of three methods. RESULTS: a total of 8,108,481 weight codes were recorded in 1,000,002 patients' EHR. Twice as many were recorded in females (n=5,208,593, 64%). The mean body mass index for "overweight" codes ranged from 31.9 kg/m2 to 46.9 kg/m2 and from 17.4 kg/m2 to 19.2 kg/m2 for "underweight" codes. PPVs for the most commonly used weight status codes ranged from 81.3% (80%-82.5%) to 99.3% (99.2%-99.4%). Across the estimation methods, and using only validated weight change codes, mean weight loss ranged from - 5.2% (SD 5.8%) to -7.9% (SD 7.3%) and mean weight gain from 4.2 % (SD 5.5%) to 7.9 % (SD 8.2%). The previous and predicted weight methods were most consistent. CONCLUSION: We have developed an internationally applicable methodology to internally validate weight-related EHR coding by using available weight measurement data. We demonstrate the UK Read codes that can be confidently used to classify weight status and weight change in the absence of weight values. We provide the first evidence from primary care that a Read code for unexpected weight loss represents a mean loss of ≥ 5 % in a 6-month period, which was broadly consistent across age groups and gender.
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Author URL.
Ozawa M, Brennan PM, Zienius K, Kurian KM, Hollingworth W, Weller D, Grant R, Hamilton W, Ben-Shlomo Y (2019). The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: a case-control study using the clinical practice research database (CPRD) (2000-2014).
BMJ Open,
9(8).
Abstract:
The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: a case-control study using the clinical practice research database (CPRD) (2000-2014).
OBJECTIVES: to evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis. DESIGN AND SETTING: Matched case-control study, using the data from Clinical Practice Research Datalink (2000-2014) from primary care consultations in the UK. METHOD: all presentations within 6 months of the index diagnosis date (cases) or equivalent (controls) were coded into 32 symptom groups. Sensitivity, specificity, positive predictive values (PPVs) and positive likelihood ratios were calculated for symptoms and combinations of symptoms with headache and cognitive features. Diagnostic odds ratios were calculated using conditional logistic regression, adjusted for age group, sex and Charlson comorbidity. Stratified analyses were performed for age group, sex and whether the tumour was of primary or secondary origin. RESULTS: We included 8,184 cases and 28,110 controls. Seizure had the highest PPV of 1.6% (95% CI 1.4% to 1.7%) followed by weakness 1.5% (1.3 to 1.7) and confusion 1.4% (1.3 to 1.5). Combining headache with other symptoms increased the PPV. For example, headache plus combined cognitive symptoms PPV 7.2% (6.0 to 8.6); plus weakness 4.4% (3.2 to 6.2), compared with headache alone PPV 0.1%. The diagnostic ORs were generally larger for patients
Abstract.
Author URL.
Watson J, Jones HE, Banks J, Whiting P, Salisbury C, Hamilton W (2019). Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy.
Br J Gen Pract,
69(684), e462-e469.
Abstract:
Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy.
BACKGROUND: Research comparing C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and plasma viscosity (PV) in primary care is lacking. Clinicians often test multiple inflammatory markers, leading to concerns about overuse. AIM: to compare the diagnostic accuracies of CRP, ESR, and PV, and to evaluate whether measuring two inflammatory markers increases accuracy. DESIGN AND SETTING: Prospective cohort study in UK primary care using the Clinical Practice Research Datalink. METHOD: the authors compared diagnostic test performance of inflammatory markers, singly and paired, for relevant disease, defined as any infections, autoimmune conditions, or cancers. For each of the three tests (CRP, ESR, and PV), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under receiver operator curve (AUC) were calculated. RESULTS: Participants comprised 136 961 patients with inflammatory marker testing in 2014; 83 761 (61.2%) had a single inflammatory marker at the index date, and 53 200 (38.8%) had multiple inflammatory markers. For 'any relevant disease', small differences were seen between the three tests; AUC ranged from 0.659 to 0.682. CRP had the highest overall AUC, largely because of marginally superior performance in infection (AUC CRP 0.617, versus ESR 0.589, P
Abstract.
Author URL.
Funston G, Van Melle M, Baun MLL, Jensen H, Helsper C, Emery J, Crosbie EJ, Thompson M, Hamilton W, Walter FM, et al (2019). Variation in the initial assessment and investigation for ovarian cancer in symptomatic women: a systematic review of international guidelines.
BMC Cancer,
19(1).
Abstract:
Variation in the initial assessment and investigation for ovarian cancer in symptomatic women: a systematic review of international guidelines
Background: Women with ovarian cancer can present with a variety of symptoms and signs, and an increasing range of tests are available for their investigation. A number of international guidelines provide advice for the initial assessment of possible ovarian cancer in symptomatic women. We systematically identified and reviewed the consistency and quality of these documents. Methods: MEDLINE, Embase, guideline-specific databases and professional organisation websites were searched in March 2018 for relevant clinical guidelines, consensus statements and clinical pathways, produced by professional or governmental bodies. Two reviewers independently extracted data and appraised documents using the Appraisal for Guidelines and Research Evaluation 2 (AGREEII) tool. Results: Eighteen documents from 11 countries in six languages met selection criteria. Methodological quality varied with two guidance documents achieving an AGREEII score ≥ 50% in all six domains and 10 documents scoring ≥50% for "Rigour of development" (range: 7-96%). All guidance documents provided advice on possible symptoms of ovarian cancer, although the number of symptoms included in documents ranged from four to 14 with only one symptom (bloating/abdominal distension/increased abdominal size) appearing in all documents. Fourteen documents provided advice on physical examinations but varied in both the examinations they recommended and the physical signs they included. Fifteen documents provided recommendations on initial investigations. Transabdominal/transvaginal ultrasound and the serum biomarker CA125 were the most widely advocated initial tests. Five distinct testing strategies were identified based on the number of tests and the order of testing advocated: 'single test', 'dual testing', 'sequential testing', 'multiple testing options' and 'no testing'. Conclusions: Recommendations on the initial assessment and investigation for ovarian cancer in symptomatic women vary considerably between international guidance documents. This variation could contribute to differences in the way symptomatic women are assessed and investigated between countries. Greater research is needed to evaluate the assessment and testing approaches advocated by different guidelines and their impact on ovarian cancer detection.
Abstract.
Nicholson BD, Aveyard P, Hamilton W, Hobbs FDR (2019). When should unexpected weight loss warrant further investigation to exclude cancer?.
BMJ,
366 Author URL.
Cross AJ, Wooldrage K, Robbins EC, Pack K, Brown JP, Hamilton W, Thompson MR, Flashman KG, Halligan S, Thomas-Gibson S, et al (2019). Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study.
Br J Cancer,
120(2), 154-164.
Abstract:
Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study.
BACKGROUND: Patients with suspected colorectal cancer (CRC) usually undergo colonoscopy. Flexible sigmoidoscopy (FS) may be preferred if proximal cancer risk is low. We investigated which patients could undergo FS alone. METHODS: Cohort study of 7375 patients (≥55 years) referred with suspected CRC to 21 English hospitals (2004-2007), followed using hospital records and cancer registries. We calculated yields and number of needed whole-colon examinations (NNE) to diagnose one cancer by symptoms/signs and subsite. We considered narrow (haemoglobin
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Author URL.
Sullivan SA, Hamilton W, Tilling K, Redaniel T, Moran P, Lewis G (2018). Association of Primary Care Consultation Patterns with Early Signs and Symptoms of Psychosis.
JAMA Netw Open,
1(7).
Abstract:
Association of Primary Care Consultation Patterns with Early Signs and Symptoms of Psychosis.
IMPORTANCE: Primary care is an important part of the care pathway for patients with psychosis; therefore, primary care physicians need to be able to accurately identify those at clinical high risk of psychosis. The difficulty of this task is increased because clinical high-risk symptoms are frequently nonspecific to psychosis. OBJECTIVE: to determine whether the consultation patterns for a prespecified set of symptoms can be used to identify primary care patients who later developed a psychotic illness. DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study used primary care consultation data collected from 530 primary care practices in 13 UK regions from January 1, 2000, through September 30, 2009. Participants included 11 690 adults with a diagnosis of psychosis and 81 793 control participants who did not have a diagnosis of psychosis individually matched by age group, sex, and primary care practice. Data were analyzed from July 1, 2015, through June 2, 2017. EXPOSURES: Prespecified symptoms selected from literature included attention-deficit/hyperactivity disorder-like symptoms, bizarre behavior, blunted affect, problems associated with cannabis, depressive symptoms, role functioning problems, social isolation, symptoms of mania, obsessive-compulsive disorder-like symptoms, disordered personal hygiene, sleep disturbance, problems associated with cigarette smoking, and suicidal behavior (including self-harm). MAIN OUTCOMES AND MEASURES: Case (diagnosis of psychosis) or control (no diagnosis of psychosis) status. Conditional logistic regression was used to investigate the association between symptoms and case-control status in the 5 years before diagnosis. Positive predictive values (PPVs) were calculated using the Bayes theorem for symptoms stratified by age group and sex. Repeated-measures Poisson regression was used to investigate symptom consultation rate. RESULTS: of the total sample of 93 483 participants, 57.4% were female and 40.0% were older than 60 years (mean [SD] age, 51.34 [21.75] years). Twelve symptoms were associated with a later psychotic diagnosis (all prespecified symptoms except disordered personal hygiene). The strongest association was with suicidal behavior (odds ratio [OR], 19.06; 95% CI, 16.55-21.95). Positive predictive values were heterogeneous across age and sex. The highest PPVs were for suicidal behavior (33.0% in men 24 years or younger [95% CI, 24.2%-43.2%] and 19.6% in women aged 25-34 years [95% CI, 13.7%-27.2%]). Pairs of symptoms were associated with an increase in PPV. Consultation rates were higher in cases and increased 3 months before diagnosis. CONCLUSIONS AND RELEVANCE: Most of the preselected nonspecific symptoms were associated with a later psychotic diagnosis, particularly among young men consulting for suicidal behavior, especially if consulting with increasing frequency. These symptoms should alert physicians to patients who may benefit from a further assessment of psychotic symptoms.
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Author URL.
Lyratzopoulos G, Mendonca SC, Gildea C, McPhail S, Peake MD, Rubin G, Singh H, Hamilton W, Walter FM, Roland M, et al (2018). Associations between diagnostic activity and measures of patient experience in primary care: a cross-sectional ecological study of English general practices.
Br J Gen Pract,
68(666), e9-e17.
Abstract:
Associations between diagnostic activity and measures of patient experience in primary care: a cross-sectional ecological study of English general practices.
BACKGROUND: Lower use of endoscopies and urgent referrals for suspected cancer has been linked to poorer outcomes for patients with cancer; it is important to examine potential predictors of variable use. AIM: to examine the associations between general practice measures of patient experience and practice use of endoscopies or urgent referrals for suspected cancer. DESIGN AND SETTING: Cross-sectional ecological analysis in English general practices. METHOD: Data were taken from the GP Patient Survey and the Cancer Services Public Health Profiles. After adjustment for practice population characteristics, practice-level associations were examined between the use of endoscopy and urgent referrals for suspected cancer, and the ability to book an appointment (used as proxy for ease of access), the ability to see a preferred doctor (used as proxy for relational continuity), and doctor/nurse communication skills. RESULTS: Taking into account practice scores for the ability to book an appointment, practices rated higher for the proxy measure of relational continuity used urgent referrals and endoscopies less often (for example, 30% lower urgent referral and 15% lower gastroscopy rates between practices in the 90th/10th centiles, respectively). In contrast, practices rated higher for doctor communication skills used urgent referrals and endoscopies more often (for example, 26% higher urgent referral and 17% higher gastroscopy rates between practices in the 90th/10th centiles, respectively). Patients with cancer in practices that were rated higher for doctor communication skills were less likely to be diagnosed as emergencies (1.7% lower between practices in the 90th than in the 10th centile). CONCLUSION: Practices where patients rated doctor communication highly were more likely to investigate and refer patients urgently but, in contrast, practices where patients could see their preferred doctor more readily were less likely to do so. This article discusses the possible implications of these findings for clinical practice.
Abstract.
Author URL.
Ankus E, Price S, Ukoumunne O, Hamilton W, Bailey S (2018). Cancer incidence in patients with a high normal platelet count: a cohort study using primary care data. Family Practice
Ranson JM, Kuźma E, Hamilton W, Lang I, Llewellyn DJ (2018). Case-finding in clinical practice: an appropriate strategy for dementia identification?.
Alzheimer's and Dementia: Translational Research and Clinical Interventions,
4, 288-296.
Abstract:
Case-finding in clinical practice: an appropriate strategy for dementia identification?
Earlier diagnosis of dementia is increasingly being recognized as a public health priority. As screening is not generally recommended, case-finding in clinical practice is encouraged as an alternative dementia identification strategy. The approaches of screening and case-finding are often confused, with uncertainty about what case-finding should involve and under what circumstances it is appropriate. We propose a formal definition of dementia case-finding with a clear distinction from screening. We critically examine case-finding policy and practice and propose evidence requirements for implementation in clinical practice. Finally, we present a case-finding pathway and discuss the available evidence for best practice at each stage, with recommendations for research and practice. In conclusion, dementia case-finding is a promising strategy but currently not appropriate due to the substantial gaps in the evidence base for several components of this approach.
Abstract.
Funston G, O’flynn H, Ryan NAJ, Hamilton W, Crosbie EJ (2018). Correction to: Recognizing Gynecological Cancer in Primary Care: Risk Factors, Red Flags, and Referrals (Adv Ther, 10.1007/s12325-018-0683-3). Advances in Therapy, 35(12).
Shephard EA, Hamilton WT (2018). Corrections: Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records (British Journal of General Practice(2018) DOI: 10.3399/bjgp18X697949).
British Journal of General Practice,
68(674).
Abstract:
Corrections: Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records (British Journal of General Practice(2018) DOI: 10.3399/bjgp18X697949)
Research by Shephard EA and Hamilton WT, Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records. Br J Gen Pract 2018; DOI: Https://doi.org/10.3399/ bjgp18X697949 showed an inaccuracy in the print version. The printed version states 'Testicular swelling alone has a PPV for cancer just below the 3% threshold, but when combined with testicular, groin or abdominal pain, particularly in men aged >50 years, the likelihood of cancer is considerably greater.' the corrected version should read 'A testicular lump alone has a PPV for cancer just below the 3% threshold, but when combined with testicular swelling, pain or abdominal pain in men
Abstract.
Zhou Y, Abel G, Hamilton W, Pritchard-Jones K, Gross C, Walter F, Renzi C, Johnson S, McPhail S, Elliss-Brookes L, et al (2018). Defining, Measuring and Preventing the Diagnosis of Cancer as an Emergency: a Critical Review of Current Evidence. Journal of Global Oncology, 4(Supplement 2), 48s-48s.
Stanciu MA, Law R-J, Nafees S, Hendry M, Yeo ST, Hiscock J, Lewis R, Edwards RT, Williams NH, Brain K, et al (2018). Development of an intervention to expedite cancer diagnosis through primary care: a protocol.
BJGP Open,
2(3).
Abstract:
Development of an intervention to expedite cancer diagnosis through primary care: a protocol.
BACKGROUND: GPs can play an important role in achieving earlier cancer diagnosis to improve patient outcomes, for example through prompt use of the urgent suspected cancer referral pathway. Barriers to early diagnosis include individual practitioner variation in knowledge, attitudes, beliefs, professional expectations, and norms. AIM: This programme of work (Wales Interventions and Cancer Knowledge about Early Diagnosis [WICKED]) will develop a behaviour change intervention to expedite diagnosis through primary care and contribute to improved cancer outcomes. DESIGN & SETTING: Non-experimental mixed-method study with GPs and primary care practice teams from Wales. METHOD: Four work packages will inform the development of the behaviour change intervention. Work package 1 will identify relevant evidence-based interventions (systematic review of reviews) and will determine why interventions do or do not work, for whom, and in what circumstances (realist review). Work package 2 will assess cancer knowledge, attitudes, and behaviour of GPs, as well as primary care teams' perspectives on cancer referral and investigation (GP survey, discrete choice experiment [DCE], interviews, and focus groups). Work package 3 will synthesise findings from earlier work packages using the behaviour change wheel as an overarching theoretical framework to guide intervention development. Work package 4 will test the feasibility and acceptability of the intervention, and determine methods for measuring costs and effects of subsequent behaviour change in a randomised feasibility trial. RESULTS: the findings will inform the design of a future effectiveness trial, with concurrent economic evaluation, aimed at earlier diagnosis. CONCLUSION: This comprehensive, evidence-based programme will develop a complex GP behaviour change intervention to expedite the diagnosis of symptomatic cancer, and may be applicable to countries with similar healthcare systems.
Abstract.
Author URL.
Zienius K, Brennan P, Ben-Shlomo Y, Ozawa M, Keeney E, Weller D, Hamilton W, Hollingworth W, Grant R (2018). EPID-07. RELATIONSHIP BETWEEN COGNITION, SPEED OF PRESENTATION AND SEMANTIC VERBAL FLUENCY TEST IN PATIENTS WITH NEW INTRA-CEREBRAL TUMORS. Neuro-Oncology, 20(suppl_6), vi81-vi81.
Koshiaris C, Van den Bruel A, Oke JL, Nicholson BD, Shephard E, Braddick M, Hamilton W (2018). Early detection of multiple myeloma in primary care using blood tests: a case-control study in primary care.
Br J Gen Pract,
68(674), e586-e593.
Abstract:
Early detection of multiple myeloma in primary care using blood tests: a case-control study in primary care.
BACKGROUND: Multiple myeloma is a haematological cancer characterised by numerous non-specific symptoms leading to diagnostic delay in a large proportion of patients. AIM: to identify which blood tests are useful in suggesting or excluding a diagnosis of myeloma. DESIGN AND SETTING: a matched case-control study set in UK primary care using routinely collected data from the Clinical Practice Research Datalink. METHOD: Symptom prevalence and blood tests were analysed up to 5 years before diagnosis in 2703 cases and 12 157 matched controls. Likelihood ratios (LR) were used to classify tests or their combinations as useful rule-in tests (LR+ = ≥5), or rule-out tests (LR- = ≤0.2). RESULTS: Raised plasma viscosity (PV) had an LR+ = 2.0, 95% confidence interval [CI] = 1.7 to 2.3; erythrocyte sedimentation rate (ESR) 1.9, 95% CI = 1.7 to 2.0; and C-reactive protein (CRP) 1.2, 95% CI = 1.1 to 1.4. A normal haemoglobin had an LR- = 0.42, 95% CI = 0.39 to 0.45; calcium LR- = 0.81, 95% CI = 0.78 to 0.83; and creatinine LR- = 0.80, 95% CI = 0.77 to 0.83. The test combination with the lowest LR- was all normal haemoglobin with calcium and PV, which had an LR- = 0.06, 95% CI = 0.02 to 0.18, though the LR- for normal haemoglobin and PV together was 0.12 (95% CI = 0.07 to 0.23). CONCLUSION: Plasma viscosity and ESR are better for both ruling in and ruling out the disease compared with C-reactive protein. A combination of a normal ESR or PV and normal haemoglobin is a simple rule-out approach for patients currently being tested in primary care.
Abstract.
Author URL.
Wong MCS, Hamilton W, Whiteman DC, Jiang JY, Qiao Y, Fung FDH, Wang HHX, Chiu PWY, Ng EKW, Wu JCY, et al (2018). Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries.
Sci Rep,
8(1).
Abstract:
Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries.
Oesophageal cancers (adenocarcinomas [AC] and squamous cell carcinomas [SCC]) are characterized by high incidence/mortality in many countries. We aimed to delineate its global incidence and mortality, and studied whether socioeconomic development and its incidence rate were correlated. The age-standardized rates (ASRs) of incidence and mortality of this medical condition in 2012 for 184 nations from the GLOBOCAN database; national databases capturing incidence rates, and the WHO mortality database were examined. Their correlations with two indicators of socioeconomic development were evaluated. Joinpoint regression analysis was used to generate trends. The ratio between the ASR of AC and SCC was strongly correlated with HDI (r = 0.535 [men]; r = 0.661 [women]) and GDP (r = 0.594 [men]; r = 0.550 [women], both p
Abstract.
Author URL.
Moore SF, Hamilton W, Llewellyn DJ (2018). Harnessing the power of intelligent machines to enhance primary care.
Br J Gen Pract,
68(666), 6-7.
Author URL.
Gray E, Butler HJ, Board R, Brennan PM, Chalmers AJ, Dawson T, Goodden J, Hamilton W, Hegarty MG, James A, et al (2018). Health economic evaluation of a serum-based blood test for brain tumour diagnosis: exploration of two clinical scenarios.
BMJ Open,
8(5).
Abstract:
Health economic evaluation of a serum-based blood test for brain tumour diagnosis: exploration of two clinical scenarios.
OBJECTIVES: to determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway. DESIGN: a model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion. SETTING: Explored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA. PARTICIPANTS: Calculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum. MAIN OUTCOME MEASURES: the primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost-effectiveness analysis. RESULTS: Results indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost-effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of £20 000-£30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately £40). CONCLUSION: Use of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway.
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Author URL.
Prout HC, Barham A, Bongard E, Tudor-Edwards R, Griffiths G, Hamilton W, Harrop E, Hood K, Hurt CN, Nelson R, et al (2018). Patient understanding and acceptability of an early lung cancer diagnosis trial: a qualitative study.
Trials,
19(1).
Abstract:
Patient understanding and acceptability of an early lung cancer diagnosis trial: a qualitative study.
BACKGROUND: the ELCID (Early Lung Cancer Investigation and Diagnosis) trial was a feasibility randomised controlled trial examining the effect on lung cancer diagnosis of lowering the threshold for referral for urgent chest x-ray for smokers and recent ex-smokers, aged over 60 years with new chest symptoms. The qualitative component aimed to explore the feasibility of individually randomising patients to an urgent chest x-ray or not and to investigate any barriers to patient recruitment and participation. We integrated this within the feasibility trial to inform the design of any future definitive trial, particularly in view of the lack of research exploring symptomatic patients' experiences of participating in diagnostic trials for possible/suspected lung cancer. Although previous studies contributed valuable information concerning screening for lung cancer and patient participation in trials, this paper is the first to explore issues relating to this specific patient group. METHODS: Qualitative interviews were conducted with 21 patients, comprising 9 who had been randomised to receive an immediate chest x-ray, 10 who were randomised to receive the standard treatment according to the National Institute for Health and Care Excellence guidelines, and 2 who chose not to participate in the trial. Interviews were analysed using a framework approach. RESULTS: the findings of this analysis showed that altruism, personal benefit and the reassurance of not having lung cancer were important factors in patient participation. However, patients largely believed that being in the intervention arm was more beneficial, highlighting a lack of understanding of clinical equipoise. Disincentives to participation in the trial included the stigmatisation of patients who smoked (given the inclusion criteria). Although the majority of patients reported that they were happy with the trial design, there was evidence of poor understanding. Last, for several patients, placing trust in health professionals was preferred to understanding the trial processes. CONCLUSIONS: the integration of a qualitative study focusing on participant experience as a secondary outcome of a feasibility trial enabled exploration of patient response to participation and recruitment. The study demonstrated that although it is feasible to recruit patients to the ELCID trial, more work needs to be done to ensure an understanding of study principles and also of smoking stigmatisation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01344005. Registered on 27 April 2011.
Abstract.
Author URL.
Merriel SWD, Funston G, Hamilton W (2018). Prostate Cancer in Primary Care.
Adv Ther,
35(9), 1285-1294.
Abstract:
Prostate Cancer in Primary Care.
Prostate cancer is a common malignancy seen worldwide. The incidence has risen in recent decades, mainly fuelled by more widespread use of prostate-specific antigen (PSA) testing, although prostate cancer mortality rates have remained relatively static over that time period. A man's risk of prostate cancer is affected by his age and family history of the disease. Men with prostate cancer generally present symptomatically in primary care settings, although some diagnoses are made in asymptomatic men undergoing opportunistic PSA screening. Symptoms traditionally thought to correlate with prostate cancer include lower urinary tract symptoms (LUTS), such as nocturia and poor urinary stream, erectile dysfunction and visible haematuria. However, there is significant crossover in symptoms between prostate cancer and benign conditions affecting the prostate such as benign prostatic hypertrophy (BPH) and prostatitis, making it very challenging to distinguish between them on the basis of symptoms. The evidence for the performance of PSA in asymptomatic and symptomatic men for the diagnosis of prostate cancer is equivocal. PSA is subject to false positive and false negative results, affecting its clinical utility as a standalone test. Clinicians need to counsel men about the risks and benefits of PSA testing to inform their decision-making. Digital rectal examination (DRE) by primary care clinicians has some evidence to show discrimination between benign and malignant conditions affecting the prostate. Patients referred to secondary care for diagnostic testing for prostate cancer will typically undergo a transrectal or transperineal biopsy, where a number of samples are taken and sent for histological examination. These biopsies are invasive procedures with side effects and a risk of infection and sepsis, and alternative tests such as multiparametric magnetic resonance imaging (mpMRI) are currently being trialled for their accuracy and safety in diagnosing clinically significant prostate cancer.
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Author URL.
Zirk-Sadowski J, Masoli JA, Delgado J, Hamilton W, Strain WD, Henley W, Melzer D, Ble A (2018). Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults.
J Am Geriatr Soc,
66(7), 1332-1338.
Abstract:
Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults.
OBJECTIVES: to estimate associations between long-term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care. DESIGN: Longitudinal analyses of electronic medical records. SETTING: England PARTICIPANTS: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age- and sex-matched controls (N=75,050). MEASUREMENTS: Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures. RESULTS: During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR-adjusted hazard ratio=1.82, 95% confidence interval=1.27-2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score- and inverse probability-weighted models. CONCLUSION: in a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short-term harms of PPIs should not divert attention from potential long-term effects of PPI prescriptions on older adults.
Abstract.
Author URL.
Funston G, O’Flynn H, Ryan NAJ, Hamilton W, Crosbie EJ (2018). Recognizing Gynecological Cancer in Primary Care: Risk Factors, Red Flags, and Referrals.
Advances in Therapy,
35(4), 577-589.
Abstract:
Recognizing Gynecological Cancer in Primary Care: Risk Factors, Red Flags, and Referrals
Early diagnosis of symptomatic gynecological cancer is likely to improve patient outcomes, including survival. The primary care practitioner has a key role to play in this—they must recognize the symptoms and signs of gynecological cancer and make prompt evidence-based decisions regarding further investigation and referral. However, this is often difficult as many of the symptoms of gynecological cancers are nonspecific and are more likely to be caused by benign rather than malignant disease. As primary care is generally the first point of patient contact, those working in this setting usually encounter cancer patients at an earlier, and possibly less symptomatic, stage than practitioners in secondary care. Despite these challenges, research has improved our understanding of the symptoms patients present to primary care with, and a range of tests and referral pathways now exist in the UK and other countries to aid early diagnosis. Primary care practitioners can also play a key role in gynecological cancer prevention. A significant proportion of gynecological cancer is preventable either through lifestyle changes such as weight loss, or, for cervical cancer, vaccination and/or engagement with screening programs. Primary care provides an excellent opportunity to discuss cancer risk with patients and to promote risk reduction strategies and lifestyle change. In this article, the first in a series discussing cancer detection in primary care, we concentrate on gynecological cancer and focus on the three most common forms that a primary care practitioner is likely to encounter: ovarian, endometrial, and cervical cancer. We outline key risk factors, briefly discuss prevention and screening strategies, and offer practical guidance on the recognition of symptoms and signs and the investigation and referral of women with suspected cancer. While this article is written from a UK primary care perspective, much of what is discussed will be of relevance to those working in other healthcare systems.
Abstract.
Shephard EA, Hamilton WT (2018). Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records.
Br J Gen Pract,
68(673), e559-e565.
Abstract:
Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records.
BACKGROUND: Testicular cancer incidence has risen over the last two decades and is expected to continue to rise. There are no primary care studies on the clinical features of testicular cancer, with recent National Institute for Health and Care Excellence (NICE) guidance based solely upon clinical consensus. AIM: to identify clinical features of testicular cancer and to quantify their risk in primary care patients, with the aim of improving the selection of patients for investigation. DESIGN AND SETTING: a matched case-control study in males aged ≥17 years, using Clinical Practice Research Datalink records. METHOD: Putative clinical features of testicular cancer were identified and analysed using conditional logistic regression. Positive predictive values (PPVs) were calculated for those aged
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Author URL.
Koo MM, Hamilton W, Walter FM, Rubin GP, Lyratzopoulos G (2018). Symptom Signatures and Diagnostic Timeliness in Cancer Patients: a Review of Current Evidence.
Neoplasia (United States),
20(2), 165-174.
Abstract:
Symptom Signatures and Diagnostic Timeliness in Cancer Patients: a Review of Current Evidence
Early diagnosis is an important aspect of contemporary cancer prevention and control strategies, as the majority of patients are diagnosed following symptomatic presentation. The nature of presenting symptoms can critically influence the length of the diagnostic intervals from symptom onset to presentation (the patient interval), and from first presentation to specialist referral (the primary care interval). Understanding which symptoms are associated with longer diagnostic intervals to help the targeting of early diagnosis initiatives is an area of emerging research. In this Review, we consider the methodological challenges in studying the presenting symptoms and intervals to diagnosis of cancer patients, and summarize current evidence on presenting symptoms associated with a range of common and rarer cancer sites. We propose a taxonomy of cancer sites considering their symptom signature and the predictive value of common presenting symptoms. Finally, we consider evidence on associations between symptomatic presentations and intervals to diagnosis before discussing implications for the design, implementation, and evaluation of public health or health system interventions to achieve the earlier detection of cancer.
Abstract.
Ozawa M, Brennan PM, Zienius K, Kurian KM, Hollingworth W, Weller D, Hamilton W, Grant R, Ben-Shlomo Y (2018). Symptoms in primary care with time to diagnosis of brain tumours.
Fam Pract,
35(5), 551-558.
Abstract:
Symptoms in primary care with time to diagnosis of brain tumours.
BACKGROUND: Brain tumours often present with varied, non-specific features with other diagnoses usually being more likely. OBJECTIVE: to examine how different symptoms and patient demographics predict variations in time to brain tumour diagnosis. METHODS: We conducted a secondary analysis of brain tumour cases from National Audit of Cancer Diagnosis in Primary Care. We grouped neurological symptoms into six domains (headache, behavioural/cognitive change, focal neurology, 'fits, faints or falls', non-specific neurological, and other/non-specific) and calculated times for patient presentation, GP referral, specialist consultation and total pathway interval. We calculated odds ratios (ORs) for symptom domains comparing the slowest to other quartiles. RESULTS: Data were available for 226 cases. Median (interquartile range) time for the total pathway interval was 24 days (7-65 days). The most common presentation was focal neurology (33.2%) followed by 'fits, faints or falls' and headache (both 20.8%). Headache only (OR = 4.11, 95% CI = 1.10, 15.5) and memory complaints (OR = 4.82, 95% CI = 1.15, 20.1) were associated with slower total pathway compared to 'fits, faints or falls'. GPs were more likely to consider that there had been avoidable delays in referring patients with headache only (OR = 4.17, 95% CI = 1.14, 15.3). CONCLUSION: Patients presenting to primary care with headache only or with memory complaints remain problematic with potentially avoidable delays in referral leading to a longer patient pathway. This may or may not impact on the efficacy and morbidity of therapies. Additional aids are required to help doctors differentiate when to refer headaches and memory complaints urgently for a specialist opinion.
Abstract.
Author URL.
Coxon D, Campbell C, Walter FM, Scott SE, Neal RD, Vedsted P, Emery J, Rubin G, Hamilton W, Weller D, et al (2018). The Aarhus statement on cancer diagnostic research: turning recommendations into new survey instruments.
BMC Health Serv Res,
18(1).
Abstract:
The Aarhus statement on cancer diagnostic research: turning recommendations into new survey instruments.
BACKGROUND: over recent years there has been a growth in cancer early diagnosis (ED) research, which requires valid measurement of routes to diagnosis and diagnostic intervals. The Aarhus Statement, published in 2012, provided methodological guidance to generate valid data on these key pre-diagnostic measures. However, there is still a wide variety of measuring instruments of varying quality in published research. In this paper we test comprehension of self-completion ED questionnaire items, based on Aarhus Statement guidance, and seek input from patients, GPs and ED researchers to refine these questions. METHODS: We used personal interviews and consensus approaches to generate draft ED questionnaire items, then a combination of focus groups and telephone interviews to test comprehension and obtain feedback. A framework analysis approach was used, to identify themes and potential refinements to the items. RESULTS: We found that many of the questionnaire items still prompted uncertainty in respondents, in both routes to diagnosis and diagnostic interval measurement. Uncertainty was greatest in the context of multiple or vague symptoms, and potentially ambiguous time-points (such as 'date of referral'). CONCLUSIONS: There are limits on the validity of self-completion questionnaire responses, and refinements to the wording of questions may not be able to completely overcome these limitations. It's important that ED researchers use the best identifiable measuring instruments, but accommodate inevitable uncertainty in the interpretation of their results. Every effort should be made to increase clarity of questions and responses, and use of two or more data sources should be considered.
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Author URL.
Chiva Giurca B, Hamilton W, Martins T (2018). The impact of health literacy on diagnosis and outcomes of symptomatic cancer by ethnicity: a systematic review protocol.
Syst Rev,
7(1).
Abstract:
The impact of health literacy on diagnosis and outcomes of symptomatic cancer by ethnicity: a systematic review protocol.
BACKGROUND: Ethnic minorities in multi-ethnic societies like the UK and USA have poorer outcomes for some cancer types when compared with the majority. The causes of ethnic inequalities in cancer outcomes are complex and not fully understood. In particular, the potential role of health literacy on symptomatic presentation and diagnostic interval (the period between first consultation within primary care and definitive diagnosis of cancer) by ethnicity is unknown. Given the increasing need for shared decision-making and patient involvement in the diagnostic process, understanding the potential impact of the differences in health literacy may help redress ethnic inequality in cancer outcomes. The present study aims to critically examine the evidence in this area. METHODS: Seven electronic databases will be searched using keywords and controlled vocabulary related to ethnicity, health literacy, cancer diagnosis and cancer outcomes. Citations and bibliography searches of included studies will be performed to identify relevant studies that have cited eligible articles. Authors of included studies will be contacted to identify unpublished studies. Eligible studies will be restricted to primary cancers. Study quality will be evaluated in using the Critical Appraisal Skills Programme (CASP) checklists. A descriptive summary of selected studies will be presented, and the synthesis will follow a narrative framework. DISCUSSION: This systematic review will summarise the evidence regarding ethnic inequality in health literacy and how this impacts on diagnosis and outcomes of cancer. The review will identify possible areas for future research, and inform clinical practice and interventions to reduce ethnic inequalities in cancer diagnosis and outcomes.
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Author URL.
Koo MM, von Wagner C, Abel GA, McPhail S, Hamilton W, Rubin GP, Lyratzopoulos G (2018). The nature and frequency of abdominal symptoms in cancer patients and their associations with time to help-seeking: evidence from a national audit of cancer diagnosis.
J Public Health (Oxf),
40(3), e388-e395.
Abstract:
The nature and frequency of abdominal symptoms in cancer patients and their associations with time to help-seeking: evidence from a national audit of cancer diagnosis.
BACKGROUND: Raising awareness of possible cancer symptoms is important for timely help-seeking; recent campaigns have focused on symptom groups (such as abdominal symptoms) rather than individual alarm symptoms associated with particular cancer sites. The evidence base supporting such initiatives is still emerging however; understanding the frequency and nature of presenting abdominal symptoms among cancer patients could inform the design and evaluation of public health awareness campaigns. METHODS: We examined eight presenting abdominal symptoms (abdominal pain, change in bowel habit, bloating/distension, dyspepsia, rectal bleeding, dysphagia, reflux and nausea/vomiting) among 15 956 patients subsequently diagnosed with cancer in England. We investigated the cancer site case-mix and variation in the patient interval (symptom-onset-to-presentation) by abdominal symptom. RESULTS: Almost a quarter (23%) of cancer patients presented with abdominal symptoms before being diagnosed with one of 27 common and rarer cancers. The patient interval varied substantially by abdominal symptom: median (IQR) intervals ranged from 7 (0-28) days for abdominal pain to 30 (4-73) days for dysphagia. This variation persisted after adjusting for age, sex and ethnicity (P < 0.001). CONCLUSIONS: Abdominal symptoms are common at presentation among cancer patients, while time to presentation varies by symptom. The need for awareness campaigns may be greater for symptoms associated with longer intervals to help-seeking.
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Author URL.
Penfold C, Joannides AJ, Sage W, Brodbelt A, Jenkinson MD, Price S, Watts C, Bell J, Johnson M, Hamilton W, et al (2018). Understanding missed opportunities for more timely diagnosis of brain cancer – what can we learn from the BRACED qualitative interview study with adult glioma patients?. Neuro-Oncology, 20(suppl_1), i2-i2.
Hamilton W (2018). Using CPRD data for public health research. British Journal of General Practice, 68(672).
Zhou Y, Mendonca S, Abel G, Hamilton W, Walter F, Johnson S, Shelton J, Elliss-Brookes L, McPhail S, Lyratzopoulos G, et al (2018). Variation in 'Fast-Track' Referrals for Suspected Cancer by Patient Characteristic and Cancer Diagnosis: Evidence from 670,000 Patients with Cancers of 35 Different Sites. Journal of Global Oncology, 4(Supplement 2), 39s-39s.
Zhou Y, Mendonca SC, Abel GA, Hamilton W, Walter FM, Johnson S, Shelton J, Elliss-Brookes L, McPhail S, Lyratzopoulos G, et al (2018). Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites.
Br J Cancer,
118(1), 24-31.
Abstract:
Variation in 'fast-track' referrals for suspected cancer by patient characteristic and cancer diagnosis: evidence from 670 000 patients with cancers of 35 different sites.
BACKGROUND: in England, 'fast-track' (also known as 'two-week wait') general practitioner referrals for suspected cancer in symptomatic patients are used to shorten diagnostic intervals and are supported by clinical guidelines. However, the use of the fast-track pathway may vary for different patient groups. METHODS: We examined data from 669 220 patients with 35 cancers diagnosed in 2006-2010 following either fast-track or 'routine' primary-to-secondary care referrals using 'Routes to Diagnosis' data. We estimated the proportion of fast-track referrals by sociodemographic characteristic and cancer site and used logistic regression to estimate respective crude and adjusted odds ratios. We additionally explored whether sociodemographic associations varied by cancer. RESULTS: There were large variations in the odds of fast-track referral by cancer (P
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Author URL.
Nicholson BD, Aveyard P, Hobbs FDR, Smith M, Fuller A, Perera R, Hamilton W, Stevens S, Bankhead CR (2018). Weight loss as a predictor of cancer and serious disease in primary care: an ISAC-approved CPRD protocol for a retrospective cohort study using routinely collected primary care data from the UK.
Diagn Progn Res,
2Abstract:
Weight loss as a predictor of cancer and serious disease in primary care: an ISAC-approved CPRD protocol for a retrospective cohort study using routinely collected primary care data from the UK.
BACKGROUND: Unexpected weight loss is a symptom of serious disease in primary care, for example between 1 in 200 and 1 in 30 patients with unexpected weight loss go on to develop cancer. However, it remains unclear how and when general practitioners (GPs) should investigate unexpected weight loss. Without clarification, GPs may wait too long before referring (choosing to watch and wait and potentially missing a diagnosis) or not long enough (overburdening hospital services and exposing patients to the risks of investigation). The overall aim of this study is to provide the evidence necessary to allow GPs to more effectively manage patients with unexpected weight loss. METHODS: a retrospective cohort analysis of UK Clinical Practice Research Datalink (CPRD) data to: (1) describe how often in UK primary care the symptom of reported weight loss is coded, when weight is measured, and how GPs respond to a patient attending with unexpected weight loss; (2) identify the predictive value of recorded weight loss for cancer and serious disease in primary care, using cumulative incidence plots to compare outcomes between subgroups and Cox regression to explore and adjust for covariates. Preliminary work in CPRD estimates that weight loss as a symptom is recorded for approximately 148,000 eligible patients > 18 years and is distributed evenly across decades of age, providing adequate statistical power and precision in relation to cancer overall and common cancers individually. Further stratification by cancer stage will be attempted but may not be possible as not all practices within CPRD are eligible for cancer registry linkage, and staging information is often incomplete. The feasibility of using multiple imputation to address missing covariate values will be explored. DISCUSSION: This will be the largest reported retrospective cohort of primary care patients with weight measurements and unexpected weight loss codes used to understand the association between weight measurement, unexpected weight loss, and serious disease including cancer. Our findings will directly inform international guidelines for the management of unexpected weight loss in primary care populations.
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Author URL.
Nicholson BD, Hamilton W, O'Sullivan J, Aveyard P, Hobbs FR (2018). Weight loss as a predictor of cancer in primary care: a systematic review and meta-analysis.
Br J Gen Pract,
68(670), e311-e322.
Abstract:
Weight loss as a predictor of cancer in primary care: a systematic review and meta-analysis.
BACKGROUND: Weight loss is a non-specific cancer symptom for which there are no clinical guidelines about investigation in primary care. AIM: to summarise the available evidence on weight loss as a clinical feature of cancer in patients presenting to primary care. DESIGN AND SETTING: a diagnostic test accuracy review and meta-analysis. METHOD: Studies reporting 2 × 2 diagnostic accuracy data for weight loss (index test) in adults presenting to primary care and a subsequent diagnosis of cancer (reference standard) were included. QUADAS-2 was used to assess study quality. Sensitivity, specificity, positive likelihood ratios, and positive predictive values were calculated, and a bivariate meta-analysis performed. RESULTS: a total of 25 studies were included, with 23 (92%) using primary care records. of these, 20 (80%) defined weight loss as a physician's coding of the symptom; the remainder collected data directly. One defined unexplained weight loss using objective measurements. Positive associations between weight loss and cancer were found for 10 cancer sites: prostate, colorectal, lung, gastro-oesophageal, pancreatic, non-Hodgkin's lymphoma, ovarian, myeloma, renal tract, and biliary tree. Sensitivity ranged from 2% to 47%, and specificity from 92% to 99%, across cancer sites. The positive predictive value for cancer in male and female patients with weight loss for all age groups ≥60 years exceeded the 3% risk threshold that current UK guidance proposes for further investigation. CONCLUSION: a primary care clinician's decision to code for weight loss is highly predictive of cancer. For such patients, urgent referral pathways are justified to investigate for cancer across multiple sites.
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Author URL.
Hope SV, Taylor PJ, Shields BM, Hattersley AT, Hamilton W (2017). Are we missing hypoglycaemia?. Elderly patients with insulin-treated diabetes present to. primary care frequently with non-specific symptoms. associated with hypoglycaemia. Primary Care Diabetes
Bailey SE, Ankus EJ, Hamilton W (2017). Authors' response.
Br J Gen Pract,
67(662), 396-397.
Author URL.
Kidney E, Greenfield S, Berkman L, Dowswell G, Hamilton W, Wood S, Marshall T (2017). Cancer suspicion in general practice, urgent referral, and time to diagnosis: a population-based GP survey nested within a feasibility study using information technology to flag-up patients with symptoms of colorectal cancer.
BJGP Open,
1(3).
Abstract:
Cancer suspicion in general practice, urgent referral, and time to diagnosis: a population-based GP survey nested within a feasibility study using information technology to flag-up patients with symptoms of colorectal cancer.
BACKGROUND: Patients with symptoms of possible colorectal cancer are not always referred for investigation. AIM: to ascertain barriers and facilitators to GP referral of patients meeting the National Institute for Health and Care Excellence (NICE) guidelines for urgent referral for suspected colorectal cancer. DESIGN & SETTING: Qualitative study in the context of a feasibility study using information technology in GP practices to flag-up patients meeting urgent referral criteria for colorectal cancer. METHOD: Semi-structured interview with 18 GPs and 12 practice managers, focusing on early detection of colorectal cancer, issues in the use of information technology to identify patients and GP referral of these patients for further investigation were audiotaped, transcribed verbatim, and analysed according to emergent themes. RESULTS: There were two main themes: wide variation in willingness to refer and uncertainty about whether to refer; and barriers to referral. Three key messages emerged: there was a desire to avoid over-referral, lack of knowledge of guidelines, and the use of individually-derived decision rules for further investigation or referral of symptoms. Some GPs were unaware that iron deficiency anaemia or persistent diarrhoea are urgent referral criteria. Alternatives to urgent referral included undertaking no investigations, trials of iron therapy, use of faecal occult blood tests (FOBt) and non-urgent referral. In minority ethnic groups (South Asians) anaemia was often accepted as normal.Concerns about over-referral were linked to financial pressures and perceived criticism by healthcare commissioners, and a reluctance to scare patients by discussing suspected cancer. CONCLUSION: GPs' lack of awareness of referral guidelines and concerns about over-referral are barriers to early diagnosis of colorectal cancer.
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Author URL.
Hopewell S, Keene DJ, Maia Schlüssel M, Dritsaki M, Dutton S, Carr A, Hamilton W, Hansen Z, Jaggi A, Littlewood C, et al (2017). Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial).
BMJ Open,
7(7).
Abstract:
Clinical and cost-effectiveness of progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: protocol for a 2x2 factorial randomised controlled trial (the GRASP trial).
INTRODUCTION: Shoulder pain is very common, with around 70% of cases due to disorders of the rotator cuff. Despite widespread provision of physiotherapy, there is uncertainty about which type of exercise and delivery mechanisms are associated with best outcomes. There is also uncertainty around the long-term benefits and harms of corticosteroid injection therapy, which is often used in addition to physiotherapy. The Getting it Right: Addressing Shoulder Pain trial will assess the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. METHODS AND ANALYSIS: We are conducting a large multicentre randomised controlled trial (2×2 factorial design). We will recruit adults ≥18 years with a new episode of shoulder pain attributable to a rotator cuff disorder as per British Elbow and Shoulder Society guidelines, not currently receiving physiotherapy or being considered for surgery, from at least eight UK National Health Service primary care-based musculoskeletal and related physiotherapy services. Participants (n=704) will be randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (≤6 physiotherapy sessions); (2) best practice advice (one physiotherapy session); (3) corticosteroid injection then progressive exercise (≤6 sessions) or (4) corticosteroid injection then best practice advice (one session). The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score at 12 months. Secondary outcomes are: pain and function SPADI subdomains; health-related quality of life (Five-Level version of the EuroQol EQ-5D-5L); sleep disturbance; return to activity; global impression of change; health resource use; out-of-pocket expenses; work disability. A parallel within-trial economic evaluation will be conducted. The primary analysis will be intention to treat. ETHICS AND DISSEMINATION: Research Ethics Committee approval (REC: 16/SC/0508) has been obtained. Results of the main trial and secondary outcomes will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN16539266; EudraCT number: 2016-002991-28.
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Stapley SA, Hamilton WT, Rubin GP, Alsina D, Rutter M, Shephard EA (2017). Clinical features of bowel disease in primary care: a large case-control study. British Journal of General Practice, 67, e336-e344.
Bailey SE, Ukoumunne OC, Shephard EA, Hamilton W (2017). Clinical relevance of thrombocytosis in primary care: a prospective cohort study of cancer incidence using English electronic medical records and cancer registry data.
Br J Gen Pract,
67(659), e405-e413.
Abstract:
Clinical relevance of thrombocytosis in primary care: a prospective cohort study of cancer incidence using English electronic medical records and cancer registry data.
BACKGROUND: Thrombocytosis (raised platelet count) is an emerging risk marker of cancer, but the association has not been fully explored in a primary care context. AIM: to examine the incidence of cancer in a cohort of patients with thrombocytosis, to determine how clinically useful this risk marker could be in predicting an underlying malignancy. DESIGN AND SETTING: a prospective cohort study using Clinical Practice Research Datalink data from 2000 to 2013. METHOD: the 1-year incidence of cancer was compared between two cohorts: 40 000 patients aged ≥40 years with a platelet count of >400 × 109/L (thrombocytosis) and 10 000 matched patients with a normal platelet count. Sub-analyses examined the risk with change in platelet count, sex, age, and different cancer sites. RESULTS: a total of 1098 out of 9435 males with thrombocytosis were diagnosed with cancer (11.6%; 95% confidence interval [CI] = 11.0 to 12.3), compared with 106 of 2599 males without thrombocytosis (4.1%; 95% CI = 3.4 to 4.9). A total of 1355 out of 21 826 females with thrombocytosis developed cancer (6.2%; 95% CI = 5.9 to 6.5), compared with 119 of 5370 females without (2.2%; 95% CI = 1.8 to 2.6). The risk of cancer increased to 18.1% (95% CI = 15.9 to 20.5) for males and 10.1% (95% CI = 9.0 to 11.3) for females, when a second raised platelet count was recorded within 6 months. Lung and colorectal cancer were more commonly diagnosed with thrombocytosis. One-third of patients with thrombocytosis and lung or colorectal cancer had no other symptoms indicative of malignancy. CONCLUSION: Thrombocytosis is a risk marker of cancer in adults; 11.6% and 6.2% cancer incidence in males and females, respectively, is worthy of further investigation for underlying malignancy. These figures well exceed the National Institute for Health and Care Excellence-mandated risk threshold of 3% risk to warrant referral for suspected cancer.
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Author URL.
Mounce LTA, Price S, Valderas JM, Hamilton W (2017). Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using electronic primary care records.
Br J Cancer,
116(12), 1536-1543.
Abstract:
Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using electronic primary care records.
BACKGROUND: Pre-existing non-cancer conditions may complicate and delay colorectal cancer diagnosis. METHOD: Incident cases (aged ⩾40 years, 2007-2009) with colorectal cancer were identified in the Clinical Practice Research Datalink, UK. Diagnostic interval was defined as time from first symptomatic presentation of colorectal cancer to diagnosis. Comorbid conditions were classified as 'competing demands' (unrelated to colorectal cancer) or 'alternative explanations' (sharing symptoms with colorectal cancer). The association between diagnostic interval (log-transformed) and age, gender, consultation rate and number of comorbid conditions was investigated using linear regressions, reported using geometric means. RESULTS: Out of the 4512 patients included, 72.9% had ⩾1 competing demand and 31.3% had ⩾1 alternative explanation. In the regression model, the numbers of both types of comorbid conditions were independently associated with longer diagnostic interval: a single competing demand delayed diagnosis by 10 days, and four or more by 32 days; and a single alternative explanation by 9 days. For individual conditions, the longest delay was observed for inflammatory bowel disease (26 days; 95% CI 14-39). CONCLUSIONS: the burden and nature of comorbidity is associated with delayed diagnosis in colorectal cancer, particularly in patients aged ⩾80 years. Effective clinical strategies are needed for shortening diagnostic interval in patients with comorbidity.
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Author URL.
Zhou Y, Abel GA, Hamilton W, Pritchard-Jones K, Gross CP, Walter FM, Renzi C, Johnson S, McPhail S, Elliss-Brookes L, et al (2017). Diagnosis of cancer as an emergency: a critical review of current evidence.
Nat Rev Clin Oncol,
14(1), 45-56.
Abstract:
Diagnosis of cancer as an emergency: a critical review of current evidence.
Many patients with cancer are diagnosed through an emergency presentation, which is associated with inferior clinical and patient-reported outcomes compared with those of patients who are diagnosed electively or through screening. Reducing the proportion of patients with cancer who are diagnosed as emergencies is, therefore, desirable; however, the optimal means of achieving this aim are uncertain owing to the involvement of different tumour, patient and health-care factors, often in combination. Most relevant evidence relates to patients with colorectal or lung cancer in a few economically developed countries, and defines emergency presentations contextually (that is, whether patients presented to emergency health-care services and/or received emergency treatment shortly before their diagnosis) as opposed to clinically (whether patients presented with life-threatening manifestations of their cancer). Consistent inequalities in the risk of emergency presentations by patient characteristics and cancer type have been described, but limited evidence is available on whether, and how, such presentations can be prevented. Evidence on patients' symptoms and health-care use before presentation as an emergency is sparse. In this Review, we describe the extent, causes and implications of a diagnosis of cancer following an emergency presentation, and provide recommendations for public health and health-care interventions, and research efforts aimed at addressing this under-researched aspect of cancer diagnosis.
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Tørring ML, Murchie P, Hamilton W, Vedsted P, Esteva M, Lautrup M, Winget M, Rubin G (2017). Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countries.
Br J Cancer,
117(6), 888-897.
Abstract:
Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countries.
BACKGROUND: the benefits from expedited diagnosis of symptomatic cancer are uncertain. We aimed to analyse the relationship between stage of colorectal cancer (CRC) and the primary and specialist care components of the diagnostic interval. METHODS: We identified seven independent data sets from population-based studies in Scotland, England, Canada, Denmark and Spain during 1997-2010 with a total of 11 720 newly diagnosed CRC patients, who had initially presented with symptoms to a primary care physician. Data were extracted from patient records, registries, audits and questionnaires, respectively. Data sets were required to hold information on dates in the diagnostic interval (defined as the time from the first presentation of symptoms in primary care until the date of diagnosis), symptoms at first presentation in primary care, route of referral, gender, age and histologically confirmed stage. We carried out reanalysis of all individual data sets and, using the same method, analysed a pooled individual patient data set. RESULTS: the association between intervals and stage was similar in the individual and combined data set. There was a statistically significant convex (∩-shaped) association between primary care interval and diagnosis of advanced (i.e. distant or regional) rather than localised CRC (P=0.004), with odds beginning to increase from the first day on and peaking at 90 days. For specialist care, we saw an opposite and statistically significant concave (∪-shaped) association, with a trough at 60 days, between the interval and diagnosis of advanced CRC (P
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Author URL.
Watson J, Nicholson BD, Hamilton W, Price S (2017). Identifying clinical features in primary care electronic health record studies: methods for codelist development.
BMJ Open,
7(11).
Abstract:
Identifying clinical features in primary care electronic health record studies: methods for codelist development.
OBJECTIVE: Analysis of routinely collected electronic health record (EHR) data from primary care is reliant on the creation of codelists to define clinical features of interest. To improve scientific rigour, transparency and replicability, we describe and demonstrate a standardised reproducible methodology for clinical codelist development. DESIGN: We describe a three-stage process for developing clinical codelists. First, the clear definition a priori of the clinical feature of interest using reliable clinical resources. Second, development of a list of potential codes using statistical software to comprehensively search all available codes. Third, a modified Delphi process to reach consensus between primary care practitioners on the most relevant codes, including the generation of an 'uncertainty' variable to allow sensitivity analysis. SETTING: These methods are illustrated by developing a codelist for shortness of breath in a primary care EHR sample, including modifiable syntax for commonly used statistical software. PARTICIPANTS: the codelist was used to estimate the frequency of shortness of breath in a cohort of 28 216 patients aged over 18 years who received an incident diagnosis of lung cancer between 1 January 2000 and 30 November 2016 in the Clinical Practice Research Datalink (CPRD). RESULTS: of 78 candidate codes, 29 were excluded as inappropriate. Complete agreement was reached for 44 (90%) of the remaining codes, with partial disagreement over 5 (10%). 13 091 episodes of shortness of breath were identified in the cohort of 28 216 patients. Sensitivity analysis demonstrates that codes with the greatest uncertainty tend to be rarely used in clinical practice. CONCLUSIONS: Although initially time consuming, using a rigorous and reproducible method for codelist generation 'future-proofs' findings and an auditable, modifiable syntax for codelist generation enables sharing and replication of EHR studies. Published codelists should be badged by quality and report the methods of codelist generation including: definitions and justifications associated with each codelist; the syntax or search method; the number of candidate codes identified; and the categorisation of codes after Delphi review.
Abstract.
Author URL.
Hamilton W, Round J (2017). Identifying frailty in primary care.
BMJ,
358 Author URL.
Neal RD, Barham A, Bongard E, Edwards RT, Fitzgibbon J, Griffiths G, Hamilton W, Hood K, Nelson A, Parker D, et al (2017). Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial.
Br J Cancer,
116(3), 293-302.
Abstract:
Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial.
BACKGROUND: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. METHODS: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. RESULTS: the trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. CONCLUSIONS: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care.
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Author URL.
Atkin W, Wooldrage K, Shah U, Skinner K, Brown JP, Hamilton W, Kralj-Hans I, Thompson MR, Flashman KG, Halligan S, et al (2017). Is whole-colon investigation by colonoscopy, computerised tomography colonography or barium enema necessary for all patients with colorectal cancer symptoms, and for which patients would flexible sigmoidoscopy suffice? a retrospective cohort study.
HEALTH TECHNOLOGY ASSESSMENT,
21(66), 1-+.
Author URL.
Schmidt-Hansen M, Berendse S, Hamilton W, Baldwin DR (2017). Lung cancer in symptomatic patients presenting in primary care: a systematic review of risk prediction tools.
Br J Gen Pract,
67(659), e396-e404.
Abstract:
Lung cancer in symptomatic patients presenting in primary care: a systematic review of risk prediction tools.
BACKGROUND: Lung cancer is the leading cause of cancer deaths. Around 70% of patients first presenting to specialist care have advanced disease, at which point current treatments have little effect on survival. The issue for primary care is how to recognise patients earlier and investigate appropriately. This requires an assessment of the risk of lung cancer. AIM: the aim of this study was to systematically review the existing risk prediction tools for patients presenting in primary care with symptoms that may indicate lung cancer DESIGN AND SETTING: Systematic review of primary care data. METHOD: Medline, PreMedline, Embase, the Cochrane Library, Web of Science, and ISI Proceedings (1980 to March 2016) were searched. The final list of included studies was agreed between two of the authors, who also appraised and summarised them. RESULTS: Seven studies with between 1482 and 2 406 127 patients were included. The tools were all based on UK primary care data, but differed in complexity of development, number/type of variables examined/included, and outcome time frame. There were four multivariable tools with internal validation area under the curves between 0.88 and 0.92. The tools all had a number of limitations, and none have been externally validated, or had their clinical and cost impact examined. CONCLUSION: There is insufficient evidence for the recommendation of any one of the available risk prediction tools. However, some multivariable tools showed promising discrimination. What is needed to guide clinical practice is both external validation of the existing tools and a comparative study, so that the best tools can be incorporated into clinical decision tools used in primary care.
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Author URL.
Newlove-Delgado TV, Ford TJ, Ukoumunne OC, Hamilton W, Stein K (2017). Prescribing of medication for attention deficit hyperactivity disorder among young people in the Clinical Practice Research Datalink 2005–2013: analysis of time to cessation. European Child and Adolescent Psychiatry
Walker S, Hamilton W (2017). Risk of cervical cancer in symptomatic women aged ≥40 in primary care: a case-control study using electronic records.
Eur J Cancer Care (Engl),
26(3).
Abstract:
Risk of cervical cancer in symptomatic women aged ≥40 in primary care: a case-control study using electronic records.
There are approximately 3,000 new UK diagnoses of cervical cancer annually, with many women presenting symptomatically. We aimed to identify and quantify features of cervical cancer in primary care in a case-control study in the UK. Putative features of cervical cancer were identified, and odd ratios and positive predictive values (PPVs) were calculated. About 1,006 women aged ≥40 years diagnosed with cervical cancer and 4,992 age-, sex- and practice-matched controls were selected from the Clinical Practice Research Datalink. Median age at diagnosis was 61 years (interquartile range 51-75). Seven symptoms and two abnormal investigations were associated with cervical cancer: post-menopausal bleeding, odds ratio 43 (95% confidence interval 25, 75); vaginal discharge or vaginitis 8.8 (5.2, 15), intermenstrual bleeding 4.7 (1.6, 14); haematuria 4.6 (2.1, 10); irregular menstruation 3.8 (1.6, 9.0); urinary tract infection 1.9 (1.3, 2.8); abdominal pain 1.8 (1.4, 2.5); high white cell count 5.1 (2.9, 8.8) and low haemoglobin 2.6 (1.8, 3.8): all p
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Author URL.
Banks J, Wye L, Hall N, Rooney J, Walter FM, Hamilton W, Gjini A, Rubin G (2017). The researchers' role in knowledge translation: a realist evaluation of the development and implementation of diagnostic pathways for cancer in two United Kingdom localities.
Health Res Policy Syst,
15(1).
Abstract:
The researchers' role in knowledge translation: a realist evaluation of the development and implementation of diagnostic pathways for cancer in two United Kingdom localities.
BACKGROUND: in examining an initiative to develop and implement new cancer diagnostic pathways in two English localities, this paper evaluates 'what works' and examines the role of researchers in facilitating knowledge translation amongst teams of local clinicians and policy-makers. METHODS: Using realist evaluation with a mixed methods case study approach, we conducted documentary analysis of meeting minutes and pathway iterations to map pathway development. We interviewed 14 participants to identify the contexts, mechanisms and outcomes (CMOs) that led to successful pathway development and implementation. Interviews were analysed thematically and four CMO configurations were developed. RESULTS: One site produced three fully implemented pathways, while the other produced two that were partly implemented. In explaining the differences, we found that a respected, independent, well-connected leader modelling partnership working and who facilitates a local, stable group that agree about the legitimacy of the data and project (context) can empower local teams to become sufficiently autonomous (mechanism) to develop and implement research-based pathways (outcome). Although both teams designed relevant, research-based cancer pathways, in the site where the pathways were successfully implemented the research team merely assisted, while, in the other, the research team drove the initiative. CONCLUSION: Based on our study findings, local stakeholders can apply local and research knowledge to develop and implement research-based pathways. However, success will depend on how academics empower local teams to create autonomy. Crucially, after re-packaging and translating research for local circumstances, identifying fertile environments with the right elements for implementation and developing collaborative relationships with local leaders, academics must step back.
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Author URL.
Mills K, Birt L, Emery JD, Hall N, Banks J, Johnson M, Lancaster J, Hamilton W, Rubin GP, Walter FM, et al (2017). Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study.
BMJ Open,
7(9).
Abstract:
Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study.
OBJECTIVE: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer. DESIGN: Qualitative analysis of semistructured in-depth interviews. Data were analysed iteratively and thematically, informed by the Model of Pathways to Treatment. PARTICIPANTS AND SETTING: Pancreatic cancer occurs rarely in younger adults, therefore patients aged ≥40 years were recruited from nine hospitals after being referred to hospital with symptoms suggestive of pancreatic cancer; all were participants in a cohort study. Interviews were conducted soon after referral, and where possible, before diagnosis. RESULTS: Twenty-six interviews were conducted (cancer n=13 (pancreas n=9, other intra-abdominal n=4), non-cancer conditions n=13; age range 48-84 years; 14 women). Time from first symptoms to first presentation to healthcare ranged from 1 day to 270 days, median 21 days. We identified three main themes. Initial symptom appraisal usually began with intermittent, non-specific symptoms such as tiredness or appetite changes, attributed to diet and lifestyle, existing gastrointestinal conditions or side effects of medication. Responses to initial symptom appraisal included changes in meal type or frequency, or self-medication. Symptom changes such as alterations in appetite and enjoyment of food or weight loss usually prompted further appraisal. Triggers to seek help included a change or worsening of symptoms, particularly pain, which was often a 'tipping point'. Help-seeking was often encouraged by others. We found no differences in symptom appraisal and help-seeking between people diagnosed with cancer and those with other conditions. CONCLUSIONS: Greater public and healthcare professional awareness of the combinations of subtle and intermittent symptoms, and their evolving nature, is needed to prompt timelier help-seeking and investigation among people with symptoms of pancreatic cancer.
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Author URL.
Sheringham J, Sequeira R, Myles J, Hamilton W, McDonnell J, Offman J, Duffy S, Raine R (2017). Variations in GPs' decisions to investigate suspected lung cancer: a factorial experiment using multimedia vignettes.
BMJ Qual Saf,
26(6), 449-459.
Abstract:
Variations in GPs' decisions to investigate suspected lung cancer: a factorial experiment using multimedia vignettes.
INTRODUCTION: Lung cancer survival is low and comparatively poor in the UK. Patients with symptoms suggestive of lung cancer commonly consult primary care, but it is unclear how general practitioners (GPs) distinguish which patients require further investigation. This study examined how patients' clinical and sociodemographic characteristics influence GPs' decisions to initiate lung cancer investigations. METHODS: a factorial experiment was conducted among a national sample of 227 English GPs using vignettes presented as simulated consultations. A multimedia-interactive website simulated key features of consultations using actors ('patients'). GP participants made management decisions online for six 'patients', whose sociodemographic characteristics systematically varied across three levels of cancer risk. In low-risk vignettes, investigation (ie, chest X-ray ordered, computerised tomography scan or respiratory consultant referral) was not indicated; in medium-risk vignettes, investigation could be appropriate; in high-risk vignettes, investigation was definitely indicated. Each 'patient' had two lung cancer-related symptoms: one volunteered and another elicited if GPs asked. Variations in investigation likelihood were examined using multilevel logistic regression. RESULTS: GPs decided to investigate lung cancer in 74% (1000/1348) of vignettes. Investigation likelihood did not increase with cancer risk. Investigations were more likely when GPs requested information on symptoms that 'patients' had but did not volunteer (adjusted OR (AOR)=3.18; 95% CI 2.27 to 4.70). However, GPs omitted to seek this information in 42% (570/1348) of cases. GPs were less likely to investigate older than younger 'patients' (AOR=0.52; 95% CI 0.39 to 0.7) and black 'patients' than white (AOR=0.68; 95% CI 0.48 to 0.95). CONCLUSIONS: GPs were not more likely to investigate 'patients' with high-risk than low-risk cancer symptoms. Furthermore, they did not investigate everyone with the same symptoms equally. Insufficient data gathering could be responsible for missed opportunities in diagnosis.
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Watson J, de Salis I, Hamilton W, Salisbury C (2016). 'I'm fishing really'--inflammatory marker testing in primary care: a qualitative study.
Br J Gen Pract,
66(644), e200-e206.
Abstract:
'I'm fishing really'--inflammatory marker testing in primary care: a qualitative study.
BACKGROUND: Inflammatory markers can be helpful as part of the diagnostic workup for specific diseases or for monitoring disease activity. A third use is as a screening and/or triage tool to differentiate between the presence or absence of disease. Most research into inflammatory markers looks at diagnosis of specific diseases and comes from secondary care. Qualitative studies to explore when and why clinicians use these tests in primary care are lacking. AIM: to identify clinicians' approaches to inflammatory marker testing in primary care. DESIGN AND SETTING: Qualitative study with 26 GPs and nurse practitioners. METHOD: Interviews were conducted using a semi-structured topic guide. Clinicians reviewed recent cases of inflammatory marker testing in their pathology inbox. Interviews were audiorecorded and transcribed. Qualitative analysis was conducted by two of the authors. RESULTS: Clinicians are uncertain about the appropriate use of inflammatory markers and differ in their approach to testing patients with undifferentiated symptoms. Normal or significantly elevated inflammatory markers are seen as helpful, but mildly raised inflammatory markers in the context of non-specific symptoms are difficult to interpret. Clinicians describe a tension between not wanting to 'miss anything' and, on the other hand, being wary of picking up borderline abnormalities that can lead to cascades of further tests. Diagnostic uncertainty is a common reason for inflammatory marker testing, with the aim to reassure; however, paradoxically, inconclusive results can generate a cycle of uncertainty and anxiety. CONCLUSION: Further research is needed to define when inflammatory marker testing is useful in primary care and how to interpret results.
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Luqmani RA, Lee E, Singh S, Gillett M, Schmidt WA, Bradburn M, Dasgupta B, Diamantopoulos AP, Forrester-Barker W, Hamilton W, et al (2016). 271 Interrater and Intrarater Analysis of Ultrasound and Histological Findings in Patients with Suspected Giant Cell Arteritis. Rheumatology, 55(suppl_1), i171-i171.
Merriel SWD, Carroll R, Hamilton F, Hamilton W (2016). Association between unexplained hypoalbuminaemia and new cancer diagnoses in UK primary care patients.
Fam Pract,
33(5), 449-452.
Abstract:
Association between unexplained hypoalbuminaemia and new cancer diagnoses in UK primary care patients.
BACKGROUND: the association between hypoalbuminaemia and a new diagnosis of cancer is as yet unknown. OBJECTIVE: This study aimed to assess whether unexplained hypoalbuminaemia was associated with an increased risk of subsequent new cancer diagnosis within the next 12 months. METHODS: a cohort study was performed using a large UK database of adult primary care patients. Patients with a serum albumin test, either low or normal, were followed for 12 months for a new diagnosis of non-skin cancer. Logistic regression was used to assess for relationships between hypoalbuminaemia and cancer diagnoses. RESULTS: a total of 100 122 participants had at least one albumin test result. of these, 5753 (5.75%) had a result
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Lim AW, Landy R, Castanon A, Hollingworth A, Hamilton W, Dudding N, Sasieni P (2016). Cytology in the diagnosis of cervical cancer in symptomatic young women: a retrospective review.
Br J Gen Pract,
66(653), e871-e879.
Abstract:
Cytology in the diagnosis of cervical cancer in symptomatic young women: a retrospective review.
BACKGROUND: Cervical cancer in young women presents a diagnostic challenge because gynaecological symptoms are common but underlying disease is rare. AIM: to explore the potential for using cytology as a diagnostic aid for cervical cancer in young women. DESIGN AND SETTING: Retrospective review of primary care records and cytology data from the national cervical screening database and national audit of cervical cancers. METHOD: Four datasets of women aged 20-29 years in England were examined: primary care records and national screening data from an in-depth study of cervical cancers; cytology from the national audit of cervical cancers; whole-population cytology from the national screening database; and general-population primary care records from the Clinical Practice Research Datalink. The authors explored the sensitivity and positive predictive value (PPV) of symptomatic cytology (earliest
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Zhelev Z, Abbott R, Rogers M, Fleming S, Patterson A, Hamilton WT, Heaton J, Thompson Coon J, Vaidya B, Hyde C, et al (2016). Effectiveness of interventions to reduce ordering of thyroid function tests: a systematic review.
BMJ Open,
6(6).
Abstract:
Effectiveness of interventions to reduce ordering of thyroid function tests: a systematic review.
OBJECTIVES: to evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Database up to May 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions. STUDY APPRAISAL AND SYNTHESIS METHODS: 2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used. RESULTS: 27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics. CONCLUSIONS: the results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified. TRIAL REGISTRATION NUMBER: CRD42014006192.
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Landy R, Castanon A, Hamilton W, Lim AWW, Dudding N, Hollingworth A, Sasieni PD (2016). Evaluating cytology for the detection of invasive cervical cancer.
Cytopathology,
27(3), 201-209.
Abstract:
Evaluating cytology for the detection of invasive cervical cancer.
OBJECTIVE: to assess the sensitivity, the number needed to screen (NNS) and the positive predictive value (PPV) of cervical cytology for the diagnosis of cancer by age in a screening population. METHODS: a retrospective cohort of women with invasive cervical cancer nested within a census of cervical cytology. All (c. 8 million) women aged 20-64 years with cervical cytology (excluding tests after an earlier abnormality). From April 2007 to March 2010, 3372 women had cervical cancer diagnosed within 12 months of such cytology in England. The sensitivity of cervical cytology to cancer, NNS to detect one cancer and predictive values of cytology were calculated for various 'referral' thresholds. These were calculated for ages 20-24, 25-34, 35-49 and 50-64 years. RESULTS: the sensitivity of at least moderate dyskaryosis [equivalent to a high-grade squamous intraepithelial lesion (HSIL) or worse] for cancer of 89.4% [95% confidence interval (CI) 88.3-90.4%] in women offered screening was independent of age. At all ages, women with borderline-early recall or mild dyskaryosis on cytology (equivalent to ASC-US and LSIL, respectively, in the Bethesda system) had a similar risk of cervical cancer to the risk in all women tested. The PPV of severe dyskaryosis/?invasive and ?glandular neoplasia cytology (equivalent to squamous cell carcinoma and adenocarcinoma/adenocarcinoma in situ, respectively, in the Bethesda System) were 34% and 12%, respectively; the PPV of severe dyskaryosis (HSIL: severe dysplasia) was 4%. The NNS was lowest when the incidence of cervical cancer was highest, at ages 25-39 years, but the proportion of those with abnormal cytology who have cancer was also lowest in younger women. CONCLUSIONS: the PPV of at least severe dyskaryosis (HSIL: severe dysplasia) for cancer was 4-10% of women aged 25-64 years, justifying a 2-week referral to colposcopy and demonstrating the importance of failsafe monitoring for such patients. The sensitivity of cytology for cervical cancer was excellent across all age groups.
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1. Bailey S, Ukoumunne OC, Shephard L, Hamilton W (2016). How useful is thrombocytosis in predicting an underlying cancer in primary care?: a systematic review. Family Practice
Hamilton W, Walter FM, Rubin G, Neal RD (2016). Improving early diagnosis of symptomatic cancer.
Nature Reviews Clinical Oncology,
13(12), 740-749.
Abstract:
Improving early diagnosis of symptomatic cancer
Much time, effort and investment goes into the diagnosis of symptomatic cancer, with the expectation that this approach brings clinical benefits. This investment of resources has been particularly noticeable in the UK, which has, for several years, appeared near the bottom of international league tables for cancer survival in economically developed countries. In this Review, we examine expedited diagnosis of cancer from four perspectives. The first relates to the potential for clinical benefits of expedited diagnosis of symptomatic cancer. Limited evidence from clinical trials is available, but the considerable observational evidence suggests benefits can be obtained from this approach. The second perspective considers how expedited diagnosis can be achieved. We concentrate on data from the UK, where extensive awareness campaigns have been conducted, and initiatives in the primary-care setting, including clinical decision support, have all occurred during a period of considerable national policy change. The third section considers the most appropriate patients for cancer investigations, and the possible community settings for identification of such patients; UK national guidance for selection of patients for investigation is discussed. Finally, the health economics of expedited diagnosis are reviewed, although few studies provide definitive evidence on this topic.
Abstract.
Offman J, Pesola F, Fitzgerald R, Hamilton W, Sasieni P (2016). Incidence and progression of Barrett's oesophagus in clinical practice: a cohort analysis for planning of the Barrett's ESophagus Trial 3 (BEST3) comparing the Cytosponge-TFF3 test with usual care. European Journal of Surgical Oncology, 42(11), s252-s253.
Nicholson BD, Mant D, Neal RD, Hart N, Hamilton W, Shinkins B, Rubin G, Rose PW (2016). International variation in adherence to referral guidelines for suspected cancer: a secondary analysis of survey data.
Br J Gen Pract,
66(643), e106-e113.
Abstract:
International variation in adherence to referral guidelines for suspected cancer: a secondary analysis of survey data.
BACKGROUND: Variation in cancer survival persists between comparable nations and appears to be due, in part, to primary care practitioners (PCPs) having different thresholds for acting definitively in response to cancer-related symptoms. AIM: to explore whether cancer guidelines, and adherence to them, differ between jurisdictions and impacts on PCPs' propensity to take definitive action on cancer-related symptoms. DESIGN AND SETTING: a secondary analysis of survey data from six countries (10 jurisdictions) participating in the International Cancer Benchmarking Partnership. METHOD: PCPs' responses to five clinical vignettes presenting symptoms and signs of lung (n = 2), colorectal (n = 2), and ovarian cancer (n = 1) were compared with investigation and referral recommendations in cancer guidelines. RESULTS: Nine jurisdictions had guidelines covering the two colorectal vignettes. For the lung vignettes, although eight jurisdictions had guidelines for the first, the second was covered by a Swedish guideline alone. Only the UK and Denmark had an ovarian cancer guideline. Survey responses of 2795 PCPs (crude response rate: 12%) were analysed. Guideline adherence ranged from 20-82%. UK adherence was lower than other jurisdictions for the lung vignette covered by the guidance (47% versus 58%; P
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Price SJ, Stapley SA, Shephard E, Barraclough K, Hamilton WT (2016). Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? a case-control study.
BMJ Open,
6(5).
Abstract:
Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? a case-control study.
OBJECTIVES: to estimate data loss and bias in studies of Clinical Practice Research Datalink (CPRD) data that restrict analyses to Read codes, omitting anything recorded as text. DESIGN: Matched case-control study. SETTING: Patients contributing data to the CPRD. PARTICIPANTS: 4915 bladder and 3635 pancreatic, cancer cases diagnosed between 1 January 2000 and 31 December 2009, matched on age, sex and general practitioner practice to up to 5 controls (bladder: n=21
718; pancreas: n=16
459). The analysis period was the year before cancer diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Frequency of haematuria, jaundice and abdominal pain, grouped by recording style: Read code or text-only (ie, hidden text). The association between recording style and case-control status (χ(2) test). For each feature, the odds ratio (OR; conditional logistic regression) and positive predictive value (PPV; Bayes' theorem) for cancer, before and after addition of hidden text records. RESULTS: of the 20 958 total records of the features, 7951 (38%) were recorded in hidden text. Hidden text recording was more strongly associated with controls than with cases for haematuria (140/336=42% vs 556/3147=18%) in bladder cancer (χ(2) test, p
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Luqmani RA, Lee E, Singh S, Gillett M, Schmidt W, Bradburn M, Dasgupta B, Diamantopoulos AP, Forrester-Barker W, Hamilton W, et al (2016). O09 Ultrasound Compared with Biopsy in the Diagnosis of Suspected Giant Cell Arteritis. Rheumatology, 55(suppl_1), i37-i37.
Lim AWW, Hamilton W, Hollingworth A, Stapley S, Sasieni P (2016). Performance characteristics of visualising the cervix in symptomatic young females: a review of primary care records in females with and without cervical cancer.
Br J Gen Pract,
66(644), e189-e192.
Abstract:
Performance characteristics of visualising the cervix in symptomatic young females: a review of primary care records in females with and without cervical cancer.
BACKGROUND: the current strategy for timely detection of cervical cancer in young females centres on visualising the cervix when females present with gynaecological symptoms, but is based on expert opinion without an evidence base. AIM: to assess visualising the cervix in primary care in young females with gynaecological symptoms. DESIGN AND SETTING: a review of primary care records for females in England aged 20-29 years with cervical cancer (nationwide interview-based study) and in the general population (Clinical Practice Research Datalink database). METHOD: from primary care records the proportion of females was identified with gynaecological symptoms who had documented cervical examination in the year before diagnosis (cancers) and in 1-year age bands (general population). of these, the proportion was identified that was then referred for suspected malignancy. RESULTS: Only 39% of young females with cervical cancer had documented examination at symptomatic presentation. Visualisation resulted in referral for suspected malignancy for 18% of those examined (95% confidence interval = 5% to 40%). Very few (
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Walter FM, Mills K, Mendonça SC, Abel GA, Basu B, Carroll N, Ballard S, Lancaster J, Hamilton W, Rubin GP, et al (2016). Symptoms and patient factors associated with diagnostic intervals for pancreatic cancer (SYMPTOM pancreatic study): a prospective cohort study.
The Lancet Gastroenterology and Hepatology,
1(4), 298-306.
Abstract:
Symptoms and patient factors associated with diagnostic intervals for pancreatic cancer (SYMPTOM pancreatic study): a prospective cohort study
Background Pancreatic cancer is the tenth most common cancer in the UK; however, outcomes are poor, in part due to late diagnosis. We aimed to identify symptoms and other clinical and sociodemographic factors associated with pancreatic cancer diagnosis and diagnostic intervals. Methods We did this prospective cohort study at seven hospitals in two regions in England. We recruited participants aged 40 years or older who were referred for suspicion of pancreatic cancer. Data were collected by use of a patient questionnaire and primary care and hospital records. Descriptive and regression analyses were done to examine associations between symptoms and patient factors with the total diagnostic interval (time from onset of the first symptom to the date of diagnosis), comprising patient interval (time from first symptom to first presentation) and health system interval (time from first presentation to diagnosis). Findings We recruited 391 participants between Jan 1, 2011, and Dec 31, 2014 (24% response rate). 119 (30%) participants were diagnosed with pancreatic cancer (41 [34%] had metastatic disease), 47 (12%) with other cancers, and 225 (58%) with no cancer. 212 (54%) patients had multiple first symptoms whereas 161 (41%) patients had a solitary first symptom. In this referred population, no initial symptoms were reported more frequently by patients with cancer than by those with no cancer. Several subsequent symptoms predicted pancreatic cancer: jaundice (51 [49%] of 105 patients with pancreatic cancer vs 25 [12%] of 211 patients with no cancer; p
Abstract.
Schmidt-Hansen M, Berendse S, Hamilton W (2016). Symptoms of Pancreatic Cancer in Primary Care: a Systematic Review.
Pancreas,
45(6), 814-818.
Abstract:
Symptoms of Pancreatic Cancer in Primary Care: a Systematic Review.
OBJECTIVES: the aim of this study was to quantify the risk of pancreatic cancer in patients presenting in primary care with symptoms that may indicate pancreatic cancer. METHODS: We searched MEDLINE, PreMEDLINE, EMBASE, the Cochrane Library, Web of Science, and ISI Proceedings (1980 to August 2014) and PsychINFO (1980 to May 2013) for diagnostic studies of symptomatic adult patients in primary care. Study quality was assessed using QUADAS-II, and data were extracted to calculate the positive predictive values (PPVs) of symptoms, singly or in combination, for pancreatic cancer. RESULTS: Eight studies with 3,438,363 patients were included. The PPV of jaundice was more than 4.1% in patients 40 years or older and increased with age, although only 30% of patients reported jaundice. The PPVs of other single symptoms were low, with the highest PPV being 1% for repeated attendance with abdominal pain in patients 60 years or older. Excluding jaundice, symptom combinations with high PPVs were those including weight loss, ranging from 1.5% to 2.7% in patients 60 years or older, apart from when weight loss was combined with malaise (PPV, 0.9%). CONCLUSION: the only high-risk feature of pancreatic cancer in primary care was jaundice, and this clearly warrants investigation. Weight loss accompanied by a second symptom may warrant investigation, although this would probably require abdominal computed tomography.
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Shephard EA, Neal RD, Rose PW, Walter FM, Hamilton W (2016). Symptoms of adult chronic and acute leukaemia before diagnosis: large primary care case-control studies using electronic records.
Br J Gen Pract,
66(644), e182-e188.
Abstract:
Symptoms of adult chronic and acute leukaemia before diagnosis: large primary care case-control studies using electronic records.
BACKGROUND: Leukaemia is the eleventh commonest UK cancer. The four main subtypes have different clinical profiles, particularly between chronic and acute types. AIM: to identify the symptom profiles of chronic and acute leukaemia in adults in primary care. DESIGN AND SETTING: Matched case-control studies using Clinical Practice Research Datalink records. METHOD: Putative symptoms of leukaemia were identified in the year before diagnosis. Conditional logistic regression was used for analysis, and positive predictive values (PPVs) were calculated to estimate risk. RESULTS: of cases diagnosed between 2000 and 2009, 4655 were aged ≥40 years (2877 chronic leukaemia (CL), 937 acute leukaemia (AL), 841 unreported subtype). Ten symptoms were independently associated with CL, the three strongest being: lymphadenopathy (odds ratio [OR] 22, 95% confidence interval [CI] = 13 to 36), weight loss (OR 3.0, 95% CI = 2.1 to 4.2), and bruising (OR 2.3, 95% CI = 1.6 to 3.2). Thirteen symptoms were independently associated with AL, the three strongest being: nosebleeds and/or bleeding gums (OR 5.7, 95% CI = 3.1 to 10), fever (OR 5.3, 95% CI = 2.7 to 10), and fatigue (OR 4.4, 95% CI = 3.3 to 6.0). No individual symptom or combination of symptoms had a PPV >1%. CONCLUSION: the symptom profiles of CL and AL have both overlapping and distinct features. This presents a dichotomy for GPs: diagnosis, by performing a full blood count, is easy; however, the symptoms of leukaemia are non-specific and of relatively low risk. This explains why many leukaemia diagnoses are unexpected findings.
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Schmidt‐Hansen M, Hamilton W (2016). The NICE primary care referral guideline for suspected bladder or renal cancer. Trends in Urology & Men's Health, 7(2), 21-24.
Luqmani R, Lee E, Singh S, Gillett M, Schmidt WA, Bradburn M, Dasgupta B, Diamantopoulos AP, Forrester-Barker W, Hamilton W, et al (2016). The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study.
HEALTH TECHNOLOGY ASSESSMENT,
20(90), 1-+.
Author URL.
Martins T, Hamilton W (2016). The influence of ethnicity on diagnosis of cancer.
Fam Pract,
33(4), 325-326.
Author URL.
Robson JC, Kiran A, Maskell J, Hutchings A, Arden N, Dasgupta B, Hamilton W, Emin A, Culliford D, Luqmani R, et al (2016). Which Patients with Giant Cell Arteritis Will Develop Cardiovascular or Cerebrovascular Disease? a Clinical Practice Research Datalink Study.
J Rheumatol,
43(6), 1085-1092.
Abstract:
Which Patients with Giant Cell Arteritis Will Develop Cardiovascular or Cerebrovascular Disease? a Clinical Practice Research Datalink Study.
OBJECTIVE: to evaluate the risk of cerebrovascular disease and cardiovascular disease (CVD) in patients with giant cell arteritis (GCA), and to identify predictors. METHODS: the UK Clinical Practice Research Datalink 1991-2010 was used for a parallel cohort study of 5827 patients with GCA and 37,090 age-, sex-, and location-matched controls. A multivariable competing risk model (non-cerebrovascular/CV-related death as the competing risk) determined the relative risk [subhazard ratio (SHR)] between patients with GCA compared with background controls for cerebrovascular disease, CVD, or either. Each cohort (GCA and controls) was then analyzed individually using the same multivariable model, with age and sex now present, to identify predictors of CVD or cerebrovascular disease. RESULTS: Patients with GCA, compared with controls, had an increased risk SHR (95% CI) of cerebrovascular disease (1.45, 1.31-1.60), CVD (1.49, 1.37-1.62), or either (1.47, 1.37-1.57). In the GCA cohort, predictors of "cerebrovascular disease or CVD" included increasing age, > 80 years versus < 65 years (1.98, 1.62-2.42), male sex (1.20, 1.05-1.38), and socioeconomic status, most deprived quintile versus least deprived (1.34, 1.01-1.78). These predictors were also present within the non-GCA cohort. CONCLUSION: Patients with GCA are more likely to develop cerebrovascular disease or CVD than age-, sex-, and location-matched controls. In common with the non-GCA cohort, patients who are older, male, and from the most deprived compared with least deprived areas have a higher risk of cerebrovascular disease or CVD. Further work is needed to understand how this risk may be mediated by specific behavioral, social, and economic factors.
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Robson JC, Kiran A, Hutchings A, Arden N, Dasgupta B, Hamilton W, Emin A, Culliford D, Luqmani R (2015). 314. Increased Risk of Cerebrovascular and Cerebrovascular Disease Outcomes in Patients with Giant Cell Arteritis Independently Associated with Social Deprivation. Rheumatology, 54(suppl_1), i171-i171.
Din NU, Ukoumunne OC, Rubin G, Hamilton W, Carter B, Stapley S, Neal RD (2015). Age and Gender Variations in Cancer Diagnostic Intervals in 15 Cancers: Analysis of Data from the UK Clinical Practice Research Datalink.
PLoS One,
10(5).
Abstract:
Age and Gender Variations in Cancer Diagnostic Intervals in 15 Cancers: Analysis of Data from the UK Clinical Practice Research Datalink.
BACKGROUND: Time from symptomatic presentation to cancer diagnosis (diagnostic interval) is an important, and modifiable, part of the patient's cancer pathway, and can be affected by various factors such as age, gender and type of presenting symptoms. The aim of this study was to quantify the relationships of diagnostic interval with these variables in 15 cancers diagnosed between 2007 and 2010 using routinely collected data from the Clinical Practice Research Datalink (CPRD) in the UK. METHODS: Symptom lists for each cancer were prepared from the literature and by consensus amongst the clinician researchers, which were then categorised into either NICE qualifying (NICE) or not (non-NICE) based on NICE Urgent Referral Guidelines for Suspected Cancer criteria. Multivariable linear regression models were fitted to examine the relationship between diagnostic interval (outcome) and the predictors: age, gender and symptom type. RESULTS: 18,618 newly diagnosed cancer patients aged ≥40 who had a recorded symptom in the preceding year were included in the analysis. Mean diagnostic interval was greater for older patients in four disease sites (difference in days per 10 year increase in age; 95% CI): bladder (10.3; 5.5 to 15.1; P
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Hamilton W, Hajioff S, Graham J, Schmidt-Hansen M (2015). Authors' reply to Steele and colleagues.
BMJ,
351 Author URL.
Robson J, Kiran A, Hutchings A, Maskell J, Arden NK, Hamilton W, Dasgupta B, Luqmani R (2015). Cardiovascular and Cerebrovascular Disease and Social Deprivation in Patients with Giant Cell Arteritis.
ARTHRITIS & RHEUMATOLOGY,
67 Author URL.
Landy R, Castanon A, Dudding N, Lim AWW, Hollingworth A, Hamilton W, Sasieni PD (2015). Cervical cytology and the diagnosis of cervical cancer in older women.
J Med Screen,
22(4), 207-212.
Abstract:
Cervical cytology and the diagnosis of cervical cancer in older women.
OBJECTIVES: Most non-screen-detected cervical cancers are advanced stage. We assess the potential for cytology to expedite diagnosis when used outside of routine call and recall screening for cervical cancer. METHODS: Two cohorts of women with cytology that did not appear to have been taken as part of routine screening, nested within a census of cervical cytology, in England between April 2007 and March 2010 were studied: 93,322 women aged 40-69 at first cytology, and 14,668 women aged ≥70. The diagnostic performance of high grade cervical squamous intraepithelial lesion (HSIL) or worse cytology was estimated. We also estimated case-fatality from stage distribution in women aged ≥66 with and without cytology in the year prior to diagnosis. RESULTS: There were 259 cancers diagnosed in women aged 40-69 at first cytology, and 78 in women aged ≥70. The sensitivity of cytology ≥ HSIL for cancer was 89% and 83% respectively, and the number of women needed to test to identify one cancer was 404 (95% confidence interval [CI]: 355-462) and 226 (95% CI: 177-292) respectively. Women aged ≥66 with cytology within a year of diagnosis had earlier stage cancers than those without, corresponding to a 17-22% reduction in case fatality. CONCLUSIONS: Cervical cytology is an excellent identifier of cancer among women tested outside routine screening call and recall. Its use as a triage tool, for instance in women with vague gynaecological symptoms, could facilitate earlier stage diagnosis and reduce cervical cancer mortality.
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Hamilton W, Barrett J, Stapley S, Sharp D, Rose P (2015). Clinical features of metastatic cancer in primary care: a case-control study using medical records.
Br J Gen Pract,
65(637), e516-e522.
Abstract:
Clinical features of metastatic cancer in primary care: a case-control study using medical records.
BACKGROUND: How metastatic cancer initially presents is largely unknown. AIM: to identify clinical features of metastatic cancer in primary care. DESIGN AND SETTING: Case-control study in 11 general practices in Devon, UK. METHOD: Cases of patients who had died with metastatic breast, colorectal, or prostate cancer were selected. In addition, two control groups were formed of patients with the same primary cancer but without metastases ('cancer controls') and patients without cancer ('healthy controls'), matched for age, sex, and practice. All symptoms, signs, and laboratory test abnormalities in the year before metastasis were identified. The primary analysis used conditional logistic regression. RESULTS: in total, 162 cases, 152 cancer controls, and 145 healthy controls were studied. Common symptoms associated with cancer were: vomiting, 40 (25%) cases and 13 (9%) cancer controls (multivariable odds ratio [OR] 3.5, 95% confidence interval [CI] = 1.3 to 9.4, P = 0.011); low back pain, 38 (24%) cases and 17 (11%) cancer controls (OR 2.5, 95% CI = 1.1 to 5.6, P = 0.032); loss of appetite, 32 (20%) cases and nine (6%) cancer controls (OR 4.0, 95% CI = 1.2 to 13.2, P = 0.021); and shoulder pain, 27 (17%) cases and eight (5%) cancer controls (OR 5.3, 95% CI = 1.6 to 18, P = 0.007). Groin pain was uncommon, but strongly associated (16 [10%] cases and one [1%] cancer control [OR 10, 95% CI = 1.2 to 82, P = 0.032]), as was pleural disease (nine [6%] cases and one [1%] cancer control [OR 10, 95% CI = 1.1 to 92, P = 0.038]). CONCLUSION: These features of disseminated cancer have been reported before in studies from secondary care, but the scarcity of specific symptoms (such as local pain) and the fairly common occurrence of non-specific symptoms (vomiting and loss of appetite) is important and may explain delays in the diagnosis of metastases.
Abstract.
Author URL.
Barrett J, Rose P, Stapley S, Sharp D, Hamilton W (2015). Clinical features of metastatic cancer in primary care; a case-control study using medical records.
EUROPEAN JOURNAL OF CANCER CARE,
24, 25-26.
Author URL.
Hamilton W, Huang H, Seiber E, Lo W (2015). Cost and outcome in pediatric ischemic stroke.
Journal of Child Neurology,
30(11), 1483-1488.
Abstract:
Cost and outcome in pediatric ischemic stroke
The cost of childhood stroke receives little notice. The authors examined potential drivers of cost and outcome to test whether (1) neonatal strokes cost less than childhood strokes, (2) associated diseases influence cost, (3) arterial ischemic stroke is more costly than sinovenous thrombosis, and (4) cost correlates with outcome. The authors reviewed records of 111 children who sustained arterial ischemic stroke or sinovenous thrombosis between 2005 and 2010 to identify costs for the following year. They assessed outcomes in 46 with the Recovery and Recurrence Questionnaire and the Pediatric Quality of Life Inventory. Neonatal strokes cost less than childhood stroke. Strokes associated with congenital heart disease or vasculopathy cost the most, while perinatal or idiopathic strokes cost the least. Higher costs are correlated with worse impairment and poorer quality of life. Stroke etiology significantly influences the cost of pediatric stroke. Future cost-benefit studies must consider etiology when estimating the incremental costs associated with stroke.
Abstract.
Coxon D, Campbell C, Walter F, Scott S, Neal R, Vedsted P, Emery J, Rubin G, Hamilton W, Weller D, et al (2015). Development of the 'Aarhus Statement Tool for Researching Intervals in Diagnosis' (ASTRID): results from a pilot study with cancer patients and their GPs.
EUROPEAN JOURNAL OF CANCER CARE,
24, 16-16.
Author URL.
Hamilton W (2015). Diagnosing symptomatic cancer in the NHS Fast track referral is one part of an improving picture.
BMJ-BRITISH MEDICAL JOURNAL,
351 Author URL.
Hamilton W (2015). Diagnosing symptomatic cancer in the NHS.
BMJ,
351 Author URL.
Astin MP, Martins T, Welton N, Neal RD, Rose PW, Hamilton W (2015). Diagnostic value of symptoms of oesophagogastric cancers in primary care: a systematic review and meta-analysis.
Br J Gen Pract,
65(639), e677-e691.
Abstract:
Diagnostic value of symptoms of oesophagogastric cancers in primary care: a systematic review and meta-analysis.
BACKGROUND: Selection of primary care patients for investigation of potential oesophagogastric cancer is difficult, as the symptoms may represent benign conditions, which are also more common. AIM: to review systematically the presenting features of oesophagogastric cancers in primary care, including open-access endoscopy clinics. DESIGN AND SETTING: Systematic review and meta-analysis. METHOD: MEDLINE®, Embase, the Cochrane Library, and CINAHL were searched for studies of adults who were symptomatic and presented in primary care or open-access endoscopy clinics. Exclusions were being asymptomatic, screening, or recurrent cancers. Data were extracted to estimate the diagnostic performance of features of oesophagogastric cancers and summarised in a meta-analysis. RESULTS: Fourteen studies were identified. The strongest summary sensitivity and specificity estimates were for: dyspepsia 0.42 (95% confidence interval [CI] 0.29 to 0.56) and 0.48 (95% CI = 0.31 to 0.65); pain 0.41 (95% CI = 0.24 to 0.62) and 0.75 (95% CI = 0.51 to 0.89); and dysphagia 0.32 (95% CI = 0.17 to 0.52) and 0.92 (95% CI = 0.81 to 0.97). Summary positive likelihood ratios (LR+) and diagnostic odds ratios were: dyspepsia 0.79 (95% CI = 0.55 to 1.15) and 0.65 (95% CI = 0.32 to 1.33); pain 1.64 (95% CI = 1.20 to 2.24) and 2.09 (95% CI = 1.57 to 2.77); and dysphagia 4.32 (95% CI = 2.46 to 7.58) and 5.91 (95% CI = 3.56 to 9.82). Sensitivity was lower for: anaemia 0.12 [95% Cl = 0.08 to 0.19] with specificity 0.97 [95% Cl = 0.94 to 0.99]; nausea/vomiting/bloating 0.17 [95% Cl = 0.05 to 0.46] and 0.84 [95% Cl = 0.60 to 0.94] respectively; reflux 0.23 [95% Cl = 0.10 to 0.46] and 0.70 [95% Cl = 0.59 to 0.80]; weight loss 0.25 [95% Cl = 0.12 to 0.43] and 0.96 [95% Cl = 0.88 to 0.98]. [corrected]. Corresponding LR+ were: anaemia 4.32 (95% CI = 2.64 to 7.08); nausea/vomiting/bloating 1.07 (95% CI = 0.52 to 2.19); reflux 0.78 (95% CI = 0.47 to 1.78) and; weight loss 5.46 (95% CI = 3.47 to 8.60). CONCLUSION: Dysphagia, weight loss, and anaemia show the strongest association but with relatively low sensitivity and high specificity. The findings support the value of investigation of these symptoms, but also suggest that, in a population of patients who are low risk but not no-risk, investigation is not currently recommended.
Abstract.
Author URL.
Price SJ, Shephard EA, Stapley SA, Barraclough K, Hamilton WT (2015). Does the GP method of recording possible cancer symptoms reflect the probability that cancer is present?.
EUROPEAN JOURNAL OF CANCER CARE,
24, 30-30.
Author URL.
Martins T, Price S, Hjertholm P, Hamilton W (2015). Doing PhD in primary care diagnosis and treatment of cancer.
EUROPEAN JOURNAL OF CANCER CARE,
24, 58-58.
Author URL.
Martins T, Ukoumunne OC, Banks J, Raine R, Hamilton W (2015). Ethnic differences in patients' preferences for prostate cancer investigation: a vignette-based survey in primary care.
Br J Gen Pract,
65(632), e161-e170.
Abstract:
Ethnic differences in patients' preferences for prostate cancer investigation: a vignette-based survey in primary care.
BACKGROUND: Minority ethnic groups in the UK have worse outcomes for some cancer types compared with the white majority. Black males have worse staging at diagnosis of prostate cancer and often present as emergencies, suggesting possible delays in the diagnostic pathway. Delay may arise from lower awareness of cancer symptoms, reluctance to report symptoms, reduced desire for investigation, or a combination of these. Reduced desire for investigation was examined in this study AIM: to investigate whether black males in the UK would choose to be tested for prostate cancer compared with the white majority. DESIGN AND SETTING: a vignette (hypothetical scenario)-based, electronic survey of male patients aged ≥40 years from four general practices in Bristol, UK. METHOD: the vignettes described possible prostate cancer symptoms (equating to risk levels of 2%, 5%, and 10%), investigative procedures, and possible outcomes. Participants indicated whether they would choose investigation in these scenarios. Analysis used logistic regression, with preference for investigation as the outcome variable and ethnicity as the main explanatory variable. RESULTS: in total, 449 (81%) of 555 participants opted for investigation, regardless of risk levels; of these, the acceptance rate was 94% (251 out of 267) among white males and 70% (198 out of 285) among black males. In multivariable analyses, preference for investigation was lower in black males, even after controlling for relevant confounding factors including specific risk level (odds ratio 0.13; 95% confidence interval = 0.07 to 0.25; P
Abstract.
Author URL.
Martins T, Hamilton W (2015). Ethnic variations in the interval between diagnostic ultrasound test request and performance of the test (in patients with suspected ovarian cancers).
EUROPEAN JOURNAL OF CANCER CARE,
24, 31-32.
Author URL.
Rose PW, Rubin G, Perera-Salazar R, Almberg SS, Barisic A, Dawes M, Grunfeld E, Hart N, Neal RD, Pirotta M, et al (2015). Explaining variation in cancer survival between 11 jurisdictions in the International Cancer Benchmarking Partnership: a primary care vignette survey.
BMJ Open,
5(5).
Abstract:
Explaining variation in cancer survival between 11 jurisdictions in the International Cancer Benchmarking Partnership: a primary care vignette survey.
OBJECTIVES: the International Cancer Benchmarking Partnership (ICBP) is a collaboration between 6 countries and 12 jurisdictions with similar primary care-led health services. This study investigates primary care physician (PCP) behaviour and systems that may contribute to the timeliness of investigating for cancer and subsequently, international survival differences. DESIGN: a validated survey administered to PCPs via the internet set out in two parts: direct questions on primary care structure and practice relating to cancer diagnosis, and clinical vignettes, assessing management of scenarios relating to the diagnosis of lung, colorectal or ovarian cancer. PARTICIPANTS: 2795 PCPs in 11 jurisdictions: New South Wales and Victoria (Australia), British Columbia, Manitoba, Ontario (Canada), England, Northern Ireland, Wales (UK), Denmark, Norway and Sweden. PRIMARY AND SECONDARY OUTCOME MEASURES: Analysis compared the cumulative proportion of PCPs in each jurisdiction opting to investigate or refer at each phase for each vignette with 1-year survival, and conditional 5-year survival rates for the relevant cancer and jurisdiction. Logistic regression was used to explore whether PCP characteristics or system differences in each jurisdiction affected the readiness to investigate. RESULTS: 4 of 5 vignettes showed a statistically significant correlation (p
Abstract.
Author URL.
Green T, Martins T, Hamilton W, Rubin G, Elliott K, Macleod U (2015). Exploring GPs' experiences of using diagnostic tools for cancer: a qualitative study in primary care.
Fam Pract,
32(1), 101-105.
Abstract:
Exploring GPs' experiences of using diagnostic tools for cancer: a qualitative study in primary care.
BACKGROUND: the UK has an estimated 5-10000 extra cancer deaths each year when compared to other European countries and diagnostic delays are thought to make a significant contribution to this. One of the initiatives in England intended to support primary care professionals has been the development of cancer risk assessment tools (RATs). These tools assist in identifying and quantifying the risk of cancer in symptomatic primary care patients. OBJECTIVE: to explore GPs' experiences of incorporating the RATs for lung and bowel cancers into their clinical practice and in so doing, identify constraints and facilitators to the wider dissemination of the tools in primary care. METHODS: We conducted semi-structured interviews over the telephone with 11 project managers who implemented the study and 23 GPs who used the tool. The interviews were digitally recorded, professionally transcribed verbatim and analysed through the construction of a 'thematic framework'. RESULTS: the training and support package was fundamental to the successful integration of the RATs into GPs' daily routines. Ongoing support from cancer networks alongside acknowledgement of the clinical expertize of the GPs by those implementing the study enhanced GPs' uptake of the tool in practice. CONCLUSION: Findings suggest that the embedding of clinical decision support tools into clinical practice is more likely to be achieved when they are perceived to support but not supersede the clinical judgement of their users. This element of our findings is a focal point of this article.
Abstract.
Author URL.
Hamilton W, Stapley S, Campbell C, Lyratzopoulos G, Rubin G, Neal RD (2015). For which cancers might patients benefit most from expedited symptomatic diagnosis? Construction of a ranking order by a modified Delphi technique.
BMC Cancer,
15Abstract:
For which cancers might patients benefit most from expedited symptomatic diagnosis? Construction of a ranking order by a modified Delphi technique.
BACKGROUND: This study aimed to answer the question 'for which cancers, in a symptomatic patient, does expediting the diagnosis provide an improvement in mortality and/or morbidity?' METHODS: an initial ranking was constructed from previous work identifying 'avoidable deaths' for 21 common cancers in the UK. In a two-round modified Delphi exercise, 22 experts, all experienced across multiple cancers, used an evidence pack summarising recent relevant publications and their own experience to adjust this ranking. Participants also answered on a Likert scale whether they anticipated mortality or morbidity benefits for each cancer from expedited diagnosis. RESULTS: Substantial changes in ranking occurred in the Delphi exercise. Finally, expedited diagnosis was judged to provide the greatest mortality benefit in breast cancer, uterine cancer and melanoma, and least in brain and pancreatic cancers. Three cancers, prostate, brain and pancreas, attracted a median answer of 'disagree' to whether they expected mortality benefits from expedited diagnosis of symptomatic cancer. CONCLUSIONS: Our results can guide future research, with emphasis given to studying interventions to improve symptomatic diagnosis of those cancers ranked highly. In contrast, research efforts for cancers with the lowest rankings could be re-directed towards alternative avenues more likely to yield benefit, such as screening or treatment.
Abstract.
Author URL.
Luqmani R, Lee E, Singh S, Gillett M, Schmidt WA, Bradburn M, Dasgupta B, Diamantopoulos AP, Forrester-Barker W, Hamilton W, et al (2015). Inter-Rater Analysis of Ultrasound and Histological Findings in Patients with Suspected Giant Cell Arteritis.
ARTHRITIS & RHEUMATOLOGY,
67 Author URL.
Neal RD, Tharmanathan P, France B, Din NU, Cotton S, Fallon-Ferguson J, Hamilton W, Hendry A, Hendry M, Lewis R, et al (2015). Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review.
Br J Cancer,
112 Suppl 1(Suppl 1), S92-107.
Abstract:
Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review.
BACKGROUND: it is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. METHODS: Systematic review of the literature and narrative synthesis. RESULTS: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. CONCLUSIONS: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.
Abstract.
Author URL.
Ridd MJ, Ferreira DLS, Montgomery AA, Salisbury C, Hamilton W (2015). Patient-doctor continuity and diagnosis of cancer: electronic medical records study in general practice.
Br J Gen Pract,
65(634), e305-e311.
Abstract:
Patient-doctor continuity and diagnosis of cancer: electronic medical records study in general practice.
BACKGROUND: Continuity of care may affect the diagnostic process in cancer but there is little research. AIM: to estimate associations between patient-doctor continuity and time to diagnosis and referral of three common cancers. DESIGN AND SETTING: Retrospective cohort study in general practices in England. METHOD: This study used data from the General Practice Research Database for patients aged ≥40 years with a diagnosis of breast, colorectal, or lung cancer. Relevant cancer symptoms or signs were identified up to 12 months before diagnosis. Patient-doctor continuity (fraction-of-care index adjusted for number of consultations) was calculated up to 24 months before diagnosis. Time ratios (TRs) were estimated using accelerated failure time regression models. RESULTS: Patient-doctor continuity in the 24 months before diagnosis was associated with a slightly later diagnosis of colorectal (time ratio [TR] 1.01, 95% confidence interval [CI] =1.01 to 1.02) but not breast (TR = 1.00, 0.99 to 1.01) or lung cancer (TR = 1.00, 0.99 to 1.00). Secondary analyses suggested that for colorectal and lung cancer, continuity of doctor before the index consultation was associated with a later diagnosis but continuity after the index consultation was associated with an earlier diagnosis, with no such effects for breast cancer. For all three cancers, most of the delay to diagnosis occurred after referral. CONCLUSION: Any effect for patient-doctor continuity appears to be small. Future studies should compare investigations, referrals, and diagnoses in patients with and without cancer who present with possible cancer symptoms or signs; and focus on 'difficult to diagnose' types of cancer.
Abstract.
Author URL.
Kidney E, Berkman L, Macherianakis A, Morton D, Dowswell G, Hamilton W, Ryan R, Awbery H, Greenfield S, Marshall T, et al (2015). Preliminary results of a feasibility study of the use of information technology for identification of suspected colorectal cancer in primary care: the CREDIBLE study.
Br J Cancer,
112 Suppl 1(Suppl 1), S70-S76.
Abstract:
Preliminary results of a feasibility study of the use of information technology for identification of suspected colorectal cancer in primary care: the CREDIBLE study.
BACKGROUND: We report the findings of a feasibility study using information technology to search electronic primary care records and to identify patients with possible colorectal cancer. METHODS: an algorithm to flag up patients meeting National Institute for Health and Care Excellence (NICE) urgent referral criteria for suspected colorectal cancer was developed and incorporated into clinical audit software. This periodically flagged up such patients aged 60 to 79 years. General practitioners (GPs) reviewed flagged-up patients and decided on further clinical management. We report the numbers of patients identified and the numbers that GPs judged to need further review, investigations or referral to secondary care and the final diagnoses. RESULTS: Between January 2012 and March 2014, 19,580 records of patients aged 60 to 79 years were searched in 20 UK general practices, flagging up 809 patients who met urgent referral criteria. The majority of the patients had microcytic anaemia (236 (29%)) or rectal bleeding (205 (25%)). A total of 274 (34%) patients needed further clinical review of their records; 199 (73%) of these were invited for GP consultation, and 116 attended, of whom 42 were referred to secondary care. Colon cancer was diagnosed in 10 out of 809 (1.2%) flagged-up patients and polyps in a further 28 out of 809 (3.5%). CONCLUSIONS: it is technically possible to identify patients with colorectal cancer by searching electronic patient records.
Abstract.
Author URL.
Delgado TN, Hamilton W, Ford T, Stein K, Ukoumunne O (2015). Psychotropic prescribing in young people with ADHD in the UK clinical practice research datalink: 2005-2014.
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY,
24, S162-S162.
Author URL.
Shephard EA, Neal RD, Rose PW, Walter FM, Hamilton WT (2015). Quantifying the risk of Hodgkin lymphoma in symptomatic primary care patients aged ≥40 years: a case-control study using electronic records.
Br J Gen Pract,
65(634), e289-e294.
Abstract:
Quantifying the risk of Hodgkin lymphoma in symptomatic primary care patients aged ≥40 years: a case-control study using electronic records.
BACKGROUND: in the UK, approximately five people are diagnosed with Hodgkin lymphoma (HL) daily. One-tenth of diagnoses are in those aged >75 years. AIM: to establish a symptom profile of HL and quantify their risk in primary care patients aged ≥40 years. DESIGN AND SETTING: Matched case-control study using Clinical Practice Research Datalink patient records. METHOD: Putative clinical features of HL were identified in the year before diagnosis. Results were analysed using conditional logistic regression and positive predictive values (PPVs) calculated for the consulting population. RESULTS: Two-hundred and eighty-three patients aged ≥40 years, diagnosed with HL between 2000 and 2009, and 1237 age, sex, and general practice-matched participants were studied. Six features were independently associated with HL: lymphadenopathy (OR 280, 95% confidence interval [CI] = 25 to 3100), head and neck mass not described as lymphadenopathy (OR 260, 95% CI = 21 to 3200), other mass (OR 12, 95% CI = 4.4 to 35), thrombocytosis (OR 6.0, 95% CI = 2.6 to 14), raised inflammatory markers (OR 5.2, 95% CI = 3.0 to 9.0), and low full blood count (OR 2.8, 95% CI = 1.6 to 4.8). Lymphadenopathy per se has a positive predictive value (PPV) of 5.6% for HL in patients aged ≥60 years. CONCLUSION: Consistent with secondary care findings, lymphadenopathy is the clinical feature with the highest risk of HL in primary care and warrants urgent investigation.
Abstract.
Author URL.
Shephard EA, Neal RD, Rose P, Walter FM, Litt EJ, Hamilton WT (2015). Quantifying the risk of multiple myeloma from symptoms reported in primary care patients: a large case-control study using electronic records.
Br J Gen Pract,
65(631), e106-e113.
Abstract:
Quantifying the risk of multiple myeloma from symptoms reported in primary care patients: a large case-control study using electronic records.
BACKGROUND: Patients with myeloma experience the longest diagnostic delays compared with patients with other cancers in the UK; 37% are diagnosed through emergency presentations. AIM: to identify and quantify the risk of myeloma from specific clinical features reported by primary care patients. DESIGN AND SETTING: Matched case-control study using General Practice Research Database primary care electronic records. METHOD: Putative clinical features of myeloma were identified and analysed using conditional logistic regression. Positive predictive values (PPVs) were calculated for the consulting population. RESULTS: a total of 2703 patients aged ≥40 years, diagnosed with myeloma between 2000 and 2009, and 12 157 age, sex, and general practice-matched controls were identified. Sixteen features were independently associated with myeloma: hypercalcaemia, odds ratio 11.4 (95% confidence interval [CI] = 7.1 to 18), cytopenia 5.4 (95% CI = 4.6 to 6.4), raised inflammatory markers 4.9 (95% CI = 4.2 to 5.8), fracture 3.1 (95% CI = 2.3 to 4.2), raised mean corpuscular volume 3.1 (95% CI = 2.4 to 4.1), weight loss 3.0 (95% CI = 2.0 to 4.5), nosebleeds 3.0 (95% CI = 1.9 to 4.7), rib pain 2.5 (95% CI = 1.5 to 4.4), back pain 2.2 (95% CI = 2.0 to 2.4), other bone pain 2.1 (95% CI = 1.4 to 3.1), raised creatinine 1.8 (95% CI = 1.5 to 2.2), chest pain 1.6 (95% CI = 1.4 to 1.8), joint pain 1.6 (95% CI = 1.2 to 2.2), nausea 1.5 (95% CI = 1.1 to 2.1), chest infection 1.4 (95% CI = 1.2 to 1.6), and shortness of breath 1.3 (95% CI = 1.1 to 1.5). Individual symptom PPVs were generally 10% for some symptoms when combined with leucopenia or hypercalcaemia. CONCLUSION: Individual symptoms of myeloma in primary care are generally low risk, probably explaining diagnostic delays. Once simple primary care blood tests are taken, risk estimates change. Hypercalcaemia and leucopenia are particularly important abnormalities, and coupled with symptoms, strongly suggest myeloma.
Abstract.
Author URL.
Shephard EA, Neal RD, Rose PW, Walter FM, Hamilton WT (2015). Quantifying the risk of non-Hodgkin lymphoma in symptomatic primary care patients aged ≥40 years: a large case-control study using electronic records.
Br J Gen Pract,
65(634), e281-e288.
Abstract:
Quantifying the risk of non-Hodgkin lymphoma in symptomatic primary care patients aged ≥40 years: a large case-control study using electronic records.
BACKGROUND: Non-Hodgkin lymphoma (NHL) is the sixth most common cancer in the UK; approximately 35 people are diagnosed and 13 die from the disease daily. AIM: to identify the primary care clinical features of NHL and quantify their risk in symptomatic patients. DESIGN AND SETTING: Matched case-control study using Clinical Practice Research Datalink patient records. METHOD: Putative clinical features of NHL were identified in the year before diagnosis. Results were analysed using conditional logistic regression and positive predictive values (PPVs). RESULTS: a total of 4362 patients aged ≥40 years, diagnosed with NHL between 2000 and 2009, and 19 468 age, sex, and general practice-matched controls were studied. Twenty features were independently associated with NHL. The five highest risk symptoms were lymphadenopathy, odds ratio (OR) 263 (95% CI = 133 to 519), head and neck mass not described as lymphadenopathy OR 49 (95% CI = 32 to 74), other mass OR 12 (95% CI = 10 to 16), weight loss OR 3.2 (95% CI = 2.3 to 4.4), and abdominal pain OR 2.5 (95% CI = 2.1 to 2.9). Lymphadenopathy has a PPV of 13% for NHL in patients ≥60 years. Weight loss in conjunction with repeated back pain or raised gamma globulin had PPVs >2%. CONCLUSION: Unexplained lymphadenopathy in patients aged ≥60 years produces a very high risk of NHL in primary care. These patients warrant urgent investigation, potentially sooner than 6 weeks from initial presentation where the GP is particularly concerned.
Abstract.
Author URL.
Rogers TK, Hamilton W, Tod A, Neal R (2015). Response to: What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK?.
Thorax,
70(2).
Author URL.
Usher-Smith J, Emery J, Hamilton W, Griffin SJ, Walter FM (2015). Risk prediction tools for cancer in primary care.
Br J Cancer,
113(12), 1645-1650.
Abstract:
Risk prediction tools for cancer in primary care.
Numerous risk tools are now available, which predict either current or future risk of a cancer diagnosis. In theory, these tools have the potential to improve patient outcomes through enhancing the consistency and quality of clinical decision-making, facilitating equitable and cost-effective distribution of finite resources such as screening tests or preventive interventions, and encouraging behaviour change. These potential uses have been recognised by the National Cancer Institute as an 'area of extraordinary opportunity' and an increasing number of risk prediction models continue to be developed. The data on predictive utility (discrimination and calibration) of these models suggest that some have potential for clinical application; however, the focus on implementation and impact is much more recent and there remains considerable uncertainty about their clinical utility and how to implement them in order to maximise benefits and minimise harms such as over-medicalisation, anxiety and false reassurance. If the potential benefits of risk prediction models are to be realised in clinical practice, further validation of the underlying risk models and research to assess the acceptability, clinical impact and economic implications of incorporating them in practice are needed.
Abstract.
Author URL.
Hamilton W, Hajioff S, Graham J, Schmidt-Hansen M (2015). SUSPECTED CANCER IN ADULTS Use of faecal occult blood tests in symptomatic patients Reply.
BMJ-BRITISH MEDICAL JOURNAL,
351 Author URL.
Hamilton W, Hajioff S, Graham J, Schmidt-Hansen M (2015). Suspected cancer (part 1--children and young adults): visual overview of updated NICE guidance.
BMJ,
350 Author URL.
Hamilton W, Hajioff S, Graham J, Schmidt-Hansen M (2015). Suspected cancer (part 1-children and young adults): visual overview of updated NICE guidance.
BMJ-BRITISH MEDICAL JOURNAL,
350 Author URL.
Hamilton W, Hajioff S, Graham J, Schmidt-Hansen M (2015). Suspected cancer (part 2--adults): reference tables from updated NICE guidance.
BMJ,
350 Author URL.
Hamilton W (2015). Suspected cancer (part 2-adults): reference tables from updated NICE guidance (vol 350, h3044, 2015).
BMJ-BRITISH MEDICAL JOURNAL,
351 Author URL.
Hall N, Birt L, Banks J, Emery J, Mills K, Johnson M, Rubin GP, Hamilton W, Walter FM (2015). Symptom appraisal and healthcare-seeking for symptoms suggestive of colorectal cancer: a qualitative study.
BMJ Open,
5(10).
Abstract:
Symptom appraisal and healthcare-seeking for symptoms suggestive of colorectal cancer: a qualitative study.
OBJECTIVES: Timely diagnosis of colorectal cancer is important to improve survival. This study explored symptom appraisal and help-seeking among patients referred to specialist services with symptoms of colorectal cancer. DESIGN: Qualitative in-depth interview study. SETTING AND PARTICIPANTS: Participants were recruited on referral to gastroenterology clinics (North East and East of England); interviews were conducted soon after referral. We purposively sampled participants to ensure a range of accounts in terms of age, sex, diagnosis and geographical location. METHODS: Data collection and analysis were underpinned by the Model of Pathways to Treatment. Framework analysis was used to explore the data within and across cases, focusing on patient beliefs and experiences, disease factors and healthcare influences. RESULTS: 40 participants were interviewed (aged 43-87
years, 17 women, 18 diagnosed with colorectal cancer). Patients diagnosed with and without colorectal cancer had similar symptom pathways. We found a range of interacting and often competing biopsychosocial, contextual and cultural influences on the way in which people recognised, interpreted and acted on their symptoms. People attempted to 'maintain normality' through finding benign explanations for their symptoms. Bodily changes were appraised within the context of usual bowel patterns, comorbidities and life events, and decisions to seek help were made in relation to expectations about the course of symptoms. The 'private nature' of colorectal cancer symptoms could affect both their identification and discussions with others including healthcare professionals. Within the context of the National Health Service, people needed to legitimise appropriate use of healthcare services and avoid being thought of as wasting doctors' time. CONCLUSIONS: Findings provide guidance for awareness campaigns on reducing stigma around appraising and discussing bowel movements, and the importance of intermittent and non-specific symptoms. Altering perceptions about the appropriate use of health services could have a beneficial effect on time to presentation.
Abstract.
Author URL.
Biswas M, Ades AE, Hamilton W (2015). Symptom lead times in lung and colorectal cancers: What are the benefits of symptom-based approaches to early diagnosis?.
British Journal of Cancer,
112(2), 271-277.
Abstract:
Symptom lead times in lung and colorectal cancers: What are the benefits of symptom-based approaches to early diagnosis?
Background: Individuals with undiagnosed lung and colorectal cancers present with non-specific symptoms in primary care more often than matched controls. Increased access to diagnostic services for patients with symptoms generates more early-stage diagnoses, but the mechanisms for this are only partially understood. Methods: We re-analysed a UK-based case-control study to estimate the Symptom Lead Time (SLT) distribution for a range of potential symptom criteria for investigation. Symptom Lead Time is the time between symptoms caused by cancer and eventual diagnosis, and is analogous to Lead Time in a screening programme. We also estimated the proportion of symptoms in lung and colorectal cancer cases that are actually caused by the cancer. Results: Mean Symptom Lead Times were between 4.1 and 6.0 months, with medians between 2.0 and 3.2 months. Symptom Lead Time did not depend on stage at diagnosis, nor which criteria for investigation are adopted. Depending on the criteria, an estimated 27-48% of symptoms in individuals with as yet undiagnosed lung cancer, and 12-32% with undiagnosed colorectal cancer are not caused by the cancer. Conclusions: in most cancer cases detected by a symptom-based programme, the symptoms are caused by cancer. These cases have a short lead time and benefit relatively little. However, in a significant minority of cases cancer detection is serendipitous. This group experiences the benefits of a standard screening programme, a substantial mean lead time and a higher probability of early-stage diagnosis.
Abstract.
Schmidt-Hansen M, Berendse S, Hamilton W (2015). Symptomatic diagnosis of cancer of the brain and central nervous system in primary care: a systematic review.
Fam Pract,
32(6), 618-623.
Abstract:
Symptomatic diagnosis of cancer of the brain and central nervous system in primary care: a systematic review.
BACKGROUND: We performed a systematic review of diagnostic studies of symptomatic patients in primary care to quantify the risk of brain/central nervous system (CNS) cancer in patients presenting in primary care with symptoms that may indicate brain/CNS cancer. OBJECTIVE: to quantify the risk of brain/CNS cancer in symptomatic patients presenting in primary care. METHODS: We searched Medline, Premedline, Embase, the Cochrane Library, Web of Science and ISI Proceedings (1980 to August 2014) and PsychInfo (1980 to February 2013) for diagnostic studies of symptomatic adult patients in primary care. Study quality was assessed using QUADAS-II and data were extracted to calculate the positive predictive values (PPVs) of symptoms, singly or in combination, for brain/CNS cancer. RESULTS: Six studies with 159938 patients were included. The PPVs of single symptoms were very low with only 'new-onset seizure' being above 1% in patients aged 18 years and above, rising to 2.3% in patients aged 60-69 years. In patients aged 15-24 years, the PPVs for the individual symptoms were also very low, with the highest, also for seizure, being 0.024%, similar to that in children aged 0-14 years of 0.02%. For symptom combinations, none of the PPVs were above 0.39%. CONCLUSIONS: all the symptoms of brain tumours are individually low risk, apart from new-onset epilepsy. This provides a real diagnostic problem, as brain tumours have all the expected features seen with cancer diagnostic delay, with high proportions presenting as an emergency and having had multiple primary care consultations before referral, and the prognosis is poor. Improving these metrics can only be done by liberalizing investigation, although the health economics of that strategy is undetermined.
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Author URL.
Walter FM, Emery J, Mendonca S, Hall N, Mills K, Dobson C, Morris H, Bankhead C, Hamilton W, Rubin G, et al (2015). Symptoms and co-morbidities associated with diagnostic intervals for colorectal cancer: a prospective cohort study.
EUROPEAN JOURNAL OF CANCER CARE,
24, 49-49.
Author URL.
Walter FM, Rubin G, Bankhead C, Morris HC, Hall N, Mills K, Dobson C, Rintoul RC, Hamilton W, Emery J, et al (2015). Symptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study.
Br J Cancer,
112 Suppl 1(Suppl 1), S6-13.
Abstract:
Symptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study.
BACKGROUND: This prospective cohort study aimed to identify symptom and patient factors that influence time to lung cancer diagnosis and stage at diagnosis. METHODS: Data relating to symptoms were collected from patients upon referral with symptoms suspicious of lung cancer in two English regions; we also examined primary care and hospital records for diagnostic routes and diagnoses. Descriptive and regression analyses were used to investigate associations between symptoms and patient factors with diagnostic intervals and stage. RESULTS: Among 963 participants, 15.9% were diagnosed with primary lung cancer, 5.9% with other thoracic malignancies and 78.2% with non-malignant conditions. Only half the cohort had an isolated first symptom (475, 49.3%); synchronous first symptoms were common. Haemoptysis, reported by 21.6% of cases, was the only initial symptom associated with cancer. Diagnostic intervals were shorter for cancer than non-cancer diagnoses (91 vs 124 days, P=0.037) and for late-stage than early-stage cancer (106 vs 168 days, P=0.02). Chest/shoulder pain was the only first symptom with a shorter diagnostic interval for cancer compared with non-cancer diagnoses (P=0.003). CONCLUSIONS: Haemoptysis is the strongest symptom predictor of lung cancer but occurs in only a fifth of patients. Programmes for expediting earlier diagnosis need to focus on multiple symptoms and their evolution.
Abstract.
Author URL.
Banks J, Hamilton W, Walter F (2015). The Discovery Programme and its impact on cancer diagnostics.
Br J Hosp Med (Lond),
76(10), 558-559.
Author URL.
Luqmani R, Lee E, Singh S, Gillett M, Schmidt WA, Bradburn M, Dasgupta B, Diamantopoulos AP, Forrester-Barker W, Hamilton W, et al (2015). The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis: a Diagnostic Accuracy and Cost-Effectiveness Study.
ARTHRITIS & RHEUMATOLOGY,
67 Author URL.
Schmidt-Hansen M, Berendse S, Hamilton W (2015). The association between symptoms and bladder or renal tract cancer in primary care: a systematic review.
Br J Gen Pract,
65(640), e769-e775.
Abstract:
The association between symptoms and bladder or renal tract cancer in primary care: a systematic review.
BACKGROUND: Appropriate selection for further investigation of patients presenting in primary care with symptoms that may indicate cancer is key to early diagnosis. AIM: to quantify the risk of urinary tract cancer in patients presenting in primary care with symptoms that may indicate bladder or renal cancer. DESIGN AND SETTING: Systematic review of studies relating to bladder or renal cancer in primary care. METHOD: Databases searched were MEDLINE, PreMEDLINE, Embase, the Cochrane Library, Web of Science (SCI and SSCI), and ISI Proceedings from 1980 to August 2014, and PsycINFO (1980-2012) and BioMed Central (inception to 2012) for retrospective, prospective, or case-control diagnostic accuracy studies of symptomatic patients presenting to primary care with one or more symptoms for whom follow-up data were available. The target conditions were bladder or renal cancer. The studies were appraised using the QUADAS-2 tool. RESULTS: Eleven studies with 3 451 675 patients were included. The positive predictive value (PPV) from meta-analysis of visible haematuria was 5.1% in adult patients. It increased with age and was higher in males. The PPVs of other single symptoms were very low, with the highest non-haematuria PPV being 1.4% for anaemia in males. Fewer data were available on the PPVs of symptom combinations. Generally, these data showed that, with the exception of symptom combinations including haematuria, these were very low. CONCLUSION: the only high-risk feature of bladder/renal cancer in primary care was visible haematuria, and this clearly warrants investigation. However, not all patients with one of these cancers experience haematuria, so a policy restricting investigation to patients with haematuria will inevitably delay the diagnosis in some patients.
Abstract.
Author URL.
Rubin G, Berendsen A, Crawford SM, Dommett R, Earle C, Emery J, Fahey T, Grassi L, Grunfeld E, Gupta S, et al (2015). The expanding role of primary care in cancer control.
Lancet Oncol,
16(12), 1231-1272.
Abstract:
The expanding role of primary care in cancer control.
The nature of cancer control is changing, with an increasing emphasis, fuelled by public and political demand, on prevention, early diagnosis, and patient experience during and after treatment. At the same time, primary care is increasingly promoted, by governments and health funders worldwide, as the preferred setting for most health care for reasons of increasing need, to stabilise health-care costs, and to accommodate patient preference for care close to home. It is timely, then, to consider how this expanding role for primary care can work for cancer control, which has long been dominated by highly technical interventions centred on treatment, and in which the contribution of primary care has been largely perceived as marginal. In this Commission, expert opinion from primary care and public health professionals with academic and clinical cancer expertise—from epidemiologists, psychologists, policy makers, and cancer specialists—has contributed to a detailed consideration of the evidence for cancer control provided in primary care and community care settings. Ranging from primary prevention to end-of-life care, the scope for new models of care is explored, and the actions needed to effect change are outlined. The strengths of primary care—its continuous, coordinated, and comprehensive care for individuals and families—are particularly evident in prevention and diagnosis, in shared follow-up and survivorship care, and in end-of-life care. A strong theme of integration of care runs throughout, and its elements (clinical, vertical, and functional) and the tools needed for integrated working are described in detail. All of this change, as it evolves, will need to be underpinned by new research and by continuing and shared multiprofessional development.
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Author URL.
Robson JC, Kiran A, Maskell J, Hutchings A, Arden N, Dasgupta B, Hamilton W, Emin A, Culliford D, Luqmani RA, et al (2015). The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK.
Annals of the Rheumatic Diseases,
74(1), 129-135.
Abstract:
The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK
Objectives: to evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls.
Abstract.
Torring ML, Murchie P, Esteva M, Hamilton W, Lautrup M, Terhaar J, Vedsted P, Winget M, Rubin G (2015). The signal and the noise in colorectal cancer diagnosis: exploring and explaining the relationship between diagnostic delays and stage at diagnosis using the Ca-PRI Colorectal Cancer Collaboration dataset.
EUROPEAN JOURNAL OF CANCER CARE,
24, 22-22.
Author URL.
Bailey S, Ukoumunne O, Shephard E, Hamilton W (2015). Thrombocytosis: an underused risk marker of cancer in primary care?.
EUROPEAN JOURNAL OF CANCER CARE,
24, 11-11.
Author URL.
Werhun A, Hamilton W (2015). Thyroid function testing in primary care: overused and under-evidenced? a study examining which clinical features correspond to an abnormal thyroid function result.
Fam Pract,
32(2), 187-191.
Abstract:
Thyroid function testing in primary care: overused and under-evidenced? a study examining which clinical features correspond to an abnormal thyroid function result.
BACKGROUND AND AIM: Diagnostic testing is increasing in primary care, including for thyroid disease. This study examined which clinical features were associated with an abnormal thyroid stimulating hormone (TSH) result. DESIGN AND SETTING: This was a cross-sectional study in one general practice of 16,487 patients in Exeter, Devon, UK. METHODS: We examined the primary care records relating to every TSH test taken in the year from August 2012, and extracted symptoms and/or the indication for testing. Associations with an abnormal result were tested using multivariable logistic regression. A cohort study was then performed of 100 patients newly recorded with each of the six features associated with an abnormal test result in the cross-sectional study, and the proportions tested for TSH and the results of that testing identified. RESULTS: Two thousand thirty-five patients (12% of the practice population) had TSH testing in the year. of these 35 (1.7%) had a TSH >4.5 mIU/l, suggesting hypothyroidism, and 7 (0.3%) had TSH
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Mills K, Hall N, Birt L, Banks J, Emery J, Hamilton W, Rubin G, Walter FM (2015). Understanding symptom appraisal and help-seeking in people with symptoms suspicious of pancreatic cancer: a qualitative interview study.
EUROPEAN JOURNAL OF CANCER CARE,
24, 52-52.
Author URL.
Stapley S, Hamilton W (2015). What is the relationship between staging and diagnostic interval in patients aged 40 years and over diagnosed with common cancers between 2000 and 2009?.
EUROPEAN JOURNAL OF CANCER CARE,
24, 51-51.
Author URL.
Jones R, Van den Bruel A, Gerada C, Hamilton W, Kendrick T, Watt G (2015). What should integrated care look like. ?.
Br J Gen Pract,
65(632), 149-151.
Author URL.
Neal RD, Hurt C, Roberts K, Rogers T, Hamilton W, Edwards RT, Tod AM, Parker D, Jones ET, Nelson A, et al (2014). A feasibility randomised controlled trial looking at the effect on lung cancer diagnosis of giving a chest X-ray to smokers aged over 60 with new chest symptoms - the ELCID trial.
LUNG CANCER,
83, S81-S82.
Author URL.
Nicholson BD, McGrath JS, Hamilton W (2014). Bladder cancer in women. BMJ (Online), 348
Nicholson BD, McGrath JS, Hamilton W (2014). Bladder cancer in women. Praxis, 103(19), 304-308.
Nicholson BD, McGrath JS, Hamilton W (2014). Blasenkarzinom bei Frauen. Praxis, 103(19), 1149-1152.
Hamilton W, Neal RD, Stapley S (2014). Building the evidence base for the early symptomatic diagnosis of cancer (the ABC-DEEP Consortium - Workstream 3).
EUROPEAN JOURNAL OF CANCER CARE,
23, 7-7.
Author URL.
Neal RD, Campbell C, Hamilton W, Stapley S, Weller D, Lyratzopoulos G, Emery J, Torring ML, Vedsted P, Rubin G, et al (2014). Building the evidence base for the early symptomatic diagnosis of cancer (the ABC-DEEP consortium) - what are the policy and research implications for the international community?.
EUROPEAN JOURNAL OF CANCER CARE,
23, 34-34.
Author URL.
Neal RD, Din NU, Hamilton W, GBRoumunne OC, Carter B, Stapley S, Rubin G (2014). Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: Analysis of data from the GBR General Practice Research Database.
British Journal of Cancer,
110(3), 584-592.
Abstract:
Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: Analysis of data from the GBR General Practice Research Database
Background:The primary aim was to use routine data to compare cancer diagnostic intervals before and after implementation of the 2005 NICE Referral Guidelines for Suspected Cancer. The secondary aim was to compare change in diagnostic intervals across different categories of presenting symptoms.Methods:Using data from the General Practice Research Database, we analysed patients with one of 15 cancers diagnosed in either 2001-2002 or 2007-2008. Putative symptom lists for each cancer were classified into whether or not they qualified for urgent referral under NICE guidelines. Diagnostic interval (duration from first presented symptom to date of diagnosis in primary care records) was compared between the two cohorts.Results:In total, 37 588 patients had a new diagnosis of cancer and of these 20 535 (54.6%) had a recorded symptom in the year prior to diagnosis and were included in the analysis. The overall mean diagnostic interval fell by 5.4 days (95% CI: 2.4-8.5; P
Abstract.
Neal RD, Din NU, Hamilton W, Ukoumunne OC, Carter B, Stapley S, Rubin G (2014). Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database.
Br J Cancer,
110(3), 584-592.
Abstract:
Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database.
BACKGROUND: the primary aim was to use routine data to compare cancer diagnostic intervals before and after implementation of the 2005 NICE Referral Guidelines for Suspected Cancer. The secondary aim was to compare change in diagnostic intervals across different categories of presenting symptoms. METHODS: Using data from the General Practice Research Database, we analysed patients with one of 15 cancers diagnosed in either 2001-2002 or 2007-2008. Putative symptom lists for each cancer were classified into whether or not they qualified for urgent referral under NICE guidelines. Diagnostic interval (duration from first presented symptom to date of diagnosis in primary care records) was compared between the two cohorts. RESULTS: in total, 37,588 patients had a new diagnosis of cancer and of these 20,535 (54.6%) had a recorded symptom in the year prior to diagnosis and were included in the analysis. The overall mean diagnostic interval fell by 5.4 days (95% CI: 2.4-8.5; P
Abstract.
Author URL.
Banks J, Walter FM, Hall N, Mills K, Hamilton W, Turner KM (2014). Decision making and referral from primary care for possible lung and colorectal cancer: a qualitative study of patients' experiences.
Br J Gen Pract,
64(629), e775-e782.
Abstract:
Decision making and referral from primary care for possible lung and colorectal cancer: a qualitative study of patients' experiences.
BACKGROUND: the challenge for GPs when assessing whether to refer a patient for cancer investigation is that many cancer symptoms are also caused by benign self-limiting illness. UK National Institute for Health and Care Excellence (NICE) referral guidelines emphasise that the patient should be involved in the decision-making process and be informed of the reasons for referral. Research to date, however, has not examined the extent to which these guidelines are borne out in practice. AIM: to assess the degree to which patients are involved in the decision to be referred for investigation for symptoms associated with cancer and their understanding of the referral. DESIGN AND SETTING: Qualitative interview study of patients referred to secondary care for symptoms suspicious of lung and colorectal cancer. Patients were recruited from two regions of England using maximum variation sampling. METHOD: Transcribed interviews were analysed thematically. RESULTS: the analysis was based on 34 patient interviews. Patients in both symptom pathways reported little involvement in the decision to be referred for investigation. This tended to be accompanied by a patient expectation for referral, however, to explain ongoing and un-resolving symptoms. It was also found that reasons for referral tended to be couched in non-specific terms rather than cancer investigation, even when the patient was on a cancer-specific pathway. CONCLUSION: GPs should consider a more overt discussion with patients when referring them for further investigation of symptoms suspicious of cancer. This would align clinical practice with NICE guidelines and encourage more open discussion between GPs and primary care patients around cancer.
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Author URL.
Lim AW, Ramirez AJ, Hamilton W, Sasieni P, Patnick J, Forbes LJ (2014). Delays in diagnosis of young females with symptomatic cervical cancer in England: an interview-based study.
Br J Gen Pract,
64(627), e602-e610.
Abstract:
Delays in diagnosis of young females with symptomatic cervical cancer in England: an interview-based study.
BACKGROUND: Diagnosis may be delayed in young females with cervical cancer because of a failure to recognise symptoms. AIM: to examine the extent and determinants of delays in diagnosis of young females with symptomatic cervical cancer. DESIGN AND SETTING: a national descriptive study of time from symptoms to diagnosis of cervical cancer and risk factors for delay in diagnosis at all hospitals diagnosing cervical cancer in England. METHOD: One-hundred and twenty-eight patients
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Rose PW, Hamilton W, Aldersey K, Barisic A, Dawes M, Foot C, Grunfeld E, Hart N, Neal RD, Pirotta M, et al (2014). Development of a survey instrument to investigate the primary care factors related to differences in cancer diagnosis between international jurisdictions.
BMC Family Practice,
15(1).
Abstract:
Development of a survey instrument to investigate the primary care factors related to differences in cancer diagnosis between international jurisdictions
Background: Survival rates following a diagnosis of cancer vary between countries. The International Cancer Benchmarking Partnership (ICBP), a collaboration between six countries with primary care led health services, was set up in 2009 to investigate the causes of these differences. Module 3 of this collaboration hypothesised that an association exists between the readiness of primary care physicians (PCP) to investigate for cancer - the 'threshold' risk level at which they investigate or refer to a specialist for consideration of possible cancer - and survival for that cancer (lung, colorectal and ovarian). We describe the development of an international survey instrument to test this hypothesis. Methods. The work was led by an academic steering group in England. They agreed that an online survey was the most pragmatic way of identifying differences between the jurisdictions. Research questions were identified through clinical experience and expert knowledge of the relevant literature.A survey comprising a set of direct questions and five clinical scenarios was developed to investigate the hypothesis. The survey content was discussed and refined concurrently and repeatedly with international partners. The survey was validated using an iterative process in England. Following validation the survey was adapted to be relevant to the health systems operating in other jurisdictions and translated into Danish, Norwegian and Swedish, and into Canadian and Australian English. Results: This work has produced a survey with face, content and cross cultural validity that will be circulated in all six countries. It could also form a benchmark for similar surveys in countries with similar health care systems. Conclusions: the vignettes could also be used as educational resources. This study is likely to impact on healthcare policy and practice in participating countries. © 2014 Rose et al.; licensee BioMed Central Ltd.
Abstract.
Coxon D, Campbell C, Walter F, Scott S, Neal R, Vedsted P, Emery J, Rubin G, Hamilton W, Weller D, et al (2014). Development of the 'Aarhus Statement Tool for Researching Intervals in Diagnosis' (ASTRID): focus groups and interviews with patients, researchers and healthcare professionals.
EUROPEAN JOURNAL OF CANCER CARE,
23, 22-22.
Author URL.
Nicholson BD, McGrath JS, Hamilton W (2014). EASILY MISSED? Bladder cancer in women.
BMJ-BRITISH MEDICAL JOURNAL,
348 Author URL.
Thompson E, Griffin T, Hamilton W, Sharp D, Wye L (2014). Economic evaluation of the Bristol Homeopathic Hospital: final results of the BISCUIT feasibility study. Homeopathy, 103(01), 79-79.
Rose P, Vedsted P, Rubin G, Harrison S, Bomb M, Groves B, Hamilton W, Team ICBPM3 (2014). Explaining variation in cancer outcomes between eleven jurisdictions in the International Cancer Benchmarking Partnership: a primary care survey.
EUROPEAN JOURNAL OF CANCER CARE,
23, 30-31.
Author URL.
Walter FM, Emery J, Morris H, Hall N, Mills K, Dobson C, Mendonca S, Bankhead C, Perera R, Hamilton W, et al (2014). Factors associated time to diagnosis and stage at diagnosis of colorectal cancer: a prospective cohort study.
EUROPEAN JOURNAL OF CANCER CARE,
23, 6-6.
Author URL.
Walter FM, Rubin G, Morris HC, Bankhead C, Hall N, Mills K, Dobson C, Perera R, Rintoul R, Hamilton W, et al (2014). Factors associated with time to diagnosis and stage at diagnosis of lung cancer: a prospective cohort study.
EUROPEAN JOURNAL OF CANCER CARE,
23, 3-3.
Author URL.
Taylor PN, Iqbal A, Minassian C, Sayers A, Draman MS, Greenwood R, Hamilton W, Okosieme O, Panicker V, Thomas SL, et al (2014). Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study.
JAMA Intern Med,
174(1), 32-39.
Abstract:
Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study.
IMPORTANCE: Rates of thyroid hormone prescribing in the United States and the United Kingdom have increased substantially. If some of the increase is due to lowering the thyrotropin threshold for treatment, this may result in less benefit and greater harm. OBJECTIVE: to define trends in thyrotropin levels at the initiation of levothyroxine sodium therapy and the risk of developing a suppressed thyrotropin level following treatment. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Retrospective cohort study using data from the United Kingdom Clinical Practice Research Datalink. Among 52,298 individuals who received a prescription for levothyroxine between January 1, 2001, and October 30, 2009, we extracted data about the thyrotropin level before levothyroxine therapy initiation, clinical symptoms, and thyrotropin levels up to 5 years after levothyroxine was initiated. We excluded persons who had a history of hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking thyroid-altering medication or if the levothyroxine prescription was related to pregnancy; and those who did not have a thyrotropin level measured within 3 months before the initiation of levothyroxine. MAIN OUTCOMES AND MEASURES: the median thyrotropin level at the time of the index levothyroxine prescription, the odds of initiation of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L or less, and the age-stratified odds of developing a low or suppressed thyrotropin level after levothyroxine therapy. RESULTS: Between 2001 and 2009, the median thyrotropin level at the initiation of levothyroxine therapy fell from 8.7 to 7.9 mIU/L. The odds ratio for prescribing levothyroxine at thyrotropin levels of 10.0 mIU/L or less in 2009 compared with 2001 (adjusted for changes in population demographics) was 1.30 (95% CI, 1.19-1.42; P <. 001). Older individuals and individuals with cardiac risk factors had higher odds of initiation of levothyroxine therapy with a thyrotropin level 10.0 mIU/L or less. At 5 years after levothyroxine initiation, 5.8% of individuals had a thyrotropin level of
Abstract.
Author URL.
Taylor T, Evangelou N, Porter H, Hamilton W, Kernick D (2014). Headache: two views on the right approach in general practice.
Br J Gen Pract,
64(626), 475-476.
Author URL.
Neal RD, Hamilton W, Rogers TK (2014). Lung cancer.
BMJ,
349 Author URL.
Price SJ, Shephard EA, Stapley SA, Barraclough K, Hamilton WT (2014). Non-visible versus visible haematuria and bladder cancer risk: a study of electronic records in primary care.
Br J Gen Pract,
64(626), e584-e589.
Abstract:
Non-visible versus visible haematuria and bladder cancer risk: a study of electronic records in primary care.
BACKGROUND: Diagnosis of bladder cancer relies on investigation of symptoms presented to primary care, notably visible haematuria. The importance of non-visible haematuria has never been estimated. AIM: to estimate the risk of bladder cancer with non-visible haematuria. DESIGN AND SETTING: a case-control study using UK electronic primary care medical records, including uncoded data to supplement coded records. METHOD: a total of 4915 patients (aged ≥40 years) diagnosed with bladder cancer between January 2000 and December 2009 were selected from the Clinical Practice Research Datalink and matched to 21 718 controls for age, sex, and practice. Variables for visible and non-visible haematuria were derived from coded and uncoded data. Analyses used multivariable conditional logistic regression, followed by estimation of positive predictive values (PPVs) for bladder cancer using Bayes' theorem. RESULTS: Non-visible haematuria (coded/uncoded data) was independently associated with bladder cancer: odds ratio (OR) 20 (95% confidence interval [CI] =12 to 33). The PPV of non-visible haematuria was 1.6% (95% CI = 1.2 to 2.1) in those aged ≥60 years and 0.8% (95% CI = 0.1 to 5.6) in 40-59-year-olds. The PPV of visible haematuria was 2.8% (95% CI = 2.5 to 3.1) and 1.2% (95% CI = 0.6 to 2.3) for the same age groups respectively, lower than those calculated using coded data alone. The proportion of records of visible haematuria in coded, rather than uncoded, format was higher in cases than in controls (P
Abstract.
Author URL.
Martins T, Hamilton W, Ukoumunne O, Banks J, Raine R (2014). Patients' views on testing for prostate cancer: a vignette-based study of primary care attendees.
EUROPEAN JOURNAL OF CANCER CARE,
23, 25-25.
Author URL.
Banks J, Hollinghurst S, Bigwood L, Peters TJ, Walter FM, Hamilton W (2014). Preferences for cancer investigation: a vignette-based study of primary-care attendees.
The Lancet Oncology,
15(2), 232-240.
Abstract:
Preferences for cancer investigation: a vignette-based study of primary-care attendees
Background: the UK lags behind many European countries in terms of cancer survival. Initiatives to address this disparity have focused on barriers to presentation, symptom recognition, and referral for specialist investigation. Selection of patients for further investigation has come under particular scrutiny, although preferences for referral thresholds in the UK population have not been studied. We investigated preferences for diagnostic testing for colorectal, lung, and pancreatic cancers in primary-care attendees. Methods: in a vignette-based study, researchers recruited individuals aged at least 40 years attending 26 general practices in three areas of England between Dec 6, 2011, and Aug 1, 2012. Participants completed up to three of 12 vignettes (four for each of lung, pancreatic, and colorectal cancers), which were randomly assigned. The vignettes outlined a set of symptoms, the risk that these symptoms might indicate cancer (1%, 2%, 5%, or 10%), the relevant testing process, probable treatment, possible alternative diagnoses, and prognosis if cancer were identified. Participants were asked whether they would opt for diagnostic testing on the basis of the information in the vignette. Findings: 3469 participants completed 6930 vignettes. 3052 individuals (88%) opted for investigation in their first vignette. We recorded no strong evidence that participants were more likely to opt for investigation with a 1% increase in risk of cancer (odds ratio [OR] 1·02, 95% CI 0·99-1·06; p=0·189), although the association between risk and opting for investigation was strong when colorectal cancer was analysed alone (1·08, 1·03-1·13; p=0·0001). In multivariable analysis, age had an effect in all three cancer models: participants aged 60-69 years were significantly more likely to opt for investigation than were those aged 40-59 years, and those aged 70 years or older were less likely. Other variables associated with increased likelihood of opting for investigation were shorter travel times to testing centre (colorectal and lung cancers), a family history of cancer (colorectal and lung cancers), and higher household income (colorectal and pancreatic cancers). Interpretation: Participants in our sample expressed a clear preference for diagnostic testing at all risk levels, and individuals want to be tested at risk levels well below those stipulated by UK guidelines. This willingness should be considered during design of cancer pathways, particularly in primary care. The public engagement with our study should encourage general practitioners to involve patients in referral decision making. Funding: the National Institute for Health Research Programme Grants for Applied Research programme. © 2014 Banks et al. Open Access article distributed under the terms of CC BY.
Abstract.
Banks J, Hollinghurst S, Bigwood L, Peters TJ, Walter FM, Hamilton W (2014). Preferences for cancer investigation: a vignette-based study of primary-care attendees.
Lancet Oncol,
15(2), 232-240.
Abstract:
Preferences for cancer investigation: a vignette-based study of primary-care attendees.
BACKGROUND: the UK lags behind many European countries in terms of cancer survival. Initiatives to address this disparity have focused on barriers to presentation, symptom recognition, and referral for specialist investigation. Selection of patients for further investigation has come under particular scrutiny, although preferences for referral thresholds in the UK population have not been studied. We investigated preferences for diagnostic testing for colorectal, lung, and pancreatic cancers in primary-care attendees. METHODS: in a vignette-based study, researchers recruited individuals aged at least 40 years attending 26 general practices in three areas of England between Dec 6, 2011, and Aug 1, 2012. Participants completed up to three of 12 vignettes (four for each of lung, pancreatic, and colorectal cancers), which were randomly assigned. The vignettes outlined a set of symptoms, the risk that these symptoms might indicate cancer (1%, 2%, 5%, or 10%), the relevant testing process, probable treatment, possible alternative diagnoses, and prognosis if cancer were identified. Participants were asked whether they would opt for diagnostic testing on the basis of the information in the vignette. FINDINGS: 3469 participants completed 6930 vignettes. 3052 individuals (88%) opted for investigation in their first vignette. We recorded no strong evidence that participants were more likely to opt for investigation with a 1% increase in risk of cancer (odds ratio [OR] 1·02, 95% CI 0·99-1·06; p=0·189), although the association between risk and opting for investigation was strong when colorectal cancer was analysed alone (1·08, 1·03-1·13; p=0·0001). In multivariable analysis, age had an effect in all three cancer models: participants aged 60-69 years were significantly more likely to opt for investigation than were those aged 40-59 years, and those aged 70 years or older were less likely. Other variables associated with increased likelihood of opting for investigation were shorter travel times to testing centre (colorectal and lung cancers), a family history of cancer (colorectal and lung cancers), and higher household income (colorectal and pancreatic cancers). INTERPRETATION: Participants in our sample expressed a clear preference for diagnostic testing at all risk levels, and individuals want to be tested at risk levels well below those stipulated by UK guidelines. This willingness should be considered during design of cancer pathways, particularly in primary care. The public engagement with our study should encourage general practitioners to involve patients in referral decision making. FUNDING: the National Institute for Health Research Programme Grants for Applied Research programme.
Abstract.
Author URL.
Rubin G, Walter F, Emery J, Neal R, Hamilton W, Wardle J (2014). Research into practice: prompt diagnosis of cancer in primary care.
Br J Gen Pract,
64(625), 428-430.
Author URL.
Birt L, Hall N, Emery J, Banks J, Mills K, Johnson M, Hamilton W, Walter FM (2014). Responding to symptoms suggestive of lung cancer: a qualitative interview study.
BMJ Open Respir Res,
1(1).
Abstract:
Responding to symptoms suggestive of lung cancer: a qualitative interview study.
BACKGROUND: Late diagnosis of lung cancer can impact on survival rates. Patients delay seeking help for a number of reasons. This study explored symptom appraisal and help-seeking decisions among patients referred to specialist respiratory services with symptoms suggestive of lung cancer. METHODS: In-depth qualitative interviews with patients as soon as possible after referral, ideally before diagnosis and mainly within 10
weeks, explored factors impacting on their pathways prior to referral. Framework analysis, underpinned by the Model of Pathways to Treatment, was used to explore the data with particular focus on patients' beliefs and experiences, disease factors and healthcare professional influences. RESULTS: 35 patients were interviewed (aged 41-88
years, 15 women, 17 with lung cancer). All described similar presenting symptoms and triggers to seek help. Appraisal of symptoms was influenced by whether they had a lung comorbidity; seriousness of symptoms was interpreted within the context of previous illness experiences. Help-seeking was triggered when: symptoms failed to respond as expected; there was an increased awareness of symptoms of lung cancer; the public nature of a cough meant others were able to endorse help-seeking. Almost half visited the general practitioner (GP) two or more times before referral; during this period they reinterpreted initial symptoms and appraised new symptoms. The meaning given to symptoms changed over time and many became increasingly concerned they may have lung cancer. The GP played a role in ensuring timely further help-seeking but often there was little guidance on how to monitor symptoms or when to reconsult. CONCLUSIONS: Patients diagnosed with and without lung cancer had similar symptom pathways. Findings provide guidance for lung cancer awareness campaigns on the importance of social networks in endorsing patient help-seeking. The importance of appropriate advice, monitoring and safety-netting procedures by GPs for people presenting with symptoms suggestive of lung cancer is also highlighted.
Abstract.
Author URL.
Walker S, Hyde C, Hamilton W (2014). Risk of breast cancer in symptomatic women in primary care: a case-control study using electronic records.
Br J Gen Pract,
64(629), e788-e793.
Abstract:
Risk of breast cancer in symptomatic women in primary care: a case-control study using electronic records.
BACKGROUND: Breast cancer is the most common cancer in the UK. GPs are encouraged to refer all women whose symptoms may represent cancer, rather than selecting those at highest risk. AIM: to identify and quantify features of breast cancer in primary care. DESIGN AND SETTING: a UK case-control study using the Clinical Practice Research Database (CPRD). METHOD: Possible features of breast cancer were identified in the year before diagnosis, and odds ratios calculated using conditional logistic regression. Positive predictive values (PPVs) were estimated for consulting women. RESULTS: a total of 3994 women aged ≥40 years with breast cancer between 2000 and 2009, and 16 873 age-, sex-, and practice-matched controls were studied. Median age at diagnosis was 63 years (interquartile range 55-74 years). Four features were significantly associated with breast cancer: breast lump (odds ratio [OR] 110; 95% confidence interval [CI] = I88 to 150), breast pain (OR = 4.2; 95% CI = 3.0 to 6.0), nipple retraction (OR = 26; 95% CI = 10 to 64), nipple discharge (OR = 19; 95% CI = 8.6 to 41): all P-values 70 years. PPVs were lower in women who also reported breast pain. CONCLUSION: Generally, the figures support current referral practice. However, the low likelihood of cancer for all the non-lump symptoms means that the current guidance recommends investigation for possible cancer at a more liberal risk threshold than for other cancers. Although supported by patients, this may not meet current NHS criteria for cost-benefit.
Abstract.
Author URL.
Ades AE, Biswas M, Welton NJ, Hamilton W (2014). Symptom lead time distribution in lung cancer: natural history and prospects for early diagnosis.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY,
43(6), 1865-1873.
Author URL.
Ades AE, Biswas M, Welton NJ, Hamilton W (2014). Symptom lead time distribution in lung cancer: natural history and prospects for early diagnosis.
Int J Epidemiol,
43(6), 1865-1873.
Abstract:
Symptom lead time distribution in lung cancer: natural history and prospects for early diagnosis.
BACKGROUND: Before their diagnosis, patients with cancer present in primary care more frequently than do matched controls. This has raised hopes that earlier investigation in primary care could lead to earlier stage at diagnosis. METHODS: We re-analysed primary care symptom data collected from 247 lung cancer cases and 1235 matched controls in Devon, UK. We identified the most sensitive and specific definition of symptoms, and estimated its incidence in cases and controls prior to diagnosis. We estimated the symptom lead time (SLT) distribution (the time between symptoms attributable to cancer and diagnosis), taking account of the investigations already carried out in primary care. The impact of route of diagnosis on stage at diagnosis was also examined. RESULTS: Symptom incidence in cases was higher than in controls 2 years before diagnosis, accelerating markedly in the last 6 months. The median SLT was under 3 months, with mean 5.3 months [95% credible interval (CrI) 4.5-6.1] and did not differ by stage at diagnosis. An earlier stage at diagnosis was observed in patients identified through chest X-ray originated in primary care. CONCLUSIONS: Most symptoms preceded clinical diagnosis by only a few months. Symptom-based investigation would lengthen lead times and result in earlier stage at diagnosis in a small proportion of cases, but would be far less effective than standard screening targeted at smokers.
Abstract.
Author URL.
Brindle LA, Hamilton W, Banerjee A, Dowswell G, Team IPCARDFS (2014). Symptoms that predict chest X-ray results suspicious for lung cancer in UK primary care: results from a prospective study.
EUROPEAN JOURNAL OF CANCER CARE,
23, 3-4.
Author URL.
Taylor PN, Minassian C, Rehman A, Iqbal A, Draman MS, Hamilton W, Dunlop D, Robinson A, Vaidya B, Lazarus JH, et al (2014). TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study.
J Clin Endocrinol Metab,
99(10), 3895-3902.
Abstract:
TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study.
CONTEXT: Thyroid dysfunction is associated with adverse obstetric outcomes, but there is limited information on pregnancy outcomes in women established on levothyroxine. OBJECTIVE: the objective of the study was to determine the relationship between TSH levels and pregnancy outcomes in levothyroxine-treated women in a large community-based database. DESIGN: This was a historical cohort analysis. PATIENTS: Individuals with a first prescription of levothyroxine from 2001 through 2009 (n = 55 501) were identified from the UK General Practice Research Database (population 5 million). of these, we identified 7978 women of child-bearing age (18-45 y) and 1013 pregnancies in which levothyroxine had been initiated at least 6 months before conception. MAIN OUTCOME MEASURES: TSH, miscarriage/delivery status, and obstetric outcomes were measured. RESULTS: Forty-six percent of levothyroxine-treated women aged 18-45 years had a TSH level greater than 2.5 mU/L (recommended upper level in the first trimester). Among pregnant women who had their TSH measured in the first trimester, 62.8% had a TSH level greater than 2.5 mU/L, with 7.4% greater than 10 mU/L. Women with TSH greater than 2.5 mU/L in the first trimester had an increased risk of miscarriage compared with women with TSH 0.2-2.5 mU/L after adjusting for age, year of pregnancy, diabetes, and social class (P =. 008). The risk of miscarriage was increased in women with TSH 4.51-10 mU/L [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.03, 3.14)] and TSH greater than 10 mU/L (OR 3.95, 95% CI 1.87, 8.37) but not with TSH 2.51-4.5 mU/L (OR 1.09, 95% CI 0.61, 1.93). CONCLUSIONS: the majority of levothyroxine-treated women have early gestational TSH levels above the recommended targets (>2.5 mU/L) with a strong risk of miscarriage at levels exceeding 4.5 mU/L. There is an urgent need to improve the adequacy of thyroid hormone replacement in early pregnancy.
Abstract.
Author URL.
Astin MP, Martins T, Neal RD, Rose PW, Hamilton W (2014). The diagnostic value of symptoms of possible oesophagogastric cancers: a systematic review and meta-analysis.
EUROPEAN JOURNAL OF CANCER CARE,
23, 27-28.
Author URL.
Price SJ, Shephard EA, Stapley SA, Barraclough K, Hamilton WT (2014). The risk of bladder cancer with non-visible haematuria: a primary care study using electronic records.
EUROPEAN JOURNAL OF CANCER CARE,
23, 32-32.
Author URL.
Hamilton F, Carroll R, Hamilton W, Salisbury C (2014). The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records.
BRITISH JOURNAL OF CANCER,
111(7), 1410-1420.
Author URL.
Hamilton F, Carroll R, Hamilton W, Salisbury C (2014). The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records.
Br J Cancer,
111(7), 1410-1412.
Abstract:
The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records.
BACKGROUND: the risk of cancer with hypercalcaemia in primary care is unknown. METHODS: This was a cohort study using calcium results in patients aged ⩾40 years in a primary care electronic data set. Diagnoses of cancer in the following year were identified. RESULTS: Participants (54 267) had calcium results: 1674 (3%) were ⩾2.6 mmol l(-1). Hypercalcaemia was strongly associated with cancer, especially in males: OR 2.92, 95% CI 2.17-3.93, P=
Abstract.
Author URL.
Bailey S, Ukoumunne O, Shephard E, Hamilton W (2014). Thrombocytosis: an underused risk marker of cancer in primary care?.
EUROPEAN JOURNAL OF CANCER CARE,
23, 5-5.
Author URL.
Sutton J, Melia J, Weller D, Campbell C, Hamilton W, Moss S (2014). Time intervals in the patient diagnostic pathway: comparison of definitions reported in the literature with the Aarhus statement.
EUROPEAN JOURNAL OF CANCER CARE,
23, 24-24.
Author URL.
Hoyle M, Hamilton W, Rudin C (2014). WHEN IT MAY NOT BE NECESSARY TO MODEL OVERALL SURVIVAL FOR ECONOMIC EVALUATIONS OF ANTI-CANCER DRUGS.
VALUE IN HEALTH,
17(7), A584-A584.
Author URL.
Nicholson BD, McGrath JS, Hamilton W (2014). [In Process Citation].
Praxis (Bern 1994),
103(19), 1149-1152.
Author URL.
Hurt CN, Roberts K, Rogers TK, Griffiths GO, Hood K, Prout H, Nelson A, Fitzgibbon J, Barham A, Thomas-Jones E, et al (2013). A feasibility study examining the effect on lung cancer diagnosis of offering a chest X-ray to higher-risk patients with chest symptoms: Protocol for a randomized controlled trial.
Trials,
14(1).
Abstract:
A feasibility study examining the effect on lung cancer diagnosis of offering a chest X-ray to higher-risk patients with chest symptoms: Protocol for a randomized controlled trial
Background: in order to improve lung cancer survival in the UK, a greater proportion of resectable cancers must be diagnosed. It is likely that resectability rates would be increased by more timely diagnosis. Aside from screening, the only way of achieving this is to reduce the time to diagnosis in symptomatic cancers. Currently, lung cancers are mainly diagnosed by general practitioners (GPs) using the National Institute for Health and Clinical Excellence (NICE) guidelines for urgent referral for chest X-ray, which recommend urgent imaging or referral for patients who have one of a number of chest symptoms for more than 3 weeks. We are proposing to expand this recommendation to include one of a number of chest symptoms of any duration in higher-risk patients.Methods/Design: We intend to conduct a trial of imaging in these higher-risk patients and compare it with NICE guidelines to see if imaging improves stage at diagnosis and resection rates. This trial would have to be large (and consequently resource-intensive) because most of these patients will not have lung cancer, making optimal design crucial. We are therefore conducting a pilot trial that will ascertain the feasibility of running a full trial and provide key information that will be required in order to design the full trial.Discussion: This trial will assess the feasibility and inform the design of a large, UK-wide, clinical trial of a change to the NICE guidelines for urgent referral for chest X-ray for suspected lung cancer. It utilizes a combination of workshop, health economic, quality of life, qualitative, and quantitative methods in order to fully assess feasibility.Trial registration: Clinicaltrials.gov NCT01344005. © 2013 Hurt et al.; licensee BioMed Central Ltd.
Abstract.
Werhun A, Hamilton W (2013). Are we overusing thyroid function tests?.
Br J Gen Pract,
63(613).
Author URL.
Shephard E, Neal R, Rose P, Walter F, Hamilton WT (2013). Clinical features of kidney cancer in primary care: a case-control study using primary care records.
Br J Gen Pract,
63(609), e250-e255.
Abstract:
Clinical features of kidney cancer in primary care: a case-control study using primary care records.
BACKGROUND: Kidney cancer accounts for over 4000 UK deaths annually, and is one of the cancer sites with a poor mortality record compared with Europe. AIM: to identify and quantify all clinical features of kidney cancer in primary care. DESIGN: Case-control study, using General Practice Research Database records. METHOD: a total of 3149 patients aged ≥40 years, diagnosed with kidney cancer between 2000 and 2009, and 14 091 age, sex and practice-matched controls, were selected. Clinical features associated with kidney cancer were identified, and analysed using conditional logistic regression. Positive predictive values for features of kidney cancer were estimated. RESULTS: Cases consulted more frequently than controls in the year before diagnosis: median 16 consultations (interquartile range 10-25) versus 8 (4-15): P
Abstract.
Author URL.
Hamilton W, Coleman MG, Rubin G (2013). Colorectal cancer. BMJ (Online), 347(7924).
Hamilton W, Coleman MG, Rubin G (2013). Colorectal cancer.
BMJ,
346 Author URL.
Prout H, Neal R, Roberts K, Hurt C, Rogers T, Hamilton W, Edwards RT, Todd A, Parker D, Jones ET, et al (2013). ELCID: early lung cancer identification and diagnosis - an embedded interview study to explore patient participation and recruitment. Trials, 14(Suppl 1).
Martins T, Hamilton W, Ukoumunne OC (2013). Ethnic inequalities in time to diagnosis of cancer: a systematic review.
BMC Fam Pract,
14Abstract:
Ethnic inequalities in time to diagnosis of cancer: a systematic review.
BACKGROUND: Minimising diagnostic delays in cancer may help improve survival. Ethnic minorities have worse outcomes in some cancer types when compared to the majority; this may relate in part to differences during the diagnostic phase. Only a few British studies have specifically explored this relationship, and no synthesis of these exists. The present study aimed to systematically review evidence on ethnic inequalities in cancer diagnosis, focussing on patient and primary care intervals of diagnosis. METHODS: Six electronic databases were searched. Included studies were those conducted in the UK or elsewhere (where access to healthcare is comparable to the NHS) and those that described a time element during diagnosis. Study quality was evaluated using the Critical Appraisal Skills Programme (CASP) checklist for cohort studies and synthesis method was narrative. RESULTS: Seven of 8,520 studies retrieved by our search met the review criteria; six conducted in the UK, and one in New Zealand. Five (including one covering several sites) focused on breast cancer, one on prostate, and one on oesophagogastric cancer. The studies employed different methods of ascertainment and definition of ethnic groups and defined diagnostic delay in a non-standardised way; therefore, narrative synthesis was performed. In breast cancer, three studies reported longer diagnostic intervals among ethnic minorities and two found no evidence of differences by ethnicity. There was some evidence of longer diagnostic and referral intervals among ethnic minorities in oesophagogastric and colorectal cancers, but no evidence of this in prostate, non-Hodgkin's lymphoma, lung, and ovarian cancers. None of the studies identified shorter patient or primary care intervals in ethnic minorities. CONCLUSIONS: Existing studies provide insufficient evidence to confirm or refute ethnic inequalities in diagnostic intervals of cancer. Further studies are necessary to examine common cancer types including those frequently found in ethnic minorities (in addition to those covered here) and using current definitions of intervals in cancer diagnosis.
Abstract.
Author URL.
Hamilton W, Green T, Martins T, Elliott K, Rubin G, Macleod U (2013). Evaluation of risk assessment tools for suspected cancer in general practice: a cohort study.
BRITISH JOURNAL OF GENERAL PRACTICE,
63(606).
Author URL.
Dommett R, Stevens M, Redaniel T, Hamilton W, Martin R (2013). FEATURES OF CANCER IN TEENAGERS AND YOUNG ADULTS (TYA) PRESENTING TO PRIMARY CARE IN THE UK: a POPULATION-BASED NESTED CASE-CONTROL STUDY.
PEDIATRIC BLOOD & CANCER,
60, 3-3.
Author URL.
Dommett RM, Redaniel MT, Stevens MCG, Hamilton W, Martin RM (2013). Features of cancer in teenagers and young adults in primary care: a population-based nested case-control study.
British Journal of Cancer,
108(11), 2329-2333.
Abstract:
Features of cancer in teenagers and young adults in primary care: a population-based nested case-control study
Background: Teenagers and young adults (TYA, 15-24 years) diagnosed with cancer report repeated visits to primary care before referral. We investigated associations of symptoms and consultation frequency in primary care with TYA cancers. Methods: Population-based, case-control study was carried out using data from the Clinical Practice Research Datalink (CPRD). A total of 1064 TYA diagnosed with cancer were matched to 13 206 controls. Symptoms independently associated with specific cancers were identified. Likelihood ratios (LRs) and positive predictive values (PPVs) were calculated. Results: in the 3 months before diagnosis, 397 (42.9%) cases consulted ≥4 times vs 593(11.5%) controls (odds ratio (OR): 12.1; 95% CI: 9.7, 15.1), yielding a PPV for any cancer of 0.018%. The LR of lymphoma with a head/neck mass was 434 (95% CI: 60, 3158), with a PPV of 0.5%. Corresponding figures in other cancers included - LR of leukaemia with lymphadenopathy (any site): 29 (95% CI: 8, 112), PPV 0.015%; LR of CNS tumour with seizure: 56 (95% CI: 19, 163), PPV 0.024%; and LR of sarcoma with lump/mass/swelling: 79 (95% CI: 24, 264), PPV 0.042%. Conclusion: Teenagers and young adults with cancer consulted more frequently than controls in the 3 months before diagnosis. Primary care features of cancer match secondary care reports, but were of very low risk; nonetheless, some features increased the likelihood of cancer substantially and should be taken seriously when assessing TYA.
Abstract.
Dommett RM, Redaniel MT, Stevens MCG, Hamilton W, Martin RM (2013). Features of cancer in teenagers and young adults in primary care: a population-based nested case-control study.
Br J Cancer,
108(11), 2329-2333.
Abstract:
Features of cancer in teenagers and young adults in primary care: a population-based nested case-control study.
BACKGROUND: Teenagers and young adults (TYA, 15-24 years) diagnosed with cancer report repeated visits to primary care before referral. We investigated associations of symptoms and consultation frequency in primary care with TYA cancers. METHODS: Population-based, case-control study was carried out using data from the Clinical Practice Research Datalink (CPRD). A total of 1064 TYA diagnosed with cancer were matched to 13,206 controls. Symptoms independently associated with specific cancers were identified. Likelihood ratios (LRs) and positive predictive values (PPVs) were calculated. RESULTS: in the 3 months before diagnosis, 397 (42.9%) cases consulted > or =4 times vs 593(11.5%) controls (odds ratio (OR): 12.1; 95% CI: 9.7, 15.1), yielding a PPV for any cancer of 0.018%. The LR of lymphoma with a head/neck mass was 434 (95% CI: 60, 3158), with a PPV of 0.5%. Corresponding figures in other cancers included - LR of leukaemia with lymphadenopathy (any site): 29 (95% CI: 8, 112), PPV 0.015%; LR of CNS tumour with seizure: 56 (95% CI: 19, 163), PPV 0.024%; and LR of sarcoma with lump/mass/swelling: 79 (95% CI: 24, 264), PPV 0.042%. CONCLUSION: Teenagers and young adults with cancer consulted more frequently than controls in the 3 months before diagnosis. Primary care features of cancer match secondary care reports, but were of very low risk; nonetheless, some features increased the likelihood of cancer substantially and should be taken seriously when assessing TYA.
Abstract.
Author URL.
Grewal K, Hamilton W, Sharp D (2013). Ovarian cancer prediction: Development of a scoring system for primary care.
BJOG: an International Journal of Obstetrics and Gynaecology,
120(8), 1016-1019.
Abstract:
Ovarian cancer prediction: Development of a scoring system for primary care
Objective Recent studies have identified specific symptoms of ovarian cancer at all stages, raising the hope of reducing diagnostic delays. We aimed to devise a scoring system for symptoms of ovarian cancer in primary care. Design Secondary analysis of data from a case-control study. Setting Thirty-nine general practices in Exeter, mid-Devon and east Devon. Population Two hundred and twelve women with ovarian cancer and 1060 age-, sex- and practice-matched controls. Methods Conditional logistic regression was used to produce an additive scoring system and its receiver operator characteristic (ROC) curve. Several different cut-offs were then tested using a simple costs model. Main outcome measures the ROC curve value. Results Each woman was assigned a score based on her symptoms in the year before diagnosis: we added a score for women aged ≥50 years, reflecting their increased incidence of ovarian cancer. The area under the ROC curve was 0.883 (95% confidence interval 0.853-0.912). The chosen cut-off had a sensitivity of 72.6% and a specificity of 91.3%. Conclusion This scoring system could potentially direct general practitioners to appropriate investigations for ovarian cancer on the basis of symptoms and save a substantial number of unnecessary ultrasound scans being requested. © 2013 RCOG.
Abstract.
Dommett RM, Redaniel T, Stevens MCG, Martin RM, Hamilton W (2013). Risk of childhood cancer with symptoms in primary care: a population-based case-control study.
Br J Gen Pract,
63(606), e22-e29.
Abstract:
Risk of childhood cancer with symptoms in primary care: a population-based case-control study.
BACKGROUND: Guidelines describing symptoms in children that should alert GPs to consider cancer have been developed, but without any supporting primary-care research. AIM: to identify symptoms and signs in primary care that strongly increase the likelihood of childhood cancer, to assist GPs in selection of children for investigation. DESIGN AND SETTING: a population-based case-control study in UK general practice. METHOD: Using electronic primary care records from the UK General Practice Research Database, 1267 children aged 0-14 years diagnosed with childhood cancer were matched to 15 318 controls. Clinical features associated with subsequent diagnosis of cancer were identified using conditional logistic regression, and likelihood ratios and positive predictive values (PPVs) were estimated for each. RESULTS: Twelve symptoms were associated with PPVs of ≥0.04%, which represents a greater than tenfold increase in prior probability. The six symptoms with the highest PPVs were pallor (odds ratio, OR = 84; PPV = 0.41% (95% confidence interval [CI] = 0.12% to 1.34%), head and neck masses (OR = 17; PPV = 0.30%; 95% CI = 0.10% to 0.84%), masses elsewhere (OR = 22; PPV = 0.11%; 95% CI = 0.06% to 0.20%), lymphadenopathy (OR = 10; PPV = 0.09%; 95% CI = 0.06% to 0.13%), symptoms/signs of abnormal movement (OR = 16; PPV = 0.08%; 95% CI = 0.04% to 0.14%), and bruising (OR = 12; PPV = 0·08%; 95% CI = 0.05% to 0.13%). When each of these 12 symptoms was combined singly with at least three consultations in a 3-month period, the probability of cancer was between 11 and 76 in 10 000. CONCLUSION: Twelve features of childhood cancers were identified, each of which increased the risk of cancer at least tenfold. These symptoms, particularly when combined with multiple consultations, warrant careful evaluation in general practice.
Abstract.
Author URL.
Walker S, Hyde C, Hamilton W (2013). Risk of uterine cancer in symptomatic women in primary care: case-control study using electronic records.
Br J Gen Pract,
63(614), e643-e648.
Abstract:
Risk of uterine cancer in symptomatic women in primary care: case-control study using electronic records.
BACKGROUND: Uterine cancer is the fourth most common cancer in women in the UK, with approximately 7700 new diagnoses and 1700 deaths annually. AIM: to identify and quantify features of uterine cancer in primary care. DESIGN AND SETTING: Case-control study using electronic primary care records in primary care in the UK. METHOD: Putative features of uterine cancer were identified in the year before diagnosis, and odds ratios (ORs) calculated using conditional logistic regression. Positive predictive values (PPVs) were calculated for women who consulted. RESULTS: a total of 2732 women aged ≥40 years with uterine cancer between 2000 and 2009, and 9537 age-, sex- and practice-matched controls were selected from the General Practice Research Database. The median age at diagnosis was 67 years. Nine features were significantly associated with uterine cancer: postmenopausal bleeding (OR = 160; 95% confidence interval [CI] = 100 to 240), excessive vaginal bleeding (OR = 22; 95% CI = 12 to 42), irregular menstruation (OR = 42; 95% CI = 27 to -63), vaginal discharge (OR = 14; 95% CI = 10 to 21), haematuria (OR = 8.7; 95% CI = 5.0 to 15), abdominal pain (OR = 2.0; 95% CI = 1.4 to 2.8), low haemoglobin (OR = 2.1; 95% CI = 1.5 to 2.9), raised platelets (OR = 1.5; 95% CI = 1.0 to 2.3), and raised glucose (OR = 1.4; 95% CI = 1.1 to 1.8); all P
Abstract.
Author URL.
Walker D, Hamilton W, Walter FM, Watts C (2013). Strategies to accelerate diagnosis of primary brain tumors at the primary-secondary care interface in children and adults.
CNS oncology,
2(5), 447-462.
Abstract:
Strategies to accelerate diagnosis of primary brain tumors at the primary-secondary care interface in children and adults
This article presents a shared view from practitioners with special interests in diagnosing and managing primary brain tumors in both primary and secondary care, in adult and pediatric disciplines; it examines the complexity of identifying whether it would be of benefit and feasible to try to identify those with brain tumors earlier, how this could be achieved and what evidence exists to justify such an approach. The experience of the HeadSmart Campaign in childhood brain tumor, using awareness as a method for driving service change, is used to illustrate how diagnostic practice can be changed across the primary and secondary care interface. This article highlights the importance of focusing upon the needs of patients with primary brain tumors as they represent a significant set of life-threatening and disabling diseases with significant implications for cancer and palliative services.
Abstract.
Robson JC, Kiran A, Maskell J, Hutchings A, Arden N, Dasgupta B, Hamilton W, Emin A, Culliford D, Luqmani RA, et al (2013). The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK.
Annals of the Rheumatic DiseasesAbstract:
The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK
Objectives: to evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. Methods: a UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. Results: Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. Conclusions: Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism.
Abstract.
Robson J, Kiran A, Maskell J, Hutchings A, Arden N, Dasgupta B, Hamilton W, Culliford D, Emin A, Luqmani R, et al (2013). The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK.
PRESSE MEDICALE,
42(4), 672-673.
Author URL.
Hamilton W (2012). A new approach to patients with lower urinary tract symptoms.
BRITISH JOURNAL OF GENERAL PRACTICE,
62(601), 408-408.
Author URL.
Hamilton WT, Watson J, Round A (2012). Authors' reply to Nestel, Choudhary and Choudhary, Al Wakeel, and Helliwell and colleagues. BMJ, 344
Rubin G, Lyratzopoulos G, Abel G, Neal R, Walter F, Hamilton W (2012). Cancer detection in primary care.
LANCET ONCOLOGY,
13(8), E325-E326.
Author URL.
Shephard EA, Stapley S, Neal RD, Rose P, Walter FM, Hamilton WT (2012). Clinical features of bladder cancer in primary care.
Br J Gen Pract,
62(602), e598-e604.
Abstract:
Clinical features of bladder cancer in primary care.
BACKGROUND: Bladder cancer accounts for over 150,000 deaths worldwide. No screening is available, so diagnosis depends on investigations of symptoms. of these, only visible haematuria has been studied in primary care. AIM: to identify and quantify the features of bladder cancer in primary care. DESIGN AND SETTING: Case-control study, using electronic medical records from UK primary care. METHOD: Participants were 4915 patients aged ≥40 years, diagnosed with bladder cancer January 2000 to December 2009, and 21,718 age, sex, and practice-matched controls, were selected from the General Practice Research Database, UK. All clinical features independently associated with bladder cancer using conditional logistic regression were identified, and their positive predictive values for bladder cancer, singly and in combination, were estimated. RESULTS: Cases consulted their GP more frequently than controls before diagnosis: median 15 consultations (interquartile range 9-22) versus 8 (4-15): P
Abstract.
Author URL.
Hamilton W (2012). Computer assisted diagnosis of ovarian cancer in primary care.
BMJ-BRITISH MEDICAL JOURNAL,
344 Author URL.
Hamilton W (2012). DIAGNOSIS Cancer diagnosis in UK primary care.
NATURE REVIEWS CLINICAL ONCOLOGY,
9(5), 251-252.
Author URL.
Torring ML, Frydenberg M, Hamilton W, Hansen RP, Lautrup MD, Vedsted P (2012). Diagnostic interval and mortality in colorectal cancer: U-shaped association demonstrated for three different datasets.
JOURNAL OF CLINICAL EPIDEMIOLOGY,
65(6), 669-678.
Author URL.
Hamilton W, Roobottom C (2012). Early diagnosis of cancer by imaging: the primary care perspective.
Radiography,
18(1), 5-8.
Abstract:
Early diagnosis of cancer by imaging: the primary care perspective
The United Kingdom (UK) performs relatively badly in cancer survival, much of which underperformance is attributed to delays in diagnosis. As a result, increased access to cancer diagnostics for general practitioners is proposed. Four cancer sites and their associated tests have been chosen: lung/chest X-ray, colorectal/colonoscopy, ovarian/trans-vaginal ultrasound and brain tumours/MRI scanning. This article elaborates on the need for these, which patients are likely to be chosen for investigation, and the effect this will have on radiology departments. © 2011 the College of Radiographers.
Abstract.
Hamilton W (2012). Emergency admissions of cancer as a marker of diagnostic delay.
Br J Cancer,
107(8), 1205-1206.
Author URL.
Mahadavan L, Loktionov A, Daniels IR, Shore A, Cotter D, Llewelyn AH, Hamilton W (2012). Exfoliated colonocyte DNA levels and clinical features in the diagnosis of colorectal cancer: a cohort study in patients referred for investigation.
Colorectal Dis,
14(3), 306-313.
Abstract:
Exfoliated colonocyte DNA levels and clinical features in the diagnosis of colorectal cancer: a cohort study in patients referred for investigation.
AIM: Selection of patients for investigation of suspected colorectal cancer is difficult. One possible improvement may be to measure DNA isolated from exfoliated cells collected from the rectum. METHOD: This was a cohort study in a surgical clinic. Participants were aged ≥40 years and referred for investigation of suspected colorectal cancer. Exclusion criteria were inflammatory bowel disease, previous gastrointestinal malignancy, or recent investigation. A sample of the mucocellular layer of the rectum was taken with an adapted proctoscope (the Colonix system). Haemoglobin, mean cell volume, ferritin, carcino-embryonic antigen and faecal occult bloods were tested. Analysis was by logistic regression. RESULTS: Participation was offered to 828 patients, of whom 717 completed the investigations. Three were lost to follow up. Seventy-two (10%) had colorectal cancer. Exfoliated cell DNA was higher (P
Abstract.
Author URL.
Dommett R, Redaniel T, Stevens M, Hamilton W, Martin R (2012). Features of childhood cancer in primary care: a population-based nested case-control study. Archives of Disease in Childhood, 97(Suppl 1).
Dommett RM, Redaniel MT, Stevens MCG, Hamilton W, Martin RM (2012). Features of childhood cancer in primary care: a population-based nested case-control study.
Br J Cancer,
106(5), 982-987.
Abstract:
Features of childhood cancer in primary care: a population-based nested case-control study.
BACKGROUND: This study investigated the risk of cancer in children with alert symptoms identified in current UK guidance, or with increased consultation frequency in primary care. METHODS: a population-based, nested case-control study used data from the General Practice Research Database. In all, 1267 children age 0-14 years diagnosed with childhood cancer were matched to 15,318 controls. Likelihood ratios and positive predictive values (PPVs) were calculated to assess risk. RESULTS: Alert symptoms recorded in the 12 and 3 months before diagnosis were present in 33.7% and 27.0% of cases vs 5.4% and 1.4% of controls, respectively. The PPV of having cancer for any alert symptom in the 3 months before diagnosis was 0.55 per 1000 children. Cases consulted more frequently particularly in the 3 months before diagnosis (86% cases vs 41% controls). of these, 36% of cases and 9% of controls had consulted 4 times or more. The PPV for cancer in a child consulting 4 times or more in 3 months was 0.13 per 1000 children. CONCLUSION: Alert symptoms and frequent consultations are associated with childhood cancer. However, individual symptoms and consultation patterns have very low PPVs for cancer in primary care (e.g. of 10,000 children with a recorded alert symptom, approximately 6 would be diagnosed with cancer within 3 months).
Abstract.
Author URL.
Taylor A, Stapley S, Hamilton W (2012). Jaundice in primary care: a cohort study of adults aged > 45 years using electronic medical records.
FAMILY PRACTICE,
29(4), 416-420.
Author URL.
Grewal K, Hamilton W, Sharp D (2012). Ovarian cancer: a scoring system for primary care.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY,
119, 158-158.
Author URL.
Hamilton WT, Watson J, Round A (2012). RAISED INFLAMMATORY MARKERS Authors' reply to Nestel, Choudhary and Choudhary, Al Wakeel, and Helliwell and colleagues.
BRITISH MEDICAL JOURNAL,
344 Author URL.
Watson J, Round A, Hamilton W (2012). RATIONAL TESTING Raised inflammatory markers.
BMJ-BRITISH MEDICAL JOURNAL,
344 Author URL.
Watson J, Round A, Hamilton W (2012). Raised inflammatory markers. Praxis, 101(11), 729-733.
Dommett R, Redaniel T, Martin R, Hamilton W, Stevens M (2012). THE RISK OF CHILDHOOD CANCER WITH SYMPTOMS/SIGNS PRESENTING IN PRIMARY CARE IN THE UK: a POPULATION-BASED CASE-CONTROL STUDY.
PEDIATRIC BLOOD & CANCER,
59(6), 994-994.
Author URL.
Weller D, Vedsted P, Rubin G, Walter FM, Emery J, Scott S, Campbell C, Andersen RS, Hamilton W, Olesen F, et al (2012). The Aarhus statement: improving design and reporting of studies on early cancer diagnosis. British Journal of Cancer
Stapley S, Peters TJ, Neal RD, Rose PW, Walter FM, Hamilton W (2012). The risk of oesophago-gastric cancer in symptomatic patients in primary care: a large case-control study using electronic records. British Journal of Cancer
Stapley S, Peters TJ, Neal RD, Rose PW, Walter FM, Hamilton W (2012). The risk of pancreatic cancer in symptomatic patients in primary care: a large case-control study using electronic records.
British Journal of Cancer,
106(12), 1940-1944.
Abstract:
The risk of pancreatic cancer in symptomatic patients in primary care: a large case-control study using electronic records
Background: over 8000 new pancreatic cancers are diagnosed annually in the UK; most at an advanced stage, with only 3% 5-year survival. We aimed to identify and quantify the risk of pancreatic cancer for features in primary care. Methods: a case-control study using electronic primary care records identified and quantified the features of pancreatic cancer. Cases, aged ≥ 40 in the General Practice Research Database, UK, with primary pancreatic cancer were matched with controls on age, sex and practice. Putative features of pancreatic cancer were identified in the year before diagnosis. Odds ratios (OR) were calculated for features of cancer using conditional logistic regression. Positive predictive values (PPV) were calculated for consulting patients. Results: in all, 3635 cases and 16 459 controls were studied. Nine features were associated with pancreatic cancer (all P1%. Conclusion: Most previously reported symptoms of pancreatic cancer were also relevant in primary care. Although predictive values were small-apart from jaundice-they provide a basis for selection of patients for investigation, especially with multiple symptoms. © 2012 Cancer Research UK all rights reserved.
Abstract.
Stapley S, Peters TJ, Neal RD, Rose PW, Walter FM, Hamilton W (2012). The risk of pancreatic cancer in symptomatic patients in primary care: a large case-control study using electronic records.
Br J Cancer,
106(12), 1940-1944.
Abstract:
The risk of pancreatic cancer in symptomatic patients in primary care: a large case-control study using electronic records.
BACKGROUND: over 8000 new pancreatic cancers are diagnosed annually in the UK; most at an advanced stage, with only 3% 5-year survival. We aimed to identify and quantify the risk of pancreatic cancer for features in primary care. METHODS: a case-control study using electronic primary care records identified and quantified the features of pancreatic cancer. Cases, aged ≥40 in the General Practice Research Database, UK, with primary pancreatic cancer were matched with controls on age, sex and practice. Putative features of pancreatic cancer were identified in the year before diagnosis. Odds ratios (OR) were calculated for features of cancer using conditional logistic regression. Positive predictive values (PPV) were calculated for consulting patients. RESULTS: in all, 3635 cases and 16,459 controls were studied. Nine features were associated with pancreatic cancer (all P
Abstract.
Author URL.
Watson J, Round A, Hamilton W (2012). [Increased inflammatory markers].
Praxis (Bern 1994),
101(11), 729-733.
Author URL.
Wye L, Thompson E, Hamilton W, Sharp D, Park A-L, McDaid D (2011). A half eaten biscuit: Mid study reflections on the feasibility of economically evaluating the Bristol Homeopathic Hospital using a matched controlled cohort approach (the BISCUIT study). European Journal of Integrative Medicine, 3(2).
Astin MP, Neal RD, Rose PW, Hamilton W (2011). Authors' response. British Journal of General Practice, 61(588).
Hamilton W, Vedsted P (2011). Cancer and primary care: the clinical and research agenda.
BRITISH JOURNAL OF GENERAL PRACTICE,
61(592), 653-654.
Author URL.
Hamilton W, Roobottom C (2011). Chronic daily headache.
BRITISH JOURNAL OF GENERAL PRACTICE,
61(583), 143-144.
Author URL.
Tørring ML, Frydenberg M, Hansen RP, Olesen F, Hamilton W, Vedsted P (2011). Erratum: Time to diagnosis and mortality in colorectal cancer: a cohort study in primary care (British Journal of Cancer (2011) 104 (934-940) DOI: 10.1038/bjc.2011.60). British Journal of Cancer, 104(12).
Hamilton W, Watson J, Round A (2011). Fatigue: Clarifications in primary care. Praxis, 100(2), 99-103.
Stapley S, Hamilton W (2011). Gynaecological symptoms reported by young women: examining the potential for earlier diagnosis of cervical cancer.
Fam Pract,
28(6), 592-598.
Abstract:
Gynaecological symptoms reported by young women: examining the potential for earlier diagnosis of cervical cancer.
BACKGROUND: Cervical cancer occurs at a younger age than most adult cancers. A pre-malignant stage can be identified at screening and treated. Screening begins at the age of 25 years in England, so in women younger than this, and in those who decline screening, cervical cancer can only be identified with symptoms. Aim. To identify the frequency of attendance for gynaecological conditions by young English women. DESIGN: Historical cohort study using electronic primary care records. METHODS: a cohort of English women aged 15-29 years was prepared from the General Practice Research Database. All gynaecological consultations were identified and collated. Frequencies of gynaecological consultation were analysed in three age bands: 15-19, 20-24 and 25-29 years and by calendar year. RESULTS: the number of women available for study for each year ranged from 32 968 to 45 807. The percentage of women having any gynaecological consultation increased from 17.7% to 33.3% over the 7 years. If contraception is excluded, the percentages are 11.3% in 2003, rising to 20.1% in 2009. The rise in consultations occurred in all age bands and across most symptom categories. Post-coital bleeding and inter-menstrual bleeding-the two classic presentations of cervical cancer-were reported by 0.5% and 1.6% of women in 2009. CONCLUSIONS: Gynaecological complaints are frequent in primary care, though the symptoms of possible cervical cancer only represent a small minority of the total. Although the chance of cancer in young women with abnormal vaginal bleeding is very small, visualization of the cervix is appropriate.
Abstract.
Author URL.
Damery S, Ryan R, Wilson S, Ismail T, Hobbs R, ICOS ICO (2011). Iron deficiency anaemia and delayed diagnosis of colorectal cancer: a retrospective cohort study.
COLORECTAL DISEASE,
13(4), E53-E60.
Author URL.
Watson J, Humphrey A, Peters-Klimm F, Hamilton W (2011). Motivation and satisfaction in GP training: a UK cross-sectional survey.
Br J Gen Pract,
61(591), e645-e649.
Abstract:
Motivation and satisfaction in GP training: a UK cross-sectional survey.
BACKGROUND: Recruitment to general practice has had periods of difficulty, but is currently going through a phase of relative popularity in the UK. AIM: to explore motivators for career choice and career satisfaction among UK GP trainees and newly qualified GPs. DESIGN AND SETTING: Cross-sectional web-based questionnaire of GP trainees and GPs within the first 5 years of qualification in the UK. METHOD: all 9557 UK GP trainees and 8013 GPs who were within the first 5 years of qualification were invited to participate by email. Further publicity was conducted via general practice publications and the internet. RESULTS: Overall, there were 2178 responses to the questionnaire (12.4% response rate, 61.5% women, 61.8% trainees). Levels of satisfaction were high, with 83% of responders stating that they would choose to be a doctor again; of these, 95% would choose to be a GP again. The most frequently cited reason for choosing general practice was 'compatibility with family life', which was chosen by 76.6% of women and 63.2% of men (P
Abstract.
Author URL.
Dommett R, Redaniel T, Hamilton W, Martin R, Stevens M (2011). PATTERNS OF PRIMARY CARE CONSULTATION IN CHILDREN AND YOUNG PEOPLE PRIOR TO THE DIAGNOSIS OF CANCER.
PEDIATRIC BLOOD & CANCER,
57(5), 740-741.
Author URL.
Coleman MP, Rachet B, Woods L, Berrino F, Butler J, Capocaccia R, Dickman P, Gavin A, Giorgi R, Hamilton W, et al (2011). Rebuttal to editorial saying cancer survival statistics are misleading. BMJ, 343(7814).
Marshall T, Lancashire R, Sharp D, Peters TJ, Cheng KK, Hamilton W (2011). The diagnostic performance of scoring systems to identify symptomatic colorectal cancer compared to current referral guidance. Gut, 60(9), 1242-1248.
Astin MP, Neal RD, Rose PW, Hamilton W (2011). The diagnostic value of symptoms for colorectal cancer in primary care response.
BRITISH JOURNAL OF GENERAL PRACTICE,
61(588), 441-441.
Author URL.
Astin M, Griffin T, Neal RD, Rose P, Hamilton W (2011). The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review.
Br J Gen Pract,
61(586), e231-e243.
Abstract:
The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review.
BACKGROUND: over 37,000 new colorectal cancers are diagnosed in the UK each year. Most present symptomatically to primary care. AIM: to conduct a systematic review of the diagnostic value of symptoms associated with colorectal cancer. DESIGN: Systematic review. METHOD: MEDLINE, Embase, Cochrane Library, and CINAHL were searched to February 2010, for diagnostic studies of symptomatic adult patients in primary care. Studies of asymptomatic patients, screening, referred populations, or patients with colorectal cancer recurrences, or with fewer than 100 participants were excluded. The target condition was colorectal cancer. Data were extracted to estimate the diagnostic performance of each symptom or pair of symptoms. Data were pooled in a meta-analysis. The quality of studies was assessed with the QUADAS tool. RESULTS: Twenty-three studies were included. Positive predictive values (PPVs) for rectal bleeding from 13 papers ranged from 2.2% to 16%, with a pooled estimate of 8.1% (95% confidence interval [CI] = 6.0% to 11%) in those aged ≥ 50 years. Pooled PPV estimates for other symptoms were: abdominal pain (three studies) 3.3% (95% CI = 0.7% to 16%); and anaemia (four studies) 9.7% (95% CI = 3.5% to 27%). For rectal bleeding accompanied by weight loss or change in bowel habit, pooled positive likelihood ratios (PLRs) were 1.9 (95% CI = 1.3 to 2.8) and 1.8 (95% CI = 1.3 to 2.5) respectively, suggesting higher risk when both symptoms were present. Conversely, the PLR was one or less for abdominal pain, diarrhoea, or constipation accompanying rectal bleeding. CONCLUSION: the findings suggest that investigation of rectal bleeding or anaemia in primary care patients is warranted, irrespective of whether other symptoms are present. The risks from other single symptoms are lower, though multiple symptoms also warrant investigation.
Abstract.
Author URL.
Shephard E, Stapley S, Hamilton W (2011). The use of electronic databases in primary care research. Family Practice, 28(4), 352-354.
Tørring ML, Frydenberg M, Hansen RP, Olesen F, Hamilton W, Vedsted P (2011). Time to diagnosis and mortality in colorectal cancer: a cohort study in primary care.
British Journal of Cancer,
104(6), 934-940.
Abstract:
Time to diagnosis and mortality in colorectal cancer: a cohort study in primary care
Background:The relationship between the diagnostic interval and mortality from colorectal cancer (CRC) is unclear. This association was examined by taking account of important confounding factors at the time of first presentation of symptoms in primary care.Methods:A total of 268 patients with CRC were included in a prospective, population-based study in a Danish county. The diagnostic interval was defined as the time from first presentation of symptoms until diagnosis. We analysed patients separately according to the general practitioner's interpretation of symptoms. Logistic regression was used to estimate 3-year mortality odds ratios as a function of the diagnostic interval using restricted cubic splines and adjusting for tumour site, comorbidity, age, and sex.Results:In patients presenting with symptoms suggestive of cancer or any other serious illness, the risk of dying within 3 years decreased with diagnostic intervals up to 5 weeks and then increased (P0.002). In patients presenting with vague symptoms, the association was reverse, although not statistically significant.Conclusion:Detecting cancer in primary care is two sided: aimed at expediting ill patients while preventing healthy people from going to hospital. This likely explains the counterintuitive findings; but it does not explain the increasing mortality with longer diagnostic intervals. Thus, this study provides evidence for the hypothesis that the length of the diagnostic interval affects mortality in CRC patients. © 2011 Cancer Research UK all rights reserved.
Abstract.
Hamilton W, Watson J, Round A (2011). [Not Available].
Praxis (Bern 1994),
100(2), 99-103.
Author URL.
Hamilton W (2010). Cancer diagnosis in primary care.
Br J Gen Pract,
60(571), 121-128.
Abstract:
Cancer diagnosis in primary care.
Around a quarter of those in the developed world die of cancer. Most cancers present to primary care with symptoms, even when there is a screening test for the particular cancer. However, the symptoms of cancer are also symptoms of benign disease, and the GP has to judge whether cancer is a possible explanation. Very little research examined this process until relatively recently. This review paper examines the process of primary care diagnosis, especially the selection of patients for rapid investigation. It concentrates on the four commonest UK cancers: breast, lung, colon, and prostate as these have been the subject of most recent studies.
Abstract.
Author URL.
Hamilton WT, Astin MP, Griffin T, Neal RD, Rose PW (2010). Colorectal cancer Secondary care data may mislead.
BRITISH MEDICAL JOURNAL,
340 Author URL.
Hamilton W, Watson J, Round A (2010). Investigating fatigue in primary care.
BMJ,
341 Author URL.
Hamilton W, Menon U (2010). Ovarian cancer. BMJ (Online), 340(7737).
Barrett J, Sharp DJ, Stapley S, Stabb C, Hamilton W (2010). Pathways to the diagnosis of ovarian cancer in the UK: a cohort study in primary care.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY,
117(8), 1033-1034.
Author URL.
Barrett J, Sharp DJ, Stapley S, Stabb C, Hamilton W (2010). Pathways to the diagnosis of ovarian cancer in the UK: a cohort study in primary care.
BJOG,
117(5), 610-614.
Abstract:
Pathways to the diagnosis of ovarian cancer in the UK: a cohort study in primary care.
OBJECTIVE: to identify the routes patients with ovarian cancer take between first symptom presentation and diagnosis. DESIGN: Cohort study. SETTING: the study took place in 39 general practices in Devon, UK. POPULATION: all ovarian cancer patients identified in the practices, with a diagnosis between 2000 and 2007 inclusive. METHODS: all patients had their cancer symptoms, referrals, and diagnoses identified and dated using their doctors' records. MAIN OUTCOME MEASURES: Numbers of patients taking specific routes to diagnosis, together with the time taken to diagnosis. RESULTS: Three main routes to diagnosis emerged. The first was the expected route of outpatient referral: 195 (92% of the total) had at least one of the seven ovarian cancer symptoms or an abdominal mass. A total of 123 (58%) were referred to a specialist, although only 65 (31%) were referred to a gynaecologist. Thirty-five (17%) were initially investigated within primary care by ultrasound scanning, and a further 35 (17%) were admitted as emergencies. The interval from first symptom to referral was similar across the different pathways, with a median (interquartile range) time between the first symptom presenting to primary care and first investigation or referral being 2.5 (0, 27.5) days. The median interval from first symptom reported in primary care to diagnosis was 74.5 (32, 159) days. CONCLUSIONS: Only a minority of ovarian cancer patients follow the expected route to diagnosis, of urgent referral to a gynaecologist. In most women, GPs rapidly identified the need to investigate. Avoidable delays generally occurred after the decision to investigate was made.
Abstract.
Author URL.
Moss-Morris R, Hamilton W (2010). Pragmatic rehabilitation for chronic fatigue syndrome. BMJ (Online), 340(7753).
Hamilton W, Watson J, Round A (2010). Rational testing: Investigating fatigue in primary care. BMJ (Online), 341(7771), 502-504.
Hamilton WT, Astin MP, Griffin T, Neal RD, Rose PW (2010). Secondary care data may mislead. BMJ (Online), 340(7755).
Rubin G, Hamilton W (2009). Alarm features of colorectal cancer.
GUT,
58(7), 1026-1026.
Author URL.
Hamilton W, Menon U (2009). Easily missed? Ovarian cancer.
BRITISH MEDICAL JOURNAL,
339 Author URL.
Hamilton W (2009). Five misconceptions in cancer diagnosis.
Br J Gen Pract,
59(563), 441-447.
Abstract:
Five misconceptions in cancer diagnosis.
Much investment has been put into facilities for early cancer diagnosis. It is difficult to know how successful this investment has been. New facilities for rapid investigation in the UK have not reduced mortality, and may cause delays in diagnosis of patients with low-risk, or atypical, symptoms. In part, the failure of new facilities to translate into mortality benefits can be explained by five misconceptions. These are described, along with suggested research and organisational remedies. The first misconception is that cancer is diagnosed in hospitals. Consequently, secondary care data have been used to drive primary care decisions. Second, GPs are thought to be poor at cancer diagnosis, yet the type of education on offer to improve this may not be what is needed. Third, symptomatic cancer diagnosis has been downgraded in importance with the introduction of screening, yet screening identifies only a small minority of cancers. Fourth, pressure is put on GPs to make referrals for those with an individual high risk of cancer - disenfranchising those with 'low-risk but not no-risk' symptoms. Finally, considerable nihilism exists about the value of early diagnosis, despite considerable observational evidence that earlier diagnosis of symptomatic cancer is beneficial.
Abstract.
Author URL.
Hamilton W, Peters TJ, Sharp D (2009). Ovarian cancer Reply.
BRITISH MEDICAL JOURNAL,
339 Author URL.
Hamilton W, Menon U (2009). Ovarian cancer.
BMJ,
339 Author URL.
Hamilton W, Peters TJ, Sharp D (2009). Ovarian cancer: Authors' reply. BMJ (Online), 339(7728).
Hamilton W, Round A, Sharp D (2009). Ovarian cancer: Not a silent killer. BMJ (Online), 339(7713).
Hamilton WT, Gallagher AM, Thomas JM, White PD (2009). Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study in primary care.
Psychol Med,
39(11), 1913-1921.
Abstract:
Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study in primary care.
BACKGROUND: Fatigue syndromes and irritable bowel syndrome (IBS) often occur together. Explanations include being different manifestations of the same condition and simply sharing some symptoms. METHOD: a matched case-control study in UK primary care, using data collected prospectively in the General Practice Research Database (GPRD). The main outcome measures were: health-care utilization, specific symptoms and diagnoses. Risk markers were divided into distant (from 3 years to 1 year before diagnosis) and recent (1 year before diagnosis). RESULTS: a total of 4388 patients with any fatigue syndrome were matched to two groups of patients: those attending for IBS and those attending for another reason. Infections were specific risk markers for both syndromes, with viral infections being a risk marker for a fatigue syndrome [odds ratios (ORs) 2.3-6.3], with a higher risk closer to onset, and gastroenteritis a risk for IBS (OR 1.47, compared to a fatigue syndrome). Chronic fatigue syndrome (CFS) shared more distant risk markers with IBS than other fatigue syndromes, particularly other symptom-based disorders (OR 3.8) and depressive disorders (OR 2.3), but depressive disorders were a greater risk for CFS than IBS (OR 2.4). Viral infections were more of a recent risk marker for CFS compared to IBS (OR 2.8), with gastroenteritis a greater risk for IBS (OR 2.4). CONCLUSIONS: Both fatigue and irritable bowel syndromes share predisposing risk markers, but triggering risk markers differ. Fatigue syndromes are heterogeneous, with CFS sharing predisposing risks with IBS, suggesting a common predisposing pathophysiology.
Abstract.
Author URL.
Hamilton W, Peters TJ, Bankhead C, Sharp D (2009). Risk of ovarian cancer in women with symptoms in primary care: Population based case-control study.
BMJ (Online),
339(7721).
Abstract:
Risk of ovarian cancer in women with symptoms in primary care: Population based case-control study
Objective: to identify and quantify symptoms of ovarian cancer in women in primary care. Design: Case-control study, with coding of participants' primary care records for one year before diagnosis. Setting: 39 general practices in Devon, England. Participants: 212 women aged over 40 with a diagnosis of primary ovarian cancer, 2000-7; 1060 controls matched by age and general practice. Main outcome measures: Odds ratios and positive predictive values for symptoms from conditional logistic regression analyses. Results: Seven symptoms were associated with ovarian cancer in multivariable analysis. The univariable positive predictive values and multivariable odds ratios (with 95% confidence intervals) for these were 2.5% (1.2% to 5.9%) and 240 (46 to 1200) for abdominal distension; 0.5% (0.2% to 0.9%) and 24 (9.3 to 64) for postmenopausal bleeding; 0.6% (0.3% to 1.0%) and 17 (6.1 to 50) for loss of appetite; 0.2% (0.1% to 0.3%) and 16 (5.6 to 48) for increased urinary frequency; 0.3% (0.2% to 0.3%) and 12 (6.1 to 22) for abdominal pain; 0.2% (0.1% to 0.4%) and 7.6 (2.5 to 23) for rectal bleeding; and 0.3% (0.2% to 0.6%) and 5.3 (1.8 to 16) for abdominal bloating. In 181 (85%) cases and 164 (15%) controls at least one of these seven symptoms was reported to primary care before diagnosis. After exclusion of symptoms reported in the 180 days before diagnosis, abdominal distension, urinary frequency, and abdominal pain remained independently associated with a diagnosis of ovarian cancer. Conclusions: Women with ovarian cancer usually have symptoms and report them to primary care, sometimes months before diagnosis. This study provides an evidence base for selection of patients for investigation, both for clinicians and for developers of guidelines.
Abstract.
Hamilton W, Peters TJ, Bankhead C, Sharp D (2009). Risk of ovarian cancer in women with symptoms in primary care: population based case-control study.
BMJ,
339Abstract:
Risk of ovarian cancer in women with symptoms in primary care: population based case-control study.
To identify and quantify symptoms of ovarian cancer in women in primary care.
Abstract.
Author URL.
Hamilton W (2009). The CAPER studies: five case-control studies aimed at identifying and quantifying the risk of cancer in symptomatic primary care patients.
Br J Cancer,
101 Suppl 2(Suppl 2), S80-S86.
Abstract:
The CAPER studies: five case-control studies aimed at identifying and quantifying the risk of cancer in symptomatic primary care patients.
BACKGROUND: This paper reviews the background to five primary care case-control studies, collectively known as the CAPER studies (Cancer Prediction in Exeter). These studies, on colorectal, lung, prostate and brain tumours, sought to identify the particular features of cancer as reported to primary care. They also sought to quantify the risk of cancer for symptoms and primary care investigations, both individually and paired together. METHODS: Two studies were on colorectal cancer: the former with 349 cases used hand searching and coding of entries, while the latter obtained 6442 cases from a national electronic database. The lung and prostate studies had 247 and 217 cases, respectively, and used manual methods. The brain study also used a national electronic database, which provided 3505 cases. RESULTS: Generally, the symptoms matched previous series from secondary care, though the risks of cancer, expressed as positive predictive values, were lower. Rectal bleeding in colorectal cancer, and haemoptysis in lung cancer both had positive predictive values of 2.4%. The risk of a brain tumour with headache was one in a thousand. INTERPRETATION: the results identify areas where current guidance on urgent referral for investigation of suspected cancer could be improved.
Abstract.
Author URL.
Hamilton W, Lancashire R, Sharp D, Peters TJ, Cheng K, Marshall T (2009). The risk of colorectal cancer with symptoms at different ages and between the sexes: a case-control study.
BMC Med,
7Abstract:
The risk of colorectal cancer with symptoms at different ages and between the sexes: a case-control study.
BACKGROUND: Colorectal cancer is generally diagnosed following a symptomatic presentation to primary care. Although the presenting features of the cancer are well described, the risks they convey are less well known. This study aimed to quantify the risk of cancer for different symptoms, across age groups and in both sexes. METHODS: This was a case-control study using pre-existing records in a large electronic primary care database. Cases were patients aged 30 years or older with a diagnosis of colorectal cancer between January 2001 and July 2006, matched to seven controls by age, sex and practice. All features of colorectal cancer recorded in the 2 years before diagnosis were identified. Features independently associated with cancer were identified using multivariable conditional logistic regression, and their risk of cancer quantified. RESULTS: We identified 5477 cases, with 38,314 age, sex and practice-matched controls. Six symptoms and two abnormal investigations (anaemia and microcytosis) were independently associated with colorectal cancer. The positive predictive values of symptoms were: rectal bleeding, positive predictive value for a male aged > or = 80 years 4.5% (95% confidence interval 3.5, 5.9); change in bowel habit 3.9% (2.8, 5.5); weight loss 0.8% (0.5, 1.3); abdominal pain 1.2% (1.0, 1.4); diarrhoea 1.2% (1.0, 1.5) and constipation 0.7% (0.6, 0.8). Positive predictive values were lower in females and younger patients. Only 27% of patients had reported either of the two higher risk symptoms. CONCLUSION: Most symptomatic colorectal cancers present with only a low-risk symptom. There is a need to find a method of identifying those at highest risk of cancer from the large number presenting with such symptoms.
Abstract.
Author URL.
Kernick D, Stapley S, Campbell J, Hamilton W (2009). What happens to new-onset headache in children that present to primary care? a case-cohort study using electronic primary care records.
Cephalalgia,
29(12), 1311-1316.
Abstract:
What happens to new-onset headache in children that present to primary care? a case-cohort study using electronic primary care records.
The aim was to describe the consulting behaviour and clinical outcomes of children presenting with headache in primary care. This was a historical cohort study using data from the UK General Practitioner Research Database. Cases were children aged 5-17 years who presented to primary care with primary headache (migraine, tension-type headache, cluster headache) or undifferentiated headache (no further descriptor). Controls were age, sex and practice matched. Their records were examined for consultations, referrals, relevant treatments and specific diseases in the subsequent year. Children with headache (n = 48 575) were identified and matched to controls. At presentation, 9321 (19.2%) of headaches were labelled primary, 549 (1.1%) secondary and 38 705 (79.7%) received no formal diagnosis. of the latter group, 2084 (5.4%) received a primary headache diagnosis in the subsequent year. Following a diagnosis of migraine, 258 (3.5%) had received a triptan and 1598 (21%) were using propranolol or pizotifen. Total consultations were higher in cases than in controls in the year before the headache: cases ages 5-8 years, mean (s.d.) 5.0 (4.0) consultations; controls 4.0 (3.5) consultations. In 1 year controls had 43 430 consultations, of which 256 (0.6%) were for headache, of whom 64 (25%) were referred to secondary care. Headache was a risk factor for benign and malignant tumours, cerebrovascular disease, primary disorders of raised intracranial pressure and depression. This risk was reduced if a diagnosis of a primary headache disorder could be made. Although there is an increased likelihood of a serious pathology with headache presentations, the risk is small particularly if a diagnosis of a primary headache is made. General practitioners are likely to be underdiagnosing migraine. This study can inform management guidelines for new presentations of headache in primary care, particularly when a secondary pathology is suspected.
Abstract.
Author URL.
Watson J, Hamilton W (2008). Clinical features of type 2 diabetes before diagnosis and pathways to the diagnosis: a case–control study.
Primary Health Care Research and Development,
9(1), 41-48.
Abstract:
Clinical features of type 2 diabetes before diagnosis and pathways to the diagnosis: a case–control study
To identify and quantify clinical features associated with a future diagnosis of type 2 diabetes, and to record pathways to the diagnosis of diabetes. The risk of type 2 diabetes posed by particular symptoms is largely unknown, especially in unselected populations like primary care. The current mode and setting of diagnosis in the UK are undescribed. This was a population-based case–control study in seven general practices in Bristol, UK. In this study, 105 cases with newly diagnosed diabetes, and 105 age- and sex-matched controls were studied. Their primary care records for two years before diagnosis were examined for symptoms previously reported to be associated with diabetes and for abnormal investigations. Differences between cases and controls were analysed by conditional logistic regression. In cases, the pathways to the diagnosis of diabetes were categorised. In all, 42 (40%) adults with newly diagnosed diabetes were asymptomatic at diagnosis and 84 (80%) were first detected in primary care. Five clinical features were independently associated with diabetes in multivariable analyses. Likelihood ratios for these were: thirst 36 (95% confidence interval 3.0, 440), P = 0.005; weight loss 5.7 (1.3, 26), P = 0.022; skin infections 4.6 (1.7, 12), P = 0.002; fasting glucose >5.6 mmol/L 38 (2.2, 640), P = 0.012; and random glucose >5.6 mmol/L 15 (2.5, 94), P = 0.003. The median time period between the onset of symptoms and diagnosis was short (8 days) in patients presenting with thirst, but much longer for those with weight loss (294 days) and skin infections (463 days). Over a quarter of patients had raised blood glucose readings, which were not followed up in the two years before diagnosis was made. Most patients with type 2 diabetes are diagnosed in primary care. Many are asymptomatic at diagnosis. Earlier diagnosis of diabetes may be possible by considering diabetes in patients with weight loss and skin infections, and ensuring that borderline abnormal tests are adequately followed up. © 2008, Cambridge University Press. All rights reserved.
Abstract.
Kernick D, Stapley S, Hamilton W (2008). GP's classification of headache: is primary headache underdiagnosed?.
British Journal of General Practice,
58(547), 102-104.
Abstract:
GP's classification of headache: is primary headache underdiagnosed?
With a high economic, social, and personal burden, headache remains an important health problem. How UK GPs diagnose headache in the UK is unknown. In this study, a large primary care database was used and diagnostic categories were described for 91 121 adult patients with new-onset headache, that is, patients who had not consulted for headache in the previous year. Seventy per cent of headaches were not given a diagnostic label, 24% were diagnosed as primary, and 6% as secondary headaches. It is suggested that GPs' difficulty in diagnosing headache presentations contributes to the high level of morbidity and unmet need in this disease. © British Journal of General Practice 2008.
Abstract.
Knowles J, Hamilton W (2008). Knowledge of risk factors in cancer. British Journal of General Practice, 58(554), 650-651.
Barrett J, Hamilton W (2008). Pathways to the diagnosis of lung cancer in the UK: a cohort study.
BMC Fam Pract,
9Abstract:
Pathways to the diagnosis of lung cancer in the UK: a cohort study.
BACKGROUND: Lung cancer is the commonest cause of cancer death in the UK. Patients generally present to their general practitioner, but the pathway of diagnosis from first symptom to diagnosis has not been mapped. We performed a cohort study of 246 patients with lung cancer in Exeter, Devon UK. All patients had their cancer symptoms, referrals and diagnoses identified and dated using their doctors' records. RESULTS: Three main routes to diagnosis emerged. The first was the expected route of outpatient referral; 150 (61% of the cohort) of patients took this route, although only 110 (45% of the whole cohort, 73% of those referred to outpatients) were referred to a respiratory department. 56 (23%) were admitted as an emergency, having previously described a lung cancer symptom to their doctor. 26 patients (11%) had no symptom of lung cancer reported before their diagnosis. The interval from first symptom to referral was similar across the different pathways. However, the referral to diagnosis interval was longer in patients misdirected to other outpatient departments (66 days, interquartile range 37,110) than those sent to respiratory clinics (29 days, 17,61) or admitted as an emergency (16 days 8,40); p < 0.001. CONCLUSION: Only a minority of lung cancer patients follow the traditional route to diagnosis. Clinical and research efforts need to consider the alternative routes if they are to maximise their impact on speed of diagnosis.
Abstract.
Author URL.
Barraclough K, Liddell WG, du Toit J, Foy C, Dasgupta B, Thomas M, Hamilton W (2008). Polymyalgia rheumatica in primary care: a cohort study of the diagnostic criteria and outcome.
Family Practice,
25(5), 328-333.
Abstract:
Polymyalgia rheumatica in primary care: a cohort study of the diagnostic criteria and outcome
Background. Polymyalgia rheumatica (PMR) is common and is usually diagnosed and managed in primary care. There are no generally accepted primary care criteria for diagnosis. Objectives. To identify what features are used to diagnose PMR, to benchmark these against diagnostic criteria and to identify features at diagnosis with prognostic significance. Methods. This was a retrospective cohort study of all patients diagnosed with PMR in three UK general practices between January 1994 and December 2003. The medical records were examined for features of PMR. The duration of steroid treatment was used as a proxy for duration of disease. Analysis of prognostic predictors was by Cox proportional hazards models. Results. One hundred and eighty-three patients were identified, giving an overall annual incidence of 11.3 per 10 000 patients aged 50 or over. The median age at diagnosis was 75 (interquartile range 69, 79) years: 138 (75%) were female. The most common diagnostic features were proximal muscle pain in 151 (82%), raised inflammatory markers in 160 (87%), clinical response to corticosteroids in 166 (91%) and normalization of inflammatory markers in 147 (81%). Twenty (11%) had normal inflammatory indices. The median duration of treatment was 1.4 years (interquartile range 0.8, 2.4). Female sex and raised inflammatory markers were independently associated with longer treatment: female hazard ratio 1.5 (1.0, 2.2) P = 0.047 and raised inflammatory markers 2.0 (1.2, 3.2) P = 0.01. Conclusions. Primary care practitioners do not use established criteria to diagnose PMR and sometimes diagnose the condition even when inflammatory markers are normal. This exposes patients to a risk of inappropriate steroid use. © the Author 2008. Published by Oxford University Press. All rights reserved.
Abstract.
Hamilton W, Lancashire R, Sharp D, Peters TJ, Cheng KK, Marshall T (2008). The importance of anaemia in diagnosing colorectal cancer: a case-control study using electronic primary care records.
Br J Cancer,
98(2), 323-327.
Abstract:
The importance of anaemia in diagnosing colorectal cancer: a case-control study using electronic primary care records.
Although anaemia is recognised as a feature of colorectal cancer, the precise risk is unknown. We performed a case-control study using electronic primary care records from the Health Improvement Network database, UK. A total of 6442 patients had a diagnosis of colorectal cancer, and were matched to 45 066 controls on age, sex, and practice. We calculated likelihood ratios and positive predictive values for colorectal cancer in both sexes across 1 g dl(-1) haemoglobin and 10-year age bands, and examined the features of iron deficiency. In men, 178 (5.2%) of 3421 cases and 47 (0.2%) of 23,928 controls had a haemoglobin
Abstract.
Author URL.
Hamilton W (2008). The price of diagnosis.
BRITISH JOURNAL OF GENERAL PRACTICE,
58(557), 837-838.
Author URL.
Kernick D, Stapley S, Goadsby PJ, Hamilton W (2008). What happens to new-onset headache presented to primary care? a case-cohort study using electronic primary care records.
Cephalalgia,
28(11), 1188-1195.
Abstract:
What happens to new-onset headache presented to primary care? a case-cohort study using electronic primary care records.
In the UK, 4% of general practitioner consultations are for headache, yet the natural history of these presentations is unknown. The objective of this study was to describe the outcome of new headache presentations to the general practitioner. This was a prospective case-control study in adults over a period of 1 year using data from the General Practitioner Research Database, UK. Records of patients who presented with primary headache (migraine, tension-type headache, cluster headache) or undifferentiated headache (no further descriptor) were examined for the subsequent year for subarachnoid haemorrhage, primary brain tumour, benign space-occupying lesion, temporal arteritis, stroke and transient ischaemic attack. We identified 21,758 primary headaches and 63,921 undifferentiated headaches. The likelihood ratio was 29 (9.9, 92) for a subarachnoid haemorrhage after an undifferentiated headache and increased with age. The 1-year risk of a malignant brain tumour with new undifferentiated headache was 0.15%, rising to 0.28% above the age of 50 years. For primary headache the risk was 0.045%. The risk for a benign space-occupying lesion was 0.05% for an undifferentiated and 0.009% for a primary headache. The risk of temporal arteritis was the highest of the conditions studied, 0.66% in the undifferentiated and 0.18% in the primary headache group. Accepting the limitations of this approach, our data can inform management guidelines for new presentations of headache in primary care and confirm the need for follow-up, even if a primary headache diagnosis is made.
Abstract.
Author URL.
Best J, Gent T, Ramsey CB, Brunning R, Cook G, Friendship-Taylor D, Hamilton WD, Jones J, Marshall PD, van der Plicht H, et al (2007). Bronze Age Burnt Mounds and Early Medieval Timber Structures at Town Farm Quarry, Burlescombe, Devon.
Archaeological journal,
164(1), 1-79.
Abstract:
Bronze Age Burnt Mounds and Early Medieval Timber Structures at Town Farm Quarry, Burlescombe, Devon
A multi-period site was exposed during topsoil stripping at Town Farm Quarry, Burlescombe, Devon, in 2005. Surviving remains included two Bronze Age burnt mounds with timber-lined troughs and pits, and a collection of well-preserved timber structures associated with a natural spring, constructed in the seventh century AD. A complete leather shoe of the same date was recovered from the fill of a hollowed tree trunk, probably used as a wellhead. A range of studies, including an extensive dendrochronological and radiocarbon dating programme, has illustrated the changing environment of the site and contributed to the interpretation of the assemblage. Early post-Roman sites remain particularly uncommon in Devon, with burnt mounds otherwise yet to be identified.
Abstract.
Cleary J, Peters TJ, Sharp D, Hamilton W (2007). Clinical features of colorectal cancer before emergency presentation: a population-based case-control study.
Fam Pract,
24(1), 3-6.
Abstract:
Clinical features of colorectal cancer before emergency presentation: a population-based case-control study.
OBJECTIVE: to identify the clinical features of colorectal cancer presenting as a surgical emergency. DESIGN: Population-based case-control study. SETTING: all general practices in Exeter Primary Care Trust, Devon, UK. Participants. 349 patients with colorectal cancer, 62 of these having an emergency presentation. Five randomly selected controls matched by age, sex and general practice for each case. DATA: the entire primary care record, from 24 months to 30 days before diagnosis, was coded using the International Classification of Primary Care-2. MAIN OUTCOME MEASURES: Symptom reporting by patients with emergency presentation of colorectal cancer compared with matched controls and non-emergency presentations. RESULTS: Eight features of colorectal cancer were associated with the 62 emergency presentations of colorectal cancer. 39 (63%) of patients had reported at least one symptom to their doctors a minimum of 30 days before the diagnosis. In multivariable analysis, three features remained independently associated with cancer: abdominal pain, odds ratio 6.2 (95% CI 2.8-14), P
Abstract.
Author URL.
Hamilton W, Kernick D (2007). Clinical features of primary brain tumours: a case-control study using electronic primary care records.
Br J Gen Pract,
57(542), 695-699.
Abstract:
Clinical features of primary brain tumours: a case-control study using electronic primary care records.
BACKGROUND: Around 4500 new primary brain tumours are diagnosed in the UK each year. Symptoms of these tumours have not previously been studied in primary care. AIM: to identify and quantify the clinical features of brain tumours in primary care. DESIGN OF STUDY: Case-control study. SETTING: the General Practice Research Database, UK. METHOD: a total of 3505 patients with primary brain tumours diagnosed between May 1988 and March 2006, and 17 173 controls, matched for age (to 1 year), sex, and general practice, were studied. Full medical records for 6 months before diagnosis were searched for reports of clinical features previously associated with brain tumours. Odds ratios were calculated for variables independently associated with cancer, using conditional logistic regression, as were the positive predictive values for patients consulting in primary care. RESULTS: Seven features were associated with brain tumours before diagnosis. Positive predictive values against a background risk of 0.013% were: new-onset seizure, 1.2% (95% confidence interval [CI] = 1.0 to 1.4); weakness (as a symptom), 3.0% (95% CI = 1.7 to 4.9); headache, 0.09% (95% CI = 0.08 to 0.10); confusion, 0.20% (95% CI = 0.16 to 0.24); memory loss, 0.036% (95% CI = 0.026 to 0.052); visual disorder, 0.035% (95% CI = 0.025 to 0.051); and the physical sign of motor loss on examination, 0.026% (95% CI = 0.024 to 0.030); all P
Abstract.
Author URL.
Hamilton W, Russell D, Stabb C, Seamark D, Campion-Smith C, Britten N (2007). The effect of patient self-completion agenda forms on prescribing and adherence in general practice: a randomized controlled trial.
Fam Pract,
24(1), 77-83.
Abstract:
The effect of patient self-completion agenda forms on prescribing and adherence in general practice: a randomized controlled trial.
BACKGROUND: What the patient wants from a general practice consultation and what the doctor believes they want are not always the same thing. This mismatch may lead to unwanted and unnecessary prescribing. AIM: to study the effect of a one-page form completed by patients before their consultation and given to the doctor at the start of the consultation, in terms of a reduction in prescribing, satisfaction with the consultation and adherence with prescribed medication. DESIGN: Randomized controlled trial. SETTING: Ten general practices in Devon and Dorset, UK. METHODS: Unselected patients attending general practice appointments were randomised to receive (or not) a self-completed agenda form (SCAF) asking five questions, including whether the patient considered they should receive a prescription. RESULTS: Approximately 4125 patients were offered entry; 3124 (76%) agreed to randomisation. In 1783 (57%) of these prescribing or satisfaction outcomes were identified. 457 of 811 (56.4%) of SCAF patients received a prescription, at a median (IQR) cost of pound 5.60 (inter-quartile range pound 2.12- pound 16.10), compared with 418 of 799 (52.3%) of controls, at a median cost of pound 5.94 ( pound 2.46- pound 18.90); both results non-significant (P=0.10 for prescribing and 0.30 for cost). Satisfaction was also similar in both groups: mean satisfaction score in SCAFs 5.37 and in controls 5.40 (P=0.64), as was adherence: at 12 weeks, adherence of 75% or greater was reported by 92 of 136 SCAF patients (68%) and 105 of 145 controls (72%) (P=0.31). CONCLUSION: the negative result could have two explanations. Either the intervention did not achieve the intention of communicating the patients' agendas, or if it did, patients may have been persuaded by doctors' explanations in the consultation.
Abstract.
Author URL.
Stanley S, Round A, Hollinghurst S, Hamilton W, Crabb T (2007). Use of medication and investigations in community hospitals and a district general hospital: a cohort study of emergency admissions in the elderly.
Primary Health Care Research and Development,
8(2), 105-111.
Abstract:
Use of medication and investigations in community hospitals and a district general hospital: a cohort study of emergency admissions in the elderly
Background: We previously studied clinical outcomes in two cohorts of emergency admissions of patients aged over 70 to one district general hospital (DGH) or five community hospitals (CHs) finding no differences in death, readmissions, or quality of life at 6 months after admission. Our objectives in this study were to examine the use and cost of medication and use and cost of investigations in the two different hospital settings. Methods: We identified and priced all medication taken on admission, during the hospital stay, and on discharge, and identified all investigations. The main outcome measures were number and cost of medications and investigations during the stay, and the difference in the patients’ routine medication before and after the hospital stay. Results: Three hundred and seventy five patients were studied (DGH 170, CH 205). The median (inter-quartile range (IQR)) number and cost of drugs used during the hospital stay was higher in DGH patients: 11 (8,17) drugs than CH patients: 8 (5,11); (P < 0.001), costing £35 (13, 90) and £16 (6, 45) respectively (P< 0.001). DGH patients had a mean of 0.55 drugs added to their routine medication, at an extra projected cost of £9.50 per month, whereas CH patients had an average of 0.11 drugs removed from their routine medication at a projected cost saving of £1.35 per month (P= 0.012 for number and
Abstract.
Hamilton W, Sharp DJ, Peters TJ, Round AP (2006). Clinical features of prostate cancer before diagnosis: a population-based, case-control study.
Br J Gen Pract,
56(531), 756-762.
Abstract:
Clinical features of prostate cancer before diagnosis: a population-based, case-control study.
BACKGROUND: Even in areas where screening is available, many prostate cancers are diagnosed after the symptoms begin. However, the risk posed by particular symptoms is largely unknown, especially in unselected populations such as primary care. AIM: to identify and quantify the features of prostate cancer before diagnosis, both individually and in combination. DESIGN OF STUDY: Population-based case-control study. SETTING: all 21 general practices in Exeter, Devon, UK. METHODS: We studied all 217 prostate cancer patients diagnosed between 1998 and 2002, and 1080 male controls, matched by age and general practice. The full medical record for 2 years before diagnosis was coded, using the International Classification of Primary Care. We calculated odds ratios for variables independently associated with cancer, using conditional logistic regression, and calculated the positive predictive values for these, both individually and in combination. RESULTS: Eight features were associated with prostate cancer before diagnosis. Their positive predictive values against a background risk of 0.35% were: urinary retention 3.1% (95% confidence interval [CI] = 1.5 to 6.0); impotence 3.0% (95% CI = 1.7 to 4.9); frequency 2.2% (95% CI = 1.3 to 3.5); hesitancy 3.0% (95% CI = 1.5 to 5.5); nocturia 2.2% (95% CI = 1.2 to 3.6); haematuria 1.0% (95% CI = 0.57 to 1.8); weight loss 0.75% (95% CI = 0.38 to 1.4); abnormal rectal examination, deemed benign 2.8% (95% CI = 1.6 to 4.6); abnormal rectal examination, deemed malignant 12% (95% CI = 5.0 to 37): all P
Abstract.
Author URL.
Hamilton W (2006). Malignancy and deep vein thrombosis [7]. British Journal of General Practice, 56(532).
Stapley S, Sharp D, Hamilton W (2006). Negative chest X-rays in primary care patients with lung cancer.
Br J Gen Pract,
56(529), 570-573.
Abstract:
Negative chest X-rays in primary care patients with lung cancer.
BACKGROUND: the main investigation for suspected lung cancer in primary care is a chest X-ray. Reports from secondary care show that some patients with normal chest X-rays transpire to have lung cancer. The assumption is that this occurs rarely in primary care. AIM: the aim of this study was to examine the frequency of misleading chest X-rays in primary care, and whether there were any particular symptoms associated with them. DESIGN OF STUDY: Retrospective cohort study of the primary care records of 247 lung cancer patients diagnosed between 1998-2002. SETTING: all general practices in Exeter Primary Care Trust, Devon, UK. METHOD: all chest X-rays and all common symptoms of lung cancer reported to primary care were identified from the medical records. X-ray results were categorised into three groups by the radiologist's report: normal; abnormal but no malignancy suspected (together classified as negative X-rays); or abnormal with possible malignancy. RESULTS: of the 247 patients, 164 (66%) had a chest X-ray taken in primary care during the year before diagnosis: 126 of these (77%) were abnormal with possible malignancy; 21 (13%) were abnormal but with no malignancy suspected; in 17 (10%) the X-ray was reported as normal. Thus, 38 of 164 patients (23%; 95% confidence interval = 16 to 32%) had a negative X-ray. Negative X-rays were less common in the 90 days before diagnosis. No particular symptoms were significantly associated with negative X-rays. CONCLUSION: Nearly a quarter of chest X-rays requested from primary care in lung cancer patients are negative. Further investigation is warranted with continuing or changing symptoms, even if the X-ray is not suggestive of malignancy.
Abstract.
Author URL.
Knight B, Shields BM, Hill A, Powell RJ, Round A, Hamilton W, Hattersley AT (2006). Offspring birthweight is not associated with paternal insulin resistance.
Diabetologia,
49(11), 2675-2678.
Abstract:
Offspring birthweight is not associated with paternal insulin resistance.
AIMS/HYPOTHESIS: Low birthweight is associated with insulin resistance and other insulin resistance-related phenotypes: diabetes, hypertension, and vascular disease in later life. The underlying mechanism is unclear. The foetal insulin hypothesis proposes that a single genetic predisposition to beta cell dysfunction/insulin resistance results in both reduced insulin-dependent foetal growth in utero, hence low birthweight, and predisposition to type 2 diabetes. The aim of this study was to test whether, as predicted by the foetal insulin hypothesis, there is an association between measures of paternal insulin resistance and offspring birthweight. SUBJECTS AND METHODS: the Exeter Family Study of Childhood Health (EFSOCH) is a community-based study within central Exeter (UK), established to test the foetal insulin hypothesis prospectively. Associations were tested between offspring birthweight and paternal insulin resistance, calculated by homeostasis model assessment analysis in 986 families using data relating to singleton, non-diabetic, UK white pregnancies. Ethics approval was given by the North and East Devon local ethics committee. RESULTS: Offspring birthweight was not significantly correlated with log paternal insulin resistance (r=0, p=0.91), log HDL cholesterol concentration (r=-0.02, p=0.47) or log triglyceride concentration (r=0, p=0.99) when corrected for paternal BMI and common confounders. Multiple linear regression analysis confirmed that paternal insulin resistance was not an independent predictor of offspring birthweight. CONCLUSIONS/INTERPRETATION: Results from a young, adult, non-diabetic population do not support the foetal insulin hypothesis as an explanation for the association of low birthweight with insulin resistance.
Abstract.
Author URL.
Barrett J, Jiwa M, Rose P, Hamilton W (2006). Pathways to the diagnosis of colorectal cancer: an observational study in three UK cities.
Family Practice,
23(1), 15-19.
Abstract:
Pathways to the diagnosis of colorectal cancer: an observational study in three UK cities
Background. Colorectal cancer can present in a variety of ways, and with any of several symptoms. Different referral routes from primary to secondary care cater for these different presentations. The route that has received most investment in the UK National Health Service is the 2-week clinic, but the proportions of patients taking this and other routes to diagnosis are largely unknown. Methods. We designed an observational audit in Exeter, Oxford and Sheffield, UK. Colorectal cancers diagnosed in 2002 from participating practices were identified and the presence and timing of seven important clinical features noted: diarrhoea, constipation, rectal bleeding, abdominal pain, the finding of an abdominal or rectal mass on examination, anaemia and positive faecal occult blood tests. The referral pathways to secondary care were identified. Results. of the 151 patients studied, 112 (74%) were referred with at least one clinical feature of colorectal cancer to a specialist. Only 43 of these (28% of the total) were referred to a 2-week clinic; 39 patients (26% of the total) had an emergency admission, of whom 10 (7%) had their emergency admission after referral to a specialist for investigation but before a diagnosis had been established. The time intervals between the first consultation with a symptom of cancer and referral were mostly short. Conclusion. Patients with colorectal cancer travel several different pathways to diagnosis. The pathway with the most resources - the 2-week clinic - is used by a minority of patients. © the Author (2005). Published by Oxford University Press. All rights reserved.
Abstract.
Barrett J, Jiwa M, Rose P, Hamilton W (2006). Pathways to the diagnosis of colorectal cancer: an observational study in three UK cities.
Fam Pract,
23(1), 15-19.
Abstract:
Pathways to the diagnosis of colorectal cancer: an observational study in three UK cities.
BACKGROUND: Colorectal cancer can present in a variety of ways, and with any of several symptoms. Different referral routes from primary to secondary care cater for these different presentations. The route that has received most investment in the UK National Health Service is the 2-week clinic, but the proportions of patients taking this and other routes to diagnosis are largely unknown. METHODS: We designed an observational audit in Exeter, Oxford and Sheffield, UK. Colorectal cancers diagnosed in 2002 from participating practices were identified and the presence and timing of seven important clinical features noted: diarrhoea, constipation, rectal bleeding, abdominal pain, the finding of an abdominal or rectal mass on examination, anaemia and positive faecal occult blood tests. The referral pathways to secondary care were identified. RESULTS: of the 151 patients studied, 112 (74%) were referred with at least one clinical feature of colorectal cancer to a specialist. Only 43 of these (28% of the total) were referred to a 2-week clinic; 39 patients (26% of the total) had an emergency admission, of whom 10 (7%) had their emergency admission after referral to a specialist for investigation but before a diagnosis had been established. The time intervals between the first consultation with a symptom of cancer and referral were mostly short. CONCLUSION: Patients with colorectal cancer travel several different pathways to diagnosis. The pathway with the most resources-the 2-week clinic-is used by a minority of patients.
Abstract.
Author URL.
Hamilton W, Britten N (2006). Patient agendas in primary care.
BMJ,
332(7552), 1225-1226.
Author URL.
Petersen I, Thomas JM, Hamilton WT, White PD (2006). Risk and predictors of fatigue after infectious mononucleosis in a large primary-care cohort.
QJM - Monthly Journal of the Association of Physicians,
99(1), 49-55.
Abstract:
Risk and predictors of fatigue after infectious mononucleosis in a large primary-care cohort
Background: Fatigue has been found to complicate infectious mononucleosis (IM) when patients are directly asked about it. We do not know whether such fatigue is clinically significant, nor whether IM is a specific risk for fatigue (or whether it can follow other common infections). Various risk markers for post-infectious fatigue have been identified, but findings are inconsistent. Aim: to determine the risk of clinically reported fatigue (compared with depression) after IM (compared with both influenza and tonsillitis) in patients attending primary care, and to examine risk markers for post-IM fatigue. Design: Comparison of matched primary-care cohorts. Methods: We identified 1438 adult patients with a positive heterophil antibody test for IM from the UK General Practice Research Database. These patients were individually matched on age, sex and practice to two comparison groups; one with a clinical diagnosis of influenza and the other of tonsillitis. Results: the odds ratios (ORs) (95%CI) for reported fatigue after IM vs. influenza and tonsillitis were 4.4 (2.9-6.9) and 6.6 (4.2-10.4), respectively. Risk markers for post-IM fatigue included female sex and premorbid mood disorder. By comparison, the ORs for depression after IM vs. influenza and tonsillitis were 1.6 (0.9-2.6) and 2.3 (1.4-3.9), respectively. Discussion: IM is a specific and significant risk for clinically reported fatigue, which is both separate from, and more common than, depression. Female sex and premorbid mood disorder are risk markers for fatigue. These can be used both to target prevention strategies and to explore aetiological mechanisms. © the Author 2005. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved.
Abstract.
Du Toit J, Hamilton W, Barraclough K (2006). Risk in primary care of colorectal cancer from new onset rectal bleeding: 10 Year prospective study.
British Medical Journal,
333(7558), 69-70.
Abstract:
Risk in primary care of colorectal cancer from new onset rectal bleeding: 10 Year prospective study
Objective: to measure the risk of colorectal cancer and adenoma with new onset rectal bleeding reported to primary care. Design: Cohort study. Setting: a rural general practice in the United Kingdom. Participants: Patients aged 45 or more with new onset rectal bleeding, irrespective of other symptoms. Main outcome measures: Percentage of participants in whom colorectal cancer or colonic adenoma was identified after investigation of the bowel. Results: During a 10 year period, 265 patients reported new rectal bleeding. of these, 15 (5.7%, 95% confidence interval 3.2% to 9.2%) had colorectal cancer, and 13 (4.9%, 2.6% to 8.4%) had colonic adenoma. Only two of the patients with cancer had had diarrhoea. Conclusions: One in 10 patients aged 45 or more with new onset rectal bleeding had colonic neoplasia, so investigation of the bowel should be offered to all such patients, whether or not they have other symptoms.
Abstract.
Stapley S, Peters TJ, Sharp D, Hamilton W (2006). The mortality of colorectal cancer in relation to the initial symptom at presentation to primary care and to the duration of symptoms: a cohort study using medical records.
Br J Cancer,
95(10), 1321-1325.
Abstract:
The mortality of colorectal cancer in relation to the initial symptom at presentation to primary care and to the duration of symptoms: a cohort study using medical records.
The association between the staging of colorectal cancer and mortality is well known. Much less researched is the relationship between the duration of symptoms and outcome, and whether particular initial symptoms carry a different prognosis. We performed a cohort study of 349 patients with primary colorectal cancer in whom all their prediagnostic symptoms and investigation results were known. Survival data for 3-8 years after diagnosis were taken from the cancer registry. Six features were studied: rectal bleeding, abdominal pain, diarrhoea, constipation, weight loss, and anaemia. Two of these were significantly associated with different staging and mortality. Rectal bleeding as an initial symptom was associated with less advanced staging (odds ratio from one Duke's stage to the next 0.50, 95% confidence interval 0.31, 0.79; P=0.003) and with reduced mortality (Cox's proportional hazard ratio (HR) 0.56 (0.41, 0.79); P=0.001. Mild anaemia, with a haemoglobin of 10.0-12.9 g dl(-1), was associated with more advanced staging (odds ratio 2.2 (1.2, 4.3); P=0.021) and worse mortality (HR 1.5 (0.98, 2.3): P=0.064). When corrected for emergency admission, sex, and the site of the tumour, the HR for mild anaemia was 1.7 (1.1, 2.6); P=0.015. No relationship was found between the duration of symptoms and staging or mortality.
Abstract.
Author URL.
Hamilton W, Round A, Sharp D, Peters TJ (2005). Clinical features of colorectal cancer before diagnosis: a population-based case-control study.
Br J Cancer,
93(4), 399-405.
Abstract:
Clinical features of colorectal cancer before diagnosis: a population-based case-control study.
Most colorectal cancers are diagnosed after the onset of symptoms. However, the risk of colorectal cancer posed by particular symptoms is largely unknown, especially in unselected populations like primary care. This was a population-based case-control study in all 21 general practices in Exeter, Devon, UK, aiming to identify and quantify the prediagnostic features of colorectal cancer. In total, 349 patients with colorectal cancer, aged 40 years or more, and 1744 controls, matched by age, sex and general practice, were studied. The full medical record for 2 years before diagnosis was coded using the International Classification of Primary Care-2. We calculated odds ratios for variables independently associated with cancer, using multivariable conditional logistic regressions, and then calculated the positive predictive values of these variables, both individually and in combination. In total, 10 features were associated with colorectal cancer before diagnosis. The positive predictive values (95% confidence interval) of these were rectal bleeding 2.4% (1.9, 3.2); weight loss 1.2% (0.91, 1.6); abdominal pain 1.1% (0.86, 1.3); diarrhoea 0.94% (0.73, 1.1); constipation 0.42% (0.34, 0.52); abnormal rectal examination 4.0% (2.4, 7.4); abdominal tenderness 1.1% (0.77, 1.5); haemoglobin 10 mmol l(-1) 0.78% (0.51, 1.1): all P < 0.001. Earlier diagnosis of colorectal cancer may be possible using the predictive values for single or multiple symptoms, physical signs or test results.
Abstract.
Author URL.
Gallagher AM, Thomas JM, Hamilton WT, White PD (2005). Erratum: Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001 (Journal of the Royal Society of Medicine (December 2004) 97 (571-575)). Journal of the Royal Society of Medicine, 98(2).
Barrett J, Hamilton W (2005). Pathways to the diagnosis of prostate cancer in a British city. A population-based study.
Scand J Urol Nephrol,
39(4), 267-270.
Abstract:
Pathways to the diagnosis of prostate cancer in a British city. A population-based study.
OBJECTIVE: to identify the pathways leading to the diagnosis of prostate cancer from a UK population perspective, including the role of prostate-specific antigen (PSA) testing. MATERIAL AND METHODS: We studied all 217 prostate cancers occurring in the region covered by Exeter Primary Care Trust, Devon, UK (population 128 700) between 1998 and 2002. The general practitioner's records for 2 years before diagnosis were used to identify the category of pathway to diagnosis. RESULTS: Symptomatic presentation to primary care initiated the diagnostic process in 166/217 men (76%). The presenting symptoms were lower urinary tract symptoms (LUTS) in 151 men (70%), systemic symptoms and no LUTS in 12 (6%) and bowel symptoms with a rectal examination revealing an abnormal prostate in 3 (1%). Eighteen cases (8%) were diagnosed as a result of PSA screening in asymptomatic men. Diagnosis as an inpatient accounted for 33 cases (15%), 25 of whom (11%) had been admitted with urological problems, and 4% of cases had been admitted for non-urological problems. of the 151 men who presented with LUTS, 91 (60%) had a PSA test in primary care, 15 (10%) had one in secondary care and 39 (17%) had a prostatectomy that revealed a cancer that had not previously been suspected. Most prostate cancers were diagnosed after presentation to primary care with LUTS. Presentation with disseminated disease was rare. CONCLUSION: Screening by means of PSA testing remains uncommon in this area of the UK, in contrast to the situation in other countries. Most PSA tests performed in patients with prostate cancer were diagnostic rather than screening tests.
Abstract.
Author URL.
Hamilton WT, Gallagher AM, Thomas JM, White PD (2005). The prognosis of different fatigue diagnostic labels: a longitudinal survey.
Fam Pract,
22(4), 383-388.
Abstract:
The prognosis of different fatigue diagnostic labels: a longitudinal survey.
BACKGROUND: Several different diagnostic labels exist for the fatigue syndromes, including chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME) and postviral fatigue syndrome (PVFS). An allied condition is fibromyalgia. No study has examined prognostic differences across these different labels. OBJECTIVE: to compare the prognoses of patients labelled with different fatigue syndromes in primary care. METHODS: We performed a longitudinal survey, using electronic records from the General Practice Research Database. All 18,122 patients diagnosed by their GP with a fatigue syndrome from 1988-2001 with a minimum of one year of records after diagnosis were collated into four groups: CFS, ME, PVFS and fibromyalgia. CFS and ME were combined for the main analysis as no code for CFS was available until 1995. The length of illness was calculated as the interval between the diagnosis and the last recorded fatigue symptom, expressed as days per year, to account for differing lengths of record after diagnosis. RESULTS: Patients with CFS/ME combined had a worse prognosis (median length of illness 80 days per year; interquartile range 0-242) than fibromyalgia (51; 0-244) or PVFS 0 (0-108), a significant difference, P < 0.001. In a subgroup analysis, ME had a worse prognosis (median length of illness in days per year 106; interquartile range 0-259) than CFS (33; 0-170), P < 0.001, in spite of a better course before diagnosis. Secondary outcome measures were consistent with these results. CONCLUSION: There were important differences in outcome between the various fatigue labels, with ME having the worst prognosis and PVFS the best. This could be an adverse effect of the label ME itself. Alternatively, patients who are destined to have a worse prognosis may preferentially attract the ME label. Our data support the first interpretation.
Abstract.
Author URL.
Hamilton W (2005). Untitled.
AMERICAN JOURNAL OF SURGERY,
189(4), 504-504.
Author URL.
Hamilton W, Peters TJ, Round A, Sharp D (2005). What are the clinical features of lung cancer before the diagnosis is made? a population based case-control study.
Thorax,
60(12), 1059-1065.
Abstract:
What are the clinical features of lung cancer before the diagnosis is made? a population based case-control study.
BACKGROUND: over 38,000 new cases of lung cancer occur each year in the UK. Most are diagnosed after initial presentation to primary care, but the relative importance of the various clinical features is largely unknown. METHODS: a population based case-control study was undertaken in all 21 general practices in Exeter, Devon, UK (population 128 700). 247 primary lung cancers were studied in subjects aged over 40 years diagnosed between 1998 and 2002 and 1235 controls matched by age, sex and general practice. The entire primary care record for 2 years before diagnosis was coded using the International Classification of Primary Care-2. Univariable and multivariable conditional logistic regression analyses were used to identify and quantify clinical features independently associated with lung cancer. The main outcome measures were odds ratios and positive predictive values for these variables. RESULTS: Seven symptoms (haemoptysis, loss of weight, loss of appetite, dyspnoea, thoracic pain, fatigue and cough), one physical sign (finger clubbing), and two abnormal investigation results (thrombocytosis and abnormal spirometry) were associated with lung cancer in multivariable analyses, as was cigarette smoking. After excluding variables reported in the final 180 days before diagnosis, haemoptysis, dyspnoea and abnormal spirometry remained independently associated with cancer. CONCLUSIONS: This study provides an evidence base for selection of patients for investigation of possible lung cancer, both for clinicians and for developers of guidelines.
Abstract.
Author URL.
Logsdon MC (2005). Why carve up your continuous.
RESEARCH IN NURSING & HEALTH,
28(6), 504-504.
Author URL.
Hamilton WT, Kessler D (2004). BMJ papers could include honesty box for research warts. BMJ, 328(7451).
Hamilton W, Sharp D (2004). Diagnosis of colorectal cancer in primary care: the evidence base for guidelines.
Fam Pract,
21(1), 99-106.
Abstract:
Diagnosis of colorectal cancer in primary care: the evidence base for guidelines.
BACKGROUND: Colorectal cancer is common, causing approximately 11% of cancer deaths in the UK. However, a GP would only expect to see one new presentation each year. Referral guidelines outlining clinical scenarios of high risk have been published. These aim to help GPs select patients for rapid investigation. OBJECTIVES: the purpose of this study was to review the presenting features of colorectal cancer in primary care, using the basic structure of the UK Referral Guidelines for Suspected Cancer. METHODS: a structured literature review was carried out. RESULTS: Two symptoms have a high predictive value for cancer: rectal bleeding and change in bowel habit towards increased looseness or increased stool frequency. Other symptoms, such as abdominal pain, are so prevalent in the community that they have little predictive value. There is little published evidence on abdominal or rectal masses and iron deficiency anaemia as presenting features for colorectal cancer. However, these are so likely to have an important cause, investigation is mandated. Two areas in the Referral Guidelines are questioned: the need to defer investigation of change in bowel habit towards increased looseness or increased stool frequency for 6 weeks, and the low risk nature of constipation. CONCLUSION: the Referral Guidelines have a reasonable evidence base.
Abstract.
Author URL.
Hamilton W, Sharp D (2004). Diagnosis of lung cancer in primary care: a structured review.
Fam Pract,
21(6), 605-611.
Abstract:
Diagnosis of lung cancer in primary care: a structured review.
BACKGROUND: Lung cancer has the highest cancer incidence and mortality in the UK. Despite this, an individual GP encounters only one new presentation approximately every 8 months, so gains relatively little experience of its diagnosis. This is partly addressed by referral guidelines which aim to help GPs in selection of patients for chest X-ray or referral for specialist investigation. OBJECTIVE: the purpose of this study was to review the primary care presenting features of lung cancer, in the light of the UK Referral Guidelines for Suspected Cancer. METHODS: a structured literature review was carried out. RESULTS: Little research has been undertaken in primary care, and the predictive values for most symptoms are unknown. Approximate likelihood ratios could be calculated for six symptoms or signs: haemoptysis 13; fatigue 5.7; cough 5.3; finger clubbing 3.9; weight loss 2.9; and dyspnoea 1.5-5.7, but none of these figures derived from single primary care studies. Three recommendations for urgent investigation of possible lung cancer in the UK Referral Guidelines are questioned: for unexplained dyspnoea, hoarseness or cervical lymphadenopathy. For all these presentations, other serious diagnoses are more likely. CONCLUSION: the UK Guidelines for referral of suspected lung cancer have a weak evidence base.
Abstract.
Author URL.
Hamilton WT, Round AP, Sharp DJ, Peters TJ (2004). High incidence of mesothelioma in an English city without heavy industrial use of asbestos.
J Public Health (Oxf),
26(1), 77-78.
Abstract:
High incidence of mesothelioma in an English city without heavy industrial use of asbestos.
BACKGROUND: Mesothelioma rates are increasing in the industrialized world, related to occupational asbestos exposure. The highest rates have been reported from areas with specific industries such as shipbuilding or mining. Lower rates have been reported from areas without such industries. We studied an area without heavy industry to examine if such a pattern occurred in England. METHODS: We studied the population of Exeter Primary Care Trust, Devon, United Kingdom, with a population of 131,849. Exeter has no mining, shipbuilding or other heavy industry. All lung cancers and mesotheliomas were identified from the local cancer registry, supplemented by searches at all primary care practices. The cancer diagnoses were checked by inspection of histology or primary care records. Occupational data were extracted from the primary care records. RESULTS: the searches revealed 291 lung cancers, 283 of which had either histological proof or strong clinical evidence for the diagnosis. Twenty-two (8 per cent) of these were pleural mesotheliomas, 17 of these occurring in men. The incidence rate of mesothelioma in men over 40 years was 12.1 per 100,000 per year (95 per cent confidence intervals 7.0-19.3), one of the highest reported rates in the world. CONCLUSION: the mesothelioma epidemic will extend to areas without local heavy industrial exposure.
Abstract.
Author URL.
Gallagher AM, Thomas JM, Hamilton WT, White PD (2004). Incidence of Fatigue Symptoms and Diagnoses Presenting in UK Primary Care from 1990 to 2001. Journal of the Royal Society of Medicine, 97(12), 571-575.
Gallagher AM, Thomas JM, Hamilton WT, White PD (2004). Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001.
Journal of the Royal Society of Medicine,
97(12), 571-575.
Abstract:
Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001
Little is known about whether the incidence of symptoms of fatigue presented in primary care, and the consequent diagnoses made, change over time. The UK General Practice Research Database was used to investigate the annual incidence of both fatigue symptoms and diagnoses recorded in UK primary care from 1990 to 2001. The overall incidence of all fatigue diagnoses decreased from 87 per 100 000 patients in 1990 to 49 in 2001, a reduction of 44%, while postviral fatigue syndromes decreased from 81% of all fatigue diagnoses in 1990 to 60% in 2001. Chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) together increased from 9% to 26% of all fatigue diagnoses. The incidence of fibromyalgia increased from less than 1 per 100 000 to 35 per 100 000. In contrast, there was no consistent change in the incidence of all recorded symptoms of fatigue, with an average of 1503 per 100000, equivalent to 1.5% per year. CFS/ME and fibromyalgia were rarely diagnosed in children and were uncommon in the elderly. All symptoms and diagnoses were more common in females than in males. The overall incidence of fatigue diagnoses in general has fallen, but the incidence rates of the specific diagnoses of CFS/ME and fibromyalgia have risen, against a background of little change in symptom reporting. This is likely to reflect fashions in diagnostic labelling rather than true changes in incidence.
Abstract.
Kessler D, Hamilton W (2004). Normalisation: Horrible word, useful idea. British Journal of General Practice, 54(500), 163-164.
Jiwa M, Hamilton W (2004). Referral of suspected colorectal cancer: Have guidelines made a difference?.
British Journal of General Practice,
54(505), 608-610.
Abstract:
Referral of suspected colorectal cancer: Have guidelines made a difference?
In the United Kingdom, patients with colorectal symptoms referred on the fast-track pathway into secondary care are offered investigation of their symptoms within 2 weeks. Audits demonstrate that a minority of patients with colorectal cancer are referred under this arrangement. We assessed referral letters to hospitals in one district in the period before and after the introduction of the 2-week wait initiative. The guidelines appear to have made little difference to the proportion of cases selected for referral on the urgent pathway. However, cancers in the earliest stages present with fewer clinical features than advanced disease and a combination of signs and symptoms are more likely to arouse suspicion in the referring agent. © British Journal of General Practice.
Abstract.
Round A, Crabb T, Buckingham K, Mejzner R, Pearce V, Ayres R, Weeks C, Hamilton W (2004). Six month outcomes after emergency admission of elderly patients to a community or a district general hospital.
Family Practice,
21(2), 173-179.
Abstract:
Six month outcomes after emergency admission of elderly patients to a community or a district general hospital
Background. Emergency admissions account for 40% of National Health Service bed usage. Recent policy is to increase the role of intermediate care, which includes the use of community hospitals (CHs). However, the proposed expansion presumes that CH care is as effective as acute hospital care. No direct comparison of outcomes between CHs and district general hospitals (DGHs) has been undertaken. Objectives. The aim of this study was to compare patient-based outcomes at 6 months following emergency admission to a DGH or CH. Methods. We designed a prospective cohort study, with strict eligibility criteria. The study was set in one DGH and five CHs in Devon, UK. Study participants were people aged >70 years with an acute illness requiring hospital admission, but whose condition could have been treated in either hospital setting. A cohort of people admitted to each setting was identified and followed-up for 6 months. The primary outcome measure was change in quality of life 6 months after admission, as measured by SF-36 and EuroQol. Secondary outcome measures were death, readmission and place of residence at 6 months. The use of drugs and investigations during the hospital stay were also measured. Results. A total of 376 patients were recruited and completed baseline measures, 254 of whom were followed-up at the 6-month stage (136 CH, 118 DGH). There were no differences in outcome between settings, with a small increase in quality of life scores at 6 months in both cohorts: the mean change in EuroQol 5D in CH was 6.6 points (95% confidence interval, 2.8-10.4) and in DGH was 6.5 (2.4-10.7); P = 0.97. Mortality and place of residence at 6 months were similar in the two groups. The numbers of investigations (median CH four investigations, DGH 22; P < 0.001) and of prescribed medications during the hospital stay (median CH eight drugs, DGH 11; P < 0.001) were significantly higher in the DGH. Conclusions. The quality of life and mortality in the CH cohort was similar to those in the DGH cohort. CH care can be used as an alternative to DGH care for a wide range of conditions requiring emergency admission. © Oxford University Press 2004, all rights reserved.
Abstract.
Hamilton W, Sharp D (2004). Symptomatic diagnosis of prostate cancer in primary care: a structured review.
Br J Gen Pract,
54(505), 617-621.
Abstract:
Symptomatic diagnosis of prostate cancer in primary care: a structured review.
BACKGROUND: Prostate cancer has the second highest cancer incidence and mortality in European men. Most prostate cancers are diagnosed after lower urinary tract symptoms (LUTS) are presented to primary care, but such symptoms more often have a benign cause. A general practitioner (GP) has to try and identify which of these patients have prostate cancer. AIMS: to review the presenting features of symptomatic prostate cancer. DESIGN OF STUDY: Structured review. METHOD: We searched Medline from 1980 to 2003 for symptoms, signs, and investigations reported in prostate cancer. This list was then expanded by secondary searches of reference lists. We excluded studies on post-diagnostic topics, such as staging, treatment, and prognosis; studies on non-Western patients; and studies on investigations that are not available in primary care. A second cycle of exclusions removed studies whose results would not guide a GP in deciding whether a patient has prostate cancer. RESULTS: No studies from primary care compared prostate cancer patients directly with controls. Two secondary care studies had enough information to allow a comparison of symptoms in cases compared with controls. In these studies, symptoms were generally more prevalent in cases, but the differences were small. Screening and secondary care studies suggest that early prostate cancer is symptomless, and that locally advanced cancer has LUTS that are similar to those for benign prostatic hypertrophy. CONCLUSION: There is a very weak evidence base for the primary care diagnosis of prostate cancer in men with lower urinary tract symptoms.
Abstract.
Author URL.
Russell D, Hamilton W, Lindbaek M, Sandvik E, Liodden K, Mjell J, Ravnsborg-Gjertsen K, Donnelly R, Manning G (2003). Ambulatory blood pressure monitoring (multiple letters). British Journal of General Practice, 53(497), 972-974.
Hamilton W, Round A, Goodchild R, Baker C (2003). Do community based self-reading sphygmomanometers improve detection of hypertension? a feasibility study.
J Public Health Med,
25(2), 125-130.
Abstract:
Do community based self-reading sphygmomanometers improve detection of hypertension? a feasibility study.
BACKGROUND: Hypertension is a major risk factor for stroke and ischaemic heart disease. Most hypertension is detected opportunistically by general practitioners. Those who rarely use medical services are less likely to have their blood pressure (BP) measured. We hypothesized that open access self-reading BP measurement would detect previously unrecognized hypertension. METHODS: Self-reading sphygmomanometers were placed at 13 public sites in Exeter, Devon, United Kingdom. Machine use was determined by users completing a proforma and by direct observation of sites. Users whose BP reading was above an action level of 135/85 mmHg were asked to attend their general practice. General practitioner records were reviewed 6 months after machine use to identify diagnoses of hypertension. A random sample of users was interviewed, and local general practices were asked about effects on their workload. RESULTS: a total of 758 first time users completed a proforma fully, although direct observations suggested total use was much higher. of the total, 221 (29.2 per cent) readings were above the action level. Eleven new hypertensives were found, 1.4 per cent (95 per cent confidence interval (CI 0.7-2.5) of the total users. User acceptability was high. All general practice replies were supportive. CONCLUSION: Open access sphygmomanometry for detection of hypertension is feasible. This scheme led to the diagnosis of hypertension in 1.4 per cent of users, and allowed many people to measure their BP in a way convenient to them. Before recommending wider implementation we suggest a study examining if our results are transferable to other settings, and if this approach reduces inequalities and is cost-effective.
Abstract.
Author URL.
Hamilton WT, Round AP, Sharp D, Peters T (2003). GPs can separate oncological wheat from chaff.
BMJ,
326(7385).
Author URL.
Hay AD, Hamilton W, Sharp D, Barrass B, Persad R (2003). Macroscopic haematuria and urological cancer.
BRITISH JOURNAL OF GENERAL PRACTICE,
53(488), 241-242.
Author URL.
Hay AD, Hamilton W, Sharp D, Barrass B, Persad R, Anderson P, Bruyninckx R, Buntinx F, Aertgeerts B, Van Casteren V, et al (2003). Macroscopic haematuria and urological cancer (multiple letters). British Journal of General Practice, 53(488), 241-243.
Hamilton W, Sharp D, Palatini P (2003). Rapid Responses from bmj.com. BMJ, 327(7418).
Hamilton WT, Hall GH (2003). Risk factors for ill health insurance claims.
J Insur Med,
35(1), 17-25.
Abstract:
Risk factors for ill health insurance claims.
OBJECTIVES: This study examined the information available at application for income protection insurance, to determine if any factors were predictive of a claim. The strength and significance of such factors were assessed and a predictive model was developed. BACKGROUND: the factors underlying life assurance risks are well known, but this is not the case for income protection insurance. For accurate underwriting of income protection insurance, it is important to know what information available at application has power to predict a claim. Improving the scientific accuracy of underwriting is good business practice, as well as answering the demands of disability legislation. METHODS: We studied all data available at application for 959 current claimants and 1417 non-claimants, using a case-control study design. Information included applicants' description of their occupation, marital status, build and habits, plus a questionnaire asking about their personal health. For some applicants medical reports were available as well. Information was transcribed onto a database, and univariate and multivariate analyses were performed. A predictive scoring system was established and its performance measured by receiver operating characteristic curves. RESULTS: Significant associations with claiming were found for many variables, including age (odds-ratio 1.04, p < 0.001), height (0.11, p = 0.03), smoking (2.10, p < 0.001), abstinence from alcohol (1.56, p = 0.01), recent medical advice (1.34, p = 0.06), and having had a lower gastrointestinal disorder (1.51, p = 0.04). Using all the information from the application, a predictive model was constructed. This model had good predictive power with an area under the receiver operating characteristic curve of 72%. CONCLUSIONS: Classical underwriting factors were generally shown to have predictive power for income protection insurance. The predictive scoring strengthens the scientific basis for underwriting and could be developed to simplify and expedite the underwriting process.
Abstract.
Author URL.
Hamilton WT, Round AP, Sharp D, Peters TJ (2003). The quality of record keeping in primary care: a comparison of computerised, paper and hybrid systems.
Br J Gen Pract,
53(497), 929-933.
Abstract:
The quality of record keeping in primary care: a comparison of computerised, paper and hybrid systems.
BACKGROUND: Computerised record keeping in primary care is increasing. However, no study has systematically examined the completeness of computer records in practices using different forms of record keeping. AIM: to compare computer-only record keeping to paper-only and hybrid systems, by measuring the number of consultations and symptoms recorded within individual consultations. DESIGN OF STUDY: Retrospective cohort study. SETTING: Eighteen general practices in the Exeter Primary Care Trust. METHOD: This study was part of a retrospective case control study of cancer patients aged over 40 years. All recorded consultations for a 2-year period were identified and coded for 1396 patients. Records were classified as paper, computer, or hybrid, depending on which medium stored the clinical information from consultations. RESULTS: More consultations were recorded in hybrid systems (median in 2 years = 11, interquartile range [IQR] = 6-18) than computer systems (median in 2 years = 9, IQR = 4-16.5) or paper systems (median in 2 years = 8, IQR = 5-14,): P
Abstract.
Author URL.
Hamilton WT, Sharp D, Marshall T, Palatini P, Brueren M, Bissery A (2002). Comparison of different measures of blood pressure. BMJ, 325(7376).
Hamilton WT, Sharp D (2002). Comparison of different measures of blood pressure - Use sphygmomanometers more, not less.
BRITISH MEDICAL JOURNAL,
325(7376), 1360-1360.
Author URL.
Kernick D, Hamilton W (2002). Headache. British Journal of General Practice, 52(483).
Hamilton W, Luthra M, Smith T, Evans P (2002). Non-attendance in general practice: a questionnaire survey. Primary Health Care Research & Development, 3(4), 226-230.
Hamilton W, Round A, Sharp D (2002). Patient, hospital, and general practitioner characteristics associated with non-attendance: a cohort study.
Br J Gen Pract,
52(477), 317-319.
Abstract:
Patient, hospital, and general practitioner characteristics associated with non-attendance: a cohort study.
Studies examining characteristics of non-attendance at hospital outpatients have given inconsistent results. We examined a cohort of 1972 referrals from 26 general practitioners, with complete follow-up. Five factors were found to be significantly associated with non-attendance: male sex, younger age, longer interval between referral and appointment, higher Jarman score and patients of a high-referring general practitioner. Targeting of strategies to reduce non-attendance is possible using these results.
Abstract.
Author URL.
Esen UI (2002). RAPID RESPONSES FROM BMJ.COM: Non-attendance at surgery. The BMJ, 327(7418).
Russell D, Hamilton W, Luthra M, Ctr RTMPH (2002). Research and consumer representation.
BRITISH JOURNAL OF GENERAL PRACTICE,
52(474), 58-58.
Author URL.
Hamilton W (2001). Chronic fatigue syndrome.
BRITISH JOURNAL OF GENERAL PRACTICE,
51(473), 1015-1015.
Author URL.
Hamilton WT, Hall GH, Round AP (2001). Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study.
Br J Gen Pract,
51(468), 553-558.
Abstract:
Frequency of attendance in general practice and symptoms before development of chronic fatigue syndrome: a case-control study.
BACKGROUND: Chronic fatigue syndrome (CFS) research has concentrated on infective, immunological, and psychological causes. Illness behaviour has received less attention, with most research studying CFS patients after diagnosis. Our previous study on the records of an insurance company showed a highly significant increase in illness reporting before development of CFS. AIM: to investigate the number and type of general practitioner (GP) consultations by patients with CFS for 15 years before they develop their condition. DESIGN OF STUDY: Case-control study in 11 general practices in Devon. SETTING: Forty-nine patients with CFS (satisfying the Centers for Disease Control criteria), 49 age, sex, and general practice matched controls, and 37 patients with multiple sclerosis (MS) were identified from the general practices' computerised databases. METHOD: the number of general practice consultations and symptoms recorded in three five-year periods (quinquennia) were counted before development of the patients' condition. RESULTS: the median number of consultations was significantly higher for CFS patients than that of matched controls in each of the quinquennia: ratios for first quinquennium = 1.88, P = 0.01; second quinquennium = 1.70, P = 0.005; last quinquennium = 2.25, P < 0.001. More CFS patients than controls attended for 13 of the 18 symptoms studied. Significant increases were found for upper respiratory tract infection (P < 0.001), lethargy (P < 0.001), and vertigo (P = 0.02). Similar results were found for CFS patients when compared with MS. CONCLUSIONS: CFS patients consulted their GP more frequently in the 15 years before development of their condition, for a wide variety of complaints. Several possibilities may explain these findings. The results support the hypothesis that behavioural factors have a role in the aetiology of CFS.
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Sharp DJ, Hamilton W (2001). Non-attendance at general practices and outpatient clinics: Local systems are needed to address local problems. British Medical Journal, 323(7321), 1081-1082.
Hamilton W (2001). The deaf GP's view. British Journal of General Practice, 51(468).
Goulding C, Hamilton W (2000). GP use of anti-D.
BRITISH JOURNAL OF FAMILY PLANNING,
26(2), 116-116.
Author URL.
Bryant G, Scott I, Worrall A, Hamilton W, Lloyd D (2000). Is norethisterone a lifestyle drug? (multiple letters). British Medical Journal, 320(7249).
Hamilton W (2000). Is norethisterone a lifestyle drug? the term lifestyle is not as clear as it may seem.
BRITISH MEDICAL JOURNAL,
320(7249), 1605-1605.
Author URL.
Hamilton W, Round A, Sharp D (2000). Non-attendance at psychiatric outpatient clinics.
BRITISH JOURNAL OF GENERAL PRACTICE,
50(451), 151-151.
Author URL.
Hamilton W, Round A, Sharp D (1999). Effect on hospital attendance rates of giving patients a copy of their referral letter: randomised controlled trial.
BMJ,
318(7195), 1392-1395.
Abstract:
Effect on hospital attendance rates of giving patients a copy of their referral letter: randomised controlled trial.
OBJECTIVES: to investigate whether sending patients a copy of their referral letter can reduce non-attendance at outpatient departments. DESIGN: Blinded randomised controlled trial. SETTING: 13 general practices in Exeter, Devon. SUBJECTS: 2078 new consultant referrals from 26 doctors. MAIN OUTCOME MEASURES: Non-attendance at outpatient departments. RESULTS: the doctors excluded 117 (5.6%) referrals, and 100 (4.8%) received no appointment. Attendance data were available for 1857 of the 1861 patients sent an appointment (99.8%). The receipt of a copy letter had no effect on the non-attendance rate: copy 50/912 (5.5%) versus control 50/945 (5.3%). CONCLUSION: Copy letters are ineffective in reducing non-attendance at outpatient departments.
Abstract.
Author URL.
Hamilton W (1999). General practice non-attendance.
BRITISH JOURNAL OF GENERAL PRACTICE,
49(445), 664-664.
Author URL.
Castan-Cameo S, Johnston J, Mcghee S, Lawlor D, Hanratty B, Hamilton W, Round A, Sharp D (1999). Non-attendance at outpatients departments. BMJ, 319(7217).
Castan-Cameo S, Johnston J, McGhee S, Lawlor D, Hanratty B, Hamilton W, Round A, Sharp D (1999). Non-attendance at outpatients departments (multiple letters) [5]. British Medical Journal, 319(7217), 1134-1135.
Hamilton W, Round A, Sharp D (1999). Non-attendance at outpatients departments - Reply.
BRITISH MEDICAL JOURNAL,
319(7217), 1135-1135.
Author URL.
Hamilton W, Bradley N (1999). Self regulation at work: a case study.
BMJ,
319(7209).
Author URL.
Hall GH, Hamilton WT, Round AP (1998). Increased illness experience preceding chronic fatigue syndrome. Journal of the Royal College of Physicians of London, 32(4).
Hall GH, Hamilton WT, Round AP (1998). Increased illness experience preceding chronic fatigue syndrome: a case control study.
J R Coll Physicians Lond,
32(1), 44-48.
Abstract:
Increased illness experience preceding chronic fatigue syndrome: a case control study.
BACKGROUND: Almost all published work on chronic fatigue syndrome (CFS) has involved retrospective surveys of cases, which may introduce recall bias. Only medical records collected before diagnosis of CFS can eliminate this. METHODS: Using data collected several years prior to the development of the illness, we performed a case control study, comparing the reported illness records of all people who subsequently made an insurance claim as a result of CFS, with those of future multiple sclerosis (MS) claimants, and those of non-claimant controls (NC). RESULTS: the study encompassed 133 CFS, 75 MS and 162 NC cases. CFS cases had recorded significantly more illnesses at time of proposal for insurance than the two control groups, and had significantly more claims between proposal and diagnosis of their disorder. Almost all disease categories were reported higher in future CFS sufferers, lethargy having the highest odds ratio after adjustment in a multivariate model. INTERPRETATION: the results of this paper on CFS patients who claim permanent health insurance do not support a specific viral or immunological explanation for CFS. We conclude that abnormal illness behaviour is of greater importance than previously recognised.
Abstract.
Author URL.
Hall GH, Hamilton WT, Lahuerta J, Ferran JR (1998). Use of medical information by UK insurers (multiple letters) [11]. Lancet, 352(9144).
Hall GH, Hamilton WT (1998). Use of medical information by UK insurers.
Lancet,
352(9144).
Author URL.
Hamilton W, Round A, Taylor P, Waterston T, Humfress H, Schmidt U (1997). Dictating clinic letters in front of the patient (multiple letters) [10]. British Medical Journal, 314(7091), 1416-1417.
Hamilton W, Round A, Taylor P (1997). Dictating clinic letters in front of the patient - Letting patients see copy of consultant's letter is being studied in trial.
BRITISH MEDICAL JOURNAL,
314(7091), 1416-1416.
Author URL.
Hamilton WT (1997). Efficacy of counselling.
BRITISH JOURNAL OF GENERAL PRACTICE,
47(414), 54-54.
Author URL.
Price J, Hamilton W (1997). Pragmatic eradication of H-pylori.
BRITISH JOURNAL OF GENERAL PRACTICE,
47(423), 660-660.
Author URL.
Price J, Hamilton W, Hawthorne AB, Hawthorne K (1997). Pragmatic eradication of H. pylori (multiple letters) [1]. British Journal of General Practice, 47(423).
Hall GH, Hamilton WT, Vallance P, Howell VM, Burnett L, Kay C, Harris H, Harris R (1996). Genetic testing [1]. Lancet, 347(9002), 685-686.
Hall GH, Hamilton WT (1996). Genetic testing.
Lancet,
347(9002).
Author URL.
Hamilton WT, Round AP, Hall GH (1995). Obtaining insurance should not depend on mechanism of diagnosis tests. BMJ, 311(7013).
HAMILTON W (1995). UNTITLED.
BRITISH JOURNAL OF GENERAL PRACTICE,
45(399), 564-564.
Author URL.
HAMILTON W, ROUND A (1995). URBAN-COMMUNITY HOSPITALS.
BRITISH JOURNAL OF GENERAL PRACTICE,
45(395), 326-327.
Author URL.
HAMILTON W, ROUND A (1994). COUNSELING IN GENERAL-PRACTICE.
BRITISH JOURNAL OF GENERAL PRACTICE,
44(386), 427-427.
Author URL.
Smyth E, Anderson E, Steel M, Hall GH, Hamilton WT (1994). Genetic testing and insurance. BMJ, 308(6926).
Hall GH, Hamilton WT (1994). Genetic testing and insurance. Withholding test results sidesteps ethical problems.
BMJ,
308(6926), 472-473.
Author URL.
HAMILTON W (1993). PERSONAL MEDICAL ATTENDANT REPORTS.
BRITISH JOURNAL OF GENERAL PRACTICE,
43(369), 172-173.
Author URL.
Round A, Hamilton W, Spencer K, Carpenter P (1993). Prenatal screening for Down's syndrome [10]. British Medical Journal, 307(6913), 1211-1212.
HALL GH, HAMILTON WT (1993). SICKNESS CERTIFICATION BY GENERAL-PRACTITIONERS.
BRITISH MEDICAL JOURNAL,
307(6908), 870-871.
Author URL.
Hall GH, Hamilton WT (1991). Coronary risk-disk [6]. British Medical Journal, 303(6809).
ROUND A, HAMILTON W (1990). CLINICAL-DIAGNOSIS OF TAMPONADE IN MALAWI.
QUARTERLY JOURNAL OF MEDICINE,
76(279), 763-766.
Author URL.
Round A, Hamilton W (1990). Clinical diagnosis of tamponade in Malawi.
QJM,
76(1), 763-766.
Abstract:
Clinical diagnosis of tamponade in Malawi
A consecutive series of 25 Malawian patients with tamponade secondary to tuberculosis were compared to 25 patients with congestive cardiac failure, without pericardial effusion in a retrospective study. More patients with tamponade had an impalpable apex beat (21/1), pulsus paradoxus (13/0), soft heart sounds (13/2), paradoxical rise in jugular venous pressure (6/0), and fewer had a murmur (1/14). All these results are significant (p
Abstract.
ROUND A, HAMILTON W (1988). PENICILLIN AND MENINGOCOCCI.
LANCET,
1(8587), 702-702.
Author URL.
Round A, Hamilton W (1988). Penicillin and meningococci. Lancet, 1(8587).
