Journal articles
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 Full text.
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.
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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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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).
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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)
© 2018 British Journal of General Practice. 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
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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.
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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.
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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.
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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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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.
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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.
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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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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).
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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 (χ2test). 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 (χ2test, p
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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.
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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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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Shephard EA (2014). Erratum: Clinical features of bladder cancer in primary care (British Journal of General Practice (2012) DOI: 10.3399/bjgp12X654560). British Journal of General Practice, 64(620).
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.
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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
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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.
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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.
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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
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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.
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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
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Temple CM, Shephard EE (2012). Exceptional lexical skills but executive language deficits in school starters and young adults with Turners syndrome: Implications for X chromosome effects on brain function. Brain and Language, 120(3), 345-359.
Shephard E, Stapley S, Hamilton W (2011). The use of electronic databases in primary care research.
Family Practice,
28(4), 352-354.
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