Journal articles
Atkins J, Masoli J, Correa-Delgado J, Pilling L, Kuo C-L, Melzer D, Kuchel G (In Press). PREEXISTING COMORBIDITIES PREDICTING COVID-19 AND MORTALITY IN THE UK BIOBANK COMMUNITY COHORT. Journal of Gerontology Series A: Biological Sciences and Medical Sciences
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
MASOLI JANEAH, MENSAH EKOW, RAJKUMAR CHAKRAVARTHI (2022). Age and ageing cardiovascular collection: blood pressure, coronary heart disease and heart failure.
AGE AND AGEING,
51(8).
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Delgado J, Evans PH, Gray DP, Sidaway-Lee K, Allan L, Clare L, Ballard C, Masoli J, Valderas JM, Melzer D, et al (2022). Continuity of GP care for patients with dementia: impact on prescribing and the health of patients.
Br J Gen Pract,
72(715), e91-e98.
Abstract:
Continuity of GP care for patients with dementia: impact on prescribing and the health of patients.
BACKGROUND: Higher continuity of GP care (CGPC), that is, consulting the same doctor consistently, can improve doctor-patient relationships and increase quality of care; however, its effects on patients with dementia are mostly unknown. AIM: to estimate the associations between CGPC and potentially inappropriate prescribing (PIP), and with the incidence of adverse health outcomes (AHOs) in patients with dementia. DESIGN AND SETTING: a retrospective cohort study with 1 year of follow-up anonymised medical records from 9324 patients with dementia, aged ≥65 years living in England in 2016. METHOD: CGPC measures include the Usual Provider of Care (UPC), Bice-Boxerman Continuity of Care (BB), and Sequential Continuity (SECON) indices. Regression models estimated associations with PIPs and survival analysis with incidence of AHOs during the follow-up adjusted for age, sex, deprivation level, 14 comorbidities, and frailty. RESULTS: the highest quartile (HQ) of UPC (highest continuity) had 34.8% less risk of delirium (odds ratio [OR] 0.65, 95% confidence interval [CI] = 0.51 to 0.84), 57.9% less risk of incontinence (OR 0.42, 95% CI = 0.31 to 0.58), and 9.7% less risk of emergency admissions to hospital (OR 0.90, 95% CI = 0.82 to 0.99) compared with the lowest quartile. Polypharmacy and PIP were identified in 81.6% (n = 7612) and 75.4% (n = 7027) of patients, respectively. The HQ had fewer prescribed medications (HQ: mean 8.5, lowest quartile (LQ): mean 9.7, P
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Masoli JAH, Pilling LC, Frayling TM (2022). Genomics and multimorbidity.
Age and Ageing,
51(12).
Abstract:
Genomics and multimorbidity
Abstract
. Multimorbidity has increased in prevalence world-wide. It is anticipated to affect over 1 in 6 of the UK population by 2035 and is now recognised as a global priority for health research. Genomic medicine has rapidly advanced over the last 20 years from the first sequencing of the human genome to integration into clinical care for rarer conditions. Genetic studies help identify new disease mechanisms as they are less susceptible to the bias and confounding that affects epidemiological studies, as genetics are assigned from conception. There is also genetic variation in the efficacy of medications and the risk of side effects, pharmacogenetics. Genomic approaches offer the potential to improve our understanding of mechanisms underpinning multiple long-term conditions/multimorbidity and guide precision approaches to risk, diagnosis and optimisation of management. In this commentary as part of the Age and Ageing 50th anniversary commentary series, we summarise genomics and the potential utility of genomics in multimorbidity.
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Masoli JAH, Sheppard JP, Rajkumar C (2022). Hypertension management in older patients - Are the guideline blood pressure targets appropriate?. Age and Ageing, 51(1).
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.
Davies M, Bramwell LR, Jeffery N, Bunce B, Lee BP, Knight B, Auckland C, Masoli JA, Harries LW (2022). Persistence of clinically relevant levels of SARS-CoV2 envelope gene subgenomic RNAs in non-immunocompromised individuals.
Int J Infect Dis,
116, 418-425.
Abstract:
Persistence of clinically relevant levels of SARS-CoV2 envelope gene subgenomic RNAs in non-immunocompromised individuals.
OBJECTIVES: This study aimed to evaluate the associations between COVID-19 severity and active viral load, and to characterize the dynamics of active SARS-CoV-2 clearance in a series of archival samples taken from patients in the first wave of COVID-19 infection in the South West of the UK. METHODS: Subgenomic RNA (sgRNA) and E-gene genomic sequences were measured in a retrospective collection of PCR-confirmed SARS-CoV-2-positive samples from 176 individuals, and related to disease severity. Viral clearance dynamics were then assessed in relation to symptom onset and last positive test. RESULTS: Whilst E-gene sgRNAs declined before E-gene genomic sequences, some individuals retained sgRNA positivity for up to 68 days. 13% of sgRNA-positive cases still exhibited clinically relevant levels of virus after 10 days, with no clinical features previously associated with prolonged viral clearance times. CONCLUSIONS: Our results suggest that potentially active virus can sometimes persist beyond a 10-day period, and could pose a potential risk of onward transmission. Where this would pose a serious public health threat, additional mitigation strategies may be necessary to reduce the risk of secondary cases in vulnerable settings.
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Türkmen D, Masoli JAH, Kuo C, Bowden J, Melzer D, Pilling LC (2022). Statin treatment effectiveness and the <i>SLCO1B1</i>*5 reduced function genotype: Long‐term outcomes in women and men.
British Journal of Clinical Pharmacology,
88(7), 3230-3240.
Abstract:
Statin treatment effectiveness and the SLCO1B1*5 reduced function genotype: Long‐term outcomes in women and men
ObjectiveTo estimate the effect of rs4149056 (SLCO1B1*5) genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications.Methods and AnalysisThis study comprised 69 185 European‐ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40‐79 years at first prescription, treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5 mmol/L) at baseline, plus treatment discontinuation.ResultsA total of 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol vs 41.7% of those with functioning SLCO1B1 (odds ratio 1.31, 95% confidence interval [CI] 1.1‐1.55, P = .001). Fewer males had high cholesterol and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (hazard ratio [HR] 1.19, 95% CI 1.03‐1.37, P = .01), amounting to five discontinuations per 100 statin‐years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3, 95% CI 1.08‐1.56, P = .006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year.ConclusionsIn this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve the effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype‐guided statin selection.
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Masoli JAH, Down K, Nestor G, Hudson S, O'Brien JT, Williamson JD, Young CA, Carroll C (2021). A report from the NIHR UK working group on remote trial delivery for the COVID-19 pandemic and beyond.
TRIALS,
22(1).
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Geriatric Medicine Research Collaborative, Covid Collaborative, Welch C (2021). Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study.
Age Ageing,
50(3), 617-630.
Abstract:
Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study.
INTRODUCTION: Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. METHODS: This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. RESULTS: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54-83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18-49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54-5.02), frailty (CFS 8 versus 1-3: HR 3.03, CI 2.29-4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1-3: odds ratio 7.00, CI 5.27-9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. CONCLUSION: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.
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Pilling LC, Turkmen D, Fullalove H, Atkins JL, Delgado J, Kuo C-L, Kuchel GA, Ferrucci L, Bowden J, Masoli JAH, et al (2021). Analysis of <i>CYP2C19</i> genetic variants with ischaemic events in UK patients prescribed clopidogrel in primary care: a retrospective cohort study.
BMJ OPEN,
11(12).
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Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, Hinsley WR, Laydon DJ, Dabrera G, Toole AO, et al (2021). Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England.
NATURE,
593(7858), 266-+.
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Masoli JAH, Kirkham FA, Rajkumar C (2021). Atrial fibrillation and oral anticoagulation in older adults: an update. Age and Ageing, 50(3), 687-689.
Kuo C-L, Pilling LC, Atkins JL, Masoli JAH, Delgado J, Tignanelli C, Kuchel GA, Melzer D, Beckman KB, Levine ME, et al (2021). Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants.
The Journals of Gerontology: Series A,
76(8), e133-e141.
Abstract:
Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants
Abstract
.
. Background
. Age and disease prevalence are the 2 biggest risk factors for Coronavirus disease 2019 (COVID-19) symptom severity and death. We therefore hypothesized that increased biological age, beyond chronological age, may be driving disease-related trends in COVID-19 severity.
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.
. Methods
. Using the UK Biobank England data, we tested whether a biological age estimate (PhenoAge) measured more than a decade prior to the COVID-19 pandemic was predictive of 2 COVID-19 severity outcomes (inpatient test positivity and COVID-19-related mortality with inpatient test-confirmed COVID-19). Logistic regression models were used with adjustment for age at the pandemic, sex, ethnicity, baseline assessment centers, and preexisting diseases/conditions.
.
.
. Results
. Six hundred and thirteen participants tested positive at inpatient settings between March 16 and April 27, 2020, 154 of whom succumbed to COVID-19. PhenoAge was associated with increased risks of inpatient test positivity and COVID-19-related mortality (ORMortality = 1.63 per 5 years, 95% CI: 1.43–1.86, p = 4.7 × 10−13) adjusting for demographics including age at the pandemic. Further adjustment for preexisting diseases/conditions at baseline (ORM = 1.50, 95% CI: 1.30–1.73 per 5 years, p = 3.1 × 10−8) and at the early pandemic (ORM = 1.21, 95% CI: 1.04–1.40 per 5 years, p =. 011) decreased the association.
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.
. Conclusions
. PhenoAge measured in 2006–2010 was associated with COVID-19 severity outcomes more than 10 years later. These associations were partly accounted for by prevalent chronic diseases proximate to COVID-19 infection. Overall, our results suggest that aging biomarkers, like PhenoAge may capture long-term vulnerability to diseases like COVID-19, even before the accumulation of age-related comorbid conditions.
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Masoli JAH, Delgado J (2021). Blood pressure, frailty and dementia.
Experimental Gerontology,
155Abstract:
Blood pressure, frailty and dementia
High blood pressure (BP) affects 75% of people aged over 70. Ageing alters BP homeostasis, resulting in postural hypotension and increased BP variability. Co-morbidity and frailty add complexity to understanding BP changes in later life. Longitudinal BP declines are likely driven by accumulating co-morbidity and are accelerated in both frailty and dementia. This narrative review summarises what is known about the association between BP and frailty, the clinical management of BP in frailty and the association between BP, cognitive decline and dementia.
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Graham MS, Sudre CH, May A, Antonelli M, Murray B, Varsavsky T, Kläser K, Canas LS, Molteni E, Modat M, et al (2021). Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study. The Lancet Public Health, 6(5), e335-e345.
Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O’Toole Á, Southgate J, Johnson R, Jackson B, Nascimento FF, et al (2021). Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell, 184(1), 64-75.e11.
Pilling LC, Türkmen D, Fullalove H, Atkins JL, Delgado J, Kuo C-L, Kuchel GA, Ferrucci L, Bowden J, Masoli JAH, et al (2021). Genetic variation in activating clopidogrel: longer-term outcomes in a large community cohort.
Abstract:
Genetic variation in activating clopidogrel: longer-term outcomes in a large community cohort
AbstractBackgroundThe antiplatelet drug clopidogrel is commonly prescribed for stroke and myocardial infarction (MI) prevention. Clopidogrel prodrug is predominantly activated by liver enzyme CYP2C19. CYP2C19 Loss-of-function (LoF) genetic variants have been linked to excess morbidity mainly in patients hospitalized for acute ischemic events and related interventions. Little is known about the magnitude of impact of LoF variants in family practice, especially over long periods of exposure. We aimed to determine whether CYP2C19 LoF alleles increase risk of ischemic stroke and MI in primary care patients prescribed clopidogrel for up to 18 years.MethodsRetrospective cohort analysis of 7,483 European-ancestry adults from the UK Biobank study with genetic and linked primary care data, aged 36 to 79 years at first clopidogrel prescription. We examined CYP2C19 LoF variant (*2-*8) associations with incident hospital-diagnosed ischemic stroke and MI in patients prescribed clopidogrel for at least 2 months using time-to-event models, with secondary analysis of the. 17 gain of function variant.Results28.7% (n=2,144/7,483) of included subjects (mean age 63 years at first clopidogrel prescription) carried at least one CYP2C19 intermediate or low metabolizer LoF variant. 1.9% of LoF variant carriers had an incident ischemic stroke whilst prescribed clopidogrel (mean 2.6 years, range 2 months to 18 years), versus 1.3% without the variants (0.6% absolute excess: Hazard Ratio 1.53: 95% CI 1.04 to 2.26, p=0.031). Additionally, 26.4% of CYP2C19 LoF variant carriers had an incident MI versus 24.1% (HR 1.14: 1.04 to 1.26, p=.008). Adjustment for aspirin co-prescription produced similar estimates. In lifetables using observed incidence rates, 22.5% (95% CI 14.4% to 34.0%) of CYP2C19 LoF carriers on clopidogrel were projected to develop an ischemic stroke by age 79 (the oldest age in the study), compared with 15.4% (95% CI 11.4% to 20.5%) in non-carriers: the absolute excess stroke incidence with LoF variants was 7.1% by age 79.ConclusionIn family practice patients on clopidogrel, CYP2C19 LoF variants are associated with substantially higher incidence of ischemic events. Genotype-guided (or routine) prescription of antiplatelet medications unaffected by CYP2C19 variants may improve outcomes in patients for whom clopidogrel is currently indicated.
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Collier DA, De Marco A, Ferreira IATM, Meng B, Datir RP, Walls AC, Kemp SA, Bassi J, Pinto D, Silacci-Fregni C, et al (2021). Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies.
NATURE,
593(7857), 136-+.
Author URL.
Masoli JAH, Todd OM, Clark CE (2021). Systolic blood pressure and outcomes in frail older adults.
British Journal of Hospital Medicine,
82(5), 1-4.
Abstract:
Systolic blood pressure and outcomes in frail older adults
Hypertension is diagnosed in the majority of older people with frailty, in whom blood pressure prognosis is not well understood. This editorial describes recent evidence on blood pressure and outcomes in older people with frailty.
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Masoli JAH, Jeffries A, Temperton B, Auckland C, Michelsen M, Warwick-Dugdale J, Manley R, Farbos A, Ellard S, Knight B, et al (2021). Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak.
Abstract:
Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak
AbstractBackgroundWe have successfully used whole-genome sequencing to provide additional information for transmission pathways in infectious spread. We report and interpret genomic sequencing results in clinical context from a large outbreak of COVID-19 with 46 cases across staff and patients in a community hospital in the UK.MethodsFollowing multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests.ResultsThirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns. Patient haplotypes were more distinct from each other but had overlap with staff haplotypes.ConclusionsThis study includes clinical and genomic epidemiological detail that demonstrates the value of a combined approach. Viral genetic sequencing has identified that staff transmission of COVID-19 was important in this community hospital outbreak.Key pointsDetailed analysis of a large community hospital outbreak in older adults and staff with concurrent clinical and genomic data, including working patterns.Staff transmission was important in this community hospital outbreak.We found plausible associations between staff and patient cases.
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Kuo C-L, Pilling LC, Atkins JL, Masoli JAH, Delgado J, Kuchel GA, Melzer D (2020). <i>ApoE</i> e4e4 genotype and mortality with COVID-19 in UK Biobank.
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ApoE e4e4 genotype and mortality with COVID-19 in UK Biobank
AbstractWe previously reported that the ApoE e4e4 genotype was associated with COVID-19 test positivity (OR=2.31, 95% CI: 1.65 to 3.24, p=1.19×10−6) in the UK Biobank (UKB) cohort, during the epidemic peak in England, from March 16 to April 26, 2020. With more COVID-19 test results (March 16 to May 31, 2020) and mortality data (to April 26, 2020) linked to UKB, we re-evaluated the ApoE e4 allele association with COVID-19 test positivity, and with all-cause mortality following test-confirmed COVID-19. Logistic regression models compared ApoE e4e4 participants (or e3e4s) to e3e3s with adjustment for sex; age on April 26th or age at death; baseline UKB assessment center in England (accounting for geographical differences in viral exposures); genotyping array type; and the top five genetic principal components (accounting for possible population admixture). ApoE e4e4 genotype was associated with increased risks of test positivity (OR=2.24, 95% CI: 1.72 to 2.93, p=3.24×10−9) and of mortality with test-confirmed COVID-19 (OR=4.29, 95% CI: 2.38 to 7.72, p=1.22×10−6), compared to e3e3s. Independent replications are needed to confirm our findings and mechanistic work is needed to understand how ApoE e4e4 results in the marked increase in vulnerability, especially for COVID-19 mortality. These findings also demonstrate that risks for COVID-19 mortality are not simply related to advanced chronological age or the comorbidities commonly seen in aging.
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Kuo C-L, Pilling LC, Atkins JL, Masoli JAH, Delgado J, Kuchel GA, Melzer D (2020). APOE e4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort.
J Gerontol a Biol Sci Med Sci,
75(11), 2231-2232.
Author URL.
Kuo C-L, Pilling LC, Atkins JL, Masoli JAH, Delgado J, Kuchel GA, Melzer D (2020). ApoE e4e4 Genotype and Mortality with COVID-19 in UK Biobank. The Journals of Gerontology: Series A, 75(9), 1801-1803.
Atkins JL, Pilling LC, Masoli JAH, Kuo C-L, Shearman JD, Adams PC, Melzer D (2020). Association of Hemochromatosis <i>HFE</i> p.C282Y Homozygosity with Hepatic Malignancy. JAMA, 324(20), 2048-2048.
Masoli JAH, Delgado J, Pilling L, Strain D, Melzer D (2020). Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.
Age Ageing,
49(5), 807-813.
Abstract:
Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.
BACKGROUND: Blood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target 150 mmHg. Associations with mortality varied between non-frail
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Kuo C-L, Pilling LC, Atkins JL, Masoli JAH, Delgado J, Tignanelli C, Kuchel GA, Melzer D, Beckman KB, Levine ME, et al (2020). COVID-19 severity is predicted by earlier evidence of accelerated aging.
Abstract:
COVID-19 severity is predicted by earlier evidence of accelerated aging
AbstractWith no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes [1]. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) [2] composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020) [3]. Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2×10−6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.
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Welch C, Welch C, McCluskey L, Wilson D, Moorey H, Majid Z, Madden K, McNeela N, Richardson S, Burton J, et al (2020). Growing research in geriatric medicine: a trainee perspective.
Age and Ageing,
49(5), 733-737.
Abstract:
Growing research in geriatric medicine: a trainee perspective
Growing research in geriatric medicine is a priority area. Currently, involvement of geriatricians in research lags behind other specialties. The reasons for this are multifactorial, but a lack of training infrastructure within geriatric medicine higher specialist training is contributory. This is widespread across European countries and internationally. The Geriatric Medicine Research Collaborative (GeMRC) offers an opportunity to engage trainees in research, regardless of their previous individual research experiences. Utilising national trainee networks, GeMRC is able to conduct large-scale projects within short periods of time that can have real impact upon patient care. We consider that embedding GeMRC within higher specialist training with formal college support will assist to upskill trainee geriatricians in research methodology. Collaboratives are internationally recognised across disciplines. Expansion across European and international countries offers the opportunity for international collaboration in geriatric medicine. International trainee-led networks will enable the conduct of large-scale global projects in geriatric medicine.
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Pilling LC, Jones LC, Masoli JAH, Delgado J, Atkins JL, Bowden J, Fortinsky RH, Kuchel GA, Melzer D (2020). Low Vitamin D Levels and Risk of Incident Delirium in 351,000 Older <scp>UK</scp> Biobank Participants.
Journal of the American Geriatrics Society,
69(2), 365-372.
Abstract:
Low Vitamin D Levels and Risk of Incident Delirium in 351,000 Older UK Biobank Participants
BACKGROUND/OBJECTIVESDelirium is common in older adults, especially following hospitalization. Because low vitamin D levels may be associated with increased delirium risk, we aimed to determine the prognostic value of blood vitamin D levels, extending our previous genetic analyses of this relationship.DESIGNProspective cohort analysis.SETTINGCommunity‐based cohort study of adults from 22 cities across the United Kingdom (the UK Biobank).PARTICIPANTSAdults aged 60 and older by the end of follow‐up in the linked hospital inpatient admissions data, up to 14 years after baseline (n = 351,320).MEASUREMENTSAt baseline, serum vitamin D (25‐OH‐D) levels were measured. We used time‐to‐event models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D deficiency and incident hospital‐diagnosed delirium, adjusted for age, sex, assessment month, assessment center, and ethnicity. We performed Mendelian randomization genetic analysis in European participants to further investigate vitamin D and delirium risk.RESULTSA total of 3,634 (1.03%) participants had at least one incident hospital‐diagnosed delirium episode. Vitamin D deficiency (<25 nmol/L) predicted a large incidence in delirium (HR = 2.49; 95% CI = 2.24–2.76; P = 3*10−68, compared with >50 nmol/L). Increased risk was not limited to the deficient group: insufficient levels (25–50 nmol/L) were also at increased risk (HR = 1.38; 95% CI = 1.28–1.49; P = 4*10−18). The association was independent of calcium levels, hospital‐diagnosed fractures, dementia, and other relevant cofactors. In genetic analysis, participants carrying more vitamin D–increasing variants had a reduced likelihood of incident delirium diagnosis (HR =. 80 per standard deviation increase in genetically instrumented vitamin D:. 73–.87; P = 2*10−7).CONCLUSIONProgressively lower vitamin D levels predicted increased risks of incident hospital‐diagnosed delirium, and genetic evidence supports a shared causal pathway. Because low vitamin D levels are simple to detect and inexpensive and safe to correct, an intervention trial to confirm these results is urgently needed.
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Bowman K, Jones L, Masoli J, Mujica-Mota R, Strain D, Butchart J, Valderas JM, Fortinsky RH, Melzer D, Delgado J, et al (2020). Predicting incident delirium diagnoses using data from primary-care electronic health records.
Age Ageing,
49(3), 374-381.
Abstract:
Predicting incident delirium diagnoses using data from primary-care electronic health records.
IMPORTANCE: risk factors for delirium in hospital inpatients are well established, but less is known about whether delirium occurring in the community or during an emergency admission to hospital care might be predicted from routine primary-care records. OBJECTIVES: identify risk factors in primary-care electronic health records (PC-EHR) predictive of delirium occurring in the community or recorded in the initial episode in emergency hospitalisation. Test predictive performance against the cumulative frailty index. DESIGN: Stage 1: case-control; Stages 2 and 3: retrospective cohort. SETTING: clinical practice research datalink: PC-EHR linked to hospital discharge data from England. SUBJECTS: Stage 1: 17,286 patients with delirium aged ≥60 years plus 85,607 controls. Stages 2 and 3: patients ≥ 60 years (n = 429,548 in 2015), split into calibration and validation groups. METHODS: Stage 1: logistic regression to identify associations of 110 candidate risk measures with delirium. Stage 2: calibrating risk factor weights. Stage 3: validation in independent sample using area under the curve (AUC) receiver operating characteristic. RESULTS: fifty-five risk factors were predictive, in domains including: cognitive impairment or mental illness, psychoactive drugs, frailty, infection, hyponatraemia and anticholinergic drugs. The derived model predicted 1-year incident delirium (AUC = 0.867, 0.852:0.881) and mortality (AUC = 0.846, 0.842:0.853), outperforming the frailty index (AUC = 0.761, 0.740:0.782). Individuals with the highest 10% of predicted delirium risk accounted for 55% of incident delirium over 1 year. CONCLUSIONS: a risk factor model for delirium using data in PC-EHR performed well, identifying individuals at risk of new onsets of delirium. This model has potential for supporting preventive interventions.
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Author URL.
Clark CE, Masoli J, Warren FC, Soothill J, Campbell JL (2020). Vitamin D and COVID-19 in older age: evidence versus expectations. British Journal of General Practice, 71(702), 10-11.
Masoli J, Correa Delgado J, Bowman K, Strain W, Henley W, Melzer D (2019). Association of blood pressure with clinical outcomes in older adults with chronic kidney disease. Age and Ageing
Welch C, McCluskey L, Wilson D, Chapman GE, Jackson TA, Treml J, Davis D, Cunningham E, Copeland C, Quinn T, et al (2019). Delirium is prevalent in older hospital inpatients and associated with adverse outcomes: Results of a prospective multi-centre study on World Delirium Awareness Day.
BMC Medicine,
17(1).
Abstract:
Delirium is prevalent in older hospital inpatients and associated with adverse outcomes: Results of a prospective multi-centre study on World Delirium Awareness Day
Background: Delirium is a common severe neuropsychiatric condition secondary to physical illness, which predominantly affects older adults in hospital. Prior to this study, the UK point prevalence of delirium was unknown. We set out to ascertain the point prevalence of delirium across UK hospitals and how this relates to adverse outcomes. Methods: We conducted a prospective observational study across 45 UK acute care hospitals. Older adults aged 65 years and older were screened and assessed for evidence of delirium on World Delirium Awareness Day (14th March 2018). We included patients admitted within the previous 48 h, excluding critical care admissions. Results: the point prevalence of Diagnostic and Statistical Manual on Mental Disorders, Fifth Edition (DSM-5) delirium diagnosis was 14.7% (222/1507). Delirium presence was associated with higher Clinical Frailty Scale (CFS): CFS 4-6 (frail) (OR 4.80, CI 2.63-8.74), 7-9 (very frail) (OR 9.33, CI 4.79-18.17), compared to 1-3 (fit). However, higher CFS was associated with reduced delirium recognition (7-9 compared to 1-3; OR 0.16, CI 0.04-0.77). In multivariable analyses, delirium was associated with increased length of stay (+ 3.45 days, CI 1.75-5.07) and increased mortality (OR 2.43, CI 1.44-4.09) at 1 month. Screening for delirium was associated with an increased chance of recognition (OR 5.47, CI 2.67-11.21). Conclusions: Delirium is prevalent in older adults in UK hospitals but remains under-recognised. Frailty is strongly associated with the development of delirium, but delirium is less likely to be recognised in frail patients. The presence of delirium is associated with increased mortality and length of stay at one month. A national programme to increase screening has the potential to improve recognition.
Abstract.
Welsh T, Masoli J (2018). Antihypertensive medications may reduce the risk of dementia in older African–Americans with hypertension. Evidence Based Nursing, 21(4), 104-104.
Delgado J, Bowman K, Ble A, Masoli J, Han Y, Henley W, Welsh S, Kuchel GA, Ferrucci L, Melzer D, et al (2018). Blood Pressure Trajectories in the 20 Years Before Death.
JAMA Intern Med,
178(1), 93-99.
Abstract:
Blood Pressure Trajectories in the 20 Years Before Death.
IMPORTANCE: There is mixed evidence that blood pressure (BP) stabilizes or decreases in later life. It is also unclear whether BP trajectories reflect advancing age, proximity to end of life, or selective survival of persons free from hypertension. OBJECTIVE: to estimate individual patient BP for each of the 20 years before death and identify potential mechanisms that may explain trajectories. DESIGN, STUDY, AND PARTICIPANTS: We analyzed population-based Clinical Practice Research Datalink primary care and linked hospitalization electronic medical records from the United Kingdom, using retrospective cohort approaches with generalized linear mixed-effects modeling. Participants were all available individuals with BP measures over 20 years, yielding 46 634 participants dying aged at least 60 years, from 2010 to 2014. We also compared BP slopes from 10 to 3 years before death for 20 207 participants who died, plus 20 207 birth-year and sex-matched participants surviving longer than 9 years. MAIN OUTCOMES AND MEASURES: Clinically recorded individual patient repeated systolic BP (SBP) and diastolic BP (DBP). RESULTS: in 46 634 participants (51.7% female; mean [SD] age at death, 82.4 [9.0] years), SBPs and DBPs peaked 18 to 14 years before death and then decreased progressively. Mean changes in SBP from peak values ranged from -8.5 mm Hg (95% CI, -9.4 to -7.7) for those dying aged 60 to 69 years to -22.0 mm Hg (95% CI, -22.6 to -21.4) for those dying at 90 years or older; overall, 64.0% of individuals had SBP changes of greater than -10 mm Hg. Decreases in BP appeared linear from 10 to 3 years before death, with steeper decreases in the last 2 years of life. Decreases in SBP from 10 to 3 years before death were present in individuals not treated with antihypertensive medications, but mean yearly changes were steepest in patients with hypertension (-1.58; 95% CI, -1.56 to -1.60 mm Hg vs -0.70; 95% CI, -0.65 to -0.76 mm Hg), dementia (-1.81; 95% CI, -1.77 to -1.87 mm Hg vs -1.41; 95% CI, -1.38 to -1.43 mm Hg), heart failure (-1.66; 95% CI, -1.62 to -1.69 mm Hg vs -1.37; 95% CI, -1.34 to -1.39 mm Hg), and late-life weight loss. CONCLUSIONS AND RELEVANCE: Mean SBP and DBP decreased for more than a decade before death in patients dying at 60 years and older. These BP decreases are not simply attributable to age, treatment of hypertension, or better survival without hypertension. Late-life BP decreases may have implications for risk estimation, treatment monitoring, and trial design.
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Author URL.
Pilling LC, Masoli J, Melzer D, Kuchel G (2018). Clinical Outcomes of CADASIL-Associated NOTCH3 Mutations in 451,424 European Ancestry Community Volunteers. Translational Stroke Research
Atkins JL, Delgado J, Pilling L, Bowman K, Masoli J, Kuchel G, Ferrucci L, Melzer D (2018). Impact of Low Cardiovascular Risk Profiles on Geriatric Outcomes: Evidence from 421,000 Participants in Two Cohorts. Journals of Gerontology: Medical Sciences
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.
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Author URL.
(2018). Using Social Media and Web-Based Networking in Collaborative Research: Protocol for the Geriatric Medicine Research Collaborative. JMIR Research Protocols, 7(10), e179-e179.
Stephenson J, Masoli J, Leitch M, Baines R (2017). P-49 ‘Is home where i want to die?’ – prognostication and preferred place of care at the end of life in older hospital inpatients. BMJ Supportive & Palliative Care, 7(Suppl 1), A18.1-A18.
Ble A, Hughes PM, Delgado J, Masoli JA, Bowman K, Zirk-Sadowski J, Mujica Mota RE, Henley WE, Melzer D (2017). Safety and Effectiveness of Statins for Prevention of Recurrent Myocardial Infarction in 12 156 Typical Older Patients: a Quasi-Experimental Study.
J Gerontol a Biol Sci Med Sci,
72(2), 243-250.
Abstract:
Safety and Effectiveness of Statins for Prevention of Recurrent Myocardial Infarction in 12 156 Typical Older Patients: a Quasi-Experimental Study.
BACKGROUND: There is limited evidence on statin risk and effectiveness for patients aged 80+. We estimated risk of recurrent myocardial infarction, muscle-related and other adverse events, and statin-related incremental costs in "real-world" older patients treated with statins versus no statins. METHODS: We used primary care electronic medical records from the UK Clinical Practice Research Datalink. Subhazard ratios (competing risk of death) for myocardial infarction recurrence (primary end point), falls, fractures, ischemic stroke, and dementia, and hazard ratios (Cox) for all-cause mortality were used to compare older (60+) statin users and 1:1 propensity-score-matched controls (n = 12,156). Participants were followed-up for 10 years. RESULTS: Mean age was 76.5±9.2 years; 45.5% were women. Statins were associated with near significant reduction in myocardial infarction recurrence (subhazard ratio = 0.84, 0.69-1.02, p =. 073), with protective effect in the 60-79 age group (0.73, 0.57-0.94) but a nonsignificant result in the 80+ group (1.06, 0.78-1.44; age interaction p =. 094). No significant associations were found for stroke or dementia. Data suggest an increased risk of falls (1.36, 1.17-1.60) and fractures (1.33, 1.04-1.69) in the first 2 years of treatment, particularly in the 80+ group. Treatment was associated with lower all-cause mortality. Statin use was associated with health care cost savings in the 60-79 group but higher costs in the 80+ group. CONCLUSIONS: Estimates of statin effectiveness for the prevention of recurrent myocardial infarction in patients aged 60-79 years were similar to trial results, but more evidence is needed in the older group. There may be an excess of falls and fractures in very old patients, which deserves further investigation.
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Author URL.
correa delgado, masoli, Bowman K, strain, Kuchel G, Walters K, Lafortune L, Brayne C, Melzer D, ble, et al (2016). OUTCOMES OF TREATED HYPERTENSION AT AGES 80 YEARS AND OLDER: COHORT ANALYSIS OF 79,376 PATIENTS. Journal of the American Geriatrics Society, 65, 995-1003.
Bowman K, Correa Delgado J, Henley W, Masoli J, Kos K, Brayne C, Thokala P, Lafortune L, Kuchel G, Ble A, et al (2016). Obesity in Older People with and Without Conditions Associated with Weight Loss: Follow-up of 955,000 Primary Care Patients. J Gerontol a Biol Sci Med Sci
Ble A, Masoli JAH, Barry HE, Winder RE, Tavakoly B, Henley WE, Kuchel GA, Valderas JM, Melzer D, Richards SH, et al (2015). Any versus long-term prescribing of high risk medications in older people using 2012 Beers Criteria: results from three cross-sectional samples of primary care records for 2003/4, 2007/8 and 2011/12.
BMC Geriatr,
15Abstract:
Any versus long-term prescribing of high risk medications in older people using 2012 Beers Criteria: results from three cross-sectional samples of primary care records for 2003/4, 2007/8 and 2011/12.
BACKGROUND: High risk medications are commonly prescribed to older US patients. Currently, less is known about high risk medication prescribing in other Western Countries, including the UK. We measured trends and correlates of high risk medication prescribing in a subset of the older UK population (community/institutionalized) to inform harm minimization efforts. METHODS: Three cross-sectional samples from primary care electronic clinical records (UK Clinical Practice Research Datalink, CPRD) in fiscal years 2003/04, 2007/08 and 2011/12 were taken. This yielded a sample of 13,900 people aged 65 years or over from 504 UK general practices. High risk medications were defined by 2012 Beers Criteria adapted for the UK. Using descriptive statistical methods and regression modelling, prevalence of 'any' (drugs prescribed at least once per year) and 'long-term' (drugs prescribed all quarters of year) high risk medication prescribing and correlates were determined. RESULTS: While polypharmacy rates have risen sharply, high risk medication prevalence has remained stable across a decade. A third of older (65+) people are exposed to high risk medications, but only half of the total prevalence was long-term (any = 38.4 % [95 % CI: 36.3, 40.5]; long-term = 17.4 % [15.9, 19.9] in 2011/12). Long-term but not any high risk medication exposure was associated with older ages (85 years or over). Women and people with higher polypharmacy burden were at greater risk of exposure; lower socio-economic status was not associated. Ten drugs/drug classes accounted for most of high risk medication prescribing in 2011/12. CONCLUSIONS: High risk medication prescribing has not increased over time against a background of increasing polypharmacy in the UK. Half of patients receiving high risk medications do so for less than a year. Reducing or optimising the use of a limited number of drugs could dramatically reduce high risk medications in older people. Further research is needed to investigate why the oldest old and women are at greater risk. Interventions to reduce high risk medications may need to target shorter and long-term use separately.
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Melzer D, Tavakoly B, Winder RE, Masoli JAH, Henley WE, Ble A, Richards SH (2015). Much more medicine for the oldest old: trends in UK electronic clinical records.
Age Ageing,
44(1), 46-53.
Abstract:
Much more medicine for the oldest old: trends in UK electronic clinical records.
BACKGROUND: the oldest old (85+) pose complex medical challenges. Both underdiagnosis and overdiagnosis are claimed in this group. OBJECTIVE: to estimate diagnosis, prescribing and hospital admission prevalence from 2003/4 to 2011/12, to monitor trends in medicalisation. DESIGN AND SETTING: observational study of Clinical Practice Research Datalink (CPRD) electronic medical records from general practice populations (eligible; n = 27,109) with oversampling of the oldest old. METHODS: we identified 18 common diseases and five geriatric syndromes (dizziness, incontinence, skin ulcers, falls and fractures) from Read codes. We counted medications prescribed ≥1 time in all quarters of studied years. RESULTS: there were major increases in recorded prevalence of most conditions in the 85+ group, especially chronic kidney disease (stages 3-5: prevalence
Abstract.
Author URL.
Masoli J, Winder R, Tavakoly B, Henley W, Ble A, Richards S, Melzer D (2014). 63. OVERDIAGNOSING AND MISSING THE POINT?. Age and Ageing, 43(suppl 2), ii19-ii19.
Butt E, Foster JAH, Keedwell E, Bell JEA, Titball RW, Bhangu A, Michell SL, Sheridan R (2013). Derivation and validation of a simple, accurate and robust prediction rule for risk of mortality in patients with Clostridium difficile infection.
BMC Infect Dis,
13Abstract:
Derivation and validation of a simple, accurate and robust prediction rule for risk of mortality in patients with Clostridium difficile infection.
BACKGROUND: Clostridium difficile infection poses a significant healthcare burden. However, the derivation of a simple, evidence based prediction rule to assist patient management has not yet been described. METHOD: Univariate, multivariate and decision tree procedures were used to deduce a prediction rule from over 186 variables; retrospectively collated from clinical data for 213 patients. The resulting prediction rule was validated on independent data from a cohort of 158 patients described by Bhangu et al. (Colorectal Disease, 12(3):241-246, 2010). RESULTS: Serum albumin levels (g/L) (P = 0.001), respiratory rate (resps /min) (P = 0.002), C-reactive protein (mg/L) (P = 0.034) and white cell count (mcL) (P = 0.049) were predictors of all-cause mortality. Threshold levels of serum albumin ≤ 24.5 g/L, C- reactive protein >228 mg/L, respiratory rate >17 resps/min and white cell count >12 × 10(3) mcL were associated with an increased risk of all-cause mortality. A simple four variable prediction rule was devised based on these threshold levels and when tested on the initial data, yield an area under the curve score of 0.754 (P
Abstract.
Author URL.
Foster JAH, Butt JEC, Bell J, Goff A, Morgan C, Hancock J, Carmichael C, Keedwell EC, Michell SLI, Sheridan RP, et al (2012). IMPROVING CLINICAL MANAGEMENT IN CLOSTRIDIUM DIFFICILE: FAECAL CALPROTECTIN DOES NOT PREDICT SEVERITY, RECURRENCE OR MORTALITY.
AGE AND AGEING,
41, 72-72.
Author URL.
