scholarly journals Antihypertensive Medications and COVID-19 Diagnosis and Mortality: Population-based Case-Control Analysis in the United Kingdom

2020 ◽  
Author(s):  
Emma Rezel-Potts ◽  
Abdel Douiri ◽  
Phil J Chowienczyk ◽  
Martin C Gulliford
Keyword(s):  
Antihypertensive Therapy ◽  
Population Based ◽  
Case Control ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Control Analysis ◽  
Antihypertensive Medications ◽  
Lower Odds ◽  
Healthcare Seeking ◽  
Increased Risk

Objectives: To evaluate antihypertensive medications and COVID-19 diagnosis and mortality, accounting for healthcare seeking behaviour. Design: A population-based case control study with additional cohort analysis. Setting: Primary care patients from the UK Clinical Practice Research Datalink (CPRD). Participants: 16 866 patients with COVID-19 events in the CPRD from 29th January to June 25th 2020 and 70 137 matched controls. Main outcome measures: We explored associations between COVID-19 diagnosis and prescriptions for angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (B), calcium-channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). We evaluated all-cause mortality among COVID-19 cases. Analyses were adjusted for covariates and consultation frequency. Results: In covariate adjusted analyses, ACEIs were associated with lower odds of COVID-19 diagnosis (0.82, 95% confidence interval 0.77 to 0.88) as were ARBs, 0.87 (0.80 to 0.95) with little attenuation from adjustment for consultation frequency. In fully adjusted analyses, C and D were also associated with lower odds of COVID-19. Increased odds of COVID-19 for B (1.19, 1.12 to 1.26), were attenuated after adjustment for consultation frequency (1.01, 0.95 to 1.08). In adjusted analyses, patients treated with ACEIs or ARBs had similar mortality to patients treated with classes B, C, D or O (1.00, 0.83 to 1.20) or patients receiving no antihypertensive therapy (0.99, 0.83 to 1.18). Conclusions: Associations were sensitive to adjustment for confounding and healthcare seeking, but there was no evidence that antihypertensive therapy is associated with increased risk of COVID-19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID-19 diagnosis.

ACE inhibitor use and risk of cataract: a case–control analysis

2019 ◽  
Vol 103 (11) ◽  
pp. 1561-1565 ◽  
Author(s):  
Claudia Becker ◽  
Susan S Jick ◽  
Christoph R Meier
Keyword(s):  
Observational Study ◽  
Index Date ◽  
Antihypertensive Drugs ◽  
Conditional Logistic Regression ◽  
Case Control ◽  
Sensitivity Analyses ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Control Analysis ◽  
Increased Risk

Background/AimUse of ACE inhibitors (ACEIs) has been associated with an increased risk of cataract in a previous observational study in humans. In contrast, ACEIs were associated with beneficial effects on cataract development in experimental studies. We assessed the risk of cataract in relation to exposure to ACEI and other antihypertensive drugs.MethodsThis is a case-control study based on data from the UK-based Clinical Practice Research Datalink (CPRD). We included first-time cataract patients aged ≥40 years between 1995 and 2015 and an equal number of cataract-free controls. We matched the controls to cases on age, sex, general practice, date of first cataract (ie, index date) and years of history in the CPRD prior to the index date. We assessed the number of prescriptions for ACEI and other antihypertensive drugs in detail and explored the use of single ACEI substances. We performed conditional logistic regression and conducted various sensitivity analyses to test the robustness of our findings. We calculated the risk of cataract associated with previous exposure to ACEI, measured as OR with 95% CIs, and adjusted the multivariable model for body mass index, smoking, diabetes, hypertension, prescriptions of systemic corticosteroids and other antihypertensive drugs.ResultsWe identified 206 931 cataract cases and the same number of matched controls. Use of ACEI was not associated with a materially altered risk of cataract compared with non-use of ACEI, neither in the main analysis (OR 1.06, 95% CI 1.04 to 1.08) nor in any of the sensitivity or stratified analyses.ConclusionIn our large observational study, use of ACEI was not associated with an altered risk of cataract.

scholarly journals Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies

Thorax ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Christos V Chalitsios ◽  
Dominick E Shaw ◽  
Tricia M McKeever
Keyword(s):  
Cumulative Dose ◽  
Inhaled Corticosteroids ◽  
Conditional Logistic Regression ◽  
Fragility Fractures ◽  
Case Control ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Case Control Studies ◽  
Increased Risk ◽  
Nested Case Control

BackgroundInhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established.MethodsWe conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated.ResultsThere was a dose–response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively.ConclusionsThe findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.

Obesity As a Risk Factor for Acute Promyelocytic Leukemia. Results from Population and Case-Control Studies Across Western Countries and Correlation with Gene Expression in the TCGA

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 448-448 ◽  
Author(s):  
Luca Mazzarella ◽  
Edoardo Botteri ◽  
Anthony Matthews ◽  
Davide Disalvatore ◽  
Vincenzo Bagnardi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factor ◽  
Acute Promyelocytic Leukemia ◽  
Population Based ◽  
Case Control ◽  
Promyelocytic Leukemia ◽  
Transcriptional Analysis ◽  
Clinical Practice Research Datalink ◽  
Case Control Studies ◽  
Increased Risk

Abstract Background. Much uncertainty remains over the aetiology of Acute Myeloid Leukemia (AML) and of its biological subtypes, of which Acute Promyelocytic Leukemia (APL) is the best defined. In recent years, an elevated Body Mass Index (BMI) has been identified as a risk factor for several diseases. Whether BMI influences risk of developing AML and APL is not well understood. Methods. We have collated information from population-based and case-control studies conducted in four different countries. In the population-based study, we obtained data from the Clinical Practice Research Datalink, that includes primary care data of 5.2 million UK citizens. We identified APL and other leukemia cases using ICD identifiers ("APL" (n=24), "non APL-AML" (n=972), lymphoid leukemias ("LL", n=2724) and "other" (n=1850). We fitted linear models to investigate the association between BMI and any of the above leukemic classes. In the case-control studies, we analysed data from patients included in the PETHEMA (Spain, n=414) and GIMEMA (Italy, n=134) databases and patients from the USA-based AML genome sequencing study (the AML TCGA cohort with 22 additional cases characterized at Washington University-St Louis, n=42) ("case" cohorts). We then created age-, gender, ethnicity- and year of diagnosis-matched control cohorts from national BMI surveys and tested deviation of observed cases from expected controls. Lastly, we applied Quantitative Set Analysis for Gene Expression (quSAGE) analysis to investigate APL- or BMI-specific gene expression signatures from TCGA data Findings. In the UK population study, the Hazard Ratio per each 5 kg/m2 increase was 1.44 for APL (95% CI 1.0-2.08), 1.17 for non APL-AML (95% CI 1.10-1.26), 1.04 for LL (95% CI 1.0-1.09) and 1.10 for other leukemias (95% CI 1.04-1.15). In the case-control studies, BMI distribution in cases was significantly higher than expected from controls for all three cohorts: (Italy p<0.001, Spain p=0.011, USA p<0.001). quSAGE transcriptional analysis revealed significant enrichment of several pathways in APL vs other AMLs, in particular arachidonic and linoleic acid metabolism and upregulation of Insulin and IGF1 receptors. Interpretation. A higher BMI was associated with increased risk of leukemia, particularly APL; increased risk of APL was confirmed in all populations examined, irrespective of gender or ethnicity. Elevated BMI should be considered a risk factor for APL development. APL is associated with a characteristic metabolic transcriptional signature that might be responsible for some of its clinical features Disclosures Breccia: Novartis: Consultancy, Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Ariad: Honoraria; Bristol Myers Squibb: Honoraria. Lo Coco:Lundbeck: Honoraria, Speakers Bureau; Novartis: Consultancy; Baxalta: Consultancy; Pfizer: Consultancy; Teva: Consultancy, Honoraria, Speakers Bureau.

Risk of osteoarthritis in an incident cohort of people with psoriatic arthritis: a population-based cohort study

2020 ◽  
pp. jrheum.200564
Author(s):  
Rachel Charlton ◽  
Amelia Green ◽  
Gavin Shaddick ◽  
Julia Snowball ◽  
Alison Nightingale ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
General Population ◽  
Population Based ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Study Cohort ◽  
Relative Risks ◽  
Population Cohort ◽  
Increased Risk ◽  
General Population Cohort

Objective To determine the risk of a diagnosis of osteoarthritis (OA) in psoriatic arthritis (PsA) patients compared to patients with psoriasis and a general population cohort. Methods Incident PsA patients aged 18-89 years at diagnosis were identified from the UK Clinical Practice Research Datalink between 1998 and 2014. All PsA patients were matched to two cohorts of patients both at a 1:4 ratio. The first cohort included patients with psoriasis (and no PsA) and the second was a general population cohort (with no psoriasis or PsA). The baseline prevalence of OA was calculated for each study cohort. The incidence of OA was calculated and adjusted relative risks (RRadj) were calculated using conditional Poisson regression. Results We identified 6,783 incident PsA patients. The baseline prevalence of OA ranged from 22.1% (CI9521.1-23.1) in the PsA cohort to 12.6% (CI9512.2-13.0) and 11.0% (CI9510.6- 11.3) in the psoriasis and general population cohorts respectively. The incidence of OA was significantly higher in the PsA cohort compared to the psoriasis and general population cohorts after adjusting for BMI (RRadj 1.68 CI951.46-1.93 and RRadj 1.86 CI951.62-2.14 respectively). Conclusion An increased risk of OA was observed in patients with PsA compared to patients with psoriasis alone and those in the general population. Further work is needed to determine whether this reflects a true increase in OA risk or misdiagnosed PsA and the extent to which it can be explained by differences in the opportunity for OA diagnosis between cohorts.

scholarly journals Infectious Disease Burden and the Risk of Alzheimer’s Disease: A Population-Based Study

2021 ◽  
pp. 1-10
Author(s):  
Antonios Douros ◽  
Christina Santella ◽  
Sophie Dell’Aniello ◽  
Laurent Azoulay ◽  
Christel Renoux ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Burden ◽  
Population Based ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Cumulative Number ◽  
Increased Risk

Background: Previous studies suggested a link between various infectious pathogens and the development of Alzheimer’s disease (AD), posing the question whether infectious disease could present a novel modifiable risk factor. Objective: To assess whether infectious disease burden due to clinically apparent infections is associated with an increased risk of AD. Methods: We conducted a population-based nested case-control study using the United Kingdom Clinical Practice Research Datalink. We included all dementia-free subjects ≥50 years of age enrolling in the database between January 1988 and December 2017. Each case of AD identified during follow-up was matched with up to 40 controls. Conditional logistic regression estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with ≥1 infection diagnosed >  2 years before the index date compared with no infection during the study period. We further stratified by time since first infection and cumulative number of infections. Results: The cohort included overall 4,262,092 individuals (mean age at cohort entry 60.4 years; 52% female). During a median follow-up of 10.5 years, 40,455 cases of AD were matched to 1,610,502 controls. Compared with having no burden of infectious disease, having a burden of infectious disease was associated with an increase in the risk of AD (OR, 1.05; 95% CI, 1.02 to 1.08). The risk increased with longer time since first infection, peaking after 12–30 years (OR, 1.11; 95% CI, 1.05–1.17). The risk did not increase with cumulative number of infections. Conclusion: The overall risk of AD associated with infectious disease burden was small but increased gradually with longer time since first infection.

Abstract P135: Varenicline and the Risk of Adverse Cardiovascular Events: A Population-Based Cohort Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Kristian B Filion ◽  
Sophie Dell'Aniello ◽  
Maria Eberg ◽  
Christel Renoux ◽  
Stella S Daskalopoulou ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cohort Study ◽  
Cardiovascular Events ◽  
Proportional Hazards Model ◽  
Population Based ◽  
Cox Proportional Hazards Model ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Increased Risk ◽  
The Mean

Background: Clinical trial results suggest that varenicline is the most efficacious smoking cessation therapy. However, its cardiovascular safety is controversial, with recent meta-analyses providing conflicting results. Our objective was to compare the effect of varenicline to that of bupropion on the risk of cardiovascular events. Methods: We conducted a population-based cohort study of new users of varenicline or bupropion using data extracted from the UK’s Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics. Our primary endpoint was a composite of myocardial infarction, coronary revascularization, stroke, and all-cause mortality. An ‘as-treated’ analysis with a Cox proportional hazards model was used, with patients censored 7 days after the end of their last prescription or upon switching smoking cessation drugs. In secondary analyses, we compared varenicline and bupropion to nicotine replacement therapy (NRT) in pairwise comparisons. All analyses used high-dimensional propensity scores to adjust for potential confounding. Results: Our primary cohort included 90,522 varenicline users and 12,640 bupropion users. The mean age was 44 years, and 48% were men. The mean treatment duration was 45 days. A total of 128 events occurred among varenicline users, and 15 occurred among bupropion users. Although estimates suggest that varenicline may modestly increase the risk of cardiovascular events compared to bupropion, they were accompanied by wide 95% CIs (Table). Both varenicline and bupropion users had significantly lower risks of cardiovascular events than NRT users (Table). Conclusions: While we cannot exclude a modestly increased risk of cardiovascular events with varenicline relative to bupropion, such events remain rare, and both varenicline and bupropion are associated with a decreased risk of cardiovascular events compared with NRT. The long-term benefits obtained due to the increased smoking abstinence with varenicline likely outweigh any increased cardiovascular risk.

scholarly journals Renal effectiveness and safety of the sodium-glucose cotransporter-2 inhibitors: a population-based cohort study

2021 ◽  
Vol 9 (2) ◽  
pp. e002496
Author(s):  
Wajd Alkabbani ◽  
Arsene Zongo ◽  
Jasjeet K Minhas-Sandhu ◽  
Dean T Eurich ◽  
Baiju R Shah ◽  
...  
Keyword(s):  
Cohort Study ◽  
Renal Disease ◽  
Disease Progression ◽  
Population Based ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Renal Disease Progression ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Significant Difference

IntroductionTo assess the comparative effectiveness and safety of renal-related outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2-i) initiation among patients with type 2 diabetes using real-world data.Research design and methodsWe conducted a population‐based cohort study using administrative healthcare data from Alberta (AB), Canada and primary care data from the Clinical Practice Research Datalink (CPRD), UK. From a cohort of new metformin users, we identified initiators of a SGLT2-i or dipeptidyl peptidase-4 inhibitor (DPP4-i) between January 1, 2014 and March 30, 2018 (AB) or between January 1, 2013 and November 29, 2018 (CPRD). Initiators of an SGLT2-i or DPP4-i were followed until death, disenrolment, therapy discontinuation, or study end date. The effectiveness outcome was renal disease progression, defined as a composite of new-onset macroalbuminuria, serum creatinine doubling with estimated glomerular filtration rate of ≤45 mL/min/1.73 m2, renal replacement therapy, hospital admission or death from renal causes. The safety outcome was hospitalization due to acute kidney injury (AKI). We adjusted for confounding using high-dimensional propensity score matching and estimated HRs using Cox proportional hazards regression. Aggregate data from each database were combined by random-effects meta‐analysis.ResultsAmong the 29 465 included patients (20 564 AB, 8901 CPRD), 37.5% were new SGLT2-i users in AB and 21.3% in CPRD. Compared with DPP4 initiators, SGLT2-i initiators were associated with a reduced risk of renal disease progression (pooled HR 0.79, 95% CI 0.62 to 1.00); however, there was no significant difference in the risk of AKI (pooled HR 0.89, 95% CI 0.58 to 1.36). These findings were consistent with other exposure definitions and antidiabetic comparators.ConclusionsOur findings support a renoprotective effect of SGLT2-i without an increased risk of AKI, compared with clinically relevant active comparators.

The concurrent use of antithrombotic therapies and the risk of bleeding in patients with atrial fibrillation

2013 ◽  
Vol 109 (03) ◽  
pp. 431-439 ◽  
Author(s):  
Laurent Azoulay ◽  
Sophie Dell’Aniello ◽  
Teresa Simon ◽  
Christel Renoux ◽  
Samy Suissa
Keyword(s):  
Atrial Fibrillation ◽  
Triple Therapy ◽  
Large Population ◽  
Population Based ◽  
Practice Research ◽  
Control Analysis ◽  
Research Database ◽  
Risk Of Bleeding ◽  
Concurrent Use ◽  
Increased Risk

SummaryPatients with atrial fibrillation (AF) often receive, in addition to warfarin, antithrombotic drugs to manage other comorbid conditions. To date, few population-based studies have quantified the bleeding risk associated with the concurrent use of these therapies. The United Kingdom General Practice Research Database was used to identify a cohort of 70,760 patients newly-diagnosed with AF between 1993 and 2008. A nested case-control analysis was conducted within that cohort, and conditional logistic regression was used to estimate adjusted rate ratios (RRs) of bleeding associated with current use of warfarin, aspirin, and clopidogrel in single therapy, as well as in dual and triple therapy, as compared with non-use of any therapy. A total of 10,850 patients experienced a bleeding event during follow-up. In single therapy, warfarin was associated with the highest increased risk (RR: 2.08, 95% confidence interval [CI]: 1.95–2.23), followed by clopidogrel (RR: 1.57, 95% CI: 1.37–1.81) and aspirin (RR: 1.25, 95% CI: 1.17–1.34). In dual therapy, combinations containing warfarin were associated with a higher increased risk (warfarin-aspirin: RR: 2.87, 95% CI: 2.58–3.19, and warfarin-clopidogrel: RR: 2.74, 95% CI: 2.14–3.51), than those not containing warfarin (aspirin-clopidogrel: RR: 1.68, 95% CI: 1.44–1.97). Triple therapy of warfarin-aspirin-clopidogrel was associated with the highest increased risk (RR: 3.75, 95% CI: 2.71–5.19). This large population-based study suggests that while all antithrombotic therapies are associated with an elevated risk of bleeding, the risks increase in an additive fashion with dual and triple therapy, particularly in combinations containing warfarin.

scholarly journals Bloodstream Infection Following Cardiac Valve Repair: A Population-Based Study

2021 ◽  
Vol 8 (11) ◽  
Author(s):  
Jack W McHugh ◽  
Khawaja M Talha ◽  
Larry M Baddour ◽  
Karen M Fischer ◽  
Juan Crestanello ◽  
...  
Keyword(s):  
Bloodstream Infection ◽  
Population Based ◽  
Case Control ◽  
Cardiac Valve ◽  
Control Analysis ◽  
Valve Repair ◽  
Population Based Study ◽  
Crude Incidence ◽  
Increased Risk ◽  
Case Control Analysis

Abstract Background The aim of this study was to determine the incidence, epidemiology, and associated risk factors of bloodstream infection (BSI) in patients who had previously undergone cardiac valve repair. Methods A population-based study that included 7 counties in southeastern Minnesota using the expanded Rochester Epidemiology Project (e-REP) for adults (≥18 years) who underwent valve repair between 1 January 2010 and 31 December 2018 was conducted. Electronic health records were screened for development of BSI and infective endocarditis (IE) from the date of valve repair through 30 July 2020. A 1:4 nested case-control analysis was performed to determine an association, if any, of male sex, Charlson comorbidity index (CCI), and county of residence with BSI. Results A total of 335 patients underwent valve repair, of whom 28 (8.3%) developed an index case of BSI, with 14 episodes occurring within 1 year of surgery. The median age of patients with BSI was 70 years, and 79% were male. The crude incidence of BSI was 1671 cases per 100000 person-years and Escherichia coli was the most common pathogen. Case-control analysis demonstrated a significant correlation between CCI and incidence of BSI (P &lt; .001). Only 4 (14.3%) patients developed IE concurrent with the onset of BSI, and no patients developed IE subsequent to BSI. Conclusions The crude incidence of BSI following valve repair was higher in our e-REP cohort than previous population-based studies, and half of the BSI cases occurred within 1 year of surgery. Patients with a higher CCI at baseline were at increased risk of subsequent BSI.

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