Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

Objective To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account. Design Two nested case-control studies. Setting General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices). Participants Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year. Main outcome measures Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets. Results 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10 000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17). Conclusions In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs

Predicting the risk of Chronic Kidney Disease in Men and Women in England and Wales: prospective derivation and external validation of the QKidney® Scores

<p>Abstract</p> <p>Background</p> <p>Chronic Kidney Disease is a major cause of morbidity and interventions now exist which can reduce risk. We sought to develop and validate two new risk algorithms (the QKidney^®Scores) for estimating (a) the individual 5 year risk of moderate-severe CKD and (b) the individual 5 year risk of developing End Stage Kidney Failure in a primary care population.</p> <p>Methods</p> <p>We conducted a prospective open cohort study using data from 368 QResearch^®general practices to develop the scores. We validated the scores using two separate sets of practices - 188 separate QResearch^®practices and 364 practices contributing to the THIN database.</p> <p>We studied 775,091 women and 799,658 men aged 35-74 years in the QResearch^®derivation cohort, who contributed 4,068,643 and 4,121,926 person-years of observation respectively.</p> <p>We had two main outcomes (a) moderate-severe CKD (defined as the first evidence of CKD based on the earliest of any of the following: kidney transplant; kidney dialysis; diagnosis of nephropathy; persistent proteinuria; or glomerular filtration rate of < 45 mL/min) and (b) End Stage Kidney Failure.</p> <p>We derived separate risk equations for men and women. We calculated measures of calibration and discrimination using the two separate validation cohorts.</p> <p>Results</p> <p>Our final model for moderate-severe CKD included: age, ethnicity, deprivation, smoking, BMI, systolic blood pressure, diabetes, rheumatoid arthritis, cardiovascular disease, treated hypertension, congestive cardiac failure; peripheral vascular disease, NSAID use and family history of kidney disease. In addition, it included SLE and kidney stones in women. The final model for End Stage Kidney Failure was similar except it did not include NSAID use.</p> <p>Each risk prediction algorithms performed well across all measures in both validation cohorts. For the THIN cohort, the model to predict moderate-severe CKD explained 56.38% of the total variation in women and 57.49% for men. The D statistic values were high with values of 2.33 for women and 2.38 for men. The ROC statistic was 0.875 for women and 0.876 for men.</p> <p>Conclusions</p> <p>These new algorithms have the potential to identify high risk patients who might benefit from more detailed assessment, closer monitoring or interventions to reduce their risk.</p

Preliminary results of a feasibility study of the use of information technology for identification of suspected colorectal cancer in primary care: the CREDIBLE study

This is the final version of the article. Available from Cancer Research UK/Nature Publishing Group via the DOI in this record.BACKGROUND: We report the findings of a feasibility study using information technology to search electronic primary care records and to identify patients with possible colorectal cancer. METHODS: An algorithm to flag up patients meeting National Institute for Health and Care Excellence (NICE) urgent referral criteria for suspected colorectal cancer was developed and incorporated into clinical audit software. This periodically flagged up such patients aged 60 to 79 years. General practitioners (GPs) reviewed flagged-up patients and decided on further clinical management. We report the numbers of patients identified and the numbers that GPs judged to need further review, investigations or referral to secondary care and the final diagnoses. RESULTS: Between January 2012 and March 2014, 19,580 records of patients aged 60 to 79 years were searched in 20 UK general practices, flagging up 809 patients who met urgent referral criteria. The majority of the patients had microcytic anaemia (236 (29%)) or rectal bleeding (205 (25%)). A total of 274 (34%) patients needed further clinical review of their records; 199 (73%) of these were invited for GP consultation, and 116 attended, of whom 42 were referred to secondary care. Colon cancer was diagnosed in 10 out of 809 (1.2%) flagged-up patients and polyps in a further 28 out of 809 (3.5%). CONCLUSIONS: It is technically possible to identify patients with colorectal cancer by searching electronic patient records.We acknowledge the General Practitioners, practice nurses, practice managers and administrative staff who supported this study, our trial co-ordinator Marie Crook, Anthony Ingold who was one of our patient representatives and MSDi for their support in developing the software algorithm. We also acknowledge the support of the National Institute for Health Research Clinical Research Network. This study was funded by the National Awareness and Early Diagnosis Initiative (NAEDI). TM is partly funded by the National Institute for Health Research (NIHR) through the Collaborations for Leadership in Applied Health Research and Care for the West Midlands (CLAHRC-WM) programme

Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

IMPORTANCE Anticholinergic medicines have short-term cognitive adverse effects, but itis uncertain whether long-term use of these drugs is associated with an increased risk of dementia.OBJECTIVE To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.DESIGN, SETTING, AND PARTICIPANTS This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.EXPOSURES The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).MAIN OUTCOMES AND MEASURES Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.RESULTS Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95%CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95%CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95%CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95%CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95%CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95%CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95%CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95%CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.CONCLUSIONS AND RELEVANCE Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people

Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: series of nested case–control studies using two primary-care databases

Background: Bisphosphonates are the most commonly prescribed osteoporosis drugs but long-term effects are unclear, although antitumour properties are known from preclinical studies. Methods: Nested case–control studies were conducted to investigate bisphosphonate use and risks of common nongastrointestinal cancers (breast, prostate, lung, bladder, melanoma, ovarian, pancreas, uterus and cervical). Patients 50 years and older, diagnosed with primary cancers between 1997 and 2011, were matched to five controls using the UK practice-based QResearch and Clinical Practice Research Datalink (CPRD) databases. The databases were analysed separately and the results combined. Results: A total of 91 556 and 88 845 cases were identified from QResearch and CPRD, respectively. Bisphosphonate use was associated with reduced risks of breast (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.87–0.97), prostate (OR: 0.87, 95% CI: 0.79–0.96) and pancreatic (OR: 0.79, 95% CI: 0.68–0.93) cancers in the combined analyses, but no significant trends with duration. For alendronate, reduced risk associations were found for prostate cancer in the QResearch (OR: 0.81, 95% CI: 0.70–0.93) and combined (OR: 0.84, 95% CI: 0.75–0.93) analyses (trend with duration P-values 0.009 and 0.001). There were no significant associations from any of the other analyses. Conclusion: In this series of large population-based case–control studies, bisphosphonate use was not associated with increased risks for any common non-gastrointestinal cancers

Prediction of cardiovascular risk using Framingham, ASSIGN and QRISK2: how well do they predict individual rather than population risk?

BACKGROUND: The objective of this study was to evaluate the performance of risk scores (Framingham, Assign and QRISK2) in predicting high cardiovascular disease (CVD) risk in individuals rather than populations. METHODS AND FINDINGS: This study included 1.8 million persons without CVD and prior statin prescribing using the Clinical Practice Research Datalink. This contains electronic medical records of the general population registered with a UK general practice. Individual CVD risks were estimated using competing risk regression models. Individual differences in the 10-year CVD risks as predicted by risk scores and competing risk models were estimated; the population was divided into 20 subgroups based on predicted risk. CVD outcomes occurred in 69,870 persons. In the subgroup with lowest risks, risk predictions by QRISK2 were similar to individual risks predicted using our competing risk model (99.9% of people had differences of less than 2%); in the subgroup with highest risks, risk predictions varied greatly (only 13.3% of people had differences of less than 2%). Larger deviations between QRISK2 and our individual predicted risks occurred with calendar year, different ethnicities, diabetes mellitus and number of records for medical events in the electronic health records in the year before the index date. A QRISK2 estimate of low 10-year CVD risk (<15%) was confirmed by Framingham, ASSIGN and our individual predicted risks in 89.8% while an estimate of high 10-year CVD risk (≥ 20%) was confirmed in only 48.6% of people. The majority of cases occurred in people who had predicted 10-year CVD risk of less than 20%. CONCLUSIONS: Application of existing CVD risk scores may result in considerable misclassification of high risk status. Current practice to use a constant threshold level for intervention for all patients, together with the use of different scoring methods, may inadvertently create an arbitrary classification of high CVD risk

An external validation of the QCOVID3 risk prediction algorithm for risk of hospitalisation and death from COVID-19: An observational, prospective cohort study of 1.66m vaccinated adults in Wales, UK

INTRODUCTION: At the start of the COVID-19 pandemic there was an urgent need to identify individuals at highest risk of severe outcomes, such as hospitalisation and death following infection. The QCOVID risk prediction algorithms emerged as key tools in facilitating this which were further developed during the second wave of the COVID-19 pandemic to identify groups of people at highest risk of severe COVID-19 related outcomes following one or two doses of vaccine. OBJECTIVES: To externally validate the QCOVID3 algorithm based on primary and secondary care records for Wales, UK. METHODS: We conducted an observational, prospective cohort based on electronic health care records for 1.66m vaccinated adults living in Wales on 8th December 2020, with follow-up until 15th June 2021. Follow-up started from day 14 post vaccination to allow the full effect of the vaccine. RESULTS: The scores produced by the QCOVID3 risk algorithm showed high levels of discrimination for both COVID-19 related deaths and hospital admissions and good calibration (Harrell C statistic: ≥ 0.828). CONCLUSION: This validation of the updated QCOVID3 risk algorithms in the adult vaccinated Welsh population has shown that the algorithms are valid for use in the Welsh population, and applicable on a population independent of the original study, which has not been previously reported. This study provides further evidence that the QCOVID algorithms can help inform public health risk management on the ongoing surveillance and intervention to manage COVID-19 related risks