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

Identifying early symptoms associated with a diagnosis of childhood, adolescent and young adult cancers: a population-based nested case-control study

Background: Childhood, teenage and young adult (CTYA, 0–24 years) cancers are rare and diverse, making timely diagnosis challenging. We aim to explore symptoms and symptom combinations associated with a subsequent cancer diagnosis and to establish their timeframe. Methods: Using the QResearch Database, we carried out a matched nested case-control study. Associations between pre-specified symptoms encountered in primary care and a subsequent diagnosis of any cancer were explored using conditional logistic regression. Median diagnostic intervals were used to split symptoms into “late” and “early” timeframes to identify relevant early symptoms. Results: 3186 cases and 50,576 controls were identified from a cohort of 3,424,771 CTYA. We identified 12 novel associations, of which hemiparesis [OR 90.9 (95%CI 24.7-335.1), PPV = 1.6%], testicular swelling [OR 186.7 (95%CI 86.1-404.8), PPV = 2.4%] and organomegaly [OR 221.6 (95%CI 28.3-1735.9), PPV = 5.4%] had significant positive predictive values (PPV). Limb pain, a known marker of serious illness in children, was a recurrent early symptom across cancer subtypes. Similar clinical presentations were observed across childhood and TYA cancers. Discussion: Using the largest cohort to date, we provide novel information on the time-varying predictive utility of symptoms in the diagnosis of CTYA cancers. Our findings will help to raise clinical and public awareness of symptoms, stratify those at higher-risk and ultimately aid earlier diagnosis

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

Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis

Background: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. Aims: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. Methods: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. Results: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin’s lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin’s lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). Conclusion: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease

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

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

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