SummaryBackgroundThe past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps.MethodsFor this population-based cohort study, we used linked primary care, hospital, and cancer registry data from the UK Clinical Practice Research Datalink to identify cohorts of survivors of the 20 most common cancers who were 18 years or older and alive 12 months after diagnosis and controls without history of cancer, matched for age, sex, and general practice. We compared risks for a range of cardiovascular disease outcomes using crude and adjusted Cox models. We fitted interactions to investigate effect modification, and flexible parametric survival models to estimate absolute excess risks over time.FindingsBetween Jan 1, 1990, and Dec 31, 2015, 126 120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630 144 controls. After exclusions, 108 215 cancer survivors and 523 541 controls were included in the main analyses. Venous thromboembolism risk was elevated in survivors of 18 of 20 site-specific cancers compared with that of controls; adjusted hazard ratios (HRs) ranged from 1·72 (95% CI 1·57–1·89) in patients after prostate cancer to 9·72 (5·50–17·18) after pancreatic cancer. HRs decreased over time, but remained elevated more than 5 years after diagnosis. We observed increased risks of heart failure or cardiomyopathy in patients after ten of 20 cancers, including haematological (adjusted HR 1·94, 1·66–2·25, with non-Hodgkin lymphoma; 1·77, 1·50–2·09, with leukaemia; and 3·29, 2·59–4·18, with multiple myeloma), oesophageal (1·96, 1·46–2·64), lung (1·82, 1·52–2·17) kidney (1·73, 1·38–2·17) and ovarian (1·59, 1·19–2·12). Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies. HRs for heart failure or cardiomyopathy and venous thromboembolism were greater in patients without previous cardiovascular disease and in younger patients. However, absolute excess risks were generally greater with increasing age. Increased risks of these outcomes seemed most pronounced in patients who had received chemotherapy.InterpretationSurvivors of most site-specific cancers had increased medium-term to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between cancer sites.FundingWellcome Trust and Royal Society.

Summary Background There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic. Methods Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8–28). Findings The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25–0·50]), depression (0·53 [0·52–0·53]), and self-harm (0·56 [0·54–0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89–1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66–0·67], eating disorders 0·62 [0·59–0·66], obsessive-compulsive disorder [0·69 [0·64–0·74]], self-harm 0·56 [0·54–0·58], severe mental illness 0·80 [0·78–0·83], stroke 0·59 [0·56–0·62], transient ischaemic attack 0·63 [0·58–0·67], heart failure 0·62 [0·60–0·64], myocardial infarction 0·72 [0·68–0·77], unstable angina 0·72 [0·60–0·87], venous thromboembolism 0·94 [0·90–0·99], and asthma exacerbation 0·88 [0·86–0·...

Objective To quantify how a period of intense media coverage of controversy over the risk:benefit balance of statins affected their use.Design Interrupted time series analysis of prospectively collected electronic data from primary care.Setting Clinical Practice Research Datalink (CPRD) in the United Kingdom.Participants Patients newly eligible for or currently taking statins for primary and secondary cardiovascular disease prevention in each month in January 2011-March 2015.Main outcome measures Adjusted odds ratios for starting/stopping taking statins after the media coverage (October 2013-March 2014).Results There was no evidence that the period of high media coverage was associated with changes in statin initiation among patients with a high recorded risk score for cardiovascular disease (primary prevention) or a recent cardiovascular event (secondary prevention) (odds ratio 0.99 (95% confidence interval 0.87 to 1.13; P=0.92) and 1.04 (0.92 to 1.18; P=0.54), respectively), though there was a decrease in the overall proportion of patients with a recorded risk score. Patients already taking statins were more likely to stop taking them for both primary and secondary prevention after the high media coverage period (1.11 (1.05 to 1.18; P<0.001) and 1.12 (1.04 to 1.21; P=0.003), respectively). Stratified analyses showed that older patients and those with a longer continuous prescription were more likely to stop taking statins after the media coverage. In post hoc analyses, the increased rates of cessation were no longer observed after six months.Conclusions A period of intense public discussion over the risks:benefit balance of statins, covered widely in the media, was followed by a transient rise in the proportion of people who stopped taking statins. This research highlights the potential for widely covered health stories in the lay media to impact on healthcare related behaviour.

ObjectiveTo investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer.DesignSystematic review and meta-analysis of randomised controlled trials and observational studies.Data sourcesMedline and Embase up until June 2018.Eligibility criteria for selecting studiesStudies were included if they investigated the risk of a specific cardiovascular disease outcome associated with use of either tamoxifen or an aromatase inhibitor, or compared the two treatments, in women with a history of non-metastatic breast cancer.Appraisal and data extractionRelevant studies were originally identified and results extracted by one researcher, with a full replication of the study identification process by a combination of two other researchers. The Cochrane Collaboration’s tool for assessing risk of bias was used to assess risk of bias in randomised controlled trials, and this tool was adapted to assess risk of bias in observational studies.Results26 studies were identified, with results for seven specific cardiovascular disease outcomes (venous thromboembolism, myocardial infarction, stroke, angina, heart failure, arrhythmia, and peripheral vascular disease). Results suggested an increased risk of venous thromboembolism in tamoxifen users compared with both non-users and aromatase inhibitor users. Results were also consistent with a higher risk of the vascular diseases myocardial infarction and angina in aromatase inhibitor users compared with tamoxifen users, but there was also a suggestion that this may be partly driven by a protective effect of tamoxifen on these outcomes. Data were limited, and evidence was generally inconsistent for all other cardiovascular disease outcomes.ConclusionThis review has collated substantial randomised controlled trial and observational evidence on the effect of endocrine therapies on several specific cardiovascular disease outcomes including venous thromboembolism and myocardial infarction, progressing knowledge. Although the choice of aromatase inhibitor or tamoxifen will primarily be based on the effectiveness against the recurrence of breast cancer, this review shows that the individual patient’s risk of venous or arterial vascular disease should be an important secondary consideration.Systematic review registrationProspero CRD42017065944.

BackgroundLaboratory evidence suggests that reduced phosphodiesterase type 5 (PDE5) expression increases the invasiveness of melanoma cells; hence, pharmacological inhibition of PDE5 could affect melanoma risk. Two major epidemiological studies have investigated this and come to differing conclusions. We therefore aimed to investigate whether PDE5 inhibitor use is associated with an increased risk of malignant melanoma, and whether any increase in risk is likely to represent a causal relationship.Methods and FindingsWe conducted a matched cohort study using primary care data from the UK Clinical Practice Research Datalink. All men initiating a PDE5 inhibitor and with no prior cancer diagnosis were identified and matched on age, diabetes status, and general practice to up to four unexposed controls. Ever use of a PDE5 inhibitor and time-updated cumulative number of PDE5 inhibitor prescriptions were investigated as exposures, and the primary outcome was malignant melanoma. Basal cell carcinoma, solar keratosis, and colorectal cancer were investigated as negative control outcomes to exclude bias. Hazard ratios (HRs) were estimated from Cox models stratified by matched set and adjusted for potential confounders.145,104 men with ≥1 PDE5 inhibitor prescription, and 560,933 unexposed matched controls were included. In total, 1,315 incident malignant melanoma diagnoses were observed during 3.44 million person-years of follow-up (mean 4.9 y per person). After adjusting for potential confounders, there was weak evidence of a small positive association between PDE5 inhibitor use and melanoma risk (HR = 1.14, 95% CI 1.01–1.29, p = 0.04). A similar increase in risk was seen for the two negative control outcomes related to sun exposure (HR = 1.15, 95% CI 1.11–1.19, p < 0.001, for basal cell carcinoma; HR = 1.21, 95% CI 1.17–1.25, p < 0.001, for solar keratosis), but there was no increased risk for colorectal cancer (HR = 0.91, 95% CI 0.85–0.98, p = 0.01). There was no evidence that risk increased with number of prescriptions received (p-trend = 0.83). In a post hoc analysis, there was strong evidence that solar keratosis was associated with future PDE5 inhibitor use (odds ratio = 1.28, 95% CI 1.23–1.34, p < 0.001), suggesting that men with higher sun exposure were more likely to become PDE5 inhibitor users. However, a limitation of our study was that we did not have individual-level data on sun exposure, so we could not directly control for this in the primary analysis.ConclusionsOur results were not consistent with PDE5 inhibitors being causally associated with melanoma risk, and strongly suggest that observed risk increases are driven by greater sun exposure among patients exposed to a PDE5 inhibitor.

ObjectiveTo compare the incidence of noncommunicable diseases between adults with and without cerebral palsy (CP).MethodsA cohort study was conducted using primary care data from the Clinical Practice Research Datalink. Cox models, stratified by matched set and adjusted for potential confounders, were fitted to compare the risk of any noncommunicable disease, cancer, cardiovascular disease, type 2 diabetes mellitus, and respiratory disease between adults with and without CP.ResultsThe analysis included 1,705 adults with CP and 5,115 age-, sex-, and general practice–matched adults without CP. There was evidence from adjusted analyses that adults with CP had 75% increased risk of developing any noncommunicable disease compared to adults without CP (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.58–1.94). Specifically, they had increased risk of cardiovascular disease (HR 1.76, 95% CI 1.48–2.11) and respiratory disease (HR 2.61, 95% CI 2.14–3.19). There was no evidence of increased risk of cancer or type 2 diabetes mellitus.ConclusionsAdults with CP had increased risk of noncommunicable disease, specifically cardiovascular and respiratory disease. These findings highlight the need for clinical vigilance regarding identification of noncommunicable disease in people with CP and further research into the etiology and management of noncommunicable disease in this population.

The World Health Organization and European Centre for Disease Prevention and Control suggest that individuals over the age of 70 years or with underlying cardiovascular disease, cancer, chronic obstructive pulmonary disease, asthma, or diabetes are at increased risk of severe COVID-19. However, the prevalence of these prognostic factors is unknown in many countries. We aimed to describe the burden and prevalence of prognostic factors of severe COVID-19 at national and county level in Sweden. We calculated the burden and prevalence of prognostic factors for severe COVID-19 based on records from the Swedish national health care and population registers for 3 years before 1st January 2016. 9,624,428 individuals were included in the study population. 22.1% had at least one prognostic factor for severe COVID-19 (2,131,319 individuals), and 1.6% had at least three factors (154,746 individuals). The prevalence of underlying medical conditions ranged from 0.8% with chronic obstructive pulmonary disease (78,516 individuals) to 7.4% with cardiovascular disease (708,090 individuals), and the county specific prevalence of at least one prognostic factor ranged from 19.2% in Stockholm (416,988 individuals) to 25.9% in Kalmar (60,005 individuals). We show that one in five individuals in Sweden is at increased risk of severe COVID-19. When compared with the critical care capacity at a local and national level, these results can aid authorities in optimally planning healthcare resources during the current pandemic. Findings can also be applied to underlying assumptions of disease burden in modelling efforts to support COVID-19 planning.

The incidence of osteonecrosis of the jaw (ONJ) in the population is low, but specifics are unknown. Potential risk factors include bisphosphonate treatment, steroid treatment, osteoporosis, and head/neck radiation. This Dental Practice-Based Research Network study estimated ONJ incidence and odds ratios from bisphosphonate exposure and other risk factors using a key word search and manual chart reviews of electronic records for adults aged ≥ 35 yrs enrolled during 1995–2006 in two large health-care organizations. We found 16 ONJ cases among 572,606 cohort members; seven additional cases were identified through dental plan resources. Among 23 cases (0.63 per 100,000 patient years), 20 (87%) had at least one risk factor, and six (26%) had received oral bisphosphonates. Patients with oral bisphosphonates were 15.5 (CI, 6.0–38.7) more likely to have ONJ than non-exposed patients; however, the sparse number of ONJ cases limits firm conclusions and suggests that the absolute risks for ONJ from oral bisphosphonates is low.