Summary Background The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood ...pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences. Method For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates. Results We identified 123 studies with 613 815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk RR 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88), stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84–0·91). However, the effect on renal failure was not significant (0·95, 0·84–1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend >0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I2 statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%. Interpretation Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease. Funding National Institute for Health Research and Oxford Martin School.
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Evidence for the use of automated or partly automated contact-tracing tools to contain severe acute respiratory syndrome coronavirus 2 is scarce. We did a systematic review of automated or partly ...automated contact tracing. We searched PubMed, EMBASE, OVID Global Health, EBSCO Medical COVID Information Portal, Cochrane Library, medRxiv, bioRxiv, arXiv, and Google Advanced for articles relevant to COVID-19, severe acute respiratory syndrome, Middle East respiratory syndrome, influenza, or Ebola virus, published from Jan 1, 2000, to April 14, 2020. We also included studies identified through professional networks up to April 30, 2020. We reviewed all full-text manuscripts. Primary outcomes were the number or proportion of contacts (or subsequent cases) identified. Secondary outcomes were indicators of outbreak control, uptake, resource use, cost-effectiveness, and lessons learnt. This study is registered with PROSPERO (CRD42020179822). Of the 4036 studies identified, 110 full-text studies were reviewed and 15 studies were included in the final analysis and quality assessment. No empirical evidence of the effectiveness of automated contact tracing (regarding contacts identified or transmission reduction) was identified. Four of seven included modelling studies that suggested that controlling COVID-19 requires a high population uptake of automated contact-tracing apps (estimates from 56% to 95%), typically alongside other control measures. Studies of partly automated contact tracing generally reported more complete contact identification and follow-up compared with manual systems. Automated contact tracing could potentially reduce transmission with sufficient population uptake. However, concerns regarding privacy and equity should be considered. Well designed prospective studies are needed given gaps in evidence of effectiveness, and to investigate the integration and relative effects of manual and automated systems. Large-scale manual contact tracing is therefore still key in most contexts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus ...set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs.
Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval CI: 49%-64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32% (95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified.
The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Risk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could ...support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening.
For model development, we used data from 216,714 ever-smokers recruited between 2006 and 2010 to the UK Biobank prospective cohort and 26,616 high-risk ever-smokers recruited between 2002 and 2004 to the control arm of the US National Lung Screening (NLST) randomised controlled trial. The NLST trial randomised high-risk smokers from 33 US centres with at least a 30 pack-year smoking history and fewer than 15 quit-years to annual CT or chest radiography screening for lung cancer. We externally validated our models among 49,593 participants in the chest radiography arm and all 80,659 ever-smoking participants in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. The PLCO trial, recruiting from 1993 to 2001, analysed the impact of chest radiography or no chest radiography for lung cancer screening. We primarily validated in the PLCO chest radiography arm such that we could benchmark against comparator models developed within the PLCO control arm. Models were developed to predict the risk of 2 outcomes within 5 years from baseline: diagnosis of lung cancer and death from lung cancer. We assessed model discrimination (area under the receiver operating curve, AUC), calibration (calibration curves and expected/observed ratio), overall performance (Brier scores), and net benefit with decision curve analysis. Models predicting lung cancer death (UCL-D) and incidence (UCL-I) using 3 variables-age, smoking duration, and pack-years-achieved or exceeded parity in discrimination, overall performance, and net benefit with comparators currently in use, despite requiring only one-quarter of the predictors. In external validation in the PLCO trial, UCL-D had an AUC of 0.803 (95% CI: 0.783, 0.824) and was well calibrated with an expected/observed (E/O) ratio of 1.05 (95% CI: 0.95, 1.19). UCL-I had an AUC of 0.787 (95% CI: 0.771, 0.802), an E/O ratio of 1.0 (95% CI: 0.92, 1.07). The sensitivity of UCL-D was 85.5% and UCL-I was 83.9%, at 5-year risk thresholds of 0.68% and 1.17%, respectively, 7.9% and 6.2% higher than the USPSTF-2021 criteria at the same specificity. The main limitation of this study is that the models have not been validated outside of UK and US cohorts.
We present parsimonious ensemble machine learning models to predict the risk of lung cancer in ever-smokers, demonstrating a novel approach that could simplify the implementation of risk-based lung cancer screening in multiple settings.
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Abstract Background As neglected tropical diseases (NTDs) have grown in prominence over the past decade, funding to tackle these diseases has increased greatly. However, whether this gain has been ...shared equitably among each disease is unclear. We aimed to resolve this uncertainty. Methods We used G-FINDER reports to assess the overall change in research and development (R&D) funding for 13 core NTDs together and for each disease individually, for 2007–11 (schistosomiasis, lymphatic filariasis, hookworm infection, ascariasis, trichuriasis, onchocerciasis, leishmaniasis, human African trypanosomiasis, Chagas disease, leprosy, trachoma, dengue, and buruli ulcer). We compared the estimated burden of each of the 13 diseases to changes in R&D funding. Findings Overall R&D funding has increased by more than 70% for the 13 core NTDs, from US$268 million in 2007, to $464 million in 2011. The gains have not been shared equitably across individual diseases: in 2011, $131 million (28%) of funding was directed towards the kinetoplastids (leishmaniasis, human African trypanosomiasis, and Chagas disease), which together are responsible for 7·5% of combined disability-adjusted life-years (DALYs) and 20% of deaths caused by NTDs. The helminthiases (lymphatic filariasis, schistosomiasis, hookworm infection, ascariasis, and trichuriasis) received only $81 million (17% of the funds disbursed in 2011), yet are responsible for 87% of DALYs and 75% of deaths caused by NTDs. Interpretation Funding for each NTD is not correlated with objective criteria such as disease burden or attributed deaths. Although use of a collective term to group the diseases has given the NTDs moral, political, and economic weight, the approach to tackling these diseases does not seem to be aligned with need. Funding None.
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IMPORTANCE: Lowering blood pressure (BP) is widely used to reduce vascular risk in individuals with diabetes. OBJECTIVE: To determine the associations between BP–lowering treatment and vascular ...disease in type 2 diabetes. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE for large-scale randomized controlled trials of BP–lowering treatment including patients with diabetes, published between January 1966 and October 2014. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted study characteristics and vascular outcome data. Estimates were stratified by baseline BP and achieved BP, and pooled using fixed-effects meta-analysis. MAIN OUTCOMES AND MEASURES: All-cause mortality, cardiovascular events, coronary heart disease events, stroke, heart failure, retinopathy, new or worsening albuminuria, and renal failure. RESULTS: Forty trials judged to be of low risk of bias (100 354 participants) were included. Each 10–mm Hg lower systolic BP was associated with a significantly lower risk of mortality (relative risk RR, 0.87; 95% CI, 0.78-0.96); absolute risk reduction (ARR) in events per 1000 patient-years (3.16; 95% CI, 0.90-5.22), cardiovascular events (RR, 0.89 95% CI, 0.83-0.95; ARR, 3.90 95% CI, 1.57-6.06), coronary heart disease (RR, 0.88 95% CI, 0.80-0.98; ARR, 1.81 95% CI, 0.35-3.11), stroke (RR, 0.73 95% CI, 0.64-0.83; ARR, 4.06 95% CI, 2.53-5.40), albuminuria (RR, 0.83 95% CI, 0.79-0.87; ARR, 9.33 95% CI, 7.13-11.37), and retinopathy (RR, 0.87 95% CI, 0.76-0.99; ARR, 2.23 95% CI, 0.15-4.04). When trials were stratified by mean baseline systolic BP at greater than or less than 140 mm Hg, RRs for outcomes other than stroke, retinopathy, and renal failure were lower in studies with greater baseline systolic BP (P interaction <0.1). The associations between BP-lowering treatments and outcomes were not significantly different, irrespective of drug class, except for stroke and heart failure. Estimates were similar when all trials, regardless of risk of bias, were included. CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes, BP lowering was associated with improved mortality and other clinical outcomes with lower RRs observed among those with baseline BP of 140 mm Hg and greater. These findings support the use of medications for BP lowering in these patients.
Objective
In men with a raised prostate-specific antigen (PSA), MRI increases the detection of clinically significant cancer and reduces overdiagnosis, with fewer biopsies. MRI as a screening tool ...has not been assessed independently of PSA in a formal screening study. We report a systematic community-based assessment of the prevalence of prostate MRI lesions in an age-selected population.
Methods and analysis
Men aged 50–75 were identified from participating general practice (GP) practices and randomly selected for invitation to a screening MRI and PSA. Men with a positive MRI or a raised PSA density (≥0.12 ng/mL
2
) were recommended for standard National Health Service (NHS) prostate cancer assessment.
Results
Eight GP practices sent invitations to 2096 men. 457 men (22%) responded and 303 completed both screening tests. Older white men were most likely to respond to the invitation, with black men having 20% of the acceptance rate of white men.
One in six men (48/303 men, 16%) had a positive screening MRI, and an additional 1 in 20 men (16/303, 5%) had a raised PSA density alone. After NHS assessment, 29 men (9.6%) were diagnosed with clinically significant cancer and 3 men (1%) with clinically insignificant cancer.
Two in three men with a positive MRI, and more than half of men with clinically significant disease had a PSA <3 ng/mL.
Conclusions
Prostate MRI may have value in screening independently of PSA. These data will allow modelling of the use of MRI as a primary screening tool to inform larger prostate cancer screening studies.
Trial registration number
NCT04063566
.
BackgroundPulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and ...when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings. We quantified the primary and secondary care referrals generated by our protocol.MethodsThe SUMMIT study (NCT03934866) is a prospective observational cohort study to examine the performance of delivering a low-dose CT (LDCT) screening service to a high-risk population. Spirometry, blood pressure, height/weight and respiratory history were assessed as part of a Lung Health Check. Individuals at high risk of lung cancer were offered an LDCT and returned for two further annual visits. This analysis is a prospective evaluation of the standardised reporting and management protocol for incidental findings developed for the study on the baseline LDCT.ResultsIn 11 115 participants included in this analysis, the most common incidental findings were coronary artery calcification (64.2%) and emphysema (33.4%). From our protocolised management approach, the number of participants requiring review for clinically relevant findings in primary care was 1 in 20, and the number potentially requiring review in secondary care was 1 in 25.ConclusionsIncidental findings are common in lung cancer screening and can be associated with reported symptoms and comorbidities. A standardised reporting protocol allows systematic assessment and standardises onward management.
Some autoimmune diseases are associated with an increased risk of cardiovascular disease. We aimed to determine whether or not this is true, and to what extent, for a broad range of autoimmune ...conditions.
In this population-based study, we used linked primary and secondary care records from the Clinical Practice Research Datalink (CPRD), GOLD and Aurum datasets, to assemble a cohort of individuals across the UK who were newly diagnosed with any of 19 autoimmune diseases between Jan 1, 2000, and Dec 31, 2017, younger than 80 years at diagnosis, and free of cardiovascular diseases up to 12 months after diagnosis. We also assembled a matched cohort with up to five individuals matched on age, sex, socioeconomic status, region, and calendar year, who were free of autoimmune disease and free of cardiovascular diseases up to 12 months after study entry. Both cohorts were followed up until June 30, 2019. We investigated the incidence of 12 cardiovascular outcomes and used Cox proportional hazards models to examine differences in patients with and without autoimmune diseases.
Of 22 009 375 individuals identified from the CPRD databases, we identified 446 449 eligible individuals with autoimmune diseases and 2 102 830 matched controls. In the autoimmune cohort, mean age at diagnosis was 46·2 years (SD 19·8), and 271 410 (60·8%) were women and 175 039 (39·2%) were men. 68 413 (15·3%) people with and 231 410 (11·0%) without autoimmune diseases developed incident cardiovascular disease during a median of 6·2 years (IQR 2·7–10·8) of follow-up. The incidence rate of cardiovascular disease was 23·3 events per 1000 patient-years among patients with autoimmune disease and 15·0 events per 1000 patient-years among those without an autoimmune disease (hazard ratio HR 1·56 95% CI 1·52–1·59). An increased risk of cardiovascular disease with autoimmune disease was seen for every individual cardiovascular disease and increased progressively with the number of autoimmune diseases present (one disease: HR 1·41 95% CI 1·37–1·45; two diseases: 2·63 2·49–2·78); three or more diseases: 3·79 3·36–4·27), and in younger age groups (age <45 years: 2·33 2·16–2·51; 55–64 years: 1·76 1·67–1·85; ≥75 years: 1·30 1·24–1·36). Among autoimmune diseases, systemic sclerosis (3·59 2·81–4·59), Addison's disease (2·83 1·96–4·09), systemic lupus erythematosus (2·82 2·38–3·33), and type 1 diabetes (2·36 2·21–2·52) had the highest overall cardiovascular risk.
These findings warrant targeted cardiovascular prevention measures, in particular in younger patients with autoimmune diseases, and further research into pathophysiological mechanisms underlying these complications.
Horizon 2020 Marie Skłodowska-Curie Actions and European Society of Cardiology.
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