Clinical factors for predicting cardiovascular risk, need for renal replacement therapy, and mortality in patients with non-dialysis-dependent stage 3-5 chronic kidney disease from the Salford Kidney Study.

BACKGROUND: Established cardiovascular risk assessment tools lack chronic kidney disease-specific clinical factors and may underestimate cardiovascular risk in non-dialysis-dependent chronic kidney disease (CKD) patients. METHODS: A retrospective analysis of a cohort of patients with stage 3-5 non-dialysis-dependent chronic kidney disease in the Salford Kidney Study (UK, 2002-2016) was performed. Multivariable Cox regression models with backward selection and repeated measures joint models were used to evaluate clinical risk factors associated with cardiovascular events (individual and composite cardiovascular major adverse cardiovascular events), mortality (all-cause and cardiovascular-specific), and need for renal replacement therapy. Models were established using 70% of the cohort and validated on the remaining 30%. Hazard ratios ([95% CIs]) were reported. RESULTS: Among 2192 patients, mean follow-up was 5.6 years. Cardiovascular major adverse cardiovascular events occurred in 422 (19.3%) patients; predictors included prior history of diabetes (1.39 [1.13-1.71]; P = 0.002) and serum albumin reduction of 5 g/L (1.20 [1.05-1.36]; P = 0.006). All-cause mortality occurred in 740 (33.4%) patients, median time to death was 3.8 years; predictors included reduction of estimated glomerular filtration of 5 mL/min/1.73 m2 (1.05 [1.01-1.08]; P = 0.011) and increase of phosphate of 0.1 mmol/L (1.04 [1.01-1.08]; P = 0.021), whereas a 10 g/L hemoglobin increase was protective (0.90 [0.85-0.95]; P < 0.001). In 394 (18.0%) patients who received renal replacement therapy, median time to event was 2.3 years; predictors included halving of estimated glomerular filtration rate (3.40 [2.65-4.35]; P < 0.001) and antihypertensive use (1.23 [1.12-1.34]; P < 0.001). Increasing age, albumin reduction, and prior history of diabetes or cardiovascular disease were risk factors for all outcomes except renal replacement therapy. CONCLUSIONS: Several chronic kidney disease-specific cardiovascular risk factors were associated with increased mortality and cardiovascular event risk in patients with non-dialysis-dependent chronic kidney disease.

How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis.

OBJECTIVES: Genome-wide association studies have revealed over 200 genetic susceptibility loci for prostate cancer (PCa). By combining them, polygenic risk scores (PRS) can be generated to predict risk of PCa. We summarize the published evidence and conduct meta-analyses of PRS as a predictor of PCa risk in Caucasian men. PATIENTS AND METHODS: Data were extracted from 59 studies, with 16 studies including 17 separate analyses used in the main meta-analysis with a total of 20,786 cases and 69,106 controls identified through a systematic search of ten databases. Random effects meta-analysis was used to obtain pooled estimates of area under the receiver-operating characteristic curve (AUC). Meta-regression was used to assess the impact of number of single-nucleotide polymorphisms (SNPs) incorporated in PRS on AUC. Heterogeneity is expressed as I2 scores. Publication bias was evaluated using funnel plots and Egger tests. RESULTS: The ability of PRS to identify men with PCa was modest (pooled AUC 0.63, 95% CI 0.62-0.64) with moderate consistency (I2 64%). Combining PRS with clinical variables increased the pooled AUC to 0.74 (0.68-0.81). Meta-regression showed only negligible increase in AUC for adding incremental SNPs. Despite moderate heterogeneity, publication bias was not evident. CONCLUSION: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone.

Epidemiology and treatment patterns of UK women diagnosed with vasomotor symptoms: Findings from the Clinical Practice Research Datalink GOLD database.

OBJECTIVES: To describe the epidemiology and treatment of vasomotor symptoms (VMS) in the UK. STUDY DESIGN: Retrospective study that used electronic medical records from UK primary care centers. MAIN OUTCOME MEASURES: The prevalence and incidence of moderate-to-severe VMS, the proportion treated, persistence with initial treatment, treatment patterns, and menopausal hormone therapy (HT) experience were investigated over the study period (Jan. 2009-Dec. 2018). The study population comprised women aged 40-65 years registered at general practitioner clinics. For incident cases, the uptake of pharmacological non-hormonal or hormonal treatment was recorded, which included experience of HT. RESULTS: Over the 10-year study period, 1,481,646 women were included from the database, among whom there were 313,031 prevalent and 90,434 incident cases of VMS. Annual prevalence and incidence rates were stable over time, with a weighted average of 21.1 % and 15.3 per 1000 person-years, respectively (results varied across age groups). Among women who were incident VMS cases, 32.4 % (29,275) were initially prescribed non-hormonal treatments for a median of 3.9 months, 49.4 % (44,700) were prescribed hormonal treatments for 4.0 months, and 18.2 % (16,459) had no treatment. Approximately one-third of treated women switched between non-hormonal and hormonal treatments. The HT experience results showed that 52.7 % (47,639) of women were HT-eligible, 13.1 % (11,872) were HT-contraindicated (they may or may not have received HT), and 34.2 % (30,923) did not receive HT. CONCLUSIONS: Variations in prescribed treatment patterns suggest that education may be needed for clinicians and women regarding the potential pharmacological options for treating VMS in the UK.

Author Correction: Introducing PIONEER: a project to harness big data in prostate cancer research.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Introducing PIONEER: a project to harness big data in prostate cancer research.

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.

Factors associated with receiving surgical treatment for menorrhagia in England and Wales: findings from a cohort study of the National Heavy Menstrual Bleeding Audit.

OBJECTIVE: To examine the factors associated with receiving surgery for heavy menstrual bleeding (HMB) in England and Wales. DESIGN: National cohort study. SETTING: National Health Service hospitals. PARTICIPANTS: Women with HMB aged 18-60 who had a new referral to secondary care. METHODS: Patient-reported data linked to administrative hospital data. Risk ratios (RR) estimated using multivariable Poisson regression. PRIMARY OUTCOME MEASURE: Surgery within 1 year of first outpatient clinic visit. RESULTS: 14 545 women were included. At their first clinic visit, mean age was 42 years, mean symptom severity score was 62 (scale ranging from 0 (least) to 100 (most severe)), 73.9% of women reported having symptoms for >1 year and 30.4% reported no prior treatment in primary care. One year later, 42.6% had received surgery. Of these, 57.8% had endometrial ablation and 37.2% hysterectomy. Women with more severe symptoms were more likely to have received surgery (most vs least severe quintile, 33.1% vs 56.0%; RR 1.6, 95% CI 1.5 to 1.7). Surgery was more likely among those who reported prior primary care treatment compared with those who did not (48.0% vs 31.1%; RR 1.5, 95% CI 1.4 to 1.6). Surgery was less likely among Asian and more likely among black women, compared with white women. Surgery was not associated with socioeconomic deprivation. CONCLUSIONS: Receipt of surgery for HMB depends on symptom severity and prior treatment in primary care. Referral pathways should be locally audited to ensure women with HMB receive care that addresses their individual needs and preferences, especially for those who do not receive treatment in primary care.

Elevated blood pressure and risk of aortic valve disease: a cohort analysis of 5.4 million UK adults.

Aims: To test two related hypotheses that elevated blood pressure (BP) is a risk factor for aortic valve stenosis (AS) or regurgitation (AR). Methods and results: In this cohort study of 5.4 million UK patients with no known cardiovascular disease or aortic valve disease at baseline, we investigated the relationship between BP and risk of incident AS and AR using multivariable-adjusted Cox regression models. Over a median follow-up of 9.2 years, 20 680 patients (0.38%) were diagnosed with AS and 6440 (0.12%) patients with AR. Systolic BP (SBP) was continuously related to the risk of AS and AR with no evidence of a nadir down to 115 mmHg. Each 20 mmHg increment in SBP was associated with a 41% higher risk of AS (hazard ratio 1.41, 95% confidence interval 1.38-1.45) and a 38% higher risk of AR (1.38, 1.31-1.45). Associations were stronger in younger patients but with no strong evidence for interaction by gender or body mass index. Each 10 mmHg increment in diastolic BP was associated with a 24% higher risk of AS (1.24, 1.19-1.29) but not AR (1.04, 0.97-1.11). Each 15 mmHg increment in pulse pressure was associated with a 46% greater risk of AS (1.46, 1.42-1.50) and a 53% higher risk of AR (1.53, 1.45-1.62). Conclusion: Long-term exposure to elevated BP across its whole spectrum was associated with increased risk of AS and AR. The possible causal nature of the observed associations warrants further investigation.

Sociodemographic differences in symptom severity and duration among women referred to secondary care for menorrhagia in England and Wales: a cohort study from the National Heavy Menstrual Bleeding Audit.

OBJECTIVE: To examine symptom severity and duration at time of referral to secondary care for heavy menstrual bleeding (HMB) by socioeconomic deprivation, age and ethnicity DESIGN: Cohort analysis of data from the National HMB Audit linked to Hospital Episode Statistics data. SETTING: English and Welsh National Health Services (secondary care): February 2011 to January 2012. PARTICIPANTS: 15 325 women aged 18-60 years in England and Wales who had a new referral for HMB to a gynaecology outpatient department METHODS: Multivariable linear regression to calculate adjusted differences in mean symptom severity and quality of life scores at first outpatient visit. Multivariable logistic regression to calculate adjusted ORs. Adjustment for body mass index, parity and comorbidities. PRIMARY OUTCOME MEASURES: Mean symptom severity score (0=best, 100=worst), mean condition-specific quality of life score (0=worst, 100=best) and symptom duration (≥1 year). RESULTS: Women were on average 42 years old and 12% reported minority ethnic backgrounds. Mean symptom severity and condition-specific quality of life scores were 61.8 and 34.7. Almost three-quarters of women (74%) reported having had symptoms for ≥1 year. Women from more deprived areas had more severe symptoms at their first outpatient visit (difference -6.1; 95% CI-7.2 to -4.9, between least and most deprived quintiles) and worse condition-specific quality of life (difference 6.3; 95% CI 5.1 to 7.5). Symptom severity declined with age while quality of life improved. CONCLUSIONS: Women living in more deprived areas reported more severe HMB symptoms and poorer quality of life at the start of treatment in secondary care. Providers should examine referral practices to explore if these differences reflect women's health-seeking behaviour or how providers decide whether or not to refer.

Incidence of G-Induced Loss of Consciousness and Almost Loss of Consciousness in the Royal Air Force.

INTRODUCTION: Exposure to sustained +Gz acceleration with inadequate G protection can result in G-induced loss of consciousness (G-LOC) or almost loss of consciousness (A-LOC). The UK Royal Air Force (RAF) last conducted a survey of G-LOC within their military aircrew in 2005 with interventions subsequently introduced. The aim of this study was to repeat the 2005 survey in order to evaluate the impact of those interventions. METHODS: An anonymous questionnaire requesting details of G-LOC and A-LOC events was mailed to all RAF pilots (N = 1878) and weapons systems operators (WSOs) (N = 473), irrespective of aircraft currently flown. RESULTS: The questionnaire was returned by 809 aircrew (34.4% response rate). There were 120 (14.8%) aircrew who reported at least one episode of G-LOC and 260 (32.2%) reported at least one episode of A-LOC. The reported prevalence of G-LOC in the previous 2005 survey was 20.1% (N = 454). There was an increased reporting of G-LOC in the Hawk, Tucano, and Grob Tutor aircraft, with 5 G-LOC and 19 A-LOC events reported in the Grob Tutor compared to none in 2005. DISCUSSION: The prevalence of reported G-LOC has decreased in the surveyed populations, which may be due to the introduction of centrifuge training, but also may be influenced by patterns of G exposure and other factors. Scope for further reduction remains through correct execution of the anti-G straining maneuver (AGSM) with centrifuge training early in flying training and use of a structured conditioning program to increase the general strength of muscles involved in the AGSM.Slungaard E, McLeod J, Green NDC, Kiran A, Newham DJ, Harridge SDR. Incidence of G-induced loss of consciousness and almost loss of consciousness in the Royal Air Force. Aerosp Med Hum Perform. 2017; 88(6):550-555.

Variation in hospital performance for heart failure management in the National Heart Failure Audit for England and Wales.

OBJECTIVE: Investigation of variations in provider performance and its determinants may help inform strategies for improving patient outcomes. METHODS: We used the National Heart Failure Audit comprising 68 772 patients with heart failure with reduced left ventricular ejection fraction (HFREF), admitted to 185 hospitals in England and Wales (2007-2013). We investigated hospital adherence to three recommended key performance measures (KPMs) for inhospital care (ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) on discharge, ß-blockers on discharge and referral to specialist follow-up) individually and as a composite performance score. Hierarchical regression models were used to investigate hospital-level variation. RESULTS: Hospital-level variation in adherence to composite KPM ranged from 50% to 97% (median 79%), but after adjustments for patient characteristics and year of admission, only 8% (95% CI 7% to 10%) of this variation was attributable to variations in hospital features. Similarly, hospital prescription rates for ACE-I/ARB and ß-blocker showed low adjusted hospital-attributable variations (7% CI 6% to 9% and 6% CI 5% to 8%, for ACE-I/ARB and ß-blocker, respectively). Referral to specialist follow-up, however, showed larger variations (median 81%; range; 20%, 100%) with 26% of this being attributable to hospital-level differences (CI 22% to 31%). CONCLUSION: Only a small proportion of hospital variation in medication prescription after discharge was attributable to hospital-level features. This suggests that differences in hospital practices are not a major determinant of observed variations in prescription of investigated medications and outcomes. Future healthcare delivery efforts should consider evaluation and improvement of more ambitious KPMs.

Influenza vaccination and risk of hospitalization in patients with heart failure: a self-controlled case series study.

Aims: Evidence supporting yearly influenza vaccination in patients with chronic heart failure (HF) is limited, consequently leading to inconsistent guideline recommendations. We aimed to investigate the impact of influenza vaccination on the risk of hospitalization in HF patients. Methods and results: We used linked primary and secondary health records in England between 1990 and 2013. Using a self-controlled case series design with conditional Poisson regression, we estimated the incidence rate ratio (IRR, 95% CI) of the number of hospitalizations in a year following vaccination with an adjacent vaccination-free year in the same individuals. We found the uptake of vaccination to be varied and generally low (49% in 2013). Among 59,202 HF patients, influenza vaccination was associated with a lower risk of hospitalization due to cardiovascular disease (0.73 [0.71, 0.76]), with more modest effects for hospitalization due to respiratory infections (0.83 [0.77, 0.90]), and all-cause hospitalizations (0.96 [0.95, 0.98]). The relative effects were somewhat greater in younger patients but with no material difference between men and women. In validation analyses, effects were not significant for consecutive years without vaccination (0.96 [0.92, 1.00]) or hospitalization due to cancer (1.02 [0.84, 1.22]). Conclusion: In HF patients, influenza vaccination is associated with reduced risk of hospitalizations, especially for cardiovascular disease. Improved efforts for wider uptake of vaccination among HF patients are needed.

Graphics and Statistics for Cardiology: Data visualisation for meta-analysis.

Graphical displays play a pivotal role in understanding data sets and disseminating results. For meta-analysis, they are instrumental in presenting findings from multiple studies. This report presents guidance to authors wishing to submit graphical displays as part of their meta-analysis to a clinical cardiology journal, such as HeartWhen using graphical displays for meta-analysis, we recommend the following: Use a flow diagram to describe the number of studies returned from the initial search, the inclusion/exclusion criteria applied and the final number of studies used in the meta-analysis.Present results from the meta-analysis using a figure that incorporates a forest plot and underlying (tabulated) statistics, including test for heterogeneity.Use displays such as funnel plot (minimum 10 studies) and Galbraith plot to visually present distribution of effect sizes or associations in order to evaluate small-study effects and publication bias).For meta-regression, the bubble plot is a useful display for assessing associations by study-level factors.Final checks on graphs, such as appropriate use of axis scale, line pattern, text size and graph resolution, should always be performed.

Referral for Specialist Follow-up and Its Association With Post-discharge Mortality Among Patients With Systolic Heart Failure (from the National Heart Failure Audit for England and Wales).

For patients admitted with worsening heart failure (HF), early follow-up after discharge is recommended. Whether outcomes can be improved when follow-up is done by cardiologists is uncertain. We aimed to determine the association between cardiology follow-up and risk of death for patients with HF discharged from hospital. Using data from the National Heart Failure Audit (England and Wales), we investigated the effect of referral to cardiology follow-up on 30-day and 1-year mortality in 68,772 patients with HF and a reduced left ventricular ejection fraction discharged from 185 hospitals from 2007 to 2013. The primary analyses used instrumental variable analysis complemented by hierarchical logistic and propensity-matched models. At the hospital level, rates of referral to cardiologists varied from 6% to 96%. The median odds ratio (OR) for referral to cardiologist was 2.3 (95% confidence interval [CI] 2.1 to 2.5), suggesting that, on average, the odds of a patient being referred for cardiologist follow-up after discharge differed ∼2.3 times from one randomly selected hospital to another one. Based on the proportion of patients (per region) referred for cardiology follow-up, referral for cardiology follow-up was associated with lower 30-day (OR 0.70; 95% CI 0.55 to 0.89) and 1-year mortality (OR 0.81; 95% CI 0.68 to 0.95) compared with no plans for cardiology follow-up (i.e., standard follow-up done by family doctors). Results from hierarchical logistic models and propensity-matched models were consistent (30-day mortality OR 0.66; 95% CI 0.61 to 0.72 and 0.66; 95% CI 0.58 to 0.76 for hierarchical and propensity matched models, respectively). For patients with HF and a reduced left ventricular ejection fraction admitted to hospital with worsening symptoms, referral to cardiology services for follow-up after discharge is strongly associated with reduced mortality, both early and late.

Blood Pressure and Risk of Vascular Dementia: Evidence From a Primary Care Registry and a Cohort Study of Transient Ischemic Attack and Stroke.

BACKGROUND AND PURPOSE: Vascular dementia is the second most common form of dementia but reliable evidence on age-specific associations between blood pressure (BP) and risk of vascular dementia is limited and some studies have reported negative associations at older ages. METHODS: In a cohort of 4.28 million individuals, free of known vascular disease and dementia and identified from linked electronic primary care health records in the United Kingdom (Clinical Practice Research Datalink), we related BP to time to physician-diagnosed vascular dementia. We further determined associations between BP and dementia in a prospective population-based cohort of incident transient ischemic attack and stroke (Oxford Vascular Study). RESULTS: For a median follow-up of 7.0 years, 11 114 initial presentations of vascular dementia were observed in the primary care cohort after exclusion of the first 4 years of follow-up. The association between usual systolic BP and risk of vascular dementia decreased with age (hazard ratio per 20 mm Hg higher systolic BP, 1.62; 95% confidence interval, 1.13-2.35 at 30-50 years; 1.26, 1.18-1.35 at 51-70 years; 0.97, 0.92-1.03 at 71-90 years; P trend=0.006). Usual systolic BP remained predictive of vascular dementia after accounting for effect mediation by stroke and transient ischemic attack. In the population-based cohort, prior systolic BP was predictive of 5-year risk of dementia with no evidence of negative association at older ages. CONCLUSIONS: BP is positively associated with risk of vascular dementia, irrespective of preceding transient ischemic attack or stroke. Previous reports of inverse associations in old age could not be confirmed.

Birth "Out-of-Hours": An Evaluation of Obstetric Practice and Outcome According to the Presence of Senior Obstetricians on the Labour Ward.

BACKGROUND: Concerns have been raised that a lack of senior obstetricians ("consultants") on the labour ward outside normal hours may lead to worse outcomes among babies born during periods of reduced cover. METHODS AND FINDINGS: We carried out a multicentre cohort study using data from 19 obstetric units in the United Kingdom between 1 April 2012 and 31 March 2013 to examine whether rates of obstetric intervention and outcome change "out-of-hours," i.e., when consultants are not providing dedicated, on-site labour ward cover. At the 19 hospitals, obstetric rotas ranged from 51 to 106 h of on-site labour ward cover per week. There were 87,501 singleton live births during the year, and 55.8% occurred out-of-hours. Women who delivered out-of-hours had slightly lower rates of intrapartum caesarean section (CS) (12.7% versus 13.4%, adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.90 to 0.98) and instrumental delivery (15.6% versus 17.0%, adj. OR 0.92; 95% CI 0.89 to 0.96) than women who delivered at times of on-site labour ward cover. There was some evidence that the severe perineal tear rate was reduced in out-of-hours vaginal deliveries (3.3% versus 3.6%, adj. OR 0.92; 95% CI 0.85 to 1.00). There was no evidence of a statistically significant difference between out-of-hours and "in-hours" deliveries in the rate of babies with a low Apgar score at 5 min (1.33% versus 1.25%, adjusted OR 1.07; 95% CI 0.95 to 1.21) or low cord pH (0.94% versus 0.82%; adjusted OR 1.12; 95% CI 0.96 to 1.31). Key study limitations include the potential for bias by indication, the reliance upon an organisational measure of consultant presence, and a non-random sample of maternity units. CONCLUSIONS: There was no difference in the rate of maternal and neonatal morbidity according to the presence of consultants on the labour ward, with the possible exception of a reduced rate of severe perineal tears in out-of-hours vaginal deliveries. Fewer women had operative deliveries out-of-hours. Taken together, the available evidence provides some reassurance that the current organisation of maternity care in the UK allows for good planning and risk management. However there is a need for more robust evidence on the quality of care afforded by different models of labour ward staffing.

Which Patients with Giant Cell Arteritis Will Develop Cardiovascular or Cerebrovascular Disease? A Clinical Practice Research Datalink Study.

OBJECTIVE: To evaluate the risk of cerebrovascular disease and cardiovascular disease (CVD) in patients with giant cell arteritis (GCA), and to identify predictors. METHODS: The UK Clinical Practice Research Datalink 1991-2010 was used for a parallel cohort study of 5827 patients with GCA and 37,090 age-, sex-, and location-matched controls. A multivariable competing risk model (non-cerebrovascular/CV-related death as the competing risk) determined the relative risk [subhazard ratio (SHR)] between patients with GCA compared with background controls for cerebrovascular disease, CVD, or either. Each cohort (GCA and controls) was then analyzed individually using the same multivariable model, with age and sex now present, to identify predictors of CVD or cerebrovascular disease. RESULTS: Patients with GCA, compared with controls, had an increased risk SHR (95% CI) of cerebrovascular disease (1.45, 1.31-1.60), CVD (1.49, 1.37-1.62), or either (1.47, 1.37-1.57). In the GCA cohort, predictors of "cerebrovascular disease or CVD" included increasing age, > 80 years versus < 65 years (1.98, 1.62-2.42), male sex (1.20, 1.05-1.38), and socioeconomic status, most deprived quintile versus least deprived (1.34, 1.01-1.78). These predictors were also present within the non-GCA cohort. CONCLUSION: Patients with GCA are more likely to develop cerebrovascular disease or CVD than age-, sex-, and location-matched controls. In common with the non-GCA cohort, patients who are older, male, and from the most deprived compared with least deprived areas have a higher risk of cerebrovascular disease or CVD. Further work is needed to understand how this risk may be mediated by specific behavioral, social, and economic factors.

Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis.

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. ß 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 I(2) 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.

Variations In Good Patient Reported Outcomes After Total Knee Arthroplasty.

This study identifies optimal OKS values that discriminate post-operative (TKA) patient satisfaction and determines the variation in threshold values by patient characteristics and expectations. It is the first to identify patient improvement using measures (PoPC) that account for patient's pre-operative symptom severity. Of 365 primary TKA patients from a London district general hospital 84% were satisfied at 12 and 24 months. Whilst the overall OKS thresholds (follow-up, change, PoPC) were stable at 12 months (31, 11, 39.7%) and 24 months (35, 12, 38.9%), patients who were older (≥75years), were underweight/normal (BMI<25), had pre-operative symptom severity (OKS≤15) and expected no pain post-surgery, required a greater (potential) improvement to be classed as satisfied. When reporting good patient outcomes, cohorts should be stratified accordingly.