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.

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.

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.

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.

The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK.

OBJECTIVES: To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. METHODS: A UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. RESULTS: Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. CONCLUSIONS: Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated.

The association between hip morphology parameters and nineteen-year risk of end-stage osteoarthritis of the hip: a nested case-control study.

OBJECTIVE: Subtle deformities of the hip joint are implicated in the etiology of osteoarthritis (OA) of the hip. Parameters that quantify these deformities may aid understanding of these associations. We undertook this study to examine relationships between such parameters and the 19-year risk of total hip arthroplasty (THA) for end-stage OA. METHODS: A new software program designed for measuring morphologic parameters around the hip was developed and validated in a reliability study. THA was the outcome measure for end-stage OA. A nested case-control study was used with individuals from a cohort of 1,003 women who were recruited at year 1 in 1989 and followed up to year 20 (the Chingford Study). All hips with THA by year 20 and 243 randomly selected control hips were studied. Pelvis radiographs obtained at year 2 were analyzed for variations in hip morphology. Measurements were compared between the THA case group and the control group. RESULTS: Patients with THA had a higher prevalence of cam deformity than did their respective controls (median alpha angle 62.4° versus 45.8° [P = 0.001]; mean modified triangular index height 28.5 mm versus 26.9 mm [P = 0.001]) as well as a higher prevalence of acetabular dysplasia (mean lateral center edge angle 29.5° versus 34.3° [P = 0.001]; median extrusion index 0.25 versus 0.185 [P = 0.009]). Logistic regression analyses clustering by subject and adjusting for radiographic hip OA at year 2 showed that these morphologic parameters were still significantly associated with THA by year 20. The alpha angle and lateral center edge angle predicted the risk of THA independently when included in the same model. CONCLUSION: This investigation describes measurements that predict the risk of THA for end-stage OA by year 20, independently of the presence of radiographic hip OA at year 2. These measurements can be made on an anteroposterior pelvis radiograph, which is an inexpensive and commonly used clinical method of investigation.

Fracture risk before and after total hip replacement in patients with osteoarthritis: potential benefits of bisphosphonate use.

OBJECTIVE: The association between osteoarthritis (OA) and fractures remains unclear. OA patients have increased bone mass, but no corresponding decrease in fracture rate. This study was undertaken to determine the fracture rates in patients with hip OA undergoing a total hip replacement (THR), as compared with disease-free controls, and to assess the association between bisphosphonate use and postsurgery fracture risk. METHODS: We conducted a population-based parallel-cohorts study. All patients in the UK General Practice Research Database undergoing a THR for hip OA between 1986 and 2006 constituted the exposed cohort (n = 14,133). Five disease-free controls were matched with each patient by age, sex, and practice site. Subjects were followed up for 5 years before and after surgery. Fracture rates and rate ratios (RRs) were estimated using Poisson regression. In addition, bisphosphonate use was identified among patients undergoing THR, and the data, stratified by the presence or absence of a previous fracture and by treatment propensity score, were assessed using fitted Cox models to study the effect of bisphosphonate use on the risk of fracture postsurgery. RESULTS: Patients undergoing a THR had a similar fracture risk as that in controls in the 5 years before THR, but had higher rates postsurgery, which peaked at years 2.5-5 (adjusted RR 1.24, 95% confidence interval [95% CI] 1.02-1.52). Use of bisphosphonates lowered the fracture risk among THR patients who received bisphosphonates as primary prevention (hazard ratio [HR] 0.56, 95% CI 0.38-0.82) and also among THR patients who had experienced a previous osteoporotic fracture (HR 0.48, 95% CI 0.23-0.99). CONCLUSION: This study identified a 25% increase in fracture risk at 2.5-5 years postsurgery among patients undergoing a THR. Bisphosphonate use reduced the post-THR risk of fracture when administered both as primary prevention and as secondary prevention, by 44% and 52%, respectively. This must be further confirmed in randomized controlled trials.