A postal questionnaire was sent to 10,000 patients more than one year after their total knee replacement (TKR). They were assessed using the Oxford knee score and were asked whether they were satisfied, unsure or unsatisfied with their TKR. The response rate was 87.4% (8231 of 9417 eligible questionnaires) and a total of 81.8% (6625 of 8095) of patients were satisfied. Multivariable regression modelling showed that patients with higher scores relating to the pain and function elements of the Oxford knee score had a lower level of satisfaction (p < 0.001), and that ongoing pain was a stronger predictor of this. Female gender and a primary diagnosis of osteoarthritis were found to be predictors of lower levels of patient satisfaction. Differences in the rate of satisfaction were also observed in relation to age, the American Society of Anesthesiologists grade and the type of prosthesis. This study has provided data on the Oxford knee score and the expected levels of satisfaction at one year after TKR. The results should act as a benchmark of practice in the United Kingdom and provide a baseline for peer comparison between institutions.

Background-We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF.

SummaryBackgroundStatins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.MethodsWe used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.FindingsData were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05–0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18–0·43), waist circumference (0·32 cm, 0·16–0·47), plasma insulin concentration (1·62%, 0·53–2·72), and plasma glucose concentration (0·23%, 0·02–0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00–1·05); the rs12916-T allele association was consistent (1·06, 1·03–1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18–1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10–0·38 in all trials; 0·33 kg, 95% CI 0·24–0·42 in placebo or standard care controlled trials and −0·15 kg, 95% CI −0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9–6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06–1·18 in all trials; 1·11, 95% CI 1·03–1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04–1·22 in intensive-dose vs moderate dose trials).InterpretationThe increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.FundingThe funding sources are cited at the end of the paper.

Background Patients with heart failure and preserved ejection fraction (HFpEF) have a poor prognosis, and no therapies have been proven to improve outcomes. It has been proposed that heart failure, including HFpEF, represents overlapping syndromes that may have different prognoses. We present an exploratory study of patients enrolled in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE) using latent class analysis (LCA) with validation using the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study to identify HFpEF subgroups. Methods and results In total, 4113 HFpEF patients randomized to irbesartan or placebo were characterized according to 11 clinical features. HFpEF subgroups were identified using LCA. Event-free survival and effect of irbesartan on the composite of all-cause mortality and cardiovascular hospitalization were determined for each subgroup. Subgroup definitions were applied to 3203 patients enrolled in CHARM-Preserved to validate observations regarding prognosis and treatment response. Six subgroups were identified with significant differences in event-free survival (p<0.001). Clinical profiles and prognoses of the 6 subgroups were similar in CHARM-Preserved. The two subgroups with the worst event-free survival in both studies were characterized by a high prevalence of obesity, hyperlipidemia, diabetes mellitus, anemia, and renal insufficiency (Subgroup C) and by female predominance, advanced age, lower body mass index, and high rates of atrial fibrillation, valvular disease, renal insufficiency, and anemia (Subgroup F). Conclusion Using a data-driven approach, we identified HFpEF subgroups with significantly different prognoses. Further development of this approach for characterizing HFpEF subgroups is warranted.

The results confirm that "hot" tonsillectomy techniques carry a substantially elevated risk of postoperative hemorrhage when diathermy is used as a dissection tool in tonsillectomy.

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models adjusting for atherosclerotic risk factors (per relevant risk scores), and predictive utility was determined by the C-statistic and categorical Net Reclassification Index. We show that eGFRcys is most strongly associated with CVD and mortality, and along with albuminuria adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Modification of the current allocation system for donor livers in the United States to incorporate recipient serum sodium concentration ([Na]) has recently been proposed. However, the impact of this parameter on posttransplantation mortality has not been previously examined in a large risk-adjusted analysis. We assessed the effect of recipient [Na] on the survival of all adults with chronic liver disease who received a first single organ liver transplant in the UK and Ireland during the period March 1, 1994 to March 31, 2005 (n ϭ 5,152) at 3 years, during the first 90 days, and beyond the first 90 days, adjusting for a wide range of recipient, donor, and graft characteristics. Compared to those with normal [Na] (135-145 meq/L; n ϭ 3,066), severely hyponatremic recipients ([Na] Ͻ130 meq/L, n ϭ 541), had a higher risk-adjusted mortality at 3 years (hazard ratio [HR] 1.28; 95% confidence interval [CI], 1.04-1.59; P Ͻ 0.02). The excess mortality was, however, confined to the first 90 days (HR 1.55; 95% CI, 1.18-2.04; P Ͻ 0.002) with no significant difference thereafter. This was also true for hypernatremic recipients ([Na] Ͼ145 meq/L, n ϭ 81), who had an even greater risk-adjusted mortality compared to normonatremic recipients (overall: HR 1.85; 95% CI, 1.25-2.73; P Ͻ 0.002; Յ90 days: HR 2.29; 95% CI, 1.42-3.70; P Ͻ 0.001; Ͼ90 days: HR 1.12; 95% CI, 0.55-2.29; P ϭ 0.8), whereas mildly hyponatremic recipients ([Na] 130-134 meq/L, n ϭ 1,127) had similar risk-adjusted mortality to those with normal [Na] at the same time points. In conclusion, recipient [Na] is an independent predictor of death following liver transplantation. Attempts to correct the [Na] toward the normal reference range are an important aspect of pretransplantation management.

BackgroundMany public health interventions cannot be evaluated using randomised controlled trials so they rely on the assessment of observational data. Techniques for evaluating public health interventions using observational data include interrupted time series analysis, panel data regression-based approaches, regression discontinuity and instrumental variable approaches. The inclusion of a counterfactual improves causal inference for approaches based on time series analysis, but the selection of a suitable counterfactual or control area can be problematic. The synthetic control method builds a counterfactual using a weighted combination of potential control units.MethodsWe explain the synthetic control method, summarise its use in health research to date, set out its advantages, assumptions and limitations and describe its implementation through a case study of life expectancy following German reunification.ResultsAdvantages of the synthetic control method are that it offers an approach suitable when there is a small number of treated units and control units and it does not rely on parallel preimplementation trends like difference in difference methods. The credibility of the result relies on achieving a good preimplementation fit for the outcome of interest between treated unit and synthetic control. If a good preimplementation fit is established over an extended period of time, a discrepancy in the outcome variable following the intervention can be interpreted as an intervention effect. It is critical that the synthetic control is built from a pool of potential controls that are similar to the treated unit. There is currently no consensus on what constitutes a ‘good fit’ or how to judge similarity. Traditional statistical inference is not appropriate with this approach, although alternatives are available. From our review, we noted that the synthetic control method has been underused in public health.ConclusionsSynthetic control methods are a valuable addition to the range of approaches for evaluating public health interventions when randomisation is impractical. They deserve to be more widely applied, ideally in combination with other methods so that the dependence of findings on particular assumptions can be assessed.