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There has been a transition from broad to more specific research questions in the practice of network meta‐analysis (NMA). Such convergence is also taking place in the context of individual registrational trials, following the recent introduction of the estimand framework, which is impacting the design, data collection strategy, analysis and interpretation of clinical trials. The language of estimands has much to offer to NMA, particularly given the "narrow" perspective of treatments and target populations taken in health technology assessment. [ABSTRACT FROM AUTHOR]

BACKGROUND:The risk of coronary heart disease associated with intake of individual trans fatty acids (TFAs) is not clear. Adipose tissue content of TFAs is a biomarker of TFA intake and metabolism. OBJECTIVE:We investigated the rate of myocardial infarction (MI) associated with the adipose tissue content of total 18:1t, isomers of 18:1t (18:1 Δ6-10t and 18:1 Δ11t) and 18:2 Δ9c, 11t. METHODS:A case-cohort study, nested within the Danish Diet, Cancer and Health cohort (n = 57,053), was conducted, which included a random sample (n = 3156) of the total cohort and all incident MI cases (n = 2148) during follow-up (14 years). Information on MI cases was obtained by linkage with nationwide registers and validated. Adipose tissue was taken from the participants buttocks and the fatty acid composition was determined by gas chromatography. RESULTS:Women with higher adipose tissue content of total 18:1t had a 57% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.57; 95% confidence interval, 1.12-2.20; P-trend = 0.011) and women with higher content of 18:1 Δ6-10t had a 76% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.76; 95% confidence interval, 1.23-2.51; P-trend = 0.002). No association between 18:1 Δ11t content and MI rate was observed. In men, no associations between adipose tissue content of total 18:1t and 18:1 Δ6-10t and MI rate were observed. However, men with higher content of 18:1 Δ11t had a 48% higher MI rate (quintiles 5 versus 1, hazard ratio, 1.48; 95% confidence interval, 1.17-1.86; P-trend = 0.003). Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men. CONCLUSIONS:Adipose tissue content of 18:2 Δ9c, 11t was not associated with MI rate in women or men, whereas higher contents of isomers of 18:1t were associated with higher MI rates but the associations for individual 18:1t isomers differed, however, in women and men.

BACKGROUND:Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI). METHODS:Population-based cohort study of patients diagnosed with incident heart failure during 2000-2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease. RESULTS:39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08-1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35-1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86-1.15 and 0.94, 95% CI: 0.89-1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes. CONCLUSIONS:Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.

INTRODUCTION With an annual incidence of 1.4 million new cases, corresponding to 23% of cancer diagnoses in women, breast cancer is the most frequent cancer among women worldwide. (1) Several [...], BACKGROUND/OBJECTIVES: The evidence regarding fatty acids and breast cancer risk is inconclusive. Adipose tissue fatty acids can be used as biomarkers of fatty acid intake and of endogenous fatty acid exposure. Fatty acids in adipose tissue are correlated owing to common dietary sources and shared metabolic pathways, which group fatty acids into naturally occurring patterns. We aimed to prospectively investigate associations between adipose tissue fatty acid patterns and long-term risk of total breast cancer and breast cancer subtypes characterised by oestrogen and progesterone receptor status (ER and PR). SUBJECTS/METHODS: This case-cohort study was based on data from the Danish cohort Diet, Cancer and Health. At baseline, a fat biopsy and information on lifestyle and reproductive factors were collected. From the 31 original fatty acids measured, patterns of fatty acids were identified using the treelet transform. During a median follow-up of 5.3 years, 474 breast cancer cases were identified. Hazard ratios and 95% confidence intervals of risk of total breast cancer and of subtypes according to quintiles of factor score were determined by weighted Cox proportional hazards regression. RESULTS: After adjustment for potential confounders, factor scores for the seven patterns identified by the treelet transform were not associated with risk of total breast cancer, nor with risk of ER+, ER -, PR+ or PR - tumours. CONCLUSIONS: No clear associations between the patterns of fatty acids at baseline and long-term risk of total breast cancer or ER+, ER-, PR+ or PR- tumours were observed. European Journal of Clinical Nutrition (2014) 68, 1088-1094; doi: 10.1038/ejcn.2014.28; published online 19 March 2014

For survival data with a large number of explanatory variables, lasso penalized Cox regression is a popular regularization strategy. However, a penalized Cox model may not always provide the best fit to data and can be difficult to estimate in high dimension because of its intrinsic nonlinearity. The semiparametric additive hazards model is a flexible alternative which is a natural survival analogue of the standard linear regression model. Building on this analogy, we develop a cyclic coordinate descent algorithm for fitting the lasso and elastic net penalized additive hazards model. The algorithm requires no nonlinear optimization steps and offers excellent performance and stability. An implementation is available in the R package ahaz. We demonstrate this implementation in a small timing study and in an application to real data.

Purpose. To compare patients with increased risk of bleeding who received combined blood reinfusion and femoral nerve block in total knee replacement (TKR) to regular patients treated routinely with respect to pain relief, blood loss, and knee function. Methods. In a consecutive series of 67 patients who underwent unilateral TKR, 12 patients with increased risk of bleeding owing to cardiac disease or previous thromboembolic events received continuous femoral nerve block and blood reinfusion, without tranexamic acid (TA) injection. The remaining 55 patients were controls who received standard postoperative treatment (TA injection, local injection of analgesics, and suction drainage without reinfusion). The volume of blood loss (drained or reinfused), pain score (using a visual analogue scale) and knee function (using the Knee Society Score [KSS]) in the 2 groups were compared. Results. In the study group, patients were 5 years older and tended to have a lower preoperative KSS function score (35 vs. 45, p=0.08) and a higher function-related pain score (6.5 vs. 6, p=0.10). The mean volume of drained blood wasted in the study group did not differ significantly from the mean total volume of drained blood in the control group (235 vs. 300 ml, p=0.14). Similarly, the mean decrease in postoperative haemoglobin concentration did not differ significantly between the respective groups (2.1 vs. 2.1 mmol/l, p=0.97). A significantly greater proportion of patients received allogenic blood transfusion in the study group than in controls (3/12 vs. 2/55, p