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SummaryBackgroundStatin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.MethodsIn this meta-analysis, randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years. We analysed individual participant data from 22 trials (n=134 537) and detailed summary data from one trial (n=12 705) of statin therapy versus control, plus individual participant data from five trials of more intensive versus less intensive statin therapy (n=39 612). We subdivided participants into six age groups (55 years or younger, 56–60 years, 61–65 years, 66–70 years, 71–75 years, and older than 75 years). We estimated effects on major vascular events (ie, major coronary events, strokes, and coronary revascularisations), cause-specific mortality, and cancer incidence as the rate ratio (RR) per 1·0 mmol/L reduction in LDL cholesterol. We compared proportional risk reductions in different age subgroups by use of standard χ2 tests for heterogeneity when there were two groups, or trend when there were more than two groups.Findings14 483 (8%) of 186 854 participants in the 28 trials were older than 75 years at randomisation, and the median follow-up duration was 4·9 years. Overall, statin therapy or a more intensive statin regimen produced a 21% (RR 0·79, 95% CI 0·77–0·81) proportional reduction in major vascular events per 1·0 mmol/L reduction in LDL cholesterol. We observed a significant reduction in major vascular events in all age groups. Although proportional reductions in major vascular events diminished slightly with age, this trend was not statistically significant (ptrend=0·06). Overall, statin or more intensive therapy yielded a 24% (RR 0·76, 95% CI 0·73–0·79) proportional reduction in major coronary events per 1·0 mmol/L reduction in LDL cholesterol, and with increasing age, we observed a trend towards smaller proportional risk reductions in major coronary events (ptrend=0·009). We observed a 25% (RR 0·75, 95% CI 0·73–0·78) proportional reduction in the risk of coronary revascularisation procedures with statin therapy or a more intensive statin regimen per 1·0 mmol/L lower LDL cholesterol, which did not differ significantly across age groups (ptrend=0·6). Similarly, the proportional reductions in stroke of any type (RR 0·84, 95% CI 0·80–0·89) did not differ significantly across age groups (ptrend=0·7). After exclusion of four trials which enrolled only patients with heart failure or undergoing renal dialysis (among whom statin therapy has not been shown to be effective), the trend to smaller proportional risk reductions with increasing age persisted for major coronary events (ptrend=0·01), and remained non-significant for major vascular events (ptrend=0·3). The proportional reduction in m...

Aims/hypothesis Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. Methods Type 2 diabetic patients (n=9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n=4,895) or placebo (n=4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n=661). Analysis was by intention-to-treat. Results During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p<0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p=0.01), with less estimated GFR loss (1.19 vs 2.03 ml min −1 1.73 m −2 annually, p<0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min −1 1.73 m −2 , p=0.065) than on placebo (6.9 ml min −1 1.73 m −2 , p<0.001), sparing 5.0 ml min

Purpose Fear of cancer recurrence (FCR) is prevalent, distressing, and long lasting. This study evaluated the impact of a theoretically/empirically based intervention (ConquerFear) on FCR. Methods Eligible survivors had curable breast or colorectal cancer or melanoma, had completed treatment (not including endocrine therapy) 2 months to 5 years previously, were age > 18 years, and had scores above the clinical cutoff on the FCR Inventory (FCRI) severity subscale at screening. Participants were randomly assigned at a one-to-one ratio to either five face-to-face sessions of ConquerFear (attention training, metacognitions, acceptance/mindfulness, screening behavior, and values-based goal setting) or an attention control (Taking-it-Easy relaxation therapy). Participants completed questionnaires at baseline (T0), immediately post-therapy (T1), and 3 (T2) and 6 months (T3) later. The primary outcome was FCRI total score. Results Of 704 potentially eligible survivors from 17 sites and two online databases, 533 were contactable, of whom 222 (42%) consented; 121 were randomly assigned to intervention and 101 to control. Study arms were equivalent at baseline on all measured characteristics. ConquerFear participants had clinically and statistically greater improvements than control participants from T0 to T1 on FCRI total ( P < .001) and severity subscale scores ( P = .001), which were maintained at T2 ( P = .017 and P = .023, respectively) and, for FCRI total only, at T3 ( P = .018), and from T0 to T1 on three FCRI subscales (coping, psychological distress, and triggers) as well as in general anxiety, cancer-specific distress (total), and mental quality of life and metacognitions (total). Differences in FCRI psychological distress and cancer-specific distress (total) remained significantly different at T3. Conclusion This randomized trial demonstrated efficacy of ConquerFear compared with attention control (Taking-it-Easy) in reduction of FCRI total scores immediately post-therapy and 3 and 6 months later and in many secondary outcomes immediately post-therapy. Cancer-specific distress (total) remained more improved at 3- and 6-month follow-up.

These results demonstrate that preoperative chemoradiation can be safely delivered to the vast majority of patients without a significant increase in treatment toxicity or surgical morbidity.