There is good evidence for the efficacy of biological agents in patients with RA. Safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.

Background 'Silent' cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). Objective To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). Methods Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. Results New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r¼0.37, p¼0.042), severity of atheroma (arch and descending aorta; r¼0.91, p<0.001, r¼0.69, p¼0.001, respectively) and catheterisation time (r¼0.45, p¼0.02) were predictors of the number of new cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary increased significantly (32.466.2 vs 36.567.2; p¼0.03) with no significant change in mental component summary (43.5611.7 vs 43.1614.3; p¼0.85). The EQ5D score and Visual Analogue Scale showed no significant change (0.5660.26 vs 0.5960.31; p¼0.70, and 54.2619 vs 58.2624; p¼0.43). Conclusion Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were 'silent' with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

Computerised cognitive-behavioural therapy (cCBT) for depression has the potential to be efficient therapy but engagement is poor in primary care trials.We tested the benefits of adding telephone support to cCBT.We compared telephone-facilitated cCBT (MoodGYM) (n = 187) to minimally supported cCBT (MoodGYM) (n = 182) in a pragmatic randomised trial (trial registration: ISRCTN55310481). Outcomes were depression severity (Patient Health Questionnaire (PHQ)-9), anxiety (Generalized Anxiety Disorder Questionnaire (GAD)-7) and somatoform complaints (PHQ-15) at 4 and 12 months.Use of cCBT increased by a factor of between 1.5 and 2 with telephone facilitation. At 4 months PHQ-9 scores were 1.9 points lower (95% CI 0.5-3.3) for telephone-supported cCBT. At 12 months, the results were no longer statistically significant (0.9 PHQ-9 points, 95% CI -0.5 to 2.3). There was improvement in anxiety scores and for somatic complaints.Telephone facilitation of cCBT improves engagement and expedites depression improvement. The effect was small to moderate and comparable with other low-intensity psychological interventions.

Based on this systematic review, there is no strong evidence to support one therapy over another as EBRT, BT and RP can all be considered as effective monotherapies for localised disease with EBRT also effective for post-operative management. All treatments have unique adverse events profiles. Further large, robust RCTs which report treatment-specific and treatment combination-specific outcomes in defined prostate cancer risk groups following established reporting standards are needed. These will strengthen the evidence base for newer technologies, help reinforce current consensus guidelines and establish greater standardisation across practices.

BackgroundThe proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low‐density lipoprotein cholesterol (LDL‐C) when added to statin therapy in patients who need additional LDL‐C reduction.Methods and ResultsWe conducted a systematic review and network meta‐analysis of randomized trials of lipid‐lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid‐lowering therapies that enrolled patients requiring further LDL‐C reduction while on maximally tolerated medium‐ or high‐intensity statin, of which 15 could be relevant for inclusion in LDL‐C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL‐C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (−74.1%; 95% credible interval −79.81% to −68.58%), alirocumab 75 mg (−20.03%; 95% credible interval −27.32% to −12.96%), and alirocumab 150 mg (−13.63%; 95% credible interval −22.43% to −5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe.Conclusions PCSK9 inhibitors added to medium‐ to high‐intensity statin therapy significantly reduce LDL‐C in patients requiring further LDL‐C reduction. The network meta‐analysis showed a significant treatment difference in LDL‐C reduction for evolocumab versus alirocumab.