Objective: To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). Methods: A study was eligible if it enrolled AIS patients older than 18 years, with an LVO treated with either successful or unsuccessful EVT, and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed using a generalized linear mixed-effects model. Results: A total of 5874 patients (mean age: 69±14 years, 50% women, median NIHSS on admission: 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common OR=0.82, 95%CI:0.80-0.85; adjusted common OR=0.88, 95%CI:0.84-0.93) and modified Ranking Scale score≤2 (unadjusted OR=0.82, 95%CI:0.79-0.85; adjusted OR=0.87, 95%CI:0.82-0.93), and a higher odds of all-cause mortality (unadjusted OR=1.18, 95%CI:1.13-1.24; adjusted OR=1.15, 95%CI:1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurological deterioration (unadjusted OR=1.14, 95%CI:1.07-1.21; adjusted OR=1.14, 95%CI:1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR=1.20, 95%CI:1.09-1.29; adjusted OR=1.20, 95%CI:1.03-1.38) after EVT. Conclusion: Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurological deterioration, three-month mortality, and worse three-month functional outcomes.

Introduction Tobacco is the world’s leading preventable cause of disease and death. People with depression are twice as likely to smoke and are less responsive to standard tobacco treatments as compared with the general population. A Cochrane systematic review of randomised controlled trials of smoking cessation treatment for smokers with current or historical depression found that adding mood management to usual smoking treatment improved quit rates. However, the review did not examine if variation in intervention delivery or intervention functions impacted on treatment effectiveness. With the aim of providing information to develop tailored approaches to treating smoking for people with current depression, we will add-on to the Cochrane review in three ways: (1) use the Template for Intervention Description and Replication checklist to determine if variations in mood management delivery have impact on intervention effectiveness, (2) use the Taxonomy of Behaviour Change techniques for smoking cessation to examine which behaviour change functions are most effective for smoking cessation in people with current depression and (3) examine the difference in change in depression scores between intervention and control arms. Methods and analysis We will include randomised controlled trials of smokers with current depression as identified by a previous Cochrane review and the in-progress update of this Cochrane review. We will use meta-regression to examine (1) if variations in delivery of mood management impact on smoking cessation intervention effectiveness, (2) determine which behaviour change functions are most effective for smoking cessation and (3) use meta-analysis of the difference in change in depression scores between treatment arms from baseline to follow-up to determine if offering smoking cessation treatment causes psychological harm. Ethics and dissemination Ethical approval is not required for this study. We will disseminate the findings of this work at national and international conferences, and to relevant patient panels. PROSPERO registration number CRD42017070741.

Meta-analysis using individual participant data (IPD-MA) from randomised controlled trials (RCTs) can strengthen evidence used for decision-making, and is considered the ‘gold standard’ approach. In this paper, we present the importance, properties, and main approaches of conducting an IPD-MA. We exemplify the main approaches of conducting an IPD-MA and how these can be used to obtain subgroup effects through estimation of interaction terms. IPD-MA has several benefits over traditional aggregate data meta-analysis. These include: standardization of definitions of outcomes and/or scales, re-analysis of eligible RCTs using the same analysis model across all studies, accounting for missing outcome data, detecting outliers, using participant-level covariates to explore intervention-by-covariate interactions, and tailoring intervention effects to participant characteristics. IPD-MA can be performed either in a two-stage or a one-stage approach. We exemplify the presented methods using two illustrative examples. The first real-life example includes six studies assessing sonothrombolysis with or without addition of microspheres against intravenous thrombolysis alone (i.e., control) in acute ischemic stroke participants with large vessel occlusions. The second real-life example includes seven studies evaluating the association between blood pressure levels after endovascular thrombectomy and functional improvement of acute ischemic stroke in patients with large vessel occlusion. IPD reviews can be associated with higher-quality statistical analysis and may differ from aggregate data reviews. Unlike individual trials that lack power, and aggregate data meta-analysis results which suffer from confounding and aggregation bias, the use of IPD allows us to explore intervention-by-covariate interactions. However, a key limitation of conducting an IPD-MA is retrieval of IPD from original RCTs. Time and resources should be carefully planned before embarking to retrieving IPD.

Objective To examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer’s dementia (AD). Design Systematic review and individual patient data (IPD) network meta-analysis (NMA) based on our previously published systematic review and aggregate data NMA. Data sources MEDLINE, Embase, Cochrane Methodology Register, CINAHL, AgeLine and Cochrane Central Register of Controlled Trials up to March 2016. Participants 80 randomised controlled trials (RCTs) including 21 138 adults with AD, and 12 RCTs with IPD including 6906 patients. Interventions Cognitive enhancers (donepezil, rivastigmine, galantamine and memantine) alone or in any combination against other cognitive enhancers or placebo. Data extraction and synthesis We requested IPD from authors, sponsors and data sharing platforms. When IPD were not available, we used aggregate data. We appraised study quality with the Cochrane risk-of-bias. We conducted a two-stage random-effects IPD-NMA, and assessed their findings using CINeMA (Confidence in Network Meta-Analysis). Primary and secondary outcomes We included trials assessing cognition with the Mini-Mental State Examination (MMSE), and adverse events. Results Our IPD-NMA compared nine treatments (including placebo). Donepezil (mean difference (MD)=1.41, 95% CI: 0.51 to 2.32) and donepezil +memantine (MD=2.57, 95% CI: 0.07 to 5.07) improved MMSE score (56 RCTs, 11 619 participants; CINeMA score: moderate) compared with placebo. According to P-score, oral rivastigmine (OR=1.26, 95% CI: 0.82 to 1.94, P-score=16%) and donepezil (OR=1.08, 95% CI: 0.87 to 1.35, P-score=30%) had the least favourable safety profile, but none of the estimated treatment effects were sufficiently precise when compared with placebo (45 RCTs, 15 649 patients; CINeMA score: moderate to high). For moderate-to-severe impairment, donepezil, memantine and their combination performed best, but for mild-to-moderate impairment donepezil and transdermal rivastigmine ranked best. Adjusting for MMSE baseline differences, oral rivastigmine and galantamine improved MMSE score, whereas when adjusting for comorbidities only oral rivastigmine was effective. Conclusions The choice among the different cognitive enhancers may depend on patient’s characteristics. The MDs of all cognitive enhancer regimens except for single-agent oral rivastigmine, galantamine and memantine, against placebo were clinically important for cognition (MD larger than 1.40 MMSE points), but results were quite imprecise. However, two-thirds of the published RCTs were associated with high risk of bias for incomplete outcome data, and IPD were only available for 15% of the included RCTs. PROSPERO registration number CRD42015023507.