Patent foramen ovale closure, antiplatelet therapy or anticoagulation in patients with patent foramen ovale and cryptogenic stroke: a systematic review and network meta-analysis incorporating complementary external evidence.

OBJECTIVE: To examine the relative impact of three management options in patients aged <60 years with cryptogenic stroke and a patent foramen ovale (PFO): PFO closure plus antiplatelet therapy, antiplatelet therapy alone and anticoagulation alone. DESIGN: Systematic review and network meta-analysis (NMA) supported by complementary external evidence. DATA SOURCES: Medline, EMBASE and Cochrane CENTRAL. STUDY SELECTION: Randomised controlled trials (RCTs) addressing PFO closure and/or medical therapies in patients with PFO and cryptogenic stroke. REVIEW METHODS: We conducted an NMA complemented with external evidence and rated certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Ten RCTs in eight studies proved eligible (n=4416). Seven RCTs (n=3913) addressed PFO closure versus medical therapy. Of these, three (n=1257) addressed PFO closure versus antiplatelet therapy, three (n=2303) addressed PFO closure versus mixed antiplatelet and anticoagulation therapies and one (n=353) addressed PFO closure versus anticoagulation. The remaining three RCTs (n=503) addressed anticoagulant versus antiplatelet therapy. PFO closure versus antiplatelet therapy probably results in substantial reduction in ischaemic stroke recurrence (risk difference per 1000 patients over 5 years (RD): -87, 95% credible interval (CrI) -100 to -33; moderate certainty). Compared with anticoagulation, PFO closure may confer little or no difference in ischaemic stroke recurrence (low certainty) but probably has a lower risk of major bleeding (RD -20, 95% CrI -27 to -2, moderate certainty). Relative to either medical therapy, PFO closure probably increases the risk of persistent atrial fibrillation (RD 18, 95% CI +5 to +56, moderate certainty) and device-related adverse events (RD +36, 95% CI +23 to +50, high certainty). Anticoagulation, compared with antiplatelet therapy, may reduce the risk of ischaemic stroke recurrence (RD -71, 95% CrI -100 to +17, low certainty), but probably increases the risk of major bleeding (RD +12, 95% CrI -5 to +65, moderate certainty). CONCLUSIONS: In patients aged <60 years, PFO closure probably confers an important reduction in ischaemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding. PROSPERO REGISTRATION NUMBER: CRD42017081567.

Antibiotics for uncomplicated skin abscesses: systematic review and network meta-analysis.

OBJECTIVE: To assess the impact of adjunctive antibiotic therapy on uncomplicated skin abscesses. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. STUDY SELECTION: A BMJ Rapid Recommendation panel provided input on design, important outcomes and the interpretation of the results. Eligible randomised controlled trials (RCTs) included a comparison of antibiotics against no antibiotics or a comparison of different antibiotics in patients with uncomplicated skin abscesses, and reported outcomes prespecified by the linked guideline panel. REVIEW METHODS: Reviewers independently screened abstracts and full texts for eligibility, assessed risk of bias and extracted data. We performed random-effects meta-analyses that compared antibiotics with no antibiotics, along with a limited number of prespecified subgroup hypotheses. We also performed network meta-analysis with a Bayesian framework to compare effects of different antibiotics. Quality of evidence was assessed with The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Fourteen RCTs including 4198 patients proved eligible. Compared with no antibiotics, antibiotics probably lower the risk of treatment failure (OR 0.58, 95% CI 0.37 to 0.90; low quality), recurrence within 1 month (OR 0.48, 95% CI 0.30 to 0.77; moderate quality), hospitalisation (OR 0.55, 95% CI 0.32 to 0.94; moderate quality) and late recurrence (OR 0.64, 95% CI 0.48 to 0.85; moderate quality). However, relative to no use, antibiotics probably increase the risk of gastrointestinal side effects (trimethoprim and sulfamethoxazole (TMP-SMX): OR 1.28, 95% CI 1.04 to 1.58; moderate quality; clindamycin: OR 2.29, 95% CI 1.35 to 3.88; high quality) and diarrhoea (clindamycin: OR 2.71, 95% CI 1.50 to 4.89; high quality). Cephalosporins did not reduce the risk of treatment failure compared with placebo (moderate quality). CONCLUSIONS: In patients with uncomplicated skin abscesses, moderate-to-high quality evidence suggests TMP-SMX or clindamycin confer a modest benefit for several important outcomes, but this is offset by a similar risk of adverse effects. Clindamycin has a substantially higher risk of diarrhoea than TMP-SMX. Cephalosporins are probably not effective.