Predictors of Oral Antibiotic Treatment Failure for Nonpurulent Skin and Soft Tissue Infections in the Emergency Department.

BACKGROUND: Current guideline recommendations for optimal management of nonpurulent skin and soft tissue infections (SSTIs) are based on expert consensus. There is a lack of evidence to guide emergency physicians regarding selection of patients for oral versus intravenous antibiotic therapy. The primary objective was to identify predictors associated with oral antibiotic treatment failure. METHODS: We performed a health records review of adults (age ≥ 18 years) with nonpurulent SSTIs treated at two tertiary care emergency departments (EDs). Oral antibiotic treatment failure was defined as any of the following after a minimum of 48 hours of oral therapy due to worsening infection: 1) hospitalization, 2) change in class of oral antibiotic, or 3) switch to intravenous therapy. Multivariable logistic regression was used to identify predictors independently associated with oral antibiotic treatment failure. RESULTS: We identified 500 patients (mean ± SD age = 64 ± 19 years, 279 male [55.8%], and 126 [25.2%] with diabetes). Of 288 patients who had received a minimum of 48 hours of oral antibiotics, there were 85 oral antibiotic treatment failures (29.5%). Tachypnea at triage (odds ratio [OR] = 6.31, 95% confidence interval [CI] = 1.80 to 22.08), chronic ulcers (OR = 4.90, 95% CI = 1.68-14.27), history of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection (OR = 4.83, 95% CI = 1.51 to 15.44), and cellulitis in the past 12 months (OR = 2.23, 95% CI = 1.01 to 4.96) were independently associated with oral antibiotic treatment failure CONCLUSION: This is the first study to evaluate predictors of oral antibiotic treatment failure for nonpurulent SSTIs treated in the ED. Tachypnea at triage, chronic ulcers, history of MRSA colonization or infection, and cellulitis within the past year were independently associated with oral antibiotic treatment failure. Emergency physicians should consider these risk factors when deciding on oral versus intravenous antimicrobial therapy for outpatient management of nonpurulent SSTIs.

Systematic review of rituximab for autoimmune diseases: a potential alternative to intravenous immune globulin.

BACKGROUND: The anti-CD20 monoclonal antibody rituximab has immune-modulatory effects similar to intravenous immunoglobulin (IVIG). We performed a systematic review and meta-analysis to determine the efficacy and safety of rituximab in autoimmune diseases that are also treated with IVIG. STUDY DESIGN AND METHODS: The most common indications for immune modulation with IVIG, as identified from a 2012 regional audit in Canada, were chronic inflammatory demyelinating polyneuropathy (CIDP), immune thrombocytopenia (ITP), myasthenia gravis, multifocal motor neuropathy, Guillain-Barré syndrome, systemic lupus erythematosus (SLE), Sjogren's syndrome, and pemphigus vulgaris. We searched MEDLINE, EMBASE, and the Cochrane Library until July 2016 for studies evaluating rituximab in each of these conditions. The primary outcome in our meta-analysis was clinical response at 6 months as defined by disease-specific criteria in randomized trials. We also calculated pooled proportions of responders within disease types from observational studies. RESULTS: Ninety-five rituximab studies were identified: 86 were observational studies in patients with ITP (n = 1746), SLE (n = 1047), pemphigus vulgaris (n = 564), Sjogren's syndrome (n = 138), myasthenia gravis (n = 66), and CIDP (n = 31) and nine were randomized controlled trials (n = 992) in patients with ITP, SLE, and Sjogren's syndrome that compared rituximab with placebo plus standard of care. Among randomized trials, response rates were higher with rituximab (relative risk, 1.38; 95% confidence interval [CI], 1.05-1.83). The pooled proportion of rituximab responses ranged from 94% (95% CI, 88%-98%) for pemphigus vulgaris to 48% (95% CI, 30%-66%) for CIDP. Rituximab was generally well tolerated in observational studies although in the randomized trials, adverse events were more common in the rituximab group. CONCLUSION: Rituximab is an immune-modulating agent with biologic activity across many autoimmune conditions. Our data support the use of comparative trials with broad eligibility criteria to evaluate rituximab as an alternative to IVIG in autoimmune diseases.

High statistical heterogeneity is more frequent in meta-analysis of continuous than binary outcomes.

OBJECTIVES: We compared the distribution of heterogeneity in meta-analyses of binary and continuous outcomes. STUDY DESIGN AND SETTING: We searched citations in MEDLINE and Cochrane databases for meta-analyses of randomized trials published in 2012 that reported a measure of heterogeneity of either binary or continuous outcomes. Two reviewers independently performed eligibility screening and data abstraction. We evaluated the distribution of I(2) in meta-analyses of binary and continuous outcomes and explored hypotheses explaining the difference in distributions. RESULTS: After full-text screening, we selected 671 meta-analyses evaluating 557 binary and 352 continuous outcomes. Heterogeneity as assessed by I(2) proved higher in continuous than in binary outcomes: the proportion of continuous and binary outcomes reporting an I(2) of 0% was 34% vs. 52%, respectively, and reporting an I(2) of 60-100% was 39% vs. 14%. In continuous but not binary outcomes, I(2) increased with larger number of studies included in a meta-analysis. Increased precision and sample size do not explain the larger I(2) found in meta-analyses of continuous outcomes with a larger number of studies. CONCLUSIONS: Meta-analyses evaluating continuous outcomes showed substantially higher I(2) than meta-analyses of binary outcomes. Results suggest differing standards for interpreting I(2) in continuous vs. binary outcomes may be appropriate.