Duration and dosing of systemic corticosteroids for acute exacerbation of COPD, protocol for a systematic review with meta-analysis of randomized trials and cohort studies.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a leading cause of deterioration in patients with otherwise stably controlled COPD. Treatments of AECOPD often require the use of corticosteroid therapy in conjunction with bronchodilators and antibiotics. However, the duration and dosage of corticosteroids still remain unclear. We propose to perform this systematic review and meta-analysis of all available randomized control trials (RCTs) and observational cohort studies to comprehensively assess the efficacy and safety of different corticosteroid duration and dosing regimen in the current body of evidence. METHODS: We will search MEDLINE, EMBASE, CENTRAL via Ovid as well as CINAHL and Web of Science for available literature comparing different corticosteroid duration and dosage in the treatment of AECOPD. We will perform title and full text screening in duplicate, then extract relevant data using a pre-piloted extraction form. We will define short duration as less than 14-day duration of treatment and long duration as greater than 14-day treatment. We will report mortality difference as our primary outcome, with additional comparisons in incidence of re-exacerbation, hospital length of stay, lung function, incidence of hyperglycemia and infection. We will perform risk of bias assessment using the ROB2.0 and ROBINS-I tool, as well as the GRADE assessment to assess the quality of evidence. RESULTS: We will publish the full results of our systematic review and meta-analysis in a peer-reviewed journal. DISCUSSIONS: To our knowledge, this represents an updated and most comprehensive review of the literature comparing different duration and dosing regimen of corticosteroid treatments in AECOPD, as we will include both RCTs and observational studies without date or language restrictions. We aim to validate prior meta-analyses and study findings on the efficacy of short duration corticosteroid therapy over longer treatments and to inform future research directions in dosing regimens.

Comparing Oral Versus Intravenous Antibiotics Administration for Cellulitis Infection: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Cellulitis is defined as an infection of the skin that is usually characterized by localized but poorly demarcated areas of erythema, swelling, and pain. Erysipelas is a subtype of cellulitis that is characterized by a more superficial infection, often involving the face. Because gram-positive bacteria are the most common infective agent, beta-lactam antibiotics such as cephalosporins are commonly used. However, guidelines and physician preference vary widely as different antibiotic options and routes of administration exist, in addition to the fact that most cases are treated empirically without microbiological lab guidance. This lack of standardization in evidence, guidelines, and physician practice prompted this systematic review and meta-analysis of both randomized trial data and cohort studies to aggregate the currently available evidence for the optimal routes of antibiotic administration in cellulitis treatment. OBJECTIVE: The primary objective of our review is to compare the efficacy of oral versus intravenous antibiotic administration for cellulitis infections, thereby providing clinicians with evidence-based guidelines for treatment. METHODS: We will search MEDLINE, Embase, and CENTRAL through Ovid as well as Web of Science and CINAHL for all available literature comparing different routes of antibiotic administration in the treatment of cellulitis and erysipelas. We will perform title and abstract as well as full-text screening in duplicate according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines and then extract the relevant data using a prepiloted data sheet. The primary outcome for our review is the duration of infection resolution, and secondary outcomes such as incidence of sepsis, mortality, hospital admission, and Clostridium difficile infection. We will assess the risk of bias in our included studies using the RoB 2.0 (revised tool for Risk of Bias in randomized trials) and ROBINS-I (Risk of bias in non-randomized studies for interventions) tools, with a final quality assessment using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework and a sensitivity analysis to examine heterogeneity. RESULTS: We will publish the final results of our systematic review in a peer-reviewed academic journal. This project received no funding or financial assistance. Data analysis is currently underway, and the results are expected to be submitted for publication in late November 2023. CONCLUSIONS: To our knowledge, this will be the most up-to-date review of the best available evidence comparing different routes of antibiotic administration for cellulitis. Because of the vast selection of antibiotic options available and the empirical nature of the treatment, we anticipate heterogeneity within our data but nonetheless hope to provide aggregated evidence on the efficacy of intravenous versus oral administration of antibiotics in cellulitis treatment. We hope the results from this study will better inform physician practices in the future for cellulitis infections. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48342.

Comparative Efficacy of Treatments for Brain Metastases from Non-Small Cell Lung Cancer without an EGFR-Mutation/ALK-Rearrangement: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: As many as 30% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BMs) over the course of their illness. Here, we quantitatively compare the efficacy of the various emerging regimens for NSCLC BMs without a definitive targetable epidermal growth factor receptor mutation/ALK rearrangement. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL, and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs that included ≥10 patients were included. We used a frequentist fixed or random-effects model for network meta-analysis. The outcomes of interest included intracranial progression-free survival (iPFS), overall survival (OS), and overall progression-free survival. RESULTS: In total, 18 studies representing 17 trials (n = 2726 patients) were identified. Immune checkpoint inhibitor regimens showed significant improvement in OS compared with chemotherapy alone, including pembrolizumab and chemotherapy (6 studies, hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21-0.62), atezolizumab alone (HR 0.54, 95% CI 0.33-0.89), and nivolumab and ipilimumab (HR 0.64, 95% CI 0.42-0.97). An improvement in overall PFS was seen with use of pembrolizumab and chemotherapy compared with chemotherapy alone (3 studies, HR 0.42, 95% CI 0.26-0.68). Studies evaluating checkpoint inhibitors did not report iPFS data, and we did not find improvement in iPFS or OS with the addition of any chemotherapy regimen to whole-brain radiation therapy. CONCLUSIONS: In this network meta-analysis, we demonstrate the promising survival benefit with use of checkpoint inhibitor-based regimens in NSCLC BMs without a targetable epidermal growth factor receptor mutation/ALK rearrangement. Moving forward, large-scale BM-focused RCTs are necessary to establish the iPFS benefit of immune checkpoint inhibitor-based immunotherapy in this patient population.

The effects of dietary nitrate supplementation on endurance exercise performance and cardiorespiratory measures in healthy adults: a systematic review and meta-analysis.

BACKGROUND: Nitrate supplementation is thought to improve performance in endurance sports. OBJECTIVE: To meta-analyze studies evaluating the effect of nitrate supplementation on endurance sports performance among adults. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science and CINAHL without language restrictions. METHODS: We included studies that: 1) compared nitrate supplementation with placebo; 2) enrolled adults engaging in an endurance-based activity; and 3) reported a performance measure or surrogate physiologic outcome. We evaluated risk of bias using the Cochrane Collaboration tool and pooled data with a random-effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate confidence in estimates. RESULTS: We included 73 studies (n = 1061). Nitrate supplementation improved power output (MD 4.6 watts, P < 0.0001), time to exhaustion (MD 25.3 s, P < 0.00001), and distance travelled (MD 163.7 m, P = 0.03). We found no significant difference on perceived exertion, time trial performance and work done. Nitrate supplementation decreased VO2 (MD - 0.04 L/min, P < 0.00001) but had no significant effect on VO2max or blood lactate levels. CONCLUSION: The available evidence suggests that dietary nitrate supplementation benefits performance-related outcomes for endurance sports.

Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Brain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements. METHODS: We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS). RESULTS: We included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24). CONCLUSIONS: In patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060.

Intravenous iron therapy for patients with preoperative iron deficiency or anaemia undergoing cardiac surgery reduces blood transfusions: a systematic review and meta-analysis.

OBJECTIVES: The benefits of preoperative intravenous (IV) iron treatment in cardiac surgery patients with preoperative anaemia or iron deficiency have not been well-established. We performed a systematic review and meta-analysis to determine the effects of treating preoperative anaemia or iron deficiency with IV iron in adult cardiac surgery patients. METHODS: We searched Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Systems Online and Excerpta Medica Database for randomized controlled trials (RCTs) and observational studies comparing IV iron to oral iron or no iron. We performed title and abstract, full-text screening, data extraction and risk of bias assessment independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence. RESULTS: We identified 4 RCTs and 7 observational studies. Pooled data from observational studies suggested a benefit of IV iron compared to no iron on mortality [relative risk 0.39, 95% confidence interval (CI) 0.23-0.65; P < 0.001, very low quality], units transfused per patient (mean difference -1.22, 95% CI -1.85 to -0.60; P < 0.001, very low quality), renal injury (relative risk 0.50, 95% CI 0.36-0.69; P < 0.001, very low quality) and hospital length of stay (mean difference -4.24 days, 95% CI -6.86 to -1.63; P = 0.001, very low quality). Pooled data from RCTs demonstrated a reduction in the number of patients transfused with IV iron compared to oral or no iron (relative risk 0.81, 95% CI 0.70-0.94; P = 0.005, moderate quality). The pooled estimates of effect from RCTs for mortality, hospital length of stay, units transfused per patient and renal injury were consistent in direction with observational studies. CONCLUSIONS: This meta-analysis suggests that IV iron improves postoperative morbidity in adult cardiac surgery patients with preoperative anaemia or iron deficiency. A large, rigorous, placebo-controlled, double-blinded, multicentre trial is needed to clarify the role of IV iron in this patient population. CLINICAL TRIAL REGISTRATION: International prospective register of systematic reviews ID Number CRD42019122844.