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Acute pediatric pain is a common reason for presenting in the emergency department (ED); however, there are multiple pharmacologic management options available and uncertainty regarding which provide the optimal benefit-to-harm ratio. Existing systematic reviews focus primarily on individual pharmacologic or non pharmacologic treatments. Our rationale is to conduct this network meta analysis to establish the relative effectiveness and harms of all available pharmacologic options for managing acute, pediatric pain. Our broad eligibility criteria (all acute, non-procedural, pediatric pain complaints managed in an outpatient setting) will allow us to explore for subgroup effects, such as whether effectiveness differs based on underlying causes of pain. This will summarize the entirety of the evidence to assist in evidence-informed management of acute pain and identify gaps in the literature for future research. We will compare our data to future publication to review results and confirm reproducibility.

Systematic Review and Network Meta-Analysis Protocol

A systematic review and network meta-analysis evaluating the efficacy of noninvasive ventilation strategies during the post-extubation period in critically ill patients.

Systematic review and network meta-analysis with the objective of evaluating the comparative efficacy of epinephrine dosing in out-of-hospital cardiac arrest.

Acute non-low back musculoskeletal pain can occur from common injuries, such as strains and sprains, and is associated with substantial morbidity and socioeconomic costs. A recently published study by Busse et al. (2020) investigated all interventions for the treatment of non-low back acute musculoskeletal pain. Due to the sheer number of interventions, this study elected to combine similar pharmacologic treatments into single nodes for analyses. Based on their analyses, they concluded that there is high- to moderate-certainty evidence that topical and oral NSAIDs have an attractive benefit-harm ratio, whereas opioids cause greater harm. The purpose of this network meta-analysis (NMA) is to solely focus on pharmacologic interventions to directly compare these treatments as separate nodes to gain a more detailed understanding of the effectiveness of each drug treatment. Busse, J. W., Craigie, S., Sadeghirad, B., Couban, R., Hong, P., Oparin, Y., May, C., Lok, A., & Guyatt, G. H. (2019). Management of acute musculoskeletal pain (excluding low back pain): protocol for a systematic review and network meta-analysis of randomised trials. BMJ open, 9(4), e024441. https://doi.org/10.1136/bmjopen-2018-024441

Systematic review and network meta-analysis with the objective of evaluating the comparative efficacy of four temperature targets for targeted temperature management in comatose survivors of out-of-hospital cardiac arrest.

Knee osteoarthritis (OA) is a leading cause of disability among older adults across the world. This common degenerative joint disease may result in pain, decreased function, and reduced quality of life. Treatments used to alleviate symptoms associated with knee OA range from exercise regimens, pharmacological interventions, to outpatient surgical procedures. IA injections of mesenchymal stem cells (MSC) have shown promising results to manage knee OA and associated symptoms. For example, a recent randomized control trial conducted by Garza et al. (2020) demonstrated that MSC injection reduces knee OA symptoms and pain intensity for at least 12 months after the intervention. Other trials, however, have reported no effect of MSC injections for chronic knee pain associated with OA. As a result of conflicting evidence in the current literature, a systematic review of randomized trials on MSC injections for knee OA is necessary.

Knee osteoarthritis (OA) is a leading cause of disability among older adults across the world. This common degenerative joint disease results in pain, reduced function, and low quality of life. Treatments used to alleviate symptoms associated with knee OA range from exercise regimens, pharmacological interventions, to outpatient surgical procedures. IA injections of mesenchymal stem cells (MSC) have shown promising results to manage knee OA and associated symptoms. For example, a recent randomized control trial conducted by Garza et al. (2020) demonstrated that MSC injection reduces knee OA symptoms and pain intensity for at least 12 months after the intervention. Other trials, however, have reported no effect of MSC injections for chronic knee pain associated with OA. As a result of conflicting evidence in the current literature, a systematic review of randomized trials on MSC injections for knee OA is necessary.

To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction.We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality.We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis.The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding.Center for Open Science ( https://osf.io/ky2gr ); registered 10 November 2020.RéSUMé: OBJECTIF: Comparer l’efficacité relative des thérapies de soutien (inotropes, vasopresseurs et assistance circulatoire mécanique [ACM]) chez les patients adultes atteints d’un choc cardiogénique compliquant un infarctus aigu du myocarde.Nous avons réalisé une revue systématique et une méta-analyse en réseau et effectué des recherches dans six bases de données depuis leur création jusqu’à décembre 2021 pour en tirer les études randomisées contrôlées (ERC). Nous avons évalué les inotropes, les vasopresseurs et les ACM dans des réseaux distincts. Deux réviseurs ont effectué la recherche, l’évaluation du texte intégral et l’extraction. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des résultats. Le critère d’évaluation d’intérêt était la mortalité toutes causes confondues à 30 jours.Nous avons inclus 17 ERC. Parmi les inotropes (sept ERC, 1145 patients), le lévosimendan a probablement réduit la mortalité par rapport au placebo (rapport de cotes [RC], 0,53; intervalle de confiance [IC] à 95 %, 0,33 à 0,87; certitude modérée), mais principalement en cas de choc de sévérité moindre. La milrinone (RC, 0,52; IC 95 %, 0,19 à 1,39; certitude faible) et la dobutamine (RC, 0,67, IC 95 %, 0,30 à 1,49; certitude faible) pourraient n’avoir aucun effet sur la mortalité par rapport au placebo. En ce qui concerne l’ACM (huit ERC, 856 patients), il pourrait n’y avoir aucun effet sur la mortalité avec un ballon intra-aortique (IABP) (RC, 0,94; IC 95 %, 0,69 à 1,28; certitude faible) ou un ACM percutané (ACMp) (RC, 0,96; IC 95 %, 0,47 à 1,98; certitude faible), par rapport à une stratégie sans ACM. L’utilisation d’un ballon intra-aortique était associée à moins de saignements majeurs par rapport à une ACMp. Nous n’avons trouvé que deux ERC évaluant les vasopresseurs, ce qui n’a pas fourni suffisamment de données pour la méta-analyse.Les résultats de cette revue systématique et de la méta-analyse en réseau indiquent que le lévosimendan réduit la mortalité par rapport au placebo chez les patients présentant un choc cardiogénique de faible gravité. Le ballon intra-aortique et l’ACMp n’ont eu aucun effet sur la mortalité par rapport à une stratégie sans ACM, mais l’ACMp était associée à des taux plus élevés de saignements majeurs. ENREGISTREMENT DE L’éTUDE: Center for Open Science ( https://osf.io/ky2gr ); enregistrée le 10 novembre 2020.

TITLE: Benefits and harms of replacement therapy with Alpha 1 Antitrypsin in patients with documented enzyme deficiency and Chronic Obstructive Pulmonary Disease: A systematic review and network meta-analysis. OBJECTIVE: To identify the available scientific evidence regarding the benefits and safety of replacement therapy with Alpha 1-Antitrypsin compared with endobronchial or surgical management for reduction of lung volume, lung transplantation, standard of care for chronic obstructive pulmonary disease, and placebo or control/no treatment in patients with documented enzyme deficiency, presenting with chronic obstructive pulmonary disease. METHODS: A systematic review and meta-analysis was conducted. MEDLINE-PubMed (via Ovid), EMBASE (via Elsevier), LILACS and the Cochrane Library of Controlled Register of Trials (CENTRAL) were assessed for randomized controlled trials (RCT); cluster, factorial, parallel-design and cross-over designs were included, from inception to May of 2021. Any restrictions regarding language, setting, report status or date of publication were included. Non-published articles in clinicaltrials.gov, and grey literature in ProQuest were also considered. Trials studying adult patients with documented Alpha-1 Antitrypsin Deficiency (A1AD) and diagnosed with Chronic Obstructive Pulmonary Disease (COPD), treated with A1A augmentation therapy or other standard care interventions (according to current guidelines for COPD treatment1) such as inhaled corticosteroids, phosphodiesterase 4 inhibitors, antibiotics, inhaled anticholinergic or beta 2 agents, anti-oxidant, lung volume reduction interventions or lung transplant were included. Patient important outcomes as well as surrogate outcomes were assessed. Risk of bias (ROB) for each included trial was independently assessed, using the Cochrane Risk of Bias tool (ROB2). DerSimonian-Laird random-effects models for all pairwise comparisons were used. Heterogeneity was calculated with Q statistic ABSTRACT TITLE: Benefits and harms of replacement therapy with Alpha 1 Antitrypsin in patients with documented enzyme deficiency and Chronic Obstructive Pulmonary Disease: A systematic review and network meta-analysis. OBJECTIVE: To identify the available scientific evidence regarding the benefits and safety of replacement therapy with Alpha 1-Antitrypsin compared with endobronchial or surgical management for reduction of lung volume, lung transplantation, standard of care for chronic obstructive pulmonary disease, and placebo or control/no treatment in patients with documented enzyme deficiency, presenting with chronic obstructive pulmonary disease. METHODS: A systematic review and meta-analysis was conducted. MEDLINE-PubMed (via Ovid), EMBASE (via Elsevier), LILACS and the Cochrane Library of Controlled Register of Trials (CENTRAL) were assessed for randomized controlled trials (RCT); cluster, factorial, parallel-design and cross-over designs were included, from inception to May of 2021. Any restrictions regarding language, setting, report status or date of publication were included. Non-published articles in clinicaltrials.gov, and grey literature in ProQuest were also considered. Trials studying adult patients with documented Alpha-1 Antitrypsin Deficiency (A1AD) and diagnosed with Chronic Obstructive Pulmonary Disease (COPD), treated with A1A augmentation therapy or other standard care interventions (according to current guidelines for COPD treatment1) such as inhaled corticosteroids, phosphodiesterase 4 inhibitors, antibiotics, inhaled anticholinergic or beta 2 agents, anti-oxidant, lung volume reduction interventions or lung transplant were included. Patient important outcomes as well as surrogate outcomes were assessed. Risk of bias (ROB) for each included trial was independently assessed, using the Cochrane Risk of Bias tool (ROB2). DerSimonian-Laird random-effects models for all pairwise comparisons were used. Heterogeneity was calculated with Q statistic Magíster en Epidemiología Maestría

Summary of searches and search strategy for POD IPDMA

Additional file 1. PRISMA-P 2015 Checklist.

Additional file 2. Search strategy and summary of searches.

Supplemental Digital Content is available in the text, Background: Opioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects. Methods: We will conduct a network meta-analysis (NMA) of randomized controlled trials evaluating opioids for CNCP. We will acquire eligible studies through systematic searches of EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, and the Cochrane Central Registry of Controlled Trials (CENTRAL). Eligible studies will have randomly allocated adult CNCP patients to an oral or transdermal opioid versus another type of opioid (or formulation) or placebo, and follow patients for ≥ 4 weeks. We will collect outcome data for pain intensity, physical function, nausea, vomiting, and constipation. Pairs of reviewers will, independently and in duplicate, abstract data from eligible trials and assess risk of bias using a modified Cochrane tool. We will assess coherence of our networks through both a global test, and by comparing direct and indirect evidence for each comparison with node-splitting. Results: Using a frequentist approach, we will conduct random effects multiple treatment meta-analysis to establish treatment effects of individual opioids for each outcome. The certainty of evidence for pooled treatment effects will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We will categorize interventions from most to least effective based on the effect estimates obtained from NMAs and their associated certainty of evidence, as follows: superior to both placebo and alternatives; superior to placebo, but inferior to alternatives; and no better than placebo. Conclusion: This NMA will determine the relative effectiveness and adverse effects of individual opioids among patients with CNCP. Our results will help inform the appropriateness of assuming similar beneficial and adverse effects of varying opioid formulations. Systematic review registration: This systematic review is registered with Prospective Register of Systematic Reviews, an international prospective register of systematic reviews (registration no.: CRD42018110331), available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=110331.

The relationship between human health and nutrition is complex and limited widely accepted guidance on proper methods of evidence synthesis is available for nutritional issues. While concepts and methods of evidence synthesis in pharmacological treatments can be mostly applied to nutritional interventions, characteristics unique to the nutrition- and dietetics-related topics can lead to distinct challenges that may not be encountered in evidence synthesis of traditional medical interventions. In addition to traditional methods for pooling the results, state-of-the-art methodologies such as GRADE or network meta-analysis, while being widely used in many medical fields, their use in the field of nutrition and food science is surprisingly rare. This thesis begins with the assessment of methodological quality of available public health guidelines on sugar intake to determine the extent to which nutritional guidelines follow currently available guidance in evidence synthesis and making practice recommendations. Subsequently, we present two examples of proper implementation of evidence synthesis methods in standard pairwise meta-analysis and indirect treatment comparison and handling of relevant challenges including applications of GRADE approach. Further, this thesis presents a network meta-analysis in the field of nutrition and child health in which the challenges of conducting multiple treatment comparison are tackled and a new approach for presenting and making conclusion from network meta-analysis results is proposed. Thesis Doctor of Philosophy (PhD)

Hang Cheng,1 Jeffrey W Clymer,1 Rana A Qadeer,2 Nicole Ferko,2 Behnam Sadeghirad,2 Chris G Cameron,2 Joseph F Amaral1 1Ethicon Inc, Cincinnati, OH, USA; 2Cornerstone Research Group, Burlington, ON, Canada Background: As compared to conventional techniques, recent meta-analyses have reported cost savings with Harmonic devices; however, only in thyroidectomy. Thus, the aim of this study was to evaluate the costs associated with Harmonic devices versus conventional techniques across a range of surgical procedures. Methods: A systematic search of MEDLINE, EMBASE, and Cochrane Library was conducted from inception to October 01, 2016 without language restrictions to identify randomized controlled trials comparing Harmonic devices to conventional techniques and reporting procedure costs (operating time plus operating equipment/consumables/device costs). Costs were pooled using the ratio of geometric means, and a random effects model was applied. Sensitivity analyses varying statistical methods, number of included studies, and cost outcomes were completed to test the robustness of the results. Results: Thirteen studies met the inclusion criteria. A total of 561 and 540 participants had procedures performed with Harmonic devices and conventional methods, respectively, with procedures including gastrectomy, thyroidectomy, colectomy, cholecystectomy, Nissen fundoplication, and pancreaticoduodenectomy. As compared to conventional methods, Harmonic devices reduced total procedure costs by 8.7% (p=0.029), resulting in an absolute reduction of US$227.77 from mean conventional technique costs, derived primarily from a reduction in operating time costs. When operating time costs, excluding operating equipment/consumables/device costs, were analyzed, costs were reduced by $544 per procedure with the use of Harmonic devices. The results from all sensitivity analyses demonstrated cost reductions with Harmonic devices. Conclusion: This systematic review and meta-analysis showed that despite a higher device cost, Harmonic devices provide a statistically significant reduction in procedure costs, derived primarily from a reduction in operating time costs, across surgical procedures. In addition to functionality benefits, Harmonic devices may represent a potentially cost saving method to reduce overall hospital resource use. Future research should focus on potential costs and benefits from use of Harmonic devices in procedures not covered here. Keywords: Harmonic, ultrasonic, meta-analysis, costs, surgery, efficiency, operating time

Overview of eligible RCTs not included in systematic reviews. (DOCX 28Â kb)

Overview of eligible RCTs not included in systematic reviews. (DOCX 28Â kb)

Objectives: To provide a perspective on the current practice of randomized clinical trials (RCTs) of diagnostic strategies focusing on patient-important outcomes. Study Design and Setting: We conducted a comprehensive search of MEDLINE and included RCTs published in full-text reports that evaluated alternative diagnostic strategies. Results: Of 56,912 unique citations, we sampled 7,500 and included 103 eligible RCTs, therefore suggesting that MEDLINE includes approximately 781 diagnostic RCTs. The 103 eligible trials reported on: mortality (n = 41; 39.8%); morbidities (n = 63; 61.2%); symptoms/quality of life/functional status (n = 14; 13.6%); and on composite end points (n = 10; 9.7%). Of the studies that reported statistically significant results (n = 12; 11.6%), we judged 7 (58.3%) as at low risk of bias with respect to missing outcome data and 4 (33.3%) as at low risk of bias regarding blinding. Of the 41 RCTs that reported on mortality, only one (2.4%) reported statistically significant results. Of 63 RCTs addressing morbidity outcomes, 11 (17.5%) reported statistically significant results, all of which reported relative effects of greater than 20%. Conclusion: RCTs of diagnostic tests are not uncommon, and sometimes suggest benefits on patient-important outcomes but often suffer from limitations in sample size and conduct. (C) 2017 Elsevier Inc. All rights reserved.

Introduction Anemia, particularly Iron Deficiency Anemia (IDA), is the most common hematological disorder during pregnancy with considerable complications in both mothers and fetuses. The estimation of anemia prevalence is an important step for health policy makers. Despite being considered a hot topic in epidemiological studies in Iran for the last twenty years, lack of a comprehensive overview on the findings encouraged the authors to carry out this study. Materials and Methods All published papers in main national and international databases were systematically searched for some specific keywords to find the related studies between the years 1993 and 2007. All published studies which had reported the prevalence of anemia were included in the study except studies on refugees, patients undergoing hemodialysis, patients with thalassemia or cancer or other selective sub-populations. Two trained reviewers independently assessed the inclusion/exclusion criteria and the quality of the selected papers, summarized them and eventually analyzed the data. Results Ten eligible papers including 11,037 participants were entered into the analysis. The maximum and minimum reported prevalence rates of anemia during pregnancy were 4.3% and 21.5%, respectively. The overall estimate of anemia prevalence in Iranian pregnant women was 13.6 (95% CI: 8.3 - 18.9). Excluding the only out-layer from the meta-analysis, the overall estimated prevalence was 12.4% (95% CI: 9.6% - 17.9%). Conclusion The prevalence of anemia in Iranian women during pregnancy is considerably lower than that of most EMRO countries or the one reported by WHO for Iran (> 40%) which had been performed on a small group 16 years ago. The lower prevalence rate of anemia in pregnant women versus the regional rates could be due to the improvements of the national health system and prenatal programs in recent years.

OBJECTIVETo determine whether probiotic prophylaxes reduce the odds ofClostridium difficileinfection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol2018;771–781