Quality and credibility of clinical practice guidelines recommendations for the management of neonatal hypoglycemia. A protocol for a systematic review and recommendations' synthesis.

IntroductionHypoglycemia is one of the most frequent metabolic conditions in neonates. Clinical practice guidelines (CPGs) influence clinical practice as high-quality CPGs facilitate the use of evidence in practice. This proposed study aims to systematically identify and appraise CPGs and CPG recommendations (CPGRs) for treating neonatal hypoglycemia (NH).Methods and analysisWe will conduct searches in MEDLINE, EMBASE, CINAHL, Cochrane Library, LILACS (Latin American & Caribbean Health Sciences Literature), and Epistemonikos. Authors will search CPGs-specific databases and grey literature. Two reviewers will independently perform the titles and abstract screening, full-text review, and data extraction. Two appraisers will assess the quality of the CPGs and their recommendations using AGREE II (Appraisal of Guidelines Research and Evaluation) and AGREE-REX (Appraisal of Guidelines Research and Evaluation-Recommendations Excellence) instruments. Scores of ≥ 60% in the rigour of development domain will be considered for defining high-quality with AGREE II tool. CPGRs with scores >60% in the three domains will be used to determine high quality with the AGREE REX tool. We will perform a synthesis of the CPGRs to identify the consistency among the CPGRs and the methodological quality of primary studies that support them.Ethics and disseminationThe results will help us to identify the methodological and quality gaps in the existing CPGs for the treatment of NH. Our findings will be submitted to peer-review journals and presented at academic conferences. Based on the study design, approval from the institutional ethics board is not required for this project.Trial registrationsSystematic Review Registration Number (PROSPERO): CRD 42021239921

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Guidelines for Feeding Very Low Birth Weight Infants

Despite the fact that feeding a very low birth weight (VLBW) neonate is a fundamental and inevitable part of its management, this is a field which is beset with controversies. Optimal nutrition improves growth and neurological outcomes, and reduces the incidence of sepsis and possibly even retinopathy of prematurity. There is a great deal of heterogeneity of practice among neonatologists and pediatricians regarding feeding VLBW infants. A working group on feeding guidelines for VLBW infants was constituted in McMaster University, Canada. The group listed a number of important questions that had to be answered with respect to feeding VLBW infants, systematically reviewed the literature, critically appraised the level of evidence, and generated a comprehensive set of guidelines. These guidelines form the basis of this state-of-art review. The review touches upon trophic feeding, nutritional feeding, fortification, feeding in special circumstances, assessment of feed tolerance, and management of gastric residuals, gastro-esophageal reflux, and glycerin enemas

Comparative effectiveness of prophylactic therapies for necrotizing enterocolitis in preterm infants: Protocol for a network meta-analysis of randomized trials

Necrotizing enterocolitis (NEC) is a common and devastating disease with high morbidity and mortality in premature infants. Current literature on the prevention of NEC has limitations including lack of direct and indirect comparisons of available therapies. We will search MEDLINE, EMBASE, Science Citation Index Expanded, Social Sciences Citation Index, CINAHL, Scopus, ProQuest Dissertations and Theses database, and grey literature sources to identify eligible trials evaluating NEC preventive therapies. Eligible studies will (1) enroll preterm (gestational age <37 weeks) and/or low birth weight (birth weight <2500 g) infants, (2) randomize infants to any preventive intervention or a placebo, or alternative active or nonactive intervention. Our outcomes of interest are severe NEC (stage II or more, based on Bell's criteria), all-cause mortality, NEC-related mortality, late-onset sepsis, duration of hospitalization, weight gain, time to establish full enteral feeds, and treatment-related adverse events. Two reviewers will independently screen trials for eligibility, assess risk of bias, and extract data. All discrepancies will be resolved by discussion. We will specify a priori explanations for heterogeneity between studies. For available comparisons between treatment and no treatment, and direct comparisons of treatments, we will conduct conventional meta-analysis using a random effects model. We will conduct a network meta-analysis using a random effects model within the Bayesian framework using Markov chain Monte Carlo methods to assess relative effects of eligible interventions. We will assess the certainty in direct, indirect, and network estimates using the Grading of Recommendations Assessment, Development and Evaluation approach. Ethics and Dissemination: We will disseminate our findings through a peer-reviewed publication and conference presentations

Intensive versus less-intensive antileukemic therapy in older adults with acute myeloid leukemia: A systematic review.

To compare the effectiveness and safety of intensive antileukemic therapy to less-intensive therapy in older adults with acute myeloid leukemia (AML) and intermediate or adverse cytogenetics, we searched the literature in Medline, Embase, and CENTRAL to identify relevant studies through July 2020. We reported the pooled hazard ratios (HRs), risk ratios (RRs), mean difference (MD) and their 95% confidence intervals (CIs) using random-effects meta-analyses and the certainty of evidence using the GRADE approach. Two randomized trials enrolling 529 patients and 23 observational studies enrolling 7296 patients proved eligible. The most common intensive interventions included cytarabine-based intensive chemotherapy, combination of cytarabine and anthracycline, or daunorubicin/idarubicin, and cytarabine plus idarubicin. The most common less-intensive therapies included low-dose cytarabine alone, or combined with clofarabine, azacitidine, and hypomethylating agent-based chemotherapy. Low certainty evidence suggests that patients who receive intensive versus less-intensive therapy may experience longer survival (HR 0.87; 95% CI, 0.76-0.99), a higher probability of receiving allogeneic hematopoietic stem cell transplantation (RR 6.14; 95% CI, 4.03-9.35), fewer episodes of pneumonia (RR, 0.25; 95% CI, 0.06-0.98), but a greater number of severe, treatment-emergent adverse events (RR, 1.34; 95% CI, 1.03-1.75), and a longer duration of intensive care unit hospitalization (MD, 6.84 days longer; 95% CI, 3.44 days longer to 10.24 days longer, very low certainty evidence). Low certainty evidence due to confounding in observational studies suggest superior overall survival without substantial treatment-emergent adverse effect of intensive antileukemic therapy over less-intensive therapy in older adults with AML who are candidates for intensive antileukemic therapy

Outcomes of long-term von Willebrand factor prophylaxis use in von Willebrand disease: A systematic literature review

Background: Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long-term prophylaxis. Aim: Systematically summarize the evidence on the clinical outcomes of secondary long-term prophylaxis in patients with VWD and severe recurrent bleedings. Methods: We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long-term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non-Randomized Studies of interventions (ROBINS-I) tool to assess the quality of the included studies. We conducted random-effects meta-analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR],.24; 95% confidence interval [CI],.17–.35; low certainty evidence), and of epistaxis (RR,.38; 95%CI,.21–.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI.12–59.57; low certainty). Evidence from four before-and-after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR.34; 95%CI,.25–.46; very low certainty evidence). Conclusion: VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits

Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at .0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of .0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures