A Systematic Literature Review of the Natural History of Respiratory, Swallowing, Feeding, and Speech Functions in Spinal Muscular Atrophy (SMA).

Background: Respiratory and bulbar dysfunctions (including swallowing, feeding, and speech functions) are key symptoms of spinal muscular atrophy (SMA), especially in its most severe forms. Demonstrating the long-term efficacy of disease-modifying therapies (DMTs) necessitates an understanding of SMA natural history.

Objective: This study summarizes published natural history data on respiratory, swallowing, feeding, and speech functions in patients with SMA not receiving DMTs.

Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis.

Purpose: Semaglutide has demonstrated safe and effective weight loss for overweight and obesity, including participants with concomitant type 2 diabetes mellitus (T2DM), in randomized placebo-controlled trials (RCTs). We conducted a systematic literature review (SLR) and network meta-analyses (NMA) to compare weekly semaglutide 2.4 mg with pharmacological comparators for weight management in overweight or obesity.

Efficacy and safety of VNS therapy or continued medication management for treatment of adults with drug-resistant epilepsy: systematic review and meta-analysis.

Vagus nerve stimulation (VNS) Therapy® is an adjunctive neurostimulation treatment for people with drug-resistant epilepsy (DRE) who are unwilling to undergo resective surgery, have had unsuccessful surgery or are unsuitable for surgery. A systematic review and meta-analysis were conducted to determine the treatment effects of VNS Therapy as an adjunct to anti-seizure medications (ASMs) for the management of adults with DRE. A literature search was performed in August 2020 of the Medline®, Medline® Epub Ahead of Print, Embase, and the Cochrane library databases.

Meta-Analysis Comparing Apixaban Versus Rivaroxaban for Management of Patients With Nonvalvular Atrial Fibrillation.

To compare the efficacy and safety of apixaban and rivaroxaban for the prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) by way of a meta-analysis informed by real-world evidence. Systematic review and meta-analysis of observational studies including patients with NVAF on apixaban and rivaroxaban, which reported stroke/systemic embolism and/or major bleeding. Prospero registration number: CRD42021251719.

Automated compounding technology and workflow solutions for the preparation of chemotherapy: a systematic review.

Objectives: The current systematic review (SR) was undertaken to summarise the published literature reporting the clinical and economic value of automation for chemotherapy preparation management to include compounding workflow software and robotic compounding systems.

Methods: Literature searches were conducted in MEDLINE, Embase and the Cochrane Library on 16 November 2017 to identify publications investigating chemotherapy compounding workflow software solutions used in a hospital pharmacy for the preparation of chemotherapy.

Results: 5175 publications were screened by title and abstract and 18 of 72 full publications screened were included.

Automation of in-hospital pharmacy dispensing: a systematic review.

Objectives: The current systematic review (SR) was undertaken to identify and summarise the published literature reporting on the clinical and economic value of automated in-hospital pharmacy services with a primary focus on systems supporting the dispensing of medicines.

Methods: Literature searches were conducted in MEDLINE, Embase and the Cochrane Library on 17 December 2017 to identify English-language publications investigating any automated dispensing systems (ADSs) in the inpatient setting to include central pharmacy and ward-based systems.

Results: 4320 publications were screened by title and abstract and 45 of 175 full publications screened were included.

Systematic review of neurotrophic tropomyosin-related kinase inhibition as a tumor-agnostic management strategy.

To conduct a systematic review and meta-analysis feasibility of clinical, quality of life and economic evidence for neurotrophic tropomyosin-related receptor tyrosine kinases () inhibitors in patients with gene fusion-positive tumors. Databases were searched for studies on inhibitors in adult and pediatric patients. 27 publications reported clinical data for seven interventions.

Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine.

D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase. By a combination of structural, chemical and mechanistic studies here we show that the inhibition of D-alanine:D-alanine ligase by the antibiotic D-cycloserine proceeds via a distinct phosphorylated form of the drug. This mechanistic insight reveals a bimodal mechanism of action for a single antibiotic on different enzyme targets and has significance for the design of future inhibitor molecules based on this chemical structure.

Tyrosine kinase inhibitor combination therapy in first-line treatment of non-small-cell lung cancer: systematic review and network meta-analysis.

Introduction: The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with + mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a promising approach to prolonging remission.

Three-dimensional evidence network plot system: covariate imbalances and effects in network meta-analysis explored using a new software tool.

Objectives: The aim of the study was to develop the three-dimensional (3D) evidence network plot system-a novel web-based interactive 3D tool to facilitate the visualization and exploration of covariate distributions and imbalances across evidence networks for network meta-analysis (NMA).

Study Design And Setting: We developed the 3D evidence network plot system within an AngularJS environment using a third party JavaScript library (Three.js) to create the 3D element of the application.

A Systematic Review of Methods for Handling Missing Variance Data in Meta-Analyses of Interventions in Type 2 Diabetes Mellitus.

Aims: Meta-analysis is of critical importance to decision makers to assess the comparative efficacy and safety of interventions and is integral to health technology assessment. A major problem for the meta-analysis of continuous outcomes is that associated variance data are not consistently reported in trial publications. The omission of studies from a meta-analysis due to incomplete reporting may introduce bias.

Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

Background: Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates.

Review of the Reporting of Survival Analyses within Randomised Controlled Trials and the Implications for Meta-Analysis.

Background: Meta-analysis is a growing approach to evidence synthesis and network meta-analysis in particular represents an important and developing method within Health Technology Assessment (HTA). Meta-analysis of survival data is usually performed using the individual summary statistic-the hazard ratio (HR) from each randomised controlled trial (RCT).

Objectives: The objectives of this study are to: (i) review the methods and reporting of survival analyses in oncology RCTs; and (ii) assess the suitability and relevance of survival data reported in RCTs for inclusion into meta-analysis.

Network Meta-Analysis Comparing Overall Survival for Fulvestrant 500 mg Versus Alternative Therapies for Treatment of Postmenopausal, Estrogen Receptor-Positive Advanced Breast Cancer Following Failure on Prior Endocrine Therapy.

Background: We conducted a review of randomized trials to compare the overall survival (OS) with fulvestrant 500 mg versus alternative treatment for estrogen receptor-positive advanced breast cancer following endocrine therapy failure.

Materials And Methods: Hazard ratios (HRs) were obtained by modeling OS data with the Weibull distribution. A fixed-effect Bayesian network meta-analysis was conducted.

Treatments for chronic myeloid leukemia: a qualitative systematic review.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI) imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib) in the first-, second-, and third-line settings.

Crystallization and preliminary X-ray analysis of a D-alanyl-D-alanine ligase (EcDdlB) from Escherichia coli.

A recombinant form of Escherichia coli DdlB (EcDdlB) has been prepared and cocrystallized with ADP and D-alanyl-D-alanine to represent the ternary complex of EcDdlB. Furthermore, EcDdlB has been cocrystallized under the same conditions with the ligands ATP and D-alanyl-D-alanine, representing the product-inhibited complex. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 53.

Design and synthesis of new hydroxyethylamines as inhibitors of D-alanyl-D-lactate ligase (VanA) and D-alanyl-D-alanine ligase (DdlB).

The Van enzymes are ATP-dependant ligases responsible for resistance to vancomycin in Staphylococcus aureus and Enteroccoccus species. The de novo molecular design programme SPROUT was used in conjunction with the X-ray crystal structure of Enterococcus faeciumd-alanyl-d-lactate ligase (VanA) to design new putative inhibitors based on a hydroxyethylamine template. The two best ranked structures were selected and efficient syntheses developed.