Application of causal inference methods in individual-participant data meta-analyses in medicine: addressing data handling and reporting gaps with new proposed reporting guidelines.

Observational data provide invaluable real-world information in medicine, but certain methodological considerations are required to derive causal estimates. In this systematic review, we evaluated the methodology and reporting quality of individual-level patient data meta-analyses (IPD-MAs) conducted with non-randomized exposures, published in 2009, 2014, and 2019 that sought to estimate a causal relationship in medicine. We screened over 16,000 titles and abstracts, reviewed 45 full-text articles out of the 167 deemed potentially eligible, and included 29 into the analysis.

Intranasal delivery of OMVs decorated with antigens induces specific local and systemic immune responses.

is an obligate intracellular pathogen responsible for the most prevalent bacterial sexually transmitted disease globally. The high prevalence of chlamydial infections underscores the urgent need for licensed and effective vaccines to prevent transmission in populations. Bacterial outer membrane vesicles (OMVs) have emerged as promising mucosal vaccine carriers due to their inherent adjuvant properties and the ability to display heterologous antigens.

A pan-influenza monoclonal antibody neutralizes H5 strains and prophylactically protects through intranasal administration.

Avian A(H5N1) influenza virus poses an elevated zoonotic threat to humans, and no pharmacological products are currently registered for fast-acting pre-exposure protection in case of spillover leading to a pandemic. Here, we show that an epitope on the stem domain of H5 hemagglutinin is highly conserved and that the human monoclonal antibody CR9114, targeting that epitope, potently neutralizes all pseudotyped H5 viruses tested, even in the rare case of substitutions in its epitope. Further, intranasal administration of CR9114 fully protects mice against A(H5N1) infection at low dosages, irrespective of pre-existing immunity conferred by the quadrivalent seasonal influenza vaccine.

Sialic acid-modified der p 2 allergen exerts immunomodulatory effects on human PBMCs.

Background: House dust mite extract-based allergen immunotherapy (AIT) to treat house dust mite allergy is substantially effective but still presents some safety and efficacy concerns that warrant improvement. Several major allergen-based approaches to increase safety and efficacy of AIT have been proposed. One of them is the use of the group 2 allergen, Der p 2.

Heterologous Display of PmpD Passenger at the Surface of OMVs.

is the bacterial pathogen that causes most cases of sexually transmitted diseases annually. To combat the global spread of asymptomatic infection, development of effective (mucosal) vaccines that offer both systemic and local immune responses is considered a high priority. In this study, we explored the expression of full-length (FL) PmpD, as well as truncated PmpD passenger constructs fused to a "display" autotransporter (AT) hemoglobin protease (HbpD) and studied their inclusion into outer membrane vesicles (OMVs) of and Typhimurium.

Fragility of statistically significant findings from randomized trials in comparing laparoscopic versus robotic abdominopelvic surgeries.

Background: Utility of robotic over laparoscopic approach has been an area of debate across all surgical specialties over the past decade. The fragility index (FI) is a metric that evaluates the frailty of randomized controlled trials (RCTs) findings by altering the status of patients from an event to non-event until significance is lost. This study aims to evaluate the robustness of RCTs comparing laparoscopic and robotic abdominopelvic surgeries through the FI.

The Effect of Chronic Kidney Disease or End-stage Kidney Disease on Perioperative Outcomes and Healthcare Utilization in Patients Undergoing Bariatric Surgery.

Background: As chronic kidney disease (CKD) has a higher prevalence in patients with obesity, there is an increasing need to understand the safety of bariatric surgery for patients with advanced CKD. This study determined if short-term bariatric surgical outcomes and healthcare utilization differ in patients with advanced CKD.

Methods: A retrospective analysis of the Healthcare Cost and Utilization Project National Inpatient Sample (NIS) was performed.

Differences in in-hospital outcomes and healthcare utilization for laparoscopic versus open approach for emergency inguinal hernia repair: a nationwide analysis.

Purpose: There has been a growing debate of whether laparoscopic or open surgical techniques are superior for inguinal hernia repair. For incarcerated and strangulated inguinal hernias, the laparoscopic approach remains controversial. This study aims to be the first nationwide analysis to compare clinical and healthcare utilization outcomes between laparoscopic and open inguinal hernia repair in an emergency setting.

Hypnotics Use Is Associated with Elevated Incident Atrial Fibrillation: A Propensity-Score Matched Analysis of Cohort Study.

We aimed to investigate the association between either or both of benzodiazepines (BZDs) and non-BZDs and the incidence of atrial fibrillation (AF) in the Taiwan National Health Insurance Database. The participants with at least two prescriptions of BZDs and/or non-BZDs were identified as hypnotics users, whereas those without any prescription of hypnotics were non-hypnotics users. The hypnotics and non-hypnotics cohorts were 1:1 matched on their propensity scores.

Update of the CHIP (CT in Head Injury Patients) decision rule for patients with minor head injury based on a multicenter consecutive case series.

Objective: To update the existing CHIP (CT in Head Injury Patients) decision rule for detection of (intra)cranial findings in adult patients following minor head injury (MHI).

Methods: The study is a prospective multicenter cohort study in the Netherlands. Consecutive MHI patients of 16 years and older were included.

Overexpression of the Bam Complex Improves the Production of MOMP in the Outer Membrane.

A licensed vaccine is not yet available. Recombinant major outer membrane protein (-MOMP), the most abundant constituent of the chlamydial outer membrane complex, is considered the most attractive candidate for subunit-based vaccine formulations. Unfortunately, -MOMP is difficult to express in its native structure in the outer membrane (OM).

Systematic Review Reveals Lack of Causal Methodology Applied to Pooled Longitudinal Observational Infectious Disease Studies.

Objectives: Among ID studies seeking to make causal inferences and pooling individual-level longitudinal data from multiple infectious disease cohorts, we sought to assess what methods are being used, how those methods are being reported, and whether these factors have changed over time.

Study Design And Setting: Systematic review of longitudinal observational infectious disease studies pooling individual-level patient data from 2+ studies published in English in 2009, 2014, or 2019. This systematic review protocol is registered with PROSPERO (CRD42020204104).

Short-Term Pre-Operative Protein Caloric Restriction in Elective Vascular Surgery Patients: A Randomized Clinical Trial.

(1) Background: Vascular surgery operations are hampered by high failure rates and frequent occurrence of peri-operative cardiovascular complications. In pre-clinical studies, pre-operative restriction of proteins and/or calories (PCR) has been shown to limit ischemia-reperfusion damage, slow intimal hyperplasia, and improve metabolic fitness. However, whether these dietary regimens are feasible and safe in the vascular surgery patient population remains unknown.

Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial.

Background: Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB.

Current trends in the application of causal inference methods to pooled longitudinal observational infectious disease studies-A protocol for a methodological systematic review.

Introduction: Pooling (or combining) and analysing observational, longitudinal data at the individual level facilitates inference through increased sample sizes, allowing for joint estimation of study- and individual-level exposure variables, and better enabling the assessment of rare exposures and diseases. Empirical studies leveraging such methods when randomization is unethical or impractical have grown in the health sciences in recent years. The adoption of so-called "causal" methods to account for both/either measured and/or unmeasured confounders is an important addition to the methodological toolkit for understanding the distribution, progression, and consequences of infectious diseases (IDs) and interventions on IDs.

IMI Prevention of Myopia and Its Progression.

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors.

Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases.

Background: Phosphorylcholine (PC) is an important pro-inflammatory damage-associated molecular pattern. Previous data have shown that natural IgM anti-PC protects against cardiovascular disease. We aimed to develop a monoclonal PC IgG antibody with anti-inflammatory and anti-atherosclerotic properties.

The Development of Swedish Military Healthcare System: Part II-Re-evaluating the Military and Civilian Healthcare Systems in Crises Through a Dialogue and Study Among Practitioners.

Introduction: Historical changes have transformed Sweden from being an offensive to a defensive and collaborative nation with national and international engagement, allowing it to finally achieve the ground for the civilian-military collaboration and the concept of a total defense healthcare. At the same time, with the decreasing number of international and interstate conflicts, and the military's involvement in national emergencies and humanitarian disaster relief, both the need and the role of the military healthcare system within the civilian society have been challenged. The recent impact of the COVID-19 in the USA and the necessity of military involvement have led health practitioners to anticipate and re-evaluate conditions that might exceed the civilian capacity of their own countries and the need to have collaboration with the military healthcare.

Predicting Progression to Advanced Age-Related Macular Degeneration from Clinical, Genetic, and Lifestyle Factors Using Machine Learning.

Purpose: Current prediction models for advanced age-related macular degeneration (AMD) are based on a restrictive set of risk factors. The objective of this study was to develop a comprehensive prediction model applying a machine learning algorithm allowing selection of the most predictive risk factors automatically.

Design: Two population-based cohort studies.

Author Correction: Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.