The biopsychosocial factors associated with development of chronic musculoskeletal pain. An umbrella review and meta-analysis of observational systematic reviews.

AIM: The aim of this umbrella review was to establish which biopsychosocial factors are associated with development of chronic musculoskeletal pain. METHODS: Ovid Medline, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PsycINFO, CINAHL, PEDro, PROSPERO, Google Scholar and grey literature were searched from database inception to 4th April 2023. Systematic reviews of observational prospective longitudinal studies, including populations with <3 months (not chronic) musculoskeletal pain, investigating biopsychosocial factors that contribute to development of chronic (>3 months) musculoskeletal pain. Two reviewers searched the literature, assessed risk of bias (Assessing the Methodological Quality of Systematic Reviews-2), and evaluated quality (Grading of Recommendations, Assessment, Development and Evaluation) to provide an overall statement on the certainty of evidence for each biopsychosocial factor. Data analysis was performed through random effects meta-analysis (including meta-analysis of meta-analyses where possible) and descriptive synthesis. RESULTS: 13 systematic reviews were included comprising 185 original research studies (n = 489,644 participants). Thirty-four biopsychosocial factors are associated with development of chronic musculoskeletal pain. Meta-analyses of odds and/or likelihood ratios were possible for 25 biopsychosocial factors. There is moderate certainty evidence that smoking (OR 1.24 [95%CI, 1.14-1.34), fear avoidance (LR+ 2.11 [95%CI, 1.59-2.8]; LR- 0.5 [95%CI, 0.35-0.71]) poorer support networks (OR 1.21 [95%CI, 1.14-1.29]), lower socioeconomic status (OR 2.0 [95%CI, 1.64-2.42]), and high levels of pain (OR 5.61 [95%CI, 3.74-8.43]) are associated with development of chronic musculoskeletal pain (all P<0.001). Remaining factors are of low or very low certainty evidence. CONCLUSIONS AND RELEVANCE: There is moderate certainty evidence that smoking, fear avoidance, poorer support networks, lower socioeconomic status, and high levels of pain are associated with development of chronic musculoskeletal pain. High risk of bias was evident in most included reviews; this highlights the need for higher quality systematic reviews.

Validation of the Scandinavian guidelines for minor and moderate head trauma in children: protocol for a pragmatic, prospective, observational, multicentre cohort study.

INTRODUCTION: Mild traumatic brain injury is common in children and it can be challenging to accurately identify those in need of urgent medical intervention. The Scandinavian guidelines for management of minor and moderate head trauma in children, the Scandinavian Neurotrauma Committee guideline 2016 (SNC16), were developed to aid in risk stratification and decision-making in Scandinavian emergency departments (EDs). This guideline has been validated externally with encouraging results, but internal validation in the intended healthcare system is warranted prior to broad clinical implementation. OBJECTIVE: We aim to validate the diagnostic accuracy of the SNC16 to predict clinically important intracranial injuries (CIII) in paediatric patients suffering from blunt head trauma, assessed in EDs in Sweden and Norway. METHODS AND ANALYSIS: This is a prospective, pragmatic, observational cohort study. Children (aged 0-17 years) with blunt head trauma, presenting with a Glasgow Coma Scale of 9-15 within 24 hours postinjury at an ED in 1 of the 16 participating hospitals, are eligible for inclusion. Included patients are assessed and managed according to the clinical management routines of each hospital. Data elements for risk stratification are collected in an electronic case report form by the examining doctor. The primary outcome is defined as CIII within 1 week of injury. Secondary outcomes of importance include traumatic CT findings, neurosurgery and 3-month outcome. Diagnostic accuracy of the SNC16 to predict endpoints will be assessed by point estimate and 95% CIs for sensitivity, specificity, likelihood ratio, negative predictive value and positive predictive value. ETHICS AND DISSEMINATION: The study is approved by the ethical board in both Sweden and Norway. Results from this validation will be published in scientific journals, and a tailored development and implementation process will follow if the SNC16 is found safe and effective. TRIAL REGISTRATION NUMBER: NCT05964764.

Evaluating patient factors, operative management and postoperative outcomes in trauma laparotomy patients worldwide: a protocol for a global observational multicentre trauma study.

INTRODUCTION: Trauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed operation. Variation likely exists in how these patients are managed and their subsequent outcomes, yet very little global data on the topic currently exists. The objective of the GOAL-Trauma study is to evaluate both patient and injury factors for those undergoing trauma laparotomy, their clinical management and postoperative outcomes. METHODS: We describe a planned prospective multicentre observational cohort study of patients undergoing trauma laparotomy. We will include patients of all ages who present to hospital with a blunt or penetrating injury and undergo a trauma laparotomy within 5 days of presentation to the treating centre. The study will collect system, patient, process and outcome data, following patients up until 30 days postoperatively (or until discharge or death, whichever is first). Our sample size calculation suggests we will need to recruit 552 patients from approximately 150 recruiting centres. DISCUSSION: The GOAL-Trauma study will provide a global snapshot of the current management and outcomes for patients undergoing a trauma laparotomy. It will also provide insight into the variation seen in the time delays for receiving care, the disease and patient factors present, and patient outcomes. For current standards of trauma care to be improved worldwide, a greater understanding of the current state of trauma laparotomy care is paramount if appropriate interventions and targets are to be identified and implemented.

Protocol for a magnetic resonance imaging study of participants in the fever RCT: Does fever control prevent brain injury in malaria?

BACKGROUND: Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy. METHODS: This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury. DISCUSSION: Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.

Protocol for a systematic review and meta-analysis on Janus kinase inhibitors in the management of vitiligo.

BACKGROUND: Vitiligo is a disease that affects people of all skin shades and can impact their quality of life. Reliable evidence on the effectiveness and adverse events associated with the recent use of Janus kinase (JAK) inhibitors to treat vitiligo is needed. This protocol for a systematic review and meta-analysis seeks to collect evidence from both randomized controlled trials (RCTs) and observational studies to determine the effectiveness and patient-centered outcomes concerning treatment with JAK inhibitors. METHODS: We will conduct a systematic review of the literature for RCTs and observational studies that used upadacitinib, ritlecitinib, brepocitinib, ifidancitinib, cerdulatinib, deglocitinib, baricitinib, tofacitinib, and ruxolitinib JAK inhibitors as treatments for vitiligo compared to placebo, no treatment, or combination therapies. We will systematically search from inception in Epistemonikos, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.gov, PsycINFO, Allied and Complementary Medicine Database, Latin American and Caribbean Health Sciences Literature, Web of Science Core Collection, relevant preprint servers, and the gray literature. Ethics approval was not sought as the protocol and systematic review will not involve human participants, but rather summarized and anonymous data from studies. Primary outcomes include quality of life, percentage repigmentation, decreased vitiligo within 1 year or more, lasting repigmentation after a 2-year follow-up, cosmetic acceptability of repigmentation and tolerability or burden of treatment, and adverse events. Secondary outcomes are patient and study characteristics. We will include full-text articles, preprints, and clinical trial data in any language and all geographic regions. For data sources unavailable in English, we will obtain translations from global collaborators via the Cochrane Engage network. We will exclude articles for which sufficient information cannot be obtained from the authors of articles and systematic reviews. At least two investigators will independently assess articles for inclusion and extract data; reliability will be assessed before subsequent selection and data extraction of remaining studies. The risk of bias and certainty of evidence with Grading of Recommendations Assessment, Development, and Evaluation guidelines will be assessed independently by at least two investigators. We will estimate treatment effects by random-effects meta-analyses and assess heterogeneity using I2. Data that cannot be included in the meta-analysis will be reported narratively using themes. DISCUSSION: The proposed systematic review and meta-analysis describe the methods for summarizing and synthesizing the evidence on the effectiveness and patient-centered outcomes concerning the treatment of vitiligo with JAK inhibitors that were recently approved for this indication. To disseminate further the results of our systematic review, we plan to present them at international conferences and meetings. Our findings will provide robust evidence to facilitate decision-making at the policy or practitioner level. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023383920.

Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis.

BACKGROUND: The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially impact a patient's quality of life, subsequently leading to the interruption or discontinuation of EGRF-TKI treatment. Clinicians, therefore, need to thoroughly assess patients to determine if they are at risk for ILD. METHODS: We searched for observational study in the following databases: MEDLINE via the PubMed, CENTRAL, and IchushiWeb. The primary outcome was risk factors for the development of ILD, while the secondary outcome was risk factors for the severity of ILD. Of the 1602 studies returned, we selected 11 for meta-analysis, performed using a random-effects model. RESULTS: Risk factors for developing ILD were sex (odds ratio (OR), 1.87; 95% confidence interval (CI), 1.08-3.22; I2 = 0%; P = 0.02), smoking history (OR, 2.13; 95% CI, 1.51-3.00; I2 = 3 4%; P = 0.0001), and history of ILD (OR = 5.95; 95% CI, 3.34-10.59; I2 = 67%; P = 0.0009). Age, previous thoracic surgery or radiotherapy, performance status, histological type of lung cancer, and treatment line were not statistically significant risk factors for ILD. Risk factors identified in one study were serum albumin level, history of nivolumab use, radiographic residual lung volume, and history of pulmonary infection. CONCLUSIONS: We identified risk factors for developing ILD in patients with non-small cell lung cancer treated with EGFR-TKIs.

Outcomes of subsequent pregnancy in women with peripartum cardiomyopathy: a systematic review and meta-analysis.

INTRODUCTION: The primary concern for women who have experienced peripartum cardiomyopathy (PPCM) is the safety of a subsequent pregnancy (SSP). To maximie decision-making, facilitate effective patient counselling, and ultimately improve maternal and fetal outcomes as a whole, it is critical to comprehend the outcomes of SSP in women who have previously experienced PPCM. This study aimed to evaluate the outcomes of SSP in women with PPCM. METHODS: Three databases (PubMed, Scopus, and ScienceDirect) were used to identify relevant studies prior to 17 October 2023. A total of 662 studies were reviewed. Following the abstract and full-text screenings, 18 observational studies were included, out of which 2 were deemed suitable for inclusion in this meta-analysis. The quality assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: This study has a total of 487 SSPs. Although recovered left ventricular (LV) function before entering SSP has the potential to be a beneficial prognostic factor, recovered LV function still has a substantial risk of relapse. The mortality rate of PPCM in an SSP ranged from 0% to 55.5%. Persistent LV dysfunction was significantly associated with an increased mortality rate (OR 13.17; 95% CI 1.54 to 112.28; p=0.02) and lower LV ejection fraction (MD -12.88; 95% CI -21.67 to -4.09; p=0.004). Diastolic and right ventricular functions remained unchanged before SSP and at follow-up. The majority of the SSP was observed alongside hypertension, while pre-eclampsia emerged as the predominant hypertensive complication in most studies. CONCLUSION: SSP increases the risk of relapse and mortality in women with a previous history of PPCM. Persistent LV dysfunction prior to the SSP has a higher mortality risk compared with recovered LV function. SSP was also associated with the worsening of LV echocardiography parameters.

Exploring vascular contributions to cognitive impairment and dementia (ENIGMA): protocol for a prospective observational study.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding the role of microvascular changes and finding markers that can predict PSCI, could be a first step towards better screening and management of PSCI. Capillary dysfunction is a pathological feature of cerebral small vessel disease and may play a role in the mechanisms underlying PSCI. Extracellular vesicles (EVs) are secreted from cells and may act as disease biomarkers. We aim to investigate the role of capillary dysfunction in PSCI and the associations between EV characteristics and cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA). METHODS: The ENIGMA study is a single-centre prospective clinical observational study conducted at Aarhus University Hospital, Denmark. Consecutive patients with AIS and TIA are included and followed for one year with follow-up visits at three and 12 months. An MRI is performed at 24 h and 12 months follow-up. EV characteristics will be characterised from blood samples drawn at 24 h and three months follow-up. Cognitive function is assessed three and 12 months after AIS and TIA using the Repeatable Battery for the Assessment of Neuropsychological Status. DISCUSSION: Using novel imaging and molecular biological techniques the ENIGMA study will provide new knowledge about the vascular contributions to cognitive decline and dementia. TRIAL REGISTRATION: The study is retrospectively registered as an ongoing observational study at ClinicalTrials.gov with the identifier NCT06257823.

Treatment of Helicobacter pylori with potassium competitive acid blockers: A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there's growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication. AIM: To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection. METHODS: This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [("Helicobacter pylori" OR "H pylori") AND ("Treatment" OR "Therapy" OR "Eradication") AND ("Vonaprazan" OR "Potassium-Competitive Acid Blocker" OR "P-CAB" OR "PCAB" OR "Revaprazan" OR "Linaprazan" OR "Soraprazan" OR "Tegoprazan")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated. RESULTS: A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively. CONCLUSION: VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Soy Product Consumption and the Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: The association between soy product consumption and cancer risk varies among studies. Therefore, this comprehensive meta-analysis of observational studies examines the association between soy product consumption and total cancer risk. METHODS: This study was conducted following the PRISMA guidelines. Up to October 2023, all eligible published studies were searched through PubMed and Web of Science databases. RESULTS: A total of 52 studies on soy product consumption were included in this meta-analysis (17 cohort studies and 35 case-control studies). High consumption of total soy products (RR: 0.69; 95% CI: 0.60, 0.80), tofu (RR: 0.78; 95% CI: 0.70, 0.86), and soymilk (RR: 0.75; 95% CI: 0.60, 0.93) were associated with reduced total cancer risk. No association was found between high consumption of fermented soy products (RR: 1.18; 95% CI: 0.95, 1.47), non-fermented soy products (RR: 0.95; 95% CI: 0.77, 1.18), soy paste (RR: 1.00; 95% CI: 0.88, 1.14), miso soup (RR: 0.99; 95% CI: 0.87, 1.12), or natto (RR: 0.96; 95% CI: 0.82, 1.11) and cancer risk. A 54 g per day increment of total soy products reduced cancer risk by 11%, a 61 g per day increment of tofu reduced cancer risk by 12%, and a 23 g per day increment of soymilk reduced cancer risk by 28%, while none of the other soy products were associated with cancer risk. CONCLUSION: Our findings suggest that high total soy product consumption, especially soymilk and tofu, is associated with lower cancer risk. More prospective cohort studies are still needed to confirm the causal relationship between soy product consumption and cancer risk.

Reconceptualizing autonomic function testing in migraine: a systematic review and meta-analysis.

BACKGROUND: Autonomic nervous system (ANS) testing has aided in our ability to evaluate autonomic dysfunction in migraine patients. We reviewed the literature in multiple databases which investigate ANS function in migraine patients and healthy subjects. METHODS: This systematic review and meta-analysis examined the respective deep breathing, Valsalva manoeuvre, orthostatic and isometric challenge results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) statements. RESULTS: Seven articles met all inclusion criteria. Fixed-effects meta-analysis showed migraine patients (n = 424), collectively, had lower interictal autonomic test results compared with healthy controls (n = 268). In detail, this was true for the standardized mean difference (g) of deep breathing (g= -0.32; 95% confidence interval (CI) -0.48, -0.16), orthostatic challenge (g= -0.28; 95% CI -0.44, -0.13) and isometric challenge (g= -0.55; 95% CI -0.71, -0.39) and for the difference of means (MD) of the Valsalva ratio (MD = -0.17; 95% CI -0.23, -0.10). CONCLUSIONS: Interictal ANS dysfunction can be identified in migraine patients when compared to healthy controls. These findings indicate the importance to evaluate ANS function in migraine patients - especially, as migraine-specific prophylactic therapies (such as anti-calcitonin gene-related peptide (CGRP) antibodies) may affect the function of the ANS.

Complications after Nuss bar removal procedure for pectus excavatum. Analysis and proposal of a safety protocol. / Complicaciones tras retirada de barra de Nuss en pectus excavatum. Análisis y propuesta de un protocolo de seguridad.

OBJECTIVE: The Nuss bar removal procedure may bring about different complications. Some are mild while others can be life-threatening. An adequate surgery setup and the fulfilment of some security steps may reduce their incidence. This study aims to analyze our experience with the complications that occurred during bar removal and our safety protocol for the prevention and management of these complications. MATERIALS AND METHODS: Observational cohort study from a retrospective chart review of all patients who underwent Nuss bar removal from November 2013 to March 2022 at a University hospital. Variables analyzed include patients' demographics; presence of comorbidities; time elapsed from bar placement to removal, and the occurrence of operative and postoperative complications. Study written under the 'PROCESS Guideline'. RESULTS: Fourty (40) patients were included in the study; 37 were male. One bar was removed in 17 patients and two in 22 patients. Median age at surgery: 17.5 years (Percentile 25-75%: 16.75-19.25). Time elapsed from placement to removal: 26 months (Percentile 25-75%: 23.75-30.25). Complications: 10 in 9 patients (22.5%); 6 Clavien-Dindo class I (67%); 2 class II (22%); 1 class IIIb, 1 class IV. The hemorrhagic complication motivated the development of a safety protocol to reduce incidence of complications. CONCLUSION: Nuss bar removal is a safe procedure with usually scant complications. Nonetheless, these may be serious sometimes. To prevent them, a protocol for a safe procedure is important.

OBJETIVO: La retirada de la barra de Nuss puede provocar diversas complicaciones, algunas leves y otras potencialmente mortales. Su incidencia puede verse reducida con una preparación quirúrgica adecuada y siguiendo ciertos pasos de seguridad. El presente estudio tiene por objeto analizar nuestra experiencia con las complicaciones acontecidas durante la retirada de la barra, así como nuestro protocolo de seguridad para la prevención y el manejo de dichas complicaciones. MATERIAL Y METODOS: Estudio de cohortes observacional llevado a cabo a partir del análisis retrospectivo de todos los pacientes sometidos a cirugía de retirada de barra de Nuss entre noviembre de 2013 y marzo de 2022 en un hospital universitario. Se analizaron las siguientes variables: demografía de los pacientes, presencia de comorbilidades, tiempo desde la colocación de la barra hasta su retirada, y complicaciones operatorias y postoperatorias. El estudio se realizó conforme a las directrices de la PROCESS Guideline. RESULTADOS: Se incluyó a 40 pacientes, 37 de ellos varones. En 17 pacientes se retiró una barra, y en 22, dos. La edad media en el momento de la cirugía fue de 17,5 años (percentil 25-75%: 16,75 - 19,25). El tiempo transcurrido desde la colocación hasta la retirada fue de 26 meses (percentil 25-75%: 23,75 - 30,25). Se registraron 10 complicaciones en 9 pacientes (22,5%), 6 de clase I según la clasificación de Clavien-Dindo (67%), 2 de clase II (22%), 1 de clase IIIb y 1 de clase IV. La complicación hemorrágica motivó la creación de un protocolo de seguridad para disminuir la incidencia de las complicaciones. CONCLUSION: La retirada de la barra de Nuss es un procedimiento seguro, habitualmente con escasas complicaciones, aunque en ocasiones pueden ser graves. Para evitarlas, es importante contar con un protocolo que garantice la seguridad.

Home versus in-centre haemodialysis for people with kidney failure.

BACKGROUND: Home haemodialysis (HHD) may be associated with important clinical, social or economic benefits. However, few randomised controlled trials (RCTs) have evaluated HHD versus in-centre HD (ICHD). The relative benefits and harms of these two HD modalities are uncertain. This is an update of a review first published in 2014. This update includes non-randomised studies of interventions (NRSIs). OBJECTIVES: To evaluate the benefits and harms of HHD versus ICHD in adults with kidney failure. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We searched MEDLINE (OVID) and EMBASE (OVID) for NRSIs. SELECTION CRITERIA: RCTs and NRSIs evaluating HHD (including community houses and self-care) compared to ICHD in adults with kidney failure were eligible. The outcomes of interest were cardiovascular death, all-cause death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, vascular access interventions, central venous catheter insertion/exchange, vascular access infection, parathyroidectomy, wait-listing for a kidney transplant, receipt of a kidney transplant, quality of life (QoL), symptoms related to dialysis therapy, fatigue, recovery time, cost-effectiveness, blood pressure, and left ventricular mass. DATA COLLECTION AND ANALYSIS: Two authors independently assessed if the studies were eligible and then extracted data. The risk of bias was assessed, and relevant outcomes were extracted. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis was performed on outcomes where there was sufficient data. MAIN RESULTS: From the 1305 records identified, a single cross-over RCT and 39 NRSIs proved eligible for inclusion. These studies were of varying design (prospective cohort, retrospective cohort, cross-sectional) and involved a widely variable number of participants (small single-centre studies to international registry analyses). Studies also varied in the treatment prescription and delivery (e.g. treatment duration, frequency, dialysis machine parameters) and participant characteristics (e.g. time on dialysis). Studies often did not describe these parameters in detail. Although the risk of bias, as assessed by the Newcastle-Ottawa Scale, was generally low for most studies, within the constraints of observational study design, studies were at risk of selection bias and residual confounding. Many study outcomes were reported in ways that did not allow direct comparison or meta-analysis. It is uncertain whether HHD, compared to ICHD, may be associated with a decrease in cardiovascular death (RR 0.92, 95% CI 0.80 to 1.07; 2 NRSIs, 30,900 participants; very low certainty evidence) or all-cause death (RR 0.80, 95% CI 0.67 to 0.95; 9 NRSIs, 58,984 patients; very low certainty evidence). It is also uncertain whether HHD may be associated with a decrease in hospitalisation rate (MD -0.50 admissions per patient-year, 95% CI -0.98 to -0.02; 2 NRSIs, 834 participants; very low certainty evidence), compared with ICHD. Compared with ICHD, it is uncertain whether HHD may be associated with receipt of kidney transplantation (RR 1.28, 95% CI 1.01 to 1.63; 6 NRSIs, 10,910 participants; very low certainty evidence) and a shorter recovery time post-dialysis (MD -2.0 hours, 95% CI -2.73 to -1.28; 2 NRSIs, 348 participants; very low certainty evidence). It remains uncertain if HHD may be associated with decreased systolic blood pressure (SBP) (MD -11.71 mm Hg, 95% CI -21.11 to -2.46; 4 NRSIs, 491 participants; very low certainty evidence) and decreased left ventricular mass index (LVMI) (MD -17.74 g/m2, 95% CI -29.60 to -5.89; 2 NRSIs, 130 participants; low certainty evidence). There was insufficient data to evaluate the relative association of HHD and ICHD with fatigue or vascular access outcomes. Patient-reported outcome measures were reported using 18 different measures across 11 studies (QoL: 6 measures; mental health: 3 measures; symptoms: 1 measure; impact and view of health: 6 measures; functional ability: 2 measures). Few studies reported the same measures, which limited the ability to perform meta-analysis or compare outcomes. It is uncertain whether HHD is more cost-effective than ICHD, both in the first (SMD -1.25, 95% CI -2.13 to -0.37; 4 NRSIs, 13,809 participants; very low certainty evidence) and second year of dialysis (SMD -1.47, 95% CI -2.72 to -0.21; 4 NRSIs, 13,809 participants; very low certainty evidence). AUTHORS' CONCLUSIONS: Based on low to very low certainty evidence, HHD, compared with ICHD, has uncertain associations or may be associated with decreased cardiovascular and all-cause death, hospitalisation rate, slower post-dialysis recovery time, and decreased SBP and LVMI. HHD has uncertain cost-effectiveness compared with ICHD in the first and second years of treatment. The majority of studies included in this review were observational and subject to potential selection bias and confounding, especially as patients treated with HHD tended to be younger with fewer comorbidities. Variation from study to study in the choice of outcomes and the way in which they were reported limited the ability to perform meta-analyses. Future research should align outcome measures and metrics with other research in the field in order to allow comparison between studies, establish outcome effects with greater certainty, and avoid research waste.

Safety of Clopidogrel vs. Ticagrelor in Dual Antiplatelet Therapy Regimens for High-Bleeding Risk Acute Coronary Syndrome Patients: A Comprehensive Meta-analysis of Adverse Outcomes.

INTRODUCTION: Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. AIM: To investigate any difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. METHODS: A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). RESULTS: We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12-1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82-1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86-2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76-1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66-1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. CONCLUSION: Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions.

Legal Services for Veterans (LSV): Protocol for evaluating the grant-based LSV initiative supporting community organizations' delivery of legal services to veterans.

BACKGROUND: 1.8 million Veterans are estimated to need legal services, such as for housing eviction prevention, discharge upgrades, and state and federal Veterans benefits. While having one's legal needs met is known to improve one's health and its social determinants, many Veterans' legal needs remain unmet. Public Law 116-315 enacted in 2021 authorizes VA to fund legal services for Veterans (LSV) by awarding grants to legal service providers including nonprofit organizations and law schools' legal assistance programs. This congressionally mandated LSV initiative will award grants to about 75 competitively selected entities providing legal services. This paper describes the protocol for evaluating the initiative. The evaluation will fulfill congressional reporting requirements, and inform continued implementation and sustainment of LSV over time. METHODS: Our protocol calls for a prospective, mixed-methods observational study with a repeated measures design, aligning to the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) and Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) frameworks. In 2023, competitively selected legal services-providing organizations will be awarded grants to implement LSV. The primary outcome will be the number of Veterans served by LSV in the 12 months after the awarding of the grant. The evaluation has three Aims. Aim 1 will focus on measuring primary and secondary LSV implementation outcomes aligned to RE-AIM. Aim 2 will apply the mixed quantitative-qualitative Matrixed Multiple Case Study method to identify patterns in implementation barriers, enablers, and other i-PARIHS-aligned factors that relate to observed outcomes. Aim 3 involves a mixed-methods economic evaluation to understand the costs and benefits of LSV implementation. DISCUSSION: The LSV initiative is a new program that VA is implementing to help Veterans who need legal assistance. To optimize ongoing and future implementation of this program, it is important to rigorously evaluate LSV's outcomes, barriers and enablers, and costs and benefits. We have outlined the protocol for such an evaluation, which will lead to recommending strategies and resource allocation for VA's LSV implementation.

Protocol on establishing a national disease registry-Swiss Pediatric Inflammatory Brain Disease Registry.

BACKGROUND: Pediatric-onset inflammatory brain diseases are a group of potentially life-threatening central nervous system disorders. Overall, pediatric-onset inflammatory brain diseases are rare and therefore difficult to study. Patient registries are well suited to study the natural history of (rare) diseases and have markedly advanced the knowledge on pediatric-onset inflammatory brain diseases in other countries. Following their example, we established a national pediatric-onset inflammatory brain disease registry in Switzerland (Swiss-Ped-IBrainD). AIMS: The Registry aims to describe epidemiology, demographics, diagnostics, management, and treatment, since these areas remain understudied in Switzerland. Additionally, we want to promote research by fostering the knowledge exchange between study centers and setting up studies such as national quality of life surveys. We further aim to facilitate the access to national and international studies for patients with a pediatric-onset inflammatory brain disease living and/or treated in Switzerland. METHODS: The Swiss-Ped-IBrainD is a multicentric, population-based, observational cohort study (IRB number: 2019-00377) collaborating with 11 neuropediatric centers in Switzerland. Patient screening, information and recruitment is mainly conducted by the local principal investigators. The data collection is organized centrally by the Executive Office of the registry. The collected data is purely observational. Medical records are the primary data source. All patients who have been diagnosed with a pediatric-onset inflammatory brain disease since 2005 are eligible. We aim to include all pediatric-onset inflammatory brain disease patients living and/or treated in Switzerland who meet the inclusion criteria. Considering existing literature and our single-center experience we anticipate 300-400 eligible patients. STATUS: Currently, all 11 neuropediatric centers have been initiated and are recruiting. As of the first of May 2023, we have identified 275 eligible participants and obtained informed consent from 101 patients and/or families. None of the informed patients and/or families have refused participation.

Statistical estimation of fatal and serious injuries saved by iRAP protocols in 74 countries.

OBJECTIVE: Road traffic crashes cause 1.19 million deaths and millions more injuries annually. The persistently high burden has drawn attention from national and international stakeholders worldwide. Unsafe road infrastructure is one of the major risk factors for traffic safety, particularly in low- and middle-income countries. METHODS: Aiming to eliminate high-risk roads in all countries, the International Road Assessment Programme (iRAP) developed a robust and evidence-based approach to support country transportation agencies. RESULTS: Thus far, the iRAP protocols have been used to collect 1.8 million kilometers of Crash Risk Mapping and 1.5 million kilometers of Star Rating and FSI estimations in 128 countries. Deploying an observational before-and-after (or pre-post) study design, this report estimated the fatal and series injuries (FSI) saved through use of the iRAP protocols. The study is based on 441,753 kilometers of assessed roads from 1,039 projects in 74 countries. Our results show that the implementation of iRAP's proposed countermeasures saves about 159,936 FSI annually. Throughout the lifetime of the implemented countermeasures, a total of 3.2 million FSI could be saved. CONCLUSION: While quantifying the success of the iRAP protocols, our results suggest an opportunity to save many millions more lives on the roads through expanding iRAP implementation to more regions and countries.

Evaluation of venous thromboembolism risk assessment models for hospital inpatients: the VTEAM evidence synthesis.

Background: Pharmacological prophylaxis during hospital admission can reduce the risk of acquired blood clots (venous thromboembolism) but may cause complications, such as bleeding. Using a risk assessment model to predict the risk of blood clots could facilitate selection of patients for prophylaxis and optimise the balance of benefits, risks and costs. Objectives: We aimed to identify validated risk assessment models and estimate their prognostic accuracy, evaluate the cost-effectiveness of different strategies for selecting hospitalised patients for prophylaxis, assess the feasibility of using efficient research methods and estimate key parameters for future research. Design: We undertook a systematic review, decision-analytic modelling and observational cohort study conducted in accordance with Enhancing the QUAlity and Transparency Of health Research (EQUATOR) guidelines. Setting: NHS hospitals, with primary data collection at four sites. Participants: Medical and surgical hospital inpatients, excluding paediatric, critical care and pregnancy-related admissions. Interventions: Prophylaxis for all patients, none and according to selected risk assessment models. Main outcome measures: Model accuracy for predicting blood clots, lifetime costs and quality-adjusted life-years associated with alternative strategies, accuracy of efficient methods for identifying key outcomes and proportion of inpatients recommended prophylaxis using different models. Results: We identified 24 validated risk assessment models, but low-quality heterogeneous data suggested weak accuracy for prediction of blood clots and generally high risk of bias in all studies. Decision-analytic modelling showed that pharmacological prophylaxis for all eligible is generally more cost-effective than model-based strategies for both medical and surgical inpatients, when valuing a quality-adjusted life-year at £20,000. The findings were more sensitive to uncertainties in the surgical population; strategies using risk assessment models were more cost-effective if the model was assumed to have a very high sensitivity, or the long-term risks of post-thrombotic complications were lower. Efficient methods using routine data did not accurately identify blood clots or bleeding events and several pre-specified feasibility criteria were not met. Theoretical prophylaxis rates across an inpatient cohort based on existing risk assessment models ranged from 13% to 91%. Limitations: Existing studies may underestimate the accuracy of risk assessment models, leading to underestimation of their cost-effectiveness. The cost-effectiveness findings do not apply to patients with an increased risk of bleeding. Mechanical thromboprophylaxis options were excluded from the modelling. Primary data collection was predominately retrospective, risking case ascertainment bias. Conclusions: Thromboprophylaxis for all patients appears to be generally more cost-effective than using a risk assessment model, in hospitalised patients at low risk of bleeding. To be cost-effective, any risk assessment model would need to be highly sensitive. Current evidence on risk assessment models is at high risk of bias and our findings should be interpreted in this context. We were unable to demonstrate the feasibility of using efficient methods to accurately detect relevant outcomes for future research. Future work: Further research should evaluate routine prophylaxis strategies for all eligible hospitalised patients. Models that could accurately identify individuals at very low risk of blood clots (who could discontinue prophylaxis) warrant further evaluation. Study registration: This study is registered as PROSPERO CRD42020165778 and Researchregistry5216. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127454) and will be published in full in Health Technology Assessment; Vol. 28, No. 20. See the NIHR Funding and Awards website for further award information.

People who are admitted to hospital are at risk of blood clots that can cause serious illness or death. Patients are often given low doses of blood-thinning drugs to reduce this risk. However, these drugs can cause side effects, such as bleeding. Hospitals currently use complex risk assessment models (risk scores, which usually include patient, disease, mobility and intervention factors) to determine the individual risk of blood clots and identify people most likely to benefit from blood-thinning drugs. There are a lot of different risk scores and we do not know which one is best. We also do not know how these scores compare to each other or whether using scores to decide who should get blood-thinning drugs provides good value for money to the NHS. We reviewed all previous studies of risk scores. We found that they did not predict blood clots very well and we could not recommend one score over another. We then created a mathematical model to simulate the use of blood-thinning drugs in people admitted to hospital. The model suggested that giving blood-thinning drugs to everyone who could have them would probably provide the best value for money, in medical patients. Our findings were the same, but less certain, for surgical patients. We also collected information from four NHS hospitals to explore possibilities for future research. Our work showed that routinely collected electronic data on blood clots and bleeding events is not very accurate and that using different scores could result in variable use of blood-thinning medications. Our findings suggest that it may be better value to the NHS and better for patients if we were to offer blood-thinning medications to everyone on admission to hospital, without using any risk score. However, this approach needs further research to ensure it is safe and effective. Such research would not be able to rely on routine electronic data to identify blood clots or bleeding events, in isolation.

Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. TRIAL REGISTRATION NUMBER: ISRCTN96296121.

Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement.

Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.