Common Outcome Research Articles

Harms to children from men’s heavy drinking: A scoping review

Background: Research has examined a range of impacts of women’s drinking on children. However, fewer studies have addressed the consequences of men’s heavy drinking on children. This review aims to identify and describe the types of behaviours and actions that arise from men's drinking and are likely to cause harm to children and to identify and describe the types of harms that children experience that stem from men's drinking. Methods: Review articles from 1990 to September 2023 were included. Four health and social databases were searched for reviews that included terms relating to men, alcohol consumption, and child harms. From 1,873 identified articles, 19 articles met the criteria for inclusion. Results: Four broad topics were identified: relationships and families; violence and maltreatment; and health, social and education outcomes for children. Children may experience both direct and indirect harms associated with men’s drinking. The former includes examples where men’s drinking was linked to disinhibition, aggression, and physical assault. In the latter, men were absent resulting in being unavailable emotionally due to drinking. Internalising and externalising behaviours were common outcomes for children exposed to men’s drinking. Contextual factors such as poverty, cultural norms and patriarchal influences were interrelated and sometimes exacerbated harm to children from men’s drinking. Conclusions: This review highlights the immediate and longer-lasting consequences of men’s drinking for children, including family conflict, maltreatment, and emotional distress. Future studies should address gender disparities and consider the social factors present in cases where children are exposed to men’s drinking.

Test for comparing the associations of multiple exposures with a common outcome

IntroductionWith advancement of medicine, alternative exposures or interventions are emerging with respect to a common outcome, and there are needs to formally test the difference in the associations of multiple exposures. MethodsThe paper proposes a duplication method-based multivariate Wald test in the Cox proportional hazard regression model to test the difference in the associations of multiple exposures with a same outcome. This method applies to continuous or categorical exposures. For illustration, the method was applied to compare the associations between alignment to two different dietary patterns (Alternative Healthy Eating Index-2010 [AHEI-2010] and reversed empirical dietary inflammatory pattern [rEDIP]), either as continuous or quartile exposures, and incident chronic diseases, defined as a composite of cardiovascular disease, cancer, and diabetes, in the Health Professional Follow-up Study (HPFS). Relevant sample codes in R that implement the proposed approach are provided. The present analysis was conducted in 2024. ResultsWith a median follow-up of 22 years, there were a total of 14,427 chronic disease incidences among N=43,185 men included in the HPFS analysis. The hazard ratios (HRs) [95% confidence interval] per increment from the 10th to the 90th percentile for incident chronic disease were 0.83 [0.79, 0.87] for AHEI-2010 and 0.76 [0.73, 0.80] for rEDIP. Although the 95% CIs were overlapped for each exposure, the proposed test was well powered to detect the difference (p=0.005). ConclusionsThe proposed duplication-method-based approach offers a flexible, formal statistical test for heterogeneity in the associations of multiple exposures with the common outcome with minimal assumptions.

An institutional approach to thick wall gall bladder and our experience of 5450 gallstone disease.

Gallstone disease (GSD) has a high prevalence in India. GSD presentation varies from being asymptomatic to severe complications. Laparoscopic cholecystectomy (LC) is the procedure of choice. Histopathological varies from chronic cholecystitis to carcinoma gall bladder (CaGB). Thick wall gall bladder (TWGB) is grey zone. Various parameters of GSD especially TWGB were evaluated to develop an approach to reduce perioperative complications and histopathological surprises. This study was conducted at the Department of Surgical Gastroenterology, Dr. RMLIMS, Lucknow. Data of all patients undergoing cholecystectomy between January 2015 and March 2023 were analysed retrospectively. Demographic profile, clinical presentation, blood investigations, radiological findings, operative findings and histopathology report were examined. Clinical and radiological features of difficult cholecystectomies, incidence and type of bile duct injury (BDI), presentation and outcomes of TWGB, incidence of incidental CaGB and its outcome, were evaluated and analysed. A total of 5450 patients underwent cholecystectomy during the study period. GSD is common in females and 4 th decade. The laparoscopic to open conversion rate was 1.2%, the most common cause was unclear anatomy. The incidence of BDI in our series was 0.11% ( n = 6). The most common histopathological outcome was chronic cholecystitis followed by xanthogranulomatous cholecystitis. Incidence of incidental carcinoma gall in our series was 0.3% ( n = 16) with an overall survival of 68.75% at a mean follow-up of 19.4 months. TWGB workup includes contrast-enhanced computed tomography, intraoperative most have difficult cholecystectomy and had a higher rate of conversion, injury and incidental CaGB. Thorough pre-operative evaluation and using the suggested algorithm may decrease perioperative complications and histopathological surprises after LC.

The genetic origins of species boundaries at subtropical and temperate ecoregions in the North American racers (Coluber constrictor).

Phylogeographically structured lineages are a common outcome of range-wide population genetic studies. In the southeastern United States, disconnection between populations found at the intersection of the southeastern coastal plains of peninsular Florida and the southeastern plains of the adjacent continent is readily apparent among many plants and animals. However, the timing and maintenance of species boundaries between these distinctly different subtropical and temperate regions remains unknown for all organisms studied there. Using genome-scale data, we examine the timing of origins, gene flow, and the movement of genes under selection in unique ecoregions within the North American racers (Coluber constrictor). Isolation-migration models along with tests of genome-wide selection, locus-environment associations, and spatial and genomic clines demonstrate that two unrecognized species are present and are in contact at the boundary of these two ecoregions. We show that selection at several loci associated with unique environments have maintained species boundaries despite constant levels of gene flow between these lineages over thousands of generations. This research provides a new avenue of research to examine speciation processes in poorly studied biodiversity hotspots.

The Role of microRNA Expression and DNA Methylation in HPV-Related Cervical Cancer: A Systematic Review

Human papillomavirus (HPV) infection is a major etiologic factor in cervical cancer, a major cause of cancer-related morbidity and mortality among women worldwide. The role of microRNA (miRNA) dysregulation in cervical carcinogenesis is still largely unknown, but epigenetic changes, including DNA methylation and miRNA regulation, are crucial factors. The integration of HPV DNA into the host genome can lead to alterations in DNA methylation patterns and miRNA expression, contributing to the progression from normal epithelium to cervical intraepithelial neoplasia and, ultimately, to cervical cancer. This review aimed to examine the relationship between epigenetic changes in the development and progression of HPV associated with cervical cancer. A systematic literature search was conducted in major databases using predefined inclusion and exclusion criteria. Studies that investigated the expression, function, and clinical significance of miRNAs, DNA methylation, and the expression of oncoproteins in HPV-related cervical cancer were included. Data extraction, quality assessment, and synthesis were performed to provide a comprehensive overview of the current state of knowledge. We provide an overview of the studies investigating miRNA expression in relation to cervical cancer progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched the Pubmed database for all articles published between January 2018 and December 2023. Our systematic review revealed a substantial body of evidence supporting the pivotal role of miRNA dysregulation in the pathogenesis of HPV-related cervical cancer and related oncoproteins. From the 28 studies retrieved, miR-124, FAM194/miR-124-2, and DNA methylation are the most frequently down- or up-regulated in CC progression. Notably, FAM194/miR-124-2 and DNA methylation emerged as a promising molecular marker for distinguishing between cases requiring immediate surgical intervention and those amenable to a more conservative wait-and-see approach. This systematic review underscores the critical involvement of microRNA in the context of HPV-related cervical cancer and sheds light on the potential clinical utility of FAM194/miR-124-2 and DNA methylation as a discriminatory tool for guiding treatment decisions. The identification of patients who may benefit from early surgical intervention versus those suitable for observation has important implications for personalized and targeted management strategies in the era of precision medicine.

Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts.

Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), a progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors to fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as a specific kidney fibroblast marker. Gucy1α1 levels significantly increased over the course of two clinically relevant murine CKD models and directly correlated with established fibrosis markers. Immunofluorescent (IF) imaging showed that Gucy1α1 comprehensively labelled cortical and medullary quiescent and activated fibroblasts in the control kidney and throughout injury progression, respectively. Unlike traditionally used markers platelet derived growth factor receptor beta (Pdgfrβ) and vimentin (Vim), Gucy1α1 did not overlap with off-target populations such as podocytes. Notably, Gucy1α1 labelled kidney fibroblasts in both male and female mice. Furthermore, we observed elevated GUCY1α1 expression in the human fibrotic kidney and lung. Studies in the murine models of cardiac and liver fibrosis revealed Gucy1α1 elevation in activated Pdgfrβ-, Vim- and alpha smooth muscle actin (αSma)-expressing fibroblasts paralleling injury progression and resolution. Overall, we demonstrate Gucy1α1 as an exclusive fibroblast marker in both sexes. Due to its multiorgan translational potential, GUCY1α1 might provide a novel promising strategy to specifically target and mechanistically examine fibroblasts.

Development and external validation of an algorithm for self-identification of risk for microvascular complications in patients with type 1 diabetes.

Microvascular complications, such as diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN), are common and serious outcomes of inadequately managed type 1 diabetes (T1D). Timely detection and intervention in these complications are crucial for improving patient outcomes. This study aimed to develop and externally validate machine learning (ML) models for self-identification of microvascular complication risks in T1D population. Utilizing data from the Chinese Type 1 Diabetes Comprehensive Care Pathway program, 911 T1D patients and 15 patient self-reported variables were included. Combined with XGBoost algorithm and cross-validation, self-identification models were constructed with 5 variables selected by feature importance ranking. For external validation, an online survey was conducted within a nationwide T1D online community (N = 157). The area under the receiver-operating-characteristic curve (AUROC) was adopted as the main metric to evaluate the model performance. The SHapley Additive exPlanation was utilized for model interpretation. The prevalence rates of microvascular complications in the development set and external validation set were as follows: DR 7.0% and 12.7% (p = 0.013), DN 5.9% and 3.2% (p = 0.162) and DPN 10.5% and 20.4% (p < 0.001). The models demonstrated the AUROC values of 0.889 for DR, 0.844 for DN and 0.839 for DPN during internal validation. For external validation, the AUROC values achieved 0.762 for DR, 0.718 for DN and 0.721 for DPN. ML models, based on self-reported data, have the potential to serve as a self-identification tool, empowering T1D patients to understand their risks outside of hospital settings and encourage early engagement with healthcare services.

Reverse Shoulder Arthroplasty in the Setting of Massive Proximal Humeral Bone Loss: A Systematic Review

Massive proximal humeral bone loss (PHBL) poses a technical challenge during reverse shoulder arthroplasty (RSA). Surgical treatment strategies include allograft-prosthetic composite (APC) reconstructions, endoprostheses, and other reverse shoulder arthroplasty constructs, however, there is a paucity of literature summarizing the outcomes and complications unique to this complex patient population. This study aimed to systematically review the literature to evaluate (1) patient-reported outcome measures (PROMs), (2) functional outcomes, and (3) complications according to surgical treatment strategy for patients with massive PHBL who undergo primary or revision shoulder arthroplasty. A systematic review of the PubMed/MEDLINE, Embase, and Cochrane databases was performed to identify studies reporting clinical outcomes and complications of reverse shoulder arthroplasty in patients with significant PHBL. Methodological quality was assessed for included studies. PROMs, radiographic outcomes, and postoperative functional outcomes were collected. Eleven studies evaluating clinical outcomes and complications of reverse shoulder arthroplasty in the setting of PHBL comprising 277 patients were included for review. The mean age was 66 years (range, 60-79 years). American Shoulder and Elbow Surgeons (ASES) score, Visual Analog Scale (VAS), and range of motion (ROM) were the most common outcomes collected, and patients exhibited significant improvements in mean scores postoperatively. Of the types of prostheses reported, there were 155 reverse shoulder arthroplasty (RSA) with allograft-prosthetic composite (APC) reconstructions, 48 proximal humeral replacement (PHR) endoprostheses, 41 RSA, 15 custom RSA, and 2 RSA with fibular strut allografts. The overall pooled complication rate was 30.1% (82/272) with revision/reoperation as the most common complication at 21% (57/272). The overall complication rate for RSA-APC reconstructions was 51% (79/155). The overall complication rate for PHR endoprostheses was 64.6% (31/48). Revision/reoperation rates were the most complication for both RSA-APC and PHR endoprostheses with rates of 20% and 31.3%, respectively. Treatment by APC reconstruction is the most common surgical technique described in the setting of massive PHBL. While shoulder arthroplasty can yield acceptable results for patients with substantial PHBL, such patients are at increased risk for complications and revision surgery.

Placental histopathological abnormalities in adverse obstetric outcomes: a retrospective cross-sectional study at Sultan Qaboos University Hospital

IntroductionPlacenta is a vital organ with highly specialized functions. According to the Perinatal Section of the Pediatric Pathology Society, placental histopathological abnormalities are typically categorized into maternal vascular hypoperfusion, fetal thrombotic vasculopathy, and inflammatory lesions. This study aims to assess the placental histopathological abnormality results in relation to adverse obstetric outcomes and to investigate whether specific placental abnormalities are associated with particular adverse outcomes.MethodsA retrospective cross-sectional study was conducted between January 2017 and January 2020 including all women who were admitted to Sultan Qaboos University Hospital with an adverse obstetric outcome who met the inclusion criteria, and whose placentas were sent for histopathological examination.ResultsA total of 191 women were included in the study. The most common adverse obstetric outcomes included preterm labor (25.1%), fetal growth restriction (FGR) (19.4%), preeclampsia and related complications (15%), placental abruption (14.1%), and chorioamnionitis (14%). 74% of women had abnormal placental findings. Among women with preterm labor, inflammatory lesions were present in 56.3% of cases (p = 0.006). Fetal thrombotic vasculopathy lesions were present in 13.5% of FGR cases (p = 0.037). In preeclampsia cases, maternal under perfusion lesions were present in 79% of cases (p = 0.013).ConclusionPlacental histopathological examination is an important tool for assessing perinatal outcomes. Correlating placental findings with specific obstetrical conditions and adverse outcomes provides valuable information that can assist obstetricians in developing appropriate management plans for future pregnancies.

Content comparison of multidimensional functional outcome measures in rehabilitation and the ICF clinical functioning information tool: A scoping literature review

Background: The ICF-based Clinical Functioning Information Tool (ClinFIT) was developed as a standardized tool to facilitate the assessment of functioning in clinical and, research settings. Objective: This review describes the contents of commonly used multidimensional outcome measures that describe functioning in rehabilitation settings and maps these measures to ICF categories covered by the ClinFIT to identify commonalities and discrepancies in the content. Methods: A scoping review included a systematic search of PubMed, Embase, Cochrane Library, and other resources. Twelve outcome measures were selected, and their meaningful concepts were linked to the ClinFIT by 2 authors using established ICF linking rules. Content density, bandwidth, and content diversity indices were calculated for each measure. Results: A total of 369 meaningful concepts from the 292 items from 12 measures were selected. Of these, 293 (79.4%) concepts were linked to the ClinFIT categories, with a majority (80.5%) linked to “activities and participation”; however, 76 (20.6%) meaningful concepts could not be linked to any ClinFIT categories. The extent of content coverage varied significantly between measures, reflecting the differences in the scope of each measure. The “activity and participation” categories had the highest bandwidth for all measures (range: 28.6%–71.4%), while the “body function” category was less represented (range: 0%–33.3%). Conclusions: ClinFIT can be the useful outcome measure for functional assessment in rehabilitation settings, as it covers wider concepts, considered important in rehabilitation settings, compared with other common functional outcome measures. It can establish comparability of a minimal data set on functional outcomes across various medical conditions and settings.

Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8+ T cell responses against an arthritogenic alphavirus.

Ross River virus (RRV) and other alphaviruses cause chronic musculoskeletal syndromes that are associated with viral persistence, which suggests deficits in immune clearance mechanisms, including CD8+ T-cell responses. Here, we used a recombinant RRV-gp33 that expresses the immunodominant CD8+ T-cell epitope of lymphocytic choriomeningitis virus (LCMV) to directly compare responses with a virus, LCMV, that strongly induces antiviral CD8+ T cells. After footpad injection, we detected fewer gp33-specific CD8+ T cells in the draining lymph node (DLN) after RRV-gp33 than LCMV infection, despite similar viral RNA levels in the foot. However, less RRV RNA was detected in the DLN compared to LCMV, with RRV localizing principally to the subcapsular region and LCMV to the paracortical T-cell zones. Single-cell RNA-sequencing analysis of adoptively transferred gp33-specific transgenic CD8+ T cells showed rapid differentiation into effector cells after LCMV but not RRV infection. This defect in RRV-specific CD8+ T effector cell maturation was corrected by local blockade of type I interferon (IFN) signaling, which also resulted in increased RRV infection in the DLN. Studies in Wdfy4-/-, CD11c-Cre B2mfl/fl, or Xcr1-Cre Ifnar1fl/fl mice that respectively lack cross-presenting capacity, MHC-I antigen presentation by dendritic cells (DCs), or type I IFN signaling in the DC1 subset show that RRV-specific CD8+ T-cell responses can be improved by enhanced direct antigen presentation by DCs. Overall, our experiments suggest that antiviral type I IFN signaling in DCs limits direct alphavirus infection and antigen presentation, which likely delays CD8+ T-cell responses.IMPORTANCEChronic arthritis and musculoskeletal disease are common outcomes of infections caused by arthritogenic alphaviruses, including Ross River virus (RRV), due to incomplete virus clearance. Unlike other viral infections that are efficiently cleared by cytotoxic CD8+ T cells, RRV infection is surprisingly unaffected by CD8+ T cells as mice lacking or having these cells show similar viral persistence in joint and lymphoid tissues. To elucidate the basis for this deficient response, we measured the RRV-specific CD8+ T-cell population size and activation state relative to another virus known to elicit a strong T-cell response. Our findings reveal that RRV induces fewer CD8+ T cells due to limited infection of immune cells in the draining lymph node. By increasing RRV susceptibility in antigen-presenting cells, we elicited a robust CD8+ T-cell response. These results highlight antigen availability and virus tropism as possible targets for intervention against RRV immune evasion and persistence.

Abstract 4136785: Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire

Introduction: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a common outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean effects do not necessarily reflect the clinical benefit experienced by patients. Objectives: To evaluate the relationship between mean KCCQ treatment effects in clinical trials and the proportions of patients experiencing clinically important improvements across a range of heart failure etiologies and interventions. Methods: We performed a patient-level meta-analysis of 11 randomized trials (9,977 patients) to examine the relationship between mean KCCQ Overall Summary Score (OSS) treatment effects and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate or larger (≥10 points) improvements. Validation was performed in 7 additional trials. Results: Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI] 4.0-8.1) in the proportion of patients improving ≥5 points and 5.0% (95% PI 3.1-7.0) in the proportion improving ≥10 points, corresponding to NNTs of 17 (95% PI 12-25) and 20 (95% PI 14-33), respectively. Similar relationships were observed in the validation studies. Conclusions: Inferences on clinical impact based on population-level mean treatment effects are misleading since even small between group differences may reflect clinically important treatment benefits at the patient level. Clinical trials should explicitly describe the distributions of patient-level KCCQ changes to support clinical interpretation of their results.

The association of Helicobacter pylori with adverse pregnancy outcomes in three European birth cohorts

BackgroundHelicobacter pylori is a prevalent infection that may complicate pregnancy, but evidence remains limited, controversial and may not apply to all pregnant women.ObjectiveThis study aims to evaluate whether Helicobacter pylori is a risk factor for adverse pregnancy outcomes and to identify vulnerable subpopulations.Study designMultiplex serology was utilized to measure blood levels of immunoglobulin G against eight Helicobacter pylori antigens in 1372 pregnant women from three European birth cohorts: BiB (United Kingdom), Rhea (Greece) and INMA (Spain). Outcomes of interest included gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth and small for gestational age neonates, as well as prenatal anxiety and depression. Adjusted logistic regression models were used to evaluate the association between Helicobacter pylori seropositivity (overall and by antigen) and antigen specific antibody levels with the outcomes. We examined effect modification of the associations by ethnicity.ResultsHelicobacter pylori seropositivity was detected in 18.8% (258/1372) of pregnant women. Preeclampsia was the least common outcome (26/830). Helicobacter pylori seropositivity was associated with the development of two or more adverse pregnancy outcomes (gestational hypertension, gestational diabetes, preterm birth, small gestational age and preeclampsia) [OR:1.32 (95% CI: 1.06–1.65), p-value: 0.01], especially in women with high antibody levels to OMP antigen [OR: 2.12 (95% CI: 1.62–2.76), p-value: 0.001]. Women with high antibody levels to Helicobacter pylori antigens GroEL and NapA were more likely to develop preeclampsia [OR: 2.34 (95% CI: 1.10–8.82), p-value: 0.03; OR: 4.09 (95% CI: 1.4-11.93), p-value 0.01)]. Helicobacter pylori seropositivity increased the odds of developing any hypertensive disorder during pregnancy among women of western ethnicity (948/1372) [OR:3.35 (95% CI: 1.29–8.74), p-value 0.03].ConclusionOur study suggests that Helicobacter pylori seropositivity is a risk factor for multiple adverse pregnancy outcomes and particularly in women of western origin for hypertensive disorders during pregnancy. Moreover, pathogen specific characteristics reflected in the antibody responses against OMP, GroEL and NapA seem to determine disease associations.

The 2-week wait pathway for suspected head and neck cancers in patients with throat and voice symptoms: referral patterns, common clinical practice and diagnostic efficacy of NICE guidelines.

The 2-week wait (2ww) referral pathway has been introduced into UK clinical practice to increase the early detection of cancer and improve survivals. The efficiency of this system for head and neck (H&N) cancers has been questioned over the years because of evidence of low pick-up rates. H&N cancers present with a wide variety of non-specific symptoms, particularly throat and voice symptoms. These symptoms need to be accurately interpreted together with risk factors if they are to be addressed adequately and overload of cancer facilities avoided. One of the most common outcomes of H&N 2ww referrals is laryngopharyngeal reflux (LPR), a common condition that could be diagnosed and managed in the primary care setting with a prescription of proton pump inhibitors (PPI) trials. We retrospectively analysed a cohort of consecutive patients referred on the 2ww pathway for throat and voice symptoms at University College London Hospital H&N cancer clinic during two months in 2019. A total of 101 patients (43.6% men, mean age 53.3 years) were included. Throat and voice symptoms were described as intermittent in 52.5% and non-lateralised in 88.1%. Diagnosis of LPR was made in 59.4% of the referrals. A PPI trial was prescribed by general practitioners (GPs) in only 7.9% of cases. The cancer pick-up rate in our cohort is 2.9%. An improved awareness of the symptoms of LPR could guide GPs to prescribe trials of PPIs in low-risk patients before rushing into a referral on a cancer pathway. This would improve the 2ww process on many levels, reduce the burden on the National Health Service and avoid patients' psychological distress.

Intratracheal Budesonide Mixed With Surfactant for Extremely Preterm Infants

Bronchopulmonary dysplasia (BPD) is a common adverse outcome in extremely preterm infants born at less than 28 weeks' gestation. Systemic corticosteroids are effective against BPD but may be associated with adverse outcomes. Corticosteroids given directly into the lungs may be effective and safer. To investigate the effectiveness of early intratracheal corticosteroid administration on survival free of BPD in extremely preterm infants. Double-blind randomized clinical trial conducted in 21 neonatal units in 4 countries (Australia, New Zealand, Canada, and Singapore), enrolling infants born at less than 28 weeks' gestation and less than 48 hours old who were mechanically ventilated (regardless of ventilator settings or oxygen requirements) or who were receiving noninvasive respiratory support and had a clinical decision to treat with surfactant. Recruitment occurred from January 2018 to March 2023. The last participant was discharged from the hospital in August 2023. Infants were randomly allocated (1:1) to receive budesonide, 0.25 mg/kg, mixed with surfactant (poractant alfa), administered via an endotracheal tube or thin catheter, or surfactant only. The primary outcome was survival free of BPD at 36 weeks' postmenstrual age. There were 15 secondary outcomes, including the 2 components of the primary outcome (survival at 36 weeks and BPD among survivors), and 9 predefined safety outcomes (adverse events). The primary analysis included 1059 infants, 524 in the budesonide and surfactant group and 535 in the surfactant-only group. Overall, infants had a mean gestational age of 25.6 weeks (SD, 1.3 weeks) and a mean birth weight of 775 g (SD, 197 g); 586 (55.3%) were male. Survival free of BPD occurred in 134 infants (25.6%) in the budesonide and surfactant group and 121 infants (22.6%) in the surfactant-only group (adjusted risk difference, 2.7% [95% CI, -2.1% to 7.4%]). At 36 weeks' postmenstrual age, 83.2% of infants were alive in the budesonide and surfactant group and 80.6% in the surfactant-only group. Of these, 69.3% and 71.9% were diagnosed with BPD, respectively. In extremely preterm infants receiving surfactant for respiratory distress syndrome, early intratracheal budesonide may have little to no effect on survival free of BPD. anzctr.org.au Identifier: ACTRN12617000322336.

Building a machine learning-based risk prediction model for second-trimester miscarriage

BackgroundSecond-trimester miscarriage is a common adverse pregnancy outcome that imposes substantial economic and psychological pressures on both the physical and mental well-being of patients and their families. Currently, there is a scarcity of research on predictive models for the risk of second-trimester miscarriage.MethodsClinical data were retrospectively collected from patients who were in the second trimester of pregnancy (between 14+0 and 27+6 weeks gestation), whose main diagnosis was “threatened abortion” and who were hospitalized at the Women and Children’s Hospital of Ningbo University from January 2020 to October 2023. Following preliminary data processing, the patient cohort was randomly stratified into a training cohort and a validation cohort at proportions of 70% and 30%, respectively. The Boruta algorithm and multifactor analysis were used to refine feature factors and determine the optimal features linked to second-trimester miscarriages. The imbalanced dataset from the training cohort was rectified by applying the SMOTE oversampling approach. Seven machine-learning models were built and subjected to a comprehensive analysis to validate and evaluate their predictive capabilities. Through this rigorous assessment, the optimal model was selected. Shapley additive explanations (SHAP) were generated to provide insights into the model’s predictions, and a visual representation of the predictive model was built.ResultsA total of 2006 patients were included in the study; 395 (19.69%) of them had second-trimester miscarriages. XGBoost was shown to be the optimal model after a comparison of seven different models utilizing metrics such as accuracy, precision, recall, the F1 score, precision-recall average precision, the receiver operating characteristic-area under the curve, decision curve analysis, and the calibration curve. The most significant feature was cervical length, and the top ten features of second-trimester miscarriage were found using the SHAP technique based on relevance rankings.ConclusionThe risk of a second-trimester miscarriage can be accurately predicted by the visual risk prediction model, which is based on the machine learning mentioned above.

Systematic Review of Obstetric and Child Outcomes of Prenatal Exposure to Inhalants in the Context of a Use Disorder.

Inhalants are often used for their psychoactive effects, producing feelings of euphoria. Inhalant and solvent use is a serious public health concern, yet little is known about their effects on perinatal, fetal, and child outcomes. The aim of our review is to evaluate the impact of inhalant use by pregnant people on maternal, fetal, neonatal, and early childhood outcomes. A systematic review was conducted on March 1, 2023, in 6 databases using relevant keywords. Bias assessment was performed using JBI Critical Appraisal Tools. Studies were included if they described a prenatal exposure to an inhalant; focused on maternal, fetal, neonatal, or early childhood outcomes; and were published as peer-reviewed reports in English. The search yielded 1101 unique references with 22 studies meeting eligibility criteria and representing 205 pregnancies and 171 infants.The most common symptom of inhalant use reported in pregnant people was altered mentation, followed by renal tubular acidosis (RTA) reported with toluene use. Most common fetal outcomes included fetal growth restriction and preterm delivery (<37 weeks), while neonatal outcomes were withdrawal symptoms, such as jitteriness, trouble feeding, and dystonia. Child outcomes included developmental delays, including cognitive and speech impairments, and postnatal growth restriction, including microcephaly. Perinatal, fetal, and child outcomes associated with inhalant use among pregnant individuals are largely based on case reports and series. Prospective studies are needed to better characterize these outcomes, reduce stigma, increase equitable access to treatment, and identify potential interventions to reduce use and potential harm.

Outcome Reporting in Studies Investigating Treatment for Caesarean Scar Ectopic Pregnancy: A Systematic Review.

Caesarean scar ectopic pregnancy (CSEP) is associated with significant maternal and foetal morbidity. However, the optimal treatment remains unknown. The aim of this study was to review outcomes reported in studies on CSEP treatment and outcome reporting quality. We reviewed 1270 articles identified through searching PubMed, MEDLINE and Google Scholar from 2014 to 2024 using the search terms 'caesarean scar ectopic pregnancy and caesarean scar pregnancy'. We included all study types evaluating any form of CSEP treatment, with a sample size of ≥ 50, where diagnosis was described, and the article was in English. Two authors independently reviewed studies and assessed outcome reporting and methodological quality. The relationship between outcome reporting quality and publication year and journal type was assessed with univariate and bivariate models. A total of 108 studies, including 17 941 women, were included. 83% of all studies originated from China. Studies reported on 326 outcomes; blood loss (86%), need for additional intervention (77%) and time for serum hCG to normalise post treatment (69%) were the most common outcomes. A primary outcome was clearly defined in 11 (10%) studies. The median quality of outcome reporting was 3 (IQR 3-4). No relationship was demonstrated between outcome reporting quality and publication year (p = 0.116) or journal type (p = 0.503). This review demonstrates that there is a wide variation in outcomes reported in studies on CSEP treatment. Development and implementation of a core outcome set by international stakeholders which includes patients is urgently needed to enable high-quality research that is both useful and relevant to patients.

Transient receptor potential channel 6 knockout ameliorates hepatic fibrosis by inhibiting the activation and proliferation of hepatic stellate cells.

Hepatic fibrosis is a common outcome of chronic liver injury and can eventually lead to cirrhosis, which is a major public health concern. Hepatic stellate cells (HSCs) are the major producers of extracellular matrix (ECM) and regulate the synthesis and decomposition of ECM, but the specific mechanism of them remains unclear. Transient receptor potential channel 6 (TRPC6), a non-selective cation channel, plays an important role in organic fibrosis. However, the role of TRPC6 in liver fibrosis is rarely studied. Here, we investigated the function of TRPC6 in the activation of the human hepatic stellate cell line LX-2 in vitro and bile duct ligation (BDL)-induced hepatic fibrosis in vivo by western blot, Ca2+ imaging, and immunohistochemistry. We first found that TRPC6 was upregulated in fibrotic liver tissues and TRPC6 knockout inhibited BDL-induced hepatic fibrosis. Transforming growth factor-β1 (TGF-β1) treatment increased TRPC6 expression and thapsigargin (Tg)-mediated SOCE in LX-2 cells, which was decreased by the TRPC6 specific inhibitor SAR7334. Blockage of TRPC6 by SAR7334 or TRPC6-shRNA transfection attenuated TGF-β1-induced LX-2 cell activation and proliferation via the PI3K/AKT/p70S6K signaling pathway. These observations suggested that TRPC6 contribute to LX-2 cell activation and hepatic fibrosis, and downregulation of TRPC6 may become a therapeutic strategy for the treatment of hepatic fibrosis in the future.

Disruptions in Transportation and Medical Care Experienced by Handlers of Assistance Dogs in Australia

ABSTRACT Anecdotal reports and limited available empirical evidence indicate that assistance-dog handlers are often denied access to places they are legally entitled to take their assistance dog. However, the frequency and contexts of access denials in Australia have not been established, and the emotional impacts of these denials are not well described. Furthermore, qualitative findings suggest that impromptu interactions with other people and dogs within the community can have both positive and negative impacts on the handler and assistance dog; larger-scale, quantitative research is needed. The aim of this study was to characterize the frequency and contexts, and emotional impacts, of assistance-dog access denials among handlers in Australia, as well as handler interactions with people and dogs. Handlers (n = 77) throughout Australia completed an online survey. Commercial passenger vehicles (CPVs, e.g., Uber/taxi) were the most commonly reported context for access denials, reportedly occurring about half the time, followed by hotels, restaurants, and cafés. Bystander support was rare in any setting. Some participants reported avoiding CPVs (52%), restaurants (13%), and medical/dental centers (13%) owing to prior access denials. The emotional impacts of the denials were very negative (e.g., annoyed, excluded, anxious, hurt). Having a visible or invisible disability had no bearing on the frequency of access denials, nor did having a conventional (e.g., Labrador Retriever) versus unconventional (e.g., Pug) breed of assistance dog. Unexpected interactions with people and other dogs were common; participants reported having a positive social interaction as a good outcome, and the dog becoming temporarily distracted as a common negative outcome. Unfortunately, eight participants (10%) had to retire a dog as an outcome of a negative interaction. Some free-text responses indicated that the reporting process for access denials is onerous and ineffective. Future research should seek to understand whether this can be remedied.