Multilevel challenges to equitable inclusion of children in trials when parents use languages other than English: A qualitative report from Children's Oncology Group's Diversity and Health Disparities Committee Language Equity Working Group.

BACKGROUND: Increasing representation in clinical trials is a priority for the National Cancer Institute and Children's Oncology Group (COG). Our survey of COG-affiliated institutions revealed that many sites have insufficient processes and resources to enroll children whose parents use languages other than English (LOE). We describe reported barriers and facilitators to enrolling children in clinical trials when parents use LOE and propose opportunities for improvement. PROCEDURES: We sent a 20-item survey to COG-affiliated institutions. Five items allowed respondents to expand on replies to questions about (a) local institutional review board (IRB) requirements regarding translation of consent documents, (b) contributors to provider discomfort consenting parents who use LOE, (c) available language services and resources, and (d) barriers to enrolling children whose parents use LOE or offer ideas about approaches to improvements. Two pairs of researchers independently coded free-text responses and compared results for concordance. RESULTS: A total of 139 (N = 230; 60%) institutions returned the survey. Respondents were mainly physician principal investigators (n = 79/139; 57%) at the United States sites (n = 118/139; 85%) serving less than 100 newly diagnosed children per year (n = 99/139, 71%). They described challenges at multiple levels. Proposed approaches to improvements included centralized provision of translated materials and video educational materials in various languages, and collaborating with IRBs on regulatory processes that protect families and facilitate equitable clinical trial access. CONCLUSIONS: Clinical trial consortia, such as COG, face challenges in enrolling representative samples. Further research is required to design and implement multilevel interventions to ensure equitable access for all, regardless of language used, and mitigate disparate research participation.

PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-driven connective tissue disorder that results in fibrosis of the skin and internal organs such as the lung. Fibroblasts are known as the main effector cells involved in the progression of SSc through the induction of extracellular matrix (ECM) proteins and myofibroblast differentiation. Here, we demonstrate that 4'-(cyclopropylmethyl)-N2-4-pyridinyl-[4,5'-bipyrimidine]-2,2'-diamine (PIK-III), known as class III phosphatidylinositol 3-kinase (PIK3C3/VPS34) inhibitor, exerts potent antifibrotic effects in human dermal fibroblasts (HDFs) by attenuating transforming growth factor-beta 1 (TGF-ß1)-induced ECM expression, cell contraction and myofibroblast differentiation. Unexpectedly, neither genetic silencing of PIK3C3 nor other PIK3C3 inhibitors (e.g., SAR405 and Autophinib) were able to mimic PIK-III-mediated antifibrotic effect in dermal fibroblasts, suggesting that PIK-III inhibits fibroblast activation through another signaling pathway. We identified that PIK-III effectively inhibits p38 activation in TGF-ß1-stimulated dermal fibroblasts. Finally, PIK-III administration significantly attenuated dermal and lung fibrosis in bleomycin-injured mice.

Non-differential misclassification of outcome under (near)-perfect specificity: a simulation study.

Mismeasurement of a dichotomous outcome yields an unbiased risk ratio estimate when there are no false positive cases (perfect specificity) and when sensitivity is non-differential with respect to exposure status. In studies where these conditions are expected, quantitative bias analysis may be considered unnecessary. We conducted a simulation study to explore the robustness of this special case to small departures from perfect specificity and stochastic departures from non-differential sensitivity. We observed substantial bias of the risk ratio with specificity values as high at 99.8%. The magnitude of bias increased directly with the true underlying risk ratio and was markedly stronger at lower baseline risk. Stochastic departure from non-differential sensitivity also resulted in substantial bias in most simulated scenarios; downward bias prevailed when sensitivity was higher among unexposed compared with exposed, and upward bias prevailed when sensitivity was higher among exposed compared with unexposed. Our results show that seemingly innocuous departures from perfect specificity (e.g., 0.2%) and from non-differential sensitivity can yield substantial bias of the risk ratio under outcome misclassification. We present a web tool permitting easy exploration of this bias mechanism under user-specifiable study scenarios.

Associations of demographic, health, and risk-taking behaviors with tattooing in a population-based cross-sectional study of ~18,000 US adults.

Background Little is known about current characteristics of individuals with tattoos. We quantified the prevalence of tattooing and associations of demographic, health, and risk-behavior factors with tattooing. Methods We computed adjusted prevalence ratios (PR) of tattooing in a population-based analysis of > 18,000 Utah adults from the 2020-2021 Behavioral Risk Factor Surveillance System survey. Results The prevalence of tattooing was 26% among women and 22% among men, with the highest prevalence among women ages 25-29 (45%). Tattoo prevalence was higher among younger individuals, individuals with a lower education level, and those without religious affiliation. Tattoo prevalence was higher among indviduals with current tobacco (women: PR = 2.89 [95% confidence interval (CI): 2.60, 3.20]; men: 3.39 [2.98, 3.86]), e-cigarette (women: 2.44 [2.21, 2.69]; men: 2.64 [2.37, 2.94]), and heavy alcohol use (women: 2.16 [1.93, 2.43]; men: 1.89 [1.63, 2.19]). Tattoo prevalence was lower among individuals receiving a flu (women: 0.84 [0.76, 0.92]; men: 0.75 [0.67, 0.84]) or COVID-19 vaccine (women: 0.65 [0.54, 0.79]; men: 0.75 [0.61, 0.92]). Conclusions Several risk-taking behaviors were associated with tattooing. Tattoo studios/conventions may present opportunities for partnership with tobacco cessation, alcohol reduction, and vaccination public health initiatives.

Impact of day-to-day variation in FEV1 on measures of change: A conceptual description.

Clinical trials often demonstrate treatment efficacy through change in forced expiratory volume in one second (FEV1), comparing single FEV1 measurements from post- versus pre-treatment timepoints. Day-to-day variation in measured FEV1 is common for reasons such as diurnal variation and intermittent health changes, relative to a stable, monthly average. This variation can alter estimation of associations between change in FEV1 and baseline in predictable ways, through a phenomenon called regression to the mean. We quantify and explain day-to-day variation in percent-predicted FEV1 (ppFEV1) from 4 previous trials, and we present a statistical, data-driven explanation for potential bias in ceiling and floor effects due to commonly observed amounts of variation. We recommend accounting for variation when assessing associations between baseline value and change in CF outcomes in single-arm trials, and we consider possible impact of variation on conventional standards for study eligibility.

Redirecting B7-H3.CAR T cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models.

PURPOSE: Clinical efficacy of CAR T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We investigated the primary chemokines secreted by OS and evaluated efficacy of B7-H3.CAR T cells expressing the cognate receptors. EXPERIMENTAL DESIGN: We developed a pipeline to identify chemokines secreted by OS by correlating RNA-seq data with chemokines detected in media from fresh surgical specimens. We identified CXCR2 and CXCR6 as promising receptors for enhancing CAR T cell homing against OS. We evaluated the homing kinetics and efficiency of CXCR2- and CXCR6.T cells and homing, cytokine production, and antitumor activity of CXCR2- and CXCR6.B7-H3.CAR T cells in vitro and in vivo. RESULTS: T cells transgenically expressing CXCR2 or CXCR6 exhibited ligand-specific enhanced migration over T cells modified with nonfunctional receptors. Differential homing kinetics were observed, with CXCR2.T cells homing quickly and plateauing early, while CXCR6.T cells homed more slowly but achieved a similar plateau. When expressed in B7-H3.CAR T cells, CXCR2- and CXCR6 modification conferred enhanced homing towards OS in vitro and in vivo. CXCR2- and CXCR6-B7-H3.CAR treated mice experienced prolonged survival in a metastatic model compared to B7-H3.CAR T cell treated mice. CONCLUSIONS: Our patient-based pipeline identified targets for chemokine receptor modification of CAR T cells targeting OS. CXCR2 and CXCR6 expression enhanced homing and anti-OS activity of B7-H3.CAR T cells. These findings support clinical evaluation of CXCR-modified CAR T cells to improve adoptive cell therapy for OS patients.

Understanding the Association Between Medical Mistrust and Unmet Medical Care Need in Gender and Sexually Diverse People of Color Assigned Female at Birth.

Purpose: The present study investigated associations of sexual orientation and/or gender identity-based medical mistrust and racial/ethnic-based medical mistrust, respectively, with unmet medical care need among lesbian, gay, bisexual, transgender, queer, and/or sexually or gender diverse (LGBTQ+) people of color (POC) assigned female at birth (AFAB). We also tested the interaction of the two types of medical mistrust on unmet medical care need. Methods: Participants were 266 LGBTQ+ POC AFAB. Participants completed measures of medical mistrust based on race/ethnicity and LGBTQ+ identity. Unmet medical care need was assessed using the item: "During the past 12 months, was there ever a time where you felt that you needed health care but you didn't receive it?" Multivariate logistic regression models were run with either type of medical mistrust, as well as their interaction, as the predictor and unmet medical care need as the outcome variable. Results: There were no significant main effects of either type of medical mistrust on unmet medical care need. However, there was an interaction between the two types of medical mistrust, such that associations between each type of medical mistrust and unmet medical care needs were stronger at higher levels of the other type of medical mistrust. Racial/ethnic medical mistrust was associated with a greater likelihood of unmet medical needs at high, but not low, levels of LGBTQ+ medical mistrust. Conclusions: Racial/ethnic medical mistrust and LGBTQ+ medical mistrust exacerbate each other's influence on unmet medical care need. These results underscore the need for inclusive clinical practices for LGBTQ+ POC.

Source-to-tap investigation of the occurrence of nontuberculous mycobacteria in a full-scale chloraminated drinking water system.

Nontuberculous mycobacteria (NTM) in drinking water are a significant public health concern. However, an incomplete understanding of the factors that influence the occurrence of NTM in drinking water limits our ability to characterize risk and prevent infection. This study sought to evaluate the influence of season and water treatment, distribution, and stagnation on NTM in drinking water. Samples were collected source-to-tap in a full-scale, chloraminated drinking water system approximately monthly from December 2019 to November 2020. NTM were characterized using culture-dependent (plate culture with matrix-assisted laser desorption ionization-time-of-flight mass spectrometry [MALDI-TOF MS] isolate analysis) and culture-independent methods (quantitative PCR and genome-resolved metagenomics). Sampling locations included source waters, three locations within the treatment plant, and five buildings receiving water from the distribution system. Building plumbing samples consisted of first draw, 5-min flush, and full flush cold-water samples. As the study took place during the COVID-19 pandemic, the influence of reduced water usage in three of the five buildings was also investigated. The highest NTM densities source-to-tap were found in the summer first draw building water samples (107 gene copies/L), which also had the lowest monochloramine concentrations. Flushing was found to be effective for reducing NTM and restoring disinfectant residuals, though flush times necessary to improve water quality varied by building. Clinically relevant NTM species, including Mycobacterium avium, were recovered via plate culture, with increased occurrence observed in buildings with higher water age. Four of five NTM metagenome-assembled genomes were identified to the species level and matched identified isolates.IMPORTANCENTM infections are increasing in prevalence, difficult to treat, and associated with high morbidity and mortality rates. Our lack of understanding of the factors that influence NTM occurrence in drinking water limits our ability to prevent infections, accurately characterize risk, and focus remediation efforts. In this study, we comprehensively evaluated NTM in a full-scale drinking water system, showing that various steps in treatment and distribution influence NTM presence. Stagnant building water contained the highest NTM densities source-to-tap and was associated with low disinfectant residuals. We illustrated the differences in NTM detection and characterization obtained from culture-based and culture-independent methods, highlighting the complementarity between these approaches. We demonstrated that focusing NTM mitigation efforts in building plumbing systems, which have the highest NTM densities source-to-tap, has potential for immediate positive effects. We also identified steps during treatment that increase NTM levels, which provides beneficial information for utilities seeking to reduce NTM in finished water.

Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.

BACKGROUND: Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. OBJECTIVE: This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. METHODS: Germ-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. RESULTS: Maternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-ß-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. CONCLUSIONS: The presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.

Health system barriers to hypertension care in Peru: Rapid assessment to inform organizational-level change.

Traditional patient- and provider-level hypertension interventions have proven insufficient to halt hypertension as the leading cause of morbidity and mortality globally. Systems-level interventions are required to address factors challenging hypertension control across a social ecological framework, an under-studied topic particularly salient in low- and middle-income countries (LMICs) such as Peru. To inform such interventions, we sought to identify key health systems barriers to hypertension care in Puno, Peru. A participatory stakeholder workshop (October 2021) and 21 in-depth interviews (October 2021-March 2022) were conducted with 55 healthcare professionals (i.e., doctors, nurses, midwives, dentists, nutritionists), followed by a deductive qualitative analysis of transcripts and notes. Participating healthcare providers indicated that low prioritization and lack of national policies for hypertension care have resulted in limited funding and lack of societal-level prevention efforts. Additionally, limited cultural consideration, both in national guidelines as well as by some providers in Puno, results in inadequate care that may not align with local traditions. Providers highlighted that patient care is also hampered by inadequate distribution and occasional shortages of medications and equipment, as well as a lack of personnel and limited opportunities for training in hypertension. Multiple incompatible health information systems, complicated referral systems, and geographic barriers additionally hinder continuity of care and care seeking. Insights gained from health providers on the healthcare system in Puno provide essential contextual information to inform development of organizational-level strategies necessary to improve provider and patient behaviors to achieve better hypertension care outcomes.

The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design.

PURPOSE: Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design. METHODS: We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007. RESULTS: For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4). CONCLUSIONS: We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.

Exploring the genomic traits of infant-associated microbiota members from a Zimbabwean cohort.

INTRODUCTION: Our understanding of particular gut microbiota members such as Bifidobacterium and Enterococcus in low-middle-income countries remains very limited, particularly early life strain-level beneficial traits. This study addresses this gap by exploring a collection of bacterial strains isolated from the gut of Zimbabwean infants; comparing their genomic characteristics with strains isolated from infants across North America, Europe, and other regions of Africa. MATERIALS AND METHOD: From 110 infant stool samples collected in Harare, Zimbabwe, 20 randomly selected samples were used to isolate dominant early-life gut microbiota members Bifidobacterium and Enterococcus. Isolated strains were subjected to whole genome sequencing and bioinformatics analysis including functional annotation of carbohydrates, human milk oligosaccharide (HMO) and protein degradation genes and clusters, and the presence of antibiotic resistance genes (ARGs). RESULTS: The study observed some location-based clustering within the main five identified taxonomic groups. Furthermore, there were varying and overall species-specific numbers of genes belonging to different GH families encoded within the analysed dataset. Additionally, distinct strain- and species-specific variances were identified in the potential of Bifidobacterium for metabolizing HMOs. Analysis of putative protease activity indicated a consistent presence of gamma-glutamyl hydrolases in Bifidobacterium, while Enterococcus genomes exhibited a high abundance of aspartyl peptidases. Both genera harboured resistance genes against multiple classes of antimicrobial drugs, with Enterococcus genomes containing a higher number of ARGs compared to Bifidobacterium, on average. CONCLUSION: This study identified promising probiotic strains within Zimbabwean isolates, offering the potential for early-life diet and microbial therapies. However, the presence of antibiotic resistance genes in infant-associated microbes raises concerns for infection risk and next-stage probiotic development. Further investigation in larger cohorts, particularly in regions with limited existing data on antibiotic and probiotic use, is crucial to validate these initial insights. IMPACT STATEMENT: This research represents the first investigation of its kind in the Zimbabwean context, focusing on potential probiotic strains within the early-life gut microbiota. By identifying local probiotic strains, this research can contribute to the development of probiotic interventions that are tailored to the Zimbabwean population, which can help address local health challenges and promote better health outcomes for infants. Another essential aspect of the study is the investigation of antimicrobial resistance genes present in Zimbabwean bacterial strains. Antimicrobial resistance is a significant global health concern, and understanding the prevalence and distribution of resistance genes in different regions can help inform public health policies and interventions.

Protocol for three-dimensional whole-mount imaging of the vascular network in the intestinal muscle.

Three-dimensional (3D) imaging of vascular networks is essential for the investigation of vascular patterning and organization. Here, we present a step-by-step protocol for the 3D visualization of the vasculature within whole-mount preparations of the mouse intestinal muscularis propria layer. We then detail the quantitative analysis of the resulting images for parameters such as vessel density, vessel diameter, the number of endothelial cells, and proliferation. The protocol can be easily extended to study cell-cell interactions such as neuro-vascular or immune-vascular interactions. For complete details on the use and execution of this protocol, please refer to Schrenk et al.1.

Sociodemographic Factors Correlate with Late Stage Pediatric Hodgkin Lymphoma and Rhabdomyosarcoma: A Report from the Children's Oncology Group Registries.

BACKGROUND: We examined association between late stage diagnosis and individual- and community-level characteristics among pediatric Hodgkin lymphoma (HL) and rhabdomyosarcoma (RMS) patients. METHODS: We obtained Children's Oncology Group (COG) data from 1999-2021 including summary stage (local (L), regional (R), distant (D)), tumor subtype, demographics, and ZIP code at diagnosis. We linked ZIP codes to county-level redlining scores (C,D=greatest redlining), Child Opportunity Index (COI), and measures of segregation (racial dissimilarity indices (DI)). Logistic regressions calculated odds ratios for late stage diagnosis, and by race within tumor subtype. RESULTS: 5,933 HL and 2,800 RMS patients were included. Late stage diagnosis of HL was correlated with Black race (ORDistant(D) vs regional/local(R&L)=1.38 [1.13-1.68]), being uninsured (ORD vs R&L=1.38 [1.09-1.75]), and subtype (Nodular sclerosis vs Other HL: ORD vs R&L=1.64 [1.34-2.01], Untyped: ORD vs R&L=1.30 [1.04-1.63]). Late stage rhabdomyosarcoma was correlated with bilingual households (ORDistant/regional(D&R) vs local(L)=2.66 [1.03-6.91]) and tumor type (Alveolar vs Embryonal ORD vs R&L=6.16 [5.00-7.58]. Community-level factors associated with late stage HL were greater Black (OR80-100%=1.83; 95% CI=1.11-3.02) and Hispanic (OR60-79%=1.30; 95%CI=1.05-1.60) DI. Late stage diagnosis for RMS was associated with more redlined census tracts within counties (OR=1.54; 95% CI =1.02-2.35) and low/very low COI (OR=1.21; 95% CI=1.02-1.45). CONCLUSION: Novel markers of community deprivation, such as redlining and racial segregation, likely affect cancer outcomes for children with HL and RMS in this first disparities study using COG registries. IMPACT: The interplay of multilevel risk factors provides important consideration for efforts to improve early detection of pediatric cancer diagnosis.

Endometriosis Typology and Ovarian Cancer Risk.

Importance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described. Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype. Design, Setting, and Participants: Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis. Exposures: Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other. Main Outcomes and Measures: Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations. Results: In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85]). Conclusions and Relevance: Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

Want to try a registered report? Here are our lessons learned.

A Registered Report is a type of research journal article in which the introduction, methods, and analysis plan are proposed and peer-reviewed prior to the execution of the study. The goal is to limit publication bias based on study findings by conducting peer review on the merits of the study before the results are known. First introduced in 2012 (Chambers, 2013; Chambers & Tzavella, 2022), this format of journal article publication has become more commonplace. Here we provide an overview of the format as well as eight core lessons we learned while preparing Registered Reports. We integrate guidelines from the literature with our experience to provide insight into the process of preparing and publishing a Registered Report for those who have not yet tried it. Though Registered Reports require researchers to invest more effort at the earlier stages of idea generation, design, and analysis planning, they will benefit from the feedback of reviewers when it is most beneficial and leave behind the fear of rejection due to unanticipated study limitations or null results. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The utility of a CT grading scale in deciding on surgical intervention for patients with suspected small bowel obstruction.

Background: A grading system was developed for computerized tomography (CT) scans evaluating patients with suspected small bowel obstruction (SBO). We hypothesized that patients with a higher grade of suspected SBO on CT scan would be more likely to require surgical intervention. Methods: Retrospective chart review of patients who presented to the Emergency Room (ER) who had a CT of the abdomen and pelvis for suspected SBO. Patients were divided into 5 groups: Grade 1 (SBO unlikely), Grade 2 (probable partial or early SBO), Grade 3 (probable high grade SBO), Grade 4 (SBO with changes concerning for ischemia) and Not Graded. Results: The CT scans of 655 patients were graded. Of the 22 patients with a grade 1 SBO, only 1 went for surgery (4.5 %). For grade 2 patients, 23 out of 299 had an operation (7.7 %), for grade 3 it was 84 out of 299 (28.1 %) and for grade 4 SBO, 25 out of 35 patients (71.4 %) had surgery. The p value is <0.00001. The three most common intraoperative findings were SBO obstruction from adhesions alone (48 % of cases), followed by incarcerated hernias (12 %) and ischemic bowel (9 %). Only 8 cases out of 133 operations (6 % of total) had no findings at time of surgery other than dilated bowel. Conclusions: The CT grading scale for SBO developed at our institution shows excellent correlation between grade and going for surgery, with few negative results, and can be a useful tool among other factors for general surgeons when deciding whether or not to operate on a patient with suspected SBO.

'Hands on', 'hands off' or 'hands poised'? Exploring intrapartum midwifery decision making through ethnographic research.

ISSUE: Injury to the perineal tissues during childbirth is a frequent occurrence with most women likely to experience perineal injury during a first birth which, in some cases, can lead to significant long-term morbidity. The techniques used to minimise perineal injury are frequently termed 'hands on' and 'hands poised' or 'hands off'. These terms are often undefined and used inconsistently in the literature, making it difficult to identify the best available evidence to inform midwifery practice. AIM: This study aimed to answer the research questions: What do midwives do to minimise perineal injury during birth and what influences their decision-making? METHODS: An ethnographic study was undertaken during 2016 in a maternity unit in the southeast of England. Data were collected through participant-observation, ethnographic and semi-structured interviews and analysed using thematic analysis, informed by the pedagogic theory of threshold concepts. FINDINGS: 31 midwives participated in the study. Evidence-based decision-making to minimise perineal injury during birth was identified as a complex concept. Within the context of threshold concept theory, three main themes were identified that contributed to the complexity: troublesome language, troublesome knowledge, and troublesome environments. CONCLUSIONS: Midwifery decision-making in the context of minimising perineal injury during birth is more varied and conceptually complex than has been previously described. Identification of the various aspects of troublesomeness in this context suggests that this element of practice is a midwifery threshold concept. Addressing this within midwifery curricula and practice education to enable evidence-based decision-making is important.

Clinical trial recruitment of people who speak languages other than English: a Children's Oncology Group report.

BACKGROUND: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Children's Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size and type as well as respondent role. RESULTS: The survey was sent to 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) of those respondents had access to short-form consent forms. Full consent form translation was required at 50% of institutions, and 12% of institutional review boards restricted use of centrally translated consent forms. Forty-six percent (n = 64) of institutions reported insufficient funding to support translation costs; 19% (n = 26) had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most frequently cited barrier (56%) to obtaining consent was lack of available in-person interpreters. Forty-seven percent (n = 65) reported that recruiting persons who speak languages other than English to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak languages other than English for clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials.

Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis.

Polymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Pulmonary exacerbations (PEx) in these conditions are associated with accelerated lung function decline and higher mortality rates. Understanding PEx ecology is challenged by high inter-patient variability in airway microbial community profiles. We analyze bacterial communities in 880 CF sputum samples collected during an observational prospective cohort study and develop microbiome descriptors to model community reorganization prior to and during 18 PEx. We identify two microbial dysbiosis regimes with opposing ecology and dynamics. Pathogen-governed PEx show hierarchical community reorganization and reduced diversity, whereas anaerobic bloom PEx display stochasticity and increased diversity. A simulation of antimicrobial treatment predicts better efficacy for hierarchically organized communities. This link between PEx, microbiome organization, and treatment success advances the development of personalized clinical management in CF and, potentially, other obstructive lung diseases.