exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids.

To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies.

Disparities in clinical trial enrollment at a Canadian comprehensive cancer center: A 15-year retrospective study.

INTRODUCTION: Disparities in clinical trials (CTs) enrollment perpetuate inequities in treatment access and outcomes, but there is a paucity of Canadian data. The objective of this study was to examine disparities in cancer CT enrollment at a large Canadian comprehensive cancer center. METHODS: Retrospective study of CT enrollment among new patient consultations from 2006 to 2019, with follow-up to 2021 (N = 154,880), with the primary outcome of enrollment as a binary variable. Factors associated with CT enrollment were evaluated using multivariable Bayesian hierarchical logistic regression with random effects for most responsible physician (MRP) and geography, adjusted for patient characteristics (sex, age, language, geography, and primary care provider [PCP]), area-level marginalization (residential instability, material deprivation, dependency, and ethnic concentration), disease (cancer site and stage), and MRP (department, sex, language, and training). A sensitivity analysis of the cumulative incidence of enrollment was conducted to account for differences in disease type and follow-up length. RESULTS: CT enrollment was 11.2% overall, with a 15-year cumulative incidence of 18%. Lower odds of enrollment were observed in patients who were female (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.78-0.86), ≥65 years (AOR vs. <40, 0.61; 95% CI, 0.56-0.66), non-English speakers (0.72; 95% CI, 0.67-0.77), living ≥250 km away (AOR vs. <15 km, 0.71; 95% CI, 0.62-0.80), and without a PCP. Disease characteristics accounted for the largest proportion of observed variation (20.8%), with significantly greater odds of enrollment in patients with genitourinary cancers and late-stage disease. CONCLUSION: Significant sociodemographic disparities were observed, suggesting the need for targeted strategies to increase diversity in access to cancer CTs in Canada.

PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors.

Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that crucial target genes regulated by PRDM16 are neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidence to support the finding that neural progenitors temporally shift the gene expression program to achieve neural cell diversity.

Forecasting the Incidence and Prevalence of Inflammatory Bowel Disease: A Canadian Nationwide Analysis.

INTRODUCTION: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. METHODS: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. RESULTS: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). DISCUSSION: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.

The NanoFlow Repository.

MOTIVATION: Extracellular particles (EPs) are the focus of a rapidly growing area of exploration due to the widespread interest in understanding their roles in health and disease. However, despite the general need for EP data sharing and established community standards for data reporting, no standard repository for EP flow cytometry data captures rigor and minimum reporting standards such as those defined by MIFlowCyt-EV (https://doi.org/10.1080/20013078.2020.1713526). We sought to address this unmet need by developing the NanoFlow Repository. RESULTS: We have developed The NanoFlow Repository to provide the first implementation of the MIFlowCyt-EV framework. AVAILABILITY AND IMPLEMENTATION: The NanoFlow Repository is freely available and accessible online at https://genboree.org/nano-ui/. Public datasets can be explored and downloaded at https://genboree.org/nano-ui/ld/datasets. The NanoFlow Repository's backend is built using the Genboree software stack that powers the ClinGen Resource, specifically the Linked Data Hub (LDH), a REST API framework written in Node.js, developed initially to aggregate data within ClinGen (https://ldh.clinicalgenome.org/ldh/ui/about). NanoFlow's LDH (NanoAPI) is available at https://genboree.org/nano-api/srvc. NanoAPI is supported by a Node.js Genboree authentication and authorization service (GbAuth), a graph database called ArangoDB, and an Apache Pulsar message queue (NanoMQ) to manage data inflows into NanoAPI. The website for NanoFlow Repository is built with Vue.js and Node.js (NanoUI) and supports all major browsers.

NK cells and monocytes modulate primary HTLV-1 infection.

We investigated the impact of monocytes, NK cells, and CD8+ T-cells in primary HTLV-1 infection by depleting cell subsets and exposing macaques to either HTLV-1 wild type (HTLV-1WT) or to the HTLV-1p12KO mutant unable to infect replete animals due to a single point mutation in orf-I that inhibits its expression. The orf-I encoded p8/p12 proteins counteract cytotoxic NK and CD8+ T-cells and favor viral DNA persistence in monocytes. Double NK and CD8+ T-cells or CD8 depletion alone accelerated seroconversion in all animals exposed to HTLV-1WT. In contrast, HTLV-1p12KO infectivity was fully restored only when NK cells were also depleted, demonstrating a critical role of NK cells in primary infection. Monocyte/macrophage depletion resulted in accelerated seroconversion in all animals exposed to HTLV-1WT, but antibody titers to the virus were low and not sustained. Seroconversion did not occur in most animals exposed to HTLV-1p12KO. In vitro experiments in human primary monocytes or THP-1 cells comparing HTLV-1WT and HTLV-1p12KO demonstrated that orf-I expression is associated with inhibition of inflammasome activation in primary cells, with increased CD47 "don't-eat-me" signal surface expression in virus infected cells and decreased monocyte engulfment of infected cells. Collectively, our data demonstrate a critical role for innate NK cells in primary infection and suggest a dual role of monocytes in primary infection. On one hand, orf-I expression increases the chances of viral transmission by sparing infected cells from efferocytosis, and on the other may protect the engulfed infected cells by modulating inflammasome activation. These data also suggest that, once infection is established, the stoichiometry of orf-I expression may contribute to the chronic inflammation observed in HTLV-1 infection by modulating monocyte efferocytosis.

Effective peripheral blood stem cell collection in a 4.6-kg child.

BACKGROUND: Due to unique technical challenges, effective peripheral blood stem cell collections (PBSCs) have not been consistently reported in patients weighing less than 5 kg. We describe three PBSCs performed in a 4.6-kg child undergoing myeloablative chemotherapy for high-grade glioma. STUDY DESIGN AND METHODS: A multidisciplinary group representing the clinical and apheresis teams adapted a PBSC protocol to accommodate the patient's size and collection targets. Special considerations included timing of the collection relative to chemotherapy, vascular access, strategies for monitoring adverse events during collection, and contingencies. RESULTS AND DISCUSSION: The patient underwent three PBSC procedures over 2 days due to suboptimal collection after the first two procedures. For procedure 1, a conservative inlet: anticoagulant (AC) ratio and AC infusion rate of 15 and 0.6 mL/min/L total blood volume (TBV) resulted in premature discontinuation due to clotting. A ratio of 8 and AC infusion rate of 1.5-1.7 mL/min/L TBV with subsequent titration to higher levels were adopted for the second and third procedures. These changes resulted in greater acid-citrate-dextrose exposure, that was managed by continuous calcium chloride infusion. There was no hypocalcemia, hypotension, or distress during any procedure. A total of 15 × 106 CD34+ cells/kg were collected. This retrospective review illustrates that PBSC can be safely undertaken in children weighing less than 5 kg.

Prevalence of Positive Childhood Experiences Among Adults - Behavioral Risk Factor Surveillance System, Four States, 2015-2021.

Positive childhood experiences (PCEs) promote optimal health and mitigate the effects of adverse childhood experiences, but PCE prevalence in the United States is not well-known. Using Behavioral Risk Factor Surveillance System data, this study describes the prevalence of individual and cumulative PCEs among adults residing in four states: Kansas (2020), Montana (2019), South Carolina (2020), and Wisconsin (2015). Cumulative PCE scores were calculated by summing affirmative responses to seven questions. Subscores were created for family-related (three questions) and community-related (four questions) PCEs. The prevalence of individual PCEs varied from 59.5% (enjoyed participating in community traditions) to 90.5% (adult in respondents' household made them feel safe), and differed significantly by race and ethnicity, age, and sexual orientation. Fewer non-Hispanic Black or African American (49.2%), non-Hispanic Alaska Native or American Indian (37.7%), and Hispanic or Latino respondents (38.9%) reported 6-7 PCEs than did non-Hispanic White respondents (55.2%). Gay or lesbian, and bisexual respondents were less likely than were straight respondents to report 6-7 PCEs (38.1% and 27.4% versus 54.7%, respectively). A PCE score of 6-7 was more frequent among persons with higher income and education. Improved understanding of the relationship of PCEs to adult health and well-being and variation among population subgroups might help reduce health inequities.

Mobile health technologies to improve walking distance in people with intermittent claudication.

BACKGROUND: Peripheral arterial disease (PAD) is the obstruction or narrowing of the large arteries of the lower limbs, which can result in impaired oxygen supply to the muscle and other tissues during exercise, or even at rest in more severe cases. PAD is classified into five categories (Fontaine classification). It may be asymptomatic or various levels of claudication pain may be present; at a later stage, there may be ulceration or gangrene of the limb, with amputation occasionally being required. About 20% of people with PAD suffer from intermittent claudication (IC), which is muscular discomfort in the lower extremities induced by exertion and relieved by rest within 10 minutes; IC causes restriction of movement in daily life. Treatment for people with IC involves addressing lifestyle risk factors. Exercise is an important part of treatment, but supervised exercise programmes for individuals with IC have low engagement levels and high attrition rates. The use of mobile technologies has been suggested as a new way to engage people with IC in walking exercise interventions. The novelty of the intervention, low cost for the user, automation, and ease of access are some of the advantages mobile health (mhealth) technologies provide that give them the potential to be effective in boosting physical activity in adults. OBJECTIVES: To assess the benefits and harms of mobile health (mhealth) technologies to improve walking distance in people with intermittent claudication. SEARCH METHODS: The Cochrane Vascular Information Specialist conducted systematic searches of the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and CINAHL, and also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov. The most recent searches were carried out on 19 December 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people aged 18 years or over with symptomatic PAD and a clinical diagnosis of IC. We included RCTs comparing mhealth interventions to improve walking distance versus usual care (no intervention or non-exercise advice), exercise advice, or supervised exercise programmes. We excluded people with chronic limb-threatening ischaemia (Fontaine III and IV). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were change in absolute walking distance from baseline, change in claudication distance from baseline, amputation-free survival, revascularisation-free survival. Our secondary outcomes were major adverse cardiovascular events, major adverse limb events, above-ankle amputation, quality of life, and adverse events. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included four RCTs involving a total of 614 participants with a clinical diagnosis of IC. The duration of intervention of the four included RCTs ranged from 3 to 12 months. Participants were randomised to either mhealth or control (usual care or supervised exercise programme). All four studies had an unclear or high risk of bias in one or several domains. The most prevalent risk of bias was in the area of performance bias, which was rated high risk as it is not possible to blind participants and personnel in this type of trial. Based on GRADE criteria, we downgraded the certainty of the evidence to low, due to concerns about risk of bias, imprecision, and clinical inconsistency. Comparing mhealth with usual care, there was no clear evidence of an effect on absolute walking distance (mean difference 9.99 metres, 95% confidence interval (CI) -27.96 to 47.93; 2 studies, 503 participants; low-certainty evidence). None of the included studies reported on change in claudication walking distance, amputation-free survival, or revascularisation-free survival. Only one study reported on major adverse cardiovascular events (MACE) and found no clear difference between groups (risk ratio 1.37, 95% CI 0.07 to 28.17; 1 study, 305 participants; low-certainty evidence). None of the included studies reported on major adverse limb events (MALE) or above-ankle amputations. AUTHORS' CONCLUSIONS: Mobile health technologies can be used to provide lifestyle interventions for people with chronic conditions, such as IC. We identified a limited number of studies that met our inclusion criteria. We found no clear difference between mhealth and usual care in improving absolute walking distance in people with IC; however, we judged the evidence to be low certainty. Larger, well-designed RCTs are needed to provide adequate statistical power to reliably evaluate the effects of mhealth technologies on walking distance in people with IC.

Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

COVID-19 Vaccination Uptake, Infection Rates, and Seropositivity Among Youth Experiencing Homelessness in the United States.

BACKGROUND: People experiencing homelessness are at greater risk of exposure and poor health outcomes from COVID-19. Yet, little data exists on the prevalence and correlates of COVID-19 among homeless populations. To mitigate the spread and severity, uptake of the COVID-19 vaccine is needed. This can be challenging among youth experiencing homelessness who are more likely to be unvaccinated when compared to stably housed youth. OBJECTIVE: We conducted this study to determine the prevalence and correlates of COVID-19 among youth experiencing homelessness. METHODS: We examined experiences of COVID-19 symptoms, self-report of infection, rates of COVID-19 antibodies and distinguished between natural and vaccinated immunity among youth experiencing homelessness (N = 265) recruited in one large metropolitan area in the South. RESULTS: Based on self-report, very few participants experienced any symptoms, and 80% had never been diagnosed with COVID-19. Of those with COVID-19 antibodies (68%), the proportion with antibodies resulting from natural infection was 44%. The vaccination rate was 42%. Younger and vaccinated participants and those in shelters were likelier to have COVID-19 antibodies. Black and Hispanic youth were more likely than White youth to have had COVID-19. Those who adopted only one or two prevention behaviors were more likely to acquire a natural infection than those who adopted three or more prevention behaviors. DISCUSSION: Youth experiencing homelessness report low vaccination rates, disrupted access to health care and social supports, and underlying chronic conditions, which may explain why they face poorer outcomes when infected with COVID-19. Vaccination and risk mitigation strategies to combat the high prevalence of COVID-19 are especially needed for sheltered youth who are at high risk yet are often asymptomatic.

A pre-implementation examination of barriers and facilitators of an electronic prospective surveillance model for cancer rehabilitation: a qualitative study.

BACKGROUND: An electronic Prospective Surveillance Model (ePSM) uses patient-reported outcomes to monitor symptoms along the cancer pathway for timely identification and treatment. Randomized controlled trials show that ePSMs can effectively manage treatment-related adverse effects. However, an understanding of optimal approaches for implementing these systems into routine cancer care is limited. This study aimed to identify barriers and facilitators prior to the implementation of an ePSM to inform the selection of implementation strategies. METHODS: A qualitative study using virtual focus groups and individual interviews was conducted with cancer survivors, oncology healthcare providers, and clinic leadership across four cancer centres in Canada. The Consolidated Framework for Implementation Research (CFIR) guided the interviews and analysis of barriers and facilitators based on five domains (intervention characteristics, individual characteristics, inner setting, outer setting, and process). RESULTS: We conducted 13 focus groups and nine individual interviews with 13 patient participants and 56 clinic staff. Of the 39 CFIR constructs, 18 were identified as relevant determinants to the implementation. The adaptability, relative advantage, and complexity of an ePSM emerged as key intervention-level factors that could influence implementation. Knowledge of the system was important at the individual level. Within the inner setting, major determinants were the potential fit of an ePSM with clinical workflows (compatibility) and the resources that could be dedicated to the implementation effort (readiness for implementation). In the outer setting, meeting the needs of patients and the availability of rehabilitation supports were key determinants. Engaging various stakeholders was critical at the process level. CONCLUSIONS: Improving the implementation of ePSMs in routine cancer care has the potential to facilitate early identification and management of treatment-related adverse effects, thereby improving quality of life. This study provides insight into important factors that may influence the implementation of an ePSM, which can be used to select appropriate implementation strategies to address these factors.

Identifying spatial neglect - an updated systematic review of the psychometric properties of assessment tools in adults post-stroke.

Spatial neglect commonly occurs after a stroke, resulting in diverse impacts depending on the type and severity. There are almost 300 tools for assessing neglect, yet there is a lack of knowledge on the psychometric properties of these tools. The objective of this systematic review, registered on Prospero (CRD42021271779), was to determine the quality of the evidence for assessing spatial neglect, categorized by neglect subtype. The following databases were searched on 3rd May 2022 from database inception: Ovid Emcare, Embase, Ovid MEDLINE, APA PsycINFO, Web of Science (SCI-EXPANDED; SSCI; A&HCI; ESCI) and Scopus. All primary peer-reviewed studies (>5 participants) of adults post stroke, reporting any psychometric property of 33 commonly used neglect assessment tools were included. The COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) risk of bias tool was used to assess the methodological quality of the studies and summarize the psychometric properties of each tool. 164 articles were included, with a total of 12,463 people with stroke. The general quality of the evidence was poor and no one tool had high-quality evidence of both validity and reliability. Eleven tools show some promise as they meet the minimum criteria for good measurement properties for both validity and reliability.

Extracellular Vesicle Refractive Index Derivation Utilizing Orthogonal Characterization.

The analysis of small particles, including extracellular vesicles and viruses, is contingent on their ability to scatter sufficient light to be detected. These detection methods include flow cytometry, nanoparticle tracking analysis, and single particle reflective image sensing. To standardize measurements and enable orthogonal comparisons between platforms, a quantifiable limit of detection is required. The main parameters that dictate the amount of light scattered by particles include size, morphology, and refractive index. To date, there has been a lack of accessible techniques for measuring the refractive index of nanoparticles at a single-particle level. Here, we demonstrate two methods of deriving a small particle refractive index using orthogonal measurements with commercially available platforms. These methods can be applied at either a single-particle or population level, enabling the integration of diameter and scattering cross section values to derive the refractive index using Mie theory.

Lessons learned from conducting a community-based, nurse-led HIV prevention trial with youth experiencing homelessness: Pivots and pitfalls.

OBJECTIVE: This article highlights key lessons learned while conducting a nurse-led community-based HIV prevention trial with youth experiencing homelessness (YEH), focusing on sexually transmitted infections testing and treatment, intervention sessions, community partnerships, and participant recruitment and retention. DESIGN: The insights and experiences shared aim to inform future research and the design of interventions targeting populations at high risk, particularly when facing unanticipated challenges. By addressing these areas, the article contributes to the decision-making for the design and delivery of effective strategies to improve the health outcomes among marginalized populations. RESULTS: The findings underscore the importance of flexibility and active participant engagement, cultivating strong relationships with community partners, utilizing technology and social media, and fostering a diverse research team that represents the heterogeneity of youth experiencing homelessness across race/ethnicity, gender identity, sexual orientation, and lived experiences. CONCLUSIONS: These recommendations aim to enhance participant access, engagement, and retention, while promoting rigorous research and meaningful study outcomes for YEH.

In-hospital end-of-life care: an appreciative analysis of bereaved family feedback.

Experience feedback data is increasingly recognised as being helpful in improving healthcare services, and in meeting patient and family needs. This end-of-life care project, based on the principles of appreciative inquiry, sought to learn from the experiences of bereaved people whose relative had died in an acute hospital setting. Informal feedback, offered during a routine telephone call, was thematically analysed and interpreted in an appreciative manner. Confirmatory representations of caring practices and behaviours were identified, categorised and disseminated in a way that enabled staff to come to know and understand end-of-life care at its best, rather than as a set of problematised events. The findings served as a benchmark for individuals and teams to assess and progress their practice reflectively. The authors conclude that staff receptiveness to informal bereaved family feedback may be enhanced by focusing on the positive qualities of end-of-life care within existing practices.

Prevalence of Salmonella in Stool During the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa. METHODS: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods. RESULTS: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P < .001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P = .04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P = .001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P = .002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%); NTS isolates were susceptible to ciprofloxacin at all sites. CONCLUSIONS: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa.

Shigella in Africa: New Insights From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: We evaluated the burden of Shigella spp from children aged 0-59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018. METHODS: Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis. RESULTS: The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%). CONCLUSIONS: A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin.

Stakeholders' perspectives on transplant metrics: the 2022 Scientific Registry of Transplant Recipients' consensus conference.

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions. Patients constituted 24% of the meeting participants. In this report, we document the proceedings and enumerate 160 recommendations, 10 of which have been highly prioritized. SRTR will use the recommendations to develop new presentations of information and metrics requested by stakeholders to support informed decision-making.

Responsiveness of Critically Ill Adults With Multimorbidity to Rehabilitation Interventions: A Patient-Level Meta-Analysis Using Individual Pooled Data From Four Randomized Trials.

OBJECTIVE: To explore if patient characteristics (pre-existing comorbidity, age, sex, and illness severity) modify the effect of physical rehabilitation (intervention vs control) for the coprimary outcomes health-related quality of life (HRQoL) and objective physical performance using pooled individual patient data from randomized controlled trials (RCTs). DATA SOURCES: Data of individual patients from four critical care physical rehabilitation RCTs. STUDY SELECTION: Eligible trials were identified from a published systematic review. DATA EXTRACTION: Data sharing agreements were executed permitting transfer of anonymized data of individual patients from four trials to form one large, combined dataset. The pooled trial data were analyzed with linear mixed models fitted with fixed effects for treatment group, time, and trial. DATA SYNTHESIS: Four trials contributed data resulting in a combined total of 810 patients (intervention n = 403, control n = 407). After receiving trial rehabilitation interventions, patients with two or more comorbidities had HRQoL scores that were significantly higher and exceeded the minimal important difference at 3 and 6 months compared with the similarly comorbid control group (based on the Physical Component Summary score (Wald test p = 0.041). Patients with one or no comorbidities who received intervention had no HRQoL outcome differences at 3 and 6 months when compared with similarly comorbid control patients. No patient characteristic modified the physical performance outcome in patients who received physical rehabilitation. CONCLUSIONS: The identification of a target group with two or more comorbidities who derived benefits from the trial interventions is an important finding and provides direction for future investigations into the effect of rehabilitation. The multimorbid post-ICU population may be a select population for future prospective investigations into the effect of physical rehabilitation.