Maternal and child nutrition services associated with nutritional knowledge and practices, India.

Objective: To evaluate whether maternal and child nutrition activities provided through the Indian Integrated Child Development Services scheme in India were associated with improved nutritional knowledge and practices among beneficiary women. Methods: We used a multistage sampling design to randomly select 4400 pregnant women or mothers of children younger than 2 years for a cross-sectional telephone survey. The respondents were beneficiaries of the scheme from across 11 Indian states. We used multivariate regression models controlling for sociodemographic factors to estimate the association between: scheme activities and nutrition messages heard; and scheme activities and nutrition practices. We also estimated the proportion of the total association with nutrition practices which was mediated by nutrition messages. Results: Among 110 regression models testing unique pairs of seven activities and 18 nutrition messages, 103 showed a statistically significant positive relationship (median risk ratio, RR: 1.14). For activities and nine nutrition practices, 39 out of 54 tested pairs were significantly associated (median RR: 1.16). We observed statistically significant mediation through nutrition messages for 28 out of 42 tested pairs of activities and nutrition practices. Conclusion: Receipt of the scheme's activities was associated with improved nutrition knowledge and practices. Improvements in practices were statistically mediated by improvements in knowledge. These findings suggest that a large-scale nutrition scheme with a strong counselling component could successfully change beneficiary behaviours.

Mortality and costs related to severe acute pancreatitis in the intensive care units of Australia and New Zealand (ANZ), 2003-2020.

BACKGROUND AND OBJECTIVE: Comprehensive data on the burden of severe acute pancreatitis (SAP) in global intensive care units (ICUs) and trends over time are lacking. Our objective was to compare trends in hospital and ICU mortality, in-hospital and ICU length of stay, and costs related to ICU admission in Australia and New Zealand (ANZ) for SAP. METHODS: We performed a retrospective, observational, cohort study of ICU admissions reported to the ANZ Intensive Care Society Adult Patient Database over three consecutive six-year time periods from 2003 to 2020. RESULTS: 12,635 patients with SAP from 189 ICUs in ANZ were analysed. No difference in adjusted hospital mortality (11.4% vs 11.5% vs 11.0%, p = 0.85) and ICU mortality rates (7.5% vs 8.0% vs 8.1%, p = 0.73) were noted over the study period. Median length of hospital admission reduced over time (13.9 days in 2003-08, 13.1 days in 2009-14 and 12.5 days in 2015-20; p < 0.01). No difference in length of ICU stay was noted over the study period (p = 0.13). The cost of managing SAP in ANZ ICUs remained constant over the three time periods. CONCLUSIONS: In critically-ill SAP patients in ANZ, no change in mortality has been noted over nearly two decades. There was a slight reduction in hospital stay (1 day), while the length of ICU stay remained unchanged. Given the significant costs related to care of patients with SAP in ICU, these findings highlight the need to prioritise resource allocation for healthcare delivery and targeted clinical research to identify treatments aimed at reducing mortality.

Anemia Etiology in Ethiopia: Assessment of Nutritional, Infectious Disease, and Other Risk Factors in a Population-Based Cross-Sectional Survey of Women, Men, and Children.

BACKGROUND: While the causes of anemia at an individual level (such as certain nutritional deficiencies, infections, and genetic disorders) are well defined, there is limited understanding of the relative burden of anemia attributable to each cause within populations. OBJECTIVES: We sought to estimate the proportion of anemia cases attributable to nutrition, infectious diseases, and other risk factors among women, men, and children in 6 regions of Ethiopia. METHODS: A population-based cross-sectional study was conducted. Data were obtained from 2520 women of reproductive age (15-49 y), 1044 adult men (15-49 y), and 1528 children (6-59 mo). Participants provided venous blood samples for assessment of their hemoglobin concentration; ferritin, folate, vitamin B12, and C-reactive protein levels; and the presence of malaria infection. Stool samples were collected to ascertain the helminth infection status. Sociodemographic questionnaires and a 24-h diet recall were administered. Population-weighted prevalences of anemia and risk factors were calculated. Multivariable-adjusted associations of risk factors with anemia and partial population attributable risk percentages were estimated using generalized linear models. RESULTS: The anemia prevalences were 17% (95% CI: 13%-21%) among women, 8% (95% CI: 6%-12%) among men, and 22% (95% CI: 19%-26%) among children. Low serum ferritin contributed to 11% (95% CI: -1% to 23%) of anemia cases among women, 9% (95% CI: 0%-17%) among men, and 21% (95% CI: 4%-34%) among children. The proportions of anemia attributable to low serum folate were estimated at 25% (95% CI: 5%-41%) among women and 29% (95% CI: 11%-43%) among men. Dietary iron intake was adequate for nearly all participants, while inadequacy was common for folate and vitamin B12. Inflammation and malaria were responsible for less than 1 in 10 anemia cases. CONCLUSIONS: Folate deficiency, iron deficiency, and inflammation appear to be important contributors to anemia in Ethiopia. Folic acid food fortification, targeted iron interventions, and strategies to reduce infections may be considered as potential public health interventions to reduce anemia in Ethiopia.

Assessing public financing for nutrition in Bhutan, Nepal and Sri Lanka.

The objective of this study was to assess public financing for nutrition in Bhutan, Nepal and Sri Lanka to identify limitations of available data and to discuss policy implications. A variant of the Scaling Up Nutrition Movement methodology was used. Budget allocations and expenditures for relevant government ministries during 2012-2018 were identified. Nutrition-related line items were tagged using definitions of nutrition-specific and nutrition-sensitive interventions. Data were aggregated by year and calculated in constant United States dollars (USD). Expenditures by year were presented as a proportion of gross domestic product and general government expenditures. The percent utilization of budget allocations and proportion of funding from central government sources were determined. Per capita expenditures on nutrition-specific interventions varied from USD 1.08-8.76 and for nutrition-sensitive interventions varied from USD 20.22-51.20. Nutrition-specific expenditures as a percent of gross domestic product ranged from 0.08% in Sri Lanka in 2017% to 0.34% in Nepal in 2016. The median utilization rate was 64% for nutrition-specific and 84% for nutrition-sensitive interventions. Nutrition-specific funding financed by the central government was 90.7% in Bhutan and 99.4% in Sri Lanka. This study revealed the need to prioritize and invest in evidence-based interventions, including balancing investments in nutrition-specific versus -sensitive interventions. Challenges in estimation of nutrition expenditures and cross-country comparison were also observed, highlighting the need for appropriate nutrition line item tagging and standardized systems for data collection.

The Global Diet Quality Score is Associated with Higher Nutrient Adequacy, Midupper Arm Circumference, Venous Hemoglobin, and Serum Folate Among Urban and Rural Ethiopian Adults.

BACKGROUND: Nutritionally inadequate diets in Ethiopia contribute to a persisting national burden of adult undernutrition, while the prevalence of noncommunicable diseases (NCDs) is rising. OBJECTIVES: To evaluate performance of a novel Global Diet Quality Score (GDQS) in capturing diet quality outcomes among Ethiopian adults. METHODS: We scored the GDQS and a suite of comparison metrics in secondary analyses of FFQ and 24-hour recall (24HR) data from a population-based cross-sectional survey of nonpregnant, nonlactating women of reproductive age and men (15-49 years) in Addis Ababa and 5 predominately rural regions. We evaluated Spearman correlations between metrics and energy-adjusted nutrient adequacy, and associations between metrics and anthropometric/biomarker outcomes in covariate-adjusted regression models. RESULTS: In the FFQ analysis, correlations between the GDQS and an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B12 adequacy were 0.32 in men and 0.26 in women. GDQS scores were inversely associated with folate deficiency in men and women (GDQS Quintile 5 compared with Quintile 1 OR in women, 0.50; 95% CI: 0.31-0.79); inversely associated with underweight (OR, 0.63; 95% CI: 0.44-0.90), low midupper arm circumference (OR, 0.61; 95% CI: 0.45-0.84), and anemia (OR, 0.59; 95% CI: 0.38-0.91) in women; and positively associated with hypertension in men (OR: 1.77, 95% CI: 1.12-2.80). For comparison, the Minimum Dietary Diversity-Women (MDD-W) was associated more positively (P < 0.05) with overall nutrient adequacy in men and women, but also associated with low ferritin in men, overweight/obesity in women, and hypertension in men and women. In the 24HR analysis (restricted to women), the MDD-W was associated more positively (P < 0.05) with nutrient adequacy than the GDQS, but also associated with low ferritin, while the GDQS was associated inversely with anemia. CONCLUSIONS: The GDQS performed capably in capturing nutrient adequacy-related outcomes in Ethiopian adults. Prospective studies are warranted to assess the GDQS' performance in capturing NCD outcomes in sub-Saharan Africa.

In situ TEM modification of individual silicon nanowires and their charge transport mechanisms.

Correlating the structure and composition of nanowires grown by the vapour-liquid-solid (VLS) mechanism with their electrical properties is essential for designing nanowire devices. In situ transmission electron microscopy (TEM) that can image while simultaneously measuring the current-voltage (I-V) characteristics of individual isolated nanowires is a unique tool for linking changes in structure with electronic transport. Here we grow and electrically connect silicon nanowires inside a TEM to perform in situ electrical measurements on individual nanowires both at high temperature and upon surface oxidation, as well as under ambient conditions. As-grown, the oxide-free nanowires have nonlinear I-V characteristics. We analyse the I-V measurements in terms of both bulk and injection limited transport models, finding Joule heating effects, bulk-limiting effects for thin nanowires and an injection-limiting effect for thick wires when high voltages are applied. When the nanowire surface is modified by in situ oxidation, drastic changes occur in the electronic properties. We investigate the relation between the observed geometry, changes in the surface structure and changes in electronic transport, obtaining information for individual nanowires that is inaccessible to other measuring techniques.

Energy needs in the treatment of uncomplicated severe acute malnutrition: Secondary analysis to optimize delivery of ready-to-use therapeutic foods.

Outpatient therapeutic feeding protocols for the treatment of uncomplicated severe acute malnutrition in children were initially based on weight gain data from inpatient settings and expert knowledge of the physiological requirements during recovery. However, weight gain and energy requirements from historic inpatient settings may differ from modern outpatient settings and therefore may not be appropriate to guide current therapeutic feeding protocols. We calculated the weight gain and average estimated total daily energy requirement of children successfully treated for uncomplicated severe acute malnutrition as outpatients in Niger (n = 790). Mean energy provided by six therapeutic feeding protocols was calculated and compared with average estimated energy requirements in the study population. Overall weight gain was 5.5 g·kg-1 ·day-1 among recovered children. Average energy requirements ranged from 92 to 110 kcal·kg-1 ·day-1 depending on the estimation approach. Two current therapeutic feeding protocols were found to provide an excess of energy after the first week of treatment in our study population, whereas four research protocols tended to provide less energy than the estimated requirement after the first week of treatment. Alternative feeding protocols have the potential to simplify and lead to important savings for programmes but should be evaluated to show adequacy to meet the energy needs of children under treatment, as well as feasibility and cost efficiency. Our findings rely on theoretical calculations based on several assumptions and should be confirmed in field studies.

Anemia prevalence and etiology among women, men, and children in Ethiopia: a study protocol for a national population-based survey.

BACKGROUND: Anemia remains a public health challenge in Ethiopia, affecting an estimated 56% of children under age 5 years, 23% of women of reproductive age and 18% of adult men. However, anemia etiology and the relative contribution of underlying risk factors for anemia remains unclear and has hindered implementation of anemia control programs. METHODS/DESIGN: Anemia Etiology in Ethiopia (AnemEE) is a population-based cross-sectional survey of six regions of Ethiopia that includes children, women of reproductive age, and men from regionally representative households. The survey will include detailed assessment of anemia, iron, inflammatory and nutritional biomarkers, diet, comorbidities, and other factors. The objectives of AnemEE are 1) to generate evidence for decision-making on the etiology of anemia in Ethiopia among men, women and children and 2) to simulate the potential effect of iron fortification and other interventions on the prevalence of anemia and risk of iron overload. DISCUSSION: AnemEE will provide the most comprehensive evaluation of anemia etiology in Ethiopia to date due to its detailed assessment of diet, biomarkers, infections and other risk factors in a population-based sample. By generating evidence and simulating potential interventions, AnemEE will inform the development of high-impact anemia control programs and policies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04002466 . Registered on 28 June 2019. Retrospectively registered.

A Systematic Review of Outcome Measures Employed in Aneurysmal Subarachnoid Hemorrhage (aSAH) Clinical Research.

Consensus on appropriate outcome measures to use in aneurysmal subarachnoid hemorrhage (aSAH) research has not been established, although the transition toward a core outcome set (COS) would provide significant benefits. To inform COS development, we conducted a systematic review to identify outcome measures included in reports of randomized clinical trials (RCTs) of interventions in patients with aSAH. Ovid Medline, EMBASE, CINAHL, and CENTRAL were searched. RCTs investigating aSAH published between January 1996 and May 2015 were included. The primary and secondary outcomes of RCTs were recorded and classified according to the OMERACT Consortium's framework. We identified 1093 potential studies of which 129 met inclusion criteria representing 24 238 patients. There were 285 unique outcome measures. The Glasgow Outcome Scale (GOS) was the most frequently used primary outcome (13/129, 10.1%). Mortality was reported in 84 trials (65.1%) with 3 months the most common time point (34/129, 26.4%). The GOS (65/129, 50.4%) and the Modified Rankin Scale (51/129, 39.5%) were the most commonly reported functional measures; however, these were reported at different time points and often dichotomized using different ranges. Patient-reported quality of life measures were used in 11 trials (8.5%). Transcranial Doppler was the most frequently used imaging modality (40/129, 31.0%). Definitions and reporting of vasospasm, delayed cerebral ischemia and imaging modality results were highly variable. The marked heterogeneity of outcomes in reports of RCTs supports the development of a core outcome set for aSAH trials. Our study has identified a wide range of outcomes for potential inclusion in a future aSAH COS.

MUAC as the sole discharge criterion from community-based management of severe acute malnutrition in Burkina Faso.

The use of mid upper arm circumference (MUAC) measurement to screen and determine eligibility for admission to therapeutic feeding programs has been established, but evidence and programmatic experience to inform guidance on the use of MUAC as a discharge criterion is limited. We present results from a large-scale nutritional program using MUAC for admission and discharge and compare program outcomes and response to treatment when determining eligibility for discharge by proportional weight gain versus discharge by MUAC. The study population included all children admitted to the Ministry of Health therapeutic feeding program supported by Médecins Sans Frontières in northern Burkina Faso from September 2007 to December 2011 (n = 50,841). Recovery was high overall using both discharge criteria, with low risks of death, nonresponse, and transfer to inpatient care and high daily gains in weight, MUAC, weight-for-height Z score, and height. When discharge was made by MUAC only, recovery increased, while all adverse program outcomes and length of stay decreased, with increasing MUAC on admission. MUAC-based programming, where MUAC is integrated into program screening, admission, and discharge, is one of several new approaches that can be used to target resources to the most at-risk malnourished children and improve program efficiency and coherency. This analysis provides additional programmatic experience on the use of MUAC-based discharge criterion, but more work may be needed to inform optimal discharge thresholds across settings.

Early childhood development coming of age: science through the life course.

Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course.

Stunting in Infancy Is Associated with Decreased Risk of High Body Mass Index for Age at 8 and 12 Years of Age.

BACKGROUND: Effects of early-life stunting on adiposity development later in childhood are not well understood, specifically with respect to age in the onset of overweight and obesity. OBJECTIVES: We analyzed associations of infant stunting with prevalence of, incidence of, and reversion from high body mass index-for-age z score (BMIZ) later in life. We then estimated whether associations of infant stunting with BMIZ varied by sex, indigenous status, and rural or urban residence. METHODS: Data were collected from 1942 Peruvian children in the Young Lives cohort study at ages 1, 5, 8, and 12 y. Multivariable generalized linear models estimated associations of stunting (height-for-age z score <-2) at age 1 y with risk of BMIZ > 1 and BMIZ > 2 prevalence, incidence (moving above a BMIZ threshold between ages), and reversion (moving below a BMIZ threshold between ages) at later ages. RESULTS: After adjustment for covariates, stunting at age 1 y was associated with a lower prevalence of BMIZ > 1 at age 8 y (RR: 0.81; 95% CI: 0.66, 1.00; P = 0.049) and 12 y (RR: 0.75; 95% CI: 0.61, 0.91; P = 0.004), as well as a lower prevalence of BMIZ > 2 at age 8 y. Stunting was not associated with incident risk of BMIZ > 1 or BMIZ > 2. Stunting was positively associated at age 5 y with risk of reversion from BMIZ > 1 (RR: 1.22; 95% CI: 1.05, 1.42; P = 0.008) and BMIZ > 2. We found evidence that the association of stunting with prevalent and incident BMIZ > 1 was stronger for urban children at ages 5 and 8 y, and for nonindigenous children at age 8 y. CONCLUSIONS: Stunting predicted a lower risk of prevalent BMIZ > 1 and BMIZ > 2, even after controlling for potential confounders. This finding may be driven in part by a higher risk of reversion from BMIZ > 1 by age 5 y. Our results contribute to an understanding of how nutritional stunting in infancy is associated with BMIZ later in life.

Participation in the Juntos Conditional Cash Transfer Program in Peru Is Associated with Changes in Child Anthropometric Status but Not Language Development or School Achievement.

BACKGROUND: It is unclear what effects a conditional cash transfer (CCT) program would have on child anthropometry, language development, or school achievement in the context of the nutrition transition experienced by many low- and middle-income countries. OBJECTIVE: We estimated the association of participation in Peru's Juntos CCT with anthropometry, language development, and school achievement among children aged 7-8 y. METHODS: We used data from the Young Lives Study of a cohort born between 2001 and 2002. We estimated associations of the Juntos program with height-for-age z score (HAZ), body mass index-for-age z score (BAZ), stunting, and overweight at age 7-8 y separately for children participating in the program for ≥2 y (n = 169) and children participating for <2 y (n = 188). We then estimated associations with receptive vocabulary and grade achievement among children who had been assessed at age 4-6 y before enrollment in Juntos (n = 243). We identified control subjects using propensity score matching and conducted difference-in-differences comparisons. RESULTS: Juntos participation was associated with increases in HAZ among boys participating for ≥2 y [average effect of treatment among the treated (ATT): 0.43; 95% CI: 0.09, 0.77; P = 0.01] and for boys participating for <2 y (ATT: 0.52; 95% CI: 0.23, 0.80; P < 0.01). Among girls participating in the program for ≥2 y, BAZ declined (ATT: -0.60; 95% CI: -1.00, -0.21; P < 0.01) as did the prevalence of overweight (ATT: -22.0 percentage points; 95% CI: -42.5, -2.7 percentage points; P = 0.03). We observed no significant associations of Juntos participation with receptive vocabulary or grade attainment. CONCLUSIONS: CCT program participation in Peru was associated with better linear growth among boys and decreased BAZ among girls, highlighting that a large-scale poverty-alleviation intervention may influence anthropometric outcomes in the context of the nutrition transition.

No global consensus: a cross-sectional survey of maternal weight policies.

BACKGROUND: Growing evidence suggests that maternal prepregnancy weight and gestational weight gain are risk factors for perinatal complications and subsequent maternal and child health. Postpartum weight retention is also associated with adverse birth outcomes and maternal obesity. Clinical guidelines addressing healthy weight before, during, and after pregnancy have been introduced in some countries, but at present a systematic accounting for these policies has not been conducted. The objective of the present study was to conduct a cross-national comparison of maternal weight guidelines. METHODS: This cross sectional survey administered a questionnaire online to key informants with expertise on the subject of maternal weight to assess the presence and content of preconceptional, pregnancy and postpartum maternal weight guidelines, their rationale and availability. We searched 195 countries, identified potential informants in 80 and received surveys representing 66 countries. We estimated the proportion of countries with guidelines by region, income, and formal or informal policy, and described and compared guideline content, including a rubric to assess presence or absence of 4 guidelines: encourage healthy preconceptional weight, antenatal weighing, encourage appropriate gestational gain, and encourage attainment of healthy postpartum weight. RESULTS: Fifty-three countries reported either a formal or informal policy regarding maternal weight. The majority of these policies included guidelines to assess maternal weight at the first prenatal visit (90%), to monitor gestational weight gain during pregnancy (81%), and to provide recommendations to women about healthy gestational weight gain (62%). Guidelines related to preconceptional (42%) and postpartum (13%) weight were less common. Only 8% of countries reported policies that included all 4 fundamental guidelines. Guideline content and rationale varied considerably between countries, and respondents perceived that within their country, policies were not widely known. CONCLUSIONS: These results suggest that maternal weight is a concern throughout the world. However, we found a lack of international consensus on the content of guidelines. Further research is needed to understand which recommendations or interventions work best with respect to maternal weight in different country settings, and how pregnancy weight policies impact clinical practices and health outcomes for the mother and child.

Defining the correlates of lymphopenia and independent predictors of poor clinical outcome in adults hospitalized with COVID-19 in Australia.

Lymphopenia is a common feature of acute COVID-19 and is associated with increased disease severity and 30-day mortality. Here we aim to define the demographic and clinical characteristics that correlate with lymphopenia in COVID-19 and determine if lymphopenia is an independent predictor of poor clinical outcome. We analysed the ENTER-COVID (Epidemiology of hospitalized in-patient admissions following planned introduction of Epidemic SARS-CoV-2 to highly vaccinated COVID-19 naïve population) dataset of adults (N = 811) admitted for COVID-19 treatment in South Australia in a retrospective registry study, categorizing them as (a) lymphopenic (lymphocyte count < 1 × 109/L) or (b) non-lymphopenic at hospital admission. Comorbidities and laboratory parameters were compared between groups. Multiple regression analysis was performed using a linear or logistic model. Intensive care unit (ICU) patients and non-survivors exhibited lower median lymphocyte counts than non-ICU patients and survivors respectively. Univariate analysis revealed that low lymphocyte counts associated with hypertension and correlated with haemoglobin, platelet count and negatively correlated with urea, creatinine, bilirubin, and aspartate aminotransferase (AST). Multivariate analysis identified age, male, haemoglobin, platelet count, diabetes, creatinine, bilirubin, alanine transaminase, c-reactive protein (CRP) and lactate dehydrogenase (LDH) as independent predictors of poor clinical outcome in COVID-19, while lymphopenia did not emerge as a significant predictor.

Dysregulation of CD4+ and CD8+ resident memory T, myeloid, and stromal cells in steroid-experienced, checkpoint inhibitor colitis.

BACKGROUND: Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear. METHODS: Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations. RESULTS: CPI colitis biopsies showed enrichment of CD4+resident memory (RM) T cells in addition to CD8+ RM and cytotoxic CD8+ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38+ HLA-DR+ CD4+ RM and cytotoxic CD8+ T cells were enriched in steroid-experienced and a validation data set of steroid-naïve CPI colitis, underscoring their pathogenic potential across steroid exposure. Distinct from ulcerative colitis, CPI colitis exhibited perturbed stromal metabolism (NAD+, tryptophan) impacting epithelial survival and inflammation. Endothelial cells in CPI colitis after anti-TNF and anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) upregulated the integrin α4ß7 ligand molecular vascular addressin cell adhesion molecule 1 (MAdCAM-1), which may preferentially respond to vedolizumab (anti-α4ß7). CONCLUSIONS: These findings nominate CD4+ RM and MAdCAM-1+ endothelial cells for targeting in specific subsets of CPI colitis patients.

What to Measure in Aneurysmal Subarachnoid Haemorrhage Research-An International Delphi Survey.

Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating condition with high mortality and morbidity. The outcome measures used in aSAH clinical research vary making it challenging to compare and combine different studies. Additionally, there may be a mismatch between the outcomes prioritized by patients, caregivers, and health care providers and those selected by researchers. We conducted an international, online, multiple round Delphi study to develop consensus on domains (where a domain is a health concept or aspect) prioritized by key stakeholders including those with lived experience of aSAH, health care providers, and researchers, funders, or industry professionals. One hundred seventy-five people participated in the survey, 59% of whom had lived experience of aSAH. Over three rounds, 32 domains reached the consensus threshold pre-defined as 70% of participants rating the domain as being critically important. During the fourth round, participants ranked the importance of each of these 32 domains. The top ten domains ranked highest to lowest were (1) Cognition and executive function, (2) Aneurysm obliteration, (3) Cerebral infarction, (4) Functional outcomes including ability to walk, (5) Delayed cerebral ischemia, (6) The overall quality of life as reported by the SAH survivor, (7) Changes to emotions or mood (including depression), (8) The basic activities of daily living, (9) Vasospasm, and (10) ICU complications. Our findings confirm that there is a mismatch between domains prioritized by stakeholders and outcomes used in clinical research. Our future work aims to address this mismatch through the development of a core outcome set in aSAH research.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.