REGENERATE-COBRA: A phase II randomized sham-controlled trial assessing the safety and efficacy of intracoronary administration of autologous bone marrow-derived cells in patients with refractory angina.

AIMS: The REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. METHODS: REGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months. CONCLUSIONS: This is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

Exploring residential relocation- differences between newcomers and settled residents in health, travel behaviour and neighbourhood perceptions.

This study explores whether people who have recently moved to an area differ from longer-term residents in their health, travel behaviour, and perceptions of the environment. Using a large, representative sample from the UKHLS, Newcomers demonstrate significantly lower mental and physical health, reduced car commuting, and a higher likelihood of liking their neighbourhood. Area deprivation, urbanicity, household income, and age emerge as influential moderators with i.e. Newcomers in affluent areas experiencing lower physical health than Settled Residents, and rural Newcomers expressing less neighbourhood satisfaction. Our findings highlight that Newcomers' perceptions of their environment diverge and environmental influences vary among population segments, potentially impacting related health behaviours such as active travel. Furthermore, residential relocation introduces Newcomers with distinct characteristics into areas, affecting the context in which potential population health interventions aiming to influence health behaviours operate. This necessitates a deeper understanding of what influences reactions to the environment as well as ongoing adaptation of environmental interventions to respond to changing contexts within the same location over time.

Maternal mental health and economic autonomy in lowland rural Nepal: Do parents-in-law provide constraint or support?

Background and objectives: In patrilocal societies, married women typically co-reside with their parents-in-law, who may act in their son's reproductive interests. These relationships may shape maternal mental health and autonomy. Few studies have examined these dynamics from an evolutionary perspective. Theoretically, marital kin may increase their fitness by increasing maternal investment or by reducing paternity uncertainty. We explored how co-residence with parents-in-law and husband is associated with maternal outcomes to evaluate whether marital kin provide support or constraint. Methodology: We analysed data from 444 households in rural lowland Nepal. Maternal mental health was assessed by General Health Questionnaire. Logistic regression models investigated whether, relative to mothers living with both husband and parents-in-law, those co-resident with other combinations of relatives had poorer mental health and lower household economic autonomy (decision-making, bargaining power), adjusting for socio-economic confounders. Results: Co-residence with husband only, or neither husband nor parents-in-law, was associated with higher odds of mothers reporting feeling worthless and losing sleep but also earning income and making household expenditure decisions. Husband co-residence was associated with overall maternal distress but also with less unpaid care work and greater decision-making responsibility. There were no differences in maternal outcomes for mothers living with parents-in-law only, relative to those living with both husbands and parents-in-law. Conclusions and implications: Co-residence of parents-in-law and husbands was associated with contrasting patterns of maternal mental health and economic autonomy. We suggest that different marital kin place different economic demands on mothers, while restricting their autonomy in different ways as forms of 'mate-guarding'.

DCM Support: cell therapy and circulatory support for dilated cardiomyopathy patients with severe ventricular impairment.

AIMS: The DCM Support trial (NCT03572660) uses a percutaneous circulatory support device (Impella CP, Abiomed, Danvers, MA, USA) to improve the safety of an intracoronary cell infusion procedure in patients with dilated cardiomyopathy (DCM) and a severely reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS: DCM Support is a single-site, single-arm Phase II trial enrolling 20 symptomatic DCM patients with an LVEF ≤ 35% despite optimal medical and device therapy. After 5 days of granulocyte colony-stimulating factor therapy and a subsequent bone marrow aspiration, patients undergo an intracoronary infusion of autologous bone-marrow-derived mononuclear cells. The Impella CP device is used to provide haemodynamic support during the infusion procedure. The trial's primary endpoint is change in LVEF from baseline at 3 months. Secondary efficacy endpoints are change in LVEF from baseline at 12 months, and change in exercise capacity, New York Heart Association class, quality of life, and N-terminal pro-B-type natriuretic peptide levels from baseline at 3 and 12 months. Safety endpoints include procedural safety and major adverse cardiac events at 3 and 12 months. CONCLUSIONS: This is the first trial to assess the safety and efficacy of cytokine and autologous intracoronary cell therapy with a procedural circulatory support device for patients with severe left ventricular impairment. This novel combination may allow us to target a patient population most at need of this therapy.

Prevalence of pre-eclampsia and adverse pregnancy outcomes in women with pre-existing cardiomyopathy: a multi-centre retrospective cohort study.

Pre-eclampsia is associated with postnatal cardiac dysfunction; however, the nature of this relationship remains uncertain. This multicentre retrospective cohort study aimed to determine the prevalence of pre-eclampsia in women with pre-existing cardiac dysfunction (left ventricular ejection fraction < 55%) and explore the relationship between pregnancy outcome and pre-pregnancy cardiac phenotype. In this cohort of 282 pregnancies, pre-eclampsia prevalence was not significantly increased (4.6% [95% C.I 2.2-7.0%] vs. population prevalence of 4.6% [95% C.I. 2.7-8.2], p = 0.99); 12/13 women had concurrent obstetric/medical risk factors for pre-eclampsia. The prevalence of preterm pre-eclampsia (< 37 weeks) and fetal growth restriction (FGR) was increased (1.8% vs. 0.7%, p = 0.03; 15.2% vs. 5.5%, p < 0.001, respectively). Neither systolic nor diastolic function correlated with pregnancy outcome. Antenatal ß blockers (n = 116) were associated with lower birthweight Z score (adjusted difference - 0.31 [95% C.I. - 0.61 to - 0.01], p = 0.04). To conclude, this study demonstrated a modest increase in preterm pre-eclampsia and significant increase in FGR in women with pre-existing cardiac dysfunction. Our results do not necessarily support a causal relationship between cardiac dysfunction and pre-eclampsia, especially given the population's background risk status. The mechanism underpinning the relationship between cardiac dysfunction and FGR merits further research but could be influenced by concomitant ß blocker use.

The role of education in child and adolescent marriage in rural lowland Nepal.

Marriage during childhood and adolescence adversely affects maternal and child health and well-being, making it a critical global health issue. Analysis of factors associated with women marrying ≥18 years has limited utility in societies where the norm is to marry substantially earlier. This paper investigated how much education Nepali women needed to delay marriage across the range of ages from 15 to ≥18 years. Data on 6,406 women aged 23-30 years were analysed from the Low Birth Weight South Asia Trial on the early-marrying and low-educated Maithili-speaking Madhesi population in Terai, Nepal. Multivariable logistic regression models assessed the associations of women's education with marrying aged ≥15, ≥16, ≥17 and ≥18 years. Cox proportional hazards regression models quantified the hazard of marrying. Models adjusted for caste affiliation. Women married at median age of 15 years and three-quarters were uneducated. Women's primary and lower-secondary education were weakly associated with delaying marriage, whether the cut-off to define early marriage was 15, 16, 17 or 18 years, with stronger associations for secondary education. Caste associations were weak. Overall, models explained relatively little of the variance in the likelihood of marriage at different ages. The joint effects of lower-secondary and higher caste affiliation and of secondary/higher education and mid and higher caste affiliation reduced the hazard of marrying. In early-marrying and low-educated societies, changing caste-based norms are unlikely to delay women's marriage. Research on broader risk factors and norms that are more relevant for delaying marriage in these contexts is needed. Gradual increases in women's median marriage age and increased secondary education may, over time, reduce child and adolescent marriage.

A longitudinal area classification of migration in Great Britain: Testing the application of Group-Based Multi-Trajectory Modelling.

The migration of people affects the geographical distribution of the population and the demographic composition of areas over the short, medium and long terms. To recognise and respond to the corresponding needs and challenges, including consequences for service provision, social cohesion and population health, there is a continuing need to understand migration patterns of the past and present. Area classifications are a useful tool to simplify the inherently complex data on migration flows and characteristics. Yet, existing classifications often lack direct migration measures or focus solely on cross-sectional data. This study addresses these limitations by employing Group-Based Multi-Trajectory Modelling (GBMTM) to create a longitudinal, migration-specific classification of Great Britain's wards from 1981 to 2011, using six migration indicators. Using U.K. census data, we reveal six distinct migration clusters that highlight the rapid growth in studentifying neighbourhoods, the continuous influx of migrants into inner cities, and a noticeable North-South divide in terms of movers' tenure enforced by persisting income selectivity. Additionally, the geographical distribution of clusters shows a common pattern in urban areas irrespective of size or location. The longitudinal perspective of our GBMTM classification highlights trends and changes in migration patterns that are not well reflected in either the general purpose or the cross-sectional migration classification that we used as comparators. We conclude that the method presented and the classification generated offer a novel lens on migration and provide new opportunities to explore the effects of migration on a variety of outcomes and at various scales.

Proangiogenic Growth Factor Therapy for the Treatment of Refractory Angina: A Meta-analysis.

Background: Refractory angina (RFA; limiting angina despite optimal medical therapy) is a growing, global problem, with limited treatment options. Therefore, we conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effect of proangiogenic growth factor therapy (in the form of vascular growth factors delivered either as recombinant proteins or gene therapy) in patients with RFA ineligible for revascularization. Methods: We performed a meta-analysis (PROSPERO: CRD42018107283) of RCTs as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. A comprehensive search of the PubMed, CENTRAL, Embase, Cochrane, ClinicalTrials.gov and Google Scholar databases, as well as scientific session abstracts, were performed. The pooled outcomes included major adverse cardiac events (MACE), mortality, myocardial perfusion, and indices of angina severity (Canadian Cardiovascular Society angina class [CCS] and exercise tolerance). A prespecified subgroup analysis was performed for delivery method, vector, and protein type. The standardized mean difference (SMD) or odds ratio (OR) was calculated to assess relevant outcomes. We assessed heterogeneity using the χ2 and I2 tests. Results: We included 16 RCTs involving 1607 patients (1052 received proangiogenic growth factor therapy and 555 received a placebo or optimal medical therapy). Our analysis showed a significant decreased risk of MACE (OR, 0.72; 95% confidence interval [CI], 0.55-0.93) and significantly improved CCS class (SMD, -0.55; 95% CI, -1.10 to 0.00), but not mortality (OR, 0.66; 95% CI, 0.28-1.54) or exercise tolerance (SMD, 0.47; 95% CI, -0.14 to 1.09), in treated patients compared to those in the control group. Conclusions: Proangiogenic growth factor therapy is a promising treatment option for RFA, with beneficial effects seen on MACE and CCS class. The results of ongoing trials are needed before it can be considered for clinical practice.

Cell administration routes for heart failure: a comparative re-evaluation of the REGENERATE-DCM and REGENERATE-IHD trials.

Aims: Given the logistical issues surrounding intramyocardial cell delivery, we sought to address the efficacy of the simpler, more accessible intracoronary route by re-evaluating REGENERATE-DCM and REGENERATE-IHD (autologous cell therapy trials for heart failure; n = 150). Methods: A retrospective statistical analysis was performed on the trials' combined data. The following end points were evaluated: left ventricular ejection fraction (LVEF), N-terminal pro brain natriuretic peptide concentration (NT-proBNP), New York Heart Association class (NYHA) and quality of life. Results: This demonstrated a new efficacy signal for intracoronary delivery, with significant benefits to: LVEF (3.7%; p = 0.01), NT-proBNP (median -76 pg/ml; p = 0.04), NYHA class (48% patients; p = 0.01) and quality of life (12 ± 19; p = 0.006). The improvements in LVEF, NYHA and quality of life scores remained significant compared to the control group. Conclusion: The efficacy and logistical simplicity of intracoronary delivery should be taken into consideration for future trials.

Trials of cell therapy for heart failure have not clearly identified the best method to deliver the cells to the heart. A small proportion of these studies have used the intracoronary method (which infuses the cells into the heart's arteries) as it was thought to be less effective. However, this is the simplest method and uses widely accessible techniques and equipment. By combining data from two previous heart failure trials, we sought to look for an efficacy signal for the intracoronary method in a larger sample size. We found that the intracoronary route demonstrated improvements in patients' heart function and symptoms. Although it may require a larger number of patients to show efficacy, this signal, alongside the intracoronary route's relative simplicity, should be taken into consideration when future trials of cell therapy for heart failure are planned.

Case report: Cytokine therapy and an intracoronary autologous bone marrow-derived cell infusion with Impella support in a patient with dilated cardiomyopathy and a severely reduced ejection fraction.

Introduction: This is the first reported case of a patient with dilated cardiomyopathy (DCM) and severely impaired left ventricular function to receive a combined treatment of granulocyte colony-stimulating factor therapy and an intracoronary delivery of autologous bone marrow-derived mononuclear cells with percutaneous circulatory assistance (the Impella CP device; Abiomed, Danvers, MA). Main symptoms and outcome: Three months post-treatment, the gentleman in his early 70s demonstrated an improvement in left ventricular ejection fraction (13-17%) and a reduction in New York Heart Association class from III to class I. There was also an improvement in his 6-minute walk test (147-357 meters), N-terminal pro-brain natriuretic peptide level (14,099-7,129 ng/l) and quality of life scores. There were no safety concerns during the treatment or follow-up. Conclusion: This case report suggests combined cell and cytokine therapy with adjunctive circulatory support could be a safe and promising treatment for patients with DCM and severely reduced ejection fraction.

Associations of age at marriage and first pregnancy with maternal nutritional status in Nepal.

Background and objectives: Women's nutritional status is important for their health and reproductive fitness. In a population where early marriage is common, we investigated how women's nutritional status is associated with their age at marriage (marking a geographical transfer between households), and at first pregnancy. Methodology: We used data from a cluster-randomized control trial from lowland Nepal (n = 4071). Outcomes including body mass index (BMI) were measured in early pregnancy and trial endpoint, after delivery. We fitted mixed-effects linear and logistic regression models to estimate associations of age at marriage and age at pregnancy with outcomes, and with odds of chronic energy deficiency (CED, BMI <18.5 kg/m2), at both timepoints. Results: BMI in early pregnancy averaged 20.9 kg/m2, with CED prevalence of 12.5%. In 750 women measured twice, BMI declined 1.2 (95% confidence interval 1.1, 1.3) kg/m2 between early pregnancy and endpoint, when CED prevalence was 35.5%. Early pregnancy was associated in dose-response manner with poorer nutritional status. Early marriage was independently associated with poorer nutritional status among those pregnant ≤15 years, but with better nutritional status among those pregnant ≥19 years. Conclusions and implications: The primary determinant of nutritional status was age at pregnancy, but this association also varied by marriage age. Our results suggest that natal households may marry their daughters earlier if food insecure, but that their nutritional status can improve in the marital household if pregnancy is delayed. Marriage age therefore determines which household funds adolescent weight gain, with implications for Darwinian fitness of the members of both households.

Girls start life on an uneven playing field: Evidence from lowland rural Nepal.

Background and objectives: Evolutionary research on the sex ratio at birth (SRB) has focused on explaining variability within and between populations, and whether parental fitness is maximized by producing daughters or sons. We tested predictors of SRB in a low-income setting, to understand whether girls differ from boys in their likelihood of being born into families with the capacity to invest in them, which has implications for their future health and fitness. Methodology: We used data from a cluster randomized control trial from lowland rural Nepal (16 115 mother-child dyads). We applied principal component analysis to extract two composite indices reflecting maternal socio-economic and reproductive (parity, age) capital. We fitted mixed-effects logistic regression models to estimate odds ratios of having a girl in association with these individual factors and indices. Results: The SRB was 112. Compared to the global reference SRB (105), there were seven missing girls per 100 boys. Uneducated, early-marrying, poorer and shorter mothers were more likely to give birth to girls. Analysing composite maternal indices, lower socio-economic and reproductive capital were independently associated with a greater likelihood of having a girl. Conclusions and implications: In this population, girls start life facing composite disadvantages, being more likely than boys to be born to mothers with lower socio-economic status and reproductive capital. Both physiological and behavioural mechanisms may contribute to these epidemiological associations. Differential early exposure by sex to maternal factors may underpin intergenerational cycles of gender inequality, mediated by developmental trajectory, education and socio-economic status.

Outcomes for Maori and European patients admitted to New Zealand intensive care units between 2009 and 2018.

AIM: To describe characteristics and outcomes of Maori and European patients admitted to New Zealand intensive care units (ICUs) between 2009 and 2018. METHODS: A retrospectively designed prospective cohort study. New Zealand Ministry of Health National Minimum Dataset matched to the Australia New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. The primary outcome was day-180 mortality. Secondary outcomes were ICU mortality, hospital mortality, discharge to home, ICU length of stay, hospital length of stay and survival time. We report associations between Maori ethnicity and each outcome, with European as the reference category, using regression analyses to adjust sequentially for site, deprivation status, sex, year of admission, the Charlson comorbidity index, age, admission source and type, ICU admission diagnosis, ventilation status and illness severity based on physiological parameters. RESULTS: Maori admitted to ICU were on average 13 years younger than European patients. A total of 968 of 9,681 (10%) Maori and 2,732 of 42,871 (5.2%) European patients were admitted after trauma, and 740 of 9,681 (7.6%) and 2,318 of 42,871 (4.4%) were admitted with sepsis respectively. A total of 1,550 of 9,681 (16.0%) Maori and 6,407 of 42,871 (14.9%) European patients died within 180 days of ICU admission; odds ratio (OR) 1.08; 95% CI, 1.02 to 1.15. When adjusted for age, the OR for day-180 mortality for Maori versus European patients increased substantially. The OR decreased after adjustment for admission source and type, and after accounting for Maori having a higher comorbidity index and more severe illness than European patients. In the final model, incorporating adjustment for all specified variables, Maori ethnicity was not associated with day-180 mortality (adjusted OR 1.01; 95%CI, 0.92 to 1.10). Findings were similar for all secondary outcomes. CONCLUSIONS: Compared to European patients, Maori were markedly more likely to be admitted to the ICU after trauma or with sepsis. Despite Maori being on average 13 years younger at ICU admission than their European counterparts, they had more co-morbidities, higher illness severity and a higher risk of dying within 180 days.

Evaluation of an Inpatient Psychiatric Mother-Baby Unit Using a Patient Reported Experience and Outcome Measure.

Understanding the patient experience of admission to a psychiatric mother-baby unit (MBU) informs service improvement and strengthens patient-centered care. This study aims to examine patients' experience, satisfaction, and change in mental health status related to MBU admission. At discharge, 70 women admitted to a public MBU completed the Patient Outcome and Experience Measure (POEM), rated the usefulness of therapeutic groups, and provided written qualitative feedback. Paired sample t-tests, correlations, and thematic content analysis were completed. Women were highly satisfied with the level of care and support received, particularly for those who were voluntarily admitted. Women reported an improvement in mental health from admission to discharge. Women appreciated the staff's interpersonal skills, provision of practical skills, education, advice, support from other women, and therapeutic groups offered. Women suggested improvements such as having greater food choices, more MBU beds, more group sessions, family visitations, which had been restricted due to COVID-19, environmental modifications, and clarity of communication surrounding discharge. This study highlights the benefits of MBUs and the specific aspects of care that are favorable in treating women with mental illnesses who are co-admitted with their baby in an MBU.

Differences in maternal and early child nutritional status by offspring sex in lowland Nepal.

OBJECTIVE: On average, boys grow faster than girls in early life but appear more susceptible to undernutrition. We investigated sex differences in early child growth, and whether maternal nutritional status and diet differed by offspring sex during and after pregnancy in an undernourished population. METHODS: We analyzed longitudinal data from a cluster-randomized trial from plains Nepal, stratifying results by child or gestational age. Children's outcomes (0-20 months) were weight, length, and head circumference and their z-scores relative to WHO reference data in 2-monthly intervals (n range: 24837 to 25 946). Maternal outcomes were mid-upper arm circumference (MUAC), and body mass index (BMI) during pregnancy (12-40 weeks) (n = 5550 and n = 5519) and postpartum (n = 15 710 and n = 15 356), and diet in pregnancy. We fitted unadjusted and adjusted mixed-effects linear and logistic regression models comparing boys with girls. RESULTS: Boys were larger than girls, however relative to their sex-specific reference they had lower length and head circumference z-scores from birth to 12 months, but higher weight-for-length z-scores from 0 to 6 months. Mothers of sons had higher MUAC and BMI around 36 weeks gestation but no other differences in pregnancy diets or pregnancy/postpartum maternal anthropometry were detected. Larger sex differences in children's size in the food supplementation study arm suggest that food restriction in pregnancy may limit fetal growth of boys more than girls. CONCLUSIONS: Generally, mothers' anthropometry and dietary intake do not differ according to offspring sex. As boys are consistently larger, we expect that poor maternal nutritional status may compromise their growth more than girls. Copyright © 2021 John Wiley & Sons, Ltd.

Biosocial life-course factors associated with women's early marriage in rural India: The prospective longitudinal Pune Maternal Nutrition Study.

OBJECTIVES: By convention, women's early marriage is considered a sociocultural decision sensitive to factors acting during adolescence such as poverty, early menarche, and less education. Few studies have examined broader risk factors in the natal household prior to marriage. We investigated whether biosocial markers of parental investment through the daughters' life-course were associated with early marriage risk in rural India. We used an evolutionary perspective to interpret our findings. MATERIALS AND METHODS: A prospective cohort recruited mothers at preconception. Children were followed from birth to age 21 years. Multivariable logistic regression models estimated odds ratios of marrying early (<19 years) associated first with wealth, age at menarche and education, and then with broader markers of maternal phenotype, natal household characteristics, and girls' growth trajectories. Models adjusted for confounders. RESULTS: Of 305 girls, 71 (23%) had married early. Early married girls showed different patterns of growth compared to unmarried girls. Neither poverty nor early menarche predicted early marriage. Girls' non-completion of lower secondary school predicted early marriage, explaining 19% of the variance. Independent of girls' lower schooling, nuclear household, low paternal education, shorter gestation, and girls' poor infant weight gain were associated with marrying early, explaining in combination 35% of the variance. DISCUSSION: Early marriage reflects "future discounting," where reduced parental investment in daughters' somatic and educational capital from early in her life favors an earlier transition to the life-course stage when reproduction can occur. Interventions initiated in adolescence may occur too late in the life-course to effectively delay women's marriage.

Why a long-term perspective is beneficial for demographers.

Although many contemporary demographers pay attention to historical demography, there is often a surprising lack of appreciation of the demographic circumstances and systems of the past, suggesting an implicit assumption that they are not relevant to the present or that the methods, data, and questions addressed by historical and contemporary demographers are different. This paper provides an overview of historical demography as published in Population Studies and how this has developed over time. Drawing on this, I demonstrate that historical and contemporary demography use similar data sources and identical methods, and they often address comparable questions. I argue that an appreciation of demographic patterns and processes is beneficial for all demographers, even those who work on the most recent time periods, and that better integration of historical and contemporary demography would be beneficial to both. The paper also considers three challenges for historical demography as it moves forward.

Comprehensive analysis of the association of seasonal variability with maternal and neonatal nutrition in lowland Nepal.

OBJECTIVE: To provide a comprehensive seasonal analysis of pregnant mothers' eating behaviour and maternal/newborn nutritional status in an undernourished population from lowland rural Nepal, where weather patterns, agricultural labour, food availability and disease prevalence vary seasonally. DESIGN: Secondary analysis of cluster-randomised Low Birth Weight South Asia Trial data, applying cosinor analysis to predict seasonal patterns. OUTCOMES: Maternal mid-upper arm circumference (MUAC), BMI, dietary diversity, meals per day, eating down and food aversion in pregnancy (≥31 weeks' gestation) and neonatal z-scores of length-for-age (LAZ), weight-for-age (WAZ) and head circumference-for-age (HCAZ) and weight-for-length (WLZ). SETTING: Rural areas of Dhanusha and Mahottari districts in plains of Nepal. PARTICIPANTS: 2831 mothers aged 13-50 and 3330 neonates. RESULTS: We found seasonal patterns in newborn anthropometry and pregnant mothers' anthropometry, meal frequency, dietary diversity, food aversion and eating down. Seasonality in intake varied by food group. Offspring anthropometry broadly tracked mothers'. Annual amplitudes in mothers' MUAC and BMI were 0·27 kg/m2 and 0·22 cm, with peaks post-harvest and nadirs in October when food insecurity peaked. Annual LAZ, WAZ and WLZ amplitudes were 0·125, 0·159 and 0·411 z-scores, respectively. Neonates were the shortest but least thin (higher WLZ) in winter (December/January). In the hot season, WLZ was the lowest (May/June) while LAZ was the highest (March and August). HCAZ did not vary significantly. Food aversion and eating down peaked pre-monsoon (April/May). CONCLUSIONS: Our analyses revealed complex seasonal patterns in maternal nutrition and neonatal size. Seasonality should be accounted for when designing and evaluating public heath nutrition interventions.

Routine Frailty Screening in Critical Illness: A Population-Based Cohort Study in Australia and New Zealand.

BACKGROUND: Frailty is associated with poor outcomes in critical illness. However, it is unclear whether frailty screening on admission to the ICU can be conducted routinely at the population level and whether it has prognostic importance. RESEARCH QUESTION: Can population-scale frailty screening with the Clinical Frailty Scale (CFS) be implemented for critically ill adults in Australia and New Zealand (ANZ) and can it identify patients at risk of negative outcomes? STUDY DESIGN AND METHODS: We conducted a binational prospective cohort study of critically ill adult patients admitted between July 1, 2018, and June 30, 2020, in 175 ICUs in ANZ. We classified frailty with the CFS on admission to the ICU. The primary outcome was in-hospital mortality; secondary outcomes were length of stay (LOS), discharge destination, complications (delirium, pressure injury), and duration of survival. RESULTS: We included 234,568 critically ill patients; 45,245 (19%) were diagnosed as living with frailty before ICU admission. Patients with vs without frailty had higher in-hospital mortality (16% vs 5%; P < .001), delirium (10% vs 4%; P < .001), longer LOS in the ICU and hospital, and increased new chronic care discharge (3% vs 1%; P < .001), with worse outcomes associated with increasing CFS category. Of patients with very severe frailty (CFS score, 8), 39% died in hospital vs 2% of very fit patients (CFS score, 1; multivariate categorical CFS score, 8 [reference, 1]; OR, 7.83 [95% CI, 6.39-9.59]; P < .001). After adjustment for illness severity, frailty remained highly significantly predictive of mortality, including among patients younger than 50 years, with improvement in the area under the receiver operating characteristic curve of the Acute Physiology and Chronic Health Evaluation III-j score to 0.882 (95% CI, 0.879-0.885) from 0.868 (95% CI, 0.866-0.871) with the addition of frailty (P < .001). INTERPRETATION: Large-scale population screening for frailty degree in critical illness was possible and prognostically important, with greater frailty (especially CFS score of ≥ 6) associated with worse outcomes, including among younger patients.