Health trends in Canada 1990-2019: An analysis for the Global Burden of Disease Study.

OBJECTIVE: Monitoring trends in key population health indicators is important for informing health policies. The aim of this study was to examine population health trends in Canada over the past 30 years in relation to other countries. METHODS: We used data on disability-adjusted life years (DALYs), years of life lost (YLL), years lived with disability, life expectancy (LE), and child mortality for Canada and other countries between 1990 and 2019 provided by the Global Burden of Disease Study. RESULTS: Life expectancy, age-standardized YLL, and age-standardized DALYs all improved in Canada between 1990 and 2019, although the rate of improvement has leveled off since 2011. The top five causes of all-age DALYs in Canada in 2019 were neoplasms, cardiovascular diseases, musculoskeletal disorders, neurological disorders, and mental disorders. The greatest increases in all-age DALYs since 1990 were observed for substance use, diabetes and chronic kidney disease, and sense organ disorders. Age-standardized DALYs declined for most conditions, except for substance use, diabetes and chronic kidney disease, and musculoskeletal disorders, which increased by 94.6%, 14.6%, and 7.3% respectively since 1990. Canada's world ranking for age-standardized DALYs declined from 9th place in 1990 to 24th in 2019. CONCLUSION: Canadians are healthier today than in 1990, but progress has slowed in Canada in recent years in comparison with other high-income countries. The growing burden of substance abuse, diabetes/chronic kidney disease, and musculoskeletal diseases will require continued action to improve population health.

RéSUMé: OBJECTIF: La surveillance des tendances des indicateurs clés de la santé de la population est importante pour éclairer les politiques de santé. Dans cette étude, nous avons examiné les tendances de la santé de la population au Canada au cours des 30 dernières années par rapport à d'autres pays. MéTHODES: Nous avons utilisé des données sur les années de vie ajustées en fonction de l'incapacité (DALY), les années de vie perdues (YLL), les années vécues avec un handicap, l'espérance de vie (LE) et la mortalité infantile pour le Canada et d'autres pays entre 1990 et 2019, fournies par l'Étude mondiale sur le fardeau de la maladie. RéSULTATS: L'espérance de vie, les YLL ajustées selon l'âge et les DALY ajustées selon l'âge ont tous connu une amélioration au Canada entre 1990 et 2019, bien que le taux d'amélioration se soit stabilisé depuis 2011. Les cinq principales causes des DALY pour tous les âges au Canada en 2019 étaient les néoplasmes, les maladies cardiovasculaires, les affections musculosquelettiques, les affections neurologiques et les troubles mentaux. Les plus fortes augmentations des DALY pour tous les âges depuis 1990 ont été observées pour l'usage de substances, le diabète et les maladies rénales chroniques, ainsi que les troubles des organes sensoriels. Les DALY ajustées selon l'âge ont diminué pour la plupart des conditions, à l'exception de l'usage de substances, du diabète et des maladies rénales chroniques, ainsi que des troubles musculosquelettiques, qui ont augmenté de 94,6 %, 14,6 % et 7,3 % respectivement depuis 1990. Le classement mondial du Canada pour les DALY ajustées selon l'âge est diminué de la 9ième place en 1990 à la 24ième place en 2019. CONCLUSION: Les Canadiens sont en meilleure santé aujourd'hui qu'en 1990, mais les progrès se sont ralentis ces dernières années par rapport à d'autres pays à revenu élevé. La croissance du fardeau lié à l'abus de substances, au diabète/maladies rénales chroniques et aux affections musculosquelettiques exigera des actions continues pour améliorer la santé de la population.

An evidence gap map of interventions for noncommunicable diseases and risk factors among children and adolescents.

Substance misuse, obesity, mental health conditions, type 1 diabetes, cancers, and cardiovascular and chronic respiratory diseases together account for 41% of disability-adjusted life years linked to noncommunicable diseases (NCDs) among children and adolescents worldwide. However, the evidence on risk factors and interventions for this age group is scarce. Here we searched four databases to generate an evidence gap map of existing interventions and research gaps for these risk factors and NCDs. We mapped 159 reviews with 2,611 primary studies; most (96.2%) were conducted in high-income countries, and only 100 studies (3.8%) were from low- and middle-income countries (LMICs). The efficacy of therapeutic interventions on biomarkers and adverse events for NCDs appears to be well evidenced. Interventions for mental health conditions appear to be moderately evidenced, while interventions for obesity and substance misuse appear to be moderate to very low evidenced. Priority areas for future research include evaluating digital health platforms to support primary NCD prevention and management, and evaluating the impact of policy changes on the prevalence of obesity and substance misuse. Our findings highlight the wide disparity of evidence between high-income countries and LMICs. There is an urgent need for increased, targeted financing to address the research gaps in LMICs.

Systematic Review of Management of Moderate Wasting in Children over 6 Months of Age.

The effective management of the 33 million children with moderate acute malnutrition (MAM) is key to reducing childhood morbidity and mortality. In this review, we aim to evaluate the effectiveness of specially formulated foods (SFFs) compared to non-food-based approaches to manage MAM in children >6 months old. We conducted a search on ten databases until 23 August 2021 and included five studies, covering 3387 participants. Meta-analysis of four studies comparing SFFs to counselling or standard of care showed that SFFs likely increase recovery rate, reduce non-response, and may improve weight-for-height z-score, weight-for-age z-score and time to recovery, but have little or no effect on MUAC gain. One study on a multicomponent intervention (SFFs, antibiotics and counselling provided to high-risk MAM) compared to counselling only was reported narratively. The intervention may increase weight gain after 24 weeks but may have little or no effect on weight gain after 12 weeks and on non-response and mortality after 12 and 24 weeks of enrollment. The effect of this intervention on recovery was uncertain. In conclusion, SFFs may be beneficial for children with moderate wasting in humanitarian contexts. Programmatic recommendations should consider context and cost-effectiveness.

Prevalence and Risk Factors for Iron Deficiency Anemia among Children under Five and Women of Reproductive Age in Pakistan: Findings from the National Nutrition Survey 2018.

INTRODUCTION: Anemia remains a global public health problem, especially in developing countries. It affects primarily children under five (CU5), women of reproductive age (WRA), and pregnant women due to their higher need for iron. The most common form of anemia is iron-deficiency anemia (IDA). IDA is estimated to cause half of all anemia cases and one million deaths per year worldwide. However, there remains a lack of well-documented and biochemically assessed prevalence of IDA based on the representative population-based samples globally and regionally. In this study, we aimed to assess the National Nutrition Survey (NNS) 2018 to identify the prevalence and risk factors of IDA in Pakistani CU5 and WRA. METHODS: Secondary analysis was conducted on the NNS 2018, a cross-sectional survey, which collected data on dietary practices, malnutrition, and food insecurity. Anemia was defined as hemoglobin levels < 11.0 g/dL in children and 12.0 g/dL in women. IDA was defined as low hemoglobin and low ferritin (<12 ng/mL) levels, adjusted for inflammation using AGP and CRP biomarkers in CU5 and WRA. Univariate and multivariable logistic regressions were conducted using Stata statistical software (version 16). We also compared the IDA rates of NNS 2018 and 2011. RESULTS: A total of 17,814 CU5 and 22,114 WRA were included in the analysis. Of the CU5, 28.9% had IDA, while 18.4% of WRA reported to experience IDA. Among the CU5, IDA was most prevalent among male children aged 6-23 months living in rural areas and with the presence of diarrhea and fevers in the last 2 weeks. Children whose mothers had no education, were aged 20-34 years, and employed, had a higher prevalence of IDA. Married WRA, who are employed, living in rural areas, and with no education, had a higher prevalence of IDA. In the multivariable logistic regression, children aged 6-23 months (AOR = 1.19, 95% CI [1.08-1.33], p < 0.001) and with the presence of diarrhea in the last 2 weeks (AOR = 1.32, 95% CI [1.13-1.54], p < 0.001) or fever (AOR = 1.16, 95% CI [1.02-1.32], p = 0.02) had higher odds of IDA. At the household level, the odds of IDA among CU5 were higher in the poorest households (AOR = 1.27, 95% CI [1.08-1.50], p = 0.005), with ≥5 CU5 (AOR = 1.99, 95% CI [1.28-3.11], p = 0.002), and with no access to improved sanitation facilities (AOR = 1.17, 95% CI [1.02-1.34], p = 0.026). For WRA, the multivariable logistic regression found that the odds of IDA were higher among women with vitamin A deficiency (Severe: AOR = 1.26, 95% CI [1.05-1.52], p = 0.013; Mild: AOR = 1.36, 95% CI [1.23-1.51], p < 0.001), zinc deficiency (AOR = 1.42, 95% CI [1.28-1.57], p < 0.001), no education (AOR = 1.53, 95% CI [1.30-1.81], p < 0.001), and from severely food insecure households (AOR = 1.20, 95% CI [1.07-1.34], p = 0.001). The odds of IDA were lower among women whose body mass index was overweight (AOR = 0.77, 95% CI [0.69-0.86], p < 0.001) or obese (AOR = 0.71, 95% CI [0.62-0.81], p < 0.001). CONCLUSIONS: The child's age, presence of diarrhea or fever, place of residence, household size, wealth status, and access to sanitation facilities were significantly associated with IDA among CU5 in Pakistan. For WRA, education, body mass index, vitamin A and zinc status, household food security status, wealth status, and access to sanitation facilities were significantly associated with IDA. Large, well-established, government-funded programmes focused on micronutrient supplementation, food fortification, the diversification of food supplies, and the treatment and prevention of infectious and parasitic diseases are needed to prevent IDA and all forms of anemia among children and women in Pakistan.

Evidence-based antenatal interventions to reduce the incidence of small vulnerable newborns and their associated poor outcomes.

A package of care for all pregnant women within eight scheduled antenatal care contacts is recommended by WHO. Some interventions for reducing and managing the outcomes for small vulnerable newborns (SVNs) exist within the WHO package and need to be more fully implemented, but additional effective measures are needed. We summarise evidence-based antenatal and intrapartum interventions (up to and including clamping the umbilical cord) to prevent vulnerable births or improve outcomes, informed by systematic reviews. We estimate, using the Lives Saved Tool, that eight proven preventive interventions (multiple micronutrient supplementation, balanced protein and energy supplementation, low-dose aspirin, progesterone provided vaginally, education for smoking cessation, malaria prevention, treatment of asymptomatic bacteriuria, and treatment of syphilis), if fully implemented in 81 low-income and middle-income countries, could prevent 5·202 million SVN births (sensitivity bounds 2·398-7·903) and 0·566 million stillbirths (0·208-0·754) per year. These interventions, along with two that can reduce the complications of preterm (<37 weeks' gestation) births (antenatal corticosteroids and delayed cord clamping), could avert 0·476 million neonatal deaths (0·181-0·676) per year. If further research substantiates the preventive effect of three additional interventions (supplementation with omega-3 fatty acids, calcium, and zinc) on SVN births, about 8·369 million SVN births (2·398-13·857) and 0·652 million neonatal deaths (0·181-0·917) could be avoided per year. Scaling up the eight proven interventions and two intrapartum interventions would cost about US$1·1 billion in 2030 and the potential interventions would cost an additional $3·0 billion. Implementation of antenatal care recommendations is urgent and should include all interventions that have proven effects on SVN babies, within the context of access to family planning services and addressing social determinants of health. Attaining high effective coverage with these interventions will be necessary to achieve global targets for the reduction of low birthweight births and neonatal mortality, and long-term benefits on growth and human capital.

Health behaviors and care seeking practices for childhood diarrhea and pneumonia in a rural district of Pakistan: A qualitative study.

Diarrhea and pneumonia are the leading causes of morbidity and mortality in children under five, and Pakistan is amongst the countries with the highest burden and low rates of related treatment coverage. We conducted a qualitative study as part of the formative phase to inform the design of the Community Mobilization and Community Incentivization (CoMIC) cluster randomized control trial (NCT03594279) in a rural district of Pakistan. We conducted in-dept interviews and focused group discussions with key stakeholders using a semi-structured study guide. Data underwent rigorous thematic analysis and major themes identified included socio-cultural dynamics, community mobilization and incentives, behavioral patterns and care seeking practices for childhood diarrhea and pneumonia, infant and young child feeding practices (IYCF), immunization, water sanitation and hygiene (WASH) and access to healthcare. This study highlights shortcomings in knowledge, health practices and health systems. There was to a certain extent awareness of the importance of hygiene, immunization, nutrition, and care-seeking, but the practices were poor due to various reasons. Poverty and lifestyle were considered prime factors for poor health behaviors, while health system inefficiencies added to these as rural facilities lack equipment and supplies, resources, and funding. The community identified that intensive inclusive community engagement and demand creation strategies tied to conditioned short term tangible incentives could help foster behavior change.

Effectiveness of Dietary Management for Moderate Wasting among Children > 6 Months of Age-A Systematic Review and Meta-Analysis Exploring Different Types, Quantities, and Durations.

Currently, no World Health Organization guidelines exist for the management of approximately 31.8 million moderately wasted children globally. The objective of this review was to synthesise evidence on the optimal type, quantity, and duration of dietary treatment for moderate wasting. Ten electronic databases were searched until the 23rd of August 2021. Experimental studies comparing interventions for the dietary management of moderate wasting were included. Meta-analyses were conducted and results were presented as risk ratios or mean differences with 95% confidence intervals. Seventeen studies comparing specially formulated foods were included involving 23,005 participants. Findings suggest little or no difference in recovery between Fortified Blended Foods (FBFs) with improved micronutrient and/or milk content (enhanced FBFs) and lipid-based nutrient supplements (LNS), whereas children treated with non-enhanced FBFs (locally produced FBFs or standard corn-soy blend) may have lower recovery rates than those treated with LNS. There was no difference in recovery when ready-to-use therapeutic and ready-to-use supplementary food were compared. Other outcomes mostly aligned with results for recovery. In conclusion, LNSs improve recovery compared to non-enhanced FBFs, but are comparable to enhanced FBFs. Programmatic choice of supplement should consider factors such as cost, cost-effectiveness, and acceptability. Further research is required to determine optimal dosing and duration of supplementation.

How Can Nutrition Research Better Reflect the Relationship Between Wasting and Stunting in Children? Learnings from the Wasting and Stunting Project.

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Prevalence of smoking and smokeless tobacco use during breastfeeding: A cross-sectional secondary data analysis based on 0.32 million sample women in 78 low-income and middle-income countries.

Background: Smoking and smokeless tobacco use during the postpartum period is well studied in high-income countries, whereas low-income and middle-income countries (LMICs) lack evidence. Methods: In this cross-sectional study we used data from the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) conducted in 78 LMICs between January 2010 and December 2019 to study tobacco use among 0.32 million sample lactating women. Age-standardized prevalence of smoking and smokeless tobacco use was estimated and presented with a 95% Confidence Interval (CI) for 78 LMICs. Pooled estimates overall and by WHO regions were obtained using random-effects meta-analyses. Country-level and community-level variance to understand contextual factors was also quantified using multilevel modelling. Findings: Pooled prevalence of any tobacco use among breastfeeding women in LMICs was 3.61% (95% CI 3.53-3.70); with the lowest prevalence in regions of the Americas (1.44%, 1.26-1.63) and the highest in the Southeast Asia region (6.13%, 6.0-6.27). The pooled prevalence of tobacco smoking was reported to be 1.16% (1.11-1.21), with the highest prevalence in the Eastern Mediterranean region (4.27%, 3.88-4.67) and the lowest in the African region (0.81%, 0.76-0.86). The pooled prevalence of smokeless tobacco use was reported to be 2.56% (2.49-2.63), with the highest prevalence in the Southeast Asia region (4.92%, 4.80-5.04). Illiterate and poor women in LMICs bore the enormous burden of tobacco use. Interpretation: The prevalence of smoking and smokeless tobacco use among lactating women in LMICs varied considerably across different WHO regions. Considering the cross-sectional design of the study, caution is required while interpreting the results. To improve mothers' and children's health and nutrition outcomes and reduce health inequalities in LMICs, reducing tobacco use through evidence-based interventions is critical. Funding: None.

Burden, Clinical Characteristics, Risk Factors, and Seasonality of Adenovirus 40/41 Diarrhea in Children in Eight Low-Resource Settings.

Background: The application of molecular diagnostics has identified enteric group adenovirus serotypes 40 and 41 as important causes of diarrhea in children. However, many aspects of the epidemiology of adenovirus 40/41 diarrhea have not been described. Methods: We used data from the 8-site Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project birth cohort study to describe site- and age-specific incidence, risk factors, clinical characteristics, and seasonality. Results: The incidence of adenovirus 40/41 diarrhea was substantially higher by quantitative polymerase chain reaction than enzyme immunoassay and peaked at ∼30 episodes per 100 child-years in children aged 7-15 months, with substantial variation in incidence between sites. A significant burden was also seen in children 0-6 months of age, higher than other viral etiologies with the exception of rotavirus. Children with adenovirus 40/41 diarrhea were more likely to have a fever than children with norovirus, sapovirus, and astrovirus (adjusted odds ratio [aOR], 1.62; 95% CI, 1.16-2.26) but less likely than children with rotavirus (aOR, 0.66; 95% CI, 0.49-0.91). Exclusive breastfeeding was strongly protective against adenovirus 40/41 diarrhea (hazard ratio, 0.64; 95% CI, 0.48-0.85), but no other risk factors were identified. The seasonality of adenovirus 40/41 diarrhea varied substantially between sites and did not have clear associations with seasonal variations in temperature or rainfall. Conclusions: This study supports the situation of adenovirus 40/41 as a pathogen of substantial importance, especially in infants. Fever was a distinguishing characteristic in comparison to other nonrotavirus viral etiologies, and promotion of exclusive breastfeeding may reduce the high observed burden in the first 6 months of life.

Fortification of salt with iron and iodine versus fortification of salt with iodine alone for improving iron and iodine status.

BACKGROUND: Iron deficiency is an important micronutrient deficiency contributing to the global burden of disease, and particularly affects children, premenopausal women, and people in low-resource settings. Anaemia is a possible consequence of iron deficiency, although clinical and functional manifestations of anemia can occur without iron deficiency (e.g. from other nutritional deficiencies, inflammation, and parasitic infections). Direct nutritional interventions, such as large-scale food fortification, can improve micronutrient status, especially in vulnerable populations. Given the highly successful delivery of iodine through salt iodisation, fortifying salt with iodine and iron has been proposed as a method for preventing iron deficiency anaemia. Further investigation of the effect of double-fortified salt (i.e. with iron and iodine) on iron deficiency and related outcomes is warranted.  OBJECTIVES: To assess the effect of double-fortified salt (DFS) compared to iodised salt (IS) on measures of iron and iodine status in all age groups. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases, and two trial registries up to April 2021. We also searched relevant websites, reference lists, and contacted the authors of included studies. SELECTION CRITERIA: All prospective randomised controlled trials (RCTs), including cluster-randomised controlled trials (cRCTs), and controlled before-after (CBA) studies, comparing DFS with IS on measures of iron and iodine status were eligible, irrespective of language or publication status. Study reports published as abstracts were also eligible. DATA COLLECTION AND ANALYSIS: Three review authors applied the study selection criteria, extracted data, and assessed risk of bias. Two review authors rated the certainty of the evidence using GRADE. When necessary, we contacted study authors for additional information. We assessed RCTs, cRCTs and CBA studies using the Cochrane RoB 1 tool and Cochrane Effective Practice and Organisation of Care (EPOC) tool across the following domains: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; and other potential sources of bias due to similar baseline characteristics, similar baseline outcome assessments, and declarations of conflicts of interest and funding sources. We also assessed cRCTs for recruitment bias, baseline imbalance, loss of clusters, incorrect analysis, and comparability with individually randomised studies. We assigned studies an overall risk of bias judgement (low risk, high risk, or unclear).  MAIN RESULTS: We included 18 studies (7 RCTs, 7 cRCTs, 4 CBA studies), involving over 8800 individuals from five countries. One study did not contribute to analyses. All studies used IS as the comparator and measured and reported outcomes at study endpoint.  With regards to risk of bias, five RCTs had unclear risk of bias, with some concerns in random sequence generation and allocation concealment, while we assessed two RCTs to have a high risk of bias overall, whereby high risk was noted in at least one or more domain(s). Of the seven cRCTs, we assessed six at high risk of bias overall, with one or more domain(s) judged as high risk and one cRCT had an unclear risk of bias with concerns around allocation and blinding. The four CBA studies had high or unclear risk of bias for most domains. The RCT evidence suggested that, compared to IS, DFS may slightly improve haemoglobin concentration (mean difference (MD) 0.43 g/dL, 95% confidence interval (CI) 0.23 to 0.63; 13 studies, 4564 participants; low-certainty evidence), but DFS may reduce urinary iodine concentration compared to IS (MD -96.86 µg/L, 95% CI -164.99 to -28.73; 7 studies, 1594 participants; low-certainty evidence), although both salts increased mean urinary iodine concentration above the cut-off deficiency. For CBA studies, we found DFS made no difference in haemoglobin concentration (MD 0.26 g/dL, 95% CI -0.10 to 0.63; 4 studies, 1397 participants) or urinary iodine concentration (MD -17.27 µg/L, 95% CI -49.27 to 14.73; 3 studies, 1127 participants). No studies measured blood pressure. For secondary outcomes reported in RCTs, DFS may result in little to no difference in ferritin concentration (MD -3.94 µg/L, 95% CI -20.65 to 12.77; 5 studies, 1419 participants; low-certainty evidence) or transferrin receptor concentration (MD -4.68 mg/L, 95% CI -11.67 to 2.31; 5 studies, 1256 participants; low-certainty evidence) compared to IS. However, DFS may reduce zinc protoporphyrin concentration (MD -27.26 µmol/mol, 95% CI -47.49 to -7.03; 3 studies, 921 participants; low-certainty evidence) and result in a slight increase in body iron stores (MD 1.77 mg/kg, 95% CI 0.79 to 2.74; 4 studies, 847 participants; low-certainty evidence). In terms of prevalence of anaemia, DFS may reduce the risk of anaemia by 21% (risk ratio (RR) 0.79, 95% CI 0.66 to 0.94; P = 0.007; 8 studies, 2593 participants; moderate-certainty evidence). Likewise, DFS may reduce the risk of iron deficiency anaemia by 65% (RR 0.35, 95% CI 0.24 to 0.52; 5 studies, 1209 participants; low-certainty evidence).  Four studies measured salt intake at endline, although only one study reported this for both groups. Two studies reported prevalence of goitre, while one CBA study measured and reported serum iron concentration. One study reported adverse effects. No studies measured hepcidin concentration. AUTHORS' CONCLUSIONS: Our findings suggest DFS may have a small positive impact on haemoglobin concentration and the prevalence of anaemia compared to IS, particularly when considering efficacy studies. Future research should prioritise studies that incorporate robust study designs and outcome measures (e.g. anaemia, iron status measures) to better understand the effect of DFS provision to a free-living population (non-research population), where there could be an added cost to purchase double-fortified salt. Adequately measuring salt intake, both at baseline and endline, and adjusting for inflammation will be important to understanding the true effect on measures of iron status.

Improving health and social systems for all children in LMICs: structural innovations to deliver high-quality services.

Despite health gains over the past 30 years, children and adolescents are not reaching their health potential in many low-income and middle-income countries (LMICs). In addition to health systems, social systems, such as schools, communities, families, and digital platforms, can be used to promote health. We did a targeted literature review of how well health and social systems are meeting the needs of children in LMICs using the framework of The Lancet Global Health Commission on high-quality health systems and we reviewed evidence for structural reforms in health and social sectors. We found that quality of services for children is substandard across both health and social systems. Health systems have deficits in care competence (eg, diagnosis and management), system competence (eg, timeliness, continuity, and referral), user experience (eg, respect and usability), service provision for common and serious conditions (eg, cancer, trauma, and mental health), and service offerings for adolescents. Education and social services for child health are limited by low funding and poor coordination with other sectors. Structural reforms are more likely to improve service quality substantially and at scale than are micro-level efforts. Promising approaches include governing for quality (eg, leadership, expert management, and learning systems), redesigning service delivery to maximise outcomes, and empowering families to better care for children and to demand quality care from health and social systems. Additional research is needed on health needs across the life course, health system performance for children and families, and large-scale evaluation of promising health and social programmes.

Effects of Lifestyle Modification Interventions to Prevent and Manage Child and Adolescent Obesity: A Systematic Review and Meta-Analysis.

The objective of this review was to assess the impact of lifestyle interventions (including dietary interventions, physical activity, behavioral therapy, or any combination of these interventions) to prevent and manage childhood and adolescent obesity. We conducted a comprehensive literature search across various databases and grey literature without any restrictions on publication, language, or publication status until February 2020. We included randomized controlled trials and quasi-experimental studies from both high income countries (HIC) and low-middle-income countries (LMICs). Participants were children and adolescents from 0 to 19 years of age. Studies conducted among hospitalized children and children with any pre-existing health conditions were excluded from this review. A total of 654 studies (1160 papers) that met the inclusion criteria were included in this review. A total of 359 studies targeted obesity prevention, 280 studies targeted obesity management, while 15 studies targeted both prevention and management. The majority of the studies (81%) were conducted in HICs, 10% of studies were conducted in upper middle income countries, while only 2% of the studies were conducted in LMICs. The most common setting for these interventions were communities and school settings. Evidence for the prevention of obesity among children and adolescents suggests that a combination of diet and exercise might reduce the BMI z-score (MD: -0.12; 95% CI: -0.18 to -0.06; 32 studies; 33,039 participants; I2 93%; low quality evidence), body mass index (BMI) by 0.41 kg/m2 (MD: -0.41 kg/m2; 95% CI: -0.60 to -0.21; 35 studies; 47,499 participants; I2 98%; low quality evidence), and body weight (MD: -1.59; 95% CI: -2.95 to -0.23; 17 studies; 35,023 participants; I2 100%; low quality evidence). Behavioral therapy alone (MD: -0.07; 95% CI: -0.14 to -0.00; 19 studies; 8569 participants; I2 76%; low quality evidence) and a combination of exercise and behavioral therapy (MD: -0.08; 95% CI: -0.16 to -0.00; 9 studies; 7334 participants; I2 74%; low quality evidence) and diet in combination with exercise and behavioral therapy (MD: -0.13; 95% CI: -0.25 to -0.01; 5 studies; 1806 participants; I2 62%; low quality evidence) might reduce BMI z-score when compared to the control group. Evidence for obesity management suggests that exercise only interventions probably reduce BMI z-score (MD: -0.13; 95% CI: -0.20 to -0.06; 12 studies; 1084 participants; I2 0%; moderate quality evidence), and might reduce BMI (MD: -0.88; 95% CI: -1.265 to -0.50; 34 studies; 3846 participants; I2 72%) and body weight (MD: -3.01; 95% CI: -5.56 to -0.47; 16 studies; 1701 participants; I2 78%; low quality evidence) when compared to the control group. and the exercise along with behavioral therapy interventions (MD: -0.08; 95% CI: -0.16 to -0.00; 8 studies; 466 participants; I2 49%; moderate quality evidence), diet along with behavioral therapy interventions (MD: -0.16; 95% CI: -0.26 to -0.07; 4 studies; 329 participants; I2 0%; moderate quality evidence), and combination of diet, exercise and behavioral therapy (MD: -0.09; 95% CI: -0.14 to -0.05; 13 studies; 2995 participants; I2 12%; moderate quality evidence) also probably decreases BMI z-score when compared to the control group. The existing evidence is most favorable for a combination of interventions, such as diet along with exercise and exercise along with behavioral therapy for obesity prevention and exercise alone, diet along with exercise, diet along with behavioral therapy, and a combination of diet, exercise, and behavioral therapy for obesity management. Despite the growing obesity epidemic in LMICs, there is a significant dearth of obesity prevention and management studies from these regions.

Delivering trauma and rehabilitation interventions to women and children in conflict settings: a systematic review.

Background: In recent years, more than 120 million people each year have needed urgent humanitarian assistance and protection. Armed conflict has profoundly negative consequences in communities. Destruction of civilian infrastructure impacts access to basic health services and complicates widespread emergency responses. The number of conflicts occurring is increasing, lasting longer and affecting more people today than a decade ago. The number of children living in conflict zones has been steadily increasing since the year 2000, increasing the need for health services and resources. This review systematically synthesised the indexed and grey literature reporting on the delivery of trauma and rehabilitation interventions for conflict-affected populations. Methods: A systematic search of literature published from 1 January 1990 to 31 March 2018 was conducted across several databases. Eligible publications reported on women and children in low and middle-income countries. Included publications provided information on the delivery of interventions for trauma, sustained injuries or rehabilitation in conflict-affected populations. Results: A total of 81 publications met the inclusion criteria, and were included in our review. Nearly all of the included publications were observational in nature, employing retrospective chart reviews of surgical procedures delivered in a hospital setting to conflict-affected individuals. The majority of publications reported injuries due to explosive devices and remnants of war. Injuries requiring orthopaedic/reconstructive surgeries were the most commonly reported interventions. Barriers to health services centred on the distance and availability from the site of injury to health facilities. Conclusions: Traumatic injuries require an array of medical and surgical interventions, and their effective treatment largely depends on prompt and timely management and referral, with appropriate rehabilitation services and post-treatment follow-up. Further work to evaluate intervention delivery in this domain is needed, particularly among children given their specialised needs, and in different population displacement contexts. PROSPERO registration number: CRD42019125221.

Improved micronutrient status and health outcomes in low- and middle-income countries following large-scale fortification: evidence from a systematic review and meta-analysis.

BACKGROUND: Micronutrient malnutrition is highly prevalent in low- and middle-income countries (LMICs) and disproportionately affects women and children. Although the effectiveness of large-scale food fortification (LSFF) of staple foods to prevent micronutrient deficiencies in high-income settings has been demonstrated, its effectiveness in LMICs is less well characterized. This is important as food consumption patterns, potential food vehicles, and therefore potential for impact may vary substantially in these contexts. OBJECTIVES: The aim of this study was to determine the real-world impact of LSFF with key micronutrients (vitamin A, iodine, iron, folic acid) on improving micronutrient status and functional health outcomes in LMICs. METHODS: All applicable published/unpublished evidence was systematically retrieved and analyzed. Studies were not restricted by age or sex. Meta-analyses were performed for quantitative outcomes and results were presented as summary RRs, ORs, or standardized mean differences (SMDs) with 95% CIs. RESULTS: LSFF increased serum micronutrient concentrations in several populations and demonstrated a positive impact on functional outcomes, including a 34% reduction in anemia (RR: 0.66; 95% CI: 0.59, 0.74), a 74% reduction in the odds of goiter (OR: 0.26; 95% CI: 0.16, 0.43), and a 41% reduction in the odds of neural tube defects (OR: 0.59; 95% CI: 0.49, 0.70). Additionally, we found that LSFF with vitamin A could protect nearly 3 million children per year from vitamin A deficiency. We noted an age-specific effect of fortification, with women (aged >18 y) attaining greater benefit than children, who may consume smaller quantities of fortified staple foods. Several programmatic/implementation factors were also reviewed that may facilitate or limit program potential. CONCLUSIONS: Measurable improvements in the micronutrient and health status of women and children are possible with LSFF. However, context and implementation factors are important when assessing programmatic sustainability and impact, and data on these are quite limited in LMIC studies.

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery.

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.).

Socio-anthropological methods to study the feasibility and acceptability of the minimally invasive autopsy from the perspective of local communities: lessons learnt from a large multi-centre study.

The minimally invasive autopsy (MIA), an innovative approach for obtaining post-mortem samples of key organs, is increasingly being recognized as a robust methodology for cause of death (CoD) investigation, albeit so far limited to pilot studies and research projects. A better understanding of the real causes of death in middle- and low-income countries, where underlying causes of death are seldom determined, would allow improved health planning, more targeted prioritization of available resources and the implementation of coherent public health policies. This paper discusses lessons learnt from the implementation of a Feasibility and Acceptability (F&A) study evaluating the MIA approach in five countries: Gabon, Kenya, Mali, Mozambique and Pakistan. This article reports the methodological choices made to document sociocultural and religious norms around death, to examine community and relatives' attitudes and perceptions towards MIA, and to identify factors motivating the MIA's acceptance and refusal. We used ethnography, grounded theory and framework method approaches. In-depth and semi-structured interviews and focus group discussions with key informants, including next of kin of deceased individuals and healthcare providers, were conducted. Participant observation and direct observation of procedures and ceremonies around death were organized in all study sites. In Mozambique, MIA procedures were observed and case studies conducted. The implementation of this F&A protocol has provided critical lessons that could facilitate the future implementation of post-mortem procedures for CoD investigation. These include the need for early community engagement, staff training and preparedness, flexibility to adapt the protocol, gathering qualitative data from diverse sources, and triangulation of the data. We have applied a rigorous, effective and culturally sensitive methodological approach to assess the F&A of MIA in resource-constrained settings. We strongly recommend that such an approach is applied in settings where MIAs or similar post-mortem sensitive procedures are to be introduced.

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study.

BACKGROUND: Optimum management of childhood diarrhoea in low-resource settings has been hampered by insufficient data on aetiology, burden, and associated clinical characteristics. We used quantitative diagnostic methods to reassess and refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study. METHODS: We re-analysed stool specimens from the multisite MAL-ED cohort study of children aged 0-2 years done at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and Loreto, Peru), which included active surveillance for diarrhoea and routine non-diarrhoeal stool collection. We used quantitative PCR to test for 29 enteropathogens, calculated population-level pathogen-specific attributable burdens, derived stringent quantitative cutoffs to identify aetiology for individual episodes, and created aetiology prediction scores using clinical characteristics. FINDINGS: We analysed 6625 diarrhoeal and 30 968 non-diarrhoeal surveillance stools from 1715 children. Overall, 64·9% of diarrhoea episodes (95% CI 62·6-71·2) could be attributed to an aetiology by quantitative PCR compared with 32·8% (30·8-38·7) using the original study microbiology. Viral diarrhoea (36·4% of overall incidence, 95% CI 33·6-39·5) was more common than bacterial (25·0%, 23·4-28·4) and parasitic diarrhoea (3·5%, 3·0-5·2). Ten pathogens accounted for 95·7% of attributable diarrhoea: Shigella (26·1 attributable episodes per 100 child-years, 95% CI 23·8-29·9), sapovirus (22·8, 18·9-27·5), rotavirus (20·7, 18·8-23·0), adenovirus 40/41 (19·0, 16·8-23·0), enterotoxigenic Escherichia coli (18·8, 16·5-23·8), norovirus (15·4, 13·5-20·1), astrovirus (15·0, 12·0-19·5), Campylobacter jejuni or C coli (12·1, 8·5-17·2), Cryptosporidium (5·8, 4·3-8·3), and typical enteropathogenic E coli (5·4, 2·8-9·3). 86·2% of the attributable incidence for Shigella was non-dysenteric. A prediction score for shigellosis was more accurate (sensitivity 50·4% [95% CI 46·7-54·1], specificity 84·0% [83·0-84·9]) than current guidelines, which recommend treatment only of bloody diarrhoea to cover Shigella (sensitivity 14·5% [95% CI 12·1-17·3], specificity 96·5% [96·0-97·0]). INTERPRETATION: Quantitative molecular diagnostics improved estimates of pathogen-specific burdens of childhood diarrhoea in the community setting. Viral causes predominated, including a substantial burden of sapovirus; however, Shigella had the highest overall burden with a high incidence in the second year of life. These data could improve the management of diarrhoea in these low-resource settings. FUNDING: Bill & Melinda Gates Foundation.