Antenatal multiple micronutrient supplements versus iron-folic acid supplements and birth outcomes: Analysis by gestational age assessment method.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

Digitalization of routine health information systems: Bangladesh, Indonesia, Pakistan.

Objective: To describe a systematic process of transforming paper registers into a digital system optimized to enhance service provision and fulfil reporting requirements. Methods: We designed a formative study around primary health workers providing reproductive, maternal, newborn and child health services in three countries in Bangladesh, Indonesia and Pakistan. The study ran from November 2014 to June 2018. We developed a prototype digital application after conducting a needs assessment of health workers' responsibilities, workflows, routine data requirements and service delivery needs. Methods included desk reviews, focus group discussions, in-depth interviews; data mapping of paper registers; observations of health workers; co-design workshops with health workers; and usability testing. Finally, we conducted an observational feasibility assessment to monitor uptake of the application. Findings: Researchers reviewed a total of 17 paper registers across the sites, which we transformed into seven modules within a digital application running on mobile devices. Modules corresponded to the services provided, including household enumeration, antenatal care, family planning, immunization, nutrition and child health. A total of 65 health workers used the modules during the feasibility assessment, and average weekly form submissions ranged from 8 to 234, depending on the health worker and their responsibilities. We also observed variability in the use of modules, requiring consistent monitoring support for health workers. Conclusion: Lessons learnt from this study shaped key global initiatives and resulted in a software global good. The deployment of digital systems requires well-designed applications, change management and strengthening human resources to realize and sustain health system gains.

Effect of multiple micronutrient supplements vs iron and folic acid supplements on neonatal mortality: a reanalysis by iron dose.

OBJECTIVE: Antenatal multiple micronutrient supplements (MMS) are a cost-effective intervention to reduce adverse pregnancy and birth outcomes. However, the current WHO recommendation on the use of antenatal MMS is conditional, partly due to concerns about the effect on neonatal mortality in a subgroup of studies comparing MMS with iron and folic acid supplements (IFA) containing 60 mg of iron. We aimed to assess the effect of MMS vs IFA on neonatal mortality stratified by iron dose in each supplement. METHODS: We updated the neonatal mortality analysis of the 2020 WHO guidelines using the generic inverse variance method and applied the random effects model to calculate the effect estimates of MMS vs. IFA on neonatal mortality in subgroups of trials (n=13) providing the same or different amounts of iron, i.e. MMS with 60 mg of iron vs IFA with 60 mg of iron; MMS with 30 mg of iron vs IFA with 30 mg of iron; MMS with 30 mg of iron vs IFA with 60 mg of iron; and MMS with 20 mg of iron vs IFA with 60 mg of iron. RESULTS: There were no statistically significant differences in neonatal mortality between MMS and IFA within any of the subgroups of trials. Analysis of MMS with 30 mg vs IFA with 60 mg of iron (7 trials, 14,114 participants), yielded a nonsignificant Risk Ratio (RR) of 1.12 (95% CI 0.83 to 1.50). CONCLUSION: Neonatal mortality did not differ between MMS and IFA regardless of iron dose in either supplement.

Development and preliminary validity of an Indonesian mobile application for a balanced and sustainable diet for obesity management.

BACKGROUND: Mobile applications such as personalized tracking tools and food choice aids may enhance weight loss programs. We developed and assessed client preferences for the content, user interface, graphics, and logic flow of a mobile application, and evaluated its validity for tracking compliance with weight control and making healthy and sustainable food choices. METHODS: Our four-stage study comprised formative research, application development, acceptance assessment, and validity. The formative research included literature reviews and six focus groups with 39 respondents aged 19-64 years at high risk for obesity. The development stage included programmer selection, defining application specifications, design, and user interface. Prototype acceptability was assessed with 53 respondents who graded 17 features of content, graphic design, and application flow (ranked as good, moderate, and poor). A feature was considered to have "good" acceptance if its mean response was higher than the mean of overall responses. The validity was assessed in 30 obese women using Bland-Altman plots to compare results from dietary intake assessment from the application to conventional paper-based methods. RESULTS: The application was named as EatsUp®. The focus group participants defined the key requirements of this app as being informative, easy, and exciting to use. The EatsUp® core features consisted of simple menu recommendations, health news, notifications, a food database, estimated portion sizes, and food pictures. The prototype had a "good" overall acceptance regarding content, graphics, and flow. Fourteen out of 17 parameters were graded as "good" from > 70% of respondents. There was no significant difference between the rated proportions for content, graphics, and app flow (Kolmogorov-Smirnov Z-test, p > .05). The agreement using the Bland-Altman plots between EatsUp® and the paper-based method of measuring food intake was good, with a mean difference of energy intake of only 2.63 ± 28.4 kcal/day (p > 0.05), well within the 95% confidence interval for agreement. CONCLUSIONS: The EatsUp® mobile application had good acceptance for graphics and app flow. This application can support the monitoring of balanced and sustainable dietary practice by providing nutritional data, and is comparable with conventional dietary assessment tools, and performed well in tracking energy, macronutrient, and selected micronutrients intakes. TRIAL REGISTRATION: NCT03469869 . The registration date was March 19, 2018.

International Validation of Reduced Major Morbidity After Minimally Invasive Distal Pancreatectomy Compared With Open Pancreatectomy.

OBJECTIVE: To quantify the nationwide impact of minimally invasive distal pancreatectomy (MIDP) on major morbidity as compared with open distal pancreatectomy (ODP). BACKGROUND: A recent randomized controlled trial (RCT) demonstrated significant reduction in time to functional recovery after MIDP compared with ODP, but was not powered to assess potential risk reductions in major morbidity. METHODS: International cohort study using the American College of Surgeons' National Quality Improvement Program (ACS-NSQIP) (88 centers; 2014-2016) to evaluate the association between surgical approach (MIDP vs ODP) and 30-day composite major morbidity (CMM; death or severe complications) with external model validation using Dutch Pancreatic Cancer Group data (17 centers; 2005-2016). Multivariable logistic regression assessed the impact of nationwide MIDP rates between 0% and 100% on postoperative CMM at conversion rates between 0% and 25%, using estimated marginal effects. A sensitivity analysis tested the impact at various scenarios and patient populations. RESULTS: Of 2921 ACS-NSQIP patients, 1562 (53%) underwent MIDP with 18% conversion, and 1359 (47%) underwent ODP. MIDP was independently associated with reduced CMM [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.42-0.60, P < 0.001], confirmed by external model validation (n = 637, P < 0.003). The association between rising MIDP implementation rates and falling postoperative morbidity was linear between 0% (all ODP) and 100% (all MIDP). The absolute risk reduction for CMM was 11% (95% CI 7.3%-15%) at observed conversion rates and improved to 14% (95% CI 11%-18%) as conversion approached 0%. Similar effects were seen across subgroups. CONCLUSION: This international study predicted a nationwide 11% risk reduction for CMM after MIDP versus ODP, which is likely to improve as conversion rates decrease. These findings confirm secondary outcomes of the recent LEOPARD RCT.

Universal health coverage in Indonesia: concept, progress, and challenges.

Indonesia is a rapidly growing middle-income country with 262 million inhabitants from more than 300 ethnic and 730 language groups spread over 17 744 islands, and presents unique challenges for health systems and universal health coverage (UHC). From 1960 to 2001, the centralised health system of Indonesia made gains as medical care infrastructure grew from virtually no primary health centres to 20 900 centres. Life expectancy improved from 48 to 69 years, infant mortality decreased from 76 deaths per 1000 livebirths to 23 per 1000, and the total fertility rate decreased from 5·61 to 2·11. However, gains across the country were starkly uneven with major health gaps, such as the stagnant maternal mortality of around 300 deaths per 100 000 livebirths, and minimal change in neonatal mortality. The centralised one size fits all approach did not address the complexity and diversity in population density and dispersion across islands, diets, diseases, local living styles, health beliefs, human development, and community participation. Decentralisation of governance to 354 districts in 2001, and currently 514 districts, further increased health system heterogeneity and exacerbated equity gaps. The novel UHC system introduced in 2014 focused on accommodating diversity with flexible and adaptive implementation features and quick evidence-driven decisions based on changing needs. The UHC system grew rapidly and covers 203 million people, the largest single-payer scheme in the world, and has improved health equity and service access. With early success, challenges have emerged, such as the so-called missing-middle group, a term used to designate the smaller number of people who have enrolled in UHC in wealth quintiles Q2-Q3 than in other quintiles, and the low UHC coverage of children from birth to age 4 years. Moreover, high costs for non-communicable diseases warrant new features for prevention and promotion of healthy lifestyles, and investment in a robust integrated digital health-information system for front-line health workers is crucial for impact and sustainability. This Review describes the innovative UHC initiative of Indonesia along with the future roadmap required to meet sustainable development goals by 2030.

Building a Digital Tool for the Adoption of the World Health Organization's Antenatal Care Recommendations: Methodological Intersection of Evidence, Clinical Logic, and Digital Technology.

BACKGROUND: One of the key mandates of the World Health Organization (WHO) is to develop guidelines, defined as "a document containing recommendations for clinical practice or public health policy." Guidelines represent the global standard for information sources shaping clinical practice and public health policies. Despite the rigorous development process and the value of guidelines for setting standards, implementing such standards within local contexts and at the point of care is a well-documented challenge. Digital technologies enable agile information management and may facilitate the adaptation of guidelines to diverse settings of health services delivery. OBJECTIVE: The objective of this paper is to detail the systematic and iterative process involved in transforming the WHO Antenatal Care (ANC) guidelines into a digital decision-support and patient-record application for routine use in primary health care settings, known as the WHO digital ANC module. METHODS: The WHO convened a team of clinical and digital health experts to develop the WHO digital ANC module as a tool to assist health care professionals in the implementation of WHO evidence-based recommendations for pregnant women. The WHO digital ANC module's creation included the following steps: defining a minimum viable product (MVP), developing clinical workflows and algorithms, algorithm testing, developing a data dictionary, and the creation of a user interface or application development. The overall process of development took approximately 1 year to reach a stable prototype and to finalize the underlying content requirements of the data dictionary and decision support algorithms. RESULTS: The first output is a reference software reflecting the generic WHO ANC guideline content, known as the WHO digital ANC module. Within it, all actionable ANC recommendations have related data fields and algorithms to confirm whether the associated task was performed. WHO recommendations that are not carried out by the health care worker are saved as pending tasks on a woman's health record, and those that are adequately fulfilled trigger messages with positive reinforcement. The second output consists of the structured documentation of the different components which contributed to the development of the WHO digital ANC module, such as the data dictionary and clinical decision support workflows. CONCLUSIONS: This is a novel approach to facilitate the adoption and adaptation of recommendations through digital systems at the health service delivery level. It is expected that the WHO digital ANC module will support the implementation of evidence-based practices and provide information for monitoring and surveillance; however, further evidence is needed to understand how the WHO digital ANC module impacts the implementation of WHO recommendations. Further, the module's implementation will inform the WHO's ongoing efforts to create a pathway to adaptive and integrated (Smart) Guidelines in Digital Systems to improve health system quality, coverage, and accountability.

Correction: Building a Digital Tool for the Adoption of the World Health Organization's Antenatal Care Recommendations: Methodological Intersection of Evidence, Clinical Logic, and Digital Technology.

[This corrects the article DOI: 10.2196/16355.].

Maternal Multiple Micronutrient Supplementation Stabilizes Mitochondrial DNA Copy Number in Pregnant Women in Lombok, Indonesia.

BACKGROUND: The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) in Lombok, Indonesia showed that maternal multiple micronutrients (MMN), as compared with iron and folic acid (IFA), reduced fetal loss, early infant mortality, and low birth weight. Mitochondria play a key role during pregnancy by providing maternal metabolic energy for fetal development, but the effects of maternal supplementation during pregnancy on mitochondria are not fully understood. OBJECTIVE: The aim of this study was to assess the impact of MMN supplementation on maternal mitochondrial DNA copy number (mtDNA-CN). METHODS: We used archived venous blood specimens from pregnant women enrolled in the SUMMIT study. SUMMIT was a cluster-randomized double-blind controlled trial in which midwives were randomly assigned to distribute MMN or IFA to pregnant women. In this study, we selected 108 sets of paired baseline and postsupplementation samples (MMN = 54 and IFA = 54). Maternal mtDNA-CN was determined by real-time quantitative polymerase chain reaction in baseline and postsupplementation specimens. The association between supplementation type and change in mtDNA-CN was performed using rank-based estimation for linear models. RESULTS: In both groups, maternal mtDNA-CN at postsupplementation was significantly elevated compared with baseline (P < 0.001). The regression revealed that the MMN group had lower postsupplementation mtDNA-CN than the IFA group (ß = -4.63, P = 0.003), especially for women with mtDNA-CN levels above the median at baseline (ß = -7.49, P = 0.007). This effect was rapid, and observed within 33 d of initiation of supplementation (ß = -7.39, P = 0.017). CONCLUSION: Maternal MMN supplementation rapidly stabilized mtDNA-CN in pregnant women who participated in SUMMIT, indicating improved mitochondrial efficiency. The data provide a mechanistic basis for the beneficial effects of MMN on fetal growth and survival, and support the transition from routine IFA to MMN supplementation.This trial was registered at www.isrctn.com as ISRCTN34151616.

Ghrelin for the management of cachexia associated with cancer.

BACKGROUND: Cancer sufferers are amongst the most malnourished of all the patient groups. Studies have shown that ghrelin, a gut hormone can be a potential therapeutic agent for cachexia (wasting syndrome) associated with cancer. A variety of mechanisms of action of ghrelin in people with cancer cachexia have been proposed. However, safety and efficacy of ghrelin for cancer-associated cachexia have not been systematically reviewed. The aim of this review was to assess whether ghrelin is associated with better food intake, body composition and survival than other options for adults with cancer cachexia. OBJECTIVES: To assess the efficacy and safety of ghrelin in improving food intake, body composition and survival in people with cachexia associated with cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase without language restrictions up to July 2017. We also searched for ongoing studies in trials registers, performed handsearching, checked bibliographic references of relevant articles and contacted authors and experts in the field to seek potentially relevant research. We applied no restrictions on language, date, or publication status. SELECTION CRITERIA: We included randomised controlled (parallel-group or cross-over) trials comparing ghrelin (any formulation or route of administration) with placebo or an active comparator in adults (aged 18 years and over) who met any of the international criteria for cancer cachexia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. Two review authors then extracted data and assessed the risk of bias for individual studies using standard Cochrane methodology. For dichotomous variables, we planned to calculate risk ratio with 95% confidence intervals (CI) and for continuous data, we planned to calculate mean differences (MD) with 95% CI. We assessed the evidence using GRADE and created 'Summary of findings' tables. MAIN RESULTS: We screened 926 individual references and identified three studies that satisfied the inclusion criteria. Fifty-nine participants (37 men and 22 women) aged between 54 and 78 years were randomised initially, 47 participants completed the treatment. One study had a parallel design and two had a cross-over design. The studies included people with a variety of cancers and also differed in the dosage, route of administration, frequency and duration of treatment.One trial, which compared ghrelin with placebo, found that ghrelin improved food intake (very low-quality evidence) and had no adverse events (very low-quality evidence). Due to unavailability of data we were unable to report on comparisons for ghrelin versus no treatment or alternative experimental treatment modalities, or ghrelin in combination with other treatments or ghrelin analogues/ghrelin mimetics/ghrelin potentiators. Two studies compared a higher dose of ghrelin with a lower dose of ghrelin, however due to differences in study designs and great diversity in the treatment provided we did not pool the results. In both trials, food intake did not differ between participants on higher-dose and lower-dose ghrelin. None of the included studies assessed data on body weight. One study reported higher adverse events with a higher dose as compared to a lower dose of ghrelin.All studies were at high risk of attrition bias and bias for size of the study. Risk of bias in other domains was unclear or low.We rated the overall quality of the evidence for primary outcomes (food intake, body weight, adverse events) as very low. We downgraded the quality of the evidence due to lack of data, high or unclear risk of bias of the studies and small study size. AUTHORS' CONCLUSIONS: There is insufficient evidence to be able to support or refute the use of ghrelin in people with cancer cachexia. Adequately powered randomised controlled trials focusing on evaluation of safety and efficacy of ghrelin in people with cancer cachexia is warranted.

Role of family support and women's knowledge on pregnancy-related risks in adherence to maternal iron-folic acid supplementation in Indonesia.

OBJECTIVE: To examine whether women's knowledge of pregnancy-related risks and family support received during pregnancy are associated with adherence to maternal iron-folic acid (IFA) supplementation. DESIGN: Secondary data analysis of the 2002-03, 2007 and 2012 Indonesia Demographic and Health Survey. Analysis of the association between factors associated with adherence (consuming ≥90 IFA tablets), including the women's knowledge and family support, was performed using multivariate logistic regression. SETTING: National household survey. SUBJECTS: Women (n 19 133) who had given birth within 2 years prior to the interview date. RESULTS: Knowledge of pregnancy-related risks was associated with increased adherence to IFA supplementation (adjusted OR=1·8; 95 % CI 1·6, 2·0), as was full family (particularly husband's) support (adjusted OR=1·9; 95 % CI 1·6, 2·3). Adequate antenatal care (ANC) visits (i.e. four or more) was associated with increased adherence (adjusted OR=2·2; 95 % CI 2·0, 2·4). However, ANC providers missed opportunities to distribute tablets and information, as among women with adequate ANC visits, 15 % reported never having received/bought any IFA tablets and 30 % had no knowledge of pregnancy-related risks. A significant interaction was observed between family support and the women's educational level in predicting adherence. Family support significantly increased the adherence among women with <9 years of education. CONCLUSIONS: Improving women's knowledge of pregnancy-related risks and involving family members, particularly the husband and importantly for less-educated women, improved adherence to IFA supplementation. ANC visit opportunities must be optimized to provide women with sufficient numbers of IFA tablets along with health information (especially on pregnancy-related risks) and partner support counselling.

Reproductive healthcare utilization in urban poor settlements of Delhi: Baseline survey of ANCHUL (Ante Natal and Child Health care in Urban Slums) project.

BACKGROUND: Disparity in utilization of reproductive healthcare services between the urban poor and the urban non-poor households in the developing nations is well known. However, disparity may also exist within urban poor households. Our objective was to document the extent of disparity in reproductive healthcare utilization among the urban poor and to identify the socio-demographic determinants of underutilization with a view to characterizing this vulnerable subpopulation. METHODS: A survey of 16,221 households was conducted in 39 clusters from two large urban poor settlements in Delhi. From 13,451 consenting households, socio-demographic data and information on births, maternal and child deaths within the previous year was collected. Details of antenatal care (ANC) was collected from 597 pregnant women. Information on ANC and postnatal care was also obtained from 596 recently delivered (within six months) mothers. All data were captured electronically using a customized and validated smart phone application. Households were categorized into quintiles of socio-economic position (SEP) based on dwelling characteristics and possession of durable assets using principal component analysis. Potential socio-demographic determinants of reproductive healthcare utilization were examined using random effects logistic regression. RESULTS: The prevalence of facility based birthing was 77% (n = 596 mothers). Of the 596 recently delivered mothers only 70% had an ANC registration card, 46.3% had ANC in their first trimester, 46% had visited a facility within 4 weeks post-delivery and 27% were using modern contraceptive methods. Low socio-economic position was the most important predictor of underutilization with a clear gradient across SEP quintiles. Compared to the poorest, the least poor women were more likely to be registered for ANC (OR 1.96, 95%CI 0.95-4.15) and more likely to have made ≥ 4 ANC visits (OR 5.86, 95%CI 2.82-12.19). They were more likely to have given birth in a facility (OR 4.87, 95%CI 2.12-11.16), to have visited a hospital within one month of childbirth (OR 3.18, 95%CI 1.62-6.26). In general, government funded health insurance and conditional cash transfers schemes were underutilized in this community. CONCLUSION: The poorest segment of the urban poor population utilizes reproductive healthcare facilities the least. Strategies to improve access and utilization of healthcare services among the poorest of the poor may be necessary to achieve universal health coverage.

Maternal agency influences the prevalence of diarrhea and acute respiratory tract infections among young Indonesian children.

To examine the relationship between measures of mother's caretaking, practice and individual agency on acute diarrhea and respiratory tract infections (ARTIs) of Indonesian children. Using population-based household data from the Indonesian Demographic Health Surveys for 2002-2003 (n = 9,151 children) and 2007 (n = 9,714 children), we selected 28 indicators related to mother' caretaking, and applied principal component analysis to derive indices for access to care, practice and experience, and agency. The association between index quartiles (level 1-4) and the prevalence of diarrhea and ARTIs in the youngest child <5 years of age was assessed with multivariate logistic regression adjusting for socioeconomic status, residence type, mother's age and education, family size, child's age and sex, immunization status and received vitamin A supplementation. Moderate levels (level 3) of practice and experience were associated with decreased diarrheal risk (adjusted OR 0.86, 95 % CI 0.75-0.98), but not for ARTIs. Children of mothers with higher levels (level 4) of agency were protected against both diarrhea (adjusted OR 0.68, 95 % CI 0.60-0.77) and ARTIs (adjusted OR 0.77, 95 % CI 0.66-0.91). Stratified analyses with child's age and mother's education, and tests of interaction, showed that agency had a stronger effect on diarrhea and ARTIs prevalence in children <2 years of age. Maternal caretaking, especially agency, is strongly associated with lower prevalence of diarrhea and ARTIs in younger children. Interventions specifically designed to promote maternal autonomy and decision-making may lead to improved child health.

Characteristics and clinical outcomes of patients with pre-delta, delta and omicron SARS-CoV-2 infection in Indonesia (2020-2023): a multicentre prospective cohort study.

Background: Limited data exist from southeast Asia on the impact of SARS-CoV-2 variants and inactivated vaccines on disease severity and death among patients hospitalised with COVID-19. Methods: A multicentre hospital-based prospective cohort was enrolled from September 2020 through January 2023, spanning pre-delta, delta, and omicron periods. The participant hospitals were conveniently sampled based on existing collaborations, site willingness and available study resources, and included six urban and two rural general hospitals from East Nusa Tenggara, Jakarta, and North Sumatra provinces. Factors associated with severe disease and day-28 mortality were examined using logistic and Cox regression. Findings: Among 822 participants, the age-adjusted percentage of severe disease was 26.8% (95% CI 22.7-30.9) for pre-delta, 50.1% (44.0-56.2) for delta, and 15.2% (9.7-20.7) for omicron. The odds of severe disease were 64% (18-84%) lower for omicron than delta (p < 0.001). One or more vaccine doses reduced the odds of severe disease by 89% (65-97%) for delta and 98% (91-100%) for omicron. Age-adjusted mortality was 11.9% (8.8-15.0) for pre-delta, 24.4% (18.8-29.9) for delta and 9.6% (5.2-14.0) for omicron. The day-28 cumulative incidence of death was lower for omicron (9.2% [5.6-13.9%]) than delta (28.6% [22.0-35.5%]) (p < 0.001). Severe disease on admission was the predominant prognostic factor for death (aHR34.0 [16.6-69.9] vs mild-or-moderate; p < 0.001). After controlling for disease severity on admission as an intermediate, the risk of death was 48% (32-60%) lower for omicron than delta (p < 0.001); and 51% (38-61%; p < 0.001) lower for vaccinated participants than unvaccinated participants overall, and 56% (37-69%; p < 0.001) for omicron, 46% (-5 to 73%; p = 0.070) for pre-delta (not estimable for delta). Interpretation: Infections by omicron variant resulted in less severe and fatal outcomes than delta in hospitalised patients in Indonesia. However, older, and unvaccinated individuals remained at greater risk of adverse outcomes. Funding: University of Oxford and Wellcome Trust.

Exploring perceptions and operational considerations for use of a smartphone application to self-monitor blood pressure in pregnancy in Lombok, Indonesia: protocol for a qualitative study.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal deaths globally and require close monitoring of blood pressure (BP) to mitigate potential adverse effects. Despite the recognised need for research on self-monitoring of blood pressure (SMBP) among pregnant populations, there are very few studies focused on low and middle income contexts, which carry the greatest burden of HDPs. The study aims to understand the perceptions, barriers, and operational considerations for using a smartphone software application to perform SMBP by pregnant women in Lombok, Indonesia. METHODS AND ANALYSIS: This study includes a combination of focus group discussions, in-depth interviews and workshop observations. Pregnant women will also be provided with a research version of the smartphone BP application to use in their home and subsequently provide feedback on their experiences. The study will include pregnant women with current or past HDP, their partners and the healthcare workers involved in the provision of antenatal care services within the catchment area of six primary healthcare centres. Data obtained from the interviews and observations will undergo thematic analyses using a combination of both inductive and deductive approaches. ETHICS AND DISSEMINATION: The study was approved by the World Health Organization (WHO) and Human Reproduction Programme (HRP) Research Project Review Panel and WHO Ethical Review Committee (A65932) as well as the Health Research Ethics Committee, Faculty of Medicine, Universitas Mataram in Indonesia (004/UN18/F7/ETIK/2023).Findings will be disseminated through research publications and communicated to the Lombok district health offices. The analyses from this study will also inform the design of a subsequent impact evaluation.

Impact of the COVID-19 pandemic on tuberculosis control in Indonesia: a nationwide longitudinal analysis of programme data.

BACKGROUND: The impact of the COVID-19 pandemic on tuberculosis control in high-burden countries has not been adequately assessed. We aimed to estimate the impact of the COVID-19 pandemic on the national tuberculosis programme in Indonesia, in association with indicators of human development and health-system capacity across all 514 districts in 34 provinces. METHODS: We did a nationwide longitudinal analysis to compare tuberculosis case notification, treatment coverage, and mortality rates in Indonesia before (2016-19) and during (2020-21) the COVID-19 pandemic. The following outcomes were assessed: the district-level quarterly reported tuberculosis case notification rate (number of all reported tuberculosis cases per 100 000 population), treatment coverage (proportion of tuberculosis patients who started treatment), and all-cause mortality rate in patients with tuberculosis (number of reported deaths per 100 000 population). District-level data on COVID-19 incidence and deaths, health-system capacity, and human development and sociodemographics were also analysed. Multilevel linear spline regression was done to assess quarterly time trends for the three outcomes. FINDINGS: During the COVID-19 pandemic, the tuberculosis case notification rate declined by 26% (case notification rate ratio 0·74, 95% CI 0·72-0·77) and treatment coverage declined by 11% (treatment coverage ratio 0·89, 95% CI 0·88-0·90), but there was no significant increase in all-cause mortality (all-cause mortality rate ratio 0·97, 95% CI 0·91-1·04) compared with the pre-pandemic period. In the second year of the pandemic, we observed a partial recovery of the case notification rate from Q1 to Q4 of 2021, a persistent decrease in treatment coverage, and a decrease in the all-cause mortality rate from Q2 of 2020 to Q4 of 2021. The multivariable analysis showed that the reduction in the tuberculosis case notification rate was associated with a higher COVID-19 incidence rate (adjusted odds ratio 3·1, 95% CI 1·1-8·6, for the highest compared with the lowest group) and fewer GeneXpert machines for tuberculosis diagnosis (3·1, 1·0-9·4, for the lowest compared with the highest group) per 100 000 population. The reduction in tuberculosis treatment coverage was associated with higher COVID-19 incidence (adjusted odds ratio 11·7, 95% CI 1·5-93·4, for the highest compared with the lowest group), fewer primary health centres (10·6, 4·1-28·0, for the lowest compared with the middle-high group), and a very low number of doctors (0·3, 0·1-0·9, for the low-middle compared with the lowest group) per 100 000 population. No factors were shown to be significantly associated with all-cause mortality. INTERPRETATION: The COVID-19 pandemic adversely and unevenly affected the national tuberculosis programme across Indonesia, with the greatest impacts observed in districts with the lowest health-system capacity. These disruptions could lead to an escalation in tuberculosis transmission in the coming years, warranting the need for intensified efforts to control tuberculosis and strengthen local health systems. FUNDING: Wellcome Africa Asia Programme Vietnam. TRANSLATION: For the Bahasa translation of the abstract see Supplementary Materials section.

Antibody Responses and Reactogenicity of a Heterologous, Full-Dose Messenger RNA-1273 Booster in Heavily SARS-CoV-2-Exposed CoronaVac-Vaccinated Health-Care Workers in Indonesia: A Real-World Observational Study.

Real-world data on heterologous boosting with messenger RNA (mRNA)-1273 (Moderna) after inactivated COVID-19 vaccination are limited. We report mRNA-1273 boosting in heavily SARS-CoV-2-exposed Indonesian health-care workers who received a two-dose CoronaVac 6 months prior. Between August and November 2021, we measured SARS-CoV-2 spike-specific IgG binding antibody (Bab) titers in all 304 participants, and neutralizing antibody titers in a random subset of 71 participants, on stored paired serum samples taken before and 28 days after a full-dose (100-µg) mRNA-1273 booster. At the time of the mRNA-1273 boost, 107 participants (35.2%) were not previously infected (naive vaccinated), 42 (13.8%) were infected before CoronaVac (infected vaccinated), and 155 (51.0%) were infected after CoronaVac (mostly during the Delta wave; vaccinated infected). At time of the mRNA-1273 boost, neutralizing antibodies could still be detected in 83% of participants (59 of 71) overall, 60% of naive-vaccinated participants (15 of 25), 95.7% of vaccinated-infected participants (22 of 23), and 95.7% of infected vaccinated participants (22 of 23). After the mRNA-1273 boost, 100% of participants (71 of 71) had neutralizing antibody activity, with increases in median Bab and neutralizing antibody serum titers of 9.3- and 27.0-fold overall, 89.1- and 2,803.4-fold in naive-vaccinated participants, 15.9- and 19.9-fold in infected-vaccinated participants, and 2.2- and 18.4-fold in vaccinated-infected participants. In the multivariable analysis, Bab titers after the mRNA-1273 boost were greatest in individuals who had a previous virus breakthrough post-CoronaVac, and when a longer time period (> 4 months) had elapsed since the most recent prior "spike antigen exposure" (either second CoronaVac or virus breakthrough). Overall, adverse reactions were mild and short-lived. In conclusion, a full-dose mRNA-1273 booster after CoronaVac was well tolerated and immunogenic after 28 days, including in those with very low antibody levels.

Anaemia in low-income and middle-income countries.

Anaemia affects a quarter of the global population, including 293 million (47%) children younger than 5 years and 468 million (30%) non-pregnant women. In addition to anaemia's adverse health consequences, the economic effect of anaemia on human capital results in the loss of billions of dollars annually. In this paper, we review the epidemiology, clinical assessment, pathophysiology, and consequences of anaemia in low-income and middle-income countries. Our analysis shows that anaemia is disproportionately concentrated in low socioeconomic groups, and that maternal anaemia is strongly associated with child anaemia. Anaemia has multifactorial causes involving complex interaction between nutrition, infectious diseases, and other factors, and this complexity presents a challenge to effectively address the population determinants of anaemia. Reduction of knowledge gaps in research and policy and improvement of the implementation of effective population-level strategies will help to alleviate the anaemia burden in low-resource settings.

Determinants of low birthweight, small-for-gestational-age and preterm birth in Lombok, Indonesia: analyses of the birthweight cohort of the SUMMIT trial.

OBJECTIVE: To examine the determinants of low birthweight (LBW), small-for-gestation (SGA) and preterm births in Lombok, Indonesia, an area of high infant mortality. METHODS: Data from The Supplementation with Multiple Micronutrient Intervention Trial (SUMMIT), a double-blind cluster-randomised controlled trial, were analysed. The odds ratio of factors known to be associated with LBW, SGA and preterm birth was assessed and adjusted for the cluster design of the trial using hierarchical logistic regression. Determinants included constitutional, demographic and psychosocial factors, toxic exposure, maternal nutrition and obstetric history and maternal morbidity during and prior to pregnancy. Population attributable risks of modifiable determinants were calculated. RESULTS: A cohort of 14,040 singleton births was available for analysis of LBW, with 13,498 observations for preterm births and 13,461 for SGA births. Determinants of LBW and SGA were similar and included infant's sex, woman's education, season at birth, mothers' residence, household wealth, maternal mid-upper arm circumference (MUAC), height and a composite variable of birth order and pregnancy interval. Socioeconomic indicators were also related to preterm births and included mother's education, residence and household wealth, while nutritional-related factors including low MUAC and birth order and interval were associated with preterm birth but not maternal height. Nausea was protective of preterm birth, while diarrhoea was associated with higher odds of preterm birth. Oedema during pregnancy was protective of SGA but associated with higher odds of preterm delivery. Around 33%, 13% and 13% of the determinants of LBW, SGA and preterm births were preventable. CONCLUSION: Women's education, maternal nutrition and household wealth and family planning are key factors to improving birth outcomes.