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Cost-effectiveness and economic returns of group-based parenting interventions to promote early childhood development: Results from a randomized controlled trial in rural Kenya

Ma, 28/09/2021 - 15:00

by Italo Lopez Garcia, Uzaib Y. Saya, Jill E. Luoto

Background

Early childhood development (ECD) programs can help address disadvantages for the 43% of children under 5 in low- and middle-income countries (LMICs) experiencing compromised development. However, very few studies from LMIC settings include information on their program’s cost-effectiveness or potential returns to investment. We estimated the cost-effectiveness, benefit–cost ratios (BCRs), and returns on investment (ROIs) for 2 effective group-based delivery models of an ECD parenting intervention that utilized Kenya’s network of local community health volunteers (CHVs).

Methods and findings

Between October 1 and November 12, 2018, 1,152 mothers with children aged 6 to 24 months were surveyed from 60 villages in rural western Kenya. After baseline, villages were randomly assigned to one of 3 intervention arms: a group-only delivery model with 16 fortnightly sessions, a mixed-delivery model combining 12 group sessions with 4 home visits, and a control group. At endline (August 5 to October 31, 2019), 1,070 children were retained and assessed for primary outcomes including cognitive and receptive language development (with the Bayley Scales of Infant Development, Third Edition) and socioemotional development (with the Wolke scale). Children in the 2 intervention arms showed better developmental outcomes than children in the control arm, although the group-only delivery model generally had larger effects on children. Total program costs included provider’s implementation costs collected during the intervention period using financial reports from the local nongovernmental organization (NGO) implementer, as well as societal costs such as opportunity costs to mothers and delivery agents. We combined program impacts with these total costs to estimate incremental cost-effectiveness ratios (ICERs), as well as BCRs and the program’s ROI for the government based on predictions of future lifetime wages and societal costs. Total costs per child were US$140 in the group-only arm and US$145 in the mixed-delivery arm. Because of higher intention-to-treat (ITT) impacts at marginally lower costs, the group-only model was the most cost-effective across all child outcomes. Focusing on child cognition in this arm, we estimated an ICER of a 0.37 standard deviation (SD) improvement in cognition per US$100 invested, a BCR of 15.5, and an ROI of 127%. A limitation of our study is that our estimated BCR and ROI necessarily make assumptions about the discount rate, income tax rates, and predictions of intervention impacts on future wages and schooling. We examine the sensitivity of our results to these assumptions.

Conclusions

To the best of our knowledge, this study is the first economic evaluation of an effective ECD parenting intervention targeted to young children in sub-Saharan Africa (SSA) and the first to adopt a societal perspective in calculating cost-effectiveness that accounts for opportunity costs to delivery agents and program participants. Our cost-effectiveness and benefit–cost estimates are higher than most of the limited number of prior studies from LMIC settings providing information about costs. Our results represent a strong case for scaling similar interventions in impoverished rural settings, and, under reasonable assumptions about the future, demonstrate that the private and social returns of such investments are likely to largely outweigh their costs.

Trial registration

This trial is registered at ClinicalTrials.gov, NCT03548558, June 7, 2018. American Economic Association RCT Registry trial AEARCTR-0002913.

Examining the relationships between early childhood experiences and adolescent and young adult health status in a resource-limited population: A cohort study

Ma, 28/09/2021 - 15:00

by Zeba A. Rasmussen, Wasiat H. Shah, Chelsea L. Hansen, Syed Iqbal Azam, Ejaz Hussain, Barbara A. Schaefer, Nicole Zhong, Alexandra F. Jamison, Khalil Ahmed, Benjamin J. J. McCormick, for the Oshikhandass Water, Sanitation, Health and Hygiene Interventions Project

Background

Adolescence is a critical point in the realization of human capital, as health and educational decisions with long-term impacts are made. We examined the role of early childhood experiences on health, cognitive abilities, and educational outcomes of adolescents followed up from a longitudinal cohort study in Pakistan, hypothesizing that early childhood experiences reflecting poverty would manifest in reduced health and development in adolescence.

Methods and findings

Adolescents/young adults previously followed as children aged under 5 years were interviewed. Childhood data were available on diarrhea, pneumonia, and parental/household characteristics. New data were collected on health, anthropometry, education, employment, and languages spoken; nonverbal reasoning was assessed. A multivariable Bayesian network was constructed to explore structural relationships between variables. Of 1,868 children originally enrolled, 1,463 (78.3%) were interviewed as adolescents (range 16.0–29.3 years, mean age 22.6 years); 945 (65%) lived in Oshikhandass. While 1,031 (70.5%) of their mothers and 440 (30.1%) of their fathers had received no formal education, adolescents reported a mean of 11.1 years of education. Childhood diarrhea (calculated as episodes/child-year) had no association with nonverbal reasoning score (an arc was supported in just 4.6% of bootstrap samples), health measures (with BMI, 1% of bootstrap samples; systolic and diastolic blood pressure, 0.1% and 1.6% of bootstrap samples, respectively), education (0.7% of bootstrap samples), or employment (0% of bootstrap samples). Relationships were found between nonverbal reasoning and adolescent height (arc supported in 63% of bootstrap samples), age (84%), educational attainment (100%), and speaking English (100%); speaking English was linked to the childhood home environment, mediated through maternal education and primary language. Speaking English (n = 390, 26.7% of adolescents) was associated with education (100% of bootstrap samples), self-reported child health (82%), current location (85%) and variables describing childhood socioeconomic status. The main limitations of this study were the lack of parental data to characterize the home setting (including parental mental and physical health, and female empowerment) and reliance on self-reporting of health status.

Conclusions

In this population, investments in education, especially for females, are associated with an increase in human capital. Against the backdrop of substantial societal change, with the exception of a small and indirect association between childhood malnutrition and cognitive scores, educational opportunities and cultural language groups have stronger associations with aspects of human capital than childhood morbidity.

Evaluation of a community-based mobile video breastfeeding intervention in Khayelitsha, South Africa: The Philani MOVIE cluster-randomized controlled trial

Ma, 28/09/2021 - 15:00

by Maya Adam, Jamie Johnston, Nophiwe Job, Mithilesh Dronavalli, Ingrid Le Roux, Nokwanele Mbewu, Neliswa Mkunqwana, Mark Tomlinson, Shannon A. McMahon, Amnesty E. LeFevre, Alain Vandormael, Kira-Leigh Kuhnert, Pooja Suri, Jennifer Gates, Bongekile Mabaso, Aarti Porwal, Charles Prober, Till Bärnighausen

Background

In South Africa, breastfeeding promotion is a national health priority. Regular perinatal home visits by community health workers (CHWs) have helped promote exclusive breastfeeding (EBF) in underresourced settings. Innovative, digital approaches including mobile video content have also shown promise, especially as access to mobile technology increases among CHWs. We measured the effects of an animated, mobile video series, the Philani MObile Video Intervention for Exclusive breastfeeding (MOVIE), delivered by a cadre of CHWs (“mentor mothers”).

Methods and findings

We conducted a stratified, cluster-randomized controlled trial from November 2018 to March 2020 in Khayelitsha, South Africa. The trial was conducted in collaboration with the Philani Maternal Child Health and Nutrition Trust, a nongovernmental community health organization. We quantified the effect of the MOVIE intervention on EBF at 1 and 5 months (primary outcomes), and on other infant feeding practices and maternal knowledge (secondary outcomes). We randomized 1,502 pregnant women in 84 clusters 1:1 to 2 study arms. Participants’ median age was 26 years, 36.9% had completed secondary school, and 18.3% were employed. Mentor mothers in the video intervention arm provided standard-of-care counseling plus the MOVIE intervention; mentor mothers in the control arm provided standard of care only. Within the causal impact evaluation, we nested a mixed-methods performance evaluation measuring mentor mothers’ time use and eliciting their subjective experiences through in-depth interviews.At both points of follow-up, we observed no statistically significant differences between the video intervention and the control arm with regard to EBF rates and other infant feeding practices [EBF in the last 24 hours at 1 month: RR 0.93 (95% CI 0.86 to 1.01, P = 0.091); EBF in the last 24 hours at 5 months: RR 0.90 (95% CI 0.77 to 1.04, P = 0.152)]. We observed a small, but significant improvement in maternal knowledge at the 1-month follow-up, but not at the 5-month follow-up. The interpretation of the results from this causal impact evaluation changes when we consider the results of the nested mixed-methods performance evaluation. The mean time spent per home visit was similar across study arms, but the intervention group spent approximately 40% of their visit time viewing videos. The absence of difference in effects on primary and secondary endpoints implies that, for the same time investment, the video intervention was as effective as face-to-face counseling with a mentor mother. The videos were also highly valued by mentor mothers and participants. Study limitations include a high loss to follow-up at 5 months after premature termination of the trial due to the COVID-19 pandemic and changes in mentor mother service demarcations.

Conclusions

This trial measured the effect of a video-based, mobile health (mHealth) intervention, delivered by CHWs during home visits in an underresourced setting. The videos replaced about two-fifths of CHWs’ direct engagement time with participants in the intervention arm. The similar outcomes in the 2 study arms thus suggest that the videos were as effective as face-to-face counselling, when CHWs used them to replace a portion of that counselling. Where CHWs are scarce, mHealth video interventions could be a feasible and practical solution, supporting the delivery and scaling of community health promotion services.

Trial registration

The study and its outcomes were registered at clinicaltrials.gov (#NCT03688217) on September 27, 2018.

The relationship between psychosocial circumstances and injuries in adolescents: An analysis of 87,269 individuals from 26 countries using the Global School-based Student Health Survey

Ma, 28/09/2021 - 15:00

by Samiha Ismail, Maria Lisa Odland, Amman Malik, Misghina Weldegiorgis, Karen Newbigging, Margaret Peden, Mark Woodward, Justine Davies

Background

Over a million adolescents die globally each year from preventable or treatable causes, with injuries (intentional and unintentional) being the leading cause of these deaths. To inform strategies to prevent these injuries, we aimed to assess psychosocial factors associated with serious injury occurrence, type, and mechanism in adolescents.

Methods and findings

We conducted a secondary analysis of cross-sectional survey data collected from the Global School-based Student Health Survey between 2009 and 2015. We used logistic regression to estimate associations between prevalence of serious injuries, injury type (effects of injury), and injury mechanism (cause of injury) and psychosocial factors (factors that relate to individuals socially, or their thoughts or behaviour, or the interrelation between these variables). Psychosocial factors were categorised, based on review of the literature, author knowledge, and discussion amongst authors. The categories were markers of risky behaviour (smoking, alcohol use, drug use, and physical activity), contextual factors (hunger, bullying, and loneliness), protective factors (number of friends and having a supportive family), and markers of poor mental health (planned or attempted suicide and being too worried to sleep). Models were adjusted for country factors (geographical area and income status, both using World Bank classification), demographic factors (age and sex), and factors to explain the survey design. A total of 87,269 adolescents living in 26 countries were included. The weighted majority were 14–15 years old (45.88%), male (50.70%), from a lower-middle-income country (81.93%), and from East Asia and the Pacific (66.83%). The weighted prevalence of a serious injury in the last 12 months was 36.33%, with the rate being higher in low-income countries compared to other countries (48.74% versus 36.14%) and amongst males compared to females (42.62% versus 29.87%). Psychosocial factors most strongly associated with serious injury were being bullied (odds ratio [OR] 2.45, 95% CI 1.93 to 3.13, p < 0.001), drug use (OR 2.08, 95% CI 1.73 to 2.49, p < 0.001), attempting suicide (OR 1.78, CI 1.55 to 2.04, p < 0.001), being too worried to sleep (OR 1.80, 95% CI 1.54 to 2.10, p < 0.001), feeling lonely (OR 1.61, 95% CI 1.37 to 1.89, p < 0.001), and going hungry (OR 1.61, 95% CI 1.30 to 2.01, p < 0.001). Factors hypothesised to be protective were not associated with reduced odds of serious injury: Number of close friends was associated with an increased odds of injury (OR 1.23, 95% CI 1.06 to 1.43, p = 0.007), as was having understanding parents or guardians (OR 1.13, 95% CI 1.01 to 1.26, p = 0.036). Being bullied, using drugs, and attempting suicide were associated with most types of injury, and being bullied or too worried to sleep were associated with most mechanisms of injury; other psychosocial factors were variably associated with injury type and mechanism. Limitations include the cross-sectional study design, making it not possible to determine the directionality of the associations found, and the survey not capturing children who did not go to school.

Conclusions

We observed strong associations between serious injury and psychosocial factors, but we note the relationships are likely to be complex and our findings do not inform causality. Nevertheless, our findings suggest that multifactorial programmes to target psychosocial factors might reduce the number of serious injuries in adolescents, in particular programmes concentrating on reducing bullying and drug use and improving mental health.

Ambient and household PM<sub>2.5</sub> pollution and adverse perinatal outcomes: A meta-regression and analysis of attributable global burden for 204 countries and territories

Ma, 28/09/2021 - 15:00

by Rakesh Ghosh, Kate Causey, Katrin Burkart, Sara Wozniak, Aaron Cohen, Michael Brauer

Background

Particulate matter <2.5 micrometer (PM2.5) is associated with adverse perinatal outcomes, but the impact on disease burden mediated by this pathway has not previously been included in the Global Burden of Disease (GBD), Mortality, Injuries, and Risk Factors studies. We estimated the global burden of low birth weight (LBW) and preterm birth (PTB) and impacts on reduced birth weight and gestational age (GA), attributable to ambient and household PM2.5 pollution in 2019.

Methods and findings

We searched PubMed, Embase, and Web of Science for peer-reviewed articles in English. Study quality was assessed using 2 tools: (1) Agency for Healthcare Research and Quality checklist; and (2) National Institute of Environmental Health Sciences (NIEHS) risk of bias questions. We conducted a meta-regression (MR) to quantify the risk of PM2.5 on birth weight and GA. The MR, based on a systematic review (SR) of articles published through April 4, 2021, and resulting uncertainty intervals (UIs) accounted for unexplained between-study heterogeneity. Separate nonlinear relationships relating exposure to risk were generated for each outcome and applied in the burden estimation.The MR included 44, 40, and 40 birth weight, LBW, and PTB studies, respectively. Majority of the studies were of retrospective cohort design and primarily from North America, Europe, and Australia. A few recent studies were from China, India, sub-Saharan Africa, and South America. Pooled estimates indicated 22 grams (95% UI: 12, 32) lower birth weight, 11% greater risk of LBW (1.11, 95% UI: 1.07, 1.16), and 12% greater risk of PTB (1.12, 95% UI: 1.06, 1.19), per 10 μg/m3 increment in ambient PM2.5. We estimated a global population–weighted mean lowering of 89 grams (95% UI: 88, 89) of birth weight and 3.4 weeks (95% UI: 3.4, 3.4) of GA in 2019, attributable to total PM2.5. Globally, an estimated 15.6% (95% UI: 15.6, 15.7) of all LBW and 35.7% (95% UI: 35.6, 35.9) of all PTB infants were attributable to total PM2.5, equivalent to 2,761,720 (95% UI: 2,746,713 to 2,776,722) and 5,870,103 (95% UI: 5,848,046 to 5,892,166) infants in 2019, respectively. About one-third of the total PM2.5 burden for LBW and PTB could be attributable to ambient exposure, with household air pollution (HAP) dominating in low-income countries. The findings should be viewed in light of some limitations such as heterogeneity between studies including size, exposure levels, exposure assessment method, and adjustment for confounding. Furthermore, studies did not separate the direct effect of PM2.5 on birth weight from that mediated through GA. As a consequence, the pooled risk estimates in the MR and likewise the global burden may have been underestimated.

Conclusions

Ambient and household PM2.5 were associated with reduced birth weight and GA, which are, in turn, associated with neonatal and infant mortality, particularly in low- and middle-income countries.

Neurocognitive outcomes in Malawian children exposed to malaria during pregnancy: An observational birth cohort study

Ma, 28/09/2021 - 15:00

by Andrea M. Weckman, Andrea L. Conroy, Mwayiwawo Madanitsa, Bruno Gnaneswaran, Chloe R. McDonald, Linda Kalilani-Phiri, Jaya Chandna, Doreen Ali, Victor Mwapasa, Carole Khairallah, Kyaw Lay Thwai, Steven R. Meshnick, Steve M. Taylor, Feiko O. ter Kuile, Kevin C. Kain, Melissa Gladstone

Background

Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring.

Methods and findings

Between April 2014 and April 2015, we followed 421 Malawian mother–baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur–Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], −7.53 [−13.04, −2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], −8.57 [−13.09, −4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies.

Conclusions

This mother–baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.

Effectiveness of cash-plus programmes on early childhood outcomes compared to cash transfers alone: A systematic review and meta-analysis in low- and middle-income countries

Ma, 28/09/2021 - 15:00

by Madison T. Little, Keetie Roelen, Brittany C. L. Lange, Janina I. Steinert, Alexa R. Yakubovich, Lucie Cluver, David K. Humphreys

Background

To strengthen the impact of cash transfers, these interventions have begun to be packaged as cash-plus programmes, combining cash with additional transfers, interventions, or services. The intervention’s complementary (“plus”) components aim to improve cash transfer effectiveness by targeting mediating outcomes or the availability of supplies or services. This study examined whether cash-plus interventions for infants and children <5 are more effective than cash alone in improving health and well-being.

Methods and findings

Forty-two databases, donor agencies, grey literature sources, and trial registries were systematically searched, yielding 5,097 unique articles (as of 06 April 2021). Randomised and quasi-experimental studies were eligible for inclusion if the intervention package aimed to improve outcomes for children <5 in low- and middle-income countries (LMICs) and combined a cash transfer with an intervention targeted to Sustainable Development Goal (SDG) 2 (No Hunger), SDG3 (Good Health and Well-being), SDG4 (Education), or SDG16 (Violence Prevention), had at least one group receiving cash-only, examined outcomes related to child-focused SDGs, and was published in English. Risk of bias was appraised using Cochrane Risk of Bias and ROBINS-I Tools. Random effects meta-analyses were conducted for a cash-plus intervention category when there were at least 3 trials with the same outcome. The review was preregistered with PROSPERO (CRD42018108017). Seventeen studies were included in the review and 11 meta-analysed. Most interventions operated during the first 1,000 days of the child’s life and were conducted in communities facing high rates of poverty and often, food insecurity. Evidence was found for 10 LMICs, where most researchers used randomised, longitudinal study designs (n = 14). Five intervention categories were identified, combining cash with nutrition behaviour change communication (BCC, n = 7), food transfers (n = 3), primary healthcare (n = 2), psychosocial stimulation (n = 7), and child protection (n = 4) interventions. Comparing cash-plus to cash alone, meta-analysis results suggest Cash + Food Transfers are more effective in improving height-for-age (d = 0.08 SD (0.03, 0.14), p = 0.02) with significantly reduced odds of stunting (OR = 0.82 (0.74, 0.92), p = 0.01), but had no added impact in improving weight-for-height (d = −0.13 (−0.42, 0.16), p = 0.24) or weight-for-age z-scores (d = −0.06 (−0.28, 0.15), p = 0.43). There was no added impact above cash alone from Cash + Nutrition BCC on anthropometrics; Cash + Psychosocial Stimulation on cognitive development; or Cash + Child Protection on parental use of violent discipline or exclusive positive parenting. Narrative synthesis evidence suggests that compared to cash alone, Cash + Primary Healthcare may have greater impacts in reducing mortality and Cash + Food Transfers in preventing acute malnutrition in crisis contexts. The main limitations of this review are the few numbers of studies that compared cash-plus interventions against cash alone and the potentially high heterogeneity between study findings.

Conclusions

In this study, we observed that few cash-plus combinations were more effective than cash transfers alone. Cash combined with food transfers and primary healthcare show the greatest signs of added effectiveness. More research is needed on when and how cash-plus combinations are more effective than cash alone, and work in this field must ensure that these interventions improve outcomes among the most vulnerable children.

Exposure to conflicts and the continuum of maternal healthcare: Analyses of pooled cross-sectional data for 452,192 women across 49 countries and 82 surveys

Ma, 28/09/2021 - 15:00

by Anu Rammohan, Astghik Mavisakalyan, Loan Vu, Srinivas Goli

Background

Violent conflicts are observed in many parts of the world and have profound impacts on the lives of exposed individuals. The limited evidence available from specific country or region contexts suggest that conflict exposure may reduce health service utilization and have adverse affects on health. This study focused on identifying the association between conflict exposure and continuum of care (CoC) services that are crucial for achieving improvements in reproductive, maternal, newborn, and child health and nutrition (RMNCHN).

Methods and findings

We combined data from 2 sources, the Demographic Health Surveys (DHS) and the Uppsala Conflict Data Program’s (UCDP) Georeferenced Event Dataset, for a sample of 452,192 women across 49 countries observed over the period 1997 to 2018. We utilized 2 consistent measures of conflict—incidence and intensity—and analyzed their association with maternal CoC in 4 key components: (i) at least 1 antenatal care (ANC) visit; (ii) 4 or more ANC visits; (iii) 4 or more ANC visits and institutional delivery; and (iv) 4 or more ANC visits, institutional delivery, and receipt of postnatal care (PNC) either for the mother or the child within 48 hours after birth. To identify the association between conflict exposure and components of CoC, we estimated binary logistic regressions, controlling for a large set of individual and household-level characteristics and year-of-survey and country/province fixed-effects. This empirical setup allows us to draw comparisons among observationally similar women residing in the same locality, thereby mitigating the concerns over unobserved heterogeneity. Around 39.6% (95% CI: 39.5% to 39.7%) of the sample was exposed to some form of violent conflict at the time of their pregnancy during the study period (2003 to 2018). Although access to services decreased for each additional component of CoC in maternal healthcare for all women, the dropout rate was significantly higher among women who have been exposed to conflict, relative to those who have not had such exposure. From logistic regression estimates, we observed that relative to those without exposure to conflict, the odds of utilization of each of the components of CoC was lower among those women who were exposed to at least 1 violent conflict. We estimated odds ratios of 0.86 (95% CI: 0.82 to 0.91, p < 0.001) for at least 1 ANC; 0.95 (95% CI: 0.91 to 0.98, p < 0.005) for 4 or more ANC; and 0.92 (95% CI: 0.89 to 0.96, p < 0.001) for 4 or more ANC and institutional delivery. We showed that both the incidence of exposure to conflict as well as its intensity have profound negative implications for CoC. Study limitations include the following: (1) We could not extend the CoC scale beyond PNC due to inconsistent definitions and the lack of availability of data for all 49 countries across time. (2) The measure of conflict intensity used in this study is based on the number of deaths due to the absence of information on other types of conflict-related harms.

Conclusions

This study showed that conflict exposure is statistically significantly and negatively associated with utilization of maternal CoC services, in each component of the CoC scale. These findings have highlighted the challenges in achieving the Sustainable Development Goal 3 in conflict settings, and the need for more concerted efforts in ensuring CoC, to mitigate its negative implications on maternal and child health.

Severe bacterial neonatal infections in Madagascar, Senegal, and Cambodia: A multicentric community-based cohort study

Ma, 28/09/2021 - 15:00

by Bich-Tram Huynh, Elsa Kermorvant-Duchemin, Rattanak Chheang, Frederique Randrianirina, Abdoulaye Seck, Elisoa Hariniaina Ratsima, Zafitsara Zo Andrianirina, Jean-Baptiste Diouf, Armya Youssouf Abdou, Sophie Goyet, Véronique Ngo, Siyin Lach, Long Pring, Touch Sok, Michael Padget, Fatoumata Diene Sarr, Laurence Borand, Benoit Garin, Jean-Marc Collard, Perlinot Herindrainy, Agathe de Lauzanne, Muriel Vray, Elisabeth Delarocque-Astagneau, Didier Guillemot, On behalf of the BIRDY study group

Background

Severe bacterial infections (SBIs) are a leading cause of neonatal deaths in low- and middle-income countries (LMICs). However, most data came from hospitals, which do not include neonates who did not seek care or were treated outside the hospital. Studies from the community are scarce, and few among those available were conducted with high-quality microbiological techniques. The burden of SBI at the community level is therefore largely unknown. We aimed here to describe the incidence, etiology, risk factors, and antibiotic resistance profiles of community-acquired neonatal SBI in 3 LMICs.

Methods and findings

The BIRDY study is a prospective multicentric community-based mother and child cohort study and was conducted in both urban and rural areas in Madagascar (2012 to 2018), Cambodia (2014 to 2018), and Senegal (2014 to 2018). All pregnant women within a geographically defined population were identified and enrolled. Their neonates were actively followed from birth to 28 days to document all episodes of SBI. A total of 3,858 pregnant women (2,273 (58.9%) in Madagascar, 814 (21.1%) in Cambodia, and 771 (20.0%) in Senegal) were enrolled in the study, and, of these, 31.2% were primigravidae. Women enrolled in the urban sites represented 39.6% (900/2,273), 45.5% (370/814), and 61.9% (477/771), and those enrolled in the rural sites represented 60.4% (1,373/2,273), 54.5% (444/814), and 38.1% (294/771) of the total in Madagascar, Cambodia, and Senegal, respectively. Among the 3,688 recruited newborns, 49.6% were male and 8.7% were low birth weight (LBW). The incidence of possible severe bacterial infection (pSBI; clinical diagnosis based on WHO guidelines of the Integrated Management of Childhood Illness) was 196.3 [95% confidence interval (CI) 176.5 to 218.2], 110.1 [88.3 to 137.3], and 78.3 [59.5 to 103] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively. The incidence of pSBI differed between urban and rural sites in all study countries. In Madagascar, we estimated an incidence of 161.0 pSBI per 1,000 live births [133.5 to 194] in the urban site and 219.0 [192.6 to 249.1] pSBI per 1,000 live births in the rural site (p = 0.008). In Cambodia, estimated incidences were 141.1 [105.4 to 189.0] and 85.3 [61.0 to 119.4] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.025), while in Senegal, we estimated 103.6 [76.0 to 141.2] pSBI and 41.5 [23.0 to 75.0] pSBI per 1,000 live births in urban and rural sites, respectively (p = 0.006). The incidences of culture-confirmed SBI were 15.2 [10.6 to 21.8], 6.5 [2.7 to 15.6], and 10.2 [4.8 to 21.3] per 1,000 live births in Madagascar, Cambodia, and Senegal, respectively, with no difference between urban and rural sites in each country. The great majority of early-onset infections occurred during the first 3 days of life (72.7%). The 3 main pathogens isolated were Klebsiella spp. (11/45, 24.4%), Escherichia coli (10/45, 22.2%), and Staphylococcus spp. (11/45, 24.4%). Among the 13 gram-positive isolates, 5 were resistant to gentamicin, and, among the 29 gram-negative isolates, 13 were resistant to gentamicin, with only 1 E. coli out of 10 sensitive to ampicillin. Almost one-third of the isolates were resistant to both first-line drugs recommended for the management of neonatal sepsis (ampicillin and gentamicin). Overall, 38 deaths occurred among neonates with SBI (possible and culture-confirmed SBI together). LBW and foul-smelling amniotic fluid at delivery were common risk factors for early pSBI in all 3 countries. A main limitation of the study was the lack of samples from a significant proportion of infants with pBSI including 35 neonatal deaths. Without these samples, bacterial infection and resistance profiles could not be confirmed.

Conclusions

In this study, we observed a high incidence of neonatal SBI, particularly in the first 3 days of life, in the community of 3 LMICs. The current treatment for the management of neonatal infection is hindered by antimicrobial resistance. Our findings suggest that microbiological diagnosis of SBI remains a challenge in these settings and support more research on causes of neonatal death and the implementation of early interventions (e.g., follow-up of at-risk newborns during the first days of life) to decrease the burden of neonatal SBI and associated mortality and help achieve Sustainable Development Goal 3.

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial

Ma, 28/09/2021 - 15:00

by Aarti Kumar, Shambhavi Mishra, Shambhavi Singh, Sana Ashraf, Peiyi Kan, Amit Kumar Ghosh, Alok Kumar, Raghav Krishna, David K. Stevenson, Lu Tian, Peter M. Elias, Gary L. Darmstadt, Vishwajeet Kumar, for the Shivgarh Emollient Research Group

Background

Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings.

Methods and findings

This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation.

Conclusions

In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility–community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function.

Trial registration

ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry—India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

Drought and child vaccination coverage in 22 countries in sub-Saharan Africa: A retrospective analysis of national survey data from 2011 to 2019

Ma, 28/09/2021 - 15:00

by Jason M. Nagata, Adrienne Epstein, Kyle T. Ganson, Tarik Benmarhnia, Sheri D. Weiser

Background

Extreme weather events, including droughts, are expected to increase in parts of sub-Saharan Africa and are associated with a number of poor health outcomes; however, to the best of our knowledge, the link between drought and childhood vaccination remains unknown. The objective of this study was to evaluate the relationship between drought and vaccination coverage.

Methods and findings

We investigated the association between drought and vaccination coverage using a retrospective analysis of Demographic and Health Surveys data in 22 sub-Saharan African countries among 137,379 children (50.4% male) born from 2011 to 2019. Drought was defined as an established binary variable of annual rainfall less than or equal to the 15th percentile relative to the 29 previous years, using data from Climate Hazards Group InfraRed Precipitation with Station (CHIRPS) data. We evaluated the association between drought at the date of birth and receipt of bacillus Calmette–Guérin (BCG), diphtheria–pertussis–tetanus (DPT), and polio vaccinations, and the association between drought at 12 months of age and receipt of measles vaccination. We specified logistic regression models with survey fixed effects and standard errors clustered at the enumeration area level, adjusting for child-, mother-, and household-level covariates and estimated marginal risk differences (RDs). The prevalence of drought at date of birth in the sample was 11.8%. Vaccination rates for each vaccination ranged from 70.6% (for 3 doses of the polio vaccine) to 86.0% (for BCG vaccination); however, only 57.6% of children 12 months and older received all recommended doses of BCG, DPT, polio, and measles vaccinations. In adjusted models, drought at date of birth was negatively associated with BCG vaccination (marginal RD = −1.5; 95% CI −2.2, −0.9), DPT vaccination (marginal RD = −1.4; 95% CI −2.2, −0.5), and polio vaccination (marginal RD = −1.3; 95% CI −2.3, −0.3). Drought at 12 months was negatively associated with measles vaccination (marginal RD = −1.9; 95% CI −2.8, −0.9). We found a dose–response relationship between drought and DPT and polio vaccinations, with the strongest associations closest to the timing of drought. Limitations include some heterogeneity in findings across countries.

Conclusions

In this study, we observed that drought was associated with lower odds of completion of childhood BCG, DPT, and polio vaccinations. These findings indicate that drought may hinder vaccination coverage, one of the most important interventions to prevent infections among children. This work adds to a growing body of literature suggesting that health programs should consider impacts of severe weather in their programming.

Gender-equitable caregiver attitudes and education and safety of adolescent girls in South Kivu, DRC: A secondary analysis from a randomized controlled trial

Ma, 28/09/2021 - 15:00

by Ilana Seff, Kathryn Falb, Gary Yu, Debbie Landis, Lindsay Stark

Background

Adolescent girls face myriad threats to their well-being and safety as a result of gender-inequitable attitudes and norms, and these risks are often exacerbated during humanitarian emergencies. While humanitarian actors have begun to address caregivers’ behaviors and gender attitudes as an approach to support and meet the needs of adolescent girls, best practices for working with caregivers to improve adolescent girls’ well-being in these settings have yet to be identified.

Methods and findings

This study uses panel data from a program evaluation to analyze associations between changes in gender-equitable attitudes among caregivers and changes in schooling and violence victimization for girls ages 10 to 14 years old in the Democratic Republic of the Congo (DRC). Participants were recruited in May 2015 for baseline (May to July 2015) and endline (August to October 2016) data collection. Baseline and endline data for both caregivers and girls were available for 732 girls. The average ages of adolescents and caregivers were 12 and 40.7, respectively, and 92% of caregivers were female. The predictor of interest was the change in caregivers’ gender-equitable attitudes between the 2 points in time, where attitudes were measured using 10 underlying survey questions. The primary outcomes of interest were dichotomous and included improvement in schooling participation and declines in physical, sexual, and emotional violence and feeling uncared for. Logistic regression was used to estimate the association between changes in caregivers’ attitudes and 5 outcomes of interest and revealed that an increase in a caregiver’s gender-equitable attitude score was associated with significantly greater odds of a girl experiencing an improvement in schooling participation (aOR = 1.08, CI [1.005, 1.154], p = 0.036) and of a girl experiencing a marginal decline in physical violence victimization (aOR = 1.07, CI [0.989, 1.158], p = 0.092). Analyses also revealed that older girls had lower odds of experiencing an improvement in schooling participation (aOR = 0.77, CI [0.686, 0.861], p < 0.001), physical violence (aOR = 0.86, CI [0.757, 0.984], p = 0.028), sexual violence (aOR = 0.86, CI [0.743, 1.003], p = 0.055), or emotional violence (aOR = 0.98, CI [0.849, 1.105], p = 0.005). Important limitations in this study include the self-reported nature of outcomes, use of single questionnaire items to construct the outcome variables, and potential self-selection bias.

Conclusions

Results suggest that supporting caregivers to increase gender equitable attitudes may be associated with benefits in dual outcomes of education and safety for adolescent girls in eastern DRC. Further research is needed to better understand how to induce a shift in these attitudes in multisectoral programming.

Trial registration

NCT02384642.

A novel intervention combining supplementary food and infection control measures to improve birth outcomes in undernourished pregnant women in Sierra Leone: A randomized, controlled clinical effectiveness trial

Ma, 28/09/2021 - 15:00

by David Taylor Hendrixson, Kristie Smith, Patrick Lasowski, Meghan Callaghan-Gillespie, Jacklyn Weber, Peggy Papathakis, Per Ole Iversen, Aminata Shamit Koroma, Mark J. Manary

Background

Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women.

Methods and findings

This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal care at one of 43 government health clinics in Western Rural Area and Pujehun districts were eligible for participation. Standard of care included a blended corn/soy flour and intermittent preventive treatment for malaria in pregnancy (IPTp). The intervention replaced the blended flour with RUSF and added azithromycin and testing and treatment for vaginal dysbiosis. Since the study involved different foods and testing procedures for the intervention and control groups, no one except the authors conducting the data analyses were blinded. The primary outcome was birth length. Secondary outcomes included maternal weight gain, birth weight, and neonatal survival. Follow-up continued until 6 months postpartum. Modified intention to treat analyses was undertaken. Participants were enrolled and followed up from February 2017 until February 2020.Of the 1,489 women enrolled, 752 were allocated to the intervention and 737 to the standard of care. The median age of these women was 19.5 years, of which 42% were primigravid. Twenty-nine women receiving the intervention and 42 women receiving the standard of care were lost to follow-up before pregnancy outcomes were obtained. There were 687 singleton live births in the intervention group and 657 in the standard of care group. Newborns receiving the intervention were 0.3 cm longer (95% confidence interval (CI) 0.09 to 0.6; p = 0.007) and weighed 70 g more (95% CI 20 to 120; p = 0.005) than those receiving the standard of care. Those women receiving the intervention had greater weekly weight gain (mean difference 40 g; 95% CI 9.70 to 71.0, p = 0.010) than those receiving the standard of care. There were fewer neonatal deaths in the intervention (n = 13; 1.9%) than in the standard of care (n = 28; 4.3%) group (difference 2.4%; 95% CI 0.3 to 4.4), (HR 0.62 95% CI 0.41 to 0.94, p = 0.026). No differences in adverse events or symptoms between the groups was found, and no serious adverse events occurred. Key limitations of the study are lack of gestational age estimates and unblinded administration of the intervention.

Conclusions

In this study, we observed that the addition of RUSF, azithromycin, more frequent IPTp, and testing/treatment for vaginal dysbiosis in undernourished pregnant women resulted in modest improvements in anthropometric status of mother and child at birth, and a reduction in neonatal death. Implementation of this combined intervention in rural, equatorial Africa may well be an important, practical measure to reduce infant mortality in this context.

Trial registration

ClinicalTrials.gov NCT03079388.

Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial

Ma, 28/09/2021 - 15:00

by Mark D. DeBoer, James A. Platts-Mills, Sarah E. Elwood, Rebecca J. Scharf, Joann M. McDermid, Anne W. Wanjuhi, Samwel Jatosh, Siphael Katengu, Tarina C. Parpia, Elizabeth T. Rogawski McQuade, Jean Gratz, Erling Svensen, Jonathan R. Swann, Jeffrey R. Donowitz, Paschal Mdoe, Sokoine Kivuyo, Eric R. Houpt, Estomih Mduma

Background

Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage.

Methods and findings

We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother–child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: −2.05 CI −2.13, −1.96, placebo: −2.05 CI −2.14, −1.97; mean difference: 0.01 CI −0.13, 0.11, p = 0.91; nicotinamide: −2.06 CI −2.13, −1.95, placebo: −2.04 CI −2.14, −1.98, mean difference 0.03 CI −0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother’s height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings.

Conclusions

In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions.

Trial registration

ClinicalTrials.gov NCT03268902.

Conditional cash transfer program and child mortality: A cross-sectional analysis nested within the 100 Million Brazilian Cohort

Ma, 28/09/2021 - 15:00

by Dandara Ramos, Nívea B. da Silva, Maria Yury Ichihara, Rosemeire L. Fiaccone, Daniela Almeida, Samila Sena, Poliana Rebouças, Elzo Pereira Pinto Júnior, Enny S. Paixão, Sanni Ali, Laura C. Rodrigues, Maurício L. Barreto

Background

Brazil has made great progress in reducing child mortality over the past decades, and a parcel of this achievement has been credited to the Bolsa Família program (BFP). We examined the association between being a BFP beneficiary and child mortality (1–4 years of age), also examining how this association differs by maternal race/skin color, gestational age at birth (term versus preterm), municipality income level, and index of quality of BFP management.

Methods and findings

This is a cross-sectional analysis nested within the 100 Million Brazilian Cohort, a population-based cohort primarily built from Brazil’s Unified Registry for Social Programs (Cadastro Único). We analyzed data from 6,309,366 children under 5 years of age whose families enrolled between 2006 and 2015. Through deterministic linkage with the BFP payroll datasets, and similarity linkage with the Brazilian Mortality Information System, 4,858,253 children were identified as beneficiaries (77%) and 1,451,113 (23%) were not. Our analysis consisted of a combination of kernel matching and weighted logistic regressions. After kernel matching, 5,308,989 (84.1%) children were included in the final weighted logistic analysis, with 4,107,920 (77.4%) of those being beneficiaries and 1,201,069 (22.6%) not, with a total of 14,897 linked deaths. Overall, BFP participation was associated with a reduction in child mortality (weighted odds ratio [OR] = 0.83; 95% CI: 0.79 to 0.88; p < 0.001). This association was stronger for preterm children (weighted OR = 0.78; 95% CI: 0.68 to 0.90; p < 0.001), children of Black mothers (weighted OR = 0.74; 95% CI: 0.57 to 0.97; p < 0.001), children living in municipalities in the lowest income quintile (first quintile of municipal income: weighted OR = 0.72; 95% CI: 0.62 to 0.82; p < 0.001), and municipalities with better index of BFP management (5th quintile of the Decentralized Management Index: weighted OR = 0.76; 95% CI: 0.66 to 0.88; p < 0.001). The main limitation of our methodology is that our propensity score approach does not account for possible unmeasured confounders. Furthermore, sensitivity analysis showed that loss of nameless death records before linkage may have resulted in overestimation of the associations between BFP participation and mortality, with loss of statistical significance in municipalities with greater losses of data and change in the direction of the association in municipalities with no losses.

Conclusions

In this study, we observed a significant association between BFP participation and child mortality in children aged 1–4 years and found that this association was stronger for children living in municipalities in the lowest quintile of wealth, in municipalities with better index of program management, and also in preterm children and children of Black mothers. These findings reinforce the evidence that programs like BFP, already proven effective in poverty reduction, have a great potential to improve child health and survival. Subgroup analysis revealed heterogeneous results, useful for policy improvement and better targeting of BFP.

Relative risks of adverse events among older adults receiving opioids versus NSAIDs after hospital discharge: A nationwide cohort study

Lu, 27/09/2021 - 15:00

by Shoshana J. Herzig, Timothy S. Anderson, Yoojin Jung, Long Ngo, Dae H. Kim, Ellen P. McCarthy

Background

Although analgesics are initiated on hospital discharge in millions of adults each year, studies quantifying the risks of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) among older adults during this transition are limited. We sought to determine the incidence and risk of post-discharge adverse events among older adults with an opioid claim in the week after hospital discharge, compared to those with NSAID claims only.

Methods and findings

We performed a retrospective cohort study using a national sample of Medicare beneficiaries age 65 and older, hospitalized in the United States hospitals in 2016. We excluded beneficiaries admitted from or discharged to a facility. We derived a propensity score that included over 100 factors potentially related to the choice of analgesic, including demographics, diagnoses, surgeries, and medication coadministrations. Using 3:1 propensity matching, beneficiaries with an opioid claim in the week after hospital discharge (with or without NSAID claims) were matched to beneficiaries with an NSAID claim only. Primary outcomes included death, healthcare utilization (emergency department [ED] visits and rehospitalization), and a composite of known adverse effects of opioids or NSAIDs (fall/fracture, delirium, nausea/vomiting, complications of slowed colonic motility, acute renal failure, and gastritis/duodenitis) within 30 days of discharge. After 3:1 propensity matching, there were 13,385 beneficiaries in the opioid cohort and 4,677 in the NSAID cohort (mean age: 74 years, 57% female). Beneficiaries receiving opioids had a higher incidence of death (1.8% versus 1.1%; RR 1.7 [1.3 to 2.3], p < 0.001, number needed to harm [NNH] 125), healthcare utilization (19.0% versus 17.4%; RR 1.1 [1.02 to 1.2], p = 0.02, NNH 59), and any potential adverse effect (25.2% versus 21.3%; RR 1.2 [1.1 to 1.3], p < 0.001, NNH 26), compared to those with an NSAID claim only. Specifically, they had higher relative risk of fall/fracture (4.5% versus 3.4%; RR 1.3 [1.1 to 1.6], p = 0.002), nausea/vomiting (9.2% versus 7.3%; RR 1.3 [1.1 to 1.4], p < 0.001), and slowed colonic motility (8.0% versus 6.2%; RR 1.3 [1.1 to 1.4], p < 0.001). Risks of delirium, acute renal failure, and gastritis/duodenitis did not differ between groups. The main limitation of our study is the observational nature of the data and possibility of residual confounding.

Conclusions

Older adults filling an opioid prescription in the week after hospital discharge were at higher risk for mortality and other post-discharge adverse outcomes compared to those filling an NSAID prescription only.

Future directions for HIV service delivery research: Research gaps identified through WHO guideline development process

Gi, 23/09/2021 - 15:00

by Nathan Ford, Ingrid Eshun-Wilson, Wole Ameyan, Morkor Newman, Lara Vojnov, Meg Doherty, Elvin Geng

Nathan Ford and co-authors discuss the systematic identification of research gaps in improving HIV service delivery.

Prevalence and incidence of young onset dementia and associations with comorbidities: A study of data from the French national health data system

Gi, 23/09/2021 - 15:00

by Laure Carcaillon-Bentata, Cécile Quintin, Marjorie Boussac-Zarebska, Alexis Elbaz

Background

Dementia onset in those aged <65 years (young onset dementia, YOD) has dramatic individual and societal consequences. In the context of population aging, data on YOD are of major importance to anticipate needs for planning and allocation of health and social resources. Few studies have provided precise frequency estimates of YOD. The aim of this study is to provide YOD prevalence and incidence estimates in France and to study the contribution of comorbidities to YOD incidence.

Methods and findings

Using data from the French national health data system (Système National des Données de Santé, SNDS) for 76% of the French population aged 40 to 64 years in 2016 (n = 16,665,795), we identified all persons with dementia based on at least 1 of 3 criteria: anti-Alzheimer drugs claims, hospitalization with the International Classification of Diseases-10th Revision (ICD-10) dementia code (F00 to F03, G30, G31.0, G31.1, or F05.1), or registration for free healthcare for dementia. We estimated prevalence rate (PR) and incidence rate (IR) and estimated the association of comorbidities with incident YOD. Sex differences were investigated. We identified 18,466 (PRstandardized = 109.7/100,000) and 4,074 incident (IRstandardized = 24.4/100,000 person-years) persons with prevalent and incident YOD, respectively. PR and IR sharply increased with age. Age-adjusted PR and IR were 33% (95% confidence interval (CI) = 29 to 37) and 39% (95% CI = 31 to 48) higher in men than women (p < 0.001 both for PR and IR). Cardio- and cerebrovascular, neurological, psychiatric diseases, and traumatic brain injury prevalence were associated with incident YOD (age- and sex-adjusted p-values <0.001 for all comorbidities examined, except p = 0.109 for antihypertensive drug therapy). Adjustment for all comorbidities explained more than 55% of the sex difference in YOD incidence. The lack of information regarding dementia subtypes is the main limitation of this study.

Conclusions

We estimated that there were approximately 24,000 and approximately 5,300 persons with prevalent and incident YOD, respectively, in France in 2016. The higher YOD frequency in men may be partly explained by higher prevalence of cardiovascular and neurovascular diseases, substance abuse disorders, and traumatic brain injury and warrants further investigation.

Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis

Ma, 21/09/2021 - 15:00

by Kathy Trieu, Saiuj Bhat, Zhaoli Dai, Karin Leander, Bruna Gigante, Frank Qian, Andres V. Ardisson Korat, Qi Sun, Xiong-Fei Pan, Federica Laguzzi, Tommy Cederholm, Ulf de Faire, Mai-Lis Hellénius, Jason H. Y. Wu, Ulf Risérus, Matti Marklund

Background

We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality.

Methods and findings

We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose–response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case–cohort, or nested case–control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels.

Conclusions

In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.

Evaluation of an mHealth-enabled hierarchical diabetes management intervention in primary care in China (ROADMAP): A cluster randomized trial

Ma, 21/09/2021 - 15:00

by Weiping Jia, Puhong Zhang, Dalong Zhu, Nadila Duolikun, Hong Li, Yuqian Bao, Xian Li, for the ROADMAP Study Group

Background

Glycemic control remains suboptimal in developing countries due to critical system deficiencies. An innovative mobile health (mHealth)-enabled hierarchical diabetes management intervention was introduced and evaluated in China with the purpose of achieving better control of type 2 diabetes in primary care.

Methods and findings

A community-based cluster randomized controlled trial was conducted among registered patients with type 2 diabetes in primary care from June 2017 to July 2019. A total of 19,601 participants were recruited from 864 communities (clusters) across 25 provinces in China, and 19,546 completed baseline assessment. Moreover, 576 communities (13,037 participants) were centrally randomized to the intervention and 288 communities (6,509 participants) to usual care. The intervention was centered on a tiered care team–delivered mHealth-mediated service package, initiated by monthly blood glucose monitoring at each structured clinic visit. Capacity building and quarterly performance review strategies upheld the quality of delivered primary care. The primary outcome was control of glycated hemoglobin (HbA1c; <7.0%), assessed at baseline and 12 months. The secondary outcomes include the individual/combined control rates of blood glucose, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C); changes in levels of HbA1c, BP, LDL-C, fasting blood glucose (FBG), and body weight; and episodes of hypoglycemia. Data were analyzed using intention-to-treat (ITT) generalized estimating equation (GEE) models, accounting for clustering and baseline values of the analyzed outcomes. After 1-year follow-up, 17,554 participants (89.8%) completed the end-of-study (EOS) assessment, with 45.1% of them from economically developed areas, 49.9% from urban areas, 60.5 (standard deviation [SD] 8.4) years of age, 41.2% male, 6.0 years of median diabetes duration, HbA1c level of 7.87% (SD 1.92%), and 37.3% with HbA1c <7.0% at baseline. Compared with usual care, the intervention led to an absolute improvement in the HbA1c control rate of 7.0% (95% confidence interval [CI] 4.0% to 10.0%) and a relative improvement of 18.6% (relative risk [RR] 1.186, 95% CI 1.105 to 1.267) and an absolute improvement in the composite ABC control (HbA1c <7.0%, BP <140/80 mm Hg, and LDL-C <2.6 mmol/L) rate of 1.9% (95% CI 0.5 to 3.5) and a relative improvement of 21.8% (RR 1.218, 95% CI 1.062 to 1.395). No difference was found on hypoglycemia episode and weight gain between groups. Study limitations include noncentralized laboratory tests except for HbA1c, and caution should be exercised when extrapolating the findings to patients not registered in primary care system.

Conclusions

The mHealth-enabled hierarchical diabetes management intervention effectively improved diabetes control in primary care and has the potential to be transferred to other chronic conditions management in similar contexts.

Trial registration

Chinese Clinical Trial Registry (ChiCTR) IOC-17011325.