Edge-Community Entropy Is a Novel Neural Correlate of Aging and Moderator of Fluid Cognition.

Decreased neuronal specificity of the brain in response to cognitive demands (i.e., neural dedifferentiation) has been implicated in age-related cognitive decline. Investigations into functional connectivity analogs of these processes have focused primarily on measuring segregation of nonoverlapping networks at rest. Here, we used an edge-centric network approach to derive entropy, a measure of specialization, from spatially overlapping communities during cognitive task fMRI. Using Human Connectome Project Lifespan data (713 participants, 36-100 years old, 55.7% female), we characterized a pattern of nodal despecialization differentially affecting the medial temporal lobe and limbic, visual, and subcortical systems. At the whole-brain level, global entropy moderated declines in fluid cognition across the lifespan and uniquely covaried with age when controlling for the network segregation metric modularity. Importantly, relationships between both metrics (entropy and modularity) and fluid cognition were age dependent, although entropy's relationship with cognition was specific to older adults. These results suggest entropy is a potentially important metric for examining how neurological processes in aging affect functional specialization at the nodal, network, and whole-brain level.

Impacts of an abbreviated personal agency training with refugee women and their male partners on economic empowerment, gender-based violence, and mental health: a randomized controlled trial in Rwanda.

INTRODUCTION: We assessed the impact of a personal agency-based training for refugee women and their male partners on their economic and social empowerment, rates of intimate partner violence (IPV), and non-partner violence (NPV). METHODS: We conducted an individually randomized controlled trial with 1061 partnered women (aged 18-45) living in a refugee camp in Rwanda. Women received two days of training, and their partners received one day of training. The follow-up survey where all relevant outcomes were assessed was carried out at 6-9 months post-intervention. RESULTS: At follow up, women in the intervention arm were more likely to report partaking in income generating activities (aIRR 1.27 (1.04-1.54), p < 0.05) and skill learning (aIRR 1.59 (1.39-1.82), p < 0.001) and reported a reduction in experience of physical or sexual NPV in the past six months (aIRR 0.65 (0.39-1.07), p < 0.09). While improved, no statistically significant impacts were seen on physical or sexual IPV (aIRR 0.80 (0.58-1.09), p = 0.16), food insecurity (ß 0.98 (0.93 to 1.03), p = 0.396), or clean cookstove uptake (aIRR 0.95 (0.88 to 1.01), p = 0.113) in the past six months. We found statistically significant reduction in physical and sexual IPV amongst those experiencing IPV at baseline (aIRR 0.72 (0.50 to 1.02), p < 0.07). Small improvements in self-efficacy scores and our indicator of adapting to stress were seen in the intervention arm. Some challenges were also seen, such as higher prevalence of probable depression and/or anxiety (aIRR 1.79 (1.00-3.22), p = 0.05) and PTSD (aIRR 2.07 (1.10-3.91), p < 0.05) in the intervention arm compared to the control arm. CONCLUSION: Our findings echo previous research showing personal agency training can support economic well-being of women. We also find potentially promising impacts on gender-based violence. However, there is some evidence that integration of evidence-based mental health support is important when enhancing agency amongst conflict-affected populations. TRIAL REGISTRATION NUMBER: The trial was registered with ClinicalTrials.gov, Identifier: NCT04081441 on 09/09/2019.

Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing.

We describe the spatiotemporal course of cortical high-gamma activity, hippocampal ripple activity and interictal epileptiform discharges during an associative memory task in 15 epilepsy patients undergoing invasive EEG. Successful encoding trials manifested significantly greater high-gamma activity in hippocampus and frontal regions. Successful cued recall trials manifested sustained high-gamma activity in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. Interictal epileptiform discharges during encoding were associated with 15% decreased odds of remembering in hippocampus (95% confidence interval 6-23%). Hippocampal interictal epileptiform discharges during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if interictal epileptiform discharges occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal interictal epileptiform discharges were followed by a transient decrease in ripple rate. We hypothesize that interictal epileptiform discharges impair associative memory in a regionally and temporally specific manner by decreasing physiological hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological interictal epileptiform discharge events competing with physiological ripples, interictal epileptiform discharges represent a promising therapeutic target for memory remediation in patients with epilepsy.

Protocol for a randomized controlled trial of mindfulness-based stress reduction to improve attentional control in older adults (HealthyAgers trial).

BACKGROUND: Mindfulness meditation is a form of mind-body intervention that has increasing scientific support for its ability to reduce age-related declines in cognitive functioning, improve affective health, and strengthen the neural circuitry supporting improved cognitive and affective health. However, the majority of existent studies have been pilot investigations with small sample sizes, limited follow-up data, and a lack of attention to expectancy effects. Here, we present the study design of a Phase I/II, efficacy trial-HealthyAgers trial-that examines the benefits of a manualized mindfulness-based stress reduction program in improving attentional control and reducing mind-wandering in older adults. METHODS: One hundred fifty older adults (ages 65-85 years) will be randomized into one of two groups: an eight-week mindfulness program or an eight-week, placebo-controlled, lifestyle education program. Behavioral and neuroimaging assessments are conducted before and after the training. Participants are then invited to booster sessions once every three months for a period of 12 months with post-intervention follow-up assessments conducted at 6-months and 12-months. The primary outcomes for the study are behavioral measures of attentional control and mind-wandering. Additional, secondary outcomes include network strength in an a priori defined neuromarker of attentional control, fluid and everyday cognition, emotion regulation strategy use, and markers of inflammation. DISCUSSION: This study will establish the efficacy of a group-based, low-cost mind-body intervention for the inter-related facets of attentional control and mind-wandering in older adults. Strengths of this study include a well-designed, placebo-controlled comparison group, use of web/mobile application to track study adherence, and longitudinal follow-up. TRIAL REGISTRATION: Clinicaltrials.gov (# NCT03626532 ). Registered August 4, 2018.

Acceptability and feasibility of a behavioral and mobile health intervention (COMBIND) shown to increase uptake of prevention of mother to child transmission (PMTCT) care in India.

BACKGROUND: A cluster-randomized trial recently demonstrated that an integrated behavioral and mobile technology intervention improved uptake of key components of a Prevention of Mother to Child Transmission (PMTCT) Option B+ program, among HIV- infected pregnant/breastfeeding women in India. To guide scale-up and optimize programmatic implementation, we conducted a mixed-methods evaluation of the feasibility and acceptability of this intervention. METHODS: The COMmunity Home Based INDia (COMBIND) study, was conducted in four districts of Maharashtra, India and randomized 119 integrated counseling and testing centers (ICTC) and their outreach workers (ORWs) to the COMBIND intervention, an integrated mHealth application that allowed digital data capture, PMTCT educational videos, SMS alerts for missed visits and reminder for visits, combined with personal empowerment and motivational interviewing training for ORWs. This qualitative evaluation was done through 15 in-depth interviews (IDIs) with ORWs and 15 IDIs with HIV-infected pregnant/breastfeeding women from the intervention arm. Utilizing a concurrent nested mixed-method evaluation approach, we assess the feasibility and acceptability of the study intervention. RESULTS: All 30 participants reported that the PMTCT videos were essential in providing easy to understand information on critical aspects of HIV and necessary care related to PMTCT practices. A majority of the ORWs reported that the personal empowerment training with motivational interviewing skills training increased their confidence, motivation and gave them the tools for effectively supporting their clients. The mHealth application improved their working style as it facilitated targeted PMTCT information support, systemized data capture, streamlined their health education delivery practice and provided a sense of work satisfaction. The SMS appointment alerts improved retention in HIV care for mother and baby to the smaller proportion that had access to their phones. Despite reported improvements in knowledge and communication, few ORWs reported that structural challenges such as limited drug stocks, lack of HIV kits or unavailability of trained staff at ICTC, may hamper the uptake of PMTCT services, thus resulting in limited significant impacts of COMBIND on PMTCT outcomes. CONCLUSION: This study found that COMBIND intervention is scalable, feasible, beneficial and very well accepted by ORWs and patients, however structural challenges in goods and services remain.

Everybody Stacks: Lessons from household energy case studies to inform design principles for clean energy transitions.

Stove stacking (concurrent use of multiple stoves and/or fuels) is a poorly quantified practice in regions where efforts to transition household energy to cleaner stoves/or fuels are on-going. Using biomass-burning stoves alongside clean stoves undermines health and environmental goals. This review synthesizes stove stacking data gathered from eleven case studies of clean cooking programs in low/middle-income country settings. Analyzed data are from ministry and program records, research studies, and informant interviews. Thematic analysis identify key drivers of stove stacking behavior in each setting. Significant (28%-100%) stacking with traditional cooking methods was observed in all cases. Reason for traditional fuel use includes: costs of clean fuel; mismatches between cooking technologies and household needs; and unreliable fuel supply. National household surveys often focus on 'primary' cookstoves and miss stove stacking data. Thus more attention should be paid to discontinuation of traditional stove use, not solely adoption of cleaner stoves/fuels. Future energy policies and programs should acknowledge the realities of stacking and incorporate strategies at the design stage to transition away from polluting stoves/fuels. Seven principles for clean cooking system program design and policy are presented, focused on a shift toward "cleaner stacking" that could yield household air pollution reductions approaching WHO targets.

Gender-based violence screening methods preferred by women visiting a public hospital in Pune, India.

BACKGROUND: Gender-based violence (GBV) is a major global public health concern and is a risk factor for adverse health outcomes. Early identification of GBV is crucial for improved health outcomes. Interactions with health care providers may provide a unique opportunity for routine GBV screening, if a safe, confidential environment can be established. METHODS: Between November 2014 and February 2015, a cross-sectional, observational study was conducted where women were interviewed about their opinions concerning GBV screening in a tertiary health care setting in Pune, India. Trained counsellors interviewed 300 women at different out-patient and in-patient departments using a semi-structured questionnaire. RESULTS: Twenty-three percent of these women reported experiencing GBV in their life. However, 90% of women said they had never been asked about GBV in a health care setting. Seventy-two percent expressed willingness to be asked about GBV by their health care providers, with the preferred provider being nurses or counsellors. More than half (53%) women reported face-to-face interview as the most preferred method for screening. There were no major differences in these preferences by GBV history status. CONCLUSIONS: Our study provides evidence for preferred GBV screening methods and optimal provider engagement as perceived by women attending a public hospital.

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.

Agency-based empowerment training enhances sales capacity of female energy entrepreneurs in Kenya.

Globally, women's involvement in clean cooking value chains has been minimal. This is partly because of the multiple challenges faced by women that impede their capacity to effectively engage in the energy sector. To better discern gender-specific differences in involvement in the energy sector, the authors conducted a randomized trial in Kenya to compare sales performance of newly trained male and female improved cookstove entrepreneurs and to test the effects of an agency-based empowerment training on business activity. A total of 257 entrepreneurs completed either a 4-day entrepreneurial training (control) or a 4-day empowerment training (intervention) and were followed for nearly 8 months documenting business activity and sales. The empowerment training led to more than doubling of sales for both genders. In addition, participants in the intervention group were significantly more likely to demonstrate business commitment over time and nearly three times more likely to be higher sellers (relative risk = 2.7, 95% CI [1.4, 5.4]), controlling for gender and rural/urban locale. Women outsold men by a margin of nearly 3 to 1 and were more likely to continue to pursue leads despite limited sales. Nonactive participants (those selling 1 improved cookstove or less) were a larger percentage of the control group (72%) than the intervention group (50%), and more men were nonactive participants (65% of men) compared with women (56% of women).These data show that women can serve as active improved cookstove entrepreneurs in both urban and rural settings and that targeted agency-based empowerment training can significantly increase women's capacity to engage effectively within the improved cookstove value chain.

TRACking health behavior in people with multiple sclerosis: Effects of a randomized trial on physical activity and working memory.

OBJECTIVE: Multiple sclerosis is associated with impairments in working memory functioning. Lifestyle physical activity interventions show promise in improving cognitive functioning; however, the evidence is limited. We examined the efficacy of a lifestyle physical activity intervention, involving step tracking and psychoeducational materials, on improving step counts, working memory functioning, and network strength in a whole-brain network of working memory. METHOD: Participants (n = 75) were randomly assigned to a group tracking steps with a pedometer (step-track), or a group tracking water intake with a smart water bottle (water-track), for 6 months. At baseline, mid, and postintervention, we assessed weekly physical activity (GT3X+ accelerometer), weekly water intake (H20 Pal Smart Bottle), and working memory functioning. Additionally, the combined network strength of a validated working memory connectome was calculated. RESULTS: We ran random intercept linear mixed models to examine differences between the groups, over time. A significant Group × Time interaction effect with steps and water intake indicated that the step-track group increased their steps, and the water-track group increased their water intake, in comparison to each other, from baseline to postintervention (p < .05). Both groups improved in behavioral working memory over time (p < .05). No significant differences were found on the network strength. CONCLUSION: Our 6-month randomized controlled trial involving physical activity tracking showed increased step count in the intervention group. Behavioral working memory improved in both groups, potentially due to practice effects. Future studies should include both active and passive control groups to discern practice effects from intervention impact. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

Growth patterns among HIV-exposed infants receiving nevirapine prophylaxis in Pune, India.

BACKGROUND: India has among the highest rates of infant malnutrition. Few studies investigating the growth patterns of HIV-exposed infants in India or the impact of timing of HIV infection on growth in settings such as India exist. METHODS: We used data from the Six Week Extended Nevirapine (SWEN) trial to compare the growth patterns of HIV-infected and HIV-exposed but uninfected infants accounting for timing of HIV infection, and to identify risk factors for stunting, underweight and wasting. Growth and timing of HIV infection were assessed at weeks 1, 2, 4, 6, 10, 14 weeks and 6, 9, 12 months of life. Random effects multivariable logistic regression method was used to assess factors associated with stunting, underweight and wasting. RESULTS: Among 737 HIV-exposed infants, 93 (13%) were HIV-infected by 12 months of age. Among HIV-infected and uninfected infants, baseline prevalence of stunting (48% vs. 46%), underweight (27% vs. 26%) and wasting (7% vs. 11%) was similar (p>0.29), but by 12 months stunting and underweight, but not wasting, were significantly higher in HIV-infected infants (80% vs. 56%, 52% vs. 29%, p< 0.0001; 5% vs. 6%, p=0.65, respectively). These differences rapidly manifested within 4-6 weeks of birth. Infants infected in utero had the worst growth outcomes during the follow-up period. SWEN was associated with non-significant reductions in stunting and underweight among HIV-infected infants and significantly less wasting in HIV-uninfected infants. In multivariate analysis, maternal CD4 < 250, infant HIV status, less breastfeeding, low birth weight, non-vaginal delivery, and infant gestational age were significant risk factors for underweight and stunting. CONCLUSION: Baseline stunting and underweight was high in both HIV-infected and uninfected infants; growth indices diverged early and were impacted by timing of infection and SWEN prophylaxis. Early growth monitoring of all HIV-exposed infants is an important low-cost strategy for improving health and survival outcomes of these infants. TRIAL REGISTRATION: NCT00061321.

Employing Connectome-Based Models to Predict Working Memory in Multiple Sclerosis.

Introduction: Individuals with multiple sclerosis (MS) are vulnerable to deficits in working memory (WM), but the search for neural correlates of WM within circumscribed areas has been inconclusive. Given the widespread neural alterations observed in MS, predictive modeling approaches that capitalize on whole-brain connectivity may better capture individual differences in WM. Materials and Methods: We applied connectome-based predictive modeling to functional magnetic resonance imaging data from WM tasks in two independent samples with relapsing-remitting MS. In the internal sample (ninternal = 36), cross-validation was used to train a model to predict accuracy on the Paced Visual Serial Addition Test from functional connectivity. We hypothesized that this MS-specific model would successfully predict performance on the N-back task in the validation cohort (nvalidation = 36). In addition, we assessed the generalizability of existing WM networks derived in healthy young adults to these samples, and we explored anatomical differences between the healthy and MS networks. Results: We successfully derived an MS-specific predictive model of WM in the internal sample (full: rs = 0.47, permuted p = 0.011), but the predictions were not significant in the validation cohort (rs = -0.047; p = 0.78, mean squared error [MSE] = 0.006, R2 = -2.21%). In contrast, the healthy networks successfully predicted WM in both MS samples (internal: rs = 0.33 p = 0.049, MSE = 0.009, R2 = 13.4%; validation cohort: rs = 0.46, p = 0.005, MSE = 0.005, R2 = 16.9%), demonstrating their translational potential. Discussion: Functional networks identified in a large sample of healthy individuals predicted significant variance in WM in MS. Networks derived in small samples of people with MS may have limited generalizability, potentially due to disease-related heterogeneity. The robustness of models derived in large clinical samples warrants further investigation. ClinicalTrials.gov ID: NCT03244696.

TRACking health behaviors in people with Multiple Sclerosis (TRAC-MS): Study protocol and description of the study sample.

Introduction: People with multiple sclerosis (PwMS) experience a range of physical, cognitive, and affective symptoms. Behavioral interventions targeting increased physical activity show promising support as low-cost methods to improve working memory, episodic memory, and processing speed in PwMS. In this randomized controlled trial, we will examine the efficacy of a pedometer-tracking intervention, designed to increase low-to-moderate levels of physical activity, for improving working memory in PwMS. Methods and Analysis: Eighty-seven PwMS, between the ages of 30-59, have been recruited for the study. Seventy-five of the eligible and interested individuals were randomized to six-month health behavior monitoring groups: a Step-track group or a Water-track group (serving as the active control). Neuropsychological measures, assessing the primary outcome of the study, were administered at pre, midpoint, and post-intervention. Exploratory factor analysis of neuropsychological measures resulted in three factors: a working memory/processing speed factor, a visual episodic memory factor, and a verbal episodic memory factor. Changes in this latent measure of working memory/processing speed is the primary outcome of the current study. Functional MRI data will be analyzed to examine changes in the functional connectivity of the neural network supporting working memory. Ethics and dissemination: The institutional review board granted approval for the study and all participants provided written informed consent. The results of this study will provide support showing that step-tracking increases overall levels of physical activity, improves working memory and processing speed, and strengthens the neural circuitry that supports better cognition. Evidence from this study will thus offer promising support for the routine use of step-tracking devices to improve cognitive functioning in PwMS. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

Impact of maternal human immunodeficiency virus infection on pregnancy and birth outcomes in Pune, India.

Little is known about birth outcomes for HIV-infected women in India. We examine maternal and neonatal birth outcomes in HIV-infected women within the context of enhanced pre-natal care associated with a randomized clinical trial conducted in Pune, India. Birth outcomes of 212 HIV-infected pregnant women were compared with those of 130 HIV-uninfected pregnant women attending a government tertiary care hospital between 2002 and 2004. These women and children were participating in the Six Week Extended-Dose Nevirapine (SWEN) study. Birth outcomes and maternal morbidity data were collected at delivery. We found no differences between HIV-infected and uninfected pregnant women with respect to the proportion with elevated intrapartum blood pressure, eclampsia, oligohydramnios, intrauterine growth restriction (IUGR), preterm delivery, or caesarean section (p>0.05). HIV-infected women were more likely to have peri-partum fever (3% versus 0%, p=0.04). There were no differences in neonatal parameters such as low birth weight (LBW), infants who were small for gestational age, or those having congenital anomalies (p>0.05). Compared with infants of HIV-infected women enrolled antenatally, infants of HIV-infected women enrolled in the post-partum ward had a higher risk of pre-term delivery (20% versus 8%, p=0.02) and LBW (41% versus 22%, p=0.002). HIV-infected women in this cohort in India were not found to have significant negative birth outcomes. Antenatal care was important as those not having received any antenatal care prior to deliver were at increased risk of having a pre-term delivery or an infant with LBW. Based on these data, regular antenatal care provided to HIV-infected women can reduce risk of adverse birth outcomes for their infants.

A mobile health-facilitated behavioural intervention for community health workers improves exclusive breastfeeding and early infant HIV diagnosis in India: a cluster randomized trial.

INTRODUCTION: India's national AIDS Control Organization implemented World Health Organization's option B+ HIV prevention of mother-to-child transmission (PMTCT) guidelines in 2013. However, scalable strategies to improve uptake of new PMTCT guidelines to reduce new infection rates are needed. This study assessed impact of Mobile Health-Facilitated Behavioral Intervention on the uptake of PMTCT services. METHODS: A cluster-randomized trial of a mobile health (mHealth)-supported behavioural training intervention targeting outreach workers (ORWs) was conducted in four districts of Maharashtra, India. Clusters (one Integrated Counselling and Testing Center (ICTC, n = 119), all affiliated ORWs (n = 116) and their assigned HIV-positive pregnant/postpartum clients (n = 1191)) were randomized to standard-of-care (SOC) ORW training vs. the COMmunity home Based INDia (COMBIND) intervention - specialized behavioural training plus a tablet-based mHealth application to support ORW-patient communication and patient engagement in HIV care. Impact on uptake of maternal antiretroviral therapy at delivery, exclusive breastfeeding at six months, infant nevirapine prophylaxis, and early infant diagnosis at six months was assessed using multi-level random-effects logistic regression models. RESULTS: Of 1191 HIV-positive pregnant/postpartum women, 884 were eligible for primary outcome assessment; 487 were randomized to COMBIND. Multivariable analyses identified no statistically significant differences in any primary outcome by study arm. COMBIND was associated with higher uptake of exclusive breastfeeding at two months (adjusted Odds Ratio (aOR), 2.10; 95% CI 1.06 to 4.15) and early infant diagnosis at six weeks (aOR, 2.19; 95% CI 1.05 to 3.98) than SOC. CONCLUSIONS: The COMBIND intervention was easily integrated into India's existing PMTCT programme and improved early uptake of two PMTCT components that require self-motivated health-seeking behaviour, thus providing preliminary evidence to support COMBIND as a potentially scalable PMTCT strategy. Further study would identify modifications needed to optimize other PMTCT outcomes.

Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials.

BACKGROUND: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. METHODS: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. FINDINGS: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). INTERPRETATION: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. FUNDING: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

Programmatic effects of a large-scale multiple-micronutrient supplementation trial in Indonesia: using community facilitators as intermediaries for behavior change.

BACKGROUND: Clinical trials can serve as an opportunity gateway for enhanced health benefits to the target population, above and beyond the specific intervention being tested. OBJECTIVE: The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a randomized, controlled clinical trial in Lombok, Indonesia, found that supplementation during pregnancy with multiple micronutrients reduced 90-day infant mortality by nearly 20% as compared with iron-folic acid. This trial was designed as both a program and research trial and used community facilitators to serve as liaisons between the study and the pregnant women. This analysis documents the programmatic impacts of SUMMIT on health-seeking and early infant mortality resulting from community facilitators' field activities. METHODS: Data on compliance, human resource practices, health-seeking, and health outcomes from the 31,290 SUMMIT enrollees were analyzed. RESULTS: Overall compliance with either iron-folic acid or multiple micronutrients was high in the program, at 85.0%. Early prenatal care visits increased significantly. Sixty-three percent of primiparous women used a skilled birth attendant (SBA); among multiparous women, the rate of use of a SBA rose from 35% for the last birth to 53%. Use of a SBA resulted in a 30% reduction in early infant mortality (RR, 0.70; 95% CI, 0.59 to 0.83; p < .0001), independently of any reductions due to multiple micronutrients. The community facilitators played a central role in improving health-seeking; however, the quality of the community facilitators' performance was associated with the impact of the micronutrient supplement on infant health. In a subsample of community facilitators, better-performing facilitators were found to markedly improve the overall impact of the multiple micronutrients on early infant mortality (RR, 0.67; 95% CI, 0.49 to 0.92; p = .0117). In contrast, infants of women with poorly performing community facilitators were found to derive no additional benefit from the multiple micronutrients (RR, 1.04; 95% CI, 0.64 to 1.72; p = .8568). CONCLUSIONS: Systematic enhancements to the quality of implementation of SUMMIT led to significant increases in use of SBAs at delivery, resulting in a 30% reduction in early infant mortality independent of the impact of micronutrient supplementation. Therefore, if women were to consume multiple micronutrients on a regular basis and were to use a SBA at delivery, the risk of early infant mortality could be reduced by nearly 50%. The impacts of community facilitators in effecting changes in women's health behaviors are notable and are applicable to other health programs. Enhancements to program implementation should be driven by evidence, be accountable to the communities the program serves, and be evaluated on the basis of measurable gains in health for women and children.

Agency-Based Empowerment Interventions: Efforts to Enhance Decision-Making and Action in Health and Development.

This paper outlines the critical role of personal agency in influencing health and development outcomes and presents a framework for implementing non-therapeutic cognitive-behavioral interventions that foster agency, especially for women, in resource-poor settings. The United Nations' Sustainable Development Goals (SDGs) has placed "empowerment" at the center of global targets, particularly to improve individuals' health and development. Despite extensive research on individual and community empowerment, there is limited focus on the role of psychological and behavioral approaches directly fostering individual and collective agency in health programs. Fundamental to this process is the understanding that decision-making is an interaction between mental processes and one's current context. Approaches that allow individuals to understand how their beliefs, values, emotions, and thoughts impact their behaviors and can be modulated to increase their personal agency are needed. This model is illustrated through a pilot behavioral intervention with women engaged in sex work in Pune, India, demonstrating substantive benefits.

Closed-Loop Acoustic Stimulation Enhances Sleep Oscillations But Not Memory Performance.

Slow oscillations and spindle activity during non-rapid eye movement sleep have been implicated in memory consolidation. Closed-loop acoustic stimulation has previously been shown to enhance slow oscillations and spindle activity during sleep and improve verbal associative memory. We assessed the effect of closed-loop acoustic stimulation during a daytime nap on a virtual reality spatial navigation task in 12 healthy human subjects in a randomized within-subject crossover design. We show robust enhancement of slow oscillation and spindle activity during sleep. However, no effects on behavioral performance were observed when comparing real versus sham stimulation. To explore whether memory enhancement effects were task specific and dependent on nocturnal sleep, in a second experiment with 19 healthy subjects, we aimed to replicate a previous study that used closed-loop acoustic stimulation to enhance memory for word pairs. The methods used were as close as possible to those used in the original study, except that we used a double-blind protocol, in which both subject and experimenter were unaware of the test condition. Again, we successfully enhanced slow oscillation and spindle power, but again did not strengthen associative memory performance with stimulation. We conclude that enhancement of sleep oscillations may be insufficient to enhance memory performance in spatial navigation or verbal association tasks, and provide possible explanations for lack of behavioral replication.