Cannabidiol-associated hepatotoxicity: A systematic review and meta-analysis.

BACKGROUND: Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). METHODS: In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted. RESULTS: Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84-8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46-9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448-0.1212), and DILI was 0.0296 (95% CI 0.0136-0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported. CONCLUSIONS: Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk.

The Effects of Malaria in Pregnancy on Neurocognitive Development in Children at 1 and 6 Years of Age in Benin: A Prospective Mother-Child Cohort.

BACKGROUND: Malaria in pregnancy (MiP) contributes significantly to infant mortality rates in sub-Saharan Africa and has consequences on survivors, such as preterm birth and low birth weight. However, its impact on long-term neurocognitive development in children remains unknown. METHODS: Our prospective cohort included pregnant women and their live-born singletons from the Malaria in Pregnancy Preventive Alternative Drugs clinical trial. MiP was assessed using microscopy and real-time quantitative polymerase chain reaction (qPCR). Neurocognitive development in children was assessed using the Mullen Scales of Early Learning and the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), at 1 and 6 years of age, respectively. RESULTS: Of 493 pregnant women, 196 (40%) were infected with malaria at least once: 121 (31%) with placental malaria diagnosed by qPCR. Multiple linear regression B-coefficients showed that impaired gross motor scores were associated with MiP at least once (-2.55; confidence interval [95% CI]: -5.15, 0.05), placental malaria by qPCR (-4.95; 95% CI: -7.65, -2.24), and high parasite density at delivery (-1.92; 95% CI: -3.86, 0.02) after adjustment. Malaria and high parasite density at the second antenatal care visit were associated with lower KABC-II Non-Verbal Index scores at 6 years (-2.57 [95% CI: -4.86, -0.28] and -1.91 [-3.51, -0.32]), respectively. CONCLUSIONS: This prospective cohort study provides evidence that MiP, particularly late term, could have important negative consequences on child development at 1 and 6 years of age. Mechanisms behind this association must be further investigated and diagnostic methods in low-income countries should be strengthened to provide adequate treatment. CLINICAL TRIALS REGISTRATION: NCT00811421.

Mediational Intervention for Sensitizing Caregivers to Improve Mental Health Outcomes in Orphaned and Vulnerable Children.

OBJECTIVE: There is an urgent need to equip community-based careworkers with the skills to address the mental health needs of orphans and vulnerable children (OVC) as an essential response to shortages in human resources for mental health in Sub-Saharan Africa. We conducted a quasi-experimental feasibility trial in South Africa to adapt and evaluate an established year-long semi-structured, manualized video-feedback caregiver intervention (the Mediational Intervention for Sensitizing Caregivers; MISC) for community-based organizations (CBOs). METHODS: Following a year-long iterative cross-cultural adaptation of MISC, we recruited 88 OVC (ages 7-11; 45.5% girls) and their CBO careworkers (N = 18; 94.4% female). Two CBOs (45 children; 9 CBO careworkers) received 12 months of MISC, and two CBOs (43 children; 9 CBO careworkers) received treatment as usual. Child mental health and quality of caregiving were assessed at 6 months into the intervention and at completion through multi-informant questionnaires and video-recordings of careworker-child interactions. Qualitative interviews were conducted to evaluate feasibility and acceptability. RESULTS: MISC-CBO was acceptable and feasible in terms of attendance and post-intervention interviews. MISC improved child mental health, as well as the quality of careworker caregiving in terms of interactive effects for affective and cognitive (Expanding) components of MISC, and main effects for the cognitive components of Rewarding and Provision of meaning. MISC components did not mediate the effects of the intervention. CONCLUSIONS: The current study shows that laypersons with no tertiary education and virtually no prior training who undergo MISC training can improve caregiving quality and the mental health of OVCs.

The Impact of Maternal Depression and Parent-Child Interactions on Risk of Parasitic Infections in Early Childhood: A Prospective Cohort in Benin.

OBJECTIVES: Maternal depression occurs in 13-20% of women from low-income countries, which is associated with negative child health outcomes, including diarrheal disease. However, few studies have investigated its impact on child risk of infectious disease. We studied the impacts of maternal depressive symptoms and parent-child interactions, independently, on the risk of Plasmodium falciparum malaria and soil-transmitted helminth infection in Beninese children. METHODS: Our population included mothers and children enrolled in a clinical trial during pregnancy (MiPPAD) in Benin. The Edinburgh Postnatal Depression Scale (EPDS) assessed maternal depressive symptoms and the home observation measurement of the environment (HOME) assessed parent-child interactions. Blood and stool sample analyses diagnosed child malaria and helminth infection at 12, 18, and 24 months. Negative binomial and Poisson regression models with robust variance tested associations. RESULTS: Of the 302 mother-child pairs, 39 (12.9%) mothers had depressive symptoms. Median number of malaria episodes per child was 3 (0-14) and 29.1% children had at least one helminth infection. Higher EPDS scores were associated with lower HOME scores; relative risk (RR) 0.97 (95% confidence interval (CI) 0.95, 0.99), particularly with lower acceptance, involvement, and variety subscales; RR 0.92 (95% CI 0.85, 0.99), RR 0.82 (95% CI 0.77, 0.88), RR 0.93 (95% CI 0.88, 0.99), respectively. However, neither exposure was associated with risk of parasitic infection in children. CONCLUSIONS FOR PRACTICE: Maternal depressive symptoms are associated with poor parent-child interactions, particularly acceptance of behavior, involvement with children, and variety of interactions, but these exposures do not independently impact risk of parasitic infection in children.

The cognitive burden of severe malaria in the Ugandan classroom and the effects of a computerized intervention.

INTRODUCTION: Due to the increased availability of anti-malarial treatments and the prevalence of malarial infection among vulnerable populations leading to cognitive impairment, malaria has become a leading cause of pediatric cognitive impairment in sub-Saharan Africa. OBJECTIVES: To examine the effects of malaria-induced cognitive impairment on school performance as an indicator of health and effects of a computerized intervention on school performance over time. DESIGN: Secondary analysis. SAMPLE: 216 school reports were collected from three hundred Ugandan children, aged five to twelve, enrolled in a randomized controlled trial. MEASUREMENTS: Academic subjects (English, reading, writing, arithmetic, and Luganda); scores were standardized on an ordinal scale from one to five. RESULTS: At baseline, malaria had no effect on academic performance, but age and socio-economic status had some effect. At one-year, there was no effect of the intervention on academic change over time; however, factors such as sex and home environment did demonstrate some effect on performance. CONCLUSIONS: The results were unable to support the hypotheses that survivors of SM would demonstrate lower school performance than healthy comparisons and that the cognitive intervention would improve the performance of survivors. This suggests that future interventions ought to consider the influence of age, sex, and socio-economic status when caring for the cognitive needs of children in order to facilitate their ability to achieve academic success and, thus, improved quality of life.

Neurodevelopmental Outcomes of Children Following In Utero Exposure to Zika in Nicaragua.

BACKGROUND: Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. METHODS: We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants' homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. RESULTS: Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P = .01) and low-birthweight infants (<2500 g) (P = .006) had lower composite ECL scores. CONCLUSIONS: In this prospective cohort of children without CZS, children with in utero ZIKV exposure had lower neurocognitive scores at 24 months.

Attention Test Improvements from a Cluster Randomized Controlled Trial of Caregiver Training for HIV-Exposed/Uninfected Ugandan Preschool Children.

OBJECTIVE: To report vigilance attention outcomes from a cluster randomized controlled trial of early childhood development caregiver training for perinatally HIV-exposed/uninfected preschool-age children in rural Uganda. The Early Childhood Vigilance Test (ECVT) provides a webcam recording of proportion of time a child views an animation periodically moving across a computer screen. STUDY DESIGN: Sixty mothers/caregivers received biweekly year-long training sessions of the Mediational Intervention for Sensitizing Caregivers (MISC), and 59 mothers received biweekly training about nutrition, hygiene, and health care. Children were tested for attention at baseline, 6 months, and 12 months with the ECVT, in terms of proportion of time spent viewing a 6-minute animation of animals greeting the child and moving across the computer monitor screen. Time viewing the animation were scored by trained observers using ProCoder program for webcam scoring of proportion of time the child faced the animation. Mixed-effects modeling was used to compare ECVT outcomes for the 2 intervention groups. RESULTS: Unadjusted and adjusted (for age, sex, height, and ECVT at baseline) group differences on ECVT significantly favored the MISC arm at 6 months (P = .03; 95% CI (0.01, 0.11), effect size = 0.46) but not at 12 months. Both groups made significant gains in sustained attention across the year-long intervention (P = .021) with no significant interaction effects between time and treatment arms or sex. CONCLUSIONS: Caregiver early childhood development training enhanced attention in at-risk Ugandan children, which can be foundational to improved working memory and learning, and perhaps related to previous language benefits reported for this cohort. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00889395.

Longitudinal Dyadic Interdependence in Depression Symptoms of Caregivers Living with HIV in Uganda and Their Dependent Children's Neurodevelopment and Executive Behavior Outcomes.

We tested a model of dyadic interdependence in depression symptoms experienced by female caregivers living with HIV in Uganda (n = 288) and behavioral problems of their HIV-infected (n = 92) and perinatally HIV-exposed uninfected (HEU) children (n = 196). Three repeated measures of caregiver depression symptoms and child neurodevelopment and behavioral outcomes were related to their own outcomes at a previous time point (actor effects), and the outcomes of the other member of the dyad (partner effects). Caregiver depression and child behavioral problem were interdependent over the 24 months of observation. Caregiver depression at Tn predicted child's behavioral problems at Tn+1 (coefficient = 0.1220, SE = 0.0313, p < 0.01); child behavioral problems at Tn predicted maternal depression at Tn+1 (coefficient = 0.0984, SE = 0.0253, p < 0.01). Results suggest the importance of services addressing behavioral needs of affected children and mental health of their mothers.

RESUMEN: Evaluamos la interdependencia en relaciones diádicas entre síntomas de depresión en mujeres viviendo con VIH en Uganda (n = 288) y medidas de neurodesarollo y comportamiento en sus hijos no infectados pero expuestos a VIH (HEU) (n = 196). Tres mediciones repetidas de síntomas de depresión en mujeres y de neurodesarollo y comportamiento en niños estuvieron relacionadas con sus propios resultados en mediciones anteriores (efecto de actor), y con los resultados del otro miembro de la pareja (efecto de pareja). Síntomas depresivos y problemas conductuales fueron interdependientes durante los 24 meses de observación. Síntomas depresivos en mujeres en Tn predijeron problemas conductuales en el niño en Tn+1 (coeficiente = 0.1220, SE = 0.0313, p < 0.01); problemas conductuales en el niño en Tn predijeron depresión en mujeres en Tn+1 (coeficiente = 0.0984 , SE = 0.0253, p < 0.01). Los resultados sugieren la importancia de servicios que se enfoquen en atender problemas conductuales y de salud mental materna.

Reducing neurodevelopmental disorders and disability through research and interventions.

We define neurodevelopment as the dynamic inter-relationship between genetic, brain, cognitive, emotional and behavioural processes across the developmental lifespan. Significant and persistent disruption to this dynamic process through environmental and genetic risk can lead to neurodevelopmental disorders and disability. Research designed to ameliorate neurodevelopmental disorders in low- and middle-income countries, as well as globally, will benefit enormously from the ongoing advances in understanding their genetic and epigenetic causes, as modified by environment and culture. We provide examples of advances in the prevention and treatment of, and the rehabilitation of those with, neurodevelopment disorders in low- and middle-income countries, along with opportunities for further strategic research initiatives. Our examples are not the only possibilities for strategic research, but they illustrate problems that, when solved, could have a considerable impact in low-resource settings. In each instance, research in low- and middle-income countries led to innovations in identification, surveillance and treatment of a neurodevelopmental disorder. These innovations have also been integrated with genotypic mapping of neurodevelopmental disorders, forming important preventative and rehabilitative interventions with the potential for high impact. These advances will ultimately allow us to understand how epigenetic influences shape neurodevelopmental risk and resilience over time and across populations. Clearly, the most strategic areas of research opportunity involve cross-disciplinary integration at the intersection between the environment, brain or behaviour neurodevelopment, and genetic and epigenetic science. At these junctions a robust integrative cross-disciplinary scientific approach is catalysing the creation of technologies and interventions for old problems. Such approaches will enable us to achieve and sustain the United Nations moral and legal mandate for child health and full development as a basic global human right.

A focus on adolescence to reduce neurological, mental health and substance-use disability.

Globally, there is a crucial need to prioritize research directed at reducing neurological, mental health and substance-use disorders in adolescence, which is a pivotal age for the development of self-control and regulation. In adolescence, behaviour optimally advances towards adaptive long-term goals and suppresses conflicting maladaptive short-lived urges to balance impulsivity, exploration and defiance, while establishing effective societal participation. When self-control fails to develop, violence, injury and neurological, mental health and substance-use disorders can result, further challenging the development of self-regulation and impeding the transition to a productive adulthood. Adolescent outcomes, positive and negative, arise from both a life-course perspective and within a socioecological framework. Little is known about the emergence of self-control and regulation in adolescents in low- and middle-income countries where enormous environmental threats are more common (for example, poverty, war, local conflicts, sex trafficking and slavery, early marriage and/or pregnancy, and the absence of adequate access to education) than in high-income countries and can threaten optimal neurodevelopment. Research must develop or adapt appropriate assessments of adolescent ability and disability, social inclusion and exclusion, normative development, and neurological, mental health and substance-use disorders. Socioecological challenges in low- and middle-income countries require innovative strategies to prevent mental health, neurological and substance-use disorders and develop effective interventions for adolescents at risk, especially those already living with these disorders and the consequent disability.

Neurodevelopment outcomes in infants born to women with Zika virus infection during pregnancy in Mexico.

BACKGROUND: Few studies have assessed neurodevelopmental outcomes in normocephalic infants born to women with Zika virus (ZIKV) infection during pregnancy in Mexico. We sought to evaluate ZIKV exposed infants in Yucatan, Mexico, with performance-based and eye-gaze measures of neurodevelopment, removing observer bias. METHODS: We enrolled 60 infants about 6-month old born to women with PCR + test for ZIKV during pregnancy. Infants were normocephalic and asymptomatic. Sixty infants born to women without a history of ZIKV infection were included as comparison. Children were assessed with the Mullen scales of early learning (MSEL), a test with scales in motor, language, and overall cognitive skills development, and the Fagan test of infant intelligence (FTII) using automated eye-tracking instrumentation to evaluate infant visual preference of human faces, where longer gaze lengths to unfamiliar (i.e., new) faces are expected. RESULTS: All MSEL subscale scores, except expressive language, were significantly lower among ZIKV exposed children compared to controls, including the overall standard composite (80 ± 10 vs. 87 ± 7.4, respectively; p < 0.001). FTII eye-tracking measures of fixation and gaze length were in the expected direction, with longer times recorded among infants in the control group (i.e., higher attention), but none reached statistical significance. In adjusted linear regressions, the FTII high novelty score (expected preference for a novel face) predicted fine motor (ß = 3.61, p = 0.04) and receptive language (ß = 2.55, p = 0.03) scores. CONCLUSIONS: Nonmicrocephalic children born to women with ZIKV during pregnancy in Mexico merit early neurodevelopmental evaluation to allow for appropriate interventions and clinical follow-up. It is possible that long-term monitoring of cognitive deficits may need to be established for a proportion of affected cases.

African Multi-Site 2-Year Neuropsychological Study of School-Age Children Perinatally Infected, Exposed, and Unexposed to Human Immunodeficiency Virus.

BACKGROUND: Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). METHODS: We enrolled 611 children aged 5 to 11 years at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda). Of these, there were 246 children living with HIV (HIV+) who were initiated on ART before 3 years of age in a prior clinical trial comparing nevirapine to lopinavir/ritonavir (International Maternal Pediatric Adolescent Acquired Immunodeficiency Syndrome Clinical Trials [IMPAACT] P1060); 183 age-matched, exposed but uninfected (HEU) children; and 182 unexposed and uninfected (HUU) children. They were compared across 3 assessment time points (Weeks 0, 48, and 96) on cognitive ability (Kaufman Assessment Battery for Children, second edition [KABC-II]), attention/impulsivity (Tests of Variables of Attention [TOVA]), motor proficiency (Bruininks-Oseretsky Test, second edition [BOT-2]), and on the Behavior Rating Inventory of Executive Function (BRIEF). The cohorts were compared using linear mixed models, adjusting for site, child's age and sex, and selected personal/family control variables. RESULTS: The HIV+ cohort performed significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, and BOT-2 performance outcomes across all 3 time points (P values < .001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests, the HIV+ children showed less improvement over time than the HUU and HEU groups. The groups did not differ significantly on the BRIEF. CONCLUSIONS: Despite initiation of ART in early childhood and good viral suppression at the time of enrollment, the HIV+ group had poorer neuropsychological performance over time, with the gap progressively worsening in planning/reasoning. This can be debilitating for self-management in adolescence.

Association between caregiver depression symptoms and child executive functioning. Results from an observational study carried out in four sub-Saharan countries.

Depressive symptoms among HIV-positive (HIV+) women may negatively impact their health and possibly that of their young children through risk of compromised caregiving. We evaluated how depression symptoms in predominantly (97%) female caregivers relate to neurodevelopmental outcomes in their HIV affected children. Data come from the IMPAACT P1104s Study, an observational cohort across six sites in four countries: Zimbabwe, South Africa, Uganda and Malawi. Participants (n = 611) were 5-11-year-old children with HIV (HIV), HIV exposed uninfected (HEU), or HIV unexposed uninfected (HUU). Primary caregivers were assessed for depression with the Hopkins Symptom Checklist (HSCL) and children with Behavior Rating Inventory for Executive Function (BRIEF) parent-report, Kauffman Assessment Battery for Children II (KABC), Bruininks-Oseretsky Test of Motor Proficiency 2nd Ed. (BOT-2), Test of Variables of Attention (TOVA), Multiple Indicators Cluster Survey, Child Disability and Development scales (MICS-4). Caregivers with higher depression scores (>1.75 mean HSCL score) reported more executive function problems in their children, regardless of HIV status. All executive function scores were significantly (p < 0.001) associated with depressive symptomatology at baseline and across time. Caregiver depressive symptomatology was not associated with other assessed neurocognitive outcomes. These results highlight the potential impact of caregiver depression on child behavioral outcomes.

Preliminary study on the effects of treatment for breast cancer: immunological markers as they relate to quality of life and neuropsychological performance.

BACKGROUND: Immunological biomarkers were related to quality of life and neuropsychological performance in women recently diagnosed with breast cancer through the first six months of treatment. A comparison group of breast cancer survivors in remission were also evaluated. METHOD: Twenty women newly diagnosed with breast cancer and 26 breast cancer survivors at least a year after treatment were evaluated four times over a course of six to 8 months. The assessments included quality-of-life, emotional and spiritual well-being, sleep quality, computerized neuropsychological performance, and cytokine immunology biomarkers using flow cytometry. The principal immunological markers examined were the CD4+, CD8+, and CD16+ counts. RESULTS: Although equivalent at enrollment, active treatment women reported higher anxiety, depression, poorer quality-of-life, and poorer processing speed and accuracy on memory, logical processes, and coding neuropsychological tasks. They also had significantly higher CD8+ and CD16+ cell count levels during treatment over the next six to eight months than comparison group women in remission. Women undergoing chemotherapy as well during treatment phase also had a significant decline in CD4+ counts. Higher percent CD8+ levels during treatment was associated with poorer quality of life and more depression, while higher CD4+ and CD8+ were associated with poorer neuropsychological memory and processing speed performance. CONCLUSION: Significant increases in CD8+ is a sensitive biomarker of a broad range of poorer quality-of-life and neurocognitive functioning outcomes during breast cancer treatment, especially in women undergoing chemotherapy. Quality of life should be monitored in breast cancer patients and psychosocial support made available as a standard of care.

Exploratory study of a screening measure for polycystic ovarian syndrome, quality of life assessment, and neuropsychological evaluation.

BACKGROUND: The universally adopted 2018 PCOS medical diagnostic and treatment guidelines for Polycystic Ovarian Syndrome (PCOS) cites the need for a brief screening measure that can be easily administered in the clinical care setting. We evaluate a 12-item questionnaire emphasizing the medical symptoms of PCOS with a group of women with PCOS as well as comparison samples of college women not diagnosed with PCOS. METHOD: Of 120 undergraduate psychology women 18 to 41 years of age, 86 screened negative on a 12-item PCOS symptoms inventory. They were compared to a group of PCOS patients diagnosed medically in a manner consistent with the Teede et al. (2018) evidence-based diagnostic guidelines. The screen-positive, screen-negative, and PCOS-confirmed groups were compared on the PCOS Quality-of-Life (QoL) questionnaire, Zung Self-Rating Depression Scale (ZDS), Spielberg State-Trait Anxiety Inventory (STAI), Fatigue Symptom Inventory (FSI), Spiritual well-being and Spiritual Beliefs Inventories, the computerized Automated Neuropsychological Assessment Metric (ANAM) battery, and an experimental tachistoscopic Bilateral Perceptual Asymmetries Letter and Dots Matching Bilateral Field Advantage (BFA) test (to evaluate the effects of early brain androgenization possible from PCOS). For each questionnaire and neuropsychological performance principal outcome, the Linear Mixed Effects (LME) model was employed to evaluate the predictive significance of demographic characteristics and group membership (confirmed cases, screen negative and screen positive cases) for these outcomes. RESULTS: The PCOS-confirmed women scored more poorly than the screen-negative (reference) and screen-positive groups on all the measures of physical, emotional, social, and spiritual well-being measures. On the ANAM neuropsychological battery, PCOS-confirmed women did more poorly on Sternberg Memory and Stimulus Response throughput measures. They also had slower correct response speed for both the unilateral and bilateral dot- and letter-matching tachistoscopic stimulus presentations. However, the bilateral field advantage throughput performance ratio did not differ among groups, which is a global measure of bilateral versus unilateral brain/behavior asymmetries. CONCLUSION: PCOS screening can be a feasible and important part of women's healthcare. PCOS-confirmed women should receive not only the medical standard of care from the 2018 guidelines, but also comprehensive psychosocial and neurocognitive support to enhance their quality of life.

Measurement of Parenting Self-efficacy Among Female HIV-Affected Caregivers in Uganda.

OBJECTIVES: Parenting self-efficacy has been associated with positive parenting behaviors, fewer parental mental health problems, less family dysfunction, and better child development outcomes. The parenting sense of competence (PSOC) scale is commonly used to measure parenting self-efficacy in high-resource settings. This study sought to examine the factor structure, internal consistency, and convergent construct validity of the PSOC in a sample of predominantly HIV-infected women in Uganda. METHODS: Using data from 155 HIV-affected caregivers who participated in a randomized controlled trial of a parenting intervention, two and three factor models of a 16-item translated version of the PSOC were tested using confirmatory factor analysis. Multivariable regression models were used to examine relationships between parenting confidence (operationalized using the best-fitting PSOC model), caregiver mental health symptoms (depression and anxiety), social support, family dysfunction, and family wealth, after adjusting for covariates. RESULTS: Neither the two- nor three-factor models of the PSOC demonstrated adequate model fit; however, adequate model fit was demonstrated for a one-factor model that included only items from the PSOC efficacy subscale. Cronbach's alpha was 0.73 for this subscale. Correlates of parenting self-efficacy in this sample included caregiver depression, family dysfunction, and family wealth, but not caregiver anxiety or social support. CONCLUSIONS FOR PRACTICE: These findings lend support for future use of the PSOC efficacy subscale among HIV-affected caregivers of children in low-resource settings such as rural Uganda.

Community-Based Caregiver and Family Interventions to Support the Mental Health of Orphans and Vulnerable Children: Review and Future Directions.

The goal of this paper was to conduct a review of studies from 2008 to 2019 that evaluated community-based caregiver or family interventions to support the mental health of orphans and vulnerable children (OVC) in sub-Saharan Africa, across four domains: (a) study methodology, (b) cultural adaptation and community participation, (c) intervention strategies, and (d) effects on child mental health. Ten interventions were identified. Findings revealed that the majority of studies used a randomized controlled trial or quasi-experimental design, but few conducted long-term follow-up; that all programs undertook cultural adaptation of the intervention using community participatory methods, or were locally developed; that the majority of interventions targeted caregiving behavior and/or caregiver-child relationships using behavioral and cognitive-behavioral strategies, or were home visiting interventions; and that interventions had mixed effects on OVC mental health. Progress and gaps revealed by these findings are discussed, as are suggestions for possible new directions in this area of intervention science.

Toxic Stress and Quality of Life in Early School-Aged Ugandan Children With and Without Perinatal Human Immunodeficiency Virus Infection.

Caregiver's and child's self-reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6-10 years old HIV-infected, HIV-exposed uninfected, and HIV-unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child- and caregiver-reported psychosocial stress were dose-dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1-14.8, effect size [ES] = 0.46-0.83). Lower allostasis was dose-dependently associated with higher QOL (b = 6.1-9.7, ES = 0.34-0.54). Given low caregiver acute stress, QOL for HIV-infected was similar to HIV-uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = -7.8, 95% CI: -12.8, -2.8; ES = -0.73) was evident for HIV-infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.

Psychosocial Adjustment in Ugandan Children: Coping With Human Immunodeficiency Virus Exposure, Lifetime Adversity, and Importance of Social Support.

Cumulative lifetime adversity and social support were investigated as determinants of psychosocial adjustment (esteem, distress, hopefulness, positive outlook/future aspirations, and sense of purpose) over 12 months in 6-10-years-old HIV-infected, HIV-exposed uninfected and HIV-unexposed uninfected children from Uganda. Each determinant and psychosocial adjustment indicator was self-reported using standardized questionnaires administered at baseline, 6, and 12 months. Linear mixed effects models were used to relate time-varying lifetime adversity and social support to psychosocial adjustment over 12 months. Regardless of HIV status, higher adversity predicted lower esteem (coefficient b = -2.98, 95% confidence interval (CI): [-4.62, -1.35]) and increased distress (b =3.96, 95% CI: [1.29, 6.62]) but was not associated with hopefulness, positive outlook or sense of purpose. Low social support predicted higher distress (b =9.05, 95% CI: [7.36, 10.73]), lower positive outlook (b = -10.56, 95% CI: [-2.34, -8.79]) and low sense of purpose (b = -9.90, 95% CI: [-11.44, -8.36]) over 12 months. Pragmatic interventions that enhance coping with adversity and provide emotional/instrumental support should be tested for effectiveness in promoting resilient psychosocial adjustment trajectory in vulnerable children.

Caregiver socioemotional health as a determinant of child well-being in school-aged and adolescent Ugandan children with and without perinatal HIV exposure.

OBJECTIVE: Caregiver socio-emotional attributes are major determinants of child well-being. This investigation in vulnerable school-aged Ugandan children estimates relationships between children's well-being and their caregiver's anxiety, depression and social support. METHODS: Perinatally HIV-infected, HIV-exposed uninfected and HIV-unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNA-polymerase chain-reaction test; status was confirmed via HIV rapid diagnostic test when children were 6-18 years old. Five indicators of child well-being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregivers' socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (ß) and corresponding 95% confidence intervals (CI) for child well-being in relation to caregiver's psychosocial status. RESULTS: As per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower self-esteem/QOL (ß = -1.3%/-2.6%; 95%CI: -5.0%,-0.2%) in their children. Child distress/hopelessness increased (ß = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and self-esteem/QOL decreased 2.3% (ß = -2.3%/-4.4%; 95%CI: -7.2%, -1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (ß = 3%; 95%CI:1.4%, 4.5%) in their children. HIV-infected/exposed children had most caregiver depression-related QOL deficit (ß = -5.2%/-6.8%; 95%CI: -12.4%, -0.2%) and HIV-unexposed children had most caregiver social support-related enhancements in positive outlook (ß=4.5%; 95%CI:1.9%, 7.1%). CONCLUSIONS: Caregiver anxiety, depressive symptoms and low social support were associated with worse well-being in school-aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving well-being of vulnerable children and adolescents in this setting.

OBJECTIF: Les attributs socio-affectifs des responsables d'enfants sont des déterminants majeurs du bien-être des enfants. Cette investigation menée auprès d'enfants ougandais vulnérables d'âge scolaire a estimé les relations entre le bien-être des enfants et l'anxiété, la dépression et le soutien social de leur responsable. MÉTHODES: Des enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à l'âge de 18 mois à l'aide du test de PCR de l'ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bien-être de l'enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l'aide de méthodes validées, adaptées à la culture et respectées et d'outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (ß) et les intervalles de confiance (IC) à 95% correspondants pour le bien-être de l'enfant par rapport au statut psychosocial de leurs responsables. RÉSULTATS: Par incrément de tertile, l'anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (ß = −1,3%/−2,6%; IC95%: −5,0%, −0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (ß = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l'estime de soi/QV diminuait de 2,3% (ß = −2,3%/−4,4%; IC95%: −7,2%, −1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (ß = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (ß = −5,2%/−6,8%; IC95%: −12,4%, −0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (ß = 4,5%; IC95%: 1,9%, 7,1%). CONCLUSIONS: L'anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bien-être précaire chez les enfants d'âge scolaire et les adolescents. L'amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bien-être des enfants et des adolescents vulnérables dans cette région.