The association between prenatal oxidative stress levels measured by isoprostanes and offspring neurodevelopmental outcomes at 36 months.

Oxidative stress during pregnancy has been a mechanistic pathway implicated in autism development, yet few studies have examined this association directly. Here, we examined the association of prenatal levels of 8-iso-PGF2α, a widely used measure of oxidative stress, and several neurodevelopmental outcomes related to autism in children. Participants included 169 mother-child pairs from the Early Autism Risk Longitudinal Investigation (EARLI), which enrolled mothers who had an autistic child from a previous pregnancy and followed them through a subsequent pregnancy and until that child reached age 3 years. Maternal urine samples were collected during the second trimester of pregnancy and were later measured for levels of isoprostanes. Child neurodevelopmental assessments included the Mullen Scales of Early Learning (MSEL), the Social Responsiveness Scale (SRS), and the Vineland Adaptive Behavior Scale (VABS), and were conducted around 36 months of age. Primary analyses examined associations between interquartile range (IQR) increases in 8-iso-PGF2α levels, and total composite scores from each assessment using quantile regression. In adjusted analyses, we did not observe statistically significant associations, though estimates suggested modestly lower cognitive scores (ß for MSEL = -3.68, 95% CI: -10.09, 2.70), and minor increases in autism-related trait scores (ß for SRS T score = 1.68, 95% CI: -0.24, 3.60) with increasing 8-iso-PGF2α. These suggestive associations between decreased cognitive scores and increased autism-related traits with increasing prenatal oxidative stress point to the need for continued investigation in larger samples of the role of oxidative stress as a mechanistic pathway in autism and related neurodevelopmental outcomes.

The longitudinal impact of an evidence-based multiple family group intervention (Amaka Amasanyufu) on oppositional defiant disorder and impaired functioning among children in Uganda: analysis of a cluster randomized trial from the SMART Africa-Uganda scale-up study (2016-2022).

BACKGROUND: Oppositional Defiant Disorders (ODDs) and other Disruptive Behavior Disorders (DBDs) are common among children and adolescents in poverty-impacted communities in sub-Saharan Africa. Without early intervention, its progression into adulthood can result in dire consequences. We examined the impact of a manualized family strengthening intervention called Amaka Amasanyufu designed to reduce ODDs and other DBDs among school-going children residing in low-resource communities in Uganda. METHODS: We used longitudinal data from the SMART Africa-Uganda study (2016-2022). Public primary schools were randomized to: (1) Control condition (receiving usual care comprising generalized psychosocial functioning literature), 10 schools; (2) intervention delivered via parent peers (Amaka-parents), 8 schools or; (3) intervention delivered via community healthcare workers (Amaka-community), 8 schools. All the participants were blinded. At baseline, 8- and 16-weeks postintervention initiation, caregivers completed the Iowa Conners Scale, which measured Oppositional Defiant Disorder (ODD) and Impairment Rating Scale to evaluate children's overall impairment and impaired functioning with peers, siblings, and parents; impaired academic progress, self-esteem, and family functioning. Three-level linear mixed-effects models were fitted to each outcome. Pairwise comparisons of postbaseline group means within each time point were performed using Sidak's adjustment for multiple comparisons. Only children positive for ODD and other DBDs were analyzed. RESULTS: Six hundred and thirty-six children screened positive for ODDs and other DBDs (Controls: n = 243; Amaka-parents: n = 194; Amaka-community: n = 199). At 8 weeks, Amaka-parents' children had significantly lower mean scores for overall impairment compared to controls, (mean difference: -0.71, p = .001), while Amaka-community children performed better on ODD (mean difference: -0.84, p = .016). At 16 weeks, children in both groups were performing better on ODD and IRS than controls, and there were no significant differences between the two intervention groups. CONCLUSIONS: The Amaka Amasanyufu intervention was efficacious in reducing ODD and impaired functioning relative to usual care. Hence, the Amaka Amasanyufu intervention delivered either by Amaka-community or Amaka-parents has the potential to reduce negative behavioral health outcomes among young people in resource-limited settings and improve family functioning. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03081195. Registered on 16 March 2017.

Family-level correlates of disruptive behavior challenges among children in Southwestern Uganda.

Introduction: This exploratory study sought to examine the extent to which family-level factors are associated with disruptive behavioral disorder (DBD) symptoms, including oppositional defiant disorder (ODD) and conduct disorder (CD) among school children in Uganda, a low-resource country in SSA. The examination of key influences within the SSA context is important to guide needed investments in mental health care and family-level support. Importantly, identifying families at higher risk can inform the development of contextualized family interventions that reinforce positive parenting practices. Method: We analyzed baseline data (N = 2110) from the NIH-funded Strengthening Mental health And Research Training in Africa (SMART Africa) scale-up study in Southwestern Uganda. Children aged 8-13 and their caregivers were recruited from 30 public primary schools. DBDs were examined using the DBD rating scale, Iowa Conners, and Impairment scales. Logistic regression analysis using cluster adjusted robust standard errors to adjust for within-school clustering was conducted to assess the association between DBD symptoms and family-level factors, including parenting practices, marital status, and family size. Results: Results indicate that poor parental supervision (OR = 1.17; CI: 1.13, 1.21; P <.001), divorced families (OR = 1.33; CI: 1.03, 1.72; P <.05), and widowed families (OR = 1.48; CI: 1.10, 2.00; P <.01) were associated with higher DBD symptoms among children. On the other hand, caregiver age (OR = 0.99; CI: 0.98, 0.99; P <.01) was associated with lower DBD symptoms among children. Moreover, caregiver employment and parental education were not statistically significant in the model. Conclusion: Findings from the study reveal an association between family-level factors and behavioral difficulties among children in Uganda suggesting that divorced and widowed families may benefit from additional support in caring for children. Moreover, caregivers may also benefit from programs that provide tools for effective parental supervision.

Pediatric, adolescent, and young adult cancer in an HIV-infected rural sub-Saharan African population.

Youth living with HIV (YLWHIV) have an increased cancer risk. Our objective is to describe the prevalence of medical record (MR) reported suspected cancers in a contemporary cohort of YLWHIV in Uganda that was assembled through MR reviews of patients 10 to 24 years old across 35 Ugandan HIV care health facilities. Clinical data were abstracted to identify suspected cancer cases and information about HIV care. Among 3728 YLWHIV, we identified eight suspected cancer cases. The most common suspected types were Kaposi sarcoma (n=4) followed by lymphoma (n=3). Challenges encountered in data abstraction were missing data for several variables and confirmatory cancer diagnostic information. In follow-up of suspected cases referred for diagnosis at the Uganda Cancer Institute (UCI), none had diagnosis records in UCI files. In addition, ∼18% of patients (n=686) were lost-to-follow-up (LTF) defined as not having returned to the clinic in ≥183 days and three patients died from presumed Kaposi sarcoma. Although our results suggest that cancer is rare in YLWHIV, the possibility that the cancer burden is higher cannot be excluded due to incomplete information in MRs and high LTF rates. Further, our study raises concern that patients referred for diagnosis are not accessing potential life-saving care.

From "4Rs and 2Ss" to "Amaka Amasanyufu" (Happy Families): Adapting a U.S.-based Evidence-Based Intervention to the Uganda Context.

In Uganda, one in five children presents mental health challenges, including disruptive behavior disorders (DBDs). DBDs can persist through adulthood and result in negative outcomes. Effective interventions for DBDs have been developed and tested in high-poverty communities in developed countries. Yet, most African countries, such as Uganda, lack such interventions. This paper describes the adaptation process of an evidence-based intervention of U.S. origin to optimize fit to context with intervention fidelity, as part of a randomized trial conducted with youth that exhibit behavioral challenges and their caregivers in 30 schools in Uganda. The process involved: initial meetings with headteachers and teachers to introduce the study and the main concepts of the intervention; initial manual review focusing on 4Rs and 2Ss content by the Uganda team; engagement of community stakeholders for additional feedback on content and cultural relevance; final revision of the manual; and collection of children's drawings for the illustration of the manual. This paper describes both similarities and differences between the original and adapted intervention content and methods of delivery. The findings also highlight the importance of involving community stakeholders in the adaptation process.

En Uganda, uno de cada cinco niños presenta problemas de salud mental, incluidos los trastornos del comportamiento disruptivo (TCD). Los TCD pueden continuar hasta la adultez y tener consecuencias negativas. Se han desarrollado intervenciones eficaces para los TCD, las cuales se han evaluado en comunidades con altos índices de pobreza en países desarrollados. Sin embargo, la mayoría de los países africanos, como Uganda, carecen de dichas intervenciones. Este artículo describe el proceso de adaptación de una intervención factual de origen estadounidense para optimizar su adaptación al contexto con la fidelidad de la intervención como parte de un ensayo aleatorizado realizado con jóvenes que presentan problemas conductuales y sus cuidadores en 30 escuelas de Uganda. El proceso consistió en reuniones iniciales con directores y maestros para presentar el estudio y los conceptos principales de la intervención; una revisión inicial del manual centrada en el contenido de la intervención "4Rs and 2 Ss" por parte del equipo de Uganda; la participación de partes interesadas de la comunidad para obtener comentarios adicionales sobre el contenido y la relevancia cultural; la revisión final del manual; y la recopilación de dibujos de los niños para la ilustración del manual. Este artículo describe tanto las similitudes como las diferencias entre el contenido de la intervención original y la adaptada y los métodos de implementación. Los resultados también destacan la importancia de hacer participar a las partes interesadas en el proceso de adaptación.

Correction to: Association of Male Circumcision with Women's Knowledge of its Biomedical Effects and With Their Sexual Satisfaction and Function: A Systematic Review.

The article Association of Male Circumcision with Women's Knowledge of its Biomedical Effects and With Their Sexual Satisfaction and Function: A Systematic Review, written by Jonathan M. Grund, Tyler S. Bryant, Carlos Toledo, Inimfon Jackson, Kelly Curran, Sheng Zhou, Jorge Martin del Campo, Ling Yang, Apollo Kivumbi, Peizi Li, Naomi Bock, Joanna Taliano, Stephanie M. Davis was originally published electronically on the publisher's internet portal (currently SpringerLink) on 24 October 2018 without open access.

Examining the relationship of social support and family cohesion on ART adherence among HIV-positive adolescents in southern Uganda: baseline findings.

Several studies in sub-Saharan Africa have linked social support to better ART (antiretroviral therapy) adherence among adults living with HIV. Less is known about the role of social support and family cohesion in ART adherence among children below 18 years. This paper focuses on HIV-infected adolescents as they transition through the vulnerable developmental stage of adolescence to examine the association between family cohesion and social support, and ART adherence in southern Uganda. We utilized baseline data from Suubi+Adherence study, a five-year randomized longitudinal clinical trial with the overall goal of examining the impact and cost associated with an innovative asset-based social intervention to increase adherence to HIV treatment for HIV-infected adolescents in Uganda. This study employed self-reports to measure social support, family cohesion and ART adherence to treatment from 702 participants in 39 clinics situated in southern Uganda. Regression results indicated that after adjusting for sociodemographic characteristics that family cohesion and social support from caregivers/family were associated with self-reported adherence to ART among HIV-infected adolescents. Social support from classmates, teachers, and friends were not associated with ART adherence. Study results suggest that strengthening family relationships and promoting social support within families caring for adolescents living with HIV can be crucial in addressing ART adherence challenges among adolescents in sub-Saharan Africa.

Prevalence of behavioral disorders and attention deficit/hyperactive disorder among school going children in Southwestern Uganda.

BACKGROUND: Disruptive Behavioral Disorders (DBDs) and Attention Deficit/Hyperactivity Disorder (ADHD) are chronic, impairing, and costly child and adolescent mental health challenges which, when untreated, can result in disruptions in school performance, friendships and family relations. Yet, there is dearth of prevalence data on child and adolescent behavioral challenges within sub-Saharan Africa, including Uganda. This study aims to estimate the prevalence rate of behavioral challenges and ADHD among young school going children and early adolescents (ages 8-13 at study enrollment), utilizing a school-based sample in southwest Uganda. METHODS: We present screening results from a 5-year scale-up study titled SMART Africa-Uganda (2016-2021), set across 30 public primary schools located in the greater Masaka region in Uganda, a region heavily impacted by poverty and HIV/AIDS. Specifically, we draw on screening data from caregivers of 2434 children that used well-established standardized measures that had been pre-tested in the region. These were: 1) oppositional defiant disorder (ODD) and conduct disorder (CD) subscales of the Disruptive Behavior Disorders (DBD) scale; and 2) the Iowa Connors and Impairment scales. Slightly over half of the children in the sample were female (52%), with a mean age of 10.27 years. RESULTS: Of the 2434 participants screened for disruptive behaviors: 1) 6% (n = 136) scored positive on ODD and 2% (n = 42) scored positive on CD subscales of the DBD scale; 2) 9.61% (n = 234), and 2.67% (n = 65) were reported to have elevated symptoms of ODD and ADHD on the Iowa Connors caregiver report scale respectively. Twenty-five percent (n = 586) of children were described by their caregivers as having experienced some form of impairment in at least four domains of the Impairment scale. CONCLUSION: The results indicate the presence of behavioral challenges and ADHD among school going children, aged 8-13 years, in Uganda. Given the negative outcomes associated with behavioral challenges as children transition to adolescence and adulthood, detecting these emerging behavioral challenges early is critical in developing appropriate interventions. School settings could be considered as one of the contextually-relevant, culturally-appropriate, and non-stigmatizing venues to implement screening procedures and to detect emerging behavioral challenges and to make necessary referrals.

Utilizing a family-based economic strengthening intervention to improve mental health wellbeing among female adolescent orphans in Uganda.

BACKGROUND: It is estimated that almost 20% of the world's adolescents have experienced or are experiencing a mental health problem. Several factors have been associated with the onset of adolescent mental health disorders, including poverty, child abuse and violence, particularly among adolescent girls. This paper examines the effect of participating in a family-based economic strengthening intervention on the mental health well-being of female adolescent orphans impacted by HIV/AIDS in rural Uganda. METHODS: Data utilized in this study was from the Bridges to the Future Study (2011-2016), an economic empowerment intervention aimed at improving health outcomes of orphaned children. Adolescents were randomly assigned to either the control condition receiving bolstered standard of care services for orphaned adolescents; or one of two treatment conditions receiving bolstered standard of care as well as an economic empowerment intervention comprising of a child development account, a mentorship program and workshops on financial management and microenterprise development. Data was collected at baseline, 12- and 24-months post intervention initiation. Multilinear regression analyses were conducted to examine the impact of an economic empowerment intervention on mental health functioning of female participants over time. Mental health functioning was measured by: (1) the Child Depression Inventory; (2) Beck Hopelessness Scale; and (3) Tennessee Self Concept Scale. RESULTS: Analysis results show an improvement in mental health functioning over time among female participants receiving the intervention compared to their control counterparts. Specifically, compared to participants in the control condition, participants receiving the intervention reported a reduction in depressive symptoms from baseline to 12-months follow-up (b = - 1.262, 95% CI - 2.476, - 0.047), and an additional 0.645-point reduction between baseline and 24-months follow-up (b = - 1.907, 95% CI - 3.192, - 0.622). Participants receiving the intervention reported significant improvement in their reported self-concept from baseline to 24 months follow-up (b = 3.503 (95% CI 1.469, 5.538) compared to participants in the control condition. CONCLUSIONS: Empowerment of young girls, either in the form of peer mentorship and/or economic strengthening seems to significantly improve the overall mental health functioning of adolescent girls impacted by HIV and AIDS in low-income settings.

Examining the organizational factors that affect health workers' attendance: Findings from southwestern Uganda.

Sub-Saharan Africa experiences human resources crisis in the health sector. Specifically, Uganda faces significant shortages in health care workforce at all levels. However, there is limited literature on factors contributing to health care workforce absenteeism. This study aims to explore reasons for absenteeism among health workers in rural Uganda. Data were collected using a demographic questionnaire and focus groups. Eight focus groups were conducted with participants (n = 27) selected from 39 selected health centers. Four main themes emerged as the reasons for absenteeism among health workers. These included personal/family related challenges, distance or transportation issues, income specifically additional sources of income, and poor support/supervision. Barriers to active engagement at work were also identified, including loss of motivation, concerns at home, patient level issues, and lack of equipment. Recommendations were also elicited from the participants. These findings are critical in formulating and developing interventions to address absenteeism and low performance among health workers.

Association of Male Circumcision with Women's Knowledge of its Biomedical Effects and With Their Sexual Satisfaction and Function: A Systematic Review.

Male circumcision (MC) is a key HIV prevention intervention for men in countries with high HIV prevalence. Women's understanding of MC is important but poorly understood. We conducted a systematic review including women's knowledge of MC's biomedical impacts and its association with female sexual satisfaction and function through October 2017. Thirty-eight articles were identified: thirty-two with knowledge outcomes, seven with sexual satisfaction, and four with sexual function (N = 38). Respondent proportions aware MC protects men from HIV were 9.84-91.8% (median 60.0%). Proportions aware MC protects men from STIs were 14.3-100% (72.6%). Proportions aware MC partially protects men from HIV were 37.5-82% (50.7%). Proportions aware MC is not proven to protect women from infection by an HIV-positive partner were 90.0-96.8% (93.0%). No increases over time were noted. Women's MC knowledge is variable. Education could help women support MC and make better-informed sexual decisions.

Suubi4Her: a study protocol to examine the impact and cost associated with a combination intervention to prevent HIV risk behavior and improve mental health functioning among adolescent girls in Uganda.

BACKGROUND: Asset-based economic empowerment interventions, which take an integrated approach to building human, social, and economic capital, have shown promise in their ability to reduce HIV risk for young people, including adolescent girls, in sub-Saharan Africa. Similarly, community and family strengthening interventions have proven beneficial in addressing mental health and behavioral challenges of adolescents transitioning to adulthood. Yet, few programs aimed at addressing sexual risk have applied combination interventions to address economic stability and mental health within the traditional framework of health education and HIV counseling/testing. This paper describes a study protocol for a 5-year, NIMH-funded, cluster randomized-controlled trial to evaluate a combination intervention aimed at reducing HIV risk among adolescent girls in Uganda. The intervention, titled Suubi4Her, combines savings-led economic empowerment through youth development accounts (YDA) with an innovative family strengthening component delivered via Multiple Family Groups (MFG). METHODS: Suubi4Her will be evaluated via a three-arm cluster randomized-controlled trial design (YDA only, YDA + MFG, Usual Care) in 42 secondary schools in the Central region of Uganda, targeting a total of 1260 girls (ages 15-17 at enrollment). Assessments will occur at baseline, 12, 24, and 36 months. This study addresses two primary outcomes: 1) change in HIV risk behavior and 2) change in mental health functioning. Secondary exploratory outcomes include HIV and STI incidence, pregnancy, educational attainment, financial savings behavior, gender attitudes, and self-esteem. For potential scale-up, cost effectiveness analysis will be employed to compare the relative costs and outcomes associated with each study arm. CONCLUSIONS: Suubi4Her will be one of the first prospective studies to examine the impact and cost of a combination intervention integrating economic and social components to reduce known HIV risk factors and improve mental health functioning among adolescent girls, while concurrently exploring mental health as a mediator in HIV risk reduction. The findings will illuminate the pathways that connect economic needs, mental health, family support, and HIV risk. If successful, the results will promote holistic HIV prevention strategies to reduce risk among adolescent girls in Uganda and potentially the broader sub-Saharan Africa region. TRIAL REGISTRATION: Clinical Trials NCT03307226 (Registered: 10/11/17).

Association between male circumcision and women's biomedical health outcomes: a systematic review.

BACKGROUND: Male circumcision reduces men's risk of acquiring HIV and some sexually transmitted infections from heterosexual exposure, and is essential for HIV prevention in sub-Saharan Africa. Studies have also investigated associations between male circumcision and risk of acquisition of HIV and sexually transmitted infections in women. We aimed to review all evidence on associations between male circumcision and women's health outcomes to benefit women's health programmes. METHODS: In this systematic review we searched for peer-reviewed and grey literature publications reporting associations between male circumcision and women's health outcomes up to April 11, 2016. All biomedical (not psychological or social) outcomes in all study types were included. Searches were not restricted by year of publication, or to sub-Saharan Africa. Publications without primary data and not in English were excluded. We extracted data and assessed evidence on each outcome as high, medium, or low consistency on the basis of agreement between publications; outcomes found in fewer than three publications were indeterminate consistency. FINDINGS: 60 publications were included in our assessment. High-consistency evidence was found for five outcomes, with male circumcision protecting against cervical cancer, cervical dysplasia, herpes simplex virus type 2, chlamydia, and syphilis. Medium-consistency evidence was found for male circumcision protecting against human papillomavirus and low-risk human papillomavirus. Although the evidence shows a protective association with HIV, it was categorised as low consistency, because one trial showed an increased risk to female partners of HIV-infected men resuming sex early after male circumcision. Seven outcomes including HIV had low-consistency evidence and six were indeterminate. INTERPRETATION: Scale-up of male circumcision in sub-Saharan Africa has public health implications for several outcomes in women. Evidence that female partners are at decreased risk of several diseases is highly consistent. Synergies between male circumcision and women's health programmes should be explored. FUNDING: US Centers for Disease Control and Prevention and Jhpiego.