Karen O’Donnell

A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection

OBJECTIVE The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 300 assessed the clinical efficacy and safety of combination zidovudine/lamivudine (ZDV/3TC) compared with either didanosine (ddI) alone or combination ZDV/ddI. STUDY DESIGN Children with symptomatic human immunodeficiency virus (HIV) infection, 6 weeks through 15 years of age, were stratified according to age and randomly assigned to receive ddI, ZDV/3TC, or ZDV/ddI. The primary endpoint was time to first progression of HIV disease or death. Enrollment in the ZDV/ddI arm stopped after 11 months on the basis of results of PACTG Protocol 152, but blinded follow-up continued. RESULTS For the 471 children who could be evaluated, the median age was 2.7 years, median CD4 cell count was 699 cells/mm3, and median log10 HIV RNA was 5.1/mL. Median follow-up was 9.4 months. Patients receiving ZDV/3TC had a lower risk of HIV disease progression or death than those receiving ddI alone (15 vs 38 failures, P = .0006) and a lower risk of death (3 vs 15 deaths, P = .0039). Weight and height growth rates, CD4+ cell counts, and RNA concentrations showed results favoring ZDV/3TC. For patients concurrently randomized to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recipients had lower risk of HIV disease progression than those who received ddI alone (P = .0026 and P = .0045). CONCLUSIONS Combination therapy with either ZDV/3TC or ZDV/ddI was superior, as determined by clinical and laboratory measures, to monotherapy with ddI.

Implementation and Randomized Controlled Trial Evaluation of Universal Postnatal Nurse Home Visiting

OBJECTIVES We evaluated whether a brief, universal, postnatal nurse home-visiting intervention can be implemented with high penetration and fidelity, prevent emergency health care services, and promote positive parenting by infant age 6 months. METHODS Durham Connects is a manualized 4- to 7-session program to assess family needs and connect parents with community resources to improve infant health and well-being. All 4777 resident births in Durham, North Carolina, between July 1, 2009, and December 31, 2010, were randomly assigned to intervention and control conditions. A random, representative subset of 549 families received blinded interviews for impact evaluation. RESULTS Of all families, 80% initiated participation; adherence was 84%. Hospital records indicated that Durham Connects infants had 59% fewer infant emergency medical care episodes than did control infants. Durham Connects mothers reported fewer infant emergency care episodes and more community connections, more positive parenting behaviors, participation in higher quality out-of-home child care, and lower rates of anxiety than control mothers. Blinded observers reported higher quality home environments for Durham Connects than for control families. CONCLUSIONS A brief universal home-visiting program implemented with high penetration and fidelity can lower costly emergency medical care and improve family outcomes.

Ultrasound Diagnosis of Fetal Anomalies Associated with in utero Cocaine Exposure: Further Support for Cocaine-Induced Vascular Disruption Teratogenesis

The dramatic increase in cocaine use over the past decade has led to a concern about its possible teratogenicity. We have identified 6 structural fetal anomalies which we postulate may have cocaine-induced vascular accidents as the teratogenic mechanism: 2 complex choroid plexus cysts, gastroschisis, meconium peritonitis, urethral stenosis, and radial hypoplasia. Two additional anomalous neonates were born to perinatal cocaine users. Eight of 51 (15.7%) cocaine-exposed perinates exhibited anomalies versus 120 of 2,194 (5.4%) perinates without known cocaine exposure during this time period. This represents a 3-fold relative risk (RR = 2.87, OR = 3.22, chi square = 9.68, p < 0.005) for the cocaine-exposed fetus. Subjects were all identified as cocaine users prior to ultrasound-detected anomaly and ultrasonologists were blinded to maternal drug history. The vascular disruption model as the plausible mechanism for cocaine-associated teratogenesis is supported by the type of anomalies reported. In addition, cocaine use was prospectively determined to have occurred at the critical developmental period in each case.

Adverse childhood experiences, psychosocial well-being and cognitive development among orphans and abandoned children in five low income countries.

BackgroundDevelopment policymakers and child-care service providers are committed to improving the educational opportunities of the 153 million orphans worldwide. Nevertheless, the relationship between orphanhood and education outcomes is not well understood. Varying factors associated with differential educational attainment leave policymakers uncertain where to intervene. This study examines the relationship between psychosocial well-being and cognitive development in a cohort of orphans and abandoned children (OAC) relative to non-OAC in five low and middle income countries (LMICs) to understand better what factors are associated with success in learning for these children.MethodsPositive Outcomes for Orphans (POFO) is a longitudinal study, following a cohort of single and double OAC in institutional and community-based settings in five LMICs in Southeast Asia and sub-Saharan Africa: Cambodia, Ethiopia, India, Kenya, and Tanzania. Employing two-stage random sampling survey methodology to identify representative samples of OAC in six sites, the POFO study aimed to better understand factors associated with child well-being. Using cross-sectional and child-level fixed effects regression analyses on 1,480 community based OAC and a comparison sample of non-OAC, this manuscript examines associations between emotional difficulties, cognitive development, and a variety of possible co-factors, including potentially traumatic events.ResultsThe most salient finding is that increases in emotional difficulties are associated with lags in cognitive development for two separate measures of learning within and across multiple study sites. Exposure to potentially traumatic events, male gender, and lower socio-economic status are associated with more reported emotional difficultiesin some sites. Being female and having an illiterate caregiver is associated with lower performance on cognitive development tests in some sites, while greater wealth is associated with higher performance. There is no significant association between orphan status per se and cognitive development, though the negative and significant association between higher emotional difficulties and lags in cognitive development hold across all orphan subgroups.ConclusionsThese findings suggest that interventions targeting psychosocial support for vulnerable children, especially vis a vis traumatic experiences, may ease strains inhibiting a child’s learning. Family based interventions to stabilize socioeconomic conditions may help overcome psychosocial challenges that otherwise would present as barriers to the child’s learning.

Randomized Controlled Trial of Universal Postnatal Nurse Home Visiting: Impact on Emergency Care

BACKGROUND AND OBJECTIVES: Although nurse home visiting has proven efficacious with small samples, scaling up to community populations with diverse families has not yet proven effective. The Durham Connects program was developed in collaboration with community leaders as a brief, universal, postnatal nurse home visiting intervention designed to screen for risk, provide brief intervention, and connect families with more intensive evidence-based services as needed. This study tested program effectiveness in reducing infant emergency medical care between birth and age 12 months. METHODS: All 4777 resident births in Durham, North Carolina across 18 months were randomly assigned, with even birth date families to intervention and odd birth date families to control. Intervention families were offered 3 to 7 contacts between 3 and 12 weeks after birth to assess family needs and connect parents with community resources to improve infant health and well-being. Hospital records were analyzed by using an intent-to-treat design to evaluate impact among a representative subset of 549 families. RESULTS: After demographic factors (ie, birth risk, Medicaid status, ethnicity, and single parenthood) were covaried, relative to control families, families assigned to intervention had 50% less total emergency medical care use (mean [M] emergency department visits and hospital overnights) (Mintervention = 0.78 and Mcontrol = 1.57; P < .001, effect size = 0.28) across the first 12 months of life. CONCLUSIONS: This brief, universal, postnatal nurse home visiting program improves population-level infant health care outcomes for the first 12 months of life. Nurse home visiting can be implemented universally at high fidelity with positive impacts on infant emergency health care that are similar to those of longer, more intensive home visiting programs. This approach offers a novel solution to the paradox of targeting by offering individually tailored intervention while achieving population-level impact.

Correlates of poor health among orphans and abandoned children in less wealthy countries: the importance of caregiver health.

Background More than 153 million children worldwide have been orphaned by the loss of one or both parents, and millions more have been abandoned. We investigated relationships between the health of orphaned and abandoned children (OAC) and child, caregiver, and household characteristics among randomly selected OAC in five countries. Methodology Using a two-stage random sampling strategy in 6 study areas in Cambodia, Ethiopia, India, Kenya, and Tanzania, the Positive Outcomes for Orphans (POFO) study identified 1,480 community-living OAC ages 6 to 12. Detailed interviews were conducted with 1,305 primary caregivers at baseline and after 6 and 12 months. Multivariable logistic regression models describe associations between the characteristics of children, caregivers, and households and child health outcomes: fair or poor child health; fever, cough, or diarrhea within the past two weeks; illness in the past 6 months; and fair or poor health on at least two assessments. Principal Findings Across the six study areas, 23% of OAC were reported to be in fair or poor health; 19%, 18%, and 2% had fever, cough, or diarrhea, respectively, within the past two weeks; 55% had illnesses within the past 6 months; and 23% were in fair or poor health on at least two assessments. Female gender, suspected HIV infection, experiences of potentially traumatic events, including the loss of both parents, urban residence, eating fewer than 3 meals per day, and low caregiver involvement were associated with poorer child health outcomes. Particularly strong associations were observed between child health measures and the health of their primary caregivers. Conclusions Poor caregiver health is a strong signal for poor health of OAC. Strategies to support OAC should target the caregiver-child dyad. Steps to ensure food security, foster gender equality, and prevent and treat traumatic events are needed.

Prevalence and Incidence of Traumatic Experiences Among Orphans in Institutional and Family-Based Settings in 5 Low- and Middle-Income Countries: A Longitudinal Study

Contrary to some conventional wisdom, in this large study that randomly sampled orphans and separated children from 5 countries, prevalence of reported traumatic events was no worse among those institutionalized than among those in family-based care. Reported incidence of physical or sexual abuse was actually higher for those in family-based care. Understanding the specific context, and elements contributing to potential harm and benefits in both family-based and institutional care, are essential to promoting the best interest of the child. Contrary to some conventional wisdom, in this large study that randomly sampled orphans and separated children from 5 countries, prevalence of reported traumatic events was no worse among those institutionalized than among those in family-based care. Reported incidence of physical or sexual abuse was actually higher for those in family-based care. Understanding the specific context, and elements contributing to potential harm and benefits in both family-based and institutional care, are essential to promoting the best interest of the child. Background: Policy makers struggling to protect the 153 million orphaned and separated children (OSC) worldwide need evidence-based research on the burden of potentially traumatic events (PTEs) and the relative risk of PTEs across different types of care settings. Methods: The Positive Outcomes for Orphans study used a 2-stage, cluster-randomized sampling design to identify 1,357 institution-dwelling and 1,480 family-dwelling orphaned and separated children in 5 low- and middle-income countries (LMICs) in sub-Saharan Africa and Asia. We used the Life Events Checklist developed by the National Center for Posttraumatic Stress Disorder to examine self-reported PTEs among 2,235 OSC ages 10–13 at baseline. We estimated prevalence and incidence during 36-months of follow-up and compared the risk of PTEs across care settings. Data collection began between May 2006 and February 2008, depending on the site. Results: Lifetime prevalence by age 13 of any PTE, excluding loss of a parent, was 91.0% (95% confidence interval (CI) = 85.6, 94.5) in institution-dwelling OSC and 92.4% (95% CI = 90.3, 94.0) in family-dwelling OSC; annual incidence of any PTE was lower in institution-dwelling (23.6% [95% CI = 19.4, 28.7]) than family-dwelling OSC (30.0% [95% CI = 28.1, 32.2]). More than half of children in institutions (50.3% [95% CI = 42.5, 58.0]) and in family-based care (54.0% [95% CI = 50.2, 57.7]) had experienced physical or sexual abuse by age 13. Annual incidence of physical or sexual abuse was lower in institution-dwelling (12.9% [95% CI = 9.6, 17.3]) than family-dwelling OSC (19.4% [95% CI = 17.7, 21.3]), indicating statistically lower risk in institution-dwelling OSC (risk difference = 6.5% [95% CI = 1.4, 11.7]). Conclusion: Prevalence and incidence of PTEs were high among OSC, but contrary to common assumptions, OSC living in institutions did not report more PTEs or more abuse than OSC living with families. Current efforts to reduce the number of institution-dwelling OSC may not reduce incidence of PTEs in this vulnerable population. Protection of children from PTEs should be a primary consideration, regardless of the care setting.

A brief assessment of learning for orphaned and abandoned children in low and middle income countries.

Assessment of children’s learning and performance in low and middle income countries has been critiqued as lacking a gold standard, an appropriate norm reference group, and demonstrated applicability of assessment tasks to the context. This study was designed to examine the performance of three nonverbal and one adapted verbal measure of children’s problem solving, memory, motivation, and attention across five culturally diverse sites. The goal was to evaluate the tests as indicators of individual differences affected by life events and care circumstances for vulnerable children. We conclude that the measures can be successfully employed with fidelity in non-standard settings in LMICs, and are associated with child age and educational experience across the settings. The tests can be useful in evaluating variability in vulnerable child outcomes.

The effectiveness of the peer delivered Thinking Healthy Plus (THPP+) Programme for maternal depression and child socio-emotional development in Pakistan: study protocol for a three-year cluster randomized controlled trial

BackgroundThe negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145–57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99–101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207–16, 2000; Clin Child Fam Psychol Rev 14(1):1–27, 2011). Given that 10–35% of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37–54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221–7, 2009; Trop Med Int Health 13(4):579–83, 2008; Br Med Bull 101(1):57–79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan.Methods/designThe THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design.DiscussionThis trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women’s depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development.Trial registrationTHPP-P ClinicalTrials.gov Identifier: NCT02111915 (registered on 9 April 2014).THPP+ ClinicalTrials.gov Identifier: NCT02658994 (registered on 21 January 2016).Sponsor: Human Development Research Foundation (HDRF).

A Qualitative Exploration of the Mental Health and Psychosocial Contexts of HIV-Positive Adolescents in Tanzania.

Although 85% of HIV-positive adolescents reside in sub-Saharan Africa, little is known about the psychosocial and mental health factors affecting their daily well-being. Identifying these contextual variables is key to development of culturally appropriate and effective interventions for this understudied and high-risk population. The purpose of this study was to identify salient psychosocial and mental health challenges confronted by HIV-positive youth in a resource-poor Tanzanian setting. A total of 24 qualitative interviews were conducted with a convenience sample of adolescents aged 12–24 receiving outpatient HIV care at a medical center in Moshi, Tanzania. All interviews were audio-recorded, transcribed, and coded using thematic analysis. Psychosocial challenges identified included loss of one or more parents, chronic domestic abuse, financial stressors restricting access to medical care and education, and high levels of internalized and community stigma among peers and other social contacts. Over half of youth (56%) reported difficulties coming to terms with their HIV diagnosis and espoused related feelings of self-blame. These findings highlight the urgent need to develop culturally proficient programs aimed at helping adolescents cope with these manifold challenges. Results from this study guided the development of Sauti ya Vijana (The Voice of Youth), a 10-session group mental health intervention designed to address the psychosocial and mental health needs of HIV-positive Tanzanian youth.