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Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population. [ABSTRACT FROM AUTHOR]

An alarmingly high prevalence of childhood sexual and physical abuse has been observed in HIV-infected men and women, with rates several times higher than observed in the general population. Childhood abuse history has been associated with worse antiretroviral adherence and negative health behaviours in HIV-infected patients. This study evaluates the relationship between childhood abuse and the timing of presentation for HIV care. Participants in a multi-center prospective cohort study, who established initial HIV care after January 1996 and had a CD4 count available within six months of initial presentation, were included in this analysis. Bivariate contingency tables and multivariate logistic regression were used to evaluate the association of childhood abuse with early presentation for HIV care (initial CD4 count≥200/mm3). Among the 186 subjects included in this analysis, 33% had childhood abuse histories and 58% had an initial CD4 count≥200/mm3. Participants with a history of childhood abuse were more likely to present early for HIV care (AOR=2.12; p=0.03), perhaps because survivors of abuse tend to have higher utilization of health services. Because HIV-infected patients with childhood abuse histories have worse antiretroviral medication adherence and are more likely to engage in high-risk sexual and injection drug use behaviours, early presentation affords clinicians the opportunity for timely institution of interventions that may improve patient outcomes and prevent secondary HIV infections. [ABSTRACT FROM AUTHOR]

Providing behavioral treatment for mental health and substance use disorders among HIV-infected individuals is critical because these disorders have been associated with negative outcomes such as poorer medication adherence. This study examines the effectiveness of an integrated treatment model for HIV-infected individuals who have both substance use and mental disorders. Study participants (n = 141) were recruited through routine mental health and substance abuse screening at tertiary Infectious Disease clinics in North Carolina. The study participants received integrated mental health and substance abuse treatment for one year and were interviewed at three-month intervals. Using linear regression analyses, we detected statistically significant decreases in participants’ psychiatric symptomatology, illicit substance use, alcohol use, and inpatient hospital days. Participants also reported fewer emergency room visits and were more likely to be receiving antiretroviral medications and adequate psychotropic medication regimens at follow-up. No changes in sexual risk, physical health, or medical adherence were detected after treatment participation. This integrated treatment model offers an option for treating HIV-infected individuals with mental health and substance use disorders that can be adapted for use in a variety of psychiatric and medical treatment settings. [ABSTRACT FROM AUTHOR]

Abstract Background The proportion of births attended by skilled health personnel is one of two indicators used to measure progress towards Millennium Development Goal 5, which aims for a 75% reduction in global maternal mortality ratios by 2015. Rwanda has one of the highest maternal mortality ratios in the world, estimated between 249–584 maternal deaths per 100,000 live births. The objectives of this study were to quantify secular trends in health facility delivery and to identify factors that affect the uptake of intrapartum healthcare services among women living in rural villages in Bugesera District, Eastern Province, Rwanda. Methods Using census data and probability proportional to size cluster sampling methodology, 30 villages were selected for community-based, cross-sectional surveys of women aged 18–50 who had given birth in the previous three years. Complete obstetric histories and detailed demographic data were elicited from respondents using iPad technology. Geospatial coordinates were used to calculate the path distances between each village and its designated health center and district hospital. Bivariate and multivariate logistic regressions were used to identify factors associated with delivery in health facilities. Results Analysis of 3106 lifetime deliveries from 859 respondents shows a sharp increase in the percentage of health facility deliveries in recent years. Delivering a penultimate baby at a health facility (OR = 4.681 [3.204 - 6.839]), possessing health insurance (OR = 3.812 [1.795 - 8.097]), managing household finances (OR = 1.897 [1.046 - 3.439]), attending more antenatal care visits (OR = 1.567 [1.163 - 2.112]), delivering more recently (OR = 1.438 [1.120 - 1.847] annually), and living closer to a health center (OR = 0.909 [0.846 - 0.976] per km) were independently associated with facility delivery. Conclusions The strongest correlates of facility-based delivery in Bugesera District include previous delivery at a health facility, possession of health insurance, greater financial autonomy, more recent interactions with the health system, and proximity to a health center. Recent structural interventions in Rwanda, including the rapid scale-up of community-financed health insurance, likely contributed to the dramatic improvement in the health facility delivery rate observed in our study.

Abstract Background The care and protection of the estimated 143,000,000 orphaned and abandoned children (OAC) worldwide is of great importance to global policy makers and child service providers in low and middle income countries (LMICs), yet little is known about rates of child labour among OAC, what child and caregiver characteristics predict child engagement in work and labour, or when such work infers with schooling. This study examines rates and correlates of child labour among OAC and associations of child labour with schooling in a cohort of OAC in 5 LMICs. Methods The Positive Outcomes for Orphans (POFO) study employed a two-stage random sampling survey methodology to identify 1480 single and double orphans and children abandoned by both parents ages 6-12 living in family settings in five LMICs: Cambodia, Ethiopia, India, Kenya, and Tanzania. Regression models examined child and caregiver associations with: any work versus no work; and with working Results The majority of OAC (60.7%) engaged in work during the past week, and of those who worked, 17.8% (10.5% of the total sample) worked 28 or more hours. More than one-fifth (21.9%; 13% of the total sample) met UNICEF's child labour definition. Female OAC and those in good health had increased odds of working. OAC living in rural areas, lower household wealth and caregivers not earning an income were associated with increased child labour. Child labour, but not working fewer than 28 hours per week, was associated with decreased school attendance. Conclusions One in seven OAC in this study were reported to be engaged in child labour. Policy makers and social service providers need to pay close attention to the demands being placed on female OAC, particularly in rural areas and poor households with limited income sources. Programs to promote OAC school attendance may need to focus on the needs of families as well as the OAC.

Background.Approximately 153 million children worldwide are orphaned and vulnerable to potentially traumatic events (PTEs). Gender differences in PTEs in low- and middle-income countries (LMIC) are not well-understood, although support services and prevention programs often primarily involve girls.Methods.The Positive Outcomes for Orphans study used a two-stage, cluster-randomized sampling design to identify 2837 orphaned and separated children (OSC) in five LMIC in sub-Saharan Africa and Asia. We examined self-reported prevalence and incidence of several PTE types, including physical and sexual abuse, among 2235 children who were ≥10 years at baseline or follow-up, with a focus on gender comparisons.Results.Lifetime prevalence by age 13 of any PTE other than loss of a parent was similar in both boys [91.7% (95% confidence interval (CI) (85.0–95.5)] and girls [90.3% CI (84.2–94.1)] in institutional-based care, and boys [92.0% (CI 89.0–94.2)] and girls [92.9% CI (89.8–95.1)] in family-based care; annual incidence was similarly comparable between institution dwelling boys [23.6% CI (19.1,−29.3)] and girls [23.6% CI (18.6,−30.0)], as well as between family-dwelling boys [30.7% CI (28.0,−33.6)] and girls [29.3% CI (26.8,−32.0)]. Physical and sexual abuse had the highest overall annual incidence of any trauma type for institution-based OSC [12.9% CI (9.6–17.4)] and family-based OSC [19.4% CI (14.5–26.1)], although estimates in each setting were no different between genders.Conclusion.Prevalence and annual incidence of PTEs were high among OSC in general, but gender-specific estimates were comparable. Although support services and prevention programs are essential for female OSC, programs for male OSC are equally important. [ABSTRACT FROM PUBLISHER]

Abstract Background In the face of the HIV/AIDS epidemic that has contributed to the dramatic increase in orphans and abandoned children (OAC) worldwide, caregiver attitudes about HIV, and HIV-related stigma, are two attributes that may affect caregiving. Little research has considered the relationship between caregiver attributes and caregiver-reported HIV-related stigma. In light of the paucity of this literature, this paper will describe HIV-related stigma among caregivers of OAC in five less wealthy nations. Methods Baseline data were collected between May 2006 through February 2008. The sample included 1,480 community-based and 192 institution-based caregivers. Characteristics of the community-based and institution-based caregivers are described using means and standard deviations for continuous variables or counts and percentages for categorical variables. We fit logistic regression models, both for the full sample and separately for community-based and institution-based caregivers, to explore predictors of acceptance of HIV. Results Approximately 80% of both community-based and institution-based caregivers were female; and 84% of institution-based caregivers, compared to 66% of community-based caregivers, said that they would be willing to care for a relative with HIV. Similar proportions were reported when caregivers were asked if they were willing to let their child play with an HIV-infected child. In a multivariable model predicting willingness to care for an HIV-infected relative, adjusted for site fixed effects, being an institution-based caregiver was associated with greater willingness (less stigma) than community-based caregivers. Decreased willingness was reported by older respondents, while willingness increased with greater formal education. In the adjusted models predicting willingness to allow one's child to play with an HIV-infected child, female gender and older age was associated with less willingness. However, willingness was positively associated with years of formal education. Conclusions The caregiver-child relationship is central to a child's development. OAC already face stigma as a result of their orphaned or abandoned status; the addition of HIV-related stigma represents a double burden for these children. Further research on the prevalence of HIV-related acceptance and stigma among caregivers and implications of such stigma for child development will be critical as the policy community responds to the global HIV/AIDS orphan crisis.

Abstract Background Religion shapes everyday beliefs and activities, but few studies have examined its associations with attitudes about HIV. This exploratory study in Tanzania probed associations between religious beliefs and HIV stigma, disclosure, and attitudes toward antiretroviral (ARV) treatment. Methods A self-administered survey was distributed to a convenience sample of parishioners (n = 438) attending Catholic, Lutheran, and Pentecostal churches in both urban and rural areas. The survey included questions about religious beliefs, opinions about HIV, and knowledge and attitudes about ARVs. Multivariate logistic regression analysis was performed to assess how religion was associated with perceptions about HIV, HIV treatment, and people living with HIV/AIDS. Results Results indicate that shame-related HIV stigma is strongly associated with religious beliefs such as the belief that HIV is a punishment from God (p < 0.01) or that people living with HIV/AIDS (PLWHA) have not followed the Word of God (p < 0.001). Most participants (84.2%) said that they would disclose their HIV status to their pastor or congregation if they became infected. Although the majority of respondents (80.8%) believed that prayer could cure HIV, almost all (93.7%) said that they would begin ARV treatment if they became HIV-infected. The multivariate analysis found that respondents' hypothetical willingness to begin ARV treatme was not significantly associated with the belief that prayer could cure HIV or with other religious factors. Refusal of ARV treatment was instead correlated with lack of secondary schooling and lack of knowledge about ARVs. Conclusion The decision to start ARVs hinged primarily on education-level and knowledge about ARVs rather than on religious factors. Research results highlight the influence of religious beliefs on HIV-related stigma and willingness to disclose, and should help to inform HIV-education outreach for religious groups.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer characterized by very poor survival outcomes. Genomic sequencing of human PDAC tissues and cell lines have identified four molecular subtypes: quasimesenchymal (QM), pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine (ADEX). QM-PDAC has the worse prognosis, but no in vivo models exist for this molecular subtype. Our preliminary analysis using publicly available data demonstrated that the epithelial-to-mesenchymal transition (EMT) transcription factor TWIST1 is upregulated in QM-PDAC. We hypothesized that the TWIST1 -dependent plasticity program was a key regulator of QM-PDAC subtype development. We created a tetracycline-inducible tissue specific Twist1 PDAC genetically engineered mouse model (GEMM) termed as PGRT. Tumor development in the mouse pancreatic ductal epithelium was directed using the Pdx1 promoter-Cre (P) allele leading to stable native expression of the LSL-KrasG12D oncogene (R) and LSL-rtTA-IRES-GFP (G) alleles. The non- Twist1 GEMM (PGR) was crossed with the Twist1-tetO-Luc (T) mouse to create the PGRT model which allows inducible expression of Twist1 and luciferase in pancreatic epithelium under doxycycline treatment (Tet-ON system). Tumor progression, lineage tracing and metastatic invasion are followed by fluorescence (GFP) and bioluminescence (BLI) imaging. The characterization of this novel PGRT mouse model showed decreased overall survival compared to control non- Twist1 containing mice (∼35 weeks PGRT (n = 17) vs ∼60 weeks PGR (n = 10)). Histological and immunohistochemistry analyses showed the PGRT pancreatic tumors resemble the QM-PDAC subtype and vimentin overexpression correlates with Twist1 -dependent induction of EMT. We attempted to confirm the QM-PDAC profile via cellular markers: GATA6-, HNF1A-, KRT81+, KRT17+, KRT20+, P63+ and ∆P63+. The PGR and standard KPC (Kras+/LSL-G12D; Trp53+LSL-R172H; Pdx1-Cre) PDAC model were also profiled. We observed that 75% of the PGRT tumors displayed a QM-PDAC profile, contrasting with the absence of such profile in both PGR and KPC tumors. Examining the tumors from PGR and KPC, 100% of the PGR and 72.27% KPC tumors exhibited a non-squamous PDAC profile while an intermediate squamous profile was observed in 25% PGRT tumors and 27.27% KPC tumors. Furthermore, Twist1 induction resulted in intra-abdominal and lung metastases. We observed 87.5% PGRT mice showed metastasis positivity, no positivity for PGR mice and 63.64% positivity in KPC mice. In conclusion, these data suggest that Twist1 overexpression cooperates with KrasG12D for PDAC tumor development mimicking the human QM-PDAC subtype to promote progression towards metastasis and early lethality. Potential uses of this novel model include testing treatment strategies to ultimately improve patient outcomes with QM-PDAC. [ABSTRACT FROM AUTHOR]