Qualitative perspectives on COVID-19, interpersonal violence, and interventions to improve well-being from adolescent girls and young women in Kisumu, Kenya.

Introduction: Adolescent girls and young women (AGYW) face a high burden of gender-based violence (GBV) worldwide. The COVID-19 pandemic and associated policies led to global increases in GBV, decreased access to resources, and disruptions of pathways to care. We aimed to understand the effects of COVID-19 on AGYW affected by GBV in Kisumu, Kenya, as well as to identify possible interventions to mitigate those effects. Methods: Focus group discussions (FGDs) were conducted with AGYW aged 15-25 with a history of exposure to GBV. AGYW were split into age-matched groups; aged 15-19 for younger groups and 19-25 for older groups. Discussions focused on how COVID-19 affected experiences of GBV, access to care services, economic and social outcomes, and opportunities for interventions to mitigate negative impacts of COVID-19 and violence. Results: Five FGDs with 46 AGYW were completed in June-September 2021. AGYW described increases in all types of GBV, particularly sexual abuse and intimate partner violence. Early marriage and subsistence transactional sex also increased. AGYW described violence as both a cause and effect of poor economic, social and health consequences related to the pandemic. Notably, AGYW emphasized stress, lack of mental health support and increased substance use as risk factors for violence, and discussed the deleterious mental health effects of violence-particularly in the wake of disruption of mental health services. COVID-19 disrupted referrals to violence-related services, and reduced access to both medical services and psychosocial services. AGYW believed that interventions focused on improving mental health as well as economic empowerment would be the most feasible and acceptable in mitigating the negative effects of COVID-19 and related exacerbations in violence. Discussion: AGYW reported increases in almost all forms of GBV during the pandemic, with related exacerbation in mental health. Concurrently, AGYW endorsed decreased access to care services. As there is no evidence that violence and mental health challenges will quickly resolve, there is an urgent need to identify and implement interventions to mitigate these negative effects.

Understanding ART Adherence among Adolescent Girls and Young Women in Western Kenya: A Cross-Sectional Study of Barriers and Facilitators.

BACKGROUND: HIV remains a leading cause of death for adolescent girls and young women (AGYW) in sub-Saharan Africa. This population has a high incidence of HIV and other comorbidities, such as experiencing violence, and low antiretroviral therapy (ART) adherence. To reach global HIV goals, data are needed on the specific adherence barriers for AGYW living with HIV, so interventions can be targeted effectively. METHODS: Cross-sectional data were collected at urban and rural health facilities in and around Kisumu County, western Kenya, from January to June 2022, from AGYW 15-24 years of age who were living with HIV. Surveys included questions on intimate partner violence, mental health issues, food security, and orphanhood. Adherence was categorized using viral load testing where available and the Center for Adherence Support Evaluation (CASE) adherence index otherwise. Logistic regression was used to assess associations between potential explanatory variables and adherence. FINDINGS: In total, 309 AGYW participated. AGYW with experiences of emotional violence (Odds Ratio [OR] = 1.94, 95% Confidence Interval [CI] = 1.03-3.66), moderate or severe depression (OR = 3.19, 95% CI = 1.47-6.94), and/or substance use (OR = 2.71, 95% CI = 1.24-5.92) had significantly higher odds of poor adherence when compared to AGYW without these respective experiences. Physical and sexual violence, food insecurity, and orphanhood were not associated with poor adherence in this cohort. INTERPRETATION: Elucidating the risk factors associated with poor adherence among AGYW living with HIV allows us to identify potential targets for future interventions to improve ART adherence and HIV care outcomes. Mental health and violence prevention interventions, including combination interventions, may prove to be promising approaches.

Progression of vertebral bone disease in mucopolysaccharidosis VII dogs from birth to skeletal maturity.

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient ß-glucuronidase activity, leading to accumulation of incompletely degraded heparan, dermatan and chondroitin sulfate glycosaminoglycans. Patients with MPS VII exhibit progressive spinal deformity, which decreases quality of life. Previously, we demonstrated that MPS VII dogs exhibit impaired initiation of secondary ossification in the vertebrae and long bones. The objective of this study was to build on these findings and comprehensively characterize how vertebral bone disease manifests progressively in MPS VII dogs throughout postnatal growth. Vertebrae were collected postmortem from MPS VII and healthy control dogs at seven ages ranging from 9 to 365 days. Microcomputed tomography and histology were used to characterize bone properties in primary and secondary ossification centers. Serum was analyzed for bone turnover biomarkers. Results demonstrated that not only was secondary ossification delayed in MPS VII vertebrae, but that it progressed aberrantly and was markedly diminished even at 365 days-of-age. Within primary ossification centers, bone volume fraction and bone mineral density were significantly lower in MPS VII at 180 and 365 days-of-age. MPS VII growth plates exhibited significantly lower proliferative and hypertrophic zone cellularity at 90 days-of-age, while serum bone-specific alkaline phosphatase (BAP) was significantly lower in MPS VII dogs at 180 days-of-age. Overall, these findings establish that vertebral bone formation is significantly diminished in MPS VII dogs in both primary and secondary ossification centers during postnatal growth.

Reaching Out for Help: An Analysis of the Differences Between Refugees Who Accept and Those Who Decline Community Mental Health Services.

In 2012, clinics in Louisville, Kentucky began to use the RHS-15 to screen for mental health issues among refugees. At the same time, mental health outreach programs were developed and implemented by the Mental Health Coordinator. Data from 563 refugee clients referred to the Mental Health Coordinator from 2012 to 2015 was analyzed to examine differences between refugees who accepted referral to community mental health services and those who declined on the variables age, gender, country of origin, time in the U.S., and referral source. Results indicate significant differences with regard to time in the U.S. and referral source. Those more likely to accept services included refugees in the U.S. more than 240 days and those referred by non-clinic sources. Findings improve our understanding of the characteristics of refugees who accept and decline mental health services and support the value of both formal screening and community outreach programs.

Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs.

BACKGROUND: We previously demonstrated the therapeutic benefits of pentosan polysulfate (PPS) in a rat model of mucopolysaccharidosis (MPS) type VI. Reduction of inflammation, reduction of glycosaminoglycan (GAG) storage, and improvement in the skeletal phenotype were shown. Herein, we evaluate the long-term safety and therapeutic effects of PPS in a large animal model of a different MPS type, MPS I dogs. We focused on the arterial phenotype since this is one of the most consistent and clinically significant features of the model. METHODOLOGY/PRINCIPAL FINDINGS: MPS I dogs were treated with daily oral or biweekly subcutaneous (subQ) PPS at a human equivalent dose of 1.6 mg/kg for 17 and 12 months, respectively. Safety parameters were assessed at 6 months and at the end of the study. Following treatment, cytokine and GAG levels were determined in fluids and tissues. Assessments of the aorta and carotid arteries also were performed. No drug-related increases in liver enzymes, coagulation factors, or other adverse effects were observed. Significantly reduced IL-8 and TNF-alpha were found in urine and cerebrospinal fluid (CSF). GAG reduction was observed in urine and tissues. Increases in the luminal openings and reduction of the intimal media thickening occurred in the carotids and aortas of PPS-treated animals, along with a reduction of storage vacuoles. These results were correlated with a reduction of GAG storage, reduction of clusterin 1 staining, and improved elastin integrity. No significant changes in the spines of the treated animals were observed. CONCLUSIONS: PPS treatment led to reductions of pro-inflammatory cytokines and GAG storage in urine and tissues of MPS I dogs, which were most evident after subQ administration. SubQ administration also led to significant cytokine reductions in the CSF. Both treatment groups exhibited markedly reduced carotid and aortic inflammation, increased vessel integrity, and improved histopathology. We conclude that PPS may be a safe and useful therapy for MPS I, either as an adjunct or as a stand-alone treatment that reduces inflammation and GAG storage.

Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs.

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient ß-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients.

Integrating family planning and prevention of mother to child HIV transmission in Zimbabwe.

OBJECTIVE: The objective was to integrate enhanced family planning (FP) and prevention of mother-to-child HIV transmission services in order to help HIV-positive Zimbabwean women achieve their desired family size and spacing as well as to maximize maternal and child health. STUDY DESIGN: HIV-positive pregnant women were enrolled into a standard-of-care (SOC, n=33) or intervention (n=65) cohort, based on study entry date, and followed for 3 months postpartum. The intervention cohort received education sessions aimed at increasing FP use and negotiation power. Both groups received care from nurses with enhanced FP training. Outcomes included FP use, FP knowledge and HIV disclosure, and were assessed with Fisher's Exact Tests, binomial tests and t tests. RESULTS: The intervention cohort reported increased control over condom use (p=.002), increased knowledge about IUDs (p=.002), increased relationship power (p=.01) and increased likelihood of disclosing their HIV status to a partner (p=.04) and having that partner disclose to them (p=.04) when compared to the SOC cohort. Long-acting reversible contraception (LARC) use in both groups increased from ~2% at baseline to >80% at 3 months postpartum (p<.001). CONCLUSIONS: FP and sexual negotiation skills and knowledge, as well as HIV disclosure, increased significantly in the intervention cohort. LARC uptake increased significantly in both the intervention and SOC cohorts, likely because both groups received care from nurses with enhanced FP training. Successful service integration models are needed to maximize health outcomes in resource-constrained environments; this intervention is such a model that should be replicable in other settings in sub-Saharan Africa and beyond. IMPLICATIONS: This study provides a rigorously evaluated intervention to integrate FP education into ante- and postnatal care for HIV-positive women and also to train providers on FP. Results suggest that this intervention had significant effects on contraception use and communication with sexual partners. This intervention should be adaptable to other areas.