Identification of sorbitol esterification of glutamic acid by LC-MS/MS in a monoclonal antibody stability assessment.

The stability of monoclonal antibodies (mAbs) is vital for their therapeutic success. Sorbitol, a common mAb stabilizer used to prevent aggregation, was evaluated for any potential adverse effects on the chemical stability of mAb X. An LC-MS/MS based analysis focusing on the post-translational modifications (PTMs) of mAb X was conducted on samples that had undergone accelerated aging at 40°C. Along with PTMs that are known to affect mAbs' structure function and stability (such as deamidation and oxidation), a novel mAb PTM was discovered, the esterification of glutamic acid by sorbitol. Incubation of mAb X with a 1:1 ratio of unlabeled sorbitol and isotopically labeled sorbitol (13C6) further corroborated that the modification was the consequence of the esterification of glutamic acid by sorbitol. Levels of esterification varied across glutamic acid residues and correlated with incubation time and sorbitol concentration. After 4 weeks of accelerated stability with isotopically labeled sorbitol, it was found that 16% of the total mAb possesses an esterified glutamic acid. No esterification was observed at aspartic acid sites despite the free carboxylic acid side chain. This study unveils a unique modification of mAbs, emphasizing its potential significance for formulation and drug development.

Safety vs price in the generic drug market: metformin.

OBJECTIVES: Generic medications represent 90% of prescriptions in the US market and provide a tremendous financial benefit for patients. Recently, multiple generic drugs have been recalled due to the presence of carcinogens, predominantly N-nitrosodimethylamine (NDMA), including an extensive recall of extended-release (ER) metformin products in 2020. STUDY DESIGN: Primary pharmaceutical quality testing and database analysis. METHODS: We tested marketed metformin immediate-release (IR) and ER tablets from a wide sample of generic manufacturers for the presence of carcinogenic impurities NDMA and N,N-dimethylformamide (DMF). We examined the association of level of impurity with drug price and the impact of the 2020 FDA recalls on unit price and prescription fill rate. RESULTS: Postrecall NDMA levels were significantly lower in metformin ER samples (standardized mean difference = -2.0; P = .01); however, we found continued presence of carcinogens above the FDA threshold in 2 of 30 IR samples (6.67%). Overall, the presence of contaminant levels was not significantly associated with price for either IR (NDMA: R2 = 0.142; P = .981; DMF: R2 = 0.382; P = .436) or ER (NDMA: R2 = 0.124; P = .142; DMF: R2 = 0.199; P = .073) samples. Despite recalls, metformin ER prescription fills increased by 8.9% while unit price decreased by 19.61% (P < .05). CONCLUSIONS: Recalls of metformin ER medications were effective in lowering NDMA levels below the FDA threshold; however, some samples of generic metformin still contained carcinogens even after FDA-announced recalls. The absence of any correlation with price indicates that potentially safer products are available on the market for the same price as poorer-quality products.

A Prolonged Outbreak of Enteric Fever Associated With Illegal Miners in the City of Matlosana, South Africa, November 2020-September 2022.

Background: In South Africa, the annual incidence of enteric fever averaged 0.1 per 100 000 persons between 2003 and 2018. During 2021 an increase in the number of enteric fever cases was observed. An outbreak investigation was conducted to determine the magnitude and source of the outbreak. Methods: We performed a cross-sectional descriptive study. Data were collected through telephonic or face-to-face interviews with cases or proxies via a standardized case investigation form. Whole genome sequencing was performed on all Salmonella Typhi isolates. Drinking water samples were collected, tested, and analyzed. Descriptive analysis was performed with Microsoft Excel. Results: Between January 2020 and September 2022, a cluster of 53 genetically highly related Salmonella Typhi isolates was identified from 5 provinces in South Africa. Isolates associated with the cluster showed ≤5 allelic differences, as determined following core genome multilocus sequence typing analysis. Most cases (60%, 32/53) were in the North West province. Males represented 68% (36/53). Of these, 72% (26/36) were aged 15 to 49 years, with a median age of 31 years. Where occupation was known within this age group, 78% (14/18) were illegal gold miners. Illegal miners reported illness onset while working underground. Five municipal tap water samples were tested and showed no evidence of fecal contamination. Conclusions: This outbreak predominantly affected illegal gold miners, likely due to the consumption of contaminated groundwater while working in a gold mine shaft. In addition, this investigation highlights the value of whole genome sequencing to detect clusters and support epidemiologic investigation of enteric fever outbreaks.

"I'd Rather Be Broke Than Harmed": A Qualitative Analysis of the Experiences of People Engaged in Commercial Sex Work During the COVID-19 Pandemic.

OBJECTIVES: People involved in commercial sex work during the COVID-19 pandemic, particularly those compelled to sell sex, faced multiple challenges to their safety and well-being. We explored, in real time, the impact of the COVID-19 pandemic on people involved in commercial sex work and the broader commercial sex industry. METHODS: Using a participatory action research approach, we interviewed 159 English- and Spanish-speaking adults who had engaged in commercial sex work under the direction of a third party in Sacramento County, California, within the past 5 years (approximately 2017-2022). As part of a larger study, our interview protocol included 1 question about the COVID-19 pandemic: "Has COVID-19 changed anything about your experience with sex work?" We transcribed and analyzed interviews using QSR-NVivo, a qualitative coding software. RESULTS: Participants described the effects of increased isolation, decreased demand, difficulty accessing social services, fear of contracting COVID-19, difficulty in following public health guidance on social distancing and wearing face masks, and how the pandemic resulted in some people entering or exiting commercial sex work. Most participants were familiar with recommended public health safety measures, but lack of agency and financial need limited their ability to comply with all recommendations. A lack of access to social services added stress to those most in need of emergency housing or substance use treatment and left them vulnerable to continued abuse. CONCLUSIONS: Stress and financial insecurity generally increased among people involved in commercial sex work during the pandemic, and no efforts were made to understand and mitigate the hardships that this population faced. Future research should address how to maintain social service availability during times of public health emergencies and other crises.

Patients' and Clinicians' Experiences with In-person, Video, and Phone Modalities for Opioid Use Disorder Treatment: A Qualitative Study.

BACKGROUND: Opioid use disorder (OUD) is a chronic condition that requires regular visits and care continuity. Telehealth implementation has created multiple visit modalities for OUD care. There is limited knowledge of patients' and clinicians' perceptions and experiences related to multi-modality care and when different modalities might be best employed. OBJECTIVE: To identify patients' and clinicians' experiences with multiple visit modalities for OUD treatment in primary care. DESIGN: Comparative case study, using video- and telephone-based semi-structured interviews. PARTICIPANTS: Patients being treated for OUD (n = 19) and clinicians who provided OUD care (n = 15) from two primary care clinics within the same healthcare system. APPROACH: Using an inductive approach, interviews were analyzed to identify patients' and clinicians' experiences with receiving/delivering OUD care via different visit modalities. Clinicians' and patients' experiences were compared using a group analytical process. KEY RESULTS: Patients and clinicians valued having multiple modalities available for care, with flexibility identified as a key benefit. Patients highlighted the decreased burden of travel and less social anxiety with telehealth visits. Similarly, clinicians reported that telehealth decreased medical intrusion into the lives of patients stable in recovery. Patients and clinicians saw the value of in-person visits when establishing care and for patients needing additional support. In-person visits allowed the ability to conduct urine drug testing, and to foster relationships and trust building, which were more difficult, but not impossible via a telehealth visit. Patients preferred telephone over video visits, as these were more private and more convenient. Clinicians identified benefits of video, including being able to both hear and see the patient, but often deferred to patient preference. CONCLUSIONS: Considerations for utilization of visit modalities for OUD care were identified based on patients' needs and preferences, which often changed over the course of treatment. Continued research is needed determine how visit modalities impact patient outcomes.

Interrater Reliability of the Scale for the Assessment and Rating of Ataxia, Berg Balance Scale, and Functional Independence Measure Motor Domain in Individuals With Hereditary Cerebellar Ataxia.

OBJECTIVE: To determine the interrater reliability of the Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), and motor domain of the FIM (m-FIM) administered by physiotherapists in individuals with a hereditary cerebellar ataxia (HCA). DESIGN: Participants were assessed by 1 of 4 physiotherapists. Assessments were video-recorded and the remaining 3 physiotherapists scored the scales for each participant. Raters were blinded to each other's scores. SETTING: Assessments were administered at 3 clinical locations in separate states in Australia. PARTICIPANTS: Twenty-one individuals (mean age=47.63 years; SD=18.42; 13 male and 8 female) living in the community with an HCA were recruited (N=21). MAIN OUTCOME MEASURES: Total and single-item scores of the SARA, BBS, and m-FIM were examined. The m-FIM was conducted by interview. RESULTS: Intraclass coefficients (2,1) for the total scores of the m-FIM (0.92; 95% confidence interval [CI], 0.85-0.96), SARA (0.92; 95% CI, 0.86-0.96), and BBS (0.99; 95% CI, 0.98-0.99) indicated excellent interrater reliability. However, there was inconsistent agreement with the individual items, with SARA item 5 (right side) and item 7 (both sides) demonstrating poor interrater reliability and items 1 and 2 demonstrating excellent reliability. CONCLUSIONS: The m-FIM (by interview), SARA, and BBS have excellent interrater reliability for use when assessing individuals with an HCA. Physiotherapists could be considered for administration of the SARA in clinical trials. However, further work is required to improve the agreement of the single-item scores and to examine the other psychometric properties of these scales.

Use of Telehealth for Opioid Use Disorder Treatment in Safety Net Primary Care Settings: A Mixed-Methods Study.

Background: The COVID-19 pandemic resulted in a marked increase in telehealth for the provision of primary care-based opioid use disorder (OUD) treatment. This mixed methods study examines characteristics associated with having the majority of OUD-related visits via telehealth versus in-person, and changes in mode of delivery (in-person, telephone, video) over time. Methods: Logistic regression was performed using electronic health record data from patients with ≥1 visit with an OUD diagnosis to ≥1 of the two study clinics (Rural Health Clinic; urban Federally Qualified Health Center) and ≥1 OUD medication ordered from 3/8/2020-9/1/2021, with >50% of OUD visits via telehealth (vs. >50% in-person) as the dependent variable and patient characteristics as independent variables. Changes in visit type over time were also examined. Inductive coding was used to analyze data from interviews with clinical team members (n = 10) who provide OUD care to understand decision-making around visit type. Results: New patients (vs. returning; OR = 0.47;95%CI:0.27-0.83), those with ≥1 psychiatric diagnosis (vs. none; OR = 0.49,95%CI:0.29-0.82), and rural clinic patients (vs. urban; OR = 0.05; 95%CI:0.03-0.08) had lower odds of having the majority of visits via telehealth than in-person. Patterns of visit type varied over time by clinic, with the majority of telehealth visits delivered via telephone. Team members described flexibility for patients as a key telehealth benefit, but described in-person visits as more conducive to building rapport with new patients and those with increased psychological burden. Conclusion: Understanding how and why telehealth is used for OUD treatment is critical for ensuring access to care and informing OUD-related policy decisions.

A 13-Year-Old Girl With Unilateral Visual Changes.

Neuroretinitis is a condition typically characterized by unilateral optic neuropathy and is most commonly a sequelae of cat scratch disease (CSD) due to infection with Bartonella henselae. Ophthalmologic examination will reveal a swollen optic nerve and may eventually reveal a canonical macular star; optical coherence tomography (OCT) will reveal flattening of the fovea, a thickened neurosensory retina, and subretinal fluid accumulation. Although CSD rarely presents with isolated neuorretinitis, it should be considered in patients presenting with unilateral visual changes. The differential diagnosis for neuroretinitis includes optic neuritis, inflammatory optic neuropathies (sarcoid, para-infectious, autoimmune), compressive, toxic, and more. We describe a pediatric patient presenting with visual changes that were initially concerning for optic neuritis and the diagnostic workup that ultimately led to a diagnosis of CSD neuroretinitis.

Anaerobic conditions are a major influence on Candida albicans chlamydospore formation.

Candidiasis now represents the fourth most frequent nosocomial infection both in the USA and worldwide. Candida albicans is an increasingly common threat to human health as a consequence of AIDS, steroid therapy, organ and tissue transplantation, cancer therapy, broad-spectrum antibiotics, and other immune defects. Unfortunately, these infections carry unacceptably high morbidity, mortality rates and important economic repercussions (estimated total direct cost of approximately 2 billion dollars in 1998 in US hospitals alone). This pathogen can grow both in yeast and filamentous forms and the pathogenic potential of C. albicans is intimately related to certain key processes including filamentation. Chlamydospores are considered to be a dormant form of C. albicans that remain understudied. Chlamydospores have been widely used as a diagnostic tool to separate C. albicans and C. dubliniensis from other Candida species. More recently, media have been developed that use chlamydopsore formation to separate C. albicans and C. dubliniensis from each other. Chlamydospore formation can be stimulated by hypoxic conditions but only on limited specific media types. Here, we show that anaerobic conditions are enough to drive chlamydospore formation in C. albicans on the surface of nutrient-rich agar.

A Qualitative Study of Two Oregon Family Medicine Clinics to Explain Parent and Child Healthcare Initiation and Engagement.

Background: Parental factors are associated with children's receipt of recommended care but not adequately described. Methods: We conducted a qualitative study of patients with at least two visits who were a primary caregiver for a child who also had at least two visits at the same clinic in 1/2018-12/2019 from two Oregon family medicine clinics. We stratified patients by child age and number of caregiver visits and randomly selected caregivers. Participants were interviewed in accordance with approval by our Institutional Review Board between 12/2020 and 4/2021. The data were analyzed using a grounded theory approach. Results: 12 caregivers (termed parents) were interviewed; half were single parents and three-quarters had a history of substance use disorder and/or a mental health condition. Parents focused on the importance of keeping themselves healthy to keep their families healthy. They described similar reasons for choosing to initiate and continue care for themselves and their children at the same clinic, including: convenience, trust, relationships, and receiving whole-person and whole-family care. Many valued having a healthcare "home" for their entire family. We developed a figure that highlights three themes that capture the interrelated factors parents identified as supporting healthcare use for themselves and their families. These overarching themes included: healthcare initiation; healthcare engagement and continuity; and parent bringing child to the same clinic for healthcare. Conclusion: Our data suggests that long-standing patient-clinic relationships for parents and children can support family-focused healthcare.

Balance on the Brain: a randomised controlled trial evaluating the effect of a multimodal exercise programme on physical performance, falls, quality of life and cognition for people with mild cognitive impairment-study protocol.

INTRODUCTION: Exercise and physical activity have been shown to improve cognition for people living with mild cognitive impairment (MCI). There is strong evidence for the benefits of aerobic exercise and medium evidence for participating in regular strength training for people with MCI. However, people living with MCI fall two times as often as those without cognitive impairment and the evidence is currently unknown as to whether balance training for people with MCI is beneficial, as has been demonstrated for older people without cognitive impairment. The aim of this study is to determine whether a balance-focused multimodal exercise intervention improves balance and reduces falls for people with MCI, compared with a control group receiving usual care. METHODS AND ANALYSIS: This single blind randomised controlled trial (Balance on the Brain) will be offered to 396 people with MCI living in the community. The multimodal exercise intervention consists of two balance programmes and a walking programme to be delivered by physiotherapists over a 6-month intervention period. All participants will be followed up over 12 months (for the intervention group, this involves 6-month intervention and 6-month maintenance). The primary outcomes are (1) balance performance and (2) rate of falls. Physical performance, levels of physical activity and sedentary behaviour, quality of life and cognition are secondary outcomes. A health economic analysis will be undertaken to evaluate the cost-effectiveness of the intervention compared with usual care. ETHICS AND DISSEMINATION: Ethics approval has been received from the South Metropolitan Health Service Human Research Ethics Committee (HREC), Curtin University HREC and the Western Australia Department of Health HREC; and approval has been received to obtain data for health costings from Services Australia. The results will be disseminated through peer-review publications, conference presentations and online platforms. TRIAL REGISTRATION NUMBER: ACTRN12620001037998; Australian New Zealand Clinical Trials Registry (ANZCTR).

Understanding the influence of health systems on women's experiences of Option B+: A meta-ethnography of qualitative research from sub-Saharan Africa.

We explored women's experiences of Option B+ in sub-Saharan African health facility settings through a meta-ethnography of 32 qualitative studies published between 2010 and 2019. First and second-order constructs were identified from the data and authors' interpretations respectively. Using a health systems lens, third-order constructs explored how the health systems shaped women's experiences of Option B+ and their subsequent engagement in care. Women's experiences of Option B+ services were influenced by their interactions with health workers, which were often reported to be inadequate and rushed, reflecting insufficient staffing or training to address pregnant women's needs. Women's experiences were also undermined by various manifestations of stigma which persisted in the absence of resources for social or mental health support, and were exacerbated by space constraints in health facilities that infringed on patient confidentiality. Sub-optimal service accessibility, drug stock-outs and inadequate tracing systems also shaped women's experiences of care. Strengthening health systems by improving health worker capacity to provide respectful and high-quality clinical and support services, improving supply chains and improving the privacy of consultation spaces would improve women's experiences of Option B+ services, thereby contributing to improved care retention. These lessons should be considered as universal test and treat programmes expand.

Rehabilitation for ataxia study: protocol for a randomised controlled trial of an outpatient and supported home-based physiotherapy programme for people with hereditary cerebellar ataxia.

INTRODUCTION: Emerging evidence indicates that rehabilitation can improve ataxia, mobility and independence in everyday activities in individuals with hereditary cerebellar ataxia. However, with the rarity of the genetic ataxias and known recruitment challenges in rehabilitation trials, most studies have been underpowered, non-randomised or non-controlled. This study will be the first, appropriately powered randomised controlled trial to examine the efficacy of an outpatient and home-based rehabilitation programme on improving motor function for individuals with hereditary cerebellar ataxia. METHODS AND ANALYSIS: This randomised, single-blind, parallel group trial will compare a 30-week rehabilitation programme to standard care in individuals with hereditary cerebellar ataxia. Eighty individuals with a hereditary cerebellar ataxia, aged 15 years and above, will be recruited. The rehabilitation programme will include 6 weeks of outpatient land and aquatic physiotherapy followed immediately by a 24- week home exercise programme supported with fortnightly physiotherapy sessions. Participants in the standard care group will be asked to continue their usual physical activity. The primary outcome will be the motor domain of the Functional Independence Measure. Secondary outcomes will measure the motor impairment related to ataxia, balance, quality of life and cost-effectiveness. Outcomes will be administered at baseline, 7 weeks, 18 weeks and 30 weeks by a physiotherapist blinded to group allocation. A repeated measures mixed-effects linear regression model will be used to analyse the effect of the treatment group for each of the dependent continuous variables. The primary efficacy analysis will follow the intention-to-treat principle. ETHICS AND DISSEMINATION: The study has been approved by the Monash Health Human Research Ethics Committee (HREC/18/MonH/418) and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (2019/3503). Results will be published in peer-reviewed journals, presented at national and/or international conferences and disseminated to Australian ataxia support groups. TRIAL REGISTRATION NUMBER: ACTRN12618000908235.

Epidemiological investigation of a typhoid fever outbreak in Sekhukhune District, Limpopo province, South Africa - 2017.

BACKGROUND: Typhoid fever remains a public health concern in South Africa, where the risk of transmission is high because of poor access to safe water and sanitation. This study describes the investigation of typhoid fever outbreak in Limpopo province. METHODOLOGY: Following notification of laboratory-confirmed cases, a descriptive study was conducted at Sekhukhune District, Limpopo province. A suspected case was defined as any person residing in Makhuduthamaga Municipality from November 2017 to January 2018, presenting with fever and gastrointestinal symptoms. Data were collected using case investigation forms. Whole-genome sequencing (WGS) was carried out on Salmonella Typhi isolates and polymerase chain reaction (PCR) test was done for Salmonella species from water samples. Location of cases and water sources were mapped using ArcGIS mapping tool. RESULTS: Amongst 122 cases, 54% (n = 66) were female and 6% (n = 7) laboratory-confirmed. The median age of the cases was 11 years (range 2-83 years), with 79% (n = 102) being children under the age of 14 years. Salmonella species were detected in 37% (10/27) of water samples and geographic information system (GIS) mapping showed clustering of cases in Tswaing-Kgwaripe and Vlakplaas villages. Six isolates were available for WGS analysis, with resulting data showing that five of the six isolates were genetically related. Phylogenetic analysis showed that the five isolates clustered together were genetically related showing < 22 single nucleotide polymorphisms when compared to each other. CONCLUSION: Molecular epidemiology of isolates suggests a common source outbreak, supported by the detection of Salmonella species from water sources. Consumption of water from contaminated open water sources, because of ongoing interruption of municipal water supply, was the likely cause of the outbreak. The investigation highlights the importance of consistent safe water supply and the ability of district surveillance systems to identify and contain outbreaks.

Health Empowers You: Impact of a School-Based Physical Activity Program in Elementary School Students, Georgia, 2015-2016.

BACKGROUND: Most youth in the United States do not meet the recommended 60 minutes of daily physical activity (PA). The school environment offers an opportunity to engage students in PA. The purpose of this study was to evaluate the impact of a comprehensive school-based physical activity program on student PA across student-level and school-level characteristics. METHODS: PA levels from 3294 fourth grade students in 24 intervention schools and 7 control schools in metropolitan Atlanta, Georgia were measured during the 2015-2016 academic year. PA measures included daily steps in school, steps taken in physical education class (PE), and percent of PE class time spent in moderate-to-vigorous physical activity (MVPA). Intervention effectiveness was assessed using generalized estimating equations adjusting for sex and school-level socioeconomic status (SES). RESULTS: After adjusting for sex and school-level SES, intervention students had significantly higher increases in average daily steps (p < .05), steps taken in PE (p < .01), and percent of PE class spent in MVPA (p < .01) than control students. CONCLUSIONS: Our findings demonstrate the effectiveness of CSPAPs in increasing PA. Further research using randomized controlled trials of large-scale implementations, longer follow-up periods, and more diverse student sample is warranted.

Availability of pharmacist prescription of contraception in rural areas of Oregon and New Mexico.

OBJECTIVE: To determine the availability of pharmacist prescribing of hormonal contraception in rural areas of two states. STUDY DESIGN: Cross-sectional survey. RESULTS: Overall, 42% of pharmacies prescribed contraception (Oregon: 46% and New Mexico 19%). A similar proportion of rural pharmacies reported offering pharmacist prescription of 37 contraception as urban locations (39% vs 46%, p = 0.26). Nearly 53% of rural and 45% of urban pharmacies report billing women, rather than insurance, directly for the cost of the pharmacist consultation. Over 80% of pharmacists in both rural and urban locations did not know if Medicaid covered the cost. CONCLUSION: Pharmacists in rural areas are as willing as their urban counterparts to prescribe hormonal contraception. Financial barriers remain a concern.

Ulipristal acetate compared to levonorgestrel emergency contraception among current oral contraceptive users: a cost-effectiveness analysis.

OBJECTIVE: To estimate the cost-effectiveness of ulipristal acetate (UPA) and levonorgestrel (LNG) emergency contraception (EC) on pregnancy prevention among combined oral contraceptive (COC) pill users with an extended pill-free interval. We accounted for the potential interaction of COCs and obesity on EC efficacy. METHODS: We built a decision-analytic model using TreeAge software to evaluate the optimal oral EC strategy in a hypothetical cohort of 100,000 twenty-five-year-old women midcycle with a prolonged "missed" pill episode (8-14 days). We used a 5-year time horizon and 3% discount rate. From a healthcare perspective, we obtained probabilities, utilities and costs inflated to 2018 dollars from the literature. We set the threshold for cost-effectiveness at a standard $100,000 per quality-adjusted life-year. We included the following clinical outcomes: number of protected cycles, unintended pregnancies, abortions, deliveries and costs. RESULTS: We found that UPA was the optimal method of oral EC, as it resulted in 720 fewer unintended pregnancies, 736 fewer abortions and 80 fewer deliveries at a total cost savings of $50,323 and 79 additional adjusted life-years. UPA continued to be the optimal strategy even in the case of obesity or COCs impacting UPA efficacy, in which a COC interaction would have to change efficacy of UPA by 160% before LNG was the dominant strategy. CONCLUSION: Our models found that UPA was the dominant choice of oral EC among COC users with a prolonged "missed" pill episode, regardless of body mass index or an adverse interaction of COCs on UPA. IMPLICATIONS: Ulipristal acetate is the dominant choice of oral emergency contraception among combined oral contraceptive users.

Bridging Public Health and Education: Results of a School-Based Physical Activity Program to Increase Student Fitness.

OBJECTIVE: Power Up for 30 (PU30) is a schoolwide intervention that encourages schools to provide an additional 30 minutes of physical activity during the school day, beyond physical education. The objective of this study was to evaluate the impact of PU30 on Georgia public elementary schools and their students. METHODS: A total of 719 of 1320 public elementary schools in Georgia that were sent a baseline survey about school physical activity during October 2013 to September 2014 completed the survey, 160 of which were asked to complete a second survey. In the interim (March to June 2015), half (80) of these schools implemented the PU30 program. The interim surveys, which were completed during March to June 2015, assessed opportunities for student physical activity and staff member professional development focused on student physical activity. RESULTS: Compared with schools that had not implemented the program, more schools using the PU30 program reported offering before- and after-school physical activity programs. Forty-four of 78 (57%) PU30 schools compared with 20 of 53 (38%) non-PU30 schools offered before-school physical activity programs. Likewise, more PU30 schools than non-PU30 schools offered after-school physical activity programs (35% vs 16%), and a greater proportion of students at PU30 schools compared with non-PU30 schools met fitness benchmarks: recess 5 days per week (91% [288 of 323] vs 80% [273 of 341]), offering ≥11 minutes per day of classroom-based physical activity (39% [53 of 136] vs 25% [47 of 189] for kindergarten through second grade; 20% [37 of 187] vs 6% [9 of 152] for grades 3 through 5), and receiving physical activity-related professional development time (42% [136 of 323] vs 14% [48 of 341]). CONCLUSIONS: The surveys provided a statewide picture of the physical activity opportunities offered to students and staff members in Georgia elementary schools and demonstrated the effective use of a comprehensive, multicomponent program to offer more school-based physical activity opportunities and to improve student fitness.

Scaling a waterfall: a meta-ethnography of adolescent progression through the stages of HIV care in sub-Saharan Africa.

INTRODUCTION: Observational studies have shown considerable attrition among adolescents living with HIV across the "cascade" of HIV care in sub-Saharan Africa, leading to higher mortality rates compared to HIV-infected adults or children. We synthesized evidence from qualitative studies on factors that promote or undermine engagement with HIV services among adolescents living with HIV in sub-Saharan Africa. METHODS: We systematically searched five databases for studies published between 2005 and 2016 that met pre-defined inclusion criteria. We used a meta-ethnographic approach to identify first, second and third order constructs from eligible studies, and applied a socio-ecological framework to situate our results across different levels of influence, and in relation to each stage of the HIV cascade. RESULTS AND DISCUSSION: We identified 3089 citations, of which 24 articles were eligible for inclusion. Of these, 17 were from Southern Africa while 11 were from Eastern Africa. 6 explored issues related to HIV testing, 11 explored treatment adherence, and 7 covered multiple stages of the cascade. Twelve third-order constructs emerged to explain adolescents' engagement in HIV care. Stigma was the most salient factor impeding adolescents' interactions with HIV care over the past decade. Self-efficacy to adapt to life with HIV and support from family or social networks were critical enablers supporting uptake and retention in HIV care and treatment programmes. Provision of adolescent-friendly services and health systems issues, such as the availability of efficient, confidential and comfortable services, were also reported to drive sustained care engagement. Individual-level factors, including past illness experiences, identifying mechanisms to manage pill-taking in social situations, financial (in)stability and the presence/absence of future aspirations also shaped adolescents HIV care engagement. CONCLUSIONS: Adolescents' initial and ongoing use of HIV care was frequently undermined by individual-level issues; although family, community and health systems factors played important roles. Interventions should prioritise addressing psychosocial issues among adolescents to promote individual-level engagement with HIV care, and ultimately reduce mortality. Further research should explore issues relating to care linkage and ART initiation in different settings, particularly as "test and treat" policies are scaled up.