Buprenorphine & methadone dosing strategies to reduce risk of relapse in the treatment of opioid use disorder.

BACKGROUND: Although there is consensus that having a "high-enough" dose of buprenorphine (BUP-NX) or methadone is important for reducing relapse to opioid use, there is debate about what this dose is and how it should be attained. We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone. METHODS: This was a secondary analysis of three comparative effectiveness trials. We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the "hybrid strategy"), and 4) keeping dose constant after the first 2 weeks of treatment. We used a longitudinal sequentially doubly robust estimator to estimate contrasts between dosing strategies on risk of relapse. RESULTS: For BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse. For methadone, holding dose constant resulted in greatest risk of relapse; the other three strategies performed similarly. For example, the hybrid strategy reduced week 12 relapse risk by 13 % (RR: 0.87, 95 %CI: 0.83-0.95) and by 20 % (RR: 0.80, 95 %CI: 0.71-0.90) for BUP-NX and methadone respectively, as compared to holding dose constant. CONCLUSIONS: Doses should be targeted toward minimum thresholds and, in the case of BUP-NX, raised when patients continue to use opioids.

"What will we do if we get infected?": An interview-based study of the COVID-19 pandemic and its effects on the health and safety of sex workers in the United States.

Emerging evidence suggests that sex workers face unique and profound risks arising from the COVID-19 pandemic. To illuminate the pandemic's effects on sex worker health and safety and identify intervention opportunities, from May-August 2020 in-depth interviews were conducted with a purposive sample of 15 sex workers, four service providers and two individuals who were both. Sampled sex workers included eight people of color, eight cisgender women, five cisgender men, three non-binary people, and one transgender woman. Using Conservation of Resources Theory to define impacts on sex worker resources and resulting health and safety implications, a deductive thematic analysis was conducted. Seven resources were threatened due to the pandemic: work opportunity, sex work venues, social support, health services, money, food, and housing. The loss of these resources was exacerbated by stigma - notably sex work criminalization - and significantly undermined health and safety by increasing food and housing instability, increasing risks of violence, and diminishing safer sex negotiation. Six resources were activated in response: social support, digital skills, health knowledge, non-sex work employment, money, and resilience. While social support had numerous benefits, investing digital skills and non-sex work employment were generally of limited impact. The pandemic's negative health and safety effects were most profound at the intersections of race, gender, class, and migration status. These findings suggest sex workers need urgent and ongoing support, with investments in social support and sex work decriminalization likely to have the greatest effects on health and safety relative to and beyond the COVID-19 pandemic.

An Integrated Primary Care Initiative for Child Health in Northern Togo.

OBJECTIVES: To determine if the Integrated Community-Based Health Systems-Strengthening (ICBHSS) initiative was effective in expanding health coverage, improving care quality, and reducing child mortality in Togo. METHODS: Population-representative cross-sectional household surveys adapted from the Demographic Household Survey and Multiple Indicator Cluster Surveys were conducted at baseline (2015) and then annually (2016-2020) in 4 ICBHSS catchment sites in Kara, Togo. The primary outcome was under-5 mortality, with health service coverage and health-seeking behavior as secondary outcomes. Costing analyses were calculated by using "top-down" methodology with audited financial statements and programmatic data. RESULTS: There were 10 022 household surveys completed from 2015 to 2020. At baseline (2015), under-5 mortality was 51.1 per 1000 live births (95% confidence interval [CI]: 35.5-66.8), and at the study end period (2020), under-5 mortality was 35.8 (95% CI: 23.4-48.2). From 2015 to 2020, home-based treatment by a community health worker increased from 24.1% (95% CI: 21.9%-26.4%) to 45.7% (95% CI: 43.3%-48.2%), and respondents reporting prenatal care in the first trimester likewise increased (37.5% to 50.1%). Among respondents who sought care for a child with fever, presenting for care within 1 day increased from 51.9% (95% CI: 47.1%-56.6%) in 2015 to 80.3% (95% CI: 74.6%-85.0%) in 2020. The estimated annual additional intervention cost was $8.84 per person. CONCLUSIONS: Our findings suggest that the ICBHSS initiative, a bundle of evidence-based interventions implemented with a community-based strategy, improves care access and quality and was associated with reduction in child mortality.

Persistent repression of tau in the brain using engineered zinc finger protein transcription factors.

Neuronal tau reduction confers resilience against ß-amyloid and tau-related neurotoxicity in vitro and in vivo. Here, we introduce a novel translational approach to lower expression of the tau gene MAPT at the transcriptional level using gene-silencing zinc finger protein transcription factors (ZFP-TFs). Following a single administration of adeno-associated virus (AAV), either locally into the hippocampus or intravenously to enable whole-brain transduction, we selectively reduced tau messenger RNA and protein by 50 to 80% out to 11 months, the longest time point studied. Sustained tau lowering was achieved without detectable off-target effects, overt histopathological changes, or molecular alterations. Tau reduction with AAV ZFP-TFs was able to rescue neuronal damage around amyloid plaques in a mouse model of Alzheimer's disease (APP/PS1 line). The highly specific, durable, and controlled knockdown of endogenous tau makes AAV-delivered ZFP-TFs a promising approach for the treatment of tau-related human brain diseases.

COVID-19 testing, case, and death rates and spatial socio-demographics in New York City: An ecological analysis as of June 2020.

We assessed the geographic variation in socio-demographics, mobility, and built environmental factors in relation to COVID-19 testing, case, and death rates in New York City (NYC). COVID-19 rates (as of June 10, 2020), relevant socio-demographic information, and built environment characteristics were aggregated by ZIP Code Tabulation Area (ZCTA). Spatially adjusted multivariable regression models were fitted to account for spatial autocorrelation. The results show that different sets of neighborhood characteristics were independently associated with COVID-19 testing, case, and death rates. For example, the proportions of Blacks and Hispanics in a ZCTA were positively associated with COVID-19 case rate. Contrary to the conventional hypothesis, neighborhoods with low-density housing experienced higher COVID-19 case rates. In addition, demographic changes (e.g. out-migration) during the pandemic may bias the estimates of COVID-19 rates. Future research should further investigate these neighborhood-level factors and their interactions over time to better understand the mechanisms by which they affect COVID-19.

Sex workers are returning to work and require enhanced support in the face of COVID-19: results from a longitudinal analysis of online sex work activity and a content analysis of safer sex work guidelines.

Sex workers confront unique challenges in the face of COVID-19. Data from an international sex work website popular with cisgender men and transgender men and women suggest that, after a period of physical distancing, many sex workers are returning to in-person work: from May to August 2020, active sex work profiles increased 9.4% (P < 0.001) and newly created profiles increased by 35.6% (P < 0.001). Analysis of sex work and COVID-19 guidelines published by five community-based organisations found that they focused on altering sexual practices, enhancing hygiene and pivoting to virtual work. To capitalise on these guidelines, funding and research for implementation and evaluation are needed to support COVID-19 risk reduction strategies for sex workers.

Identifying inequities in maternal and child health through risk stratification to inform health systems strengthening in Northern Togo.

OBJECTIVE: In Togo, substantial progress in maternal and child health is needed to reach global development goals. To better inform clinic and community-based health services, this study identifies factors associated with maternal and child health care utilization in the Kara region of Northern Togo. METHODS: We conducted a population-representative household survey of four health clinic catchment areas of 1,075 women of reproductive age in 2015. Multivariable logistic regression was used to model individual and structural factors associated with utilization of four maternal and child health services. Key outcomes were: facility-based delivery, maternal postnatal health check by a health professional within the first six weeks of birth, childhood vaccination, and receipt of malaria medication for febrile children under age five within 72 hours of symptom onset. RESULTS: 83 percent of women who gave birth in the last 2 years delivered at a health facility. In adjusted models, the strongest predictor of facility delivery in the rural catchment areas was proximity to a health center, with women living under three kilometers having 3.7 (95% CI 1.7, 7.9) times the odds of a facility birth. Only 11 percent of women received a health check by a health provider at any time in the postnatal period. Postnatal health checks were less likely for women in the poorest households and for women who resided in rural areas. Children of polygamous mothers had half the odds of receiving malaria medication for fever within 72 hours of symptom onset, while children with increased household wealth status had increased odds of childhood vaccination and receiving treatment for malaria. CONCLUSION: Our analysis highlights the importance of risk stratification analysis to inform the delivery and scope of maternal and child health programs needed to reach those with the least access to care.