Population Effectiveness of Dolutegravir Implementation in Uganda: A Prospective Observational Cohort Study (DISCO), 48-Week Results.

BACKGROUND: Tenofovir/lamivudine/dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen for people with HIV (PWH), including those who were previously virologically suppressed on nonnucleoside reverse transcriptase inhibitors (NNRTIs). We sought to estimate the real-world effectiveness of the TLD transition in Ugandan public-sector clinics. METHODS: We conducted a prospective cohort study of PWH aged ≥18 years who were transitioned from NNRTI-based ART to TLD. Study visits were conducted on the day of TLD transition and 24 and 48 weeks later. The primary end point was viral suppression (<200 copies/mL) at 48 weeks. We collected blood for retrospective viral load (VL) assessment and conducted genotypic resistance tests for specimens with VL >500 copies/mL. RESULTS: We enrolled 500 participants (median age 47 years; 41% women). At 48 weeks after TLD transition, 94% of participants were in care with a VL <200 copies/mL (n = 469/500); 2% (n = 11/500) were lost from care or died; and only 2% (n = 9/500) had a VL >500 copies/mL. No incident resistance to DTG was identified. Few participants (2%, n = 9/500) discontinued TLD due to adverse events. CONCLUSIONS: High rates of viral suppression, high tolerability, and lack of emergent drug resistance support use of TLD as the preferred first-line regimen in the region. CLINICAL TRIALS REGISTRATION: NCT04066036.

Diabetes risk and provision of diabetes prevention activities in 44 low-income and middle-income countries: a cross-sectional analysis of nationally representative, individual-level survey data.

BACKGROUND: The global burden of diabetes is rising rapidly, yet there is little evidence on individual-level diabetes prevention activities undertaken by health systems in low-income and middle-income countries (LMICs). Here we describe the population at high risk of developing diabetes, estimate diabetes prevention activities, and explore sociodemographic variation in these activities across LMICs. METHODS: We performed a pooled, cross-sectional analysis of individual-level data from nationally representative, population-based surveys conducted in 44 LMICs between October, 2009, and May, 2019. Our sample included all participants older than 25 years who did not have diabetes and were not pregnant. We defined the population at high risk of diabetes on the basis of either the presence of impaired fasting glucose (or prediabetes in countries with a haemoglobin A1c available) or overweight or obesity, consistent with the WHO Package of Essential Noncommunicable Disease Guidelines for type 2 diabetes management. We estimated the proportion of survey participants that were at high risk of developing diabetes based on this definition. We also estimated the proportion of the population at high risk that reported each of four fundamental diabetes prevention activities: physical activity counselling, weight loss counselling, dietary counselling, and blood glucose screening, overall and stratified by World Bank income group. Finally, we used multivariable Poisson regression models to evaluate associations between sociodemographic characteristics and these activities. FINDINGS: The final pooled sample included 145 739 adults (86 269 [59·2%] of whom were female and 59 468 [40·4%] of whom were male) across 44 LMICs, of whom 59 308 (40·6% [95% CI 38·5-42·8]) were considered at high risk of diabetes (20·6% [19·8-21·5] in low-income countries, 38·0% [37·2-38·9] in lower-middle-income countries, and 57·5% [54·3-60·6] in upper-middle-income countries). Overall, the reach of diabetes prevention activities was low at 40·0% (38·6-41·4) for physical activity counselling, 37·1% (35·9-38·4) for weight loss counselling, 42·7% (41·6-43·7) for dietary counselling, and 37·1% (34·7-39·6) for blood glucose screening. Diabetes prevention varied widely by national-level wealth: 68·1% (64·6-71·4) of people at high risk of diabetes in low-income countries reported none of these activities, whereas 49·0% (47·4-50·7) at high risk in upper-middle-income countries reported at least three activities. Educational attainment was associated with diabetes prevention, with estimated increases in the predicted probability of receipt ranging between 6·5 (3·6-9·4) percentage points for dietary fruit and vegetable counselling and 21·3 (19·5-23·2) percentage points for blood glucose screening, among people with some secondary schooling compared with people with no formal education. INTERPRETATION: A large proportion of individuals across LMICs are at high risk of diabetes but less than half reported receiving fundamental prevention activities overall, with the lowest receipt of these activities among people in low-income countries and with no formal education. These findings offer foundational evidence to inform future global targets for diabetes prevention and to strengthen policies and programmes to prevent continued increases in diabetes worldwide. FUNDING: Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program and the EU's Research and Innovation programme Horizon 2020.

Do Patients With Multiple Myeloma Enrolled in Clinical Trials Live Longer?

OBJECTIVES: Enrollment in clinical trials is thought to improve survival outcomes through the trial effect. In this retrospective observational cohort study, we aimed to discern differences in survival outcomes by clinical trial enrollment and race-ethnicity. MATERIALS AND METHODS: Of 1285 patients receiving care for multiple myeloma at an National Cancer Institute designated cancer center from 2012 to 2018, 1065 (83%) were nontrial and 220 (17%) were trial participants. Time to event analyses were used to adjust for baseline characteristics and account for clinical trial enrollment as a time-varying covariate. We analyzed propensity-matched cohorts of trial and nontrial patients to reduce potential bias in observational data. RESULTS: Trial patients were younger (mean age in years: 60 vs. 63; P<0.001), underwent more lines of therapy (treatment lines ≥6: 39% vs. 17%; P<0.001), and had more comorbidities than nontrial patients. After controlling for baseline characteristics and clinical trial enrollment as a time-varying covariate, no significant difference in survival was found between trial and nontrial participants (hazard ratio [HR]=1.34, 95% confidence intervals [CIs]: 0.90-1.99), or between propensity-matched trial and nontrial participants (205 patients in each cohort, HR=1.36, 95% CIs: 0.83-2.23). Subgroup analyses by lines of therapy confirmed results from overall analyses. We did not observe survival differences by race-ethnicity (Logrank P=0.09), though hazard of death was significantly increased for nontrial Black/Hispanic patients compared with trial White patients (HR=1.76, 95% CIs=1.01-3.08). CONCLUSIONS: This study did not find evidence of a significant survival benefit to trial enrollment among patients with multiple myeloma. Patients enrolled in clinical trials underwent more lines of therapy, suggesting they may have had more treatment-resistant cancers. A small survival benefit in this cohort may be obscured by the lack of difference in survival between trial and nontrial patients.