Assessment of epidemiological and genetic characteristics and clinical outcomes of resistance to bedaquiline in patients treated for rifampicin-resistant tuberculosis: a cross-sectional and longitudinal study.

BACKGROUND: Bedaquiline improves outcomes of patients with rifampicin-resistant and multidrug-resistant (MDR) tuberculosis; however, emerging resistance threatens this success. We did a cross-sectional and longitudinal analysis evaluating the epidemiology, genetic basis, and treatment outcomes associated with bedaquiline resistance, using data from South Africa (2015-19). METHODS: Patients with drug-resistant tuberculosis starting bedaquiline-based treatment had surveillance samples submitted at baseline, month 2, and month 6, along with demographic information. Culture-positive baseline and post-baseline isolates had phenotypic resistance determined. Eligible patients were aged 12 years or older with a positive culture sample at baseline or, if the sample was invalid or negative, a sample within 30 days of the baseline sample submitted for bedaquiline drug susceptibility testing. For the longitudinal study, the first surveillance sample had to be phenotypically susceptible to bedaquiline for inclusion. Whole-genome sequencing was done on bedaquiline-resistant isolates and a subset of bedaquiline-susceptible isolates. The National Institute for Communicable Diseases tuberculosis reference laboratory, and national tuberculosis surveillance databases were matched to the Electronic Drug-Resistant Tuberculosis Register. We assessed baseline resistance prevalence, mutations, transmission, cumulative resistance incidence, and odds ratios (ORs) associating risk factors for resistance with patient outcomes. FINDINGS: Between Jan 1, 2015, and July 31, 2019, 8041 patients had surveillance samples submitted, of whom 2023 were included in the cross-sectional analysis and 695 in the longitudinal analysis. Baseline bedaquiline resistance prevalence was 3·8% (76 of 2023 patients; 95% CI 2·9-4·6), and it was associated with previous exposure to bedaquiline or clofazimine (OR 7·1, 95% CI 2·3-21·9) and with rifampicin-resistant or MDR tuberculosis with additional resistance to either fluoroquinolones or injectable drugs (pre-extensively-drug resistant [XDR] tuberculosis: 4·2, 1·7-10·5) or to both (XDR tuberculosis: 4·8, 2·0-11·7). Rv0678 mutations were the sole genetic basis of phenotypic resistance. Baseline resistance could be attributed to previous bedaquiline or clofazimine exposure in four (5·3%) of 76 patients and to primary transmission in six (7·9%). Odds of successful treatment outcomes were lower in patients with baseline bedaquiline resistance (0·5, 0·3-1). Resistance during treatment developed in 16 (2·3%) of 695 patients, at a median of 90 days (IQR 62-195), with 12 of these 16 having pre-XDR or XDR. INTERPRETATION: Bedaquiline resistance was associated with poorer treatment outcomes. Rapid assessment of bedaquiline resistance, especially when patients were previously exposed to bedaquiline or clofazimine, should be prioritised at baseline or if patients remain culture-positive after 2 months of treatment. Preventing resistance by use of novel combination therapies, current treatment optimisation, and patient support is essential. FUNDING: National Institute for Communicable Diseases of South Africa.

Implementing and Adapting the SAFETY Treatment for Suicidal Youth: The Incubator Model, Telehealth, and the Covid-19 Pandemic

The Safe Alternatives for Teens and Youth (SAFETY) treatment was developed to decrease the risk of repeat suicidal and self-harm behavior in youth presenting with elevated suicide risk. This paper uses case illustrations to demonstrate the SAFETY treatment, building upon the companion paper describing our “incubator” treatment development model and process (Asarnow et al., 2021). As illustrated in the second case illustration, the incubator model approach was particularly useful during the COVID-19 pandemic switch to telehealth. SAFETY specifically targets suicide and self-harm risk reduction using an individually tailored principle-guided approach, grounded in a case conceptualization that identifies cognitive-behavioral processes and reactions that contribute to increased suicide attempt risk and explains the youth’s suicidal/self-harm behavior within the context of his or her broader social systems. The SAFETY treatment has been tested in two treatment development trials, and results support the efficacy of SAFETY for preventing suicide attempts in adolescents presenting with recent self-harm.

Impact of the COVID-19 pandemic on adults with current and prior depression: initial findings from the longitudinal Texas RAD study.

BACKGROUND: Emerging work has suggested worsening mental health in the general population during the COVID-19 pandemic, but there is minimal data on individuals with a prior history of depression. METHODS: Data regarding depression, anxiety and quality of life in adult participants with a history of a depressive disorder (n = 308) were collected before and during the COVID-19 pandemic. Mixed effects regression models were fit for these outcomes over the period May - August 2020, controlling for pre-pandemic depressive groups (none, mild, moderate-to-severe), demographic characteristics, and early COVID-19 related experiences (such as disruptions in routines, mental health treatment, and social supports). RESULTS: In pre-to-early pandemic comparisons, the 3 pre-pandemic depressive categories varied significantly in anxiety (Fdf=2,197 = 7.93, p < 0.0005) and psychological QOL (Fdf=2,196 = 8.57, p = 0.0003). The mildly depressed group (Fdf=1,201 = 6.01, p = 0.02) and moderate-to-severely depressed group (Fdf=1,201 = 38.51, p < 0.0001) had a significant reduction in anxiety. There were no changes among the groups in any outcome from May to August 2020. However, early impact on mental health care access and disruption in routines predicted worse outcomes during this time. LIMITATIONS: Follow-up data were self-reported. Furthermore, the duration was a relatively short span into the pandemic. CONCLUSIONS: Symptoms of depression, anxiety, and quality of life were generally stable from 2019 throughout August 2020 in adults with a history of depression. Disruption in mental health care access and routines in May 2020 predicted worse symptom outcomes through August 2020.