What we learned in the development of a third-year medical student curricular project.

The application of continuous systems improvement in medical education can provide actionable information for curriculum development, improvement, and future planning (as reported by Bowe and Armstrong, Acad Med 92:585-92, 2017). After receiving a medical education grant, we developed a curriculum to teach medical students how to use quality improvement (QI) to address health disparities in vulnerable populations. During the process of developing and implementing this curriculum, we learned several lessons.One of the major surprises was that our proposed project work took much longer to complete than anticipated. This was mainly because we did not have the right team assembled from the beginning. Specifically, we were missing a team member with evaluation expertise, and therefore we did not devise a systematic process for evaluation and assessment. Without periodic checks or timely assessments built into our curriculum design, we received feedback from students after it was too late to implement changes. We realized that our initial research design had some methodological flaws, which we later rectified.We encountered additional technical challenges during the curriculum implementation. We struggled with various online learning platforms. Through this, we learned the importance of being knowledgeable upfront about the features of learning platforms and adaptable to changing educational technologies. We also learned our curriculum could and should evolve to meet the needs of our learners and faculty. Moving forward, we realize the benefit of applying a quality improvement process to our curriculum development and implementation, which will help us to continuously transform medical education for future health care needs

Proximity soundings of thundersnow in the central United States

[1] Proximity balloon soundings for snow events with lightning and thunder during the period 1961 through 1990 reveal a less statically stable environment than similar nonthundering snow events. When thundersnow is present, a less stable environment (and in some cases subsequent upright convection) is found aloft in all of the thundering cases examined here; all of the events feature their most unstable parcel originating above a frontal inversion. In fact, only events in the cold air north of an extratropical cyclone are included in this study. Events with a lake effect or orographic enhancement are eliminated from the sample. The basic composite derived by averaging temperatures at an established interval reveals a nearly saturated lower atmosphere, below 0°C throughout its depth, with the frontal inversion present and its most unstable parcel occurring just above the top of the inversion. The feature-preserving composite approach of R

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Third-Year Medical Students' Self-perceived Knowledge About Health Disparities and Community Medicine.

IntroductionMedical providers' attitudes about caring for vulnerable populations have significant implications for persistent health disparities. Therefore, assessing medical students' self-perceived knowledge about community-based medicine and care for underserved populations can provide insights for improving health care delivery to achieve health equity. We evaluated third-year medical students' perceptions of their knowledge and attitudes about community medicine, and addressing health care needs of vulnerable populations.MethodsFrom October 2, 2017 to July 12, 2019, third-year medical students at a private, urban medical school were asked to complete an assessment survey during their family medicine clerkship orientation. The anonymous survey assessed students' self-perceived knowledge and attitudes regarding community medicine and care of vulnerable populations. We examined differences in survey responses by student demographics.ResultsA total of 401 students participated in the survey; 50.5% of respondents agreed that they had knowledge to assess health literacy of the patient, while only 22.2% of students agreed that they had knowledge about how to identify a community and conduct a community health needs assessment. Additionally, students agreed with being most comfortable providing care to adolescents (73.0%) and the elderly (69.5%), and that they were least comfortable caring for incarcerated individuals (31.7%) and immigrants/refugees (44.1%).ConclusionAssessment of learners' self-perceived knowledge can help highlight areas for educational interventions. Our findings suggest the need for improving medical student knowledge in areas of community health and health care for specific vulnerable populations