Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study.

BACKGROUND & AIMS: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. METHODS: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). RESULTS: The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups. CONCLUSIONS: Guselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. CLINICALTRIALS: gov number: NCT04033445.

The association of acculturation with accelerometer-assessed and self-reported physical activity and sedentary behavior: The Hispanic Community Health Study/Study of Latinos.

The adoption of US culture among immigrants has been associated with higher leisure-time physical activity and sedentary behavior. However, most research to date assesses this association using single measures of acculturation and physical activity. Our objective was to describe the cross-sectional association between acculturation and both physical activity and sedentary behavior among US Hispanic/Latino adults. Participants included Hispanic/Latinos 18-74 years living in four US locations enrolled in the Hispanic Community Health Study/Study of Latinos from 2008 to 2011. Acculturation was measured using acculturation scales (language and social), years in the US, language preference, and age at immigration. Physical activity and sedentary behavior were measured using the Global Physical Activity Questionnaire (N = 15,355) and Actical accelerometer (N = 11,954). Poisson, logistic, and linear regression were used, accounting for complex design and sampling weights. English-language preference was positively associated with self-reported leisure-time and transportation physical activity and accelerometer-assessed moderate-to-vigorous physical activity (MVPA). Social acculturation was positively associated with self-reported leisure-time and transportation physical activity and MVPA. Years in the US and age at immigration were positively associated with accelerometer-assessed MVPA. Language acculturation, years in the US, and age at immigration were associated with occupational physical activity among those who reported employment. Most acculturation measures were associated with self-reported sitting but not with accelerometer-assessed sedentary behavior. Different measures of acculturation, capturing various domains acculturation, were associated with physical activity and sedentary behavior. However, the direction of the association was dependent on the measures of acculturation physical activity/sedentary behavior, highlighting the complexity of these relationships.

Spirometry Reference Equations from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos).

RATIONALE: Accurate reference values for spirometry are important because the results are used for diagnosing common chronic lung diseases such as asthma and chronic obstructive pulmonary disease, estimating physiologic impairment, and predicting all-cause mortality. Reference equations have been established for Mexican Americans but not for others with Hispanic/Latino backgrounds. OBJECTIVES: To develop spirometry reference equations for adult Hispanic/Latino background groups in the United States. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) recruited a population-based probability sample of 16,415 Hispanics/Latinos aged 18-74 years living in the Bronx, Chicago, Miami, and San Diego. Participants self-identified as being of Puerto Rican, Cuban, Dominican, Mexican, or Central or South American background. Spirometry was performed using standardized methods with central quality control monitoring. Spirometric measures from a subset of 6,425 never-smoking participants without respiratory symptoms or disease were modeled as a function of sex, age, height, and Hispanic/Latino background to produce background-specific reference equations for the predicted value and lower limit of normal. MEASUREMENTS AND MAIN RESULTS: Dominican and Puerto Rican Americans had substantially lower predicted and lower limit of normal values for FVC and FEV1 than those in other Hispanic/Latino background groups and also than Mexican American values from NHANES III (Third National Health and Nutrition Examination Survey). CONCLUSIONS: For patients of Dominican and Puerto Rican background who present with pulmonary symptoms in clinical practice, use of background-specific spirometry reference equations may provide more appropriate predicted and lower limit of normal values, enabling more accurate diagnoses of abnormality and physiologic impairment.

Designing and implementing a cultural competence OSCE: lessons learned from interviews with medical students.

PURPOSE: Objective structured clinical examinations (OSCEs) use standardized patients (SPs) to teach and evaluate medical students' skills. Few studies describe using OSCEs for cultural competence education, now a Liaison Committee on Medical Education accreditation standard for medical schools. We designed an OSCE station emphasizing cross-cultural communication skills (ccOSCE) and interviewed students to better understand and improve upon this tool. METHOD: Two investigators conducted semistructured interviews with 22 second-year Harvard medical students who completed the ccOSCE. Three investigators coded and analyzed the interview transcripts by using qualitative methods to explore students' perspectives on the station and its focus on cultural competence. RESULTS: Themes that emerged pertinent to design and implementation of the station were grouped into four categories: learning goals, logistical issues, faculty feedback, and SPs. Students were positive about the overall experience. They appreciated the practical focus on nonadherence. Some found the learning goals complex, and others felt the format promoted stereotypes. Logistical issues included concerns about marginalizing cross-cultural care by creating a separate station. Faculty feedback was helpful when specific about sociocultural issues students did or did not explore well. Students found SPs realistic but inconsistent in how easily they revealed information. CONCLUSION: Designing a ccOSCE experience is challenging but feasible. Students' perspectives highlight a tension between presenting cultural competence in a dedicated station (potentially marginalizing the topic and promoting stereotypes) and spreading it across stations (limiting opportunity for focused teaching). Learning goals should be clear, concise, and effectively communicated to faculty and SPs so their feedback can be standardized and specific.