Validation of Real-World Case Definitions for COVID-19 Diagnosis and Severe COVID-19 Illness Among Patients Infected with SARS-CoV-2: Translation of Clinical Trial Definitions to Real-World Settings (preprint)

Purpose: This study assessed the performance of International Classification of Diseases 10th Revision, Clinical Modification (ICD-10-CM) coronavirus disease 2019 (COVID-19) diagnostic code U07.1 against polymerase chain reaction (PCR) test results (Objective 1), and electronic medical record (EMR)-based codified algorithm for severe COVID-19 illness based on endpoints used in the Pfizer-BioNTech COVID-19 vaccine trial against chart review (Objective 2). Methods: This retrospective, longitudinal cohort study used EMR data from the Mass General Brigham COVID-19 Data Mart (3/1/2020-11/19/2020) for adult patients with [≥]1 PCR test, antigen test, or code U07.1 (Objective 1) and adult patients with a positive PCR test hospitalized with COVID-19 (Objective 2). Results: Among 354,124 patients in Objective 1, 96% had [≥]1 PCR test (including 6% with [≥]1 positive PCR test; 11% with [≥]1 code U07.1). Code U07.1 had low sensitivity (54%) and positive predictive value (PPV; 63%) but high specificity (97%) against the PCR test. Among 300 patients hospitalized for COVID-19 randomly sampled for chart review in Objective 2, the EMR-based case definition for severe COVID-19 illness had high PPV (>95%), showing better performance than severe/critical COVID-19 endpoints defined by the World Health Organization (PPV: 79%). Conclusions: COVID-19 diagnosis based on ICD-10-CM code U07.1 had inadequate sensitivity and requires confirmation by PCR testing. The EMR-based case definition showed high PPV and can be used to identify cases of severe COVID-19 illness in real-world datasets. These findings highlight the importance of validating outcomes in real-world data, and can guide researchers analyzing COVID-19 data when PCR tests are not readily available.

Coarse particulate matter air quality in East Asia: implications for fine particulate nitrate

Air quality network data in China and South Korea show very high year-round mass concentrations of coarse particulate matter (PM), as inferred by the difference between PM10 and PM2.5. Coarse PM concentrations in 2015 averaged 52 µg m-3 in the North China Plain (NCP) and 23 µg m-3 in the Seoul Metropolitan Area (SMA), contributing nearly half of PM10. Strong daily correlations between coarse PM and carbon monoxide imply a dominant source from anthropogenic fugitive dust. Coarse PM concentrations in the NCP and the SMA decreased by 21 % from 2015 to 2019 and further dropped abruptly in 2020 due to COVID-19 reductions in construction and vehicle traffic. Anthropogenic coarse PM is generally not included in air quality models but scavenges nitric acid to suppress the formation of fine particulate nitrate, a major contributor to PM2.5 pollution. GEOS-Chem model simulation of surface and aircraft observations from the Korea–United States Air Quality (KORUS-AQ) campaign over the SMA in May–June 2016 shows that consideration of anthropogenic coarse PM largely resolves the previous model overestimate of fine particulate nitrate. The effect is smaller in the NCP which has a larger excess of ammonia. Model sensitivity simulations for 2015–2019 show that decreasing anthropogenic coarse PM directly increases PM2.5 nitrate in summer, offsetting 80 % the effect of nitrogen oxide and ammonia emission controls, while in winter the presence of coarse PM increases the sensitivity of PM2.5 nitrate to ammonia and sulfur dioxide emissions. Decreasing coarse PM helps to explain the lack of decrease in wintertime PM2.5 nitrate observed in the NCP and the SMA over the 2015–2021 period despite decreases in nitrogen oxide and ammonia emissions. Continuing decrease of fugitive dust pollution means that more stringent nitrogen oxide and ammonia emission controls will be required to successfully decrease PM2.5 nitrate.

Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies.

BACKGROUND: Etrasimod, a once-daily, oral, sphingosine 1-phosphate (S1P) receptor modulator that selectively activates S1P receptor subtypes 1, 4, and 5, with no detectable activity on S1P2,3, is in development for the treatment of immune-mediated diseases, including ulcerative colitis. In these two phase 3 trials, we aimed to evaluate the safety and efficacy of etrasimod in adult patients with moderately to severely active ulcerative colitis. METHODS: In two independent randomised, multicentre, double-blind, placebo-controlled, phase 3 trials, ELEVATE UC 52 and ELEVATE UC 12, adults with active moderate-to-severe ulcerative colitis and an inadequate or loss of response or intolerance to at least one approved ulcerative colitis therapy were randomly assigned (2:1) to once-daily oral etrasimod 2 mg or placebo. Patients in ELEVATE UC 52 were enrolled from 315 centres in 40 countries. Patients in ELEVATE UC 12 were enrolled from 407 centres in 37 countries. Randomisation was stratified by previous exposure to biologicals or Janus kinase inhibitor therapy (yes vs no), baseline corticosteroid use (yes vs no), and baseline disease activity (modified Mayo score [MMS]; 4-6 vs 7-9). ELEVATE UC 52 comprised a 12-week induction period followed by a 40-week maintenance period with a treat-through design. ELEVATE UC 12 independently assessed induction at week 12. The primary efficacy endpoints were the proportion of patients with clinical remission at weeks 12 and 52 in ELEVATE UC 52 and week 12 in ELEVATE UC 12. Safety was evaluated in both trials. ELEVATE UC 52 and ELEVATE UC 12 were registered with ClinicalTrials.gov, NCT03945188 and NCT03996369, respectively. FINDINGS: Patients in ELEVATE UC 52 were enrolled between June 13, 2019, and Jan 28, 2021. Patients in ELEVATE UC 12 were enrolled between Sept 15, 2020, and Aug 12, 2021. ELEVATE UC 52 and ELEVATE UC 12 screened 821 patients and 606 patients, respectively, with 433 and 354 subsequently undergoing random assignment. The full analysis set of ELEVATE UC 52 comprised 289 patients assigned to etrasimod and 144 to placebo. In ELEVATE UC 12, 238 patients were assigned to etrasimod and 116 to placebo. In ELEVATE UC 52, a significantly greater proportion of patients in the etrasimod group achieved clinical remission compared with patients in the placebo group at completion of the 12-week induction period (74 [27%] of 274 patients vs ten [7%] of 135 patients; p<0·0001) and at week 52 (88 [32%] of 274 patients vs nine [7%] of 135 patients; p<0·0001). In ELEVATE UC 12, 55 (25%) of 222 patients in the etrasimod group had clinical remission compared with 17 (15%) of 112 patients in the placebo group at the end of the 12-week induction period (p=0·026). Adverse events were reported in 206 (71%) of 289 patients in the etrasimod group and 81 (56%) of 144 patients in the placebo group in ELEVATE UC 52 and 112 (47%) of 238 patients in the etrasimod group and 54 (47%) of 116 patients in the placebo group in ELEVATE UC 12. No deaths or malignancies were reported. INTERPRETATION: Etrasimod was effective and well tolerated as an induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Etrasimod is a treatment option with a unique combination of attributes that might address the persistent unmet needs of patients with ulcerative colitis. FUNDING: Arena Pharmaceuticals.

Targeted marketing to the underserved: Examining the factors that influence college intent and choice for minority male high school students in Edgecombe County, North Carolina

This mixed-methods study investigates the real and perceived barriers that African American male Edgecombe County high school students face when considering college enrollment to inform potential interventions to improve college enrollment of this market segment. Phase I of the study design included a survey of current, African American, male college students to determine potential barriers African American high school students may face when considering college. Phase II included semi-structured group interviews of African American male Edgecombe County high school students. "Uncertainty" and "frustration" were revealed as the main barriers these students face when considering postsecondary enrollment. Participants indicated uncertainty about college majors, college cost, paying for college, student loans, money, and self-efficacy. Additionally, participants indicated frustration related to course choices in college programs, mathematics classes, as well as their high school GPA not being an accurate indicator of their ability. Phase III included the development of career and technical education (CTE) certificates to create more dual enrollment options for underserved students. Finally, a focus group review of 9-14 pathway samples by African American male students was used to develop a student-informed template for future 9-14 pathways utilized by Edgecombe Community College. Responses from study participants and subsequent meetings with key stakeholders show opportunities to improve the college approach to recruiting students from this demographic. More dual-enrollment certificate options and clearly defined educational pathways (from high school through college) with job market analysis incorporated in those pathways were tools that this study has indicated may help create more postsecondary opportunities for African American male high students in the Edgecombe Community College service area. Additionally, financial aid literacy initiatives for both students and parents and increased recruiting visits to area high schools as the Novel Corona Virus pandemic begins to wane were also indicated as outreach and recruitment strategies. The findings of this study helped develop intentional, dual enrollment certificate options and 9-14 educational pathways the college will utilize to create more postsecondary opportunities for African American males and other underserved groups of students. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

EMERGENCY REMOTE ASSESSMENT (ERA) NARRATIVES FROM THE UK ENGLISH FOR ACADEMIC PURPOSES (EAP) SECTOR: Examining Validity and Longevity of Technology-Driven Solutions

In this chapter, we provide insights into the challenges, innovative strategies, and in many cases, the opportunities which arose in relation to assessment as English for Academic Purposes (EAP) staff in various UK higher education contexts tackled the shifting landscape of the COVID-19 pandemic. Drawing on both quantitative and qualitative data from a large-scale research study, we present the approaches adopted in an attempt to provide effective measurement of EAP constructs and we discuss these with reference to current approaches to validity. The COVID-19 crisis served as a catalyst which has inevitably changed the future landscape of EAP assessment. In grappling with seemingly insurmountable challenges and acute time pressure, ideas about what is possible have expanded and aspects previously on the development agenda have been expedited. Research seems to suggest that the opportunity to rethink teaching, to question learning outcomes, and to re-evaluate testing processes and instruments has resulted in more authentic and meaningful assessment. Establishing the validity of these newly developed technology-driven assessments, however, is an ongoing process which requires further attention. © 2023 selection and editorial matter, Karim Sadeghi;individual chapters, the contributors.

Effectiveness of telemental health during the COVID-19 pandemic: A propensity score noninferiority analysis of outcomes.

The COVID-19 pandemic forced governments to implement a range of public health measures that disrupted the personal and professional lives of many, including an abrupt adoption of telemental health services. Using data from a nonprofit counseling practice, we tested whether telemental health services delivered during the pandemic were inferior to face-to-face services delivered prior to the pandemic. We first characterized patients seeking therapy services before and during the pandemic to ascertain whether the demographics and presenting concerns of patients pre- and during COVID-19 differed and found that pandemic patients reported greater anxiety, greater overall distress, were more likely female and not partnered, and earned less than before the pandemic. We used a propensity score matching analysis to account for these differences and investigated whether or not telemental health therapy was inferior to face-to-face therapy. Based on the propensity-matched samples (2,180 patients in each condition), telemental health services were found not to be inferior to in-person services, allaying concerns about the effectiveness of telemental health services delivered during the COVID-19 pandemic. The present study also illustrates the usefulness of propensity matching for examining treatment effects in naturalistic settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Health Effects of 72 Hours of Simulated Wind Turbine Infrasound: A Double-Blind Randomized Crossover Study in Noise-Sensitive, Healthy Adults.

BACKGROUND: Large electricity-generating wind turbines emit both audible sound and inaudible infrasound at very low frequencies that are outside of the normal human range of hearing. Sufferers of wind turbine syndrome (WTS) have attributed their ill-health and particularly their sleep disturbance to the signature pattern of infrasound. Critics have argued that these symptoms are psychological in origin and are attributable to nocebo effects. OBJECTIVES: We aimed to test the effects of 72 h of infrasound (1.6-20 Hz at a sound level of ∼90 dB pk re 20µPa, simulating a wind turbine infrasound signature) exposure on human physiology, particularly sleep. METHODS: We conducted a randomized double-blind triple-arm crossover laboratory-based study of 72 h exposure with a >10-d washout conducted in a noise-insulated sleep laboratory in the style of a studio apartment. The exposures were infrasound (∼90 dB pk), sham infrasound (same speakers not generating infrasound), and traffic noise exposure [active control; at a sound pressure level of 40-50 dB LAeq,night and 70 dB LAFmax transient maxima, night (2200 to 0700 hours)]. The following physiological and psychological measures and systems were tested for their sensitivity to infrasound: wake after sleep onset (WASO; primary outcome) and other measures of sleep physiology, wake electroencephalography, WTS symptoms, cardiovascular physiology, and neurobehavioral performance. RESULTS: We randomized 37 noise-sensitive but otherwise healthy adults (18-72 years of age; 51% female) into the study before a COVID19-related public health order forced the study to close. WASO was not affected by infrasound compared with sham infrasound (-1.36 min; 95% CI: -6.60, 3.88, p=0.60) but was worsened by the active control traffic exposure compared with sham by 6.07 min (95% CI: 0.75, 11.39, p=0.02). Infrasound did not worsen any subjective or objective measures used. DISCUSSION: Our findings did not support the idea that infrasound causes WTS. High level, but inaudible, infrasound did not appear to perturb any physiological or psychological measure tested in these study participants. https://doi.org/10.1289/EHP10757.

COVID-19 stressors and symptoms of anxiety and depression in a community sample of children and adolescents.

BACKGROUND: The COVID-19 public health crisis has created abrupt and unparalleled disruptions to the daily lives of children and adolescents across the world, placing them at significant risk for developing symptoms of anxiety and depression. METHOD: The current study used two data collection periods to determine which types of COVID-19-related stressors were associated with the greatest risk of anxiety and depression symptoms in a community sample of children and adolescents in the United States (U.S.) from May-August 2020 (T1) to February-April 2021 (T2). Seventy-nine youth (ages 10-17; M = 13.41, SD = 2.10; 54.4% female) completed a battery of online standardized questionnaires about COVID-19 stress and psychiatric symptoms at T1 and 56 of these also participated at T2. RESULTS: The majority of children and adolescents reported experiencing the COVID-19-related stressors in multiple domains including daily routines, interpersonal relationships, education, finances, and health. A substantial proportion of the sample reported clinical levels of depression and anxiety symptoms at both T1 and T2. Multiple linear regression analyses revealed that, controlling for T1 anxiety and depression symptoms, T2 interpersonal stressors were significantly associated with elevated depression and anxiety scores at T2. CONCLUSIONS: The findings highlight the salience of social connection for children and adolescents, and may also underscore the risk associated with lockdown restrictions, social distancing, and school closures during the pandemic.

Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial.

BACKGROUND: Despite the introduction of new monoclonal antibodies and oral therapies for the treatment of ulcerative colitis, clinical remission rates remain low, underscoring the need for innovative treatment approaches. We assessed whether guselkumab plus golimumab combination therapy was more effective for ulcerative colitis than either monotherapy. METHODS: We did a randomised, double-blind, controlled, proof-of-concept trial at 54 hospitals, academic medical centres, or private practices in nine countries. Eligible adults (aged ≥18 to 65 years) had a confirmed diagnosis of ulcerative colitis at least 3 months before screening and moderately-to-severely active ulcerative colitis (Mayo score 6-12) with a centrally-read baseline endoscopy subscore of 2 or higher. Patients were randomly assigned (1:1:1) using a computer-generated randomisation schedule to combination therapy (subcutaneous golimumab 200 mg at week 0, subcutaneous golimumab 100 mg at weeks 2, 6, and 10, and intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab monotherapy 100 mg every 8 weeks for 32 weeks), golimumab monotherapy (subcutaneous golimumab 200 mg at week 0 followed by subcutaneous golimumab 100 mg at week 2 and every 4 weeks thereafter for 34 weeks), or guselkumab monotherapy (intravenous guselkumab 200 mg at weeks 0, 4, and 8, followed by subcutaneous guselkumab 100 mg every 8 weeks thereafter for 32 weeks). The primary endpoint was clinical response at week 12 (defined as a ≥30% decrease from baseline in the full Mayo score and a ≥3 points absolute reduction with either a decrease in rectal bleeding score of ≥1 point or a rectal bleeding score of 0 or 1). Efficacy was analysed in the modified intention-to-treat population up to week 38, which included all randomly assigned patients who received at least one (partial or complete) study intervention dose. Safety was analysed up to week 50, according to study intervention received among all patients who received at least one (partial or complete) dose of study intervention. This trial is complete and is registered with ClinicalTrials.gov, NCT03662542. FINDINGS: Between Nov 20, 2018, and Nov 15, 2021, 358 patients were screened for eligibility, of whom 214 patients were randomly assigned to combination therapy (n=71), golimumab monotherapy (n=72), or guselkumab monotherapy (n=71). Of the 214 patients included, 98 (46%) were women and 116 (54%) were men and the mean age was 38·4 years (SD 12·0). At week 12, 59 (83%) of 71 patients in the combination therapy group had achieved clinical response compared with 44 (61%) of 72 patients in the golimumab monotherapy group (adjusted treatment difference 22·1% [80% CI 12·9 to 31·3]; nominal p=0·0032) and 53 (75%) of 71 patients in the guselkumab monotherapy group (adjusted treatment difference 8·5% [-0·2 to 17·1; nominal p=0·2155). At week 50, 45 (63%) of 71 patients in the combination therapy group, 55 (76%) of 72 patients in the golimumab monotherapy group, and 46 (65%) of 71 patients in the guselkumab monotherapy group had reported at least one adverse event. The most common adverse events were ulcerative colitis, upper respiratory tract infection, headache, anaemia, nasopharyngitis, neutropenia, and pyrexia. No deaths, malignancies, or cases of tuberculosis were reported during the combination induction period. One case of tuberculosis was reported in the combination therapy group and one case of colon adenocarcinoma was reported in the guselkumab monotherapy group; both occurred after week 12. Two deaths were reported after the final dose of study intervention (poisoning in the combination therapy group and COVID-19 in the guselkumab monotherapy group). INTERPRETATION: Data from this proof-of-concept study suggest that combination therapy with guselkumab and golimumab might be more effective for ulcerative colitis than therapy with either drug alone. These findings require confirmation in larger trials. FUNDING: Janssen Research and Development.

A Telemedicine Approach for Monitoring COPD: A Prospective Feasibility and Acceptability Cohort Study.

Background: Telemedicine may help the detection of symptom worsening in patients with chronic obstructive pulmonary disease (COPD), potentially resulting in improved outcomes. This study aimed to determine the feasibility and acceptability of telemedicine among patients with COPD and physicians and facility staff in Japan. Methods: This was a 52-week multicenter, prospective, single-arm, feasibility and acceptability cohort study of Japanese patients ≥40 years of age with COPD or asthma-COPD overlap. Participants underwent training to use YaDoc, a telemedicine smartphone App, which included seven daily symptom questions and weekly COPD Assessment Test (CAT) questions. The primary endpoint was participant compliance for required question completion. The secondary endpoint was participant and physician/facility staff acceptability of YaDoc based on questionnaires completed at Week 52. The impact of the Japanese COVID-19 pandemic state of emergency on results was also assessed. Results: Of the 84 participants enrolled (mean age: 68.7 years, 88% male), 72 participants completed the study. Completion was high in the first six months but fell after that. Median (interquartile range [IQR]) compliance for daily questionnaire entry was 66.6% (31.0-91.8) and 81.0% (45.3-94.3) for weekly CAT entry. Positive participant responses to the exit questionnaire were highest regarding YaDoc ease of use (83.8%), positive impact on managing health (58.8%), and overall satisfaction (53.8%). Of the 26 physicians and facility staff enrolled, 24 completed the study. Of these, the majority (66.7%) responded positively regarding app facilitation of communication between physicians and participants to manage disease. Compliance was similar before and after the first COVID-19 state of emergency in Japan. Conclusion: Daily telemedicine monitoring is potentially feasible and acceptable to both patients and physicians in the management of COPD. These results may inform potential use of telemedicine in clinical practice and design of future studies. Clinical Trial Registration: JapicCTI-194916.

Targeted marketing to the underserved: Examining the factors that influence college intent and choice for minority male high school students in Edgecombe County, North Carolina

This mixed-methods study investigates the real and perceived barriers that African American male Edgecombe County high school students face when considering college enrollment to inform potential interventions to improve college enrollment of this market segment. Phase I of the study design included a survey of current, African American, male college students to determine potential barriers African American high school students may face when considering college. Phase II included semi-structured group interviews of African American male Edgecombe County high school students. "Uncertainty" and "frustration" were revealed as the main barriers these students face when considering postsecondary enrollment. Participants indicated uncertainty about college majors, college cost, paying for college, student loans, money, and self-efficacy. Additionally, participants indicated frustration related to course choices in college programs, mathematics classes, as well as their high school GPA not being an accurate indicator of their ability. Phase III included the development of career and technical education (CTE) certificates to create more dual enrollment options for underserved students. Finally, a focus group review of 9-14 pathway samples by African American male students was used to develop a student-informed template for future 9-14 pathways utilized by Edgecombe Community College. Responses from study participants and subsequent meetings with key stakeholders show opportunities to improve the college approach to recruiting students from this demographic. More dual-enrollment certificate options and clearly defined educational pathways (from high school through college) with job market analysis incorporated in those pathways were tools that this study has indicated may help create more postsecondary opportunities for African American male high students in the Edgecombe Community College service area. Additionally, financial aid literacy initiatives for both students and parents and increased recruiting visits to area high schools as the Novel Corona Virus pandemic begins to wane were also indicated as outreach and recruitment strategies. The findings of this study helped develop intentional, dual enrollment certificate options and 9-14 educational pathways the college will utilize to create more postsecondary opportunities for African American males and other underserved groups of students. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

The Effect of Guselkumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Results at Week 12 by Prior Inadequate Response or Intolerance to Advanced Therapy

Introduction: QUASAR (NCT04033445) is a phase 2b randomized, double-blind, placebo-controlled study that evaluates guselkumab (GUS), an interleukin-23 p19 subunit antagonist, as induction treatment in patients with moderately to severely active ulcerative colitis (UC) who had an inadequate response or intolerance to conventional (ie, thiopurines or corticosteroids) or advanced therapy (ADT;ie, tumor necrosis factor alpha antagonists, vedolizumab, or tofacitinib). Conclusion: Treatment with GUS resulted in greater improvements compared with placebo across key clinical and endoscopic/histologic outcome measures at Week 12 in patients with moderately to severely active UC with or without a history of inadequate response/intolerance to ADT. Efficacy at Week 12 by prior response/intolerance to ADT Placebo IV (N=105) GUS 200 mg IV (N=101) GUS 400 mg IV (N=107) GUS Combined(N=208) Patients with a history of inadequate response/intolerance to ADT 51 46 51 97  Clinical response a1,b,c,d,e (95% CI) 25.5% (14.3, 39.6) 54.3%* (39.0, 69.1) 47.1%* (32.9, 61.5) 50.5%* (40.2, 60.8)  Clinical remission a2,b,c,d,e (95% CI) 7.8% (2.2, 18.9) 17.4% (7.8, 31.4) 17.6% (8.4, 30.9) 17.5% (10.6, 26.6)  Symptomatic remission a3,b,c,d,e (95% CI) 17.6% (8.4, 30.9) 39.1%* (25.1, 54.6) 37.3%* (24.1, 51.9) 38.1%* (28.5, 48.6)  Endoscopic improvement a4,b,c,d,e (95% CI) 9.8% (3.3, 21.4) 23.9% (12.6, 38.8) 21.6% (11.3, 35.3) 22.7% (14.8, 32.3)  Histo-endoscopic mucosal improvement a5,b,c,d,e (95% CI) 5.9% (1.2, 16.2) 13.0% (4.9, 26.3) 19.6%* (9.8, 33.1) 16.5% (9.7, 25.4)  Endoscopic normalization a6,b,c,d,e (95% CI) 5.9% (1.2, 16.2) 10.9% (3.6, 23.6) 5.9% (1.2, 16.2) 8.2% (3.6, 15.6) Patents with no history of inadequate response/intolerance to ADT 54 55 56 111  Clinical response a1,b,c,d,e (95% CI) 29.6% (18.0, 43.6) 67.3%** (53.3, 79.3) 73.2%** (59.7, 84.2) 70.3%** (60.9, 78.6)  Clinical remission a2,b,c,d,e (95% CI) 11.1% (4.2, 22.6) 32.7%* (20.7, 46.7) 32.1%* (20.3, 46.0) 32.4%* (23.9, 42.0)  Symptomatic remission a3,b,c,d,e (95% CI) 22.2% (12.0, 35.6) 58.2%** (44.1, 71.3) 57.1%** (43.2, 70.3) 57.7%** (47.9, 67.0)  Endoscopic improvement a4,b,c,d,e (95% CI) 14.8% (6.6, 27.1) 36.4%* (23.8, 50.4) 39.3%* (26.5, 53.2) 37.8%* (28.8, 47.5)  Histo-endoscopic mucosal improvement a5,b,c,d,e (95% CI) 11.1% (4.2, 22.6) 27.3%* (16.1, 41.0) 33.9%* (21.8, 47.8) 30.6%* (22.2, 40.1)  Endoscopic normalization a6,b,c,d,e (95% CI) 7.4% (2.1, 17.9) 23.6%* (13.2, 37.0) 21.4%* (11.6, 34.4) 22.5%* (15.1, 31.4) * Nominal p-value < 0.05. ** Nominal p-value < 0.001. a1 Clinical response is defined as decrease from induction baseline in the modified Mayo score by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1. a2 Clinical remission is defined as stool frequency subscore of 0 or 1 with no increase from induction baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. a3 Symptomatic remission is defined as a stool frequency subscore of 0 or 1 with no increase from induction baseline and a rectal bleeding subscore of 0. a4 Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. a5 Histo-endoscopic mucosal improvement is defined as achieving a combination of histologic improvement (neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement, a6 Endoscopic normalization is defined as an endoscopy subscore of 0. b Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an adverse event of worsening of UC prior to the Week 12 visit were considered not to have achieved the endpoint. c Data after discontinuation of study agent due to COVID-19 related reasons (excluding COVID-19 infection) were considered to be missing. d Patients who were issing one or more components pertaining to a specified endpoint at Week 12 were considered not to have achieved the endpoint. e The p-values were based on the Cochran-Mantel-Haenszel (CMH) chi-square test.

Induction Combination Therapy With Guselkumab and Golimumab Followed by Guselkumab Monotherapy Maintenance: Results of the Phase 2a, Randomized, Double-Blind, Proof-of-Concept VEGA Study

GUS Clinical remission c,d 16 (22.2) 22 (31.0) 31 (43.7) 21.5 (11.9, 31.2) 0.006 12.7 (2.7, 22.7) 0.109 Clinical remission (based on mMayo) c,e 15 (20.8) 22 (31.0) 34 (47.9) 27.1 (17.7, 36.6) < 0.001 16.9 (7.0, 26.8) 0.033 Symptomatic remission c,f 43 (59.7) 49 (69.0) 49 (69.0) 9.4 (-0.6, 19.4) 0.238 0.0 (-9.7, 9.7) 1.000 Endoscopic improvementc.g 16 (22.2) 23 (32.4) 35 (49.3) 27.2 (17.6, 36.7) < 0.001 16.9 (7.0, 26.8) 0.033 Endoscopic normalization c,h 5 (6.9) 11 (15.5) 18 (25.4) 18.5 (11.1, 25.9) 0.002 9.9 (1.6, 18.2) 0.134 Histologic remission c,i 18 (25.0) 29 (40.8) 36 (50.7) 25.8 (16.1, 35.5) 0.001 9.9 (-0.4, 20.1) 0.224 Both histologic remission and endoscopic improvement c,g,i 10 (13.9) 15 (21.1) 30 (42.3) 28.5 (19.6, 37.4) < 0.001 21.1 (11.8, 30.5) 0.005 Both histologic remission and endoscopic normalization c,h,i 4 (5.6) 9 (12.7) 17 (23.9) 18.5 (11.3, 25.6) 0.002 11.3 (3.3, 19.2) 0.074 a The adjusted treatment difference between the combination therapy vs. the monotherapy groups and the confidence interval were based on the Wald statistic with the Cochran-Mantel-Haenszel (CMH) weight. b The p-value was based on the 2-sided CMH chi-square test, stratified by corticosteroid use at baseline (Yes, No). All P-values are nominal. c Pts who had an ostomy or colectomy, had a protocol-prohibited change in concomitant UC medications, or discontinued study intervention due to lack of a therapeutic effect or an adverse event of worsening UC, or discontinued study agent early due to COVID-19 related reasons (excluding COVID-19 infection) prior to the wk 38 visit were considered to not have achieved the binary endpoints. Pts with missing data at wk 38 were considered to not have achieved the binary endpoints. d Clinical remission is defined as Mayo score ≤2, with no individual subscore >1. e Clinical remission (based on the mMayo) is defined as a stool frequency subscore of 0 or 1, where the stool frequency subscore has not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on endoscopy. f Symptomatic remission is defined as Mayo stool frequency subscore of 0 or 1, where the stool frequency subscore has not increased from baseline, and a rectal bleeding subscore of 0. g Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. h Endoscopic normalization is defined as an endoscopy subscore of 0. i Histologic remission is defined as absence of neutrophils from the mucosa (both lamina propria and epithelium), no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system.

Growing up in rheumatology: An Evaluation of a Young Adult Rheumatology Service

Introduction/Background: Young people with juvenile onset rheumatic disease are treated in paediatric centres until they are required to transfer to an adult centre. Transitional care is a process which begins in early adolescence and prepares young people for this change. There is a rapidly evolving evidence base to support transitional care for young people with long term health conditions with European rheumatology-specific guidance available. The third stage of transitional care, i.e. that which follows transfer to adult care, however, is the least researched. Description/Method: The aim of the study is to evaluate rheumatology service provision for the third stage of transition, i.e. young adult rheumatology provision, at a large NHS trust. A retrospective case-note review was conducted. Relevant patients were identified from young adult rheumatology clinic lists from 2017 to 2022. Of note, no clinics took place during the COVID 19 pandemic lock down in 2020 and transfer of patients during that time was postponed until face to face clinics resumed in adult practice. Patients were assigned study numbers and data was then collected from clinical letters, general correspondence and other annotations uploaded to the Electronic Patient Records (EPR). Patient records searched included those up to 24 years old on current adult rheumatology clinic lists. Discussion/Results: 86 patients (79.1% female, n = 68) were identified. The mean age at transfer was 17.1 years with 53.4% having inflammatory arthritis (n = 46). 59.3% (n = 51) had more than 1 diagnosis. 64% (n = 55) had no other named specialties involved in care at transfer. The median number of medications at transfer was 3, range 0-11. Of those taking medications, 86.7% (n = 72) were self-managing these.59.3% (n = 51) had a transfer letter. 29.1% (n = 25) had a transfer summary completed. 14% (n = 12) had no transfer documentation. Transition readiness checklists were identified in 41.9% records (n = 36). At the time of transfer, copy clinic letters were addressed solely to parents in 4 (4.7%).Young people had attended a median of 5 appointments (range 1-12) in the 12 months prior to transfer. 59.3% (n = 51) attended more than 50% of these appointments independently. 26.7% (n = 23) did not attend between 1-2 of their scheduled appointments in the 12 months pre-transfer.The mean duration between last paediatric and first adult appointment was 4 months (range 1-12). 47.7% (n = 41) did not attend at least one appointment in the 12 months post-transfer, with 23.3% (n = 20) not attending 3 or more appointments.67% (n = 58) of the final paediatric letters covered at least one of 11 psychosocial topics, with a median of 2 topics covered (range 1-5). In the first adult clinic letter a median of 3 topics (range 1-7) were covered in 82.6% (n = 71) letters.Around the time of transfer, disease activity was addressed in only 18 patients (20.9%) with a median score for Physician Global Assessment of 0 (0-10). 36% of patients (n = 31) had a CHAQ score documented, median score 0.5 (0-1.875). 29.1% (n = 25) had pain scores recorded, median 16, range 0-87. Self-reported wellbeing scores were recorded for 23.3% (n = 20), median 16.5, range 0-75. Key learning points/Conclusion: We describe a cohort of young people recently transferred from paediatric rheumatology care with the majority having inflammatory arthritis, being female and being on medication. A third had other specialties involved thus requiring greater coordination at the time of transfer. Transitional care preparation appeared effective with the majority seeing professionals independently prior to transfer, self-managing their medication and in receipt of clinic letters copied to them rather than their parents. Documentation of transitional care is important for multidisciplinary care but was sub- optimal with less than half of the records having transition check lists and a minority with formal transfer documentation. With limited clinic time and a childhood onset disease, a brief summary of relevant information including previous medications tried is important for the adult team and core to current transitional care guidance.The time between last paediatric and first adult appointment has been reported to be important in transitional care and it was reassuring to see this was a median of 4 months. There were higher rates of non-attendance in the young adult clinic compared to paediatrics which could reflect this wide range for continuity and will be an important area for future attention to ensure engagement of young people and the avoidance of lapses in care and potential disease flares. Disease activity was poorly documented in the peri-transfer period however, so it is difficult to comment on prevalence of uncontrolled disease at this time.Documentation of routine psychosocial screening was better post transfer but may reflect that these appointments are essentially a new patient appointment and therefore reflects the adult team getting to know the young person.This service evaluation has therefore identified areas of good transitional care practice as well as areas for improvement in this service and will be a useful baseline for future development.

Pharmacy students' knowledge and confidence of COVID-19 following an interactive didactic class.

Background: COVID-19 education for the pharmacy workforce is important to ensure pharmacists are optimizing patient care for the prevention and management of COVID-19. However, there are currently no reports to our knowledge of education and training experiences for COVID-19 prevention and management in the Doctor of Pharmacy (PharmD) curricula. Objective: To evaluate pharmacy students' knowledge and confidence regarding COVID-19 prevention and management before and after an interactive didactic class (IDC). Methods: A multicenter, quasi-experimental, cross-sectional survey study was performed among pharmacy students before and after IDC on COVID-19 at two schools of pharmacy. The IDC on COVID-19 consisted of student-led presentations on a COVID-19 drug, an infectious disease pharmacist faculty-led interactive lecture on COVID-19 prevention and management, and clinical case vignettes to assess COVID-19 management strategies. An anonymous, voluntary, electronic survey was distributed to students (n = 85) before and after. The pre- and postintervention survey contained 10 COVID-19 knowledge-based questions and multi-step, 5-point Likert scale statements related to COVID-19 prevention and management confidence. The postintervention survey also evaluated students' perceptions of the COVID-19 IDC. Descriptive statistics were performed, and Student t test was used to compare pre- and postintervention responses. Results: About 61 surveys were completed resulting in a response rate of 72%. COVID-19 knowledge scores (mean ± SD) increased overall following the IDC (5.9 ± 1.31 vs 8.6 ± 1.29). Pharmacy students' COVID-19 confidence scores (mean ± SD) also improved following the IDC (2.66 ± 0.75 vs 4.03 ± 0.53). Students performed well on the COVID-19 clinical case vignettes with a mean ± SD score of 22.41 ± 0.46 out of 25. Pharmacy students' perceptions of the IDC on COVID-19 were also positive overall. Conclusion: Pharmacy students' knowledge and confidence of COVID-19 prevention and management improved following an IDC. This may be an effective strategy to provide COVID-19 education during the PharmD curricula.

Serological testing for SARS-CoV-2 antibodies of employees shows low transmission working in a cancer center.

BACKGROUND: The COVID-19 pandemic led to emergency measures to continue patient care and research at a comprehensive cancer center while protecting both employees and patients. Determining exposure and infection rates with SARS-CoV-2 were important to adjust workplace policies over time. METHODS: Dana-Farber Cancer Institute (DFCI) has over 7,000 employees. Participation was voluntary. After consent, participants completed questionnaire of demographics, exposures and risk factors for COVID-19 illness at each time point (baseline, 3, 6, and 12 months) along with blood draws for SARS-CoV-2 antibody testing. Primary measure was determination of titers of SARS-CoV-2 spike protein IgG over time. RESULTS: In total, 745 employees enrolled from May 2020 to February 2021 (mean [SD] age, 40[14] years; 572[80%] women). From May to July 2020, 47 of 519 employees (9.2%, 95% confidence interval [CI] 6.7-12.0%) tested positive for SARS-CoV-2 spike protein IgG antibodies. Three months later, 40 of 428 employees had positive antibodies (8.5%, 95% CI 6.0-11.0%) with 17 newly positive. At month 6, 78.5% of participants reported having received at least one dose of vaccine and the positivity rate for those vaccinated was 98% (95% CI, 95-100%). Spike protein IgG titers for those vaccinated were 7.9 times higher than participants not vaccinated (median IgG titer = 0.28 for positive antibody but not vaccinated versus 2.2 for vaccinated) but demonstrate evidence of waning over time. CONCLUSIONS: SARS-CoV-2 antibody positivity remained less than 10% at a single comprehensive cancer center prior to vaccination and there is evidence of waning IgG titers over time after vaccination.

Coping with COVID-19 stress: Associations with depression and anxiety in a diverse sample of U.S. adults.

The COVID-19 pandemic has brought unprecedented levels of stress to individuals in the U.S. and throughout the world. These high stress levels place individuals at risk for symptoms of anxiety, depression, and other psychiatric disorders. The current study applies a control-based model of coping to contribute to the development of evidence-based interventions to promote resilience. Data were collected online from April 22 through July 12, 2020. Data from two samples of U. S. community adults who completed an online battery of standardized questionnaires were combined (N = 709). More than a quarter reported moderate to severe levels of depression symptoms, and more than one-fifth reported moderate to severe levels of anxiety symptoms; symptom levels were higher among adults who reported more COVID-19-related stress. As hypothesized, multiple regression analyses indicated that greater use of primary and secondary control coping was associated with lower symptom levels, whereas greater use of disengagement coping was associated with higher symptom levels, above and beyond the association of stress with symptoms. Race and ethnicity emerged as important moderators of these associations, indicating that what constitutes adaptive coping varies according to characteristics of the individual. Implications for public health policy and clinical practice are discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-021-02444-6.

Summary of fourth annual MCBK public meeting: Mobilizing computable biomedical knowledge-metadata and trust.

The exponential growth of biomedical knowledge in computable formats challenges organizations to consider mobilizing artifacts in findable, accessible, interoperable, reusable, and trustable (FAIR+T) ways1. There is a growing need to apply biomedical knowledge artifacts to improve health in Learning Health Systems, health delivery organizations, and other settings. However, most organizations lack the infrastructure required to consume and apply computable knowledge, and national policies and standards adoption are insufficient to ensure that it is discoverable and used safely and fairly, nor is there widespread experience in the process of knowledge implementation as clinical decision support. The Mobilizing Computable Biomedical Knowledge (MCBK) community formed in 2016 to address these needs. This report summarizes the main outputs of the Fourth Annual MCBK public meeting, which was held virtually July 20 to July 21, 2021 and convened over 100 participants spanning diverse domains to frame and address important dimensions for mobilizing CBK.

Defining comprehensive biomarker-related testing and treatment practices for advanced non-small-cell lung cancer: Results of a survey of U.S. oncologists.

BACKGROUND: An ASCO taskforce comprised of representatives of oncology clinicians, the American Cancer Society National Lung Cancer Roundtable (NLCRT), LUNGevity, the GO2 Foundation for Lung Cancer, and the ROS1ders sought to: characterize U.S. oncologists' biomarker ordering and treatment practices for advanced non-small-cell lung cancer (NSCLC); ascertain barriers to biomarker testing; and understand the impact of delays on treatment decisions. METHODS: We deployed a survey to 2374 ASCO members, targeting U.S. thoracic and general oncologists. RESULTS: We analyzed 170 eligible responses. For non-squamous NSCLC, 97% of respondents reported ordering tests for EGFR, ALK, ROS1, and BRAF. Testing for MET, RET, and NTRK was reported to be higher among academic versus community providers and higher among thoracic oncologists than generalists. Most respondents considered 1 (46%) or 2 weeks (52%) an acceptable turnaround time, yet 37% usually waited three or more weeks to receive results. Respondents who waited ≥3 weeks were more likely to defer treatment until results were reviewed (63%). Community and generalist respondents who waited ≥3 weeks were more likely to initiate non-targeted treatment while awaiting results. Respondents <5 years out of training were more likely to cite their concerns about waiting for results as a reason for not ordering biomarker testing (42%, vs. 19% with ≥6 years of experience). CONCLUSIONS: Respondents reported high biomarker testing rates in patients with NSCLC. Treatment decisions were impacted by test turnaround time and associated with practice setting and physician specialization and experience.