The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial

Objectives: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. Trial design: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. Participants: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

The psychological science accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data

The Psychological Science Accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

In her own words: The personal perspectives of Mina Rees

Mathematician Mina S. Rees (1902–1997) broke many barriers during her long and varied career. Known for being a strong and dedicated leader, she was also an insightful and compassionate educator. She wore many hats over the years, all of them traditionally male: mathematics professor, college dean, college president, second in command of a war-time research panel, deputy science director of the Office of Naval Research, pioneer in early computing. Significantly, she was the first female president of the American Association for the Advancement of Science. She accomplished all this with personal strength and integrity. Though she was outspoken when it came to research and education, she rarely spoke of her personal life. In this chapter, we will explore her amazing career, laying special focus on her personal journey. Rees wrote a “Biographical Letter” in the AWM Newsletter in 1970 and gave several interviews in which she did share several personal stories. These stories, along with other personal comments she made over the years, will guide our look at the groundbreaking career of a remarkable woman. Many of her sentiments are still relevant today as education strives to service an ever-diversifying student body

School factors related to the emotional wellbeing and resettlement outcomes of students from refugee backgrounds: protocol for a systematic review

Abstract Background Schools can play a vital role in the resettlement of refugee children and their families. Yet, the body of research examining school environmental factors that support the mental health and acculturation of refugee children is methodologically heterogeneous, investigates numerous and disparate school factors, and is often “hidden” in broader qualitative studies. This limits the capacity to apply the findings in a practical manner. Methods Based on PRISMA statement principles, we review the relevant literature to investigate the relationship between school climate and the emotional wellbeing and resettlement outcomes of refugee students. Six electronic databases will be systematically searched: MEDLINE, PsycINFO, Embase, CINAL, Web of Science, and ERIC, supplemented by a systematic review of the grey literature, relevant international websites, and sequential, site-specific internet searches. Finally, subject area experts will be consulted and backward and forward citation searches of included articles will be completed. Two independent reviewers will screen identified articles against eligibility criteria and extract data for included studies. Quality of included studies will be assessed using the Mixed Methods Appraisal Tool (MMAT) for mixed studies reviews. Data will be synthesised using a convergent qualitative narrative approach. Discussion Given the centrality of school in the daily lives of resettled refugee children, it is vital to assess the impact of school climate on the psychosocial wellbeing and resettlement trajectories of this population. This review will identify evidence-based school factors which support good mental health and resettlement outcomes for refugee students and make recommendations for translation of this knowledge into the school environment. Systematic review registration PROSPERO CRD4201707757

An Analysis of the Last Clinical Encounter before Outpatient Mortality among Children with HIV Infection and Exposure in Lilongwe, Malawi.

Human immunodeficiency virus (HIV) contributes to nearly 20% of all deaths in children under five years of age in Malawi. Expanded coverage of antiretroviral therapy has allowed children to access treatment on an outpatient basis. Little is known about characteristics of the final outpatient encounter prior to mortality in the outpatient setting.This retrospective cohort study assessed clinical factors associated with mortality among HIV-exposed infants and HIV-infected children less than 18 years of age at the Baylor College of Medicine Abbott Fund Children's Center of Excellence in Lilongwe, Malawi. We compared clinical indicators documented from the final outpatient encounter for patients who died in the outpatient setting versus those who were alive after their penultimate clinical encounter.Of the 8,546 patients who were attended to over a 10-year period at the Baylor Center of Excellence, 851 had died (10%). Of children who died, 392 (46%) were directly admitted to the hospital after their last clinical encounter and died as inpatients. Of the remaining 459 who died as outpatients after their last visit, 53.5% had a World Health Organization (WHO) stage IV condition at their last visit, and 25% had a WHO stage III condition. Multivariate regression analysis demonstrated that poor nutritional status, female gender, shorter time as a patient, more clinical encounters in the prior month, if last visit was an unscheduled sick visit, and if the patient had lost weight since their prior visit independently predicted increased mortality in the outpatient setting after the final clinical encounter.Clinical indicators may assist in identifying children with HIV who have increased risk of mortality in the outpatient setting. Recognizing these indicators may aid in identifying HIV-infected children who require a higher level of care or closer follow-up