Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Childhood Adversity Moderates Change in Latent Patterns of Psychological Adjustment during the COVID-19 Pandemic: Results of a Survey of U.S. Adults

Emerging evidence suggests that the consequences of childhood adversity impact later psychopathology by increasing individuals' risk of experiencing difficulties in adjusting to stressful situations later in life. The goals of this study were to: (a) identify sociodemographic factors associated with subgroups of psychological adjustment prior to and after the onset of the COVID-19 pandemic and (b) examine whether and to what extent types of childhood adversity predict transition probabilities. Participants were recruited via multiple social media platforms and listservs. Data were collected via an internet-based survey. Our analyses reflect 1942 adults (M = 39.68 years);39.8% reported experiencing at least one form of childhood adversity. Latent profile analyses (LPAs) and latent transition analyses (LTAs) were conducted to determine patterns of psychological adjustment and the effects of childhood adversity on transition probabilities over time. We identified five subgroups of psychological adjustment characterized by symptom severity level. Participants who were younger in age and those who endorsed marginalized identities exhibited poorer psychological adjustment during the pandemic. Childhood exposure to family and community violence and having basic needs met as a child (e.g., food, shelter) significantly moderated the relation between latent profile membership over time. Clinical and research implications are discussed. © 2023 by the authors.

THE ALPHA COLLABORATION FOR RANDOMISED MEGA-STUDIES TO IMPROVE MORTALITY AND DISABILITY

Background: COVID-19 trials took <1 year to identify therapies reducing death in >30,000 patients but the Australian Placental Transfusion Study took >12 years to show that delaying cord clamping reduced death or major disability (cerebral palsy, severe visual loss, deafness, or cognitive delay) in 1,531 preterm infants. What can this teach us? Further, as composite outcomes of death or major disability can be inconclusive if each is unequally affected (as in the NeOProM Collaboration1) 2 important aims are (i) global co-operation (https://www.alphacollaboration.com/) to identify core Participant-Intervention-Comparator-Outcome questions for trials assessing mortality, a key outcome, and (ii) to answer those questions in much larger, faster trials. Such trials will also yield much more precise estimates of disability in survivors than was previously typical - a major benefit. Method: To inform these aims we compared enrolment in 2 COVID-19 trials and in 10 trials by IMPACT collaborators with samples >1,500 in high- or low-or-middle-income countries (HIC/LMIC). Results: The COVID-19 trials took 3-9 months, enrolling 13 - 219 per-site-per-year. Perinatal trials took 16-86 months, enrolling 5 - 1,700 per site per year. Trials in pregnant women or LMIC (n = 53,092) enrolled 5 times more than trials in newborns or restricted to HIC (n = 9,014). (Table) Conclusions: Greater international collaboration could resolve questions of shared relevance and priority more rapidly. Megatrials addressing mortality may benefit from highly streamlined processes for enrolment and minimal data collection, e.g., RECOVERY's one-page outcome form.

Reassessing Undergraduate Polymer Chemistry LaboratoryExperiments for Virtual Learning Environments br

Chemistry laboratory experiments are invaluable tostudents'acquisition of necessary synthetic, analytical, andinstrumental skills during their undergraduate studies. However,the COVID-19 pandemic rendered face-to-face (f2f), in-personteaching laboratory experiences impossible from late 2019-2020and forced educators to rapidly develop new solutions to deliverchemistry laboratory education remotely. Unfortunately, achievinglearning and teaching objectives to the same caliber of in-personexperiments is very difficult through distance learning. Toovercome these hurdles, educators have generated many virtual and remote learning options for not only foundational chemistrycourses but also laboratory experiments. Although the pandemic challenged high-level chemistry education, it has also created anopportunity for both students and educators to be more cognizant of virtual learning opportunities and their potential benefits withinchemistry curriculum. Irrespective of COVID-19, virtual learning techniques, especially virtual lab experiments, can complement f2flaboratories and offer a cost-efficient, safe, and environmentally sustainable alternative to their in-person counterparts.Implementation of virtual and distance learning techniques???including kitchen chemistry and at-home laboratories, prerecordedvideos, live-stream video conferencing, digital lab environment, virtual and augmented reality, and others???can provide a wide-ranging venue to teach chemistry laboratories effectively and encourage diversity and inclusivity in thefield. Despite their relevanceto real-world applications and potential to expand upon fundamental chemical principles, polymer lab experiments areunderrepresented in the virtual platform. Polymer chemistry education can help prepare students for industrial and academicpositions. The impacts of polymers in our daily life can also promote students'interests in science and scientific research. Hence, thetranslation of polymer lab experiments into virtual settings improves the accessibility of polymer chemistry education. Herein, weassess polymer experiments in the emergence of virtual learning environments and provide suggestions for further incorporation ofeffective polymer teaching and learning techniques into virtual settings

Peasant farmers and pandemics: the role of seasonality and labor-leisure trade-off decisions in economy-wide models

Pandemics attack the primary asset (labor) of peasant households and the rural poor. Peasant households must simultaneously allocate labor between farm and household activities, where the demand for agricultural labor is seasonal, which limits intra-temporal substitution, without perfect foresight. A pandemic reduces the supply of labor, through deaths and morbidity, with the scale of reductions in labor supply depending on the seasons in which a pandemic occurs. The analyses, using a recursive dynamic economy-wide model for Bhutan, demonstrate that outbreaks in high labor demand seasons cause increases in wage rates almost three times as high as for outbreaks in low labor demand seasons. Increases in wage rates induce peasant households to reallocate labor time between farm and household activities through the labor-leisure trade-off mechanism. Such changes in the allocation of labor time are important elements of peasants’ mitigation responses, and can reduce the negative economic implications of a pandemic. © 2021 The International Input--Output Association.

Evaluating 'creating caring communities': A medical student pilot wellness program to aid in the transition to medical school during COVID-19

Objective: The transition to medical school is challenging;even more so with the added stress and isolation from the COVID-19 pandemic. While studies have examined medical student wellness programs, few have been implemented during a pandemic, a time of high uncertainty and change. The purpose of this study was to evaluate a novel wellness program, Creating Caring Communities (CCC), its impact on students, and its helpfulness in their transition to medical school during COVID-19. Methods: All incoming first-year medical students (N=183) were required to participate in the mandatory first two of six, one-hour virtual sessions of CCC;a checkin with 10 students and 2 trained facilitators to create a safe space for connectivity and sharing. An online SurveyMonkey was administered to all participants after the sixth session to assess program impact, social isolation, meaningful experience, and helpfulness of CCC in the transition to medical school. Descriptive and bivariate analyses, including crosstabs, were completed using SPSS.25. Openended questions were thematically analyzed. Results: 126 M1 participants completed the post-CCC evaluation (68.9% response rate). Social isolation scores were consistent with the national average for the U.S. general adult population (M=51.96, SD=6.94). M1s who attended more than two sessions (39%) had significantly greater reports of meaningful experiences and helpfulness in transitioning to medical school (respectively, 58.1%;70.8%) compared to M1s who attended two or fewer sessions (respectively, 41.9%;29.2%;p<.05). When asked about the most valuable aspects of CCC, the most common themes reported were: building connections (49.6%), having a safe place to share experiences (17.0%), and not feeling alone (12.6%). Conclusion: Many students found that CCC was helpful with their transition to medical school. Future program refinement should consider whether sessions should be mandatory, the timing and length of the program, and participant input prior to starting CCC for group placement based on individual needs and interests.

Understanding public perception of COVID-19 social distancing on twitter

Background: Managing and changing public opinion and behavior are vital for social distancing to successfully slow transmission of COVID-19, preserve hospital resources, and prevent overwhelming the healthcare system's resources. We sought to leveraging organic, large-scale discussion on Twitter about social distancing to understand public's beliefs and opinions on this policy. Methods: Between March 27 and April 10, 2020, we sampled 574,903 English tweets that matched the two most trending social distancing hashtags at the time, #socialdistancing and #stayathome. We used natural language processing techniques to conduct a sentiment analysis that identifies tweet polarity and emotions. We also evaluated the subjectivity of tweets and estimated the frequency of discussion of social distancing rules. We then identified clusters of discussion using topic modeling and compared the sentiment by topic. Results: There was net positive sentiment toward both #socialdistancing and #stayathome with mean sentiment scores of 0.150 (standard deviation [SD], 0.292) and 0.144 (SD, 0.287) respectively. Tweets were also more likely to be objective (median, 0.40;IQR, 0 to 0.6) with approximately 30% of all tweets labeled as completely objective. Approximately half (50.4%) of all tweets primarily expressed joy and one-fifth expressed fear and surprise each (Figure 1). These trends correlated well with topic clusters identified by frequency including leisure activities and community support (i.e., joy), concerns about food insecurity and effects of the quarantine (i.e., fear), and unpredictability of COVID and its unforeseen implications (i.e., surprise) (Table 1). Conclusion: The positive sentiment, preponderance of objective tweets, and topics supporting coping mechanisms led us to believe that Twitter users generally supported social distancing measures in the early stages of their implementation. (Table Presented).

How pets factor into healthcare decisions for COVID-19: A One Health perspective

There is evidence that prioritizing pets' welfare can impact the health and well-being of their owners, especially when pet owners have a strong bond with their pet. This carries public health implications, particularly in a global public health emergency such as COVID-19. The study objective was to understand pet owners' consideration of their pets' welfare when making personal healthcare decisions specific to COVID-19. A large sample (n = 1356) of adult pet owners in the U.S. completed an online survey in April and May of 2020, coinciding with the onset of social distancing measures to prevent the spread of COVID-19. Respondents were asked if they would delay or avoid testing or treatment for COVID-19 due to concern for their pets' welfare, and a follow-up question asked them to elaborate. Multinomial logistic regression models showed that attachment to pets and socioeconomic resources were important factors in pet owners' hypothetical decisions regarding testing and treatment for COVID-19. Qualitative analysis of responses to the follow-up question revealed explanations across three themes: (1) the need to find pet accommodation prior to seeking healthcare;(2) pet-related concerns;and, (3) human-related concerns. Pet owners often cited concern for their pets' welfare as a factor contributing to their decision making;participants' lack of a concrete plan for pet care was most commonly cited as the reason for their delay in seeking healthcare. Results from this study indicate that pet owners experience unique obstacles to accessing healthcare related to COVID-19, which has implications for future public health emergencies. Increased disease spread and prevalence of poor health outcomes could result if pet owners delay or avoid testing or treatment. Communities can benefit from a One Health/One Welfare approach to collaboration between human and animal health and service providers to reduce COVID-19 spread and secure the well-being of people and their pets.