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In Spring 2020, colleges across the nation swiftly transitioned their operations--including both classes and student support services--to remote delivery on an emergency basis in response to the crisis posed by the COVID-19 pandemic. While prior research has documented that the transition was associated with decrements in student outcomes, there remains limited understanding of the organizational factors that might have mitigated these negative associations during the pandemic. Drawing on administrative data from the California Community College system, along with a novel survey conducted among distance education leaders, our study reveals that the degree of declines in course completion and course passing rates varied based on pre-COVID online education resources (such as the ratio of distance education personnel to students and the availability of pre-COVID professional development programs in online learning): Colleges with greater pre-COVID online resources experienced more modest declines in student performance. To a lesser extent, we also found that declines in student performance during the onset of the pandemic varied depending on the responses implemented in reaction to the pandemic, such as the extent of technology delivery to students. The implications of our findings extend to the realm of planning for the continuity of operations in potential future crises.

Abstract Proteomics offers unique insights into human biology and drug development, but few studies have directly compared the utility of different proteomics platforms. We measured plasma levels of 2168 proteins in 3976 Chinese adults using both Olink Explore and SomaScan platforms. The correlation of protein levels between platforms was modest (median rho = 0.29), with protein abundance and data quality parameters being key factors influencing correlation. For 1694 proteins with one-to-one matched reagents, 765 Olink and 513 SomaScan proteins had cis-pQTLs, including 400 with colocalising cis-pQTLs. Moreover, 1096 Olink and 1429 SomaScan proteins were associated with BMI, while 279 and 154 proteins were associated with risk of ischaemic heart disease, respectively. Addition of Olink and SomaScan proteins to conventional risk factors for ischaemic heart disease improved C-statistics from 0.845 to 0.862 (NRI: 12.2%) and 0.863 (NRI: 16.4%), respectively. These results demonstrate the utility of these platforms and could inform the design and interpretation of future studies.

Abstract Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR

Background and Purpose Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclear. We investigated how changes in infarct volume at 24 hours alter the probability of achieving good clinical outcome (modified Rankin Scale [mRS] 0–2). Methods Data are from endovascular thrombectomy patients from the randomized controlled ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial. Infarct volume at 24 hours was manually segmented on non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. Probabilities of achieving good outcome based on infarct volume were obtained from a multivariable logistic regression model. The probability of good outcome was plotted against infarct volume using linear spline regression. Results A total of 1,099 patients were included in the analysis (median final infarct volume 24.9 mL [interquartile range: 6.6–92.2]). The relationship between total infarct volume and good outcome probability was nearly linear for infarct volumes between 0 mL and 250 mL. In this range, a 10% increase in the probability of achieving mRS 0–2 required a decrease in infarct volume of approximately 34.0 mL (95% confidence interval: -32.5 to -35.6). At infarct volumes above 250 mL, the probability of achieving mRS 0–2 probability was near zero. The relationships of tissue-specific infarct volumes and parenchymal hemorrhage volume generally showed similar patterns, although variability was high. Conclusion There seems to be a near-linear association between total infarct volume and probability of achieving good outcome for infarcts up to 250 mL, whereas patients with infarct volumes greater than 250 mL are highly unlikely to have a favorable outcome.

Background and Purpose The safety and efficacy of tenecteplase in patients with ischemic stroke due to medium vessel occlusion (MeVO) are not well studied. We aimed to compare tenecteplase with alteplase in stroke due to MeVO. Methods Patients with baseline M2-middle cerebral artery (MCA), M3/M4-MCA, P2/P3/P4-posterior cerebral artery (PCA), A2/A3/A4-anterior cerebral artery (ACA) occlusions from the Alteplase Compared to Tenecteplase (AcT) trial were included. Primary outcome was the proportion of 90-day modified Rankin Scale (mRS) 0–1. Secondary outcomes were 90-day mRS 0–2, ordinal mRS, mortality, quality of life measures (EuroQol 5-Dimension 5-Level, EuroQol visual analog scale), and symptomatic intracerebral hemorrhage (sICH). Initial and final successful reperfusion were reported in patients undergoing endovascular thrombectomy (EVT). Results Among 1,558 patients with available baseline computed tomography angiography; 455 (29.2%) had MeVO of which 27.5% (125/455) were proximal M2; 16.3% (74/455) were distal M2; 35.2% (160/455) were M3/M4; 7.5% (34/455) were A2/A3/A4; and 13.6% (62/455) were P2/P3/P4 occlusions. EVT was performed in 87/455 (19.1%) patients. mRS 0–1 at 90 days was achieved in 37.9% in the tenecteplase versus 34.7% in the alteplase group (adjusted risk ratio [aRR] 1.07; 95% confidence interval [CI] 0.91–1.25). Rates of 90-day mRS 0–2, sICH, and mortality were similar in both groups. No statistical difference was noted in initial successful reperfusion rates (13.0% vs. 7.5%) among the 87 patients who underwent endovascular thrombectomy. However, final successful reperfusion was higher in the tenecteplase group (71.7% vs. 60.0%, aRR 1.29, 95% CI 1.04–1.61). Conclusion Intravenous tenecteplase had comparable safety, functional outcomes and quality of life compared to intravenous alteplase among patients with MeVO. Among those treated with EVT, tenecteplase was associated with higher successful reperfusion rates than alteplase.

Background Genetic and familial contributions to early‐onset atrial fibrillation are described primarily in individuals of European ancestry. However, the role of racial and familial contributions in the pathogenesis of early‐onset atrial flutter (EOAFL) is unclear. Methods and Results In this cross‐sectional study, participants were enrolled prospectively from 2015 to 2021 in multiple academic centers with a diagnosis of atrial flutter (AFL) confirmed by ECG. EOAFL was defined as a diagnosis of AFL before age 66 years with no concomitant or previous diagnosis of atrial tachyarrhythmias. Family history was adjudicated through baseline questionnaires and direct family interviews about the diagnosis of atrial tachyarrhythmias, stroke, and cardiomyopathy. The primary exposure was a positive family history in first‐degree relatives, and the primary outcome was the odds of EOAFL versus late‐onset AFL. A total of 909 patients were enrolled. Participants with a positive family history of atrial tachyarrhythmias were younger, less likely to be of Black race, and more likely to have EOAFL. The adjusted odds ratio (OR) for EOAFL in those with a positive family history was 1.8 (95% CI, 1.1–3.0). There was an increased odds of EOAFL in those of Black race (OR, 2.1 [95% CI, 1.4–3.2]), alcohol use (OR, 1.6 [95% CI, 1.0–2.6]), and obstructive sleep apnea (OR, 1.9 [95% CI, 1.0–3.4]). Use of cardioselective β blockers or calcium channel blockers before the diagnosis of AFL were associated with a lower odds of EOAFL (OR, 0.5 [95% CI, 0.2–0.9]). Conclusions These findings suggest a potentially hereditary predisposition to EOAFL across race and ethnicity, warranting further study of the genetic contributions to AFL.

Abstract Background Paramedics are increasingly being called to attend patients dying from advanced incurable conditions. However, confidence to deal with such calls varies, with many feeling relatively unskilled in this aspect of their role. A number of interventions have been piloted to improve their skills in end-of-life care (EoLC) but without a fully specified theoretical model. Theory of Change models can provide theoretical and testable links from intervention activities to proposed long-term outcomes and indicate the areas for assessment of effectiveness. This study aimed to develop an intervention for improving paramedic EoLC for patients in the community. Methods A Theory of Change approach was used as the overarching theoretical framework for developing an intervention to improve paramedic end-of-life skills. Nine stakeholders - including specialist community paramedics, ambulance call handlers and palliative care specialists - were recruited to five consecutive online workshops, ranging between 60 and 90 min. Each workshop had 2–3 facilitators. Over multiple workshops, stakeholders decided on the desired impact, short- and long-term outcomes, and possible interventions. During and between these workshops a Theory of Change model was created, with the components shared with stakeholders. Results The stakeholders agreed the desired impact was to provide consistent, holistic, patient-centred, and effective EoLC. Four potential long-term outcomes were suggested: (1) increased use of anticipatory and regular end-of-life medications; (2) reduced end-of-life clinical and medication errors; (3) reduced unnecessary hospitalisations; (4) increased concordance between patient preferred and actual place of death. Key interventions focused on providing immediate information on what to do in such situations including: appraising the situation, developing an algorithm for a treatment plan (including whether or not to convey to hospital) and how to identify ongoing support in the community. Conclusions A Theory of Change approach was effective at identifying impact, outcomes, and the important features of an end-of-life intervention for paramedics. This study identified the need for paramedics to have immediate access to information and resources to support EoLC, which the workshop stakeholders are now seeking to develop as an intervention.

Background American Heart Association guidelines specify infarct core volume as 1 determinant of eligibility for endovascular thrombectomy. Therefore, it is important to understand how time‐dependent infarct core growth translates to a patient's declining probability of thrombectomy eligibility. Modeling the probability that a patient with suspected large‐vessel occlusion would qualify for thrombectomy on the basis of their expected time from stroke onset to treatment can help inform the optimal prehospital emergency transport protocols, maximizing the likelihood of an excellent patient outcome. Methods We extended a published physiological model of infarct core growth to derive a decay curve of thrombectomy eligibility (based on a given infarct core volume threshold) as a function of time from stroke onset. We then adapted an existing model of the time‐dependent probability of an excellent outcome to incorporate this decay curve. Using the adapted model, we determined the optimal prehospital emergency transport protocols in Alberta, Canada, and compared these with the protocols that assumed all patients were thrombectomy eligible. Results The probability of qualifying for thrombectomy decays exponentially as time elapses from stroke onset. We found that the area where mothership is the optimal transport protocol increased by 18.6% after incorporating our decay curve of thrombectomy eligibility into the underlying optimization model. The benefit of mothership versus drip‐and‐ship also increased in the areas where mothership was favored, and in areas where drip‐and‐ship was favored, the benefit of drip‐and‐ship weakened. We also performed a number of sensitivity analyses to observe how these results change on the basis of our assumptions for model parameters. Conclusion This methodology provides a novel, physiology‐based approach to derive a thrombectomy eligibility curve. These models are necessary to better optimize prehospital transport decisions and consequently improve outcomes of patients with suspected large‐vessel occlusion.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Aguilar-Ramirez et al. examine cross-sectional associations between adiposity and metabolic traits among Mexican adults. Their findings suggest that higher total and central adiposity relate adversely, whilst higher gluteo-femoral adiposity relates favourably, to numerous metabolic factors relevant to disease risk.

Background: Saliva has been considered a suitable sample material for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA testing, but uncertainty remained regarding sensitivity and reliability of different saliva collection methods. Objectives: This study aimed to investigate the potential utility of expectorated saliva (ES) and drooled saliva (DS) for community mass testing. Study design: Self-collected ES and DS samples were obtained in a prospective cohort study with 2,878 participants. The utility of saliva for SARS-CoV-2 qRT-PCR testing was assessed by comparing the capacity to detect SARS-CoV-2 positive cases with results for self-collected combined throat and nose (CTN) swabs. Additionally, quantification cycle (Cq) values were compared. Results: ES- and DS-based tests showed the same high level of concordance (98% vs 98%) with CTN swab-based results. Sensitivity was higher for DS (94%) than for ES (83%) or CTN swab (90%) but differences were statistically not significant. Comparing only symptomatic cases, however, a significantly higher sensitivity of DS (96%) than of ES (76%) or CTN swab (91%) was observed. Cq values of saliva and swab specimen were significantly correlated and appeared to be not impacted by age or other potentially confounding factors. Conclusions: Saliva-based SARS-CoV-2 RNA testing showed high diagnostic accuracy and can be considered an alternative where swabbing may not be tolerated or operationally feasible. DS yielded the same or better diagnostic performance compared to ES and may present a preferred option with reduced aerosol risk and increased compliance.

Patients who have contracted coronavirus disease 2019 (COVID-19) have a wide variety of complications, many of them involving the respiratory system. One noted complication has been pneumomediastinum. The 63-year-old gentleman, in this case, had contracted COVID-19 and was admitted to the hospital for hypoxemia. He required high-flow nasal canula oxygen but did not get intubated. On day 12 of admission, the patient had a rapid hypoxemic episode after rising from a chair and fell. Diffuse airspace infiltrates were seen on chest x-ray, signifying a possible pneumomediastinum. A CT scan confirmed pneumomediastinum, and the likely mechanism was a tracheal breach just superior to the carina. This case highlights a unique mechanism as few papers have described this etiology with such clear imaging. Surgical treatment options were considered since the likely etiology could be traced to the tracheal defect, but the patient was ultimately managed conservatively with high flow nasal cannula oxygen.

Here, the authors design a multiplex serology platform to quantitatively measure antibodies against 20 infectious agents in UK Biobank participants and confirm associations of antibody responses with sociodemographic characteristics, HLA genetic variants, and disease outcomes.

Introduction Although higher risks of infectious diseases among individuals with diabetes have long been recognized, the magnitude of these risks is poorly described, particularly in lower income settings. This study sought to assess the risk of death from infection associated with diabetes in Mexico.Research design and methods Between 1998 and 2004, a total of 159 755 adults ≥35 years were recruited from Mexico City and followed up until January 2021 for cause-specific mortality. Cox regression yielded adjusted rate ratios (RR) for death due to infection associated with previously diagnosed and undiagnosed (HbA1c ≥6.5%) diabetes and, among participants with previously diagnosed diabetes, with duration of diabetes and with HbA1c.Results Among 130 997 participants aged 35–74 and without other prior chronic diseases at recruitment, 12.3% had previously diagnosed diabetes, with a mean (SD) HbA1c of 9.1% (2.5%), and 4.9% had undiagnosed diabetes. During 2.1 million person-years of follow-up, 2030 deaths due to infectious causes were recorded at ages 35–74. Previously diagnosed diabetes was associated with an RR for death from infection of 4.48 (95% CI 4.05–4.95), compared with participants without diabetes, with notably strong associations with death from urinary tract (9.68 (7.07–13.3)) and skin, bone and connective tissue (9.19 (5.92–14.3)) infections and septicemia (8.37 (5.97–11.7)). In those with previously diagnosed diabetes, longer diabetes duration (1.03 (1.02–1.05) per 1 year) and higher HbA1c (1.12 (1.08–1.15) per 1.0%) were independently associated with higher risk of death due to infection. Even among participants with undiagnosed diabetes, the risk of death due to infection was nearly treble the risk of those without diabetes (2.69 (2.31–3.13)).Conclusions In this study of Mexican adults, diabetes was common, frequently poorly controlled, and associated with much higher risks of death due to infection than observed previously, accounting for approximately one-third of all premature mortality due to infection.

Academic CVs are ubiquitous and play an integral role in the assessment of researchers. They define and portray what activities and achievements are considered important in the scientific system. Developing their content and structure beyond the traditional, publication-focused CV has the potential to make research careers more diverse and their assessment fairer and more transparent. This comment presents ten ways to further develop the content and structure of academic CVs. The recommendations are inspired by a workshop of the CV Harmonization Group (H-Group), a joint initiative between researchers on research, academic data infrastructure organizations, and representatives from >15 funding organizations. The proposed improvements aim at inspiring development and innovation in academic CVs for funding agencies and hiring committees.

Mobile phones are increasingly used in community health programmes, but the use of video job-aids that can be displayed on smart phones has not been widely exploited. We investigated the use of video job-aids to support the delivery of seasonal malaria chemoprevention (SMC) in countries in West and Central Africa. The study was prompted by the need for training tools that could be used in a socially distanced manner during the COVID-19 pandemic. Animated videos were developed in English, French, Portuguese, Fula and Hausa, illustrating key steps for administering SMC safely, including wearing masks, washing hands, and social distancing. Through a consultative process with the national malaria programmes of countries using SMC, successive versions of the script and videos were reviewed to ensure accurate and relevant content. Online workshops were held with programme managers to plan how to use the videos in SMC staff training and supervision, and the use of the videos was evaluated in Guinea through focus groups and in-depth interviews with drug distributors and other staff involved in SMC delivery and through direct observations of SMC administration. Programme managers found the videos useful as they reinforce messages, can be viewed at any time and repeatedly, and when used during training sessions, provide a focus of discussion and support for trainers and help retain messages. Managers requested that local specificities of SMC delivery in their setting be included in tailored versions of the video for their country, and videos were required to be narrated in a variety of local languages. In Guinea, SMC drug distributors found the video covered the all the essential steps and found the video easy to understand. However, not all key messages were followed as some of the safety measures, social distancing and wearing masks, were perceived by some as creating mistrust amongst communities. Video job-aids can potentially provide an efficient means of reaching large numbers of drug distributors with guidance for safe and effective distribution of SMC. Not all distributors use android phones, but SMC programmes are increasingly providing drug distributors with android devices to track delivery, and personal ownership of smartphones in sub-Saharan Africa is growing. The use of video job-aids for community health workers to improve the quality delivery of SMC, or of other primary health care interventions, should be more widely evaluated. Author summary During the COVID-19 pandemic, it was important to ensure that core malaria prevention strategies continued. Seasonal malaria chemoprevention (SMC) is the monthly administration of chemoprevention drugs to children to prevent malaria in areas with highly seasonal malaria transmission. In partnership with 13 National Malaria Control Programmes in West and Central Africa, we developed a user-friendly training video to support safe delivery of SMC during COVID-19. The use of the video was evaluated through a case study in Guinea and an online workshop with the programme coordinators. SMC drug distributors found the video covered all the essential steps and was easy to understand. However, not all key messages were followed as social distancing and wearing masks were perceived by some as creating mistrust. Programme coordinators found the video useful as it reinforces messages and can be viewed many times. Video content needed to be adapted to the local setting and narrated in local languages. Not all distributors use android phones but many SMC programmes now provide drug distributors with android devices to use during SMC delivery, so that video job-aids could be more widely used.

Abstract Introduction Retrospective trauma scores are often used to categorise trauma, however, they have little utility in the prehospital or hyper-acute setting and do not define major trauma to non-specialists. This study employed a Delphi process in order to gauge degrees of consensus/disagreement amongst expert panel members to define major trauma. Method A two round modified Delphi technique was used to explore subject-expert consensus and identify variables to define major trauma through systematically collating questionnaire responses. After initial descriptive analysis of variables, Kruskal-Wallis tests were used to determine statistically significant differences (p 70% was achieved on many variables which included the identification of life/limb threatening injuries, deranged physiology, need for intensive care interventions and that extremes of age need special consideration. It was also acknowledged that retrospective injury severity scoring has a role to play but is not the only method of defining major trauma. Various factors had a majority of agreement/disagreement but did not meet the pre-set criteria of 70% agreement. These included the topics of burns, spinal immobilisation and whether a major trauma centre is the only place where major trauma can be managed. Conclusion Based upon the output of this Delphi study, major trauma may be defined as: “Significant injury or injuries that have potential to be life-threatening or life-changing sustained from either high energy mechanisms or low energy mechanisms in those rendered vulnerable by extremes of age”.

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

Summary: Background: Dengue is a mosquito-borne viral infection with increasing global prevalence. It is endemic in more than 100 countries, with a heavy burden in Asia. Ultrasound findings including gallbladder wall thickening, ascites, and pleural effusions secondary to plasma leakage have been described in dengue. We aimed to determine if the presence of point-of-care ultrasound findings early in suspected dengue could predict clinical worsening in ambulatory pediatric patients. Methods: We did a prospective, single-blinded, observational cohort study at a children's hospital in Siem Reap, Cambodia during periods of dengue outbreak. Ambulatory patients were screened and children ages > 3 month and ≤ 16 years with suspected acute, non-severe dengue were enrolled. Subjects had chest and abdominal ultrasound exams. Independently, subjects were evaluated by a blinded physician who determined a treatment plan as per usual practice. Follow-up was conducted 7-10 days after the initial visit. Analysis of ultrasound findings was performed to determine their relationship with outcome measures including need for unplanned hospital visits or admissions. Findings: A total of 2,186 children were screened during periods of national dengue outbreak in Cambodia in consecutive years 2018-2019, and 253 children met eligibility criteria. Results showed patients with gallbladder wall thickening (> 3·0 mm) who were discharged had a significantly more likely need for unplanned visit or hospitalization than those with normal gallbladder wall, 67% (95% CI 44 – 84) versus 17% (95% CI 12 – 24), p < 0.0001. Subjects with any abnormal ultrasound finding were more likely to be directly admitted versus discharged upon initial presentation, 62·2% (95% CI 46.1 – 76.0) versus 19.5% (95% CI 14.8 – 25.4), p < 0.0001. Interpretation: Point-of-care ultrasound findings, particularly gallbladder wall thickening, in suspected early dengue can help predict disease progression in ambulatory patients. Ultrasound has potential to help guide management of suspected dengue patients and resource management during periods of dengue outbreak. Funding: Society for Academic Emergency Medicine Foundation.

Research evaluation is often understood as something similar to a competition, where an evaluation panel’s task is to award the most excellent researchers. This interpretation is challenging, in as far as excellence it is at best a multi-dimensional concept and at worst an ill-defined term because it assumes that there exists some ground truth as to who the very best researchers are and all that an evaluation panel needs to do is uncover this ground truth. Therefore, instead of focusing on competition, the Swiss National Science Foundation focused on active decision-making and sought inspiration in the deliberation proceedings of a jury trial for the design of a new evaluation procedure of an academic award. The new evaluation procedure is based upon fully anonymised documents consisting of three independent parts (achievements, impact and prominence). Before the actual evaluation meeting, the panel, which includes non-academic experts, pre-evaluates all nominations through a pseudo-randomly structured network, such that every nomination is reviewed by six members of the panel only. Evaluation decisions are based upon anonymous votes, structured discussions in the panel, ranking as opposed to rating of nominees and data-rich figures providing an overview of the positioning of the nominee along various dimensions and the ranking provided by the individual panel members. The proceedings are overseen by an academic chair, focusing on content, and a procedural chair, focusing on the process and compliance. Combined, these elements form a highly-structure deliberation procedure, consisting of individual steps, through which nominations proceed and which each either feed into the next step or into the final verdict. The proposed evaluation process has been successfully applied in the real world in the evaluation of the Swiss Science Prize Marcel Benoist, Switzerland’s most prestigious academic award.

Abstract Background Older adults in the emergency department (ED) are at high risk for functional decline, unrecognized delirium, falls, and medication interactions. Holistic assessment by a multidisciplinary team in the ED decreases these adverse outcomes and decreases admissions, but there are many barriers to incorporating this type of care during the ED visit. Methods This is a hybrid type II effectiveness-implementation study using a pre-/post-cohort design (n = 380) at a tertiary care academic ED with an ED observation unit (Obs Unit). The intervention is a two-step protocol of (step 1) ED nurses screening adult patients ≥ 65 years old for geriatric needs using the Delirium Triage Screen, 4-Stage Balance Test, and the Identifying Seniors at Risk score. Patients who have geriatric needs identified by this screening but who do not meet hospital admission criteria will (step 2) be placed in the Obs Unit for multidisciplinary geriatric assessment by the hospital’s geriatric consultation team, physical therapists, occupational therapists, pharmacists, and/or case managers. Not all patients may require all elements of the multidisciplinary geriatric assessment. The Consolidated Framework for Implementation Research: Care Transitions Framework was used to identify barriers to implementation. Lean Six Sigma processes will be used to overcome these identified barriers with the goal of achieving geriatric screening rates of > 80%. Implementation success and associated factors will be reported. For the effectiveness aim, pre-/post-cohorts of adults ≥ 65 years old cared for in the Obs Unit will be followed for 90 days post-ED visit (n = 150 pre and 230 post). The primary outcome is the prevention of functional decline. Secondary outcomes include health-related quality of life, new geriatric syndromes identified, new services provided, and Obs Unit metrics such as length of stay and admission rates. Discussion A protocol for implementing integrated multidisciplinary geriatric assessment into the ED setting has the potential to improve patient functional status by identifying and addressing geriatric issues and needs prior to discharge from the ED. Using validated frameworks and implementation strategies will increase our understanding of how to improve the quality of ED care for older adults in the acute care setting. Trial registration ClinicalTrials.gov Identifier, NCT04068311 , registered 28 August 2019

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India – Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.

Objectives: Pre-pause imaging during cardiopulmonary resuscitation (CPR) involves the acquisition of poor-quality, brief images immediately prior to stopping CPR to allow shorter, better-quality images during the pause. We hypothesize that pre-pause imaging is associated with a decrease in CPR pause length and shorter image acquisition time. Methods: Prospective, interventional cohort study enrolling out-of-hospital (OOH) cardiac arrest patients. Pre-pause imaging involves pre-localizing of the approximate sonographic window during CPR to support subsequent fine tuning when CPR pauses. Physicians were educated on pre-pause imaging and data was recorded prior- and post- introduction of pre-pause imaging into American cardiac life support (ACLS). Timing of CPR pauses and identification of interventions and events during pause were recorded (e.g., intubation, defibrillation, multiple cardiac ultrasounds). Ultrasound (US) images were reviewed for image quality using a 5-point scale. Primary outcome was length of CPR pause with and without pre-pause imaging. Secondary outcome included US length. Results: One hundred and forty five subjects presenting after OOH cardiac arrest were enrolled over 13 months, 70 during the baseline period prior to pre-pause imaging and 75 after pre-pause imaging was integrated into ACLS. Pre-pause imaging decreased CPR pause length from 28.3 s (95%CI 25.1–31.5) to 12.8 s (95%CI 11.9–13.7). US image acquisition time decreased with pre-pause imaging from 20.4 (95%CI 18.0–22.7) to 11.0 s (95%CI 10.1–11.8). US image quality was unchanged despite the decrease in image acquisition time. (3.0 (95%CI 2.8–3.2) vs 2.7 (95%CI 2.5–2.9)). Multivariate modeling showed that ultrasound did not prolong CPR pause length. Conclusion: Pre-pause imaging was associated with significant decrease in CPR pause length and US image acquisition time. Pre-pause imaging should be encouraged for any clinicians who use ultrasound during ACLS.

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India – Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India – Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs.

Like all educational institutions, community colleges rapidly shifted to online instruction in the wake of the COVID-19 pandemic. However, little is known about what factors shaped individual college responses. This survey of distance education leaders (N = 45) in the California community colleges system aimed to: a) characterize pre-COVID distance education resources, emergency responses to the pandemic, and readiness for online instruction in the fall, and b) determine how pre-COVID distance education resources, emergency responses, and fall readiness relate to each other. We find wide variability in pre-COVID distance education resources. These pre-existing resources were related to institutions’ responses: Colleges with fewer pre-COVID resources focused on foundational efforts such as creating online student services, while institutions with greater pre-COVID resources offered somewhat broader responses to training students and faculty in skills to successfully transition online. Finally, although colleges improved their readiness for continued remote instruction in the fall term in terms of training faculty and providing students with technology to access classes, respondents estimated that roughly a third of students would still face barriers accessing remote classes.

Background: UK Biobank is a large prospective study that recruited 500,000 participants aged 40 to 69 years, between 2006-2010.The study has collected (and continues to collect) extensive phenotypic and genomic data about its participants. In order to enhance further the value of the UK Biobank resource, a wide range of biochemistry markers were measured in all participants with an available biological sample. Here, we describe the approaches UK Biobank has taken to minimise error related to sample collection, processing, retrieval and assay measurement. Methods: During routine quality control checks, the laboratory team observed that some assay results were lower than expected for samples acquired during certain time periods. Analyses were undertaken to identify and correct for the unexpected dilution identified during sample processing, and for expected error caused by laboratory drift of assay results. Results: The vast majority (92%) of biochemistry serum assay results were assessed to be not materially affected by dilution, with an estimated difference in concentration of less than 1% (i.e. either lower or higher) than that expected if the sample were unaffected; 8.3% were estimated to be diluted by up to 10%; very few samples appeared to be diluted more than this. Biomarkers measured in urine (creatinine, microalbumin, sodium, potassium) and red blood cells (HbA1c) were not affected. In order to correct for laboratory variation over the assay period, all assay results were adjusted for date of assay, with the exception of those that had a high biological coefficient of variation or evident seasonal variability: vitamin D, lipoprotein (a), gamma glutamyltransferase, C-reactive protein and rheumatoid factor. Conclusions: Rigorous approaches related to sample collection, processing, retrieval, assay measurement and data analysis have been taken to mitigate the impact of both systematic and random variation in epidemiological analyses that use the biochemistry assay data in UK Biobank.

Background: Antibodies against the HPV16 oncoprotein E6 are promising biomarkers for HPV16-driven oropharyngeal cancer (HPV16-OPC) due to their high sensitivity and specificity, and prospective manifestation. In previous studies, 0•7% of controls without HPV-associated malignancies were HPV16 E6 seropositive of which only a minority is expected to develop HPV16-driven cancer. We aimed to characterise HPV16 E6 antibodies in individuals without HPV-associated malignancies. Methods: We analysed serum antibodies against HPV16 E6, E7, L1 and HPV18 L1 in a random sample (n = 9,695) of the prospective UK Biobank cohort (UKB). Excluding individuals with potentially HPV-associated malignancies (n = 192), we assessed risk factors for seropositivity by logistic regression. Findings: In individuals without potentially HPV-associated malignancies (n = 9,503), the HPV16 E6 seroprevalence was 0•8%. Seropositivity against HPV16 E6 and all other HPV antigens was strongly associated with sexual behaviour. The seroprevalence of HPV16 E6, L1 and HPV18 L1 increased with the number of lifetime sex partners (ptrend

Background: UK Biobank is a large prospective study that recruited 500,000 participants aged 40 to 69 years, between 2006-2010.The study has collected (and continues to collect) extensive phenotypic and genomic data about its participants. In order to enhance further the value of the UK Biobank resource, a wide range of biochemistry markers were measured in all participants with an available biological sample. Here, we describe the approaches UK Biobank has taken to minimise error related to sample collection, processing, retrieval and assay measurement. Methods: During routine quality control checks, the laboratory team observed that some assay results were lower than expected for samples acquired during certain time periods. Analyses were undertaken to identify and correct for the unexpected dilution identified during sample processing, and for expected error caused by laboratory drift of assay results. Results: The vast majority (92%) of biochemistry serum assay results were assessed to be not materially affected by dilution, with an estimated difference in concentration of less than 1% (i.e. either lower or higher) than that expected if the sample were unaffected; 8.3% were estimated to be diluted by up to 10%; very few samples appeared to be diluted more than this. Biomarkers measured in urine (creatinine, microalbumin, sodium, potassium) and red blood cells (HbA1c) were not affected. In order to correct for laboratory variation over the assay period, all assay results were adjusted for date of assay, with the exception of those that had a high biological coefficient of variation or evident seasonal variability: vitamin D, lipoprotein (a), gamma glutamyltransferase, C-reactive protein and rheumatoid factor. Conclusions: Rigorous approaches related to sample collection, processing, retrieval, assay measurement and data analysis have been taken to mitigate the impact of both systematic and random variation in epidemiological analyses that use the biochemistry assay data in UK Biobank.

Background Door-to-needle time (DTN) has an important impact on thrombolysis and reperfusion outcomes in the treatment of acute ischaemic stroke. This systematic review is a critical synthesis of studies evaluating DTN reduction strategies.Method Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, CINAHL, ProQuest dissertations and LILACS were used as bibliographic databases for primary literature. CIHI, Health Quality Council of Alberta, Health Quality Ontario and websites of heart and stroke associations in Canada, USA, UK, Australia and New Zealand were used as sources of grey literature. Searched reports were screened by title and abstract, and full texts were located for review. Articles quality was evaluated using National Institute of Health’s Study Quality Assessment tools. Methods for improving DTN were categorised under 13 DTN reduction strategies, primarily adapted from the Target: Stroke Phase II recommendations, and including two additional categories: Strategies not encompassed by any Target: Stroke recommendation, and Combinations of Interventions.Results 96 studies (4 randomised control trials, 1 review, 91 observational pre/post studies) were included in the review. All strategies and interventions resulted in a reduction of DTN. Approaches using combinations of interventions were the most effective at reducing DTN (33.77% DTN reduction, standard mean difference=1.857, 95% CI=1.510–2.205), and were more effective than approaches using only a single strategy (p=0.040). DTN reduction was associated with the duration of the DTN reduction programme at each facility (p=0.006).Interpretation The greatest reductions in DTN were observed when implementing combinations of DTN reduction strategies, although there was no significant advantage to implementing more than two strategies simultaneously.PROSPERO registration number 42016036215.

Background: Vitamin D deficiency has been associated with multiple diseases, but the causal relevance and underlying processes are not fully understood. Elucidating the mechanisms of action of drug treatments in humans is challenging, but application of functional genomic approaches in randomized trials may afford an opportunity to systematically assess molecular responses. Methods: In the Biochemical Efficacy and Safety Trial of Vitamin D (BEST-D), a double-blind, placebo-controlled, dose-finding, randomized clinical trial, 305 community-dwelling individuals aged over 65 years were randomly allocated to treatment with vitamin D3 4000 IU, 2000 IU or placebo daily for 12 months. Genome-wide genotypes at baseline, and transcriptome and plasma levels of cytokines (IFN-γ, IL-10, IL-8, IL-6 and TNF-α) at baseline and after 12 months, were measured. The trial had >90% power to detect 1.2-fold changes in gene expression. Findings: Allocation to vitamin D for 12-months was associated with 2-fold higher plasma levels of 25-hydroxy-vitamin D (25[OH]D, 4000 IU regimen), but had no significant effect on whole-blood gene expression (FDR

Background: Randomised controlled trials demonstrating improved longevity are needed to justify high-dose vitamin D supplementation for older populations. Objectives: To demonstrate the feasibility of a large trial (n ≈ 20,000) of high-dose vitamin D in people aged 65–84 years through general practitioner (GP) practices, and to cluster randomise participating practices between open-label and double-blind randomisation to compare effects on recruitment, compliance and contamination. Design: Twenty GP practices were randomised in matched pairs between open-label and double-blind allocation. Within each practice, patients were individually randomised to vitamin D or control (i.e. no treatment or placebo). Participants were invited to attend their GP practice to provide a blood sample and complete a lifestyle questionnaire at recruitment and again at 2 years. Randomisation by telephone followed receipt of a serum corrected calcium assay confirming eligibility ( 400 IU vitamin D per day at 2 years was 5.0% in open practices and 4.8% in double-blind practices. Mean serum 25(OH)D concentration was 51.5 nmol/l [95% confidence interval (CI) 50.2 to 52.8 nmol/l] with 82.6% of participants

This article uses fixed effects models to estimate differences in contemporaneous and downstream academic outcomes for students who take courses virtually and face-to-face—both for initial attempts and for credit recovery. We find that while contemporaneous outcomes are positive for virtual students in both settings, downstream outcomes vary by attempt type. For first-time course takers, virtual course taking is associated with decreases in the likelihood of taking and passing follow-on courses and in graduation readiness (based on a proxy measure). For credit recovery students, virtual course taking is associated with an increased likelihood of taking and passing follow-on courses and being in line for graduation. Supplemental analyses suggest that selection on unobservables would have to be substantial to render these results null.

Introduction Emergency department (ED)-initiated palliative care has been shown to improve patient-centred outcomes in older adults with serious, life-limiting illnesses. However, the optimal modality for providing such interventions is unknown. This study aims to compare nurse-led telephonic case management to specialty outpatient palliative care for older adults with serious, life-limiting illness on: (1) quality of life in patients; (2) healthcare utilisation; (3) loneliness and symptom burden and (4) caregiver strain, caregiver quality of life and bereavement.Methods and analysis This is a protocol for a pragmatic, multicentre, parallel, two-arm randomised controlled trial in ED patients comparing two established models of palliative care: nurse-led telephonic case management and specialty, outpatient palliative care. We will enrol 1350 patients aged 50+ years and 675 of their caregivers across nine EDs. Eligible patients: (1) have advanced cancer (metastatic solid tumour) or end-stage organ failure (New York Heart Association class III or IV heart failure, end-stage renal disease with glomerular filtration rate

BackgroundObservational studies have reported that higher plasma 25-hydroxyvitamin D (25[OH]D) concentrations are associated with lower risks of diabetes, but it is unclear if these associations are causal. The aim of this study was to test the relevance of 25(OH)D for type 2 diabetes using genetically instrumented differences in plasma 25(OH)D concentrations.Methods and findingsData were available on four 25(OH)D single nucleotide polymorphisms (SNPs; n = 82,464), plasma 25(OH)D concentrations (n = 13,565), and cases with diabetes (n = 5,565) in the China Kadoorie Biobank (CKB). The effects on risk of diabetes were assessed by a genetic score using two 25(OH)D synthesis SNPs (DHCR7-rs12785878 and CYP2R1-rs10741657), with and without the addition of SNPs affecting the transport (GC/DBP-rs2282679) and catabolism (CYP24A1-rs6013897) of 25(OH)D. The CKB results were combined in a meta-analysis of 10 studies for the 2 synthesis SNPs (n = 58,312 cases) and 7 studies for all 4 SNPs (n = 32,796 cases). Mean (SD) 25(OH)D concentration was 62 (20) nmol/l in CKB, and the per allele effects of genetic scores on 25(OH)D were 2.87 (SE 0.39) for the synthesis SNPs and 3.54 (SE 0.32) for all SNPs. A 25-nmol/l higher biochemically measured 25(OH)D was associated with a 9% (95% CI: 0%-18%) lower risk of diabetes in CKB. In a meta-analysis of all studies, a 25-nmol/l higher genetically instrumented 25(OH)D concentration was associated with a 14% (95% CI: 3%-23%) lower risk of diabetes (p = 0.01) using the 2 synthesis SNPs. An equivalent difference in 25(OH)D using a genetic score with 4 SNPs was not significantly associated with diabetes (odds ratio 8%, 95% CI: -1% to 16%, lower risk, p = 0.07), but had some evidence of pleiotropy. A limitation of the meta-analysis was the access only to study level rather than individual level data.ConclusionsThe concordant risks of diabetes for biochemically measured and genetically instrumented differences in 25(OH)D using synthesis SNPs provide evidence for a causal effect of higher 25(OH)D for prevention of diabetes.