Developing and testing an arts-based, digital knowledge translation tool for parents about childhood croup Croup is a common viral illness affecting 80,000 children annually in Canada. Between 7-31% of children seen in an ED for croup are admitted to hospital due to health care provider apprehension. However, over 60% of children with croup experience mild symptoms that can be safely managed at home. Emerging evidence suggests that initiatives targeting healthcare consumers (i.e., patients, parents, families) can inform decision making and shape treatment expectations. Previous research demonstrates that innovative media are superior to traditional standard health sheets for transferring information to consumers.

The purpose of this project was to develop, refine, and test the usability of a whiteboard animation video for parents about childhood croup. Parents rated the tools highly across all usability items, suggesting that creative tools developed using multi-method development processes can help facilitate the uptake of health information in parents.
Covid-19 Associated Hepatitis in children (CAHC) during the second wave of SARS-CoV-2 infections in Central India: Is it a complication or transient phenomenon. Objective: While pediatric population has largely remained free of severe COVID-19, in some cases SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). We mention another unique presentation subsequent to asymptomatic infection of SARS-CoV-2, a unique form of hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The contrasting clinical presentations, temporal association and viral parameters of CAH-C cases, to the MIS-C cases are presented here. Methods: As a retrospective and follow-up observational study we reviewed all children testing positive for SARS-CoV-2 during study period. Children presenting with sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice, lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis or previous underlying liver disease (b) multi-system involvement were classified as CAH-C, are described here. Results: Among 475 children who tested positive, 47 patients presented with hepatitis, 37 patients who had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers and uneventful recovery following supportive treatment. Whereas remaining 10 MIS-C hepatitis had protracted illness, multiple system involvement, required admission to critical care, and had mortality of 30%. Conclusion: With the emergence of newer variants of concern (VOC) including the Delta variant which predominated the second wave of infections in India and has now spread to more than 142 countries with changing presentations, CAH-C might be one of them. Cases of such new entities need to be identified early and differentiated from other emerging syndromes in children during the ongoing pandemic for preventing adversities by timely intervention.
Remote exposure to secondhand tobacco smoke is associated with lower exercise capacity through effects on oxygen pulse, a proxy of cardiac stroke volume BackgroundPast exposure to secondhand tobacco smoke (SHS) is associated with exercise limitation. Pulmonary factors including air trapping contribute to this limitation but the contribution of cardiovascular factors is unclear.

ObjectiveTo determine contribution of cardiovascular mechanisms to SHS-associated exercise limitation.

MethodsWe examined the cardiovascular responses to maximum effort exercise in 245 never-smokers with remote, prolonged occupational exposure to SHS and no known history of cardiovascular disease. We estimated the contribution of oxygen-pulse (proxy for cardiac stroke volume) and changes in systolic (SBP) and diastolic blood pressures (DBP) and heart rate (HR) towards exercise capacity, and examined whether the association of SHS with exercise capacity was mediated through these variables.

ResultsAt peak exercise (highest workload completed [WattsPeak]=156{+/-}46 watts [135{+/-}33 %predicted]), oxygen consumption (VO2Peak) and oxygen-pulse (O2-PulsePeak) were 1,557{+/-}476 mL/min (100{+/-}24 %predicted) and 11.0{+/-}3.0 mL/beat (116{+/-}25 %predicted), respectively, with 29% and 3% participants not achieving their predicted normal range. Oxygen saturation at peak exercise was 98{+/-}1% and remained >93% in all participants. Sixty-six percent showed hypertensive response to exercise. In models adjusted for covariates, WattsPeak was associated directly with O2-PulsePeak, HRPeak, and SBPPeak and inversely with SHS, air trapping (RV/TLC), and rise of SBP over workload (all P<0.01). Moreover, SHS exposure association with WattsPeak was substantially (41%) mediated through its effect on O2-PulsePeak (P<0.038). Although not statistically significant, a considerable proportion (36%) of air trapping effect on WattsPeak seemed to be mediated through O2-PulsePeak (P=0.078). The likelihood of having baseline respiratory symptoms (modified Medical Research Council score [&ge;]1) was associated with steeper rise in SBP over workload (P<0.01).

ConclusionIn a never-smoker population with remote exposure to SHS, abnormal escalation of afterload and an SHS-associated reduction in cardiac output contributed to lower exercise capacity.

Key messagesO_ST_ABSWhat is the key question?C_ST_ABSWhat are the cardiovascular health effects of past exposure to secondhand tobacco smoke in never-smokers? How do pulmonary and cardiovascular systems interact in this setting?

What is the bottom line?Healthy never-smokers with history of remote past exposure to secondhand tobacco smoke have an abnormal cardiovascular response to exercise, which is characterized by a stroke volume and thus an exercise capacity that are reduced proportional to their years of exposure to secondhand tobacco smoke.

Why read on?The abnormal cardiovascular response to exercise in this population reveals the presence of an occult or subclinical pathology that impairs the cardiopulmonary functional reserve and reduces the efficiency of bodys oxygen delivery machinery, which could be disadvantageous during the times of increased cardiopulmonary output demands as in physiological distress or disease. CD19+IgD+CD27- naive B Cells as predictors of humoral response to COVID 19 mRNA vaccination in immunocompromised patients Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19+IgD+CD27- naive B cells was strongly associated with antibody levels ({rho}=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-{micro}l increase, 95%CI 1.02-1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at [&ge;]61 naive B cells per {micro}l to discriminate between patients with and without an optimal antibody response. Consequently, measuring naive B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response. Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis: a cohort study in UK Biobank ObjectivesTo evaluate the benefit of combining polygenic risk scores (PRS) with the QCancer-10 (colorectal cancer) non-genetic risk prediction model to identify those at highest risk of colorectal cancer (CRC).

DesignPopulation based cohort study. Six different PRS for CRC were developed (using LDpred2 PRS software, clumping and thresholding approaches, and genome-wide significant models). The top-performing genome-wide and GWAS-significant PRS were then combined with QCancer-10 and performance compared to QCancer-10 alone. Case-control (logistic regression) and time-to-event (Cox proportional hazards) analyses were used to evaluate risk model performance in men and women.

Setting and participantsUK Biobank Study. A total of 434587 individuals with complete genetic and QCancer-10 predictor data were included in the QCancer-10+PRS modelling cohorts.

Main outcome measuresPrediction of colorectal cancer diagnosis by genetic, non-genetic and combined risk models.

FindingsPRS derived using the LDpred2 program performed best, with an odds-ratio per standard deviation of 1.58, and top age- and sex-adjusted C-statistic of 0.733 (95% confidence interval 0.710 to 0.753) in logistic regression models in the validation cohort. Integrated QCancer-10+PRS models out-performed QCancer-10 alone. In men, the integrated LDpred2 (QCancer-10+LDP) model produced a C-statistic of 0.730 (0.720 to 0.741) and explained variation of 28.1% (26.3% to 30.0%), compared with 0.693 (0.682 to 0.704) and 21.0% (18.9% to 23.1%) for QCancer-10 alone. Performance improvements in women were similar. In the top 20% of individuals at highest absolute risk, the sensitivity of QCancer-10+LDP models for predicting CRC diagnosis within 5 years was 47.6% in men and 42.5% in women, with respective 3.49-fold and 2.75-fold absolute increases in the top 5% of risk compared to average. Decision curve analysis showed that adding PRS to QCancer-10 improved net-benefit and interventions avoided, across most probability thresholds.

ConclusionsIntegrating PRS with QCancer-10 significantly improves risk prediction over QCancer-10 alone. Evaluation of risk stratified population screening using this approach is warranted.

Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIRisk stratification based on genetic or environmental risk factors could improve cancer screening outcomes
C_LIO_LINo previously published study has examined integrated models combining genome-wide PRS and non-genetic risk factors beyond age
C_LIO_LIQCancer-10 (colorectal cancer) is the top-performing non-genetic risk prediction model for CRC
C_LI

What this study addsO_LIAdding PRS to the QCancer-10 (colorectal cancer) risk prediction model improves performance and clinical benefit, with greatest gain from the LDpred2 genome-wide PRS, to a level that suggests utility in stratifying CRC screening and prevention
C_LI Deep learning for caries detection using optical coherence tomography Early detection of dental caries has been one of the most predominant topics studied over the last few decades. Conventional examination through visual-tactile inspection and radiography can be inaccurate and destructive to the tooth structure. The development of optical coherence tomography (OCT) has given dentistry an alternative diagnostic technique, which has been proven by numerous studies, that it has better sensitivity, specificity, and non-invasive characteristics. The growing popularity of artificial intelligence (AI) also contributes to a more efficient and effective way of image-based detection and decision-making. However, previous studies, which have attempted to employ AI for caries assessment, did not incorporate high-quality ground truth data. Therefore, this study aims to bypass this issue and highlights the importance of high-quality data. A two-phase study was carried out to explore different methods for caries detection. Initially, the comparison of caries detection based on OCT and apical radiography by 5 experienced clinicians was conducted. Then, five convolutional neural networks (CNNs), including AlexNet, VGG-16, ResNet-152, Xception, and ResNext-101, in the scope of AI were employed to detect caries and compared with the findings of the 5 clinicians. The data was preprocessed and labeled with the ground truth corresponding to microcomputed tomography (micro-CT) with rigorous definition. The weighted Kappa statistics suggested that OCT ({varkappa}= .699, SD = .090) showed a higher accuracy rate than radiography ({varkappa}= .407, SD = .049), and CNNs ({varkappa}= .860, SD = .049) were rated higher than clinicians ({varkappa}= .679, SD = .113), both at a .05 significance level. The best result was carried out by ResNet-152, which demonstrated a high accuracy rate of 95.21% and a sensitivity of 98.85%. These findings illustrate the importance of ground truth data for AI training and the potential of deep CNN algorithms combined with OCT for diagnosing dental caries. Genetic factors affecting immune phenotypes in type 1 diabetes Large inter-individual variability in immunological cell composition and function determines immune responses in general and susceptibility to immune-mediated diseases in particular. While much has been learned about the genetic variants relevant for type 1 diabetes, the pathophysiological mechanisms through which these variations exert their effects are unknown. In this study, we characterize the genetic factors influencing immune responses in patients with type 1 diabetes. Genetic variants that determine susceptibility to T1D significantly affect T cell composition. Specifically, the CCR5+ regulatory T cells associate with T1D through the CCR region, suggesting a shared genetic regulation. Genome-wide quantitative trait loci (QTL) mapping analysis of immune traits revealed 15 genetic loci that influence immune responses in T1D. Among them, 12 have never been reported in healthy population studies, implying a disease-specific genetic regulation. Altogether this study provides new insights into the genetic factors that affect immunological responses in T1D. A wind speed threshold for increased outdoor transmission of coronavirus: An ecological study BackgroundTo examine whether outdoor transmission may contribute to the COVID-19 epidemic, we hypothesized that slower outdoor wind speed is associated with increased risk of transmission when individuals socialize outside.

MethodsDaily COVID-19 incidence reported in Suffolk County, NY, between March 16th - December 31st, 2020, was the outcome. Average wind speed and maximal daily temperature were collated by the National Oceanic and Atmospheric Administration. Negative binomial regression was used to model incidence rates while adjusting for susceptible population size.

ResultsCases were very high in the initial wave but diminished once lockdown procedures were enacted. Most days between May 1st, 2020, and October 24th, 2020, had temperatures 16-28{degrees}C and wind speed diminished slowly over the year and began to increase again in December 2020. Unadjusted and multivariable-adjusted analyses revealed that days with temperatures ranging between 16-28{degrees}C where wind speed was <8.85 kilometers per hour (KPH) had increased COVID-19 incidence (aIRR=1.45, 95% C.I.=[1.28-1.64], P<0.001) as compared to days with average wind speed [&ge;]8.85 KPH.

ConclusionThroughout the U.S. epidemic, the role of outdoor shared spaces such as parks and beaches has been a topic of considerable interest. This study suggests that outdoor transmission of COVID-19 may occur by noting that the risk of transmission of COVID-19 in the summer was higher on days with low wind speed. Outdoor use of increased physical distance between individuals, improved air circulation, and use of masks may be helpful in some outdoor environments where airflow is limited. Combination of Mifepristone and Methotrexate for the Treatment of Ectopic Pregnancy: A Systematic Review Protocol AimThe increase in ectopic pregnancies (EP) in recent years and their impact on female fertility forces physicians to find an effective medical treatment that can avoid surgery as soon as possible. Methotrexate and mifepristone are widely used in conservative treatments, but the effectiveness of this combination is not completely clear. Therefore, the aims in this meta-analysis are to systematically analyze the efficacy of mifepristone combined with methotrexate in the treatment of EP through existing studies and draw a conclusion, to evaluate the advantages and disadvantages of inclusion trials and propose improvement measures and scientific designing schemes.

MethodsSix databases will be searched, including PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure(CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang Database (WF). Randomized controlled trials published up to October 2020 will be selected. Search terms include mifepristone, methotrexate, EP, and random (free word/synonym expansion). We will include trials in which the experimental group was treated with combination of mifepristone and methotrexate, and the control group was treated with mifepristone alone. Revman 5.4 will be used to evaluate the quality of the trials, and the effect model will be selected to analyze the results. Cure rate will be the main outcome index.

ResultOnly when we finish this meta analysis can we get the result.

DiscussionThe results of this study will provide evidence for the efficacy of mifepristone combined with methotrexate therapy in the treatment of EP. The site of onset of pregnancy should be taken into account.

PROSPERO registration numberCRD42021246757 Spatial Allocation of Scarce COVID-19 Vaccines The COVID-19 Vaccines Global Access (COVAX) is an initiative led by the World Health Organization (WHO) and other partners that aims for an equitable access of COVID-19 vaccines. Despite a potential heterogeneous disease burden across space, countries receiving allotments of vaccines via COVAX may want to follow WHOs allocation rule and distribute vaccines to their jurisdictions based on the jurisdictions relative population size. Utilizing economic-epidemiological modeling, we benchmark the performance of this ad hoc allocation rule by comparing it to the rule that minimizes the economic damages and expenditures over time, including a penalty cost representing the social costs of deviating from the ad hoc allocation. Under different levels of vaccine scarcity and different demographic characteristics, we consider scenarios where length of immunity and compliance to travel restrictions vary, and consider the robustness of the rules when assumptions regarding these factors are incorrect. The benefits from deviating are especially high when immunity is permanent, when there is compliance to travel restrictions, when the supply of vaccine is low, and when there is heterogeneity in demographic characteristics. Interestingly, a lack of compliance to travel restrictions pushes the optimal allocations of vaccine towards the ad hoc and improves the relative robustness of the ad hoc rule, as the mixing of the populations reduces the spatial heterogeneity in disease burden.

JEL ClassificationC61, H12, H84, I18, Q54 The Unequal Burden of the Covid-19 Pandemic: Racial/Ethnic Disparities in US Cause-Specific Mortality ObjectivesTo quantify changes in all-cause and cause-specific mortality by race and ethnicity between 2019 and 2020.

MethodsUsing 2019 and 2020 provisional death counts from the National Center for Health Statistics and population estimates from the US Census Bureau, we estimate age-standardized death rates by race/ethnicity and attribute changes in mortality to various causes of death. We also examine how patterns of change across racial/ethnic groups vary by age and sex.

ResultsCovid-19 death rates in 2020 were highest in the Hispanic community whereas Black individuals had the largest increase in all-cause mortality between 2019 and 2020. Increases in mortality from heart disease, diabetes, and external causes of death accounted for the adverse trend in all-cause mortality within the Black population. Percentage increases in all-cause mortality were similar for men and women and for ages 25-64 and 65+ for Black and White populations, but increases were greatest for working-aged men among the Hispanic population.

ConclusionsExamining increases in non-Covid-19 causes of death is essential for fully capturing both the direct and indirect impact of the Covid-19 pandemic on racial/ethnic mortality disparities. Prospectively validated disease-agnostic predictive medicine with augmented intelligence Despite numerous superhuman achievements in complex challenges1,2, standalone AI does not free life science from the long-term bottleneck of linearly extracting new knowledge from exponentially growing new data3, severely limiting the success rate of drug discovery4. Inspired by the state-of-the-art AI training methods, we trained a human-centric hybrid augmented intelligence5 (HAI) to learn a foundation model6 that extracts all-encompassing knowledge of human physiology and diseases. To evaluate the quality of HAIs extracted knowledge, we designed the public, prospective prediction of pivotal ongoing clinical trial outcomes at large scale (PROTOCOLS) challenge to benchmark HAIs real-world performance of predicting drug clinical efficacy without access to human data. HAI achieved a 10.5-fold improvement from the baseline with 99% confidence7 in the PROTOCOLS validation, readily increasing the average clinical success rate of investigational new drugs from 7.9%8 to 90% for almost any human diseases9,10. The validated HAI confirms that exponentially extracted knowledge alone is sufficient for accurately predicting drug clinical efficacy, effecting a total reversal of Erooms law4. HAI is also the worlds first clinically validated model of human aging that could substantially speed up the discovery of preventive medicine for all age-related diseases11. Our results demonstrate that disruptive breakthroughs necessitate the smallest team size to attain the largest HAI for optimal knowledge extraction from high-dimensional low-quality data space, thus establishing the first prospective proof of the previous discovery that small teams disrupt12. The global adoption of training HAI provides a well-beaten economic path to mass-produce scientific and technological breakthroughs via exponential knowledge extraction and better designs of data labels for training better-performing AI13. Tau pathology mediates the effects of amyloid on neocortical tau propagation and neurodegeneration among non-demented individuals Amyloid-{beta}(A{beta}) pathology is associated with greater tau pathology and facilitates tau propagation from the medial temporal lobe (MTL) to the neocortex, where tau is closely associated with local neurodegeneration. The degree of the involvement of A{beta} versus existing tau pathology in tau propagation and neurodegeneration has not been fully elucidated in human studies. Careful quantification of these effects can inform the development and timing of therapeutic interventions. We conducted causal mediation analyses to investigate these questions in two longitudinal studies of individuals without dementia. As proxies of neurodegeneration, we investigated cerebral blood flow (CBF), glucose metabolism, and regional volume. We first confirmed that A{beta} moderates the association between tau in the entorhinal cortex and in the inferior temporal gyrus, a neocortical region exhibiting early tau pathology (amyloid group x entorhinal tau interaction term {beta} = 0.486, SE = 0.126, p < 0.001 in the Baltimore Longitudinal Study of Aging [BLSA]; {beta} = 0.658, SE = 0.137, p < 0.001 in the Alzheimers Disease Neuroimaging Initiative [ADNI]). In causal mediation analyses accounting for this facilitating effect of amyloid, amyloid positivity had a statistically significant direct effect on inferior temporal tau as well as an indirect effect via entorhinal tau (average direct effect [ADE]= 0.46, p < 0.001 and average causal mediation effect [ACME]= 0.46, p = 0.0012 in BLSA; ADE= 0.47, p < 0.001 and ACME= 0.254, p = 0.021 in ADNI). Entorhinal tau mediated up to 50% of the total effect of amyloid on inferior temporal tau. Higher inferior temporal tau was associated with lower colocalized CBF, glucose metabolism, and regional volume, whereas amyloid had only an indirect effect on these measures via tau, implying tau as the primary driver of neurodegeneration (amyloid-CBF indirect effect ACME = -0.29, p = 0.014 in BLSA; amyloid-volume indirect effect ACME = -0.23, p < 0.001 in ADNI). Our findings suggest targeting amyloid or MTL tau might slow down neocortical spread of tau and subsequent neurodegeneration, but a combination therapy may yield better outcomes. Using controlled interrupted time series to estimate the population-level effects of Ontario's recently implemented overdose prevention sites and consumption and treatment services BackgroundOntario recently implemented overdose prevention sites and consumption and treatment services (OPS/CTS) to stem the harms of the opioid epidemic. We tested whether operating any site improved local opioid-related health service use and mortality rates.

MethodsWe used monthly counts of all opioid-related emergency department (ED) visits, hospitalizations, and deaths between January 2014 and December 2020 for our outcomes. For each public health unit (PHU) that implemented any OPS/CTS, we created a synthetic control as a weighted combination of unexposed PHU. We estimated the population-level effects of operating any site using controlled interrupted time series with segmented regression and adjusted for time varying confounders (i.e. OPS/CTS capacity, naloxone kits distributed, and persons receiving opioid agonist treatment per 100,000 population). We repeated the analysis using a multiple baseline approach to estimate province-wide effects.

ResultsBetween 2017 and 2020, nine out of 34 PHU implemented at least one OPS/CTS. ED visit (RR=0.96, 95%CI: 0.92 - 0.99) and hospitalization (RR=0.95, 95%CI: 0.92 - 0.98) trends declined faster among treated units. Improvements in local ED visit rate trends were observed for the majority of treated units. Hospitalization rates declined faster for London (RR=0.97, 95%CI: 0.95 - 0.99) and Niagara (RR=0.95, 95%CI: 0.92 - 0.98); while mortality rates declined faster for Hamilton (RR=0.93, 95%CI: 0.90 - 0.96), Niagara (RR=0.97, 95%CI: 0.94 - 0.99) and Guelph (RR=0.94, 95%CI: 0.88 - 1.00).

ConclusionAlthough OPS/CTS are not sufficient to stem the harms of the opioid overdose epidemic on their own, they play a critical role in local harm reduction strategies. The effect of stimulus duration on preferences for gain adjustments when listening to speech ObjectivesIn the personalisation of hearing aid fittings, gain is often adjusted to suit patient preferences using live speech. When using brief sentences as stimuli, the minimum gain adjustments necessary to elicit consistent preferences ( preference thresholds) were previously found to be much greater than typical adjustments in current practice. The current study examined the role of duration on preference thresholds.

DesignParticipants heard 2, 4 and 6-s segments of a continuous monologue presented successively in pairs. The first segment of each pair was presented at each individuals real-ear or prescribed gain. The second segment was presented with a {+/-}0-12 dB gain adjustment in one of three frequency bands. Participants judged whether the second was "better", "worse" or "no different" from the first.

Study SampleTwenty-nine adults, all with hearing-aid experience.

ResultsThe minimum gain adjustments needed to elicit "better" or "worse" judgments decreased with increasing duration for most adjustments. Inter-participant agreement and intra-participant reliability increased with increasing duration up to 4 s, then remained stable.

ConclusionsProviding longer stimuli improves the likelihood of patients providing reliable judgments of hearing-aid gain adjustments, but the effect is limited, and alternative fitting methods may be more viable for effective hearing-aid personalisation. Development of machine learning models for the prediction of complications after colonic, colorectal and small intestine anastomosis in psychiatric and non-psychiatric patient collectives (PSTUDY) Psychiatric and psychosomatic diseases are an increasingly cumbersome burden for the medical system. Indeed, hospital costs associated with mental health conditions have been constantly on the rise in recent years. Moreover, psychiatric conditions are likely to have a negative effect on the treatment of other medical conditions and surgical outcomes, in addition to their direct effects on the overall quality of life. Our study aims to investigate the impact of preoperative Risk factor, psychiatric and psychosomatic diseases on the outcomes of colorectal surgery and length of hospital stay via predictive modeling techniques.

MethodPatient data will be collected from several participating national and international surgical centers The machine learning models will be calculated and coded, but also published according to the TRIPOD guidelines (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis).

ResultIt is conceivable to arrive at generalizable models predicting the abovementioned endpoints through large amounts of data from several centers. The models will be subsequently deployed as a free-to-use web-based prediction tool using the Shiny environment [47]. The cost for the hosting server and digital infrastructure will be covered by Dr. Anas Taha. The sponsor will store the data for ten years. Children develop robust and sustained cross-reactive spike-specific immune responses following SARS-CoV-2 infection SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody responses against spike and receptor binding domain (RBD) were high in children and seroconversion boosted antibody responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Seroneutralisation assays against alpha, beta and delta SARS-CoV-2 variants demonstrated comparable neutralising activity between children and adults. T cell responses against spike were >2-fold higher in children compared to adults and displayed a TH1 cytokine profile. SARS-CoV-2 spike-specific T cells were also detected in many seronegative children, revealing pre-existing responses that were cross-reactive with seasonal Alpha and Beta-coronaviruses. Importantly, all children retained high antibody titres and cellular responses at 6 months after infection whilst relative antibody waning was seen in adults. Spike-specific responses in children also remained broadly stable beyond 12 months. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focussed specificity against spike protein. These observations demonstrate novel features of SARS-CoV-2-specific immune responses in children and may provide insight into their relative clinical protection. Furthermore, this information will help to guide the introduction of vaccination regimens in the paediatric population. Survey of Contaminated Percutaneous Injuries in Anesthesia Practitioners BackgroundAnesthesia practitioners are at inherent risk for percutaneous injuries by blood-contaminated needles and sharp objects. These exposures may result in transmission of HIV and hepatitis viruses. Data about this occupational hazard from contaminated needles and sharp devices is limited and decades old. We conducted a web-based survey to assess the occurrence, reporting, characteristics, and outcome of contaminated percutaneous injuries (CPI) in anesthesia residents, fellows, and attendings.

MethodsAfter institutional research board approval, an email was sent to 217 anesthesia practitioners requesting their participation in an online survey about contaminated percutaneous injuries. Responses were collected from February through March 2020. Results are reported as absolute numbers and proportions with 95% confidence interval (CI).

ResultsThe overall survey response rate was 51% (110/217). 59% (65/110) (95% CI, 50-68) of participants reported having one or more contaminated percutaneous injury during their years of anesthesia practice (42% (21/50) of residents, 50% (4/8) of fellows, 77% (40/52) of anesthesia attendings). Prevalence of injuries related to attendings years of anesthesia practice was 69% (95% CI, 44-94) for 5-10 years, 62.5% (95% CI, 29-96) for 10-15 years, and 79% (95% CI, 63- 95) for greater than 15 years of practice.

35% (95% CI, 26-44) of participants reported having one or more CPI within the last 5 years (40% of residents, 50% of fellows, 29% of attendings). Occurrence of CPI within the last 5 years based on attending anesthesiologist years of practice was 57% for less than 5 years, 37.5% for 10-15 years, and 20% for 15-20 years of practice. 75% (95% CI, 65-85) reported the incident at the time of injury. 59% (95% CI, 48-70) of injuries were due to hollow bore needles. 50% (95% CI, 39-61) of total injuries were high risk. 26% of injured anesthesia practitioners received post-exposure prophylaxis and there were zero seroconversions.

ConclusionMost anesthesiologists will sustain a contaminated percutaneous injury during their careers. Incidence of these injuries decreases with years of practice. Occurrence of these injuries is high among anesthesia residents, with the majority reporting their injuries. Half of the injuries are high risk with a quarter requiring postexposure prophylaxis. More education and interventions are needed to reduce percutaneous injuries and improve reporting. Knee-extensor strength, symptoms, and need for surgery after two, four, or six exercise sessions/week using a home-based one-exercise program: A randomized dose-response trial of knee-extensor resistance exercise in patients eligible for knee replacement (the QUADX-1 trial). ObjectiveTo investigate firstly the efficacy of three different dosages of one home-based, knee-extensor resistance exercise on knee-extensor strength in patients eligible for knee replacement, and secondly, the influence of exercise on symptoms, physical function and decision on surgery.

MethodOne-hundred and forty patients eligible for knee replacement were randomized to three groups: 2, 4 or 6 home-based knee-extensor resistance exercise-sessions per week (group 2, 4 and 6 respectively) for 12 weeks. Primary outcome: isometric knee-extensor strength. Secondary outcomes: Oxford Knee Score, Knee injury and Osteoarthritis Outcome Score, average knee pain last week (0-10 numeric rating scale), 6-minute walk test, stair climbing test, exercise adherence and "need for surgery".

ResultsPrimary analysis: Intention-to-treat analysis of 140 patients did not find statistically significant differences between the groups from baseline to after 12 weeks of exercise in isometric knee-extensor strength: Group 2 vs. 4 (0.003 Nm/kg (0.2%) [95% CI -0.15 to 0.15], P=0.965) and group 4 vs. 6 (-0.04 Nm/kg (-2.7%) [95% CI -0.15 to 0.12], P=0.628). Secondary analysis: Intention-to-treat analyses showed statistically significant differences between the two and six sessions/week groups in favor of the two sessions/week group for Oxford Knee Score: 4.8 OKS points (15.2%) [1.3 to 8.3], P=0.008) and avg. knee pain last week (NRS 0-10): - 1.3 NRS points (-19.5%) [-2.3 to -0.2], P=0.018. After the 12-week exercise intervention, data were available for 117 patients (N=39/group): 38 (32.5%) patients wanted surgery and 79 (67.5%) postponed surgery. This was independent of exercise dosage.

ConclusionIn patients eligible for knee-replacement we found no between-group differences in isometric knee extensor strength after 2, 4 and 6 knee-extensor resistance exercise sessions per week. We saw no indication of an exercise dose-response relationship for isometric knee-extensor strength and only clinically irrelevant within group changes. For some secondary outcome (e.g. KOOS subscales) we found clinically relevant within group changes, which could help explain why only one in three patients decided to have surgery after the simple home-based exercise intervention.

Trial registrationClinicalTrials.gov identifier: NCT02931058. Preprint: https://doi.org/10.1101/2021.04.07.21254965. The incidence of delirium in an acute geriatric community hospital: an observational cohort feasibility study. ObjectivesDelirium in hospitalised older adults is associated with negative health outcomes. Admission to an alternative care setting may lower the incidence of delirium. The Acute Geriatric Community Hospital (AGCH) was recently opened in the Netherlands and uses a multi-component non-pharmacological intervention strategy to prevent delirium. The objective of this study was to describe the incidence of delirium at the AGCH and compare this incidence to existing rates from literature. If a possible effect on delirium is seen in this comparison this would support conducting a larger prospectively controlled study on delirium in this new care setting.

DesignProspective cohort feasibility study; exploratory meta-analysis of proportions.

Setting and ParticipantsThe AGCH is an acute geriatric unit in a skilled nursing facility for patients aged >65 years with acute medical conditions.

MethodsDelirium assessment using the Confusion Assessment Method (CAM) upon admission and on day one, two and three or until delirium had resolved. Patients charts were reviewed if CAM was missing. In an linear mixed-effects model, the delirium incidence rate in AGCH was compared to pooled delirium incidence rates from six studies found in a high-quality review.

Results214 patients from the AGCH (mean age 81.9 years, 47% male, 12% with a history of dementia) were included in the analysis. Delirium developed in 8% (18/214) (95% confidence interval [CI] 5-13%) of patients during AGCH admission compared to 16% (95% CI 12-21%) in hospitals. Admission to the AGCH was associated with a decreased delirium incidence rate compared to the hospital control group (OR[odds ratio]= 0.49, 95% CI 0.24-0.98, p-value=0.044).

Conclusions and implicationsThe delirium incidence in the AGCH was low compared to those incidences found in general hospitals in literature. Based on these findings a controlled observational or randomized study measuring delirium in this care setting is recommended. COMPARISON OF sPLA2-IIA PERFORMANCE WITH HIGH-SENSITIVE CRP, NEUTROPHIL PERCENTAGE, PCT AND LACTATE TO IDENTIFY BACTERIAL INFECTION: A PROSPECTIVE STUDY Early bacterial infection (BI) identification in resource-limiting Emergency Departments (ED) is challenging especially in low- and middle-income counties (LMIC). Misdiagnosis predisposes to antibiotic overuse and propagates antimicrobial resistance. This study evaluates new emerging biomarkers, secretory phospholipase A2 group IIA (sPLA2-IIA), and compares with other biomarkers on their performance characteristic of BI detection in Malaysia, an LMIC. A prospective cohort study was conducted involving 151 consecutive patients admitted to the ED. A single measurement was taken upon patient arrival in ED and was analysed for serum levels of sPLA2-IIA, high-sensitive C-reactive protein (CRP), procalcitonin (PCT), neutrophil percentage (N%), and lactate. All biomarkers performance was compared for the outcomes using area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. The performance of sPLA2-IIA (AUROC 0.93 [95% CI: 0.89-0.97]; Sn 80% [95% CI: 72-87] Sp 94% [95% CI: 81-89]) was the highest among all. It was comparable with high-sensitive CRP (AUROC 0.93 [95% CI: 0.88-0.97]; Sn 75% [95% CI: 66-83]; Sp 91 [95% CI: 77-98]) but had a higher Sn and Sp. The sPLA2-IIA was also found superior to N%, PCT, and lactate. This finding suggested sPLA2-IIA was recommended biomarkers for BI detection in LMIC. I wanna live and not think about the future; What place for advance care planning for people living with severe multiple sclerosis and their families? A qualitative study BackgroundLittle is known about how people with multiple sclerosis and their families comprehend advance care planning (ACP) and its relevance in their lives.

AimTo explore under what situations, with whom, how, and why do people with MS and their families engage in ACP

MethodsWe conducted a qualitative study comprising interviews with people living with MS and their families followed by an ethical discussion group with five health professionals representing specialties working with people affected by MS and their families. Twenty-seven people with MS and 17 family members were interviewed between June 2019 and March 2020. Interviews and the ethical discussion group were audio-recorded and transcribed verbatim. Data were analysed using the framework approach.

ResultsParticipants narratives focused on three major themes :(i) planning for an uncertain future; (ii) perceived obstacles to engaging in ACP that included uncertainty concerning MS disease progression, negative previous experiences of ACP discussions and prioritising symptom management over future planning; (iii) Preferences for engagement in ACP included a trusting relationship with a health professional and that information then be shared across services. Health professionals accounts from the ethical discussion group departed from viewing ACP as a formal document to that of an ongoing process of seeking preferences and values. They voiced similar concerns to people with MS about uncertainty and when to initiate discussions. Some shared concerns of a lack of confidence when having ACP discussions.

ConclusionThese findings support the need for a whole systems strategic approach where information about the potential benefits of ACP in all its forms can be shared with people with MS. Moreover, they highlight the need for health professionals to be skilled and trained in engaging in ACP discussions and where information is contemporaneously and seamlessly shared across services. Diagnostic Model of in-Hospital Mortality in Patients with Acute ST-Segment Elevation Myocardial Infarction Used Artificial Intelligence Methods BackgroundPreventing in-hospital mortality in Patients with ST-segment elevation myocardial infarction (STEMI) is a crucial step.

ObjectivesThe objective of our research was to to develop and externally validate the diagnostic model of in-hospital mortality in acute STEMI patients used artificial intelligence methods.

MethodsWe divide non-randomly the American population with acute STEMI into a training set, a test set,and a validation set. We converted the unbalanced data into balanc ed data. We used artificial intelligence methods to develop and externally validate the dia gnostic model of in-hospital mortality in acute STEMI patients. We used confusion matrix combined with the area under the receiver operating characteristic curve (AUC) to evaluat e the pros and cons of the above models.

ResultsThe strongest predictors of in-hospital mortality were age, gender, cardiogenic shock, atrial fibrillation(AF), ventricular fibrillation(VF),third degree atrioventricular block,in-hospital bleeding, underwent percutaneous coronary intervention(PCI) during hospitalization, underwent coronary artery bypass grafting (CABG) during hospitalization, hypertension history, diabetes history, and myocardial infarction history.The F2 score of logistic regression in the training set, the test set, and the validation data set were 0.81, 0.6, and 0.59 respectively.The AUC of logistic regression in the training set, the test set, and the validation data set were 0.77, 0.78, and 0.8 respectively. The diagnostic model built by logistic regression was the best.

ConclusionWe had used artificial intelligence methods developed and externally validated the diagnostic model of in-hospital mortality in acute STEMI patients.

We registered this study with WHO International Clinical Trials Registry Platform (ICTRP) (registration number: ChiCTR1900027129; registered date: 1 November 2019). A Randomised Trial of a Wearable UV dosimeter for Skin Cancer Prevention BackgroundNon-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States, affecting 5 million people and costing $8.1 billion per year. Despite well-defined guidelines on ultraviolet radiation (UVR) avoidance, it remains difficult for people to assess their individual exposure, as UVR is invisible and the onset of symptoms due to UVR damage are delayed.

MethodsIn a prospective, randomized-controlled trial, 97 patients with a history of actinic keratoses were enrolled from March 2018 to July 2018 and followed over 6 months. 50 patients were given a wearable device that measured UV exposure and a smartphone application that provided both real-time and cumulative UV exposure information, and 47 patients were provided with UV protection counseling by a dermatologist.

ResultsWe observed a significant decrease in the incidence rate of NMSC in the intervention group compared to the control group over 3 months (p = 0.02). We did not observe a significant decrease in the incidence rate of actinic keratoses (AK) in the intervention group compared to the control group. The observed clinical benefit was not accompanied by psychological side effects such as anxiety and depression.

ConclusionsThis study suggests that providing real-time UV exposure data using a wearable UV dosimeter is a safe and effective behavioral change strategy to prevent NMSC. (Funded by the National Cancer Institute, contract HHSN261201700005C; ClinicalTrials.gov number NCT03315286.)