Community factors associated with local RSV epidemic patterns: a spatiotemporal modeling study BackgroundRespiratory syncytial virus (RSV) causes a large burden of morbidity in infants, young children, and the elderly. The timing of RSV seasonal epidemics exhibits strong spatial patterns within the United States. Spatial variability in the timing of RSV epidemics provides an opportunity to probe the factors driving transmission of the virus.

MethodsWe evaluated competing hypotheses about the associations between RSV epidemic timing at the ZIP-code level and household size, population density, school district boundaries, commuting patterns, and geographic proximity. We used hierarchical Bayesian models with monthly ZIP-code level hospitalization data from New York, New Jersey, and Connecticut between July 1997 and June 2014 to investigate these hypotheses.

ResultsEarly epidemic timing across ZIP codes was associated with large household sizes and high population density, and nearby ZIP codes shared similar epidemic timing. Variations in epidemic timing attributed to commuting patterns or school district boundaries are negligible.

ConclusionOur results suggest RSV epidemics take off faster in areas with more household crowding and higher population density, and that epidemic spread follows a spatial diffusion process based on geographic proximity. With several vaccines against RSV under development, it is important to understand the drivers of RSV transmission and disease in order to maximize population protection of a vaccine program. Our findings can inform more effective control measures against RSV, such as vaccine programs and household infection control, and guide future studies on the transmission dynamics of RSV.
Association between Fat-Infiltrated Axillary Lymph Nodes on Screening Mammography and Cardiometabolic Disease ObjectiveEctopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index. Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms.

MethodsA cross-sectional study was conducted on 834 women presenting for full-field digital screening mammography. The status of fat-infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non-alcoholic fatty liver disease.

ResultsFat-infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p-value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve).

ConclusionFat-infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat-infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography.
A SIMPLE, HOME-THERAPY ALGORITHM TO PREVENT HOSPITALIZATION FOR COVID-19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL MATCHED-COHORT STUDY BackgroundEffective simple, home-treatment algorithms implemented on the basis of a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalization of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health care providers.

MethodsThis academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians from October 2020 to January 2021 according to the proposed recommendation algorithm with those of 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalization. Analyses were by intention-to-treat.

FindingsAll patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the  recommended schedule cohort and 14 [7-30] days in the matched  control cohort (p=0{middle dot}033). Minor symptoms persisted in a lower percentage of patients in the  recommended than in the  control cohort (23{middle dot}3% versus 73{middle dot}3%, respectively, p<0{middle dot}0001) and for a shorter period (p=0{middle dot}0107). Two patients in the  recommended cohort were hospitalized compared to 13 (14{middle dot}4%) controls (Log-rank test, p=0{middle dot}0038). Prevention algorithm abated the days and cumulative costs of hospitalization by >90% (from 481 to 44 days and from 296 to 28 thousand Euros, respectively. 1{middle dot}2 patients had to be treated to save one hospitalization event.

InterpretationImplementation of an early, home-treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but almost blunted the risk of hospitalization and related treatment costs.

RO_SCPLOWESEARCHC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWINC_SCPLOW CO_SCPLOWONTEXTC_SCPLOWO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and the Cochrane Library for peer-reviewed articles published in any language up to March 19, 2021, using the search terms ("2019-nCoV" or "SARS-CoV-2" or "COVID-19") and ("early" or "outpatient" or "treatment" or "home"). Our search did not identify any randomised clinical trials or observational studies that assessed the effectiveness of treatment regimens targeting early mild symptoms of COVID-19 in the outpatient setting.

Added value of this studyIn this fully academic, observational matched-cohort study, we found that early home-treatment of 90 consecutive patients with mild COVID-19 by their family physicians according to the proposed recommendation algorithm, designed on the basis of a pathophysiologic and pharmacologic rationale, significantly reduced the risk of hospitalisation compared to 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Days of hospitalization and related treatment costs were reduced by more than 90%. Just 1.2 patients needed to be treated to save one hospitalization event. The  recommended schedule cohort required a few more days to achieve resolution of major symptoms, including fever, dyspnea, musculoskeletal pain, headache and cough compared to the  control cohort. Symptoms, such as anosmia and ageusia/dysgeusia, persisted less commonly and for a shorter period in the  recommendation than in the  control cohort.

Implications of the available evidenceThe finding that the implementation of the proposed simple treatment algorithm during the initial, mild phase of COVID-19 has the potential to prevent disease progression, eventually limiting the need of hospital admission may have major implications for patients and health care providers. Indeed, preventing hospitalisations due to worsening of COVID-19 will not only save lives, but will also contribute to remarkably reduce treatment costs and to reshape health care systems that are overburdened because of the pandemic effects. Hemodynamic Differences Between Women and Men with Elevated Blood Pressure in China: A Non-Invasive Assessment of 45,082 Adults Using Impedance Cardiography BackgroundWhether there are sex differences in hemodynamic profiles among people with elevated blood pressure is not well understood and could guide personalization of treatment.

Methods and resultsWe described the clinical and hemodynamic characteristics of adults with elevated blood pressure in China using impedance cardiography. We included 45,082 individuals with elevated blood pressure (defined as systolic blood pressure of [&ge;]130 mmHg or a diastolic blood pressure of [&ge;]80 mmHg), of which 35.2% were women. Overall, women had a higher mean systolic blood pressure than men (139.0 [{+/-}15.7] mmHg vs 136.8 [{+/-}13.8] mmHg, P<0.001), but a lower mean diastolic blood pressure (82.6 [{+/-}9.0] mmHg vs 85.6 [{+/-}8.9] mmHg, P<0.001). After adjusting for age, region, and body mass index, women <50 years old had lower systemic vascular resistance index (beta-coefficient [{beta}] -31.7; 95% CI: -51.2, -12.2) and higher cardiac index ({beta} 0.07; 95% CI: 0.04, 0.09) than men of their same age group, whereas among those [&ge;]50 years old women had higher systemic vascular resistance index ({beta} 120.4; 95% CI: 102.4, 138.5) but lower cardiac index ({beta} -0.15; 95% CI: -0.16, -0.13). Results were consistent with a propensity score matching sensitivity analysis, although the magnitude of the SVRI difference was lower and non-significant. However, there was substantial overlap between women and men in the distribution plots of these variables, with overlapping areas ranging from 78% to 88%.

ConclusionsOur findings indicate that there are sex differences in hypertension phenotype, but that sex alone is insufficient to infer an individuals profile. Right Anterior Temporal Degeneration, Emotions, and Loss of Nonverbal Semantics: The Emotional Semantic Variant Frontotemporal Dementia It has been proposed that focal anterior temporal lobe (ATL) degeneration is a specific, unitary FTLD-TDP-related disease that initially preferentially affects the left or right hemisphere. Patients with early left ATL (lATL) atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia (svPPA) and semantic dementia, prompting appropriate neurological care. There is less consensus regarding the symptoms in right ATL (rATL) predominant cases, who most often present with behavioral and emotional changes leading to a misdiagnosis of a psychiatric disorder, and later of behavioral variant frontotemporal dementia (bvFTD). Uncertainties regarding early symptoms and lack of an overarching framework continues to hinder proper diagnosis and care of patients with rATL disease. Here, we present symptom chronology, cognitive and socioemotional profiles of a large, well-characterized, longitudinally followed cohort of patients with rATL-predominant degeneration and propose new criteria and nosology for the syndrome.

We identified individuals with a clinical diagnosis of bvFTD or svPPA and a structural MRI (n=478). Based on neuroimaging criteria, we identified three groups: patients with rATL-predominant atrophy with relative sparing of the frontal lobes (n=46), patients with frontal-predominant atrophy with relative sparing of the rATL (n=79), and patients with lATL-predominant atrophy with relative sparing of the frontal lobes (n=75). Seventy-eight patients had undergone autopsy. We analyzed patients clinical, neuropsychological, genetic, anatomical, and pathological profiles.

In the rATL-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%), and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in emotional theory of mind, identifying famous people from names and face, and facial affect naming (despite preserved face perception) than the lATL- and frontal-predominant groups. The clinical features were highly sensitive (81%) and specific (84%) in differentiating rATL from bvFTD in the first three years of the disease. FTLD-TDP (84%) was the most common pathology.

Our results suggest that rATL-predominant degeneration is characterized by early loss of empathy and person-specific knowledge, deficits that are caused by progressive loss of semantic memory for concepts of social-emotional relevance. Although this syndrome exists along a clinical, anatomical, and pathological continuum with svPPA, patients present with progressive behavioral changes. To facilitate early identification and care in clinical and research settings, we propose specific diagnostic criteria and the term "emotional semantic variant frontotemporal dementia" to distinguish this syndrome from other forms of frontotemporal dementia. Distinct temporal characteristics of circulating alveolar epithelial and endothelial injury markers in ARDS with COVID-19: a preliminary retrospective report The time course and specific contributions of alveolar epithelial and endothelial injury to the pathogenesis of acute respiratory distress syndrome (ARDS) with coronavirus disease (COVID-19) remain unclear. Here, we evaluated the characteristics of circulating markers of alveolar epithelial and endothelial injury in serum samples from eleven ARDS patients and ten non-ARDS patients, all with COVID-19. Our results indicates that the alveolar epithelial injury at the very early disease stage and the endothelial injury which continues to exacerbate during the later disease stage seem to be the hallmarks of ARDS with COVID-19. Caffeine and Methylliberine: A Human Pharmacokinetic Interaction Study Methylliberine and theacrine are methylurates found in the leaves of various Coffea species and Camellia assamica var. kucha, respectively. We previously demonstrated that the methylxanthine caffeine increased theacrines oral bioavailability in humans. Consequently, we conducted a double-blind, placebo-controlled study pharmacokinetic study in humans administered methylliberine, theacrine, and caffeine to determine methylliberines pharmacokinetic interaction potential with either caffeine or theacrine. Subjects (n = 12) received an oral dose of either methylliberine (25 or 100 mg), caffeine (150 mg), methylliberine (100 mg) plus caffeine (150 mg), or methylliberine (100 mg) plus theacrine (50 mg) using a randomized, double-blind, crossover design. Blood samples were collected over 24 hours and analyzed for methylliberine, theacrine, and caffeine using UPLC-MS/MS. Methylliberine exhibited linear pharmacokinetics that were unaffected by co-administration of either caffeine or theacrine. However, methylliberine co-administration resulted in decreased oral clearance (41.9 {+/-} 19.5 vs. 17.1 {+/-} 7.80 L/hr) and increased half-life (7.2 {+/-} 5.6 versus 15 {+/-} 5.8 hrs) of caffeine. Methylliberine had no impact on caffeines maximum concentration (440 {+/-} 140 vs. 458 {+/-} 93.5 ng/mL) or oral volume of distribution (351 {+/-} 148 vs. 316 {+/-} 76.4 L). We previously demonstrated theacrine bioavailability was enhanced by caffeine, however, caffeine pharmacokinetics were unaffected by theacrine. Herein, we found that methylliberine altered caffeine pharmacokinetics without a reciprocal interaction, which suggests caffeine may interact uniquely with different methylurates. Understanding the mechanism(s) of interaction between methylxanthines and methylurates is of critical importance in light of the recent advent of dietary supplements containing both purine alkaloid classes. COVID Outcome Prediction in the Emergency Department (COPE): Development and validation of a model for predicting death and need for intensive care in COVID-19 patients Background and aimCOVID-19 is putting extraordinary pressure on emergency departments (EDs). To support decision making in the ED, we aimed to develop a simple and valid model for predicting mortality and need for intensive care unit (ICU) admission in suspected COVID-19 patients.

MethodsFor model development, we retrospectively collected data of patients who were admitted to 4 large Dutch hospitals with suspected COVID-19 between March and August 2020 (first wave of the pandemic). Based on prior literature we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. Logistic regression analyses with post-hoc uniform shrinkage was used to obtain predicted probabilities of in-hospital death and of the need for ICU admission, both within 28 days after hospital admission. We assessed model performance (Area Under the ROC curve (AUC); calibration plots) with temporal validation in patients who presented between September and December 2020 (second wave). We used multiple imputation to account for missing values.

ResultsThe development data included 5,831 patients, of whom 629 (10.8%) died and 5,070 (86.9%) were discharged within 28 days after admission. ICU admission was fully recorded for 2,633 first wave patients in 2 hospitals, with 214 (8%) ICU admissions within 28 days. A simple model - COVID Outcome Prediction in the Emergency Department (COPE) - with age, respiratory rate, C-reactive protein, lactic dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well-calibrated and showed good discrimination in 3,252 second wave patients (AUC in 4 hospitals: 0.82 [0.78; 0.86]; 0.82 [0.74; 0.90]; 0.79 [0.70; 0.88]; 0.83 [0.79; 0.86]). COPE was also able to identify patients at high risk of needing IC in 706 second wave patients with complete information on ICU admission (AUC: 0.84 [0.78; 0.90]; 0.81 [0.66; 0.95]). The models are implemented in web-based and mobile applications.

ConclusionCOPE is a simple tool that is well able to predict mortality and need for ICU admission for patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making.

CONTRIBUTION TO THE LITERATUREO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIPrediction models have the potential to support decision making about hospital admission of patients presenting to the emergency department with suspected COVID-19
C_LIO_LIMost currently available models that were independently assessed contain a high risk of bias
C_LIO_LIPromising models were developed in different patient selections and included predictors that are not quickly and objective obtainable in emergency departments
C_LI

What this study addsO_LIA simple and objective tool ("COPE") is well able to predict mortality and need for ICU admission for patients who present to the ED with suspected COVID-19
C_LIO_LICOPE may support ED physicians to identify high-risk patients - i.e. those at high risk of deterioration and/or death - requiring treatment in the ICU, intermediate-risk patients requiring admission to the clinical ward, and low-risk patients who can potentially be sent home
C_LI How Informative Were Early SARS-CoV-2 Treatment and Prevention Trials? A longitudinal cohort analysis of trials registered on clinicaltrials.gov BackgroundEarly in the SARS-CoV-2 pandemic, commentators warned that some COVID trials were inadequately conceived, designed and reported. Here, we retrospectively assess the prevalence of informative COVID trials launched in the first 6 months of the pandemic.

MethodsWe created a cohort of SARS-CoV-2 treatment and prevention efficacy trials that were initiated from 2020-01-01 to 2020-06-30 using ClinicalTrials.gov registration records. We evaluated trials on 3 criteria of informativeness: potential redundancy, design quality and feasibility of patient-participant recruitment. The study protocol was prospectively registered with the Open Science Framework (https://osf.io/fp726/).

ResultsWe included 500 trials in our cohort, 58% of which were Phase 2 and 84.8% were directed towards the treatment of SARS-CoV-2. Close to one third of trials met all three criteria and were deemed informative (29.0% (95% Confidence Interval 23.7 - 36.9)). The proportion of potentially redundant trials in our cohort was 4.1%. Over half of the trials in our cohort (56.2%) did not meet our criteria for high quality trial design. The proportion of trials with infeasible patient-participant recruitment was 22.6%.

ConclusionsLess than one third of COVID-19 trials registered on ClinicalTrials.gov during the first six months met all three criteria for informativeness. Shortcomings in trial design, recruitment feasibility and redundancy reflect longstanding weaknesses in the clinical research enterprise that were likely amplified by the exceptional circumstances of a pandemic. Hyperreflective foci, OCT progression indicators in age-related macular degeneration, include transdifferentiated retinal pigment epithelium PurposeBy optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Muller glia.

MethodIn clinical OCT (61 eyes, 44 AMD patients, 79.4 {+/-} 7.7 years; 29 female; follow-up = 4.7 {+/-} 0.9 years) one HRF type, RPE plume, was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy (GA), 6; 3 neovascular AMD (nvAMD). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semi-quantitatively by one observer (none, some cells, all cells).

ResultsTrajectories of RPE plume and cellular debris paralleled Muller glia, whether ordered or subsident, near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Muller glia remained CRALBP-positive. Plume cells approached and contacted retinal capillaries.

ConclusionGain- and loss-of-function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Down-regulated RPE retinoid handling may impair rod vision while Muller glia sustain cone vision. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial-mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.

PrecisHyperreflective foci (HRF) are OCT progression risk indicators in age-related macular degeneration. Abnormal RPE cells including some that correspond to HRF lose immunoreactivity for retinoid markers and gain immunoreactivity for immune markers, indicating molecular transdifferentiation. 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. Patient attrition in Molecular Tumour Boards: A Systematic Review Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision making within precision medicine. Though these meetings are in use globally reporting often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatment. A literature review was performed to understand patient attrition within MTBs and barriers to patients receiving treatment. A total of 54 papers were reviewed spanning a 6 year period from 11 different countries. 20% of patients received treatment through the MTB process. Of those that did not receive treatment the main reasons were no mutations identified (26%), no actionable mutations (22%) and clinical deterioration (15%). However, the data was often incomplete due to inconsistent reporting of MTBs with only 53% reporting on patients having no mutations, 48% reporting on presence of actionable mutations with no treatment options and 57% reporting on clinical deterioration. As patient attrition in MTBs is an issue which is very rarely alluded to in reporting, more transparent reporting is needed to understand barriers to treatment and integration of new technologies is required to process increasing omic and treatment data. 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. Macronutrient mass intake explains deferential weight and fat loss in isocaloric diets Differential weight and fat losses under isocaloric diets of distinct macronutrient composition are well-documented findings in obesity research.1-6 Such data are considered a result of inadequate methodology as it disagree with the energy balance theory.7 A recent mathematical analysis of this paradigm has found, however, serious analytical contradictions in its foundations.8 As an alternative, a mass balance model was proposed to explain the aforesaid body composition alterations. Here, we expand on this observation by contrasting both models. We show that mass balance explains a wide range of fending experiments including those concurring with the energy balance principle. The latter, however, is less flexible and results in poor forecasts in settings consistent with mass balance. The energy balance theory is thus an unsatisfactory model of body composition changes. Consequently, by shifting to a mass balance paradigm of obesity a much deeper understanding of this disease may follow in the near future. COVID-19 Acceleration and Vaccine Status in France - Summer 2021 ObjectivesThis note provides an assessment of COVID-19 acceleration among groups with different vaccine status in France.

MethodsWe assess viral acceleration using a novel indicator introduced in Baunez et al. (2021). The acceleration index relates the percentage change of tests that have been performed on a given day to the percentage change in the associated positive cases that same day. We compare viral acceleration among vaccinated and unvaccinated individuals in France over the period May 31st - August 29, 2021.

ResultsOnce the state of the epidemic within each groups is accounted for, it turns out that viral acceleration has since mid-July converged to similar levels among vaccinated and unvaccinated individuals in France, even though viral speed is larger for the latter group compared to the former.

ConclusionOur results call for an increasing testing effort for both vaccinated and unvaccinated individuals, in view of the fact that viral circulation is currently accelerating at similar levels for both groups in France. Complementary frailty and mortality prediction models on older patients as a tool for assessing palliative care needs BackgroundPalliative care (PC) has demonstrated benefits for life-limiting illnesses. Cancer patients have mainly accessed these services, but there is growing consensus about the importance of promoting access for patients with non-malignant disease. Bad survival prognosis and patients frailty are usual dimensions to decide PC inclusion.

ObjectivesThe main aim of this work is to design and evaluate three quantitative models based on machine learning approaches to predict frailty and mortality on older patients in the context of supporting PC decision making: one-year mortality, survival regression and one-year frailty classification.

MethodsThe dataset used in this study is composed of 39,310 hospital admissions for 19,753 older patients (age >= 65) from January 1st, 2011 to December 30th, 2018. All prediction models were based on Gradient Boosting Machines. From the initial pool of variables at hospital admission, 20 were selected by a recursive feature elimination algorithm based on the random forests GINI importance criterion. Besides, we run an independent grid search to find the best hyperparameters in each model. The evaluation was performed by 10-fold cross-validation and area under the receiver operating characteristic curve and mean absolute error were reported. The Cox proportional-hazards model was used to compare our proposed approach with classical survival methods.

ResultsThe one-year mortality model achieved an AUC ROC of 0.87 {+/-} 0.01; the mortality regression model achieved an MAE of 329.97 {+/-} 5.24 days. The one-year frailty classification reported an AUC ROC of 0.9 {+/-} 0.01. The Spearmans correlation between the admission frailty index and the survival time was -0.1, while the point-biserial correlation between one-year frailty index and survival time was -0.16.

ConclusionsOne-year mortality model performance is at a state-of-the-art level. Frailty Index used in this study behaves coherently with other works in the literature. One-year frailty classifier demonstrated that frailty status within the year could be predicted accurately. To our knowledge, this is the first study predicting one-year frailty status based on a frailty index. We found mortality and frailty as two weakly correlated and complementary PC needs assessment criteria. Predictive models are available online at http://demoiapc.upv.es. Treatment interruption is a risk factor for sickness presenteeism: a large-scale cross-sectional study during the COVID-19 pandemic ObjectivesThis study examined the relationship between interruption to routine medical care during the coronavirus disease 2019 pandemic and sickness presenteeism among workers in Japan.

MethodsA cross-sectional study using data obtained from an internet monitor questionnaire was conducted. Interruption to medical care was defined based on the response "I have not been able to go to the hospital or receive treatment as scheduled." The fraction of sickness presenteeism days in the past 30 days was employed as the primary outcome. A fractional logit model was used for analysis to treat bounded data.

ResultsOf the 27,036 participants, 17,526 (65%) were workers who did not require routine medical care, 8,451 (31%) were using medical care as scheduled, and 1,059 (4%) experienced interrupted medical care. The adjusted odds ratio (aOR) of sickness presenteeism was significantly higher among workers who experienced interrupted medical care (3.44; 95% confidence interval [CI]: 3.04-3.89) than those who did not require routine medical care. In terms of symptoms, the highest aOR was observed among workers with mental health symptoms (aOR: 5.59, 95%CI: 5.04-6.20).

ConclusionsThis study suggests the importance of continuing necessary treatment during a pandemic to prevent presenteeism. Relationship Between Patient Sex and Serum Tumor Necrosis Factor Antagonist Drug and Anti-Drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Cohort Study BackgroundAnti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease

MethodsA nationwide multicenter retrospective cohort study was conducted by evaluating patients charts from July 2018 until September 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across 7 hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. Geometric means were calculated, and multiple linear regression was used to estimate the adjusted ratio of geometric means (RoGM) and their 95% confidence intervals (CI).

ResultsIn the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30-2.27, p-value <0.001) compared to females. Additionally, infliximab serum drug concentrations among males were lower compared to females (2.6 vs. 4.1 ug/ml; aRoGM = 0.62, 95% CI: 0.44-0.88, p-value = 0.007). In the subgroup analysis (n = 359), male compared to female patients on combination therapy with infliximab and immunomodulators had similar anti-drug antibody concentrations (30.2 vs. 21.9 AU/ml; aRoGM = 1.38, 95% CI: 0.79-2.40, p-value = 0.254). There was no difference in the anti-drug antibody and serum drug concentrations among males and females on adalimumab.

ConclusionIn patients receiving infliximab, anti-drug antibodies were higher in males than females. Consistent with this, serum drug concentrations were lower in males than females on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among males and females on adalimumab. In addition, no difference in anti-drug antibodies between males and females receiving anti-TNF combination therapy was observed. Subpopulation-specific Machine Learning Prognosis for Underrepresented Patients with Double Prioritized Bias Correction Many clinical datasets are intrinsically imbalanced, dominated by overwhelming majority groups. Off-the-shelf machine learning models that optimize the prognosis of majority patient types (e.g., healthy class) may cause substantial errors on the minority prediction class (e.g., disease class) and demographic subgroups (e.g., Black or young patients). For example, our work found that missed death cases are 3.14 times higher than missed survival cases in a mortality prediction model. In the typical one-machine-learning-model-fits-all paradigm, racial and age disparities are likely to exist, but unreported. What makes it worse is the deceptive nature of widely used whole-population metrics, such as AUC-ROC. We show that some metrics fail to reflect serious prediction deficiencies. To mitigate representational biases, we design a double prioritized (DP) bias correction technique. Our method trains customized models for specific ethnicity or age groups, a substantial departure from the one-model-predicts-all convention. We report our findings on four prognosis tasks over two imbalanced clinical datasets. DP reduces relative disparities among race and age groups, 5.6% to 86.8% better than the 8 existing sampling solutions being compared, in terms of the minority class' recall. Simple risk scores to predict hospitalization or death in outpatients with COVID-19 including the Omicron variant ImportanceOutpatient physicians need guidance to support their clinical decisions regarding management of patients with COVID-19, in particular whether to hospitalize a patient and if managed as an outpatient, how closely to follow them.

ObjectiveTo develop and prospectively validate a clinical prediction rule to predict the likelihood of hospitalization for outpatients with COVID-19 that does not require laboratory testing or imaging.

DesignDerivation and temporal validation of a clinical prediction rule, and prospective validation of two externally derived clinical prediction rules.

SettingPrimary and Express care clinics in a Pennsylvania health system.

ParticipantsPatients 12 years and older presenting to outpatient clinics who had a positive polymerase chain reaction test for COVID-19.

Main outcomes and measuresClassification accuracy (percentage in each risk group hospitalized) and area under the receiver operating characteristic curve (AUC).

ResultsOverall, 7.4% of outpatients in the early derivation cohort (5843 patients presenting before 3/1/21) and 5.5% in the late validation cohort (3806 patients presenting 3/1/21 or later) were ultimately hospitalized. We developed and temporally validated three risk scores that all included age, dyspnea, and the presence of comorbidities, adding respiratory rate for the second score and oxygen saturation for the third. All had very good overall accuracy (AUC 0.77 to 0.78) and classified over half of patients in the validation cohort as very low risk with a 1.7% or lower likelihood of hospitalization. Two externally derived risk scores identified more low risk patients, but with a higher overall risk of hospitalization (2.8%).

Conclusions and relevanceSimple risk scores applicable to outpatient and telehealth settings can identify patients with very low (1.6% to 1.7%), low (5.2% to 5.9%), moderate (14.7% to 15.6%), and high risk (32.0% to 34.2%) of hospitalization. The Lehigh Outpatient COVID Hospitalization (LOCH) risk score is available online as a free app: https://ebell-projects.shinyapps.io/LehighRiskScore/. Deceased donor kidney degradomics indicates cytoskeletal proteolytic alterations impacting post-transplant function. BackgroundIn brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys that adversely impacts the quality of grafts. Here, we hypothesized that DBD kidneys may undergo proteolytic processes that renders grafts susceptible to post-transplant dysfunction.

Material & MethodsUsing mass spectrometry and immunoblotting analyses, we profiled degradation patterns of cytoskeletal proteins in deceased (n=55) and living (n=10) donor kidneys.

ResultsWe found that in DBD kidneys, key podocyte cytoskeletal proteins had been proteolytically cleaved. Generated degradation profiles were not associated to donor related demographic and clinical factors but were associated to suboptimal post-transplant function. Strikingly, -actinin -4 and Talin-1 degradation profiles were not observed in circulatory-death or living-donor kidneys. As Talin-1 is a specific proteolytic target of Calpain-1, we investigated a potential trigger of Calpain activation and Talin-1 degradation using ex-vivo precision-cut human kidney slices and in-vitro immortalised human podocytes. Notably, we found that Transforming-Growth Factor-{beta} (TGF-{beta}) activated Calpain-1 and proteolytically cleaved Talin-1 to generate distinct peptide fragments. These peptide fragments were of similar size and matched the degradation patterns observed in DBD kidneys. Talin-1 degradation was prevented in vitro by Calpain-1 inhibition.

ConclusionsHere, we provide initial evidence that DBD kidneys are susceptible to cytoskeletal protein degradation that impacts posttransplant kidney function. Subsequent studies should aim to further investigate the link between brain death and activation of proteolytic pathways exploring new therapeutic opportunities. 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. Mixed ancestry analysis of whole-genome sequencing identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves Posterior urethral valves (PUV) are the commonest cause of end-stage renal disease in children, but the genetic architecture of this rare disorder remains largely unknown. We analyzed whole-genome sequencing (WGS) data from 132 unrelated PUV cases and 23,727 controls of mixed ancestry and identified statistically significant associations with common variants at 12q24.21 (P=7.8x10-12; OR 0.4) and rare variants at 6p21.1 (P=2x10-8; OR 7.2), that were replicated in an independent European cohort. Bayesian fine mapping and functional annotation mapped these loci to the transcription factor TBX5 and planar cell polarity gene PTK7, respectively, with the encoded proteins detected in the normal human developing urinary tract. These findings represent the first known genetic associations of PUV, providing novel insights into the underlying biology of this poorly understood disorder and demonstrate that a mixed ancestry WGS approach can increase power for disease locus discovery and facilitate fine-mapping of causal variants. Croup during the COVID-19 Omicron Variant Surge Croup is a common upper respiratory disease usually associated with parainfluenza virus, resulting in stridor, hoarse voice, barky cough, and variable respiratory distress. Here we examine the data at our center confirming a sharp increase in cases of croup associated with the Omicron variant. Data was retrospectively extracted from patient charts among those seen in the Emergency Department at Seattle Childrens Hospital. Inclusion criteria were patients who were assigned a diagnosis containing "croup" during either 5/30/2021-11/30/2021, a time period correlating with predominance of the COVID-19 Delta variant (B.1.617.2), or the initial phase of the Omicron variant surge (12/1/2021-1/15/2022). Contemporaneous publicly available local data on the proportion of SARS-CoV-2 samples in surrounding King County, Washington, with spike gene target failure on TaqPath PCR assays was used as a proxy for the proportion of infections caused by the Omicron variant. A total of 401 patients were diagnosed with croup during the Delta surge and 107 patients were diagnosed with croup during the Omicron surge. Patients who presented during the Omicron surge were more likely to test positive for COVID-19 (48.2% vs 2.8%, p < 0.0001). Children with a clinical diagnosis of croup during the Omicron surge were more likely to be prescribed racemic epinephrine as part of their care (21.5% vs 13.0%, p = 0.032). There were no differences in presenting age, rate of admission, rate of return to the ED within 72 hours, or admission among those who returned within 72 hours. During the Omicron surge, the incidence of croup nearly doubled compared to the rate in prior months, while at the same time the number of cases of parainfluenza virus identified decreased. Consistent with prior case reports, we have identified a sharp rise in cases of croup seen in our pediatric ED in parallel with the replacement of the SARS-CoV-2 Delta variant by Omicron as the dominant variant in our community. Symptoms of depression and anxiety among Vietnamese immigrants in Japan during the COVID-19 pandemic: a cross-sectional web-based study ObjectiveWe aimed to examine the mental health status and related factors among Vietnamese immigrants in Japan during the coronavirus disease 2019 (COVID-19) pandemic.

DesignOnline cross-sectional survey administered from September 21 to October 21, 2021

SettingOnline survey of Vietnamese immigrants in Japan

ParticipantsThe inclusion criteria for participation were 1) Vietnamese citizenship or Japanese citizenship in those of Vietnamese descent, current residence in Japan, and 2) age [&ge;]18 years.

Main OutcomesPatient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item (GAD-7) scores were considered the main outcome measures. Multivariable logistic regression was used to identify factors related to symptoms of depression and anxiety, and the chosen variables were entered simultaneously in the survey.

ResultsAmong 621 participants (age: 26.0{+/-}4.8 years; male: 347 [55.9%]) who completed the questionnaire, 73.7% reported a decrease in income when compared with the period before the COVID-19 pandemic, and 60.4% reported being recently affected by poor socioeconomic status. Moderate-to-severe symptoms of depression (PHQ-9 score [&ge;]10 points) and mild-to-severe symptoms of anxiety (GAD-7 [&ge;]5 points) were observed in 203 (32.7%) and 285 (45.9%) individuals, respectively. Factors related to depressive symptoms were age (odds ratio [OR]=0.94, p=0.043), medical or psychiatric co-morbidity (OR=2.46, p<0.001), and low socioeconomic status (OR=2.47, p<0.001). Factors related to anxiety symptoms were being single (OR=1.72, p=0.044), medical or psychiatric co-morbidity (OR=2.52, p<0.001), low socioeconomic status (OR=2.72, p<0.001), and absence of a partner with whom to discuss ones health (OR=1.66, p=0.013).

ConclusionsThe current findings demonstrate that, when compared with Japanese citizens, Vietnamese immigrants experienced a decrease in income, worsening working conditions, and poor mental health status during the COVID-19 pandemic. These findings highlight the potential contribution of low socioeconomic status and social isolation to poor mental health status.

Strengths and limitations of this studyO_LIVietnamese immigrants, who are the second largest immigrant group in Japan, were studied. No previous assessment of their mental health during the COVID-19 pandemic has been carried out.
C_LIO_LIThis study provided a non-contact approach to prevent infection using online surveys. Therefore, we received a wide range of responses from areas with low COVID-19 infection rate area to high COVID-19 infection rate area in Japan.
C_LIO_LIThe survey may not be a complete representation of all Vietnamese immigrants living in Japan, as some elderly Vietnamese immigrants may not have been able to participate due to the online format.
C_LI