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Abstract Introduction The use of artificial intelligence (AI) as a diagnostic and decision-support tool is increasing in dermatology. The accuracy of image-based AI tools is incumbent on images in training sets, which requires patient consent for sharing. This study aims to understand individuals’ willingness to share their images for AI and variables that influence willingness. Methods In an online survey administered via Amazon Mechanical Turk, sketches of the hand, face, and genitalia assigned to two use cases employing AI (research vs. personal medical care) were shown. Participants rated willingness to share the image on a 7-point Likert scale. Results Of the 1010 participants, individuals were most willing to share images of their hands (81.2%), face (70.3%), and lastly genitals (male: 56.8%, female: 46.7%). Individuals were more willing to share for personal care versus research (OR 0.77 [95% CI 0.69–0.86]). Willingness to share was higher among males, participants with higher education, tech-savvy participants, and frequent social media users. Most participants were willing to share images if offered monetary compensation, with face images requiring the highest payment (mean $18.25, SD 20.05). Only 38.7% of individuals refused image sharing regardless of any monetary compensation, with the majority of this group unwilling to share images of the genitals. Conclusions This study demonstrates overall public support for sharing images to AI-based tools in dermatology, with influencing factors including image type, context, education level, technology comfort, social media use, and monetary compensation.

Social media tools are widely used by dermatologic patients. Eczema and psoriasis, two of the most common inflammatory skin diseases, are well-represented on the social media site Reddit. We used natural language processing tools to examine comments in subreddits r/psoriasis and r/eczema (combined user base >187,000), tracking commenters’ interest levels and sentiments related to common treatments for psoriasis and eczema as well as discussions of adverse drug reactions. All comments from 2014–2020 from the subreddits r/eczema (n = 196,571) and r/psoriasis (n = 123,144) were retrieved and processed using natural language processing tools. Comment volume in r/eczema related to antibacterial therapies, lifestyle changes, and prednisone decreased from 2014–2020, whereas phototherapy comments remained stable, and dupilumab comment volume increased. Comment volume in r/psoriasis for newer therapeutics (including biologics and apremilast) increased after Food and Drug Administration approval, whereas older therapies such as etanercept, adalimumab, and methotrexate decreased over time. Sentiment scores tended to decrease in the years after Food and Drug Administration approval. Among psoriasis treatments, calcipotriene and branded calcipotriene/betamethasone foam had the highest sentiment, whereas apremilast had the lowest overall sentiment score. These analyses also identified changes in patient interest levels and sentiment related to eczema and psoriasis treatments, suggesting an area for additional research.

Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.

Abstract Background Saccharomyces cerevisiae is often used as a cell factory for the production of S-adenosyl-l-methionine (SAM) for diverse pharmaceutical applications. However, SAM production by S. cerevisiae is negatively influenced by glucose repression, which is regulated by a serine/threonine kinase SNF1 complex. Here, a strategy of alleviating glucose repression by deleting REG1 (encodes the regulatory subunit of protein phosphatase 1) and overexpressing SNF1 (encodes the catalytic subunit of the SNF1 complex) was applied to improve SAM production in S. cerevisiae. SAM production, growth conditions, glucose consumption, ethanol accumulation, lifespan, glycolysis and amino acid metabolism were analyzed in the mutant strains. Results The results showed that the multiple effects of REG1 deletion and/or SNF1 overexpression exhibited a great potential for improving the SAM production in yeast. Enhanced the expression levels of genes involved in glucose transport and glycolysis, which improved the glucose utilization and then elevated the levels of glycolytic intermediates. The expression levels of ACS1 (encoding acetyl-CoA synthase I) and ALD6 (encoding aldehyde dehydrogenase), and the activity of alcohol dehydrogenase II (ADH2) were enhanced especially in the presence of excessive glucose levels, which probably promoted the conversion of ethanol in fermentation broth into acetyl-CoA. The gene expressions involved in sulfur-containing amino acids were also enhanced for the precursor amino acid biosynthesis. In addition, the lifespan of yeast was extended by REG1 deletion and/or SNF1 overexpression. As expected, the final SAM yield of the mutant YREG1ΔPSNF1 reached 8.28 g/L in a 10-L fermenter, which was 51.6% higher than the yield of the parent strain S. cerevisiae CGMCC 2842. Conclusion This study showed that the multiple effects of REG1 deletion and SNF1 overexpression improved SAM production in S. cerevisiae, providing new insight into the application of the SNF1 complex to abolish glucose repression and redirect carbon flux to nonethanol products in S. cerevisiae.

Abstract Clinically feasible multiparameter continuous physiological monitoring technologies are needed for use in resource-constrained African healthcare facilities to allow for early detection of critical events and timely intervention for major morbidities in high-risk neonates. We conducted a prospective clinical feasibility study of a novel multiparameter continuous physiological monitoring technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of Sibel’s Advanced Neonatal Epidermal (ANNE) technology to reference technologies, including Masimo’s Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) measurements and Spengler’s Tempo Easy non-contact infrared thermometer for temperature measurements. We evaluated key performance criteria such as up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies in an uncontrolled, real-world setting. Between September 15 and December 15, 2020, we collected and analyzed 503 h of ANNE data from 109 enrolled neonates. ANNE’s up-time was 42 (11%) h more for HR, 77 (25%) h more for RR, and 6 (2%) h less for SpO2 compared to the Rad-97. However, ANNE’s ratio of up-time to total attached time was less than Rad-97’s for HR (0.79 vs 0.86), RR (0.68 vs. 0.79), and SpO2 (0.69 vs 0.86). ANNE demonstrated adequate performance in identifying high and low HR and RR and high temperature events; however, showed relatively poor performance for low SpO2 events. The normalized spread of limits of agreement were 8.4% for HR and 52.2% for RR and the normalized root-mean-square deviation was 4.4% for SpO2. Temperature agreement showed a spread of limits of agreement of 2.8 °C. The a priori-identified optimal limits were met for HR and temperature but not for RR or SpO2. ANNE was clinically feasible for HR and temperature but not RR and SpO2 as demonstrated by the technology’s up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies.

Objective: This study aimed to investigate the effect of a two-week machine massage on the physical properties of the erector spinae and serum biochemical indexes of adolescent athletes after training.Methods: Sixteen male adolescent wrestlers were recruited (age: 15 ± 1 year; height: 166 ± 7 cm; weight: 56 ± 7 kg) and randomly assigned to machine massage (MA, 8) and control (CO, 8) groups. Participants in the MA group received machine massage for 20 min after each wrestling training from Monday to Saturday (except on Thursday) for two weeks, while the participants in the CO group recovered naturally. Over the course of two weeks, all the participants underwent similar wrestling training program under the guidance of a professional coach. Before and after the intervention, serum urea and creatine kinase (CK) levels were measured in a fasting state. A Myoton Pro digital muscle evaluation system was used to measure the physical properties of the erector spinae, including the oscillation frequency, logarithmic decrement of a muscle’s natural oscillation, and dynamic stiffness.Results: After two weeks of machine massage treatment, the dynamic stiffness of the erector spinae in the MA group decreased by 12.90% and that in the CO group increased by 2.34%, indicating a significant difference between the two groups (p = 0.04, ƞ2 = 0.286). The decrease in the logarithmic decrement of a muscle’s natural oscillation value in the MA was significantly greater than that in the CO (p = 0.003, ƞ2 = 0.286). Moreover, the serum CK values decreased by 33.84% in the MA group and by 1.49% in the CO group, despite a trend of change between the groups (p = 0.062, ƞ2 = 0.084). No significant difference was found in the improvement in serum urea levels between the two groups after two weeks of treatment.Conclusion: Results of the present study indicated that a two-week machine massage had a positive effect on the improvement of the physical properties of the erector spinae of wrestlers during training.

Abstract Multiparameter continuous physiological monitoring (MCPM) technologies are critical in the clinical management of high-risk neonates; yet, these technologies are frequently unavailable in many African healthcare facilities. We conducted a prospective clinical feasibility study of EarlySense’s novel under-mattress MCPM technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of EarlySense’s technology to Masimo’s Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR) and respiratory rate (RR) measurements using up-time, clinical event detection performance, and accuracy. Between September 15 and December 15, 2020, we collected and analyzed 470 hours of EarlySense data from 109 enrolled neonates. EarlySense’s technology’s up-time per neonate was 2.9 (range 0.8, 5.3) hours for HR and 2.1 (range 0.9, 4.0) hours for RR. The difference compared to the reference was a median of 0.6 (range 0.1, 3.1) hours for HR and 0.8 (range 0.1, 2.9) hours for RR. EarlySense’s technology identified high HR and RR events with high sensitivity (HR 81%; RR 83%) and specificity (HR 99%; RR 83%), but was less sensitive for low HR and RR (HR 0%; RR 14%) although maintained specificity (HR 100%; RR 95%). There was a greater number of false negative and false positive RR events than false negative and false positive HR events. The normalized spread of limits of agreement was 9.6% for HR and 28.6% for RR, which met the a priori-identified limit of 30%. EarlySense’s MCPM technology was clinically feasible as demonstrated by high percentage of up-time, strong clinical event detection performance, and agreement of HR and RR measurements compared to the reference technology. Studies in critically ill neonates, assessing barriers and facilitators to adoption, and costing analyses will be key to the technology’s development and potential uptake and scale-up.

Abstract The All of Us Research Program was designed to enable broad-based precision medicine research in a cohort of unprecedented scale and diversity. Hypertension (HTN) is a major public health concern. The validity of HTN data and definition of hypertension cases in the All of Us (AoU) Research Program for use in rule-based algorithms is unknown. In this cross-sectional, population-based study, we compare HTN prevalence in the AoU Research Program to HTN prevalence in the 2015–2016 National Health and Nutrition Examination Survey (NHANES). We used AoU baseline data from patient (age ≥ 18) measurements (PM), surveys, and electronic health record (EHR) blood pressure measurements. We retrospectively examined the prevalence of HTN in the EHR cohort using Systemized Nomenclature of Medicine (SNOMED) codes and blood pressure medications recorded in the EHR. We defined HTN as the participant having at least 2 HTN diagnosis/billing codes on separate dates in the EHR data AND at least one HTN medication. We calculated an age-standardized HTN prevalence according to the age distribution of the U.S. Census, using 3 groups (18–39, 40–59, and ≥ 60). Among the 185,770 participants enrolled in the AoU Cohort (mean age at enrollment = 51.2 years) available in a Researcher Workbench as of October 2019, EHR data was available for at least one SNOMED code from 112,805 participants, medications for 104,230 participants, and 103,490 participants had both medication and SNOMED data. The total number of persons with SNOMED codes on at least two distinct dates and at least one antihypertensive medication was 33,310 for a crude prevalence of HTN of 32.2%. AoU age-adjusted HTN prevalence was 27.9% using 3 groups compared to 29.6% in NHANES. The AoU cohort is a growing source of diverse longitudinal data to study hypertension nationwide and develop precision rule-based algorithms for use in hypertension treatment and prevention research. The prevalence of hypertension in this cohort is similar to that in prior population-based surveys.

ABSTRACT The use of anti-spike (S) serologic assays as surrogate measurements of SARS-CoV-2 vaccine induced immunity will be an important clinical and epidemiological tool. The characteristics of a commercially available anti-S antibody assay (Roche Elecsys anti-SARS-CoV-2 S) were evaluated in a cohort of vaccine recipients. Levels were correlated with pseudotype neutralizing antibodies (NAb) across SARS-CoV-2 variants. We recruited adults receiving a two-dose series of mRNA-1273 or BNT162b2 and collected serum at scheduled intervals up to 8 months post-first vaccination. Anti-S and NAb levels were measured, and correlation was evaluated by (i) vaccine type and (ii) SARS-CoV-2 variant (wild-type, Alpha, Beta, Gamma, and three constructs Day 146*, Day 152*, and RBM-2). Forty-six mRNA vaccine recipients were enrolled. mRNA-1273 vaccine recipients had higher peak anti-S and NAb levels compared with BNT162b2 (P

Background Myocardial injury in patients with COVID‐19 is associated with increased mortality during index hospitalization; however, the relationship to long‐term sequelae of SARS‐CoV‐2 is unknown. This study assessed the relationship between myocardial injury (high‐sensitivity cardiac troponin T level) during index hospitalization for COVID‐19 and longer‐term outcomes. Methods and Results This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS‐CoV‐2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high‐sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high‐sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low‐level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow‐up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID‐19–related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status. Conclusions Myocardial injury during index hospitalization for COVID‐19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID‐19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin‐positive patients.

Background and objectives: Changes in a patient's condition over time are a backbone of clinical decision making. However, most currently used methods for identification of patients in intensive care units (ICUs) at high risk for death do not make effective use of the temporal dimension of available data. We therefore conducted a study to determine whether longitudinal data analysis using recurrent neural networks (RNN) with attention mechanism can identify novel temporal data patterns predictive of adverse outcomes. Methods: We analyzed data on patients admitted to the Medical Intensive Care Unit (MICU) of Asan Medical Center between 2010 and 2017. Static (demographics, diagnoses, procedures, medications) and longitudinal (vitals, laboratory tests, Glasgow Coma Scale) variables were included in the analysis. We used an RNN model with long short-term memory (RNN-LSTM) with attention mechanism to identify and test novel data patterns predictive of ICU death. We also compared accuracy of prediction of ICU mortality between a logistic regression and RNN-LSTM models with and without attention. Results: Among 4896 patients admitted to the MICU, 548 (11.19%) died. RNN-LSTM model with attention identified several high-risk longitudinal variable patterns that were predictive of ICU mortality in a confirmatory analysis, including sustained low blood oxygen content (OR 2.33; 95% CI 1.16 to 4.70) and high frequency of serum sodium measurements (OR 1.27; 95% CI 1.04 to 1.56). RNN-LSTM models with and without attention achieved numerically, but not statistically significantly higher c-statistics for prediction of ICU mortality compared to logistic regression. Conclusions: RNN-LSTM model with attention identified novel temporal data patterns predictive of ICU mortality. These predictors were both statistically significant and clinically plausible, likely representing progressive respiratory failure (sustained low oxygen saturation) and close monitoring of a clinically deteriorating patient (frequent sodium measurements).

BackgroundNeonatal multiparameter continuous physiological monitoring (MCPM) technologies assist with early detection of preventable and treatable causes of neonatal mortality. Evaluating accuracy of novel MCPM technologies is critical for their appropriate use and adoption.MethodsWe prospectively compared the accuracy of Sibel's Advanced Neonatal Epidermal (ANNE) technology with Masimo's Rad-97 pulse CO-oximeter with capnography and Spengler's Tempo Easy reference technologies during four evaluation rounds. We compared accuracy of heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), and skin temperature using Bland-Altman plots and root-mean-square deviation analyses (RMSD). Sibel's ANNE algorithms were optimized between each round. We created Clarke error grids with zones of 20% to aid with clinical interpretation of HR and RR results.ResultsBetween November 2019 and August 2020 we collected 320 hours of data from 84 neonates. In the final round, Sibel's ANNE technology demonstrated a normalized bias of 0% for HR and 3.1% for RR, and a non-normalized bias of -0.3% for SpO2 and 0.2°C for temperature. The normalized spread between 95% upper and lower limits-of-agreement (LOA) was 4.7% for HR and 29.3% for RR. RMSD for SpO2 was 1.9% and 1.5°C for temperature. Agreement between Sibel's ANNE technology and the reference technologies met the a priori-defined thresholds for 95% spread of LOA and RMSD. Clarke error grids showed that all HR and RR observations were within a 20% difference.ConclusionOur findings suggest acceptable agreement between Sibel's ANNE and reference technologies. Clinical effectiveness, feasibility, usability, acceptability, and cost-effectiveness investigations are necessary for large-scale implementation.

Abstract Objective Emergency clinicians face elevated rates of burnout that result in poor outcomes for clinicians, patients, and health systems. The objective of this single‐arm pilot study was to evaluate the feasibility of a Transcendental Meditation (TM) intervention for emergency clinicians during the coronavirus disease 2019 (COVID‐19) pandemic and to explore the potential effectiveness in improving burnout, sleep, and psychological health. Methods Emergency clinicians (physicians, nurses, and physician‐assistants) from 2 urban hospitals were recruited to participate in TM instruction (8 individual or group in‐person and remote sessions) for 3 months. Session attendance was the primary feasibility outcome (prespecified as attending 6/8 sessions), and burnout was the primary clinical outcome. Participant‐reported measures of feasibility and validated measures of burnout, depression, anxiety, sleep disturbance, and stress were collected at baseline and the 1‐month and 3‐month follow‐ups. Descriptive statistics and linear mixed‐effects models were used. Results Of the 14 physicians (46%), 7 nurses (22%), and 10 physician‐assistants (32%) who participated, 61% were female (n = 19/32). TM training and at‐home meditation practice was feasible for clinicians as 90.6% (n = 29/32) attended 6/8 training sessions and 80.6% self‐reported meditating at least once a day on average. Participants demonstrated significant reductions in burnout (P

Background: Heart rate (HR) and respiratory rate (RR) can be challenging to measure accurately and reliably in neonates. The introduction of innovative, non-invasive measurement technologies suitable for resource-constrained settings is limited by the lack of appropriate clinical thresholds for accuracy comparison studies. Methods: We collected measurements of photoplethysmography-recorded HR and capnography-recorded exhaled carbon dioxide across multiple 60-second epochs (observations) in enrolled neonates admitted to the neonatal care unit at Aga Khan University Hospital in Nairobi, Kenya. Trained study nurses manually recorded HR, and the study team manually counted individual breaths from capnograms. For comparison, HR and RR also were measured using an automated signal detection algorithm. Clinical measurements were analyzed for repeatability. Results: A total of 297 epochs across 35 neonates were recorded. Manual HR showed a bias of -2.4 (-1.8%) and a spread between the 95% limits of agreement (LOA) of 40.3 (29.6%) compared to the algorithm-derived median HR. Manual RR showed a bias of -3.2 (-6.6%) and a spread between the 95% LOA of 17.9 (37.3%) compared to the algorithm-derived median RR, and a bias of -0.5 (1.1%) and a spread between the 95% LOA of 4.4 (9.1%) compared to the algorithm-derived RR count. Manual HR and RR showed repeatability of 0.6 (interquartile range (IQR) 0.5-0.7), and 0.7 (IQR 0.5-0.8), respectively. Conclusions: Appropriate clinical thresholds should be selected a priori when performing accuracy comparisons for HR and RR. Automated measurement technologies typically use a smoothing or averaging filter, which significantly impacts accuracy. A wider spread between the LOA, as much as 30%, should be considered to account for the observed physiological nuances and within- and between-neonate variability and different averaging methods. Wider adoption of thresholds by data standards organizations and technology developers and manufacturers will increase the robustness of clinical comparison studies.

We conducted a randomized controlled trial in older adults with hematologic malignancies to determine the impact of geriatrician consultation embedded in our oncology clinic alongside standard care. From February 2015 to May 2018, transplant-ineligible patients aged ≥75 years who presented for initial consultation for lymphoma, leukemia, or multiple myeloma at Dana-Farber Cancer Institute (Boston, MA, USA) were eligible. Pre-frail and frail patients, classified based on phenotypic and deficit-accumulation approaches, were randomized to receive either standard oncologic care with or without consultation with a geriatrician. The primary outcome was 1-year overall survival. Secondary outcomes included unplanned care utilization within 6 months of follow-up and documented end-of-life (EOL) goals-of-care discussions. Clinicians were surveyed as to their impressions of geriatric consultation. One hundred sixty patients were randomized to either geriatric consultation plus standard care (n=60) or standard care alone (n=100). The median age of the patients was 80.4 years (standard deviation = 4.2). Of those randomized to geriatric consultation, 48 (80%) completed at least one visit with a geriatrician. Consultation did not improve survival at 1 year compared to standard care (difference: 2.9%, 95% confidence interval: -9.5% to 15.2%, P=0.65), and did not significantly reduce the incidence of emergency department visits, hospital admissions, or days in hospital. Consultation did improve the odds of having EOL goals-of-care discussions (odds ratio = 3.12, 95% confidence interval: 1.03 to 9.41) and was valued by surveyed hematologic-oncology clinicians, with 62.9%-88.2% of them rating consultation as useful in the management of several geriatric domains.

Abstract Background Smoking is the principal modifiable environmental risk factor for chronic obstructive pulmonary disease (COPD) which affects 300 million people and is the 3rd leading cause of death worldwide. Most of the genetic studies of smoking have relied on self-reported smoking status which is vulnerable to reporting and recall bias. Using data from the Lung Health Study (LHS), we sought to identify genetic variants associated with quantitative smoking and cessation in individuals with mild to moderate COPD. Methods The LHS is a longitudinal multicenter study of mild-to-moderate COPD subjects who were all smokers at recruitment. We performed genome-wide association studies (GWASs) for salivary cotinine (n = 4024), exhaled carbon monoxide (eCO) (n = 2854), cigarettes per day (CPD) (n = 2706) and smoking cessation at year 5 follow-up (n = 717 quitters and 2175 smokers). The GWAS analyses were adjusted for age, gender, and genetic principal components. Results For cotinine levels, SNPs near UGT2B10 gene achieved genome-wide significance (i.e. P

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.

Introduction: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there is any significant sex-related differences in FEV1 responses to ipratropium bromide. Methods: Data from the Lung Health Study (n = 5887; 37% females) were used to determine changes in FEV1 with ipratropium or placebo in male and female subjects with mild to moderate COPD over 5 years. Lung Expression Quantitative Trait Loci (eQTL) dataset was used to determine whether there were any sex-related differences in gene expression for muscarinic (M2 and M3) receptors in lungs of male and female patients. Results: After 4 months, ipratropium therapy increased FEV1 by 6.0% in female and 2.9% in male subjects from baseline values (p = 2.42 × 10−16). This effect was modified by body mass index (BMI) such that the biggest improvements in FEV1 with ipratropium were observed in thin female subjects (p for BMI ∗ sex interaction = 0.044). The sex-related changes in FEV1 related to ipratropium persisted for 2 years (p = 0.0134). Female compared with male lungs had greater gene expression for M3 relative to M2 receptors (p = 6.86 × 10−8). Conclusion: Ipratropium induces a larger bronchodilator response in female than in male patients and the benefits are particularly notable in non-obese females. Female lungs have greater gene expression for the M3 muscarinic receptor relative to M2 receptors than male lungs. Female patients are thus more likely to benefit from ipratropium than male COPD patients.

BACKGROUND:Pediatric hospital mortality from infectious diseases in resource constrained countries remains unacceptably high. Improved methods of risk-stratification can assist in referral decision making and resource allocation. The purpose of this study was to create prediction models for in-hospital mortality among children admitted with suspected infectious diseases. METHODS:This two-site prospective observational study enrolled children between 6 months and 5 years admitted with a proven or suspected infection. Baseline clinical and laboratory variables were collected on enrolled children. The primary outcome was death during admission. Stepwise logistic regression minimizing Akaike's information criterion was used to identify the most promising multivariate models. The final model was chosen based on parsimony. RESULTS:1307 children were enrolled consecutively, and 65 (5%) of whom died during their admission. Malaria, pneumonia and gastroenteritis were diagnosed in 50%, 31% and 8% of children, respectively. The primary model included an abnormal Blantyre coma scale, HIV and weight-for-age z-score. This model had an area under the curve (AUC) of 0.85 (95% CI, 0.80-0.89) with a sensitivity and specificity of 83% and 76%, respectively. The positive and negative predictive values were 15% and 99%, respectively. Two alternate models with similar performance characteristics were developed withholding HIV and weight-for-age z-score, for use when these variables are not available. CONCLUSIONS:Risk stratification of children admitted with infectious diseases can be calculated based on several easily measured variables. Risk stratification at admission can be used for allocation of scarce human and physical resources and to guide referral among children admitted to lower level health facilities.

BACKGROUND:Children discharged from hospitals in developing countries are at high risk of morbidity and mortality. However, few data describe these outcomes among children seen and discharged from rural outpatient centers. OBJECTIVE:The objective of this exploratory study was to identify predictors of immediate and follow-up morbidity and mortality among children visiting a rural health center in Uganda. METHODS:Subjects 0-12 years of age seeking care with a caregiver were consecutively enrolled from a single rural health center in Southwestern Uganda. Baseline variables were collected by research nurses and outcomes of referral, admission or death were recorded (immediate events). Death, hospital admission and health seeking occurring during the 30 days following the clinic visit were also determined (follow-up events). Univariate logistic regression was performed to identify baseline variables associated with immediate outcome and follow-up outcomes. RESULTS:Over the four-month recruitment period 717 subjects were enrolled. There were 85 (11.9%) immediate events (10.1% were admitted, 2.2% were referred, none died). Forty-seven (7.8%) events occurred within 30 days after the visit (7.3% sought care from a health provider, 1.5% were admitted and 0.5% died). Variables associated with immediate events included living more than 30 minutes from the health center, age older than 5 years, having received an antimalarial prior to the visit, having seen a community health worker prior to the visit, elevated respiratory rate or temperature, and depressed weight-for-age z score or decreased oxygen saturation. These variables were not associated with follow-up events. CONCLUSIONS:Sick-child visits at a rural health center in South Western Uganda were associated with rates of mortality and subsequent admission of less than 2% in the period following the sick child visits. Other types of health seeking behavior occurred in approximately 7% of subjects during this same period. Several variables were associated with immediate events but there were no reliable predictors of follow-up events, possibly due to low statistical power.

The reduction in the deaths of millions of children who die from infectious diseases requires early initiation of treatment and improved access to care available in health facilities. A major challenge is the lack of objective evidence to guide front line health workers in the community to recognize critical illness in children earlier in their course.We undertook a prospective observational study of children less than 5 years of age presenting at the outpatient or emergency department of a rural tertiary care hospital between October 2012 and April 2013. Study physicians collected clinical signs and symptoms from the facility records, and with a mobile application performed recordings of oxygen saturation, heart rate and respiratory rate. Facility physicians decided the need for hospital admission without knowledge of the oxygen saturation. Multiple logistic predictive models were tested.Twenty-five percent of the 3374 assessed children, with a median (interquartile range) age of 1.02 (0.42-2.24), were admitted to hospital. We were unable to contact 20% of subjects after their visit. A logistic regression model using continuous oxygen saturation, respiratory rate, temperature and age combined with dichotomous signs of chest indrawing, lethargy, irritability and symptoms of cough, diarrhea and fast or difficult breathing predicted admission to hospital with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval -CI: 0.87 to 0.90). At a risk threshold of 25% for admission, the sensitivity was 77% (95% CI: 74% to 80%), specificity was 87% (95% CI: 86% to 88%), positive predictive value was 70% (95% CI: 67% to 73%) and negative predictive value was 91% (95% CI: 90% to 92%).A model using oxygen saturation, respiratory rate and temperature in combination with readily obtained clinical signs and symptoms predicted the need for hospitalization of critically ill children. External validation of this model in a community setting will be required before adoption into clinical practice.

The recommended method for measuring respiratory rate (RR) is counting breaths for 60 s using a timer. This method is not efficient in a busy clinical setting. There is an urgent need for a robust, low-cost method that can help front-line health care workers to measure RR quickly and accurately. Our aim was to develop a more efficient RR assessment method. RR was estimated by measuring the median time interval between breaths obtained from tapping on the touch screen of a mobile device. The estimation was continuously validated by measuring consistency (% deviation from the median) of each interval. Data from 30 subjects estimating RR from 10 standard videos with a mobile phone application were collected. A sensitivity analysis and an optimization experiment were performed to verify that a RR could be obtained in less than 60 s; that the accuracy improves when more taps are included into the calculation; and that accuracy improves when inconsistent taps are excluded. The sensitivity analysis showed that excluding inconsistent tapping and increasing the number of tap intervals improved the RR estimation. Efficiency (time to complete measurement) was significantly improved compared to traditional methods that require counting for 60 s. There was a trade-off between accuracy and efficiency. The most balanced optimization result provided a mean efficiency of 9.9 s and a normalized root mean square error of 5.6%, corresponding to 2.2 breaths/min at a respiratory rate of 40 breaths/min. The obtained 6-fold increase in mean efficiency combined with a clinically acceptable error makes this approach a viable solution for further clinical testing. The sensitivity analysis illustrating the trade-off between accuracy and efficiency will be a useful tool to define a target product profile for any novel RR estimation device.

Purpose: Penile cancer is rare, with significant morbidity and limited literature assessing utility of peripheral and deep en face margin assessment (PDEMA) vs traditional margin assessment (vertical sections) on treatment outcomes. Materials and Methods: This was a 32-year retrospective multicenter cohort study at 3 academic tertiary care centers. The cohort consisted of 189 patients with histologic diagnosis of in situ or T1a cutaneous squamous cell carcinoma of the penis at Brigham and Women's, Massachusetts General Hospital (1988-2020), and Memorial Sloan Kettering Cancer Center (1995-2020) treated with PDEMA surgical excision, excision/circumcision, or penectomy/glansectomy. Local recurrence, metastasis, and disease-specific death were assessed via multivariable Cox proportional hazard models. Results: The cohort consisted of 189 patients. Median age at diagnosis was 62 years. Median tumor diameter was 1.3 cm. The following outcomes of interest occurred: 30 local recurrences, 13 metastases, and 5 diseasespecific deaths. Primary tumors were excised with PDEMA (N = 30), excision/circumcision (N = 110), or penectomy/glansectomy (N = 49). Of patients treated with traditional margin assessment (non-PDEMA), 12% had narrow or positive margins. Five-year proportions were as follows with respect to local recurrence-free survival, metastasis-free survival, and disease-specific survival/progression-free survival, respectively: 100%, 100%, and 100% following PDEMA; 82%, 96%, and 99% following excision/circumcision; 83%, 91%, and 95% following penectomy/glansectomy. A limitation is that this multi-institutional cohort study was not externally validated. Conclusions: Initial results are encouraging that PDEMA surgical management effectively controls earlystage penile squamous cell carcinoma. [ABSTRACT FROM AUTHOR]