Mechanically ventilated COVID-19 patients admitted to the intensive care unit in the United States with or without respiratory failure secondary to COVID-19 pneumonia: a retrospective comparison of characteristics and outcomes.

BACKGROUND: There is increasing heterogeneity in the clinical phenotype of patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19,) and reasons for mechanical ventilation are not limited to COVID pneumonia. We aimed to compare the characteristics and outcomes of intubated patients admitted to the ICU with the primary diagnosis of acute hypoxemic respiratory failure (AHRF) from COVID-19 pneumonia to those patients admitted for an alternative diagnosis. METHODS: Retrospective cohort study of adults with confirmed SARS-CoV-2 infection admitted to nine ICUs between March 18, 2020, and April 30, 2021, at an urban university institution. We compared characteristics between the two groups using appropriate statistics. We performed logistic regression to identify risk factors for death in the mechanically ventilated COVID-19 population. RESULTS: After exclusions, the final sample consisted of 319 patients with respiratory failure secondary to COVID pneumonia and 150 patients intubated for alternative diagnoses. The former group had higher ICU and hospital mortality rates (57.7% vs. 36.7%, P<0.001 and 58.9% vs. 39.3%, P<0.001, respectively). Patients with AHRF secondary to COVID-19 pneumonia also had longer ICU and hospital lengths-of-stay (12 vs. 6 days, P<0.001 and 20 vs. 13.5 days, P=0.001). After risk-adjustment, these patients had 2.25 times higher odds of death (95% confidence interval, 1.42-3.56; P=0.001). CONCLUSIONS: Mechanically ventilated COVID-19 patients admitted to the ICU with COVID-19-associated respiratory failure are at higher risk of hospital death and have worse ICU utilization outcomes than those whose reason for admission is unrelated to COVID pneumonia.

Characteristics of Moyamoya Syndrome in Pediatric Patients With Neurofibromatosis Type 1.

BACKGROUND: Moyamoya syndrome (MMS) is a progressive cerebral arteriopathy with increased incidence in children with neurofibromatosis type 1 (NF1). Despite the potential for significant neurological morbidity including stroke, little is known about the natural history, and no guidelines exist for screening and management of NF1-associated MMS. METHODS: We identified 152 literature cases of children aged ≤18 years with NF1-associated MMS. A meta-analysis was performed evaluating clinical and neuroimaging findings and patient outcomes. Data from 19 patients with NF1-associated MMS from our center treated from January 1995 to July 2020 were abstracted via chart review and similarly analyzed for clinical and neuroimaging features. RESULTS: Meta-analysis of literature cases showed a median age of MMS diagnosis of 6 years (interquartile range 3 to 10.8 years). Optic pathway gliomas were more common in patients with MMS (42%) compared with historical prevalence. Stroke or transient ischemic attack (TIA) was present at diagnosis in 46%. TIA and stroke were more common in patients with bilateral versus unilateral MMS (62% vs 34%, P = 0.001) and in children aged <4 years versus those aged ≥4 years (61% vs 40%, P = 0.02). Compared with the literature cases, our cohort was more frequently asymptomatic (42% vs 25%) and less likely to present with TIA or stroke (32% vs 46%) at diagnosis. CONCLUSIONS: These data suggest there is an aggressive form of MMS in children with NF1 <4 years of age. Therefore, early screening should be considered to facilitate early detection and treatment of cerebral arteriopathy.

A comparison of timely completion of hypofractionated and traditional adjuvant radiation therapy in early-stage breast cancer: Evidence of impact on reducing racial and socioeconomic disparities.

BACKGROUND: Timely completion of adjuvant radiation after breast conservation therapy is associated with decreased mortality and increased disease-free survival. Few data exist comparing timely completion between hypofractionated radiation and traditional radiation at a national level or across racial and socioeconomic cohorts. METHODS: A retrospective review of the National Cancer Database (2012-2016) on patients undergoing breast conservation therapy for early-stage breast cancer, specifically T1 or T2, N0, M0 patients, was performed. Multivariable logistic regression models were used to compare timely completion of hypofractionated radiation (within 5 weeks of initiation) and traditional radiation (within 7 weeks) across patient, tumor, and facility characteristics. RESULTS: In total, 210,816 patients met criteria, with 59.4% receiving traditional radiation (n = 125,140) and 40.6% receiving hypofractionated radiation (n = 85,676). Overall, 82.8% of patients achieved timely completion of radiation. Among hypofractionated radiation patients, 94.5% of patients achieved timely completion, whereas only 74.8% of traditional radiation patients achieved timely completion (P < .0001). Regarding race/ethnicity, all groups benefited substantially in timely completion of hypofractionated radiation over traditional radiation. However, both treatment cohorts demonstrated that Black (odds ratio (hypofractionated radiation) = 0.842, odds ratio (traditional radiation) = 0.821) and Hispanic (odds ratio (hypofractionated radiation) = 0.917, odds ratio (traditional radiation) = 0.907) patients had lower odds of timely completion compared to White patients (P < .0001). Lower high school graduation rate, median income for patients' ZIP code, and Medicaid were also associated with lower odds of timely completion for both hypofractionated radiation and traditional radiation (both P < .0001). CONCLUSION: Timely completion of radiation therapy in breast conservation therapy is greater for patients receiving hypofractionated radiation than traditional radiation across racial and socioeconomic cohorts. Disparities in timely completion were substantially reduced with hypofractionated radiation utilization. However, there are treatment disparities across racial and socioeconomic cohorts that persist in both treatment groups.

Seizure latency and epilepsy localization as predictors of recurrence following epilepsy surgery.

OBJECTIVE: The primary purpose is to determine whether the time between epilepsy surgery and first seizure recurrence can estimate the timing of the next seizure event for temporal and extratemporal epilepsy. A secondary endpoint aimed to compare temporal and extratemporal epilepsy surgery and examine which subgroup has a higher hazard of subsequent seizure recurrence. METHODS: Data used were from a retrospective database at Thomas Jefferson University Hospital. Records were stratified into temporal (n = 943) and extratemporal (n = 125) surgeries. Analyses were done using SAS and utilized Cox proportional hazards models while controlling for demographics and clinical factors. The primary predictor of time between surgery and first recurrence was treated as a nominal variable binned into six segments, whereas secondary endpoints used a categorical predictor of epilepsy location while controlling for seizure latency. RESULTS: Generally, as seizure latency following surgery increased, the time between first seizure and second seizure increased. These results were statistically meaningful in the temporal set (Wald chi-squared = 40.4715, df = 5, p < .0001). Outcomes could also be interpreted based on predictor group; for instance, if Seizure 1 occurred 1-2 months following surgery in the temporal set, the median number of days until the next seizure was 35.5 days (95% confidence interval [CI] = 21-89 days). Secondary analysis showed that temporal lobe epilepsy had a lower hazard of a second seizure than extratemporal lobe epilepsy (89.2% reduction in hazard; 95% CI = .015-.795). SIGNIFICANCE: This analysis provides a framework to use initial seizure latency to predict the median number of days until the next seizure event, while stratifying based on epilepsy location and controlling for multiple variables. It also suggests that the hazard of seizure recurrence in temporal lobe epilepsy is lower than in extratemporal lobe epilepsy.

Association of race/ethnicity and socioeconomic status with COVID-19 30-day mortality at a Philadelphia medical center using a retrospective cohort study.

COVID-19 has disproportionately affected low-income communities and people of color. Previous studies demonstrated that race/ethnicity and socioeconomic status (SES) are not independently correlated with COVID-19 mortality. The purpose of our study is to determine the effect of race/ethnicity and SES on COVID-19 30-day mortality in a diverse, Philadelphian population. This is a retrospective cohort study in a single-center tertiary care hospital in Philadelphia, PA. The study includes adult patients hospitalized with polymerase-chain-reaction-confirmed COVID-19 between March 1, 2020 and June 6, 2020. The primary outcome was a composite of COVID-19 death or hospice discharge within 30 days of discharge. The secondary outcome was intensive care unit (ICU) admission. The study included 426 patients: 16.7% died, 3.3% were discharged to hospice, and 20.0% were admitted to the ICU. Using multivariable analysis, race/ethnicity was not associated with the primary nor secondary outcome. In Model 4, age greater than 75 (odds ratio [OR]: 11.01; 95% confidence interval [CI]: 1.96-61.97) and renal disease (OR: 2.78; 95% CI: 1.31-5.90) were associated with higher odds of the composite primary outcome. Living in a "very-low-income area" (OR: 0.29; 95% CI: 0.12-0.71) and body mass index (BMI) 30-35 (OR: 0.24; 95% CI: 0.08-0.69) were associated with lower odds of the primary outcome. When controlling for demographics, SES, and comorbidities, race/ethnicity was not independently associated with the composite primary outcome. Very-low SES, as extrapolated from census-tract-level income data, was associated with lower odds of the composite primary outcome.

Trends in Use of Hypofractionated Whole Breast Radiation in Breast Cancer: An Analysis of the National Cancer Database.

PURPOSE: Use of hypofractionated radiation (HR) as a component of breast-conserving treatment (BCT) in breast cancer is relatively low in the United States despite studies demonstrating its efficacy and guidelines supporting its use from the American Society for Radiation Oncology (ASTRO) in 2011 and 2018. Little is known regarding national trends in uptake and factors associated with uptake of HR in the US since the 2011 ASTRO guidelines. METHODS AND MATERIALS: We performed a retrospective review of the National Cancer Database (2012-2016) on patients undergoing BCT. Logistic regression modeling was used to identify relationships between patient, hospital, and tumor factors with the use of HR or traditional radiation (TR). RESULTS: A total of 259,342 cases of BCT were identified with 60% (n = 155,447) undergoing TR and 40% (n = 103,895) undergoing HR. There was an increase in use among patients meeting 2011 ASTRO criteria from 26.2% in 2012 to 67.0% in 2016. The odds of use of HR increased with year of diagnosis, patient age, higher median income, private insurance, treatment at an academic center, travel distance to treatment >20 miles, smaller tumors, lymph node-negative disease, and without use of chemotherapy (P values <.0001, Table 1). CONCLUSION: Guidelines supporting the use of HR in BCT have been associated with a dramatic increase in use of HR in the US. However, there are substantial, identifiable disparities in the uptake of HR at patient and facility levels. By understanding which patient populations are at risk of not receiving the benefit of this therapy, we can improve our use of HR in the US, potentially leading to reduced health care costs and increased patient satisfaction.

Contrasting cumulative risk and multiple individual risk models of the relationship between Adverse Childhood Experiences (ACEs) and adult health outcomes.

BACKGROUND: A very large body of research documents relationships between self-reported Adverse Childhood Experiences (srACEs) and adult health outcomes. Despite multiple assessment tools that use the same or similar questions, there is a great deal of inconsistency in the operationalization of self-reported childhood adversity for use as a predictor variable. Alternative conceptual models are rarely used and very limited evidence directly contrasts conceptual models to each other. Also, while a cumulative numeric 'ACE Score' is normative, there are differences in the way it is calculated and used in statistical models. We investigated differences in model fit and performance between the cumulative ACE Score and a 'multiple individual risk' (MIR) model that enters individual ACE events together into prediction models. We also investigated differences that arise from the use of different strategies for coding and calculating the ACE Score. METHODS: We merged the 2011-2012 BRFSS data (N = 56,640) and analyzed 3 outcomes. We compared descriptive model fit metrics and used Vuong's test for model selection to arrive at best fit models using the cumulative ACE Score (as both a continuous or categorical variable) and the MIR model, and then statistically compared the best fit models to each other. RESULTS: The multiple individual risk model was a better fit than the categorical ACE Score for the 'lifetime history of depression' outcome. For the outcomes of obesity and cardiac disease, the cumulative risk and multiple individual risks models were of comparable fit, but yield different and complementary inferences. CONCLUSIONS: Additional information-rich inferences about ACE-health relationships can be obtained from including a multiple individual risk modeling strategy. Results suggest that investigators working with large srACEs data sources could empirically derive the number of items, as well as the exposure coding strategy, that are a best fit for the outcome under study. A multiple individual risk model could also be considered in addition to the cumulative risk model, potentially in place of estimation of unadjusted ACE-outcome relationships.

No Significant Effect of Maternal Perception of the Food Environment on Reproductive Success or Pup Outcomes in C57BL/6J Mice.

OBJECTIVE: Prior work concerning maternal perception of the food environment suggests that perceived disparities in food resources resulted in reduced pup mass and dam reproductive success. This study attempted to replicate this result with increased sample size and additional measures. METHODS: Female C57BL/6J mice (n = 160; 3 weeks old) were randomly assigned to either subject or peer and were pair housed in partitioned cages with olfactory and visual contact. After a 6-week maturation period on an energy-rich cafeteria diet, cages were randomly assigned to Control (subject and peer fed pelleted diet) or Treatment (subject fed pellets, peer fed cafeteria diet), and subjects were bred. After weaning, one pup from each sex per litter was reared to 5 months. RESULTS: Treatment did not affect the number of births, pup size at birth, or the proportion of pups surviving to weaning (P > 0.09). Treatment did not affect dam body or fat mass at parturition (P > 0.22), but these measures were higher in some Treatment dams at weaning (P < 0.05). Smaller female pups were weaned from Treatment dams pregnant on the first breeding attempt (P = 0.01), but no other pup effects were observed (P > 0.07). CONCLUSIONS: Exposure to food-environment disparity in this study did not replicate previous findings or affect pup growth after weaning.

Randomization to randomization probability: Estimating treatment effects under actual conditions of use.

Blinded randomized controlled trials (RCT) require participants to be uncertain if they are receiving a treatment or placebo. Although uncertainty is ideal for isolating the treatment effect from all other potential effects, it is poorly suited for estimating the treatment effect under actual conditions of intended use-when individuals are certain that they are receiving a treatment. We propose an experimental design, randomization to randomization probabilities (R2R), which significantly improves estimates of treatment effects under actual conditions of use by manipulating participant expectations about receiving treatment. In the R2R design, participants are first randomized to a value, π, denoting their probability of receiving treatment (vs. placebo). Subjects are then told their value of π and randomized to either treatment or placebo with probabilities π and 1-π, respectively. Analysis of the treatment effect includes statistical controls for π (necessary for causal inference) and typically a π-by-treatment interaction. Random assignment of subjects to π and disclosure of its value to subjects manipulates subject expectations about receiving the treatment without deception. This method offers a better treatment effect estimate under actual conditions of use than does a conventional RCT. Design properties, guidelines for power analyses, and limitations of the approach are discussed. We illustrate the design by implementing an RCT of caffeine effects on mood and vigilance and show that some of the actual effects of caffeine differ by the expectation that one is receiving the active drug. (PsycINFO Database Record

Comparisons of Fatty Acid Taste Detection Thresholds in People Who Are Lean vs. Overweight or Obese: A Systematic Review and Meta-Analysis.

Given the increasing evidence that supports the ability of humans to taste non-esterified fatty acids (NEFA), recent studies have sought to determine if relationships exist between oral sensitivity to NEFA (measured as thresholds), food intake and obesity. Published findings suggest there is either no association or an inverse association. A systematic review and meta-analysis was conducted to determine if differences in fatty acid taste sensitivity or intensity ratings exist between individuals who are lean or obese. A total of 7 studies that reported measurement of taste sensations to non-esterified fatty acids by psychophysical methods (e.g.,studies using model systems rather than foods, detection thresholds as measured by a 3-alternative forced choice ascending methodology were included in the meta-analysis. Two other studies that measured intensity ratings to graded suprathreshold NEFA concentrations were evaluated qualitatively. No significant differences in fatty acid taste thresholds or intensity were observed. Thus, differences in fatty acid taste sensitivity do not appear to precede or result from obesity.

Urban Park Development and Pediatric Obesity Rates: A Quasi-Experiment Using Electronic Health Record Data.

INTRODUCTION: Childhood obesity affects ~20% of children in the United States. Environmental influences, such as parks, are linked with increased physical activity (PA). OBJECTIVE: To examine whether changes in Body Mass Index (BMI) z-score were associated with construction of a new park. METHODS: A quasi-experimental design was used to determine whether living in proximity of a park was associated with a reduction in BMI z-score. Children were selected from health clinics within an 11 mile radius of the park. A repeated-measure ANOVA was employed for analysis of the relationship between exposure (new park) and BMI z-score. RESULTS: Participants were 1443 (median age 10.3 range (2-17.9 years), BMI: z-score 0.84 ± 1.09) African American (77.4%) adolescents. Change in BMI z-score was not statistically different for children living at different distances from the park after controlling for age, gender, race, ethnicity, or payer type (p = 0.4482). We did observe a small 0.03 increase in BMI z-score from pre- to post-park (p = 0.0007). There was a significant positive association between child's baseline age and BMI z-score (p < 0.001). CONCLUSIONS: This study found proximity to a park was not associated with reductions in BMI z-score. Additional efforts to understand the complex relationship between park proximity, access, and PA are warranted.

Incorrect statistical method in parallel-groups RCT led to unsubstantiated conclusions.

The article by Aiso et al. titled "Compared with the intake of commercial vegetable juice, the intake of fresh fruit and komatsuna (Brassica rapa L. var perviridis) juice mixture reduces serum cholesterol in middle-aged men: a randomized controlled pilot study" does not meet the expected standards of Lipids in Health and Disease. Although the article concludes that there are some significant benefits to their komatsuna juice mixture, these claims are not supported by the statistical analyses used. An incorrect procedure was used to compare the differences in two treatment groups over time, and a large number of outcomes were tested without correction; both issues are known to produce high rates of false positives, making the conclusions of the study unjustified. The study also fails to follow published journal standards regarding clinical trial registration and reporting.

Common scientific and statistical errors in obesity research.

This review identifies 10 common errors and problems in the statistical analysis, design, interpretation, and reporting of obesity research and discuss how they can be avoided. The 10 topics are: 1) misinterpretation of statistical significance, 2) inappropriate testing against baseline values, 3) excessive and undisclosed multiple testing and "P-value hacking," 4) mishandling of clustering in cluster randomized trials, 5) misconceptions about nonparametric tests, 6) mishandling of missing data, 7) miscalculation of effect sizes, 8) ignoring regression to the mean, 9) ignoring confirmation bias, and 10) insufficient statistical reporting. It is hoped that discussion of these errors can improve the quality of obesity research by helping researchers to implement proper statistical practice and to know when to seek the help of a statistician.

Re: Errors in Zhao et al (2015), Impact of enteral nutrition on energy metabolism in patients with Crohn's disease.

We report invalidating errors related to the statistical approach in the analysis and data inconsistencies in a published single cohort study of patients with Crohn's disease. We provide corrected calculations from the available data and request that a corrected analysis be provided by the authors. These errors should be corrected.

Black and Hispanic Men Perceived to Be Large Are at Increased Risk for Police Frisk, Search, and Force.

Social justice issues remain some of the most pressing problems in the United States. One aspect of social justice involves the differential treatment of demographic groups in the criminal justice system. While data consistently show that Blacks and Hispanics are often treated differently than Whites, one understudied aspect of these disparities is how police officers' assessments of suspects' size affects their decisions. Using over 3 million cases from the New York Police Department (NYPD) Stop, Question, and Frisk (SQF) Database, 2006-2013, this study is the first to explore suspects' race, perceived size, and police treatment. Results indicate that tall and heavy black and Hispanic men are at the greatest risk for frisk or search. Tall and heavy suspects are at increased risk for experiencing police force, with black and Hispanic men being more likely to experience force than white men across size categories.