Corticosteroid outcome may be dependent of duration of use in severe COVID-19.

BACKGROUND/AIMS: For patients hospitalized with coronavirus disease 2019 (COVID-19) who require supplemental oxygen, the evidence of the optimal duration of corticosteroid is limited. This study aims to identify whether long-term use of corticosteroids is associated with decreased mortality. METHODS: Between February 10, 2020 and October 31, 2021, we analyzed consecutive hospitalized patients with COVID-19 with severe hypoxemia. The patients were divided into short-term (≤ 14 days) and long-term (> 14 days) corticosteroid users. The primary outcome was 60-day mortality. We performed propensity score (PS) analysis to mitigate the effect of confounders and conducted Kaplan-Meier curve analysis. RESULTS: There were 141 (52%) short-term users and 130 (48%) long-term corticosteroid users. The median age was 68 years and the median PaO2/FiO2 at admission was 158. Of the patients, 40.6% required high-flow nasal cannula, 48.3% required mechanical ventilation, and 11.1% required extracorporeal membrane oxygenation. The overall 60-day mortality rate was 23.2%, and that of patients with hospital-acquired pneumonia (HAP) was 22.9%. The Kaplan-Meier curve for 60- day survival in the PS-matched cohort showed that corticosteroid for > 14 days was associated with decreased mortality (p = 0.0033). There were no significant differences in bacteremia and HAP between the groups. An adjusted odds ratio for the risk of 60-day mortality in short-term users was 5.53 (95% confidence interval, 1.90-18.26; p = 0.003). CONCLUSION: For patients with severe COVID-19, long-term use of corticosteroids was associated with decreased mortality, with no increase in nosocomial complications. Corticosteroid use for > 14 days can benefit patients with severe COVID-19.

Real-world data on the incidence and risk of Guillain-Barré syndrome following SARS-CoV-2 vaccination: a prospective surveillance study.

Increasing evidence suggests an association between SARS-CoV-2 vaccines and Guillain-Barré syndrome (GBS). Nevertheless, little is understood about the contributing risk factors and clinical characteristics of GBS post SARS-CoV-2 vaccination. In this prospective surveillance study of 38,828,691 SARS-CoV-2 vaccine doses administered from February 2021 to March 2022 in the Gyeonggi Province, South Korea, 55 cases of GBS were reported post vaccination. We estimated the incidence rate of GBS per million doses and the incidence rate ratio for the vaccine dose, mechanism, age, and sex. Additionally, we compared the clinical characteristics of GBS following mRNA-based and viral vector-based vaccinations. The overall incidence of GBS following SARS-CoV-2 vaccination was 1.42 per million doses. Viral vector-based vaccines were associated with a higher risk of GBS. Men were more likely to develop GBS than women. The third dose of vaccine was associated with a lower risk of developing GBS. Classic sensorimotor and pure motor subtypes were the predominant clinical subtypes, and demyelinating type was the predominant electrodiagnostic subtype. The initial dose of viral-vector based vaccine and later doses of mRNA-based vaccine were associated with GBS, respectively. GBS following SARS-CoV-2 vaccination may not be clinically distinct. However, physicians should pay close attention to the classic presentation of GBS in men receiving an initial dose of viral vector-based SARS-CoV-2 vaccines.

Correlations Between Psychological Status and Perception of Facial Expression.

OBJECTIVE: Facial affect recognition is associated with neuropsychological status and psychiatric diseases. We hypothesized that facial affect recognition is associated with psychological status and perception of other affects. METHODS: A total of 80 images depicting facial affect, including 20 Neutral, 20 Angry, 20 Fear, and 20 Sad, were screened for use in our research. A total of 100 healthy individuals were asked to rate these images using a 10-point Likert scale and complete psychological scales assessing the emotional statuses and cognitive functions. RESULTS: The participants' emotional state of aggression, attention, and impulsivity may have been associated with their interpretation of the Angry facial expressions. The participants often rated the Angry facial expressions as Fear. The participants rated Fear images as Angry or Sad. In response to a Sad facial expression, the participants reported psychological statuses of attention and impulsivity which were associated with the facial expression rating. The participants rated the Sad expression as Angry or Fear. CONCLUSION: The psychological statuses of the participants were significantly correlated with their interpretation of facial affects. In particular, a psychological state of attention was often correlated with incorrect affect ratings. Attention and impulsivity could affect the rating of the sad facial expressions.

E-cigarette-associated Severe Pneumonia in Korea Using Data Linkage between the Korea National Health and Nutrition Examination Survey (KNHANES, 2013-2019) and the National Health Insurance Service (NHIS) Claims Database.

BACKGROUND: This study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database. METHODS: We conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay. RESULTS: The final analysis included 28,950 individuals, of which 578 (2.0%) were EC users. EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000). CONCLUSIONS: Since e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.

Appropriate number of observations for determining hand hygiene compliance among healthcare workers.

We sought to determine the minimum number of observations needed to determine hand hygiene (HH) compliance among healthcare workers. The study was conducted at a referral hospital in South Korea. We retrospectively analyzed the result of HH monitoring from January to December 2018. HH compliance was calculated by dividing the number of observed HH actions by the total number of opportunities. Optimal HH compliance rates were calculated based on adherence to the six-step technique recommended by the World Health Organization. The minimum number of required observations (n) was calculated by the following equation using overall mean value (ρ), absolute precision (d), and confidence interval (CI) (1 - α) [the equation: [Formula: see text]]. We considered ds of 5%, 10%, 20%, and 30%, with CIs of 99%, 95%, and 90%. During the study period, 8791 HH opportunities among 1168 healthcare workers were monitored. Mean HH compliance and optimal HH compliance rates were 80.3% and 59.7%, respectively. The minimum number of observations required to determine HH compliance rates ranged from 2 ([Formula: see text]: 30%, CI: 90%) to 624 ([Formula: see text]: 5%, CI: 99%), and that for optimal HH compliance ranged from 5 ([Formula: see text]: 30%, CI: 90%) to 642 ([Formula: see text]: 5%, CI: 99%). Therefore, we found that our hospital required at least five observations to determine optimal HH compliance.

Risk of fracture in antidepressant users with concurrent use of benzodiazepines: A self-controlled case-series analysis.

OBJECTIVE: Despite the fracture risk associated with both antidepressant (AD) medication and benzodiazepines (BDZs), they are commonly prescribed simultaneously. However, studies elucidating the effects of concurrent use of BDZs and ADs on the risk fracture are scant. The objective of this study was to evaluate the risk of fracture associated with concurrent use of BDZs in AD users, using a self-controlled case-series analysis. METHODS: A self-controlled case-series analysis, in which the participants act as their own control, was conducted using the Korean National Health Insurance Service-National Sample Cohort database (2002-2015). We studied AD users who were prescribed BDZs and diagnosed with a fracture. The risk periods were subdivided into consecutive periods (1-30, 31-60, and > 60 days) after receiving a BDZ. A 2-week pre-exposure period and a 2-week post-exposure period were also included. The incidence rate ratio (IRR) was estimated after adjusting for age and use of co-medications. RESULTS: A total of 3020 patients were identified during the study period. There was an increased fracture risk in the first 30 days following BDZ use (IRR: 1.88, 95% confidence interval [CI] 1.66-2.12), in the 31-60-day period (1.73, 95% CI 1.48-2.02), and beyond the 60-day period (IRR: 1.68, 95% CI 1.47-1.91). The risks of fracture were greater in men and older patients. CONCLUSION: The concomitant use of BDZs and ADs was related to a significant increase in fracture risk. AD users should be aware of the fracture risk with concomitant BDZ use, especially for first-time BDZ users and for elderly patients.

A Bayesian semiparametric approach to correlated ROC surfaces with stochastic order constraints.

In application of diagnostic accuracy, it is possible that a priori information may exist regarding the test score distributions, either between different disease populations for a single test or between multiple correlated tests. Few have considered constrained diagnostic accuracy analysis when the true disease status is binary; almost none when the disease status is ordinal. Motivated by a study on diagnosing endometriosis, we propose an approach to estimating diagnostic accuracy measures that can incorporate different stochastic order constraints on the test scores when an ordinal true disease status is in consideration. We show that the Dirichlet process mixture provides a convenient framework to both flexibly model the test score distributions and embed the a priori ordering constraints. We also utilize the Dirichlet process mixture to model the correlation between multiple tests. In taking a Bayesian perspective to inference, we develop an efficient Markov chain Monte Carlo algorithm to sample from the posterior distribution and provide posterior estimates of the receiver operating characteristic surfaces and the associated summary measures. The proposed approach is evaluated with extensive simulation studies, and is demonstrated with an application to the endometriosis study.

A correlated Bayesian rank likelihood approach to multiple ROC curves for endometriosis.

In analysis of diagnostic data with multiple tests, it is often the case that these tests are correlated. Modeling the correlation explicitly not only produces valid inference results but also enables borrowing of information. Motivated by the Physician Reliability Study (PRS) that investigated the diagnostic performance of physicians in diagnosing endometriosis, we construct a correlated modeling framework to estimate ROC curves and the associated area under the curves. This correlated approach is quite appealing for the PRS data set that suffers from the problem of small sample sizes, as it enables information borrowing between physician groups and sessions. Given that the test scores appear to be non-normal even after logarithm transformation, we use the ranks of the data to conduct likelihood estimation and inference. We use the deviance information criterion to select competing models and conduct simulation studies to assess model performances. In application to the PRS data set, we found that the physicians are not significantly different in their diagnostic performance between groups; however, they are different between the sessions. This suggests that clinical information may play a more important role in physicians' diagnostic performance than their experiences. Our empirical evidence also demonstrates that when using both woman- and physician-specific random effects, the model parameter estimates are much smoother.

A Bayesian multi-dimensional couple-based latent risk model with an application to infertility.

Motivated by the Longitudinal Investigation of Fertility and the Environment (LIFE) Study that investigated the association between exposure to a large number of environmental pollutants and human reproductive outcomes, we propose a joint latent risk class modeling framework with an interaction between female and male partners of a couple. This formulation introduces a dependence structure between the chemical patterns within a couple and between the chemical patterns and the risk of infertility. The specification of an interaction enables the interplay between the female and male's chemical patterns on the risk of infertility in a parsimonious way. We took a Bayesian perspective to inference and used Markov chain Monte Carlo algorithms to obtain posterior estimates of model parameters. We conducted simulations to examine the performance of the estimation approach. Using the LIFE Study dataset, we found that in addition to the effect of PCB exposures on females, the male partners' PCB exposures play an important role in determining risk of infertility. Further, this risk is subadditive in the sense that there is likely a ceiling effect which limits the probability of infertility when both partners of the couple are at high risk.

Preterm birth and air pollution: Critical windows of exposure for women with asthma.

BACKGROUND: Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied. OBJECTIVE: We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk. METHODS: Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate matter with aerodynamic diameter of less than 10 microns, ozone (O3), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO) per interquartile range. For each gestational week 23 to 36, exposures among women who delivered were compared with those remaining pregnant. Three-month preconception, whole pregnancy, weeks 1 to 28, and the last 6 weeks of gestation averages were also evaluated. RESULTS: On assessing PTB by gestational week, we found that significant asthma interactions were sporadic before 30 weeks but more common during weeks 34 to 36, with higher risk among mothers with asthma for NOx, CO, and SO2 exposure and an inverse association with O3 in week 34. Odds of PTB were significantly higher among women with asthma for CO and NOx exposure preconception and early in pregnancy. In the last 6 weeks of pregnancy, PTB risk associated with particulate matter with aerodynamic diameter of less than 10 microns was higher among women with asthma. CONCLUSIONS: Mothers with asthma may experience a higher risk for PTB after exposure to traffic-related pollutants such as CO and NOx, particularly for exposures 3-months preconception and in the early weeks of pregnancy.

Preterm Birth in the Context of Increasing Income Inequality.

OBJECTIVE: Preterm birth is a leading cause of infant morbidity and mortality. Little is known about the contextual effect of U.S. income inequality on preterm birth, an issue of increasing concern given that the current economic divide is the largest since 1928. METHODS: We examined changes in inequality over time in relation to preterm birth among singleton deliveries from an electronic medical record-based cohort (n = 223,512) conducted in 11 U.S. states and the District of Columbia from 2002 to 2008. Increasing income inequality was defined as a positive change in state-level Gini coefficient from the year prior to birth. Multi-level models estimated the independent effect of increasing inequality on preterm birth (>22 and <37 weeks) controlling for maternal demographics, health behaviors, insurance status, chronic medical conditions, and state-level poverty and unemployment during the year of birth. RESULTS: The preterm birth rate was 12.3% where inequality increased and 10.9% where it did not. After adjustment, increasing inequality remained significantly associated with preterm birth (adjusted odds ratio 1.07, 95% confidence interval 1.04, 1.11). We observed no significant interaction by insurance status or race, suggesting that increasing inequality had a broad effect across the population. CONCLUSIONS: The contextual effect of increasing income inequality on preterm birth risk merits further study.

Does maternal asthma contribute to racial/ethnic disparities in obstetrical and neonatal complications?

PURPOSE: To examine whether maternal asthma contributes to racial/ethnic differences in obstetrical and neonatal complications. METHODS: Data on white (n = 110,603), black (n = 50,284), and Hispanic (n = 38,831) singleton deliveries came from the Consortium on Safe Labor. Multilevel logistic regression models, with an interaction term for asthma and race/ethnicity, estimated within-group adjusted odds ratios (aORs) for gestational diabetes, gestational hypertension, pre-eclampsia, placental abruption, premature rupture of membranes, preterm delivery, maternal hemorrhage, neonatal intensive care unit admissions, small for gestational age, apnea, respiratory distress syndrome, transient tachypnea of the newborn, anemia, and hyperbilirubinemia after adjustment for clinical and demographic confounders. Nonasthmatics of the same racial/ethnic group were the reference group. RESULTS: Compared with nonasthmatics, white asthmatics had increased odds of pre-eclampsia (aOR, 1.28; 95% confidence interval [CI], 1.15-1.43) and maternal hemorrhage (aOR, 1.14; 95% CI, 1.04-1.23). White and Hispanic infants were more likely to have neonatal intensive care unit admissions (aOR, 1.19; 95% CI, 1.11-1.28; aOR, 1.16; 95% CI, 1.02-1.32, respectively) and be small for gestational age (aOR, 1.11; 95% CI, 1.02-1.20; aOR, 1.26; 95% CI, 1.10-1.44, respectively), and Hispanic infants were more likely to have apnea (aOR, 1.32; 95% CI, 1.02-1.69). CONCLUSIONS: Maternal asthma did not affect most obstetrical and neonatal complication risks within racial/ethnic groups. Despite their increased risk for both asthma and many complications, our findings for black women were null. Asthma did not contribute to racial/ethnic disparities in complications.

An Integrated Bayesian Nonparametric Approach for Stochastic and Variability Orders in ROC Curve Estimation: An Application to Endometriosis Diagnosis.

In estimating ROC curves of multiple tests, some a priori constraints may exist, either between the healthy and diseased populations within a test or between tests within a population. In this paper, we proposed an integrated modeling approach for ROC curves that jointly accounts for stochastic and variability orders. The stochastic order constrains the distributional centers of the diseased and healthy populations within a test, while the variability order constrains the distributional spreads of the tests within each of the populations. Under a Bayesian nonparametric framework, we used features of the Dirichlet process mixture to incorporate these order constraints in a natural way. We applied the proposed approach to data from the Physician Reliability Study that investigated the accuracy of diagnosing endometriosis using different clinical information. To address the issue of no gold standard in the real data, we used a sensitivity analysis approach that exploited diagnosis from a panel of experts. To demonstrate the performance of the methodology, we conducted simulation studies with varying sample sizes, distributional assumptions and order constraints. Supplementary materials for this article are available online.

Semiparametric Bayesian joint modeling of a binary and continuous outcome with applications in toxicological risk assessment.

Many dose-response studies collect data on correlated outcomes. For example, in developmental toxicity studies, uterine weight and presence of malformed pups are measured on the same dam. Joint modeling can result in more efficient inferences than independent models for each outcome. Most methods for joint modeling assume standard parametric response distributions. However, in toxicity studies, it is possible that response distributions vary in location and shape with dose, which may not be easily captured by standard models. To address this issue, we propose a semiparametric Bayesian joint model for a binary and continuous response. In our model, a kernel stick-breaking process prior is assigned to the distribution of a random effect shared across outcomes, which allows flexible changes in distribution shape with dose shared across outcomes. The model also includes outcome-specific fixed effects to allow different location effects. In simulation studies, we found that the proposed model provides accurate estimates of toxicological risk when the data do not satisfy assumptions of standard parametric models. We apply our method to data from a developmental toxicity study of ethylene glycol diethyl ether.

Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial.

Shorter telomeres have been associated with poor health behaviors, age-related diseases, and early mortality. Telomere length is regulated by the enzyme telomerase, and is linked to exposure to proinflammatory cytokines and oxidative stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation lowered the concentration of serum proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length, telomerase, and oxidative stress. In addition to testing for group differences, changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence, absorption, and metabolism. The double-blind four-month trial included 106 healthy sedentary overweight middle-aged and older adults who received (1) 2.5g/day n-3 PUFAs, (2) l.25g/day n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values were 15% lower in the two supplemented groups compared to placebo. Although group differences for telomerase and telomere length were nonsignificant, changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention's impact: telomere length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions. This translational research broadens our understanding of the potential impact of the n-6:n-3 PUFA balance. ClinicalTrials.gov identifier: NCT00385723.

Depressive symptoms enhance stress-induced inflammatory responses.

Depression is a risk factor for morbidity and mortality, and immune dysregulation may be partially responsible for this link. Proinflammatory cytokines such as interleukin 6 (IL-6) are reliable predictors of quality of life, morbidity, and many causes of mortality. The current study evaluated relationships between depressive symptoms, as assessed by the CES-D, and stress-induced inflammation. The participants, 138 healthy adults, were evaluated at rest, and after a standardized laboratory speech and mental arithmetic stressor. Compared with individuals with fewer depressive symptoms, those with more depressive symptoms produced more IL-6 in response to the stressor, as well as significantly higher levels of IL-6 both 45 min and 2 h after the stressor. These findings add to our emerging understanding of the complex interactions among stress, depression, and immune dysregulation, and provide one potential pathway to explain relationships between depressive symptoms and disease.

Omega-3 supplementation lowers inflammation in healthy middle-aged and older adults: a randomized controlled trial.

Observational studies have linked lower levels of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) with inflammation and depression. This study was designed to determine whether n-3 supplementation would decrease serum cytokine production and depressive symptoms in 138 healthy middle-aged and older adults (average age=51.04, SD=7.76) who were sedentary and overweight (average BMI=30.59, SD=4.50). This three-arm randomized, placebo-controlled, double-blind 4-month trial compared responses to (1) 2.5 g/d n-3 PUFAs, or (2) 1.25 g/d n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Serum interleukin-6 decreased by 10% and 12% in our low and high dose n-3 groups, respectively, compared to a 36% increase in the placebo group. Similarly, low and high dose n-3 groups showed modest 0.2% and -2.3% changes in serum tumor necrosis factor alpha, compared to a 12% increase in the control group. Depressive symptoms were quite low at baseline and did not change significantly in response to supplementation. Our data suggest that n-3 PUFAs can reduce inflammation in overweight, sedentary middle-aged and older adults, and thus could have broad health benefits. These data provide a window into the ways in which the n-3 PUFAs may impact disease initiation, progression, and resolution. ClinicalTrials.gov identifier: NCT00385723.

Adiponectin, leptin, and yoga practice.

To address the mechanisms underlying hatha yoga's potential stress-reduction benefits, we compared adiponectin and leptin data from well-matched novice and expert yoga practitioners. These adipocytokines have counter-regulatory functions in inflammation; leptin plays a proinflammatory role, while adiponectin has anti-inflammatory properties. Fifty healthy women (mean age=41.32, range=30-65), 25 novices and 25 experts, provided fasting blood samples during three separate visits. Leptin was 36% higher among novices compared to experts, P=.008. Analysis of adiponectin revealed a borderline effect of yoga expertise, P=.08; experts' average adiponectin levels were 28% higher than novices across the three visits. In contrast, experts' average adiponectin to leptin ratio was nearly twice that of novices, P=.009. Frequency of self-reported yoga practice showed significant negative relationships with leptin; more weeks of yoga practice over the last year, more lifetime yoga sessions, and more years of yoga practice were all significantly associated with lower leptin, with similar findings for the adiponectin to leptin ratio. Novices and experts did not show even marginal differences on behavioral and physiological dimensions that might represent potential confounds, including BMI, central adiposity, cardiorespiratory fitness, and diet. Prospective studies addressing increased risk for type II diabetes, hypertension, and cardiovascular disease have highlighted the importance of these adipocytokines in modulating inflammation. Although these health risks are clearly related to more extreme values then we found in our healthy sample, our data raise the possibility that longer-term and/or more intensive yoga practice could have beneficial health consequences by altering leptin and adiponectin production.

Sympathetic and parasympathetic activity in cancer-related fatigue: more evidence for a physiological substrate in cancer survivors.

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. This study evaluated relationships between fatigue and both sympathetic and parasympathetic nervous system activity in breast cancer survivors. Norepinephrine and heart rate variability (HRV) were evaluated at rest, as well as during and after a standardized laboratory speech and mental arithmetic stressor. The participants, 109 women who had completed treatment for stage 0-IIIA breast cancer within the past two years, were at least two months post surgery, radiation or chemotherapy, whichever occurred last. Women who reported more fatigue had significantly higher norepinephrine and lower HRV before and after the stressor than their less fatigued counterparts. Fatigue was not related to treatment or disease variables including treatment type, cancer stage, time since diagnosis, and time since treatment. Importantly, the relationship between HRV and cancer-related fatigue was sizeable. Based on research that has demonstrated characteristic age-related HRV decrements, our findings suggest a 20-year difference between fatigued and non-fatigued cancer survivors, raising the possibility that fatigue may signify accelerated aging. Furthermore, lower HRV and elevated norepinephrine have been associated with a number of adverse health outcomes; accordingly, fatigue may also signal the need for increased vigilance to other health threats.