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It is well established that light affects both visual and non-visual systems. Laboratory studies have shown that, depending upon the time of exposure, short-wavelength light of sufficient amount and exposure duration will either entrain or disrupt the synchrony between our biological clock and our local position on Earth. Laboratory studies have also shown that light across the entire visible spectrum can enhance alertness, both day and night. Scant attention has been given to testing the effects of light on building occupants' non-visual responses, and, consequently, lighting specifiers have been offered little guidance on the design and application of lighting for non-visual effects. The present study helps to fill that gap through field-testing of light exposures from a novel luminaire designed to promote entrainment and alertness throughout the day in actual office environments. The data support the inference that light exposures, when properly applied, can promote circadian entrainment and increase alertness. [ABSTRACT FROM AUTHOR]

This study considers a fully-parametric but uncongenial multiple imputation (MI) inference to jointly analyze incomplete binary response variables observed in a correlated data settings. Multiple imputation model is specified as a fully-parametric model based on a multivariate extension of mixed-effects models. Dichotomized imputed datasets are then analyzed using joint GEE models where covariates are associated with the marginal mean of responses with response-specific regression coefficients and a Kronecker product is accommodated for cluster-specific correlation structure for a given response variable and correlation structure between multiple response variables. The validity of the proposed MI-based JGEE (MI-JGEE) approach is assessed through a Monte Carlo simulation study under different scenarios. The simulation results, which are evaluated in terms of bias, mean-squared error, and coverage rate, show that MI-JGEE has promising inferential properties even when the underlying multiple imputation is misspecified. Finally, Adolescent Alcohol Prevention Trial data are used for illustration. [ABSTRACT FROM PUBLISHER]

Understanding the genetic contributions to complex diseases will require consideration of interaction across multiple genes and environmental factors. At the same time, capturing information on allelic phase, that is, whether alleles within a gene are in cis (on the same chromosome) or in trans (on different chromosomes), is critical when using haplotypic approaches in disease association studies. This paper proposes a combination of mixed modeling and multiple imputation for assessing high-order genotype-phenotype associations while accounting for the uncertainty in phase inherent in population-based association studies. This method provides a flexible statistical framework for controlling for potential confounders and assessing gene-environment and gene-gene interactions in studies of unrelated individuals where the haplotypic phase is generally unobservable. The proposed method is applied to a cohort of 626 subjects with human immunodeficiency virus (HIV) to assess the potential contribution of four genes, apolipoprotein-C-III, apolipoprotein-E, endothelial lipase and hepatic lipase in predicting lipid abnormalities. A simulation study is also presented to describe the method performance. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: Treatment information collected by cancer registries can be used to monitor the provision of guideline-recommended chemotherapy to colorectal cancer patients. Incomplete information may bias comparisons of these rates. We developed statistical methods that combine data from a registry and physicians' records to assess hospital quality.Data: From California Cancer Registry data, we selected all patients (n=12,594) newly diagnosed with stage III colon cancer or stage II or III rectal cancer from 428 hospitals during the years 1994 to 1998. To assess rates and predictors of underreporting of chemotherapy, we surveyed physicians treating 1449 of these patients from 98 hospitals during the years 1996 to 1997.Methods: Using Bayesian statistical models, we imputed unobserved treatments. We studied the impact of underreporting on provider profiling by comparing rankings, estimates, and credible intervals based only on registry data to those incorporating physician survey data.Results: Analyses that account for incompleteness of reporting yielded wider credible intervals for provider profiles than those that ignored such incompleteness. Among the 109 (25%) hospitals in the highest quartile of chemotherapy rates according to the registry data, 16 were not so classified when incomplete reporting was taken into account. With the more comprehensive model, 12 hospitals could be identified that ranked in the top quartile with probability>0.90.Conclusion: Estimates of adjusted hospital chemotherapy rates based solely on cancer registry data overstate the precision of assessments of hospital quality. Using additional information from a physician survey and applying rigorous statistical models, better inferences can be drawn about provider quality. [ABSTRACT FROM AUTHOR]

Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized low-density lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (P<0.026 and P<0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (P<0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (P<0.001). oxLDL correlated with MDA positively (P=0.008), and PON1 negatively (P=0.008). A negative correlation between MDA and PON1 (P=0.014) was detected. MDA correlated positively with both SBP and DBP (P=0.001), while PON1 correlated with both of them negatively (P=0.01 and P=0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P=0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.Journal of Human Hypertension (2004) 18, 523-528. doi:10.1038/sj.jhh.1001697 Published online 26 February 2004 [ABSTRACT FROM AUTHOR]

Background:The relationship between oxidative stress and osteoarthritis (OA) has been widely investigated. Serum malondialdehyde (MDA), nitric oxide (NO), and Cu/Zn superoxide dismutase (SOD) levels are useful markers of oxidative stress. Because of the importance of oxidative stress markers in the pathogenesis of OA, treatment might involve modification of these markers to control oxidative stress.Objective:The aim of this study was to compare the effects of 2 conventionalNSAIDs on markers of oxidative stress in patients with OA of the knee.Methods:This 3-week, prospective, randomized, open-label, active- and placebo-controlled study was conducted at the Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Adult patients with clinically and radiographically diagnosed moderate OA of the knee who were previously untreated were enrolled. Patients were randomly assigned to 1 of 3 treatment groups: flurbiprofen 100 mg PO (tablets) BID, tiaprofenic acid 300 mg PO (tablets) BID, or placebo tablets BID. Patients were evaluated using clinical assessment and laboratory testing before treatment (week 0; baseline) and at the end of week 3. The primary end points were the differences in serum MDA, NO, and SOD levels versus placebo. Clinical parameters-pain at rest and on motion-were evaluated using a 10-cm visual analog scale (0 = no pain to 10 = worst pain imaginable). The duration (in minutes) of morning stiffness was recorded by patients, using patient diaries. The differences between treatment groups were assessed using multivariate analysis.Results:Thirty-nine patients (20 women, 19 men; mean [SD] age, 59.0 [11.3] years) were included in the study. Mean serum MDA and NO levels were significantly decreased at 3 weeks compared with baseline in the 2 active-treatment groups (all, P < 0.001); these values remained statistically similar to baseline in the placebo group. Serum SOD levels were increased significantly from baseline in the 2 active-treatment groups (both, P < 0.001), but not in the placebo group. No significant differences in serum MDA and NO levels were found between the group receiving flurbiprofen and that receiving tiaprofenic acid. Serum SOD levels were significantly higher in the flurbiprofen group compared with the tiaprofenic acid and placebo groups (both, P < 0.01). The mean (SD) score for pain at rest was significantly lower at 3 weeks compared with baseline with flurbiprofen and tiaprofenic acid (both, P < 0.001), but not with placebo. The mean score for pain on motion was significantly reduced from baseline values only with tiaprofenic acid (P < 0.001). The duration of morning stiffness was significantly shorter at 3 weeks compared with baseline in all 3 study groups (all, P < 0.001). The mean scores for pain on motion and duration of morning stiffness were significantly reduced with tiaprofenic acid compared with placebo (both, P < 0.05). The study had some limitations (ie, small sample size, no blinding, the short duration of the study, and the weak correlation between serum and synovial fluid levels of NO).Conclusions:In this comparison of the effects of 3 weeks of treatment withflurbiprofen 100 mg BID and tiaprofenic acid 300 mg BID in patients with knee OA, both treatments effectively reduced serum MDA and NO levels compared with placebo. Only tiaprofenic acid significantly improved pain at rest and on motion and duration of morning stiffness compared with placebo. [ABSTRACT FROM AUTHOR]

Purpose: We measured corticosteroid medication adherence (CMA) in sarcoidosis patients and analyzed if demographic and clinical factors, beliefs about medications, corticosteroid side-effects, psychosocial status, and the doctor-patient relationship were associated with corticosteroid adherence., Methods: Sarcoidosis patients receiving corticosteroids were eligible to participate. CMA was measured using the Medication Adherence Response Scale-10 (MARS-10), a validated patient reported outcome measure (PRO). Data collection included patient demographics and clinical variables to assess their sarcoidosis phenotype. The patients were administered additional PROs concerning their psychosocial status, beliefs about medication use, corticosteroid side-effects and the strength of their doctor-patient relationship., Results: 132 patients were enrolled. Their mean prednisone dose was 9.9 ± 7.5 mg/day. 75% (99/132) were adherent with corticosteroids (MARS-10 ≥ 6) and 25% (33/132) were nonadherent (MARS-10 < 6). All demographic features, education level, and annual family income were not associated with CMA. Most clinical variables including spirometry, use of additional sarcoidosis drugs, number of organs involved with sarcoidosis were not associated with CMA. Almost all PROs including a better attitude toward medication use, less psychological issues, less corticosteroid side-effects, and a stronger doctor-patient relationship were associated with better CMA. A multi-logistic regression found that patient-doctor communication and the patient's intrinsic beliefs about the use of medications remained associated with CMA., Conclusion: We found no significant relationship between demographic or socioeconomic factors and CMA. Few clinical factors were associated with CMA. In a univariate analysis, CMA was associated with physician-doctor communication, beliefs about medication use, psychological/emotional issues, and corticosteroid side-effects. Only the first two of these factors remained associated with CMA in a multi-logistic analysis. These data suggest that CMA is heavily influenced by sarcoidosis patient beliefs about medications, and less so by patient demographics., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: DNA methylation integrates environmental signals with transcriptional programs. COVID-19 infection induces changes in the host methylome. While post-acute sequelae of COVID-19 (PASC) is a long-term complication of acute illness, its association with DNA methylation is unknown. No universal blood marker of PASC, superseding single organ dysfunctions, has yet been identified., Methods: In this single centre prospective cohort study, PASC, post-COVID without PASC, and healthy participants were enrolled to investigate their symptoms association with peripheral blood DNA methylation data generated with state-of-the-art whole genome sequencing. PASC-induced quality-of-life deterioration was scored with a validated instrument, SF-36. Analyses were conducted to identify potential functional roles of differentially methylated loci, and machine learning algorithms were used to resolve PASC severity., Findings: 103 patients with PASC (22.3% male, 77.7% female), 15 patients with previous COVID-19 infection but no PASC (40.0% male, 60.0% female), and 27 healthy volunteers (48.1% male, 51.9% female) were enrolled. Whole genome methylation sequencing revealed 39 differentially methylated regions (DMRs) specific to PASC, each harbouring an average of 15 consecutive positions, that differentiate patients with PASC from the two control groups. Motif analyses of PASC-regulated DMRs identify binding domains for transcription factors regulating circadian rhythm and others. Some DMRs annotated to protein coding genes were associated with changes of RNA expression. Machine learning support vector algorithm and random forest hierarchical clustering reveal 28 unique differentially methylated positions (DMPs) in the genome discriminating patients with better and worse quality of life., Interpretation: Blood DNA methylation levels identify PASC, stratify PASC severity, and suggest that DNA motifs are targeted by circadian rhythm-regulating pathways in PASC., Funding: This project has been funded by the following agencies: NIH-AI173035 (A. Jaitovich and R. Alisch); and NIH-AG066179 (R. Alisch)., Competing Interests: Declaration of interests AM, RA and AJ share pending patent application (20220364187): “Detecting, predicting severity of, and/or predicting treatment response to respiratory virus infection”., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate whether the acoustic measure of cepstral peak prominence changes during typical development in children 2-7., Methods: Data were retrospectively analyzed from the Arizona Child Acoustic Database Repository in this longitudinal cohort study. The Repository contains longitudinal data recordings from 63 total children between 2 and 7 years of age. Thirty-one children met the inclusion criteria for the current analysis (at least five time points of usable speech data, no history of speech or language difficulties, no significant dysphonia, and were monolingual speakers of American English). Cepstral peak prominence measures were calculated in Praat for each child, at each timepoint. Additional acoustic measures of vocal fundamental frequency, vocal intensity, and stimuli length were also calculated. These measures were chosen as previous work has shown they may impact cepstral peak prominence values., Results: Linear mixed-effects regression models examined the relationship between cepstral peak prominence and age, after controlling for vocal fundamental frequency, vocal intensity, and stimuli length. Within-participant effects of age were found, indicating a trajectory change in which cepstral peak prominence increases with age in this population. This positive relationship between a cepstral peak prominence and age was nonlinear, with a steeper slope between age and cepstral peak prominence after 5 years of age., Conclusions: This is the first study to examine the typical developmental trajectory of cepstral peak prominence children between 2 and 7 years, a critical period of vocal development. Cepstral peak prominence increased with age, suggesting an increase in periodicity of vocal fold vibration that coincides with the significant vocal fold structural changes occurring during this time. Outcomes present important normative information on vocal development, essential for effectively understanding the difference between what vocal changes are part of normative development and what changes indicate a voice disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women., Objective: To determine whether baseline or 1-year changes in plasma amyloid-β40 (Aβ40), Aβ42, ratio of Aβ42 to Aβ40, total tau (t-tau), phosphorylated tau 231 (p-tau231), glial fibrillary acidic protein (GFAP), and/or neurofilament light chain (NFL) are associated with neuropsychological performance (NP) among women living with HIV (WLWH) and women living without HIV (WLWOH)., Design, Setting, and Participants: This longitudinal, prospective, cohort study with 1-year repeated clinical measures (NP only measured once) and biospecimen collection occurred between 2017 and 2019. Participants were women aged 40 years or older from 10 clinical research sites in cities across the US that were part of the Women's Interagency HIV Study. Data analysis was conducted from April to December 2022., Exposure: Laboratory-confirmed HIV status and AD biomarkers., Main Outcomes and Measures: Sociodemographically adjusted NP T-scores (attention and working memory, executive function, processing speed, memory, learning, verbal fluency, motor function, and global performance) were the primary outcomes. Baseline and 1-year fasting plasma Aβ40, Aβ42, t-tau, p-tau231, GFAP, and NFL levels were measured and analyzed using multivariable linear regression., Results: The study consisted of 307 participants (294 aged ≥50 years [96%]; 164 African American or Black women [53%]; 214 women with a high school education or higher [70%]; 238 women who were current or former smokers [78%]; and 236 women [77%] who were overweight or obese [body mass index >25]) including 209 WLWH and 98 WLWOH. Compared with WLWOH at baseline, WLWH performed worse on learning (mean [SD] T-score 47.8 [11.3] vs 51.4 [10.5]), memory (mean [SD] T-score 48.3 [11.6] vs 52.4 [10.2]), verbal fluency (mean [SD] T-score 48.3 [9.8] vs 50.7 [8.5]), and global (mean [SD] T-score 49.2 [6.8] vs 51.1 [5.9]) NP assessments. Baseline median Aβ40, GFAP, and NFL levels were higher among WLWH vs WLWOH. There were no differences in 1-year biomarker change by HIV serostatus. Lower learning, memory, and motor NP were associated with 1-year Aβ40 increase; lower learning and motor with Aβ42 increase; lower motor with p-tau231 increase; and lower processing speed, verbal fluency and motor with NFL increase in the entire sample. Among WLWH, a 1-year increase in Aβ40 from baseline to follow-up was associated with worse learning, memory, and global NP; a 1-year increase in t-tau with worse executive function; and a 1-year increase in NFL with worse processing speed. Among WLWOH, a 1-year increase in Aβ40 and Aβ42 were associated with poorer memory performance and NFL was associated with poorer motor performance., Conclusions and Relevance: These findings suggest that increases in certain plasma AD biomarkers are associated with NP in WLWH and WLWOH and may be associated with later onset of AD, and measuring these biomarkers could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV.

Over the last years, the use of peripheral blood-derived big datasets in combination with machine learning technology has accelerated the understanding, prediction, and management of pulmonary and critical care conditions. The goal of this article is to provide readers with an introduction to the methods and applications of blood omics and other multiplex-based technologies in the pulmonary and critical care medicine setting to better appreciate the current literature in the field. To accomplish that, we provide essential concepts needed to rationalize this approach and introduce readers to the types of molecules that can be obtained from the circulating blood to generate big datasets; elaborate on the differences between bulk, sorted, and single-cell approaches; and the basic analytical pipelines required for clinical interpretation. Examples of peripheral blood-derived big datasets used in recent literature are presented, and limitations of that technology are highlighted to qualify both the current and future value of these methodologies.

Purpose: We performed a retrospective analysis of a sarcoidosis cohort who had sACE obtained at their initial clinic visit, but the treating physician was blinded to the results. We examined the relationship between sACE and the treating physician's decision to escalate sarcoidosis treatment., Methods: Treatment was considered escalated if the prednisone dose was increased or if the prednisone dose was not changed but an additional anti-sarcoidosis drug was added or the dose was increased., Results: 561 sarcoidosis patients were analyzed. The most common target organ was the lung (84%). Using a cut-off of > 82 units/L for an elevated sACE, 31/82 (38%) with an elevated sACE had treatment escalation whereas 91/497 (18%) had treatment escalation with a normal sACE (p < 0.0001). For the need of treatment escalation, a sACE (cut-off of > 82) had sensitivity 0.25, specificity 0.89, positive predictive value 0.38, negative predictive value 0.81. These results were not appreciably different using other sACE cut-off values such as 70, 80, 90, or 100. A multivariable logistic regression model that included demographics, the target organ, spirometry results estimated that sACE level and lower FVC were significantly associated with the likelihood of treatment escalation. These findings held when sACE > 82 replaced sACE level in the multivariable logistic regression model., Conclusions: Although there was a strong correlation between sACE at the initial sarcoidosis clinic visit and subsequent treatment escalation of sarcoidosis, the predictive power was such that sACE is not adequately reliable to be used in isolation to make this determination., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study was to investigate whether risk estimates for childhood acute lymphoblastic leukemia change when restricting model comparison groups to "nonpesticide exposure" (NPE10) households., Methods: Cases ( n = 1810) 15 years or younger were identified through Children's Cancer Group institutions between 1989 and 1993 and age-/sex-matched to controls ( n = 1951). Household pesticide use during pregnancy/month prior was collected via telephone. NPE10 comparison group reporting no parental exposure to 10 pesticide classes was identified., Results: Adjusted odds ratios increased from 15% to 49% when limiting the comparison to NPE10. Maternal termite insecticide exposure was associated with greatest risk (adjusted odds ratio, 4.21; 95% confidence interval, 2.00-8.88). There was minimal evidence of interaction by child sex or occupational pesticide exposure, and no monotonic dose-response pattern with frequency of use (times per year)., Conclusions: Elevated risks are consistent with published pooled-/meta-analyses and DNA damage. The consistency and magnitude of these associations warrant product labeling, exposure reduction interventions, or both., Competing Interests: Conflict of interest: None declared., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

Objective: To evaluate the demographic, maternal, and community-level predictors of pediatric respiratory syncytial virus (RSV) and influenza diagnosis among an urban population of children residing in Rochester, NY., Study Design: A test-negative case-control design was used to investigate various non-clinical determinants of RSV and influenza diagnosis among 1,808 children aged 0-14 years who presented to the University of Rochester Medical Center (URMC) or an affiliated health clinic in Rochester, NY between 2012-2019. These children were all tested for RSV and influenza via polymerase-chain-reaction (PCR) method, including RSV and influenza diagnosis of all severity types. Test results were linked to medical records, birth certificates, questionnaires administered through the Statewide Perinatal Data System, and the US census by census tracts to obtain information on child, maternal, demographic, and socio-economic characteristics., Results: Overall the strongest predictor of RSV and influenza diagnosis was child's age, with every year increase in child's age, risk for RSV decreased (OR: 0.75; 95% CI: 0.71, 0.79) and risk for influenza increased (OR: 1.20; 95%: 1.16, 1.24). In addition to age, non-private insurance type was positively associated with influenza diagnosis. When considering the proportion of positive cases for RSV and influenza over all PCR tests by respiratory season, a spike in influenza cases was observed in 2018-2019., Conclusions: Age was a strong predictor of RSV and influenza diagnosis among this urban sample of children., Competing Interests: Conflicts of Interest Authors have no conflicts of interest to declare.

The HIV epidemic continues to grow in Kazakhstan and HIV stigma remains a major barrier to HIV prevention and treatment in the country. HIV stigma in healthcare setting may also discourage people living with HIV (PLHIV) from getting the care needed. Therefore, studying the attitudes of healthcare workers towards PLHIV is important and requires well-constructed measurement tools adapted to the specific cultural context. In our study, we aimed to adapt and re-validate a brief questionnaire on HIV stigma among healthcare workers in Almaty, Kazakhstan. We held focus group discussions to obtain input on an existing questionnaire and surveyed 448 primary healthcare providers to psychometrically evaluate the scale. The final HIV-stigma scale consisted of 15 items, 6 of them measuring negative opinions about PLHIV and the rest assessing stigmatizing health facility policies towards PLHIV. Both HIV-stigma subscales demons6trated adequate psychometric properties (with Cronbach's alpha α = 0.57 for the first and α = 0.86 for the second subscale, and with factor loadings >0.35 within each subscale). High numbers of respondents holding negative attitudes towards PLHIV, detected in this sample (87%; n = 380), may suggest the need for immediate actions addressing HIV stigma in healthcare in Kazakhstan., Competing Interests: The authors have declared that no competing interests exist.

Background: The optimal treatment strategy for cardiac sarcoidosis has not been standardized. We examined the effectiveness of three prednisone-tapering treatment regimens for cardiac sarcoidosis., Methods: We retrospectively reviewed prednisone-tapering treatment regimens for cardiac sarcoidosis that contained prednisone alone (P), prednisone plus methotrexate (P-M), and prednisone plus infliximab containing regimens (P-I). We defined the success of each regimen as the ability to lower the daily prednisone dose to 7.5 mg or less for 6 or more months without developing an adverse cardiac event. We also examined the lowest effective daily prednisone dose achieved without developing an adverse cardiac event., Results: We identified 61 treatment regimens in 33 cardiac sarcoidosis patients that were analyzed. The success rate of prednisone-tapering regimens was significantly different P: 8/30, 27%; P-M: 3/23, 13%; P-I: 6/8, 75%., p = 0.04. The lowest effective daily prednisone dose for the regimens was also significantly different: P: 14.1 ± 10.1 mg; P-M: 16.9 ± 9.4 mg; infliximab: 7.8 ± 4.9 mg, (p = 0.03); by both measures the success was greatest with the P-I regimen., Conclusions: For the treatment of cardiac sarcoidosis, prednisone-tapering regimens containing infliximab are superior to those containing prednisone alone or prednisone plus methotrexate in terms of reaching 7.5 mg/day of prednisone for more than 6 months and achieving the lowest effective prednisone., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Marc A. Judson reports a relationship with Mallinckrodt LLC that includes: funding grants. Marc A. Judson reports a relationship with aTyr Pharma that includes: funding grants. Marc A. Judson reports a relationship with Star Therapeutics, Inc. that includes: funding grants. Marc A. Judson reports a relationship with Kinevant that includes: funding grants., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Maintaining good mental health among Emergency Department healthcare workers (ED HCW) is paramount to well-functioning healthcare. We measured mental health and COVID-19 symptoms in ED HCW at a COVID-19 epicenter., Methods: A cross-sectional, convenience sample of adult (≥18 years) ED HCW in Brooklyn, New York, USA, who were employed at ≥50% of a full-time effort, was surveyed September-December, 2020 with reference period March-May 2020. An anonymous email-distributed survey assessed gender, age, race, healthcare worker status (clinical versus non-clinical), SARS-CoV-2 testing, number of people to talk to, COVID-19-related home problems, mental health care interruption during COVID-19, loneliness, and survey date. Outcomes included symptoms of depression, psychological distress, perceived stress, post-traumatic stress disorder (PTSD), anxiety, and resilience measured using validated scales., Results: Of 774 HCW, 247 (31.9%) responded (mean age 38.2±10.8 years; 59.4% White; 52.5% men; 80.1% clinical; 61.6% SARS-CoV-2 tested). Average mental health scores were significantly higher among clinical vs non-clinical HCW (P's<0.0001-0.019). The proportion reporting a clinically-relevant psychological distress symptom burden was higher among clinical vs non-clinical HCW (35.8% vs 13.8%, p=0.019); and suggested for depression (53.9% clinical vs 35.7% non-clinical, p=0.072); perceived stress (63.6% clinical vs 44.8% non-clinical, p=0.053); and PTSD (18.2% clinical vs 3.6% non-clinical, p=0.064). Compared to non-clinical staff, Medical Doctors and Doctors of Osteopathy reported 4.8-fold higher multivariable-adjusted odds of clinically-relevant perceived stress (95%CI 1.8-12.9, p=0.002); Emergency Medical Technicians reported 15.5-fold higher multivariable-adjusted odds of clinically-relevant PTSD (95%CI 1.6-150.4, p=0.018). Increasing age, number of COVID-19-related home problems and people to talk to, loneliness and mental health care interruption were adversely associated with mental health; being male and SARS-CoV-2 testing were beneficial., Conclusions: COVID-19-related mental health burden was high among ED HCW in Brooklyn. Mental health support services are essential for ED HCW., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest related to this study.

Introduction: The impact of common measures to assess sarcoidosis have not been compared longitudinally to outcomes that are meaningful to patients. We prospectively examined the relationship of baseline measurements of sarcoidosis status to outcomes of interest to patients longitudinally over 6 months., Methods: Sarcoidosis patients cared for at 6 US medical centers were "phenotyped" at baseline with measurements of pulmonary function, organ involvement, health related quality of life (HRQoL) instruments, and their anti-sarcoidosis treatment history. These patients were followed for 6 months by monitoring outcomes of interest to patients (OIPs) including steps walked, calories expended, sleep, HRQoL measures, workdays missed and health care utilization. For each baseline phenotypic measurement, patients were dichotomized into two groups above and below a specified cutoff value. The area under the OIP versus time curve was compared between these two groups., Results: The cutoff values for many baseline phenotypic measures distinguished the patients into groups with significantly different 6-month OIPs. The chosen cutoff for the patient global estimate of health status distinguished the most OIPs (13/15). The 6-min walk distance cutoff was associated with more OIPs than spirometric measures. All of the HRQOL measure cutoffs were associated with many OIPs, although most of them were other HRQOL measures., Interpretation: Cutoffs for most of the phenotypic measures used to assess sarcoidosis distinguished groups of sarcoidosis patients with differing OIPs over the subsequent 6 months. The patients' global assessment of their disease was the most accurate of these measures., Clinical Trial Registration Number: NCT04342403., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To evaluate the relationship between metabolic risk (MR) and depression in a sample of older Mexican Americans and examine whether the association differs by age at migration., Methods: Longitudinal study using data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (HEPESE) (N=807, mean age = 84.3). The analytical sample was compiled from wave 6 (2007) to wave 7 (2010-2011) of HEPESE. Random-effect logistic regression examined the association between MR and depression and tested the model stratified by nativity status and age at migration., Results: MR was associated with higher odds of depression for US-born Mexican Americans after controlling for potential confounders. Similarly, among Mexican Americans who migrated before age 20, MR was associated with higher odds of depression., Conclusion: The findings highlight the importance of age at migration when evaluating the health of foreign-born Mexican Americans from a life-course perspective. Particularly among Mexican Americans who migrated before age 20, those with MR were more vulnerable to depression than their counterparts without MR., Competing Interests: Competing Interests: None declared., (Copyright © 2021, Ethnicity & Disease, Inc.)

On March 12th, 2020, the WHO declared COVID-19 as a pandemic. The collective impact of environmental and ecosystem factors, as well as biodiversity, on the spread of COVID-19 and its mortality evolution remain empirically unknown, particularly in regions with a wide ecosystem range. The aim of our study is to assess how those factors impact on the COVID-19 spread and mortality by country. This study compiled a global database merging WHO daily case reports with other publicly available measures from January 21st to May 18th, 2020. We applied spatio-temporal models to identify the influence of biodiversity, temperature, and precipitation and fitted generalized linear mixed models to identify the effects of environmental variables. Additionally, we used count time series to characterize the association between COVID-19 spread and air quality factors. All analyses were adjusted by social demographic, country-income level, and government policy intervention confounders, among 160 countries, globally. Our results reveal a statistically meaningful association between COVID-19 infection and several factors of interest at country and city levels such as the national biodiversity index, air quality, and pollutants elements (PM 10, PM 2.5 , and O 3 ). Particularly, there is a significant relationship of loss of biodiversity, high level of air pollutants, and diminished air quality with COVID-19 infection spread and mortality. Our findings provide an empirical foundation for future studies on the relationship between air quality variables, a country's biodiversity, and COVID-19 transmission and mortality. The relationships measured in this study can be valuable when governments plan environmental and health policies, as alternative strategy to respond to new COVID-19 outbreaks and prevent future crises., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The number of highly destructive disasters is increasing in regions of the United States where the Hispanic population is growing fastest. Up-to-date studies of disaster preparedness are needed that include housing measures and other factors that may account for differences in disaster preparedness between Hispanics and other racial and ethnic groups. This study fills this gap in the literature by using data from the 2017 American Housing Survey, which includes a topical module on disaster planning along with the core measures of housing and neighborhood characteristics, including housing tenure. The results reveal that Hispanics are generally less prepared than non-Hispanic Whites regarding resource- and action-based measures, with a few exceptions. Hispanics, Blacks, and Asians are significantly more likely than Whites to have at least 3 gallons of water per person, and Hispanics and Blacks are significantly more likely than Whites and Asians to have flood insurance. The findings show that housing and residential characteristics are consistently significant in predicting preparedness-controlling for other relevant variables-although they do not attenuate the disadvantages that Hispanics and Blacks face in their disaster preparedness relative to Whites. Future research would benefit from further exploration of the linkage between racial and ethnic inequalities in housing and neighborhood characteristics and household disaster preparedness.

Background: There are limited data examining the diagnostic accuracy of thoracic ultrasonography (TUS) in distinguishing transudative from exudative pleural effusions., Research Question: What is the diagnostic accuracy of TUS in distinguishing transudative from exudative effusions in consecutive patients with pleural effusion?, Study Design and Methods: Consecutive patients who underwent TUS and subsequently a diagnostic thoracentesis with a pleural fluid analysis were identified. TUS images of the pleural effusions were interpreted by previously published criteria. We evaluated the diagnostic performance of TUS findings in predicting a transudative vs exudative pleural effusions and specific pleural diagnoses., Results: We evaluated 300 consecutive pleural effusions in 285 patients. The pleural effusions were classified as exudative in 229 of 300 cases (76%). TUS showed anechoic effusions in 122 of 300 cases (40%) and complex effusions in 178 of 300 cases (60%). An anechoic appearance on TUS was associated with exudative effusions (68/122; 56%) as compared with transudative effusions (54/122; 44%). The presence of a complex-appearing effusion on TUS was highly predictive of an exudative effusion (positive predictive value of 90%). However, none of the four TUS characteristics were highly specific of a pleural diagnosis., Interpretation: Thoracic ultrasonography is inadequate to diagnose a transudative pleural effusion reliably. Although the TUS findings of a complex effusion may suggest an exudative pleural effusion, specific pleural diagnoses cannot be predicted confidently., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Antimicrobial peptides and proteins (AMPs) provide an important line of defence against invading microorganisms. However, the activity of AMPs against the human fungal pathogen Aspergillus fumigatus remains poorly understood. Therefore, the aim of this study was to characterise the anti- Aspergillus activity of specific human AMPs, and to determine whether A. fumigatus can possess resistance to specific AMPs, as a result of in-host adaptation. AMPs were tested against a wide range of clinical isolates of various origins (including cystic fibrosis patients, as well as patients with chronic and acute aspergillosis). We also tested a series of isogenic A. fumigatus isolates obtained from a single patient over a period of 2 years. A range of environmental isolates, obtained from soil in Scotland, was also included. Firstly, the activity of specific peptides was assessed against hyphae using a measure of fungal metabolic activity. Secondly, the activity of specific peptides was assessed against germinating conidia, using imaging flow cytometry as a measure of hyphal growth. We showed that lysozyme and histones inhibited hyphal metabolic activity in all the A. fumigatus isolates tested in a dose-dependent fashion. In addition, imaging flow cytometry revealed that histones, β-defensin-1 and lactoferrin inhibited the germination of A. fumigatus conidia.

Background/objectives: Information on recent changes in overweight, obesity, and adiposity among American Indians is scarce. To assess changes in size and adiposity among American Indian youth, data from two samples of Akwesasne Mohawk youth, were compared., Subjects/methods: Both project 1, conducted in 1979 (n = 75) and Project 2, conducted between 1996 and 1999 (n = 206), sampled youth 10-14 years of age from the Akwesasne Mohawk Reservation (aka St. Regis) that borders New York state, and Ontario and Quebec provinces. Heights, weights, and skinfold thicknesses were converted to z-scores using CDC reference values. BMI status was calculated in terms of WHO age-specific cutoffs and CDC cutoffs., Results: z-Scores for heights differed little between projects. The between-project difference in weight z-score is twice the between-project z-score difference for height. Differences among males are larger and more often significant. Triceps and subscapular skinfold thickness are significantly greater in Project 2. The rate of overweight and obesity combined, increased 3.3-fold. In multiple regression analyses with sex, height, and age in the model, project is a significant predictor of weight and skinfolds., Conclusions: Weight and adiposity have increased substantially from 1979 to 1996-99. Overweight and obesity became significantly more common. Given the increase in adiposity, these youth may be facing significant health risks as adults in terms of cardiovascular disease, cancer, and type II diabetes unless weight and adiposity is reduced.

Background: Cross-sectional studies have linked greater polychlorinated biphenyl (PCB) exposure to adverse neuropsychological effects in older adults, including learning, memory, and depressive symptoms. However, no studies among older adults have evaluated the association over time., Objectives: To assess the effect of serum PCB levels on neuropsychological function over a 14-year period in a cohort of older men and women from a PCB-contaminated area of New York State., Methods: In 2000-2002, we assessed serum PCB levels and neuropsychological function (including the California Verbal Learning Test Trial 1 (CVLTT1) for verbal memory and learning, and the Beck Depression Index (BDI) for depressive symptoms) in 253 men and women, ages 55-74 years. A total of 116 (46%) persons repeated the PCB and neuropsychological assessment 14 years later. To assess the association over time, we used generalized estimating equations with clustering variables time, total PCB (∑PCB), and ∑PCB × time, and adjusted for baseline age, sex, smoking, and total serum-lipids. For statistically significant ∑PCB × time interactions, we evaluated the association between PCBs and either verbal memory and learning or depressive symptoms while holding ∑PCB constant at the 10th and 90th percentiles to clarify the direction of the interaction., Results: Over the study period, serum ∑PCB levels (wet-weight) declined by 22%, and were associated with different patterns of change over time for memory (∑PCB × Time β = 0.08 p = 0.009) and depressive symptoms (∑PCB × Time β = -0.16 p = 0.013). Specifically, verbal memory and learning decreased (β = -0.08 p = 0.008) and depressive symptoms increased (β = 0.17 p = 0.008) among persons with low exposure (∑PCB levels at the 10th percentile), while persons with high exposure (90th percentile) showed non-significant improvements., Discussion: In this cohort, declining ∑PCB levels were likely due at least in part to low rates of local fish consumption in recent decades, given the ban since 1976. The decreased verbal memory and learning and increased depressive symptoms over time among persons with low serum ∑PCB levels is consistent with studies of normative aging. However, the small improvements in those outcomes among those with high serum ∑PCB levels was unexpected. Healthy survivor selection bias or uncontrolled confounding may explain this result. It may also indicate that the neurotoxic impacts of PCBs in older adults are not permanent, but future studies are needed to confirm this possibility., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Purpose: Classification of overdose deaths is often geographically and demographically inconsistent. Incomplete surveillance records may distort estimates of drug overdose rates across time and place. We examined incomplete toxicology reporting among drug overdose decedents by demographic and geographic characteristics, measuring changes in missingness rates and their associations with decedent characteristics over time., Methods: We estimated the percentage of overdose deaths reported in the National Vital Statistics System with missing toxicology results from 2010 to 2016, overall and by decedents' demographic and geographic characteristics. Multilevel logistic regression models evaluated prevalence of missingness by decedent characteristics, accounting for geographic clustering., Results: Overall, 20.3% of death certificates did not indicate a specific drug, declining from 24.4% in 2010 to 14.6% in 2016. Deaths were less likely to have missing information if they occurred in counties with medical examiners versus coroners. Female decedents were more likely to have missing information than males, as were non-Hispanic whites compared with Hispanics and non-Hispanic blacks., Conclusions: The percentage of deaths with missing toxicology information declined over time, but demographic and geographic differences in missingness persist. This yields detection biases that skew temporal trends and understanding of groups impacted by the opioid epidemic., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although it is the general consensus that sarcoidosis patients who present with sarcoidosis-related symptoms have a worse outcome than patients whose disease is detected incidentally without symptoms, this premise has not been rigorously examined., Methods: Consecutive patients followed longitudinally at one US university sarcoidosis clinic were questioned concerning the onset and description of sarcoidosis-related symptoms at disease presentation. The patients were classified into those with no sarcoidosis-related symptoms at presentation (NSP group) and those with symptoms at presentation (SP group). The following outcomes were examined in the NSP and SP groups: most recent spirometry, organ involvement, need for sarcoidosis therapy, most recent health related quality of life (HRQOL) as measured by the Sarcoidosis Assessment Tool (SAT), most recent chest imaging Scadding stage results., Results: 660 sarcoidosis patients were analyzed, with 175 in the NSP group and 485 in the SP group. Compared to the NSP group, the SP group had a more frequent requirement for any sarcoidosis treatment, corticosteroid treatment, and non-corticosteroid treatment at some time and within the most recent year of follow up (at least 50% more than the NP group with strong statistical differences with p values all 0.01 or less). In addition, the SP group had significantly more organ involvement (p < 0.001) and several worse SAT domains (p < 0.022) than the NP group. There were no differences between the groups in terms of final spirometry or development of Scadding stage 4 chest radiographs. These findings held even after adjusting for age, sex, race, and time between presentation and the most recent follow-up visit using a multivariable logistic regression framework., Conclusions: In our sarcoidosis cohort, compared to the absence of symptoms at presentation, the presence of symptoms was associated with a greater need for treatment, more organ involvement, and worse HRQOL., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Research demonstrates significant variability in mental health clinicians' overall and domain-specific effectiveness with their patients. Despite calls to increase patient access to performance information, little is known about patients' relative valuing of this information in the context of other treatment factors., Objective: We aimed to obtain an understanding of patients' relative valuing of provider performance track records and other therapist and treatment characteristics for their mental health care decision making., Method: Participants were 403 (M age = 41.20; 66.5% female) community mental health patients who completed a multicomponent survey that included an adapted delayed-discounting paradigm to examine the relative valuing. Multiple descriptive, quantitative indices of relative valuing were calculated, as well as an exploratory latent profile analysis to ascertain the presence of homogenous relative-valuing subgroups., Results: Overall, participants valued provider track record information. They also evidenced relatively higher preference values for working with therapists who had specific efficacy in treating their primary problem domain, charged less, and with whom there is a high likelihood of establishing a good alliance. Two latent profiles were identified: one representing higher valuing of provider performance and another consistently representing less emphasis. Participants with higher track-record valuing were younger, believed that therapists are not interchangeable, and endorsed trust in the collection and use of performance information., Conclusion: Harnessing clinician information to make more personalized and informed treatment decisions could potentially promote better treatment engagement, retention, and outcomes. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Introduction: The significance of mediastinal lymphadenopathy in bacterial pneumonia is unclear., Methods: We performed a retrospective analysis of mediastinal lymph node size determined by chest CT in patients with bacteremic pneumococcal pneumonia. All patients who had positive blood cultures for streptococcus pneumonia over an 11-year period and had a chest CT scan (index CT) within 2 weeks of the positive blood culture were included in the study. Two thoracic radiologists and one pulmonologist independently examined the index CT plus any chest CT scans performed prior (pre-CT) or after (post-CT) the bacteremic episode., Results: The study cohort of 49 patients was 57% male, 65% White, with mean age of 53 (SD = 20) years. Mediastinal lymphadenopathy was detected in 25/49 (51%) of the cases. The mean size of the largest mediastinal lymph node in short axis was 0.99 (SD = 0.71), ranging from 0.0 to 2.05 cm. There was no correlation noted between the number of lobes involved with pneumonia, and the size of the largest mediastinal lymph node (p = 0.33) or the number of pathologically enlarged mediastinal lymph nodes (p = 0.08). There was a statistically significant increase in the mean size of the largest lymph node between the pre-CT and index-CT group (p = 0.02), and decrease between the index-CT group and the post-CT (p = 0.03)., Conclusion: Pneumococcal pneumonia with bacteremia is associated with mild mediastinal lymph node enlargement. The presence of marked mediastinal lymphadenopathy (short axis LN size > 2 cm) should not be assumed from pneumococcal pneumonia.

Background: Vitamin D dysregulation may occur in sarcoidosis patients and result in hypercalciuria, hypercalcemia, nephrolithiasis, and renal impairment. We performed an open label pilot study of highly purified (H.P.) Acthar® Gel (repository corticotropin injection) (RCI) on patients with sarcoidosis-induced vitamin D dysregulation and hypercalciuria. Methods: Nine patients with sarcoidosis-induced vitamin D dysregulation and hypercalciuria on stable maintenance anti-sarcoidosis therapy received 80 units of RCI subcutaneously twice weekly for 12 weeks. 24-hour urinary calcium excretion was measured at baseline and at 12 weeks. Other parameters measured over 16 weeks (including 4 weeks post the last RCI dose) included the following serum values: calcium, 25-OH vitamin D, 1,25- diOH vitamin D and serum parathyroid hormone (PTH). In addition, the Sarcoidosis Health Questionnaire (SHQ) and Short Form-36 (SF-36) as well as a urinary symptom score were measured in all subjects. Results: There was no significant change in the 24-hour urinary calcium excretion over 12 weeks of the study. However, there was evidence that RCI improved sarcoidosis-induced vitamin D dysregulation in that the serum 1,25- diOH vitamin D level significantly declined over 12 weeks. There was also improvement in most of the domains of the quality of life measures, although only a few of them reached statistical significance. There was also a trend toward improvement in urinary symptoms over the study period. The was evidence of the development corticosteroid side effects in the cohort, in that weight significantly increased over the study period. Conclusions: In this small pilot open label trial, 12 weeks of RCI did not significantly improve sarcoidosis-induced hypercalciuria. However, some statistically significant changes in serum vitamin D and PTH levels were demonstrated that were consistent with some amelioration of sarcoidosis-induced vitamin D dysregulation. Several corticosteroid-related side effects were demonstrated in this cohort. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 192-197) ., (Copyright: © 2018.)

Minimal data exist regarding the neurotoxicity of perfluoroalkyl substances (PFASs) in aging populations and the possible mediating effects of thyroid hormones (THs). Hence, the aims of this study were to: (i) assess associations between PFASs and neuropsychological function, and (ii) determine if such associations are mediated by changes in circulating THs in an aging population. We measured perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), total thyroxine (T4) and free thyroxine (fT4) in serum and performed neuropsychological tests in 126 men and women aged 55-74 years and living in upper Hudson River communities. Multivariable linear regressions were conducted to assess associations between PFASs and neuropsychological test scores. Mediation analyses were performed in a subset of 87 participants for whom information was available on both PFASs and THs. We calculated TH-mediated, non-TH mediated, and total effects of PFASs on neuropsychological test scores. Higher PFOA was associated with better performance in tasks of the California Verbal Learning Test and the Wisconsin Card Sorting Test. Higher PFOS was associated with improved performance in a Wechsler Memory Scale subtest and Block Design Subtest (BDT) total scores. There was no evidence of mediation by THs for PFOA-neuropsychological function associations. However, T4 and fT4 partially mediated the protective effect of PFOS on BDT total scores. Our findings do not suggest that PFASs are associated with poor neuropsychological function. There was some evidence of mediation for the association between PFASs and neuropsychological functions by THs, although some other modes of action also appear likely., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background: Previous studies demonstrated that SAA staining of sarcoidosis granulomas was qualitatively and quantitatively different from other granulomatous diseases. These data suggest that positive SAA staining of granulomatous tissue may have adequate specificity to establish a diagnosis of sarcoidosis. Our objective was to determine the diagnostic specificity of SAA staining for sarcoidosis relative to other granulomatous disorders., Methods: Pathological specimens demonstrating granulomatous inflammation were retrospectively identified at one institution, plus 4 specimens were obtained from New York City firefighters with biopsy-confirmed World Trade Center "sarcoidosis-like" pulmonary disease. Specimens were analyzed if specific diagnoses related to the granulomatous inflammation were confirmed through medical record review. SAA staining was performed using previously developed methods. Two pathologists, blinded to each other and the diagnoses, determined if the stained material was SAA positive or negative. Discordant results were adjudicated by the two pathologists., Measurements and Main Results: 106 specimens were analyzed from 100 patients, with 36 biopsies (34%) from sarcoidosis tissues and 70 (66%) from other granulomatous disorders. The Cohen Kappa correlation between the two pathologists for SAA staining positivity was excellent (0.85, 0.73-0.98). The overall specificity of SAA staining for the diagnosis of sarcoidosis was 84% (59/70). The sensitivity was 44% (16/36)., Conclusions: Although SAA staining of various granulomatous tissues was fairly specific for the diagnosis of sarcoidosis, the specificity was inadequate for SAA staining to be used as a diagnostic test for sarcoidosis in isolation. These data suggest that SAA production may not be a universal mechanism in the development of sarcoidosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Overt thyroid dysfunction is recognized as a risk factor for neuropsychological deficits in aging populations, yet evidence for how changes in levels of circulatory thyroid hormones impact specific neuropsychological domains is limited. Here we report cross-sectional associations between serum thyroid hormone concentrations and several neuropsychological function domains among men and women aged 55-74years. We administered neuropsychological tests to assess memory, learning, executive function, measures of attention, visuospatial function, affective state, and motor function. Multivariable linear regression analyses were performed adjusting for age, sex, education, and cigarette smoking. Effects were reported as differences in test scores per one interquartile range (IQR) increase in hormone concentration. Higher total thyroxine (T4) and free thyroxine (fT4) were associated with improved visuospatial function, as measured by Block Design Subtest total scores; associated increments per IQR differences in T4 and fT4 were 15% and 19%, respectively (false discovery rate q-values <0.05). We also detected statistical interactions between age and fT4 for effects in tasks of memory and learning. Concurrent increases in age and fT4 were associated with deficits in memory and learning as measured by California Verbal Learning Test subtests (10% and 16% deficits in t-score and short delay free recall score, respectively). Our findings suggest that changes in thyroid hormones may have important implications for neuropsychological function in aging populations. Further large-scale studies with comprehensive thyroid function and neuropsychological outcome assessments are warranted to confirm these results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: This study examines whether aging in place (community-based living before admission to a nursing home) delays nursing home admission among New York State home health care recipients., Design: Retrospective cohort study (January 2007-December 2012)., Setting: New York State., Participants: Adults age 65+ who received home health services for at least 2 months before permanent nursing home admission., Measurement and Analysis: Permanent transition is defined as home care patients who are discharged to and stay at a nursing home for more than 3 months. Data were abstracted from the Minimum Data Set (MDS) and Outcome and Assessment Information Set (OASIS). Descriptive and bivariate Kruskal-Wallis and χ(2) tests were performed., Results: The average age of nursing home residents at admission remained steady at 83 years between 2007 and 2012. The proportion of minority populations (Asian, black, Hispanic/Latino) increased, whereas the white population declined (P < .0001). The average length of stay at home increased 8 months, from 17 months in 2007 to 25 months in 2012 (P < .0001). Chronic conditions with significant increases in prevalence during the study period were hypertension (P < .0009), dementia (P < .0001), heart failure (P = .05), urinary incontinence (P < .0001), and bowel incontinence (P < .0001). Increases in functional disabilities requiring extensive human assistance included toileting, dressing, personal hygiene, and transferring (all P < .001)., Conclusion: Home health services enabled recipients to remain at home 8 months longer, thus delaying nursing home entry. Given the increase in prevalence of comorbidities and disability, we anticipate a concomitant increase in support services at the nursing home. These results may inform policy and staffing decisions regarding adjustments in required caregivers' credentials and nurse-patient ratios., (Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Both sarcoidosis and its treatment may worsen health related quality of life (HRQoL). We performed a propensity analysis of sarcoidosis-specific HRQoL patient reported outcome measures (PRO) to disentangle the effects of sarcoidosis and corticosteroid therapy on HRQoL in sarcoidosis outpatients., Methods: Consecutive outpatient sarcoidosis patients were administered modules from two sarcoidosis-specific HRQoL PROs: the Sarcoidosis Health Questionnaire (SHQ) and the Sarcoidosis Assessment Tool (SAT). Patients were divided into those that received ≤500 mg of prednisone (PRED-LOW) versus >500 mg of prednisone (PRED-HIGH) over the previous year. SAT and SHQ scores were initially compared in the two corticosteroid groups. Then a multivariate analysis was performed using a propensity score analysis adjusted for race, age, gender and the severity of illness., Results: In the unadjusted analysis, the PRED-HIGH group demonstrated the following worse HRQoL scores compared to the LOW-PRED group: SHQ Daily (p = 0.02), SAT satisfaction (p = 0.03), SAT daily activities (p = 0.03). In the propensity analysis, the following domains demonstrated worse HRQoL in the PRED-HIGH group than the PRED-LOW group: SAT fatigue (p < 0.0001), SAT daily activities (p = 0.03), SAT satisfaction (p = 0.03). All these differences exceeded the established minimum important difference for these SAT domains. The SHQ Physical score appeared to demonstrate a borderline improved HRQoL in the PRED-HIGH versus the PRED-LOW group (p = 0.05).). In a post-hoc exploratory analysis, the presence of cardiac sarcoidosis may have explained the quality of life differences between the two corticosteroid groups., Conclusions: Our cohort of sarcoidosis clinic patients who received ≤500 mg of prednisone in the previous year had an improved HRQoL compared to patients receiving >500 mg on the basis of two sarcoidosis-specific PROs after adjusting for severity of illness. These data support the need to measure HRQoL in sarcoidosis trials, and suggest that the search should continue for effective alternative medications to corticosteroids., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Current understanding of the thyroid disruptive properties of perfluoroalkyl substances (PFASs), particularly in aging populations, is limited. The objectives of this study were to (i) assess associations between thyroid function, as measured by serum thyrotropin (thyroid stimulating hormone, TSH), free thyroxine (fT4), total thyroxine (T4), and total triiodothyronine (T3), and serum perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in an aging population and (ii) determine if other persistent organic pollutants with thyroid disruptive properties including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) modify such associations. We conducted a cross-sectional study of 87 men and women 55 to 74years of age, without clinically-diagnosed thyroid disease, who resided in upper Hudson River communities in New York. Geometric means (standard deviations) of serum PFOS and PFOA were 31.6 (1.7) ng/mL and 9.17 (1.72) ng/mL, respectively. Multivariable linear regression analyses indicated that one interquartile range difference in PFOS corresponded to 4% and 9% increases in fT4 and T4 respectively. We detected statistical interactions between PFOA and age for effects on fT4 and T4; joint increases in PFOA and age were associated with increases in fT4 and T4, of 3% and 7%, respectively. We also detected statistical interactions between PFOS and total PCBs for the effect on T3 and between PFOA and total PBDEs for the effect on TSH. Our results suggest that PFASs are associated with subtle alterations in thyroid hormone levels in this population, and that these associations are likely to vary by age, and levels of PCBs and PBDEs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: The Fatigue Assessment Scale (FAS) is a 10-item patient reported outcome (PRO) questionnaire that is used to measure fatigue in sarcoidosis. After several months of use, we began to question the reliability of the FAS in our clinic population. Therefore, we administered an additional fatigue PRO, the Patient Reported Outcomes Measurement Information Systems (PROMIS) Fatigue Instrument (PFI). Our hypothesis was that the internal consistency/reliability (Cronbach's alpha) of the PFI would be superior to the FAS in sarcoidosis patients because two of the ten FAS items (items #4 and #10) required reverse scoring (these items were scaled in the opposite direction to the other 8 items)., Methods: The FAS and PFI were administered during the same clinic visit to consecutive patients in our sarcoidosis clinic. We calculated a) the Cronbach's alpha for a) the FAS; b) the FAS without items #4 and #10; and c) the PFI., Results: 107 consecutive sarcoidosis patients underwent FAS and PFI testing. The Cronbach's alpha was 0.740, 0.911, and 0.963 for the FAS, FAS with items #4 and #10 removed, and the PFI respectively. In female patients, the Cronbach's alpha of the FAS was 0.663, which is considered as "questionable" in terms of internal consistency., Conclusion: We found that the PFI had "excellent" consistency in our sarcoidosis clinic. The FAS did not demonstrate the same degree of internal consistency. The Cronbach's estimate of the FAS with items #4 and #10 removed was vastly superior to the FAS. These data support our contention that FAS items #4 and #10 detract from the internal consistency of this PRO. They also suggest that the PFI is superior to the FAS in terms of reliability.

The objective of the study was to evaluate whether mental health problems identified through screens administered in first grade are related to poorer academic achievement test scores in the fourth grade. The government of Chile uses brief teacher- and parent-completed measures [Teacher Observation of Classroom Adaptation-Revised (TOCA-RR) and Pediatric Symptom Checklist (PSC-Cl)] to screen for mental health problems in about one-fifth of the country's elementary schools. In fourth grade, students take the national achievement tests (SIMCE) of language, mathematics and science. This study examined whether mental health problems identified through either or both screens predicted achievement test scores after controlling for student and family risk factors. A total of 17,252 students had complete first grade teacher forms and these were matched with fourth grade SIMCE data for 11,185 students, 7,903 of whom also had complete parent form data from the first grade. Students at risk on either the TOCA-RR or the PSC-Cl or both performed significantly worse on all SIMCE subtests. Even after controlling for covariates and adjusting for missing data, students with mental health problems on one screen in first grade had fourth grade achievement scores that were 14-18 points (~1/3 SD) lower than students screened as not at risk. Students at risk on both screens had scores that were on average 33 points lower than students at risk on either screen. Mental health problems in first grade were one of the strongest predictors of lower achievement test scores 3 years later, supporting the premise that for children mental health matters in the real world.

In designed longitudinal studies, information from the same set of subjects are collected repeatedly over time. The longitudinal measurements are often subject to missing data which impose an analytic challenge. We propose a functional multiple imputation approach modeling longitudinal response profiles as smooth curves of time under a functional mixed effects model. We develop a Gibbs sampling algorithm to draw model parameters and imputations for missing values, using a blocking technique for an increased computational efficiency. In an illustrative example, we apply a multiple imputation analysis to data from the Panel Study of Income Dynamics and the Child Development Supplement to investigate the gradient effect of family income on children's health status. Our simulation study demonstrates that this approach performs well under varying modeling assumptions on the time trajectory functions and missingness patterns., (Copyright © 2011 John Wiley & Sons, Ltd.)

Self-care is recommended to kidney transplant recipients as a vital component to maintain long-term graft function. However, little is known about the effects of physical activity, fluid intake, and smoking history on graft function. This longitudinal study examined the relationship between self-care practices on graft function among 88 new kidney transplant recipients in Chicago, IL and Albany, NY between 2005 and 2008. Participants were interviewed, completed surveys, and medical charts were abstracted. Physical activity, fluid intake, and smoking history at baseline were compared with changes in estimated glomerular filtration rate (eGFR) (every 6 months up to 1 year) using bivariate and multivariate regression analysis, while controlling for sociodemographic and clinical transplant variables. Multivariate analyses revealed that greater physical activity was significantly (P < 0.05) associated with improvement in GFR at 6 months; while greater physical activity, absence of smoking history, and nonwhite ethnicity were significant (P < 0.05) predictors of improvement in GFR at 12 months. These results suggest that increasing physical activity levels in kidney recipients may be an effective behavioral measure to help ensure graft functioning. Our findings suggest the need for a randomized controlled trial of exercise, fluid intake, and smoking history on GFR beyond 12 months.

Objective: To evaluate if children with special health care needs (CSHCN) residing in states with more generous public insurance programs were less likely to report delayed or forgone care., Methods: We used multilevel modeling to evaluate state policy characteristics after controlling for individual characteristics. We used the 2001 National Survey of CSHCN for individual-level data (N=33,317) merged with state-level data, which included measures of the state's public insurance programs (Medicaid eligibility and enrollment, spending on Medicaid, SCHIP and Title V, and income eligibility levels), state poverty level and provider supply (including pediatric primary care and specialty providers). We also included a variable for state waivers for CSHCN requiring institutional level care., Results: Delayed or forgone care significantly varied among CSHCN between states, net of individual characteristics. Of all the state characteristics studied, only the Medicaid income eligibility levels influenced the risk of experiencing delayed care. CSHCN living in states with higher income eligibility thresholds or more generous eligibility levels were less likely to experience delayed care (OR 0.89(0.80,0.99); P