Peripheral Blood Omics and Other Multiplex-based Systems in Pulmonary and Critical Care Medicine.

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.

The Relationship Between Serum Angiotensin Converting Enzyme Level and the Decision to Escalate Treatment of Sarcoidosis.

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.

Variability of essential and non-essential trace elements in the follicular fluid of women undergoing in vitro fertilization (IVF).

Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct "snapshot" of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exposure misclassification. Our objectives were to investigate sources of trace element variability, to estimate FF biomarker reliability among women undergoing IVF (n = 34), and to determine the minimum number of follicles required to estimate subject-specific mean concentrations. We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. Inter-subject (between-women) variability contributed most of the variability in FF element concentrations, with ovarian, follicular, and analytical as smaller sources of variability. The proportion of variability attributable to sources between-follicles differed by age, body mass index (BMI), race, and cigarette smoking for Cu, Se, and Zn, by BMI and cigarette smoking for As, by primary infertility diagnosis for Hg, Cu, Se, and Zn, and by ovarian stimulation protocol for Mn and Se. Four to five individual follicles were sufficient to estimate subject-specific mean Cu, Se, and Zn concentrations, while >14 were necessary for As, Hg, Cd, Pb, and Mn. Overall, our results suggest that FF is a suitable source of biomarkers of As and Hg exposure in ovarian follicles. Although limited in size, our study offers the most comprehensive exploration of biological variation in FF trace elements to date and may provide guidance for future studies of ovarian trace element exposures.

Trends in height, weight, BMI, skinfolds, and measures of overweight and obesity from 1979 through 1999 among American Indian Youth: The Akwesasne Mohawk.

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.

Seafood consumption is associated with higher follicular fluid arsenic (As) and mercury (Hg) concentrations in women undergoing in vitro fertilization (IVF).

Human exposure to non-essential toxic metals such as cadmium (Cd), mercury (Hg), and lead (Pb), and metalloids such as arsenic (As) commonly occurs through diet. Toxic trace element exposures have been reported in association with fertility and fecundity in epidemiologic studies even at low to moderate levels. While most previous studies employed blood and urine biomarkers of exposure, few have assessed toxic trace elements in ovarian follicular fluid (FF), which surrounds the developing oocyte and hence may better reflect concentrations potentially affecting reproductive outcomes. Our objective was to identify dietary predictors of FF toxic trace elements in n = 56 women (mean age: 38.3 years) undergoing in vitro fertilization (IVF) at the University of California at San Francisco. We determined As, Hg, Cd, and Pb in 197 FF specimens, collected on the day of oocyte retrieval, using inductively coupled plasma tandem mass spectrometry. A comprehensive food frequency questionnaire was used to assess the weekly and annual dietary "patterns" of participants. Consumption of specific seafood items and turkey were correlated with individual FF toxic trace elements. We also found that each unit higher seafood consumption in the past week dominated by mollusks, shrimp, and bass was associated with 60% higher FF As (95% confidence interval (CI): 25%, 105%) and FF Hg (95%CI: 7%, 136%) concentrations. Higher annual seafood consumption dominated by urchin, crab, and trout was associated with 16% higher FF As (95%CI: -2%, 38%) and 31% higher FF Hg (95%CI: 7%, 60%) concentrations per unit intake. No associations were noted between diet and Cd and Pb levels in FF. Overall, our results suggest that higher seafood consumption contributes to elevated levels of As and Hg in FF. These findings are consistent with previous IVF studies that assessed toxic trace element exposures in blood and urine. To our knowledge, this is the first study to report that diet might be a source of As, Hg, Cd, and Pb in FF.

Muslim-Non-Muslim Locational Attainment in Philadelphia: A New Fault Line in Residential Inequality?

This study examines Muslim-non-Muslim disparities in locational attainment. We pool data from the 2004, 2006, and 2008 waves of the Public Health Management Corporation's Southeastern Pennsylvania Household Survey. These data contain respondents' religious identities and are geocoded at the census-tract level, allowing us to merge American Community Survey data and examine neighborhood-level outcomes to gauge respondents' locational attainment. Net of controls, our multivariate analyses reveal that among blacks and nonblacks, Muslims live in neighborhoods that have significantly lower shares of whites and greater representations of blacks. Among blacks, Muslims are significantly less likely than non-Muslims to reside in suburbs. The Muslim disadvantages for blacks and nonblacks in neighborhood poverty and neighborhood median income, however, become insignificant. Our results provide support for the tenets of the spatial assimilation and place stratification models and suggest that Muslim-non-Muslim disparities in locational attainment define a new fault line in residential stratification.

Metabolic Syndrome Among Asian Indians in the United States.

INTRODUCTION: Metabolic syndrome (MetS), a clustering of cardiometabolic risk factors of type 2 diabetes and cardiovascular disease, disproportionately affects Asian Indians (AIs). We examined prevalence of MetS using 3 ethnicity-specific MetS criteria among immigrant AIs in the United States. We also examined associations between MetS and health promotion behaviors. OBJECTIVE: To present MetS prevalence estimates by the 3 ethnicity-specific criteria and investigate differences in health promotion behaviors among AIs with and without MetS to highlight the critical need for lifestyle modification strategies for this population. DESIGN: We analyzed data from a national cross-sectional study of 1037 AIs in the United States (2004-2006). We used the consensus criteria, International Diabetes Federation criteria, and modified criteria to estimate MetS prevalence. The Health Promotion Lifestyle Profile II scale measured health promotion behaviors. Bioclinical data (fasting blood glucose, triglyceride levels) were collected. Directed acyclic graphs and Likelihood Ratio Test assisted with model selection. Multiple imputation inference incorporated uncertainty due to missing data and made use of all available data. Adjusted multivariable logistic regression analysis tested for associations. RESULTS: Out of all participants, 40.3% met the consensus criteria, 34.8% met the International Diabetes Federation criteria, and 52.5% met the modified criteria. We found no statistically significant associations between engagement in health promotion measures and the prevalence of MetS and its criteria. CONCLUSION: Our study confirmed the high prevalence of MetS in the immigrant AI population in the United States. Our results showed that AIs with MetS did not exhibit an increased level of engagement in health promotion behaviors. We recommend continued refining of criteria for diagnosis and culturally suitable, age-appropriate strategies to increase engagement in healthier lifestyles among this high-risk population.

Assessment of Mediastinal Lymph Node Size in Pneumococcal Pneumonia with Bacteremia.

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.

Occupational exposure to perfluoroalkyl substances and serum levels of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in an aging population from upstate New York: a retrospective cohort study.

PURPOSE: Perfluoroalkyl substances (PFASs) are environmentally persistent amphiphilic compounds. Exposure to two PFASs, perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) is linked to specific occupations and industries. This study examines the contribution of past occupational PFAS exposure to serum PFOS and PFOA levels among 154 older adults in New York State. METHODS: Serum PFOS and PFOA levels were compared to data from the National Health and Nutrition Examination Survey (NHANES). Potential occupational exposure to any PFAS was determined from work histories, reviewed by an industrial hygienist, and assessed in relation to current serum PFOS and PFOA levels using exposure probability, duration and cumulative exposure. RESULTS: We observed 25% higher serum PFOS and 80% higher PFOA levels in study participants compared to NHANES. No participants reported PFAS chemical manufacturing work, but n = 68 reported work in occupations and industries known to use PFASs. We found that participants with high cumulative workplace exposure had 34% higher serum PFOS levels compared to participants without occupational exposure, adjusted for age, sex and income. Serum PFOS levels were 26% higher for participants with longer occupational exposure durations. The probability of occupational PFAS exposure metric was not associated with serum PFOS. Serum PFOA was not associated with any measure of occupational exposure. CONCLUSION: Occupational exposure may contribute to total PFOS body burden in this study population, even among workers not directly involved in manufacturing PFASs. PFAS exposure assessments should evaluate the workplace as a potential source, even when workplace exposures are assumed to be low or moderate.

The Assessment of Cough in a Sarcoidosis Clinic Using a Validated instrument and a Visual Analog Scale.

PURPOSE: Cough is a common symptom of pulmonary sarcoidosis. We analyzed the severity of cough and factors associated with cough in a university sarcoidosis clinic cohort. METHODS: Consecutive patients completed the Leicester Cough Questionnaire (LCQ) and a cough visual analog scale (VAS). Clinical and demographic data were collected. Means of the LCQ were analyzed in patients who had multiple visits in terms of constant variables (e.g., race, sex). RESULTS: 355 patients completed the LCQ and VAS at 874 visits. Cough was significantly worse in blacks than whites as determined by the LCQ-mean (16.5 ± 2.6 vs. 17.8 ± 3.0, p < 0.001) and VAS-mean (3.8 ± 3.0 vs. 2.0 ± 2.6, p < 0.0001). Cough was worse in women than men as measured by the VAS-mean (2.7 ± 2.9 vs. 2.2 ± 2.7, p = 0.002), one of the LCQ-mean domains (LCQ-Social-mean 5.4 ± 0.9 vs. 5.2 ± 1.0, p = 0.03), but not the total LCQ-mean score. Cough was not significantly different by either measure in terms of smoking status, age, or spirometric parameter (FVC % predicted, FEV1 % predicted, FEV1/FVC). In a multivariable linear regression analysis, cough was significantly worse in blacks than whites and in pulmonary sarcoidosis than non-pulmonary sarcoidosis with both cough measures, in women than men for the VAS only, and not for spirometric parameters, Scadding stage, or age. The LCQ and VAS were strongly correlated. CONCLUSIONS: In a large university outpatient sarcoidosis cohort, cough was worse in blacks than whites. Cough was not statistically significantly different in terms of age, spirometric measures, Scadding stage, or smoking status. The LCQ correlated strongly with a visual analog scale for cough.

Variability in follicular fluid high density lipoprotein particle components measured in ipsilateral follicles.

PURPOSE: The purpose of this study was to examine the biological variability of follicular fluid (FF) high density lipoprotein (HDL) particle components measured in ipsilateral ovarian follicles. METHODS: We collected FF from two ipsilateral follicles among six women undergoing in vitro fertilization (IVF). We measured concentrations of 19 FF HDL particle components, including HDL cholesterol, free cholesterol, four cholesteryl esters, phospholipids, triglycerides, paraoxonase and arylesterase activities, apolipoproteins A-1 and A-2 (ApoA-1 and ApoA-2), and seven lipophilic micronutrients, by automated analysis and with high-performance liquid chromatography. We assessed biological variability using two-stage nested analysis of variance and compared values with those previously published for contralateral follicles. RESULTS: For most FF HDL analytes, there was little variability between follicles relative to the variability between women (i.e., %σ(2) F:%σ(2) B <0.5). Intraclass correlation coefficients were >0.80 for HDL cholesterol (0.82), phospholipids (0.89), paraoxonase (0.96), and arylesterase (0.91) activities, ApoA-1 (0.89), and ApoA-2 (0.90), and single specimen collections were required to estimate the subject-specific mean, demonstrating sufficient reliability for use as biomarkers of the follicular microenvironment in epidemiologic and clinical studies. CONCLUSIONS: These preliminary results raise the possibility for tighter regulation of HDL in follicles within the same ovary vs. between ovaries. Thus, collection of a single FF specimen may be sufficient to estimate HDL particle components concentrations within a single ovary. However, our results should be interpreted with caution as the analysis was based on a small sample.

Sensitivity to imputation models and assumptions in receiver operating characteristic analysis with incomplete data.

Modern statistical methods using incomplete data have been increasingly applied in a wide variety of substantive problems. Similarly, receiver operating characteristic (ROC) analysis, a method used in evaluating diagnostic tests or biomarkers in medical research, has also been increasingly popular problem in both its development and application. While missing-data methods have been applied in ROC analysis, the impact of model mis-specification and/or assumptions (e.g. missing at random) underlying the missing data has not been thoroughly studied. In this work, we study the performance of multiple imputation (MI) inference in ROC analysis. Particularly, we investigate parametric and non-parametric techniques for MI inference under common missingness mechanisms. Depending on the coherency of the imputation model with the underlying data generation mechanism, our results show that MI generally leads to well-calibrated inferences under ignorable missingness mechanisms.

Lifecourse socioeconomic position and 16 year body mass index trajectories: differences by race and sex.

OBJECTIVE: The aim of this study is to evaluate the association between lifecourse socioeconomic position (SEP) and changes in body mass index (BMI), and assess disparities in these associations across racial/ethnic groups. METHODS: With longitudinal data from 4 waves of the Americans' Changing Lives Study (1986-2002), we employed mixed-effects modeling to estimate BMI trajectories for 1174 Blacks and 2323 White adults. We also estimated associations between these trajectories and lifecourse SEP variables, including father's education, perceived childhood SEP, own education, income, wealth, and financial security. RESULTS: Blacks had higher baseline BMIs, and steeper increases in BMI, compared to Whites. Childhood SEP, as measured by high father's education, was associated with lower baseline BMI among Whites. High education was associated with a lower baseline BMI within both race and sex categories. Income had contrasting effects among men and women. Higher income was associated with higher BMI only among males. Associations between indicators of SEP and BMI trajectories were only found for Whites. CONCLUSIONS: Our study demonstrates that lifecourse SEP may influence adult BMI differently within different racial and sex groups.

A computationally efficient sequential regression imputation algorithm for multilevel data.

Due to the computational burden, especially in high-dimensional settings, sequential imputation may not be practical. In this paper, we adopt computationally advantageous methods by sampling the missing data from their perspective predictive distributions, which leads to significantly improved computation time in the class of variable-by-variable imputation algorithms. We assess the computational performance in a comprehensive simulation study. We then compare and contrast the performance of our algorithm with commonly used alternatives. The results show that our method has a significant advantage over the commonly used alternatives with respect to computational efficiency and inferential quality. Finally, we demonstrate our methods in a substantive problem aimed at investigating the effects of area-level behavioral, socioeconomic, and demographic characteristics on poor birth outcomes in New York State among singleton births.

Longitudinal Evaluation of Cepstral Peak Prominence in Children.

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.

Blood DNA methylation in post-acute sequelae of COVID-19 (PASC): a prospective cohort study.

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).

Organ Donation Willingness Among Asian Americans: Results from a National Study.

Asian Americans are the fastest growing racial group in the USA, but their health disparities are often overlooked. Although their needs for transplantable organs are substantial, they have the lowest rates of organ donation per million compared to other Americans by race. To better understand Asian Americans' disposition toward organ donation, a self-administered survey was developed based on formative data collection and guidance from a Community Advisory Board composed of Asian American stakeholders. The instrument was deployed online, and quota sampling based on the 2017 American Community Survey was used to achieve a sample representative (N = 899) of the Asian American population. Bivariate tests using logistic regression and the chi-square test of independence were performed. Over half (58.1%) of respondents were willing to be organ donors. A majority (81.8%) expressed a willingness to donate a family member's organs, but enthusiasm depended on the family member's donor wishes. Only 9.5% of respondents indicated that the decision to donate their organs was theirs alone to make; the remainder would involve at least one other family member. Other key sociodemographic associations were found. This study demonstrates both the diversity of Asian Americans but also the centrality of the family's role in making decisions about organ donation. Practice and research considerations for the field are also presented.

Maternal and Paternal Household Pesticide Exposure During Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia.

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.

Organizational Health Literacy and Health Among New York State Medicaid Members.

BACKGROUND: The definition of health literacy has recently expanded beyond the idea of individual skills to include the system and environment the individual interacts with to receive care, known as organizational health literacy (OHL). However, neither the prevalence of OHL nor the impact of OHL on individuals' perceptions of their health and healthcare have been examined in New York's Medicaid managed care population. OBJECTIVE: This study aimed to estimate the prevalence of organizational health literacy in the New York State (NYS) Medicaid Managed Care (MMC) program. METHODS: A brief measure to assess organizational health literacy was developed from responses to two questions in the 2018 NYS Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Generalized Estimating Equation models were developed to analyze the association between organizational health literacy and three aspects of perceptions of health and health care, controlling for demographic differences and clustering effects from health insurance plans. Missing data were handled using multiple imputation. KEY RESULTS: Among 3,598 members included in the study, 20% of the MMC members reported inadequate organizational health literacy. These members were more likely to be older, less educated, from racial and ethnic minority groups, and less fluent with English. They are more likely to have poorer self-reported health (odds ratio [OR] 1.49), lower perceived access to health care (OR 6.97), and lower satisfaction with their health care (OR 6.49) than members who did not report inadequate organizational health literacy. CONCLUSIONS: Our results suggest that a proportion of the NYS MMC population faces inadequate organizational health literacy, which can present a barrier to health care access and result in patients having a significantly poorer health care experience. Using an existing data source that is part of existing data collection allows for routine assessment of organizational health literacy, which can help inform health plans about areas for potential improvement. [HLRP: Health Literacy Research and Practice. 2023;7(3):e154-e164.].

PLAIN LANGUAGE SUMMARY: Our study looked at the impact of organizational health literacy on the perceptions of health and health care of NYS Medicaid Managed Care population. We used existing CAHPS questions to assess organizational health literacy and found that lower organizational health literacy led to worse perceptions of health and health care. This article illustrates an opportunity to demonstrate how organizational health literacy can be measured with annual CAHPS collections.

Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV.

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-ß40 (Aß40), Aß42, ratio of Aß42 to Aß40, 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 Aß40, Aß42, 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 Aß40, 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 Aß40 increase; lower learning and motor with Aß42 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 Aß40 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 Aß40 and Aß42 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.