Prescription Opioids and Brain Structure in Community-Dwelling Older Adults.

OBJECTIVE: To evaluate the associations between prescription opioid exposures in community-dwelling older adults and gray and white matter structure by magnetic resonance imaging. METHODS: Secondary analysis was conducted of a prospective, longitudinal population-based cohort study employing cross-sectional imaging of older adult (≥65 years) enrollees between November 1, 2004, and December 31, 2017. Gray matter outcomes included cortical thickness in 41 structures and subcortical volumes in 6 structures. White matter outcomes included fractional anisotropy in 40 tracts and global white matter hyperintensity volumes. The primary exposure was prescription opioid availability expressed as the per-year rate of opioid days preceding magnetic resonance imaging, with a secondary exposure of per-year total morphine milligram equivalents (MME). Multivariable models assessed associations between opioid exposures and brain structures. RESULTS: The study included 2185 participants; median (interquartile range) age was 80 (75 to 85) years, 47% were women, and 1246 (57%) received opioids. No significant associations were found between opioids and gray matter. Increased opioid days and MME were associated with decreased white matter fractional anisotropy in 15 (38%) and 16 (40%) regions, respectively, including the corpus callosum, posterior thalamic radiation, and anterior limb of the internal capsule, among others. Opioid days and MME were also associated with greater white matter hyperintensity volume (1.02 [95% CI, 1.002 to 1.036; P=.029] and 1.01 [1.001 to 1.024; P=.032] increase in the geometric mean, respectively). CONCLUSION: The duration and dose of prescription opioids were associated with decreased white matter integrity but not with gray matter structure. Future studies with longitudinal imaging and clinical correlation are warranted to further evaluate these relationships.

Critical Values of Daily Sedentary Time and Its Longitudinal Association with Mild Cognitive Impairment Considering APOE ε4: A Prospective Cohort Study.

BACKGROUND: Long sedentary time and physical inactivity are negatively related to cognition, but the cut-off value remains unclear, and apolipoprotein E polymorphism ε4 (APOE ε4) is a known genetic risk factor of mild cognitive impairment (MCI). OBJECTIVES: To explore longitudinal association of sedentary time and MCI, and to identify a cutoff value that increases the risk of developing MCI, taking into account APOE ε4 stratification and its interactions. DESIGN: A prospective cohort study. SETTING: Population-based study. PARTICIPANTS: We included 4932 older adults from Tianjin Elderly Nutrition and Cognition (TENC) cohort study recruited from March 2018 to June 2021 with 3.11 years of median follow-up time. MEASUREMENTS: The primary outcome was newly diagnosed MCI, which was diagnosed by a modified version of the Petersen's criteria. The information of sedentary time (hours/day) and physical activity (MET-h/week) were obtained by questionnaire. Cox proportional hazard regression models and restricted spline curve were conducted. RESULTS: A total of 4932 participants were included (mean [SD] age, 67.85 [4.96] years; 2627 female [53.3%] and 2305 male [46.7%]), 740 newly onset MCI patients were identified. Longer sedentary time was associated with higher risk of MCI for all participants (HR:1.069, 95%CI: 1.034, 1.105), especially in APOE ε4 non-carriers (HR:1.083, 95%CI: 1.045, 1.123) whether adjusted potential confounders. Sedentary time had synergistic interactions with APOE ε4 (ß:1.503, 95%CI: 1.163, 1.942) and physical activities (ß: 1.495, 95%CI: 1.210, 1.846). Restricted spline curve showed a cut-off value of 3.03 hours/day. CONCLUSIONS: Long sedentary time (≥3.03 hours/day) could increase MCI risk, especially in APOE ε4 non-carriers, people with higher PA, aged 65 and above.

Tirzepatide Reduces Fat Mass and Provides Good Glycaemic Control in Type 2 Diabetes Patients Undergoing Haemodialysis: A Single-Centre Retrospective Study.

OBJECTIVE: Tirzepatide is an injectable peptide approved by the US Food and Drug Administration for the treatment of Type 2 diabetes (T2DM). Its weight-loss effect primarily targets fat reduction; however, such effect on patients with chronic kidney disease (CKD) undergoing haemodialysis (HD) has not been reported. METHODS: Nine patients with CKD undergoing HD received weekly tirzepatide doses (2.5-7.5 mg) once a week. Evaluations encompassed tirzepatide's impact on dry weight (DW) and body composition assessed at baseline and study conclusion using bioelectrical impedance analysis. This longitudinal study included nine patients, with a median age of 53 years and median HD duration of 4 years. RESULTS: Tirzepatide treatment significantly decreased glycated albumin compared with the value at baseline (22.7 ± 5.4 vs. 18.3 ± 2.5%, p = 0.028, respectively). Significant reductions were observed in DW (-1.0 kg, p = 0.024) and body mass index (-0.6 kg/m2, p = 0.050) following tirzepatide administration. Total fat mass was also reduced, but not significantly (- 2.51% from baseline, p = 0.214). In contrast, skeletal muscle mass was not decreased (-1.02% from baseline, p = 0.722). No serious side effects other than nausea were observed during the study period. CONCLUSION: Tirzepatide effectively provides good glycaemic control in T2DM patients undergoing HD, decreasing DW by reducing body fat mass without increasing frailty risk.

Longitudinal patterns of natural hazard exposures and anxiety and depression symptoms among young adults in four low- and middle-income countries.

We estimated the effect of community-level natural hazard exposure during prior developmental stages on later anxiety and depression symptoms among young adults and potential differences stratified by gender. We analyzed longitudinal data (2002-2020) on 5585 young adults between 19 and 26 years in Ethiopia, India, Peru, and Vietnam. A binary question identified community-level exposure, and psychometrically validated scales measured recent anxiety and depression symptoms. Young adults with three exposure histories ("time point 1," "time point 2," and "both time points") were contrasted with their unexposed peers. We applied a longitudinal targeted minimum loss-based estimator with an ensemble of machine learning algorithms for estimation. Young adults living in exposed communities did not exhibit substantially different anxiety or depression symptoms from their unexposed peers, except for young women in Ethiopia who exhibited less anxiety symptoms (average causal effect [ACE] estimate = - 8.86 [95% CI: - 17.04, - 0.68] anxiety score). In this study, singular and repeated natural hazard exposures generally were not associated with later anxiety and depression symptoms. Further examination is needed to understand how distal natural hazard exposures affect lifelong mental health, which aspects of natural hazards are most salient, how disaster relief may modify symptoms, and gendered, age-specific, and contextual differences.

Physical fitness decline and career paths: a longitudinal study of medical undergraduates.

INTRODUCTION: Exercise enhances one's health and competitiveness. A strong physical fitness status can pave the way for a promising future. This study presents the time-based trends in physical fitness indicators-including height, weight, BMI, lung capacity, dash, long-distance running, and standing long jump-among medical undergraduates during their university years. Additionally, we analyzed the impact of students' physical fitness on their career paths. METHOD: We conducted a retrospective database study by collecting physical fitness test data and career paths information for 634 medical students from a university in southwestern China. These students graduated in 2022. The career paths included pursuits in further studies, employment, and unemployment. To detect differences in these aspects, we used the t-test and Chi-square test. RESULTS: Our study indicates a significant declining trend in the physical fitness of medical students during their university years. The changes observed between the first and fourth tests are as follows: Weight (kg): 58.52 ± 10.48 to 60.73 ± 12.07, P < 0.00 BMI (kg/m^2): 20.79 ± 2.74 to 21.24 ± 3.06, P < 0.00 50-m dash (s): 8.91 ± 0.99 to 9.25 ± 1.11, P < 0.00 Standing long jump (cm): 187.74 ± 30.98 to 182.59 ± 32.25, P < 0.00 800-m run for females (min): 3.84 ± 0.47 to 4.48 ± 0.85, P < 0.00 1000-m run for males (min): 3.98 ± 0.63 to 4.62 ± 0.87, P < 0.00 Sit-ups for females (count): 30.39 ± 7.5 to 29.03 ± 8.82, P < 0.00 Upon analyzing the correlation between changes in physical fitness and career paths, students with stable or decreased BMI had better post-graduation outcomes compared to students with increased BMI. CONCLUSIONS: Medical students show a declining trend in physical fitness during their undergraduate years. A good physical health status is beneficial for achieving better career paths. Medical students should place greater emphasis on physical exercise during their time in school.

Cross-border mobility in the Meuse-Rhine Euroregion: impact of COVID-19 border restrictions on everyday activities and visiting social network members.

Introduction: Cross-border mobility (CBM) to visit social network members or for everyday activities is an important part of daily life for citizens in border regions, including the Meuse-Rhine Euroregion (EMR: neighboring regions from the Netherlands, Belgium, and Germany). We assessed changes in CBM during the COVID-19 pandemic and how participants experienced border restrictions. Methods: Impact of COVID-19 on the EMR' is a longitudinal study using comparative cross-border data collection. In 2021, a random sample of the EMR-population was invited for participation in online surveys to assess current and pre-pandemic CBM. Changes in CBM, experience of border restrictions, and associated factors were analyzed using multinomial and multivariable logistic regression analysis. Results: Pre-pandemic, 82% of all 3,543 participants reported any CBM: 31% for social contacts and 79% for everyday activities. Among these, 26% decreased social CBM and 35% decreased CBM for everyday activities by autumn 2021. Negative experience of border restrictions was reported by 45% of participants with pre-pandemic CBM, and was higher (p < 0.05) in Dutch participants (compared to Belgian; aOR= 1.4), cross-border [work] commuters (aOR= 2.2), participants with cross-border social networks of friends, family or acquaintances (aOR= 1.3), and those finding the measures 'limit group size' (aOR= 1.5) and 'minimalize travel' (aOR= 2.0) difficult to adhere to and finding 'minimalize travel' (aOR= 1.6) useless. Discussion: CBM for social contacts and everyday activities was substantial in EMR-citizens, but decreased during the pandemic. Border restrictions were valued as negative by a considerable portion of EMR-citizens, especially when having family or friends across the border. When designing future pandemic control strategies, policy makers should account for the negative impact of CBM restrictions on their citizens.

Giving a Voice to Patients With Smell Disorders Associated With COVID-19: Cross-Sectional Longitudinal Analysis Using Natural Language Processing of Self-Reports.

BACKGROUND: Smell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or phantosmia (smells perceived without an odor source being present). Similar to the difficulty that people experience when talking about their smell experiences, patients find it difficult to express or label the symptoms they experience, thereby complicating diagnosis. The complexity of these symptoms can be an additional burden for patients and health care providers and thus needs further investigation. OBJECTIVE: This study aims to explore the smell disorder concerns of patients and to provide an overview for each specific smell disorder by using the longitudinal survey conducted in 2020 by the Global Consortium for Chemosensory Research, an international research group that has been created ad hoc for studying chemosensory dysfunctions. We aimed to extend the existing knowledge on smell disorders related to COVID-19 by analyzing a large data set of self-reported descriptive comments by using methods from natural language processing. METHODS: We included self-reported data on the description of changes in smell provided by 1560 participants at 2 timepoints (second survey completed between 23 and 291 days). Text data from participants who still had smell disorders at the second timepoint (long-haulers) were compared with the text data of those who did not (non-long-haulers). Specifically, 3 aims were pursued in this study. The first aim was to classify smell disorders based on the participants' self-reports. The second aim was to classify the sentiment of each self-report by using a machine learning approach, and the third aim was to find particular food and nonfood keywords that were more salient among long-haulers than those among non-long-haulers. RESULTS: We found that parosmia (odds ratio [OR] 1.78, 95% CI 1.35-2.37; P<.001) as well as hyposmia (OR 1.74, 95% CI 1.34-2.26; P<.001) were more frequently reported in long-haulers than in non-long-haulers. Furthermore, a significant relationship was found between long-hauler status and sentiment of self-report (P<.001). Finally, we found specific keywords that were more typical for long-haulers than those for non-long-haulers, for example, fire, gas, wine, and vinegar. CONCLUSIONS: Our work shows consistent findings with those of previous studies, which indicate that self-reports, which can easily be extracted online, may offer valuable information to health care and understanding of smell disorders. At the same time, our study on self-reports provides new insights for future studies investigating smell disorders.

Socio-economic inequalities in the breadth of internet use before and during the COVID-19 pandemic among older adults in England.

Understanding digital exclusion in older adults during the COVID-19 pandemic could help tailor responses to future outbreaks. This cohort study used data from older adults aged 60+ years in England who participated in wave nine (2018/2019) of the main English Longitudinal Study of Ageing (ELSA) survey, and/or wave one of the ELSA COVID-19 sub-study (June/July 2020). Using latent class analysis and latent transition analysis, we aimed to identify distinct subgroups of older adults characterised by different patterns of internet use pre- and intra-pandemic, explore the extent to which individuals remained in the same subgroup or transitioned to a different subgroup during the COVID-19 pandemic, and examine longitudinal associations of socio-economic factors (education, occupational class, and wealth) with latent class membership. Preliminary tests showed that the types of internet activities differed between men and women; therefore, subsequent analyses were stratified by biological sex. Three clusters (low, medium, and high) were identified in male participants at both timepoints. Among female participants, three clusters were distinguished pre-pandemic and two (low versus high) during the pandemic. The latent classes were characterised by participants' breadth of internet use. Higher education, occupational class, and wealth were associated with greater odds of membership in the medium and/or high classes, versus the low class, in men and women. A high degree of stability in latent class membership was observed over time. However, men experienced a stark decrease in online health information-seeking. Our results highlight that inequality regarding the range of functional and social opportunities provided by the internet prevailed during the pandemic. Policymakers should ensure that digital access and upskilling initiatives are equitable for all.

Understanding associations between the COVID-19 pandemic and menstrual hygiene management among adolescent girls in Ethiopia: findings from a mixed-methods longitudinal study.

OBJECTIVE: To understand the relationship between the COVID-19 pandemic and menstrual hygiene management (MHM) among adolescent girls in Ethiopia and to explore which girls were most affected by pandemic disruptions. DESIGN: Two rounds of data from surveys and interviews were collected with adolescent girls immediately prior to and during the COVID-19 pandemic. The primary analysis is cross-sectional, controlling for pre-COVID-19 covariates. SETTING: The setting was three zones in two regions of Ethiopia: East Hararghe and East Shewa Zones in Oromia and South Gondar Zone in Amhara. Data were collected in December 2019-March 2020 and September 2020-February 2021. PARTICIPANTS: 742 adolescent girls, ages 11-25 years. OUTCOME MEASURES: Four primary outcomes were explored (1) the number of challenges girls experienced; (2) adolescent-identified challenges managing menstrual hygiene; (3) adolescent-identified difficulties accessing MHM products and (4) adolescent-identified difficulties accessing soap or water. RESULTS: Girls who were more vulnerable to COVID-19 were more likely to have worse MHM outcomes. An SD increase in household vulnerability to COVID-19 was associated with an 8.7 percentage point increase in the likelihood that the respondent had difficulty getting MHM products (p<0.001), a 6 percentage point increase in the likelihood that she reported facing a challenge managing her menstruation (p=0.003) and a 5.2 percentage point increase in the likelihood she lacked soap or water (p=0.001). Qualitative themes, used to triangulate the quantitative findings, suggest that mobility restrictions, shutdowns of the local market, disruptions in supply chains, poverty, stigma and fear about contracting COVID-19 affected girls' access to MHM supplies. CONCLUSIONS: The results of this study suggest that MHM was left behind in the COVID-19 response. New programming and policy interventions need to address financial hardship and disruptions to supplies to manage menstruation as well as tackle the inequitable gender norms that stigmatise menstruation during emergencies.

Development and validation of a predictive model for the risk of sarcopenia in the older adults in China.

BACKGROUND: Sarcopenia is a progressive age-related disease that can cause a range of adverse health outcomes in older adults, and older adults with severe sarcopenia are also at increased short-term mortality risk. The aim of this study was to construct and validate a risk prediction model for sarcopenia in Chinese older adults. METHODS: This study used data from the 2015 China Health and Retirement Longitudinal Study (CHARLS), a high-quality micro-level data representative of households and individuals aged 45 years and older adults in China. The study analyzed 65 indicators, including sociodemographic indicators, health-related indicators, and biochemical indicators. RESULTS: 3454 older adults enrolled in the CHARLS database in 2015 were included in the final analysis. A total of 997 (28.8%) had phenotypes of sarcopenia. Multivariate logistic regression analysis showed that sex, Body Mass Index (BMI), Mean Systolic Blood Pressure (MSBP), Mean Diastolic Blood Pressure (MDBP) and pain were predictive factors for sarcopenia in older adults. These factors were used to construct a nomogram model, which showed good consistency and accuracy. The AUC value of the prediction model in the training set was 0.77 (95% CI = 0.75-0.79); the AUC value in the validation set was 0.76 (95% CI = 0.73-0.79). Hosmer-Lemeshow test values were P = 0.5041 and P = 0.2668 (both P > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. ROC and DCA showed that the nomograms had good predictive properties. CONCLUSIONS: The constructed sarcopenia risk prediction model, incorporating factors such as sex, BMI, MSBP, MDBP, and pain, demonstrates promising predictive capabilities. This model offers valuable insights for clinical practitioners, aiding in early screening and targeted interventions for sarcopenia in Chinese older adults.

Fetal and Infancy Exposure to Phenols, Parabens, and Phthalates and Anthropometric Measurements up to 36 Months, in the Longitudinal SEPAGES Cohort.

BACKGROUND: Endocrine-disrupting chemicals may play a role in adiposity development during childhood. Until now literature in this scope suffers from methodologic limitations in exposure assessment using one or few urine samples and missing assessment during the infancy period. OBJECTIVES: We investigated the associations between early-life exposure to quickly metabolized chemicals and post-natal growth, relying on repeated within-subject urine collections over pregnancy and infancy. METHODS: We studied the associations of four phenols, four parabens, seven phthalates, and one nonphthalate plasticizer from weekly pooled urine samples collected from the mother during second and third trimesters (median 18 and 34 gestational weeks, respectively) and infant at 2 and 12 months of age, and child growth until 36 months. We relied on repeated measures of height, weight and head circumference from study visits and the child health booklet to predict growth outcomes at 3 and 36 months using the Jenss-Bayley nonlinear mixed model. We assessed associations with individual chemicals using adjusted linear regression and mixtures of chemicals using a Bayesian kernel machine regression model. RESULTS: The unipollutant analysis revealed few associations. Bisphenol S (BPS) at second trimester was positively associated with all infant growth parameters at 3 and 36 months, with similar patterns between exposure at third trimester and all infant growth parameters at 3 months. Mono-n-butyl phthalate (MnBP) at 12 months was positively associated with body mass index (BMI), weight, and head circumference at 36 months. Mixture analysis revealed positive associations between exposure at 12 months and BMI and weight at 36 months, with MnBP showing the highest effect size within the mixture. CONCLUSIONS: This study suggests that exposure in early infancy may be associated with increased weight and BMI in early childhood, which are risk factors of obesity in later life. Furthermore, this study highlighted the impact of BPS, a compound replacing bisphenol A, which has never been studied in this context. https://doi.org/10.1289/EHP13644.

A surge in food insecurity during the COVID-19 pandemic in a cohort in Mexico City.

BACKGROUND: The COVID-19 pandemic has not only caused tremendous loss of life and health but has also greatly disrupted the world economy. The impact of this disruption has been especially harsh in urban settings of developing countries. We estimated the impact of the pandemic on the occurrence of food insecurity in a cohort of women living in Mexico City, and the socioeconomic characteristics associated with food insecurity severity. METHODS: We analyzed data longitudinally from 685 women in the Mexico City-based ELEMENT cohort. Food insecurity at the household level was gathered using the Latin American and Caribbean Food Security Scale and measured in-person during 2015 to 2019 before the pandemic and by telephone during 2020-2021, in the midst of the pandemic. Fluctuations in the average of food insecurity as a function of calendar time were modeled using kernel-weighted local polynomial regression. Fixed and random-effects ordinal logistic regression models of food insecurity were fitted, with timing of data collection (pre-pandemic vs. during pandemic) as the main predictor. RESULTS: Food insecurity (at any level) increased from 41.6% during the pre-pandemic period to 53.8% in the pandemic stage. This increase was higher in the combined severe-moderate food insecurity levels: from 1.6% pre-pandemic to 16.8% during the pandemic. The odds of severe food insecurity were 3.4 times higher during the pandemic relative to pre-pandemic levels (p<0.01). Socioeconomic status quintile (Q) was significantly related to food insecurity (Q2 OR = 0.35 p<0.1, Q3 OR = 0.48 p = 0.014, Q4 OR = 0.24 p<0.01, and Q5 OR = 0.17 p<0.01), as well as lack of access to social security (OR = 1.69, p = 0.01), and schooling (OR = 0.37, p<0.01). CONCLUSIONS: Food insecurity increased in Mexico City households in the ELEMENT cohort as a result of the COVID-19 pandemic. These results contribute to the body of evidence suggesting that governments should implement well-designed, focalized programs in the context of economic crisis such as the one caused by COVID-19 to prevent families from the expected adverse health and well-being consequences associated to food insecurity, especially for the most vulnerable.

The milk study protocol: A longitudinal, prospective cohort study of the relationship between human milk metabolic hormone concentration, maternal body composition, and early growth and satiety development in Samoan infants aged 1-4 months.

BACKGROUND: Current research suggests that energy transfer through human milk influences infant nutritional development and initiates metabolic programming, influencing eating patterns into adulthood. To date, this research has predominantly been conducted among women in high income settings and/or among undernourished women. We will investigate the relationship between maternal body composition, metabolic hormones in human milk, and infant satiety to explore mechanisms of developmental satiety programming and implications for early infant growth and body composition in Samoans; a population at high risk and prevalence for overweight and obesity. Our aims are (1) to examine how maternal body composition influences metabolic hormone transfer from mother to infant through human milk, and (2) to examine the influences of maternal metabolic hormone transfer and infant feeding patterns on early infant growth and satiety. METHODS: We will examine temporal changes in hormone transfers to infants through human milk in a prospective longitudinal cohort of n = 80 Samoan mother-infant dyads. Data will be collected at three time points (1, 3, & 4 months postpartum). At each study visit we will collect human milk and fingerpick blood samples from breastfeeding mother-infant dyads to measure the hormones leptin, ghrelin, and adiponectin. Additionally, we will obtain body composition measurements from the dyad, observe breastfeeding behavior, conduct semi-structured interviews, and use questionnaires to document infant hunger and feeding cues and satiety responsiveness. Descriptive statistics, univariate and multivariate analyses will be conducted to address each aim. DISCUSSION: This research is designed to advance our understanding of variation in the developmental programming of satiety and implications for early infant growth and body composition. The use of a prospective longitudinal cohort alongside data collection that utilizes a mixed methods approach will allow us to capture a more accurate representation on both biological and cultural variables at play in a population at high risk of overweight and obesity.

Open-source data pipeline for street-view images: A case study on community mobility during COVID-19 pandemic.

Street View Images (SVI) are a common source of valuable data for researchers. Researchers have used SVI data for estimating pedestrian volumes, demographic surveillance, and to better understand built and natural environments in cityscapes. However, the most common source of publicly available SVI data is Google Street View. Google Street View images are collected infrequently, making temporal analysis challenging, especially in low population density areas. Our main contribution is the development of an open-source data pipeline for processing 360-degree video recorded from a car-mounted camera. The video data is used to generate SVIs, which then can be used as an input for longitudinal analysis. We demonstrate the use of the pipeline by collecting an SVI dataset over a 38-month longitudinal survey of Seattle, WA, USA during the COVID-19 pandemic. The output of our pipeline is validated through statistical analyses of pedestrian traffic in the images. We confirm known results in the literature and provide new insights into outdoor pedestrian traffic patterns. This study demonstrates the feasibility and value of collecting and using SVI for research purposes beyond what is possible with currently available SVI data. Our methods and dataset represent a first of its kind longitudinal collection and application of SVI data for research purposes. Limitations and future improvements to the data pipeline and case study are also discussed.

Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

Association between disability and cognitive function in older Chinese people: a moderated mediation of social relationships and depressive symptoms.

Objective: Many previous studies have found that disability leads to cognitive impairment, and in order to better understand the underlying mechanisms between disability and cognitive impairment, the present study aimed to investigate the moderating role of social relationships, including their role as mediators between disability and cognitive impairment in depressive symptoms. Study design: This is a cross-sectional study. Methods: A total of 5,699 Chinese older adults from the 2018 China Longitudinal Healthy Longevity Survey (CLHLS) were included in this study, and PROCESS macro was used to perform simple mediator and moderator mediator analyses, which were used to analyze the relationship between depressive symptoms and social relationships between disability and cognitive impairment. Results: The results of this study showed significant correlations between disability, cognitive impairment, depressive symptoms, and social relationships, and that depressive symptoms mediated the relationship between disability and cognitive functioning [B = -0.232; 95% CI: (-0.304, -0.164)], and that social relationships mediated disability and cognitive functioning through pathway a (Disability-Depressive Symptoms) [B = 0.190; 95% CI: (0.020, 0.036)], path b (depressive symptoms-cognitive impairment) [B = 0.029; 95% CI: (0.015, 0.042)], and path c' (incapacitation-cognitive impairment) [B = 0.492; 95% CI: (0.298, 0.685)] to modulate the effect of incapacitation on cognitive impairment. In addition, social activities and social networks moderated the mediation model directly or indirectly, whereas social support moderated only the direct effect. Conclusion: This study explains the intrinsic link between incapacitation and cognitive impairment in Chinese older adults, and that social relationships and depressive symptoms can directly or indirectly modulate the effects between them. This provides a basis for healthcare professionals to be able to better develop interventions that can be used to improve the level of cognitive functioning and mental health of older adults.

Evolution of interconsultal activity to endocrinology and nutrition in hospitalization floor in a third level hospital.

INTRODUCTION: Endocrinology and Nutrition (EyN) is an outpatient and hospital medical specialty. This study aims to understand the evolution of the activity of interdepartmental consultation (IC) carried out by EyN in hospitalization floor of a third level hospital, comparing its evolution with other medical specialties, and comparing endocrine IC with nutritional IC. MATERIAL AND METHODS: Longitudinal and retrospective study which analyzes IC notes of EyN and other medical specialties between 01-01-2013 and 31-12-2022. RESULTS: A total of 76093 IC notes (12623 patients) were performed by the EyN service (average age 65.4 years; 59% male) with an average of 4.8 notes per patient. Average annual growth was 7% in notes and 4% in patients (versus 6% and 3% of all other medical services, differences statistically significant). Of all patients hospitalized for 4 or more days, EyN went from attending 7.9% (2013) to 12.3% (2022). 66% of the IC performed by EyN was for nutritional cause and 34% for other pathologies. CONCLUSIONS: The EyN service is the one that most patients attend in hospital IC activity, with growth over the last few years greater than other medical specialties. Nutritional pathology is the main reason for IC.

Chronic Health Conditions and Longitudinal Employment in Survivors of Childhood Cancer.

Importance: Employment is an important factor in quality of life and provides social and economic support. Longitudinal data on employment and associations with chronic health conditions for adult survivors of childhood cancer are lacking. Objective: To evaluate longitudinal trends in employment among survivors of childhood cancer. Design, Setting, and Participants: Retrospective cohort study of 5-year cancer survivors diagnosed at age 20 years or younger between 1970 and 1986 enrolled in the multi-institutional Childhood Cancer Survivor Study (CCSS). Sex-stratified employment status at baseline (2002 to 2004) and follow-up (2014 to 2016) was compared with general population rates from the Behavioral Risk Factor Surveillance System cohort. Data were analyzed from July 2021 to June 2022. Exposures: Cancer therapy and preexisting and newly developed chronic health conditions. Main Outcomes and Measures: Standardized prevalence ratios of employment (full-time or part-time, health-related unemployment, unemployed, not in labor force) among adult (aged ≥25 years) survivors between baseline and follow-up compared with the general population. Longitudinal assessment of negative employment transitions (full-time to part-time or unemployed at follow-up). Results: Female participants (3076 participants at baseline; 2852 at follow-up) were a median (range) age of 33 (25-53) years at baseline and 42 (27-65) years at follow-up; male participants (3196 participants at baseline; 2557 at follow-up) were 33 (25-54) and 43 (28-64) years, respectively. The prevalence of full-time or part-time employment at baseline and follow-up was 2215 of 3076 (71.3%) and 1933 of 2852 (64.8%) for female participants and 2753 of 3196 (85.3%) and 2079 of 2557 (77.3%) for male participants, respectively, with declining standardized prevalence ratios over time (female participant baseline, 1.01; 95% CI, 0.98-1.03; follow-up, 0.94; 95% CI, 0.90-0.98; P < .001; male participant baseline, 0.96; 95% CI, 0.94-0.97; follow-up, 0.92; 95% CI, 0.89-0.95; P = .02). While the prevalence of health-related unemployment increased (female participants, 11.6% to 17.2%; male participants, 8.1% to 17.1%), the standardized prevalence ratio remained higher than the general population and declined over time (female participant baseline, 3.78; 95% CI, 3.37-4.23; follow-up, 2.23; 95% CI, 1.97-2.51; P < .001; male participant baseline, 3.12; 95% CI, 2.71-3.60; follow-up, 2.61; 95% CI, 2.24-3.03; P = .002). Among survivors employed full-time at baseline (1488 female participants; 1933 male participants), 285 female participants (19.2%) and 248 male participants (12.8%) experienced a negative employment transition (median [range] follow-up, 11.5 [9.4-13.8] years). Higher numbers and grades of chronic health conditions were significantly associated with these transitions. Conclusions and Relevance: In this retrospective analysis of adult survivors of childhood cancer, significant declines in employment and increases in health-related unemployment among cancer survivors compared with the general population were identified. A substantial portion of survivors in the midcareer age range fell out of the workforce. Awareness among clinicians, caregivers, and employers may facilitate clinical counseling and occupational provisions for supportive work accommodations.

Adolescents' trajectories of depression and anxiety symptoms prior to and during the COVID-19 pandemic and their association with healthy sleep patterns.

The COVID-19 pandemic has seen a rise in anxiety and depression among adolescents. This study aimed to investigate the longitudinal associations between sleep and mental health among a large sample of Australian adolescents and examine whether healthy sleep patterns were protective of mental health in the context of the COVID-19 pandemic. We used three waves of longitudinal control group data from the Health4Life cluster-randomized trial (N = 2781, baseline Mage = 12.6, SD = 0.51; 47% boys and 1.4% 'prefer not to say'). Latent class growth analyses across the 2 years period identified four trajectories of depressive symptoms: low-stable (64.3%), average-increasing (19.2%), high-decreasing (7.1%), moderate-increasing (9.4%), and three anxiety symptom trajectories: low-stable (74.8%), average-increasing (11.6%), high-decreasing (13.6%). We compared the trajectories on sociodemographic and sleep characteristics. Adolescents in low-risk trajectories were more likely to be boys and to report shorter sleep latency and wake after sleep onset, longer sleep duration, less sleepiness, and earlier chronotype. Where mental health improved or worsened, sleep patterns changed in the same direction. The subgroups analyses uncovered two important findings: (1) the majority of adolescents in the sample maintained good mental health and sleep habits (low-stable trajectories), (2) adolescents with worsening mental health also reported worsening sleep patterns and vice versa in the improving mental health trajectories. These distinct patterns of sleep and mental health would not be seen using mean-centred statistical approaches.

Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.