Impact of lower-respiratory tract infections on healthcare utilization and mortality in older adults: a Swedish population-based cohort study.

BACKGROUND: Lower respiratory tract infections (LRTIs) have an immediate significant impact on morbidity and mortality among older adults. However, the impact following the infectious period of LRTI remains understudied. We aimed to assess the short- to long-term impact of LRTIs on hospitalization, mortality, and healthcare utilization in older adults. METHODS: Data from the Swedish National Study of Aging and Care in Kungsholmen (SNAC-K) was analyzed, with data from 2001 to 2019 for mortality and 2001-2016 for healthcare utilization. LRTI-exposed participants were identified and matched with LRTI-nonexposed based on sociodemographics, lifestyle factors, and functional and clinical characteristics. Statistical models evaluated post-LRTI hospitalization risk, days of inpatient hospital admissions, healthcare visits, and mortality. RESULTS: 567 LRTIs-exposed participants during the study period and were matched with 1.701 unexposed individuals. LRTI-exposed individuals exhibited increased risk of hospitalization at 1-year (HR 2.14, CI 1.74, 2.63), 3-years (HR 1.74, CI 1.46, 2.07), and 5-years (HR 1.59, CI 1.33, 1.89). They also experienced longer post-LRTI hospital stays (IRR 1.40, CI 1.18, 1.66), more healthcare visits (IRR 1.47, CI 1.26, 1.71), specialist-care visits (IRR 1.46, CI 1.24, 1.73), and hospital admissions (IRR 1.57, CI 1.34, 1.83) compared to nonexposed participants over 16-years of potential follow-up. Additionally, the 19-year risk of mortality was higher among LRTI-exposed participants (HR 1.45, CI 1.24, 1.70). Men exhibited stronger associations with these risks compared to women. CONCLUSIONS: LRTIs pose both short- and long-term risks for older adults, including increased risks of mortality, hospitalization, and healthcare visits that transpire beyond the acute infection period, although these effects diminish over time. Men exhibit higher risks across these outcomes compared to women. Given the potential preventability of LRTIs, further public health measures to mitigate infection risk are warranted.

Sex differences in clinical characteristics of migraine and its burden: a population-based study.

BACKGROUND AND PURPOSE: Understanding migraine in a sex-specific manner is crucial for improving clinical care, diagnosis and therapy for both females and males. Here, data on sex differences are provided in the presentation of migraine in a large European-based population cohort, which is representative of the general population. METHODS: A population-based study of 62,672 Danish blood donors (both present and previous donors), of whom 12,658 had migraine, was performed. All participants completed a 105-item diagnostic migraine questionnaire sent via an electronic mailing system (e-Boks) between May 2020 and August 2020. The questionnaire allowed for correct diagnosis of migraine according to the International Classification of Headache Disorders, third edition. RESULTS: The migraine questionnaire was in-cohort validated and had a positive predictive value of 97% for any migraine, a specificity of 93% and a sensitivity of 93%. There were 9184 females (mean age 45.1 years) and 3434 males (mean age 48.0 years). The 3-month prevalence of migraine without aura was 11% in females and 3.59% in males. The 3-month prevalence of migraine with aura was 1.72% in females and 1.58% in males. In females, the age-related 3-month prevalence of migraine without aura increased markedly during childbearing age. In males, migraine both with and without aura showed less age variation. Females had a higher frequency of migraine attacks (odds ratio [OR] 1.22) but a lower frequency of non-migraine headaches (OR = 0.35). Females also had a greater intensity of pain, more unilateral and pulsatile pain, and exacerbation by physical activity (OR = 1.40-1.49) as well as more associated symptoms (OR = 1.26-1.98). Females carried 79% of the total migraine disease burden, which was almost exclusively driven by migraine without aura (77%), whilst there was no sex difference in the disease burden of migraine with aura. CONCLUSION: Females have more severe disease, resulting in a much higher migraine disease burden than indicated by prevalence alone.

Sex differences in risk factors that predict progression from mild cognitive impairment to Alzheimer's dementia.

OBJECTIVES: To evaluate whether cerebrospinal fluid biomarkers, apolipoprotein e4, neuroimaging abnormalities, and neuropsychological data differentially predict progression from mild cognitive impairment (MCI) to dementia for men and women. METHODS: Participants who were diagnosed with MCI at baseline (n = 449) were classified as either progressing to Alzheimer's dementia at follow-up or as not progressing. Men and women were first compared using bivariate analyses. Sex-stratified Cox proportional hazard regressions were performed examining the relationship between baseline data and the likelihood of progressing to dementia. Sex interactions were subsequently examined. RESULTS: Cox proportional hazard regression controlling for age and education indicated that all variables significantly predicted subsequent progression to dementia for men and women. Sex interactions indicated that only Rey Auditory Verbal Learning Test (RAVLT) delayed recall and Functional Activities Questionnaire (FAQ) were significantly stronger risk factors for women. When all variables were entered into a fully adjusted model, significant risk factors for women were Aß42, hippocampal volume, RAVLT delayed recall, Boston Naming Test, and FAQ. In contrast, for men, Aß42, p-tau181, p-tau181/Aß42, hippocampal volume, category fluency and FAQ were significant risk factors. Interactions with sex were only significant for p-tau181/Aß42 and RAVLT delayed recall for the fully adjusted model. CONCLUSIONS: Men and women with MCI may to differ for which factors predict subsequent dementia although future analyses with greater power are needed to evaluate sex differences. We hypothesize that brain and cognitive reserve theories may partially explain these findings.

Association of Physical Activity With Cognitive Function Among Older Adults in Rural Sichuan, China.

The purpose of this study was to explore the relationship between total physical activity and different dimensions of cognitive function (orientation, attention, and memory) among older adults in rural Sichuan, China. This cross-sectional study involved 715 older adults (average age of 72 years). Total PA was measured by the Physical Activity Scale for the Elderly, and cognitive function was assessed by the Telephone Interview for Cognitive Status (TICS) questionnaire. The multivariate linear regression analysis indicated that total PA and household PA were significantly associated with the overall Telephone Interview for Cognitive Status score (ß = 0.143, p < .001; ß = 0.115, p = .002, respectively), the orientation dimension (ß = 0.142, p < .001; ß = 0.131, p = .001, respectively), and the memory dimension (ß = 0.179, p < .001; ß = 0.134, p = .001, respectively). The study showed a positive association between total PA, household PA, and cognitive function in older adults, especially in the orientation dimension and the memory dimension of cognitive function.

Tongue Carcinoma - 20-Year Comparative Survival and Mortality Analysis by Age, Sex, Race, Stage, Grade, Cohort Entry Time-Period and Disease Duration.

Cancer of the tongue is an uncommon cancer site, with only 31,378 cases in the SEER 1975-2017 database, fewer than 1% of all reported cancers. This article updates trends in incidence, prevalence, short and long-term survival and mortality of tongue carcinoma.

Non-Hodgkin Lymphoma - Nodal and Extranodal: 20-Year Comparative Mortality, Survival & Biologic Behavior Analysis by Age, Sex, Race, Stage, Cell Morphology/Histology, Cohort Entry Time-Period and Disease Duration: A Systematic Review of 384,651 Total NHL Cases Including 261,144 Nodal and 123,507 Extranodal Cases for Diagnosis Years 1975-2016: (SEER*Stat 8.3.6).

During the past 5 decades, there have been reports of increases in the incidence and mortality rates of non-Hodgkin lymphoma (NHL) in the United States and globally. The ability to address the epidemiologic diversity, prognosis and treatment of NHL depends on the use of an accurate and consistent classification system. Historically, uniform treatment for NHL has been hampered by the lack of a systematic taxonomy of non-Hodgkin lymphoma. Before 1982, there were 6 competing classification schemes with contending terminologies for NHL: the Rappaport, Lukes-Collins, Kiel, World Health Organization, British, and Dorfman systems without consensus as to which system is most satisfactory regarding clinical relevance, scientific accuracy and reproducibility and presenting a difficult task for abstractors of incidence information. In 1982, the National Cancer Institute sponsored a workshop1 that developed a working formulation designed to: 1) provide clinicians with prognostic information for the various types of NHLs, and 2) provide a common language that might be used to compare clinical trials from various treatment centers around the world. Studies imply that prognosis is dependent on tumor stage and histology rather than the primary localization per se.2 This study utilizes the National Cancer Institute PDQ adaptation of the World Health Organization's (WHO) updated REAL (Revised European American Lymphoma) classification3 of lymphoproliferative diseases, and the SEER*Stat 8.3.6 database (released Aug 8, 2019) for diagnosis years 1975-2016. In this article, we make use of 40 years of data to examine patterns of incidence, survival and mortality, and selected cell bio-behavioral characteristics of NHL in the United States. OBJECTIVE: -To update trends in incidence and prevalence in the United States of non-Hodgkin lymphoma, examine, compare and contrast short and long-term patterns of survival and mortality, and consider the outcome impacts of anatomic location of NHL nodal and extranodal subdivisions, utilizing selected ICD-O-3 histologic oncotypes stratified by age, sex, race/ethnicity, stage, cell behavioral morphology and histologic typology, cohort entry time-period and disease duration, employing the statistical database of the National Cancer Institute SEER*Stat 8.3.6 program for diagnosis years 1975-2016.4 Methods.- A retrospective, population-based cohort study using nationally representative data from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program to evaluate 384,651 NHL cases for diagnosis years 1975-2016 comparing multiple variables of age, sex, race, stage, cell behavioral morphology, cohort entry time-period, disease duration and histologic oncotype. Relative survival statistics were analyzed in two cohorts: 1975-1995 and 1996-2016. Survival statistics were derived from SEER*Stat Database: Incidence - SEER 9 Regs Research Data, November 2018 Submission (1975-2016) released April 2019, based on the November 2018 submission. RESULTS: - Incidence rates, relative frequency distributions, survival and mortality by age, sex, stage and cell behavioral morphology, of adult nodal (N) and extranodal (EN) NHL in 2 entrant time-periods as recorded in the SEER Program of the National Cancer Institute for diagnosis years 1975-2016 (SEER Stat 8.3.6) are summarized. Shifts in trends over time are identified, and the findings are correlated with prognosis, including short and long-term observed (actual), expected and relative survival, median observed and relative survival, mortality rates and excess death rates per 1000 people. CONCLUSIONS: - Trends in SEER incidence, prevalence, survival and mortality by age, sex, race, stage, cell behavioral morphology, cohort entry time-period, relative frequency and percent distribution, were examined to provide a current epidemiologic and medical-actuarial risk assessment framework for nodal (N) and extranodal (EN) non-Hodgkin's lymphoma in the 1975-2016 timeframe.

Breast Cancer: 20-Year Comparative Mortality and Survival Analysis by Age, Sex, Race/Ethnicity, Stage, Grade, Disease Duration, Selected ICD-O-3 Oncophenotypes, and Cohort Entry Time-Period.

Breast cancer remains the most common non-cutaneous malignancy in women in both Europe and the United States and the second leading cause of cancer-related deaths. In this breast cancer mortality and survival study, a US retrospective population-based analysis of 656,501 microscopically confirmed breast cancer cases, 1975-2019, data is derived from the NCI Surveillance Epidemiology & End Results Program, SEER*Stat 8.4.0.1.

The importance of correct stratifications when comparing directly and indirectly estimated reference intervals.

OBJECTIVES: There are generally two major reasons for the comparison of reference intervals (RIs): when externally determined RIs (from the literature or provided by a manufacturer) are compared with presently used intra-laboratory RIs and when indirectly estimated RIs are compared with directly established RIs. Discrepancies within these comparisons may occur for two reasons: 1. the pre-analytical and/or analytical conditions do not agree and/or 2. biological variables influencing the establishment of RIs have not been considered adequately. If directly and indirectly estimated reference intervals (RIs) are compared with each other, they very often agree. Sometimes, however, a comparison may differ, with the reason for any discrepancy not being further studied. A major reason for differences in the comparison of RIs is that the requirement for stratification has been neglected. METHODS: The present report outlines the consequences to RI comparison if stratification is neglected during RI determination with the main variables affecting RIs being sex and age. Alanine aminotransferase was chosen as an example in which the RIs depend on both these factors. RESULTS: Both direct and indirect approaches lead to erroneous RIs if stratification for variables which are known to affect the estimation of RIs is not performed adequately. However, failing to include a required stratification in procedures for directly determined RIs affects the outcome in a different way to indirectly determined RIs. CONCLUSIONS: The resulting difference between direct and indirect RIs is often misinterpreted as an incorrect RI estimation of the indirect method.

Diet quality and anxiety: a critical overview with focus on the gut microbiome.

Anxiety disorders disproportionally affect females and are frequently comorbid with eating disorders. With the emerging field of nutritional psychiatry, focus has been put on the impact of diet quality in anxiety pathophysiology and gut microbiome underlying mechanisms. While the relationship between diet and anxiety is bidirectional, improving dietary habits could better facilitate the actions of pharmacological and psychological therapies, or prevent their use. A better understanding of how gut bacteria mediate and moderate such relationship could further contribute to develop personalized programs and inform probiotics and prebiotics manufacturing. To date, studies that look simultaneously at diet, the gut microbiome, and anxiety are missing as only pairwise relationships among them have been investigated. Therefore, this study aims at summarizing and integrating the existing knowledge on the dietary effects on anxiety with focus on gut microbiome. Findings on the effects of diet on anxiety are critically summarized and reinterpreted in relation to findings on (i) the effects of diet on the gut microbiome composition, and (ii) the associations between the abundance of certain gut bacteria and anxiety. This novel interpretation suggests a theoretical model where the relationship between diet and anxiety is mediated and/or modulated by the gut microbiome through multiple mechanisms. In parallel, this study critically evaluates methodologies employed in the nutritional field to investigate the effects of diet on anxiety highlighting a lack of systematic operationalization and assessment strategies. Therefore, it ultimately proposes a novel evidence-based approach that can enhance studies validity, reliability, systematicity, and translation to clinical and community settings.

Comprehensive Sex-Stratified Genetic Analysis of 28 Blood Biomarkers and Depression Reveals a Significant Association between Depression and Low Levels of Total Protein in Females.

Introduction: Major depression (MD) is more common amongst women than men, and MD episodes have been associated with fluctuations in reproductive hormones amongst women. To investigate biological underpinnings of heterogeneity in MD, the associations between depression, stratified by sex and including perinatal depression (PND), and blood biomarkers, using UK Biobank (UKB) data, were evaluated, and extended to include the association of depression with biomarker polygenic scores (PGS), generated as proxy for each biomarker. Method: Using female (N = 39,761) and male (N = 38,821) UKB participants, lifetime MD and PND were tested for association with 28 blood biomarkers. A GWAS was conducted for each biomarker and genetic correlations with depression subgroups were estimated. Using independent data from the Australian Genetics of Depression Study, PGS were constructed for each biomarker, and tested for association with depression status (n [female cases/controls] = 9,006/6,442; n [male cases/controls] = 3,106/6,222). Regions of significant local genetic correlation between depression subgroups and biomarkers highlighted by the PGS analysis were identified. Results: Depression in females was significantly associated with levels of twelve biomarkers, including total protein (OR = 0.90, CI = [0.86, 0.94], p = 3.9 × 10-6) and vitamin D (OR = 0.94, CI = [0.90, 0.97], p = 2.6 × 10-4), and PND with five biomarker levels, also including total protein (OR = 0.88, CI = [0.81, 0.96], p = 4.7 × 10-3). Depression in males was significantly associated with levels of eleven biomarkers. In the independent Australian Genetics of Depression Study, PGS analysis found significant associations for female depression and PND with total protein (female depression: OR = 0.93, CI = [0.88, 0.98], p = 3.6 × 10-3; PND: OR = 0.91, CI = [0.86, 0.96], p = 1.1 × 10-3), as well as with vitamin D (female depression: OR = 0.93, CI = [0.89, 0.97], p = 2.0 × 10-3; PND: OR = 0.92, CI = [0.87, 0.97], p = 1.4 × 10-3). The male depression sample did not report any significant results, and the point estimate of total protein (OR = 0.98, CI = [0.92-1.04], p = 4.7 × 10-1) did not indicate any association. Local genetic correlation analysis highlighted significant genetic correlation between PND and total protein, located in 5q13.3 (rG = 0.68, CI = [0.33, 1.0], p = 3.6 × 10-4). Discussion and Conclusion: Multiple lines of evidence from genetic analysis highlight an association between total serum protein levels and depression in females. Further research involving prospective measurement of total protein and depressive symptoms is warranted.

Dose-Response Relationships of Moderate to Vigorous Physical Activity and Sedentary Time With Renal Function Indices in Adolescents With Reduced Renal Function: A Cross-Sectional Study.

BACKGROUND: This study aimed to explore the associations between moderate to vigorous physical activity (MVPA) and sedentary time with renal function indices in adolescents with kidney disease. METHODS: A cross-sectional study was conducted on 719 adolescents (median age 15 y, 40.6% female) with kidney disease from the National Health and Nutrition Examination Survey 2007-2016. The exposures were MVPA time and sedentary time. Renal metabolic parameters included serum uric acid (SUA), creatinine, blood urea nitrogen, the estimated glomerular filtration rate (eGFR), and the albumin creatinine ratio. Weighted multivariate regression analysis was used to estimate associations between exposures and outcomes. RESULTS: After stratifying MVPA time, the regression effect values ß (95% CI) for MVPA on SUA (Q2: -0.22 [-0.41 to -0.03]; Q3: -0.32 [-0.53 to -0.11]) and creatinine (Q2: -0.08 [-0.15 to -0.01]; Q3: -0.04 [-0.11 to 0.03]) gradually decreased with increasing MVPA time. In males (-0.76 [-1.19 to -0.32]), MVPA time was significantly associated with lower SUA levels compared with females (-0.14 [-0.38 to 0.10]). Notably, female adolescents who had an MVPA time exceeding 420 minutes exhibited lower albumin creatinine ratio (-75.37 [-146.63 to -4.11]). In addition, both recreational MVPA time (-0.26 [-0.45 to -0.06]) and sedentary time (-3.15 [-5.83 to -0.46]) were negatively associated with eGFR. CONCLUSIONS: Our study found an association between MVPA and lower levels of SUA in male adolescents with kidney disease and albuminuria in female adolescents with kidney disease. In addition, MVPA was also negatively associated with creatinine and eGFR, whereas sedentary time was only associated with eGFR. Further studies are needed to confirm these findings.

The Representation of Females in Studies on Antihypertensive Medication over the Years: A Scoping Review.

BACKGROUND: The leading global risk factor for cardiovascular-disease-related morbidity and mortality is hypertension. In the past decade, attention has been paid to increase females' representation. The aim of this study is to investigate whether the representation of females and presentation of sex-stratified data in studies investigating the effect of antihypertensive drugs has increased over the past decades. METHODS: After systematically searching PubMed and Embase for studies evaluating the effect of the five major antihypertensive medication groups until May 2020, a scoping review was performed. The primary outcome was the proportion of included females. The secondary outcome was whether sex stratification was performed. RESULTS: The search resulted in 73,867 articles. After the selection progress, 2046 studies were included for further analysis. These studies included 1,348,172 adults with a mean percentage of females participating of 38.1%. Female participation in antihypertensive studies showed an increase each year by 0.2% (95% CI 0.36-0.52), p < 0.01). Only 75 (3.7%) studies performed sex stratification, and this was the highest between 2011 and 2020 (7.2%). CONCLUSION: Female participation showed a slight increase in the past decade but is still underrepresented compared to males. As data are infrequently sex-stratified, more attention is needed to possible sex-related differences in treatment effects to different antihypertensive compounds.

Nutrition risk and cognitive performance in community-living older adults without cognitive impairment: a cross-sectional analysis of the Canadian Longitudinal Study on Aging.

Malnutrition is correlated with poor cognition; however, an understanding of the association between nutrition risk, which precedes malnutrition, and cognition is lacking. This study aimed to determine if nutrition risk measured with the SCREEN-8 tool is associated with cognitive performance among cognitively healthy adults aged 55+, after adjusting for demographic and lifestyle covariates. Sex- and age-stratified analyses were also explored. Baseline data from the Canadian Longitudinal Study on Aging was used. Cognition was determined using a 6-measure composite score based on four executive functions and two memory tasks, taking into account age, sex, and education. Multivariable linear regression was performed while adjusting for body mass index (BMI), lifestyle, and health covariates in the entire sample (n = 11 378) and then stratified by sex and age. Approximately half of participants were female (54.5%) aged 65+ (54.1%). Greater nutrition risk was associated with poorer cognitive performance in the entire sample (F[1, 11 368] = 5.36, p = 0.021) and among participants aged 55-64 (n = 5227; F[1, 5217] = 5.45, p = 0.020). Sex differences in lifestyle and health factors associated with cognition were apparent, but nutrition risk was not associated with cognition in sex-stratified models. Based on this analysis, there may be an association between nutrition risk and cognitive performance in older adults. When screening for either cognitive impairment or nutrition risk, complementary assessments for these conditions is warranted, as early intervention may provide benefit.

Relevance of sex, age and gait kinematics when predicting fall-risk and mortality in older adults.

Approximately one-third of elderly people fall each year with severe consequences, including death. The aim of this study was to identify the most relevant features to be considered to maximize the accuracy of a logistic regression model designed for prediction of fall/mortality risk among older people. This study included 261 adults, aged over 65 years. Men and women were analyzed separately because sex stratification was revealed as being essential for our purposes of feature ranking and selection. Participants completed a 3-m walk test at their own gait velocity. An inertial sensor attached to their lumbar spine was used to record acceleration data in the three spatial directions. Signal processing techniques allowed the extraction of 21 features representative of gait kinematics, to be used as predictors to train and test the model. Age and gait speed data were also considered as predictors. A set of 23 features was considered. These features demonstrate to be more or less relevant depending on the sex of the cohort under analysis and the classification label (risk of falls and mortality). In each case, the minimum size subset of relevant features is provided to show the maximum accuracy prediction capability. Gait speed has been largely used as the single feature for the prediction fall risk among older adults. Nevertheless, prediction accuracy can be substantially improved, reaching 70% in some cases, if the task of training and testing the model takes into account some other features, namely, sex, age and gait kinematic parameters. Therefore we recommend considering sex, age and step regularity to predict fall-risk.

The Importance of Sex Stratification in Autoimmune Disease Biomarker Research: A Systematic Review.

The immune system is highly dynamic and regulated by many baseline characteristic factors. As such, significant variability may exist among different patient groups suffering from the same autoimmune disease (AD). However, contemporary research practices tend to take the reductionist aggregate approach: they do not segment AD patients before embarking on biomarker discovery. This approach has been productive: many novel AD biomarkers have recently been discovered. Yet, subsequent validation studies of these biomarkers tend to suffer from a lack of specificity, sensitivity, and reproducibility which hamper their translation for clinical use. To enhance reproducibility in validation studies, an optimal discovery-phase study design is paramount: one which takes into account different parameters affecting the immune system biology. In this systematic review, we highlight need for stratification in one such parameter, i.e., sex stratification. We will first explore sex differences in immune system biology and AD prevalence, followed by reported sex-bias in the clinical phenotypes of two ADs-one which more commonly affects females: systemic lupus erythematosus, and one which more commonly affects males: ankylosing spondylitis. The practice of sex stratification in biomarker research may not only advance the discovery of sex-specific AD biomarkers but more importantly, promote reproducibility in subsequent validation studies, thus easing the translation of these novel biomarkers from bench to bedside to improve AD diagnosis. In addition, such practice will also promote deeper understanding for differential AD pathophysiology in males and females, which will be useful for the development of more effective interventions for each sex type.