Multiple Linear Mixed Models Research Articles

A 10-year Retrospective Clinical Study to Identify Risk Indicators for Peri-Implant Bone Loss and Implant Failure.

To evaluate long-term survival and success of dental implants and evaluate indicators affecting the long-term outcome. Implant survival, success and crestal bone loss (BL) over time were evaluated. For covariates at patient level, Kaplan-Meier estimates of implant survival were compared between groups with the log-rank test. Observed mean bone loss (MBL) was plotted as a function of time. Cumulative frequencies of BL were plotted for different post-op times. Uni- and multivariate analysis was performed. Simple linear mixed and multiple linear mixed models for BL at 1, 5 and 10 years were fitted. 407 patients (221 women, 186 men; mean age 64.86 years (range 28-92, SD 10.11)), with 1482 implants, responded. Absolute implant survival was 94.74%; MBL was 0.81 mm (SD 1.58, range 0.00-17.00) after an average follow-up of 10.66 years (range 10-14, SD 0.87). Implant survival was influenced on implant level by smoking, implant width and early bone loss (EBL) > 0.5 mm; on patient level by a history of periodontitis. Indicators influencing MBL after the 1st year were abutment height, type of surgery and implant width, while after 5 and 10 years of function were abutment height, EBL > 0.5 mm and smoking. Implant survival was significantly affected by a history of periodontitis on patient level and by smoking, implant width and EBL > 0.5 mm on implant level. Late bone loss was significantly affected by abutment height, EBL > 0.5 mm and smoking. B670201524796.

Biomarkers of atrial fibrillation-related pathways and left atrial structure and function in an overweight and obese population.

Exploring longitudinal associations of blood biomarkers with left atrial (LA) structure and function can enhance our understanding of atrial fibrillation (AF) etiopathogenesis. We studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults with metabolic syndrome. At baseline, 3 and 5 years after randomization, participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models. The participants in this analysis had a mean age of 65.0 (SD 4.8) years, and 40% were females. At baseline, increased NT-proBNP and hsTnT were associated with larger LAVi and worse LA function as measured by the LAFi, LASi, and LA PSLS. Longitudinally, higher NT-proBNP, but not higher hsTnT, was associated with increased LAVi and worsening LA function. Over 5 years, 1 unit increase in log(NT-proBNP) was associated with steeper decline in LA PSLS (-0.19%, 95% CI -0.35%, -0.02%) and greater increase in LAVi (0.28 mL/m2, 95% CI 0.10, 0.45) each year. PICP, hsCRP, and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years. In an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for the prevention and prediction of AF warrant further investigation.

Lifestyle deterioration linked to elevated inflammatory cytokines over a two-month follow-up

Healthy lifestyle reduces the risk of inflammation-related diseases. This study assessed how lifestyle changes affect inflammatory cytokines over 2 months. Involving 179 apparently healthy participants recruited from community, collecting data on lifestyles (smoking, alcohol, BMI, daily activity, sleep, diet) and measured inflammatory cytokines (TNF-α, IL-1β, IL-17A, CRP, IL-8, IL-18, IFN-γ) plus pepsinogens (PG I, PG II) at the baseline and 2-month follow-up. The combined adverse lifestyle score is the sum of scores across six lifestyles, with higher scores indicating more adverse lifestyle factors. Use multiple linear regression and mixed linear models to analyze the relationship between the changes in lifestyle and inflammatory cytokines (follow-up values minus baseline values). For every 1-point increase in combined adverse lifestyle score, IL-17A increased by 0.98 (95% CI 0.23, 1.73) pg/mL, IFN-γ increased by 1.79 (95% CI 0.39, 3.18) pg/mL. Decreased changes in daily activity were associated with higher IL-17A (β = 1.83, 95% CI 0.53, 3.13) and IFN-γ (β = 2.59, 95% CI 0.9, 4.98). Excluding daily activity, changes in combined adverse lifestyle scores were not associated with changes in inflammatory cytokines. Lifestyle improvements at 2-month intervals may reduce TNF-α, IL-17A and IFN-γ, with daily activity making the greatest contribution.

Pharmacological and non-pharmacological predictors of the LSD experience in healthy participants

The pharmacodynamic effects of lysergic acid diethylamide (LSD) are diverse and different in different individuals. Effects of other psychoactive substances have been shown to be critically influenced by non-pharmacological factors such as personality traits and mood states. The aim of this study was to determine pharmacological and psychological predictors of the LSD effects in healthy human subjects. This analysis is based on nine double-blind, placebo-controlled, cross-over studies with a total of 213 healthy subjects receiving between 25–200 µg LSD. The influence of sex, age, dose, body weight, pharmacogenetic, drug experience, personality, setting, and mood before drug intake on the peak autonomic and total subjective responses to LSD was investigated using multiple linear mixed effects models and Least Absolute Shrinkage and Selection Operator regression. Results were adjusted for LSD dose and corrected for multiple testing. LSD dose emerged as the most influential predictor, exhibiting a positive correlation with most response variables. Pre-drug mental states such as “Well-Being”, “Emotional Excitability”, and “Anxiety” were also important predictor for a range of subjective effects but also heart rate and body temperature. The trait “Openness to Experiences” was positively correlated with elevated ratings in “Oceanic Boundlessness” and mystical-type effects. Previous experiences with hallucinogens have been negatively associated with the overall altered state of consciousness and particularly with “Anxious Ego Dissolution”. Acute anxiety negatively correlated with the genetically determined functionality of the Cytochrome 2D6 enzyme. In summary, besides the amount of drug consumed, non-pharmacological factors such as personal traits and current mood also significantly predicted the subjective drug experience. Sex and body weight were not significant factors in influencing the drug experience.

Simultaneous Inference Using Multiple Marginal Models.

This tutorial describes single-step low-dimensional simultaneous inference with a focus on the availability of adjusted p values and compatible confidence intervals for more than just the usual mean value comparisons. The basic idea is, first, to use the influence of correlation on the quantile of the multivariate t-distribution: the higher the less conservative. In addition, second, the estimability of the correlation matrix using the multiple marginal models approach (mmm) using multiple models in the class of linear up to generalized linear mixed models. The underlying maxT-test using mmm is discussed by means of several real data scenarios using selected R packages. Surprisingly, different features are highlighted, among them: (i) analyzing different-scaled, correlated, multiple endpoints, (ii) analyzing multiple correlated binary endpoints, (iii) modeling dose as qualitative factor and/or quantitative covariate, (iv) joint consideration of several tuning parameters within the poly-k trend test, (v) joint testing of dose and time, (vi) considering several effect sizes, (vii) joint testing of subgroups and overall population in multiarm randomized clinical trials with correlated primary endpoints, (viii) multiple linear mixed effect models, (ix) generalized estimating equations, and (x) nonlinear regression models.

Breast milk dominant phyla and probiotic bacteria in the obese lactating women compared with normal weights

The main purpose was to determine the abundance of dominant phyla, Bifidobacterium spp., and Lactobacillus in breast milk of obese mothers versus normal-weights in fourth month of lactation in Iranian population. Sixty health women at the fourth month of breastfeeding, aged 18–40 years, were included and categorized based on body mass index (BMI) to the obese (BMI ≥ 30 kg/m2) and normal-weights (18.5 ≤ BMI ≤ 24.9). Bacterial DNA was extracted and qPCR of the 16S region was performed after human milk donation in a sterile condition. A multiple linear mixed model was used to determine the effective factors on the phyla population. Bifidobacterium spp. was significantly higher in milk of normal-weight group than the obese. The current weight showed a significant effect on the Actinobacteria abundance in milk. The Bacteroidetes and Firmicutes were significantly lower in mother’s milk with cesarean section (p = 0.04). Pre-pregnancy obesity decreased the Firmicutes and Lactobacillus abundance in maternal milk (p = 0.04 and p = 0.01). The Actinobacteria and Bifidobacterium spp. showed a significant effect on infant’s height (p = 0.008 and p = 0.04). The maternal current and pre-pregnancy weight showed an important effect on abundance of Actinobacteria and Bifidobacterium spp., as the good phyla and genus in milk which are associated with the infant’s height.

The influence of age, sex and player position on skill demands in junior Australian football

ABSTRACT This study aimed to investigate how ecological constraints influence individual player skill demands in community-level junior Australian Football (AF). Footage from 68 junior AF games, incorporating 1874 unique players, were analysed for individual skill demands such as disposals, kicks, handballs, tackles, marks, and shots at goal per player per game. Multiple linear mixed effect models were created for each skill, using player as a random effect. The impact of age, relative area per player (RAPP), number of players on the team, quarters in midfield, and weather on skill demands was assessed in U9-U14 boys. Finally, the influence of sex on the same skills was explored in U11-U14 boys and girls. Younger players were found to have fewer disposals and handballs, but more tackles, per player than older players (all p < 0.05). Further, more quarters in the midfield increased all skill demands (all p < 0.001). Finally, girls had fewer disposals and marks, but more tackles, per player than boys (all p < 0.05). Overall, age, sex, and position significantly impacted players’ exposure to skills in junior AF. Game designers should consider methods to improve skill involvement and reduce tackling exposure early in the junior pathway, with further emphasis on the girls’ game.

Prenatal ozone exposure and variations of the gut microbiome: Evidence from a Chinese mother-infant cohort

BackgroundThe gut microbiome is central to human health, but the potential impact of ozone (O3) exposure on its establishment in early life has not been thoroughly examined. Therefore, this study aimed to investigate the relationship between prenatal O3 exposure and the variations of the human gut microbiome during the first two years of life. DesignA cohort study design was used. Pregnant women in the third trimester were recruited from an obstetric clinic, and long-term follow-ups were conducted after delivery. The gut microbiome was analyzed using the 16 S rRNA V3-V4 gene regions. Functional pathway analyses of gut microbial communities in neonates were performed using Tax4fun. The average concentrations of ambient O3 and other air pollutants from pregnancy to delivery were calculated using the China High Air Pollutants (CHAP) dataset, based on the permanent residential addresses of participants. Multiple linear regression and mixed linear models were utilized to investigate the associations between prenatal O3 exposure and gut microbiome features. ResultsPrenatal O3 exposure did not significantly affect the gut microbial alpha diversity of mothers and neonates. However, it was found to be positively associated with the gut microbial alpha diversity in 24-month-old infants. Prenatal O3 exposure explained 13.1 % of the variation in neonatal gut microbial composition. After controlling for potential covariates, prenatal O3 exposure was associated with neonatal-specific gut microbial taxa and functional pathways. Furthermore, the mixed linear models showed that prenatal O3 exposure was negatively associated with variations of Streptococcus (p-value = 0.001, q-value = 0.005), Enterococcus (p-value = 0.001, q-value = 0.005), Escherichia-Shigella (p-value = 0.010, q-value = 0.025), and Bifidobacterium (p-value = 0.003, q-value = 0.010). ConclusionsThis study is the first to examine the effects of prenatal O3 exposure on gut microbial homeostasis and variations. It demonstrates that prenatal O3 exposure is associated with variations in certain aspects of the gut microbiome. These findings provide novel insights into the dynamics and establishment of the human microbiome during the first two years of life.

Fluctuations in therapist responsiveness facing clients with borderline personality disorder: Starting therapy on the right foot

Objective The present paper focuses on therapist responsiveness during the initial therapy session with clients with borderline personality disorder (BPD), aiming to analyze therapist responsiveness at short intervals during the initial session and determine if it can predict therapeutic alliance from both therapist and client viewpoints. Method A sample of 47 clients participated in the study for 10 sessions of therapy. Therapeutic alliance from therapists’ and clients’ perspectives was rated after each session; external raters assessed therapist responsiveness during the initial session. Multiple linear regression models and linear mixed models with backward variable selection based on AIC were run to analyze whether specific therapist behaviors during session one predicted therapeutic alliance rated from therapists’ and clients’ perspectives. Results The results indicate that therapists normalizing and validating clients’ experiences during the first session are crucial for establishing therapeutic alliance for BPD clients; however, for therapists, the increase in variability of emotions verbalized by clients during the initial session negatively impacts therapeutic alliance. Conclusion The study contributes to further understand the impact of therapists’ behavior at the beginning of therapy with BPD clients. Therapist responsiveness is crucial for therapy outcome but is methodologically challenging; therefore, efforts in this direction should be pursued.

Cross-sectional and longitudinal associations of Iron biomarkers and cardiovascular risk factors in pre- and postmenopausal women: leveraging repeated measurements to address natural variability

BackgroundThe association between iron biomarkers and cardiovascular disease risk factors (CVD-RFs) remains unclear. We aimed to (1) evaluate the cross-sectional and longitudinal associations between iron biomarkers (serum ferritin, transferrin saturation (TSAT), transferrin) and CVD-RFs among women, and (2) explore if these associations were modified by menopausal status.MethodCross-sectional and longitudinal analyses including 2542 and 1482 women from CoLaus cohort, respectively. Multiple linear regression and multilevel mixed models were used to analyse the associations between Iron biomarkers and CVD-RFs. Variability of outcomes and iron markers between surveys was accessed using intraclass correlation (ICC).ResultsAfter multivariable adjustment, elevated serum ferritin levels were associated with increased insulin and glucose levels, while higher transferrin levels were linked to elevated glucose, insulin and total cholesterol, and systolic and diastolic blood pressure (p < 0.05). No association was observed between CVD-RFs and TSAT (p > 0.05). Iron biomarkers demonstrated low reliability across reproductive stages but exhibited stronger associations in the perimenopausal group. In longitudinal analysis, we found association only for transferrin with lower glucose levels [β = − 0.59, 95% CI (− 1.10, − 0.08), p = 0.02] and lower diastolic blood pressure [β = − 7.81, 95% CI (− 15.9, − 0.56), p = 0.04].ConclusionIn cross-sectional analysis, transferrin was associated with several CVD-RFs, and the associations did not change according to menopausal status. Conversely, in the longitudinal analyses, changes in transferrin were associated only with lower glucose and diastolic blood pressure levels. These differences might stem from the substantial longitudinal variation of iron biomarkers, underscoring the need for multiple iron measurements in longitudinal analyses.

Bone health and physical activity in adolescents with juvenile idiopathic arthritis: a cross-sectional case-control study

BackgroundAdolescents with juvenile idiopathic arthritis (JIA) tend to engage in less physical activity than their typically developing peers. Physical activity is essential for bone development and reduced physical activity may detrimentally effect bone health. Thus, we examined differences in total body bone mineral content (BMC) and areal bone mineral density (aBMD) between adolescents with JIA and adolescent controls without JIA. We also examined associations between moderate-to-vigorous physical activity (MVPA), lean mass, and bone outcomes.MethodsParticipants included 21 adolescents with JIA (14 females, 7 males) and 21 sex- and age-matched controls aged 10–20 years. Assessments included: height; weight; triple-single-leg-hop distance (TSLH); MVPA by accelerometry; and total body BMC, aBMD, and lean mass measured using dual X-ray absorptiometry. Height-adjusted z-scores were calculated for BMC and aBMD and used for all analyses. Multiple linear mixed effects models examined group differences in BMC and aBMD, adjusting for sex, maturity, MVPA, TSLH, and lean mass. Participants clusters, based on sex and age (within 18 months), were considered random effects.ResultsAdolescents with JIA had lower total body aBMD z-scores [β (95% CI); -0.58 (-1.10 to -0.07), p = 0.03] and BMC z-scores [-0.47 (-0.91 to -0.03), p = 0.04] compared with controls. Mean daily MVPA was 22.0 min/day lower in adolescents with JIA than controls; however, MVPA was not associated with aBMD [-0.01 (-0.01 to 0.01), p = 0.32] or BMC [0.00 (-0.01 to 0.00), p = 0.39]. Lean mass was positively associated with aBMD [0.05 (0.01 to 0.09) g/cm2, p = 0.03] and BMC [0.06 (0.03 to 0.10) g, p < 0.001].ConclusionAdolescents with JIA had lower total body aBMD and BMC compared with sex- and age-matched controls without JIA. Group differences in bone outcomes were not associated with the lower MVPA participation of adolescents with JIA. Despite this, physical activity should still be encouraged as it promotes physical well-being.

Factors impacting antibody kinetics, including fever and vaccination intervals, in SARS-CoV-2-naïve adults receiving the first four mRNA COVID-19 vaccine doses

To evaluate the antibody response following the initial four doses of mRNA vaccines (BNT162b2 or mRNA-1273) in SARS-CoV-2-naïve healthy adults and investigate factors influencing antibody titer increases, this prospective cohort study was conducted in Japan from March 2021. The study included participants who received either the 1st and 2nd doses (n = 467), 3rd dose (n = 157), or 4th dose (n = 89). Blood samples were collected before and up to 6 months after each dose, and anti-receptor-binding domain antibody levels were measured. Multivariate analysis (usin multiple linear regression or linear mixed models) revealed several factors significantly associated with higher post-vaccination antibody levels, including mRNA-1273 vaccine (after the 1st and 2nd dose), male gender (after the 3rd and 4th doses), younger age (after the 1st and 2nd dose), non-smoking status (after the 2nd dose), non-use of immunosuppressive agents (after the 1st dose), higher pre-vaccination antibody titers (after the 2nd, 3rd, and 4th doses), and higher post-vaccination fever (after the 2nd and 4th doses). Furthermore, longer intervals since the last dose were significantly associated with higher antibody levels after the 3rd and 4th doses. These findings provide valuable insights for optimizing vaccination strategies.

Associations of Alcohol Consumption With Left Atrial Morphology and Function in a Population at High Cardiovascular Risk.

Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. We studied 503 participants from the PREDIMED-Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy-reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow-up. Cross-sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18-1.11]) and lower left atrial reservoir and contractile strain (-0.44% [95% CI, -0.87 to -0.01]; and -0.44% [95% CI, -0.75 to -0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow-up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17-1.26]). In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. URL: http://www.controlled-trials.com; Unique identifier: ISRCTN89898870.

Abstract P110: Biomarkers of Atrial Fibrillation-Related Pathways and Left Atrial Structure and Function in an Overweight and Obese Population

Background: Blood biomarkers of atrial fibrillation (AF)-related pathways can characterize the atrial substrate promoting the development of AF. Exploring associations of blood biomarkers with left atrial (LA) structure and function could enhance our understanding of AF etiopathogenesis and inform AF prevention strategies. Methods: We studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults (55-75 years) with the metabolic syndrome in Spain. The trial objective was to test a lifestyle intervention for primary prevention of cardiovascular disease. At baseline, 3 and 5 years after randomization, these participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (CRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models: 1) baseline biomarkers and LA outcomes; 2) baseline biomarkers and change in LA outcomes from baseline through year 5; 3) concomitant changes in biomarkers and LA outcomes from baseline to year 5. Results: The participants in this analysis had a mean age of 65 (SD 4.8) years, 40% females, and BMI of 32.2 (SD 3.3) kg/m 2 . At baseline, increased NT-proBNP was associated with worse LAVi (0.78 mL/m 2 , 95% CI 0.04, 1.52), LAFi (-3.61, 95% CI -6.75, -0.46), and LASi (0.02, 95% CI 0.00, 0.04). Higher baseline NT-proBNP was associated with a greater decrease in LA PSLS at year 3 (-0.82%, 95% CI -1.57, -0.06) but not year 5 (-0.01%, 95% CI -0.77, 0.75), and an increase in LASi at years 3 (0.04, 95% CI 0.01, 0.06) and 5 (0.02, 95% CI 0.00, 0.04). Over 5 years, larger elevation in NT-proBNP was associated with more decline in LA PSLS (-0.19%, 95% CI -0.35, -0.02) and more elevation in LAVi (0.28 mL/m 2 , 95% CI 0.10, 0.45) each year. PICP, hsTnT, CRP and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years. Conclusion: In an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for prevention and prediction of AF warrant further investigation.

Determinants of immunoglobulin G responses to respiratory syncytial virus and rhinovirus in children and adults.

Exposure to respiratory viruses is a significant cause of morbidity and affects virus-specific antibody levels. Little is known about determinants associated with immune response to these viruses. We aimed to investigate the determinants of respiratory syncytial virus (RSV)- and rhinovirus (RV)- specific IgG responses in both children and adults. The study is based on the EGEA cohort, composed of 530 samples of children in EGEA1 (1991-95) and 1241 samples of adults in EGEA2 (2003-07). Cumulative RV-specific IgG levels (species A, B and C) and IgG levels to RSV-G protein were measured by using micro-array technoloy. Multiple linear mixed models (random effect to account for familial dependence) were performed to assess associations between age, sex, body mass index (BMI), tobacco smoke exposure and season of blood sampling with RSV-and RV-specific IgG levels. In children (11.1 ± 2.8 years old, 57% boys), higher RV-specific IgG levels were associated with older age (only for RV-B), female sex and lower BMI, while only older age was associated with higher RSV-specific IgG levels. In adults (43.5 ± 16.7 years old, 48% men), younger age, female sex, lower BMI, active smoking and all seasons except summer were associated with higher RV-specific IgG levels. Older age, active smoking and all seasons except summer were associated with higher RSV-specific IgG levels. Personal and seasonal determinants of RSV- and RV-specific IgG levels seem to vary according to the respiratory virus type and between children and adults, suggesting different patterns of responses along the life course.

Impact of Prefracture Cognitive Impairment and Postoperative Delirium on Recovery after Hip Fracture Surgery

ObjectivesThis study aimed to examine the impact of prefracture cognitive impairment (CI) severity and postoperative delirium on recovery after hip fracture surgery in older patients. DesignProspective study with a 1-year follow-up. Setting and ParticipantsWe included 355 patients aged ≥80 years from 2 acute hospitals in Japan. MethodsBarthel Index (BI) ambulation scores were assessed prefracture and at 1, 3, 6, and 12 months postoperatively. The score at each time point minus the prefracture score was used as the ambulation recovery variable. The 21-item Dementia Assessment Sheet for the Community-based Care System (DASC-21) and Confusion Assessment Method were used to assess CI severity and delirium, respectively. The impacts of CI severity and delirium on recovery at 1 month and by 12 months postoperatively were examined. Linear multiple regression and linear mixed effects models were used. ResultsBI ambulation scores remained the same or improved from prefracture levels in 26.8%, 34.4%, 33.0%, and 30.4% of patients at 1, 3, 6, and 12 months, respectively. Ten patients (2.8%) had fall-related hip fractures, 20 (5.6%) were rehospitalized, and 43 (12.1%) died during this period. Although DASC-21 CI severity significantly affected the recovery both at 1 month and by 12 months postoperatively [standardized β (Stdβ) = −0.39, P < .0001, and Stdβ = −0.37, P < .0001, respectively], delirium did not. Other variables affecting recovery by 12 months postoperatively included prefracture BI ambulation scores, Mini Mental State Examination scores, age, fracture type, place of residence, and time. Conclusions and ImplicationsPostoperative ambulation recovery, excluding the effect of death and other poor outcomes, is influenced by prefracture CI severity, and the presence of delirium itself may not be the moderating variable. These results emphasize the importance of treatment planning based on prefracture CI severity and indicate that assessments such as the DASC-21 may be useful in implementing such a plan.

Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis

BackgroundCharacterisation of the long-term outcome of patients with ‘difficult to treat’ (D2T) rheumatoid arthritis and factors contributing to its evolution are unknown. Herein, we explored the heterogeneity and contributing factors...

The association between timing of dietary macronutrient and sodium consumption and sleep duration and quality.

The objective of this study was to examine the association between the timing of dietary macronutrients and sodium intake and sleep quantity and quality. This was a cross-sectional study that included 34 adults between 21 and 50 years of age. The main outcome measures were objective sleep measures assessed from three nights of wrist actigraphy including sleep duration, fragmentation, and wake after sleep onset (WASO), and one night of polysomnography (PSG), including rapid eye movement (REM) sleep, non-REM stage 2 (N2), stage 3 (N3), and WASO. Multiple linear regression models and linear mixed models were used to estimate the associations between sleep measures and dietary measures (carbohydrates, fats, saturated fats, proteins, and sodium). Dietary timing was examined in two ways: (1) the average amount of each nutrient consumed within 3 hours of sleep start, and (2) the interval between the final intake of each nutrient and sleep. Average fat intake within 3 hours of sleep was associated with greater WASO from PSG (β = 4.48, p = 0.01). No other associations were found between the macronutrients or sodium intake (p > 0.05) within 3 hours of sleep and the sleep parameters from PSG or actigraphy. Similarly, no associations were found between any of the PSG or actigraphy sleep measures and the interval between final nutrient intakes and sleep with sleep duration. The study suggests that greater fat but not carbohydrate, protein, saturated fat, or sodium intake close to sleep may be associated with greater sleep disruption; however, no other associations were observed.

MARKERS OF GLUCOSE METABOLISM ARE ASSOCIATED WITHCCOGNITIVE DECLINE AMONG FAMILIES WITH EXCEPTIONAL SURVIVAL

Abstract Although the connection between type 2 diabetes (T2D) and dementia is known, it is less clear whether this relationship extends to cognitive decline. Our aim was to examine whether baseline fasting plasma glucose, insulin, HOMA-IR, and HbA1c, and T2D status predict cognitive decline in a multicenter cohort study of families with a clustering of exceptional survival. We analyzed change across five cognitive tests collected over 7.9 years: Mini-Mental State Examination, Digit Span, Logical Memory, Animal Fluency and Digit Symbol Substitution. Among 2,175 family members (mean age 63±11 years (range 32-100); 54% women), 39.8% had prediabetes and 6.8% had T2D. Multiple linear mixed models were adjusted for age, sex, field center, education, APOEε4 status, BMI and family relatedness. A trend was observed for immediate (p=0.047) and delayed (p=0.037) memory, with normal glucose tolerance (NGT) predicting increased scores, prediabetes showing no change, and T2D predicting decreased scores. Among those without T2D (N=2,026), each standard deviation (SD) higher glucose (11.5 mg/dl) was related to a greater decline in delayed memory (-0.34±0.16mg/dl; p=0.032), each SD higher HbA1c (0.32%) was related to a greater decline in immediate (-0.36±0.15 mg/dl; p=0.016) and delayed (-0.31±0.16 %; p=0.05) memory, while each SD higher HOMA-IR (1.5) was related to a greater decline in Digit Span Backwards (-0.13±0.06; p=0.047). Findings suggest that among individuals with a clustering of exceptional survival, T2D, glucose, and HbA1c may predict greater decline in episodic memory, an ability typically affected early in Alzheimer dementia. The possible mechanisms, including genetic and metabolic mediators, warrant further investigation.

Region‐Specific Associations of Human Astrocytic Endfoot Genes with Alzheimer’s Disease Neuropathology and Cognitive Decline

AbstractBackgroundWe completed a well‐powered bulk transcriptomic analysis of the astrocytic water channel aquaporin‐4 (AQP4) and related glymphatic molecules and discovered significant associations with Alzheimer’s disease (AD) neuropathological and cognitive outcomes. Genes included AQP4 and dystrophin‐associated complex components, namely DMD, DTNA, DAG1, and SNTA1, which encode proteins responsible for anchoring the AQP4 channel to the astrocytic endfoot membrane.MethodLeveraging regional brain RNA sequencing from the ROS/MAP dataset (Table 1), we determined the effects of transcript‐level variation on neuropathological outcomes at autopsy and longitudinal cognition using multiple linear regression models and mixed effects models, respectively. Discrete brain regions included: the dorsolateral prefrontal cortex (DLPFC, N = 921), caudate nucleus (CN, N = 705), and posterior cingulate cortex (PCC, N = 516). Square‐root transformed neuropathological measures of amyloid and tau burden at autopsy were quantified using immunohistochemistry. Cognitive performance was assessed longitudinally with global cognition calculated as a composite score derived from 19 neuropsychological tests. All model covariates included age at death, sex, educational attainment, and post‐mortem interval. Longitudinal models also included latency to death and the fixed and random effect of interval between current and last visit.ResultHigher AQP4 expression in the DLPFC related to higher amyloid pathology (β = 0.21, P.fdr = 0.04). Similarly, higher DTNA expression was associated with higher tau burden (βDLPFC = 0.36, P.fdrDLPFC = 0.008) and a faster rate of cognitive decline (βDLPFC = ‐0.036, P.fdrDLPFC = 0.0004; βPCC = ‐0.037, P.fdrPCC = 0.02). Higher SNTA1 in the CN related to a faster rate of cognitive decline (β = ‐0.038, P.fdr = 0.03). A summary of significant associations is presented in Table 2 and select plots are provided in Figure 2. AQP4, DTNA, and SNTA1 showed comparable associations with clinical AD in independent datasets within the AMP‐AD project (https://agora.adknowledgeportal.org/).ConclusionOur results indicate that gene expression at the AQP4‐dystrophin axis relates to both AD neuropathology and cognition, particularly in the prefrontal cortex. Future analyses will incorporate single‐nucleus measures of gene expression and cell‐type deconvolution to clarify cell‐type specific contributions in this pathway. Together, these results highlight a set of genes relevant to glymphatic function that should be prioritized for future mechanistic studies.