Linear Mixed Models Research Articles

Social Media Mentions are a Stronger Predictor of Citations than 5-Year Impact Factor in Neurosurgical Research

BACKGROUND AND OBJECTIVES: X (formerly known as Twitter) is a social media platform gaining popularity in neurosurgery. Other disciplines have demonstrated a positive correlation between Twitter activity and traditional citation metrics. This study aims to determine if X activity is a greater predictor of citation rates than a journal's 5-year impact factor (IF) among major neurosurgical journals. METHODS: Using a mixed linear model, we compared the predictive value between alternative metrics (such as mentions on X and Altmetric attention score, a weighted aggregate of the attention an article receives on various platforms) and traditional citation metrics (5-year journal IF) on the number of citations an article received by analyzing 7592 articles published from January 2022 to December 2023 in 18 neurosurgical journals. It was necessary to also account for the confounding variable time since publication in the model to determine the true effect of altmetrics. The relative importance (RI) of each predictor variable was determined through permutation testing. RESULTS: X mentions, time since publication, 5-year journal IF, and Altmetric attention score all significantly predict citation rates (P < .001). RI of X mentions on citation rates indicate that X (RI = 0.13) is approximately 8.7x times greater of a predictor of citations than 5-year IF (RI = 0.015) and 5.4x times greater of a predictor than the Altmetric attention score (RI = 0.024). Time of publication remains the strongest predictor (RI = 0.83). CONCLUSION: Our study shows that in neurosurgical research, while social media mentions (X mentions) are significant, they are weaker predictors of citation rates than time since publication. Traditional journal IF and Altmetric attention scores have weaker predictive value. These findings indicate that altmetrics, especially X mentions, can complement traditional citation metrics.

Spray Deposition and Drift as Influenced by Wind Speed and Spray Nozzles from a Remotely Piloted Aerial Application System

The phenomenal growth of remotely piloted aerial application systems (RPAASs) in recent years has raised questions about their impact on the off-target movement of plant protection products. The spray droplet spectrum is one of the important determining factors that govern droplet trajectories and off-target movement of pesticide particles. A field study was conducted to compare in-swath and downwind spray deposition on ground samplers from a 20 L RPAAS platform, equipped with three different nozzles, which provided fine, medium, and extra-coarse droplet spectra. A fluorescent dye was used as a tracer to determine spray deposition. Airborne spray droplets were measured at 10 and 20 m downwind. Downwind deposition measured on ground samplers showed that the extra-coarse nozzle received significantly fewer deposits than the medium or the fine nozzle. Similarly, the airborne deposition for the extra-coarse nozzle was significantly less compared to either the fine or the medium nozzle. Linear mixed effects modeling confirmed these results and showed that wind speed served as a covariate by refining the deposition differences among nozzles. Results indicated that spray drift from RPAAS platforms may be mitigated by using appropriate nozzles that produce larger droplet spectra. These results will provide aerial applicators with a better understanding of the best management practices to mitigate drift.

Promoting water consumption among children through a social network intervention: a cluster randomized controlled trial on a Caribbean island

Abstract Aim This study examined the effect of the evidence-based adapted social network intervention named Kies Awa (translation: Choose Water) on children’s water and sugar-sweetened beverages (SSB) consumption. It also examined the moderating role of children’s descriptive and injunctive norms of water and SSB consumption on the intervention’s effect. Subject and methods We conducted a cluster randomized control trial (RCT) where schools were randomized to one of two clusters: the intervention group (IG; Kies Awa intervention; 156 participants; M = 11.08, SD = 1.00; 53.8% girls) or the control group (CG; no intervention; 144 participants; M = 11.32, SD = 0.96; 52.8% girls). The primary outcome measure was water consumption and the secondary outcome was SSB consumption. Results Linear mixed modeling analyses showed that water consumption increased significantly more among IG participants than in the CG (β = 0.141; p = 0.015). The effect on SSB consumption was moderated by perceived injunctive norms, which refer to social disapproval of consuming SSBs. Specifically, the intervention reduced SSB consumption for participants reporting high levels of injunctive norms (β = -0.052; p = 0.037). Conclusion These findings suggest that Kies Awa, an evidence-based adapted intervention, could be implemented in other Caribbean islands to improve children’s water consumption. This approach could be integrated into school health programs, contributing to public health. These findings may help achieve the United Nations’ goal of ensuring healthy lives for all children, even in under-researched world regions. Clinical Trial Registration: Main ID number: NL-OMON26157, preregistration date 2018-12-20. https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON26157.

Gamified Web-Delivered Attentional Bias Modification Training for Adults With Chronic Pain: Randomized, Double-Blind, Placebo-Controlled Trial

Background Attentional bias to pain-related information has been implicated in pain chronicity. To date, research investigating attentional bias modification training (ABMT) procedures in people with chronic pain has found variable success, perhaps because training paradigms are typically repetitive and monotonous, which could negatively affect engagement and adherence. Increasing engagement through the gamification (ie, the use of game elements) of ABMT may provide the opportunity to overcome some of these barriers. However, ABMT studies applied to the chronic pain field have not yet incorporated gamification elements. Objective This study aimed to investigate the effects of a gamified web-delivered ABMT intervention in a sample of adults with chronic pain via a randomized, double-blind, placebo-controlled trial. Methods A final sample of 129 adults with chronic musculoskeletal pain, recruited from clinical (hospital outpatient waiting list) and nonclinical (wider community) settings, were included in this randomized, double-blind, placebo-controlled, 3-arm trial. Participants were randomly assigned to complete 6 web-based sessions of nongamified standard ABMT (n=43), gamified ABMT (n=41), or a control condition (nongamified sham ABMT; n=45) over a period of 3 weeks. Active ABMT conditions trained attention away from pain-related words. The gamified task included a combination of 5 game elements. Participant outcomes were assessed before training, during training, immediately after training, and at 1-month follow-up. Primary outcomes included self-reported and behavioral engagement, pain intensity, and pain interference. Secondary outcomes included anxiety, depression, cognitive biases, and perceived improvement. Results Results of the linear mixed model analyses suggest that across all conditions, there was an overall small to medium decline in self-reported task-related engagement between sessions 1 and 2 (P<.001; Cohen d=0.257; 95% CI 0.13-0.39), sessions 1 and 3 (P<.001; Cohen d=0.368; 95% CI 0.23-0.50), sessions 1 and 4 (P<.001; Cohen d=0.473; 95% CI 0.34-0.61), sessions 1 and 5 (P<.001; Cohen d=0.488; 95% CI 0.35-0.63), and sessions 1 and 6 (P<.001; Cohen d=0.596; 95% CI 0.46-0.73). There was also an overall small decrease in depressive symptoms from baseline to posttraining assessment (P=.007; Cohen d=0.180; 95% CI 0.05-0.31) and in pain intensity (P=.008; Cohen d=0.180; 95% CI 0.05-0.31) and pain interference (P<.001; Cohen d=0.237; 95% CI 0.10-0.37) from baseline to follow-up assessment. However, no differential effects were observed over time between the 3 conditions on measures of engagement, pain intensity, pain interference, attentional bias, anxiety, depression, interpretation bias, or perceived improvement (all P values>.05). Conclusions These findings suggest that gamification, in this context, was not effective at enhancing engagement, and they do not support the widespread clinical use of web-delivered ABMT in treating individuals with chronic musculoskeletal pain. The implications of these findings are discussed, and future directions for research are suggested. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000803998; https://anzctr.org.au/ACTRN12620000803998.aspx International Registered Report Identifier (IRRID) RR2-10.2196/32359

Longitudinal cardiac imaging for assessment of myocardial injury in non-hospitalised community-dwelling individuals after COVID-19 infection: the Rotterdam Study

BackgroundThe aim of this study was to assess the presence of myocardial injury after COVID-19 infection and to evaluate the relation between persistent cardiac symptoms after COVID-19 and myocardial function...

Enhancing resilience: the impact of a near-peer mentoring program on medical students

IntroductionEmerging adulthood is a vulnerable period and can be a crisis for many youth, leading to serious mental health problems. Medical students are especially vulnerable due to their high exposure to stressors, requiring enhanced resilience to cope with academic challenges. This study measured the effectiveness of a near-peer mentoring program in terms of resilience.MethodsA non-randomised controlled trial was conducted at Semmelweis University involving 133 medical students. The case group (n = 94) comprised students who participated in a mentoring program as mentors or mentees. The control group (n = 39) did not participate in mentoring. Data was collected at two points, 5 months apart, at the semester’s start (August 2022) and end (February 2023). Self-report measures included sociodemographics, resilience (Connor-Davidson Resilience Scale), and depression (Depression Anxiety and Stress Scale). Statistical analysis involved descriptive statistics and mixed linear models for repeated-measures ANOVA.ResultsResults showed a significant increase in resilience for the case group compared to the control group (F (1, 129) = 5.578, p = 0.020), with no significant main effect of time. There was a significant interaction effect between intervention and time on resilience (F (1.000, 129.000) = 4.915, p = 0.028). Depression scores showed no significant group difference but a significant main effect of time (F (1.000, 129.000) = 4.725, p = 0.032) and the interaction effect between intervention and time on depression (F (1.000, 129.000) = 4.018, p = 0.047).DiscussionThis mentoring program effectively increased resilience and helped maintain mental health, contributing to developing skilled healthcare professionals—where resilience remains a key strength for 21st-century doctors.

FlexLMM: a nextflow linear mixed model framework for GWAS

Abstract Summary Linear mixed models are a commonly used statistical approach in genome-wide association studies when population structure is present. However, naive permutations of the phenotype to empirically estimate the null distribution of a statistic of interest are not appropriate in the presence of population structure or covariates. This is because the samples are not exchangeable with each other under the null hypothesis, and because permuting the phenotypes breaks the relationship among those and eventual covariates. For this reason we developed FlexLMM, a Nextflow pipeline that can perform appropriate permutations in linear mixed models while allowing for flexibility in the definition of the exact statistical model to be used. FlexLMM can set a significance threshold via permutations, thanks to a two-step process where the population structure is first regressed out, and only then are the permutations performed on the uncorrelated residuals. We envision this pipeline will be particularly useful for researchers working on multi-parental crosses among inbred lines of model organisms or farm animals and plants. Availability and implementation The source code and documentation for the FlexLMM is available at https://github.com/birneylab/flexlmm.

The Long‐Term Effect of Childhood Otitis Media on Speech‐in‐Noise Testing at Ages 9 and 13

ABSTRACTObjectiveTo investigate the relationship between a history of otitis media (OM) in early childhood and speech reception thresholds (SRT) in later childhood, using the Dutch digits‐in‐noise (DIN) test at ages 9 and 13 years.MethodsThis study was conducted within the Generation R study, a prospective birth cohort in Rotterdam, the Netherlands. Children underwent pure‐tone audiometry and DIN testing at ages 9 (2011–2015) and 13 (2016–2020) years. Regression analyses and a linear mixed model were used to examine associations between OM history and SRT in noise, accounting for repeated measurements within individuals.ResultsAt baseline (age 9 years), 2063 children were included with a mean SRT of −5.6 (SD = 2.0). At follow‐up (age 13 years), 3382 children were included with a mean SRT of −7.4 (SD = 1.4). A positive association was found between recurrent acute OM (RAOM) and DIN test outcomes, with an estimated coefficient of 0.55 (95% CI = 0.26, 0.84; t‐value = 3.70). Socioeconomic status and multilingualism did not significantly predict DIN test performance.ConclusionA history of RAOM may potentially influence SRT outcomes in later childhood, with higher DIN scores observed in the RAOM group. While the effect sizes between the groups are small to moderate, these findings highlight the importance of considering the potential long‐term effects of OM in both clinical practice and future research. Further studies are needed to better understand these relationships.Level of Evidence2 (cohort study).

Anterior-temporal network hyperconnectivity is key to Alzheimer's disease: from ageing to dementia

Abstract Curing Alzheimer’s disease remains hampered by an incomplete understanding of its pathophysiology and progression. Exploring dysfunction in medial temporal lobe networks, particularly the anterior-temporal (AT) and posterior-medial (PM) systems, may provide key insights, as these networks exhibit functional connectivity alterations along the entire Alzheimer’s continuum, potentially influencing disease propagation. However, the specific changes in each network and their clinical relevance across stages are not yet fully understood. This requires considering commonly used biomarkers, clinical progression, individual variability, and age confounds. Here, we leveraged monocentric longitudinal data from 261 participants spanning the adult lifespan and the Alzheimer’s continuum. The sample included cognitively unimpaired adults aged 19 to 85 years (n = 209; eight out of 64 older adults over 60 were Aβ-positive) and Aβ-positive patients fulfilling diagnostic criteria for mild cognitive impairment (MCI, n = 26; 18 progressed to Alzheimer-dementia within seven years) or Alzheimer’s type dementia (n = 26). Participants underwent structural and resting-state functional (f) MRI, florbetapir and FDG-PET, and global cognitive assessments, with up to three visits over a maximum period of 47 months. Network connectivity was assessed using seed-based analyses with the perirhinal and parahippocampal cortices as seeds, within data-driven masks reflecting the AT and PM networks. Generalized additive and linear mixed models were run to assess age-specific effects and Alzheimer’s-related alterations. In this context, we explored various markers of pathological and clinical severity, including cerebral amyloid uptake, glucose metabolism, hippocampal volume, global cognition, diagnostic staging, and time to dementia onset. Our findings revealed distinct patterns of connectivity linked to normal aging or Alzheimer’s disease. Advancing age throughout adulthood was associated with lower PM connectivity and more subtle changes in AT connectivity, while Alzheimer’s disease was characterised by AT hyperconnectivity without global changes in PM connectivity. Specifically, AT connectivity was higher in MCI and Alzheimer-dementia patients compared to older controls and was positively associated with amyloid burden, glucose hypometabolism, hippocampal atrophy, and global cognitive deficits in older adults, ranging from unimpaired to demented. Additionally, higher AT connectivity correlated with faster progression to Alzheimer-dementia in MCI patients. This comprehensive approach allowed to reveal that excessive connectivity within the AT network is intrinsically linked to the pathological and clinical progression of Alzheimer’s disease. These insights may guide future research to better understand cascading events leading to the disease and hold promise for developing prognostic tools and therapeutic interventions targeting these specific network alterations.

Image-based robotic (ROSA® knee system) total knee arthroplasty with inverse kinematic alignment compared to conventional total knee arthroplasty

IntroductionIn 2020, 368 million people globally were affected by knee osteoarthritis, and prevalence is projected to increase with 74% by 2050. Relatively high rates of dissatisfactory results after total knee arthroplasty (TKA), as reported by approximately 20% of patients, may be caused by sub-optimal knee alignment and balancing. While mechanical alignment has traditionally been the goal, patient-specific alignment strategies are gaining interest. Robotic assistance could potentially facilitate implementation of these alignment strategies through data-based surgical planning, accurate execution of the surgical plan and validation. The clinical value of surgical assistance in diverging from mechanical alignment remains to be investigated. In the present study, robotic-assisted TKA will be performed to pursue inverse kinematic alignment (iKA) within predefined boundaries, focusing on restoring native tibia joint line.MethodsThis randomized controlled trial evaluates clinical effectiveness of robotic-assisted TKA (ROSA® Knee System, Zimmer Biomet, Montreal, Quebec, Canada) aiming for iKA compared to conventional TKA aiming for mechanical alignment. A total of 150 participants will be randomized (1:1) to either treatment to provide an 80% power for a 4.8-point clinically important difference in the primary outcome measure, the Oxford Knee Score (OKS) 12 months after surgery. Allocation was achieved using computer-based randomization. Outcomes will be analyzed using linear mixed models with time and group as main factors and interaction-term. Secondary outcomes include clinical metrics (leg alignment, implant and patient survival), surgical parameters (adverse events, surgery duration, blood loss, hospital stay length, medication use), patient-reported outcomes (symptoms, quality of life, pain), mobility and physical activity measurements, metabolic syndrome, cost-efficacy, and gait and continuous glucose monitoring.Ethics and disseminationThis study has been approved by the Medical Ethical Committee Zuyd and Zuyderland Medical Centre (NL79161.096.21/METCZ20220006), September 2022.Trial registration numberNCT05685693 (clinicaltrials.gov).

Spatial characteristics of soil potassium in the early stage of vegetation restoration and influencing factors in southwest China’s karst region

The study established experimental transects in undisturbed areas of the Caohai Nature Reserve in Weining, Guizhou Province. The study aims to examine complete successional transects in different landscapes: non-karst, karst, and vegetation restoration, using the spatiotemporal substitution method. It analyzes the distribution patterns of Total potassium (TK) and Avail potassium (AK) in the soil and employs a Generalized Linear Mixed Model (GLMM) to investigate the effects of geomorphology, soil aggregates, and their interactions on the changes in soil potassium(K) elements. Furthermore, it explores the synergistic effects of K cycling during the vegetation restoration process in karst soils. The findings indicated that: (1) In karst areas, the overall TK content was higher than in non-karst areas, while the AK content in the topsoil was higher in non-karst areas. The TK content in the karst areas tended to approach that of the vegetation restoration zone. (2) After restoration, the dominant plants changed from Gramineae to Gramineae + Asteraceae, and the vegetation richness increased, thereby improving the soil fertility and potassium fixation capacity. (3) The GLMM showed that the karst landscape had a significant effect on the TK and AK contents of surface soil. In the early stage of vegetation restoration, the joint effect of soil and vegetation affected the TK and AK contents in soil.

CoGames: Development of an adaptive smartphone-based and gamified monitoring tool for cognitive function in Multiple Sclerosis

AimAs part of the development of a smartphone-based app for monitoring MS disease activity and progression (dreaMS, NCT05009160), we developed six gamified tests with multiple difficulty levels as a monitoring tool for cognition. This study quantified the relative difficulty between levels and investigated their reliability, ability to depict practice effects, and user acceptance.MethodsHealthy volunteers played each game, covering five cognitive domains, twice per day for 11 consecutive days. Linear mixed models determined the relative difficulty of the levels. Spearman's correlation of the two daily repetitions measured test–retest reliability. Difficulty increased daily except for days 2, 6, and 11, when the easiest level (“Beginner”) was repeated to estimate practice effects. Participants rated enjoyment and other components of acceptance on a 5-point scale.ResultsWe included 82 participants from April to July 2023 in Basel, Switzerland, of which 76 (51 female, age: 40.3 ± 13.9 years, range 18–69) completed the study according to protocol. Generally, mean performances decreased with higher difficulty levels. Across all levels of all games, the median test–retest correlation was 0.825 (range of medians 0.55–0.9). Mean performance in level “Beginner” improved across all games. The mean enjoyment rating was 3.9 (range: 3.1–4.3).ConclusionOur study showed that the CoGames yield reliable measures across different cognitive domains and difficulty levels and were enjoyable to play. The observed practice effects must be considered, but also indicate sensitivity to change. These results support the hypothesis that adaptive gamified digital tests can serve as a reliable and well-accepted monitoring tool of cognition in PwMS.

Tibial tubercle transfer SurgeRy and physiothErapy Versus physIotherapy only for chronic paTellofemorAL paIn: study protocol for a randomiSed controllEd trial (REVITALISE)

BackgroundPatellofemoral pain (PFP) is a common musculoskeletal disorder resulting in anterior knee pain. Physiotherapy is the current standard treatment, while surgical intervention (tibial tubercle transfer [TTT]) is reserved for chronic cases when nonoperative treatment has failed. TTT can result in clinically meaningful improvement in patients with patellofemoral maltracking without instability. However, to date, no randomised controlled trials (RCT) have compared TTT combined with a physiotherapy (PT) programme to PT alone as the initial treatment for PFP.MethodsA single-centre nonblinded RCT in 40 patients with chronic PFP (> 1 year) and tibial tubercle-trochlear groove (TT-TG) > 15 mm will be randomised to either TTT followed by PT or to PT alone in a 1:1 ratio in a concealed manner. The primary outcome is knee pain at 18 weeks for the TTT group (6 weeks splint phase + 12 weeks PT) and at 12 weeks for the PT group, measured by the visual analog scale (VAS). Secondary outcomes include Patient-Reported Outcome Measures (PROMs) using the Kujala score, International Knee Documentation Committee (IKDC) ‘Subjective Knee Form’, Tegner Activity score and EuroQol 5D-5 L for quality of life. Range of motion (ROM) is measured using the decline step-down test (DSDT). Between-group differences will be analysed using multivariable linear regression analysis, while longitudinal differences will be assessed with linear mixed models for repeated measures. The difference in direct medical costs will also be assessed.DiscussionThe REVITALISE study is the first randomised study to compare surgical intervention (TTT) followed by PT to PT alone in patients with chronic PFP. This study will generate level-1 evidence on the most effective treatment for chronic PFP, which can be integrated into the national guideline to aid orthopaedic surgeons and physiotherapists in their decision-making and ultimately improve our care for patients with chronic PFP.Trial registrationStudy Identifier NCT06227806, registered on 26 Jan 2024 on ClinicalTrials.gov. The study underwent independent peer review and received approval from the ethical review board (number NL80956.091.22).

Clinical features and factors associated with outcomes of antibody-negative autoimmune encephalitis in patients requiring intensive care

Background and objectivesAntibody-negative autoimmune encephalitis (AE) is a form of encephalitis characterized by the absence of detectable autoimmune antibodies, despite immunological evidence. However, data on management of patients with antibody-negative AE in the intensive care unit (ICU) are limited. This study aimed to explore the characteristics and subtypes of antibody-negative AE, assess the effects of immunotherapy, and identify factors independently associated with poor functional outcomes in patients requiring intensive care.MethodsThis retrospective, single-center study analyzed consecutive adult patients diagnosed with antibody-negative AE and admitted to the ICU of a large tertiary hospital between 2019 and 2023. Multivariate regression analysis was used to identify factors linked to poor functional outcomes six months after ICU admission, as defined by a modified Rankin Scale score of 3–6. Generalized linear mixed models were applied to evaluate the effect of immunotherapy on longitudinal changes in the Clinical Assessment Scale in Autoimmune Encephalitis and modified Rankin Scale scores.ResultsOf the 1220 patients with severe encephalitis admitted to the ICU, 107 were diagnosed with antibody-negative AE and included in the analysis. Six months after ICU admission, 67 patients (62.6%) had poor functional outcomes, including 28 deaths (26.2%). Factors independently associated with poor outcomes were high-dose corticosteroid therapy (odds ratio [OR] 8.734, 95% confidence interval [CI] 2.483–30.717), older age at onset (OR 1.063, 95% CI 1.028–1.099), acute respiratory failure at ICU admission (OR 10.931, 95% CI 2.062–57.751), and dyskinesia/dystonia (OR 14.109, 95% CI 1.336–148.957). The generalized linear mixed model also indicated that high-dose corticosteroid therapy was associated with poorer longitudinal outcomes.ConclusionsWhile high-dose corticosteroids are frequently used to treat AE, their risks may outweigh their benefits in severe antibody-negative AE cases. Older patients and those with dyskinesia/dystonia or respiratory failure, may require more careful monitoring and timely intervention for improved outcomes. However, prospective validation of these findings is necessary to confirm their applicability and guide future treatment strategies.

Associations between cardiovascular-kidney-metabolic syndrome and disability in activities of daily living: a nationwide longitudinal study among the middle-aged and older adults in China

BackgroundActivities in daily living (ADLs) disability triggered by aging population and chronic diseases in the middle-aged and older adults has become a major public health challenge. Cardiovascular-kidney-metabolic (CKM) syndrome, as a combination of several chronic conditions, has not yet been studied to explore its association with ADLs disability. We examined the association between CKM syndrome and ADLs disability among middle-aged and older adults in China and whether it varied by age and socioeconomic status.MethodsParticipants were from China Health and Retirement Longitudinal Study (CHARLS), which conducted four waves of surveys from 2011 to 2018. CKM stage was calculated through disease and physical examination data from CHARLS database. Meanwhile, the degree of disability was assessed through the ADL scale. Generalized linear mixed model was used to perform multivariate analysis to explore the association between CKM syndrome and the risk of ADLs disability.ResultsThe proportion of CKM stage 0, 1, 2, and 3 among the 5,898 eligible participants (median age 60 years, 60.27% women) in 2011 were 14.70, 30.23, 41.39, and 13.68%. The risk of ADL disability was increased by 16% (odds ratio [95% confidence interval]; 1.16 [1.00–1.33]) and 33% (1.33 [1.12–1.58]) in CKM stages 2 and 3 compared with stage 0. In addition, there was a greater risk of BADL disability in 75+ age group compared to other age groups, but no significant association with IADL disability. In the subgroup aged 75+, the risk of BADL disability was increased for CKM stage 2/3 (1.48 [1.01–2.18]/1.67 [1.06–2.64]) compared with stage 0. Only in the lowest quartile of socioeconomic status group CKM stage rise was strongly associated with the risk of disability. The risk of ADL disability was greater for CKM stage 2/3 (1.45 [1.15–1.83]/1.48 [1.11–1.98]) compared to CKM stage 0 in the lowest economic status quartile.ConclusionFor middle-aged and older adults in China, CKM syndrome is a key risk factor for ADLs disability. Therefore, effective measures should be taken to manage CKM stage at the lowest possible level, especially in older and economically disadvantaged populations.

Maximal mouth opening in infants and toddlers with spinal muscular atrophy: a prospective controlled study

BackgroundBulbar function is frequently impaired in patients with spinal muscular atrophy (SMA). Although extremely important for the patient’s quality of life, it is difficult to address therapeutically. Due to bulbar dysfunction, maximum mouth opening (MMO) is suspected to be reduced in children with SMA. However, no published MMO values exist for SMA children younger than 24 months. This study presents a novel approach to measuring MMO in infants and toddlers with SMA and compares it with healthy controls.MethodsChildren with SMA (0–24 months) who received disease-modifying therapy at a single neuropediatric center and similarly aged healthy children were prospectively recruited. MMO was measured using a cardboard scale and a custom-designed instrument.ResultsA total of 115 children were included (SMA = 24, healthy controls = 91). Inter-rater reliability between two examiners was excellent (ICC = 0.987, 95% CI 0.959 to 0.995), as was the reliability between the cardboard scale and the custom-designed instrument (ICC = 0.986, 95% CI 0.968 to 0.994). A mixed linear model showed a significant increase of MMO with age, and a significantly wider mouth opening in healthy controls (p < .001).ConclusionFor future research, MMO can provide valuable information about the involvement of cranial nerves, particularly in the context of disease-modifying therapies, even at a very early age.

Proteins and pathways involved in inflammation are longitudinally associated with total body bone mineral density among primarily hispanic overweight/obese adolescents and young adults.

Bone mineral density (BMD), an important marker of bone health, is regulated by a complex interaction of proteins. Plasma proteomic analyses can contribute to identification of proteins associated with changes in BMD. This may be especially informative in stages of bone accrual and peak BMD achievement (i.e., adolescence and young adulthood), but existing research has focused on older adults. This analysis in the Study of Latino Adolescents at Risk for Type 2 Diabetes (SOLAR; n = 304; baseline age 8-13, 100% Hispanic) explored associations between baseline proteins (n = 653 proteins) measured with Olink® plasma protein profiling and repeated annual DXA measures of BMD (average of 3.2 visits per participant). Covariate-adjusted linear mixed effect regression models were applied to estimate longitudinal protein-BMD associations using an adjusted p-value cutoff (P < 0.00068). Identified proteins were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to determine significantly enriched protein pathways. Forty-four proteins, many of which are involved in inflammatory processes, were associated with longitudinal changes in total body BMD, including several proteins previously linked to bone health such as osteopontin (SPP1) and microfibrillar-associated protein 5 (MFAP5; both P < 0.00068). These 44 proteins were associated with enrichment of pathways including PI3K-Akt Signaling Pathway and Cytokine-Cytokine Receptor Interaction, supporting results from existing proteomics analyses in older adults. To evaluate whether protein associations were consistent into young adulthood, linear mixed effect models were repeated in a young adult cohort (n = 169; baseline age 17-22; 62.1% Hispanic) with 346 available overlapping Olink® protein measures. While there were no significant overlapping longitudinal protein associations between the cohorts, these findings suggest differences in protein regulation at different ages and provide novel insight on longitudinal protein associations with BMD in overweight/obese adolescents and young adults of primarily Hispanic origin, which may inform the development of biomarkers for bone health in youth.

Antibiotic Use and Subsequent Cognitive Decline and Dementia Risk in Healthy Older Adults.

Antibiotics rapidly reduce intestinal bacterial diversity, leading to dysbiosis that persists for months to years. Although emerging evidence from retrospective and claims-based studies has linked dysbiosis to cognitive function, prospective data are lacking. We aim to examine the prospective association of antibiotics with cognitive aging among initially healthy older adults. We leveraged data from prospective follow-up and observational extension of ASPirin in Reducing Events in the Elderly, a completed randomized trial of community-based Australian older adults. Among participants whose prescription records were available and without dementia during the first 2 years of follow-up, we identified any or repeated antibiotic use based on the Anatomical Therapeutic Chemical code (J01). We assessed the associations of antibiotic use during the first 2 years with longitudinal changes in standardized composite and domain-specific cognitive scores (global cognition, episodic memory, language and executive function, and psychomotor speed) using linear mixed models, and with incident, clinically adjudicated dementia (Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria) and incident cognitive impairment, no dementia (CIND, without a dementia trigger but with significant, nontransient decline), using Cox proportional hazard models. Over a median of 4.7 years after the second follow-up visit, we documented 461 dementia and 2,576 CIND cases among 13,571 participants (mean age ± SD 75.0 ± 4.1 years, 54.3% female). Compared with nonuse, antibiotic use was not associated with increased risks for dementia (hazard ratio [HR] 1.03; 95% CI 0.84-1.25), CIND (HR 1.02; 95% CI 0.94-1.11), or subsequent declines in cognitive scores, after adjusting for sociodemographic, lifestyle factors, family history of dementia, baseline cognitive function, and medications known to affect cognition. There were also no associations according to the cumulative frequency of antibiotic use, long-term use, specific antibiotic classes (e.g., beta-lactams, tetracyclines, and sulfonamides), and subgroups defined by risk factors. Among initially healthy older adults, any or repeated antibiotic use was not associated with incident dementia, CIND, or accelerated cognitive decline. Although prescription data may not reflect the actual use, we examined the frequency of antibiotics within a defined period to capture the extent and duration of antibiotic exposure. Our results do not support an association between antibiotic-associated gut microbiome disruption and dementia risk.

The impact of co-housing on murine aging studies.

Analysis of preclinical lifespan studies often assume that outcome data from co-housed animals are independent. In practice, treatments, such as controlled feeding or putative life-extending compounds, are applied to whole housing units, and as a result, the outcomes are potentially correlated within housing units. We consider intra-class (here, intra-cage) correlation in three published and two unpublished lifespan studies of aged mice encompassing more than 20,000 observations. We show that the independence assumption underlying common analytic techniques does not hold in these data, particularly for traits associated with frailty. We describe and demonstrate various analytical tools available to accommodate this study design and highlight a limitation of standard variance components models (i.e., linear mixed models) which are the usual statistical tools for handling correlated errors. Through simulations, we examine the statistical biases resulting from intra-cage correlations with similar magnitudes as observed in these case studies and discuss implications for power and reproducibility.

Analyzing Gait Dynamics and Recovery Trajectory in Lower Extremity Fractures Using Linear Mixed Models and Gait Analysis Variables

In a prospective study, we examined the recovery trajectory of patients with lower extremity fractures to better understand the healing process in the absence of complications. Using a chest-mounted inertial measurement unit (IMU) device for gait analysis and collecting patient-reported outcome measures, we focused on 12 key gait variables, including Mean Leg Lift Acceleration, Stance Time, and Body Orientation. We employed a linear mixed model (LMM) to analyze these variables over time, incorporating both fixed and random effects to account for individual differences and the time since injury. This model also adjusted for varying intervals between assessments. Our study provided insights into gait recovery across different fracture types using data from 318 patients who experienced no complications or readmissions during their recovery. Through LMM analysis, we found that Tibia-Distal fractures demonstrated the fastest recovery, particularly in terms of mobility and strength. Tibia-Proximal fractures showed balanced improvements in both mobility and stability, suggesting that rehabilitation should target both strength and balance. Femur fractures exhibited varied recovery, with Diaphyseal fractures showing clear improvements in stability, while Distal fractures reflected gains in limb strength but with some variability in stability. To examine patients with readmissions, we conducted a Chi-squared test of independence to determine whether there was a relationship between fracture type and readmission rates, revealing a significant association (p &lt; 0.001). Pelvis fractures had the highest readmission rates, while Tibia-Diaphyseal and Tibia-Distal fractures were more prone to infections, highlighting the need for enhanced infection control strategies. Femur fractures showed moderate readmission and infection rates, indicating a mixed risk profile. In conclusion, our findings emphasize the importance of fracture-specific rehabilitation strategies, focusing on infection prevention and individualized treatment plans to optimize recovery outcomes.