Linear Mixed-effects Regression Analysis Research Articles

Implementation and engagement of the SMART Work & Life sitting reduction intervention: an exploratory analysis on intervention effectiveness

BackgroundTo enhance the impact of interventions, it is important to understand how intervention engagement relates to study outcomes. We report on the level of implementation and engagement with the SMART Work & Life (SWAL) programme (delivered with (SWAL plus desk) and without a height-adjustable desk (SWAL)) and explore the effects of different levels of this on change in daily sitting time in comparison to the control group.MethodsThe extent of intervention delivery by workplace champions and the extent of engagement by champions and participants (staff) with each intervention activity was assessed by training attendance logs, workplace champion withdrawal dates, intervention activities logs and questionnaires. These data were used to assess whether a cluster met defined criteria for low, medium, or high implementation and engagement or none of these. Mixed effects linear regression analyses tested whether change in sitting time varied by: (i) the number of intervention activities implemented and engaged with, and (ii) the percentage of implementation and engagement with all intervention strategies.ResultsWorkplace champions were recruited for all clusters, with 51/52 (98%) attending training. Overall, 12/27 (44.4%) SWAL and 9/25 (36.0%) SWAL plus desk clusters implemented all main intervention strategies. Across remaining clusters, the level of intervention implementation varied. Those in the SWAL (n = 8 (29.6%) clusters, 80 (32.1%) participants) and SWAL plus desk (n = 5 (20.0%) clusters, 41 (17.1%) participants) intervention groups who implemented and engaged with the most intervention strategies and had the highest percentage of cluster implementation and engagement with all intervention strategies sat for 30.9 (95% CI -53.9 to -7.9, p = 0.01) and 75.6 (95% CI -103.6 to -47.7, p < 0.001) fewer minutes/day respectively compared to the control group at 12 month follow up. These differences were larger than the complete case analysis. The differences in sitting time observed for the medium and low levels were similar to the complete case analysis.ConclusionsMost intervention strategies were delivered to some extent across the clusters although there was large variation. Superior effects for sitting reduction were seen for those intervention groups who implemented and engaged with the most intervention components and had the highest level of cluster implementation and engagement.Trial RegistrationISRCTN11618007. Registered on 24 January 2018. https://www.isrctn.com/ISRCTNISRCTN11618007.

Association of red cell omega-3 fatty acids, particularly EPA, with cognitive performance in atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Whether or not omega-3 Fatty Acids (n-3 FAs) have neuroprotective effects is controversial. We therefore aimed to determine the correlation of n-3 FAs with cognitive function in a large cohort of AF patients. Methods Red cell n-3 FAs levels were determined by gas chromatography and mass spectrometry in 2359 patients from the prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF). To assess the overall cognitive performance of patients, we used several validated neurocognitive assessment tools, including the Montreal Cognitive Assessment (MoCA), Semantic Fluency Tests (SF), Trail Making Test (TMT A&amp;B), and the Digit Symbol Substitution Test (DST). We also used a summary score that we have previously developed (the cognitive construct (CoCo) score). We performed mixed-effect linear regression analyses. Two adjustment models were applied; model 1 (adjusted for age, sex, and educational level) and model 2 (adjusted for age, sex, educational level, history of stroke/TIA, AF type, heart rate, arterial hypertension, diabetes, coronary artery disease, BMI, chronic kidney disease, smoking status, alcohol consumption, geriatric depression scale, use of oral anticoagulation and antiplatelet medication). We also included a random intercept to control for center-effect in both models. Results The mean age of our study population was 73 years (standard deviation [SD] 8.4), and 662 patients were females (28%), 318 had a history of stroke (13%), and 716 suffered from coronary artery disease (30%). We observed statistically significant associations of total n-3 FAs levels (EPA + DHA + DPA + ALA) with all neurocognitive assessments, as seen in figure a. Individual n-3 FAs levels (EPA and ALA) were positively associated with MoCA score in both models. EPA was significantly associated with multiple neurocognitive assessments including MoCA, SF, TMT-B, DST, and overall CoCo score in both models (figure b). We found that a 1% red cell EPA level increase was associated with 0.19 (Model 1, 95%CI 0.06-0.31, p=0.003) and 0.14 (Model 2, 95% CI 0.01-0.26, p=0.02) units increase in the standardized MoCA score. Conclusions Red cell n-3 FAs levels are associated with better cognitive performance in AF patients. We observed a particularly strong association of EPA levels with all neurocognitive assessments.

Final Analysis of the Daliah Trial: A Randomized Phase III Trial of Interferon-α Versus Hydroxyurea in Patients with MPN

Background: Hydroxyurea (HU) is the most commonly used first-line cytoreductive treatment option for patients with myeloproliferative neoplasms (MPN) worldwide. However, increasing evidence on the efficacy and safety of pegylated interferon-alpha2 (IFNα) is emerging, and optimal first-line treatment is to be established. Aims: To compare the efficacy and safety of HU vs. low-dose IFNα in patients with MPN over five years. Methods: DALIAH (NCT01387763) was a randomized phase III trial of HU vs. IFNα in newly diagnosed or untreated patients with MPN (essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic myelofibrosis (PreMF), and primary myelofibrosis (PMF)). Patients &amp;gt; age 60 were randomized (1:1:1) to HU, IFNα-2a, or IFNα-2b whereas patients ≤ age 60 were randomized to IFNα-2a or IFNα-2b. The primary outcome was the JAK2V617F molecular response (MR) rate at 18, 36, and 60 months per 2009 European LeukemiaNetwork (ELN) (ET, PV, PreMF) or 2005 European Myelofibrosis Network (EUMNET) (PMF) criteria. Secondary outcomes included the complete clinicohematologic response (CHR) rate at 12 months. The JAK2V617F allele burden was measured using quantitative polymerase chain reaction (qPCR) on peripheral blood (assay sensitivity: 0.1%). Primary and secondary outcomes were compared between groups (HU vs. IFNα or HU vs. IFNα &amp;gt; 60 years) using Fisher's exact test (categorical variables) or Wilcoxon rank-sum test (continuous variables). Paired comparisons (within groups) were made using Wilcoxon signed-rank test. Serial JAK2V617F measurements were compared by unadjusted mixed-effects linear regression analysis. Results: We included 203 patients (ET: 73 (36%), PV: 89 (44%), PreMF: 16 (8%), and PMF: 25 (12%)) in the modified intention-to-treat (ITT) population. Baseline characteristics were well balanced except for median age (HU: 68 years vs. IFNα: 59 years, p&amp;lt;0.0001) ( Table 1). The MR rate by ITT analysis was similar between HU and IFNα (18 months: 19% vs. 21%, p=1.00; 36 months: 19% vs. 26%, p=0.64; 60 months: 23% vs. 24%, p=1.00) (Figure 1A). However, the JAK2V617F allele burden was significantly lower in the IFNα group at month 36 and beyond (Figure 1B) and the absolute median (IQR) change in JAK2V617F allele burden (baseline to 60 months) was greater with IFNα (-20% (-9;-49) vs. -7% (3;-15), p=0.0053) (Figure 1C). Two patients (IFNα: n=2) were in complete molecular remission (undetectable JAK2V617F) at 60 months. The CHR rate by ITT analysis was higher with HU at 18 months (58% vs. 38%, p=0.03) but similar at all other time points (12 months: 50% vs. 36%, p=0.21; 60 months: 24% vs. 22%, p=0.83) ( Figure 1D). A post hoc subgroup analysis comparing HU with IFNα &amp;gt; age 60 showed comparable efficacy results. Among patients remaining on treatment (per-protocol analysis), the MR and CHR rates were superior in the IFNα group compared to the HU group at 36 months and beyond. The MR and CHR rates (HU vs. IFNα) by per-protocol analysis were: MR at 36 months: 23% vs. 56%, p=0.01; MR at 48 months: 27% vs. 59%, p=0.02; MR at 60 months: 35% vs. 67%, p=0.03; CHR at 36 months: 33% vs. 67%, p=0.002; CHR at 60 months: 38% vs. 62%, p=0.05. Overall treatment discontinuation at 60 months was 60% (HU: 37% vs. IFNα: 65%, p=0.0019). The most common cause of treatment discontinuation was adverse events (HU: 6/38 (16%); IFNα: 71/165 (43%)). Adverse events ≥ grade 3 occurred in 46% (HU: 58% vs. IFNα: 45%, p=0.15). Nineteen major thrombotic events were reported in 16 patients (HU: 4 events in 4 patients; IFNα&amp;gt;60: 12 events in 10 patients; IFNα≤60: 3 events in 2 patients), corresponding to an incidence rate of 2.6 per 100 person-years for HU and 3.4 per 100 person-years for IFNα (IFNα&amp;gt;60: 6.2; IFNα≤60: 1.2). None of the patients transformed into secondary acute myeloid leukemia. Five patients died during follow-up (HU: 2; IFNα: 3). Bone marrow histologic remission rates at 36 and 60 months will be presented at the meeting. Conclusion: ITT analysis detected no significant difference in the MR or CHR rates between HU and IFNα with long-term treatment (5 years) among patients with MPN, reflecting a higher treatment discontinuation rate in the IFNα group (65%). Thus, using the per-protocol principle, the MR and CHR rates were superior in the IFNα group at 36 months and beyond.

Associations between nutritional intake, stress and hunger biomarkers, and anxiety and depression during the treatment of anorexia nervosa in adolescents and young adults

Adolescents and young adults (AYA) with anorexia nervosa (AN) frequently have co-occurring anxiety and depression, which can negatively impact prognosis. To inform treatment of co-occurring anxiety and depression, we assessed the association of nutritional intake and hunger/stress hormones on anxiety and depression using a six-month longitudinal study of 50 AYA females receiving care for AN. At baseline and six months, we measured anxiety (Spielberger State/Trait Anxiety Inventory [STAI]), depression (Beck Depression Inventory [BDI]), body mass index (BMI), 3-day dietary intake (total calories and proportion of fat, carbohydrate, protein), and serum cortisol, leptin, and adiponectin. We performed mixed effects linear regression analyses, adjusting for age, duration of AN, and percentage of median BMI (%mBMI). At baseline, median age was 16.3 (interquartile range [IQR] = 2.5) years, duration of AN was 6 (IQR = 8.8) months and %mBMI was 87.2 (IQR = 10.5)%. Fifty-six percent had clinically significant anxiety; 30 % had depression. Over 6 months, participants had significant improvements in %mBMI (+2.2[IQR = 9.2]%, p < .01), STAI (−9.0[IQR = 25.0], p < .01), and BDI (−5.0[IQR = 13.8], p < .01) scores. Participants with larger improvements in caloric intake had greater improvements in STAI (p = .03) and BDI scores (p = .04). Larger improvement in BDI was significantly associated with increased fat intake (p < .01), but not carbohydrate or protein intake. Change in STAI was not associated with changes in fat, carbohydrate, or protein intake. Changes in STAI or BDI scores were not associated with changes in cortisol, leptin, or adiponectin. Increased caloric intake may augment treatment of co-occurring anxiety and depression, and increased fat intake may improve depression for AYA with AN.

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD.

Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1.73 m 2 ( n =569). NiCK is a single-center cross-sectional study of participants aged 8-25 years with eGFR<90 ml/min per 1.73 m 2 ( n =60) and matched healthy controls ( n =67). Untargeted metabolomic quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed: intelligence, attention regulation, working memory, and parent ratings of executive function. Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular versus nonglomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR. There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, and NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared with healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide-and with intelligence: γ -glutamyl amino acids and aconitate. Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction, and altered energy metabolism, circulating toxins, and redox homeostasis. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_17_CJN0000000000000318.mp3.

Independent effect of Aβ burden on cognitive impairment in patients with small subcortical infarction

BackgroundThe effect of amyloid-β (Aβ) on cognitive impairment in patients with small subcortical infarction remains controversial, although a growing body of evidence shows a substantial overlap between Alzheimer’s disease (AD) and subcortical ischemic vascular dementia, another form of cerebral small vessel disease (cSVD). Therefore, we investigated the relationships between Aβ positivity and the development of post-stroke cognitive impairment (PSCI) in patients with small subcortical infarction.MethodsWe prospectively recruited 37 patients aged ≥ 50 years, with first-ever small subcortical infarction, who underwent amyloid positron emission tomography, 3 months after stroke at Korea University Guro Hospital. We also enrolled CU participants matched for age and sex with stroke patients for comparison of Aβ positivity. Patients were followed up at 3 and 12 months after the stroke to assess cognitive decline. Logistic and linear mixed-effect regression analyses were performed to identify the effect of Aβ positivity on PSCI development and long-term cognitive trajectories.ResultsAt 3 months after stroke, 12/37 (32.4%) patients developed PSCI, and 11/37 (29.7%) patients had Aβ deposition. Aβ positivity (odds ratio [OR] = 72.2, p = 0.024) was predictive of PSCI development regardless of cSVD burden. Aβ positivity (β = 0.846, p = 0.014) was also associated with poor cognitive trajectory, assessed by the Clinical Dementia Rating-Sum of Box, for 1 year after stroke.ConclusionsOur findings highlight that Aβ positivity is an important predictor for PSCI development and cognitive decline over 1 year. Furthermore, our results provide evidence that anti-AD medications may be a strategy for preventing cognitive decline in patients with small subcortical infarctions.

Effect of speed and water depth on limb and back kinematics in Thoroughbred horses walking on a water treadmill

Water treadmill (WT) exercise may induce limb and back kinematics that meet specific training and rehabilitation goals. The study aimed to investigate the effects of walk speed, at different water depths (WDs), on limb and back kinematics of six Thoroughbreds exercising on a WT. Horses walked at 2.8/4.3/5.5/6.0 km/h (i.e. 0.8/1.2/1.5/1.7 m/s) at dry, metacarpophalangeal and carpal WD. Videography captured limb movement in the sagittal plane. Motion-capture measured thoracolumbosacral flexion-extension (FE), and lateral bend (LB) ranges of movement (ROM) using skin surface markers on the sixth, tenth, thirteenth, eighteenth thoracic, third and fifth lumbar, and third sacral spinous processes. Inertial-motion-sensors measured poll, withers and pelvic displacements. Following preliminary univariable analyses, multivariable mixed-effects linear-regression analyses were used to examine the relationship between speed, WD and each outcome variable (P < 0.05). Peak metacarpophalangeal, carpal and tarsal joint flexion increased with speed (P ≤ 0.002) and depth combined (P 0.001) while peak metatarsophalangeal flexion increased with WD only (P 0.001). Thoracolumbar FE-ROM between T10 and L3 and hindlimb retraction was increased by speed and WD combined (P 0.001). Hindlimb protraction was increased by speed (P 0.001) while hindlimb retraction was increased by speed and WD combined (P 0.001). Dorsoventral poll displacement was increased by speed (P 0.001) and carpal WD (P = 0.013), craniocaudal poll displacement was increased by speed and WD combined (P 0.001). Pelvic (tubera coxae and sacrum) dorsoventral displacements increased with speed and WD combined (P 0.001). Understanding the effects of speed and WD on limb, back and pelvic kinematics will improve decision making relating to dry and WT exercise within training.

Relationship between lexicon and grammar in children and youth who use augmentative and alternative communication

The present study investigated the relationship between lexicon and grammar in individuals who use graphic symbol-based aided augmentative and alternative communication (AAC). Data came from 60 transcripts of generalization sessions that were part of two previous intervention studies, aimed at improving the expressive vocabulary and grammar of 12 children and youth who used graphic symbol-based AAC. The specific aims of the current study were to (a) describe vocabulary composition across different levels of expressive vocabulary and (b) analyze the relationship between global measures of expressive vocabulary and the use of grammar in individuals who use aided AAC. A series of multiple linear mixed effect regression analyses showed a positive predictive association between overall vocabulary size and the use of closed-class words, and a positive relationship between the use of verbs and the use of closed-class words. Additionally, the use of verbs had a significant positive association with the use of inflectional morphology, while the use of nouns did not. Theoretical and practical implications of these findings are discussed.

CSF metabolites associated with biomarkers of Alzheimer's disease pathology.

Metabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer's disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease. The relative abundance of untargeted metabolites was assessed in 161 individuals from the Wisconsin Registry for Alzheimer's Prevention. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals from then Wisconsin Alzheimer's Disease Research Center. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study. Metabolome-wide association study results showed several significantly associated metabolites for all the biomarkers except Aβ42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid β (Aβ40), α-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for Aβ40 and α-synuclein. This study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.

Immediate versus conventional loading of mandibular implant-retained overdentures: a 3-year follow-up of a randomized controlled trial.

There is a scarcity of randomized clinical trials (RCT) that report medium- and long-term results and a lack of consensus in the literature on the predictability of immediately loaded unsplinted narrow diameter implants supporting mandibular overdentures. This RCT compared the performance of conventional (CL) and immediate loading (IL) of mandibular overdentures retained by two narrow-diameter implants for 3years. Patients from an RCT treated with CL or IL were invited to attend to 2- and 3-year follow-ups. Clinical, radiographic, functional, and oral health-related quality of life parameters were evaluated. Prosthetic maintenance events, biological complications, and success and survival rates were also recorded. The data were tested by multilevel mixed-effects linear regression analysis and chi-squared tests. The 1-year survival rates of 90% in the CL group and 85% in the IL group were maintained as no implants were lost between 1 and 3years. The marginal bone loss (MBL) in the IL group was significantly lower after year 3 (-0.04; p < 0.01). Significant changes were found only for the intra-group comparisons in the third year of function: (i) CL and IL presented similar progression of implant stability, MBL, and posterior bone area resorption; (ii) while CL started deteriorating of masticatory function, IL still exhibited functional evolution and (iii) oral comfort domain in the CL and pain domain in the IL were improved. Although IL experienced the lowest MBL after 3years, the outcomes showed that both loading protocols result in predictable medium-term rehabilitation when monitored annually. It can be expected that in the third year of function, patients with immediate loading may present more complaints related to general performance even with acceptable masticatory function and self-reported improvements in oral comfort.

The Relationship Between Rural-Urban Place of Residence and Subjective Well-Being is Nonlinear and its Substantive Significance is Questionable

Research on rural-urban differences in subjective well-being revealed inconsistent findings. I argue that the inconsistencies in the literature may be due to very small effect sizes and nonlinear associations. The aims of the present contribution were twofold: (1) to determine the effect size of the relationship between living in rural-urban areas and subjective well-being; (2) to investigate whether categories of rural-urban areas are nonlinearly related to subjective well-being. The present research used data from 507,452 participants from 115 countries provided by the European Values Study Trend File 1981–2017 and the World Values Survey time-series dataset (1981–2022). Self-reports of satisfaction with life and happiness were used to measure subjective well-being. Multilevel mixed-effects linear regression analysis revealed that, after adjusting for important sociodemographic variables such as gender, age, education, employment status, marital status, and income, the relationship between rural-urban place of residence and subjective well-being was statistically significant. However, the magnitude of these associations (i.e., effect size) was very small or even negligible. Moreover, pairwise comparisons of the estimated marginal means for life satisfaction and happiness revealed a pattern of nonlinear relationships. The results of the current research question the practical significance and usefulness of the relationship between rural-urban place of residence alone and subjective well-being.

Weekly, Seasonal, and Festive Period Weight Gain Among Australian Adults

Obesity is a major global health concern. A better understanding of temporal patterns of weight gain will enable the design and implementation of interventions with potential to alter obesity trajectories. To describe changes in daily weight across 12 months among Australian adults. This cohort study conducted between December 1, 2019, and December 31, 2021 in Adelaide, South Australia, involved 375 community-dwelling adults aged 18 to 65 years. Participants wore a fitness tracker and were encouraged to weigh themselves, preferably daily but at least weekly, using a body weight scale. Data were remotely gathered using custom-developed software. Time assessed weekly, seasonally, and at Christmas/New Year and Easter. Data were visually inspected to assess the overall yearly pattern in weight change. Data were detrended (to remove systematic bias from intraindividual gradual increases or decreases in weight) by calculating a line of best fit for each individual's annual weight change relative to baseline and subtracting this from each participant's weight data. Multilevel mixed-effects linear regression analysis was used to compare weight across days of the week and seasons and at Christmas/New Year and Easter. Of 375 participants recruited, 368 (mean [SD] age, 40.2 [5.9] years; 209 [56.8%] female; mean [SD] baseline weight, 84.0 [20.5] kg) provided at least 7 days of weight data for inclusion in analyses. Across the 12-month period, participants gained a median of 0.26% body weight (218 g) (range, -29.4% to 24.0%). Weight fluctuated by approximately 0.3% (252 g) each week, with Mondays and Tuesdays being the heaviest days of the week. Relative to Monday, participants' weight gradually decreased from Tuesday, although not significantly so (mean [SE] weight change, 0.01% [0.03%]; P = .83), to Friday (mean [SE] weight change, -0.18% [0.03%]; P < .001) and increased across the weekend to Monday (mean [SE] weight change for Saturday, -0.16% [0.03%]; P < .001; mean [SE] weight change for Sunday, -0.10% [0.03%]; P < .001). Participants' weight increased sharply at Christmas/New Year (mean [SE] increase, 0.65% [0.03%]; z score, 25.30; P < .001) and Easter (mean [SE] weight change, 0.29% [0.02%], z score, 11.51; P < .001). Overall, participants were heaviest in summer (significantly heavier than in all other seasons), were lightest in autumn (mean [SE] weight change relative to summer, -0.47% [0.07%]; P < .001), regained some weight in winter (mean [SE] weight change relative to summer, -0.23% [0.07%]; P = .001), and became lighter in spring (mean [SE] weight change relative to summer, -0.27% [0.07%]; P < .001). In this cohort study of Australian adults with weekly and yearly patterns in weight gain observed across 12 months, high-risk times for weight gain were Christmas/New Year, weekends, and winter, suggesting that temporally targeted weight gain prevention interventions may be warranted.

Health Professionals can Sustain Proficiency in Motivational Interviewing With a Moderate Amount of Training: An Intervention Fidelity Study.

Motivational interviewing (MI) proficiency may erode quickly, limiting its effectiveness. We examined whether health professionals completing a 2-day workshop, with 3 to 5 hours of personalized coaching, and twice-yearly group reflections sustained proficiency for the duration of a hip fracture rehabilitation trial and whether intervention was implemented as intended. A fidelity study was completed as part of a process evaluation of the trial that tested whether physical activity increased among hip fracture patients randomly allocated to receive MI (experimental) compared with dietary advice (control) over ten 30-minute sessions. Twelve health professionals (none were proficient in MI before trial commencement) delivered the intervention for up to 952 days. Two hundred experimental sessions (24% of all sessions, 83 patients) were randomly selected to evaluate proficiency using the MI Treatment Integrity scale; along with 20 control sessions delivered by four dietitians. Linear mixed-effects regression analyses determined whether proficiency was sustained over time. Dose was assessed from all experimental sessions ( n = 840, 98 patients). Intervention was implemented as intended; 82% of patients received at least eight 30-minute sessions. All motivational interviewers were proficient, whereas dietitians did not inadvertently deliver MI. Time had no effect on MI proficiency (est < 0.001/d, P = .913, 95% CI, -0.001 to 0.001). MI proficiency was sustained in a large trial over 2.6 years by completing a 2-day workshop, 3 to 5 hours of personalized coaching, and twice-yearly group reflections, even for those without previous experience; further research needs to establish the maximum duration of training effectiveness.

1518-P: Plasma Biomarker Concentrations of Alzheimer’s Disease Are Associated with Insulin Resistance—Results from a Pilot RCT in Adults with Diabetes Risk

Background: Recent research confirms insulin resistance (IR) not only as risk factor for type 2 diabetes mellitus (T2DM) but also for Alzheimer’s disease (AD). Diet restrictions in patients with T2DM or obesity alone may, thus, not only improve insulin sensitivity (IS) of the CNS but may beneficially affect AD-related biomarkers known to early recognize long-term AD risks. To prove this hypothesis, we investigated the effects of a controlled, potentially health-promoting dietary intervention on both glucose metabolism (IR) and AD biomarkers in cognitively healthy, obese adults. Methods: One-hundred-and-eleven adults (60±7y, BMI 31.1±3.5kg/m², 47 males) were randomized either to the intervention group consuming a plant-based diet or the control group maintaining their habitual Western diet. Both diets were isoenergetic to ensure a constant body weight. At baseline and after 6 weeks intervention, OGTT was performed and HOMA-IR and OGIS were calculated. Fasting plasma levels of AD biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid-beta (Aβ) 42/40, and phosphorylated tau (p-tau) 181 and 231; Simoa assay), glucose, HbA1c and serum insulin were measured. Data were analyzed via linear mixed-effect models and regression analyses. Results: Fasting glucose and insulin levels were in borderline high physiological ranges; a possible IR was indicated. After 6 weeks, there were no diet-induced differences in fasting levels of glucose, insulin, AD biomarkers, and IR measures (all p&amp;gt;0.05). However, a positive association of fasting levels of p-tau181 and HOMA-IR (β=0.464, p=0.038) and p-tau231 and HbA1c (β=2.693, p=0.029) and a negative trend for Aβ40 and OGIS (β=−0.049; p=0.055) were found. Conclusion: Impaired insulin sensitivity is associated with unfavorable changes in AD-related biomarker levels in adults with diabetes risk, highlighting the relevance of glucose metabolism in cognitive health. Disclosure H.Huber: None. M.Simon: None. N.J.Ashton: None. L.Weinhold: None. M.Schmid: None. M.Coenen: None. B.Stoffel-wagner: None. K.Blennow: Other Relationship; Acumen, BioArctic, Eisai, Biogen, Eisai Co., Ltd., Lilly, Novartis, Ono Pharmaceutical Co., Ltd., Prothena, Roche Diagnostics, Siemens, Brain Biomarker Solutions, Julius Clinical, ALZPath. P.Stehle: None. H.Zetterberg: None. Funding German Federal Ministry of Education and Research (01EA1707, 01EA1809A); Swedish Research Council (2017-00915, 2022-00732, 2022-01018); Swedish Alzheimer Foundation (AF-930351, AF-939721, AF-968270); Hjärnfonden, Sweden (FO2017-0243, ALZ2022-0006, FO2022-0270); Swedish State (ALFGBG-715986, ALFGBG-965240, ALFGBG-71320); European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236, JPND2021-00694); Alzheimer’s Association (ZEN-21-848495, SG-23-1038904 QC); European Union’s Horizon Europe Research and Innovation Programme (101053962, 860197); Alzheimer Drug Discovery Foundation (201809-2016862); AD Strategic Fund/Alzheimer's Association (ADSF-21-831376-C, ADSF-21-831381-C, ADSF-21-831377-C); Bluefield Project; Olav Thon Foundation; Erling-Persson Family Foundation; Stiftelsen för Gamla Tjänarinnor; UK Dementia Research Institute (UKDRI-1003)

Association between meaningful activities at home and subjective well-being in older adults with long-term care needs: A cross-sectional study

For this study, we examined whether engaging in meaningful activities at home is associated with subjective well-being (SWB) in older adults with long-term care needs according to their preference for going out. We distributed a self-administered questionnaire to long-term care facilities in Japan and performed a linear mixed-effects model regression analysis of the responses. The dependent variable was SWB, and the independent variables were the number of meaningful home activities, preference for going out, and the interaction between them. In our survey (n = 217), we found that both number of meaningful home activities (B = 0.43; 95%CI: 0.17, 0.70) and its interaction with preference (B = −0.43; 95%CI: −0.79, −0.08) were associated with SWB. These results suggest the importance of engaging in meaningful activities at home for older adults who do not prefer going out. We should encourage older adults to participate in activities that match their preference.

A farmer-friendly tool for estimation of weights of pigs kept by smallholder farmers in Uganda

Pig keeping is important to the livelihoods of many rural Ugandans. Pigs are typically sold based on live weight or a carcass weight derived from this; however this weight is commonly estimated due to the lack of access to scales. Here, we explore the development of a weigh band for more accurate weight determination and potentially increased farmer bargaining power on sale price. Pig weights and varied body measurements (heart girth, height, and length) were collected on 764 pigs of different ages, sex, and breed types, from 157 smallholder pig keeping households in Central and Western Uganda. Mixed-effects linear regression analyses, with household as a random effect and the varied body measurements as a fixed effect, were performed to determine the best single predictor for cube root of weight (transformation of weight for normality), for 749 pigs ranging between 0 and 125 kg. The most predictive single body measurement was heart girth, where weight in kg = (0.4011 + heart girth in cm × 0.0381)3. This model was found to be most suitable for pigs between 5 and 110 kg, notably more accurate than farmers’ estimates, but still with somewhat broad confidence intervals (for example, ±11.5 kg for pigs with a predicted weight of 51.3 kg). We intend to pilot test a weigh band based on this model before deciding on whether it is suitable for wider scaling.

Assessment of factors affecting flicker ERGs recorded with RETeval from data obtained from health checkup screening.

To determine the factors significantly associated with the amplitudes and implicit times of the flicker electroretinograms (ERGs) recorded with the RETeval system by analyzing the comprehensive data obtained during a health checkup screening. Flicker ERGs were recorded with the RETeval system from 373 individuals who had a normal fundus and optical coherence tomography images. The sex, age, anthropometric, ophthalmologic, and hematologic data were collected from all participants who were 40- to 89-years-of-age. Univariable and multivariable linear mixed effects regression analyses were performed to identify factors that were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Univariable linear mixed effects regression analysis showed significant correlations between the implicit times and the best-corrected visual acuity, the age, the axial length, the blood sugar level, and the blood urea nitrogen level. Analyses by multivariable linear mixed effects regression identified that the axial length (β = 0.28), the age (β = 0.24), and the blood sugar level (β = 0.092) were three independent factors that were significantly correlated with the implicit times of the RETeval flicker ERGs. Univariable linear mixed effects regression analysis also showed significant correlations between the amplitudes of the RETeval flicker ERGs and the age, the platelet count, and the creatinine level. Multivariable linear mixed effects regression models identified the age (β = -0.092), the platelet count (β = 0.099), and the creatinine level (β = -0.12) as three independent factors that were significantly correlated with the amplitudes of the RETeval flicker ERGs. However, the smoking habits, body mass index, and the blood pressure were not significantly correlated with either the implicit times or amplitudes of the RETeval flicker ERGs. Our results indicate that the age and some ophthalmologic and hematologic findings but not the anthropometric findings were significantly associated with the implicit times and amplitudes of the RETeval flicker ERGs. Thus, clinicians should remember these factors when analyzing the RETeval flicker ERGs.

Factors affecting the micronutrient status of adolescent girls living in complex agro-aquatic ecological zones of Bangladesh

Inadequate intake of both macro and micronutrients is the major determinant of micronutrient deficiencies in adolescent girls. This study assessed multiple micronutrient status including vitamin D, iron, vitamin A, and urinary iodine concentration among adolescent girls through two seasonal cross-sectional surveys conducted during dry and wet seasons. Mixed-effects linear and logistic regression analysis were conducted to assess associations between micronutrient status, salinity and seasonality. The mean age of the girls was 14 years. Vitamin (OH)D insufficiency was significantly higher in freshwater areas in wet season compared to dry season (wet season: 58% and dry season: 30%, P < 0.001). In wet season, risk of vitamin (OH)D insufficiency was three times higher compared to dry season (AOR: 3.03, 95% CI 1.71, 5.37, P < 0.001). The odds of vitamin (OH)D insufficiency was 11 times higher in fresh water areas compared to high saline areas (AOR: 11.51, 95% CI 3.40, 38.93, P < 0.001). The girls had higher risk of iron deficiency in wet season. Despite the environment being enriched with micronutrient-contained aquatic food, adolescent girls in coastal areas experience different micronutrient deficiencies. The high prevalence of vitamin (OH)D insufficiency in freshwater locations and seasonal iron deficiency in high saline areas needs attention.

Contrast-enhanced subharmonic aided pressure estimation for assessment of intracranial pressure in vivo.

Intracranial pressure (ICP) monitoring in children currently requires invasive techniques. Subharmonic aided pressure estimation (SHAPE) uses contrast-enhanced ultrasound (CEUS) to measure intravascular and interstitial pressure, but utility in ICP measurements has yet to be explored. The objective of this study was to investigate SHAPE as a novel tool for noninvasive ICP measurements in fetal lambs. Eighteen fetal lambs at 107-139days gestational age (term = 145days) underwent subdural ICP catheter placement. The brain was imaged in the coronal plane in CEUS mode optimized for SHAPE, while infusing an US contrast agent into the fetal circulation. After SHAPE calibration, saline was infused via the subdural catheter to increase ICP. Five-second SHAPE cine clips were obtained at various ICPs. Subharmonic intensity values of the whole brain and thalami were correlated with ICP values using mixed effects linear regression analyses and the strength of the relationship was evaluated by Spearman's rank-order correlation. Forty-nine experiments produced 723 datapoints, including SHAPE intensity values and mean ICP measurements. There was a statistically significant inverse relationship between SHAPE intensity values and ICP measurements in the whole brain and thalami (median rho value - 0.58 and - 0.56, respectively). SHAPE intensity values of the brain demonstrate an inverse and statistically significant correlation with in vivo ICP measurements in an animal model.

Association of Race and Poverty Status With DNA Methylation–Based Age

The Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE) measure is a newly constructed DNA methylation (DNAm) biomarker associated with morbidity, mortality, and adverse childhood experiences in several cohorts with European ancestry. However, there are few studies of the DunedinPACE measure among socioeconomically and racially diverse cohorts with longitudinal assessments. To investigate the association of race and poverty status with DunedinPACE scores in a socioeconomically diverse middle-aged cohort of African American and White participants. This longitudinal cohort study used data from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study. HANDLS is a population-based study of socioeconomically diverse African American and White adults aged 30 to 64 years at baseline in Baltimore, Maryland, with follow-up approximately every 5 years. The current study was restricted to 470 participants with blood samples at 2 time points: August 14, 2004, to June 22, 2009 (visit 1), and June 23, 2009, to September 12, 2017 (visit 2). Genome-wide DNAm was assessed at visit 1 (chronological age, 30-64 years) and visit 2. Data were analyzed from March 18, 2022, to February 9, 2023. DunedinPACE scores were estimated for each participant at 2 visits. DunedinPACE scores are values scaled to a mean of 1, interpretable with reference to a rate of 1 year of biological aging per 1 year of chronological aging. Linear mixed-model regression analysis was used to examine the trajectories of DunedinPACE scores by chronological age, race, sex, and poverty status. Among 470 participants, the mean (SD) chronological age at visit 1 was 48.7 (8.7) years. Participants were balanced by sex (238 [50.6%] were men and 232 [49.4%] were women), race (237 [50.4%] African American and 233 [49.6%] White), and poverty status (236 [50.2%] living below poverty level and 234 [49.8%] living above poverty level). The mean (SD) time between visits was 5.1 (1.5) years. Overall, the mean (SD) DunedinPACE score was 1.07 (0.14), representing a 7% faster pace of biological aging than chronological aging. Linear mixed-effects regression analysis revealed an association between the 2-way interaction between race and poverty status (White race and household income below poverty level: β = 0.0665; 95% CI, 0.0298-0.1031; P < .001) and significantly higher DunedinPACE scores and an association between quadratic age (age squared: β = -0.0113; 95% CI, -0.0212 to -0.0013; P = .03) and significantly higher DunedinPACE scores. In this cohort study, household income below poverty level and African American race were associated with higher DunedinPACE scores. These findings suggest that the DunedinPACE biomarker varies with race and poverty status as adverse social determinants of health. Consequently, measures of accelerated aging should be based on representative samples.