Random Slope Research Articles

How important is the linearity assumption in a sample size calculation for a randomised controlled trial where treatment is anticipated to affect a rate of change?

BackgroundFor certain conditions, treatments aim to lessen deterioration over time. A trial outcome could be change in a continuous measure, analysed using a random slopes model with a different slope in each treatment group. A sample size for a trial with a particular schedule of visits (e.g. annually for three years) can be obtained using a two-stage process. First, relevant (co-) variances are estimated from a pre-existing dataset e.g. an observational study conducted in a similar setting. Second, standard formulae are used to calculate sample size. However, the random slopes model assumes linear trajectories with any difference in group means increasing proportionally to follow-up time. The impact of these assumptions failing is unclear.MethodsWe used simulation to assess the impact of a non-linear trajectory and/or non-proportional treatment effect on the proposed trial’s power. We used four trajectories, both linear and non-linear, and simulated observational studies to calculate sample sizes. Trials of this size were then simulated, with treatment effects proportional or non-proportional to time.ResultsFor a proportional treatment effect and a trial visit schedule matching the observational study, powers are close to nominal even for non-linear trajectories. However, if the schedule does not match the observational study, powers can be above or below nominal levels, with the extent of this depending on parameters such as the residual error variance. For a non-proportional treatment effect, using a random slopes model can lead to powers far from nominal levels.ConclusionsIf trajectories are suspected to be non-linear, observational data used to inform power calculations should have the same visit schedule as the proposed trial where possible. Additionally, if the treatment effect is expected to be non-proportional, the random slopes model should not be used. A model allowing trajectories to vary freely over time could be used instead, either as a second line analysis method (bearing in mind that power will be lost) or when powering the trial.

Derivation of paediatric blood pressure percentiles from electronic health records

Identification of abnormal blood pressure (BP) in children requires normative data. We sought to examine the feasibility of using "real-world" office BP data obtained from electronic health records (EHR) to generate age-, sex- and height-specific BP percentiles for children. Using data collected 01/01/2009-8/31/2021 from eight large children's healthcare organisations in PEDSnet, we applied a mixed-effects polynomial regression model with random slopes to generate Z-scores and BP percentiles and compared them with currently used normative BP distributions published in the 2017 American Academy of Paediatrics (AAP) Clinical Practise Guidelines (CPG). We identified a study sample of 292,412 children (1,085,083 BP measurements), ages 3-17 years (53% female), with no chronic medical conditions, who were not overweight/obese and who were primarily seen for general paediatric care in outpatient settings. Approximately 45,000-75,000 children contributed data to each age category. The PEDSnet systolic BP percentile values were 1-4mmHg higher than AAP CPG BP values across age-sex-height groups, with larger differences observed in younger children. Diastolic BP values were also higher in younger children; starting with age 7 years, diastolic BP percentile values were 1-3mmHg lower than AAP CPG values. Cohen's Kappa was 0.90 for systolic BP, 0.66 for diastolic BP, and 0.80 overall indicating excellent agreement between PEDSnet and 2017 AAP CPG data for systolic BP and substantial agreement for diastolic BP. Our analysis indicates that real-word EHR data can be used to generate BP percentiles consistent with current clinical practise on BP management in children. Funding for this work was provided by the Preserving Kidney Function in Children with Chronic Kidney Disease (PRESERVE) study; Patient-Centred Outcomes Research Institute (PCORI) RD-2020C2020338 (Principal Investigator: Dr. Forrest; Co-Principal Investigator: Dr. Denburg).

Polygenic risk scores for Alzheimer's disease in relation to cognitive change: A representative sample from the general population followed over 16 years.

BackgroundPolygenic risk scores for Alzheimer's disease (AD-PRSs) have been associated with cognition. However, few studies have examined the effect of AD-PRS beyond the APOE gene, and the influence of genetic variants related to level of cognitive ability (COG-PRS) on cognitive performance over time in the general older population. MethodA population-based sample of 965 individuals born in 1930, with genetic and standardized cognitive data on six psychometric tests (Thurstone's picture memory, immediate recall of 10 words, Block design, word fluency, figure identification, delayed recall of 12 items), were examined at age 70, 75, 79, and 85 years. Non-APOE AD-PRSs and COG-PRSs (P < 5e−8, P < 1e−5, P < 1e−3, P < 1e−1) were generated from recent genome-wide association studies. Linear mixed effect models with random intercepts and slope were used to analyze the effect of APOE ε4 allele, AD-PRSs, and COG-PRSs, on cognitive performance and rate of change. Analyses were repeated in samples excluding dementia. ResultsAPOE ε4 and AD-PRS predicted change in cognitive performance (APOE ε4*age: β = −0.03, P < 0.0001 and AD-PRS *age: β = −0.01, P = 0.02). The results remained similar in the sample excluding those with dementia. COG-PRS predicted level of cognitive performance, while APOE ε4 and AD-PRS did not. COG-PRSs did not predict change in cognitive performance. ConclusionWe found that genetic predisposition of AD predicted cognitive decline among 70-year-olds followed over 16 years, regardless of dementia status, while polygenic risk for general cognitive performance did not.

Changes in Body Mass Index and Incident Mild Cognitive Impairment Among African American Older Adults.

Previous research suggests a decline in body mass index (BMI) among older adults is associated with negative health outcomes, including mild cognitive impairment (MCI) and incident dementia. However, no studies have examined the effects of education or developing MCI on BMI trajectories over time. The purpose of this investigation was to characterize trajectories of change in BMI among older adults who develop MCI. Participants were from the Minority Aging Research Study (MARS), a longitudinal cohort study of cognitive decline and Alzheimer's disease in older African Americans living in the greater Chicago, Illinois, area. The study included annual clinical evaluations of cognitive status, as well as measurements of height and weight for BMI calculation. Older African American participants without cognitive impairment at baseline were included in the present analysis (N = 436, 78% women, mean baseline age = 72 [SD = 5.7], mean education = 15 [SD = 3.5]). In piecewise linear mixed-effects models that included a random intercept and 2 random slopes, BMI declined over time (B = -0.20, SE = 0.02, p < .001), with a faster decline after MCI diagnosis (additional decline, B = -0.15, SE = 0.06, p = .019). Older age was associated with lower baseline BMI (B = -0.19, SE = 0.05, p < .001), as was higher education (B = -0.34, SE = 0.09, p < .001). Further, higher education was associated with a slower decline in BMI before MCI (B = 0.02, SE = 0.006, p = .001), but a faster decline after MCI (B = -0.06, SE = 0.022, p = .003). These results suggest an accelerated decline in BMI following an MCI diagnosis, with higher education related to an even faster BMI decline.

Changes in myocardial perfusion after coronary sinus reducer implantation for refractory angina - assessment using fully automated quantitative stress perfusion cardiac MRI

Abstract Introduction Previous reports show angina improvement after Coronary Sinus Reducer (CSR) implantation [1,2]. However, the mechanistic basis remains unconfirmed. Preliminary studies using semi-quantitative metrics derived from stress perfusion cardiac MRI (CMR), have suggested improved myocardial perfusion particularly in ischaemic segments [3]. To date, assessment by fully automated quantitative myocardial perfusion CMR has not been reported. Purpose To assess the effect of CSR implantation on quantitative regional myocardial blood flow in patients with refractory angina and advanced coronary artery disease (CAD). Methods Prospective cohort study of patients undergoing CSR implantation. CMR was performed at baseline and median 7 months follow-up. Automated segmentation into a 16-segment American Heart Association model was performed to quantify segmental rest and stress myocardial blood flow (MBF, ml/min/g) and myocardial perfusion reserve (MPR). Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. Wilcoxon matched-pairs sign rank tests were used to compare paired global and segmental perfusion values. A linear mixed-effects model with random slopes and intercepts was used to assess the relationship between baseline segmental MPR and associated change in MPR (ΔMPR) after CSR implantation. Results 12 patients (10M:2F; mean age 67) were included. Median Canadian Cardiovascular Society class was 3. Globally, there was no change in rest (P=0.90), stress MBF (P=0.34) or MPR (P=0.72) from baseline to follow-up. However, ΔMPR was related to the degree of baseline ischaemia (panel A). Segments with baseline MPR&amp;lt;2.45 increased in MPR whereas segments with baseline MPR ≥2.45 experienced a decrease (P=0.003, conditional R2: 0.81). In segments with MPR&amp;lt;2.45 (n=138), median ΔMPR was +0.18 (15.4%; P&amp;lt;0.0001); whereas with MPR≥2.45 (n=52) it was -0.41 (-12.7%; P=0.03; panel B). When assessed by myocardial layer, significant increases in MPR were observed in both subendocardial (+0.19 [15.6%]; P&amp;lt;0.0001) and subepicardial (+0.19 [12.3%]; P&amp;lt;0.0002) segments with baseline MPR&amp;lt; 2.45 (panel C). Conversely, in segments with baseline MPR≥2.45, there was a significant reduction in MPR in the subendocardium (-0.43 [-15.9%]; P=0.04) but not in the subepicardium (-0.36 [-9.90%]; P=0.08; panel D). Conclusion To our knowledge, this is the first study showing changes in quantitative myocardial perfusion after CSR implantation by fully automated inline quantitative perfusion CMR. Our analysis shows a relationship between baseline MPR and change in MPR after CSR implantation, supporting redistribution of perfusion into both subendocardial and subepicardial layers as potential mechanisms of action of CSR. Further studies are needed to confirm these preliminary results.

The Use of Two-Piece Transmucosal Implants Designed with a Convergent Neck: A 6-Year Clinical Prospective Cohort Study Evaluating the Impact on Soft and Hard Tissues.

This prospective study evaluated the marginal bone level and periodontal parameters 6 years after placement of a convergent transmucosal neck implant. In total, 71 implants were placed in 60 patients. Of these, 52 implants were placed with a flapless technique and with the convergent neck exposed by 1 mm (early and delayed placement), while 19 implants were placed immediately after extraction (immediate placement). At least 3 months after insertion, customized abutments were applied and provisional resin crowns were cemented, while being careful to prevent any tissue compression. After 3 weeks, definitive metal-ceramic crowns were designed with the finish line at the soft tissue level and free from any compression. The implant survival rate at 6 years, marginal bone level changes (ΔMBL, mm), and Pink Esthetic Score (PES) were evaluated. Gingival phenotype was determined before the implant surgeries (thin/thick). A three-level hierarchical model was examined with a random intercept and random slope on follow-up time at the patient level and a random intercept at the implant level. In all, 57 patients with 67 implants reached the 6-year point; 3 patients (5.0%) dropped out. The implant survival rate was 100%. ΔMBL from baseline to 24 months was 0.58 mm (95% CI: 0.48, 0.68), while ΔMBL from 24 to 72 months was 0.33 mm (95% CI: 0.19, 0.47). PES improved steadily from 6 to 48 months (+0.96; 95% CI: 0.71, 1.20), with overall stability at 72 months. No correlation between MBL and PES was observed. A significant association was found between thick gingival phenotype and less MBL variation. Greater implant diameter offered more MBL stability after 3 years but resulted in lower PES values. The use of convergent transmucosal neck implants placed with a flapless transmucosal approach with the crown margin positioned at the gingival level preserved marginal bone and guided gingival morphology for up to 72 months. The gingival phenotype was the parameter that most affected the soft and hard tissues. In the long term, implant placement timing was not related to MBL.

Interaction and joint association of gestational diabetes mellitus and subsequent weight gain rate on macrosomia

Background & aimsGestational diabetes mellitus (GDM) and gestational weight gain are two crucial modifiable nutritional factors during pregnancy in preventing macrosomia, warranting appropriate management of both glycemic levels and weight gain to prevent macrosomia, particularly in individuals with GDM. Unfortunately, current general weight targets appear not to apply to individuals with GDM, suggesting that weight gain, specifically following an oral glucose tolerance test (OGTT), may affect risk of macrosomia dependent on GDM status. Therefore, this study aims to evaluate the interaction and joint association of GDM and post-OGTT weight gain rate (PWGR) in relation to macrosomia. MethodsThis was a population-based cohort study of 59,421singleton pregnant women in South China during 2017-2020. Among them, 9,856 were diagnosed with GDM while 49,565 did not have the condition. All participants underwent an OGTT between 20 and 28 weeks of pregnancy, typically occurring between 24 and 28 weeks. PWGR was defined as the average rate of change in maternal weight with gestational weeks following OGTT, which was estimated using a repeated linear mixed effects model including a random intercept and slope for each individual. The relative risk (RR) of macrosomia associated with GDM and PWGR was estimated using a multivariate generalized linear model. ResultsThere was a significant interaction between GDM and PWGR in increasing the risk of macrosomia. The combination of GDM and a 1-SD increase in PWGR was associated with a 2.26-fold higher risk of macrosomia (95% CI 1.92 to 2.65), with the interaction of these two factors contributing to 58.0% (95% CI 31.4% to 84.7%) of this association. Moreover, we observed a significant heterogeneity in susceptibility to macrosomia due to increased PWGR between GDM and non-GDM populations, with the highest PWGR quartile having respective RRs of 2.27 (95% CI 1.62 to 3.18) and 1.41 (95% CI 1.18 to 1.69) compared to the lowest quartile category, which was corresponded to 55.9% (95% CI 38.3% to 68.6%) and 29.1% (95% CI 15.3% to 40.8%) preventable proportions of macrosomia cases in these populations. ConclusionsGDM and PWGR had a synergistic effect in increasing the risk of macrosomia. Furthermore, individuals with GDM exhibited a heightened susceptibility to macrosomia due to elevated PWGR. These findings emphasize the importance of appropriate weight interventions during late pregnancy and suggest the need for different weight targets between these two populations, with a stricter PWGR potentially being more effective for the GDM population.

How Past Work Stressors Influence Psychological Well-Being in the Face of Current Adversity: Affective Reactivity to Adversity as an Explanatory Mechanism

This study advances the understanding of the mechanisms that link past challenge and hindrance stressors to resilience outcomes, as indicated by emotional and psychosomatic strain in the face of current adversity. Building on the propositions of Conservation of Resources Theory and applying them to the challenge-hindrance framework, we argue that challenge and hindrance stressors experienced in the past relate to different patterns of affective reactivity to current adversity, which in turn predict resilience outcomes. To test these assumptions, we collected data from 134 employees who provided information on work stressors between April 2018 and November 2019 (T0). During the first COVID-19 lockdown (March/April 2020), the same individuals participated in a weekly study over the course of 6 weeks (T1–T6). To test our assumptions, we combined the pre- and peri-pandemic data. We first conducted multilevel random slope analyses and extracted individual slopes indicating affective reactivity to COVID-19 adversity in positive and negative affect. Next, results of path analyses showed that past challenge stressors were associated with lower affective reactivity to COVID-19 adversity in positive affect, and in turn with lower levels of emotional and psychosomatic strain. Past hindrance stressors were associated with greater affective reactivity to COVID-19 adversity in positive and negative affect, and in turn to higher strain. Taken together, our study outlines that past work stressors may differentially affect employees’ reactivity and resilient outcomes in the face of current nonwork adversity. These spillover effects highlight the central role of work stressors in shaping employee resilience across contexts and domains.

Abstract 17257: Aortopulmonary Collateral Burden in the Fontan Circulation: Longitudinal Changes and Relationship With Clinical Outcomes

Background: Aortopulmonary collaterals (APC) are a common source of volume load in patients with a Fontan circulation and their burden can be quantified by CMR. Longitudinal trends in APC flow and their relationship with outcomes have not been described. Hypothesis: Higher APC flow will be associated with worse clinical outcomes in Fontan patients. Aims: To assess longitudinal changes in APC flow in the Fontan circulation using CMR and their relationship with outcomes. Methods: Single-center retrospective analysis of Fontan patients who had at least 1 CMR with APC flow data. APC flow was estimated as the difference between aortic and systemic venous flows and also expressed as a percent of aortic flow. Primary outcome was a composite of death or heart transplantation; secondary outcomes included protein losing enteropathy, ascites, chylothorax, and hemoptysis. The baseline (time at Fontan=time 0) and trend in APC flow were estimated using a linear mixed model with a random intercept and slope for each patient. Results: Analysis included 758 CMRs from 356 patients; 123 of whom had ≥ 2 CMRs. Median age at first CMR was 14 y (IQR 10-19 y) and median CMRs per patient were 2 (range 1-12). Baseline APC flow was 0.6 (±0.5) L/min/m 2 or 17 (±10) % of aortic flow. Increasing APC flow over time correlated with increasing trend in ventricular dilation and decreasing trend in SaO 2 . Over a median follow-up of 17 years, 22 patients (6%) had the composite outcome. High baseline APC flow as well as an increasing trend in APC flow were associated with clinical outcomes including an independent association with death or heart transplantation (Table). Conclusions: APCs represent a significant hemodynamic burden in functional single ventricle hearts palliated to the Fontan circulation. Higher and increasing APC flow is associated with worse clinical outcomes. Factors contributing to APC development and whether APC occlusion results in a lasting reduction in the burden remain to be elucidated.

PSIII-13 Effects of Weather, Body Weight, and Feed Intake on Total and Liquid Water Intake in Beef Bulls

Abstract Research conducted in the 1950s to determine water requirements used cattle that vary greatly from the animals being raised today. Changes in lean composition and growth rate in young cattle and milk production and mature size in cows have likely altered water requirements. Furthermore, most of the research has been conducted on animals being fed for slaughter, rather than bulls or reproductive females. The objective of this study was to analyze the effect of weather variables, dry matter intake (DMI), and body weight (BW) on total daily water intake (TDWI) in growing beef bulls. Angus (n = 15) and Simmental x Angus bulls (n = 29) with an average initial BW of 362.5 ± 27.0 kg were housed in an open front, monoslope building at the SDSU Cow-Calf Education and Research Facility (CCERF) from November 9, 2021, to March 1, 2022. Bulls were provided with ad libitum access to feed (1.15 Mcal NEg/kg dry matter, 14% crude protein, 52.2% dry matter) and water using the Insentec Roughage Intake Control system (Hokofarm, Marknesse, Netherlands). Feed and water disappearance were assumed to be caused by intake. Water intake was measured in kg; however, the data were converted to L based on a correction factor determined by weighing a known amount of water. Body weights were taken every 28 d to determine ADG and predict daily BW during the duration of the study. Daily weather variables were collected from the South Dakota Mesonet station located 3.86 km from the CCERF. Weather variables analyzed included: average windchill (°C), solar radiation (W/m2), and wind speed (km/h); and minimum, maximum, and average relative humidity (%) and average temperature (°C). R-studio (R-4.1.2.pkg) was used to develop a linear mixed effects model with random intercept and slope used to account for the within subject correlations. Total daily water intake increased with increasing DMI (1.921 L TDWI per kg DMI; P &amp;lt; 0.0001), BW (0.025 L TDWI per kg BW; P = 0.0055), and maximum daily temperature (0.171 L TDWI per 1°C; P = 0.0023). For every 1% increase in the minimum relative humidity, TDWI tended to increase by 0.041 L (P = 0.0616). Warmer wind chill also tended to increase TDWI (0.463 L per 1°C; P = 0.0707). The effects of DMI, BW, maximum daily temperature, minimum relative humidity, and wind chill were predictive of TDWI in growing beef bulls fed during the winter months in South Dakota. This model will be useful for predicting TDWI in growing beef bulls that are raised in areas that experience similar winter weather conditions.

Impact of a Trampoline-Based Exercise Program on Strength and Endurance in Pediatric Stem Cell Transplant Patients

P Glogowski and L Thérond contributed equally to this work. Background Pediatric patients receive physiotherapy support during hematopoietic stem cell transplantation (HSCT) to prevent the deterioration of condition and musculature and to promote rehabilitation. Despite the good arguments in favor of physiotherapy, children often do not enjoy the exercises, or even refuse to participate. In our prospective study we show that our unique training program on the trampoline is convincing and superior to the standard physical therapy during HSCT. Patients and Methods In this monocentric, randomized, prospective study of the University Children's Hospital Tübingen, 52 HSCT patients between 5 and 22 years of age were followed during the in-patient stay in the context of HSCT, as well as in the post-transplant period until day +200 after HSCT. The therapy group (TG; n=26; TG) received a specially created exercise program five days a week with elements of strength and endurance training using a trampoline and an exercise ball. The TG was compared with a control group (CG; n=26) that received standard physical therapy. After in-patient discharge, TG patients were given an exercise plan and an exercise diary to complete independently at home. On six predefined approximate observation days (baseline: day of in-patient admission before HSCT, between day +3 to +8 after leukocyte/granulocyte “take”, after HSCT, day +60, day +100, day +150, and day +200 after HSCT), patients in both groups were assessed for muscle strength (full-ball bump, triple hop), stamina and endurance (timed-up-and-go, 6-minute walking), muscle development (muscle circumferences of M. triceps surae and M. quadriceps), emotional state and quality of life (questionnaires: SAM, KINDL-Onco-module). Data from the training tests, as well as from the questionnaires was used to fit linear mixed models. The equation used to fit the models can be described by DV ijk = β 0j + β 1j * day k + ϑ 0i + ϑ 1i + ε ijk. In this model equation DV ijk denotes the dependent variable of patient i = 1, ..., 52, in group j = 1 (CG) or 2 (TG), at day k = -53, ..., 367 after HSCT. β 0j and β 1j denote the fixed effects where β 0j is the intercept estimate (i.e. the dependent variable at day 0 after HSCT) and β 1j is the slope estimate (i.e. how much the dependent variable decreases or increases each day) for the respective group j. ϑ 0i and ϑ 1i describe the individual specific random intercept and slopes, while ε ijk is the error term. Results A total of 52 patients with a median age of 9.8 years (range 5.2 to 20.3 years), 29 of whom were females (55.8%), were included in this study. Of the patients, 45 (86.5%) and 7 (13.5%) underwent allogeneic or autologous HSCT, respectively. The underlying diseases were malignant in 63.5% of the cases (e.g., acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma) and non-malignant in 36.5% of the cases (e.g., beta-thalassemia, sickle cell disease). The granulocyte and leukocyte take were each reached at a median of day +17 (range day +8 to day +30). The estimated fixed effects of the slopes of the analyzed data for the training tests and questionnaires can be found in the table. In the TG, there was a significant increase in the results of the walking test, the triple hop, the full ball bump, and triceps and quadriceps circumferences. No significant improvement over time was found in the CG. Looking at the difference between groups, the improvement in the TG was significantly greater for the walking test, the triple hop, and the quadriceps circumferences. For the questionnaire data, it was shown that both the CG and the TG had a significant decrease in debilitating physical, as well as debilitating psychological symptoms over time (KINDL body and KINDL mind). There was no significant difference between groups in these scales. For self-reported anxiety (SAM) and illness-related worries (KINDL disease) there was a significant decrease, while the scales KINDL friends and KINDL school increased significantly in the TG but not in the CG. For anxiety and the KINDL school scale this improvement was significantly greater in the TG than in the CG. Conclusions Our unique and new trampoline-based exercise program was able to counter standard physical therapy with significant improvements in muscle strength, endurance, as well as a reduction in anxiety and worry and an improved quality of life for the patients. And most importantly, our patients had an incredible amount of fun doing it.

Association of Higher Intake of Plant-Based Foods and Protein With Slower Kidney Function Decline in Women With HIV.

We investigated whether there exists an association between dietary acid load and kidney function decline in women living with HIV (WLWH) receiving antiretroviral therapy (ART). One thousand six hundred eight WLWH receiving ART in the WIHS cohort with available diet data and a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/minute/1.73 m2. A brief dietary instrument conducted from 2013 to 2016 under the Food Insecurity Sub-Study was used for assessing fruits and vegetables (FV) and protein intake. A mixed-effects model with random intercept and slope was used to estimate subjects' annual decline rate in eGFR and the association between FV intake and eGFR decline, adjusting for sociodemographics, serum albumin, comorbidities, time on ART, ART drugs, HIV markers, and baseline eGFR. We evaluated whether markers of inflammation mediated the effect of FV intake on decline in eGFR, using causal mediation analysis. We found a dose-response relationship for the association of FV intake and eGFR decline, with lesser annual decline in eGFR in the middle and highest tertiles of FV intake. An increase of 5 servings of FV intake per day was associated with a lower annual eGFR decline (-1.18 [-1.43, -0.94]). On average, 39% of the association between higher FV intake and slower eGFR decline was explained by decreased levels of inflammation. Plant-rich diet was associated with slower decline in kidney function. Inflammation is a potential path through which diet may affect kidney function. The findings support an emerging body of literature on the potential benefits of plant-rich diets for prevention of chronic kidney disease.

What is the association between adverse childhood experiences and late-life cognitive decline? Study of Healthy Aging in African Americans (STAR) cohort study

ObjectivesAdverse childhood experiences (ACEs) are associated with higher risk of chronic disease, but little is known about the association with late life cognitive decline. We examined the longitudinal association between...

Time Effect on Acute Postoperative Pain After Total Knee Replacement Surgery: An Exploratory Study Using the Experience Sampling Method.

Acute postoperative pain (APP) is the main cause of postoperative dissatisfaction; however, traditional methods of pain assessment provide limited insights into the dynamics and development of APP. This study used the experience sampling method (ESM) to understand the dynamics of APP over time in relation to various patient factors. Forty patients scheduled to undergo total knee replacement surgery were recruited in this study. Following an initial assessment, a short report questionnaire was sent to the patients via 10 digital alerts per day to assess the pain levels during two preoperative and the first 6 postoperative days. The data were analyzed using multilevel regression including random intercept and slope. Thirty-two patients submitted the pre-specified minimum of 30% of their short reports, yielding 1217 records. The analysis revealed significant (P<0.001) linear and quadratic decreases in APP and a quadratic time effect. The lowest between-days and within-day pain levels were observed on postoperative day 4.8 and during the time slot 3.8 or approximately 19:15, respectively. Significant random intercepts and slopes were noted, indicating variations in the mean pain level between patients and a decrease in pain. None of the 10 patient factors had any confounding effect. Using ESM data combined with multilevel analysis, we were able to evaluate the postoperative pain course while considering inter-individual differences in the baseline pain level and non-linear pain course over time. The findings of this study could aid clinicians in personalizing the treatment for APP.

25 Update to: The Predictive Utility of Various Subjective Cognitive Complaints Using Item Level Data from the Everyday Cognition (ECog) Scales

Objective:Early identification of individuals at risk for dementia provides an opportunity for risk reduction strategies. Many older adults (30-60%) report specific subjective cognitive complaints, which has also been shown to increase risk for dementia. The purpose of this study is to identify whether there are particular types of complaints that are associated with future: 1) progression from a clinical diagnosis of normal to impairment (either Mild Cognitive impairment or dementia) and 2) longitudinal cognitive decline.Participants and Methods:415 cognitively normal older adults were monitored annually for an average of 5 years. Subjective cognitive complaints were measured using the Everyday Cognition Scales (ECog) across multiple cognitive domains (memory, language, visuospatial abilities, planning, organization and divided attention). Cox proportional hazards models were used to assess associations between self-reported ECog items at baseline and progression to impairment. A total of 114 individuals progressed to impairment over an average of 4.9 years (SD=3.4 years, range=0.8-13.8). A subset of individuals (n=352) underwent repeat cognitive assessments for an average of 5.3 years. Mixed effects models with random intercepts and slopes were used to assess associations between baseline ECog items and change in episodic memory or executive function on the Spanish and English Neuropsychological Assessment Scales. Time in years since baseline, the ECog items, and the interaction were key terms of interest in the models. Separate models for both the progression analyses and mixed effects models were fit for each ECog item that included age at the baseline visit, gender, and years of education as covariates.Results:More complaints on five of the eight memory items, three of the nine language items, one of the seven visuospatial items, two of the five planning items, and one of the six organization items were associated with progression to impairment (HR=1.25 to 1.59, ps=0.003 to 0.03). No items from the divided attention domain were significantly associated with progression to impairment. In individuals reporting no difficulty on ECog items at the baseline visit there was no significant change over time in episodic memory(p&gt;0.4). More complaints on seven of the eight memory items, two of the nine language items, and three of the seven visuospatial items were associated with more decline in episodic memory (ps=0.003 to 0.04). No items from the planning, organization, or divided attention domains were significantly associated with episodic memory decline. Among those reporting no difficulty on ECog items at the baseline visit there was slight decline in executive function (ps=&lt;0.001 to 0.06). More complaints on three of the eight memory items and three of the nine language items were associated with decline in executive function (ps=0.002 to 0.047). No items from the visuospatial, planning, organization, or divided attention domains were significantly associated with decline in executive function.Conclusions:These findings suggest that, among cognitively normal older adults at baseline, specific complaints across several cognitive domains are associated with progression to impairment. Complaints in the domains of memory and language are associated with decline in both episodic memory and executive function.

Psychosocial stress in children with Tourette syndrome and chronic tic disorder

BackgroundThis study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder. MethodsConsecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated. The stressful events and YGTSS measurements were used and treated as time-varying variables in the analyses. Models that controlled for non-independence among the repeated observations using a random intercept and random slope model were employed. Each participant was treated as a random factor in the modelling. ResultsFamily-related stress, personal relationship stress and school-related stress were independently associated with increasing YGTSS global severity, total tic score, and impairment rating over time. An increased number of stressful events were associated with increased severity of tics. ConclusionFamily, personal relationships, and school-related stress were consistently associated with the exacerbation of tics. Managing these stressful events is important in the treatment of TS and chronic tic disorder.

Harnessing cognitive trajectory clusterings to examine subclinical decline risk factors.

Cognitive decline in Alzheimer's disease and other dementias typically begins long before clinical impairment. Identifying people experiencing subclinical decline may facilitate earlier intervention. This study developed cognitive trajectory clusters using longitudinally based random slope and change point parameter estimates from a Preclinical Alzheimer's disease Cognitive Composite and examined how baseline and most recently available clinical/health-related characteristics, cognitive statuses and biomarkers for Alzheimer's disease and vascular disease varied across these cognitive clusters. Data were drawn from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal cohort study of adults from late midlife, enriched for a parental history of Alzheimer's disease and without dementia at baseline. Participants who were cognitively unimpaired at the baseline visit with ≥3 cognitive visits were included in trajectory modelling (n = 1068). The following biomarker data were available for subsets: positron emission tomography amyloid (amyloid: n = 367; [11C]Pittsburgh compound B (PiB): global PiB distribution volume ratio); positron emission tomography tau (tau: n = 321; [18F]MK-6240: primary regions of interest meta-temporal composite); MRI neurodegeneration (neurodegeneration: n = 581; hippocampal volume and global brain atrophy); T2 fluid-attenuated inversion recovery MRI white matter ischaemic lesion volumes (vascular: white matter hyperintensities; n = 419); and plasma pTau217 (n = 165). Posterior median estimate person-level change points, slopes' pre- and post-change point and estimated outcome (intercepts) at change point for cognitive composite were extracted from Bayesian Bent-Line Regression modelling and used to characterize cognitive trajectory groups (K-means clustering). A common method was used to identify amyloid/tau/neurodegeneration/vascular biomarker thresholds. We compared demographics, last visit cognitive status, health-related factors and amyloid/tau/neurodegeneration/vascular biomarkers across the cognitive groups using ANOVA, Kruskal-Wallis, χ2, and Fisher's exact tests. Mean (standard deviation) baseline and last cognitive assessment ages were 58.4 (6.4) and 66.6 (6.6) years, respectively. Cluster analysis identified three cognitive trajectory groups representing steep, n = 77 (7.2%); intermediate, n = 446 (41.8%); and minimal, n = 545 (51.0%) cognitive decline. The steep decline group was older, had more females, APOE e4 carriers and mild cognitive impairment/dementia at last visit; it also showed worse self-reported general health-related and vascular risk factors and higher amyloid, tau, neurodegeneration and white matter hyperintensity positive proportions at last visit. Subtle cognitive decline was consistently evident in the steep decline group and was associated with generally worse health. In addition, cognitive trajectory groups differed on aetiology-informative biomarkers and risk factors, suggesting an intimate link between preclinical cognitive patterns and amyloid/tau/neurodegeneration/vascular biomarker differences in late middle-aged adults. The result explains some of the heterogeneity in cognitive performance within cognitively unimpaired late middle-aged adults.

Teachers' emotion regulation strategies and preschool expulsion risk: Suppression and reappraisal

Teacher stress has been implicated in decision-making related to preschool children's expulsion risk. The current study examines whether teachers' emotion regulation strategies moderate the relationship between child behavior and expulsion risk. In the study, 44 preschool teachers (68% lead and 32% assistant) completed surveys on their own emotion regulation strategies and child behavior (inhibitory control), student-teacher conflict, and expulsion risk for four randomly selected students in their classroom (n = 176). In multilevel models, higher inhibitory control was related to lower total expulsion risk and subscales of classroom disruption and stress in random slope models, controlling for student-teacher conflict and child gender. In conditional models, teachers' use of suppression moderated the link between inhibitory control and classroom disruption (p = .032) and reappraisal moderated the link between inhibitory control and child-related stress (p = −.016), supporting the exploration of teachers' emotion regulation as a critical aspect of expulsion prevention.

A 15-Year Longitudinal Study ofBody Composition inFinnish Military Divers.

Finnish military divers perform a great variety of tasks all year round, all of which require good physical health and fitness. Poor physical fitness can hinder the ability to cope with different situations. A high body fat percentage has been suggested to increase the risk of decompression sickness, whereas low muscle mass has been associated with an increased risk of musculoskeletal disorders and trauma. However, a low-fat composition may render divers vulnerable to cold and hypothermia during a dive in cold Arctic conditions. The aim of this study was to evaluate possible changes in body composition of Finnish military divers during a 15-year follow-up period (2007-2021). We used body composition measures from military divers' fit-to-dive evaluations from the Finnish Defence Forces' Diving Medical Centre. Measurements were taken with two bioimpedance devices that function based on the electrical conductivity properties of the human body. The data from both devices were compared with Bland-Altman plots to show that the devices produced congruent data and the results from both devices could be included in the study. Possible changes in body composition were evaluated with a linear mixed model with random intercepts and slopes for each variable. Results from the two bioimpedance devices showed no significant differences. This allowed us to combine the results in the same data analysis. There were no apparent differences in the age of the divers between the years during the follow-up. The majority of the divers were between 25 and 30 years of age. Age correlated significantly with most measures, the clinically most significant being a higher fat percentage in older divers. However, all measures were within target values defined by the Diving Medical Centre. The divers were able to retain sufficient muscle mass in all age groups. According to this study, Finnish military divers have managed to maintain a surprisingly good muscle mass in all age groups despite body composition changes due to aging in older subjects. A slight increase in fat mass can be observed with increasing age; nevertheless, the values have remained within fit-to-dive target levels. The current training routines of Finnish military divers are adequate for maintaining solid physical fitness and body composition over the course of the diving career.

The Longitudinal Mean Arterial Pressure among congestive heart failure patients at Felege Hiwot Referral Hospital, Bahir Dar, Ethiopia

BACKGROUND Congestive heart failure could be defined as a condition where there is a performance or structural impairment of the heart. So this study was targeted on the determinants of the longitudinal mean arterial pressure among heart failure patients treated from January 2016 to December 2019 at Felege Hiwot Referral Hospital in Bahir Dar, Ethiopia. METHODS Hospital-based retrospective data were assembled from the medical chart of 218 randomly selected congestive heart failure patients. The linear mixed effects model corresponding to unstructured_ _covariance structure was employed to spot out the determinants of mean arterial pressure among in patients with congestive heart failure. RESULTS Individual profile plot of mean arterial pressure showed the existence of variability among and between those patients. Moreover, the mean profile plot demonstrated a linearly increasing pattern over the follow-up times. The random intercept and slope model corresponding to unstructured covariance structure was the best fit (AIC: 6001.9(χ^2=80.83), P &lt; 0.0001) as compared to the remaining models. The estimates for age, left ventricle ejection fraction, serum sodium concentration, visit times, serum hemoglobin concentration, residence(rural) and New York Heart Association Classes I, II, and III were given as 0.3758(P-value: &lt;0.0001), 0.2933(P-value: &lt;0.0001), 0.1941(P-value: &lt;0.0001), 0.4471(P-value: 0.0059), 0.5501(P-value: 0.0053), -9.9858(P-value: &lt;0.0001), 18.8943(P-value: 0.0001), 10.8833(P-value: &lt;0.0001) and 2.7318(P-value: 0.0001) respectively, and they are statistically associated with the longitudinal mean arterial pressure of congestive heart failure patients. CONCLUSION The linear mixed effects model corresponding to unstructured covariance structure provides an information on the existence of within and between subjects variations and correlations in addition to identifying the significant factors associated with the longitudinal mean arterial pressure of congestive heart failure patients. So, an application of standard models may ignore such a variation among successive measurements. Thus mixed effects model is recommended for such longitudinal data.