Longitudinal Outcomes Research Articles

Predictive Partly Conditional Models for Longitudinal Ordinal Outcomes with Application to Alzheimer’s Disease Progression

AbstractAssessing time-dependent risk factors in relation to the risk of disease progression is challenging, yet important, especially for chronic diseases with slow progression. In this paper, the partly conditional model is extended for characterizing disease progression at time t with longitudinal ordinal outcomes in the presence of time-dependent covariates at time s$$(s < t)$$ ( s < t ) and time-dependent effects. Advantages of the method include direct modeling of disease progression, use of longitudinal risk factors, and flexibility in target period of progression $$u = t - s$$ u = t - s . A generalized estimating equation approach is adopted for parameter estimation, and a new regularity condition requiring a fixed prediction time window $$u_0$$ u 0 is established to consistently estimate the covariance of the estimated parameters. Extensive simulation studies are conducted to assess the properties of the proposed model alongside with an explicit demonstration of the implementation using existing statistical software. The proposed method is applied to a longitudinal Alzheimer’s disease dataset from the National Alzheimer’s Coordinating Center to assess effect of time-dependent cognitive complaint on Alzheimer’s Disease progression.

Longitudinal adaptive behavioral outcomes in Ogden syndrome by seizure status and therapeutic intervention.

Ogden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011 and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia, and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. The current study involves a total of 58 distinct participants; of these, 43 caregivers were interviewed using the Vineland-3 and answered a survey regarding therapy and other questions, 10 of whom completed the Vineland-3 but did not answer the survey, and 5 participants who answered the survey but have not yet performed the Vineland-3 due to language constraints. The average age at the time of the most recent assessment was 12.4 years, with individuals ranging in age from 11 months to 40.2 years. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome (n = 53). Sub-domain analysis found the decline to be present across all modalities. In addition, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. A therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy, with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status, and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome.

Contemporary Predictors of Major Adverse Cardiovascular Events Following Percutaneous Coronary Intervention: A Nationally Representative US Sample.

Background: Patient outcomes after percutaneous coronary intervention (PCI) have improved over the last 30 years due to better techniques, therapies, and care processes. This study evaluated contemporary predictors of post-PCI major adverse cardiovascular events (MACE) and summarized risk in a parsimonious risk prediction model. Methods: The Cardiovascular Patient-Level Analytical Platform (CLiPPeR) is an observational dataset of baseline variables and longitudinal outcomes from the American College of Cardiology's CathPCI Registry® and national claims data. Cox regression was used to evaluate 2-6 years of patient follow-up (mean: 2.56 years), ending in December 2017, after index PCI between 2012 and 2015 (N = 1,450,787), to examine clinical and procedural predictors of MACE (first myocardial infarction, stroke, repeat PCI, coronary artery bypass grafting, and mortality). Cox analyses of post-PCI MACE were landmarked 28 days after index PCI. Results: Overall, 12.4% (n = 179,849) experienced MACE. All variables predicted MACE, with cardiogenic shock, cardiac arrest, four diseased coronary vessels, and chronic kidney disease having hazard ratios (HRs) ≥ 1.50. Other major predictors of MACE were in-hospital stroke, three-vessel disease, anemia, heart failure, and STEMI presentation. The index revascularization and discharge prescription of aspirin, P2Y12 inhibitor, and lipid-lowering medication had HR ≤ 0.67. The primary Cox model had c-statistic c = 0.761 for MACE versus c = 0.701 for the parsimonious model and c = 0.752 for the parsimonious model plus treatment variables. Conclusions: In a nationally representative US sample of post-PCI patients, predictors of longitudinal MACE risk were identified, and a parsimonious model efficiently encapsulated them. These findings may aid in assessing care processes to further improve care post-PCI outcomes.

Impact of early intervention on health status outcomes in peripheral artery disease patients with chronic total occlusion lesions using the PORTRAIT registry

ObjectiveTo analyze the impact of noninvasive and early invasive treatments on health status in patients with lower extremity peripheral arterial disease (PAD) without and with chronic total occlusions (CTOs) after 12 months of follow-up. MethodsUsing the international (the United States, the Netherlands, and Australia) observational longitudinal Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories registry, we included patients with recent PAD symptoms between June 2011 and December 2015. We assessed the PAD-specific health status at initial visit and the 3-, 6-, and 12-month follow-up using the Peripheral Arterial Questionnaire. On a propensity matched-weighted cohort, we compared patients' characteristics by CTO status and treatment groups as early invasive (revascularization in the 3 months) vs noninvasive (exercise, medical therapies, or smoking cessation). We then assessed the health status trajectory over 12 months, as a three-way interaction between CTO status, treatment groups, and months, using a multilevel generalized linear regression model for repeated measures adjusted for baseline health status with random effects at the site and patient levels. ResultsWe included 581 participants, with a mean age of 66.62 ± 9.33 years, 34.3% female, and 90.8% White, of whom 353 (60.8%) were without and 228 (39.2%) had a CTO lesion. Respectively, 96 (27.2%) and 70 (30.7%) patients underwent early invasive treatment (d = 0.07). Although patients with CTO were more likely to have lower resting ABI, multilevel disease, and to experience severe claudication vs their counterparts (|d| ≥ 0.20), patient health status at baseline with CTO was not different from those without CTO, with mean summary scores of 45.14 ± 20.26 vs 45.90 ± 21.24 (d = 0.04), respectively. The trajectory did not differ by CTO status (interaction CTO status × month; P = .517) and was higher in early invasive vs noninvasive treatment (treatment × month; P < .001), regardless of CTO status (CTO status × treatment; P = .981 and CTO status × treatment × month; P = .264). The score increased over time with the largest improvement occurring at 3 months in both noninvasive (non-CTO, +7.82 [95% confidence interval (CI), 4.03-11.60] and CTO, +9.27 95% CI, 4.45-14.09) and early invasive (non-CTO, +26.17 [95% CI, 20.06-32.28] and CTO, +24.52 [95% CI, 17.40-31.64] groups. The mean score in CTO vs non-CTO groups did not differ at each timepoint, with a 12-month mean score of 70.26 (95% CI, 67.87-74.65) vs 71.17 (95% CI, 65.91-76.44) (P = .99) in the noninvasive treatment and 84.93 (95% CI, 78.90-90.97) vs 79.20 (95% CI, 72.77-86.14) (P = .31) in the early invasive treatment. ConclusionsPatients with symptomatic PAD undergoing early revascularization exhibited better health status over time vs those undergoing noninvasive treatment strategy, irrespective of the presence of CTOs. The degree of the improvement was greater in the 3 months after the initial visit, especially in patients undergoing early revascularization.

Sex-specific effects of birth weight on longitudinal behavioural outcomes in children and adolescents: findings from the raine study.

Previous cross-sectional studies suggest that birth weight (BW) is associated with aggression-, social- and attention problems differently in boys and girls. We sought to test if these differences could be confirmed in a longitudinal study. The 1989 Raine Study provided prospectively collected data on perinatal variables and repeated child behaviour checklist assessments from ages 5 to 17. Linear mixed effects models provided crude and adjusted relationships between BW and childhood behaviour at a conservative significance threshold using prenatal maternal covariables in adjusted models. Sensitivity analyses included an age10 teacher assessment. Data on behaviour, BW and sex, was available in 2269 participants. Male sex was associated with increased aggression problems at lower BW compared to females in the crude model (Interaction B: -0.436, 98.3%CI: [-0.844, -0.0253]), but not the adjusted model (Interaction B: -0.310, 98.3%CI: [-0.742, 0.140]). Male sex was associated with increased attention problems at lower BW compared to females in both the crude model (Interaction B: -0.334, 98.3%CI: [-0.530, -0.137]) and the adjusted model (Interaction B: -0.274, 98.3%CI: [-0.507, -0.0432]). Male sex was associated with increased social problems at lower BW compared to females in both the crude model (Interaction B: -0.164, 98.3%CI: [-0.283, -0.0441]) and the adjusted model (Interaction B: -0.148, 98.3%CI: [-0.285, -0.00734]). Using repeated measures from ages 5-17 we were able to show a crude and adjusted male vulnerability to lower BW in the development of attention problems and social problems. We did not find a BW x sex interaction for the development of aggressive behaviour.

Profiles of executive functions in middle childhood and prediction of later self-regulation.

Most research on the development of executive functions (EF) has applied variable-oriented approaches, neglecting the potential inter- and intraindividual interplay of these capacities. In a person-oriented approach, the present study identified varying profiles of performance for three cool EF facets: inhibition, working-memory updating, and cognitive flexibility, as well as two hot EF facets: affective decision-making and delay of gratification, in a community sample of 1,657 children (T1; age: 6-11 years, M = 8.36 years, 52.1% female) via latent profile analysis. The best-fitting model allowed for partial dependence across the three cool EF and included four profiles: all-average (69.4% of the children), low-delay (19.0%), regulated-decision-making (7.0%), and low-inhibition (4.6%). Age, binary sex, socio-economic status, multilingualism, and processing speed were identified as significant characteristics of EF profile membership. Longitudinally, a higher probability of belonging to the low-inhibition profile predicted lower rates of the self-regulatory outcome of inhibitory control 1 year later, while belonging to the regulated-decision-making profile predicted lower rates of the ability to plan and organize 3 years later. These results not only demonstrate the existence of subgroups with different concurrent within-person expressions of EF performance, but also identify related characteristics and longitudinal outcomes of subgroup membership. In turn, these conclusions stress the importance of person-oriented research to inform on differing weaknesses or strengths in EF performance for varying individuals, thereby providing valuable insight for educational and clinical research into the design of effective personalized support or interventions during middle childhood.

Randomized controlled trial of an Acceptance and Commitment Therapy and compassion-based group intervention for persons with inflammatory bowel disease: the LIFEwithIBD intervention.

This study tested the acceptability and efficacy of an Acceptance and Commitment Therapy and compassion-based intervention (LIFEwithIBD) in people with IBD through a two-arm RCT. Participants were recruited at the Gastroenterology Department of the Coimbra University Hospital between June and September 2019. Of the 355 patients screened, those who accepted to participate were randomly assigned to one of two conditions: experimental group (LIFEwithIBD; n = 25) or control group (waitlist; n = 29). Participants completed self-report measures at baseline (T0), post-intervention (T1), and 3-month (T2) and 12-month (T3) follow-ups. Intervention acceptability was assessed. Efficacy was examined using intent-to-treat ANCOVA at post-intervention after adjusting for baseline values of depressive, anxiety, and stress symptoms (primary outcomes). Linear mixed models for all longitudinal outcomes were also analysed. Inflammatory and disease biomarkers were determined at T0 and T3. Acceptability results revealed a high level of satisfaction and perceived usefulness regarding the intervention. Both groups experienced a significant decrease in stress symptoms and IBD symptom perception at T1. No significant differences were observed at follow-up for the primary outcomes. The experimental group reported significantly lower Crohn's disease Symptom severity at T2 than the control group. Post-hoc analyses designed to mitigate floor effects revealed substantial treatment effects for the experimental group regarding anxiety symptoms. No significant differences were observed in clinical biomarkers from T0 to T3. The LIFEwithIBD intervention shows promising, although preliminary, benefits for managing disease activity and reducing anxiety symptoms in IBD patients with high severity of psychological distress.Clinical trial registration: https://www.clinicaltrials.gov/ct2/show/NCT03840707, identifier NCT03840707.

Geospatial and Socioeconomic Disparities Influencing the Management of Craniosynostosis.

Various social determinants of health have been described as predictors of clinical outcomes for the craniosynostosis population. However, literature lacks a granular depiction of socioeconomic factors that impact these outcomes, and little is known about the relationship between patients' proximity to the care center and management of the condition. This study retrospectively evaluated patients with craniosynostosis who presented to a tertiary children's hospital between 2000 and 2019. Outcomes of interest included age at presentation for surgery, incidence of reoperation, and length of follow-up. Patient addresses were geocoded and plotted on two separate shapefiles containing block group information within San Diego County. The shapefiles included percent parental educational attainment (bachelor's degree or higher) and median household income from 2010. The year 2010 was chosen for the shapefiles because it is the median year of data collection for this study. Multivariate linear, logistic, and polynomial regression models were used to analyze the relationship between geospatial and socioeconomic predictors and clinical outcomes. There were 574 patients with craniosynostosis included in this study. The mean ± SD Haversine distance from the patient's home coordinates to the hospital coordinates was 107.2 ± 321.2 miles. After adjusting for the suture fused and insurance coverage, there was a significant positive correlation between distance to the hospital and age at index surgery (P = 0.018). There was no correlation between distance and incidence of reoperation (P = 0.266) or distance and duration of follow-up (P = 0.369). Using the same statistical adjustments, lower parental percent educational attainment and lower median household income correlated with older age at index surgery (P = 0.008 and P = 0.0066, respectively) but were not correlated with reoperation (P = 0.986 and P = 0.813, respectively) or duration of follow-up (P = 0.107 and P = 0.984, respectively). The results offer evidence that living a greater distance from the hospital and socioeconomic disparities including parental education and median household income may serve as barriers to prompt recognition of diagnosis and timely care in this population. However, the geospatial and socioeconomic factors studied do not seem to hinder incidence of reoperation or length of follow-up, suggesting that, once care has been initiated, longitudinal outcomes may be less impacted.

Longitudinal health outcomes in caregivers of military members with traumatic brain injury.

To examine longitudinal change in health-related quality of life (HRQOL) in caregivers of service members/veterans with traumatic brain injury and factors associated with clinically elevated symptoms. Caregivers (N = 220) completed nine HRQOL outcome measures and 10 risk factor measures at a baseline evaluation and follow-up evaluation 3 years later. Caregiver's responses on the nine HRQOL outcome measures were classified into four clinical change categories based on the presence/absence of clinically elevated T-scores (≥ 60 T) at baseline and follow-up: (a) Persistent (baseline ≥ 60T + follow-up ≥ 60 T), (b) Developed (baseline < 60 T + follow-up ≥ 60 T), (c) Improved (baseline ≥ 60 T + follow-up < 60 T), and (d) Asymptomatic (baseline < 60 T + follow-up < 60 T). A clinical change composite score was calculated by summing the number of Persistent or Developed HRQOL outcome measures and used to create three clinical change groups: (a) No Symptoms (n = 69, zero measures), (b) Some Symptoms (n = 88, one to three measures), and (c) Numerous Symptoms (n = 63, four to nine measures). Of the nine HRQOL outcome measures, Bodily Pain, Perceived Stress, Sleep-Related Impairment, and Fatigue were most frequently classified as Persistent or Developed from baseline to follow-up in the entire sample. A linear relationship was found between the vast majority of risk factors across the three clinical change groups at baseline and follow-up (Numerous > Some > None). The risk factors were correlated with the number of elevated HRQOL symptoms at baseline and follow-up. Most Asymptomatic or Persistent caregivers did not have meaningful change (≥ 1 SD) in HRQOL scores. A sizable proportion of Developed or Improved caregivers had either meaningful or no change in HRQOL scores. There is a need for ongoing clinical services for military caregivers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Prevalence and contributing factors of neck and low back pain among university students during examination periods: A survey based study at Jazan University

ABSTRACT Background: Neck and low back pain (LBP) are frequently experienced by university students during examination periods due to prolonged sitting, impaired posture, and increased stress. The objectives of this study were to examine the prevalence and contributing factors for neck and LBP among students at Jazan University during their examinations. Methodology: A survey-based study was conducted on 100 students aged 19–24 years from various academic disciplines. An electronic questionnaire distributed through social media collected data on personal demographics, study habits, pain occurrence, and frequency, intensity, and pain management practices. Results: Descriptive statistics summarized the data; results show that female students suffer from neck and LBP more frequently and intensely than male students. The study found that the use of electronic devices, lack of physical activity, poor knowledge of posture, and stress were all significantly related to the prevalence of pain. Conclusions: Multifactorial causes of neck and LBP during examination periods require comprehensive strategies involving ergonomic education, stress management, and promoting physical activity among students. Future research should explore longitudinal outcomes and the effectiveness of specific interventions across diverse academic settings.

Fasting Plasma Glucose Levels and Longitudinal Motor and Cognitive Outcomes in Parkinson's Disease Patients.

Hyperglycemia and diabetes mellitus have been identified as poor prognostic factors for motor and nonmotor outcomes in patients with Parkinson's disease (PD), although there is some controversy with this finding. In the present study, we investigated the effects of fasting plasma glucose (FPG) levels on longitudinal motor and cognitive outcomes in PD patients. We included a total of 201 patients who were diagnosed with PD between January 2015 and January 2020. The patients were categorized based on FPG level into euglycemia (70 mg/dL < FPG < 100 mg/dL), intermediate glycemia (100 mg/dL ≤ FPG < 126 mg/dL), and hyperglycemia (FPG ≥ 126 mg/dL), and longitudinal FPG trajectories were analyzed using group-based trajectory modeling. Survival analysis was conducted to determine the time until motor outcome (Hoehn and Yahr stage ≥ 2) and the conversion from normal cognition to mild cognitive impairment. Among the patient cohort, 82 had euglycemia, 93 had intermediate glycemia, and 26 had hyperglycemia. Intermediate glycemia (hazard ratio 1.747, 95% confidence interval [CI] 1.083-2.816, p = 0.0221) and hyperglycemia (hazard ratio 3.864, 95% CI 1.996-7.481, p < 0.0001) were found to be significant predictors of worsening motor symptoms. However, neither intermediate glycemia (hazard ratio 1.183, 95% CI 0.697-2.009, p = 0.5339) nor hyperglycemia (hazard ratio 1.297, 95% CI 0.601-2.800, p = 0.5078) demonstrated associations with the longitudinal progression of cognitive impairment. Diabetes mellitus, defined by self-reported medical history, was not related to poor motor or cognitive impairment outcomes. Our. suggest that both impaired glucose tolerance and hyperglycemia could be associated with motor progression in PD patients.

Cognition and Amyloid-β in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes.

Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer's disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition. The cluster analysis identified 3 groups. Group 1 (n = 128) had average-to-above average cognition with low amyloid burden. Group 2 (n = 72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (n = 28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. Psychiatric and health factors likely contributed to Group 2's low memory and language performance. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans' co-morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. These results could have important implications for the implementation of AD-modifying drugs in older Veterans.

Bayesian joint modeling of multivariate longitudinal and survival outcomes using Gaussian copulas.

There is an increasing interest in the use of joint models for the analysis of longitudinal and survival data. While random effects models have been extensively studied, these models can be hard to implement and the fixed effect regression parameters must be interpreted conditional on the random effects. Copulas provide a useful alternative framework for joint modeling. One advantage of using copulas is that practitioners can directly specify marginal models for the outcomes of interest. We develop a joint model using a Gaussian copula to characterize the association between multivariate longitudinal and survival outcomes. Rather than using an unstructured correlation matrix in the copula model to characterize dependence structure as is common, we propose a novel decomposition that allows practitioners to impose structure (e.g., auto-regressive) which provides efficiency gains in small to moderate sample sizes and reduces computational complexity. We develop a Markov chain Monte Carlo model fitting procedure for estimation. We illustrate the method's value using a simulation study and present a real data analysis of longitudinal quality of life and disease-free survival data from an International Breast Cancer Study Group trial.

Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder

Abstract Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson’s disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson’s disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43–87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1–3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson’s disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio &amp;lt; 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson’s disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson’s disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson’s disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.

Neurocognitive outcomes in moderately preterm born adolescents

BackgroundEarly preterm (EP) born children are at risk of neurocognitive impairments persisting into adulthood. Less is known about moderately to late (MLP) preterm born children, especially after early childhood. The aim of this study was to assess neurocognitive functioning of MLP adolescents regarding intelligence, executive and attentional functioning, compared with EP and full-term (FT) adolescents. MethodsThis study was part of the Longitudinal Preterm Outcome Project (LOLLIPOP), a large community-based observational cohort study. In total 294 children (81 EP, 130 MLP, and 83 FT) were tested at age 14 to 16 years, regarding intelligence, speed of processing, attention, and executive functions. We used the Dutch version of the Wechsler Intelligence Scale for Children-Third Edition-Dutch Version (WISC-III-NL), the Test of Everyday Attention for Children, and the Behavioural Assessment of the Dysexecutive Syndrome for Children. We assessed differences between preterm-born groups with the FT group as a reference. ResultsCompared to the FT group, MLP adolescents scored significantly lower on two subtasks of the WISC-III-NL, i.e. Similarities and Symbol Search. EP adolescents performed significantly lower on all neuropsychological tests than their FT peers, except for the subtask Vocabulary. The MLP adolescents scored in between FT and EP adolescents on all tasks, except for three WISC-III-NL subtasks. ConclusionsNeurocognitive outcomes of MLP adolescents fell mostly in between outcomes of their EP and FT peers. MLPs generally performed on a low-average to average level, and appeared susceptible to a variety of moderate neurodevelopmental problems at adolescent age, which deserves attention in clinical practice.

Changed sleep according to weighted blanket adherence in a 16-week sleep intervention among children with attention-deficit/hyperactivity disorder.

To examine differences in sample characteristics and longitudinal sleep outcomes according to weighted blanket (WB) adherence. Children with attention-deficit/hyperactivity disorder (n = 94), mean age 9.0 (standard deviation 2.2, range 6-14) participated in a 16-week sleep intervention with WBs. Children were classified as WB adherent (use of WB ≥ 4 nights/wk) or nonadherent (use of WB ≤ 3 nights/wk). Changes in objectively measured sleep by actigraphy, parent-reported sleep problems (Children's Sleep Habits Questionnaire) and child-reported Insomnia Severity Index were evaluated according to adherence with mixed effect models. Sex, age, and attention-deficit/hyperactivity disorder subtype were examined as potential moderators. Children adherent to WBs (48/94) showed an early response in sleep outcomes and an acceptance of the WB after 4 weeks of use as well as a decrease in parent-reported (Children's Sleep Habits Questionnaire) (-5.73, P = .000) and child-reported (Insomnia Severity Index) (-4.29, P = .005) sleep problems after 16 weeks. The improvement in sleep was larger among WB adherent vs nonadherent (between-group difference: Children's Sleep Habits Questionnaire: -2.09, P = .038; Insomnia Severity Index: -2.58, P = .007). Total sleep time was stable for children adherent to WB but decreased for nonadherent (between-group difference: +16.90, P = .019). An early response in sleep and acceptance of the WB predicted later adherence to WBs. Improvements in sleep were more likely among WB adherents vs nonadherents. Children with attention-deficit/hyperactivity disorder may thus benefit from using WBs to handle their sleep problems. Lönn M, Svedberg P, Nygren J, Jarbin H, Aili K, Larsson I. Changed sleep according to weighted blanket adherence in a 16-week sleep intervention among children with attention-deficit/hyperactivity disorder. J Clin Sleep Med. 2024;20(9):1455-1466.

The effect of obesity phenotype changes on cardiovascular outcomes in adults older than 40 years in the prospective cohort of the Tehran lipids and glucose study (TLGS): joint model of longitudinal and time-to-event data

BackgroundObesity is a worldwide health concern with serious clinical effects, including myocardial infarction (MI), stroke, cardiovascular diseases (CVDs), and all-cause mortality. The present study aimed to assess the association of obesity phenotypes and different CVDs and mortality in males and females by simultaneously considering the longitudinal and survival time data.MethodsIn the Tehran Lipid and Glucose Study (TLGS), participants older than three years were selected by a multi-stage random cluster sampling method and followed for about 19 years. In the current study, individuals aged over 40 years without a medical history of CVD, stroke, MI, and coronary heart disease were included. Exclusions comprised those undergoing treatment for CVD and those with more than 30% missing information or incomplete data. Joint modeling of longitudinal binary outcome and survival time data was applied to assess the dependency and the association between the changes in obesity phenotypes and time to occurrence of CVD, MI, stroke, and CVD mortality. To account for any potential sex-related confounding effect on the association between the obesity phenotypes and CVD outcomes, sex-specific analysis was carried out. The analysis was performed using packages (JMbayes2) of R software (version 4.2.1).ResultsOverall, 6350 adults above 40 years were included. In the joint modeling of CVD outcome among males, literates and participants with a family history of diabetes were at lower risk of CVD compared to illiterates and those with no family history of diabetes in the Bayesian Cox model. Current smokers were at higher risk of CVD compared to non-smokers. In a logistic mixed effects model, odds of obesity phenotype was higher among participants with low physical activity, family history of diabetes and older age compared to males with high physical activity, no family history of diabetes and younger age. In females, based on the results of the Bayesian Cox model, participants with family history of diabetes, family history of CVD, abnormal obesity phenotype and past smokers had a higher risk of CVD compared to those with no history of diabetes, CVD and nonsmokers. In the obesity varying model, odds of obesity phenotype was higher among females with history of diabetes and older age compared to those with no history of diabetes and who were younger. There was no significant variable associated with MI among males in the Bayesian Cox model. Odds of obesity phenotype was higher in males with low physical activity compared to those with high physical activity in the obesity varying model, whereas current smokers were at lower odds of obesity phenotype than nonsmokers. In females, risk of MI was higher among those with family history of diabetes compared to those with no history of diabetes in the Bayesian Cox model. In the logistic mixed effects model, a direct and significant association was found between age and obesity phenotype. In males, participants with history of diabetes, abnormal obesity phenotype and older age were at higher risk of stroke in the Bayesian Cox model compared to males with no history of diabetes, normal obesity phenotype and younger persons. In the obesity varying model, odds of obesity phenotype was higher in males with low physical activity, family history of diabetes and older age compared to those with high physical activity, no family history of diabetes and who were younger. Smokers had a lower odds of obesity phenotype than nonsmokers. In females, past smokers and those with family history of diabetes were at higher risk of stroke compared to nonsmokers and females with no history of diabetes in the Bayesian Cox model. In the obesity varying model, females with family history of diabetes and older ages had a higher odds of obesity phenotype compared to those with no family history of diabetes and who were younger. Among males, risk of CVD mortality was lower in past smokers compared to nonsmokers in the survival model. A direct and significant association was found between age and CVD mortality. Odds of obesity phenotype was higher in males with a history of diabetes than in those with no family history of diabetes in the logistic mixed effects model.ConclusionsIt seems that modifications to metabolic disorders may have an impact on the heightened incidence of CVDs. Based on this, males with obesity and any type of metabolic disorder had a higher risk of CVD, stroke and CVD mortality (excluding MI) compared to those with a normal body mass index (BMI) and no metabolic disorders. Females with obesity and any type of metabolic disorder were at higher risk of CVD(, MI and stroke compared to those with a normal BMI and no metabolic disorders suggesting that obesity and metabolic disorders are related. Due to its synergistic effect on high blood pressure, metabolic disorders raise the risk of CVD.

First report from the European registry for anomalous aortic origin of coronary artery (EURO-AAOCA).

Anomalous aortic origin of a coronary artery (AAOCA) is a group of rare congenital heart defects with various clinical presentations. The lifetime-risk of an individual living with AAOCA is unknown, and data from multicentre registries are urgently needed to adapt current recommendations and guide optimal patient management. The European AAOCA Registry (EURO-AAOCA) aims to assess differences with regard to AAOCA management between centres. EURO-AAOCA is a prospective, multicentre registry including 13 European centres. Herein, we evaluated differences in clinical presentations and management, treatment decisions and surgical outcomes across centres from January 2019 to June 2023. A total of 262 AAOCA patients were included, with a median age of 33 years (12-53) with a bimodal distribution. One hundred thirty-nine (53.1%) were symptomatic, whereas chest pain (n = 74, 53.2%) was the most common complaint, followed by syncope (n = 21, 15.1%). Seven (5%) patients presented with a myocardial infarction, 2 (1.4%) with aborted sudden cardiac death. Right-AAOCA was most frequent (150, 57.5%), followed by left-AAOCA in 51 (19.5%), and circumflex AAOCA in 20 (7.7%). There were significant differences regarding diagnostics between age groups and across centres. Seventy-four (28.2%) patients underwent surgery with no operative deaths; minor postoperative complications occurred in 10 (3.8%) cases. Currently, no uniform agreement exists among European centres with regard to diagnostic protocols and clinical management for AAOCA variants. Although surgery is a safe procedure in AAOCA, future longitudinal outcome data will hopefully shed light on how to best decide towards optimal selection of patients undergoing revascularization versus conservative treatment.

Association of elevated tricuspid regurgitation velocity with cerebrovascular and kidney disease in children with sickle cell disease.

Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the association between TRV and surrogate markers of end-organ disease. We conducted a cross-sectional study that evaluated the prevalence of elevated TRV ≥2.5m/s and its associations with renal and cerebrovascular outcomes in children with sickle cell disease (SCD) 1-21years of age in two large sickle cell cohorts, the University of Alabama at Birmingham (UAB) sickle cell cohort, and the Sickle Cell Clinical Research and Intervention Program (SCCRIP) cohort at St. Jude Children's Research Hospital. We hypothesized that patients with SCD and elevated TRV would have higher odds of having either persistent albuminuria or cerebrovascular disease. We identified 166 children from the UAB cohort (mean age: 13.49±4.47years) and 325 children from the SCCRIP cohort (mean age: 13.41±3.99years) with echocardiograms. The prevalence of an elevated TRV was 21% in both UAB and SCCRIP cohorts. Elevated TRV was significantly associated with cerebrovascular disease (odds ratio [OR] 1.88, 95% confidence interval [CI]: 1.12-3.15; p=.017) and persistent albuminuria (OR 1.81, 95% CI: 1.07-3.06; p=.028) after adjusting for age, sex, treatment, and site. This cross-sectional, multicenter study identifies associations between surrogate markers of pulmonary hypertension with kidney disease and cerebrovascular disease. A prospective study should be performed to evaluate the longitudinal outcomes for patients with multiple surrogate markers of end-organ disease.