Developmental trajectories of non-suicidal self-injury in adolescence: The effect of social support and socioeconomic status.

BACKGROUND: Non-suicidal self-injury (NSSI) in early adolescence has been amply documented. However, there has been little research on the progression of NSSI over time. Most studies have focused on the risk factors for NSSI, with less attention devoted to understanding the role of protective factors. This paper aimed to expand existing knowledge about the development of NSSI, with an emphasis on the impacts of protective factors such as social support and socioeconomic status (SES). METHODS: A total of 436 adolescents completed self-report surveys that addressed social support including friend, family, and teacher support, objective and subjective SES, and NSSI at three different points in time for 2 years. RESULTS: Latent growth curve analyses revealed that NSSI increased across early adolescence to mid-adolescence. Support from friends and family negatively predicted adolescents' initial NSSI level. Furthermore, subjective SES negatively predicted the rate of NSSI. CONCLUSIONS: These findings contribute to an understanding of the influences of both social support and SES on NSSI over time. NSSI interventions and education should include considerations of both the value of support from friends and family as well as subjective SES.

Training Outcomes and Satisfaction in Canadian MD/PhD and MD/MSc Programs: Findings from a National Survey.

PURPOSE: Despite the impact of physician-scientists on scientific discovery and translational medicine, several reports have signalled their declining workforce, reduced funding, and insufficient protected research time. Given the paucity of outcome data on Canadian MD/PhD programs, this study presents a national portrait of the sociodemographic characteristics, training trajectories, productivity, and satisfaction in trainees and alumni from Canadian MD/PhD and MD/MSc programs. METHODS: Quantitative data were collected in a national survey launched in 2021. Respondents included 74 MD/PhD alumni and 121 trainees across 12 Canadian MD/PhD and MD/MSc programs. RESULTS: Among MD/PhD alumni, 51% were independent practitioners/researchers while others underwent residency training. Most trainees (88%) were in MD/PhD programs. Significantly more alumni identified as men than did trainees. Significantly more alumni conducted clinical and health services research, while more trainees conducted basic science research. Average time to MD/PhD completion was 8 years, with no correlation to subsequent research outcomes. Self-reported research productivity was highest during MD/PhD training. Concerning training trajectories, most alumni completed residency, pursued additional training, and practised in Canada. Finally, regression models showed that trainees and alumni were satisfied with programs, with significant moderators in trainee models. CONCLUSION: Survey findings showed Canadian MD/PhD and MD/MSc programs recruit more diverse cohorts of trainees than before, provide productive research years, and graduate alumni who pursue training and academic employment in Canada. Both alumni and trainees are largely satisfied with these training programs. The need to collect in-depth longitudinal data on Canadian MD/PhD graduates to monitor diversity and success metrics is discussed.

The contribution of chronic peer victimization in elementary school to depressive symptoms in adolescence.

Throughout his career, John Schulenberg challenged us to understand adolescent development as the confluence of distal and proximal experiences along with critical transitions. Heeding this call, we examined whether chronic childhood peer victimization predicted adolescents' depressive symptoms via early-emerging depression growth trajectories, continued victimization into adolescence, and stress-amplification at the middle school transition. Self-reported depressive symptoms and teacher-reported and self-reported peer victimization were obtained from 636 youth (338 girls; Mage = 7.96 years, 66.7% White, 21.7% Black, 11.6% other) in the 2nd-9th grades. Latent growth curve analyses revealed that, by 7th grade, chronic childhood peer victimization was associated with depressive symptoms only through an indirect association with peer victimization in adolescence, underscoring how interrelated historical and ongoing interpersonal stressors contribute to adolescent psychopathology.

Keratan sulfate proteoglycan: putative template for neuroblast migratory and axonal fascicular pathways and fetal expression in globus pallidus, thalamus, and olfactory bulb.

Keratan sulfate (KS) is a proteoglycan secreted in the fetal brain astrocytes and radial glia into extracellular parenchyma as granulofilamentous deposits. KS surrounds neurons except dendritic spines, repelling glutamatergic and facilitating GABAergic axons. The same genes are expressed in both neuroblast migration and axonal growth. This study examines timing of KS during morphogenesis of some normally developing human fetal forebrain structures. Twenty normal human fetal brains from 9-41 weeks gestational age were studied at autopsy. KS was examined by immunoreactivity in formalin-fixed paraffin sections, plus other markers including synaptophysin, S-100ß protein, vimentin and nestin. Radial and tangential neuroblast migratory pathways from subventricular zone to cortical plate were marked by KS deposits as early as 9wk GA, shortly after neuroblast migration initiated. During later gestation this reactivity gradually diminished and disappeared by term. Long axonal fascicles of the internal capsule and short fascicles of intrinsic bundles of globus pallidus and corpus striatum also appeared as early as 9-12wk, as fascicular sleeves before axons even entered. Intense KS occurs in astrocytic cytoplasm and extracellular parenchyma at 9wk in globus pallidus, 15wk thalamus, 18wk corpus striatum, 22wk cortical plate, and hippocampus postnatally. Corpus callosum and anterior commissure do not exhibit KS at any age. Optic chiasm shows reactivity at the periphery but not around intrinsic subfasciculi. We postulate that KS forms a chemical template for many long and short axonal fascicles before axons enter and neuroblast migratory pathways at initiation of migration. Cross-immunoreactivity with aggrecan may render difficult molecular distinction.

Dynapenia and sarcopenia identify walking speed decline in women but not in men.

OBJECTIVE: To determine the best indicator of mobility decline between dynapenia, low skeletal muscle mass index (SMMI), and sarcopenia defined by the EWGSOP2 using different cutoff points for grip strength. METHODS: A longitudinal study was conducted with a follow-up of eight years, involving 2,680 individuals aged 60 and older who participated in the ELSA study with a walking speed greater than 0.8 m/s at baseline. Dynapenia was defined using different cutoff points for grip strength. SMMI was defined by the 20th percentile of the entire ELSA sample distribution and sarcopenia was defined based on the EWGSOP2, using different cutoff points for grip strength. Mobility was analysed using the walking speed test. RESULTS: Over time, the greatest decline in walking speed occurred in dynapenic women with grip strength < 17 kg (-0.005 m/s per year; 95 % CI: -0.01 to -0.001) and < 20 kg (-0.007 m/s per year; 95 % CI: -0.01 to -0.001). With regards to sarcopenia, the greatest walking speed decline occurred in women with probable sarcopenia when defined by grip strength < 17 kg [(-0.006 m/s per year; 95 % CI: -0.01 to -0.001) or grip strength < 20 kg (-0.007 m/s per year; 95 % CI: -0.01 to -0.001)]. Dynapenia in men as well as low SMMI and sarcopenia in men and women did not enable identifying the risk of mobility decline. CONCLUSION: Dynapenia and probable sarcopenia defined by grip strength < 17 kg and < 20 kg enabled identifying walking speed decline over time only in women.

Developmental change of brain volume in Rett syndrome in Taiwan.

OBJECTIVE: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults. METHODS: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil. RESULTS: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison. CONCLUSIONS: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.

Clinical characteristics associated with functioning trajectories following admission to a psychiatric institution: A prospective cohort study of individuals with psychosis.

Psychotic disorders can be severely enabling, and functional recovery is often difficult to achieve. Admission to a psychiatric unit represents a key opportunity to implement strategies that will improve functional outcomes. In the current literature, there is a lack of consensus on which factors influence functional recovery. Therefore, the present longitudinal cohort study aimed to identify factors associated with functional trajectories following hospital admission for acute psychosis. A sample of 453 individuals with acute psychosis was extracted from the Signature Biobank database. Participants were followed for up to a year following admission. Various clinical indicators were documented over time. Functional trajectories were calculated based on the World Health Organization Disability Assessment Schedule 2.0. Three groups were identified: "improving", "stable", and "worsening" function. Individuals with a more severe symptomatic presentation at baseline were found to have better functional improve more over time. Over time, individuals in the "improving" and "stable" groups had significant improvements in their psychiatric symptoms. Finally, individuals following a "worsening" functional trajectory initially improved in terms of psychotic symptoms, but it did not persist over time. These results highlight the importance of studying function as a key component of recovery rather than solely focusing on relapse prevention.

Phenotyping variability in early socio-communicative skills in young children with autism and its influence on later development.

Children with autism spectrum disorder (ASD) often face challenges in early social communication skills, prompting the need for a detailed exploration of specific behaviors and their impact on cognitive and adaptive functioning. This study aims to address this gap by examining the developmental trajectories of early social communication skills in preschoolers with ASD aged 18-60 months, comparing them to age-matched typically developing (TD) children. Utilizing the early social communication scales (ESCS), the research employs a longitudinal design to capture changes over time. We apply a principal component analysis (PCA) to ESCS variables to identify underlying components, and cluster analysis to identify subgroups based on preverbal communication profiles. The results reveal consistent differences in early social communication skills between ASD and TD children, with ASD children exhibiting reduced skills. PCA identifies two components, distinguishing objects-directed behaviors and social interaction-directed behaviors. Cluster analysis identifies three subgroups of autistic children, each displaying specific communication profiles associated with distinct cognitive and adaptive functioning trajectories. In conclusion, this study provides a nuanced understanding of early social communication development in ASD, emphasizing the importance of low-level behaviors. The identification of subgroups and their unique trajectories contributes to a more comprehensive understanding of ASD heterogeneity. These findings underscore the significance of early diagnosis, focusing on specific behaviors predicting cognitive and adaptive functioning outcomes. The study encourages further research to explore the sequential development of these skills, offering valuable insights for interventions and support strategies.

Changes in subjective well-being and stress of older adults before, during and after the COVID-19 pandemic: a longitudinal study in Switzerland.

PURPOSE: Despite the concerns about older adults' overall quality of life during the COVID-19 pandemic, they often demonstrated better resilience, adaptability, and subjective well-being (SWB) than younger individuals. However, longer-term trends remain unclear. This study aims to describe older adults' trajectories in SWB dimensions before, during, and after the pandemic spanning 2017-2022. METHODS: This study used piecewise growth curve analysis on a subsample of the Swiss Household Panel to investigate the population-average (n individuals = 3086; n = observations = 13,780) trajectories of SWB dimensions and stress among adults aged 65 and older between 2017 and 2022. We also tested whether these trajectories differed by age, gender, and household income. RESULTS: Life satisfaction and positive affect remained stable among older people during the pandemic (2019-2021) but declined after. Negative affect increased during the pandemic and decreased afterward, while stress levels increased slightly before and significantly after the pandemic. The trajectories did not differ by gender or household income, but the oldest-old (> 75-year-old) had a more significant decline in positive affect and life satisfaction pre-pandemic (2017-2019) and stress during the pandemic (2020-2021). CONCLUSION: Research shows that older adults possess adaptation skills and emotional competencies, which enable them to navigate pandemic challenges. However, we show that the post-pandemic era presents more substantial challenges for this older population, who perhaps face more difficulties adapting to the new uncertain post-pandemic world. Further research needs to examine if these findings replicate in other contexts, for instance, where pandemic containment measures have been more stringent.

Late adolescent outcomes of different developmental trajectories of ADHD symptoms in a large longitudinal study.

There exists substantial heterogeneity in the developmental trajectories of ADHD symptoms, with distinctions often made between persistent versus remittent, and early- versus late-onset. However, how these trajectories relate to late adolescent functioning and whether, in particular, later onset trajectories mark a milder subtype remains unclear. Building on earlier work that has examined early life predictors of ADHD symptom trajectories up to age 14, we applied latent class growth analysis to data from the UK Millennium Cohort Study (N = 10,262) to evaluate whether developmental trajectories of ADHD symptoms up to age 17 (from age 3) were similar to those identified up to age 14 and associated with differing levels of impairment in peer victimisation, mental health, substance use, and delinquency outcomes at age 17. Our optimal model included five trajectory groups, labelled unaffected (37.6%), mildly affected (34.8%), subclinical remitting (14.4%), adolescent onset (7.6%), and stable high (5.6%). Adolescent onset and stable high trajectories were similarly impaired across all outcomes, other than substance use. Subclinical remitting individuals were impaired on self-esteem and well-being compared to unaffected individuals. By the end of mid-adolescence, those with a later onset have similar impairments to those following an early onset/persistent trajectory. Residual impairment may remain for those on a remitting trajectory.

Double vision: 2D and 3D mosquito trajectories can be as valuable for behaviour analysis via machine learning.

BACKGROUND: Mosquitoes are carriers of tropical diseases, thus demanding a comprehensive understanding of their behaviour to devise effective disease control strategies. In this article we show that machine learning can provide a performance assessment of 2D and 3D machine vision techniques and thereby guide entomologists towards appropriate experimental approaches for behaviour assessment. Behaviours are best characterised via tracking-giving a full time series of information. However, tracking systems vary in complexity. Single-camera imaging yields two-component position data which generally are a function of all three orthogonal components due to perspective; however, a telecentric imaging setup gives constant magnification with respect to depth and thereby measures two orthogonal position components. Multi-camera or holographic techniques quantify all three components. METHODS: In this study a 3D mosquito mating swarm dataset was used to generate equivalent 2D data via telecentric imaging and a single camera at various imaging distances. The performance of the tracking systems was assessed through an established machine learning classifier that differentiates male and non-male mosquito tracks. SHAPs analysis has been used to explore the trajectory feature values for each model. RESULTS: The results reveal that both telecentric and single-camera models, when placed at large distances from the flying mosquitoes, can produce equivalent accuracy from a classifier as well as preserve characteristic features without resorting to more complex 3D tracking techniques. CONCLUSIONS: Caution should be exercised when employing a single camera at short distances as classifier balanced accuracy is reduced compared to that from 3D or telecentric imaging; the trajectory features also deviate compared to those from the other datasets. It is postulated that measurement of two orthogonal motion components is necessary to optimise the accuracy of machine learning classifiers based on trajectory data. The study increases the evidence base for using machine learning to determine behaviours from insect trajectory data.

Trajectories of BMI before and after diagnosis of type 2 diabetes in a real-world population.

AIMS/HYPOTHESIS: Few studies have examined the clinical characteristics associated with changes in weight before and after diagnosis of type 2 diabetes. Using a large real-world cohort, we derived trajectories of BMI before and after diabetes diagnosis, and examined the clinical characteristics associated with these trajectories, including assessing the impact of pre-diagnosis weight change on post-diagnosis weight change. METHODS: We performed an observational cohort study using electronic medical records from individuals in the Scottish Care Information Diabetes Collaboration database. Two trajectories were calculated, based on observed BMI measurements between 3 years and 6 months before diagnosis and between 1 and 5 years after diagnosis. In the post-diagnosis trajectory, each BMI measurement was time-dependently adjusted for the effects of diabetes medications and HbA1c change. RESULTS: A total of 2736 individuals were included in the study. There was a pattern of pre-diagnosis weight gain, with 1944 individuals (71%) gaining weight overall, and 875 (32%) gaining more than 0.5 kg/m2 per year. This was followed by a pattern of weight loss after diagnosis, with 1722 individuals (63%) losing weight. Younger age and greater social deprivation were associated with increased weight gain before diagnosis. Pre-diagnosis weight change was unrelated to post-diagnosis weight change, but post-diagnosis weight loss was associated with older age, female sex, higher BMI, higher HbA1c and weight gain during the peri-diagnosis period. When considering the peri-diagnostic period (defined as from 6 months before to 12 months after diagnosis), we identified 986 (36%) individuals who had a high HbA1c at diagnosis but who lost weight rapidly and were most aggressively treated at 1 year; this subgroup had the best glycaemic control at 5 years. CONCLUSIONS/INTERPRETATION: Average weight increases before diagnosis and decreases after diagnosis; however, there were significant differences across the population in terms of weight changes. Younger individuals gained weight pre-diagnosis, but, in older individuals, type 2 diabetes is less associated with weight gain, consistent with other drivers for diabetes aetiology in older adults. We have identified a substantial group of individuals who have a rapid deterioration in glycaemic control, together with weight loss, around the time of diagnosis, and who subsequently stabilise, suggesting that a high HbA1c at diagnosis is not inevitably associated with a poor outcome and may be driven by reversible glucose toxicity.

Routines, disruptions, revised decisions: A biographical analysis of vaccination trajectories among Filipino caregivers.

BACKGROUND: Individuals' vaccine attitudes and practices are not static, but instead are shaped and iteratively revised based on new information and experiences. Understanding shifts over the life course could inform novel approaches and indicate opportune points for communicating vaccine information, but little is known about individuals' vaccination biographies, particularly in low- and middle-income countries. METHODS: To explore vaccination biographies in a setting marked by high proportions of vaccine hesitancy and recent large-scale vaccination discourses, we conducted and biographically analyzed n = 29 narrative in-depth interviews with caregivers of small children in the Philippines. RESULTS: Our results outline how the perceived relevance of vaccination and an individual's own attitudes and practices repeatedly changed over the course of their life. While respondents narrated vague memories of early vaccine encounters in their families, at schools, or during vaccination campaigns, vaccine relevance accelerated drastically during respondents' or their partner's first perinatal period. Over the following life phase as caregivers, respondents described iterative shifts in their vaccine stance (based on their own experiences, broader discourses, or changing contexts) until their youngest child 'graduated' from immunization. Respondents' later adulthood and old age were commonly marked by little engagement with immunization (except for the COVID-19 vaccines), until the birth of grandchildren sparked renewed motivation to guide younger generations (whether for or against vaccination). CONCLUSIONS: The relevance of vaccination and associated attitudes or practices repeatedly change over the life course. Vaccine promotion efforts could incorporate these biographical dynamics to align with respondents' informational needs, for example by increased engagement in first perinatal periods, eye-level communication at later phases to acknowledge caregivers' increased sense of expertise, and encouragement of vaccine confident grandparents to engage in younger generations' vaccination decisions. Future research should explore transgenerational vaccine trajectories and the potential of biographically targeted promotion efforts.

Socio-Ecologic Influences on Weight Trajectories Among Children with Obesity Living in Rural and Urban Settings.

Background: Childhood obesity is a risk factor for poor cardiovascular, metabolic, and respiratory health. The studies examining influences of socio-ecologic factors on weight trajectories using longitudinal data are limited, often examine single measures (e.g., proximity to parks), and have not examined the specific trajectories of children with obesity. Methods: We examined influences on weight among 1518 children, 6-12 years of age, who had obesity using body mass index (BMI) criteria. BMI slope trajectories were categorized as decreasing, flat, or increasing, with a median of 2.1 years of follow-up. We examined socio-ecologic exposures, stratified by rural and urban settings, using census tracts to map indices, including food access, proximity to parks, normalized difference vegetation index, and area deprivation index (ADI). We used ordinal logistic regression to examine the associations between the socio-ecologic factors and BMI trajectories. Results: Among the 1518 children, 360 (24%) had a decreasing BMI trajectory with the remainder having flat (23%) or increasing (53%) trajectories. Children in rural areas were more likely to live in high disadvantage areas, 85%, compared with urban children, 46%. In the multivariable ordinal model, living in a lower ADI census tract had a 0.78 (95% CI 0.61-0.99) lower odds of being in an increasing BMI slope group, and no other socio-ecologic factor was associated. Conclusions: The area deprivation index captures a range of resources and social context compared with the built environment indicators, which had no association with BMI trajectory. Further work examining how to develop effective interventions in high deprivation areas is warranted.

Metabolic Clusters of Early-Lactating Dairy Cows Based on Blood ß-hydroxybutyrate Trajectories and Predicted from Milk Compounds.

High-yielding dairy cows encounter metabolic challenges in early lactation. Typically, ß-hydroxybutyrate (BHB), measured at a specific time point is employed to diagnose the metabolic status of cows based on a predetermined threshold. However, in early lactation, BHB is highly dynamic, and there is high interindividual variability in its time profile. This could limit the effectiveness of the single measurement and threshold-based diagnosis probably contributing to the disparities in reports linking metabolic status with productive and reproductive outcomes. This research delves into the examination of the trajectories of BHB to unveil inter-cow variations and identify latent metabolic groups. We compiled a data set from 2 observational studies involving a total of 195 lactations from multiparous Holstein Friesian cows. The data set encompasses measurements of BHB, NEFA, and insulin from blood samples collected at 3, 6, 9, and 21 d in milk (DIM), along with weekly determinations of milk composition and fatty acids (FA) proportions in milk fat. In both experiments, milk yield (MY) and feed intake were recorded daily during the first month of lactation. We explored interindividual and intraindividual variations in metabolic responses using the trajectories of blood BHB and evaluated the presence of distinct metabolic groups based on such variations. For this purpose, we employed the growth mixture model (GMM), a trajectory clustering technique. Our findings unveil novel insights into the diverse metabolic responses among cows, encompassing both trajectory patterns and the magnitude of blood BHB concentrations. Specifically, we identified 3 latent metabolic groups: the "QuiBHB" cluster (≈10%) exhibited a higher initial BHB concentration than other clusters, peaking on d 9 (average maximum BHB of 2.4 mM) and then declining by d 21; the "SloBHB" cluster (≈23%) started with a lower BHB concentration, gradually increasing until d 9, and at the highest BHB concentration at d 21 (1.6 mM serum BHB at the end of the experimental period); and the "LoBHB" cluster (≈67%) began with the lowest serum BHB concentration (serum BHB <0.75 mM), remaining relatively stable throughout the sampling period. Notably, the 3 metabolic groups exhibited significant physiological disparities, evident in blood NEFA and insulin concentrations. The QuiBHB and SloBHB cows exhibited higher NEFA and lower insulin concentrations as compared with the LoBHB cows. Interestingly, these metabolic differences extended to MY and DMI during the first month of lactation. The elevated BHB concentrations observed in QuiBHB cows were linked with lower DMI and MY as compared with SloBHB and LoBHB cows. Accordingly, these animals were considered metabolically impaired. Conversely, SloBHB cows displayed higher MY along with increased DMI, and thus the elevated BHB might be indicative of an adaptive response for these cows. The QuiBHB cows also displayed higher proportions of unsaturated FA (UFA), monounsaturated FA (MUFA), and total C18:1 FA in milk during the first week of lactation. Prediction of the QuiBHB cows using these FA and test day variables resulted in moderate predictive accuracy (ROCAUC > 0.7). Given the limited sample size for the development of prediction models, and the variation in DIM among samples in the same week, the result is indicative of the predictive potential of the model and room for model optimization. In summary, distinct metabolic groups of cows could be identified based on the trajectories of blood BHB in early lactation.

Reply to Commentary on "Adult Smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months After Initially Purchasing a JUUL e-Cigarette" and the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study.

BACKGROUND: This is authors' reply to the Commentary on our publication entitled "Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette." METHODS AND RESULTS: Analyses addressed questions about follow-up rates and missed responses in the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study. Results demonstrate limited potential for selection bias, as participants who missed surveys were similar to those with complete data, and re-contact of participants who missed a follow-up indicated almost half were not smoking. Imputing smoking behavior for missing data would likely introduce bias and is not appropriate. The study demonstrated that JUUL products can facilitate high rates of complete switching away from cigarettes as suggested in previous experimental and observational studies. The ADJUSST cohort, including baseline nonsmokers, demonstrates a net reduction in smoking prevalence. Moreover, population modeling considering both benefits and harms demonstrated a net population benefit. CONCLUSION: While the ADJUSST Study is not without limitations, the findings are consistent with multiple streams of real-world evidence that indicate that ENDS can facilitate switching among adults who smoke, and provide population benefits.

Multicentric Assessment of a Multimorbidity-Adjusted Disability Score to Stratify Depression-Related Risks Using Temporal Disease Maps: Instrument Validation Study.

BACKGROUND: Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for the assessment and prediction of disease progression. Our study proposes a novel methodology, the Multimorbidity-Adjusted Disability Score (MADS), which integrates disease trajectory methodologies with advanced techniques for assessing interdependencies among concurrent diseases. This approach is designed to better assess the clinical burden of clusters of interrelated diseases and enhance our ability to anticipate disease progression, thereby potentially informing targeted preventive care interventions. OBJECTIVE: This study aims to evaluate the effectiveness of the MADS in stratifying patients into clinically relevant risk groups based on their multimorbidity profiles, which accurately reflect their clinical complexity and the probabilities of developing new associated disease conditions. METHODS: In a retrospective multicentric cohort study, we developed the MADS by analyzing disease trajectories and applying Bayesian statistics to determine disease-disease probabilities combined with well-established disability weights. We used major depressive disorder (MDD) as a primary case study for this evaluation. We stratified patients into different risk levels corresponding to different percentiles of MADS distribution. We statistically assessed the association of MADS risk strata with mortality, health care resource use, and disease progression across 1 million individuals from Spain, the United Kingdom, and Finland. RESULTS: The results revealed significantly different distributions of the assessed outcomes across the MADS risk tiers, including mortality rates; primary care visits; specialized care outpatient consultations; visits in mental health specialized centers; emergency room visits; hospitalizations; pharmacological and nonpharmacological expenditures; and dispensation of antipsychotics, anxiolytics, sedatives, and antidepressants (P<.001 in all cases). Moreover, the results of the pairwise comparisons between adjacent risk tiers illustrate a substantial and gradual pattern of increased mortality rate, heightened health care use, increased health care expenditures, and a raised pharmacological burden as individuals progress from lower MADS risk tiers to higher-risk tiers. The analysis also revealed an augmented risk of multimorbidity progression within the high-risk groups, aligned with a higher incidence of new onsets of MDD-related diseases. CONCLUSIONS: The MADS seems to be a promising approach for predicting health risks associated with multimorbidity. It might complement current risk assessment state-of-the-art tools by providing valuable insights for tailored epidemiological impact analyses of clusters of interrelated diseases and by accurately assessing multimorbidity progression risks. This study paves the way for innovative digital developments to support advanced health risk assessment strategies. Further validation is required to generalize its use beyond the initial case study of MDD.

Effect of gestational diabetes on fetal growth rate and later overweight in the offspring.

CONTEXT: Children of women with gestational diabetes (GDM) are often born with a higher birthweight and have an increased risk of overweight during childhood. High fetal growth rate is also associated with being overweight in childhood. OBJECTIVE: To examine excessive fetal growth rate as a mediator between GDM and overweight in the offspring. METHODS: This was a longitudinal cohort study, using routinely collected data on children born 2008-2014 in Aarhus, Denmark. Fetal biometrics were extracted from the patient records at Aarhus University Hospital and childhood weight from the health records at Aarhus Municipality Healthcare Service. We calculated growth trajectories for fetuses affected by GDM and for unaffected fetuses using cubic mixed model regression. We extracted individual fetal growth rate and estimated the contributing effect of fetal growth rate on the risk of being overweight in the 5-9 year-old offspring. RESULTS: We included 6794 mother-child pairs, 295 with GDM. Fetal growth was higher in women with GDM from week 25, and the offspring had an increased risk of being overweight (OR: 2.02 (95%CI: 1.44 - 2.84)). When adjusting for fetal growth rate in week 28 the effect attenuated by 15%, and to 1.10 (95%CI: 0.76 - 1.60) when further adjusting for pre-pregnancy BMI. CONCLUSION: Pregnancies affected by GDM had higher fetal growth rate and the offspring had a higher risk of being overweight at 5-9 years. Fetal growth rate in early third trimester was a mediator of up to 15% of this association, but pre-pregnancy BMI contributed strongly as well.

The progression of cognitive impairment and its influencing factors in older adults based on longitudinal item response theory.

BACKGROUND: Understanding the development of cognitive impairment and its influencing factors in older adults is crucial for formulating early intervention strategies. PURPOSE: To identify the early dimensions of cognitive impairment and provide a comprehensive description of the trajectories of cognitive decline in older adults prior to death. METHODS: Based on the data of 9883 older adults in the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018, a longitudinal item response theory (Longitudinal IRT) model including covariates was applied to estimate the following parameters. The items in which older adults encountered obstacles first had the least difficulty parameters (δ). The earlier the information curve of an item is lifted, the more information it provides in the early stages of cognitive impairment. Regression coefficient (ß) represents the relative rate of cognitive decline. The cognitive impairment values estimated from the Longitudinal IRT were fitted to a mixed-effects model to examine cognitive impairment trajectories. RESULTS: 'Draw the figure on B Card' (δ = -0.816) was the most challenging item, followed by 'recalling 'clothes" (δ = 0.348) and 'recalling 'apples" (δ = 0.419), while 'name the 'pen" (δ = 4.402) was the simplest instruction for the old adults. The curves of the items in the recall dimension began to rise in the early stages of cognitive impairment. Cognitive impairment of older adults who were women (ß = 0.061), elder (ß = 0.111), smokers (ß = 0.060), living in rural areas (ß = 0.052), not participating in organised social activities (ß = 0.092), suffering from hypertension (ß = 0.022), hyperglycaemia (ß = 0.035), dyslipidaemia (ß = 0.314), low education levels (ß = 0.128), manual labourers (ß = 0.027), and eventual development of dementia (ß = 0.212) exhibited a more accelerated progression. These individuals also had poorer cognitive trajectories. CONCLUSION: Recall is the earliest dimension of cognitive impairment. The subjects who were women, elder, smokers, living in rural areas, not participating in organised social activities, suffering from hypertension, hyperglycaemia, dyslipidaemia, low education, manual labourers, and eventually development of dementia, had a faster descending speed and poorer trajectories.

Associations between sleep duration trajectories and risk of cardio-metabolic disease among middle-aged and older Chinese adults.

BACKGROUND: The association of a single time-point measure of sleep duration with cardio-metabolic disease has been extensively studied, but few studies have focused on the impact of sleep duration trajectory. This study aims to model the sleep duration trajectory as predictors for the subsequent development of cardio-metabolic disease. METHODS: This study recruited a notably large population (n = 9883) of subjects aged at least 45 years from the China Health and Retirement Longitudinal Study (CHARLS), who participated in sequential surveys conducted in 2011, 2013, 2015, and 2018. Sleep duration trajectories were plotted using data of night sleep duration recorded at intervals from 2011 to 2015 by latent class trajectory model. The onset of cardio-metabolic diseases from 2015 to 2018 were confirmed and then the risk of different sleep duration trajectories on incident cardio-metabolic disease was examined using cox proportional hazards regression model. RESULTS: We identified four sleep duration trajectories. Compared to the normal-stable trajectory, the short-stable trajectory was significantly associated with higher risk of incident stroke (hazard ratio [HR], 1.32; 95 % confidence interval [CI], 1.02 to 1.70), dyslipidemia (HR, 1.22; 95%CI, 1.01 to 1.49), and diabetes (HR, 1.42; 95%CI, 1.13 to 1.78) within three years of follow-up, and the short-increasing trajectory predicted a higher risk of incident stroke (HR, 2.38; 95%CI, 1.25 to 4.55). CONCLUSIONS: Short sleep trajectory could increase the risk of incident stroke, dyslipidemia, and diabetes, and an increasing sleep trajectory was associated with increased risk of incident stroke among middle-aged and older Chinese adults.