Longitudinal Patterns Research Articles

Modeling longitudinal change patterns of self-regulation from early to middle childhood: Methodological innovations and individual differences.

Patterns of change in self-regulation from the ages of 2.5 to 12 years were modeled using repeated measures of self-regulation for a sample of 399 African American (n = 180, 45%) and Latinx (n = 219, 55%) children from families experiencing low income. Measures included both direct assessment and parent report. Results confirmed four components of self-regulation: working memory, inhibitory control, complex response inhibition, and set shifting. Furthermore, these components of self-regulation were more differentiated at younger ages but grew increasingly integrated as children developed. During early childhood, Latinx children displayed greater levels of working memory and higher levels of inhibitory control, and African American children displayed greater complex response inhibition and set shifting, but these ethnic differences reversed by early elementary school. By late middle childhood, ethnic differences in self-regulation had virtually disappeared altogether. Few differences by child gender or family poverty status were identified. Recommendations are provided to facilitate the modeling of self-regulation over extended periods of development including (a) utilizing measures that overlap time points, (b) standardizing the measurement scales, and (c) utilizing a flexible latent variable model. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Evaluating Criteria for Symptoms Suggestive of Early Osteoarthritis Over Two Years Post-Anterior Cruciate Ligament Reconstruction: Data From the New Zealand Anterior Cruciate Ligament Registry.

The objectives were to determine the prevalence of meeting criteria for symptoms suggestive of early osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) and to characterize the longitudinal changes in these symptoms during the first two years post-ACLR. We analyzed data from 10,231 patients aged 14 to 40 years in the New Zealand ACL Registry who completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6, 12, and 24 months post-ACLR. Symptoms suggestive of early OA were defined as scoring ≤85% on at least two of four KOOS subscales. Longitudinal patterns of change were categorized as persistent, resolution, new, inconsistent, or no symptoms across the three visits. Prevalence and odds ratios (ORs) of symptoms were compared across visits, sex, and age groups using generalized estimating equations, and longitudinal patterns of symptom change were analyzed using multinomial logistic regression. Prevalence of meeting criteria of symptoms suggestive of early OA was 68% at 6 months, 54% at 12 months, and 46% at 24 months post-ACLR. Longitudinally, 33% had persistent symptoms, 23% had no symptoms, 29% showed symptom resolution, 6% developed new symptoms, and 9% had inconsistent symptoms. Women consistently showed higher odds of symptoms (OR range 1.17-1.52). Older age groups demonstrated higher odds of symptoms, particularly at 6 months (OR range 1.64-2.45). Symptoms suggestive of early OA are highly prevalent within two years post-ACLR, with one third of patients experiencing persistent symptoms. These findings indicate that symptoms are more likely to persist rather than newly develop, emphasizing the importance of early identification and targeted interventions.

The Effects of COVID-19 on Antifungal Prescribing in the UK—Lessons to Learn

Fungal infections are increasingly prevalent; however, antifungal stewardship attracts little funding or attention. Previous studies have shown that knowledge of guidelines and scientific evidence regarding antifungals is poor, leading to prescribing based on personal experiences and the inherent biases this entails. We carried out a retrospective study of inpatient antifungal usage at two major hospitals. We assessed the longitudinal trends in antifungal usage and the effect of COVID-19 on antifungal prescription, alongside levels of empirical and diagnostically targeted antifungal usage. Our results showed that the longitudinal patterns of total systemic antifungal usage within the trusts were similar to national prescribing trends; however, the composition of antifungals varied considerably, even when looking exclusively at the more homogenous group of COVID-19 patients. We showed a high level of empirical antifungal use in COVID-19 patients, with neither trust adhering to international recommendations and instead appearing to follow prior prescribing habits. This study highlights the significant challenges to optimise antifungal use with prescribing behaviour largely dictated by habit, a lack of adherence to guidelines, and high rates of empirical non-diagnostic-based prescribing. Further research and resources are required to understand the impact of antifungal stewardship on improving antifungal prescribing behaviours in this setting and the effects on outcome.

Abstract 4126731: Cumulative Cardiovascular Health in Young Adulthood and Systemic Target Organ Damage: The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Introduction: Cardiovascular health (CVH) in young adulthood (YA) is strongly associated with subclinical and clinical outcomes in later life. Longitudinal patterns of CVH exposure through YA (e.g., cumulative CVH exposure) may be particularly important. However, no studies have assessed cumulative CVH in YA and its association with target organ damage (TOD). Methods: CVH was defined using Life’s Essential 8 (LE8) score. CARDIA participants (ppts) with CVH assessed at ≥3 exams over 20 years of follow-up in YA (year [Y]0 to Y20 exams; mean ages 25 to 45 years) were included. Cumulative LE8 scores (cumLE8; higher = better CVH over time) were calculated as the sum of LE8 scores through YA carried forward between exams measured as point*years. Eight markers of TOD (listed in Results) were measured at subsequent exams (Y20 or Y25) including cardiac, renal, pulmonary, and neurologic markers. Associations of cumLE8 with markers of TOD were assessed using partial effects regression models adjusted for race, sex, and maximal education. Results: There were 3,485 ppts (43.4% men, 46.2% Black) with mean cumLE8 score of 1,448.6 (SD 211.4) point*years. Higher cumLE8 in YA was linearly associated with lower measures of cardiac (left ventricular mass index, carotid intima media thickness, prevalence of coronary artery calcium), renal (estimated glomerular filtration rate [eGFR] in men), and neurologic damage (proportion of white matter hyperintensity on brain MRI) ( Figure ). Higher cumLE8 was also linearly associated with better lung function (forced expiratory volume in 1 second, forced vital capacity). Urine albumin-creatinine ratio (in men and women) and eGFR (in women) were non-linearly associated with cumLE8. Conclusions: Our findings underscore the importance of high cumLE8 in YA and its association with reduced onset of TOD later in life. Primordial prevention strategies are needed to achieve and maintain high CVH through the critical period of YA.

Continuity and change in early material hardship domains on the development of children’s behavioral self-regulation in middle childhood

Child poverty adversely impacts children’s behavioral self-regulation; however, the extent to which this association varies across different forms of material hardship (i.e., food, housing, bill-paying, utility, and medical) from infancy to early childhood is not well understood. The current study aims to identify the longitudinal patterns of early material hardship in five domains, examine demographic factors to distinguish class membership, and assess how hardship class membership predicts children’s behavioral self-regulation in middle childhood. We used data from the Future of Families and Child Wellbeing Study (N = 4,677) across ages 1 to 9. The Multidimensional Growth Mixture Model identified four trajectory classes: Low Stable (n = 2,215, 47.4%), Increasing Bill and Utility Hardship (n = 1,180, 25.2%), High Infancy Bill Hardship (n = 799, 17.1%), and Persistent and Pervasive (n = 483, 10.3%). White, married mothers, mothers who were employed, families with income above 200% of the federal poverty threshold, and those who did not receive SNAP had higher odds of being in the Low Stable class than the three other classes. Children in the Persistent and Pervasive class exhibited the lowest levels of behavioral self-regulation in middle childhood compared to the other three classes. Children in the Increasing Bill and Utility Hardship and High Infancy Bill Hardship classes had lower behavioral self-regulation than those in the Low Stable class. These findings underscore the need for tailored interventions to alleviate the prolonged effects of financial adversity and exposure to early material deprivation experienced by children. Findings also highlight the importance of implementing intervention programs designed specifically to support the development of behavioral self-regulation among economically disadvantaged children.

Roles of Social Support and Strain in Predicting Older Adults’ Sleep Disturbances

Sleep disturbances impact the well-being of older adults, but there has been limited research on their longitudinal patterns and how they are affected by the quality of social relationships. This study explored longitudinal sleep disturbance patterns and examined the influence of social support and social strain on sleep disturbances in older adults using data from the Health and Retirement Study (HRS) spanning from 2010 to 2018. Group-based trajectory modeling identified distinct trajectory groups. Multinomial logistic regression and a fixed effects model investigated the relationship between sleep disturbances, social support, social strain, and sociodemographic factors. Three sleep disturbance trajectories were identified: high sleep disturbances, moderate sleep disturbances, and low sleep disturbances. Multinomial logistic regression showed that higher social support decreased the likelihood of classification in the high and moderate sleep disturbance groups. Conversely, higher social strain scores increased the likelihood of belonging to the high and moderate sleep disturbance groups. The fixed effects model confirmed the role of social support in predicting sleep disturbances over time, but social strain was not a significant predictor. These findings suggest the need for tailored interventions addressing social support to reduce sleep disturbances in this population.

Identifying childhood pesticide exposure trajectories and critical window associated with behavioral problems at 10 years of age: Findings from SMBCS

BackgroundPesticides may impact children’s neurodevelopment. As children’s metabolic function and neural plasticity change throughout their growth and development, the effects of pesticide exposure may also vary. ObjectivesWe aimed to identify the trajectories of combined pesticide exposure during childhood, and examine the associations of the exposure trajectories with children’s neurobehavior at the age of 10. MethodsWe involved repeated measurements of three pesticide metabolites [Pentachlorophenol (PCP), 3,5,6-Trichloro-2-pyridinol (TCPy), and Carbofuran phenol (CFP)], in urine samples collected from children in a cohort study at ages 1, 2, 3, 6, 7, 8, 9, and 10 years. The group-based multi-trajectory model (GBMT) and latent class analysis (LCA) were separately utilized to describe the distinct trajectories and patterns of pesticide mixture exposure during childhood. Meanwhile, the Strengths and Difficulties Questionnaire (SDQ) and attention deficit hyperactivity disorder (ADHD) Criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) list were applied to assess behavioral disorders in children. The associations between exposure trajectories and behavioral problem scores were then examined. ResultsThe GBMT model delineated three distinct trajectories of combined pesticide exposure among children: consistently low, higher levels in early childhood transitioning to lower levels during pre-school age, and lower levels in early childhood followed by higher levels in the middle childhood. The LCA model identified three similar longitudinal exposure patterns. Further, the children in the second trajectory group identified by GBMT, characterized by higher early childhood exposure levels, exhibited significantly elevated hyperactivity/inattention scores of the SDQ compared to the other two groups (β = 0.46, 95 %CI: 0.11, 0.81; β = 0.44, 95 %CI: 0.02, 0.86). ConclusionsOur study revealed that exposure to pesticides during early childhood (especially before the age of two), rather than other age periods, was linked to hyperactivity/inattention problems in children aged 10 years. We also provided a novel perspective on characterizing the fluctuation in repeated measurements of multiple environmental chemicals and identifying the potential critical windows.

Process Mining on National Health Care Data for the Discovery of Patient Journeys of Older Adults

ObjectiveUnderstanding the longitudinal patterns of health care utilization among older adults is crucial for designing effective patient journeys and enhancing care coordination across settings. This study aims to uncover the most common patient journeys of older adults. DesignThis explorative study used process mining techniques to analyze national health care data from 2017 to 2019, focusing on patient care journeys of older adults (aged ≥65 years) in the Netherlands. Setting and ParticipantsData were sourced from Statistics Netherlands, encompassing all residents aged ≥65 years as of January 1, 2017. Health care usage declarations from various care settings during 2017-2019 were included. Patient journeys were exclusively selected if their initiation points were certain. MethodsData underwent rigorous preprocessing, merging, and filtering to create a single event log file suitable for process mining. Patients were categorized by age and medication use, and differences in patient journeys were analyzed. Process mining techniques generated visualizations illustrating the connections between care forms and the impact of changes in one form on others. ResultsThe study included 3,177,203 individuals aged 65 years and older, with 44% experiencing 1 or more patient journeys totaling 2,469,663 journeys in 2017-2019. Most care journeys for older adults were simple and short. The top 10 most frequent journeys had 4 or fewer care forms, with 95% of journeys for the 65+ population and 90% for the 85+ population having 4 or fewer care transitions. Long-term care forms, such as home care, personal care, and long-term care, accounted for the majority of time spent in the system. Conclusions and ImplicationsThis pioneering study used process mining to show that most older adults tend to have a straightforward health care need, often involving the emergency department and hospitalizations. However, a smaller group among the population requires more complex and prolonged care, especially in the 85+ population. Reducing the number of transitions for this population, although impacting fewer people, might result in a larger effect on the overall system.

Regional and longitudinal dynamics of human milk protein components assessed by proteome analysis on a fast and robust micro-flow LC–MS/MS system

An in-depth exploration of molecular composition of human milk could provide a scientific basis for the development of substitutes. The present study was conducted to analyze human milk proteins from 110 individuals from five regions of China and across three stages of lactation to investigate the change patterns. We developed a micro-flow liquid chromatography tandem mass spectrometry (μLC–MS/MS) system with data-independent acquisition (DIA) proteomics technology that can rapidly and stably characterize the human milk proteome. In total, 2796 proteins were identified. Among these proteins, CPM, ACSL1, and RPL13 changed significantly during lactation, and SCP2, GALK1 and GALE changed significantly between regions. Bioinformatics analysis revealed that human milk is altered by complex interactions between genetic and environmental factors. Our results not only reveal the regional and longitudinal patterns of change in human milk proteome but also provide theoretical basis and technical support for the production and quality control of infant formula.

Longitudinal patterns of alcohol and cannabis use among US young adults: Correlates and implications for problematic health outcomes.

Alcohol and cannabis use are common during young adulthood. Less is known regarding correlates of alcohol-cannabis use patterns and related problematic health outcomes. Using longitudinal survey data (Fall 2018, 2019, 2020) from 2,194 young adults (YAs; ages 18-34), bivariate analyses and multivariable logistic regressions examined: (1) Wave 1 (W1) sociodemographics and psychosocial factors (i.e., adverse childhood experiences [ACEs], depressive symptoms, personality traits, parent and peer alcohol and cannabis use) in relation to W3 past-month use group (i.e., use of neither, alcohol only, cannabis only, both/co-use); and (2) W3 use group in relation to W5 problematic alcohol use (Alcohol Use Disorder Identification Test), problematic cannabis use (Cannabis Use Disorder Identification Test), and depressive/anxiety symptoms (Patient Health Questionnaire - 4 item). Overall, 42.3% reported W3 alcohol-only use, 34.9% co-use, 17.8% no use, and 5.0% cannabis-only use. Those reporting W3 co-use reported greater W1 extraversion, openness, friend alcohol/cannabis use, and were more likely to report parent cannabis use (vs. no use); reported less conscientiousness, greater friend cannabis use, and were more likely to report depressive symptoms and parent cannabis use (vs. alcohol-only use); and reported greater friend alcohol use, and were more likely to report parent alcohol use (vs. cannabis-only use). W3 co-use was associated with higher odds of W5 problematic alcohol use (vs. alcohol-only use) and problematic cannabis use (vs. cannabis-only use). Substance use messaging and interventions should consider YAs' alcohol-cannabis co-use and the unique correlates of such use.

Preadolescent individual, familial, and social risk factors associated with longitudinal patterns of adolescent alcohol, cannabis, and other illicit drug use in a population-representative cohort.

The aim of this exploratory study was to identify developmental patterns of adolescent concurrent alcohol, cannabis, and other illicit drug use and their preadolescent individual, familial, and social risk factors in a population-representative cohort from the province of Quebec, Canada (N = 1,593; 48.4% male). Age 12-17 years self-reports of alcohol, cannabis, and other illicit drug use were collected. Latent growth modeling was used to analyze developmental patterns of single- or polysubstance use (SU/PSU), and multinomial regression examined their association with risk factors assessed at age 10-12 years. Five developmental patterns were revealed, including nonusers (12.8% sample) and four classes reflecting different levels of SU/PSU (5.8%-37.5%), varying in severity based on onset, frequency, and type of substances used. Boys and girls were similarly represented throughout SU/PSU patterns. In comparisons with nonusers, several preadolescent risk factors were associated with increasing severity of SU/PSU. Possibly indexing fearlessness/disinhibition, low internalizing symptoms were common to all adolescent users. An earlier onset of substance use and increasing use of substances throughout adolescence were linked with having deviant peers for all user classes but later-onset users. Preadolescents manifesting externalizing problems and exposed to family adversity in addition to the above risk factors showed the earliest onset and most frequent adolescent SU/PSU, especially those also exposed to less appropriate parenting. Consistent with the developmental model of substance use, the nature, number, and severity of preadolescent risk factors distinguished between the type and severity of SU/PSU patterns in adolescence and call for a consistent strategy of universal, selective, and indicated preventive interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Longitudinal evaluation of liver stiffness reveals hepatic cholesterol as the determinant of fibrosis progression in mice

AimsThe metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 30 % of the global population. While excessive consumption of dietary fat induces steatosis, it does not develop fibrosis, indicating that additional factors are required as “second hits” for further progression of MASLD. Here, based on shear wave elastography, we compared the longitudinal patterns of fibrogenesis induced by different diets and show the crucial role of cholesterol accumulation in fibrosis progression. Materials and methodsMice were fed chow, high-fat (HFD), high-fat high-cholesterol (HFHCD), choline-deficient, L-amino acid-defined high-fat (CDAHFD), or 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine diets over 12 weeks. Key findingsMice fed with HFD gained significant amounts of body weight but did not show an increase in liver stiffness. In contrast, the addition of cholesterol in the same diet robustly induced liver stiffening starting from the first week, which was comparable to the CDAHFD-induced fibrosis model. Longitudinal tracking of liver stiffness revealed a two-step progression of fibrosis after prolonged feeding of HFHCD and CDAHFD, likely due to cellular cholesterol accumulation over a certain threshold after the transition point. Biochemical analyses suggested the critical role of both total and hepatic cholesterol accumulation in liver fibrosis development. SignificanceCollectively, our results underscore the significance of cholesterol in liver fibrosis development, also highlighting the benefit of monitoring liver stiffness to understand the pathogenesis of liver fibrosis.

Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer.

Cell-free DNA blood tests (cf-bDNA) and next-generation stool tests could change colorectal cancer (CRC) screening. To estimate the clinical and economic impacts of novel CRC screening tests. Cost-effectiveness analysis using MOSAIC (Model of Screening and Surveillance for Colorectal Cancer). Published data. Average-risk persons. Ages 45 to 100 years. Health sector. Novel versus established CRC screening tests. Incidence and mortality of CRC, quality-adjusted life-years (QALYs), costs. For colonoscopy every 10 years, annual fecal immunochemical test (FIT), and triennial next-generation multitarget stool DNA, FIT-RNA, cf-bDNA (Guardant Shield), or cf-bDNA (Freenome), the relative rates (RRs) and 95% uncertainty intervals (UIs) versus no screening for CRC incidence were 0.21 (0.19 to 0.22), 0.29 (0.27 to 0.31), 0.33 (0.32 to 0.36), 0.32 (0.30 to 0.34), 0.58 (0.55 to 0.61) and 0.58 (0.55 to 0.60), respectively; the RRs for CRC death were 0.19 (0.17 to 0.20), 0.25 (0.23 to 0.27), 0.28 (0.27 to 0.30), 0.28 (0.26 to 0.30), 0.44 (0.42 to 0.47), and 0.46 (0.44 to 0.49), respectively. The cf-bDNA test (Shield; list price $1495) cost $89 600 ($74 800 to $102 300) per QALY gained versus no screening; alternatives were less costly and more effective. Incremental costs exceeded incremental benefits when novel test intervals were shortened to 2 or 1 years. The cf-bDNA test matched FIT's impact on CRC mortality at 1.35 (1.30 to 1.40)-fold FIT's uptake rate, assuming equal colonoscopy follow-up. If persons who accept colonoscopy or stool tests shifted to cf-bDNA, CRC deaths increased. This adverse effect was overcome if every 3 such substitutions were counterbalanced by cf-bDNA uptake by 2 or more persons refusing alternatives, assuming equal colonoscopy follow-up. Longitudinal test-specific participation patterns are unknown. First-generation cf-bDNA tests may deliver net benefit or harm, depending on the balance between achieving screening in persons who decline alternatives versus substituting cf-bDNA for more effective alternatives. The Gorrindo Family Fund.

Mechanical dyssynchrony and response to cardiac resynchronization therapy in heart failure patients with right ventricular pacing: a pre-specified subgroup analysis of the BUDAPEST CRT Upgrade trial

Abstract Introduction The BUDAPEST CRT Upgrade trial has established the strong clinical benefit of upgrading heart failure patients with a reduced left ventricular (LV) ejection fraction (HFrEF) and a high right ventricular pacing (RVP) burden to cardiac resynchronization therapy with defibrillator (CRT-D). Importantly, however, the CRT upgrade response is not homogeneous regarding LV reverse remodeling and associated clinical outcomes. The presence of mechanical dyssynchrony (MD) assessed by echocardiography has been linked to more CRT benefits; still, its change in response to CRT and added prognostic value in HFrEF patients with high RVP are scarcely investigated. Purpose Accordingly, we aimed to assess the prevalence, clinical characteristics, CRT response rate, and prognostic value of RVP-induced MD in the BUDAPEST CRT Upgrade cohort. Methods The multicentre, randomized, controlled trial enrolled 360 HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD) and significant RVP (≥ 20%) who were randomly assigned to receive CRT-D upgrade or ICD in a 3:2 ratio. Protocol echocardiography was performed at baseline and at 12-month follow-up visits and was evaluated at a central core lab. Beyond LV end-diastolic (EDV) and end-systolic volumes (ESV), longitudinal strain-derived septal deformation patterns by speckle tracking were assessed to determine the presence of RVP-induced MD. The endpoints were volumetric non-response (defined by a relative decrease in LV ESV <15%) and the composite of volumetric non-response or HF hospitalization. Results The echocardiographic assessment was feasible in 325 patients at baseline; 133 (41%) patients presented with MD. Females were more likely to present with MD (female vs. male, 65% vs. 38%, p=0.003). MD patients had higher LV EDV (MD vs. no-MD, 248±78 vs. 219±78 mL, p=0.001) and LV ESV (190±67 vs. 165±64 mL, p<0.001) at baseline. In the CRT-D group, 126 (75%) patients were volumetric responders, and 41 (25%) were non-responders at 12 months. CRT patients with baseline MD were less likely to experience volumetric non-response (OR 0.35 [95% CI 0.15-0.82], p=0.015) or the composite endpoint (OR 0.37 [95% CI 0.17-0.77], p=0.008). Out of 57 CRT patients with baseline MD who had follow-up assessment available, 52 (91%) patients had a favorable change: the MD pattern disappeared. Patients with MD resolution at 12 months were less likely to experience volumetric non-response or the composite endpoint (OR 0.39 [95% CI 0.17-0.93], p=0.034; OR 0.38 [95% CI 0.16-0.86], p=0.021, respectively). CRT patients with resolved MD were less likely of ischemic etiology and had 100% posterior or lateral LV lead location. Conclusions The presence of RVP-induced MD and its resolution is associated with better clinical response in HFrEF patients undergoing CRT-D upgrade. MD assessment can refine patient selection algorithms of CRT.Figure 1

Characterizing the progression of subclinical cardiac amyloidosis through artificial intelligence applied to electrocardiographic images and echocardiograms

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) follows an indolent course and may remain undiagnosed for many years before resulting in clinical disease. Purpose To assess the utility of scalable artificial intelligence (AI) methods applied to electrocardiographic (ECG) images and echocardiograms in detecting longitudinal changes that precede the clinical diagnosis of ATTR-CM. Methods Across 5 hospitals of a large U.S.-based hospital system, we identified a total of 234 patients (age 79 [IQR:70-85] years, n=56 (23.9%) women) with ATTR-CM, defined by the presence of a positive bone scintigraphy scan (or pharmacotherapy with an approved transthyretin stabilizer) between 2015 and 2023. Using 10:1 age- and sex-matched controls, we independently trained convolutional neural network algorithms to discriminate ATTR-CM from controls using i) ECG images (AUROC 0.915) or ii) echocardiographic studies by incorporating all available views (AUROC 0.93). In a leave-out testing set of n=82 individuals with serial ECGs and n=49 individuals with serial echocardiograms we characterized longitudinal patterns in the evolution of the AI ECG and echo-based scores, and estimated the percentage of individuals that would have screened positive across distinct time intervals. Results In the leave-out testing set 52.4% and 34.7% of all individuals who went on to receive a diagnosis of ATTR-CM would have screened positive by AI deployed to ECGs and echocardiograms, respectively, 1 to 3 years before their confirmatory testing, with the percentage increasing to 75.6% and 69.4% in the 12 months before their eventual diagnosis (A). Across both modalities, there was a longitudinal increase in AI predictions when comparing the median of all studies performed more than a year before diagnosis versus the median of any studies performed within 12 months of diagnosis (AI-Echo: 0.20 [IQR: 0.04-0.35] to 0.49 [0.24-0.59] & AI-ECG: 0.07 [0.02-0.20] to 0.32 [0.11-0.49], p<0.001 for both) (B), consistent with evolution in the ECG and echocardiographic signature of ATTR-CM before its clinical diagnosis. Conclusions We demonstrate that AI applied directly to ECG images and echocardiography may enable scalable monitoring of subclinical ATTR-CM progression.

Supplemental Material for Preadolescent Individual, Familial, and Social Risk Factors Associated With Longitudinal Patterns of Adolescent Alcohol, Cannabis, and Other Illicit Drug Use in a Population-Representative Cohort

Supplemental Material for Preadolescent Individual, Familial, and Social Risk Factors Associated With Longitudinal Patterns of Adolescent Alcohol, Cannabis, and Other Illicit Drug Use in a Population-Representative Cohort

The association between trajectories of structural disadvantage and mental wellbeing for Māori youth

Abstract Background Youth mental health is a major global concern with substantial inequities for Indigenous and other young people from minoritised ethnic groups. In New Zealand, Māori, the Indigenous people, experience poorer mental health than other young people, especially those living in high deprivation. Cultural connectedness is related to positive mental wellbeing, however, its potential to buffer against the harms of structural disadvantage for young Māori mental health has not been investigated. Methods We used data from 1224 Māori young people in the longitudinal Growing Up in New Zealand study. Structural disadvantage measures included material hardship, deprivation, employment, residential mobility. We conducted Latent Class Analysis and Social Sequence Analysis to identify clusters and longitudinal patterns of structural disadvantage. Cultural connectedness and mental wellbeing (depression & anxiety symptoms, quality of life) were measured at age 12. Linear regression analysis was used to determine associations between structural disadvantage, cultural connectedness and mental health. Results We identified 3 trajectories of structural disadvantage for Māori youth: 21% experienced persistent high structural disadvantage, 35% intermittent high structural disadvantage and 44% persistent relatively low structural disadvantage. Few differences in mental health were found between groups. Cultural connectedness was independently associated with positive mental wellbeing, yet there was mixed evidence it might buffer the impacts of structural disadvantage on mental health. Conclusions Our results highlight the importance of policies that uphold Indigenous rights to health and address structural disadvantage as a persistent threat to Indigenous wellbeing. Our findings call for holistic, early-life, family-centred strategies and to reduce barriers to accessing support. We highlight the need for policies that enable young people to flourish in their identity and culture. Key messages • Many Māori young people experience pervasive structural disadvantage starting before they are born, persisting throughout childhood and adolescence which is an omnipresent threat to their wellbeing. • Supporting cultural connectedness for Indigenous youth is important but cannot substitute for policies addressing structural disadvantages that contribute to health inequities.

Objective detection of wheeze at home by parents through a digital device: usage patterns and relationship with SABA administration.

Wheezing is an important indicator of exacerbated respiratory symptoms in early childhood and must be monitored to regulate pharmacological therapy. However, parents' subjective perception of wheezing in their children is not always precise. We investigated the objective identification of children's wheezing by parents using a digital wheeze detector (WheezeScanTM, OMRON Healthcare Co. Ltd), its longitudinal usage patterns, and its relationship with SABA administration. We conducted a secondary nested analysis of data from the intervention arm of a multi-center randomized controlled trial completed in 2021-2022 in Berlin (Germany), London (United Kingdom), and Istanbul (Turkey). Children aged 4 to 84 months with doctor's diagnosed wheezing (GINA step 1 or 2) were included. Using an electronic diary (Wheeze-MonitorTM, TPS), parents monitored and recorded for 120 days at home the presence or absence of their child's wheezing, detected both, with WheezeScanTM ("objective" wheezing), and subjective ("perceived" wheezing). Parents also recorded the child's symptoms, medication intake, and family quality of life. Questionnaires regarding symptom control, quality of life, and parental self-efficacy were answered at baseline and after 90 and 120 days. Eighty-one/87 families completed the intervention arm of the study. WheezeScanTM was on average used 0.7 (SD 0.6) times a day, with each patient reporting a positive, negative, or "error" outcome on average in 57%, 39%, and 5% of measurements, respectively. The use of WheezeScanTM declined slightly during the first 90 days of monitoring and steeply thereafter. Repeated usage of WheezeScanTM in the same day was more frequent after a "wheeze" (HR 1.5, 95% CI 1.37-1.65, p < 0.001) and an "error" (HR 2.01, 95% CI 1.70-2.38, p < 0.001) result, compared to a "no wheeze" outcome. The average per-patient daily agreement between "objective" and "perceived" wheezing/non-wheezing was 75% at the start of the monitoring period and only weakly persisted as time passed (Spearman's rho=0.09). The frequency of short-acting beta-2-agonists (SABA) administration was lower in days with closely interspaced consecutive device uses during which the patient's status was perceived as "never wheeze" (32/455, 7%) than in those perceived as "persistent wheeze" (53/119, 44%; OR 36.6, 95% CI [14.3, 94.1]). Daily use of a digital WheezeScanTM at home allows parents to detect their child's unperceived wheezing and discloses to caregivers the longitudinal patterns of a child's wheezing disorder. Digital monitoring of wheezing also highlights poor adherence to guidelines in SABA administration for wheezing children, with under-treatment being much more frequent than over-treatment. This pioneering study opens new perspectives for further investigation of digital wheeze detectors in the early diagnosis and proper self-management of wheezing disorders in childhood.

A genetic assessment of natural barriers for isolating a proposed Greenback Cutthroat Trout reintroduction area

AbstractObjectiveNative inland trout conservation efforts rely on physical barriers to exclude nonnative salmonids from target habitats. We used genetic techniques to evaluate a series of natural waterfalls for their potential to serve as barriers to prevent nonnative salmonids from entering a proposed reintroduction area for federally threatened Greenback Cutthroat Trout Oncorhynchus virginalis stomias.MethodsGenetic samples were collected from nonnative Brook Trout Salvelinus fontinalis at 11 sampling reaches above and below natural waterfalls (height: ~1–3 m under base flow conditions) along a 33‐km segment of Colorado's upper Cache la Poudre River near the outflow of the proposed reintroduction area. To evaluate whether upstream movement of Brook Trout is restricted by any of these waterfalls, we characterized longitudinal trends in genetic diversity along the river corridor and examined patterns of genetic differentiation and population structure in relation to waterfall locations using a panel of microsatellites.ResultWe found no evidence that the waterfalls served as complete movement barriers for nonnative Brook Trout based on genetic clustering analyses, estimates of population differentiation, and longitudinal genetic patterns. Our multilocus assessment did not identify alleles restricted to downstream reaches, and the river segment was genetically homogenized.ConclusionOur evaluation suggests that the existing waterfalls do not fully prevent upstream movement by nonnative Brook Trout, and thus barrier modification would be needed to establish an isolated Greenback Cutthroat Trout population in the proposed wilderness area.

Respiratory Trajectories and Correlation with Serum Biochemical Indices in Spinal and Bulbar Muscular Atrophy

Background/Objectives: The primary life-threatening complication in spinal–bulbar muscular atrophy (SBMA) is ventilatory failure. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years. Methods: We collected data from 9 genetically confirmed SBMA patients. Spirometric measurements [maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)], serum biochemical indices and SBMA functional rating scale (SBMAFRS) were collected every 6 months for 11 years. An average time curve was utilized to assess the changes in both pulmonary tests and serum biochemical indices of the patients. One-way repeated-measures ANOVA was applied to assess statistical differences. The Spearman’s rank correlation coefficient was utilized to evaluate the correlations between the respiratory function tests and serum biochemical and clinical indices. Results: A progressive decrease was observed in the respiratory function tests; the slope of the linear regression was significantly non-zero (p &lt; 0.0001) for all three time curves. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with FVC (r = 0.27), MIP (r = 0.53) and MEP (r = 0.51). MIP and MEP correlated with creatine phosphokinase (r = 0.3, r = 0.25, respectively) and MIP with creatinine levels (r = 0.31). Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in SBMA patients. The decline appears to be related to clinical deterioration and muscle denervation. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.