Functional Trajectories Research Articles

Nationwide lung function monitoring from infancy in newborn-screened children with cystic fibrosis.

Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor. This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study. 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment. Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.

Longitudinal developmental trajectories of functional connectivity reveal regional distribution of distinct age effects in infancy.

Prior work has shown that different functional brain networks exhibit different maturation rates, but little is known about whether and how different brain areas may differ in the exact shape of longitudinal functional connectivity growth trajectories during infancy. We used resting-state functional magnetic resonance imaging (fMRI) during natural sleep to characterize developmental trajectories of different regions using a longitudinal cohort of infants at 3weeks (neonate), 1year, and 2years of age (n = 90; all with usable data at three time points). A novel whole brain heatmap analysis was performed with four mixed-effect models to determine the best fit of age-related changes for each functional connection: (i) growth effects: positive-linear-age, (ii) emergent effects: positive-log-age, (iii) pruning effects: negative-quadratic-age, and (iv) transient effects: positive-quadratic-age. Our results revealed that emergent (logarithmic) effects dominated developmental trajectory patterns, but significant pruning and transient effects were also observed, particularly in connections centered on inferior frontal and anterior cingulate areas that support social learning and conflict monitoring. Overall, unique global distribution patterns were observed for each growth model indicating that developmental trajectories for different connections are heterogeneous. All models showed significant effects concentrated in association areas, highlighting the dominance of higher-order social/cognitive development during the first 2 years of life.

Kidney function monitoring and trajectories in patients with atrial fibrillation.

Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently co-exist. The frequency of kidney monitoring and range of kidney function in patients with AF in clinical practice are uncertain. All adult Albertans with AF between 2008 and 2017 were identified using ICD-9 and -10 codes 427.3 and I48. Kidney Disease Improving Global Outcomes (KDIGO) risk categories were defined using eGFR by the Chronic Kidney Disease Epidemiology Collaborative equation and albuminuria results within 6months of eGFR measurement. eGFR trajectories were compared from baseline to maximum value within the following year. Among 105,946 patients with AF, 16.0% were KDIGO category G1 (eGFR ≥ 90), 49.0% G2 (60-89.9), 19.8% G3a (45-59.9), 11.4% G3b (30-44.9), and G4 3.8% (15-29.9). Albuminuria was normal/mild 83.4%, moderate 11.7%, and severe 4.9%. Kidney monitoring was more common among people with lower eGFR and worse albuminuria, from approximately twice annually for G1-2/A1-2 to 8 times annually in stage G4A3. Approximately 60-80% of patients received guideline-recommended monitoring, consistent across KDIGO stages. With lower baseline eGFR, annual change in eGFR decreased while the relative proportion of patients who worsened compared to improved increased: for baseline eGFR 60-89.9, 16.7% worsened vs 6.7% improved, but for eGFR 30-44.9, 8.8% worsened but only 1.0% improved. The frequency of kidney function monitoring in patients with AF increased with worsening KDIGO risk category and adhered to KDIGO guidelines in approximately three quarters of patients. A minority of patients had moderate to severe eGFR impairment, of whom most remained stable over 1year.

Long-Term Pulmonary Function Trajectories After Allogeneic Bone Marrow Transplantation

Long-Term Pulmonary Function Trajectories After Allogeneic Bone Marrow Transplantation

Eight-year trajectories and predictors of cognitive function in community-dwelling Korean older adults with cardiovascular diseases.

This study aims to identify longitudinal patterns and predictors of cognitive function trajectories among Korean older adults with cardiovascular diseases. This study is a longitudinal panel analysis based on secondary data. Data from the the Korean Longitudinal Study of Ageing (KLoSA) were used for analysis. The KLoSA is a representative panel survey of older Koreans. We analyzed responses from 301 participants aged ≥65 years who completed the same survey more than three times out of five waves between 2012 and 2020. Latent class growth modeling identified two trajectories of cognitive function in older people with cardiovascular diseases: "low and declining" (n = 81, 26.9%) and "high and declining" (n = 220, 73.1%). Participants in "the low and declining trajectory group" were more likely to have a low educational level, weak handgrip strength, depression, and low social participation at baseline than those in "the high and declining trajectory group." Our results indicate a need to develop community-based tailored interventions for improving handgrip strength, mental health, and social participation in delaying cognitive decline in older people with cardiovascular diseases considering their educational level. Healthcare providers should be more concerned about older people with a weaker handgrip, depression, and low social activities as a high-risk group for cognitive decline over time in cardiovascular care. Therefore, it is necessary to evaluate them early with standardized tools and make subsequent strategies for the older population with cardiovascular diseases.

Combined effects of temperature and monsoon on seasonal variations of atmospheric polycyclic aromatic hydrocarbons in the coastal Shanghai, China

An intensive sampling program was conducted at two coastal sites of megacity Shanghai - the emerging town Lingang New Area (LGNA), and the petrochemical-industry zone Jinshan Area (JSA) from July 2016–June 2017, to study the occurrence, sources, environmental behavior and fate of atmospheric polycyclic aromatic hydrocarbons (PAHs). Results showed the median concentrations of total atmospheric PAHs were 18 ng m−3 and 12 ng m−3 in JSA and LGNA, respectively, which were lower than those recently detected in northern coastal China, and previously detected in urban/suburban Shanghai. There was strong/opposite temperature dependence for gaseous and particle-bound PAHs, indicating the importance of ongoing local and nearby volatilization; While the gas-particle partitions of individual PAH compound changed dramatically with seasons, with most easily adsorbed on particles during colder months. The potential source contribution function (PSCF) and concentration weight trajectory (CWT) model demonstrated the interactions of terrestrial and marine air mass regulated by the East Asian monsoon. Specifically, PAHs released by wintertime coal heating in northern China and summertime marine shipping in East China Sea, that transported through northwest and southeast monsoon, respectively, and aggravated the pollution of coastal Shanghai, especially for the background site in LGNA. The positive matrix factorization (PMF) source apportionment suggested the dominance of petrogenic sources for gaseous PAHs, coal and biomass combustion sources for particle-bound PAHs, and further demonstrated the seasonal variations of these potential sources. Atmospheric PAHs would deposit to the coastal waters, with gaseous absorption fluxes almost an order of magnitude higher than those of particle-bound deposition.

Cumulative exposure to extreme heat and trajectories of cognitive decline among older adults in the USA

BackgroundThe projected increase in extreme heat days is a growing public health concern. While exposure to extreme heat has been shown to negatively affect mortality and physical health, very little...

Association of Childhood and Midlife Neighborhood Socioeconomic Position With Cognitive Decline

Early-life socioeconomic adversity may be associated with poor cognitive health over the life course. To examine the association of childhood and midlife neighborhood socioeconomic position (nSEP) with cognitive decline. This cohort study included 5711 men and women enrolled in the community-based Atherosclerosis Risk in Communities (ARIC) Study with repeated cognitive data measured over a median 27.0 years (IQR, 26.0-27.9 years) (1990-2019). Statistical analysis was performed from December 2022 through March 2023. Residence addresses for ARIC Study cohort participants were obtained at midlife (1990-1993) and as recalled addresses at 10 years of age (childhood). A composite nSEP z score was created as a sum of z scores for US Census-based measures of median household income; median value of owner-occupied housing units; percentage of households receiving interest, dividend, or net rental income; percentage of adults with a high school degree; percentage of adults with a college degree; and percentage of adults in professional, managerial, or executive occupations. Childhood nSEP and midlife nSEP were modeled as continuous measures and discretized into tertiles. A factor score for global cognition was derived from a battery of cognitive tests administered at 5 in-person visits from baseline to 2019. The rate of cognitive decline from 50 to 90 years of age was calculated by fitting mixed-effects linear regression models with age as the time scale and adjusted for race, sex, birth decade, educational level, and presence of the apolipoprotein E ε4 allele. Among 5711 ARIC Study participants (mean [SD] baseline age, 55.1 [4.7] years; 3372 women [59.0%]; and 1313 Black participants [23.0%]), the median rate of cognitive decline was -0.33 SDs (IQR, -0.49 to -0.20 SDs) per decade. In adjusted analyses, each 1-SD-higher childhood nSEP score was associated with a slower (β, -9.2%; 95% CI, -12.1% to -6.4%) rate of cognitive decline relative to the sample median. A comparable association was observed when comparing the highest tertile with the lowest tertile of childhood nSEP (β, -17.7%; 95% CI, -24.1% to -11.3%). Midlife nSEP was not associated with the rate of cognitive decline. In this cohort study of contextual factors associated with cognitive decline, childhood nSEP was inversely associated with trajectories of cognitive function throughout adulthood.

Incidence of hospital-acquired acute kidney injury and trajectories of glomerular filtration rate in older adults

BackgroundIn older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI.MethodsWe used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities.ResultsOut of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1–29.6); higher for men than women (33.9 (29.5–38.7) vs. 21.2 (18.1–24.6)). IR (CI) were lowest for persons aged 70–75 (13.1; 10.0-16.8) and highest for ≥ 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities.ConclusionAKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

Cognitive and functional trajectories in geriatric outpatients after a pharmacologic multidisciplinary intervention: A study protocol

BackgroundPolypharmacy is a common condition among older adults and is associated with adverse drug reactions and health outcomes, including falls, functional and cognitive impairment, and frailty. MethodsA prospective observational study will be conducted on older adults with polypharmacy. The aim is to assess the impact of a specialized outpatient clinic focused on pharmacotherapy optimization recently integrated into daily clinical practice in a Spanish public tertiary teaching hospital on patients’ functional and cognitive abilities. Patients who attend a first consultation and meet inclusion criteria (≥75 years old, have a life expectancy≥3 months, and polypharmacy (≥5 prescribed medications) will be invited to participate in the study, until reach a calculated sample size of 104 participants. Patients will be excluded if they are enrolled in a clinical trial related to medication or in the event of a no-show or cancellation of the appointment at the first visit. Participants will receive usual care: a first consultation including multidisciplinary pharmacological optimization in the context of a CGA and subsequent face-to-face and/or telephone follow-up (∼3 and ∼6 months). The primary endpoint will be the functional (Barthel index) and cognitive change in capacities (IPCR – Índice de Incapacidad psíquica de la Cruz Roja). Secondary endpoints include medication changes, changes in patients’ quality of life, rate of falling, and use of healthcare resources. DiscussionWe expect that the close collaboration between professionals from different disciplines working together will be an effective strategy to improve the functional and cognitive abilities of older adults. Trial registrationClinicalTrials.gov: NCT05408598 (March 1, 2022).

Long-Term Trajectories of Biomarkers, Functional, and Echocardiographic Parameters in Patients with Chronic Heart Failure from Dilated or Ischaemic Cardiomyopathy

Introduction: The long-term evolution of clinical, echocardiographic, and laboratory parameters of cardiac function in patients with chronic heart failure (HF) with either reduced (HFrEF) or mildly reduced (HFmrEF) left ventricular ejection fraction (LVEF) is incompletely characterised. Methods: We identified patients with chronic stable HF who presented at least twice to a university HF outpatient clinic between 1995 and 2021. Trajectories of NYHA functional class, LVEF, left ventricular internal end-diastolic diameter (LVIDD), NT-proBNP concentrations, and HF treatment over 10 years of follow-up were analysed using fractional polynomials. Analyses were repeated after stratifying patients according to aetiology (ischaemic vs. dilated) or HF category (HFrEF vs. HFmrEF). Results: A total of 2,132 patients were included, of whom 51% had ischaemic and 49% had dilated HF. Eighty six percent and 14% were classified as HFrEF and HFmrEF, respectively. Mean LVEF was 28 ± 10%, and median NT-proBNP and estimated glomerular filtration rate values were 1,170 (385–3,176) pmol/L and 81 (62–100) mL/min/1.73 m², respectively. Median follow-up was 5.2 (2.6–9.2) years. Overall, NYHA functional class and LVIDD trajectories were U-shaped, whereas LVEF and NT-proBNP concentrations markedly improved during the first year and remained stable thereafter. However, the evolution of HF parameters significantly differed with respect to HF category and aetiology, with greater improvements seen in patients with HFrEF of non-ischaemic origin. Improvements in HF variables were associated with optimization of HF therapy, notably with initiation and up-titration of renin-angiotensin-system blockers. Conclusion: This study provides insights into the natural history of HF in a large cohort of well-treated chronic HF outpatients with respect to subgroups of HF and different aetiologists.

CKD and Rapid Kidney Function Decline During the COVID-19 Pandemic

The direct and indirect effects of the coronavirus disease 2019 (COVID-19) pandemic on kidney function in the chronic kidney disease (CKD) population are not well understood. Cohort study. Retrospective study of kidney function trajectories using deidentified administrative claims and laboratory data for Medicare Advantage and commercially insured enrollees with CKD stages G3-4 between 2018 and2021. COVID-19 infection. Rapid kidney function decline defined as annual estimated glomerular filtration rate (eGFR) decline of≥40%. Propensity score matching was used to identify individuals without COVID-19 infection matched 1:1 to a COVID-19 infected cohort and indexed on the date of diagnosing COVID-19 infection, age, sex, race or ethnicity, and Charlson comorbidity index score. Outpatient kidney function was compared during the prepandemic period (January 1, 2018, to February 29, 2020) with the pandemic period (March 1, 2020, to August 31, 2021). Two creatinine measurements, after the infection date and≥60 days apart, were required to reduce correlation with acute infection. Of 97,203 enrollees with CKD G3-4, 9% experienced a COVID-19 infection. Characteristics of 8,901 propensity matched enrollees include mean age 74 years, 58% women, 67% White, and 63% CKD G3a, 28% CKD G3b, and 9% CKD G4. Median overall annual eGFR change was -2.65ml/min/1.73m2, with 76% of the cohort experiencing worsened eGFR in the pandemic period. Rapid kidney function decline was observed in 1.9% and 2.0% of enrollees in the prepandemic and pandemic periods, respectively. Rapid kidney function decline was observed in 2.5% of those with COVID-19 infection and 1.5% of those without COVID-19 infection (P<0.05). Factors associated with increased odds of rapid kidney function decline during pandemic included Asian race, higher Charlson comorbidity index, advancing CKD stage, prepandemic rapid kidney function decline, and COVID-19 infection. Retrospective study design with potential bias. COVID-19 infection increased odds of rapid kidney function decline during the pandemic. The downstream impact of pandemic-related eGFR decline on health outcomes, such as kidney failure or mortality, requires further study. We used a cohort of insured individuals with moderate-to-severe chronic kidney disease (CKD) to compare the rates of rapid kidney function decline in prepandemic and pandemic periods and to evaluate the impact of the coronavirus disease 19 (COVID-19) on kidney function decline. We found that overall rates of rapid kidney function decline did not change during the prepandemic and pandemic periods but were significantly higher in both periods among individuals with a COVID-19 infection. As CKD severity increased, rates of both rapid kidney function decline and COVID-19 increased. Advancing CKD, higher comorbid condition, Asian race, prepandemic rapid kidney function decline, and COVID-19 were all associated with higher odds of rapid kidney function decline in the pandemic. These findings suggest close monitoring is warranted for individuals with CKD and COVID-19.

Trajectories of physical function and quality of life in people with osteoarthritis: results from a 10-year population-based cohort

ObjectiveTo identify long-term trajectories of physical function and health-related quality of life (HRQoL) among people with hip and/or knee osteoarthritis (HKOA) and the sociodemographic, lifestyle, and clinical factors associated with different trajectories.MethodsParticipants with HKOA from the EpiDoC study, a 10-year follow-up (2011–2021) population-based cohort, were considered. Sociodemographic, lifestyle, and clinical variables were collected at baseline in a structured interview and clinical appointment. Physical function and HRQoL were evaluated with the Health Assessment Questionnaire (HAQ) and EuroQoL, respectively, at baseline and the three follow-ups. Group-based trajectory modeling identified physical function and HRQoL trajectories. Multinomial logistic regression analyzed the associations between the covariates of interest and trajectory assignment (p < 0.05).ResultsWe included 983 participants with HKOA. We identified three trajectories for each outcome: “consistently low disability” (32.0%), “slightly worsening moderate disability” (47.0%), and “consistently high disability” (21.0%) for physical function; “consistently high HRQoL” (18.3%), “consistently moderate HRQoL” (48.4%) and “consistently low HRQoL” (33.4%) for HRQoL. Age ≥ 75 years, female sex, multimorbidity, and high baseline clinical severity were associated with higher risk of assignment to poorer physical function and HRQoL trajectories. Participants with high education level and with regular physical activity had a lower risk of assignment to a poor trajectory. Unmanageable pain levels increased the risk of assignment to the “consistently moderate HRQoL” trajectory.ConclusionAlthough the trajectories of physical function and HRQoL remained stable over 10 years, approximately 70% of people with HKOA maintained moderate or low physical function and HRQoL over this period. Modifiable risk factors like physical activity, multimorbidity and clinical severity were associated with poorer physical function and HRQoL trajectories. These risk factors may be considered in tailored healthcare interventions.

Physical and mental functioning trajectory classes among older adults and their association with specialized healthcare use

BackgroundSex-specific physical and mental functioning trajectory classification could offer a way of understanding the differences in healthcare use at older age.MethodsUsing latent growth mixture models, sex-specific physical and mental functioning trajectory classes were formed for 1991 participants (mean age 61.5 years) of the Helsinki Birth Cohort Study. Physical and mental functioning were evaluated with the SF-36 survey conducted in clinical examinations in 2001–2004, 2011–2013, and 2017–2018. First and follow-up outpatient visits, emergency visits, and hospital days were extracted from a national register between the first clinical examination and the year 2017. We used regression models to examine the associations between healthcare use and trajectory classes.ResultsTwo physical and mental functioning trajectory classes, high and intermediate, were observed for both sexes. The intermediate physical functioning trajectory class was associated with higher utilization rates of all examined specialized healthcare services (fully-adjusted IRRs varying 1.36–1.58; 95% CI = 1.03–1.79, 95% CI = 1.21–2.05) compared to the high trajectory class. Relative to the high trajectory class, the intermediate mental trajectory class was associated with the use of first outpatient visits (fully-adjusted IRRs 1.17, 95% CI = 1.03–1.33 for men, and 1.16, 95% CI = 1.04–1.30 for women). The findings were similar among both sexes.ConclusionsCompared to the high trajectory class, the intermediate physical functioning trajectory class was associated with greater specialized healthcare use and the intermediate mental trajectory class with first outpatient visits. Public health interventions should be considered to support functioning with aging.

Lung function tracking in children with perinatally acquired HIV following early antiretroviral therapy initiation

IntroductionLung disease remains a frequent complication in children with perinatal HIV infection (CHIV) and exposure without infection (CHEU), resulting in diminished lung function. In CHIV, early antiretroviral therapy (ART) initiation...

Intrinsic capacity and 5-year late-life functional ability trajectories of Chinese older population using ICOPE tool: the Rugao Longevity and Ageing Study.

Knowledge of how intrinsic capacity (IC) shape functional ability (FA) trajectories in later life remains unclear. We investigated the changes in IC and their impact on 5-years FA trajectories in the Chinese older population. A total of 1640 older adults from the Rugao Longitudinal Ageing Study were included and analyzed. FA was assessed by The Lawton Instrumental Activities of Daily Living Scale (IADLs). We used cognition, psychology, locomotion, sensory capacity, and vitality to capture the multiple domains of IC according to the ICOPE method. The IC was derived retrospectively from variables collected before this was described by WHO. At baseline, a higher IC was associated with higher IADLs (β = 0.98, 95% CI 0.90, 1.06, P < 0.001). Individuals with declines in IC between wave1 and wave2 experienced a faster decline in IADLs over time (β = - 0.28, 95% CI - 0.40, - 0.16, P < 0.001) after considering covariates. One or more impairment IC scores at baseline strongly predicted death (HR = 1.20, 95% CI 1.11, 1.30, P < 0.001). In addition, according to the IC scores at baseline, we stratify IC in low, middle, and high, compared with those in the high IC score, those in the low were associated with a 2.56-fold (95% CI 1.64, 4.01, P < 0.001) higher risk of mortality, after adjustment for variables. Changes in IC shape FA trajectories. IC impairment is associated with an increased risk of death. Assessing intrinsic capacity would facilitate early identification of older adults at high risk of adverse outcomes and prompt targeted interventions.

Lung Function Trajectories and Associated Mortality among Adults with and without Airway Obstruction.

Rationale: Spirometry is essential for diagnosis and assessment of prognosis in patients with chronic obstructive pulmonary disease (COPD). Objectives: To identify FEV1 trajectories and their determinants on the basis of annual spirometry measurements among individuals with and without airway obstruction (AO) and to assess mortality in relation to trajectories. Methods: From 2002 through 2004, individuals with AO (FEV1/VC < 0.70, n = 993) and age- and sex-matched nonobstructive (NO) referents were recruited from population-based cohorts. Annual spirometry until 2014 was used in joint-survival latent-class mixed models to identify lung function trajectories. Mortality data were collected during 15 years of follow-up. Measurements and Main Results: Three trajectories were identified among the subjects with AO and two among the NO referents. Trajectory membership was driven by baseline FEV1% predicted (FEV1%pred) in both groups and also by pack-years in subjects with AO and current smoking in NO referents. Longitudinal FEV1%pred depended on baseline FEV1%pred, pack-years, and obesity. The trajectories were distributed as follows: among individuals with AO, 79.6% in AO trajectory 1 (FEV1 high with normal decline), 12.8% in AO trajectory 2 (FEV1 high with rapid decline), and 7.7% in AO trajectory 3 (FEV1 low with normal decline) (mean, 27, 72, and 26 ml/yr, respectively) and, among NO referents, 96.7% in NO trajectory 1 (FEV1 high with normal decline) and 3.3% in NO trajectory 2 (FEV1 high with rapid decline) (mean, 34 and 173 ml/yr, respectively). Hazard for death was increased for AO trajectories 2 (hazard ratio [HR], 1.56) and 3 (HR, 3.45) versus AO trajectory 1 and for NO trajectory 2 (HR, 2.99) versus NO trajectory 1. Conclusions: Three different FEV1 trajectories were identified among subjects with AO and two among NO referents, with different outcomes in terms of FEV1 decline and mortality. The FEV1 trajectories among subjects with AO and the relationship between low FVC and trajectory outcome are of particular clinical interest.

Predictors of executive function trajectories in adolescents with and without ADHD: Links with academic outcomes.

Changes in executive function (EF) occur during adolescence with several factors (e.g., parenting styles, socioeconomic status) influencing the development of EF abilities. These changes are important as EF has been strongly linked with a range of outcomes including academic achievement, job performance, and social-emotional well-being. However, few studies have examined variability in EF trajectories during this critical developmental period, or trajectories in samples known to have specific impairments with EF, such as adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD). The present study examined differential trajectories of three domains of parent-rated EF in 302 adolescents (167 males; Mage = 13.17 years) with and without ADHD (53.6% with ADHD) from grade 8 to 10. The study also explored whether adolescent ADHD, parent ADHD, and parents' own EF predicted EF trajectories in addition to the longitudinal relation between trajectories and academic outcomes. Findings suggest that adolescence is marked by significant variability in EF development due to factors such as ADHD status, parent ADHD, and parent EF ability. Additionally, adolescents who displayed poor EF abilities throughout middle and high school had significantly lower grade point averages and poorer parent-, teacher-, and self-reported academic outcomes. Implications for interventions targeting EF deficits among adolescents with and without ADHD are discussed.

Supranormal lung function: Prevalence, associated factors and clinical manifestations across the lifespan.

It is now well established that there are different life-long lung function trajectories in the general population, and that some are associated with better or worse health outcomes. Yet, the prevalence, clinical characteristics and risk factors of individuals with supranormal FEV1 or FVC values (above the upper-limit of normal [ULN]) in different age-bins through the lifetime in the general population are poorly understood. To address these questions, we investigated the prevalence of supranormal FEV1 and FVC values in the LEAD (Lung, hEart, sociAl and boDy) study, a general population cohort in Austria that includes participants from 6 to 82 years of age. We found that: (1) the prevalence of supranormal pre-bronchodilator FEV1 and FVC values was 3.4% and 3.1%, respectively, and that these figures remained relatively stable through different age-bins except for participants >60 years., in whom they increased (5.0% and 4.2%, respectively). Approximately 50% of supranormal individuals had both increased FEV1 and FVC values; (2) supranormal spirometric values were consistently accompanied by higher static lung volumes and lower specific airway resistance through the lifespan, indicating better overall lung function; and (3) multivariate regression analysis identified that female sex, higher muscle mass (FFMI), less diabetes and fewer respiratory symptoms were consistently associated with supranormal FEV1 and FVC values. Supranormal FEV1 and/or FVC values occur in about 3% of the general population in different age bins and are associated with better health markers.

Association of intrinsic capacity with incidence and mortality of cardiovascular disease: Prospective study in UK Biobank.

The World Health Organization proposed the concept of intrinsic capacity (IC; the composite of all the physical and mental capacities of the individual) as central for healthy ageing. However, little research has investigated the interaction and joint associations of IC with cardiovascular disease (CVD) incidence and CVD mortality in middle- and older-aged adults. Using data from 443130 UK Biobank participants, we analysed seven biomarkers capturing the level of functioning of five domains of IC to calculate a total IC score (ranging from 0 [better IC] to +4 points [poor IC]). Associations between IC score and incidence of six long-term CVD conditions (hypertension, stroke/transient ischaemic attack stroke, peripheral vascular disease, atrial fibrillation/flutter, coronary artery disease and heart failure), and grouped mortality from these conditions were estimated using Cox proportional models, with a 1-year landmark analysis to triangulate the findings. Over 10.6years of follow-up, CVD morbidity grouped (n=384380 participants for the final analytic sample) was associated with IC scores (0 to +4): mean hazard ratio (HR) [95% confidence interval, CI] 1.11 [1.08-1.14], 1.20 [1.16-1.24], 1.29 [1.23-1.36] and 1.56 [1.45-1.59] in men (C-index=0.68), and 1.17 [1.13-1.20], 1.30 [1.26-1.36], 1.52 [1.45-1.59] and 1.78 [1.67-1.89] in women (C-index=0.70). In regard to mortality, our results indicated that the higher IC score (+4 points) was associated with a significant increase in subsequent CVD mortality (mean HR [95% CI]: 2.10 [1.81-2.43] in men [C-index=0.75] and 2.29 [1.85-2.84] in women [C-index=0.78]). Results of all sensitivity analyses by full sample, sex and age categories were largely consistent independent of major confounding factors (P<0.001). IC deficit score is a powerful predictor of functional trajectories and vulnerabilities of the individual in relation to CVD incidence and premature death. Monitoring an individual's IC score may provide an early-warning system to initiate preventive efforts.