Longitudinal Cohort Research Articles

Sex Differences in the Severity and Progression of Neuropsychiatric Symptoms Across Different Dementia Types.

Dementia presents not only differing neuropsychiatric symptoms (NPS) across Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) but also subjective cognitive decline (SCD). This study examined sex-based variations in NPS severity and progression across these conditions. We performed a longitudinal cohort study including 1,068 participants. Hierarchical generalized linear mixed models were used to model NPS as a function of disease severity and biological sex at birth. Female participants with AD exhibited NPS more frequently than male participants. In FTD, female participants had more frequent delusions, hallucinations, and depression/dysphoria, while male participants had higher instances of agitation/aggression, apathy, disinhibition, and irritability/lability. In DLB, male participants showed higher instances of depression, and female participants more frequently experienced anxiety. In SCD, female participants showed higher nighttime behaviors. The trajectory of NPS significantly differed between sexes. These findings highlight sex-specific NPS impact in different neurodegenerative conditions.

Olfactory dysfunction and long-term trajectories of sleep disorders among early Parkinson's disease: findings from a longitudinal cohort.

Previous studies have suggested a connection between impaired olfactory function and an increased risk of rapid eye movement sleep behavior disorder (RBD) in individuals diagnosed with Parkinson's disease (PD). However, there is a gap in knowledge regarding the potential impact of olfactory dysfunction on the long-term patterns of sleep disorders among early PD patients. Data from the Parkinson's Progression Markers Initiative program included 589 participants with assessments of sleep disorders using the Epworth Sleepiness Scale (ESS) and RBD Screening Questionnaire (RBDSQ). Olfactory dysfunction at baseline was measured using the University of Pennsylvania Smell Identification Test. Trajectories of sleep disorders over a 5-year follow-up were identified using group-based trajectory modeling, and the relationship between olfactory dysfunction and sleep disorder trajectories was examined through binomial logistic regression. Two distinct trajectories of sleep disorders over the 5-year follow-up period were identified, characterized by maintaining a low or high ESS score and a low or high RBDSQ score. An inversion association was observed between olfactory function measures and trajectories of excessive daytime sleepiness (EDS) (odds ratio [OR]=0.97, 95% confidence interval [CI] 0.95, 1.00, P=0.038), after controlling for potential covariates. Similarly, olfactory function showed a significant association with lower trajectories of probable RBD (pRBD) (OR=0.96, 95% CI 0.94, 0.98, P=0.001) among early PD individuals. Consistent findings were replicated across alternative analytical models. Our findings indicated that olfactory dysfunction was associated with unfavorable long-term trajectories of sleep disorders among early Parkinson's disease.

Making Choices: A Multi-institutional, Longitudinal Cohort Study Assessing Changes in Treatment Outcome Valuation for Low-Risk Thyroid Cancer.

To evaluate the relative importance of treatment outcomes to patients with low-risk thyroid cancer (TC). Overuse of total thyroidectomy (TT) for low-risk TC is common. Emotions from a cancer diagnosis may lead patients to choose TT resulting in outcomes that do not align with their preferences. Adults with clinically low-risk TC enrolled in a prospective, multi-institutional, longitudinal cohort study from 11/2019-6/2021. Participants rated treatment outcomes at the time of their surgical decision and again 9 months later by allocating 100 points amongst 10 outcomes. T-tests and Hotelling's T2 statistic compared outcome valuation within and between subjects based on chosen extent of surgery (TT vs. lobectomy). Of 177 eligible patients, 125 participated (70.6% response) and 114 completed the 9-month follow-up (91.2% retention). At the time of the treatment decision, patients choosing TT valued the risk of recurrence more than those choosing lobectomy and the need to take thyroid hormone less (P<0.05). At repeat valuation, all patients assigned fewer points to cancer being removed and the impact of treatment on their voice, and more points to energy levels (P<0.05). The importance of the risk of recurrence increased for those who chose lobectomy and decreased for those choosing TT (P<0.05). The relative importance of treatment outcomes changes for patients with low-risk TC once the outcome has been experienced to favor quality of life over emotion-related outcomes. Surgeons can use this information to discuss the potential for asthenia or changes in energy levels associated with total thyroidectomy.

Using Machine Learning Models to Identify Factors Associated With 30-Day Readmissions After Posterior Cervical Fusions: A Longitudinal Cohort Study.

Readmission rates after posterior cervical fusion (PCF) significantly impact patients and healthcare, with complication rates at 15%-5% and up to 12% 90-day readmission rates. In this study, we aim to test whether machine learning (ML) models that capture interfactorial interactions outperform traditional logistic regression (LR) in identifying readmission-associated factors. The Optum Clinformatics Data Mart database was used to identify patients who underwent PCF between 2004-2017. To determine factors associated with 30-day readmissions, 5 ML models were generated and evaluated, including a multivariate LR (MLR) model. Then, the best-performing model, Gradient Boosting Machine (GBM), was compared to the LACE (Length patient stay in the hospital, Acuity of admission of patient in the hospital, Comorbidity, and Emergency visit) index regarding potential cost savings from algorithm implementation. This study included 4,130 patients, 874 of which were readmitted within 30 days. When analyzed and scaled, we found that patient discharge status, comorbidities, and number of procedure codes were factors that influenced MLR, while patient discharge status, billed admission charge, and length of stay influenced the GBM model. The GBM model significantly outperformed MLR in predicting unplanned readmissions (mean area under the receiver operating characteristic curve, 0.846 vs. 0.829; p<0.001), while also projecting an average cost savings of 50% more than the LACE index. Five models (GBM, XGBoost [extreme gradient boosting], RF [random forest], LASSO [least absolute shrinkage and selection operator], and MLR) were evaluated, among which, the GBM model exhibited superior predictive performance, robustness, and accuracy. Factors associated with readmissions impact LR and GBM models differently, suggesting that these models can be used complementarily. When analyzing PCF procedures, the GBM model resulted in greater predictive performance and was associated with higher theoretical cost savings for readmissions associated with PCF complications.

Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh

COVID-19 vaccines have been effective in preventing severe illness, hospitalization and death, however, the effectiveness diminishes with time. Here, we evaluated the longevity of antibodies generated by COIVD-19 vaccines and the risk of (re)infection in Bangladeshi population. Adults receiving two doses of AstraZeneca, Pfizer, Moderna or Sinopharm vaccines were enrolled at 2–4 weeks after second dosing and followed-up at 4-monthly interval for 1 year. Data on COVID-like symptoms, confirmed COVID-19 infection, co-morbidities, and receipt of booster dose were collected; blood was collected for measuring spike (S)- and nucleocapsid (N)-specific antibodies. S-specific antibody titers reduced by ~ 50% at 1st follow-up visit and continued to decline unless re-stimulated by booster vaccine dose or (re)infection. Individuals infected between follow-up visits showed significantly lower S-antibody titers at preceding visits compared to the uninfected individuals. Pre-enrolment infection between primary vaccination dosing exhibited 60% and 50% protection against reinfection at 5 and 9 months, respectively. mRNA vaccines provided highest odds of protection from (re)infection up to 5 months (Odds Ratio (OR) = 0.08), however, protection persisted for 9 months in AstraZeneca vaccine recipients (OR = 0.06). In conclusion, vaccine-mediated protection from (re)infection is partially linked to elevated levels of S-specific antibodies. AstraZeneca vaccine provided the longest protection.

Associations of Area-Level and Parental Individual-Level Social Deprivation with Glycemic Control over Time among Children with Type 1 Diabetes in France: A Longitudinal Cohort Study

Background. Poor glycemic control in patients with type 1 diabetes (T1D) is associated with greater social deprivation. However, the evidence is inconsistent in terms of the type of social deprivation (individual-level or area-level) and whether glycemic control changes over time. Here, we investigated the impacts of individual-level and area-level social deprivation on the glycated hemoglobin (HbA1c) trajectory from the time of T1D diagnosis. Materials and Methods. We retrospectively analyzed a cohort of children who were diagnosed with T1D between 2017 and 2020 at Bordeaux University Hospital. Social deprivation was assessed using both parental individual indicator (EPICES score) and ecological indicator (European Deprivation Index (EDI) score). Piecewise linear mixed-effects models were used to estimate the effects of social deprivation on HbA1c trajectory. Results. We included 168 patients. The most-deprived group included 29% and 22% of all patients, as revealed by the respective EPICES and EDI scores. The two indicators were poorly correlated. The short-term decrease in HbA1c level tended to be smaller in the most-deprived patients over the first 4 months after diagnosis than in other patients (slope difference of 2.68% per year compared with the slope among the least-deprived patients, P=0.056). The long-term trajectory was influenced by area-level deprivation (EDI score); the least-deprived patients (quintile 1) exhibited more stable mean HbA1c levels. Conclusions. Social deprivation may partially explain poor glycemic control in some patients; both short-term individual deprivation and long-term area-level deprivation may be involved. Further research is needed to determine how to integrate this information into a therapeutic strategy.

The impact of incident stroke on cognitive trajectories in later life

BackgroundCognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals.Methods19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke.ResultsDuring a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants.ConclusionsThese findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

Modifiable protective factors for mental health resilience in the offspring of depressed parents: A high‐risk longitudinal cohort spanning adolescence and adulthood

AbstractBackgroundSeveral protective factors have been identified for mental health (MH) resilience in adolescent offspring of depressed parents. However, it is unclear if these effects persist into adulthood.MethodsDepressed parents and their offspring (N = 188) from the Early Prediction of Adolescent Depression study were assessed four times (mean offspring ages 12.39, 13.77, 14.82, and 23.41). Mental health resilience was examined using residual scores (better‐than‐expected mood‐, behaviour‐, or anxiety‐related MH at mean age 23 given risk exposure), and categorically as sustained good MH across adolescence and young adulthood.ResultsOnly 9.2% of young adults demonstrated sustained good MH. Parents of resilient individuals showed lower comorbidity (anxiety, antisocial behaviour and harmful drinking) and higher depression remission. Considering adolescent protective factors, weak evidence was observed of associations of mood‐resilience with adolescent peer‐relationship quality (β = −0.20, 95%CI:−0.36, −0.04); friendship quality (β = −0.14, 95%CI:−0.31, 0.02); risk adjustment (β = −0.16, 95%CI:‐0.34, 0.03) and dysfunctional attitudes (β = 0.18, 95%CI:0.01, 0.35). There was weak evidence of behavioural‐resilience association with parent positive expressed emotion (β = −0.15, 95%CI:−0.31, 0.02) and offspring exercise (β = −0.37, 95%CI:−0.77, 0.03). No adolescent protective factors showed an association with anxiety‐resilience. For sustained good MH, there was weak evidence of an association with inhibitory control (OR = 0.39, 95%CI:0.14, 1.07). Strong evidence was observed for associations between young adult‐reported peer relationship quality and mood‐resilience (β = −0.35, 95%CI:−0.53, −0.17), behavioural‐resilience (β = −0.33, 95%CI:−0.51, −0.14) and anxiety‐resilience (β = −0.34, 95%CI:−0.53, −0.14), while weak evidence was observed of an association of social activities with anxiety‐resilience (β = −0.51, 95%CI:−0.97, −0.06).ConclusionsWe found limited evidence for the long‐lasting effects of adolescent protective factors on adult MH resilience. Social factors remained protective into young adulthood, while family factors did not. Early preventative intervention might not be sufficient to maintain good long‐term MH, and young people will likely require more prolonged support.

Mediterranean Diet and Mental Health in Children and Adolescents: A Systematic Review.

Childhood and adolescence are periods of critical importance in the development of mental health disorders. The Mediterranean diet (MD) has been linked to multiple positive health outcomes, including reduced incidence of mental health disorders and fewer psychiatric symptoms. This study aimed to investigate the association between adherence to an MD and mental health outcomes in children and adolescents. A systematic literature review was conducted of original research that explored the relationship between psychiatric symptoms or disorders and adherence to an MD. The literature search was conducted on PubMed, Scopus, Web of Science, MEDES, Dialnet, and Latindex from inception to November 2022, and the Newcastle-Ottawa Scale was used to evaluate the quality of studies. A total of 13 studies (6 cross-sectional, 4 case-control, 2 randomized clinical trials, and 1 longitudinal cohort) out of 450 met the inclusion criteria. A total of 3058 children or adolescents with a mean age range from 8.6 to 16.2 years were included. Among the reviewed studies, 5 (71.42%) of those looking at attention-deficit/hyperactivity disorder, 4 (80%) examining depression, and 2 (50%) assessing anxiety found a significant protective association. Seven articles (53.84%) were found to be of high quality and 6 (46.15%) of moderate quality. Adherence to an MD could be a protective factor for mental health in child and adolescent populations. This suggests that promoting an MD could help prevent the onset of clinical psychiatric symptoms, reduce symptom severity, and improve prognosis in young patients. PROSPERO registration no. CRD42021276316.

Clinical HIV outcome trajectories associated with a history of child protective service out-of-home care: Longitudinal cohort findings with women living with HIV in Canada.

Knowledge gaps exist regarding the effects of experiencing child protective services (CPS) out-of-home care (e.g. foster homes) among women with HIV. We examined whether CPS out-of-home care was associated with HIV clinical outcome trajectories among women with HIV in a longitudinal cohort study in Ontario, British Columbia, and Quebec, Canada. At three timepoints across 5 years (2013-2018), we examined self-reported current antiretroviral therapy (ART) use and viral load (VL) detectability (>50 copies/mL). We used latent class growth analysis (LCGA) to identify trajectories of ART use and VL outcomes across study waves. LCGA identifies subgroups (classes) with similar trajectories within the sample. We assessed whether HIV outcome trajectories could be predicted by CPS history. We then conducted a mediation analysis to test whether a mental health latent construct mediated the association between CPS history and detectable VL. Nearly one-fifth (n = 272; 19%) of participants (n = 1422; mean age 42.8 years) reported CPS out-of-home care. Most participants (89%) were in classes that consistently used ART and had an undetectable VL. Individuals with CPS out-of-home care histories were twice as likely to have a consistently detectable VL (β = 0.72, p = 0.02); there were no differences in ART use trajectories. In mediation analyses, we found an indirect path from CPS history to a consistently detectable VL via baseline mental health status (β = 0.02, 95% confidence interval 0.005-0.04, p = 0.02), with a significant odds ratio (1.12, z = 2.43, p = 0.02). Among women with HIV in Canada, experiencing childhood CPS out-of-home care was associated with a reduced likelihood of achieving viral suppression, via poorer mental health.

The CATFISH study: An evaluation of a water fluoridation program in Cumbria, UK.

The objective was to assess the effectiveness of a Water Fluoridation program on a contemporary population of children. The study used a longitudinal prospective cohort design. In Cumbria, England, two groups of children were recruited and observed over a period of 5-6 years. The Birth Cohort consisted of families recruited from two hospitals in Cumbria where children were conceived after water fluoridation was reintroduced. The systemic and topical effects of community water fluoridation were evaluated in the Birth Cohort. The Older Cohort were approximately 5 years old and recruited from primary schools in Cumbria, shortly after water fluoridation was reintroduced. The predominantly topical effects of fluoridated water were evaluated in the Older Cohort. The primary outcome was the proportion of children with clinical evidence of caries experience in their primary (Birth Cohort) or permanent teeth (Older Cohort). Unadjusted and adjusted regression models were used for analysis. The final clinical examinations for the Birth Cohort involved 1444 participants (mean age 4.8 years), where 17.4% of children in the intervention group were found to have caries experience, compared to 21.4% in the control group. A beneficial effect of water fluoridation was observed adjusting for deprivation (a socioeconomic measure), sex, and age, (adjusted odds ratio 0.74 95% CI 0.55 to 0.98). The final Older Cohort clinical examinations involved 1192 participants (mean age 10.8 years) where 19.1% of children in the intervention group were found to have caries experience compared to 21.9% in the control group (adjusted odds ratio 0.80, 95% CI 0.58 to 1.09). For both the Birth Cohort and Older Cohort there was evidence of a beneficial effect on dmft/DMFT count (IRR 0.61, 95% CI 0.44, 0.86) and (IRR 0.69, 95% CI 0.52, 0.93) respectively. No conclusive proof was found to indicate that the effectiveness of water fluoridation differed across area deprivation quintiles. In the contemporary context of lower caries levels and widespread use of fluoride toothpaste, the impact of water fluoridation on the prevalence of caries was smaller than previous studies have reported. It is important to consider the clinical importance of the absolute reduction in caries prevalence against the use of other dental caries preventive measures.

Long-Term Outcomes Associated With β-Lactam Allergies

β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug events and antibiotic-resistant infections during inpatient health care encounters, but the understanding of the long-term outcomes of patients with BL allergies remains limited. To evaluate the long-term clinical outcomes of patients with BL allergies. This longitudinal retrospective cohort study was conducted at a single regional health care system in western Pennsylvania. Electronic health records were analyzed for patients who had an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007 and 2008. Patients were followed-up until death or the end of 2018. Data analysis was performed from January 2022 to January 2024. The presence of any BL class antibiotic in the allergy section of a patient's electronic health record, evaluated at the earliest occurring observed health care encounter. The primary outcome was all-cause mortality, derived from the Social Security Death Index. Secondary outcomes were defined using laboratory and microbiology results and included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, or vancomycin-resistant Enterococcus (VRE) and severity and occurrence of acute kidney injury (AKI). Generalized estimating equations with a patient-level panel variable and time exposure offset were used to evaluate the odds of occurrence of each outcome between allergy groups. A total of 20 092 patients (mean [SD] age, 62.9 [19.7] years; 12 231 female [60.9%]), of whom 4211 (21.0%) had BL documented allergy and 15 881 (79.0%) did not, met the inclusion criteria. A total of 3513 patients (17.5%) were Black, 15 358 (76.4%) were White, and 1221 (6.0%) were another race. Using generalized estimating equations, documented BL allergies were not significantly associated with the odds of mortality (odds ratio [OR], 1.02; 95% CI, 0.96-1.09). BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with C difficile infection (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14). Documented BL allergies were not associated with the long-term odds of mortality but were associated with antibiotic-resistant infections. Health systems should emphasize accurate allergy documentation and reduce unnecessary BL avoidance.

Agreement between audiometric hearing loss and self-reported hearing difficulty on the Revised Hearing Handicap Inventory differs by demographic factors.

New standardised measures of self-reported hearing difficulty can be validated against audiometric hearing loss. This study reports the influence of demographic factors (age, sex, race and socioeconomic position (SEP)) on the agreement between audiometric hearing loss and self-reported hearing difficulty. Participants were 1558 adults (56.9% female; 20.0% racial minority; mean age 63.7 (SD 14.1) years) from the Medical University of South Carolina Longitudinal Cohort Study of Age-Related Hearing Loss (1988-current). Audiometric hearing loss was defined as the average of pure-tone thresholds at frequencies 0.5, 1.0, 2.0 and 4.0 kHz >25 dB HL in the worse ear. Self-reported hearing difficulty was defined as ≥6 points on the Revised Hearing Handicap Inventory (RHHI) or RHHI screening version (RHHI-S). We report agreement between audiometric hearing loss and the RHHI(-S), defined by sensitivity, specificity, accuracy, positive predictive value, negative predictive value and observed minus predicted prevalence. Estimates were stratified to age group, sex, race and SEP proxy. The prevalence of audiometric hearing loss and self-reported hearing difficulty were 49.0% and 48.8%, respectively. Accuracy was highest among participants aged <60 (77.6%) versus 60-70 (71.4%) and 70+ (71.9%) years, for white (74.6%) versus minority (68.0%) participants and was similar by sex and SEP proxy. Generally, agreement of audiometric hearing loss and RHHI(-S) self-reported hearing difficulty differed by age, sex and race. Relationships of audiometric hearing loss and self-reported hearing difficulty vary by demographic factors. These relationships were similar for the full (RHHI) and screening (RHHI-S) versions of this tool.

Left Atrial Mechanics Following Preeclamptic Pregnancy.

Preterm preeclampsia is a pregnancy complication associated with myocardial dysfunction and premature cardiovascular disease morbidity and mortality. Left atrial (LA) strain is a noninvasive index of left ventricular end diastolic pressure and an early marker of heart failure risk. This study aimed to evaluate LA strain during the postpartum period in participants with and without preterm preeclampsia and to assess whether this varied in the presence of hypertension and/or cardiac dysfunction. In this longitudinal cohort study, 321 women from 28 hospitals with preterm preeclampsia (cases) underwent cardiovascular assessment 6 months postpartum. This is a secondary analysis of the PHOEBE study (ISRCTN01879376). An uncomplicated pregnancy control group (n=30) was recruited from a single center for comparison. A full cross-sectional transthoracic echocardiogram was performed, and from these images, the myocardial strain of the left atrium, including reservoir, conduit, and contractile strain, as well as LA stiffness, were calculated. At 6 months postpartum, compared with controls, prior preeclampsia was associated with a significantly attenuated LA reservoir, conduit, and contractile strain, as well as increased LA stiffness (all P<0.001). LA strain was further reduced in preeclamptic women who had and had not developed hypertension, systolic, or diastolic dysfunction at 6 months postpartum (all P<0.05). LA mechanics were significantly attenuated at 6 months postpartum in participants with preterm preeclampsia, whether or not they remained hypertensive or had evidence of ventricular dysfunction. Further studies are needed to determine whether postnatal LA strain may identify women at greater risk for future cardiovascular disease.

The effect of the COVID-19 pandemic on pediatric emergency department utilization in three regions in Switzerland.

The COVID-19 pandemic was associated with a decrease in emergency department (ED) visits. However, contradictory, and sparse data regarding children could not yet answer the question, how pediatric ED utilization evolved throughout the pandemic. Our objectives were to investigate the impact of the pandemic in three language regions of Switzerland by analyzing trends over time, describe regional differences, and address implications for future healthcare. We conducted a retrospective, longitudinal cohort study at three Swiss tertiary pediatric EDs (March 1st, 2018-February 28th, 2022), analyzing the numbers of ED visits (including patients` age, triage categories, and urgent vs. non-urgent cases). The impact of COVID-19 related non-pharmaceutical interventions (NPIs) on pediatric ED utilization was assessed by interrupted time series (ITS) modelling. Based on 304'438 ED visits, we found a drop of nearly 50% at the onset of NPIs, followed by a gradual recovery. This primarily affected children 0-4years, and both non-urgent and urgent cases. However, the decline in urgent visits appeared to be more pronounced in two centers compared to a third, where also hospitalization rates did not decrease significantly during the pandemic. A subgroup analysis showed a significant decrease in respiratory and gastrointestinal diseases, and an increase in the proportion of trauma patients during the pandemic. The COVID-19 pandemic had substantial effects on number and reasons for pediatric ED visits, particularly among children 0-4years. Despite equal regulatory conditions, the utilization dynamics varied markedly between the three regions, highlighting the multifactorial modification of pediatric ED utilization during the pandemic. Furthermore, future policy decisions should take regional differences into account.

A functional survey of the regulatory landscape of estrogen-receptor-positive breast cancer evolution.

Only a handful of somatic alterations have been linked to endocrine therapy resistance in hormone-dependent breast cancer (HDBC), potentially explaining ~40% of relapses. If other mechanisms underlie the evolution of HDBC under adjuvant therapy is currently unknown. In this work, we employ functional genomics to dissect the contribution of cis-regulatory elements (CREs) to cancer evolution by focusing on 12 megabases of non-coding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Parallel epigenetic perturbation (CRISPRi) in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies a limited set of non-coding changes potentially involved in therapy resistance. Overall, our data uncover how endocrine therapies triggers the emergence of transient features which could ultimately be exploited to hinder the adaptive process.

Genetic Architectures of Adolescent Depression Trajectories in 2 Longitudinal Population Cohorts

Adolescent depression is characterized by diverse symptom trajectories over time and has a strong genetic influence. Research has determined genetic overlap between depression and other psychiatric conditions; investigating the shared genetic architecture of heterogeneous depression trajectories is crucial for understanding disease etiology, prediction, and early intervention. To investigate univariate and multivariate genetic risk for adolescent depression trajectories and assess generalizability across ancestries. This cohort study entailed longitudinal growth modeling followed by polygenic risk score (PRS) association testing for individual and multitrait genetic models. Two longitudinal cohorts from the US and UK were used: the Adolescent Brain and Cognitive Development (ABCD; N = 11 876) study and the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 8787) study. Included were adolescents with genetic information and depression measures at up to 8 and 4 occasions, respectively. Study data were analyzed January to July 2023. Trajectories were derived from growth mixture modeling of longitudinal depression symptoms. PRSs were computed for depression, anxiety, neuroticism, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism in European ancestry. Genomic structural equation modeling was used to build multitrait genetic models of psychopathology followed by multitrait PRS. Depression PRSs were computed in African, East Asian, and Hispanic ancestries in the ABCD cohort only. Association testing was performed between all PRSs and trajectories for both cohorts. A total sample size of 14 112 adolescents (at baseline: mean [SD] age, 10.5 [0.5] years; 7269 male sex [52%]) from both cohorts were included in this analysis. Distinct depression trajectories (stable low, adolescent persistent, increasing, and decreasing) were replicated in the ALSPAC cohort (6096 participants; 3091 female [51%]) and ABCD cohort (8016 participants; 4274 male [53%]) between ages 10 and 17 years. Most univariate PRSs showed significant uniform associations with persistent trajectories, but fewer were significantly associated with intermediate (increasing and decreasing) trajectories. Multitrait PRSs-derived from a hierarchical factor model-showed the strongest associations for persistent trajectories (ABCD cohort: OR, 1.46; 95% CI, 1.26-1.68; ALSPAC cohort: OR, 1.34; 95% CI, 1.20-1.49), surpassing the effect size of univariate PRS in both cohorts. Multitrait PRSs were associated with intermediate trajectories but to a lesser extent (ABCD cohort: hierarchical increasing, OR, 1.27; 95% CI, 1.13-1.43; decreasing, OR, 1.23; 95% CI, 1.09-1.40; ALSPAC cohort: hierarchical increasing, OR, 1.16; 95% CI, 1.04-1.28; decreasing, OR, 1.32; 95% CI, 1.18-1.47). Transancestral genetic risk for depression showed no evidence for association with trajectories. Results of this cohort study revealed a high multitrait genetic loading of persistent symptom trajectories, consistent across traits and cohorts. Variability in univariate genetic association with intermediate trajectories may stem from environmental factors. Multitrait genetics may strengthen depression prediction models, but more diverse data are needed for generalizability.

Chronic use of Antihypertensive Medications and Peak Exercise Blood Pressure in Adult Men and Women from the BALL ST Cohort.

To determine if individuals chronically (>1 year) prescribed antihypertensive medications have a normal BP response to peak exercise compared to unmedicated individuals. Participants included 2,555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 year were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the Amercian Heart Association. The unmedicated group had a greater prevalence (p < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence (p < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher (p < 0.01) in medicated compared to unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP (p = 0.613), risk factors (p = 0.104), or cardiorespiratory fitness (p = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP (p = 0.039), but not for men (p = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors and cardiorespiratory fitness (p = 0.022). Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension.

How do labour market conditions explain the development of mental health over the life-course? a conceptual integration of the ecological model with life-course epidemiology in an integrative review of results from the Northern Swedish Cohort

BackgroundThe aim of this study was to contribute to the theoretical development within the field of labour market effects on mental health during life by integrating Bronfenbrenner’s ecological model with mainly earlier theoretical work on life-course theory.MethodsAn integrative review was performed of all 52 publications about labour market conditions in relation to mental health from the longitudinal Northern Swedish Cohort study. Inductive and deductive qualitative content analysis were performed in relation to Bronfenbrenner’s ecological framework combined with life-course theories.ResultsThe following nine themes were identified: 1. Macroeconomic recession impairs mental health among young people. 2. The mental health effects on individuals of youth unemployment seem rather insensitive to recession. 3. Small but consistent negative effect of neighbourhood unemployment and other work-related disadvantaged on individuals’ mental health over life. 4. Youth unemployment becomes embodied as scars of mental ill-health over life. 5. Weak labour market attachment impairs mental health over life. 6. Bidirectional relations between health and weak labour market attachment over life. 7. Macrolevel structures are of importance for how labour market position cause poor health. 8. Unequal gender relations at work impacts negatively on mental health. 9. The agency to improve health over life in dyadic relations. Unemployment in society permeates from the macrolevel into the exolevel, defined by Bronfenbrenner as for example the labour market of parents or partners or the neighbourhood into the settings closest to the individual (the micro- and mesolevel) and affects the relations between the work, family, and leisure spheres of the individual. Neighbourhood unemployment leads to poor health among those who live there, independent of their employment status. Individuals’ exposure to unemployment and temporary employment leads to poorer mental health over the life-course. Temporal dimensions were identified and combined with Bronfenbrenner levels into a contextual life-course modelConclusionCombining the ecosocial theory with life-course theories provides a framework for understanding the embodiment of work-related mental health over life. The labour market conditions surrounding the individual are of crucial importance for the embodiment of mental health over life, at the same time as individual agency can be health promoting. Mental health can be improved by societal efforts in regulations of the labour market.

Non-cardiac birth defects and long-term risk of cardiovascular hospitalisation

BackgroundPatients with heart defects are at risk of developing cardiovascular disease. Our objective was to determine if non-cardiac birth defects are associated with the risk of cardiovascular hospitalisation.MethodsWe conducted a...