Longitudinal Study Research Articles

Neurodevelopment at Age 9 Years Among Children Born at 32 to 36 Weeks’ Gestation

ImportanceAlthough children born moderate to late preterm (MLP; 32-36 weeks’ gestation) have more neurodevelopmental problems compared with children born early term or later (≥37 weeks’ gestation), detailed understanding of affected domains at school age is lacking. Little is known of risk factors for poorer development.ObjectiveTo examine whether being born MLP compared with being born early term or later is associated with neurodevelopmental outcomes at age 9 years and to describe factors associated with poorer neurodevelopment in children born MLP.Design, Setting, and ParticipantsThis prospective, longitudinal cohort study recruited children born MLP and children born early term or later with healthy birth weight (≥2500 g) at a single tertiary hospital in Melbourne, Victoria, Australia, between December 7, 2009, and March 26, 2014. Nine-year follow-up occurred between June 20, 2019, and February 27, 2024.ExposureModerate to late preterm birth.Main Outcomes and MeasuresCognitive ability, academic performance, motor function, behavior, and social communication skills, assessed at 9-year follow-up. Group differences were estimated using linear, logistic, or quantile regression adjusted for multiple birth and socioeconomic risk. Multiple imputation was used to account for missing data. Associations of antenatal and neonatal factors and developmental delay at 2 years with poorer 9-year neurodevelopment were explored using univariable regression.ResultsOf 201 recruited children born MLP and 201 born early term or later, 159 born MLP (79.1%; 72 [45.3%] male) and 137 born early term or later (68.2%; 75 [54.7%] male) were assessed. Compared with children born early term or later, children born MLP had lower mean (SD) full-scale IQ scores (105.2 [13.6] vs 110.1 [13.0]; adjusted mean difference, −4.4 [95% CI, −7.7 to −1.0]) and poorer performance for cognitive domains, including verbal comprehension, visuospatial, and working memory. They also had poorer academic performance: pseudoword decoding (mean [SD] score, 103.0 [11.3] vs 107.3 [10.5]; adjusted mean difference, −4.0 [95% CI, −7.0 to −1.1]) and mathematics (mean [SD] score, 96.6 [14.7] vs 101.5 [14.5]; adjusted mean difference, −5.0 [95% CI, −8.8 to −1.2]). Children born MLP had similar manual dexterity to those born early term or later (mean [SD] score, 8.4 [3.5] vs 9.1 [3.4]; adjusted mean difference, −0.9 [95% CI, −1.8 to 0.04]) but more behavioral difficulties (50 of 158 [31.7%] vs 29 of 135 [21.5%]; adjusted risk ratio, 1.57 [95% CI, 1.06-2.33]). Developmental delay at 2 years was associated with poorer 9-year neurodevelopment across multiple domains.Conclusions and RelevanceIn this longitudinal cohort study of children born MLP, neurodevelopmental challenges persisted into school age. An assessment at age 2 years may assist in identifying children born MLP who are at risk of school-age impairments.

Why Do Optimal Targets for Itch and Skin Clearance Matter in Atopic Dermatitis Treatment? Insights from TARGET-DERM AD Registry

Introduction/Background: Atopic dermatitis (AD) patients undergoing treatment may only experience partial improvement in itch and skin lesions, often leading to suboptimal outcomes. The Aiming High in Eczema/Atopic Dermatitis (AHEAD) treat-to-target recommendations emphasize the importance of achieving optimal treatment targets, such as complete or near-complete itch relief and skin clearance. However, there is limited evidence on the impact of achieving these higher efficacy targets on patient-reported outcomes and quality of life in AD. Objectives: To evaluate the independent and combined effects of achieving optimal treatment targets for itch and skin clearance on patient-reported outcomes (PROs) in AD, based on the AHEAD treat-to-target recommendations. Method: A cross-sectional analysis was conducted on adult participants in TARGET-DERM AD, a longitudinal study with over 4,000 participants across 52 U.S. and Canadian clinical-practice sites (2019-2024). Itch severity was measured using the PROMIS Itch-Severity question (NRS-Itch, 0–10 scale), with scores of 0/1 indicating no or minimal itch. Skin severity was assessed using the validated Investigator Global Assessment (vIGA-AD), where 0/1 represents clear or almost clear skin. Associations between itch and skin severity with optimal patient outcomes including POEM 0–2 (clear/almost-clear disease), DLQI 0/1 (minimal/no impact on quality of life), NRS-Sleep 0/1, and NRS-Pain 0/1 were evaluated. Logistic regression models examined the main and interaction effects of itch and skin severity. Results: Among 1,920 patients (58.6% female; 54.5% Non-Hispanic White; 93.8% US; mean age 45 years), optimal DLQI, POEM, NRS-Sleep, and NRS-Pain occurred most frequently among those achieving the optimal treatment targets for itch (WI-NRS 0/1; 52.1%, 53.7%, 57.3%, and 83.1%, respectively) and skin clearance (vIGA-AD 0/1; 44.7%, 44.3%, 44.7%, and 74.3%, respectively). Compared to partial improvement, the adjusted odds ratios (aOR) of optimal PROs were greatest for participants with complete or near-complete resolution of both itch and skin lesions (DLQI 0/1: 20.0; POEM 0-2: 41.7; Sleep-NRS: 16.1; Pain-NRS: 6.0). Conclusions: Achieving optimal treatment targets for both itch and skin lesions markedly enhances patient-reported outcomes in AD. The results of this real-world study support treat-to-optimal targets to assess therapeutic effectiveness and optimize patient outcomes.

Relationships between high school students’ learning interest, learning motivation, and ocean literacy: a longitudinal study

Relationships between high school students’ learning interest, learning motivation, and ocean literacy: a longitudinal study

Rising Prevalence of Multiple Sclerosis in Switzerland - Results from the Swiss Multiple Sclerosis Registry

Introduction: Understanding the prevalence of multiple sclerosis (MS) provides information for healthcare planning and helps identify trends and patterns of disease occurrence. For Switzerland, the number of persons with MS (pwMS) was last estimated at approximately 15,000 in 2016. The study’s objectives are to update estimates of MS prevalence and characterise the change in MS prevalence in Switzerland between 2016 and 2021, the last year with complete administrative data. Methods: The Swiss MS Registry (SMSR) is an ongoing, longitudinal study in Switzerland. It has previously established a methodology to assess the epidemiology of MS in Switzerland by integrating SMSR data with administrative data on reimbursement approvals for disease-modifying therapies (DMTs). Subsequently, the benchmark-multiplier method is applied to the combined data. Using the same methodology, we calculated overall and sex- and age-specific prevalence rates for 2021. Furthermore, we descriptively analysed changes since 2016 by comparing the prevalence figures and demographic and clinical characteristics of pwMS in both years. Results: We estimated the population of pwMS in Switzerland at 18,140 [95% simulation interval 17,550-18,750], corresponding to a period prevalence of 200.8-214.5/100,000 inhabitants. Peak prevalence was observed in the 50 to 55-year age group. Compared to 2016, the 2021 estimate corresponds to a 20% increase (n=3,000). Extrapolating from Swiss population growth, we estimated that one-fifth of the observed prevalence increase may be attributed to a rising population. The proportion of pwMS in the age range from 50 to 64 (32.5% vs. 35.9%) and above 65 (8.0% vs. 11.1%) years increased. Consequently, the median [interquartile range] age increased from 47 [37-55] to 49 [38-57] years. The median age at diagnosis (36 [28-45] years) and the female-to-male ratio (2.7:1) remained stable since 2016. The proportion of pwMS treated with DMTs increased from 62.1% to 69.0%, with the largest change observed in infusion therapies (15.7% vs. 23.3%). Conclusion: The estimated MS prevalence in Switzerland has increased since the previous estimate in 2016, with a shift in peak prevalence towards older ages. Population growth explained around one-fifth of this increase, thus leaving room for contributions by additional factors, which require further investigation. The rising MS prevalence has several implications for healthcare, research and society.

Adverse Childhood Experiences are associated with Mental Health Problems later in life: An Umbrella Review of Systematic Review and Meta-analysis

Introduction: Evidence suggested a link between early adversity and mental health problems. However, it is unclear how much adverse childhood experiences (ACEs) contribute to mental health problems because researchers have produced inconsistent findings. Therefore, the objective of this umbrella review was to combine the contradictory data regarding the effect of ACEs on the development of mental health problems later in life in the global context. Methods: PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus, and Google Scholar which reported the effect of ACEs on the development of mental health problems were searched. The quality of the included studies was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed. Results: Forty-three SRM with 14707614 study participants were included. The pooled effect of ACEs on the development of mental health problems later in life in the global context is found to be (AOR=1.66 (1.46, 1.87)). Subgroup analysis based on country revealed (AOR=1.67(1.23, 2.11)) in UK, (AOR=0.61(0.41, 0.81)) in Canada, (AOR=1.55(1.40, 1.69)) in Brazil, (AOR=5.65(4.12, 7.18)) in Ethiopia, (AOR=1.92(1.45, 2.38)) in USA, (AOR=2.30(1.89, 2.72)) in Australia and (AOR=1.66(1.46, 1.87)) in irland. While subgroup analysis based on types of adverse childhood adverse experience: domestic violence ((AOR=4.13(1.96, 6.30)), maltreatment (AOR=1.5(0.79, 2.21)), physical abuse(AOR=1.56(1.43,1.63), sexual abuse (AOR=2.07(1.63, 2.51)), child abuse (AOR=5.66(4.12,7.18)), parental mental health problem (AOR=1.73(1.39,2.08)), bullying (AOR=1.99(1.69, 2.29), neglect(AOR=2.11(1.53,2.69)), and parental divorce (AOR=1.66(1.46,1.87)). Based on the type of mental health problem the pooled effect size is 1.87(1.45, 2.30) for depression and 1.67(1.22, 2.13) for anxiety. Conclusion: This umbrella review revealed that adverse childhood experience is significantly associated (with 66% increased risk) with anxiety and depression later in life in a global context. This association is most noticeable when one is subjected to domestic violence, maltreatment, physical abuse, sexual abuse, child abuse, parental mental health problems, bullying, neglect, and parental divorce. Childhood periods are a critical window of opportunity for reducing the risk of developing mental illness in the future and for implementing intervention measures. Preventing childhood maltreatment and addressing psychiatric risk factors can prevent psychopathology. Longitudinal studies are needed to optimize healthcare responses to ACEs. Increased awareness and public health interventions are needed to prevent childhood adversity and prevent mental problems among these victims. To optimize healthcare responses to unfavorable outcomes of childhood adversities, longitudinal and intervention research findings, more public health initiatives, and awareness are required.

Is Countermovement Jump an Indirect Marker of Neuromuscular Mechanism? Relationship with Isometric Knee Extension Test

Several studies have shown that force application is influenced by different neuromuscular mechanisms depending on the time of force application analysis in isometric knee extension test (IKE), and a countermovement jump (CMJ) has contributions from knee extension, so some CMJ variables could be indicators of such mechanisms. Purpose: The aim of this study was to determine the level of relationship of variables of IKE and bilateral CMJ tests. Methods: Male college soccer players (n = 25; corporal mass = 72 ± 8 kg; height = 171 ± 5 cm; age = 22 ± 2 years) performed the IKE at two angles (60° and 75°) on an isokinetic machine and the CMJ on two uniaxial force platforms. To determine the level of relationship, Pearson’s correlation coefficient was analyzed between the test variables. Results: Trivial to moderate correlations (r = −0.45 to 0.62; p < 0.05) were found between CMJ variables and IKE in both knee angles (60° and 75°); Conclusions: The variables of IKE have a trivial to moderate correlation with the variables of CMJ, so the variables of CMJ could not be considered interchangeably with those of IKE and therefore considered indicators of neuromuscular mechanisms isolated from the knee extensor function. Longitudinal design (fatigue or training protocols) should be realized to corroborate these results.

Dupilumab Improves Patient-Reported Outcomes as Early as 1 Month among Adults with Prurigo Nodularis in Clinical Practice: Initial Results from the RELIEVE-PN Study

Introduction: Dupilumab is a monoclonal antibody approved in the United States (US) for patients aged ≥18 years with prurigo nodularis (PN). This analysis evaluated the real-world initial impact of dupilumab therapy on symptoms and treatment satisfaction among US adults with PN. Methods: RELIEVE-PN is an ongoing longitudinal prospective patient survey study assessing the real-world effectiveness of dupilumab in the treatment of adult patients with PN. Adults with PN were recruited through the US dupilumab patient support program and surveyed before (baseline) and 1 month after dupilumab initiation. PN symptoms over the last 7 days were assessed using the worst-itch numeric rating scale (WI-NRS), average-itch NRS, skin pain NRS, and skin burning or stinging/tingling NRS (range 0 [no symptom] to 10 [most severe symptom] for all). Treatment satisfaction with current therapy was evaluated using a 7-point Likert scale from “extremely satisfied” to “extremely dissatisfied”. Results: Of 84 patients (mean age, 57.5 years; 79.8% female; 83.3% White) completing the baseline survey and initiating dupilumab, 62 (mean age, 56.4 years; 77.4% female; 83.9% White) completed the Month 1 survey. At baseline, mean (SD) WI-NRS, average itch NRS, skin pain NRS, and skin burning/tingling NRS were 7.70 (2.24), 6.45 (2.25), 5.06 (2.87), and 5.51 (3.02), respectively. By month 1, mean (SD) WI-NRS, average itch NRS, skin pain NRS, and skin burning or stinging/tingling NRS improved to 5.56 (2.89), 4.35 (2.23), 3.40 (2.46), and 3.76 (2.60), respectively (p<0.001 for all). Additionally, significantly more patients reported they were satisfied with current PN treatment(s) at 1 month after dupilumab treatment initiation vs prior to starting dupilumab (77.4% vs 13.1%; p<0.001). Conclusion: Early results from the RELIEVE-PN study demonstrate improvement in symptoms and patient satisfaction with therapy as early as 1-month from treatment initiation of dupilumab. Further comparative research is needed to confirm these findings. Acknowledgment: Research was funded by Sanofi and Regeneron Pharmaceuticals Inc.

Associations of Clinical Characteristics With Sudden Cardiac Arrest in People With Type 2 Diabetes With and Without Cardiovascular Disease: A Longitudinal Case-Control Study Using Routine Primary Care Data

OBJECTIVE To assess longitudinal associations with sudden cardiac arrest (SCA) of clinical characteristics recorded in primary care in people with type 2 diabetes (T2D), both with and without cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We performed a case-control study, with SCA case subjects with T2D from the Amsterdam Resuscitation Studies (ARREST) registry of out-of-hospital resuscitation attempts in the Dutch Noord-Holland region (2010–2020) and up to five matched (age, sex, T2D, general practitioner [GP] practice) non-SCA control subjects. We collected relevant clinical measurements, medication use, and medical history from GPs’ electronic health care records. We analyzed the associations of clinical characteristics and medication use with SCA in the total sample and in subgroups with or without CVD using multivariable time-dependent Cox regression (hazard ratios, 95% confidence intervals). RESULTS We included 689 SCA case subjects and 3,230 non-SCA control subjects. In multivariable models, low fasting glucose (<4.5 mmol/mol: 1.91 [1.00–3.64]), antihypertensive (1.80 [1.39–2.33]), glucose lowering (oral only: 1.32 [1.06–1.63]; insulin only: 2.31 [1.71–3.12]; oral and insulin: 1.64 [1.21–2.22]), heart failure (1.91 [1.55–2.35]), and QTc-prolonging prokinetic (1.78 [1.27–2.50]), antibiotic (1.35 [1.05–1.73]), and antipsychotic (2.10 [1.42–3.09]) medication were associated with SCA in the total sample. In subgroup effect modification analyses, QTc-prolonging antibiotic (1.82 [1.26–2.63]) and antipsychotic (3.10 [2.09–4.59]) medication use were associated with SCA only in those without CVD. CONCLUSIONS In people with T2D, low fasting glucose and QTc-prolonging prokinetic, antibiotic, or antipsychotic medication use and a history of heart failure are associated with SCA risk. Subgroup analyses indicate antibiotic and antipsychotic medication use increases SCA risk specifically in those without CVD.

Longitudinal interactions of L2 learners’ motivations and strategic behavior in strategies-based writing instruction

Abstract Strategic behavior for self-regulated learning (SRL) is crucial for academic success in L2 writing. Yet little is known about how learners’ motivation-related factors develop as their strategic behavior progresses during classroom instruction in L2 writing contexts. Informed by SRL theory, this longitudinal case study adopted multiple assessment approaches to explicating the development trajectories of two Chinese L2 writers’ motivational factors relating to expectancy, value, and goal orientation (i.e., self-efficacy, task value, and goal orientations) and strategic behavior in the classroom ecology of self-regulation strategies-based instruction. Participants were one high-proficiency writer and one low-proficiency writer who were enrolled in the self-regulation strategies-based writing course. They voluntarily participated in this study and completed semi-structured interviews and reflective journals at the beginning (T1), the middle (T2), and the end of the instruction (T3). Field notes were used to complement the primary data sources. The qualitative analyses revealed both students’ limited understanding of SRL strategies at the initial stage. Their strategic behavior progressed with the social and metacognitive scaffolding at T2, but only the high-proficiency writer sustained active engagement at T3. With different goal orientations and linguistic self-efficacy at the initial stage, both students reported noticeable increases in their intrinsic goal orientation, task value, and self-efficacy in classroom performance at T2 and T3. Their motivational states were also affected by linguistic proficiency, metacognitive scaffolding, and social interactions during the instruction. This study is expected to provide insights into how L2 writers’ strategic behavior progresses with their changes in motivations.

Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis

AbstractObjectiveBaseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS‐related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision‐making and guiding development of novel disease‐modifying treatments (DMTs).MethodsThis study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5‐ or 10‐year follow‐ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow‐up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures.ResultsDMT use was associated with lower odds of new PRL appearance (for high‐efficacy DMTs: odds ratio = 0.088, p = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (B = 0.527 additional PRLs, p = 0.013). A 24‐month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power.InterpretationEarly MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs.

Profiling serum immunodominance following SARS-CoV-2 primary and breakthrough infection reveals distinct variant-specific epitope usage and immune imprinting

Over the course of the COVID-19 pandemic, variants have emerged with increased mutations and immune evasive capabilities. This has led to breakthrough infections (BTI) in vaccinated individuals, with a large proportion of the neutralizing antibody response targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike glycoprotein. Immune imprinting, where prior exposure of the immune system to an antigen can influence the response to subsequent exposures, and its role in a population with heterogenous exposure histories has important implications in future vaccine design. Here, we develop an accessible approach to map epitope immunodominance of the neutralizing antibody response in sera. By using a panel of mutant Spike proteins in a pseudotyped virus neutralization assay, we observed distinct epitope usage in convalescent donors infected during wave 1, or infected with the Delta, or BA.1 variants, highlighting the antigenic diversity of the variant Spikes. Analysis of longitudinal serum samples taken spanning 3 doses of COVID-19 vaccine and subsequent breakthrough infection, showed the influence of immune imprinting from the ancestral-based vaccine, where reactivation of existing B cells elicited by the vaccine resulted in the enrichment of the pre-existing epitope immunodominance. However, subtle shifts in epitope usage in sera were observed following BTI by Omicron sub-lineage variants. Antigenic distance of Spike, time after last exposure, and number of vaccine boosters may play a role in the persistence of imprinting from the vaccine. This study provides insight into RBD neutralizing epitope usage in individuals with varying exposure histories and has implications for design of future SARS-CoV-2 vaccines.

Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer’s disease

AbstractDisease-modifying therapies for Alzheimer’s disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating mutation carriers from non-carrier controls 10-20 years before the estimated onset of clinical symptoms, depending on the statistical model used. However, after symptom onset the rate of change in CSF NfL continued to increase steadily, whereas the rate of change in plasma NfL leveled off. Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration. These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients.

Factors Influencing Outcome After Shoulder Arthroplasty (FINOSA Study): Protocol of a Prospective Longitudinal Study With Randomized Group Allocation

Background There is an increasing need for evidence-based postoperative rehabilitation strategies to optimize patient outcome. Knowledge of potential prognostic factors could steer the development of rehabilitation protocols and could result in better treatment outcomes and higher patient satisfaction. Objective This study aimed to investigate which potential prognostic factors predict baseline shoulder pain and function and its evolution in the first 2 years following surgery, in patients with total shoulder arthroplasty. The secondary objective is to investigate which potential prognostic factors predict baseline quality of life and its evolution in the first two years following surgery. Methods To reach the aims of this project, a prospective longitudinal study, running from January 2020 to March 2025, will be carried out with a follow-up of 48 months. Patients will be randomized based on sling wear. We will study factors such as shoulder function, patient expectations, psychosocial factors, lifestyle factors, sling wear, soft tissue integrity, and physiotherapy treatment. Test moments will take place preoperatively, at 6 weeks, 12 weeks, 6 months, 12 months, and 24 months. Descriptive statistics will be used to describe the patient population characteristics. Based on literature review, expert opinion, and univariate analyses, potential prognostic factors will be chosen as covariates. A mixed regression model for repeated measures will be used to assess both the evolution of the Shoulder Pain and Disability Index within persons from baseline over time and the differences in evolution between participants. Correlation analyses will be used to investigate associations between the other outcome measures such as the Constant and Murley Score, shoulder range of motion, shoulder muscle strength, and proprioception, and the primary outcome measure, the Shoulder Pain and Disability Index score. Potential prognostic factors not included in the model will be presented in a descriptive manner. Results Data collection started in January 2020. In April 2023 the sample size was reached. Data collection will end in April 2025. Analyses will follow when data collection is completed. Conclusions Knowledge of potential prognostic factors will have implications toward better rehabilitation strategies of patients after total shoulder arthroplasty. Trial Registration ClinicalTrials.gov NCT04258267; https://clinicaltrials.gov/study/NCT04258267 International Registered Report Identifier (IRRID) DERR1-10.2196/56522

Epigenetic Alterations in Post-Traumatic Stress Disorder: Comprehensive Review of Molecular Markers

Background: Post-traumatic stress disorder (PTSD) can occur after a traumatic event. PTSD is characterized by nightmares, flashbacks and avoidance of stressors. It currently affects 2–8% of the population, with military personnel particularly susceptible. Studies show that environmental stressors can induce various epigenetic changes that shape the PTSD phenotype. Despite the significant impact of epigenetic factors on PTSD symptoms and susceptibility, they have not been widely discussed in the literature. This review focuses on describing epigenetic mechanisms in PTSD, especially DNA methylation, chromatin regulation, and noncoding RNA. Summary: The article includes relevant studies published from 2013 to 2023, excluding non-English-language studies or studies with insufficient data. This review investigated gene methylation changes in association with PTSD, including those related to the hypothalamic-pituitary-adrenal axis, brain-derived neurotrophic factor, neurotransmitters, and immune system functioning, as well as the role of histones and regulatory noncoding RNAs. Key Messages: Epigenetic alterations play a crucial role in shaping PTSD susceptibility, symptomatology, and long-term outcomes, highlighting their potential as important markers and therapeutic targets. Understanding these alterations can aid in developing clinical strategies to better predict, prevent, and treat PTSD. However, further large-scale longitudinal studies are needed to establish the temporal relationship between epigenetic changes and the onset of PTSD, as well as to classify other potential epigenetic mechanisms.

Impact of Therapeutic Inertia on Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis: A 12-Month Longitudinal Study from the TARGET-DERM AD Registry

Background: Therapeutic inertia, the delay or reluctance to modify treatment when goals are unmet, is a significant challenge in managing chronic diseases, including atopic dermatitis (AD). This inertia can lead to suboptimal disease control and affect patient outcomes. Objectives: This study evaluates the effect of therapeutic inertia on patient-reported outcomes (PROs) in moderate-to-severe AD patients undergoing systemic treatment over 3 to 12 months. Methods: We analyzed longitudinal data from the TARGET-DERM AD registry, which includes 3,457 patients with moderate-to-severe AD from 39 centers across the U.S. and Canada. Eligible patients had documented patient-reported outcomes (PROs) at the initiation of systemic therapy and at subsequent 3-month intervals up to 12 months of follow-up. We assessed the proportion of patients not meeting treatment targets based on expert consensus. Patients had a validated Investigator Global Assessment (vIGA-AD) score of 3 or more at initiation of either an advanced systemic therapy (AST) such as biologics or JAK inhibitors or a conventional systemic therapy (CST) such as cyclosporine, methotrexate, or prednisone. PROs were evaluated at 3-month intervals up to 12 months, assessing achievement against the predefined treatment targets. PRO measures included Worst-Itch (PROMIS Itch-Severity), POEM, PO-SCORAD, NRS-sleep, and NRS-pain with specific moderate and optimal target levels established for each. Itch-Severity (range: 0–10; moderate target: ≥4-point reduction, optimal target: score ≤1), POEM (range: 0-28; moderate target: ≥4-point reduction, optimal target: score ≤2), PO-SCORAD (range: 0-103; moderate target: score ≤24; optimal target: score ≤10), NRS-sleep and NRS-pain (range: 0-10; moderate target: reduction ≥3-points; optimal target: score ≤1). Results: Out of 2107 patients with moderate-to-severe AD, 445 qualifying participants were included (63.8% adult, 62.0% female, 45.4% Non-Hispanic White, mean age of 31 years). Most patients (88.8%) initiated AST, with dupilumab being the most common (86.5%). At 6 months, significant proportions of AST-treated patients failed to reach moderate and optimal targets for itch (67% and 79%, respectively), POEM (46% and 69%), and NRS-sleep (59% and 47%). By 12 months, these figures were similar, with 66% and 88% failing to meet itch targets, 53% and 73% failing to meet POEM targets, and 62% and 45% failing to meet NRS-sleep targets, respectively. A similar pattern was observed for other PROs. CST-treated patients exhibited similar trends. Conclusions: The study highlights the profound impact of therapeutic inertia on the quality of life of patients with moderate-to-severe AD. Despite systemic therapy, a considerable proportion failed to meet treatment targets over a 12-month period, underscoring the need for more proactive and responsive treatment strategies in AD management.

Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina

Abstract Objective Long COVID is a condition characterised by persistent symptoms after a SARS-CoV-2 infection, with neurological manifestations being particularly frequent. Existing research suggests that long COVID patients not only report cognitive symptoms but also exhibit measurable cognitive impairment. Neuroimaging studies have identified structural alterations in brain regions linked to cognitive functions. However, most of these studies have focused on patients within months of their initial infection. This study aims to explore the longer-term cognitive effects and brain structural changes in long COVID patients, approximately two years post-infection, in a cohort from San Martín, Buenos Aires, Argentina. Methods We conducted a cross-sectional study involving 137 participants: 109 with long COVID symptoms and 28 healthy controls. The participants underwent an initial clinical assessment, completed a structured questionnaire and standardised scales, underwent a cognitive assessment, and had a brain MRI scan. Structural MRI images were processed via FreeSurfer and FSL to obtain volumetric measures for subcortical and cortical regions, along with regional cortical thickness. Differences between groups for these variables were analysed using ANCOVA, with permutation tests applied to correct for multiple comparisons. Results Long COVID patients reported persistent cognitive symptoms such as memory problems and brain fog, with higher levels of fatigue and reduced quality of life compared to controls. Despite subjective cognitive complaints, cognitive tests did not reveal significant differences between groups, except for the TMT-A (p = 0.05). MRI analysis revealed decreased volume in the cerebellum (p = 0.03), lingual gyrus (p = 0.04), and inferior parietal regions (p = 0.03), and reduced cortical thickness in several areas, including the left and right postcentral gyri (p = 0.02, p = 0.03) and precuneus (p = 0.01, p = 0.02). Conclusions This study highlights the enduring impact of long COVID on quality of life and physical activity, with specific brain structural changes identified two years post-infection. Although cognitive tests did not show clear impairment, the observed brain atrophy and significant reduction in quality of life emphasize the need for comprehensive interventions and further longitudinal studies to understand the long-term effects of long COVID on cognition and brain health.

Interactive math comics: An analysis of Indonesian and Spanish students’ responses

This study investigates the responses of Indonesian and Spanish students to the use of interactive mathematics comics in their education. The research aims to see the practicality of these comics on student engagement, comprehension, and retention of mathematical concepts across different cultural contexts. Using a quantitative approach, the study analyzes data through normality and homogeneity tests to ensure the reliability and consistency of responses. Results show that Indonesian and Spanish students respond positively to interactive mathematics comics, demonstrating increased motivation and interest. However, cultural differences significantly influence the perception of specific indicators such as content quality, technical quality, and language usage. Indonesian students, who are generally accustomed to traditional teaching methods, found the comics engaging and helpful in understanding complex concepts. On the other hand, Spanish students, who are more familiar with interactive and student-centered learning, showed mixed responses depending on their educational experiences and expectations. Despite these differences, both groups recognized the value of interactive comics as a supplementary educational tool. Future research could explore a larger and more diverse sample size, including longitudinal studies to assess the sustained impact of such tools and further investigate the integration of other multimedia elements like augmented reality to enhance interactivity. From these results, the Mathematics Comic on Cartesian coordinates material developed is practical and can be used in mathematics learning. This is because the Mathematics Comic on Cartesian coordinates material received a good response, and students hope that learning mathematics will be more fun and effective.

A multilevel analysis of factors associated with wasting in children one to two years old in Hamadan city

AbstractThe study aimed to identify risk factors for childhood wasting in 1–2 year-olds in Hamadan city, focusing on this age group due to infection and malnutrition risks. Unlike previous cross-sectional studies on children under 5 years old, this longitudinal study tracked weight-to-height changes over time. Data were analyzed from 455 mother-child pairs, aged 1–2 years, collected from health centers and recorded in the Integrated Electronic Health System (SIB). The weight-for-height index, an ordinal response with three categories (wasting, normal, and overweight), was measured several times. A two-level longitudinal ordinal model was used to identify factors associated with wasting. The analysis of data from 230 girls and 225 boys identified several factors associated with wasting: lower birth weight (Adjusted Odds Ratio (AOR) = 0.77), age 12–15 months (AOR = 1.15), lack of health insurance (AOR = 3.09), mother-child residence (AOR = 3.80), maternal height (AOR = 0.92), and age at pregnancy < 24 years (AOR = 4.71). The results of this study showed that most of the factors contributing to childhood wasting can be controlled and prevented. Therefore, implementation of targeted policies and appropriate interventions for mothers before, during, and after pregnancy could reduce the burden of childhood wasting.

Provision of supportive care by an NGO in the face of a dual challenge: cancer and wartime

Abstract Purpose In this study, we explored the work of Halasartan (Stop Cancer), an Israeli nongovernmental organization (NGO) and unique social support network for cancer patients and survivors aged 18–44, during a war period. Drawing on the conservation of resources (COR) theory, we examined whether self-efficacy, social support, psychological distress, and participation in activities that were geared toward alleviating the war situation at Time 1 (T1) would predict engagement in such activities at Time 2 (T2). Methods A longitudinal design with two time-points was used, and NGO members completed self-report questionnaires. At T1, the cohort comprised 250 members (cancer patients/ survivors); at T2, there were 213. However, only 90 NGO members completed the questionnaires at both time-points. Results A significant reduction in psychological distress was observed over time among participants engaged in the NGO’s activities, but no differences were observed in participants’ self-efficacy or social support. Moreover, participation in NGO activities during wartime at T2 was predicted by biological sex (female), lower self-efficacy, and participation in NGO activities at T1. Conclusion Halasartan (Stop Cancer) played a pivotal role in offering a sense of normalcy, community, and support to young-adult cancer patients and survivors during a period of war. The study underscores the essential nature of NGO activities tailored to the unique needs of this demographic, particularly in times of crisis. A broader implementation of such supportive interventions to enhance the well-being of vulnerable populations is suggested.

Associations Between Interpersonal Trauma and Intolerance of Uncertainty in an International Multi-Site Sample

AbstractPrior psychologically traumatic experiences have been linked to increased risk for mental health conditions. However, there remain questions about the relationship between prior interpersonal trauma, particularly that of neglect and abuse, and transdiagnostic dimensions such as intolerance of uncertainty (IU: the tendency to find uncertainty aversive). To address this gap, we conducted a secondary analysis of survey data from an international multi-site sample (n = 2510). Questionnaires included: Interpersonal trauma by type (e.g. emotional neglect, physical abuse, psychological abuse, sexual abuse) and IU. The findings revealed that: (1) experiencing different forms of interpersonal trauma was associated with higher IU, and (2) experiencing multiple forms of neglect and abuse was associated with higher IU. When comparing across the interpersonal trauma types and IU, emotional neglect compared to the other types of abuse, was specifically related to higher IU. These effects remained when controlling for broader negative beliefs about the self and others. However, the observed relationships and overall amount of variance explained by IU was rather small. Overall, these findings demonstrate that interpersonal trauma, particularly emotional neglect, is associated with IU. Future longitudinal research is required to examine if, how, and when after adversity, higher IU may emerge.