Lecanemab, an antibody directed at Aβ-protofibrils and plaque, showed meaningful delay in disease progression and biological effects consistent with disease modification in the phase 3 Clarity AD trial.

The objective of this paper is to present efficacy and safety results in ApoE ε4 non-carriers or heterozygotes population of Clarity AD.

Clarity AD is an 18-month, randomized study (core) in participants with early AD, with an open-label extension phase (OLE) phase.

Academic and clinical centers.

All eligible ApoE ε4 participants were randomized 1:1 across 2 treatment groups (placebo and lecanemab 10 mg/kg biweekly); the results presented herein are for the ApoE4 heterozygote or non-carrier participants.

Endpoints included change from baseline at 18 months in the global cognitive and functional scale, CDR-SB, amyloid positron emission tomography (PET), Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), and health-related quality-of-life (HRQoL) assessments. Amyloid imaging related abnormalities (ARIA) occurrence was monitored throughout the study by central reading of magnetic resonance imaging. Following 18 months treatment in the Core, eligible participants transitioned to the OLE where they received open-label lecanemab. Clinical outcomes (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL) were evaluated by examining 'delayed start' (core:placebo followed by OLE:lecanemab) and 'early start' (core:lecanemab followed by OLE:lecanemab) cohorts as well as natural history cohorts. Time to progression to next stage of AD was also evaluated through 36 months.

1795 participants with early AD were enrolled in Clarity AD, of which 1521 were ApoE ε4 heterozygotes or non-carriers (85 %). Lecanemab significantly reduced clinical decline on CDR-SB at 18 months compared to placebo in the ApoEε4 heterozygotes or non-carriers subgroup. Amyloid PET, ADAS-Cog14, ADCS-MCI-ADL, and HRQoL results were consistent with the CDR-SB findings. In the analysis subgroup, the most common adverse reactions for lecanemab were infusion-related reactions (26 %), ARIA-H (13 %), fall (11 %), headache (11 %), and ARIA-E (9 %). In the OLE, lecanemab-treated participants continued to accrue benefit in CDR-SB through 36 months, with continued separation through 36 months relative to the ADNI natural history cohort. Delayed start results follow a parallel trajectory relative to early start results, but do not catch up, confirming a disease modifying effect and reflecting importance of early treatment initiation. Results were similar for ADAS-Cog14 and ADCS-MCI-ADL. Lecanemab reduced the risk of progression to next stage of AD by 28 % on lecanemab as compared to the ADNI natural history cohort.

In the ApoE ε4 heterozygotes or non-carrier subgroup of Clarity AD, lecanemab slowed decline in disease progression and reduced markers of amyloid, with expanding benefit over time.

Clarity AD NCT03887455.

Cannabis use is prevalent among patients receiving medication for opioid use disorder (MOUD). However, little is known about factors associated with frequent cannabis use.

To describe correlates, patterns, and motivations for cannabis use among individuals treated with MOUD.

Participants from a randomized trial (n = 303) investigating a mind-body intervention adjunct to MOUD were compared based on frequent cannabis use (≥3 days/week) versus less frequent or no use, assessing demographic and clinical characteristics. Individuals with frequent cannabis use were invited to participate in a telephone survey exploring reasons for cannabis use, cannabis usage in treating symptoms/conditions, route, tetrahydrocannabinol/cannabidiol content, and cannabis use disorder screening.

47.5% of participants (n = 144) endorsed cannabis use, and 27% used cannabis frequently (≥3 days/week). Frequent cannabis use was associated with anxiety (P = .04), nausea/vomiting (P < .001), and lower employment (P = .03). Employment was associated with less frequent cannabis use (OR = 0.54, 95% CI = 0.29-0.99, P = .049), and higher interoceptive awareness was associated with lower odds of frequent cannabis use (OR = 0.64, 95% CI = 0.43-0.96, P = .03). In a subsample (n = 27) of individuals with frequent cannabis use, 56% used cannabis for both recreation and symptom management, 30% for symptom management only, and 15% for recreation only. Participants who reported medical use of cannabis used it to manage a variety of conditions, including stress (100%), anxiety (83%), insomnia (79%), pain (75%), depression (75%), and posttraumatic stress disorder (n = 67%). Fifty-two percent wanted to cut down.

Frequent cannabis use among individuals on MOUD was associated with anxiety, nausea, and lower employment, with no significant differences in key MOUD outcomes including substance use and retention. Individuals with frequent cannabis use reported treating stress, pain, and mental health conditions with cannabis. More attention to screening and treatment of these conditions is warranted.

Survivorship care in head and neck cancer (HNC) is complex, influenced by tumor site, treatment modality, and social determinants of health. Neighborhood-level factors may affect cancer outcomes, yet the impact of neighborhood disadvantage on HNC survival remains underexplored. This study examined the association between neighborhood disadvantage and overall survival in HNC survivors. We conducted a retrospective cohort study of patients diagnosed with HNC (n = 440) at a single institution (2013-2023). Neighborhood disadvantage was measured using the Area Deprivation Index (ADI) national percentile and stratified into quintiles. Clinical, demographic, and treatment data were extracted from electronic health records. Overall survival was analyzed using Kaplan-Meier curves and the Cox proportional hazards model. Multiple linear regression identified predictors of ADI. Significant differences across ADI quintiles were observed for age at diagnosis (p = 0.025), HPVp16 status (p < 0.001), and comorbidity count (p = 0.028). In multivariable regression, only age (p = 0.04) and HPVp16 status (p < 0.001) remained significant. Median survival did not differ significantly; however, survival status at study end was notable, with >50% of participants in the most disadvantaged quintile deceased or lost to follow-up. Kaplan-Meier curves demonstrated variation in survival by ADI quintile. Neighborhood disadvantage influences HNC survivorship. Integrating community-level and lifestyle-based interventions (e.g., nutrition education, physical activity promotion, stress reduction, and behavioral health support) into survivorship care may mitigate effects of social inequities. Incorporating neighborhood context into survivorship planning may improve outcomes and promote equity in HNC care.

Epidemiological studies have established that autoimmune diseases (AD) increase cardiovascular disease (CVD) risk. We aimed to elucidate their shared genetic architecture and clinical implications.

We conducted a cross-trait multivariate genome-wide association study (GWAS) for three autoimmune diseases (type 1 diabetes, systemic lupus erythematosus, and rheumatoid arthritis) and four cardiovascular diseases (coronary artery disease, heart failure, stroke, and peripheral artery disease). We performed both genome-wide and locus-based analysis including fine-mapping, functional annotation, enrichment analyses, transcriptome-wide association studies (TWAS), and proteome-wide and drug-repurposing Mendelian randomization (MR). We constructed a polygenic risk score (PRS) and explored its pleiotropic effects beyond AD and CVD in the UK Biobank population.

In the multivariate GWAS, we identified 259 genome-wide significant association signals that were enriched primarily in arterial tissues and lipid metabolism pathways. Through convergent evidence from TWAS and MR analyses, we prioritized 15 therapeutic targets including TGFB1 and IL6R, and identified histone deacetylase inhibitors as candidate drugs. The polygenic risk score showed discriminative ability in cardiovascular risk stratification among autoimmune patients, with individuals in the highest PRS decile exhibiting significantly elevated CVD risk compared to those in the 2nd-9th deciles (hazard ratios: 1.60 [95% CI: 1.19-2.15] for type 1 diabetes, 2.28 [95% CI: 1.14-4.56] for systemic lupus erythematosus, and 2.33 [95% CI: 1.94-2.80] for rheumatoid arthritis). Additionally, the PRS revealed pleiotropic associations with risk of various health conditions, including polyneuropathy, chronic renal failure, and depressive episodes.

Our study unveils the shared genetic architecture between autoimmune and cardiovascular diseases, providing insights for therapeutic development and risk stratification.

Boredom has been historically overlooked in clinical settings. However, substantial research suggests that one's vulnerability to boredom (boredom proneness) is linked to numerous psychiatric conditions and negative mental health outcomes, including domains and facets implicated in the Alternative Model for Personality Disorders (AMPD). Boredom appears to have specific relevance to the classifications of Borderline and Antisocial Personality Disorders (BPD; APD), and theoretical work has suggested that boredom may be positively affected by an evidence-based treatment for BPD, Dialectical Behavior Therapy (DBT). In two studies, we examined the links between boredom proneness, recent boredom experiences, and personality in terms of traits and behavioral symptoms. Study 1 (n = 290) demonstrated positive associations between boredom proneness, recent boredom, general personality functioning, and traits associated with BPD and APD in a large online sample. Moreover, a unique relationship was observed between boredom and BPD symptoms when controlling for APD traits and general personality functioning. Study 2 (n = 34) examined the role of boredom in an intensive outpatient DBT program, demonstrating links between boredom, suicide ideation, and self-injury urges across treatment timepoints. Boredom was significantly associated with borderline symptom severity and predicted more severe BPD symptoms at the midpoint and endpoint of treatment. Together, these findings suggest that boredom plays a robust role in various dimensions of personality psychopathology, and that addressing boredom within treatments for these conditions may impact outcomes.

Background/Objectives: Adolescence represents a critical period for the formation of lifestyle habits that often persist into adulthood, significantly shaping long-term health outcomes and contributing to the development of non-communicable diseases. This study aims to assess the impact of Food Game, a secondary school-based programme, delivered throughout the academic year, to promote healthy eating, physical activity, and sustainability awareness among students. Methods: As part of the Food Game programme, 184 adolescents aged 14-16 years from the Milan area (Italy) completed two questionnaires, administered before and after the intervention (November 2024, April 2025), evaluating dietary habits, lifestyle behaviours, and attitudes toward sustainability. This uncontrolled intervention study assessed dietary changes using a composite score [0-14], with higher scores indicating healthier eating patterns. Pre-post intervention differences were analysed using paired t-tests for continuous variables and McNemar's test for categorical variables. Results: After participation in Food Game, a significant improvement in mean dietary score from 7.6 to 8.2 (p < 0.001) occurred. Overall, 28.3% of the students worsened their score and 53.2% improved (≥1-point increase), including a significant improvement (≥2-point increase) in 29.4%. Fruit, vegetable, and fish intake increased, while consumption of meat, processed meat, and snacks decreased (p < 0.05). Waste recycling did not change (94.6%), and tap water non-significantly increased. No significant changes were observed in water intake, physical activity, screen time, or addictive behaviours. Conclusions: These findings support the potential of peer-led gamified interventions to promote healthier eating in youth. Future controlled studies are required to rigorously evaluate the Food Game programme's effectiveness in relation to adolescents' diet, lifestyle, and sustainability habits.

Background/Objectives: Sugar-sweetened beverage (SSB) consumption has been linked to obesity, metabolic diseases, and rising healthcare costs. This study aimed to assess the impact of a 20% excise tax on SSBs in Brazil on obesity/overweight prevalence, seven musculoskeletal and cardiovascular diseases, and related healthcare costs, with their associated impacts on health inequalities. Methods: Using 2017/2018 Brazilian Household Budget Survey data for baseline consumption and own- and cross-price elasticities for taxed beverages, we estimated changes in caloric consumption for the entire population and for lower- and upper-income quartiles. The PRIMEtime dynamic individual-level simulation model projected body weight changes, lifetime Quality-Adjusted Life-Years (QALYs), healthcare costs (discounted at 5%), and disease cases (20-year horizon). Results: A 20% excise SSB tax was projected to reduce obesity prevalence by 1.7 percentage points in men and 1.5 percentage points in women, from baseline rates of 19.8% and 23.6%, respectively. Lifetime gains were estimated at 17,878 QALYs per million men and 12,181 per million women, alongside healthcare cost savings of Int$520 million. Impacts varied by income, with smaller health gains in the lowest quartile and higher among the wealthiest. Over 20 years, the tax could avert 1784 cases of type 2 diabetes mellitus/100,000 adults (52% in men) and 1070 cases of ischemic heart disease/100,000 adults (80% in men). Conclusions: A 20% excise SSB tax in Brazil could yield large health and cost benefits. With the recent approval of the Selective Tax under Complementary Law 214/2025, Brazil has a timely opportunity to translate these projected benefits into effective public health policy.

Background/Objectives: It is well documented that people with human immunodeficiency virus (HIV) have nearly twice the risk of incident acute myocardial infarction compared to the general population. The elevated risk stems from a multi-layered interplay of factors such as persistent immune activation inherent to HIV infection and higher prevalence of traditional risk factors associated with nutritional needs. A large proportion of people living with HIV (PWH) reside in Sub-Saharan African countries such as Tanzania; however, there is a dearth of data on nutrition, particularly fruit and vegetable (F&V) intake, a key factor in the prevention of cardiovascular disease (CVD). This study aimed to contribute to the growing literature on CVD prevention for PWH globally. Methods: We conducted secondary analyses of original data collected from a study using the World Health Organization (WHO) STEPS survey among PWH and the general population in Mwanza City between December 2018 and May 2019. Approval for the parent study was obtained from Bugando Medical Center. Multinomial logistic regression analysis examined F&V intake and associated factors between PWH and people living without HIV (PWoH) using sex, employment, and BMI. Results: A total of 537 participants (277 PWoH and 260 PWH) were included in the analysis. PWH were more likely to consume fruits ≥ 4 days per week than PWoH (38% vs. 25%, p = 0.002), whereas vegetable intake did not differ significantly between groups. Fruit intake was higher in males (OR = 5.63; 95% CI: 2.48-12.79) and employed individuals (OR = 3.85; 95% CI: 1.82-8.14). Conclusions: PWH were more likely to consume more fruits than PWoH in this study, a phenomenon that is more novel than previous research. These findings are encouraging to support nutrition-based interventions for PWH who are at a higher risk of CVD.

Background: Lifestyle challenges such as prolonged sitting, irregular dietary habits, high stress levels, and lack of physical activity have become increasingly common among working professionals. All these factors contribute to the risk of chronic diseases such as diabetes, heart disease, obesity, and high blood pressure, which in turn result in reduced work performance and quality of life and may further affect health services access through increase healthcare needs. The teaching environment, like many other work environments, is mentally, emotionally, and practically demanding, and it puts extra pressure on those who work in it. Academicians, who devote themselves to guiding young minds, often make unhealthy daily choices and face significant work-related stress, which can lead to serious long-term health problems. This review highlights that health and well-being are shaped not by a single factor such as diet, work patterns, or habits, but by their combined effect. Methods: A study of around 113 studies has highlighted that academicians usually feel drained and physically exhausted. Result: The factors like prolonged fasts, insufficient water intake, long-standing hours, long and continuous talking, and extended periods in the sitting position have added to their stress levels at the workplace. The most critical finding is that these factors do not affect in isolation but impact as a combined interaction. These issues influence each other, thus increasing the vulnerability to lifestyle disorders. Conclusions: This critical problem can be addressed with a Multimodal Assessment Framework that integrates teachers' data on dietary habits, workplace ergonomics, sleep quality, and levels of physical activity. The presented work also proposes a statistical technique with an Artificial Intelligence (AI) model, and generates Vulnerability Quotient (VQ) that show lifestyle disease-related exposure of the teachers, which may be further used to provide remedial interventions. These insights can further guide institutions and policymakers to design healthier, supportive, and sustainable teaching environments.