Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Medical faculty's perception of students' mental health: a qualitative survey study / Percepción de los profesores de medicina sobre la salud mental de los estudiantes: un estudio cualitativo / Percepção dos docentes de medicina sobre a saúde mental dos estudantes: um estudo qualitativo

This study sought to explore the perspective of medical faculty on the mental health of their students. This qualitative study based on a focus group is part of a longitudinal research that studied the mental health of Brazilian students. One group was conducted with faculty employed at a medical school. Topics discussed covered the concept of mental health and medical education. Six professors participated in one group. The mental health of medical students is a construct that encompasses emotional aspects, ability to solve problems and multiple facets of a human being, according to the participants. Artistic practices, moments of socialization and leisure were perceived as stimulating students' good mental health. Excessive demands generate competitiveness and the teacher's expectation of the student's good performance based on their own experience can harm the student's mental health. Participants also highlighted that a pedagogical reformulation that makes sense for the student's learning process is necessary to update traditional curricula. Medical students' mental health is influenced by experiences and exchanges during the medical school, mainly between professor and student, understood as necessary and inherent to the process of becoming physician. The findings of this study show the need for curriculum changes in the medical education process and updating teacher training for good practices that reinforce good mental health.

Este estudio buscó explorar la perspectiva de los profesores de medicina sobre la salud mental de sus estudiantes. Este estudio cualitativo basado en un grupo focal es parte de una investigación longitudinal que estudió la salud mental de estudiantes brasileños. Un grupo se llevó a cabo con profesores empleados en una escuela de medicina. Los temas tratados abarcaron el concepto de salud mental y educación médica. Seis docentes participaron en un grupo. La salud mental de los estudiantes de medicina es un constructo que abarca aspectos emocionales, capacidad de resolución de problemas y múltiples facetas del ser humano, según los participantes. Las prácticas artísticas, los momentos de socialización y el ocio fueron percibidos como estimulantes de la buena salud mental de los estudiantes. Las exigencias excesivas generan competitividad y la expectativa del docente sobre el buen desempeño del estudiante basándose en su propia experiencia puede perjudicar la salud mental del estudiante. Los participantes también resaltaron que es necesaria una reformulación pedagógica que tenga sentido para el proceso de aprendizaje del estudiante para actualizar los currículos tradicionales. La salud mental de los estudiantes de medicina está influenciada por las experiencias y los intercambios durante la carrera de medicina, principalmente entre profesor y estudiante, entendidos como necesarios e inherentes al proceso de convertirse en médico. Los hallazgos de este estudio muestran la necesidad de cambios curriculares en el proceso de formación médica y de actualización de la formación docente hacia buenas prácticas que refuercen la buena salud mental.

Este estudo buscou explorar a perspectiva dos docentes de medicina sobre a saúde mental de seus alunos. Este estudo qualitativo baseado em grupo focal faz parte de uma pesquisa longitudinal que estudou a saúde mental de estudantes brasileiros. Um grupo foi conduzido com professores empregados em uma faculdade de medicina. Os temas discutidos abrangeram o conceito de saúde mental e educação médica. Seis professores participaram de um grupo. A saúde mental dos estudantes de medicina é um construto que engloba aspectos emocionais, capacidade de resolução de problemas e múltiplas facetas do ser humano, segundo os participantes. As práticas artísticas, os momentos de socialização e de lazer foram percebidos como estimuladores da boa saúde mental dos estudantes. Exigências excessivas geram competitividade e a expectativa do professor pelo bom desempenho do aluno com base na própria experiência pode prejudicar a saúde mental do aluno. Os participantes destacaram também que é necessária uma reformulação pedagógica que faça sentido para o processo de aprendizagem do aluno para atualizar os currículos tradicionais. A saúde mental dos estudantes de medicina é influenciada pelas experiências e trocas durante o curso de medicina, principalmente entre professor e aluno, entendidas como necessárias e inerentes ao processo de tornar-se médico. Os achados deste estudo mostram a necessidade de mudanças curriculares no processo de formação médica e de atualização da formação docente para boas práticas que reforcem a boa saúde mental.

Loneliness and Social Isolation Factors Under the Prolonged COVID-19 Pandemic in Japan: 2-Year Longitudinal Study.

BACKGROUND: Worsening loneliness and social isolation during the COVID-19 pandemic have become serious public health concerns worldwide. Despite previous research reporting persistent loneliness and social isolation under repeated emergency declarations and prolonged pandemics, long-term studies are needed to identify the actual conditions of loneliness and social isolation, and the factors that explain them. OBJECTIVE: In this study, 3 web-based surveys were conducted at 1-year intervals during the 2 years after the first state of emergency to examine changes in loneliness and social isolation and the psychosocial factors associated with them in the Japanese population. METHODS: The first survey (phase 1, May 11-12, 2020) was conducted at the end of the first emergency declaration period, the second survey (phase 2, June 14-20, 2021) was conducted at the end of the third emergency declaration period, and the third survey (phase 3, May 13-30, 2022) was conducted when the state of emergency had not been declared but many COVID-19-positive cases occurred during this period. We collected data on 3892 inhabitants (n=1813, 46.58% women; age: mean 50.3, SD 13.4 y) living in the 4 prefectures where emergency declaration measures were applied in phases 1 and 2. A linear mixed model analysis was performed to examine the association between psychosocial variables as explanatory variables and loneliness scores as the dependent variable in each phase. RESULTS: While many psychosocial and physical variables showed improvement for the 2 years, loneliness, social isolation, and the relationship with familiar people deteriorated, and the opportunities for exercise, favorite activities, and web-based interaction with familiar people decreased. Approximately half of those experiencing social isolation in phase 1 remained isolated throughout the 2-year period, and a greater number of people developed social isolation than those who were able to resolve it. The results of the linear mixed model analysis showed that most psychosocial and physical variables were related to loneliness regardless of the phase. Regarding the variables that showed a significant interaction with the phase, increased altruistic preventive behavior and a negative outlook for the future were more strongly associated with severe loneliness in phase 3 (P=.01 to <.001), while the association between fewer social networks and stronger loneliness tended to be more pronounced in phase 2. Although the interaction was not significant, the association between reduced face-to-face interaction, poorer relationships with familiar people, and increased loneliness tended to be stronger in phase 3. CONCLUSIONS: This study found that loneliness and social isolation remained unresolved throughout the long-term COVID-19 pandemic. Additionally, in the final survey phase, these issues were influenced by a broader and more complex set of factors compared to earlier phases.

Spatial and angular alterations in the dental arch after premature loss of primary molars: Immediate and 9-month computed tomography evaluation.

BACKGROUND: Contemporary imaging methods and quickly advancing technologies have increased the number of diagnostic tools available in medicine and orthodontics. The current study aimed to determine three-dimensional (3D) space changes that occurred after the extraction of either the maxillary or mandibular primary molars during the mixed dentition period. MATERIALS AND METHODS: The present study was a longitudinal split-mouth study with a study group and a control group. The sample consisted of 20 children aged between 6 and 9 years. Clinical examination, radiological analysis, and 3D digital images of the plaster casts were used sequentially to gather all the data. The dental cast measurements recorded were arch width, arch length, hemi-perimeter, dental space at the extraction site, and angulation of the first permanent molar. The children were recalled for follow-up after 9 months, and all dental cast measurements were repeated using nondestructive 3D computed tomography software. For repeated measurements, the test applied was a paired t-test, and for independent samples, the test was a Student's t-test. RESULTS: A significant decrease in arch width (P = 0.001), arch length (P < 0.001), hemi-perimeter (P < 0.001), D-space (P < 0.001), and E-space (P = 0.001) was observed following extraction. A significant increase in angulation measurements was observed (P = 0.001). CONCLUSION: The study revealed a comparative reduction in mandibular arch width, a reduction in arch length in both the maxilla and the mandible, a reduced hemi-perimeter of dental arches, loss of dental extraction space, and a change in angulation of the erupted first permanent molars following premature loss of the primary molar.

Relationships Between Hepatic Steatosis and Frailty Differ by HIV Serostatus.

BACKGROUND: Frailty is associated with obesity-related comorbidities, but the relationship with nonalcoholic fatty liver disease (NAFLD) in people with HIV has been incompletely described. Our objective was to assess the associations between NAFLD and frailty. METHODS: Cross-sectional and longitudinal analysis of men in the Multicenter AIDS Cohort Study. NAFLD was defined as a liver/spleen ratio <1.0 on abdominal computed tomography scans; frailty was defined by the frailty phenotype as having 3 of the following: weakness, slowness, weight loss, exhaustion, and low physical activity. RESULTS: Men without (n = 200) and with HIV (n = 292) were included. NAFLD prevalence was 21% vs 16% and frailty 12% vs 17%, respectively. Among men with NAFLD, frailty was more prevalent in men without HIV (21% vs 11%). In multivariate analysis, NAFLD was significantly associated with frailty after controlling for significant variables. Men without HIV and NAFLD had 2.6 times higher probability [95% confidence interval (CI): 1.2- to 5.7] of frailty relative to men with neither HIV nor NAFLD. This association was not seen in men with HIV. The probability of frailty was higher among men without HIV with NAFLD (27% vs 10% in men without NAFLD) but lower among men with HIV with NAFLD (14% vs 19% in men without NAFLD). No significant relationships were found in longitudinal analyses. CONCLUSIONS: NAFLD was independently associated with frailty among men without HIV but not men with HIV, despite increased prevalence of frailty among men with HIV. The mechanisms of the muscle-liver-adipose tissue axis underlying NAFLD might differ by HIV serostatus.

Frequent Cocaine Use is Associated With Larger HIV Latent Reservoir Size.

BACKGROUND: Cocaine-one of the most frequently abused illicit drugs among persons living with HIV [people living with HIV (PLWH)]-slows the decline of viral production after antiretroviral therapy and is associated with higher HIV viral load, more rapid HIV progression, and increased mortality. SETTING: We examined the impact of cocaine use on the CD4+ T-cell HIV latent reservoir (HLR) in virally suppressed PLWH participating in a national, longitudinal cohort study of the natural and treated history of HIV in the United States. METHODS: CD4+ T-cell genomic DNA from 434 women of diverse ancestry (ie, 75% Black, 14% Hispanic, 12% White) who self-reported cocaine use (ie, 160 cocaine users, 59 prior users, 215 non-users) was analyzed using the Intact Proviral HIV DNA Assay, measuring intact provirus per 106 CD4+ T cells. FINDINGS: HIV latent reservoir size differed by cocaine use (ie, median [interquartile range]: 72 [14-193] for never users, 165 [63-387] for prior users, 184 [28-502] for current users), which was statistically significantly larger in both prior (P = 0.023) and current (P = 0.001) cocaine users compared with never users. CONCLUSIONS: Cocaine use may contribute to a larger replication competent HLR in CD4+ T cells among virologically suppressed women living with HIV. Our findings are important because women are underrepresented in HIV reservoir studies and in studies of the impact of cocaine use on outcomes among PLWH.

Navigating the school transition: Within- and between-person associations between adolescents' academic self-efficacy, school relatedness, and intrinsic academic motivation.

Adolescents with higher levels of the basic psychological needs of competence, autonomy, and relatedness report better school functioning compared to their peers with lower levels of these needs. This study extended previous work by examining associations in within-person changes of these psychological needs in the school context, with a special focus on the secondary school transition period. We examined within-person relations between academic self-efficacy, intrinsic academic motivation, and school relatedness. Dutch adolescents (N = 290; Mage = 11.58 years, SD = 0.44 at T1) who were in their last year of primary school were followed for four waves across 2 years. Results from random-intercept cross-lagged panel models (RI-CLPMs) showed moderate to strong positive concurrent associations between academic self-efficacy, intrinsic academic motivation, and school relatedness at both the within- and between-person levels. Moreover, within-person increases in school relatedness predicted increases in intrinsic academic motivation 6 months later. Thus, it is vital that researchers, teachers, and educators are aware that social connections and belongingness are important after the school transition for increasing intrinsic academic motivation.

School belonging mediates the longitudinal effects of racial/ethnic identity on academic achievement and emotional well-being among Black and Latinx adolescents.

Social Identity Theory proposes that a positive in-group social identification fosters students' academic motivation and psychological well-being. The present study, grounded in Social Identity Theory, investigated the roles of racial/ethnicity identity (REI) in the development of school adjustment among Black and Latinx youth as well as the psychological mechanisms underlying these longitudinal associations. We hypothesized that REI would positively predict the development of academic achievement and emotional symptoms. In addition, we hypothesized that the development of school belonging would mediate the predictive effects of REI on the growth of academic achievement and emotional symptoms. Participants were 475 (n = 182 Black, 48.9% female; 293 Latinx, 47.8% female) students in Grades 7-9. Students self-reported their REI, school belonging, and emotional symptoms. Academic achievement was assessed using standardized achievement test scores. The longitudinal mediation models indicated that REI indirectly predicted the development of academic achievement and emotional symptoms through students' sense of school belonging. Specifically, higher REI embedded achievement and lower REI awareness of racism predicted higher school belonging in Grade 7. Higher Grade 7 school belonging in turn predicted faster academic growth in Grade 7 to Grade 9 as well as lower emotional symptoms in Grade 7. In addition, the three dimensions of REI also directly predicted the growth of academic achievement and emotional symptoms in Grades 7-9. The mediated effects were smaller in size than the direct effects. These findings highlight the importance of fostering positive REI and a strong sense of school belonging in promoting school adjustment among racial/ethnic minoritized, academically at-risk youth.

Racial stereotype and Black adolescents' math achievement: Unpacking the socio-cognitive mechanisms.

Racial stereotypes are salient to Black adolescents and to the academic domain of mathematics; however, few studies have examined the socio-cognitive mechanisms through which racial stereotypes impact math achievement. This 2-year longitudinal study (N = 790 Grade 6, 8, and 10 students during Year 1; 50.7% girls and 49.3% boys) investigated (a) the extent to which the endorsement of positively and negatively biased racial stereotypes predicted Black adolescents' math performance through their cognitive engagement and ability mindset and (b) whether gender and ethnic-racial identity moderated these links. Results suggested that endorsement of negatively biased stereotypes was associated with diminished cognitive engagement and lower math scores across 2 years (p < .05). Additionally, adolescents' ethnic-racial identity commitment moderated the negative links between stereotype endorsement and math cognitive engagement in Year 2 (p < .05). When considering the mediating role of math ability mindsets, the endorsement of both positively and negatively biased racial stereotypes operated on math performance via its links to stronger fixed ability mindset beliefs in both years (p < .05). Gender also moderated the effects of racial stereotype endorsement on math mindset beliefs in Year 1 (p < .01). This study's findings advance the field's understanding of the psychosocial mechanisms through which racial stereotypes operate, thus enabling educators to develop tailored practices that facilitate equitable access to math learning opportunities.

Childhood Maltreatment, Revictimization, and Partner Violence Victimization Through Midlife: A Prospective Longitudinal Investigation.

Existing research suggests that prior victimizations during a person's lifetime, particularly childhood traumas and maltreatment, are risk factors for abuse and revictimization in adulthood, although longitudinal evidence is sparse. Using data from a 30-year ongoing longitudinal study of the long-term consequences of childhood maltreatment, this paper describes the extent to which childhood maltreatment predicts subsequent victimization and partner violence victimization at two time points in adulthood. Data were obtained from a prospective cohort design study in which children with court-substantiated cases of maltreatment (ages 0-11 years) and demographically matched controls were followed into adulthood and interviewed over several waves. Childhood maltreatment was assessed through juvenile and adult court records from 1967 to 1971 in a midwestern county area in the United States. Victimization experiences were assessed from 2000 to 2002 (Mage = 39.5 years) and 2009 to 2010 (Mage = 47.5) and included two types based on information from the lifetime trauma and victimization history instrument and questions about past year partner violence victimization. Individuals with histories of childhood maltreatment were more likely to report physical and sexual assaults and kidnapping and stalking victimization than controls through age 39.5. In contrast, the two groups did not differ at the later assessment at age 47.5, except maltreated individuals reported greater risk for sexual assault/abuse than controls. For intimate partner violence victimization at age 39.5, maltreated and control groups differed only in terms of victimization involving injury. Later in adulthood, more individuals with histories of childhood maltreatment reported partner physical violence victimization compared to controls. Although these longitudinal findings showed a general decline in victimization experiences over the two time points, these results demonstrate that childhood maltreatment increases risk for subsequent revictimization in middle adulthood, specifically for sexual assault/abuse and intimate partner physical violence victimization. These findings have implications for prevention and intervention efforts targeting maltreated children.

Lifetime Revictimization: Evidence From the Wisconsin Longitudinal Study.

Despite the documented increasing prevalence of elder abuse victimization and its devastating health effects, a life-course view of the victimization experiences of older adults has rarely been adopted in the elder abuse literature. The current study investigated lifetime links between victimization experiences by examining the indirect effect of adverse childhood experiences (ACE) on elder abuse victimization via intimate partner violence (IPV) victimization in middle adulthood, and whether this indirect association would differ by gender. Using data from the Wisconsin Longitudinal Study, we analyzed the previous and current victimization experiences of a total of 5,391 older adults in their early 70s and estimated mediational and moderated mediation models. The key results indicated that a higher ACE score was associated with exposure to IPV victimization in middle adulthood, which was in turn associated with exposure to elder abuse victimization. This indirect association was stronger for women than for men. Regarding specific types of childhood victimization, parental physical abuse, sexual abuse, and witnessing domestic violence significantly predicted elder abuse victimization via IPV victimization. Our results support the phenomenon of lifetime victimization, whereby an individual experiences reoccurring forms of victimization across the life course from childhood to late adulthood. Findings highlight the compelling need for the assessment of cumulative victimization experiences and their impact on elder abuse victims. A life-course-based, trauma-informed approach would greatly enhance prevention and intervention services for elder abuse.

Barriers and Facilitators to Sustainable Technology Implementation in Care for People With Disabilities-Real World Data From a Three-Year Implementation Programme.

BACKGROUND: Implementation issues often impede the realisation of the potential benefits of technology in disability care organisations for people with disabilities. Therefore, we conducted a longitudinal study to gain insights into the barriers and facilitators to implementation. METHODS: From 2019 to 2022, data were collected using questionnaires and interviews during 28 implementation projects in 26 disability care organisations. RESULTS: Barriers and facilitators were identified using 9 themes and 26 subthemes. The main themes identified were finances, disability care organisations, internal collaborations, external collaborations, technology, care staff, project teams, people with disabilities, and context. Most factors mentioned as barriers in one organisation were mentioned as facilitators in others. This suggests that barriers can be resolved to improve implementation. CONCLUSION: A large number of barriers and facilitators spanning the organisation suggests that the implementation of technology should be considered an organisational reform. Acting upon them is crucial for the successful implementation of technology.

Longitudinal Epidemiology of Mucormycosis Within the Veterans Health Administration: A Retrospective Cohort Study Over a 20-Year Period.

BACKGROUND: Mucormycosis is a rare but critical infection. Due to its rarity, there is scarce evidence about the longitudinal changes in the epidemiology of mucormycosis in the US. OBJECTIVES: We investigated the longitudinal epidemiology, detailed clinical characteristics, treatment and outcomes of patients with mucormycosis within the US Veterans Health Administration (VHA) over 20-year period. PATIENTS/METHODS: All adult patients who were admitted to an acute-care hospital with a diagnosis of mucormycosis within the VHA from January 2003 to December 2022. RESULTS: Our study included 201 patients from 68 hospitals. Incidence rates of mucormycosis increased from 1.9 per 100,000 hospitalisations in 2003 to 3.3 per 100,000 hospitalisations in 2022, with a peak incidence at 5.9 per 100,000 hospitalisations in 2021, when the Delta wave of COVID-19 hit the US. Rhino-orbital (37.3%) and pulmonary mucormycosis (36.8%) were the most common types of infection. Diabetes mellitus (59.1%) and leukaemia (28.9%) were most common comorbidities predisposing to mucormycosis. Use of posaconazole or isavuconazole increased over time. The 90-day and 1-year mortalities were 35.3% and 49.8%, respectively. The mortality was lower in more recent years (2013-2017, 2018-2022) compared to earlier years (2003-2007). Age ≥65 (adjusted odds ratio [aOR]: 3.47, 95% CI 1.59-7.40), leukaemia as a comorbidity (aOR: 2.66, 95% CI 1.22-5.89) and central nervous system infection (aOR: 10.59, 95% CI 2.81-44.57) were significantly associated with higher 90-day mortality. CONCLUSIONS: Our longitudinal cohort study suggests the increasing incidence rates but lower mortality of mucormycosis over this 20-year period.

Privacy Risk Assessment for Synthetic Longitudinal Health Data.

INTRODUCTION: A modern approach to ensuring privacy when sharing datasets is the use of synthetic data generation methods, which often claim to outperform classic anonymization techniques in the trade-off between data utility and privacy. Recently, it was demonstrated that various deep learning-based approaches are able to generate useful synthesized datasets, often based on domain-specific analyses. However, evaluating the privacy implications of releasing synthetic data remains a challenging problem, especially when the goal is to conform with data protection guidelines. METHODS: Therefore, the recent privacy risk quantification framework Anonymeter has been built for evaluating multiple possible vulnerabilities, which are specifically based on privacy risks that are considered by the European Data Protection Board, i.e. singling out, linkability, and attribute inference. This framework was applied to a synthetic data generation study from the epidemiological domain, where the synthesization replicates time and age trends previously found in data collected during the DONALD cohort study (1312 participants, 16 time points). The conducted privacy analyses are presented, which place a focus on the vulnerability of outliers. RESULTS: The resulting privacy scores are discussed, which vary greatly between the different types of attacks. CONCLUSION: Challenges encountered during their implementation and during the interpretation of their results are highlighted, and it is concluded that privacy risk assessment for synthetic data remains an open problem.

Gender disparities in multi-state health transitions and life expectancy among the ≥50-year-old population: A cross-national multi-cohort study.

Background: Understanding how disability progresses with ageing is important for shaping policies aimed at improving older adults' quality of life, especially when considering the global trends in ageing, life expectancy (LE), and gender disparity. We aimed to assess the health transition probabilities of daily living activities and their implications on LE and gender gaps in global middle-aged and elderly populations. Methods: In this multi-cohort study with a sample of 74 101 individuals aged ≥50 years, we analysed data from six international cohorts: the China Health and Retirement Longitudinal Study (CHARLS), the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS) in the USA, the Mexican Longitudinal Study of Ageing (MHAS), the Korean Longitudinal Study of Ageing (KLoSA), and the Survey of Health, Ageing and Retirement in Europe (SHARE). We estimated probabilities between robust health; disabilities related to instrumental activities of daily living (IADL) and basic activities of daily living (BADL); and mortality through multi-state Markov models. We included gender as a covariate in the models to calculate hazard ratios (HRs), while we calculated LE within the distinct health states of robust health, IADL disabilities, BADL disabilities, and mortality using the stochastic population analysis for complex events (SPACE) microsimulation. Results: Women had higher progressions to disability (IADL: HR = 1.392; BADL: HR = 1.356) compared to men, who conversely showed lesser progression from IADL to BADL disability (HR = 0.856) and lower mortality rates (span of HRs = 0.232-0.692). LE at age 50 favoured women (32.16-38.22 years) over men (28.99-33.58 years), yet they spent more time in states of disability. We otherwise observed significant regional and gender disparities in healthy LE. Conclusions: We identified ageing patterns in which longer lives are often coupled with extended periods of disability. Pronounced gender and regional differences indicate a need for targeted health interventions to address inequities and improve seniors' quality of life. Our findings highlight the necessity for policy interventions focussed on health equity to more completely respond to the demographic shift towards older populations.

Dynamics and implications of anti-drug antibodies against adalimumab using ultra-sensitive and highly drug-tolerant assays.

Background: Adalimumab induces the production of anti-drug antibodies (ADA) that may lead to reduced drug concentration and loss-of-response, posing significant clinical challenges. However, traditional immunoassays have limitations in terms of sensitivity and drug-tolerance, hindering the insights of ADA response. Methods: Herein, we developed an integrated immunoassay platform combining the electrochemiluminescence immunoassay with immunomagnetic separation strategy. A longitudinal cohort study involving 49 patients with ankylosing spondylitis was carried out to analyze the dynamic profiles of ADA and to investigate the impact of ADA on adalimumab pharmacokinetics using a population pharmacokinetic model. Additionally, cross-sectional data from 12 patients were collected to validate the correlation between ADA levels and disease relapse. Results: The ADA assay demonstrated high sensitivity (0.4 ng/mL) and drug-tolerance (100 µg/mL), while the neutralizing antibodies (NAB) assay showed a sensitivity of 100 ng/mL and drug-tolerance of 20 µg/mL. Analysis of the longitudinal cohort revealed that a majority of patients (44/49, 90%) developed persistent ADA within the first 24 weeks of treatment. ADA levels tended to plateau over time after an initial increase during the early immune response phase. Further, nearly all of the tested patients (26/27, 96%) were classified as NAB positive, with a strong correlation between ADA levels and neutralization capacity (R2 = 0.83, P < 0.001). Population pharmacokinetic modeling revealed a significant positive association between model-estimated individual clearance and observed ADA levels. Higher ADA levels were associated with adalimumab clearance and disease relapse in a cross-sectional cohort, suggesting a promising ADA threshold of 10 for potential clinical application. Moreover, the IgG class was the primary contributor to ADA against adalimumab and the apparent affinity exhibited an increasing trend over time, indicating a T-cell dependent mechanism for ADA elicitation by adalimumab. Conclusion: In summary, this integrated immunoassay platform shows promise for in-depth analysis of ADA against biologics, offering fresh insights into immunogenicity and its clinical implications.

COVID-19 vaccines are not associated with axonal injury in patients with multiple sclerosis.

Objective: To evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage. Methods: Single-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded. Results: Fifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77-0.98, p=0.022). Larger studies are needed to validate these results. Conclusion: COVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients.