Long-term Longitudinal Studies Research Articles

Exploring the association between sleep problems and loneliness in adolescents: Potential mediating effects of rumination and resilience.

Sleep problems positively predict loneliness to a large extent, which would harm adolescent health. However, little is known about the underlying mechanism. This research investigates the potential mediating roles of rumination and resilience in the relation among adolescents and further examines the changing relationships. In Study 1, 1056 adolescents from two schools completed self-reported measures of sleep problems, loneliness, rumination, and resilience. We found that sleep problems were positively associated with loneliness, and that rumination and resilience mediated this relationship, both individually and sequentially. To examine the varying relationship between rumination, resilience, and loneliness, Study 2 adopted the cross-lagged design in a long-term longitudinal study of 131 students and found that rumination and resilience at T1 significantly predict loneliness at T2. To further directly explore the changing relationship between sleep problems and loneliness, we performed a short-term longitudinal study across 7weeks of 242 adolescents in Study 3. The results replicated the findings of Study 2 and found sleep problems at T1 positively predicted loneliness at T2. These results underscore the significance of sleep problems in contributing to loneliness through mediating mechanisms and unveil the possible causal relationships, offering robust insights to alleviate adolescent loneliness.

No effect of infant nursery rearing on laboratory rhesus monkey dams’ social behavior or long-term cortisol profiles

While the behavioral and physiological impacts of nursery rearing in laboratory-housed infant monkeys have been well characterized, to date no studies have examined the impact on nonhuman primate dams of their infants being removed for rearing in the nursery. Despite the lack of evidence on the topic, anti-animal research groups often cite mother-infant separation and infant nursery rearing (NR) as a welfare concern for laboratory monkey mothers. As such, important policy decisions regarding research activities may result without adequate evidence. Therefore, we designed this study to examine behavioral and hormonal responses in laboratory monkey dams, who were part of independent long-term longitudinal studies, in response to their infants being NR or mother-peer-reared (MPR). We assessed social, self-care, environmental exploration, and abnormal behaviors for 30 days before and 30 days after parturition in rhesus monkey dams (Macaca mulatta, N=49). Infants were randomly assigned to be either NR (N = 27) or MPR (N = 22). We also analyzed hair samples for cortisol concentrations three times across the study period (Pregnancy, Neonatal Period, Peak Lactation). Dams of NR infants showed no gross behavioral differences relative to dams of MPR infants (all p’s>0.05). Dams of MPR infants showed expected increases in social grooming and social contact, and concomitant decreases in foraging and locomotion, in the 30 days post-partum compared to the 30 days pre-partum (p<0.01). Dams whose infants were NR or MPR showed no differences in hair cortisol concentrations across the study period (p>0.05). We conclude that, with respect to the behavioral and endocrine measures we assessed, nursery rearing of their infants is not detrimental to the welfare of laboratory-housed macaque dams.

A Multicenter, Longitudinal Maternal and Birth Cohort Study in Latin America to Assess Prevalent Respiratory Tract Infections in Children from 0 to 5 Years of Age. The MINERVAL Study

Abstract Background A maternal and birth cohort study can assess the etiology and clinical course of lower respiratory tract infections and offers the opportunity to evaluate the relationship between sociodemographic, clinical, host characteristics and disease severity. In Latin America, a consortium of clinical research centers in Colombia and Panama has demonstrated its ability to conduct long-term longitudinal studies involving active surveillance of thousands of children with consistent retention rates. The MINERVAL cohort study aims to estimate the incidence, etiology, severity, and burden of lower respiratory tract infections (LRTI) and to identify microbiome and transcriptome profiles to help predict risk and assess disease severity in children from birth to 5 years of age. Methods We are establishing a maternal/birth cohort study in four sites (Cali, Bogota, Barranquilla and Panama), and will be recruiting 542 participants per center. Enrolled pregnant women between 24 and 27 weeks of gestation, and newborns under 4 weeks of age, will be closely followed with active surveillance weekly during the first 2 years for early detection of LRTI. Monthly telephone follow-up calls will continue until five years of age to assess the development of long-term respiratory morbidity and complications, including recurrent wheezing episodes. Clinical samples (NP swabs -for respiratory pathogen detection and microbiome analysis-, and blood -for cytokine and transcriptome analysis-) will be obtained in pregnant women, and in infants in the first 4 weeks of life and every 6 months for two years. Women and children who develop LRTI during the longitudinal follow-up will be evaluated clinically and samples will be collected. Results This cohort will provide prospective data and biological samples at crucial stages of children’s development, to allow estimation of the incidence and burden of LRTI by age and etiology, and the identification of risk factors and possible targets for intervention. Furthermore, the use of transcriptional profiling will allow early identification of variables to predict and guide clinical management in children, the use of antivirals and monoclonal antibodies, and to prioritize the population to be vaccinated according to age and risk factors. Conclusion The establishment of observational maternal and birth cohorts in Latin America could provide information to guide the development of strategies to prevent and mitigate the impact of respiratory tract infections in young children. Collaboration among investigators in the region and partnerships with international investigators optimizes resources and allows standardization of good surveillance practices, data exchange and the generation of new knowledge for future studies.

Typology of Leadership Styles Depending on the Nature of Decision-Making and Business/Person Orientation

The purpose of the study is to develop a classification of leadership styles based on a combination of two indicators: the degree of employees’ involvement in the decision-making process and the prevailing orientation at the enterprise either towards achieving organizational results or towards ensuring employees’ satisfaction. The scientific novelty of the work is in the approach to solving the stated problem, namely, the creation of the authors’ typology of management styles (individual authoritarian, paternalistic, collective, communal), based on a combination of the degree of staff participation in making management decisions and target orientation towards business/relationships. The results obtained show that this methodology helps to reveal most efficiently the features of management at modern Russian enterprises. This methodology was used as a basis for the analyses of the aspects determining the nature of the leadership. There was revealed its relationship with various socio-economic factors. Long-term longitudinal studies conducted at Naberezhnye Chelny enterprises provided the authors of the article with empirical material, on the basis of which it was concluded that authoritarianism and paternalism were the most characteristic of the modern domestic managers’ style. The practical significance of the study is in the possibility of applying its results at enterprises in various sectors of the economy. The proposed classification of management styles can be used as a methodological toolkit in studying the effectiveness of management work at different organizations, as well as in the process of training, retraining and advanced training of personnel.

Integration of livelihood support with MHPSS in rehabilitation of torture survivors in LMICs: Addressing poverty and mental health dynamics.

The integration of livelihood support with mental health and psycho-social support (MHPSS) seems crucial for the rehabilitation of torture survivors in low- and middle-income countries (LMICs). This study aimed to explore the intersec-tionality of poverty and mental health, and the integration of livelihood support with-in MHPSS frameworks related to the rehabilitation of torture survivors in LMICs. A cross-sectional study was conducted using a semi-structured questionnaire distributed to members of the International Rehabilitation Council for Torture Victims (IRCT) in LMICs (n=25). The questionnaire explored the perception of IRCT centres in LMIC countries regard-ing the extent to which poverty contributes to poor mental health outcomes among torture sur-vivors and the effectiveness of integrating livelihood support into MHPSS interventions. The study highlighted the significant economic challenges faced by torture survivors, indicating a high prevalence of extreme poverty among this group. The study found that 92% of respondents believed that poverty and mental health outcomes of torture survivors are strongly linked. Eco-nomic and social inequalities were identified as key determinants of mental health, emphasizing the need to address these inequalities in rehabilitation programs for torture survivors. The study underscores the critical connection between poverty, mental health, and the experience of torture. In the view of most IRCT centres, the integration of livelihood support with MHPSS is essential for addressing economic disparities and promoting long-term resilience among survivors. The results highlight the need to conduct long-term longitudinal studies that provide support to this perception. The study recommends enhancing coordination among stakeholders, addressing cultural and social barriers, securing sustainable funding, and developing strategies to integrate livelihood support with MHPSS for torture survivors. According to participants, rehabilitation programmes should include economic empowerment, mental health support, and social integration, to contribute to a holistic recovery, long-term resilience, and overall well-being.

Predicting Regression of Barrett's Esophagus-Can All the King's Men Put It Together Again?

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett's esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age (p < 0.007); lower platelet levels (p < 0.02); rectal p87 elevation in SR (p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) (p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR.

Effect of Sport Activity on Uncomplicated Bicuspid Aortic Valve: Long-Term Longitudinal Echocardiographic Study.

The bicuspid aortic valve (BAV) is a congenital heart defect that can lead to certain complications (aortic stenosis, regurgitation, dilatation and endocarditis), the diagnosis and clinical monitoring of which are effectively entrusted to transthoracic echocardiography (TTE). The impact of training on the natural history of the disease remains unclear. A retrospective cohort of athletes with uncomplicated BAV aged 18-50 years, who underwent at least 2 TTEs with a minimum follow-up of 5 years, subdivided according to the level of physical activity during follow-up into ''untrained'' and ''trained'', was collected. 47 athletes (87.3% male, median 21.0, (18.0; 33.0) years) were included. Median follow-up was 11.6 (8.4; 16.3) years. No statistically significant difference in the growing rate of aorta, left ventricle, nor a significant worsening of aortic stenosis and regurgitation was found. Moreover, there was no significant correlation between weekly training minutes during follow-up and the echocardiographic parameters related to heart size and function. In BAV without major complications, high training volumes do not correspond to a more rapid and significant deterioration in valve function nor to a more rapid increase in aortic or cardiac chamber size.

Transition and management of patients with Duchenne Muscular Dystrophy: a narrative review based on Italian experts' opinion and real-world experience.

Duchenne Muscular Dystrophy (DMD) is a severe, progressive, X-linked disorder resulting in muscle wasting, progressive functional loss and cardiomyopathy. Therapeutic strategies feature glucocorticoid corticosteroids plus gene therapy/stop codon read-through, plus standards of care. Prolonged survival, delayed loss of ambulation (LoA), and innovative treatment prescriptions pose new clinical challenges, including identification of new outcome measures/targets and implementation of continuity of care. We report on the results of an Italian experts' meeting held in Rome, Italy on 20th April 2022. We aimed to: discuss challenges linked to transitioning from the ambulatory to the non-ambulatory phase, and from pediatric to adult care; collect experience on the importance of ongoing care and treatment in advanced disease stages and on the need to measure clinically relevant outcomes during disease progression after LoA. Following LoA the main management focus shifts to cardiac, respiratory, orthopaedics, nutrition and upper limbs function. More data on clinical needs, available treatments, standards of care, frequency of follow-up, and transition should be collected in order to facilitate management optimisation. Shared protocols should be developed, especially to improve patients' management in the acute setting. Transition from paediatric to adult services and from the ambulatory to the non-ambulatory phase require a multidisciplinary approach and the Identification of clinically meaningful outcome measures, which should be described in long-term longitudinal studies.

Epicardial and liver fat implications in albuminuria: a retrospective study

BackgroundAlbuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status.MethodsA retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome.ResultsAfter a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]).ConclusionsIdentification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction.

Clinical impact of restless legs syndrome in patients with migraine: a 12-year, single-center, longitudinal study

AbstractAlthough many studies have indicated a significant association between migraine and restless legs syndrome (RLS), few long-term longitudinal studies have examined RLS in patients with migraine. We conducted a single-center, 12-year, longitudinal study of migraine patients and assessed whether RLS was present in 2010, 2017, or 2022 to evaluate its associations with clinical factors. Headache-related disability was assessed using the Migraine Disability Assessment (MIDAS). Sleep quality, daytime sleepiness, and depressive symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and the Beck Depression Inventory-II (BDI-II), respectively. Of the 262 patients included at baseline (2010), 101 were available after 7 years (2017), and 74 were available after 12 years (2022). The RLS incidence rates were 13.7%, 20.8%, and 24.3% in 2010, 2017, and 2022, respectively. The RLS severity score did not significantly differ among the three time points. The persistent RLS group, defined as those who were positive for RLS at the last evaluation in addition to the first and/or second evaluations, had significantly higher MIDAS, BDI-II, PSQI and ESS scores than did the never RLS group, defined as those who did not exhibit RLS at any of the three time points. Our 12-year longitudinal study revealed significant impacts of RLS on the burden of patients with migraine.

Depression Among LGBT Adults in Relation to Societal Stigma and Discrimination

This study has conducted a comprehensive analysis of the association between depression and 13 social stigma and discrimination among LGBT adults from India. The data was conducted using the Google form, a user-friendly and dynamic online data collection tool, to collect data from 46 adults between the ages of 21 and 30 years old. The discrimination and stigma scale DISC-12, which evaluates the extent to which an individual is subject to prejudice and stigmatization based on sexual orientation, was used to measure the prevalence of depression in the study population. The aim of the study is to gain a better understanding of the relationship between discrimination and stigma and depression in the LGBT community. This research has revealed a strong correlation between depression and unfair treatment, halting self-reflection and depression, stopping self-and unfair treatment, overcoming stigma and depression, and positive treatment and stigma. The findings of this research have implications for individuals, healthcare professionals, policy makers, and society at large. Recommendations for future research include long-term longitudinal studies, intersectionality, cultural considerations, mental health promotion strategies, social support groups and parental support groups.

Validity of self-assessment pubertal Tanner stages by realistic color images and Pubertal Development Scale in a longitudinal cohort study.

To date, the reliability of pubertal development self-assessment tools is questioned, and very few studies have explored the comparison between these tools in longitudinal studies. Hence, this study aimed to examine the reliability of pubertal development self-assessment using realistic color images (RCIs) and the Pubertal Development Scale (PDS) in a longitudinal cohort study. Our longitudinal study recruited 1,429 participants (695 boys and 734 girls), aged 5.8-12.2 years old, in Chongqing, China. We conducted two surveys, 6 months apart. Tanner stages were examined by trained medical students at each visit. RCIs and PDS scores were used to self-assess puberty at each visit. Agreement between physical examination and self-assessment was determined using weighted kappa (wk), accuracy, and Kendall rank correlation. The concordance of puberty self-assessment using RCIs at baseline and the first follow-up was almost perfect in girls and boys, wk >0.800 (p < 0.001). At baseline, the concordance of genital development self-assessment using RCIs was fair in boys, wk = 0.285 (p < 0.001), and that of boys' pubic hair development self-assessment using RCIs was poor, wk = 0.311 [95% confidence interval (CI) -0.157 to 0.818]. The wk of the PDS was less than 0.300, except for breast development. The reliability and validity of the PDS in this study population were low, and the consistency of the PDS was not good. The concordance of RCIs is better than that of the PDS. Pubertal development self-assessment using RCIs is reliable, while the reliability and validity of the PDS are unacceptable. Therefore, RCIs are recommended as a reliable pubertal development self-assessment tool to measure pubertal development for large-scale epidemiological investigations and long-term longitudinal studies in China.

A 10-Year Longitudinal Study of Brain Cortical Thickness in People with First-Episode Psychosis Using Normative Models.

Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Structural magnetic resonance imaging (MRI) from people with first-episode psychosis and controls (n = 79 and 218) were obtained at enrollment, after 12 months (n = 67 and 197), and 10 years (n = 23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n = 42 983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive and Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects models assessed effects of diagnosis, time, and their interactions on cortical deviations plus associations with symptoms. LMEs revealed conditional main effects of diagnosis and time × diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.

Social Environment, Lifestyle, and Genetic Predisposition With Dementia Risk: A Long-Term Longitudinal Study Among Older Adults.

The role of social environment, that is, the aggregate effect of social determinants of health (SDOHs), in determining dementia is unclear. We developed a novel polysocial risk score for dementia based on 19 SDOH among 5199 participants in the Health and Retirement Study, United States, to measure the social environmental risk. We used a survival analysis approach to assess the association between social environment and dementia risk in 2006-2020. We further studied the interaction between social environment and lifestyles, and explored racial disparities. The study participants (mean age = 73.4 years, SD = 8.3; 58.0% female; 11.6% African American) were followed up for an average of 6.2 years, and 1089 participants developed dementia. Every 1-point increase in the polysocial risk score (ranging from 0 to 10) was associated with a 21.6% higher risk (adjusted hazard ratio [aHR] = 1.21, 95% confidence intervals [95% CI] = 1.15-1.26) of developing dementia, other things being equal. Among participants with high social environmental risk, regular exercise and moderate drinking were associated with a 43%-60% lower risk of developing dementia (p < .001). In addition, African Americans were 1.3 times (aHR = 2.28, 95% CI = 1.96-2.66) more likely to develop dementia than European Americans, other things being equal. An adverse social environment is linked to higher dementia risk, but healthy lifestyles can partially offset the increased social environmental risk. The polysocial risk score can complement the existing risk tools to identify high-risk older populations, and guide the design of targeted social environmental interventions, particularly focusing on improving the companionship of the older people, to prevent dementia.

Continual Release of Differentially Private Synthetic Data from Longitudinal Data Collections

Motivated by privacy concerns in long-term longitudinal studies in medical and social science research, we study the problem of continually releasing differentially private synthetic data from longitudinal data collections. We introduce a model where, in every time step, each individual reports a new data element, and the goal of the synthesizer is to incrementally update a synthetic dataset in a consistent way to capture a rich class of statistical properties. We give continual synthetic data generation algorithms that preserve two basic types of queries: fixed time window queries and cumulative time queries. We show nearly tight upper bounds on the error rates of these algorithms and demonstrate their empirical performance on realistically sized datasets from the U.S. Census Bureau's Survey of Income and Program Participation.

Evaluation of Kidney Function in Bipolar Patients: A Cross-Sectional Study

Bipolar disorder is a chronic disease that represents a significant problem to the affected individual. To date, the mainstay treatment for bipolar disorder consists in mood stabilizers, mainly lithium, which have been linked to acute and chronic kidney injury. To investigate the association between Estimated Glomerular Filtration Rate (eGFR) and sociodemographic and clinical characteristics in a group of patients with bipolar disorder (BD) undergoing lithium treatment, with or without concomitant use of other psychopharmaceuticals. In this cross-sectional study data was collected using the instruments: 1 – Clinical and sociodemographic data questionnaire, developed by the Brazilian Consortium for Bipolar Disorder Research; 2 – Structured Clinical Interview for the DSM-IV Axis I Disorders; 3 – Hamilton’s Rating Scale for Depression, to evaluate depressive symptoms and 4 – Young’s Rating Scale for Mania to evaluate mania symptoms. Renal function was calculated through the CKD/EPI formula for eGFR. 95 patients were included in the final analysis. 26 (27.4%) patients presented reduction in eGFR, 21 (22,1%) with eGFR between 60 to 89 and 5 (5,2%) below 60. Higher serum lithium levels and age were associated with such reduction (β = -18.06 [95% CI: -34.70 to -1.42]); (β = -0.72 (95% CI: -1.10 to -0.33)), respectively. Although lithium is considered the “gold standard” in the treatment of BD, its toxicity and tolerability profile in relation to renal function still needs to be better understood. The results of this study reinforce the idea that periodic control of lithium levels is essential for preserving renal function. Long-term longitudinal studies are needed to assess the relationship between renal function and lithium therapy in BD patients. Keywords Lithium, Bipolar Disorder, Kidney, Renal Insufficiency

The relationship between visual hallucinations, functioning, and suicidality over the course of illness: a 10-year follow-up study in first-episode psychosis

Visual hallucinations in psychosis are under-researched despite associations with increased illness severity, functional impairments, and suicidality in the few existing studies. Further, there are no long-term longitudinal studies, making it impossible to conclude if these associations are state or trait phenomena. In the current prospective longitudinal study, 184 individuals with first-episode psychosis were assessed with semi-structured clinical interviews and self-report questionnaires at baseline and 10-year follow-up. Participants were grouped based on lifetime experience of visual hallucinations: before or at baseline (VH+/+), first during follow-up (VH−/+), or never (VH−/−). Associations with functioning, suicide attempts, childhood trauma and other markers of illness severity were tested using multinomial logistic regression analysis. At baseline, the VH+/+ group (37.5%), but not VH−/+ (12.5%), had poorer functioning, higher symptom severity, a lower age at onset, and included more individuals with a history of multiple suicide attempts than the VH−/− group (50%). At follow-up, the VH−/+ group, but not VH+/+, had poorer functioning and higher symptom severity than the VH−/− group. However, the number of participants who committed multiple suicide attempts during the follow-up period was again significantly higher in the VH+/+ group. There was no association with childhood trauma. Hence, visual hallucinations are associated with impaired functioning and higher symptom severity, but only in the short-term. However, visual hallucinations that arise early in the course of illness are a risk indicator for repeated suicide attempts throughout the illness course. These findings highlight the relevance of assessing visual hallucinations and monitoring their development over time.

Seroprevalence of SARS-CoV-2 antibodies among Japanese healthcare workers from 2020 to 2022 as assayed by two commercial kits

Antibody tests are used as surveillance tools for informing health policy making. However, results may vary by type of antibody assay and timing of sample collection following infection. Long-term longitudinal cohort studies on antibody assay seropositivity have remained limited, especially among Asian populations. Using blood samples obtained at health physicals (2020–2022) of healthcare workers (mass vaccinated with mRNA COVID-19 vaccines) at a Japanese medical center, we measured N-specific antibodies using two commercially available systems. Roche Elecsys Anti-SARS-CoV-2 measures total antibodies and Abbott Alinity SARS-CoV-2 IgG measures only IgG. Among 2538 participants, seroprevalence was found to be 16.6% via total antibody assay versus 12.9% by IgG-only (including grayzone) by mid-June 2022. For 219 cases with a previous PCR-confirmed infection, positivity was 97.3% using total antibody assay versus 76.3% using IgG-only assay at the 2022 health physical. Using PCR positive test date as day 0, while the positivity of the total antibody assay was retained for the entire study period (until more than 24-months post-infection), the IgG-only assay’s positivity declined after month 4. The Mantel–Haenszel test found a significant difference in the two assays’ seropositivity, between stratified groups of “within 3 months” and “4 months or more” from infection (P < 0.001). Our study found significant differences in seropositivity over time of total antibody versus IgG-only assays, suggesting an optimal assay for retaining sensitivity over the entire infection period when designing seroprevalence studies.

Long-Term Risk and Prediction of Progression in Primary Angle Closure Suspect

Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS. To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC). This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up. The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84%]). By the 14-year follow-up visit, 93 eyes (25%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 μm from the scleral spur (OR, 0.86 [95% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 μm from the scleral spur (OR, 0.93 [95% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 μm (OR, 0.89 [95% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model's performance. This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 μm and light-room ARA at 750 μm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.

Clinical Meaningfulness in Alzheimer's Disease Clinical Trials. A Report from the EU-US CTAD Task Force.

Recent positive results of three phase III anti-amyloid monoclonal antibody trials are transforming the landscape of disease-modifying therapeutics for Alzheimer's disease, following several decades of failures. Indeed, all three trials have met their primary endpoints. However, the absolute size of the benefit measured in these trials has generated a debate on whether the change scores observed on clinical outcome assessments represent a clinically meaningful benefit to patients. An evidence-based conclusion is urgently required to inform decision-making related to the approval, reimbursement, and ultimately, the management of emerging therapies in clinical practice. The EU-US CTAD Task Force met in Boston to address this important question. The current state-of-the-art knowledge for interpreting clinical meaningfulness of AD clinical trial results, including the point of view of patients and study partners on what is clinically meaningful, was discussed and is summarized here. A combination of methodologies to address the challenges emerged. There remain gaps in the understanding of clinical meaningfulness that only long-term longitudinal studies will be able to address.