Case-cohort Study Research Articles

Pooled prevalence and associated factors of depression among high school students in Ethiopia

BackgroundDepression among high school students is a public health concern in Ethiopia. Studies have indicated that estimates of the prevalence of depression and its predicting factors among high school students are inconsistent. A systematic review and meta-analysis are essential to determine the pooled prevalence of depression and associated factors among high school students to help health care managers design appropriate interventions.MethodsA wide-ranging search was used in international databases, such as PubMed, Scopus, Web of Science, EMBASE, Google Scholar, and Advanced Google. Observational studies (with cross-sectional study designs and case‒control, cohort and longitudinal studies) that reported the proportion of depression and associated factors in Ethiopia were included. In this study, unpublished and published primary studies were included. Two reviewers autonomously extracted all essential data elements using the Microsoft Excel worksheet and transferred them to Stata V.18 for analysis. The I2 statistic test was determine the presence of heterogeneity among included studies and Egger’s regression test and funnel plot checked the publication bias.ResultsIn this review, a total of 10 primary studies with 6988 participants were included to estimate the combined prevalence. The pooled prevalence of depression among high school students in Ethiopia was 30% (26%, 34%). The subgroup analysis showed that the pooled prevalence of depression was higher in Tigray 35% (95% CI 33%, 38%) and a lower prevalence of depression was observed in Oromia 28% (95% CI 25%, 31%) and Amhara 28% (95% CI 18%, 37%). The results of the meta-analysis showed that being female (OR = 1.98; 95% CI 1.34, 2.61), alcohol use (OR = 2.59, 95% CI 1.64, 3.55), and parental neglect (OR = 2.64; 95% CI 1.86, 3.42) were significantly associated with depression among high school students in Ethiopia.ConclusionsIn this study, the overall pooled prevalence of depression among high school students in Ethiopia was high. Being female, alcohol use and parental neglect were potential factors associated with depression among high school students in Ethiopia. Therefore, it is important to pay special attention and design interventions to address depression among high school students in Ethiopia.PROSPERO registration number: CRD42024543877.

Urinary tartaric acid as a biomarker of wine consumption and cardiovascular risk: the PREDIMED trial.

Moderate wine consumption has been associated with lower cardiovascular disease (CVD) risk in older populations. However, wine consumption information through self-reports is prone to measurement errors inherent to subjective assessments. The aim of this study was to evaluate the association between urinary tartaric acid, an objective biomarker of wine consumption, and the rate of a composite clinical CVD event. A case-cohort nested study was designed within the PREDIMED trial with 1232 participants: 685 incident cases of CVD and a random subcohort of 625 participants (including 78 overlapping cases). Wine consumption was registered using validated food frequency questionnaires. Liquid chromatography-tandem mass spectrometry was used to measure urinary tartaric acid at baseline and after one year of intervention. Weighted Cox regression models were used to estimate hazard ratios (HRs) of CVD. Tartaric acid was correlated with self-reported wine consumption at baseline [r = 0.46 (95% CI 0.41; 0.50)]. Five categories of post hoc urinary tartaric acid excretion were used for better representation of risk patterns. Concentrations of 3-12 and 12-35 μg/mL, which reflect ∼3-12 and 12-35 glasses/month of wine, were associated with lower CVD risk [HR 0.62 (95% CI 0.38; 1.00), P = .050 and HR 0.50 (95% CI 0.27; 0.95), P = .035, respectively]. Less significant associations between self-reported wine consumption and CVD risk were observed. Light-to-moderate wine consumption, measured through an objective biomarker (tartaric acid), was prospectively associated with lower CVD rate in a Mediterranean population at high cardiovascular risk.

Examining causal relationships between educational attainment and type 2 diabetes using genetic analysis: findings from the EPIC-InterAct study through Mendelian randomisation

IntroductionObservational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such...

Trends and determinants of time spent in the emergency department among Australian hospital presenting self-harm cases

AimsWaiting time (WT) and length of stay (LOS) are important metrics used to assess service delivery in emergency departments (EDs), and have been associated with subsequent re-presentations in EDs. This study investigated socio-demographic and health service determinants of WT and LOS among hospital treated self-harm (SH) cases presenting to EDs in Australian based hospitals. MethodsThis study employed a retrospective cohort study of all SH cases (N=6203) presenting to public hospital EDs in the Western Sydney catchment area from January 2016 to December 2022. Cox proportional hazard models were used to analyse demographic and service factors related to WT and LOS in Australian hospitals along with a description of secular trends in WT and LOS. ResultsLonger WT was evident for patients aged 15-64 than 0-14 years, non-admitted patients and patients arriving at the ED via transport other than ambulance whereas longer LOS was associated with older patients (65+ years). The inflow of non-SH cases to the ED did not have an impact on WT or LOS among SH cases. WT and LOS increased over time, particularly post the onset of the COVID-19 pandemic. The number of current self-harm cases receiving treatment in ED at the time of patient’s arrival also increased WT and LOS. ConclusionsWT and LOS have increased, especially post the onset of the COVID-19 pandemic. These findings necessitate the urgent need for updated strategies to manage ED resources, and suggest initiatives relating to ED diversion where appropriate for patients presenting to hospital following SH.

Association of maternal blood metabolomics and gestational diabetes mellitus risk: a systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has short- and long-term adverse effects. Therefore, further exploration of the pathophysiology of GDM and related biomarkers is important. In this study, we performed a systematic review and meta-analysis to investigate the associations between metabolites in blood detected via metabolomics techniques and the risk of GDM and to identify possible biomarkers for predicting the occurrence of GDM. We retrieved case‒control and cohort studies of metabolomics and GDM published in PubMed, Embase, and Web of Science through March 29, 2024; extracted metabolite concentrations, odds ratios (ORs), or relative risks (RRs); and evaluated the integrated results with metabolites per-SD risk estimates and 95% CIs for GDM. We estimated the results via the random effects model and the inverse variance method. Our study is registered in PROSPERO (CRD42024539435). We included a total of 28 case‒control and cohort studies, including 17,370 subjects (4,372 GDM patients and 12,998 non-GDM subjects), and meta-analyzed 67 metabolites. Twenty-five of these metabolites were associated with GDM risk. Some amino acids (isoleucine, leucine, valine, alanine, aspartate, etc.), lipids (C16:0, C18:1n-9, C18:1n-7, lysophosphatidylcholine (LPC) (16:0), LPC (18:0), and palmitoylcarnitine), and carbohydrates and energy metabolites (glucose, pyruvate, lactate, 2-hydroxybutyrate, 3-hydroxybutyrate) were discovered to be associated with increased GDM risk (hazard ratio 1.06-2.77). Glutamine, histidine, C14:0, and sphingomyelin (SM) (34:1) were associated with lower GDM risk (hazard ratio 0.75-0.84). These findings suggest that these metabolites may play essential roles in GDM progression, and serve as biomarkers, contributing to the early diagnosis and prediction of GDM.

Impact of inappropriate empirical antibiotic therapy on in-hospital mortality: a retrospective multicentre cohort study of patients with bloodstream infections in Chile, 2018–2022

IntroductionEmpirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital...

Occupational risks of COVID-19: a case-cohort study using health insurance claims data in Germany

BackgroundStudies on occupation and COVID-19 infection that cover a range of occupational groups and adjust for important confounders are lacking. This study aimed to estimate occupational risks of hospitalization with COVID-19 by taking into account sociodemographic factors and previous comorbidities.MethodsWe applied a case-cohort design using workers insured with one of Germany’s largest statutory health insurers as a data source for occupational and demographical information as well as for information on comorbidities. Cox regression models with denominator weights for cases and controls assessed relative risks of hospitalization with COVID-19 in 2020.ResultsThe study consisted of 11,202 COVID-19 cases and 249,707 non-cases. After adjusting for age, sex, number of pre-existing comorbidities, and socioeconomic status, we found at least doubled risks for occupations in theology and church work (HR = 3.05; 95% CI 1.93–4.82), occupations in healthcare (HR = 2.74; 95% CI 2.46–3.05), for bus and tram divers (HR = 2.46; 95% CI 2.04–2.97), occupations in meat processing (HR = 2.16; 95% CI 1.57–2.98), and professional drivers in passenger transport (e.g. taxi drivers) (HR = 2.00; 95% CI 1.59–2.51). In addition, occupations in property marketing and management, social workers, laboratory workers, occupations in personal care (e.g. hairdressers), occupations in housekeeping and occupations in gastronomy all had statistically significantly increased risks compared to the reference population (administrative workers).ConclusionsWe identified occupations with increased risks for hospitalization with COVID-19. For those having a doubled risk it can be assumed that COVID-19 diseases are predominantly occupationally related. By identifying high-risk occupations in non-healthcare professions, effective measures to prevent infections in the workplace can be developed, also in case of a future pandemic.

Feature screening for case-cohort studies in the presence of interval censoring

A great literature has been established for both feature screening under various situations and the analysis of case-cohort studies. Also several methods have been proposed for feature screening when one faces case-cohort studies but all of the existing methods apply only to right-censored failure time data. In this paper, we discuss feature screening for case-cohort studies in the presence of interval censoring, a type of censoring that occurs more generally and includes right censoring as a special case. For the problem, two methods, a model-based procedure and a model-free procedure, are proposed. The former, an inverse probability weighted joint likelihood screening approach, is developed under the proportional hazards model, the most commonly used model for failure time data analysis. The latter is a weighted smooth partial rank screening method that allows for both ultrahigh-dimensional covariates and covariate-dependent censoring. For the proposed methods, the sure screening properties are established under mild regularity conditions. An extensive simulation study is conducted to assess the performance of the proposed methods and indicates that they work well in practical situations.

Association of Pro-inflammatory Cytokines with Gastric Cancer Risk: A Case-Cohort Study.

This study aimed to assess the association between inflammatory cytokines and the risk of gastric cancer (GC). We conducted a case-cohort study using Korean National Cancer Center Community (KNCCC) cohort data to investigate the associations between pro-inflammatory, anti-inflammatory cytokines, inflammatory mediators, and GC risk in the Korean general population (GC cases: n=159, subcohort: n=822). Serum levels of inflammatory cytokines were measured using Quantikine® ELISA and analyzed using a Cox proportional hazards regression model. Compared to those with the lowest serum interleukin 6 (IL-6) levels, the risk of GC significantly increased in the second (HR: 3.48 [1.73-6.99]), third (HR: 3.74 [1.91-7.29], and fourth quartiles (HR: 3.79 [1.93-7.48]). Elevated levels of interleukin 1β (IL-1β) (HR: 1.57 [1.12-2.21]) and interferon gamma (IFN-γ) (HR: 2.49 [1.73-3.58]) were also associated with an increased risk of GC. The findings of this study indicate associations between pro-inflammatory cytokines (IL-6, IL-1β, and IFN-γ) and the risk of GC, suggesting that regulating these cytokine levels may aid in GC prevention.

Abstract 4122486: Multicenter Study of Primary Fetal Cardiomyopathy: Clinical Outcomes And Genetic Etiologies, A Fetal Heart Society Research Collaborative Study

Background: Fetal cardiomyopathy (FCM) affects 8 per 100,000 live births, often with unknown etiology. Progress in fetal cardiac screening, genetic testing and management may have impacted historically poor outcomes. Aims: We sought to investigate genetic associations and clinical outcomes of FCM in the current era. Methods: This was a retrospective Fetal Heart Society Research Collaborative cohort study of FCM cases diagnosed from January 2017-December 2021 in 39 centers. Cases of fetal myocardial disease attributable to maternal diabetes, structural heart disease, arrhythmia or extra-cardiac conditions were excluded. Data including outcomes to 1 year after birth were collected. Significance of genetic testing results and FCM subtype were classified by each center. Results: There were 138 FCM cases diagnosed at a median gestational age of 27 +4 weeks (range 13-39 weeks). Suspected fetal heart disease (41%, 56/138) was the most common referral indication. There was a known family history of CM in 19% (26/138). FCM phenotypes included 38% (52/138) dilated, 24% (33/138) hypertrophic, 17% (24/138) non-compacted, 10% (14/138) mixed, 5% (7/138) restrictive, 3% (4/138) ventricular aneurysm, 3% (4/138) unspecified. Hydrops was present at diagnosis in 15% (20/138) and by delivery or at fetal demise in 26% (36/138). Of 128 continued pregnancies, 7% (9/128) had a fetal demise, 92% (118/128) a live birth and one was lost to follow-up. Among live births, 10% (12/118) received only palliative care. Of 106 actively treated, 75% (80/106) survived to 1 year; 7% (7/106) required ECMO, and 22% (23/106) were listed for transplant with 18 of these successfully transplanted. Of the cohort, a total of 80% (110/138) had genetic testing (including 30 with invasive prenatal testing), with 38% (52/138) having a confirmed genetic etiology and 28% (38/138) with a variant of uncertain significance (VUS) (Figure 1). Transplant-free survival to 1 year was similar for those with and without a genetic diagnosis (40%,21/52 vs 47%,40/86, p=0.48). Conclusion: Outcomes remain poor in FCM, with <50% 1-year survival overall. Confirmed genetic etiologies are now identified in nearly 40%, highlighting the importance of genetic testing.

Risk factors of post discharge falls in patients undergoing total knee arthroplasty: An integrative review.

Total knee arthroplasty (TKA) is a widely performed surgical procedure aimed at alleviating pain and restoring functionality in individuals suffering from knee osteoarthritis. Despite substantial benefits of TKA, patients are exposed to potential risks, including the occurrence of falls during their recovery period following discharge from the hospital. This integrative review endeavors to comprehensively investigate the existing body of literature to identify and assess the diverse factors that contribute to occurrence of post-discharge falls among TKA patients. Through the synthesis of available research, this study seeks to offer valuable insights that can guide clinical practices and interventions designed to mitigate the incidence of post-TKA falls, ultimately enhancing patient outcomes and quality of healthcare. An integrative review was conducted and databases were searched including Pubmed, PEDro, Cochrane, and SPORTDiscus from 2000 to 2024. A thorough search was performed to retrieve articles missed through databases as well as unpublished grey literature. Methodological quality assessment was performed using Newcastle-Ottawa Scale for Case Control and Cohort studies and AXIS tool for cross-sectional study. Eleven articles finally met the inclusion criteria and were included in the review based on eligibility. There were 8 cohort studies (7 prospective cohorts, 1 retrospective cohort), 2 case control studies, and 1 cross-sectional study. The prospective cohort studies included in the review collected data in real-time as events occurred, making them particularly relevant for studying post-TKA falls. Patients who underwent TKA are at risk of post-discharge falls. Several key risk factors have been identified, including advancing age, female gender, reduced proprioception, psychiatric disorders, living alone, and knee pain in the operated knee. It is important to recognize that the significance of these risk factors can vary depending on individual circumstances and contexts.

17α-hydroxylase/17,20-lyase deficiency (17-OHD): A Meta-analysis of Reported Cases.

Homozygous pathogenic variants in the CYP17A1 gene result in defective activity of the steroidogenic enzymes 17α-hydroxylase/17,20-lyase resulting in the clinical syndrome 17-OHD characterised by hypertension, hypokalaemia, and disorders of sexual development. Pathogenic variants of CYP17A1 lead to complete or partial loss of enzymatic activity and clinical presentations of varying severity. This study aimed to examine relationships between CYP17A1 genotype and clinical presentation in a global cohort. We searched PubMed and Scopus for case reports and cohort studies reporting clinical data on patients with 17-OHD published between 1988 and 2022. Of 451 studies, 178 met inclusion criteria comprising a total of 465 patients. We pooled patient data and examined associations between causative variants and their clinical presentations. There were 465 unique patients with a mean age of 18·9 (9·0) years, 52·5% (n=244) were XY and 6·4% (n=29) were phenotypically male. Homozygous variants were seen in 48·0% (n=223) of patients. Common clinical presentations were hypertension (57·0%, n=256), hypokalaemia (45·4% n=211), primary amenorrhoea (38·3%, n=178), cryptorchidism (15·3%, n=71), and atypical genitalia (14·2%, n=66). Frequently occurring variants included p.Y329Kfs (n=86), p.D487_F489del (n=44) and p.W406R (n=39). More severe variants, such as p.Y329Kfs, were associated with hypocortisolism (p<0·05), combined hypokalaemia and hypertension (p<0·01), and DSD (p<0·01). 17-OHD is a rare, frequently misdiagnosed disease. Male patients are typically diagnosed earlier due to genital dysplasia associated with less severe variants, while female patients are typically diagnosed later due to primary amenorrhoea and hypertension. Patients presenting with DSD and hypertension should be investigated for 17-OHD.

A Systematic Literature Review of Real-World Outcomes Following Anti-Interleukin-5 and Anti-Interleukin-5 Receptor Alpha Treatment for Hypereosinophilic Syndrome: Case Reports and Cohort Studies

A Systematic Literature Review of Real-World Outcomes Following Anti-Interleukin-5 and Anti-Interleukin-5 Receptor Alpha Treatment for Hypereosinophilic Syndrome: Case Reports and Cohort Studies

Proteomic analysis of APOEε4 carriers implicates lipid metabolism, complement and lymphocyte signaling in cognitive resilience

BackgroundApolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOEε4 carriers to maintain normal cognitive functioning in older adulthood.MethodsAPOEε4 carriers and APOEε3 homozygotes enrolled in the Women’s Health Initiative Memory Study (WHIMS) from 1996 to 1999 were classified as resilient if they remained cognitively unimpaired beyond age 80, and as non-resilient if they developed cognitive impairment before or at age 80. AD pathology (Aß42/40) and neurodegeneration (NfL, tau) biomarkers, as well as 1007 proteins (Olink) were quantified in blood collected at study enrollment (on average 14 years prior) when participants were cognitively normal. We identified plasma proteins that distinguished between resilient and non-resilient APOEε4 carriers, examined whether these associations generalized to APOEε3 homozygotes, and replicated these findings in the UK Biobank.ResultsA total of 1610 participants were included (baseline age: 71.3 [3.8 SD] years; all White; 42% APOEε4 carriers). Compared to resilient APOEε4 carriers, non-resilient APOEε4 carriers had lower Aß42/40/tau ratio and greater NfL at baseline. Proteomic analyses identified four proteins differentially expressed between resilient and non-resilient APOEε4 carriers at an FDR-corrected P < 0.05. While one of the candidate proteins, a marker of neuronal injury (NfL), also distinguished resilient from non-resilient APOEε3 homozygotes, the other three proteins, known to be involved in lipid metabolism (ANGPTL4) and immune signaling (PTX3, NCR1), only predicted resilient vs. non-resilient status among APOEε4 carriers (protein*genotype interaction-P < 0.05). Three of these four proteins also predicted 14-year dementia risk among APOEε4 carriers in the UK Biobank validation sample (N = 9420). While the candidate proteins showed little to no association with targeted biomarkers of AD pathology, protein network and enrichment analyses suggested that natural killer (NK) cell and T lymphocyte signaling (via PKC-θ) distinguished resilient from non-resilient APOEε4 carriers.ConclusionsWe identified and replicated a plasma proteomic signature associated with cognitive resilience among APOEε4 carriers. These proteins implicate specific immune processes in the preservation of cognitive status despite elevated genetic risk for AD. Future studies in diverse cohorts will be needed to assess the generalizability of these results.

Assessing the Pharmacotherapy and Clinical Outcomes After Deep Brain Stimulation for Treatment-Refractory Obsessive-Compulsive Disorder: A Case-Cohort Study.

Background: In the search for effective treatments for refractive obsessive-compulsive disorder (OCD), deep brain stimulation (DBS) serves as an alternative option for those with minimal response to pharmacotherapy. The rarity of reports regarding DBS use for OCD is attributed to the invasive nature of the procedure: placement of electrodes within targeted areas of the brain to provide neuromodulation. This treatment of last resort may decrease functional impairment and pharmacologic complications for a debilitating mental illness. This study compares the pharmacotherapy utilization and treatment outcomes of five treatment-refractory OCD patients after the placement of DBS with those of a matched cohort. Methods: This retrospective, single-center, case-cohort study reviewed the electronic medical records of five subjects treated with DBS for treatment-refractory OCD and compared them to a similar treatment-refractory cohort whose OCD was treated without the use of DBS. Control subjects were matched by age, sex, years since diagnosis, number of previous medication class trials, and additional clinical factors. Inclusion criteria were defined as those that are at least eighteen years of age, assigned a primary diagnosis of OCD per the ICD-10 classification, and received DBS treatment for refractory OCD. Exclusion criteria included comorbid psychotic disorders, unstable neurological or coagulation disorder(s), and/or an eating disorder diagnosis. The primary endpoint was the change in the number of psychotropic medications two years after implantation for the DBS cohort and two years after psychiatric decompensation for the comparator cohort. Secondary endpoints included: Y-BOCS (the Yale-Brown Obsessive-Compulsive Scale) changes over time, duration quantity of psychotropic medication classes prescribed, and additional symptomology scale changes. Results: Patients receiving DBS were more likely to be on fewer medications and trialed fewer medications after treatment. One out of the five patients was found to be a responder in Y-BOCS scoring after DBS treatment. A reduction in anxiety and depression symptoms was also seen in the HAM-A and HAM-D scales for those that received DBS. Conclusions: A reduction in psychiatric medications trialed during therapy was observed, as well as varying reductions in OCD, anxiety, and depression symptomology following DBS. Results from this study indicate that DBS implantation may contribute to a reduction in polypharmacy while displaying DBS's potential impact on comorbid anxiety and depression symptoms. Given that the small sample size limits generalizability, additional prospective, randomized trials comparing the efficacy of DBS for OCD-specific symptomology and its overall impact on pharmacotherapy are needed in order to further establish the role of DBS as an accepted treatment option for OCD.

Clinical Implications of Social Anxiety Disorder (SAD) and its Detection Methods- A Systematic Review

Background: A common symptom of SAD is significant impairment in interpersonal relationships that can affect various aspects of life as well as daily functioning and lead to decreased quality of life. Individuals with high social anxiety will tend to withdraw from social environments. Purpose: This can eventually lead to loneliness and depression. Therefore, early detection is needed to find a diagnosis early on and prevent the condition from worsening. This review aims to determine the clinical picture in patients with SAD and to find out the instruments that /have been used for clinical enforcement in the field. Methods: We conducted a comprehensive search for full-text articles comprising case reports, case-control studies, cohort studies, and cross-sectional studies published between January 1, 2013, and December 30, 2023. The search encompassed databases such as PubMed, ScienceDirect, SAGE, and Scopus. It's important to note that this review does not delve into other clinical conditions associated with Social Anxiety Disorder (SAD), such as anxiety and depression, as they have been addressed in separate discussions. Additionally, the identification of anxiety and depression is excluded from this review. Results: Out of 78 articles that were screened, only 56 met the eligibility criteria to be selected for further review. The initial steps that need to be taken include 1) defining the research objectives; 2) establishing inclusion criteria; 3) developing a search strategy for data retrieval or study selection; 4) collecting data; 5) assessing the quality of studies; and 6) synthesizing the results. Risk of bias was performed using FEAT principles and reviewers’ discussion. A total of 11 final articles that were reviewed showed a significant correlation between anxiety disorder and detection. Conclusion: As individuals with SAD are large in number, based on this review, early detection is required using methods used by local health regions such as through interviews or clinical symptom assessment. This aims to find cases as quickly as possible and provide appropriate interventions.

Proprotein convertase subtilisin/kexin type 9 levels and the risk of cardiovascular events in statin-treated patients with cardiovascular disease

Abstract Background Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events. Although PCSK9 is cleaved by furin and becomes biologically inactive, previous studies have employed measurement methods which cannot distinguish furin-cleaved and uncleaved form of PCSK9. Methods This study is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The substudy primary endpoint was a composite of major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In a case-cohort study, sub-cohort was randomly selected samples from the total cohort as tripling the number of cases with MACCE. Serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among participants who subsequently developed MACCE and among randomly selected participants. Their relationships with cardiovascular events were assessed according to the quartiles. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Results From 1,478 patients in the sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of primary endpoint in patients in the highest quartile of mature PCSK9 concentrations was similar to the lowest quartile (HR 0.809; 95%CI, 0.541-1.209). Similarly, HRs for the highest to lowest quartiles of furin-cleaved PCSK9s was 0.948 [95%CI, 0.645-1.392] (P=0.784). As compared to the lowest quartile, both serum mature and furin-cleaved PCSK9 levels did not predict the cardiovascular events. Conclusions Serum mature and furin-cleaved PCSK9 levels did not provide useful information in the assessment of future cardiovascular events in statin-treated patients with stable CAD.Study FlowThe weighted Kaplan-Meier cueves

Unraveling Social Health Inequalities during COVID-19 in Belgium: The Vital Role of Data Linkages

Abstract Background During the COVID-19 crisis, data linkages were set up to efficiently monitor the outbreak and identify vulnerable population groups. Yet, considerable technical, administrative and data security issues have hindered the effectiveness of data linkages as a critical instrument during public health emergencies. This workshop aims to provide a practical demonstration of the challenges encountered in a Belgian data linkage during the COVID-19 crisis, along with the strategies implemented to overcome these challenges. This case study offers insights into the development of a highly sensitive linkage between COVID-19 hospital data and information related to social and health use in Belgium. Methods The HELICON data linkage is developed at the individual level to investigate the risk of COVID-19 hospitalization and the influence of various social and biomedical factors during and after the crisis. Data are drawn from data collections on hospitalization from the COVID-19 health surveillance (Sciensano), on the socioeconomic and sociodemographic context (Statistics Belgium), and on healthcare use and reimbursement (InterMutualistic Agency). Results A representative case-cohort study is established comprising 1,149,264 million randomly selected Belgians and 44,508 hospitalized patients. Annual follow-up is scheduled over a four-year span, allowing the investigation of pre- and post-pandemic health data from July 2020 to January 2026. Conclusions The HELICON data linkage took 3.5 years to complete. Among the many challenges, we were faced with complicated approval procedures, ambiguous data security guidelines, unclear cost estimates, and technical issues related to the analysis environment. Building on these experiences, we explore the strengths and weaknesses of data linkages as a research instrument during the COVID-19 pandemic and discuss which lessons should be drawn to for the post-pandemic era.

Genetic liability estimated from large-scale family data improves genetic prediction, risk score profiling, and gene mapping for major depression

Large biobank samples provide an opportunity to integrate broad phenotyping, familial records, and molecular genetics data to study complex traits and diseases. We introduce Pearson-Aitken Family Genetic Risk Scores (PA-FGRS), a method for estimating disease liability from patterns of diagnoses in extended, age-censored genealogical records. We then apply the method to study a paradigmatic complex disorder, major depressive disorder (MDD), using the iPSYCH2015 case-cohort study of 30,949 MDD cases, 39,655 random population controls, and more than 2 million relatives. We show that combining PA-FGRS liabilities estimated from family records with molecular genotypes of probands improves three lines of inquiry. Incorporating PA-FGRS liabilities improves classification of MDD over and above polygenic scores, identifies robust genetic contributions to clinical heterogeneity in MDD associated with comorbidity, recurrence, and severity and can improve the power of genome-wide association studies. Our method is flexible and easy to use, and our study approaches are generalizable to other datasets and other complex traits and diseases.

A Comprehensive Review of TRPS1 as a Diagnostic Immunohistochemical Marker for Primary Breast Carcinoma: Latest Insights and Diagnostic Pitfalls.

Immunohistochemical expression of TRPS1 (trichorhinophalangeal syndrome type 1) protein is usually used by pathologists to confirm breast origin for triple-negative breast cancers (TNBC) or metastatic carcinomas of unknown primary. However, recent studies have reported TRPS1 expression in a variety of non-breast lesions. This review aims to provide a comprehensive evaluation of TRPS1 expression across various tumor types, highlighting both its diagnostic utility and potential pitfalls that may arise in clinical practice. A thorough search of the PubMed database on TRPS1 immunoexpression in tumor pathology was conducted. While the gene itself has been known for several decades, most studies regarding its use in immunohistochemistry emerged in the late 2010s. Particular emphasis was placed on case reports and cohort studies that examined the implications of TRPS1 expression in non-breast tissues, as well as variations in the results between commercially available TRPS1 clones, which may influence the staining intensity and specificity. TRPS1 demonstrated a strong diagnostic utility in identifying primary breast lesions, particularly in TNBC cases. However, its expression in a growing number of non-breast cancers, such as lung adenocarcinoma, prostate adenocarcinoma, urothelial carcinoma, ovarian high-grade serous carcinoma, and endometrial adenocarcinoma, as well as up to 96% of synovial sarcomas with SS18-SSX fusion, emphasizes the need for caution when interpreting TRPS1 positivity and suggests a multi-marker approach in order to increase the diagnostic accuracy. While TRPS1 remains a highly sensible immunohistochemical marker for confirming breast primary lesions, pathologists should be aware of its low specificity and incorporate complementary diagnostic methods in order to ensure accurate clinical management. Further research should focus on elucidating the molecular pathways regulating TRPS1 expression in various tumor types, which may better define its clinical utility.