In cohort studies, it can be infeasible to collect specimens on an entire cohort. For example, to estimate sensitivity of multiple Multi-Cancer Detection (MCD) assays, we desire an extra 80mL of cell-free DNA (cfDNA) blood, but this much extra blood is too expensive for us to collect on everyone. We propose a novel epidemiologic study design that efficiently oversamples those at highest baseline disease risk from whom to collect specimens, to increase the number of future cases with cfDNA blood collection. The variance reduction ratio from our risk-based subsample versus a simple random (sub)sample (SRS) depends primarily on the ratio of risk model sensitivity to the fraction of the cohort selected for specimen collection subject to constraining the risk model specificity. In a simulation where we chose 34% of Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort at highest risk of lung cancer for cfDNA blood collection, we could enrich the number of lung cancers 2.42-fold and the standard deviation of lung-cancer MCD sensitivity was 31-33% reduced versus SRS. Risk-based collection of specimens on a subsample of the cohort could be a feasible and efficient approach to collecting extra specimens for molecular epidemiology.

The determination of risk factors for disease incidence has been the subject of much epidemiologic research. With this goal a common study design entails the follow-up of an initially disease-free cohort, keeping track of the dates of disease incidence (onset) and ascertaining covariate (putative risk factor) information on the full cohort. However, the collection of certain covariate information on all study subjects may be prohibitively expensive and, therefore, the nested case-control study has commonly been used. The high cost of full covariate information on all subjects also arises when determining risk factors for \"failure,\" death say, \"following\" disease onset, in particular, in a prevalent cohort study with follow-up; in such a study a cohort of subjects with existing disease is followed. We here adapt nested case-control designs to the setting of a prevalent cohort study with follow-up, a topic previously not addressed in the literature. We provide the partial likelihood under risk set sampling and state the asymptotic properties of the estimated covariate effects and baseline cumulative hazard. We address the following design questions in the context of prevalent cohort studies with follow-up: How many subjects should be included in the sampled risk sets for efficient estimation? In what way is the proportion of censored subjects associated with the benefit of a nested case-control design? What proportion of overall variance is attributable to risk set sampling? This work is motivated by the anticipated analysis of data on survival with Parkinson\'s Disease, being collected as part of the ongoing Canadian Longitudinal Study on Aging.
La détermination des facteurs de risque pour l’incidence d’une maladie est le sujet de nombreuses études épidémiologiques. À cet effet, un plan d’expérience commun consiste à suivre une cohorte initialement en santé en prenant note de la date à laquelle la maladie se manifeste (début) et en évaluant les covariables (facteurs de risque présumés) pour la cohorte en entier. Lorsque la collecte de certaines covariables pour tous les individus s’avère trop onéreuse, une étude cas-témoins peut eˆtre considérée. Un problème similaire de couˆts élevés pour la collecte d’information sur tous les sujets peut également se présenter lorsque les facteurs de risque pour un « échec », disons le décès, doivent eˆtre déterminés après le début de la maladie. Une telle situation peut survenir dans une étude sur une cohorte prévalente avec suivi, mais la question n’a pas encore été traitée dans la littérature. Les auteurs développent la vraisemblance partielle pour un échantillonnage dans l’ensemble à risque et décrivent les propriétés asymptotiques des estimés de l’effet des covariables et de la fonction cumulative du risque de base. Ils répondent à certaines questions émergeant d’un plan d’expérience pour une cohorte prévalente avec suivi, notamment le nombre de sujets à inclure dans l’ensemble de risque pour obtenir une estimation efficace, les façons dont la proportion de sujets censurés est liée aux bénéfices d’un plan cas-témoin imbriqué, et la proportion de variance globale attribuable à l’échantillonnage dans l’ensemble à risque. Le développement de ces méthodes est motivé par l’analyse imminente de données de survie de patients atteints de la maladie de Parkinson dont la collecte est en cours dans le cadre de l’é tude longitudinale canadienne sur le vieillissement.

OBJECTIVE: Antidepressants are widely used by individuals with type 2 diabetes mellitus (T2DM). This study aimed to explore the correlation between antidepressant use, considering specific antidepressant subclasses or cumulative doses, and diabetic foot ulcer (DFU) risk.
METHODS: This nested case-control study was conducted using a representative population-based Korean cohort database from 2002 to 2019. Participants with DFUs were matched with participants without DFUs based on age, sex, date of T2DM diagnosis, and follow-up duration. In total, 791 DFUs and 3900 controls were included. The association between antidepressant use or cumulative dose of each antidepressant subclass, DFU risk and amputation risk was examined using a conditional logistic regression model.
RESULTS: Antidepressant ever-use was associated with an increased incidence of DFUs compared with non-use. Furthermore, an increase in DFU risk was evident with increasing cumulative antidepressant dosage, particularly among tricyclic antidepressant (TCA) ever-users and selective serotonin reuptake inhibitors (SSRIs) ever-users. Additionally, antidepressant ever-users displayed a higher risk of DFUs requiring amputation, which was consistently observed when the cumulative dosages of overall antidepressants and TCAs were considered.
CONCLUSIONS: Caution is advised when administering TCAs and SSRIs in antidepressant-naïve T2DM patients to reduce DFU and the consequent amputation risk.

As two line trends - aging disability and disability aging - continue to emerge, hearing disability is becoming increasingly prevalent among older adults in china. This study aimed to investigate the incidence of hearing disability among older adults and identify the various factors contributing to its development.
In this matched nested case-control study, data from the China Health and Retirement Longitudinal Study from 2011 to 2018 were analyzed. A total of 4,523 older adults were recruited from a national sample database, of which 1,094 individuals were eligible for inclusion in the hearing disability cohort, while 3,429 older adults who had not been diagnosed with hearing disability were considered non-hearing disability controls. Hearing disability was assessed by a self-reported question. These controls were matched to hearing disability cases in a 1:1 ratio based on age and sex. The logistic regression models were used to find out various factors of hearing disability in the target population.
Totally 1,094 individuals (24.14%) developed hearing disability during the follow-up period. After 1:1 matching, 2,182 subjects were included in the study, with 1,091 cases in the case group. Factors that influenced the incidence of hearing disability in older adults included annual per capita household income (OR = 0.985, p = 0.003), cognitive function (OR = 0.982, p = 0.015), depression level (OR = 1.027, p < 0.001), somatic mobility (OR = 0.946, p = 0.007), history of kidney disease (OR = 1.659, p < 0.001), history of asthma (OR = 1.527, p = 0.008), history of accidental injuries (OR = 1.348, p = 0.015), whether there is a place for recreational and fitness activities in the community (OR = 0.672, p < 0.001), and whether there is a health service center/health center in the community (OR = 0.882, p = 0.006).
The incidence of hearing disabilities among older adults in China is high. The protective and risk factors that contribute to the incidence of disability should be fully considered in the care of older adults.

UNASSIGNED: In Benin, due to the unavailability of comprehensive data on road crashes, road safety policies are mainly based on partial statistics provided by the police. These remain unreliable in terms of injury severity and risk factors. This study aims to determine the factors influencing the severity of injuries after a road crash in Benin.
UNASSIGNED: The present nested case-control study, matched for age and sex, was based on a hospital cohort of road crash victims set up in five hospitals in Benin between July 2019 and January 2020. A sample of severely injured patients according to the Abbreviated Injury Scale (cases) was compared to non-severely injured patients (controls).
UNASSIGNED: The severe crash occurred mainly during the night between 8 p.m. and midnight (36.2% of cases vs. 24.4% of controls) and on main roads (57.8% of cases vs. 34.7% of controls). Factors associated with injury severity were the time of the crash: night between 8 p.m. and midnight [Adjusted Odd Ratio (AOR): 2.1; CI 95%: 1.4-3.2], major roads (national interstate roads and national roads) (AOR: 2.8; CI 95%: 2.0-4.0) and non-work-related travel (AOR: 1.8; CI 95%: 1.2-2.7).
UNASSIGNED: Factors associated with road crash severity in Benin were night-time, main roads, and non-work related travel. Raising user awareness about compliance with traffic rules and improving public lighting, especially along main roads could help reduce the number of serious injuries.

There is a lack of consensus about the association between psoriasis (PSO) and carotid intima-media thickness (cIMT) in literature, since previous studies considered dermatologic clinic patients or general population. This study aimed to compare cIMT levels according to PSO in a sample of 10,530 civil servants form the ELSA-Brasil cohort study and analyze its association with the disease. The PSO cases and disease duration were identified by medical diagnosis self-reported at study enrollment. A paired group was identified by propensity score matching among all the participants without PSO. Mean cIMT values were considered for continuous analysis while cIMT above 75th percentile was considered for categorical analysis. Multivariate conditional regression models were used to analyze association between cIMT and PSO diagnosis, by comparing PSO cases against paired controls and overall sample without disease. A total of n = 162 PSO cases were identified (1.54%) and no difference in cIMT values was observed between participants with PSO and overall sample or control group. PSO was not associated with linear increment of cIMT (vs. overall sample: β = 0.003, p = 0.690; vs. matched controls: β = 0.004, p = 0.633) neither with increased chance of having cIMT above 75th percentile (vs. overall sample: OR = 1.06, p = 0.777; vs. matched controls: OR = 1.19, p = 0.432; conditional regression: OR = 1.31, p = 0.254). There was no relationship between disease duration and cIMT (β = 0.000, p = 0.627). Although no significant relationship between mild cases of psoriasis and cIMT was observed among a wide cohort of civil servants, longitudinal investigation about cIMT progression and severity of disease are still needed.

The increased risk of venous thromboembolism associated with the use of hormonal contraception is well recognized, but evidence regarding hormonal contraception containing natural estradiol is limited. This study aimed to assess the associations between the patterns of use of different systemic hormonal contraceptives and the risk of venous thromboembolism during 2017-2019.
All fertile-aged women (15-49 years) living in Finland in 2017 and using hormonal contraception in 2017 and their 1:1 age- and residence-matched controls not using hormonal contraception in 2017 (altogether 587 559 women) were selected from the Prescription Centre. All incident venous thromboembolism cases during 2018-2019 and their 4:1 age-matched controls were further analyzed in a prospective nested case-control design to assess the associations between the use (starting, stopping, continuous vs no use) of different hormonal contraception types and venous thromboembolism.
Altogether, 1334 venous thromboembolism cases occurred during the follow-up period (incidence rate 1.14 per 1000 person-years, 95% confidence interval [CI] 1.08-1.20), with an incidence rate ratio of hormonal contraception vs no hormonal contraception use of 1.42 (95% CI 1.27-1.58). Compared with non-use, starting the use of gestodene and ethinylestradiol (adjusted odds ratio [aOR] 2.85; 95% CI 1.62-5.03), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 0.98-2.44), desogestrel and ethinylestradiol (aOR 1.97; 95% CI 0.99-3.92), and transdermal patch releasing norelgestromin and ethinylestradiol (aOR 5.10; 95% CI 1.12-23.16), as well as continuing the use of gestodene and ethinylestradiol (aOR 2.60; 95% CI 1.61-4.21), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 1.02-2.37), cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.66; 95% CI 1.06-2.61), and vaginal ring releasing etonogestrel and ethinylestradiol (aOR 3.27; 95% CI 1.95-5.48) were associated with venous thromboembolism risk. Regarding the type of estrogen, the highest risk was associated with current use (vs non use in the previous 180 days) of ethinylestradiol-containing preparations (aOR 2.20; 95% CI 1.82-2.65), followed by estradiol-containing preparations (aOR 1.39; 95% CI 1.04-1.87) with no risk for progestin-only hormonal contraception. Current use of estradiol-containing preparations was not associated with venous thromboembolism risk after exclusion of cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.05; 95% CI 0.66-1.66).
An increased risk of venous thromboembolism is associated with ethinylestradiol-containing combined preparations. The use of estradiol-containing combined preparations confers only a slightly increased risk, possibly driven by cyproterone-containing combined oral contraceptives, whereas the use of progestin-only contraception is not associated with venous thromboembolism.

The association between lipid levels and uric acid disorders remains controversial. We evaluated the association between dyslipidemia and gout in a large cohort from the Korean National Health Insurance Service-Health Screening Cohort. Among the 514,866 participants aged ≥40 years, 16,679 gout participants were selected and matched with 66,716 control participants for income, region of residence, sex, and age. We used the ICD-10 codes to define dyslipidemia (E78) and gout (M10) and diagnosis was confirmed when each was reported ≥2 times. The odds ratios (ORs) of dyslipidemia history were calculated using conditional logistic regression in crude, partial, and fully adjusted models. The days of statin use, systolic and diastolic blood pressure, fasting glucose level, total cholesterol, obesity, Charlson comorbidity index, alcohol consumption, and smoking were used as covariates. Patients with gout had a significantly higher dyslipidemia history than those without gout (33.1% vs. 24.0%, p < 0.001). The association was significant after adjustment (OR in partial adjusted model = 1.50, 95% confidence interval (CI) = 1.44−1.57; OR in fully adjusted model = 1.43, 95% CI = 1.37−1.49). These findings were consistent with the subgroup analysis. Our findings suggest that dyslipidemia history is more likely in patients with gout aged ≥40 years than in healthy controls among Korean population.

UNASSIGNED: The association between hypernatremia and delirium after cardiac surgery has rarely been investigated. This study aimed to determine whether hypernatremia increases the risk of delirium after exposure.
UNASSIGNED: From April 2016 to June 2021, 7,831 consecutive patients receiving cardiac surgery were screened for potential enrollment. The primary outcome was postoperative delirium (POD). For the respective case of delirium, 10 controls were matched according to the index date within the nested case-control design. Hypernatremia exposure was defined as serum sodium > 145 mmol/L within 7 days before the index date. A generalized estimation equation was performed to assess excess risks for POD associated with hypernatremia, adjusted for demographics and clinical variables.
UNASSIGNED: About 7,277 patients were included in the final analyses. About 669 (9.2%) patients with POD were assigned to the case group, and 6,690 controls were identified from the whole population. About 66.5% of the cases and 36.3% of the controls had hypernatremia exposure. After being adjusted to certain well-recognized confounding factors, hypernatremia showed a significant correlation with increased risk of delirium after cardiac surgery (adjusted OR, 1.73; 95% CI, 1.41~2.12). An e-value analysis suggested the robustness to unmeasured confounding.
UNASSIGNED: Hypernatremia was associated with an increased risk of delirium after cardiac surgery. This finding could have implications for risk stratification, early detection, and management of delirium in patients receiving cardiac surgery.

We investigated the relationship between \'epigenetic age\' (EA) derived from DNA methylation (DNAm) and myocardial infarction (MI)/acute coronary syndrome (ACS). A random population sample was examined in 2003/2005 (n = 9360, 45-69, the HAPIEE project) and followed up for 15 years. From this cohort, incident MI/ACS (cases, n = 129) and age- and sex-stratified controls (n = 177) were selected for a nested case-control study. Baseline EA (Horvath\'s, Hannum\'s, PhenoAge, Skin and Blood) and the differences between EA and chronological age (CA) were calculated (ΔAHr, ΔAHn, ΔAPh, ΔASB). EAs by Horvath\'s, Hannum\'s and Skin and Blood were close to CA (median absolute difference, MAD, of 1.08, -1.91 and -2.03 years); PhenoAge had MAD of -9.29 years vs. CA. The adjusted odds ratios (ORs) of MI/ACS per 1-year increments of ΔAHr, ΔAHn, ΔASB and ΔAPh were 1.01 (95% CI 0.95-1.07), 1.01 (95% CI 0.95-1.08), 1.02 (95% CI 0.97-1.06) and 1.01 (0.93-1.09), respectively. When classified into tertiles, only the highest tertile of ΔAPh showed a suggestion of increased risk of MI/ACS with OR 2.09 (1.11-3.94) independent of age and 1.84 (0.99-3.52) in the age- and sex-adjusted model. Metabolic modulation may be the likely mechanism of this association. In conclusion, this case-control study nested in a prospective population-based cohort did not find strong associations between accelerated epigenetic age markers and risk of MI/ACS. Larger cohort studies are needed to re-examine this important research question.