Nested Case Control Study Research Articles

An in-depth comparison of vascular inflammation on ultrasound, FDG-PET/CT and MRI in patients with suspected giant cell arteritis.

Giant cell arteritis (GCA) is a difficult to diagnose large vessel vasculitis. CDUS, FDG-PET/CT and MRI are increasingly used for GCA diagnosis. This study aims to assess vascular wall lesions in GCA suspected patients, directly comparing CDUS, FDG-PET/CT and MRI with each other. In a nested-case control study, consecutive GCA suspected patients were included. Scans were retrospectively assessed by two experts per imaging modality. Inter- and intraobserver agreement using Cohen's or Fleiss Kappa were calculated to assess agreement between experts, a few duplicated scans and between imaging modalities. Sensitivity and specificity of the imaging modalities for overall diagnostic performance and for individual arteries were calculated. In total, 42 patients were included. Overall diagnostic performance of imaging modalities was comparable. Sensitivity and specificity were highest in the temporal artery for CDUS (76% and 93%; Kappa > 0.7) and MRI (60% and 100%; Kappa > 0.7), and in the vertebral (61% and 100%; Kappa 0.56) and maxillary artery (52% and 100%; Kappa 0.75) for FDG-PET/CT. Agreement between all modalities for a positive temporal artery was 0.76, but only 0.28 between CDUS and FDG-PET/CT. Agreement for the axillary artery was 0.7 between CDUS and FDG-PET/CT. The temporal artery can be assessed by CDUS and MRI with good sensitivity and high specificity, and the axillary artery by CDUS and FDG-PET/CT with high agreement between the two modalities. In addition, the vertebral and maxillary artery can be assessed by FDG-PET/CT with good sensitivity and specificity, however the vertebral artery had moderate interobserver agreement.

Study on the effect of occupational exposure on hypertension of steelworkers based on Lasso-Logistic regression model.

This study aimed to use a stable and predictive method: Lasso regression model to analyze hypertension's influencing factors and explore the interactions between occupational exposures. This has been a nested case-control study. The case group consisted of 959 patients with high blood pressure found during the study. 959 hypertensive patients, matched 1:1 from the cohort based on the age ±2 years and same gender distribution, served as the control group. Logistic regression has been performed to analyze the relationship between occupational exposures and hypertension after the variables were screened by the Lasso regression model and to explore the interactions between the various occupational exposures. The incidence rate of hypertension among steelworkers was 33.95%. Noise, dust, high temperature, carbon monoxide (CO), and shift work have been found to be significantly associated with the risk of hypertension, which is 1.329, 1.370, 1.900, 1.309, and 1.427 times higher than that of the control group, respectively. In addition, a multiplicative interaction between dust and noise has been found (P=0.038). The study suggested that exposure to dust, high temperature, CO, noise, and shift work increases the risk of hypertension among steelworkers and that the risk of hypertension is more pronounced among workers exposed to both dust and noise.

Fetal cardiac function in pregnancy affected by congenital heart disease: protocol for a multicentre prospective cohort study

BackgroundCongenital heart disease (CHD) is the most common fetal malformation, and it can result first in cardiac remodeling and dysfunction and later in cardiac failure and hydrops. A limited number of studies have evaluated cardiac function in fetuses affected by CHD. Functional parameters could potentially identify fetuses at risk of cardiac failure before its development. However, these techniques have not translated from research to clinical settings, due to a lack of standardization and poor repeatability. We seek to evaluate whether application of automated techniques to a cohort with fetal pathology could overcome these factors.MethodsA multicenter cohort study will be carried out in eight teaching hospitals across Europe, Australia, and Middle East. Based on a previous observed standard deviation, a total sample of 381 pregnancies is required to achieve 80% power to detect a difference of 0.03 in mean myocardial performance index (MPI) with a two-sided type I error rate of 5%. After adjustments allowing for patient exclusions or incomplete datasets, a total of 330 healthy singleton pregnancies and 165 diagnosed with CHD will be recruited. Two fetal cardiac function evaluations at 19 + 6–28 + 6 and 32 + 6–36 + 6 weeks will be offered assessing automated pulsed wave doppler (PWD) MPI, spatio-temporal image correlation (STIC) annular and septal plane excursion (TAPSE, MAPSE and SAPSE), alongside cardiac morphometric and Doppler evaluations of flow across the valves. A secondary nested case–control study will evaluate fetuses with hydrops compared to those without. Differences in functional parameters between cases and controls and over time will be assessed using generalized linear mixed models. Logistic regression will estimate the association between cardiac parameters and hydrops’ incidence.DiscussionThis study will provide evidence as to whether automated functional parameters could be significantly different in pregnancy affected by CHD versus healthy pregnancies. The primary objective is to compare automated PWD-MPI and STIC TAPSE, MAPSE and SAPSE in fetuses affected by CHD versus healthy. The secondary objective is to estimate whether these automated parameters could improve the predictive value of the classical cardiovascular profile score in case of hydrops.Trial registrationThe study protocol has been registered in the ClinicalTrials.gov Protocol Registration System, identification number NCT05698277.

Effectiveness of a tailored forest package of interventions, including topical repellents, in reducing malaria incidence in Myanmar

BackgroundIn Myanmar, progress towards malaria elimination has stagnated in some areas requiring deployment of new tools and approaches to accelerate malaria elimination. While there is evidence that networks of community-based malaria workers and insecticide-treated nets (ITNs) can reduce malaria transmission in a variety of settings, evidence for the effectiveness of other interventions, such as topical repellents, is limited. Since malaria transmission in Myanmar occurs outdoors, mainly among forest-goers, this study tested the effectiveness of topical repellents in combination with supplemental ITN distribution and strengthened networks of malaria workers.MethodsThirty-eight villages in the Tanintharyi Region and Rakhine State were initially selected for the study based on malaria incidence in previous years. An additional 31 villages were included as comparison areas. The implementation of interventions began in March 2020 and continued through June 2021. Malaria cases were detected in all villages through surveillance at health facilities and a network of malaria workers. Data were analysed by interrupted time series. A nested case–control study was also conducted where forest-goers who tested positive for malaria by RDT were matched to up to three forest-goers who tested negative.ResultsA decrease in mean monthly incidence was observed in the intervention villages from 6.0 (95% CI 4.9–7.1) to 3.7 (95% CI 2.4–4.9) cases per 1000 people at risk before and after the interventions. For the comparison villages, the mean monthly incidence increased from 1.1 (95% CI 0.8–1.5) to 5.7 (95% CI 2.1–9.3) cases per 1000 people at risk. Malaria incidence was significantly lower following the implementation of the interventions (RR = 0.117; 95% CI 0.061–0.223; p < 0.001) in the intervention villages, whereas that of comparison villages was higher after the implementation of the interventions (RR = 3.558; 95% CI 0.311–40.750; p = 0.308). However, a significant trend for increasing malaria incidence after implementation was observed in the intervention villages (RR = 1.113; 95% CI 1.021–1.214, p = 0.015), suggesting a waning effect. The nested case–control analysis showed that the odds of topical repellent use were significantly lower among cases than controls (aOR: 0.063, 95% CI 0.013–0.313, p < 0.001).ConclusionThe tailored intervention package for forest-goers helped reduce malaria incidence in Myanmar. Topical repellents may help to further reduce malaria transmission in elimination settings where high-risk populations such as forest-goers do not have easy access to routine health services or are less likely to use ITNs for malaria prevention.

An overlap-weighted analysis on the association of constipation symptoms with disease progression and survival in amyotrophic lateral sclerosis: a nested case-control study.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing and rare neurodegenerative disease. Therefore, evaluating the risk factors affecting the survival of patients with ALS is crucial. Constipation, a common but overlooked symptom of ALS, can be effectively managed. It is currently unknown whether constipation contributes to the progression and survival of ALS. This study aimed to investigate the association between constipation and ALS development and survival using a novel overlap-weighted (OW) method to enhance the robustness and reliability of results. This prospective matching nested case-control (NCC) study was conducted within an ongoing ALS cohort at the Second Hospital of Hebei Medical University. Baseline data were collected from patients meeting the inclusion and exclusion criteria, with constipation as the exposure factor. A 9-month follow-up was conducted, with death as the endpoint event. We primarily used the OW method in NCC studies to examine the association between constipation and ALS development and survival. Weighted Cox proportional hazards model was used to assess risk factors associated with overall survival. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Finally, the bioinformatic analysis explored common pathways between ALS and constipation. Among the 190 patients included, the prevalence of constipation was 50%. Patients with ALS constipation exhibited faster disease progression (p < 0.001), with a positive correlation between constipation severity and progression rate (r = 0.356, p < 0.001). The constipation group had poorer survival before and after OW (log-rank test, p < 0.0001). In the Cox proportional hazards model of 114 patients, constipation was a risk factor for ALS both before (hazard ratio (HR) = 5.840, 95% confidence interval (CI) = 1.504-22.675, p = 0.011) and after (HR = 5.271, 95% CI = 1.241-22.379, p = 0.024) OW. Constipation in individuals with ALS is associated with faster disease progression and reduced survival rates, potentially through the peroxisome proliferator-activated receptor pathway.

The Relationship between Hearing Impairment and Dementia in Primary Care: A Nested Case-Control Study

Background: Dementia is a major cause of morbidity and mortality in older persons, and it has socio-economic impact on the society. Globally, it is the fifth leading cause of mortality, and the prevalence has been projected to triple by 2050. There is increasing evidence of a link between dementia and hearing loss, but the direction of cause and effect, and strength of association is unclear. Therefore, a nested case control study within one of the largest available databases of primary care records in the UK was used to check the association between hearing impairment and dementia. Aim: To estimate the proportion of exposure to hearing impairment in dementia cases and, to quantify the association by estimating the risk ratio. To establish whether the calculated risk ratio varies according to the timing of exposure from less than one month to over three years in cases compared to controls. Methods: A Nested Case-Control study was used to investigate the association between dementia, and hearing impairment and other closely related hearing problems by following-up 137,270 incident cases of dementia with 450,704 matched controls by age and gender who were 50 years and above in the UK primary care setting. Conditional logistic regression was used for the unadjusted risk ratio while multiple conditional logistic regression analysis was used to find an independent association between hearing impairment and dementia. Results: From the sample population, 25.7% of the cases and 23.9% of the controls were exposed to hearing impairment. There was a 10% (RR=1.10, 95% CI=1.08-1.12) increased risk of dementia after exposure to hearing impairment and this risk was greatest within four weeks of exposure (RR=1.68, 95% CI=1.52-1.85). However, the association was confounded by referral to ENT. Conclusion: This study shows that hearing impairment could precedes the development of dementia, and it could increase the risk of dementia by 10%, but this link is greatest within a month of exposure to hearing impairment. Consequently, hearing impairment could be an indicator to screen for before the development of dementia.

Plasma Transcriptome Profile Associated with Chronic Kidney Disease Progression

Introduction: Understanding the molecular signals associated with the progression of kidney disease is vital for risk stratification and targeted treatment. Recent advances in RNA-sequencing technique have enabled us to characterize extracellular transcriptome profiles for precision diagnostics. Method: We evaluated the plasma mRNA profile of participants exhibiting slow (n = 119) and fast (n = 119) decline in estimated glomerular filtration rate (eGFR) among the Chronic Renal Insufficiency Cohort (CRIC) in a nested case control study. The two groups were matched for age, sex, race, baseline eGFR, proteinuria, and diabetes status. The next-generation sequencing data were analyzed using edgeR to identify differentially expressed genes (DEGs) and ingenuity pathway analysis was done to identify the associated pathways. We also compared the top plasma DEGs with gene expression in microdissected human chronic kidney disease (CKD) kidney. Results: We identified fragments from ∼28,000 annotated genes, of which 783 transcripts exhibited differential expression between slow and fast CKD progressors. Among 629 protein coding genes, 469 were overexpressed in slow progressors, while 157 showed increased expression in fast progressors. Expression of GLI2, CUX1, NOTCH1, and LRP1 transcripts were amplified in slow progressors. Pathway analysis linked these DEG to WNT/β-catenin signaling, IL-12 signaling and production in macrophages, Netrin-1 Signaling and Epithelial-Mesenchymal Transition pathways. Many of the plasma DEGs were also upregulated in microdissected human CKD kidney. Conclusion: Warranting further validation, circulating levels of aberrantly expressed transcripts hold potential to be used as biomarkers for fast CKD progression.

Gabapentinoid use and the risk of fractures in patients with inflammatory arthritis: nested case–control study in the Clinical Practice Research Datalink Aurum

BackgroundGabapentinoids are increasingly prescribed in inflammatory arthritis (IA), despite no trial evidence for efficacy at managing pain in this population. Observational studies in non-IA populations suggest gabapentinoids are associated with fractures but are limited by methodological heterogeneity/potential residual confounding. Patients with IA generally have an increased risk of fracture so may be particularly vulnerable. We examined the relationship between fractures and gabapentinoids in patients with IA who had all been prescribed a gabapentinoid at some point (to minimise confounding by indication).MethodsOur matched case–control study used linked national data from English primary care (Clinical Practice Research Datalink Aurum) and Hospital Episode Statistics. A cohort was constructed of adults with IA, contributing data 01/01/2004–31/03/2021, and ever prescribed oral gabapentinoids. Cases with an incident fracture post-cohort inclusion were ascertained and 1:5 risk set-matched (on age/gender/gabapentinoid type) with controls. Gabapentinoid prescription exposure was categorised as follows: (a) current (overlapping with fracture date); (b) recent (ending 1–60 days pre-fracture); and (c) remote (ending > 60 days pre-fracture). Conditional logistic regression models determined ORs with 95% CIs for fractures with current or recent vs. remote gabapentinoid use, adjusting for confounders.ResultsA total of 2485 cases (mean age 63.0 years; 79.4% female) and 12,244 controls (mean age 62.7 years; 79.6% female) were included. Of cases: 1512 received gabapentin, 910 pregabalin, and 63 both drugs; 65.6% were remote, 5.5% recent, and 28.9% current users. In adjusted models, current gabapentinoid use had an increased risk of fracture (OR vs. remote: 1.36 [95% CI 1.22, 1.51]). Similar associations were seen with gabapentin (OR 1.38 [1.19, 1.60]) and pregabalin (OR 1.40 [1.18, 1.66]). Similar or higher levels of association were seen for all gabapentin/pregabalin doses except moderate/very high dose gabapentin. Associations were strongest in those starting gabapentinoids more recently.ConclusionsOur study suggests a modest association between current gabapentinoid use and fractures in patients with IA, after accounting for measured and time-invariant unmeasured confounding. Whilst other unmeasured confounding remains possible, given the absence of evidence for gabapentinoid efficacy in patients with IA who are particularly vulnerable to fractures, this highlights a need for efforts to deliver safer gabapentinoid prescribing in this population.

Epidemiology and risk factors of non-esophageal eosinophilic gastrointestinal diseases in Japan: A population-based study

BackgroundNon-esophageal eosinophilic gastrointestinal diseases (non-EoE EGIDs) are allergic conditions where Th-2-predominant inflammation causes symptoms related to gastrointestinal tract dysfunction. No studies have reported the incidence of non-EoE EGIDs. In addition, little is known about the influence of lifestyle factors on the condition. MethodsWe used a large health claim database from January 2005 to September 2022. Non-EoE EGIDs cases were identified on the basis of the International Classification of Diseases-tenth Revision code, K52.8. The incidence and prevalence of non-EoE EGIDs were estimated by Poisson and binomial distribution, respectively. For each case, 10 controls were randomly selected for a nested case–control study to identify potential risk factors of non-EoE EGIDs. ResultsOf 15,200,895 individuals, 1,368 new cases of non-EoE EGIDs were identified. The incidence and prevalence of non-EoE EGIDs in 2022 were 3.07 (95% CI 2.67–3.52) per 100,000 person-years and 17.23 (95% CI 16.38–18.11) per 100,000 individuals, respectively, which were approximately 6 and 9 times higher than those in 2010. Allergic rhinitis (OR 1.63 (95% CI 1.16–2.29), p = 0.005), chronic sinusitis (OR 2.41 (95% CI 1.58–3.66), p < 0.001), and urticaria (OR 2.32 (95% CI 1.45–3.70), p < 0.001) were related to an increased risk of adult non-EoE EGIDs. Whilst atopic dermatitis (OR 2.28 (95% CI 1.35–3.86), p = 0.006) and the perinatal factors (OR 3.68 (95% CI 1.13–12.02), p = 0.031) were associated with an increased risk of pediatric non-EoE EGIDs. No association was seen with lifestyle factors such as obesity, smoking and alcohol consumption. ConclusionsThe incidence and prevalence of non-EoE EGIDs have increased over the past two decades.

Seroprevalence of Helicobacter pylori and incident myocardial infarction - A population-based Swedish nested case-control study.

Helicobacter pylori (H. pylori) and its Cytotoxin associated gene A (CagA) have been associated with myocardial infarction (MI), but existing data are conflicting possibly due to limitations in study designs and lack of data on important confounders. The aim of this study was to determine whether H. pylori or CagA seropositivity are associated with incident MI, including MI phenotypes, and to describe temporal trends. We used the Northern Sweden Health and Disease study, a prospective biobank with data from residents enrolled in a population-based cohort from health examinations between 1986 and 2006. A total of 826 first time MI cases with available blood samples from their index health examination were identified up to 2006. Each case was 1:2 matched with controls by age, sex, sample date and geographical area. Blood samples were analysed using ELISA to determine seroprevalence of H. pylori and CagA, which were then used to study the association with incident MI. The median age at baseline was 50 years, and 71% of participants were male. Seroprevalence of H. pylori and CagA was 46.5% and 32.1% in cases, respectively, compared to 43.7% and 30.6% in controls. Overall, H. pylori prevalence decreased over the study period. After multivariable adjustments, no significant association was observed between H. pylori seropositivity and incident MI (odds ratio 1.15, 95% CI 0.94-1.42) nor between CagA-positive H. pylori and incident MI. In a Swedish population-based cohort, no significant association was observed between H. pylori or CagA seropositivity and incidence of MI.

Plasma levels of matrix metalloproteinases in early psychosis, anxiety and depression: Evidence from the ALSPAC cohort

BackgroundConverging evidence supports the role of Matrix Metalloproteinases (MMPs) in psychiatric disorders. Originally identified as regulators of the extracellular matrix (ECM), MMPs’ functions span multiple processes, including inflammation, synaptic plasticity, neuronal migration, and blood–brain barrier maintenance. Tissue Inhibitors of Metalloproteinases (TIMPs) are major regulators of MMPs. In the present study we examined the associations of plasma MMPs and TIMPs with mental disorders in young adults aged 24 years in the Avon Longitudinal Study of Parents and Children (ALSPAC). MethodsThe present study was a nested case control study within the Avon Longitudinal Study of Parents and Children and comprised 374 participants who met criteria for psychiatric disorders (35 met the criteria for psychotic disorder, 201 for mild/moderate depressive disorder, and 266 for generalised anxiety disorder) and 401 controls. All cases and controls had were selected from the group of 4019 participants who had attended at age 24 years, completed psychiatric assessments and provided plasma samples. Plasma concentrations of MMP2, MMP3, MMP9 and TIMP-4 were quantified using proximity extension assays available on Olink® Cardiovascular Panel III. Logistic regression analysis compared standardised MMPs and TIMPs levels in cases and controls. Models were adjusted for sex, body mass index, and cigarette smoking. ResultsThere was evidence for an association between MMP3 and depressive disorder (Odds ratio [OR] 1.35, 95 % confidence interval [CI] 1.06–1.73). There was evidence for an association between TIMP4 and depressive disorder (OR 1.51, 95 % CI 1.22–1.88) and generalised anxiety disorder (OR 1.43, 95 % CI 1.19–1.72). There was no evidence for an association between MMPs and psychotic disorders. ConclusionsThe study revealed that 24-year-olds with depressive and anxiety disorders exhibited elevated plasma concentrations of TIMP-4 compared to controls. There was evidence for an association between MMP3 and depressive disorder. These findings provide further support for the involvement of metalloproteinases as biomarkers in the pathophysiology of mental disorders during early adulthood.

Longitudinal history of mammographic breast density and breast cancer risk by familial risk, menopausal status, and initial mammographic density level in a high risk cohort: a nested case–control study

BackgroundElevated mammographic density is associated with increased breast cancer risk. However, the contribution of longitudinal changes in mammographic density to breast cancer risk beyond initial mammographic density levels, considering familial breast cancer risk and menopausal status, remains uncertain but holds important clinical implications.MethodsIn a nested case–control study within the Sister Study (323 cases, 899 controls; 12,095 mammograms), a cohort enriched for family history of breast cancer, we examined case–control status in relation to the largest annual change in percent density and dense area using mammograms available spanning 5.4 years, on average, using multivariable logistic regression and to the rate of mammographic density change using linear mixed-effects models. We considered effect modification by: mammographic density level of the earlier mammogram, the extent of family history, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation (BOADICEA) risk strata, and menopausal status.ResultsCases (diagnosed < 60 years) had greater initial percent density and dense area levels and a slower rate of decline in dense area than controls. Women with stable mammographic density (≤ 10% annual change) had an increased breast cancer risk as compared with women whose largest mammographic density change was > 10% annual decline (e.g., Odds Ratio (OR) 2.34, 95% Confidence Interval (CI) 1.63–3.37 for dense area). Increasing vs. decreasing dense area was also associated with elevated risk, especially in women with the highest dense area levels at the earlier mammogram (OR: 2.56, 95%CI 1.50–4.36). Although generally similar across menopausal and familial risk categories, the associations of MD change with risk appeared stronger in pre-menopausal and lower-risk women.ConclusionsWomen who maintain higher levels of mammographic density (i.e. do not decrease over time) or have increasing mammographic density over time have a higher risk of subsequent breast cancer than women with high mammographic density that decreases over time. These findings suggest potential for incorporating mammographic density trajectories in clinical risk assessment, and the importance of additional breast cancer monitoring in women not experiencing declines in mammographic density over time.

Plasma sTWEAK, diabetes mellitus, and bone fractures in postmenopausal women

BackgroundCytokines, such as tumor necrosis factor alpha (TNFα) and TNF-like weak inducer of apoptosis (TWEAK), may have pivotal roles in regulating bone remodeling in osteoporosis. Therefore, this study aims to investigate the potential association between plasma sTWEAK levels and bone fractures in diabetes mellitus (DM) and postmenopausal conditions. MethodsA nested case–control study was conducted within a cohort comprising 1057 postmenopausal women in Santa Maria. We analyzed 52 subjects who reported major bone fractures (defined as hip, forearm, humerus, or clinical vertebral fractures occurring after the age of 45 years, excluding high-impact fractures) and 110 subjects who did not experience fractures. Participants completed a questionnaire regarding clinical data, and anthropometric evaluations were conducted. Blood samples were collected for biochemical profiling, and sTWEAK plasma concentrations were determined via enzyme-linked immunosorbent assay (ELISA). Logarithmic transformation was applied to asymmetric variables. Student's t-test or Mann–Whitney test was utilized to compare data between two groups, while ANOVA or Chi-square test was employed for comparisons involving more than two groups. ResultsDiabetic subjects exhibited lower plasma levels of sTWEAK (p = 0.002). However, no significant differences were observed concerning the presence of bone fractures. ConclusionsPlasma levels of sTWEAK were not found to be associated with bone fragility in postmenopausal women. Nonetheless, reduced plasma levels of this cytokine were linked to diabetes mellitus.

Evaluation of systemic medications associated with diabetic retinopathy: a nested case–control study from the UK Biobank

AimsThis study aims to investigate the associations between commonly used systemic medications and diabetic retinopathy (DR).MethodsIndividuals with linked primary care prescription data from the UK Biobank were included. Cases were...

Comorbidities associated with chronic kidney disease among young people living with HIV in Uganda. A nested case control study.

Chronic kidney disease (CKD) is often complicated by disorders in multiple body systems, associated with higher mortality and morbidity. Young people living with HIV (YPLHIV) have an increased risk of multisystem chronic comorbidities. However, there are few data describing comorbidities associated with CKD among YPLHIV. We conducted a case-control study in seven ART clinics in Kampala, Uganda. Cases were YPLHIV (aged 10-24 years) diagnosed with CKD and controls were those without CKD. We collected data on demographic and clinical factors: blood pressure, fasting glucose levels, anaemia, electrolytes, parathyroid hormone, and cognitive impairment. We summarized the demographic and clinical factors and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for associations between CKD comorbidities, adjusted for age, sex and viral suppression. A total of 292 participants (96 cases and 196 controls) were recruited. Cases were mostly male (59.4% vs 36.5%), and younger (88.5% vs 46.4% aged <17 years) compared to controls. CKD was associated with having a detectable HIV viral load (OR=3.73; 95% CI 1.53-9.12) and proteinuria (aOR=4.19; 95% CI 2.28-7.72). CKD was also associated with low haematocrit, hypochloraemia, hyperphosphatemia, and high mean corpuscular volume. There was no evidence of an association of CKD with hypertension, anaemia, or stunting. The pattern of comorbidities among YPLHIV with CKD is uncertain and difficulties may relate to difficulty determining true kidney function and normal ranges in this population. Further studies are needed to discern the pattern of CKD complications to improve management efforts and clinical outcomes.

A genome-wide association study in Swedish colorectal cancer patients with gastric- and prostate cancer in relatives

BackgroundA complex inheritance has been suggested in families with colorectal-, gastric- and prostate cancer. Therefore, we conducted a genome-wide association study (GWAS) in colorectal cancer patients, who’s relatives had prostate-, and/or gastric cancer.MethodsThe GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model. Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case–control study.ResultsCandidate loci/genes on ten chromosomal regions were suggested with odds ratios between 1.71–3.62 and p-values < 5 × 10–8 in the analysis. The regions suggested were 1q32.2, 3q29, 4q35.1, 4p15.31, 4q26, 8p23.1, 13q33.3, 13q13.3, 16q23.3 and 22q11.21. All regions, except one on 1q32.2, had protein coding genes, many already shown to be involved in cancer, such as ZDHHC19, SYNPO2, PCYT1A, MYO16, TXNRD2, COMT, and CDH13. Sequencing of DNA from 122 colorectal cancer patients with gastric- and/or prostate cancer in their families was performed to search for candidate variants in the haplotype regions. The identified candidate variants were tested in a nested case–control study of similar colorectal cancer cases and controls. There was some support for an increased risk of colorectal-, gastric-, and/or prostate cancer in all the six loci tested.ConclusionsThis study demonstrated a proof of principle strategy to identify risk variants found by GWAS, and identified ten candidate loci that could be associated with colorectal, gastric- and prostate cancer.Graphical

Incidence of Central Serous Chorioretinopathy and its Association with Gynecological Diseases in Women: a Population-based Nested Case–Control Study

Purpose: Although the exact pathogenesis of central serous chorioretinopathy (CSC) remains unclear, some factors are known to be sex-specific. We aimed to investigate the incidence and systemic associations for CSC in women. Methods: This population-based nested case–control study included East Asian women whose medical claims data were obtained from the Korean National Health Insurance Service database. Patients newly diagnosed with CSC between 2017 and 2019 were assigned to the CSC group and matched to healthy controls in a 1:4 ratio by age, gender, and index date. The incidence of CSC in women and its association with gynecologic comorbidities and corticosteroid use before the index date (2008-2017) were analyzed. Results: The study matched 3,789 patients with CSC with 15,156 controls. The 3-year cumulative incidence of CSC in women was 27.13 (95% confidence interval [CI], 27.06–27.19) per 100,000 people. Multivariate logistic analysis showed a significantly increased association of CSC in patients with pre-eclampsia (adjusted odds ratio [aOR], 2.66; 95% CI, 1.86–3.81) (P&lt;0.001), endometriosis (aOR, 1.19; 95% CI, 1.03–1.38) (P&lt;0.001), steroid injections alone (aOR, 1.29; 95% CI, 1.16–1.43) (P&lt;0.001), and combination use of oral and injected steroid (aOR, 1.34; 95% CI, 1.23–1.47) (P&lt;0.001) compared to the controls. Conclusions: This study provides nationwide population-based data on the incidence of CSC in Asian women and suggests that exposure to specific gynecological comorbidities and intensive corticosteroid use are associated with the development of CSC in women.

Increased risk of clinically relevant neurodevelopmental disorders in survivors of congenital diaphragmatic hernia: a population-based study.

Neurodevelopmental disorders (ND) have been recognized as the most common and potentially most disabling outcome of congenital diaphragmatic hernia (CDH). Our aim was to evaluate the incidence of ND in patients with a history of CDH referred for ND assessment on the basis of clinically relevant symptoms rather than through a screening process. The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children who survived the newborn period in Sweden during the observational period from 1st January 1982 until 31st December 2015. In the study period, 641 non-syndromic CDH survivors were identified, and 3080 control cases were selected. Significantly higher incidence of clinically relevant any ND (11.5% vs 5.6%,p < 0.001), ASD (3.9% vs 2.1%,p:0.011), and intellectual disorder (6.6% vs 0.7%,p < 0.001) were observed in CDH compared to controls. When compared with controls, those with CDH were found to have a 2.179 times higher risk to develop any ND (p < 0.001), 1.867 times higher risk for ASD (p = 0.008), and 10.63 times higher for intellectual disorder (p < 0.001). CDH survivors have a higher risk of clinically relevant ND than the general population, independent of the effect of screening.

Survival rate changes in children with congenital diaphragmatic hernia over the past three decades: a nationwide, population-based prospective nested case-control study.

The survival rate (SR) for neonates born with congenital diaphragmatic hernia (CDH) remains high. Our aim was to investigate the change in SR in children with CDH over the past decades. The study was a nationwide, population-based prospective nested case-control study within a cohort of newborn children who was born in Sweden during the observational period from 1st January 1982 to 31st December 2015. In the study period, 4654 (99.6%) control children and 684 children with CDH (70.4%, p < 0.001) were with a survival of 2years of age. Any patients who were born with CDH had a overall 5.8 times higher chance for not surviving 2years of age than children without CDH. The SR improved significantly in CDH in the past 3 decades. Significantly higher number of patients were prematurely born in the CDH group than in the controls (23.3 vs 6.1%, p < 0.001). The SR of premature and non-premature born CDH patients has increased significantly over the past 3 decades. The SR of CDH patients were significantly increased in the past 3 decades. The 2-year survival remains 5.8 times higher than those who were not born with CDH. These changes were mainly attributed to the improved SR of premature and non-premature born CDH patients.

Bipolar disorder in people with HIV.

To assess whether bipolar disorders are associated with the risk of HIV infection and whether the risk of bipolar disorders is increased among people with HIV (PWH) and their siblings. Nationwide, population-based, combined matched nested case-control and cohort study of PWH of Danish origin (1995-2021), a comparison cohort from the background population, matched on date of birth and sex, and sibling cohorts. Conditional logistic regression and Cox regression was used to calculate adjusted odds ratios (aORs) for HIV infection and hazard ratios among PWH for bipolar disorder and receipt of lithium. We included 5322 PWH and 53 220 comparison cohort members. In the case-control study, bipolar disorder was associated with an increased risk of HIV infection [aOR: 1.9, 95% confidence interval (CI): 1.2-3.0], especially when injection drug use was the route of infection (aOR: 7.6, 95% CI: 2.0-28.9). In the cohort study, we observed an increased risk of bipolar disorders among PWH, especially in the first 2 years of observation (hazard ratio: 4.2, 95% CI: 2.4-7.4), whereas the risk of receipt of lithium was lower and the CI crossed 1. The 20-year risk of bipolar disorders for PWH was approximately 1%. Siblings of PWH also had an increased risk of bipolar disorder but not to the same degree as PWH and not of receipt of lithium. Bipolar disorders are associated with the risk of HIV infection, and PWH have increased risk of bipolar disorder and receipt of lithium beyond what familial factors could explain.