scholarly journals Are infectious diseases risk factors for sarcoidosis or a result of reverse causation? Findings from a population-based nested case–control study

2020 ◽  
Vol 35 (11) ◽  
pp. 1087-1097 ◽  
Author(s):  
Marios Rossides ◽  
Susanna Kullberg ◽  
Johan Askling ◽  
Anders Eklund ◽  
Johan Grunewald ◽  
...  

AbstractFindings from molecular studies suggesting that several infectious agents cause sarcoidosis are intriguing yet conflicting and likely biased due to their cross-sectional design. As done in other inflammatory diseases to overcome this issue, prospectively-collected register data could be used, but reverse causation is a threat when the onset of disease is difficult to establish. We investigated the association between infectious diseases and sarcoidosis to understand if they are etiologically related. We conducted a nested case–control study (2009–2013) using incident sarcoidosis cases from the Swedish National Patient Register (n = 4075) and matched general population controls (n = 40,688). Infectious disease was defined using inpatient/outpatient visits and/or antimicrobial dispensations starting 3 years before diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression and tested for robustness assuming the presence of reverse causation bias. The aOR of sarcoidosis associated with history of infectious disease was 1.19 (95% confidence interval [CI] 1.09, 1.29; 21% vs. 16% exposed cases and controls, respectively). Upper respiratory and ocular infections conferred the highest OR. Findings were similar when we altered the infection definition or varied the infection-sarcoidosis latency period (1–7 years). In bias analyses assuming one in 10 infections occurred because of preclinical sarcoidosis, the observed association was completely attenuated (aOR 1.02; 95% CI 0.90, 1.15). Our findings, likely induced by reverse causation due to preclinical sarcoidosis, do not support the hypothesis that common symptomatic infectious diseases are etiologically linked to sarcoidosis. Caution for reverse causation bias is required when the real disease onset is unknown.

2021 ◽  
Author(s):  
Yuri Kitamura ◽  
Ling Zha ◽  
Rong Liu ◽  
Masayuki Shima ◽  
Tomoki Nakaya ◽  
...  

Abstract BackgroundAlthough a causal relationship between mesothelioma and asbestos exposure is well known, few studies have shown a relationship to non-occupational exposure, including neighborhood exposure, most likely because of the large effect size of occupational exposure. The aim of this study was to quantify the risk of malignant mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, by properly adjusting for occupational exposure. MethodsThis was a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with neighborhood exposure were estimated by a conditional logistic-regression model that adjusted for other asbestos exposures. We adopted cumulative indices that considered residence-specific asbestos (crocidolite) concentrations and durations during the potential exposure period of 1957-1975 to evaluate individual neighborhood exposures.ResultsThere was an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrated by ORs in the highest quintile category that were 21.4 (95%CI: 5.8 to 79.2) for all, 23.7 (95% CI: 3.8-147.2) for males and 26.0 (95% CI: 2.8-237.5) for females, compared to the lowest quintile, respectively. These results clearly demonstrated no substantial differences between males and females in relation to the magnitude of risk from neighborhood exposure.Our findings suggest that the risk of mesothelioma death associated with neighborhood exposure persists and will not be diminished for many years, even though it has been decades since the AC plant closed. ConclusionsBy adjusting for occupational and other asbestos exposures, a dose-dependent relationship was demonstrated between mesothelioma death and neighborhood asbestos exposure from a large-scale AC plant.


RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001867
Author(s):  
Hao-Guang Li ◽  
Dan-Min Wang ◽  
Feng-Cai Shen ◽  
Shu-Xin Huang ◽  
Zhi-Duo Hou ◽  
...  

ObjectiveTo evaluate the clinical characteristics of juvenile-onset non-radiographic axial spondyloarthritis (nr-axSpA) and to investigate risk factors associated with progression to juvenile-onset ankylosing spondylitis (JoAS).MethodsA nested case–control study was conducted using the retrospectively collected data of 106 patients with juvenile-onset nr-axSpA (age at disease onset, <16 years) in the Clinical characteristic and Outcome in Chinese Axial Spondyloarthritis study cohort. Baseline demographic and clinical characteristics and prognosis were reviewed. Logistic regression analyses were performed to investigate risk factors associated with progression to JoAS.ResultsOverall, 58.5% of patients with juvenile-onset nr-axSpA presented with peripheral symptoms at disease onset. In 82.1% of these patients, axial with peripheral involvement occurred during the disease course. The rate of disease onset at >12 years and disease duration of ≤10 years were significantly higher in those with progression to JoAS than in those without progression to JoAS (83.0% vs 52.8%, p=0.001; 92.5% vs 56.6%, p<0.001, respectively). Multivariable logistic regression analysis revealed that inflammatory back pain (IBP) (OR 13.359 (95% CI 2.549 to 70.013)), buttock pain (OR 10.171 (95% CI 2.197 to 47.085)), enthesitis (OR 7.113 (95% CI 1.670 to 30.305)), elevated baseline C reactive protein (CRP) levels (OR 7.295 (95% CI 1.984 to 26.820)) and sacroiliac joint-MRI (SIJ-MRI) positivity (OR 53.821 (95% CI 9.705 to 298.475)) were significantly associated with progression to JoAS.ConclusionPeripheral involvement was prevalent in juvenile-onset nr-axSpA. IBP, buttock pain, enthesitis, elevated baseline CRP levels and SIJ-MRI positivity in patients with the disease are associated with higher risk of progression to JoAS.


Gut ◽  
2020 ◽  
pp. gutjnl-2020-322308 ◽  
Author(s):  
Jonathan Blackwell ◽  
Sonia Saxena ◽  
Irene Petersen ◽  
Matthew Hotopf ◽  
Hanna Creese ◽  
...  

ObjectiveDepression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD.DesignWe conducted a nested case–control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn’s disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5–5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status.ResultsWe identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38).ConclusionsDepression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.


2019 ◽  
Vol 104 (11) ◽  
pp. 5529-5539 ◽  
Author(s):  
Xiaoxu Huo ◽  
Jing Li ◽  
Yun-Feng Cao ◽  
Sai-Nan Li ◽  
Ping Shao ◽  
...  

Abstract Objectives This study aimed to investigate the associations between trimethylamine N-oxide (TMAO) and related metabolites in early pregnancy and the risk of gestational diabetes mellitus (GDM). Design A prospective cohort of 22,302 pregnant women from 2010 to 2012 in Tianjin, China, was used to perform a nested case-control study. A total of 243 women with GDM and 243 women without GDM matched by maternal age (±1 year) were used as cases and controls, respectively. Conditional logistic regression and restricted cubic spline were used to examine the full-range risk associations between individual TMAOs metabolites at the first antenatal care visit with GDM. Trimethylamine conversion ratio (TMAR) was defined as trimethylamine (TMA)/its precursors, and trimethylamine N-oxide conversion ratio (TMAOR) was defined as TMAO/TMA. An additive interaction between high TMAR and low TMAOR indicates a state of TMA accumulation, and a mathematical interaction between high TMAR and high TMAOR indicates accumulation of TMAO. Results TMA was linearly associated with GDM, whereas TMA precursors and TMAO were inversely associated with GDM with clear threshold effects, i.e., 16 nmol/mL for TMAO, 200 nmol/mL for betaine, 112 nmol/mL for l-carnitine, and 110 and 270 nmol/mL for cholinechloride (a U-shaped relationship). Copresence of TMAR >0.35 and TMAOR ≤0.15 was associated with a markedly higher OR (11.16; 95% CI, 5.45 to 22.8), compared with TMAR >0.35 only (OR = 1.71; 95% CI, 0.42 to 6.95) or TMAOR ≤0.15 only (OR = 2.06; 95% CI, 1.09 to 3.90), with a significant additive interaction. However, the mathematical interaction was nonsignificant. Conclusions TMAO metabolites in the early pregnancy were associated with the risk of GDM, whereas TMA was more likely to play a causal role in GDM.


2008 ◽  
Vol 26 (36) ◽  
pp. 5923-5929 ◽  
Author(s):  
Norie Kurahashi ◽  
Motoki Iwasaki ◽  
Manami Inoue ◽  
Shizuka Sasazuki ◽  
Shoichiro Tsugane

PurposeThe incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy.Patients and MethodsWe conducted a nested case-control study within the Japan Public Health Center–based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone.ResultsPlasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; Ptrend= .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; Ptrend= .03) and 0.43 (95% CI, 0.22 to 0.82; Ptrend= .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer.ConclusionIsoflavones may prevent the development of prostate cancer.


2021 ◽  
Vol 7 (1) ◽  
pp. 00944-2020
Author(s):  
Ivy Fong ◽  
Jingqin Zhu ◽  
Yaron Finkelstein ◽  
Teresa To

RationaleAntibiotics are among the most common medications dispensed to children and youths. The objective of this study was to characterise and compare antibiotic use patterns between children and youths with and without asthma.MethodsWe conducted a population-based nested case–control study using health administrative data from Ontario, Canada, in 2018. All Ontario residents aged 5–24 years with asthma were included as cases. Cases were matched to controls with a 1:1 ratio based on age (within 0.5 year), sex and location of residence. Multivariable conditional logistic regression was used to obtain an odds ratio and 95% confidence interval for having filled at least one antibiotic prescription, adjusted for socioeconomic status, rurality, and presence of common infections, allergic conditions and complex chronic conditions.ResultsThe study population included 1 174 424 Ontario children and youths aged 5–24 years. 31% of individuals with asthma and 23% of individuals without asthma filled at least one antibiotic prescription. The odds of having filled at least one antibiotic prescription were 34% higher among individuals with asthma compared to those without asthma (OR 1.34, 95% CI 1.32–1.35). In the stratified analysis, the odds ratios were highest in the youngest group of children studied, aged 5–9 years (OR 1.45, 95% CI 1.41–1.48), and in females (OR 1.36, 95% CI 1.34–1.38).ConclusionAsthma is significantly associated with increased antibiotic use in children and youths. This association is the strongest in younger children and in females.


2021 ◽  
Author(s):  
Peng Tang ◽  
Jun Liang ◽  
Qian Liao ◽  
Huishen Huang ◽  
Xiaojing Guo ◽  
...  

Abstract A growing number of epidemiologic studies have estimated the associations between endocrine-disrupting chemicals and gestational diabetes mellitus (GDM). However, reports on the association between bisphenol A (BPA) substitutes and GDM are limited. This investigation aimed to explore the associations of maternal serum BPA, bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) with the risk of GDM. A nested case-control study was performed among 500 pregnant women. Associations between the serum bisphenol levels and the risk of GDM were assessed by conditional logistic regression analysis and two-mixture modeling approaches (Bayesian kernel machine regression [BKMR] and quantile g-computation). BPA and TBBPA were negatively associated with the risk of GDM in the adjusted models, respectively. Intermediate BPS levels were associated with increased odds (OR: 1.84; 95% CI: 1.04, 3.27) of GDM compared with the low concentration groups only based on the single-bisphenol models. Associations between BPA, BPS, and TBBPA with the risk of GDM were also found in the BKMR analysis. The quantile g-computation (OR: 0.55; 95% CI: 0.43, 0.69) and BKMR models revealed a statistically significant and negative joint effect of the five bisphenols on the risk of GDM. This study demonstrates the association between exposure to BPS with the increased risk of GDM. In addition, exposure to BPA and TBBPA were associated with the reduced risk of GDM. Moreover, exposure to the mixture of the five bisphenols was negatively associated with the risk of GDM.


BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e034710 ◽  
Author(s):  
Loes L Cornelissen ◽  
Camila Caram-Deelder ◽  
Johanna G van der Bom ◽  
Rutger A Middelburg ◽  
Jaap Jan Zwaginga

IntroductionHaemato-oncological patients often receive platelet count driven prophylactic platelet transfusions to prevent bleeding. However, many prophylactically transfused patients still bleed. More knowledge on risk factors for bleeding is therefore needed. This will enable identification of bleeding risk profiles on which future transfusion policy can be optimised. The present BITE study (Bleeding In Thrombocytopenia Explained) aims to identify clinical conditions and biomarkers that are associated with clinically relevant bleeding events.Methods and analysisA matched case–control study nested in a cohort of haemato-oncological patients in the Netherlands. We collect a limited number of variables from all eligible patients, who together form the source population. These patients are followed for the occurrence of clinically relevant bleeding. Consenting patients of the source population form the cohort. Cases from the cohort are frequency matched to selected control patients for the nested case–control study. Of both case and control patients more detailed clinical data is collected.Study populationAdult haemato-oncological patients, who are admitted for intensive chemotherapeutic treatment or stem cell transplantation, or who received such treatments in the past and are readmitted for disease or treatment-related adverse events.Statistical analysisBleeding incidences will be calculated for the total source population, as well as for different subgroups. The association between potential risk factors and the occurrence of bleeding will be analysed using conditional logistic regression, to account for matching of case and control patients.Ethics and disseminationThe study was approved by the Medical Research Ethics Committee Leiden Den Haag and Delft, and the Radboudumc Committee on Research Involving Human Subjects. Approval in seven other centres is foreseen. Patients will be asked for written informed consent and data is coded before analyses, according to Dutch privacy law. Results will be published in peer-reviewed journals.Trial registration numberNL62499.058.17. NCT03505086; Pre-results.


Gut ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2008-2015 ◽  
Author(s):  
Rachael Stolzenberg-Solomon ◽  
Andriy Derkach ◽  
Steven Moore ◽  
Stephanie J Weinstein ◽  
Demetrius Albanes ◽  
...  

ObjectiveTo assess whether prediagnostic metabolites were associated with incident pancreatic ductal adenocarcinoma (PDAC) in a prospective cohort study.DesignWe conducted an untargeted analysis of 554 known metabolites measured in prediagnostic serum (up to 24 years) to determine their association with incident PDAC in a nested case-control study of male smokers (372 matched case-control sets) and an independent nested case-control study that included women and non-smokers (107 matched sets). Metabolites were measured using Orbitrap Elite or Q-Exactive high-resolution/accurate mass spectrometers. Controls were matched to cases by age, sex, race, date of blood draw, and follow-up time. We used conditional logistic regression adjusted for age to calculate ORs and 95% CIs for a 1 SD increase in log-metabolite level separately in each cohort and combined the two ORs using a fixed-effects meta-analysis.ResultsThirty-one metabolites were significantly associated with PDAC at a false discovery rate <0.05 with 12 metabolites below the Bonferroni-corrected threshold (p<9.04×10–5). Similar associations were observed in both cohorts. The dipeptides glycylvaline, aspartylphenylalanine, pyroglutamylglycine, phenylalanylphenylalanine, phenylalanylleucine and tryptophylglutamate and amino acids aspartate and glutamate were positively while the dipeptides tyrosylglutamine and α-glutamyltyrosine, fibrinogen cleavage peptide DSGEGDFXAEGGGVR and glutathione-related amino acid cysteine-glutathione disulfide were inversely associated with PDAC after Bonferroni correction. Five top metabolites demonstrated significant time-varying associations (p<0.023) with the strongest associations observed 10–15 years after participants’ blood collection and attenuated thereafter.ConclusionOur results suggest that prediagnostic metabolites related to subclinical disease, γ-glutamyl cycle metabolism and adiposity/insulin resistance are associated with PDAC.


Author(s):  
Angelita M. Hensman ◽  
Debra A. Erickson-Owens ◽  
Mary C. Sullivan ◽  
Brian J. Quilliam

Abstract Objective The aim of this study was to estimate the incidence and identify the factors associated with neonatal readmission among healthy term infants. Study Design A nested case–control study with matching was conducted at a large level III perinatal hospital with approximately 8,700 deliveries each year. Each case infant (n = 130) was matched to two control infants (n = 260) on the case infant's date of birth (±7 days) and the mother's maternal age (<20 years, 20–29, 30–39, and >39 years). All infants were selected from a cohort of eligible term, healthy, in-state infants admitted to the newborn unit postdelivery from January 1, 2016 to May 8, 2017. Data were analyzed using hierarchical conditional logistic regression. Results The incidence of neonatal readmission was 2.2%, and all readmissions occurred within 8.6 days of birth. Earlier gestational age (37 weeks; odds ratio [OR]: 4.11, 95% confidence interval [CI]: 1.79–9.45; 38 weeks OR: 1.29, CI 0.60–2.75; [ref] 39 weeks), jaundice on day two of life (OR: 2.45; CI: 1.40–4.30), maternal group B streptococcus chemoprophylaxis (OR: 2.55; CI: 1.23–5.28 [Ref N/A]) were associated with readmission. Delivery by cesarean section (OR: 0.31, CI: 0.12–0.79) and each milliliter of formula [first three days] (OR: 0.96; CI: 0.993–0.999) were protective. Conclusion Neonatal readmission in healthy term infants may potentially be reduced with identification of modifiable determinants of readmission prior to discharge. Policies to capture the true incidence of neonatal readmissions should include admissions to hospitals other than the birth hospital.


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