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Associations between selected immune-mediated diseases and tuberculosis: record-linkage studies.

ABSTRACT: BACKGROUND: Previous studies have suggested that there may be an association between some immune-mediated diseases and risk of tuberculosis (TB). METHODS: We analyzed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999 to 2011), and a similar database (the Oxford Record Linkage Study (ORLS)) for a region of southern England in an earlier period. Rate ratios for TB were determined, comparing immune-mediated disease cohorts with comparison cohorts. RESULTS: In the all-England dataset, there were significantly elevated risks of TB after hospital admission for the following individual immune-mediated diseases: Addison's disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active hepatitis, coeliac disease, Crohn's disease, dermatomyositis, Goodpasture's syndrome, Hashimoto's thyroiditis, idiopathic thrombocytopenia purpura (ITP), myasthenia gravis, myxedema, pemphigoid, pernicious anemia, polyarteritis nodosa, polymyositis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, scleroderma, Sjögren's syndrome, systemic lupus erythematosus (SLE), thyrotoxicosis and ulcerative colitis. Particularly high levels of risk were found for Addison's disease (rate ratio (RR) = 11.9 (95% CI 9.5 to 14.7)), Goodpasture's syndrome (RR = 10.8 (95% CI 4.0 to 23.5)), SLE (RR = 9.4 (95% CI 7.9 to 11.1)), polymyositis (RR = 8.0 (95% CI 4.9 to 12.2)), polyarteritis nodosa (RR = 6.7 (95% CI 3.2 to 12.4)), dermatomyositis (RR = 6.6 (95% CI 3.0 to 12.5)), scleroderma (RR = 6.1 (95% CI 4.4 to 8.2)) and autoimmune hemolytic anemia (RR = 5.1 (95% CI 3.4 to 7.4)). CONCLUSIONS: These two databases show that patients with some immune-mediated diseases have an increased risk of TB, although we cannot explicitly state the direction of risk or exclude confounding. Further study of these associations is warranted, and these findings may aid TB screening, control and treatment policies.

SUBMITTER: Ramagopalan SV

PROVIDER: S-EPMC3616814 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Associations between selected immune-mediated diseases and tuberculosis: record-linkage studies.

Ramagopalan Sreeram V SV Goldacre Raph R Skingsley Andrew A Conlon Chris C Goldacre Michael J MJ

BMC medicine 20130404

<h4>Background</h4>Previous studies have suggested that there may be an association between some immune-mediated diseases and risk of tuberculosis (TB).<h4>Methods</h4>We analyzed a database of linked statistical records of hospital admissions and death certificates for the whole of England (1999 to 2011), and a similar database (the Oxford Record Linkage Study (ORLS)) for a region of southern England in an earlier period. Rate ratios for TB were determined, comparing immune-mediated disease coh ...[more]

PMID: 23557090

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Project description:IntroductionIFN-γ release assays (IGRAs) are one of the referral tests for diagnosing tuberculosis infection (TBI). To improve IGRAs accuracy, several markers have been investigated. Patients with immune-mediated inflammatory diseases (IMID), taking biological drugs, have a higher risk to progress to TB-disease compared to the general population. In several guidelines, annual TBI screening is recommended for patients undergoing biological therapy. Aim of this study was to investigate, within the QuantiFERON-TB-Plus (QFT-Plus) platform, if beside IFN-γ, alternative biomarkers help to diagnose TBI-IMID patients.MethodsWe enrolled 146 subjects: 46 with TB disease, 20 HD, 35 with TBI and 45 with TBI and IMID. Thirteen IMID subjects with a QFT-Plus negative result were diagnosed as TBI based on radiological evidence of TBI. We evaluated the IP-10 level in response to TB1 and TB2 peptides of QFT-Plus assay and we compared these results with the standardized assay based on IFN-γ. Multiplex immune assay was performed on plasma from TB1 and TB2 tubes and results were analyzed by a gradient boosting machine (GBM) as learning technique.ResultsTBI-IMID showed a significant decreased IP-10 level in response to TB1 and TB2 stimulation compared to TBI-NO IMID (p < 0.0001 and p = 0.0002). The TBI-IMID showed a moderate agreement between the IP-10-based assay and QFT-Plus scores. In TBI-IMID, QFT-Plus showed 70% sensitivity for TBI detection whereas the IP-10-based assay reached 61%. Tests combination increased the sensitivity for TBI diagnosis up to 77%. By a GBM, we explored alternative biomarkers for diagnosing TBI in IMID population reaching 89% sensitivity. In particular, the signature based on IL-2, IP-10, and IL-9 detection was associated with TB status (infection/disease). However, by applying the cut-off identified by ROC analysis, comparing TB and TBI with the HD group, within the IMID population, we did not improve the accuracy for TBI-diagnosis. Similarly, this signature did not improve TBI diagnosis in IMID with radiological evidence of TBI but negative QFT-Plus score.DiscussionTo develop alternative strategies for TBI immune-diagnosis, future studies are needed to evaluate the memory response of TBI defined by radiological tools. These results may help in tuberculosis management of patients taking lifelong immune-suppressive drugs.

Project description:BackgroundThere is an increasing use of cesarean delivery (CD) based on preference rather than on medical indication. However, the extent to which nonmedically indicated CD benefits or harms child survival remains unclear. Our hypothesis was that in groups with a low indication for CD, this procedure would be associated with higher child mortality and in groups with a clear medical indication CD would be associated with improved child survival chances.Methods and findingsWe conducted a population-based cohort study in Brazil by linking routine data on live births between January 1, 2012 and December 31, 2018 and assessing mortality up to 5 years of age. Women with a live birth who contributed records during this period were classified into one of 10 Robson groups based on their pregnancy and delivery characteristics. We used propensity scores to match CD with vaginal deliveries (1:1) and prelabor CD with unscheduled CD (1:1) and estimated associations with child mortality using Cox regressions. A total of 17,838,115 live births were analyzed. After propensity score matching (PSM), we found that live births to women in groups with low expected frequencies of CD (Robson groups 1 to 4) had a higher death rate up to age 5 years if they were born via CD compared with vaginal deliveries (HR = 1.25, 95% CI: 1.22 to 1.28; p < 0.001). The relative rate was greatest in the neonatal period (HR = 1.39, 95% CI: 1.34 to 1.45; p < 0.001). There was no difference in mortality rate when comparing offspring born by a prelabor CD to those born by unscheduled CD. For the live births to women with a CD in a prior pregnancy (Robson group 5), the relative rates for child mortality were similar for those born by CD compared with vaginal deliveries (HR = 1.05, 95% CI: 1.00 to 1.10; p = 0.024). In contrast, for live births to women in groups with high expected rates of CD (Robson groups 6 to 10), the child mortality rate was lower for CD than for vaginal deliveries (HR = 0.90, 95% CI: 0.89 to 0.91; p < 0.001), particularly in the neonatal period (HR = 0.84, 95% CI: 0.83 to 0.85; p < 0.001). Our results should be interpreted with caution in clinical practice, since relevant clinical data on CD indication were not available.ConclusionsIn this study, we observed that in Robson groups with low expected frequencies of CD, this procedure was associated with a 25% increase in child mortality. However, in groups with high expected frequencies of CD, the findings suggest that clinically indicated CD is associated with a reduction in child mortality.

Project description:We aimed to detect cross-sectional phenotype and polygenic risk score (PRS) associations between sleep duration and prevalent diseases using the Partners Biobank, a hospital-based cohort study linking electronic medical records (EMR) with genetic information. Disease prevalence was determined from EMR, and sleep duration was self-reported. A PRS for sleep duration was derived using 78 previously associated SNPs from genome-wide association studies (GWAS) for self-reported sleep duration. We tested for associations between (1) self-reported sleep duration and 22 prevalent diseases (n = 30 251), (2) the PRS and self-reported sleep duration (n = 6903), and (3) the PRS and the 22 prevalent diseases (n = 16 033). For observed PRS-disease associations, we tested causality using two-sample Mendelian randomization (MR). In the age-, sex-, and race-adjusted model, U-shaped associations were observed for sleep duration and asthma, depression, hypertension, insomnia, obesity, obstructive sleep apnea, and type 2 diabetes, where both short and long sleepers had higher odds for these diseases than normal sleepers (p < 2.27 × 10-3). Next, we confirmed associations between the PRS and longer sleep duration (0.65 ± 0.19 SD minutes per effect allele; p = 7.32 × 10-04). The PRS collectively explained 1.4% of the phenotypic variance in sleep duration. After adjusting for age, sex, genotyping array, and principal components of ancestry, we observed that the PRS was also associated with congestive heart failure (CHF; p = 0.015), obesity (p = 0.019), hypertension (p = 0.039), restless legs syndrome (RLS; p = 0.041), and insomnia (p = 0.049). Associations were maintained following additional adjustment for obesity status, except for hypertension and insomnia. For all diseases, except RLS, carrying a higher genetic burden of the 78 sleep duration-increasing alleles (i.e. higher sleep duration PRS) associated with lower odds for prevalent disease. In MR, we estimated causal associations between genetically defined longer sleep duration with decreased risk of CHF (inverse variance weighted [IVW] OR per minute of sleep [95% CI] = 0.978 [0.961-0.996]; p = 0.019) and hypertension (IVW OR [95% CI] = 0.993 [0.986-1.000]; p = 0.049), and increased risk of RLS (IVW OR [95% CI] = 1.018 [1.000-1.036]; p = 0.045). By validating the PRS for sleep duration and identifying cross-phenotype associations, we lay the groundwork for future investigations on the intersection between sleep, genetics, clinical measures, and diseases using large EMR datasets.

Project description:BackgroundChildren born preterm (<37 completed weeks' gestation) have a higher risk of infection-related morbidity than those born at term. However, few large, population-based studies have investigated the risk of infection in childhood across the full spectrum of gestational age. The objectives of this study were to explore the association between gestational age at birth and infection-related hospital admissions up to the age of 10 years, how infection-related hospital admission rates change throughout childhood, and whether being born small for gestational age (SGA) modifies this relationship.Methods and findingsUsing a population-based, record-linkage cohort study design, birth registrations, birth notifications and hospital admissions were linked using a deterministic algorithm. The study population included all live, singleton births occurring in NHS hospitals in England from January 2005 to December 2006 (n = 1,018,136). The primary outcome was all infection-related inpatient hospital admissions from birth to 10 years of age, death or study end (March 2015). The secondary outcome was the type of infection-related hospital admission, grouped into broad categories. Generalised estimating equations were used to estimate adjusted rate ratios (aRRs) with 95% confidence intervals (CIs) for each gestational age category (<28, 28-29, 30-31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42 weeks) and the models were repeated by age at admission (<1, 1-2, 3-4, 5-6, and 7-10 years). An interaction term was included in the model to test whether SGA status modified the relationship between gestational age and infection-related hospital admissions. Gestational age was strongly associated with rates of infection-related hospital admissions throughout childhood. Whilst the relationship attenuated over time, at 7-10 years of age those born before 40 weeks gestation were still significantly higher in comparison to those born at 40 weeks. Children born <28 weeks had an aRR of 6.53 (5.91-7.22) during infancy, declining to 3.16 (2.50-3.99) at ages 7-10 years, in comparison to those born at 40 weeks; whilst in children born at 38 weeks, the aRRs were 1·24 (1.21-1.27) and 1·18 (1.13-1.23), during infancy and aged 7-10 years, respectively. SGA status modified the effect of gestational age (interaction P<0.0001), with the highest rate among the children born at <28 weeks and SGA. Finally, study findings indicated that the associations with gestational age varied by subgroup of infection. Whilst upper respiratory tract infections were the most common type of infection experienced by children in this cohort, lower respiratory tract infections (LRTIs) (<28 weeks, aRR = 10.61(9.55-11.79)) and invasive bacterial infections (<28 weeks, aRR = 6.02 (4.56-7.95)) were the most strongly associated with gestational age at birth. Of LRTIs experienced, bronchiolitis (<28 weeks, aRR = 11.86 (10.20-13.80)), and pneumonia (<28 weeks, aRR = 9.49 (7.95-11.32)) were the most common causes.ConclusionsGestational age at birth was strongly associated with rates of infection-related hospital admissions during childhood and even children born a few weeks early remained at higher risk at 7-10 years of age. There was variation between clinical subgroups in the strength of relationships with gestational age. Effective infection prevention strategies should include focus on reducing the number and severity of LRTIs during early childhood.

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Associations between selected immune-mediated diseases and tuberculosis: record-linkage studies.

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Associations between selected immune-mediated diseases and tuberculosis: record-linkage studies.

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