Pulmonary Function and Quality of Life in Adults with Cystic Fibrosis.

PURPOSE: People living with cystic fibrosis (CF) experience impaired quality of life, but the extent to which pulmonary function is associated with quality of life in CF remains unclear METHODS: Using baseline data from a trial of specialist palliative care in adults with CF, we examined the association between pulmonary obstruction and quality of life (measured with the Functional Assessment of Chronic Illness Therapy Total Score). RESULTS: Among 262 participants, median age was 33, and 78% were on modulator therapy. The median quality of life score was higher in those with mild obstruction (135, IQR 110-156) compared to moderate (125, IQR 109-146) and severe obstruction (120, IQR 106-136). In an unadjusted model, we observed a non-significant trend toward lower quality of life with increased obstruction-compared to participants with mild obstruction, those with moderate obstruction had quality of life score 7.46 points lower (95% CI -15.03 to 0.10) and those with severe obstruction had a score 9.98 points lower (95% CI -21.76 to 1.80). However, this association was no longer statistically significant in the adjusted model, which may reflect confounding due to sex, age, BMI, and modulator therapy. Comorbidities (depression and anxiety) and social determinants of health (financial insecurity and education) were also associated with quality of life. CONCLUSION: Advancing our understanding of patient-centered markers of quality of life, rather than focusing on pulmonary function alone, may help identify novel interventions to improve quality of life in this patient population.

Linezolid Exposure Is Associated with Cytopenias in Patients Treated for Multidrug-Resistant Tuberculosis.

Although linezolid is effective for multidrug-resistant TB (MDR-TB) tuberculosis treatment, it is associated with cytopenias after 4 weeks of administration. Data on toxicities with long-term use of linezolid and drug pharmacodynamics in MDR-TB treatment are limited, and concerns about toxicity present barriers to wider implementation. This was a secondary analysis of a prospective cohort study of patients treated for MDR-TB in the country of Georgia from 2015 to 2017. Intensive blood sampling 4 to 6 weeks after treatment initiation with linezolid 600 mg daily was performed for pharmacokinetic (PK) analysis, including linezolid trough concentration (Cmin) and area under the curve from 0 to 24 hours (AUC0-24). Linezolid exposure was defined using literature-reported thresholds. Cytopenias were defined using an NIH adverse event (AE) scale. Logistic regression was used to evaluate the relationship between linezolid exposure and cytopenias. Among 76 patients receiving linezolid in their baseline treatment regimen and who had PK data available, cytopenia AEs occurred in 30 (39.5%) for an incidence rate of 46 per 100 person-years. The median duration of linezolid therapy was 526 days. No patients required dose reduction or interruption due to cytopenias. Median linezolid Cmin was 0.235 mg/L (interquartile range [IQR], 0.069 to 0.529), and median AUC0-24 was 89.6 mg·h/L (IQR, 69.2 to 116.2). Cytopenias were associated with linezolid PK parameters (Cmin > 2 mg/L and AUC0-24 > 160 mg·h/L). Cytopenias occurred frequently with long-term use of linezolid 600 mg/day and were associated with PK parameters but did not result in the need for treatment interruption in the management of a cohort of patients with MDR-TB.

Contribution of Smoking to Tuberculosis Incidence and Mortality in High-Tuberculosis-Burden Countries.

Globally, 10 million incident cases of tuberculosis (TB) are reported annually, and 95% of TB cases and 80% of tobacco users reside in low- and middle-income countries. Smoking approximately doubles the risk of TB disease and TB mortality. We estimated the proportion of annual incident TB cases and TB mortality attributable to tobacco smoking in 32 high-TB-burden countries. We obtained country-specific estimates of TB incidence, TB mortality, and smoking prevalence from the World Health Organization Global TB Report (2017), tobacco surveillance reports (2015), and the Tobacco Atlas. Risk ratios for the effect of smoking on TB incidence and TB mortality were obtained from published meta-analyses. An estimated 17.6% (95% confidence interval (CI): 8.4, 21.4) of TB cases and 15.2% (95% CI: 1.8, 31.9) of TB mortality were attributable to smoking. Among high-TB-burden countries, Russia had the highest proportion of smoking-attributable TB disease (31.6%, 95% CI: 15.9, 37.6) and deaths (28.1%, 95% CI: 3.8, 51.4). Men had a greater proportion of TB cases attributable to smoking (30.3%, 95% CI: 14.7, 36.6) than did women (4.3, 95% CI: 1.7, 5.7). Our findings highlight the need for tobacco control in high-TB-burden countries to combat TB incidence and TB mortality.

Stress Hyperglycemia in Patients with Tuberculosis Disease: Epidemiology and Clinical Implications.

PURPOSE OF REVIEW: The intersection of tuberculosis (TB) disease and type 2 diabetes mellitus is severely hindering global efforts to reduce TB burdens. Diabetes increases the risk of developing TB disease and negatively impacts TB treatment outcomes including culture conversion time, mortality risk, and TB relapse. Recent evidence also indicates plausible mechanisms by which TB disease may influence the pathogenesis and incidence of diabetes. We review the epidemiology of stress hyperglycemia in patients with TB and the pathophysiologic responses to TB disease that are related to established mechanisms of stress hyperglycemia. We also consider clinical implications of stress hyperglycemia on TB treatment, and the role of TB disease on risk of diabetes post-TB. RECENT FINDINGS: Among patients with TB disease, the development of stress hyperglycemia may influence the clinical manifestation and treatment response of some patients and can complicate diabetes diagnosis. Research is needed to elucidate the relationship between TB disease and stress hyperglycemia and determine the extent to which stress hyperglycemia impacts TB treatment response. Currently, there is insufficient data to support clinical recommendations for glucose control among patients with TB disease, representing a major barrier for efforts to improve treatment outcomes for patients with TB and diabetes.

Risk factors and epidemiology of Clostridium difficile infection in hematopoietic stem cell transplant recipients during the peritransplant period.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients represent a high-risk group for developing Clostridium difficile (CD) infection (CDI). We aimed to identify specific risk factors for CDI in an HSCT patient population during the peritransplant period. METHODS: We performed a case-control study within a cohort of HSCT patients who received a transplant from November 2010 to March 2013. Cases had a clinical presentation compatible with CDI and a positive stool sample Xpert® C. difficile test. Controls were CDI negative and matched on age, gender, and transplant type. Peritransplant period was defined as -30 days or time of stem cell mobilization maneuver to 30 days post transplant in autologous SCT or 90 days post transplant in allogeneic SCT. RESULTS: Of 781 HSCTs performed during the study period, 650 (83.2%) had a stool sample submitted for CD testing. Eight-six (13.2%) cases with CDI were identified. Most of the cases were diagnosed within a week after transplantation (median of 5 days). In adjusted analysis, prior hospitalization (odds ratio [OR]: 2.01, 95% confidence interval [CI] 1.2-3.36), prior cephalosporin administration (OR 2.72, 95% CI: 1.54-4.83), and prior chemotherapy (OR: 3.26, 95% CI: 1.92-5.5) were significantly associated with CDI. CONCLUSIONS: Hospitalization, and prior antibiotic and chemotherapy use are risk factors that are not easily modifiable, which emphasizes the need to start investigating preventive or prophylactic strategies in this high-risk population.

Associations Between Vitamin D Level and Hospitalizations With and Without an Infection in a National Cohort of Medicare Beneficiaries.

Research has implicated low 25-hydroxyvitamin D (25(OH)D) level as a risk factor for infection; however, results have not been consistent. To further determine the nature of this relationship, we conducted a cohort study using Medicare beneficiaries participating in the 2001-2002 and 2003-2004 cycles of the National Health and Nutrition Examination Survey with data individually linked to hospital records from the Centers for Medicare and Medicaid Services. The primary exposure was a 25(OH)D level of <15 ng/mL versus ≥15 ng/mL. The outcomes were a hospitalization with or without an infection within 1 year of participation in the National Health and Nutrition Examination Survey, as determined from the final hospital discharge codes (International Classification of Diseases, Ninth Revision, Clinical Modification). Of 1,713 individuals, 348 had a baseline serum 25(OH)D level of <15 ng/mL, 77 experienced a hospitalization with an infection, and 287 experienced a hospitalization without an infection. In multivariable analyses, a serum 25(OH)D level of <15 ng/mL was associated with a higher risk of hospitalization with an infection (risk ratio = 2.8, 95% confidence interval: 1.3, 5.9, P < 0.01) but not of hospitalization without an infection (risk ratio = 1.4, 95% confidence interval: 0.9, 2.1, P = 0.1). In this study, we found an association between a serum 25(OH)D concentration of <15 ng/mL and a higher subsequent risk for hospitalization with an infection among Medicare beneficiaries.

Acquired Drug Resistance in Mycobacterium tuberculosis and Poor Outcomes among Patients with Multidrug-Resistant Tuberculosis.

Rates and risk factors for acquired drug resistance and association with outcomes among patients with multidrug-resistant tuberculosis (MDR TB) are not well defined. In an MDR TB cohort from the country of Georgia, drug susceptibility testing for second-line drugs (SLDs) was performed at baseline and every third month. Acquired resistance was defined as any SLD whose status changed from susceptible at baseline to resistant at follow-up. Among 141 patients, acquired resistance in Mycobacterium tuberculosis was observed in 19 (14%); prevalence was 9.1% for ofloxacin and 9.8% for capreomycin or kanamycin. Baseline cavitary disease and resistance to >6 drugs were associated with acquired resistance. Patients with M. tuberculosis that had acquired resistance were at significantly increased risk for poor treatment outcome compared with patients without these isolates (89% vs. 36%; p<0.01). Acquired resistance occurs commonly among patients with MDR TB and impedes successful treatment outcomes.

Tobacco smoking and tuberculosis treatment outcomes: a prospective cohort study in Georgia.

OBJECTIVE: To assess the effect of tobacco smoking on the outcome of tuberculosis treatment in Tbilisi, Georgia. METHODS: We conducted a prospective cohort study of adults with laboratory-confirmed tuberculosis from May 2011 to November 2013. History of tobacco smoking was collected using a standardized questionnaire adapted from the global adult tobacco survey. We considered tuberculosis therapy to have a poor outcome if participants defaulted, failed treatment or died. We used multivariable regressions to estimate the risk of a poor treatment outcome. FINDINGS: Of the 591 tuberculosis patients enrolled, 188 (31.8%) were past smokers and 271 (45.9%) were current smokers. Ninety (33.2%) of the current smokers and 24 (18.2%) of the participants who had never smoked had previously been treated for tuberculosis (P < 0.01). Treatment outcome data were available for 524 of the participants, of whom 128 (24.4%) - including 80 (32.9%) of the 243 current smokers and 21 (17.2%) of the 122 individuals who had never smoked - had a poor treatment outcome. Compared with those who had never smoked, current smokers had an increased risk of poor treatment outcome (adjusted relative risk, aRR: 1.70; 95% confidence interval, CI: 1.00-2.90). Those who had ceased smoking more than two months before enrolment did not have such an increased risk (aRR: 1.01; 95% CI: 0.51-1.99). CONCLUSION: There is a high prevalence of smoking among patients with tuberculosis in Georgia and smoking increases the risk of a poor treatment outcome.

Social, behavioral, and sleep characteristics associated with depression symptoms among undergraduate students at a women's college: a cross-sectional depression survey, 2012.

BACKGROUND: The association between student characteristics and depression among students attending women's colleges (single-sex institutions of higher education that exclude or limit males from admission) is poorly understood. Our objective was to estimate the prevalence of depression and determine behavioral and social characteristics associated with depression among students attending a women's college. METHODS: We administered a cross-sectional Internet-based survey between April and May 2012 to students (n = 277) enrolled at a private women's college in the southeastern US. Center for Epidemiologic Studies Depression (CES-D) and Depression Anxiety Stress Scale 21 (DASS-21) instruments measured self-reported depression. Bivariate and multivariable logistic regression methods were used to estimate adjusted associations. RESULTS: Prevalence of depression measured by CES-D and DASS-21 instruments was 26.3% (95% confidence interval [CI] 20.8-32.3%) and 26.0% (95% CI 20.4-32.3%), respectively. After adjusting for confounders, absence of strong social support (prevalence odds ratio [OR] = 4.3, 95% CI 1.4-13.7), history of mental health disorder (OR = 4.8 95% CI 1.9-12.4), and poor sleep hygiene (OR = 2.8, 95% CI 1.3-5.8) were associated with depression. CONCLUSIONS: This cross-sectional survey identified absence of strong social support, history of mental health disorder, and poor sleep hygiene as potential predictors of depression among students attending a women's college. Further investigation of these factors may inform depression interventions for students attending women's colleges and other undergraduate student populations.

Household income and poor treatment outcome among patients with tuberculosis in Georgia: a cohort study.

BACKGROUND: Poverty is associated with increased risk of active tuberculosis (TB) disease onset, but the relation between household income and TB treatment outcomes is not well understood. The objective of this study was to determine household income characteristics associated with poor TB treatment outcome among newly diagnosed patients with pulmonary TB in the country of Georgia. METHODS: A prospective cohort study was conducted among newly diagnosed smear positive pulmonary TB patients. Clinical and household data were collected from all consecutive patients seeking care at TB facilities in two major cities and one rural region in Georgia. Patients were followed prospectively during anti-TB regimens to determine treatment outcome. Bivariate analyses were used to determine the association of individual patient and household level characteristics with poor TB treatment outcome. A multivariable logistic model was used to estimate the adjusted association between patient household characteristics and poor TB treatment outcome. RESULTS: After six months TB therapy, treatment outcome was available for 193 of 202 enrolled patients, of these 155 (80.3%) had a favorable TB treatment outcome. Compared to TB patients with poor treatment outcome, those with favorable treatment outcomes were younger (median 33.0 vs. 42.5 years), reported higher household monthly income (median $137 USD vs. $85 USD), were less likely to be unemployed (38.7 vs. 47.4%), and had higher level of education (38.7% vs. 31.6% with college education or greater). In multivariable analysis adjusted for age, sex, and socio-economic indicators, only low household income was remained statistically significantly associated with poor TB treatment outcome. Compared with patients from households with the highest tertile of monthly income, those in the middle tertile (aOR 4.28 95% CI 1.36, 13.53) and those in the lowest category of income (aOR 6.18 95% CI 1.83, 20.94) were significantly more likely to have poor treatment outcomes. CONCLUSION: We demonstrated that TB patients in Georgia with lower household income were at greater risk of poor TB treatment outcomes. Providing targeted social assistance to TB patients and their households may improve clinical response to anti-TB therapy.

Tuberculosis infection and hypertension: prevalence estimates from the US National Health and Nutrition Examination Survey.

OBJECTIVES: Tuberculosis infection (TBI) is marked by dynamic host-pathogen interactions with persistent low-grade inflammation and is associated with increased risk of cardiovascular diseases (CVD) including acute coronary syndrome, myocardial infarction and stroke. However, few studies assess the relationship between TBI and hypertension, an intermediate of CVD. We sought to determine the association between TBI and hypertension using data representative of the adult US population. METHODS: We performed cross-sectional analyses using data from the 2011-2012 US National Health and Nutrition Examination Survey (NHANES). Eligible participants included adults with valid QuantiFERON-TB Gold In-Tube (QFT-GIT) test results who also had blood pressure measures and no history of TB disease. TBI was defined by a positive QFT-GIT. We defined hypertension by either elevated measured blood pressure levels (ie, systolic ≥130 mm Hg or diastolic ≥80 mm Hg) or known hypertension indications (ie, self-reported previous diagnosis or use of antihypertensive medications). Analyses were performed using robust quasi-Poisson regressions and accounted for the stratified probability sampling design of NHANES. RESULTS: The overall prevalence of TBI was 5.7% (95% CI 4.7% to 6.7%) and hypertension was present among 48.9% (95% CI 45.2% to 52.7%) of participants. The prevalence of hypertension was higher among those with TBI (58.5%, 95% CI 52.4% to 64.5%) than those without TBI (48.3%, 95% CI 44.5% to 52.1%) (prevalence ratio (PR) 1.2, 95% CI 1.1 to 1.3). However, after adjusting for confounders, the prevalence of hypertension was similar for those with and without TBI (adjusted PR 1.0, 95% CI 1.0 to 1.1). The unadjusted prevalence of hypertension was higher among those with TBI versus no TBI, especially among individuals without CVD risk factors including those with normal body mass index (PR 1.6, 95% CI 1.2 to 2.0), euglycaemia (PR 1.3, 95% CI 1.1 to 1.5) or non-smokers (PR 1.2, 95% CI 1.1 to 1.4). CONCLUSIONS: More than half of adults with TBI in the USA had hypertension. Importantly, we observed a relationship between TBI and hypertension among those without established CVD risk factors. SUMMARY: The prevalence of hypertension was high (59%) among adults with TBI in the USA. In addition, we found that the prevalence of hypertension was significantly higher among adults with positive QFT without established hypertension risk factors.

Metformin reduces the risk of poor treatment outcomes among individuals with rifampicin-resistant tuberculosis and type-2 diabetes mellitus.

We conducted a retrospective cohort study among individuals with rifampicin-resistant tuberculosis and diabetes to determine the association between metformin use and tuberculosis treatment outcomes. We found that individuals with metformin use had a significantly lower risk of poor tuberculosis treatment outcomes (adjusted RR=0.25, 95%CI 0.06 - 0.95) compared to those without.

Lack of weight gain and increased mortality during and after treatment among adults with drug-resistant tuberculosis in Georgia, 2009-2020.

Background: While low body mass index (BMI) is associated with poor tuberculosis (TB) treatment outcomes, the impact of weight gain during TB treatment is unclear. To address this knowledge gap, we assessed if lack of weight gain is associated with all-cause mortality during and after TB treatment. Methods: We conducted a retrospective cohort study among adults with newly diagnosed multi- or extensively drug-resistant (M/XDR) pulmonary TB in Georgia between 2009-2020. The exposure was a change in BMI during the first 3-6 months of TB treatment. All-cause mortality during and after TB treatment was assessed using the National Death Registry. We used competing-risk Cox proportional hazard models to estimate adjusted hazard ratios (aHR) between BMI change and all-cause mortality. Results: Among 720 adult participants, 21% had low BMI (<18.5 kg/m 2 ) at treatment initiation and 9% died either during (n=16) or after treatment (n=50). During the first 3-6 months of TB treatment, 17% lost weight and 14% had no weight change. Among 479 adults with normal baseline BMI ( ≥18.5-24.9 kg/m 2 ), weight loss was associated with an increased risk of death during TB treatment (aHR=5.25; 95%CI: 1.31-21.10). Among 149 adults with a low baseline BMI, no change in BMI was associated with increased post-TB treatment mortality (aHR=4.99; 95%CI: 1.25-19.94). Conclusions: Weight loss during TB treatment (among those with normal baseline BMI) or no weight gain (among those with low baseline BMI) was associated with increased rates of all-cause mortality. Our findings suggest that scaling up weight management interventions among those with M/XDR TB may be beneficial. Summary: Among a cohort of persons with drug resistant tuberculosis (TB), failure to gain weight during TB treatment was associated with an increased risk of all-cause mortality during and after completion of treatment.

HIV co-infection increases the risk of post-tuberculosis mortality among persons who initiated treatment for drug-resistant tuberculosis.

Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant and multi/extensively drug-resistant (RR and M/XDR) TB reported to the country of Georgia's TB surveillance during 2009-2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia's death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) died during treatment and 87 (8.7%) died post-TB treatment. Among those who died post-TB treatment, the median time to death was 21 months (interquartile range 7-39) post-TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR=3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first three years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates.

Diabetes mellitus is associated with an increased risk of unsuccessful treatment outcomes among drug-susceptible tuberculosis patients in Ethiopia: A prospective health facility-based study.

Background: The impact of diabetes mellitus on tuberculosis (TB) treatment outcomes has not been well investigated in most sub-Saharan countries including Ethiopia. The current study aimed to determine the association between diabetes mellitus and unsuccessful TB treatment outcomes among drug-susceptible TB patients treated at selected health facilities in Addis Ababa, Ethiopia. Methods: This health facility-based prospective cohort study was conducted at six randomly selected public health centers in Addis Ababa, from August 2020 until November 2021. Clinically diagnosed adult pulmonary and extra pulmonary TB patients were recruited at the time of treatment initiation. A multivariable logistic regression analysis was used to estimate the association between diabetes and unsuccessful TB treatment outcomes. Results: Among the total 267 enrolled participants, 9.7% of patients with TB were identified to have diabetes comorbidity. Of patients with diabetes and TB, 9 (34.6%) were newly diagnosed based on glucose test results. Despite an overall high TB treatment success rate (94.0%), more than one-fourth (26.9%) of patients with diabetes had a poor TB treatment outcome (26.9%), which was remarkably higher compared to patients without diabetes (3.7%). In multivariable regression, the adjusted odds of poor TB treatment outcome among those with diabetes was 14.8 (95% CI 3.5 - 62.7) times the odds of poor outcome patients without diabetes. Conclusion: Diabetes was significantly associated with increased odds of poor TB treatment outcomes among patients in Addis Ababa, Ethiopia.

Diabetes Mellitus and Tuberculosis Treatment Outcomes: Interaction Assessment Between Hyperglycemia and Human Immunodeficiency Virus in the State of Georgia, 2015-2020.

Background: Diabetes mellitus and human immunodeficiency virus (HIV) are independent risk factors for poor outcomes among people with tuberculosis (TB). To date, information on the joint impact of diabetes and HIV on TB outcomes is limited. We aimed to estimate (1) the association between hyperglycemia and mortality and (2) the effect of joint exposure to diabetes and HIV on mortality. Methods: We conducted a retrospective cohort study among people with TB in the state of Georgia between 2015 and 2020. Eligible participants were 16 or older, did not have a previous TB diagnosis, and were microbiologically confirmed or clinical cases. Participants were followed during TB treatment. Robust Poisson regression was used to estimate risk ratios for all-cause mortality. Interaction between diabetes and HIV was assessed on the additive scale using the attributable proportion and on the multiplicative scale with product terms in regression models. Results: Of 1109 participants, 318 (28.7%) had diabetes, 92 (8.3%) were HIV positive, and 15 (1.4%) had diabetes and HIV. Overall, 9.8% died during TB treatment. Diabetes was associated with an increased risk of death among people with TB (adjusted risk ratio [aRR] = 2.59; 95% confidence interval [CI], 1.62-4.13). We estimated that 26% (95% CI, -43.4% to 95.0%) of deaths among participants with diabetes mellitus and HIV were due to biologic interaction. Conclusions: Diabetes alone and co-occurring diabetes and HIV were associated with an increased risk of all-cause mortality during TB treatment. These data suggest a potential synergistic effect between diabetes and HIV.

Longitudinal trends in glycated hemoglobin during and after tuberculosis treatment.

AIMS: To investigate the impact of pulmonary TB on glycemic status during and after TB treatment, and associations of glycemic trends with antidiabetic therapy and TB outcomes. METHODS: Data from two prospective cohort studies of adults in Chennai, India, with pulmonary TB were combined for this analysis. Participants were classified by baseline hemoglobin A1c (A1C) as having normoglycemia (NG; n = 74), prediabetes (pre-DM; n = 110), or diabetes (DM; n = 244). Repeat A1C measurements were performed at TB treatment months 3 and 6, and then 6 and 12 months after TB treatment completion. RESULTS: Median A1C at baseline declined after TB treatment initiation in all groups. No baseline NG or pre-DM participants progressed to DM by end of study, while 16.7% of baseline DM participants shifted to pre-DM or NG levels of A1C. In the baseline DM group, rising A1C after the intensive phase of TB treatment was significantly associated with adverse TB outcomes. CONCLUSIONS: Incident TB promotes transient glucose elevation but was not conclusively shown to promote chronic dysglycemia. Rising A1C during and after TB treatment may predict unfavorable treatment response in persons presenting with A1C ≥ 6.5 % at the time of TB diagnosis.

Prediabetes and risk of active tuberculosis: a cohort study from Northern Taiwan.

BACKGROUND: Diabetes mellitus (DM) is a well-established risk factor for active tuberculosis (TB) infection. Despite the worldwide rapid increase in the prevalence of prediabetes, its impact on the risk of active TB remains largely unknown. This study aimed to investigate the relationship between prediabetes and risk of active TB in a large cohort study. METHODS: A total of 119 352 participants were screened from a community-based health screening programme in Northern Taiwan. Diabetes mellitus and prediabetes were defined by baseline fasting plasma glucose (FPG) and prescription of anti-diabetic drugs. Incident cases of active TB were identified from the National Tuberculosis Registry. Kaplan-Meier curves and Cox regression analysis were employed to estimate the hazard ratios for prediabetes and DM compared with normoglycaemia. Spline regression was performed to investigate the dose-response relationship between FPG level and risk of TB disease. RESULTS: At baseline, 27 404 (22.96%) participants had prediabetes and 10 943 (9.17%) participants had DM. After an average follow-up of 7.2 years, 322 TB cases occurred. The adjusted hazard ratio of developing active TB disease was 0.73 [95% confidence interval (CI) 0.55-0.97] for prediabetic and 1.48 (95% CI 1.11-1.98) for diabetic participants compared with normoglycaemic individuals. Spline regression revealed a U-shaped association between FPG level and risk of active TB disease, with the lowest risk at FPG around110 mg/dl. Sensitivity analyses were conducted to exclude factors such as potential confounders (including body mass index), misclassification of glycaemic level, and selection bias, and results showed that those factors could not explain the lower risk of active TB. CONCLUSIONS: Prediabetes was associated with a 27% reduced risk of active TB disease compared with normoglycaemia. The biological mechanism of this inverse association and its implication for global nutrition transition and TB control should be further investigated.

Tuberculosis infection and hypertension: Prevalence estimates from the US National Health and Nutrition Examination Survey.

Objectives: Latent Tuberculosis infection (LTBI) is marked by dynamic host-pathogen interactions with persistent low-grade inflammation and is associated with increased risk of cardiovascular diseases (CVD) including acute coronary syndrome, myocardial infarction, and stroke. However, few studies assess the relationship between LTBI and hypertension, an intermediate of CVD. We sought to determine the association between LTBI and hypertension using data representative of the adult US population. Methods: We performed cross-sectional analyses using data from the 2011-2012 US National Health and Nutrition Examination Survey (NHANES). Eligible participants included adults with valid QuantiFERON-TB Gold In-Tube (QFT-GIT) test results who also had blood pressure measures and no history of TB disease. LTBI was defined by a positive QFT-GIT. We defined hypertension by either elevated measured blood pressure levels (i.e., systolic ≥130mmHg or diastolic ≥80mmHg) or known hypertension indications (i.e., self-reported previous diagnosis or use of antihypertensive medications). Analyses were performed using robust quasi-Poisson regressions and accounted for the stratified probability sampling design of NHANES. Results: The overall prevalence of LTBI was 5.7% (95%CI 4.7-6.7) and hypertension was present among 48.9% (95%CI 45.2-52.7) of participants. The prevalence of hypertension was higher among those with LTBI (58.5%, 95%CI 52.4-64.5) than those without LTBI (48.3%, 95%CI 44.5-52.1) (prevalence ratio [PR]=1.2, 95%CI 1.1-1.3). However, after adjusting for confounders, the prevalence of hypertension was similar for those with and without LTBI (adjusted PR=1.0, 95%CI 0.9 -1.1). Among individuals without CVD risk factors of elevated BMI (PRnormal BMI=1.6, 95%CI 1.2-2.0), hyperglycemia (PReuglycemia=1.3, 95%CI 1.1-1.5), or cigarette smoking (PRnon-smokers=1.2, 95%CI 1.1-1.4), the unadjusted prevalence of hypertension was higher among those with LTBI vs. no LTBI. Conclusions: More than half of adults with LTBI in the US had hypertension. Importantly, we observed a relationship between LTBI and hypertension among those without established CVD risk factors.