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Background: Limited evidence suggests elevated risks of cardiovascular disease (CVD) among people diagnosed with tuberculosis (TB) disease, though studies have not adjusted for pre-existing CVD risk. We carried out a cohort study using two separate datasets, estimating CVD incidence in people with TB versus those without., Methods: Using data from the United States (Veterans Health Administration) and the United Kingdom (Clinical Practice Research Datalink) for 2000-2020 we matched adults with incident TB disease and no CVD history 2-years before TB diagnosis (US n=2,121; UK n=15,820) with up to 10 people without TB on the basis of age, sex, race/ethnicity and healthcare practice. Participants were followed beginning 2-years before TB diagnosis and for 2-years subsequently. The acute period was defined as 3-months before/after TB diagnosis. TB, CVD and covariates were identified from electronic routinely collected data (primary and secondary care; mortality). Poisson models estimated incident rate ratios (IRR) for CVD events in people with TB compared to those without., Results: CVD incidence was consistently higher in people with TB, including during the baseline period (pre-TB) and particularly in the acute period: IRRs were US 3.5 (95% Confidence Interval 2.7-4.4), UK 2.7 (2.2-3.3). Rate Ratios remained high after adjusting for differences in pre-existing CVD risk: US 3.2 (2.2-4.4), UK 1.6 (1.2-2.1)., Conclusion: Increased CVD incidence was observed in people with TB versus those without, especially within months of TB diagnosis, persistent after adjustment for differences in pre-existing risk. Enhancing CVD screening and risk management may improve long-term outcomes in people with TB., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Tuberculosis infection (TBI) has been associated with increased cardiovascular risks. We aimed to characterize abnormal blood pressure (BP) readings in individuals with TBI. We conducted a retrospective study of adults with TBI presenting for their initial medical visit at a large midwestern U.S. public health clinic between 2019 and 2020. Abnormal BP was defined as having a systolic BP ≥ 130 mmHg and/or a diastolic BP ≥ 80 mmHg. Of 310 individuals with TBI, median age was 36 years (interquartile range 27-48), 34% were male, 64% non-US-born; 58 (18.7%) were previously diagnosed with hypertension. The prevalence of any hypertension (i.e., had a history of hypertension and/or an abnormal BP reading) was 64.2% (95% confidence interval 58.7-69.4). Any hypertension was independently associated with older age, male sex, higher body mass index, and individuals of Black race. In conclusion, any hypertension was present in over half of the adults evaluated for TBI in our clinic. Established hypertension risk factors were also common among this group, suggesting that individuals with TBI could benefit from clinical and public health interventions aiming to reduce the risk of future cardiovascular events.

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]) and post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant or multi/extensively drug-resistant (RR or 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. The median time to post-TB death was 21 months (interquartile range 7-39) after 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 3 years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates., (© 2024. The Author(s).)

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., Competing Interests: The authors have no conflicts of interest to declare.

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., Competing Interests: CONFLICT OF INTEREST We have no conflict of interest to declare.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Investments in digital health technologies such as artificial intelligence, wearable devices, and telemedicine may support Africa achieve United Nations (UN) Sustainable Development Goal for Health by 2030. We aimed to characterize and map digital health ecosystems of all 54 countries in Africa in the context of endemic infectious and non-communicable diseases (ID and NCD). We performed a cross-national ecological analysis of digital health ecosystems using 20-year data from the World Bank, UN Economic Commission for Africa, World Health Organization, and Joint UN Programme on HIV/AIDS. Spearman's rank correlation coefficients were used to characterize ecological correlations between exposure (technology characteristics) and outcome (IDs and NCDs incidence/mortality) variables. Weighted linear combination model was used as the decision rule, combining disease burden, technology access, and economy, to explain, rank, and map digital health ecosystems of a given country. The perspective of our analysis was to support government decision-making. The 20-year trend showed that technology characteristics have been steadily growing in Africa, including internet access, mobile cellular and fixed broadband subscriptions, high-technology manufacturing, GDP per capita, and adult literacy, while many countries have been overwhelmed by a double burden of IDs and NCDs. Inverse correlations exist between technology characteristics and ID burdens, such as fixed broadband subscription and incidence of tuberculosis and malaria, or GDP per capita and incidence of tuberculosis and malaria. Based on our models, countries that should prioritize digital health investments were South Africa, Nigeria, and Tanzania for HIV; Nigeria, South Africa, and Democratic Republic of the Congo (DROC) for tuberculosis; DROC, Nigeria, and Uganda for malaria; and Egypt, Nigeria, and Ethiopia for endemic NCDs including diabetes, cardiovascular disease, respiratory diseases, and malignancies. Countries such as Kenya, Ethiopia, Zambia, Zimbabwe, Angola, and Mozambique were also highly affected by endemic IDs. By mapping digital health ecosystems in Africa, this study provides strategic guidance about where governments should prioritize digital health technology investments that require preliminary analysis of country-specific contexts to bring about sustainable health and economic returns. Building digital infrastructure should be a key part of economic development programs in countries with high disease burdens to ensure more equitable health outcomes. Though infrastructure developments alongside digital health technologies are the responsibility of governments, global health initiatives can cultivate digital health interventions substantially by bridging knowledge and investment gaps, both through technology transfer for local production and negotiation of prices for large-scale deployment of the most impactful digital health technologies., (© 2023. The Author(s).)

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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

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 A1 c (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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection are associated with increased mortality in people with HIV (PWH), and hyperglycemia is a common comorbidity in PWH. In this study, we used routinely collected clinical data to assess the associations between HBV and HCV seropositivity with all-cause mortality and whether this relationship differs by hyperglycemia status., Methods: Eligible participants included adult PWH (≥15 years) who initiated antiretroviral therapy between May 2005 and June 2016 in Myanmar. HBV and HCV serostatus and hyperglycemia were measured at enrollment to HIV care using HBV surface antigen, HCV antibody tests, and random blood glucose (≥140 mg/dL), respectively., Results: Among 27 722 PWH, 2260 (8%) were HBV seropositive, 2265 (9%) were HCV seropositive, 178 (0.6%) were HBV-HCV seropositive, and 1425 (5%) had hyperglycemia. During the median follow-up (interquartile range) of 3.1 (1.5-5.1) years, 3655 (13%) PWH died, and the overall mortality rate was 3.8 (95% CI, 3.7-3.9) per 100-person-years (PY). The mortality rate (per 100 PY) among PWH who were HBV seropositive was 4.6, among PWH who were HCV seropositive it was 5.1, and among PWH who were HBV-HCV seropositive it was 7.1. When stratified by glycemic status, the mortality rate was higher among patients with hyperglycemia compared with those with euglycemia (5.4 vs 4.0 per 100 PY), and the difference in mortality rate between patients with hyperglycemia and euglycemia was highest among those with HCV seropositivity (9.8 vs 5.0 per 100 PY)., Conclusions: Increased mortality rates associated with HBV and HCV seropositivity in PWH differed by their glycemic status. PWH with HCV seropositivity and hyperglycemia had the highest mortality rates., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: There are limited data on post-hospital discharge clinic attendance rates and outcomes among patients with diabetic foot ulcers (DFUs)., Methods: Retrospective study of patients hospitalized with a DFU from 2016 to 2019 in a large public hospital. We measured rates and predictors of clinic attendance with providers involved with DFU care within 30 days of hospital discharge ("30-day post-discharge clinic attendance"). Log-binomial regression was used to estimate risk ratios (RR) and 95 % confidence intervals (CI)., Results: Among 888 patients, 60.0 % were between 45 and 64 years old, 80.5 % were Black, and 24.1 % were uninsured. Overall, 478 (53.8 %) attended ≥1 30-day post-discharge clinic appointment. Initial hospital outcomes were associated with clinic attendance. For example, the RR of 30-day post-discharge clinic attendance was 1.39 (95%CI 1.19-1.61) among patients who underwent a major amputation compared to patients with DFUs without osteomyelitis and did not undergo an amputation during the initial hospitalization. Among 390 patients with known 12-month outcome, 71 (18.2 %) had a major amputation or died ≤12 months of hospital discharge., Conclusion: We found a low post-discharge clinic attendance and high post-discharge amputation and death rates among patients hospitalized with DFUs. Interventions to increase access to outpatient DFU care are needed and could prevent amputations., Competing Interests: Declaration of competing interest Guillermo E. Umpierrez has received unrestricted research support (to Emory University) from Astra Zeneca and Dexcom Inc. The other authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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 ( C min ) and area under the curve from 0 to 24 hours (AUC 0-24 ). 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 C min was 0.235 mg/L (interquartile range [IQR], 0.069 to 0.529), and median AUC 0-24 was 89.6 mg·h/L (IQR, 69.2 to 116.2). Cytopenias were associated with linezolid PK parameters ( C min  > 2 mg/L and AUC 0-24  > 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.

Background: It is uncertain whether diabetes affects the risk of developing latent tuberculosis infection (LTBI) following exposure to Mycobacterium tuberculosis ( Mtb ). We assessed the relationship of diabetes or prediabetes and LTBI among close and household contacts (HHCs) of patients with active pulmonary tuberculosis (TB) disease in Addis Ababa, Ethiopia., Methods: In this cross-sectional study, we performed interferon-γ release assays, TB symptom screening, and point-of-care glycolated hemoglobin (HbA1c) testing among HHCs of active TB cases. Diabetes status was classified into diabetes (HbA1c ≥6.5% or self-reported diagnosis), prediabetes (5.7%-6.4%), and euglycemia (≤5.6%). Multivariable logistic regression was used to determine the association of diabetes with LTBI., Results: Among 597 study participants, 123 (21%) had dysglycemia including diabetes (n = 31) or prediabetes (n = 92); 423 (71%) participants were diagnosed with LTBI. Twelve of 31 (39%) HHCs with diabetes were previously undiagnosed with diabetes. The prevalence of LTBI among HHCs with diabetes, prediabetes, and euglycemia was 87% (27/31), 73% (67/92), and 69% (329/474), respectively. In multivariable analysis adjusted for age, sex, and HIV status, the odds of LTBI among HHCs with diabetes were 2.33 (95% confidence interval [CI], .76-7.08) times the odds of LTBI without diabetes. When assessing interaction with age, the association of diabetes and LTBI was robust among participants aged ≥40 years (adjusted odds ratio [aOR], 3.68 [95% CI, .77-17.6]) but not those <40 years (aOR, 1.15 [95% CI, .22-6.1])., Conclusions: HHCs with diabetes may be more likely to have LTBI than those with euglycemia. Further investigations are needed to assess mechanisms by which diabetes may increase risk of LTBI after Mtb exposure., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BACKGROUND: Loss to follow-up (LTFU) is common among patients with drug-resistant TB (DR-TB) receiving second-line TB treatment; however, little is known about outcomes after LTFU, including mortality. OBJECTIVE: To determine rates of and factors associated with all-cause mortality among patients with DR-TB who were LTFU. METHODS: Retrospective cohort study of adult patients with DR-TB in Georgia who initiated second-line TB treatment during 2011-2014 and were LTFU. Survival analyses were used to estimate all-cause mortality rates and adjusted hazard ratios (aHR). RESULTS: During 2011-2014, 2,437 second-line treatment episodes occurred and 695 patients were LTFU. Among 695 LTFU patients, 143 (21%) died during 2,686 person-years (PY) post-LTFU (all-cause mortality rate 5.1%, 95% CI 4.3-6.0 per 100 PY). In multivariable analysis, low weight (BMI < 18.5 kg/m²) at treatment initiation (aHR 3.2, 95% CI 2.2-4.7), return to treatment after LTFU (aHR 3.1, 95% CI 2.2-4.4), <12 months of treatment (aHR 2.4, 95% CI 1.4-4.1) and a pre-LTFU positive culture (aHR 3.3, 95% CI 2.2-4.9) were associated with all-cause mortality. CONCLUSION: High all-cause mortality occurred among patients with DR-TB after LTFU despite a low HIV prevalence. Providing additional assistance for patients during DR-TB treatment to prevent LTFU and use of new and shorter treatment regimens may reduce mortality among LTFU.

Objective: In cross-sectional U.S. studies, patients with diabetes had twice the prevalence of latent tuberculosis infection (LTBI) compared with those without diabetes. However, whether LTBI contributes to diabetes risk is unknown. We used longitudinal data to determine if LTBI is associated with increased diabetes incidence., Research Design and Methods: We conducted a retrospective cohort study among U.S. Veterans receiving care in the Veterans Health Administration from 2000 to 2015. Eligibility included all patients without preexisting diabetes who received a tuberculin skin test (TST) or interferon-γ release assay (IGRA). We excluded patients with a history of active TB and those diagnosed with diabetes before or within 2 years after LTBI testing. Patients were followed until diabetes diagnosis, death, or 2015. LTBI was defined as TST or IGRA positive. Incident diabetes was defined by use of ICD-9 codes in combination with a diabetes drug prescription., Results: Among 574,113 eligible patients, 5.3% received both TST/IGRA, 79.1% received TST only, and 15.6% received IGRA only. Overall, 6.6% had LTBI, and there were 2,535,149 person-years (PY) of follow-up after LTBI testing (median 3.2 years). The diabetes incidence rate (per 100,000 PY) was greater in patients with LTBI compared with those without (1,012 vs. 744; hazard ratio [HR] 1.4 [95% CI 1.3-1.4]). Increased diabetes incidence persisted after adjustment for covariates (adjusted HR [aHR] 1.2 [95% CI 1.2-1.3]) compared with those without LTBI. Among patients with LTBI, diabetes incidence was similar in those treated for LTBI compared with those who were not treated (aHR 1.0 [95% CI 0.9-1.1])., Conclusions: Comprehensive longitudinal data indicate that LTBI is associated with increased diabetes incidence. These results have implications for people with LTBI, ∼25% of the global population., (© 2022 by the American Diabetes Association.)

Objectives: Low BMI and hyperglycemia are each important risk factors for tuberculosis (TB). However, the contribution of synergy between low BMI and hyperglycemia to risk of TB among people living with HIV (PWH) is unexplored. We compared TB incidence among PWH with different exposure profiles to low BMI (BMI < 18.5 kg/m2) and hyperglycemia (random blood glucose ≥140 mg/dl)., Design and Methods: We conducted a cohort study using data of PWH (≥15 years) who enrolled in Myanmar's Integrated HIV Care Program between 2011 and 2017. We used their follow-up data until 2018 to determine TB incidence., Results: Among 20 865 PWH included in this study, 7610 (36%) had low BMI only, 1324 (6%) had hyperglycemia only, and 465 (2%) patients had concurrent low BMI and hyperglycemia (joint exposure) at baseline. During a median follow-up of 2.2 years (interquartile range: 0.5, 4.2), 3628 (17%) developed TB [6.7, 95% confidence interval (CI): 6.5,7.0 cases per 100 person-years (PY)]. TB incidence among PWH with joint exposure was 21.0 (95% CI: 18.0, 24.7), with low BMI only was 10.9 (95% CI: 10.4, 11.4), with hyperglycemia only was 5.2 (95% CI: 4.4, 6.3) and with no exposure was 4.6 (95% CI: 4.4, 4.9) cases per 100 PY. The attributable proportion of incident TB due to synergy between low BMI and hyperglycemia was 0.23 (95% CI: 0.06, 0.36)., Conclusion: Synergy between low BMI and hyperglycemia was associated with increased excess TB incidence in PWH. TB preventive treatment, nutritional support, and hyperglycemia management should be evaluated as interventions to reduce TB risk in PWH with joint exposure., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study is to compare the prevalence of latent TB infection (LTBI) among patients with type-2 diabetes mellitus (T2DM) to healthy controls without T2DM. To achieve this objective, we conducted a case-control study in a large hospital in Atlanta from 2016 to 2019., Results: We enrolled 98 cases; 119 potential controls were screened, 84 of which had HbA1c  ≥  5.7% and one did not have QFT result, leaving 34 (28.6%) individuals enrolled as controls. LTBI prevalence was 9.2% among cases and 14.7% among controls (crude odds ratio 0.59, 95% CI 0.19-2.04). After adjusting for age and sex, the adjusted odds of LTBI among patients with T2DM was 0.45 (95% CI 0.13, 1.71) times the controls. We did not observe a statistically significant association between LTBI and T2DM. However, we reported a positive correlation between HbA1c level and nil count among individuals with LTBI (R 2   =  0.55, p  <  0.01). In addition, we reported a high prevalence of LTBI among adults with T2DM and family members without T2DM.

Background: Among pediatric patients with multidrug-resistant tuberculosis (MDR-TB), limited data exist regarding treatment outcomes in the context of the new and repurposed second-line TB drugs (SLDs). We aimed to describe the treatment outcomes among pediatric MDR-TB patients receiving new and repurposed SLDs including the proportion who achieved favorable outcomes., Methods: We conducted a retrospective cohort study among pediatric patients (age ≤18 years) treated for MDR-TB in the country of Georgia from 2009 to 2016. A "new and repurposed" SLD regimen was defined as a regimen that included linezolid, bedaquiline, and/or delamanid. Favorable treatment outcome was defined by treatment completion or documented microbial "cure" status at the end of treatment. We assessed the association between the use of the new and repurposed SLDs with MDR-TB treatment outcomes using bivariate analyses and log-binomial regression., Results: There were 124 pediatric MDR-TB patients (median age: 13.7; interquartile range: 4.6-16.0) initiating treatment; 119 (96.0%) had a treatment outcome recorded and were included in our analyses. Eighteen (15.1%) patients received new and repurposed SLDs from 2015 or later. After adjusting for potential confounders, the proportion achieving favorable MDR-TB treatment outcomes was higher among patients treated with SLD regimens that included new and/or repurposed drugs when compared with those treated without (adjusted risk ratio: 1.17; 95% confidence interval: 0.51-2.72)., Conclusions: We observed a high proportion of favorable treatment outcomes among pediatric patients with MDR-TB receiving the new and repurposed SLDs. Further studies to evaluate the efficacy and children's tolerability of the new and repurposed SLDs are still warranted., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: High rates of loss to follow-up (LFU) exist among patients with multidrug and extensively drug-resistant tuberculosis (M/XDR TB). We aimed to identify long-term clinical outcomes of patients who were LFU during second-line TB treatment., Methods: We conducted a follow-up study among adults who received second-line TB treatment in the country of Georgia during 2011-2014 with a final outcome of LFU. We attempted to interview all LFU patients, administered a structured questionnaire, and obtained sputum samples. Active TB at follow-up was defined by positive sputum Xpert-TB/RIF or culture., Results: Follow-up information was obtained for 461 patients. Among these patients, 107 (23%) died and 177 (38%) were contacted. Of those contacted, 123 (69%) consented to participate and 92 provided sputum samples. Thirteen (14%) had active TB with an estimated infectious time period for transmitting drug-resistant TB in the community of 480 days (interquartile range = 803). In multivariable analysis, positive culture at the time of LFU was associated with active TB at the time of our study (adjusted risk ratio = 13.3; 95% confidence interval, 4.2-42.2)., Conclusions: Approximately one quarter of patients on second-line TB treatment who were LFU died. Among those LFU evaluated in our study, 1 in 7 remained in the community with positive sputum cultures. To reduce death and transmission of disease, additional strategies are needed to encourage patients to complete treatment., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Diabetes might confer a modestly increased risk of latent tuberculosis infection, which without treatment can progress to active tuberculosis disease. Three recent analyses of the National Health and Nutrition Examination Survey found a positive association between diabetes and a positive test for Mycobacterium tuberculosis infection. This study examines whether prevalence of a positive test still varies by diabetes status after stratifying by race/ethnicity., Methods: This cross-sectional analysis used the public-use National Health and Nutrition Examination Survey 2011-2012 data sets and was conducted in 2018-2019. Interview and examination results for 5,560 adult participants yielded estimates for 219 million U.S. adults in the 4 largest race/ethnicity groups. The weighted prevalence of positive tuberculin skin test or interferon-gamma release assay by diabetes status was ascertained in each group., Results: Among white and black adults, diabetes was associated with no difference in positive skin test prevalence and little difference in positive interferon-gamma release assay prevalence. The positive assay prevalence difference was +14.5% (95% CI=2.3%, 26.7%) among Hispanic and +9.9% (95% CI=1.2%, 18.6%) among Asian adults, when comparing those with diabetes with those with neither diabetes nor prediabetes. Based on assay results, 23.6% (95% CI=14.0%, 36.9%) of Hispanic and 27.2% (95% CI=19.6%, 36.5%) of Asian adults with diabetes also had latent tuberculosis infection., Conclusions: Hispanic and Asian subpopulation results drove much of the previously reported positive association between diabetes and a positive test for M. tuberculosis infection. Hispanic and Asian adults with diabetes might particularly benefit from screening and treatment for latent tuberculosis infection., (Published by Elsevier Inc.)

Background: Diabetes is associated with increased prevalence of TB infection in the US. We assessed associations between diabetes and interferon-gamma (IFN-γ) TB antigen response among adults with TB infection using US representative data., Methods: National Health and Nutrition Examination (NHANES) participants >19 years from 2011 to 2012 with positive QuantiFERON®-TB Gold-In-Tube (QFT) results were eligible. Diabetes was defined by combination of self-report and glycated hemoglobin (HbA1c). Quantitative IFN-γ TB antigen was classified as high (≥10 IU/mL), intermediate (1.01-9.99 IU/mL), or low (0.35-1.00 IU/mL). Analyses accounted for NHANES weighted design., Results: Among NHANES participants >19 years, n = 513 had positive QFT (5.9%). Among those with positive QFT, diabetes prevalence was 22.2% and pre-diabetes was 25.9%. Overall, 16.7% of positive QFT participants had high IFN-γ TB antigen levels including 21.7% among those with diabetes, 20.8% among those with pre-diabetes, and 12.6% among euglycemic participants. In adjusted analyses, high IFN-γ TB antigen response was more common among those with pre-diabetes (aOR 1.9, 95%CI 1.0, 3.6) compared to euglycemic participants., Conclusion: Higher antigen responses may reflect immunopathy consistent with an exaggerated inflammatory but ineffectual response to TB or a reflection of more Mtb replication in participants with pre-diabetes or diabetes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Understanding the link between tuberculosis (TB) and diabetes is increasingly important as public health responds to the growing global burden of noncommunicable diseases. Genetic association studies have identified numerous host genetic variants linked to TB; however, potential host genetic mechanisms linking TB and diabetes remain unexplored., Methods: We used genetic and phenotypic data from the UK Biobank to evaluate the association of 6 previously reported TB-related host genetic variants (genome-wide significant associations from published studies) with diabetes. The study included 409   692 adults of European ancestry including 2177 with type 1 diabetes mellitus (T1DM) and 13   976 with type 2 diabetes mellitus (T2DM), defined by ICD-10 diagnosis codes., Results: Of the 6 TB-associated single nucleotide polymorphisms (SNPs), 2 were associated with T1DM and 3 with T2DM, after adjusting for age, sex, body mass index, smoking, alcohol use, and population structure. After correction for multiple testing, SNPs rs2894257 and rs3135359 ( HLA-DRA-DQA1 ) were associated with T1DM (rs2894257: odds ratio [OR], 1.32; 95% confidence interval [CI], 1.21-1.45; rs3135359: OR, 1.72; 95% CI, 1.57-1.88) and T2DM (rs2894257: OR, 1.11; 95% CI, 1.08-1.15; rs3135359: OR, 1.06; 95% CI, 1.025-1.096). The associations with T2DM weakened for rs2894257 and rs3135359 after further exclusion of probable T1DM cases defined by International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. SNP rs4733781 on chromosome 8 ( ASAP1 gene) was associated with T2DM after exclusion of T1DM cases., Conclusions: Our findings suggest that common host genetic effects may play a role in the molecular mechanism linking TB and diabetes. Future large genetic studies of TB and diabetes should focus on developing countries with high burdens of infectious and chronic diseases., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Antihypertension medications have been associated with prevention of cardiovascular events, although less is known about the comparative effectiveness of different medication classes., Objective: To compare contemporary aggregated first-in-trial cardiovascular events among patients with hypertension and no substantial comorbidities., Data Sources: The PubMed, Embase, and Cochrane Library databases were systematically searched for articles published between January 1, 1990, and October 24, 2017., Study Selection: Randomized clinical trials that tested commonly used antihypertension medications (angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, nondihydropyridine calcium channel blockers, β-blockers, angiotensin receptor blockers, and diuretics) and that reported selected cardiovascular outcomes for at least 6 months of follow-up., Data Extraction and Synthesis: The analysis was conducted from October 2017 to December 2019. Two reviewers extracted the number of cardiovascular events at the end of treatment for all study groups. For each outcome, a frequentist network meta-analysis was used to compare risk reductions between medication classes (random-effects models weighted by the inverse variance). The dose-response association between a 10-mm Hg reduction of systolic blood pressure and a 5-mm Hg reduction of diastolic blood pressure and the risk of first-in-trial cardiovascular events was estimated., Main Outcomes and Measures: First-in-trial cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and revascularization., Results: In this systematic review and network meta-analysis, data were pooled from 46 eligible clinical trials (248 887 total participants with a mean [SD] age of 65.6 [5.8] years; 52.8% men). In the network meta-analysis, compared with placebo, angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, and thiazide diuretics were reported to be similarly effective in reducing overall cardiovascular events (25%), cardiovascular death (20%), and stroke (35%); angiotensin-converting enzyme inhibitors were reported to be the most effective in reducing the risk of myocardial infarction (28%); and diuretics were reported to be the most effective in reducing revascularization (33%). In the metaregression analyses, each 10-mm Hg reduction in systolic blood pressure and 5-mm Hg reduction in diastolic blood pressure was significantly associated with a lower risk of cardiovascular death, stroke, and overall cardiovascular events., Conclusions and Relevance: In this network meta-analysis of clinical trials of patients with hypertension and no substantial comorbidities, different classes of antihypertension medications were associated with similar benefits in reducing cardiovascular events. Future studies should compare the effectiveness of combinations of antihypertension medications in reducing cardiovascular events.

Aims: To develop and pilot test a taxonomy that empirically estimates health intervention effectiveness from efficacy data., Methods: We developed a taxonomy to score health interventions across 11 items on a scale from 0-100. The taxonomy was pilot-tested in efficacy and effectiveness diabetes prevention studies identified in two separate systematic reviews; here, the face validity, inter-rater reliability and factor structure of the taxonomy were established. Random effects meta-analyses were used to obtain weight loss and diabetes incidence pooled effects across studies. These effects and taxonomy scores were used to down calibrate efficacy estimates to effectiveness estimates as follows: Efficacy effect*[Efficacy score/highest possible score]., Results: We scored 82 effectiveness lifestyle modification studies (mean score 49.2), 32 efficacy lifestyle modification studies (mean score 69.8) and 20 efficacy studies testing medications (mean score 77.4). The taxonomy had face validity and good inter-rater reliability (ICC = 0.9 [0.87, 0.93]). The between-groups down calibrated weight loss estimate was similar to that observed in the effectiveness meta-analysis (1.7 and 1.8 kg, respectively). The down calibrated diabetes relative risk reduction was also similar to that observed in the effectiveness meta-analysis (30.6% over 2.7 years and 29% over 2 years, respectively)., Conclusions: The taxonomy is a promising tool to estimate the real-world impact of health interventions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs). OBJECTIVE: To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB). DESIGN: A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010-2012 in Tbilisi, Georgia. RESULTS: Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without ( P < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03-1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05-1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02-1.07). CONCLUSION: Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.

Objectives: To estimate the incidence of diabetes, acute myocardial infarction (AMI), and stroke; and to determine factors associated with diabetes, AMI, and stroke incidence among patients previously treated for tuberculosis (TB) disease., Methods: A retrospective cohort study was conducted among non-pediatric TB patients registered in the Taiwan National Health Insurance Research Database (NHIRD) from 2002-2013. Diabetes, AMI, and stroke incidence were defined by International Classification of Diseases (ICD)-9 codes, drug prescriptions, and records of patient's clinic visits. Cox proportional hazard models were used to estimate the hazard rate ratio (HR) of incident diabetes, AMI, and stroke., Results: From 2002-2013, there were 157,444 patients treated for TB registered in NHIRD. Among 129,453 patients with no prior history of diabetes, the age-adjusted incidence rate (IR) of diabetes was 3.85 (95%CI 3.70-4.01) per 1000 person-years. Among 143,646 patients with no prior history of AMI, the age-adjusted IR of AMI as 3.26 (95%CI 3.13-3.40). Among 118,774 patients with no prior history of stroke, the age-adjusted IR of stroke was 16.08 (95%CI 15.76-16.32)., Conclusions: Chronic non-communicable disease risk factors like dyslipidemia, hypertension, and chronic kidney disease diagnosed before time of TB diagnosis were predictive of diabetes, AMI, and stroke incidence., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the United States, multistate Salmonella outbreaks are most commonly linked to a food source; however, contact with live animals can also result in outbreaks of human illness. To characterize Salmonella outbreaks linked to animal contact and examine differences compared to foodborne outbreaks, we analysed data reported to the Centers for Disease Control and Prevention through the National Outbreak Reporting System (NORS) from 2009 to 2014 with a primary mode of transmission listed as "animal contact" or "food." Four hundred and eighty-four outbreaks with animal contact or foodborne transmission were reported through NORS; of these outbreaks, 99 (20.5%) resulted from Salmonella transmission through animal contact and 385 (79.5%) resulted from foodborne transmission, which resulted in 3,604 (19.8%) and 13,568 (80.2%) illnesses, respectively. A higher proportion of illnesses among children aged <1 year and children aged 1-4 years were linked to animal contact outbreaks compared to foodborne outbreaks (15.2% vs. 1.4%, p < 0.01 and 24.5% vs. 5.6%, p < 0.01, respectively). Illnesses resulting in hospitalizations (OR: 1.81, 95% CI: 1.62, 2.02) were more likely to be associated with animal contact compared to food. Animal contact outbreaks reported to NORS were more likely to be multistate compared to foodborne outbreaks (OR: 5.43, 95% CI: 3.37, 8.76) and had a longer median duration (99.0 days vs. 9.0 days, p < 0.01). Characterizing the differences between outbreaks of illness linked to animal contact and outbreaks linked to food provides useful information to investigators to improve public health response., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose: The purpose of this study was to determine if a negative tuberculin skin test (TST) result is associated with increased risk of mortality during tuberculosis (TB) treatment., Methods: We conducted a retrospective cohort study among patients aged ≥15 years with culture-positive TB reported to the Georgia State Electronic Notifiable Disease Surveillance System from 2009 to 2014. TST positivity was defined by the US Centers for Disease Control guidelines. All-cause mortality during TB treatment as well as HIV, diabetes, and end-stage renal disease status were collected from surveillance data. Log-binomial regression was used to estimate adjusted risk ratios and 95% confidence intervals., Results: Among 1186 culture-confirmed TB patients, 780 (65.8%) with a valid TST and TB treatment outcomes were eligible. Nearly one-third (242/780) had a negative TST result, and 5.6% died during treatment. The highest risk of death was observed among patients with a negative TST and HIV (12.5%) and a negative TST and diabetes (15.4%). Adjusting for confounders, the risk of death among patients with a negative TST was significantly greater compared with those with a positive TST (adjusted risk ratio 2.33 95% confidence interval 1.23-4.43)., Conclusions: A negative TST was associated with more than twice the risk of mortality during TB treatment after adjusting for immunosuppressive conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) remains the most robust thoracic surgical database in the world, providing participating institutions semiannual risk-adjusted performance reports and facilitating multiple quality improvement initiatives each year. In 2018, the STS GTSD Data Collection Form was substantially revised to acquire the most important variables with the least data manager burden. In addition, a composite quality measure for all pulmonary resections for cancer was developed, and the impact that minimally invasive approaches have on the model was assessed. The 2018 database audit found that the accuracy of the database remains high, ranging from 92.5% to 98.4%. In 2019, the STS GTSD Task Force plans to focus on increasing generalizability of the database, initiating esophagectomy outcome public reporting, and creating customizable real-time dashboards. This review summarizes all national aggregate outcome, quality measurement, and improvement initiatives from the STS GTSD over the past 12 months., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Post-treatment morbidity among subjects with drug-resistant tuberculosis (DR-TB) is unclear., Methods: This was a cross-sectional study of patients from Tbilisi, Georgia with cavitary DR-TB and an outcome of cure. Participants had a chest X-ray (CXR), St. George Respiratory Quality (SGRQ) survey, and pulmonary function tests (PFTs) performed. Correlations between SGRQ and PFT results and factors associated with pulmonary impairment were examined., Results: Among 58 subjects (median age 31 years), 40% used tobacco, 59% had prior TB, and 47% underwent adjunctive surgical resection. The median follow-up time was 41 months. Follow-up CXR revealed fibrosis in 30 subjects (52%) and bronchiectasis in seven (12%). The median forced expiratory volume (FEV 1 )/forced vital capacity (FVC) ratio was 0.72, with 24 subjects (41%) having a ratio of ≤0.70. Significant correlations existed between PFT measures and overall and component SGRQ scores. In linear regression, age, prior TB, and CXR fibrosis or bronchiectasis were significantly associated with decreased pulmonary function. Adjunctive surgery was significantly associated with a higher percent predicted FEV 1 and FVC., Conclusions: A high proportion of DR-TB subjects had residual pulmonary impairment, particularly with recurrent TB and severe radiological disease. The association of surgical resection with improved lung function deserves further study. PFTs and SGRQ may both be useful to evaluate lung health., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

[This corrects the article DOI: 10.1093/ofid/ofy355.].

Setting: Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection., Objective: To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV)., Design: A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014., Results: Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82)., Conclusion: Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

Background: Parameters defining attainment and maintenance of proficiency in thoracoscopic video-assisted thoracic surgery (VATS) lobectomy remain unknown. To address this knowledge gap, this study investigated the institutional performance curve for VATS lobectomy by using risk-adjusted cumulative sum (Cusum) analysis., Methods: Using The Society of Thoracic Surgeons General Thoracic Surgery Database, the study investigators identified centers that had performed a total of 30 or more VATS lobectomies. Major morbidity, mortality, and blood transfusion were deemed primary outcomes, with expected incidence derived from risk-adjusted regression models. Acceptable and unacceptable failure rates for outcomes were set a priori according to clinical relevance and informed by regression model output., Results: Between 2001 and 2016, 24,196 patients underwent VATS lobectomy at 159 centers with a median volume of 103 (range, 30 to 760). Overall rates of operative mortality, major morbidity, and transfusion were 1% (244 of 24,189), 17.1% (4,145 of 24,196), and 4% (975 of 24,196), respectively. Of the highest-volume centers (≥100 cases), 84% (65 of 77) and 82 % (63 of 77) (p = 0.48) were proficient by major morbidity standards by their 50th and 100th cases, respectively. Similarly, 92% (71 of 77) and 90% (69 of 77) (p = 0.41) of centers showed proficiency by transfusion standards by their 50th and 100th cases, respectively. Three performance patterns were observed: (1) initial and sustained proficiency, (2) crossing unacceptability thresholds with subsequent improved performance; and (3) crossing unacceptability thresholds without subsequent improved performance., Conclusions: VATS lobectomy outcomes have improved with lower mortality and transfusion rates. The majority of high-volume centers demonstrated proficiency after 50 cases; however, maintenance of proficiency is not ensured. Cusum provides a simple yet powerful tool that can trigger internal audits and performance improvement initiatives., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: There is limited empirical evidence on the relationship between hyperglycemia, tuberculosis (TB) comorbidity, and mortality in the context of HIV. We assessed whether hyperglycemia at enrollment in HIV care was associated with increased risk of all-cause mortality and whether this relationship was different among patients with and without TB disease., Methods: We conducted a retrospective analysis of adult (≥15 years) HIV-positive patients enrolled into HIV care between 2011 and 2016 who had random blood glucose (RBG) measurements at enrollment. We used hazards regression to estimate associations between RBG and rate of all-cause mortality., Results: Of 25 851 patients, 43% were female, and the median age was 36 years. At registration, the median CD4 count (interquartile range [IQR]) was 162 (68-310) cell/mm 3 , the median RBG level (IQR) was 88 (75-106) mg/dL, and 6.2% (95% confidence interval [CI], 6.0%-6.5%) had hyperglycemia (RBG ≥140 mg/dL). Overall 29% of patients had TB disease, and 15% died during the study period. The adjusted hazard of death among patients with hyperglycemia was significantly higher (adjusted hazard ratio [aHR], 1.2; 95% CI, 1.1-1.4) than among those with normoglycemia without TB disease, but not among patients with TB disease (aHR, 1.0; 95% CI, 0.8-1.2). Using 4 categories of RBG and restricted cubic spline regression, aHRs for death were significantly increased in patients with RBG of 110-140 mg/dL (categorical model: aHR, 1.3; 95% CI, 1.2-1.4; restricted spline: aHR, 1.1; 95% CI, 1.0-1.1) compared with those with RBG <110 mg/dL., Conclusions: Our findings highlight an urgent need to evaluate hyperglycemia screening and diagnostic algorithms and to ultimately establish glycemic targets for PLHIV with and without TB disease.

The intersection of tuberculosis (TB) with non-communicable diseases (NCDs), including diabetes mellitus (DM), chronic lung disease (CLD), and cardiovascular disease (CVD), has emerged as a critical clinical and public health challenge. Rapidly expanding NCD epidemics threaten TB control in low- and middle-income countries, where the prevention and treatment of TB disease remain a great burden. However, to date, the notion that TB may adversely impact NCD risk and severity has not been well explored. This review summarizes biomedical hypotheses, findings from animal models, and emerging epidemiologic data related to the progression of DM, CLD and CVD during and after active TB disease. We conclude that there is sufficient empirical evidence to justify a greater research emphasis on the syndemic interaction between TB and NCD.

Setting: Identification and screening of contacts of patients with active tuberculosis (TB) is infrequent in low- and middle-income countries. Objective: To estimate the incidence, prevalence and risk factors of latent tuberculous infection (LTBI) and active TB among contacts of newly reported smear-positive TB patients. Design: A population-based contact investigation of sputum smear-positive pulmonary TB (PTB) cases diagnosed between April and December 2012 in Georgia was conducted. LTBI was assessed using the tuberculin skin test (TST). Contacts with active TB were identified from the National TB Program surveillance database. Results: Among 896 index patients with active TB, 3133 contacts were identified and 1157 (37%) underwent a TST, 34% of whom were positive. Most contacts were household contacts (86%) and female (58%). Among contacts, the 1-year period prevalence of active TB was 3.3% (95%CI 2.70-3.98); the incidence rate was 1101 per 100 000 person-years (95%CI 822-1443). In multivariable analysis, household contacts were more likely to have LTBI (adjusted OR [aOR] 2.28, 95%CI 1.49-3.49) than close contacts. Conclusions: A high prevalence of both LTBI and active TB was identified among contacts of PTB cases. Efforts aimed at active case finding among TB contacts should improve early case detection and enhance TB control efforts., Competing Interests: Conflicts of interest: none declared.

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.

Mentoring is a critical component of career development for research scientists and is related to mentee success both in terms of career selection and advancement. However, there are limited data on the role of mentoring in low- and middle-income countries (LMICs). Cross-cultural mentorship programs have the potential to foster the transfer of knowledge and the development of capacity to resource-poor settings. This formative evaluation explores the cultural context of mentoring in the countries of Georgia and Ethiopia. Results were used to build culturally relevant mentor training programs for two Global Infectious Disease Research Training Programs focused on tuberculosis funded by the Fogarty International Center at the US National Institutes of Health. Four focus group discussions were conducted with research trainees and mentors to explore the perceptions of mentorship, identify obstacles for successful mentoring, and generate recommendations to strengthen mentoring in each program situated in a LMIC. Data revealed the barriers to mentoring in Ethiopia and Georgia included gaps in knowledge about mentoring roles and responsibilities, lack of knowledge about the responsibilities of the trainee in a mentoring relationship, and the need to set clear expectations between mentors and trainees. All of the focus group participants desired formal mentor training. These data informed six key components of the development and implementation of the mentor training programs in both countries. The topics included the following: a foundation in mentoring, establishing expectations between mentees and mentors, increasing interactions between mentees and mentors, additional mentor training, a case study curriculum, and methods of evaluating mentoring relationships.

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.

Aims: We aim to determine the association between prediabetes and diabetes with latent TB using National Health and Nutrition Examination Survey data., Methods: We performed a cross-sectional analysis of 2011-2012 National Health and Nutrition Examination Survey data. Participants ≥20 years were eligible. Diabetes was defined by glycated hemoglobin (HbA1c) as no diabetes (≤5.6% [38 mmol/mol]), prediabetes (5.7-6.4% [39-46 mmol/mol]), and diabetes (≥6.5% [48 mmol/mol]) combined with self-reported diabetes. Latent TB infection was defined by the QuantiFERON®-TB Gold In Tube (QFT-GIT) test. Adjusted odds ratios (aOR) of latent TB infection by diabetes status were calculated using logistic regression and accounted for the stratified probability sample., Results: Diabetes and QFT-GIT measurements were available for 4958 (89.2%) included participants. Prevalence of diabetes was 11.4% (95%CI 9.8-13.0%) and 22.1% (95%CI 20.5-23.8%) had prediabetes. Prevalence of latent TB infection was 5.9% (95%CI 4.9-7.0%). After adjusting for age, sex, smoking status, history of active TB, and foreign born status, the odds of latent TB infection were greater among adults with diabetes (aOR 1.90, 95%CI 1.15-3.14) compared to those without diabetes. The odds of latent TB in adults with prediabetes (aOR 1.15, 95%CI 0.90-1.47) was similar to those without diabetes., Conclusions: Diabetes is associated with latent TB infection among adults in the United States, even after adjusting for confounding factors. Given diabetes increases the risk of active TB, patients with co-prevalent diabetes and latent TB may be targeted for latent TB treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In 2004, there existed limited tuberculosis (TB) research capacity in the country of Georgia. In response, a collaborative research training program (RTP) supported by a National Institutes of Health Fogarty International Center Global Infectious Diseases grant was formed between a U.S. academic institution and the National Center for Tuberculosis and Lung Disease (NCTLD) and other institutions in Georgia. We sought to assess outcomes of this RTP. The TB RTP combined didactic and mentored research training for Georgian trainees. Long-term trainees were supported for a 2-year period and with posttrainee career development mentoring. Metrics used to measure program performance included publications, grants received, and career advancement. From 2004 to 2015, 20 trainees participated in the program with 15 (75%) authoring a total of 65 publications in PubMed-listed journals. The median number of publications per trainee was six (interquartile range 2-14). A total of 16 (80%) trainees remain working in the area of TB; nine were promoted to leadership positions and three to lead research units at Georgian institutions. Ten (50%) trainees were the principal investigator (PI) of a peer-reviewed external grant after Fogarty-supported training, and 40% served as research mentors. Annual TB-related research funding at the NCTLD increased from $5,000 in 2005 to ∼$1.5 million in 2017. A Georgian Fogarty trainee was either PI, site PI, or coinvestigator on > 90% of all research funding. We believe that the NIH Fogarty-funded TB research training grant has made critical contributions to increasing the TB-related research infrastructure and capacity in Georgia, particularly at the NCTLD.