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 2016–2019 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 45–64 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.

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.

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: Tuberculosis (TB) health care facilities throughout Georgia. OBJECTIVE: To describe smoking behaviors among health care workers (HCWs) at TB facilities and determine HCWs' knowledge and beliefs regarding the impact of tobacco use on anti-tuberculosis treatment.DESIGN: Cross-sectional survey from May to December 2014 in Georgia. Adult HCWs (age 718 years) at TB facilities were eligible. We administered a 60-question anonymous survey about tobacco use and knowledge of the effect of smoking on anti-tuberculosis treatment. RESULTS: Of the 431 HCWs at TB facilities who participated, 377 (87.5%) were female; the median age was 50 years (range 20-77). Overall, 59 (13.7%) HCWs were current smokers and 35 (8.1%) were past smokers.Prevalence of current smoking was more common among physicians than among nurses (18.6% vs.7.9%, P , 0.0001). Among HCWs, 115 (26.7%) believed smoking does not impact anti-tuberculosis treatment, and only 25.3% of physicians/nurses received formal training in smoking cessation approaches.Physicians who smoked were significantly more likely to believe that smoking does not impact anti-tuberculosis treatment than non-smoking physicians (aOR 5.11, 95%CI 1.46-17.90). CONCLUSION: Additional education about the effect of smoking on TB treatment outcomes is needed for staff of TB health care facilities in Georgia. Nurses and physicians need more training about smoking cessation approaches for patients with TB.

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.

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.

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.

In 2004, there existed limited tuberculosis (TB) research capacity in the country of Georgia. In response, a collaborative research training program (RTP) supported by aNational Institutes ofHealth Fogarty International Center Global Infectious Diseases grantwas formed between a U.S. academic institution and theNationalCenter 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, andcareer advancement. From2004 to 2015, 20 traineesparticipated in theprogram with 15 (75%) authoring a total of 65 publications in PubMed-listed journals. Themedian number of publications per traineewas 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 atGeorgian 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.Webelieve that theNIH 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.

Background.  Diabetes is a risk factor for active tuberculosis (TB), but little is known about the relationship between diabetes and multidrug-resistant (MDR) TB. We aimed to assess risk factors for primary MDR TB, including diabetes, and determine whether diabetes reduced the rate of sputum culture conversion among patients with MDR TB. Methods.  From 2011 to 2014, we conducted a cohort study at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. Multidrug-resistant TB was defined as resistance to at least rifampicin and isoniazid. Patients with capillary glycosylated hemoglobin (HbA1c) ≥ 6.5% or previous diagnosis were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare rates of sputum culture conversion in patients with and without diabetes. Results.  Among 318 patients with TB, 268 had drug-susceptibility test (DST) results. Among patients with DST results, 19.4% (52 of 268) had primary MDR TB and 13.4% (36 of 268) had diabetes. In multivariable analyses, diabetes (adjusted odds ratio [aOR], 2.51; 95% confidence interval [CI], 1.00-6.31) and lower socioeconomic status (aOR, 3.51; 95% CI, 1.56-8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The rate of sputum culture conversion was lower among patients with diabetes (adjusted hazard ratio [aHR], 0.34; 95% CI, .13-.87) and among smokers (aHR, 0.16; 95% CI, .04-.61). Conclusions.  We found diabetes was associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a longer time to sputum culture conversion.

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.