Low BMI increases all-cause mortality rates in patients with drug-resistant TB.

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.

Rates and risk factors for nephrotoxicity and ototoxicity among tuberculosis patients in Tbilisi, Georgia.

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.

IPT in people living with HIV in Myanmar: a five-fold decrease in incidence of TB disease and all-cause mortality.

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.

Convergence of non-communicable diseases and tuberculosis: a two-way street?

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.

A population-based tuberculosis contact investigation in the country of Georgia.

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.

Contexte : Identifier et dépister les contacts des patients atteints de tuberculose (TB) active n'est pas souvent réalisé dans les pays à revenu faible et moyen.Objectif : Estimer l'incidence, la prévalence et les facteurs de risque d'infection tuberculeuse latente (LTBI) et de TB active parmi les contacts de patients TB nouveaux à frottis positif.Schéma : Une investigation en population a été réalisée à la recherche des contacts de cas de TB pulmonaire à frottis positif diagnostiqués entre avril et décembre 2012 en Géorgie ; la LTBI a été évaluée grâce à un test cutané à la tuberculine (TST). Les contacts atteints de TB active ont été identifiés à partir de la base de données de surveillance du Programme National TB.Résultats : Parmi 896 patients index atteints de TB active, 3133 contacts ont été identifiés et 1157 (37%) ont eu un TST, dont 34% ont été positifs. La majorité des contacts ont été des contacts domiciliaires (86%) et des femmes (58%). Parmi les contacts, la prévalence sur un an de la TB active a été de 3,3% (IC95% 2,70­3,98) tandis que le taux d'incidence a été de 1101 par 100 000 années-personne (IC95% 822­1443). En analyse multivariée, les contacts domiciliaires ont été plus susceptibles d'avoir une LTBI (OR ajusté [ORa] 2,28 ; IC95% 1,49­3,49) comparés aux contacts étroits.Conclusion : Une prévalence élevée à la fois de LTBI et de TB active a été identifiée parmi les contacts des cas de TB pulmonaire. Les efforts visant à une recherche active de cas parmi les contacts de TB devraient améliorer une détection précoce des cas et renforcer les efforts de lutte contre la TB.

Marco de referencia: La localización y la investigación de contactos de pacientes con tuberculosis (TB) activa rara vez se siguen en los países con ingresos bajos y medianos.Objetivo: Estimar la incidencia, la prevalencia y los factores de riesgo de contraer la infección tuberculosa latente (LTBI) y la TB activa en los contactos de los casos nuevos de TB con baciloscopia positiva notificados.Método: Se llevó a cabo una investigación de base poblacional de los contactos de casos de TB pulmonar con baciloscopia positiva diagnosticados de abril a diciembre del 2012 en Georgia; se investigó la LTBI mediante la prueba cutánea de la tuberculina (TST). Los contactos con TB activa se localizaron en la base de datos de vigilancia del Programa Nacional contra la Tuberculosis.Resultados: Se reconocieron 3133 contactos de los 896 casos iniciales con TB activa y se practicó la TST en 1157 (37%), de los cuales el 34% obtuvo un resultado positivo. La mayoría de los contactos fueron contactos domiciliarios (86%) y de sexo femenino (58%). En los contactos, la prevalencia a un año de TB activa fue 3,3% (IC95% 2,70­3,98) y la tasa de incidencia fue 1101 por 100 000 años-persona (IC95% 822­1443). El análisis multivariante reveló que la probabilidad de padecer la ITL era mayor en los contactos domiciliarios (cociente de posibilidades ajustado 2,28; IC95% 1,49­3,49) que los contactos directos (no domiciliarios).Conclusiones: Se encontró una alta prevalencia de LTBI y de TB activa en los contactos de los casos de TB pulmonar. Las iniciativas de búsqueda activa de casos en los contactos de los pacientes con TB deberían mejorar la detección temprana y reforzar los esfuerzos de control de la TB.

Tuberculosis and diabetes in low and moderate tuberculosis incidence countries.

In countries with low and moderate incidence of tuberculosis (TB), the disease tends to concentrate in specific high-risk populations such as people with diabetes mellitus (DM). We review the updated evidence on the association between 1) DM and active TB, and 2) DM and latent tuberculous infection (LTBI), and 3) we summarize the findings on the population-level impact of DM on TB epidemiology, with particular focus on low- and moderate-incidence settings. We conducted an updated review of studies on DM and active TB, and found 11 more cohort studies published after the previous systematic review from 2008. The updated pooled relative risk (RR) (2.03, 95%CI 1.62-2.55) of all the studies was substantially lower than the three-fold risk increase in the previous review. Substantial heterogeneity of RR across studies was found. Possible reasons for such heterogeneity include different levels of residual confounding, the effect of modification by age, and different levels of glycemic control in the population. In a recently published systematic review on DM and LTBI, one cohort study and 12 cross-sectional studies were identified. The results from cross-sectional studies suggest a significant but modestly increased risk of LTBI among patients with DM (pooled odds ratio 1.18, 95%CI 1.06-1.30). We reviewed evidence on the population-level impact of DM on TB epidemiology in studies using population-attributable fraction analysis and infectious disease modelling. Those studies revealed that DM accounted for a substantial TB burden in low- and moderate-incidence countries. Finally, we discussed the complex association of obesity, DM and TB risk and the impact of the global obesity pandemic on TB epidemiology.

Racial Differences in Eating Patterns and Food Purchasing Behaviors among Urban Older Women.

OBJECTIVE: To examine differences in diet and food purchasing behaviors between Black and White older women living in urban neighborhoods. DESIGN: Cross-sectional observational study. SETTING: Urban neighborhoods in Washington, DC, USA. PARTICIPANTS: Community-dwelling White and Black women of age 65 and older. MEASUREMENTS: Participants were queried on diet via 24-hour recalls, food purchasing habits, their use of neighborhood resources and local travel patterns. Frequency and location of self-reported food purchasing and consumption were compared by race. RESULTS: In 2014 and 2015, 49 White and 44 Black older women were enrolled in the study. Compared to Whites, Blacks reported lower daily caloric intake (mean (SD) 1314 (404) vs. 1529 (448), p=0.02), with a higher percent of calories from protein and fat 1.8 (7.0), p=0.03), and a slightly higher polyunsaturated to saturated fat ratio (p=0.05). Blacks had substantially lower alternate healthy eating index (AHEI) (33.5 (10.2) vs. 43.9 (10.8) of 80 possible points, p<0.001), daily intake (grams) of total fiber (15.3 (8.1) vs. 22.9 (8.5), p<0.001), insoluble fiber (10.8 (6.9) vs. 15.9 (6.5), p<0.001), and soluble fiber (4.5 (2.0) vs. 6.9 (2.8), p<0.001). Blacks had lower intake of micronutrients, alcohol and caffeine. Blacks shopped for groceries less often (4.4 (3.0) vs. 6.2 (3.0) monthly; p=0.006) and spent a longer time traveling to stores (15.8 (9.1) vs. 11.5 (7.2) minutes per trip, p=0.02). A lower percent of Blacks walked to stores (14% vs. 40%, p=0.003) and a higher percent of Blacks rode in a car with someone else (33% vs. 6%, p<0.001). CONCLUSIONS: In an urban setting, food consumption and purchasing behaviors differed substantially between older Black and White women, which should be further investigated and considered to promote healthy eating in older populations.

A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Smoking behavior and beliefs about the impact of smoking on anti-tuberculosis treatment among health care workers.

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 18 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.

Racial Differences in Misclassification of Healthy Eating Based on Food Frequency Questionnaire and 24-Hour Dietary Recalls.

OBJECTIVES: To examine the agreement in nutrient intake and alternate healthy eating indices (AHEI) between a self-administered Food Frequency Questionnaire (FFQ) and 24-hour recall (24HR) measurements of diet by race, among urban older women. DESIGN: Cross-sectional observational study. SETTING: Urban neighborhoods in Washington, DC, USA. PARTICIPANTS: Community-dwelling White and Black women aged 65 and older. MEASUREMENTS: In 2014 and 2015, 49 White and 44 Black older women were queried on diet using both FFQ and 24-hour recalls. The correlation coefficients of 55 nutrient intake measures and agreements on healthy eating classification between the two instruments were compared overall and by race. RESULTS: The mean correlation coefficient (rho) was 0.46 for Whites and 0.23 for Blacks. For 47 measures, rho was lower for Blacks. Whites had a strong correlation of ≥0.5 for 28 items, while Blacks had strong correlations for only 3 items. Based on FFQ, the mean (SD) of AHEI were 54.0 (10.3) for Whites and 45.9 (8.8) for Blacks (p<0.001). Based on 24HR, the mean (SD) were 43.9 (10.8) for Whites and 33.2 (9.6) for Blacks (p<0.001). Using 32 as the cutoff (40% of maximum AHEI score), 50% of Blacks and 14% of Whites were classified as eating unhealthy based on the 24HR, versus 2.6% and 0% based on the FFQ. CONCLUSION: The FFQ has limited ability to accurately assess nutrient intake among older Black women, and tends to underestimate racial differences in healthy eating. The FFQ should be further improved for use in racial disparities research of healthy eating in older age, using a larger sample of older women with racial and geographic diversities.

Diabetes mellitus and extrapulmonary tuberculosis: site distribution and risk of mortality.

Scarce data exist on the relationship between diabetes and extrapulmonary tuberculosis (EPTB). We evaluated whether diabetes impacts site of TB and risk of death in patients with EPTB. We evaluated a cohort of TB cases from the state of Georgia between 2009 and 2012. Patients aged ⩾16 years were classified by diabetes status according to medical records. Site of EPTB was determined by culture and/or state TB classification. Death was defined by all-cause mortality. Of 1325 eligible reported TB cases, 369 (27·8%) had any EPTB including 258 (19·5%) with only EPTB and 111 (8·4%) with pulmonary TB and EPTB. Of all TB cases, 158 had diabetes (11·9%). In multivariable analysis, the odds of any EPTB was similar in patients with and without diabetes [adjusted odds ratio 1·04, 95% confidence interval (CI) 0·70-1·56]. The risk of death was 23·8% in patients with EPTB and diabetes vs. 9·8% in those with no diabetes (P < 0·01); after adjusting for covariates the difference was not significant (aRR 1·19, 95% CI 0·54-2·63). Diabetes was common in patients with EPTB and risk of death was high. Improved understanding of the relationship between diabetes and EPTB is critical to determine the extent that diabetes affects TB diagnosis and clinical management.

Increased risk of latent tuberculous infection among persons with pre-diabetes and diabetes mellitus.

SETTING: Although diabetes mellitus (DM) is an established risk factor for active tuberculosis (TB) disease, little is known about the association between pre-DM, DM, and latent tuberculous infection (LTBI). OBJECTIVE: To estimate the association between DM and LTBI. DESIGN: We conducted a cross-sectional study among recently arrived refugees seen at a health clinic in Atlanta, GA, USA, between 2013 and 2014. Patients were screened for DM using glycosylated-hemoglobin (HbA1c), and for LTBI using the QuantiFERON(®)-TB (QFT) test. HbA1c and QFT results, demographic information, and medical history were abstracted from patient charts. RESULTS: Among 702 included patients, 681 (97.0%) had HbA1c and QFT results. Overall, 54 (7.8%) patients had DM and 235 (33.8%) had pre-DM. LTBI was prevalent in 31.3% of the refugees. LTBI prevalence was significantly higher (P < 0.01) among patients with DM (43.4%) and pre-DM (39.1%) than in those without DM (25.9%). Refugees with DM (adjusted OR [aOR] 2.3, 95%CI 1.2-4.5) and pre-DM (aOR 1.7, 95%CI 1.1-2.4) were more likely to have LTBI than those without DM. CONCLUSION: Refugees with DM or pre-DM from high TB burden countries were more likely to have LTBI than those without DM. Dysglycemia may impair the immune defenses involved in preventing Mycobacterium tuberculosis infection.

Diabetes mellitus is associated with cavities, smear grade, and multidrug-resistant tuberculosis in Georgia.

SETTING: National tuberculosis (TB) treatment facility in the country of Georgia. OBJECTIVE: To determine the prevalence of diabetes mellitus (DM) and pre-DM among patients with TB using glycosylated-hemoglobin (HbA1c), and to estimate the association between DM and clinical characteristics and response to anti-tuberculosis treatment. DESIGN: A cohort study was conducted from 2011 to 2014 at the National Centre for TB and Lung Disease in Tbilisi. Patients aged ⩾ 35 years with pulmonary TB were included. HbA1c was used to define DM (⩾ 6.5%), pre-DM (⩾ 5.7-6.4%), and no DM (<5.7%). Interviews and medical chart abstraction were performed. Regression analyses estimated associations between DM and 1) baseline TB characteristics and 2) anti-tuberculosis treatment outcomes. RESULTS: A total of 318 newly diagnosed patients with TB were enrolled. The prevalence of DM and pre-DM was 11.6% and 16.4%, respectively. In multivariable analyses, patients with TB-DM had more cavitation (adjusted OR [aOR] 2.26), higher smear grade (aOR 2.37), and more multidrug-resistant TB (MDR-TB) (aOR 2.27) than patients without DM. The risk of poor anti-tuberculosis treatment outcomes was similar among patients with and those without DM (28.1% vs. 23.6%). CONCLUSION: DM and pre-DM were common among adults with newly diagnosed pulmonary TB in Tbilisi, Georgia, and DM was associated with more clinical symptoms, and MDR-TB, at presentation.

Global confluence of infectious and non-communicable diseases -- the case of type 2 diabetes.

Globally the prevalence and public health importance of non-communicable diseases (NCD) is increasing in high-, middle-, and low-income countries alike. Concomitant to the NCD burden, control of key infectious diseases (i.e., group B Streptococcus, hepatitis C, tuberculosis, and HIV) in most regions of the world remains elusive. With new epidemiologic trends in disease burden, the allocation of resources and expertise to simultaneously control infectious diseases and NCD becomes increasingly difficult. Using the case of diabetes and three co-occurring infectious diseases, we demonstrate the importance of generating innovative strategies to attack the old (infectious diseases) and new (NCD) disease agendas together.

Immune response and survival of refractory cancer patients who received TGF-ß2 antisense/GM-CSF gene modified autologous tumor cell (TAG) vaccine.

TAG vaccine is a novel 'triad vaccine' that involves transfection of autologous tumor with a dual plasmid, TGFß2 antisense gene and GM-CSF gene. Patients with advanced cancer who failed standard therapy were treated. IFN-γ ELISPOT analysis (Enzyme-Linked Immunospot Assay for Interferon Gamma) using TAG autologous vaccine target cells was performed prior to vaccination and at week 12 after the third vaccination. The purpose of this assessment was to correlate the IFN-γ ELISPOT immune response with long-term survival of advanced cancer patients who received TAG vaccination. Twenty-three of 28 patients received ≥ 3 TAG vaccinations (two patients withdrew consent and three had disease progression prior to the third vaccination). Eleven patients demonstrated a positive ELISPOT response (>10 spots and ≥ 2 × baseline) at week 12 and 12 patients did not (P=0.002). Median survival from time of treatment between ELISPOT-positive and -negative groups was significantly different (550 vs 159 days, P=0.036), as was median survival from the time of procurement (627 vs 257 days, respectively, P=0.043). In conclusion, the IFN-γ ELISPOT assay may provide an effective measure of immune response following treatment with 'triad vaccines', but additional patient numbers and/or other immune modulatory parameters are necessary for future testing.

Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

OBJECTIVES: Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. METHODS: During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. RESULTS: Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (p<0.05). In patients without and with previous TB treatment, the prevalence of multidrug-resistant TB was 23% and 26%, respectively, among patients without diabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. CONCLUSIONS: Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome.

Potential for pharmacokinetic interactions between ambrisentan and cyclosporine.

Ambrisentan (ABS), approved for the treatment of pulmonary arterial hypertension and administered as an oral dose once daily, is an ET(A)-selective endothelin receptor antagonist (ERA) and a potential substrate for cytochrome P450 (CYP) 3A4, organic anion-transporting polypeptide (OATP), and P-glycoprotein (P-gp). Cyclosporin A (CsA), an inhibitor of CYP3A4, P-gp, and OATP, may be used concomitantly with ABS. In this open-label, parallel-treatment study, 28 healthy subjects received steady-state ABS (5 mg q.d.) either alone or with steady-state CsA (100-150 mg b.i.d.), and 24 other subjects received steady-state CsA either alone or with steady-state ABS. In the presence of CsA, ABS maximum plasma concentration (C(max)) increased 1.5-fold, and area under the plasma concentration-time curve (AUC)(0-τ) increased twofold. Marginal increases were observed for CsA C(max) (906 vs. 1,014 ng/ml) and AUC(0-τ) (3.05 vs. 3.37 µg·h/ml) in the presence of ABS. Frequent adverse events (AEs) were headache and gastrointestinal disorders. The addition of ABS to steady-state CsA appeared less tolerable as compared with the addition of CsA to steady-state ABS. A maximum ABS dose of 5 mg is recommended if it is coadministered with CsA. No change in CsA dose is recommended if it is coadministered with ABS.

Evaluation of soluble CD30 as an immunologic marker in heart transplant recipients.

CD30 is an immunologic molecule that belongs to the TNF-R superfamily. CD30 serves as a T-cell signal transducing molecule that is expressed by a subset of activated T lymphocytes, CD45RO+ memory T cells. Augmentation of soluble CD30 during kidney transplant rejection has been reported. Our study sought to determine whether the level of sCD30 prior to heart transplant could categorize patients into high versus low immunologic risk for a poor outcome. A significant correlation was observed between high levels of soluble CD30 and a reduced incidence of infection. None of the 35 patients with high pretransplant levels of sCD30 level (>90 U/mL) developed infections posttransplantation. However, 9 of 65 patients who had low levels of sCD30 (<90 U/mL) developed infections posttransplantation (P < .02). No remarkable differences were noted among the other clinical parameters. The results also showed that the high-definition flow-bead (HDB) assay detected both weak and strong class I and class II HLA antibodies, some of which (weak class II HLA Abs) were undetectable by the anti-human globulin cytotoxicity method. In addition, more antibody specificities were detected by HDB. In conclusion, we have observed that high levels of sCD30 prior to heart transplant may be associated with greater immunologic ability and therefore produce a protective effect on the development of infection post heart transplant. We have also shown that the HDB assay is superior to the visual cytotoxicity method to detect HLA antibodies, especially those to class II HLA antigens.

Degenerative spondylolysis: a concise report of scintigraphic observations.

OBJECTIVES: Spondylolysis is traditionally thought to be a diagnosis of adolescence and childhood, and is ascribed to mechanical stress through the immature pars interarticularis. Over the last 4 yr we have noted a presentation of spondylolysis in association with hypertrophic zygapophyseal joint disease in the lumbar spine in an older age group. METHODS: Records of 94 patients presenting with low back pain were examined. A pattern of intense zygapophyseal joint uptake in association with extended uptake in the pars interarticularis was ascribed as degenerative spondylolysis. RESULTS: The ages of the 94 cases ranged from 33 to 80 yr (mean 64 yr). There were 53 males and 41 females. In the group with degenerative spondylolysis the mean age was 72 yr, with four females and two males. None of these six patients gave a history of childhood spinal disease or back pain and all were relatively inactive in terms of current participation in sport. All cases of spondylolysis were confirmed by computed tomography scanning. CONCLUSION: The finding of hypertrophic zygapophyseal joint disease in association with spondylolysis is easily recognized by scintigraphic tomographic imaging.