Genotyping and spatial analysis of pulmonary tuberculosis and diabetes cases in the state of Veracruz, Mexico.

BACKGROUND: Genotyping and georeferencing in tuberculosis (TB) have been used to characterize the distribution of the disease and occurrence of transmission within specific groups and communities. OBJECTIVE: The objective of this study was to test the hypothesis that diabetes mellitus (DM) and pulmonary TB may occur in spatial and molecular aggregations. MATERIAL AND METHODS: Retrospective cohort study of patients with pulmonary TB. The study area included 12 municipalities in the Sanitary Jurisdiction of Orizaba, Veracruz, México. Patients with acid-fast bacilli in sputum smears and/or Mycobacterium tuberculosis in sputum cultures were recruited from 1995 to 2010. Clinical (standardized questionnaire, physical examination, chest X-ray, blood glucose test and HIV test), microbiological, epidemiological, and molecular evaluations were carried out. Patients were considered "genotype-clustered" if two or more isolates from different patients were identified within 12 months of each other and had six or more IS6110 bands in an identical pattern, or < 6 bands with identical IS6110 RFLP patterns and spoligotype with the same spacer oligonucleotides. Residential and health care centers addresses were georeferenced. We used a Jeep hand GPS. The coordinates were transferred from the GPS files to ArcGIS using ArcMap 9.3. We evaluated global spatial aggregation of patients in IS6110-RFLP/ spoligotype clusters using global Moran´s I. Since global distribution was not random, we evaluated "hotspots" using Getis-Ord Gi* statistic. Using bivariate and multivariate analysis we analyzed sociodemographic, behavioral, clinic and bacteriological conditions associated with "hotspots". We used STATA® v13.1 for all statistical analysis. RESULTS: From 1995 to 2010, 1,370 patients >20 years were diagnosed with pulmonary TB; 33% had DM. The proportion of isolates that were genotyped was 80.7% (n = 1105), of which 31% (n = 342) were grouped in 91 genotype clusters with 2 to 23 patients each; 65.9% of total clusters were small (2 members) involving 35.08% of patients. Twenty three (22.7) percent of cases were classified as recent transmission. Moran`s I indicated that distribution of patients in IS6110-RFLP/spoligotype clusters was not random (Moran`s I = 0.035468, Z value = 7.0, p = 0.00). Local spatial analysis showed statistically significant spatial aggregation of patients in IS6110-RFLP/spoligotype clusters identifying "hotspots" and "coldspots". GI* statistic showed that the hotspot for spatial clustering was located in Camerino Z. Mendoza municipality; 14.6% (50/342) of patients in genotype clusters were located in a hotspot; of these, 60% (30/50) lived with DM. Using logistic regression the statistically significant variables associated with hotspots were: DM [adjusted Odds Ratio (aOR) 7.04, 95% Confidence interval (CI) 3.03-16.38] and attending the health center in Camerino Z. Mendoza (aOR18.04, 95% CI 7.35-44.28). CONCLUSIONS: The combination of molecular and epidemiological information with geospatial data allowed us to identify the concurrence of molecular clustering and spatial aggregation of patients with DM and TB. This information may be highly useful for TB control programs.

The lack of effect of aerobic exercise training on propranolol pharmacokinetics in young and elderly adults.

The effects of exercise training on the pharmacokinetics of orally administered propranolol were studied in young and elderly healthy volunteers. Twenty-three young (30 +/- 5 years of age) and 20 elderly (67 +/- 5 years of age) adults were randomly assigned to endurance training (N = 12 young subjects, 10 elderly subjects) or nonexercising control (N = 11 young subjects, 10 elderly subjects) groups. Training consisted of treadmill walking, stair climbing, or both three times per week for 40 minutes at 70-85% of maximal heart rate reserve for 16 weeks. Resting plasma propranolol concentrations after a single dose of 80 mg of oral propranolol were measured by high performance liquid chromatography with fluorescence detection, and estimated hepatic blood flow measured was measured using indocyanine green during supine test. Aerobic training increased maximal oxygen uptake (VO2 max) by 13% and 14% in the exercising young and elderly groups, respectively. There was no change in VO2 max in either control group. Adjusted mean estimated hepatic blood flow after exercise corrected for body weight for the young subjects who did not exercise (15.6 mL/min/Kg) and those who did (18.2 mL/min/Kg) groups were of borderline significance. No statistical differences were detected in the experimental propranolol pharmacokinetic parameters (maximal concentration, time of maximal concentration, terminal half-life, area under the curve, and protein binding) or derived pharmacokinetic parameters (intrinsic clearance, bioavailability, clearance, and volume of distribution). These results provide evidence that changes in aerobic fitness do not produce corresponding changes in propranolol pharmacokinetics in young or elderly adults.