Correlation between MMP-9 and extracellular cytokine HMGB1 in prediction of human ischemic stroke outcome

AbstractIschemic stroke (IS) outcome predictors include clinical features, biochemical parameters and some risk factors. The relations between two main players in the ischemic brain, MMPs and HMGB1, were estimated in the plasma of ischemic stroke patients stratified according to the Glasgow Outcome Scale and the Oxfordshire Community Stroke Project classification. IS patients exhibited higher plasma concentration of MMP-9 and the inflammatory cytokine HMGB1 compared with healthy controls. A full-blown correlation between MMP-9 activation and increased plasma MMP-9 concentration was observed in case of IS patients. A similar activity of MMP-2 and MMP-12 was characteristic of healthy volunteers and IS patients. In patients with ischemic stroke increased plasma levels of MMP-9 and HMGB1 are associated with a poor functional outcome and are significantly correlated with each other (P=0.0054). We suggest that diagnostic benefits will be obtained if plasma HMGB1 levels are measured for IS patients in addition to MMP-9

Adjunctive surgery improves treatment outcomes among patients with multidrug-resistant and extensively drug-resistant tuberculosis

SummaryObjectivesTo determine risk factors for poor outcomes among patients with pulmonary multidrug- or extensively drug-resistant (M/XDR) tuberculosis (TB) in Georgia.MethodsThis was a prospective, population-based observational cohort study.ResultsAmong 380M/XDR-TB patients (mean age 38 years), 179 (47%) had a poor outcome: 59 (16%) died, 37 (10%) failed, and 83 (22%) defaulted. Newly diagnosed M/XDR-TB cases were significantly more likely to have a favorable outcome than retreatment cases (odds ratio (OR) 4.26, 95% confidence interval (CI) 1.99–9.10, p<0.001). In the multivariable analysis, independent risk factors for a poor treatment outcome included previous treatment history (OR 2.92, 95% CI 1.29–6.58), bilateral disease (OR 1.90, 95% CI 1.20–3.01), body mass index (BMI, kg/m2) ≤18.5 (OR 1.91, 95% CI 1.11–3.29), and XDR-TB (OR 2.28, 95% CI 1.11–4.71). Patients who underwent surgical resection (OR 0.27, 95% CI 0.11–0.64) and had sputum culture conversion by 4 months (OR 0.33, 95% CI 0.21–0.52) were significantly less likely to have poor treatment outcomes.ConclusionsAdjunctive surgery appeared to be beneficial in treating patients with M/XDR-TB. Retreatment cases, XDR-TB, bilateral disease, and low BMI were associated with a poor outcome. Additional studies are needed to further define the apparent beneficial role of surgery in the treatment of M/XDR-TB

Self-medication with antibiotics in Georgian population

Background: Self-medication with antibiotics is a global phenomenon and a potential contributor to human pathogen resistance to antibiotics. It involves obtaining medication without a prescription, taking medicines based on the advice of friends and relatives, or previous treatment experience. Self-medication is common in both developed and developing countries; however, the prevalence of self-medication is higher in developing countries. The aim of this study was to determine the characteristics of antimicrobial self-medication in Georgia and its potential to influence the overall situation regarding antimicrobial consumption in the country.Methods: We conducted a cross-sectional study using a random sampling method and developed a self-administered questionnaire to collect the data. The survey was conducted via the Internet using the Google Forms platform.Results: The overall number of respondents was 742 adults living in Georgia. The results showed that 23.8% (n = 177) of adults had consumed antibiotics without a doctor’s prescription, and 12.7% (n = 94) confirmed the use of antibiotics by their own decision to treat minor family members. The total prevalence of self-medication was 32.6%. The data analysis revealed a correlation between factor F1 (“personal experience”) and gender (p = 0.042, F = 2.6), and between age and factor F2 (“lack of trust in medical practitioners”) (p = 0.047, F = 2.691). The correlation was stronger among young adults (aged 18–24) and senior adults (aged 60+). The correlation between the level of education and factor F2 was stronger (p = 0.00; F1 = 7.9) than with factor F1 (p = 0.04; F = 2.2).Conclusion: Self-medication is prevalent in Georgia; pharmacies are the main sources of antimicrobials. No correlation was found between factor F2, pertaining to “lack of trust in medical practitioners” and gender, between age and factor F1, linked to “personal experience.” The study uncovered a lack of knowledge about self-medication with antibiotics and emphasized the importance of public awareness campaigns and implementing effective interventions to regulate the sales of antibiotics without a doctor’s prescription

Tobacco Smoking and Tuberculosis Treatment Outcomes: A Prospective Cohort Study in Georgia

Objective To assess the effect of tobacco smoking on the outcome of tuberculosis treatment in Tbilisi, Georgia. Methods We conducted a prospective cohort study of adults with laboratory-confirmed tuberculosis from May 2011 to November 2013. History of tobacco smoking was collected using a standardized questionnaire adapted from the global adult tobacco survey. We considered tuberculosis therapy to have a poor outcome if participants defaulted, failed treatment or died. We used multivariable regressions to estimate the risk of a poor treatment outcome. Findings Of the 591 tuberculosis patients enrolled, 188 (31.8%) were past smokers and 271 (45.9%) were current smokers. Ninety (33.2%) of the current smokers and 24 (18.2%) of the participants who had never smoked had previously been treated for tuberculosis (P \u3c 0.01). Treatment outcome data were available for 524 of the participants, of whom 128 (24.4%) – including 80 (32.9%) of the 243 current smokers and 21 (17.2%) of the 122 individuals who had never smoked – had a poor treatment outcome. Compared with those who had never smoked, current smokers had an increased risk of poor treatment outcome (adjusted relative risk, aRR: 1.70; 95% confidence interval, CI: 1.00–2.90). Those who had ceased smoking more than two months before enrolment did not have such an increased risk (aRR: 1.01; 95% CI: 0.51–1.99). Conclusion There is a high prevalence of smoking among patients with tuberculosis in Georgia and smoking increases the risk of a poor treatment outcome

Use of a Molecular Diagnostic Test in AFB Smear Positive Tuberculosis Suspects Greatly Reduces Time to Detection of Multidrug Resistant Tuberculosis

Background: The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB). There are limited data on the performance and impact of these tests in field settings. Methods: The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST) using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program. Results: Among 500 AFB smear-positive sputum specimens, 458 (91.6%) had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH) resistanc

Sputum culture results for all AFB smear positive tuberculosis suspects and corresponding complete MTBDRplus assay results.

<p>Sputum culture results for all AFB smear positive tuberculosis suspects and corresponding complete MTBDRplus assay results.</p

Eliminating the category II retreatment regimen from national tuberculosis programme guidelines: the Georgian experience

PROBLEM: The category II retreatment regimen for management of tuberculosis in previously treated patients was first introduced in the early 1990s. It consists of 8 months of total therapy with the addition of streptomycin to standard first-line medications. A review of 6500 patients on category II therapy in Georgia showed poor outcomes and high rates of streptomycin resistance. APPROACH: The National Tuberculosis Program used an evidence-based analysis of national data to convince policy-makers that category II therapy should be eliminated from national guidelines in Georgia. LOCAL SETTING: The World Health Organization tuberculosis case-notification rate in Georgia is 102 per 100 000 population. All patients receive culture and drug susceptibility testing as a standard part of tuberculosis diagnosis. In 2009, routine surveillance found multidrug-resistant tuberculosis in 10.6% of newly diagnosed patients and 32.5% of previously treated cases. RELEVANT CHANGES: Category II retreatment regimen is no longer used in Georgia. Treatment is guided by results of drug susceptibility testing - using rapid, molecular tests where possible - for all previously treated tuberculosis patients. LESSONS LEARNT: There was little resistance to policy change because the review was initiated and led by the National Tuberculosis Program. This experience can serve as a successful model for other countries to make informed decisions about the use of category II therapy

Performance parameters of MTBDR<i>plus</i> in detecting INH R^∧, RIF R^∧, and MDR^∧ compared to conventional DST (reference standard)^#.

#<p>Values are percentages with 95% confidence interval in parentheses.</p><p>*PPV = positive predictive value, NPV = negative predictive value.</p>∧<p>INH R = isoniazid resistance, RIF R = rifampin resistance, MDR = multidrug resistance.</p

Pattern of genetic mutations in phenotypic drug-resistant <i>Mycobacterium tuberculosis</i> isolates using the Genotype MTBDRplus assay.

<p>*Definitions of abbreviations: INH = isoniazid; RIF = rifampicin; MDR = multidrug-resistant.</p>∧<p>Values are numbers, with percentages in parentheses.</p