Modelling the effect of short-course multidrug-resistant tuberculosis treatment in Karakalpakstan, Uzbekistan

Background: Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9-11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization. Methods: We construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions. Results: Based on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates. Conclusions: In addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable

International Consensus on Guiding Recommendations for Management of Patients with Nonsteroidal Antiinflammatory Drugs Induced Gastropathy-ICON-G

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs), one of the most commonly used medications worldwide, are frequently associated with gastrointestinal adverse events. Primary care physicians often face the challenge of achieving adequate pain relief with NSAIDs, while keeping their adverse events to a minimum. This is especially true when long-term use of NSAIDs is required such as in patients with osteoarthritis and rheumatoid arthritis. To help primary care physicians deal with such challenges more effectively, a panel of expert gastroenterologists came together with the aim of developing practice recommendations. Methods: A modified ‘Delphi’ process was used to reach consensus and develop practice recommendations. Twelve gastroenterologists from nine countries provided their expert inputs to formulate the recommendations. These recommendations were carefully developed taking into account existing literature, current practices, and expert opinion of the panelists. Results: The expert panel developed a total of fifteen practice recommendations. Following are the key recommendations: NSAIDs should be prescribed only when necessary; before prescribing NSAIDs, associated modifiable and non-modifiable risk factors should be considered; H. pylori infection should be considered and treated before initiating NSAIDs; patients should be properly educated regarding NSAIDs use; patients who need to be on long-term NSAIDs should be prescribed a gastroprotective agent, preferably a proton pump inhibitor and these patients should be closely monitored for any untoward adverse events. Conclusion/clinical significance: These practice recommendations will serve as an important tool for primary care physicians and will guide them in making appropriate therapeutic choices for their patients. Keywords: Gastropathy, Gastroprotective agents, Non-prescription drugs, Nonsteroidal Anti-inflammatory Agents, Proton pump inhibitor. How to cite this article: Hunt R, Lazebnik LB, Marakhouski YC, Manuc M, Ramesh GN, Aye KS, Bordin DS, Bakulina NV, Iskakov BS, Khamraev AA, Stepanov YM, Ally R, Garg A. International Consensus on Guiding Recommendations for Management of Patients with Nonsteroidal Anti-inflammatory Drugs Induced Gastropathy-ICON-G. Euroasian J Hepatogastroenterol, 2018;8(2):148-160. Source of support: Nil Conflict of interest: Richard Hunt has served as a consultant for INSYS, Dr Reddy's, Takeda, and Novartis. He has received an honorarium from Novartis, Danone, Dr Reddy's, and Takeda. He has been on the speaker's bureau for Takeda and Dr Reddy's and on scientific advisory board for INSYS. Dmitry S Bordin has served as a lecturer for Astellas, AstraZeneca, KRKA and Abbott. For the remaining authors, there are no conflicts of interest

Mechanism of Improving the Innovative Activity of the Insurance Services Market in Uzbekistan

The article is devoted to the issues of innovative development of the insurance services market, which is based on the need and importance of creating innovations in the industry. Barriers to the introduction of innovations have also been identified and appropriate ways for their elimination have been identified

Electrochemical dehydrogenative C(sp2)−H amination

A transition-metal-free direct electrolytic C−H amination involving an electrochemically generated nitrenium ion intermediate has been developed. The electrosynthesis takes place in the absence of any organoiodine catalysts and is enabled by an in situ generated electrolyte. A novel, efficient intramolecular and intermolecular C−H amination has been demonstrated using a simple reaction setup

Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

Background: In 2016, World Health Organization guidelines conditionally recommended standardised shorter 9-12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan. Methods: Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion. Results: Of 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8-44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression. Conclusions: Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility