Publications by authors named "Achar J"

Improving regulatory confidence and acceptance of in silico toxicology methods for chemical risk assessment requires assessment of associated uncertainties. Therefore, there is a need to identify and systematically categorize sources of uncertainty relevant to the methods and their predictions. In the present study, we analyzed studies that have characterized sources of uncertainty across commonly applied in silico toxicology methods.

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Background And Objectives: Limited evidence guides the efficacy and safety of cannabis for therapeutic purposes (CTP). Healthcare providers lack requisite knowledge to advise and support patients. This study aimed to describe and compare several aspects of initial CTP interactions across different provider types.

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Article Synopsis
  • - This study developed a method to analyze both implicit and explicit uncertainties in Quantitative Structure-Activity Relationship (QSAR) modeling, specifically using neurotoxicity as a case study.
  • - Through text content analysis, the researchers identified various uncertainty sources, revealing that most uncertainties were expressed implicitly, particularly in 13 out of 20 categories, with explicit uncertainties noted in only three.
  • - Key concerns highlighted included Mechanistic plausibility, Model relevance, and Model performance, indicating significant areas where uncertainty exists; the findings underscore the need for researchers to consider the broader QSAR literature in their analyses.
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Background: Isoniazid (INH, H) resistance is the most common drug-resistant TB pattern, with treatment success rates lower than those in drug-susceptible TB. The WHO recommends a 6-month regimen of rifampicin (RIF, R), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (Lfx) (6REZLfx) for INH-resistant, RIF-susceptible TB (HR-TB). Uzbekistan has a high burden of TB (62/100,000 population) and multidrug-resistant TB (12/100,000 population).

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In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe.

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Background: The Global Drug Facility (GDF) of the Stop TB Partnership was launched in 2001 with the goal of increasing access to quality-assured tuberculosis (TB) drugs and products. We aimed to describe the TB drugs and prices available from the GDF over time and to assess trends.

Methods: We searched the internet, including an internet archive, for past and recent GDF Product Catalogs and extracted the listed TB drugs and prices.

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Background: In 2020, WHO guidelines prioritised the use of a standard fully oral short treatment regimen (STR) consisting of bedaquiline, levofloxacin or moxifloxacin, ethionamide, ethambutol, high-dose isoniazid, pyrazinamide, and clofazimine for the management of rifampicin-resistant tuberculosis. A high prevalence of resistance to constituent drugs precluded its widespread use by countries in the WHO European region. We evaluated three 9-month fully oral modified STRs (mSTRs) in which ethionamide, ethambutol, isoniazid, and pyrazinamide were replaced by linezolid, cycloserine, or delamanid (or a combination).

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The first step in the hazard or risk assessment of chemicals should be to formulate the problem through a systematic and iterative process aimed at identifying and defining factors critical to the assessment. However, no general agreement exists on what components an in silico toxicology problem formulation (PF) should include. The present work aims to develop a PF framework relevant to the application of in silico models for chemical toxicity prediction.

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Tajikistan has a high burden of rifampicin-resistant TB (RR-TB), with 2,700 new cases estimated for 2021 (28/100,000 population). TB is spread among household members through close interaction and children exposed through household contact progress to disease rapidly and frequently. We retrospectively analysed programmatic data from household contact tracing in Dushanbe over 50 months.

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These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents. Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.

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Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study.

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Tuberculosis (TB) programs depend on a continuous supply of large amounts of high-quality TB drugs. When TB programs procure TB drugs from international suppliers, such as the Global Drug Facility, they can incur import costs for international transport, customs clearance, and national transport. We assessed the drug costs and import costs of 18 longer (≥18 months), 10 shorter (9-12 months), and 8 short (≤6 months) drug regimens for drug-sensitive (DS) and multidrug-resistant (MDR)-TB treatment.

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Article Synopsis
  • A study evaluated the effectiveness of the Xpert MTB/RIF Ultra assay in detecting tuberculosis (TB) in fresh stool samples from children under 15 years old in Dushanbe, Tajikistan, enrolling 688 participants from April 2019 to October 2021.
  • The assay showed a sensitivity of 68.8% and a high specificity of 98.7%, indicating it can effectively identify TB in this population, despite challenges like staffing shortages and outdated protocols due to COVID-19.
  • This report, being one of the first from Central Asia and a low-middle-income country, supports the WHO's recommendation to use fresh stool as an acceptable sample for TB testing in young children, who struggle to provide sputum samples.
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Background: Tuberculosis (TB) drugs and their import are costly. We assessed how shorter TB drug regimens, which were non-inferior or superior in recent TB trials, can affect the costs for purchasing and importing TB drugs.

Methods: We estimated the drug costs and import costs of 39 longer and shorter TB drug regimens using TB drug prices from the Global Drug Facility and import cost estimates for a TB program in Karakalpakstan, Uzbekistan.

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Background: There is concern that the COVID-19 pandemic has damaged global childhood tuberculosis management. Quantifying changes in childhood tuberculosis notifications could support more targeted interventions to restore childhood tuberculosis services. We aimed to use time-series modelling to evaluate the impact of COVID-19 on child tuberculosis notifications.

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Children affected by rifampicin-resistant tuberculosis (RR-TB; TB resistant to at least rifampicin) are a neglected group. Each year an estimated 25,000-30,000 children develop RR-TB disease globally. Improving case detection and treatment initiation is a priority since RR-TB disease is underdiagnosed and undertreated.

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Introduction: Vaccinations for COVID-19 are being distributed, yet vaccine hesitance is placing many people at risk for infection, negative outcomes, and compromising public health. Given primary care clinics are where people most often interact with health care providers, understanding factors associated with this hesitance may help providers in integrated primary care settings best address this hesitance.

Method: Between September and November of 2020, a survey was sent to all primary care patients within a large southern California health system, with over 10,000 responding (22% response rate).

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Background: The introduction of new and often shorter tuberculosis (TB) drug regimens affects the cost of TB programmes.

Methods: We modelled drug purchase and import costs for 20-month, 9-month and 4- to 6-month TB drug regimens based on 2016-2020 treatment numbers from a TB programme in Karakalpakstan, Uzbekistan, and 2021 Global Drug Facility prices.

Results: On average, 2225±374 (±sd) people per year started TB treatment, 30±2.

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Water temperature rises due to thermal discharge and global warming and the potential resulting impacts on the ecotoxicity of emerging chemicals are a growing concern. Benzophenone-3 (BP-3) is an ultraviolet filter added to personal care and plastic products, which is detected at highest concentrations during the hot summer season. This study aimed to investigate the effect of elevated temperature on acute (48 h) and chronic (21 d) BP-3 toxicity in Daphnia magna.

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Adverse effects of microplastics (MPs) are exacerbated by plastic additives such as benzophenone-3 (BP-3). The aim of the present study was to evaluate the role of extracellular polymeric substances (EPS) of Chlorella vulgaris in leaching BP-3 additive (3.0 ± 0.

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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.

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Treatment outcomes for Multidrug/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) remain poor across the globe and in the Russian Federation. Treatment of XDR-TB is challenging for programmes and patients often resulting in low success rates and onward transmission of drug-resistant strains. Analysis of factors affecting culture conversion rate among XDR-TB patients may serve as a basis for optimization of treatment regimens.

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The global proportion of successful treatment outcomes of Multidrug-Resistant/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) remains unacceptably low. Time to culture conversion is important in making treatment-related decisions and is used as an interim predictor of pulmonary MDR/RR-TB treatment success. No previous studies have been conducted to assess determinants of time to culture conversion for MDR/RR-TB patients in Lithuania.

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