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Chronic hepatitis C genotype 1 treatment roadmap for resource constrained settings.

ABSTRACT: To use existing hepatitis C virus (HCV) antiviral therapies as access to new treatments is limited.A PubMed search for randomised control trials or meta-analysis related to response-guided therapy of HCV genotype 1 patients was undertaken using pegylated interferon and ribavirin (PR), boceprevir (B) and telaprevir (T) and lead-in where response-guided therapy at TW4(TW4), 8(TW8), 10(TW10), or 12(TW12) based on HCVRNA(+) or HCVRNA(-). Studies presented at major conferences were also used. Where necessary, a post-hoc analysis was performed. A response-guided management roadmap was created based on sustained virological response (SVR).Starting with PR, those with HCVRNA(-) at TW4 have > 86% SVR, while those are HCVRNA(+) have 34%-41.7% SVR. HCVRNA(-) TW4 patients can have 24 wk PR if HCVRNA < 400000 IU/mL. Alternatively, 28 wk BPR has similar SVR. If HCVRNA(+) at TW4, 72 wk PR leads to 53% SVR, hence BPR is a better option, and if HCVRNA(-) by TW8, 28 wk therapy is sufficient. If HCVRNA(+) at TW8, then HCVRNA should be checked at TW10 and TW12. By TW12, HCVRNA ? 100 IU/mL activates the stopping rule. This roadmap is applicable for treatment-naïve, treatment failures and cirrhotic patients. Validation from an Asia Pacific early access boceprevir program confirmed the findings that HCVRNA(-) at TW4, or TW8 conferred > 80% SVR, leading to the "80-80" rule.Using a roadmap based on HCVRNA(-) at TW4 or TW8 (the "80-80" rule), high SVR can be achieved, and guide the best choices for treatment, and also reduces drug exposure in poor responders.

SUBMITTER: Lim SG

PROVIDER: S-EPMC4323477 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Chronic hepatitis C genotype 1 treatment roadmap for resource constrained settings.

Lim Seng Gee SG

World journal of gastroenterology 20150201 6

<h4>Aim</h4>To use existing hepatitis C virus (HCV) antiviral therapies as access to new treatments is limited.<h4>Methods</h4>A PubMed search for randomised control trials or meta-analysis related to response-guided therapy of HCV genotype 1 patients was undertaken using pegylated interferon and ribavirin (PR), boceprevir (B) and telaprevir (T) and lead-in where response-guided therapy at TW4(TW4), 8(TW8), 10(TW10), or 12(TW12) based on HCVRNA(+) or HCVRNA(-). Studies presented at major confere ...[more]

PMID: 25684966

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Project description:IntroductionSexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings.MethodsWe prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.Results and discussionsThe diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions.ConclusionsThe WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

Project description:AimTo determine whether intermediate hyperglycaemia, defined by fasting plasma glucose and HbA1c criteria, is associated with mortality in a 10-year cohort of people in a Latin American country.MethodsAnalysis of the PERU MIGRANT Study was conducted in three different population groups (rural, rural-to-urban migrant, and urban). The baseline assessment was conducted in 2007/2008, with follow-up assessment in 2018. The outcome was all-cause mortality, and the exposure was intermediate hyperglycaemia, using three definitions: (1) impaired fasting glucose, defined according to American Diabetes Association criteria [fasting plasma glucose 5.6-6.9 mmol/l (100-125 mg/dl)]; (2) intermediate hyperglycaemia defined according to American Diabetes Association criteria [HbA1c levels 39-46 mmol/mol (5.7-6.4%)]; and (3) intermediate hyperglycaemia defined according to the International Expert Committee criteria [HbA1c levels 42-46 mmol/mol (6.0-6.4%)]. Crude and adjusted hazard ratios and 95% CIs were estimated using Cox proportional hazard models.ResultsAt baseline, the mean (sd) age of the study population was 47.8 (11.9) years and 52.5% of the cohort were women. The study cohort was divided into population groups as follows: 207 people (20.0%) in the rural population group, 583 (59.7%) in the rural-to-urban migrant group and 198 (20.3%) in the urban population group. The prevalence of intermediate hyperglycaemia was: 6%, 12.9% and 38.5% according to the American Diabetes Association impaired fasting glucose definition, the International Expert Committee HbA1c -based definition and the American Diabetes Association HbA1c -based definition, respectively, and the mortality rate after 10 years was 63/976 (7%). Intermediate hyperglycaemia was associated with all-cause mortality using the HbA1c -based definitions in the crude models [hazard ratios 2.82 (95% CI 1.59-4.99) according to the American Diabetes Association and 2.92 (95% CI 1.62-5.28) according to the International Expert Committee], whereas American Diabetes Association-defined impaired fasting glucose was not [hazard ratio 0.84 (95% CI 0.26-2.68)]. In the adjusted model, however, only the American Diabetes Association HbA1c -based definition was associated with all-cause mortality [hazard ratio 1.91 (95% CI 1.03-3.53)], whereas the International Expert Committee HbA1c -based and American Diabetes Association impaired fasting glucose-based definitions were not [hazard ratios 1.42 (95% CI 0.75-2.68) and 1.09 (95% CI 0.33-3.63), respectively].ConclusionsIntermediate hyperglycaemia defined using the American Diabetes Association HbA1c criteria was associated with an elevated mortality rate after 10 years in a cohort from Peru. HbA1c appears to be a factor associated with mortality in this Peruvian population.

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Chronic hepatitis C genotype 1 treatment roadmap for resource constrained settings.

Publications

Chronic hepatitis C genotype 1 treatment roadmap for resource constrained settings.

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