Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid arthritis: a systematic review of randomized controlled trials.

Even though new drugs for the treatment of rheumatoid arthritis (RA) have been developed, methotrexate (MTX) remains a commonly used drug for RA management. In addition to monitoring disease activity during RA treatment, bone erosion should be closely assessed throughout long-term RA management. In this review article, we present a systematic review of MTX effectiveness in reducing the risk of bone erosion. We reviewed randomized controlled trial studies that involved MTX monotherapy or MTX in combination with placebo. Evaluation of the progression of bone erosion was examined by radiographic assessment such as total Sharp score (TSS) or van der Heijde score (SvdH or vdH TSS), joint space narrowing (JSN), erosion score (ERO), and proportion of radiographic nonprogressors. Several key factors were found to influence the response to MTX treatment, such as gene polymorphism. The exact mechanism of the prevention of bone erosion by MTX remains unclear, which warrants future investigations. The variability of RA disease activity in study subjects resulted in variations in the results reported by individual studies. Collective analysis suggests that MTX could slow down the progression of bone erosion based on a radiographic score of less than 0.5-1/year.

Management and treatment outcomes of MDR-TB: results from a setting with high rates of drug resistance.

SETTINGS: Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about the management and treatment outcomes of MDR-TB patients in Pakistan. OBJECTIVE: To evaluate management and predictors of unsuccessful treatment outcomes among MDR-TB patients. METHODS: In this observational cohort study, 196 MDR-TB patients enrolled at the Programmatic Management Unit for drug-resistant TB of Lady Reading Hospital, Peshawar, Pakistan, between 1 January 2012 and 28 February 2013 were included. Patients were followed until an outcome was recorded or 31 January 2015. RESULTS: Extensive concurrent resistance to ofloxacin (OFX) and pyrazinamide (54.6%) was observed. Among 181 patients for whom treatment outcome was available, 135 (74.6%) were cured, 1 (0.6%) completed treatment, 35 (19.3%) died, 8 (4.4%) failed treatment and 2 (1.1%) defaulted. In multivariate analysis, predictors of unsuccessful treatment outcome (death, failure and default) were age >40 years (OR 3.412, P = 0.009), baseline body weight <40 kg (OR 2.966, P = 0.020), concurrent comorbidity (OR 3.785, P = 0.023), resistance to OFX (OR 2.777, P = 0.023), lung cavitations at baseline chest X-ray (OR 5.253, P < 0.001) and regimen modification due to adverse events (OR 3.492, P = 0.037). CONCLUSION: The treatment outcome results were encouraging. Patients with identifiable predictors of poor treatment outcome should receive enhanced clinical management. Early detection and management of mild adverse effects can help prevent regimen modification and may improve treatment outcomes.

Duration of treatment in pulmonary tuberculosis: are international guidelines on the management of tuberculosis missing something?

BACKGROUND: Despite evidence of an association between tuberculosis (TB) treatment outcomes and the performance of national tuberculosis programmes (NTP), no study to date has rigorously documented the duration of treatment among TB patients. As such, this study was conducted to report the durations of the intensive and continuation phases of TB treatment and their predictors among new smear-positive pulmonary tuberculosis (PTB) patients in Malaysia. STUDY DESIGN: Descriptive, non-experimental, follow-up cohort study. METHODS: This study was conducted at the Chest Clinic of Penang General Hospital between March 2010 and February 2011. The medical records and TB notification forms of all new smear-positive PTB patients, diagnosed during the study period, were reviewed to obtain sociodemographic and clinical data. Based on standard guidelines, the normal benchmarks for the durations of the intensive and continuation phases of PTB treatment were taken as two and four months, respectively. A patient in whom the clinicians decided to extend the intensive phase of treatment by ≥2 weeks was categorized as a case with a prolonged intensive phase. The same criterion applied for the continuation phase. Multiple logistic regression analysis was performed to find independent factors associated with the duration of TB treatment. Data were analyzed using Predictive Analysis Software Version 19.0. RESULTS: Of the 336 patients included in this study, 261 completed the intensive phase of treatment, and 226 completed the continuation phase of treatment. The mean duration of TB treatment (n = 226) was 8.19 (standard deviation 1.65) months. Half (49.4%, 129/261) of the patients completed the intensive phase of treatment in two months, whereas only 37.6% (85/226) of the patients completed the continuation phase of treatment in four months. On multiple logistic regression analysis, being a smoker, being underweight and having a history of cough for ≥4 weeks at TB diagnosis were found to be predictive of a prolonged intensive phase of treatment. Diabetes mellitus and the presence of lung cavities at the start of treatment were the only predictors found for a prolonged continuation phase of treatment. CONCLUSIONS: The average durations of the intensive and continuation phases of treatment among PTB patients were longer than the targets recommended by the World Health Organization. As there are no internationally agreed criteria, it was not possible to judge how well the Malaysian NTP performed in terms of managing treatment duration among PTB patients.

Development and validation of RP-HPLC-UV method for the determination of Glipizide in human plasma.

A simple, sensitive and selective HPLC method with UV detection for determination of Glipizide in human plasma was developed. Liquid-liquid extraction method was used to extract the drug from the plasma samples. Chromatographic separation of Glipizide was achieved using C18 column (ZORBAX ODS 4.6 × 150 mm). The mobile phase was comprised of 0.01 M potassium dihydrogen phosphate and acetonitrile (65:35, v/v) adjusted to pH 4.25 with glacial acetic acid. The analysis was run at a flow rate of 1.5 mL/min with an injection volume was 20 µL. The detector was operated at 275 nm. The calibration curve was linear over a concentration range of 50-1600 ng/mL. Intra-day and inter-day precision and accuracy values were below 15%. The limit of quantification was 50 ng/mL and the mean recovery was above 98%. Freeze-thaw, short-term, long-term and post-preparative stability studies showed that Glipizide in plasma sample was stable. The method may be successfully applied to analyze the Glipizide concentration in plasma samples for bioavailability and bioequivalence studies.