Methadone in post-herpetic neuralgia: A pilot proof-of-concept study

OBJECTIVE:

This research was designed as a pilot proof-of-concept study to evaluate the use of low-dose methadone in post-herpetic neuralgia patients who remained refractory after first and second line post-herpetic neuralgia treatments and had indications for adding an opioid agent to their current drug regimens.

METHODS:

This cross-over study was double blind and placebo controlled. Ten opioid naïve post-herpetic neuralgia patients received either methadone (5 mg bid) or placebo for three weeks, followed by a 15-day washout period and a second three-week treatment with either methadone or placebo, accordingly. Clinical evaluations were performed four times (before and after each three-week treatment period). The evaluations included the visual analogue scale, verbal category scale, daily activities scale, McGill pain questionnaire, adverse events profile, and evoked pain assessment. All patients provided written informed consent before being included in the study. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01752699","term_id":"NCT01752699"}}NCT01752699

RESULTS:

Methadone, when compared to placebo, did not significantly affect the intensity of spontaneous pain, as measured by the visual analogue scale. The intensity of spontaneous pain was significantly decreased after the methadone treatment compared to placebo on the category verbal scale (50% improved after the methadone treatment, none after the placebo, p = 0.031). Evoked pain was reduced under methadone compared to placebo (50% improved after the methadone treatment, none after the placebo, p = 0.031). Allodynia reduction correlated with sleep improvement (r = 0.67, p = 0.030) during the methadone treatment. The side effects profile was similar between both treatments.

CONCLUSIONS:

Methadone seems to be safe and efficacious in post-herpetic neuralgia. It should be tried as an adjunctive treatment for post-herpetic neuralgia in larger prospective studies.     

Effects of 980-nm diode laser on the ultrastructure and fracture resistance of dentine

Few reports have addressed the effects of diode laser irradiation at 980 nm on the morphology and fracture resistance of dentine. The purpose of this study is to evaluate the effects of 980-nm diode laser on the ultrastructure and fracture resistance of root dentine. The roots of 90 extracted canine teeth were divided into three groups according to the type of irrigating solution (water, NaOCl, and NaOCl/EDTA) and subdivided into three subgroups (n?=?10) according to the amount of laser irradiation (without irradiation, 1.5 W/100 Hz and 3.0 W/100 Hz). The roots were filled with an epoxy resin-based sealer and gutta-percha and then subjected to a fracture resistance test. Data were analyzed by ANOVA and the Tukey test (p?<?0.05). Additionally, 18 canine teeth were prepared using the same irrigation/irradiation protocols and evaluated by scanning electron microscopy (SEM). The SEM showed greater changes when the laser power increased, and the changes also varied according to the irrigating solution. A modified smear layer was observed in specimens that were treated with water and then laser-irradiated. The laser treatment did not alter the fracture resistance of roots treated with 1.5 W/100 Hz (246.3?±?29.5 N) and 3.0 W/100 Hz (215.3?±?25.1 N) laser power. The roots treated with NaOCl were more susceptible to fracture (199.4?±?15.1 N) than those irrigated with water (254.2?±?23.0 N) (p?<?0.05). The 980-nm diode laser altered the morphology of the dentine but did not affect the fracture resistance of the roots.     

Measuring Adherence to Antiretroviral Treatment: The Role of Pharmacy Records of Drug Withdrawals

This study aimed to evaluate adherence to antiretroviral treatment (ART) among HIV + adults, assess its association with HIV viral load (VL) and identify factors associated to adherence. A survey involving a random sample of adults followed at a HIV/AIDS reference center in S?o Paulo city, Brazil, from 2007 to 2009 was done. A questionnaire was applied and data were retrieved from the pharmacy and medical records. The study involved 292 subjects: 70.2% men; median age: 43 years; median duration of ART: 8 years. 89.3% self-reported taken all prescribed pills in the last 3 days but only 39.3% picked up ≥95% of the prescribed ART from the pharmacy in the last 12 months. At the multivariate analysis having symptoms prior to ART, taking fewer ART pills, and not missing medical appointments were independently associated to higher adherence. Adherence was strongly associated with undetectable HIV VL. Rates of undetectable HIV VL did not differ from 80 to ≥95% of adherence.     

The application of quality by design in the development of the liquid chromatography method to determine empagliflozin in the presence of its organic impurities

Analysis of impurities is an important step in the quality control of pharmaceutical ingredients and final products. From drug synthesis or excipients, even in small concentrations, impurities may affect efficacy and safety. The method was developed following Quality by Design (QbD) for the analysis of the antidiabetic empagliflozin. The concept of QbD is used as a tool for the development of methods and formulations. Through predefined objectives and risk analysis, robust methodologies and reduced solvent consumption are developed. A simple HPLC method was developed and validated for the quantitative determination of empagliflozin and its organic impurities from the synthesis process. The method was carried out in a Shim-pack phenyl column with a mobile phase consisting of an acetonitrile/water mixture (72 : 28), with isocratic elution and the detector wavelength was 230 nm. The validation process, in accordance with international guidelines, shows that the method was linear, precise and accurate for empagliflozin, impurity 1 and impurity 2. Limits of detection (0.01, 0.02 and 0.01 μg mL⁻¹) and quantification (0.10, 0.10 and 0.05 μg mL⁻¹) were determined for EMPA, IMP1 and IMP2, respectively. The HPLC method for impurity determination in empagliflozin was linear, precise, accurate and robust. It can be successfully applied in the quality control of empagliflozin and the synthesis of impurities, being adequate for routine analysis.

Analysis of impurities is an important step in the quality control of pharmaceutical ingredients and final products.