A Randomized, Naturalistic, Parallel-Group Study for the Long-Term Treatment of Panic Disorder With Clonazepam or Paroxetine

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [ SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

A retrospective serologic survey of hantavirus infections in the county of Cassia dos Coqueiros, state of Sao Paulo, Brazil

Introduction: In recent years, hantavirus infections producing severe diseases have obtained an increased attention from public health authorities from the countries of Eurasia to the Americas. Brazil has reported 1,300 cases of hantavirus cardiopulmonary syndrome (HCPS) from 1993 to 2010, with about 80 of them occurring in the northeast of the state of Sao Paulo, with 48% fatality rate. Araraquara virus was the causative agent of HCPS in the region. Considering that hantaviruses causing human disease in the Americas were unknown until 1993, we have looked for hantavirus infections in the population of Cassia dos Coqueiros county, northeast of the state of Sao Paulo, Brazil, before this time. This county has about 2,800 inhabitants and an economy based on agriculture, including cultivation of Brachiaria decumbens grass. The grass seeds are an important rodent attraction, facilitating transmission of hantavirus to man. Four HCPS cases were reported so far in the county. Methods: In this study, 1,876 sera collected from 1987 to 1990 were tested for IgG to hantavirus by IgG-ELISA, using the N recombinant protein of Araraquara virus as antigen. Results: Positive results were observed in 89 (4.7%) samples, which were all collected in 1987. The positivity among urban inhabitants was 5.3%, compared with 4.3% among those living in rural areas. Conclusions: Our results showed that hantavirus infections occurred in Cassia dos Coqueiros, completely unrecognized, even before hantaviruses were described in the Americas.

Enantioselective analysis of unbound tramadol, O-desmethyltramadol and N-desmethyltramadol in plasma by ultrafiltration and LC-MS/MS: Application to clinical pharmacokinetics

This study describes the enantioselective analysis of unbound and total concentrations of tramadol and its main metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2) in human plasma. Sample preparation was preceded by an ultrafiltration step to separate the unbound drug. Both the ultrafiltrate and plasma samples were submitted to liquid/liquid extraction with methyl t-butyl ether. Separation was performed on a Chiralpak (R) AD column and tandem mass spectrometry consisting of an electrospray ionization source, positive ion mode and multiple reaction monitoring was used as the detection system. Linearity was observed in the following ranges: 0.2-600 and 0.5-250 ng/mL for analysis of total and unbound concentrations of the tramadol enantiomers, respectively, and 0.1-300 and 0.25-125 ng/mL for total and unbound concentrations of the M1 and M2 enantiomers, respectively. The lower limits of quantitation were 0.2 and 0.5 ng/mL for analysis of total and unbound concentration of each tramadol enantiomer, respectively, and 0.1 and 0.25 ng/mL for total and unbound concentrations of M1 and M2 enantiomers, respectively. Intra- and interassay reproducibility and inaccuracy did not exceed 15%. Clinical application of the method to patients with neuropathic pain showed plasma accumulation of (+)-tramadol and (+)-M2 after a single oral dose of racemic tramadol. Fractions unbound of tramadol, M1 or M2 were not enantioselective in the patients investigated. (C) 2011 Elsevier B.V. All rights reserved.

The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: Guideline methodology

Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.

A retrospective serologic survey of hantavirus infections in the county of Cássia dos Coqueiros, State of São Paulo, Brazil

INTRODUCTION: In recent years, hantavirus infections producing severe diseases have obtained an increased attention from public health authorities from the countries of Eurasia to the Americas. Brazil has reported 1,300 cases of hantavirus cardiopulmonary syndrome (HCPS) from 1993 to 2010, with about 80 of them occurring in the northeast of the State of São Paulo, with 48% fatality rate. Araraquara virus was the causative agent of HCPS in the region. Considering that hantaviruses causing human disease in the Americas were unknown until 1993, we have looked for hantavirus infections in the population of Cássia dos Coqueiros county, northeast of the State of São Paulo, Brazil, before this time. This county has about 2,800 inhabitants and an economy based on agriculture, including cultivation of Brachiaria decumbens grass. The grass seeds are an important rodent attraction, facilitating transmission of hantavirus to man. Four HCPS cases were reported so far in the county. METHODS: In this study, 1,876 sera collected from 1987 to 1990 were tested for IgG to hantavirus by IgG-ELISA, using the N recombinant protein of Araraquara virus as antigen. RESULTS: Positive results were observed in 89 (4.7%) samples, which were all collected in 1987. The positivity among urban inhabitants was 5.3%, compared with 4.3% among those living in rural areas. CONCLUSIONS: Our results showed that hantavirus infections occurred in Cássia dos Coqueiros, completely unrecognized, even before hantaviruses were described in the Americas.