Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study).

BACKGROUND: Catheter ablation (CA) is a highly effective therapy for the treatment of paroxysmal atrial fibrillation (AF) when compared with antiarrhythmic drug therapy (ADT). No randomized studies have compared the two strategies in persistent AF. The present randomized trial aimed to compare the effectiveness of CA vs. ADT in treating persistent AF. METHODS AND RESULTS: Patients with persistent AF were randomly assigned to CA or ADT (excluding patients with long-standing persistent AF). Primary endpoint at 12-month follow-up was defined as any episode of AF or atrial flutter lasting >24 h that occurred after a 3-month blanking period. Secondary endpoints were any atrial tachyarrhythmia lasting >30 s, hospitalization, and electrical cardioversion. In total, 146 patients were included (aged 55 ± 9 years, 77% male). The ADT group received class Ic (43.8%) or class III drugs (56.3%). In an intention-to-treat analysis, 69 of 98 patients (70.4%) in the CA group and 21 of 48 patients (43.7%) in the ADT group were free of the primary endpoint (P = 0.002), implying an absolute risk difference of 26.6% (95% CI 10.0-43.3) in favour of CA. The proportion of patients free of any recurrence (>30 s) was higher in the CA group than in the ADT group (60.2 vs. 29.2%; P < 0.001) and cardioversion was less frequent (34.7 vs. 50%, respectively; P = 0.018). CONCLUSION: Catheter ablation is superior to medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up. CLINICAL TRIAL REGISTRATION INFORMATION: NCT00863213 (http://clinicaltrials.gov/ct2/show/NCT00863213).

Methodological quality in pharmacogenetic studies with binary assessment of treatment response: a review.

OBJECTIVE: To evaluate the reporting of critical design issues and methods of statistical analysis in pharmacogenetic studies published in the medical literature. STUDY DESIGN AND SETTINGS: Systematic review of 65 original pharmacogenetic studies published in the literature over the last 15 years. RESULTS: The sample size determination and the planned sample size were lacking in 63 papers. The study design characterization was lacking in 43 papers. The number of patients analyzed ranged from 36 to 1400 (median=161 and interquartile range of 119-250). The Pearson's χ2 test and the Fisher's test were the most common forms of analysis. Multiple statistical testing was relevant to 59 papers, but only 11 addressed the issue of multiplicity (Bonferroni correction). Sources of multiplicity were multiple association assessment (45 papers), analysis of both genotype and allelic frequencies (44), and multiple analysis methods (unadjusted and adjusted). Hardy-Weinberg equilibrium was tested in 12 of 45 papers performing allelic analysis and was fully reported in four of them. The results of association analyses were commonly reported as P values but rarely as estimates of an association measure (odds ratio or relative risk) and its accuracy. CONCLUSIONS: These results show that there is considerable room for improvement in the current standards of design, analysis, and reporting of pharmacogenetic research.

[Estimated prevalence of chronic renal failure among patients with type 2 diabetes in Spain]. / Prevalencia estimada de insuficiencia renal crónica en España en pacientes con diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: The aim of this study was to estimate the current prevalence of Chronic Renal Insufficiency (RI) in ambulatory patients with type 2 Diabetes (T2DM) assisted in Endocrinology Departments all over Spain. PATIENTS AND METHODS: This was an observational, cross sectional, multicenter study. From each participant the following data were retrospective collected: demographic, anthropometric, renal function, diabetes, cardiovascular risk factors, comorbidities and treatment. RI was defined by a glomerular filtration rate lower than 60ml/min/1.73m(2), using the shortened MDRD method. RESULTS: 541 patients with T2DM were included, 53% were men, the mean age (DS) was 63 years old (7.9) and the HbA(1)c was 7.6 % (1.3). The prevalence (CI95%) of RI was 22.9% (19.4-26.7), higher than the previous estimate, witch was 5,7% (3.9-8.0, p<0,0001). The associated risk factor for RI were age (OR 2.07; 95%CI: 1.47-2.91 per each ten year period of increase), female gender (OR 2.25; 95%CI: 1.36-3.71) and hyperuricemia (OR 3.15; 95% CI: 1.56-6.37). There were no differences in the metabolic control between patients with RI vs those without RI. CONCLUSIONS: 22.9% of T2DM ambulatory patients followed by endocrinologist had RI, but just a quarter of them had previously been diagnosed. The automated determination of creatinine clearance could increase the proportion of diagnosis and facilitate the improvement of the metabolic control in these patients.

Satisfaction survey with DNA cards method to collect genetic samples for pharmacogenetics studies.

BACKGROUND: Pharmacogenetic studies are essential in understanding the interindividual variability of drug responses. DNA sample collection for genotyping is a critical step in genetic studies. A method using dried blood samples from finger-puncture, collected on DNA-cards, has been described as an alternative to the usual venepuncture technique. The purpose of this study is to evaluate the implementation of the DNA cards method in a multicentre clinical trial, and to assess the degree of investigators' satisfaction and the acceptance of the patients perceived by the investigators. METHODS: Blood samples were collected on DNA-cards. The quality and quantity of DNA recovered were analyzed. Investigators were questioned regarding their general interest, previous experience, safety issues, preferences and perceived patient satisfaction. RESULTS: 151 patients' blood samples were collected. Genotyping of GST polymorphisms was achieved in all samples (100%). 28 investigators completed the survey. Investigators perceived patient satisfaction as very good (60.7%) or good (39.3%), without reluctance to finger puncture. Investigators preferred this method, which was considered safer and better than the usual methods. All investigators would recommend using it in future genetic studies. CONCLUSION: Within the clinical trial setting, the DNA-cards method was very well accepted by investigators and patients (in perception of investigators), and was preferred to conventional methods due to its ease of use and safety.

[Cost-effectiveness of an intervention based on the Global INitiative for Asthma (GINA) recommendations using a computerized clinical decision support system: a physicians randomized trial]. / Coste-efectividad de una intervención basada en las recomendaciones de la Global INitiative for Asthma (GINA), mediante un sistema informatizado de apoyo a la decisión clínica: un ensayo con aleatorización de médicos.

BACKGROUND AND OBJECTIVE: To assess the cost-effectiveness of an intervention based on the Global INitiative for Asthma (GINA) recommendations as compared to usual care. SUBJECTS AND METHOD: Pragmatic, cluster-randomised trial. Ten pneumologists and 10 general practitioners were randomised to an intervention or control group, recruiting 98 and 100 asthma patients, respectively. The intervention consisted of an education program and a clinical decision support system (CDSS) providing recommendations based on the GINA. The control group was characterized by usual care. Effectiveness was assessed by the health related quality of life as measured by the St. George's Respiratory Questionnaire (SGRQ). Costs were computed from the resource consumption recorded during a 12 months follow-up period, and the cost-effectiveness of the intervention was investigated in an incremental analysis. RESULTS: The intervention effect on the SGRQ total score was estimated as a 6.8 point reduction (95% confidence interval, 2.5-11.1; p = 0.0021), and a significant improvement in the SGRQ subscores and in the symptoms-free periods were also observed. From the social perspective, the mean total costs showed savings of -1,022 Euros (95% confidence interval, -2,165 to 122; p = 0.0795) in intervention group as compared to usual care. The incremental analysis confirmed that the intervention was cost-effective. CONCLUSIONS: The implementation of an asthma management program based in GINA recommendations improved the patient's health related quality of life and was cost-effective as compared to usual care.

[Electronic data capture. Impact on the quality of the clinical research]. / Captura electrónica de datos. Impacto en la calidad de la investigación clínica.

Electronic data capture helps improving the quality of clinical research; mainly yielding a more reliable data collection process, but also introducing new resources for controlling the execution of clinical trials and facilitating the monitoring tasks. The protocol can be implemented rather than followed, and tools are at hand to help minimising the human error. The principal difficulty in the use of the electronic data capture lays in a more complex set up. This forces the adaptation of the people involved in the execution of clinical trials to a different workflow. In the future, most of the clinical research will use electronic data capture systems, and the paper shall be left for a few particular cases.

Oropharyngeal examination to predict sleep apnea severity.

OBJECTIVE: To evaluate the usefulness of the examination of the upper airway, paying special attention to the Friedman tongue position (FTP), to confirm obstructive sleep apnea syndrome (OSAS) and its severity. DESIGN: Prospective, single-center, cross-sectional study. SETTING: Sleep disorders unit of a community hospital. PATIENTS: A total of 301 consecutive patients admitted to the sleep disorders unit due to suspicion of OSAS. Assessments included body mass index calculated as weight in kilograms divided by height in meters squared (BMI); neck perimeter measurement; oropharyngeal examination; fiberendoscopy; rhinomanometry; and a sleep study. MAIN OUTCOME MEASURES: Apnea-hypopnoea index (AHI), FTP, the uvula size, and certain complementary examinations (sex, age, BMI, cervical perimeter, nasal flow) whose importance has not been clearly established, and to explore their potential value as predictors of the AHI. RESULTS: Findings included the following: the mean (SD) age of the patients was 51 (12) years; 71.1% were male; the mean (SD) BMI was 29.8 (4.6); and the mean (SD) cervical perimeter, 40.5 (3.7) cm. In 94.0% of the patients the AHI value was at least 5.0/hour. Patients with FTP scores of 2 and 3 accounted for 74.1% of the whole cohort: 14.3% had an FTP score of 1, and only 11.6% had a score of 4. Of the 6.0% of cases with a normal AHI, 16 patients were classified as having FTP scores of 1, and 2 as having a score of 2. Tonsil size score (P = .005), uvula score (P = .003), BMI (P < .001), cervical perimeter (P < .001), nasal flow at 150 Pa (P = .02), and age (P = .007) were related to OSAS severity. Curiously, AHI in patients who had undergone tonsillectomy was higher than in the TS1 group (tonsils inside the tonsillar fossa) and quite similar to the TS 2 group (tonsils that extend beyond the tonsillar pillars). In the multiple regression model, only the FTP score showed a relevant relationship to OSAS severity. CONCLUSIONS: First, since the FTP score is almost the only parameter related to OSAS severity, a simple oropharyngeal examination can provide key information on this issue. Second, tonsillectomy does not seem to protect against development of OSAS.

Incidence of spontaneous notifications of adverse reactions with aceclofenac, meloxicam, and rofecoxib during the first year after marketing in the United Kingdom.

The objective was to compare the incidence of adverse reactions reported with three nonsteroidal anti-inflammatory drugs with different cyclo-oxygenase (COX)-2 selectivity. All spontaneous adverse reaction notifications in the pharmacovigilance database of the World Health Organisation Collaborating Centre for International Drug Monitoring with aceclofenac, meloxicam, and rofecoxib that were recorded during the first year of marketing were included. The incidence rate (adverse reactions/10(6) defined daily dose) and 95% confidence interval for total adverse reactions was 8.7 (6.1-12.0) for aceclofenac, 24.8 (23.1-26.6) for meloxicam, and 52.6 (49.9-55.4) for rofecoxib. Aceclofenac had a lower incidence of gastrointestinal bleeding, abdominal pain, and arterial hypertension than meloxicam and a lower incidence of gastrointestinal bleeding, abdominal pain, liver toxicity, thromboembolic cardiovascular events, arterial hypertension, and edema than rofecoxib. The incidence of total and gastrointestinal adverse reactions was significantly lower with aceclofenac than with meloxicam or rofecoxib, thus raising doubts about the hypothetical advantage of COX-2 selective inhibitors.