Amiodarone Prevents Symptomatic Atrial Fibrillation and Reduces the Risk of Cerebrovascular Accidents and Ventricular Tachycardia after Open Heart Surgery: Results of the Atrial Fibrillation Suppression Trial (AFIST)

Background: Atrial fibrillation (AF) is a common complication after cardiothoracic surgery (CTS). The role of amiodarone added to beta blocker as a preventive strategy in elderly patients undergoing CTS is not known. The Atrial Fibrillation Suppression Trial (AFIST) was a double blind, placebo-controlled trial that evaluated the efficacy of oral amiodarone in patients 60 years or older undergoing CTS. Beta blockers were administered as part of a critical pathway. Methods: Elderly patients (n = 220, mean age 72 ± 6.7 years) received amiodarone (n = 120) or placebo (n = 100). Patients enrolled less than 5 days before CTS received 6 g of drug over 6 days beginning on the day prior to OHS. Patients enrolled 5 days before CTS received 7 g of study drug over 9–10 days, starting on preoperative day 4 or 5. Results: Amiodarone treated patients had a lower incidence of AF (22.5% vs. 38%, p = 0.01), symptomatic AF (4.2% vs. 18%, p = 0.001), cerebral vascular accident (1.7 vs. 7.0%, p = 0.04), and ventricular tachycardia (1.7% vs. 7.0%, p = 0.04) vs. placebo. Beta blocker use (87.5% vs. 91.0% ), nausea (26.7% vs. 16%, p = 0.056), symptomatic bradycardia (7.5% vs. 7%, p = 0.89), hypotension (14.2% vs. 10.0%) and 30 day mortality (3.3 vs. 4.0%, p = 0.79) were similar. Amiodarone treated patients receiving the 4/5 day preoperative regimen had a reduced incidence of AF (19.6% vs. 38%, p = 0.013), while those receiving the 1-day preoperative regimen showed a trend (25% vs. 38%, p = 0.06) vs. placebo. Conclusions: In an elderly population undergoing CTS, Amiodarone prophylaxis reduces AF, the incidence of symptomatic AF, cerebrovascular accident and ventricular tachycardia.     

Facilitating Electrical Cardioversion of Persistant Atrial Fibrillation by Antiarrhythmic Drugs: Update on Clinical Trial Results

Results from clinical trials suggest that antiarrhythmic drugs (AD) can facilitate electrical cardioversion (EC) for persistent atrial fibrillation (AF) (duration >48 hours, no spontaneous termination) by suppression of immediate reinitiation of AF following the procedure. Class IC agents may increase the atrial defibrillation threshold (DFT) by significantly reducing the availability of Na+-channel for depolarization. In contrast, class III agents may decrease the atrial DFT by markedly prolonging atrial refractoriness. Among all AD, ibutilide and amoidarone have been shown to be most effective in enhancing the acute outcome of EC.In patients who are over 65 years of age at high risks of stroke (e.g., atherosclerotic cardiovascular disease, diabetes, hypertension, previous thromboembolism, etc.), the rhythm control strategy offers no survival advantage over the rate control strategy and frequently subjects patients to serious adverse effects of AD therapy. It can not be overemphasized that adequate anticoagulation (INR 2.0-3.0) with warfarin is needed regardless of whichever strategy is chosen unless there are contraindications. On the other hand, in patients who are under 65 years of age without structural heart disease or other risk factors of stroke, rhythm control can be the treatment of choice. Specifically, if a patient has failed EC alone or if the patient has characteristics (e.g., duration of AF >6 months, left atrium >50 mm, etc.) that EC could fail, AD may be given before the procedure to facilitate EC. In the subgroup of patients who are symptomatic with hypertrophic cardiomyopathy and severe diastolic dysfunction requiring maintenance of sinus rhythm to have sufficient ventricular function for optimization of cardiac output, an aggressive approach for rhythm control with amiodarone along with adequate anticoagulation with warfarin should be encouraged.     

Ethical aspects of clinical trials: the attitudes of the public and out-patients

OBJECTIVES: To investigate attitudes to clinical research amongst potential research participants. DESIGN: Questionnaire-survey. SETTING: Two medical out-patient clinics and the background population. SUBJECTS: A total of 508 randomly selected citizens in Copenhagen County (64% responded) and 200 consecutive patients attending the out-patient clinics (64% responded). OUTCOME MEASURES: Attitudes toward different aspects of clinical research. RESULTS: Positive attitudes toward medical research were disclosed. The majority found scientific testing necessary, although only a minority considered participation a moral obligation. Both personal benefits and altruistic motives for participation were highly rated, whereas former positive experiences from trial participation had only minor impact on decisions. Several respondents stated former trial participation had changed their attitudes negatively. Lack of feedback of results was of major importance for this change. Attitudes are significantly influenced by the presence of independent research ethics committees, whereas trial technicalities such as drawing lots and blinding was found problematic by only a few respondents. Altruistic motives of physicians to conduct trials were highly rated by a majority of respondents, but the motive of promoting doctors' careers was also judged important. Respondents rated nondiscomforting procedures as acceptable or having only a small impact or strain on their lives. CONCLUSION: Attitudes toward medical research are positive amongst out-patients and the general public. Altruistic and nonaltruistic motives both concerning trial participation and concerning the motives of physicians to conduct medical research were rated highly. Lack of feedback concerning results of trials to participants was important for a negative change in attitude toward participation.     

Towards a Consensus in Rate Versus Rhythm Control for Management of Atrial Fibrillation: Insights from the PIAF Trial

Knowledge on the pathophysiology of atrial fibrillation is rapidly expanding and identification of focally localized triggers have led to the development of new treatment options for this arrhythmia. Conversely, the clinical decision whether to restore and maintain sinus rhythm or simply control the ventricular rate has remained a matter of intense debate. The Pharmacological Intervention in Atrial Fibrillation (PIAF) trial was the first pilot-study to prospectively assess the symptomatic benefits of rate versus rhythm control in patients with persistent symptomatic AF. Since the publication of PIAF, results from three additional randomized clinical trials have confirmed and extended the PIAF notion of equivalent outcomes with regard to symptoms, quality of life, and cardiovascular events. This review summarizes the rationale and results of PIAF in an attempt to update and discuss the clinical relevance of these findings in the light of the other studies and with regard to individual treatment options.     

Baseline nocturnal glucose change: A predictor of the treatment effect of bolus intensification in insulin-treated type 2 diabetes

This post hoc analysis of an 18-week randomized trial explored the utility of calculating baseline glycated haemoglobin (HbA1c), postprandial glucose (PPG) increments and nocturnal glucose change in predicting efficacy and safety outcomes in response to bolus insulin intensification in people with type 2 diabetes (T2D). Analyses were conducted on 236 participants with T2D receiving metformin: 116 received fast-acting insulin aspart (faster aspart) basal–bolus therapy and 120 received basal-only insulin. Participants were grouped according to baseline HbA1c, PPG increments and nocturnal glucose change variables; analyses were performed on the end-of-trial treatment differences between “high” and “low” baseline values. The change from baseline in end-of-trial mean HbA1c and mean PPG increments was in favour of faster aspart across all subgroups. Significantly greater treatment differences were observed in participants with high (vs. low) baseline nocturnal glucose change and PPG increments. For baseline HbA1c, significantly greater treatment differences were observed for change in end-of-trial PPG increments, but not end-of-trial HbA1c. In conclusion, both nocturnal glucose change and PPG increments may be more useful than HbA1c for identifying subgroups of people with T2D who would most benefit from bolus intensification.     

External cardioversion of atrial fibrillation: role of paddle position on technical efficacy and energy requirements

AIM—To define the effect of defibrillator paddle position on technical success and dc shock energy requirements of external cardioversion of atrial fibrillation.
METHODS—301 patients (mean (SD) age 62 (11) years) with stable atrial fibrillation were randomly assigned to elective external cardioversion using anterolateral paddle position (ventricular apex-right infraclavicular area; group AL (151 patients)) or anteroposterior paddle position (sternal body-angle of the left scapula; group AP (150 patients)). A step up protocol was used, delivering a 3 J/kg body weight dc shock, then a 4 J/kg shock (maximum 360 J), and finally a second 4 J/kg shock using the alternative paddle location.
RESULTS—The two groups were comparable for the all clinical variables evaluated. The cumulative percentage of patients successfully converted to sinus rhythm was 58% in group AL and 67% in group AP with low energy dc shock (NS); this rose to 76% in group AL and to 87% in group AP with high energy dc shock (p = 0.013). Thirty seven patients in group AL and 19 in group AP experienced dc shock with the alternative paddle position; atrial fibrillation persisted in 10/37 in group AL and in 10/19 in group AP. Mean dc shock energy requirements were lower for group AP patients than for group AL patients, at 383 (235) v 451 (287) J, p = 0.025. Arrhythmia duration was the only factor that affected the technical success of external cardioversion (successful: 281 patients, 80 (109) days; unsuccessful: 20 patients, 193 (229) days; p < 0.0001). The success rate was lower if atrial fibrillation persisted for > 6 months: 29 of 37 (78%) v 252 of 264 (95%); p = 0.0001.
CONCLUSIONS—An anteroposterior defibrillator paddle position is superior to an anterolateral location with regard to technical success in external cardioversion of stable atrial fibrillation, and permits lower dc shock energy requirements. Arrhythmia duration is the only clinical variable that can limit the restoration of sinus rhythm.


Keywords: atrial fibrillation; cardioversion; electric countershock     

Randomized clinical trials of osteoarthritis: a review

Aim: The objective of this study was to review published randomized clinical trials (RCTs) of osteoarthritis (OA) in three time periods to determine the characteristics of RCTs and the types of outcome measures used and whether any changes have occurred. Methods: We identified RCTs assessing clinical efficacy of treatments for osteoarthritis published in English in 1987/1988, 1997/1998 and 2001/2002, using MEDLINE. RCTs were then assessed for baseline disease characteristics, treatment type and outcome measures utilized. We classified outcome measures into 10 broad subgroups. Results: The number of RCTs increased with each time period (31 in 1987/1988; 36 in 1997/1998; 91 in 2001/2002). The majority of RCTs were of knee, hip or both (94% in 1987/1988, 69% in 1997/1998, 71% in 2001/2002). The median duration of RCTs for all three time periods was ≤ 3 months. In 1987/1988, nonsteroidal anit‐inflammatory drugs (NSAIDs) accounted for 65% of RCTs. In 1997/1998, NSAID/COX‐2 trials accounted for 41.7%, with glucosamine (14%) and hyaluronan (11%). In 2001/2002, 28% of RCTs were related to NSAID/COX‐2 inhibitors and 25% to complementary therapies. The median number of participants was unchanged over the three time periods. The median number of outcome measures used at all three time periods was four (range 1–8). The most commonly used outcome measures were: (i) symptoms (pain, stiffness); (ii) function; (iii) global assessment (patient, physician); and (iv) composite scores (such as Western Ontario and McMaster [WOMAC] Osteoarthritis index) in order of use. There has been significant increase in use of function and composite score as outcome measures. Conclusion: There has been a recent increase in both the number and variety of therapeutic interventions for OA. This study shows that currently a wide variety of outcome measures are used. This reinforces the importance of using standardized responder criteria, such as the OMERACT‐OARSI set of responder criteria, which incorporate pain, function and patient's global assessment.     

心房颤动患者经静脉体内电复律术后早期心房颤动复发及电生理机制的研究

目的观察经体内低能量心房颤动（房颤）除颤术后不同电生理参数与房颤早期复发的关系。方法对４２例（男３０例,女１２例）,平均年龄（６０±１１）岁的慢性房颤患者行经静脉体内Ｒ波同步双相电波除颤术并转为窦性心律后,有１２例（２９％）发生房颤早期复发（２分钟内）。对房颤早期复发患者和窦律维持患者的Ｐ波时限、房性早搏（房早）密度、房早耦联间期等进行了测量与分析。结果１２例房颤早期复发患者共５３次成功转复窦律过程中,窦性心律平均维持（１９．０±１７．３）秒。该组患者房早密度为（８．７±１１．９）次／ｍｉｎ。与成功维持窦律者（２．５±２．２）次／ｍｉｎ相比,房早密度差异有极显著性（Ｐ＜０．００１）。结论经静脉体内低能量房颤转复是有效复律方法,但房颤早期复发仍是待解决的问题之一。房早密度可作为预计房颤早期复发的指标。强调除颤后抑制房早措施对预防房颤早发具有重要性。     

Cost Evaluation of Rhythm Control Methods for Atrial Fibrillation: Evidence from CTAF

Atrial fibrillation (AF) is a highly prevalent arrhythmia that is difficult to treat and generates important health care costs. One consideration in the selection of various therapeutic options is the cost of a given treatment compared to that of alternatives. The Canadian Trial of Atrial Fibrillation (CTAF) evaluated the effectiveness of sinus rhythm maintenance with amiodarone compared to propafenone or sotalol in a prospective, randomized fashion. A subsequent CTAF substudy of the medical costs associated with amiodarone vs. propafenone/sotalol found that amiodarone decreased AF-related costs. This paper reviews the results of the CTAF cost-analysis substudy in the context of other analyses in the literature of the cost effectiveness of amiodarone in AF. The costs associated with amiodarone therapy are no greater than for other sinus rhythm maintenance drugs, and for some cost categories and some patient subgroups are likely to be less, despite amiodarone's greater therapeutic efficacy. However, additional considerations are important in evaluating the clinical place of amiodarone, including its adverse effect and pharmacokinetic profile. As well, the results of recent randomized clinical trials have highlighted the limitations of sinus rhythm maintenance as a primary therapeutic objective in AF. The decision about whether and at what point to use amiodarone in a given patient requires a careful analysis of the individual case, in terms of symptomatology during AF, the response to previous treatment regimes, and risk factors for various forms of adverse drug reactions.     

Adherence to a low‐fat vs. low‐carbohydrate diet differs by insulin resistance status

Previous research shows diminished weight loss success in insulin‐resistant (IR) women assigned to a low‐fat (LF) diet compared to those assigned to a low‐carbohydrate (LC) diet. These secondary analyses examined the relationship between insulin‐resistance status and dietary adherence to either a LF‐diet or LC‐diet among 81 free‐living, overweight/obese women [age = 41.9 ± 5.7 years; body mass index (BMI) = 32.6 ± 3.6 kg/m²]. This study found differential adherence by insulin‐resistance status only to a LF‐diet, not a LC‐diet. IR participants were less likely to adhere and lose weight on a LF‐diet compared to insulin‐sensitive (IS) participants assigned to the same diet. There were no significant differences between IR and IS participants assigned to LC‐diet in relative adherence or weight loss. These results suggest that insulin resistance status may affect dietary adherence to weight loss diets, resulting in higher recidivism and diminished weight loss success of IR participants advised to follow LF‐diets for weight loss.     

Effect of Rater Training on Reliability and Accuracy of Mini-CEX Scores: A Randomized, Controlled Trial

Background  Mini-CEX scores assess resident competence. Rater training might improve mini-CEX score interrater reliability, but evidence is lacking. Objective  Evaluate a rater training workshop using interrater reliability and accuracy. Design  Randomized trial (immediate versus delayed workshop) and single-group pre/post study (randomized groups combined). Setting  Academic medical center. Participants  Fifty-two internal medicine clinic preceptors (31 randomized and 21 additional workshop attendees). Intervention  The workshop included rater error training, performance dimension training, behavioral observation training, and frame of reference training using lecture, video, and facilitated discussion. Delayed group received no intervention until after posttest. Measurements  Mini-CEX ratings at baseline (just before workshop for workshop group), and four weeks later using videotaped resident–patient encounters; mini-CEX ratings of live resident–patient encounters one year preceding and one year following the workshop; rater confidence using mini-CEX. Results  Among 31 randomized participants, interrater reliabilities in the delayed group (baseline intraclass correlation coefficient [ICC] 0.43, follow-up 0.53) and workshop group (baseline 0.40, follow-up 0.43) were not significantly different (p = 0.19). Mean ratings were similar at baseline (delayed 4.9 [95% confidence interval 4.6–5.2], workshop 4.8 [4.5–5.1]) and follow-up (delayed 5.4 [5.0–5.7], workshop 5.3 [5.0–5.6]; p = 0.88 for interaction). For the entire cohort, rater confidence (1 = not confident, 6 = very confident) improved from mean (SD) 3.8 (1.4) to 4.4 (1.0), p = 0.018. Interrater reliability for ratings of live encounters (entire cohort) was higher after the workshop (ICC 0.34) than before (ICC 0.18) but the standard error of measurement was similar for both periods. Conclusions  Rater training did not improve interrater reliability or accuracy of mini-CEX scores. Clinical trials registration  clinicaltrials.gov identifier NCT00667940 Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Chromium supplementation in overweight and obesity: a systematic review and meta‐analysis of randomized clinical trials

The increased prevalence of obesity has made the use of dietary supplements as weight reducing agents highly popular, but their efficacy has not been proven. One such supplement is chromium. The purpose of this review was to evaluate the evidence for or against the efficacy of chromium supplementation in overweight and obese individuals. Electronic searches were conducted in Medline, Embase, Amed and The Cochrane Library. The bibliographies of located articles were also searched. No age, gender or language restrictions were imposed. The reporting quality of identified randomized clinical trials (RCTs) was assessed using a methodological checklist adapted from the Consolidated Standard of Reporting Trials Statement and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Thirty‐nine trials were identified and 20 were included. There were variations in reporting quality of included studies. A meta‐analysis of 11 studies showed a statistically significant difference in weight loss favouring chromium over placebo (mean difference (MD): ?0.50 kg; 95% confidence interval (CI): ?0.97, ?0.03). There was a high statistical heterogeneity. Adverse events included watery stools, vertigo, headaches and urticaria. The evidence from available RCTs shows that chromium supplementation generates statistically significant reductions in body weight. The magnitude of the effect is small, and the clinical relevance is uncertain. Future trials should last at least 16 weeks and greater uniformity in the measuring and assessment tools for body composition is recommended.