Prabashni Reddy

Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial

BACKGROUND Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is unknown. We have assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery. METHODS We did a randomised, double-blind placebo-controlled trial in which patients undergoing open-heart surgery (n=220, average age 73 years) received amiodarone (n=120) or placebo (n=100). Patients enrolled less than 5 days before surgery received 6 g of amiodarone or placebo over 6 days beginning on preoperative day 1. Patients enrolled at least 5 days before surgery received 7 g over 10 days beginning on preoperative day 5. FINDINGS Patients on amiodarone had a lower frequency of any atrial fibrillation (22.5% vs 38.0%; p=0.01; absolute difference 15.5% [95% CI 3.4-27.6%]), and there were significant differences in favour of the active drug for symptomatic atrial fibrillation (4.2% vs 18.0%, p=0.001), cerebrovascular accident (1.7% vs 7.0%, p=0.04), and postoperative ventricular tachycardia (1.7% vs 7.0%, p=0.04). Beta-blocker use (87.5% amiodarone vs 91.0% placebo), nausea (26.7% vs 16.0%), 30-day mortality (3.3% vs 4.0%), symptomatic bradycardia (7.5% vs 7.0%), and hypotension (14.2% vs 10.0%) were similar. INTERPRETATION Oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and symptomatic fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.

The effects of Panax ginseng on quality of life

Summary Panax ginseng is marketed and used to maintain natural energy, increase mental and physical abilities, improve mood and promote general health and well‐being. Panax ginseng has been studied in a number of randomized clinical trials investigating its effect on physical and psychomotor performance, cognitive function, immunomodulation, diabetes mellitus and herpes simples type‐II infections. Equivocal results have been demonstrated for many of these indications. P. ginseng is also commonly used to promote quality of life (QoL). As a result, ginsengs effect on QoL has become an increasingly important endpoint in clinical trials. We reviewed all studies (n = 9) that determined the effect of P. ginseng on QoL. P. ginsengs has been evaluated at dosages of 80–400 mg. Study duration has spanned from 2 to 9 months. Several QoL measures have been used, ranging from widely accepted core instruments to unpublished investigator‐derived questionnaires. In addition, many of the investigators utilized ginseng extracts that were supplemented with vitamins and minerals while others used only standardized ginseng extract. Populations evaluated also differed in terms of underlying morbidity. Nearly every study evaluated (n = 8) demonstrated some degree of QoL improvement. Beneficial effects were evident within instrument summary component scores but improvement in overall composite scores of QoL was rarely seen. However, findings were equivocal. While populations evaluated varied in terms of underlying morbidity, there did not appear to be a substantial difference in their response to ginseng with respect to QoL. Despite some positive results, improvement in overall health‐related quality of life cannot, given the current research, be attributed to P. ginseng. However, the possibility that various facets of QoL may have improved and the potential of early transient effects cannot be discounted.

Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: The atrial fibrillation suppression trial II (AFIST II)

Background—The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown. Methods and Results—Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2×2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (P =0.037 and P =0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P =0.047 and P =0.040, respectively). Conclusions—Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.

Effects of Panax Ginseng on Quality of Life

OBJECTIVE: To assess the time-dependent effects of Panax ginseng on health-related quality of life (HRQOL) by use of a general health status questionnaire. METHODS: Subjects were randomized in a double-blind manner to P. ginseng 200 mg/d (n = 15) or placebo (n = 15) for 8 weeks. The Short Form-36 Health Survey version 2 (SF-36v2), a validated general health status questionnaire, was used to assess HRQOL at baseline and at 4 and 8 weeks. HRQOL between the groups was compared by use of repeated-measures analysis of covariance. A p value <0.05 was considered statistically significant. RESULTS: There were no significant differences in baseline demographics and SF-36v2 scores between the groups. After 4 weeks of therapy, higher scores in social functioning (P. ginseng 54.9 ± 4.6 vs. placebo 49.2 ± 6.5; p = 0.014), mental health (P. ginseng 52.2 ± 7.7 vs. placebo 47.2 ± 7.3; p = 0.075), and the mental component summary (P. ginseng 51.3 ± 7.4 vs. placebo 44.3 ± 8.3; p = 0.019) scales were observed in patients randomized to P. ginseng; these differences did not persist to the 8-week time point. The incidence of adverse effects was 33% in the P. ginseng group compared with 17% in the placebo group (p = 0.40). Subjects given P. ginseng (58%) were more likely to state that they received active therapy than subjects given placebo (17%; p < 0.05). CONCLUSIONS: P. ginseng improves aspects of mental health and social functioning after 4 weeks of therapy, although these differences attenuate with continued use.

A comparison of two individual amiodarone regimens to placebo in open heart surgery patients.

BACKGROUND This study compares the ability of two oral amiodarone regimens to reduce the risk of atrial fibrillation (AF) as compared with the placebo among elderly open heart surgery (OHS) patients receiving beta blockade. METHODS This is a randomized, double-blinded, placebo-controlled trial of 220 patients undergoing OHS. Patients (average age, 73 years) received 7 g of oral amiodarone more than 10 days starting 5 days before OHS (slow load; n = 56), a 6 g oral amiodarone regimen more than 6 days starting 1 day before OHS (fast load; n = 64), or matching placebo in one of the two previously mentioned regimens (n = 100). RESULTS Patients receiving the slow load amiodarone regimen had a significant reduction in the risk of AF (48.4%; p = 0.013), AF lasting more than 24 hours (76.5%; p = 0.003), symptomatic AF (90.0%; p = 0.002), and recurrent AF (64.5%; p = 0.025) as compared with the placebo. Patients receiving the fast load amiodarone regimen had significant reductions in the risk of AF lasting more than 24 hours (52.6%; p = 0.038) and symptomatic AF (65.0%; p = 0.024), but the incidence of any AF or any recurrence of AF only showed a trend toward significance (34.0% and 45.5%; p = 0.054 and 0.09, respectively). CONCLUSIONS Oral amiodarone in a slow loading regimen provides significant suppression of all AF factors and can be used when a patient has started it at least 5 days before OHS. If a patient has less than 5 days before OHS, the fast loading regimen is an efficacious alternative as it provides significant benefits in preventing AF from lasting more than 24 hours and for preventing symptomatic AF. Both regimens were well tolerated and safe in elderly patients receiving beta blockade according to the hospitals standard protocol.

Possible Gatifloxacin-Induced Fulminant Hepatic Failure

OBJECTIVE: To report a case of fulminant hepatic failure associated with the use of gatifloxacin. CASE SUMMARY: A 76-year-old white man was found to have an approximate 1-week history of worsening jaundice on the last day of a 10-day course of gatifloxacin for treatment of impetigo while at his skilled nursing facility. Liver function tests including aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio, activated partial thromboplastin time, and ammonia concentrations were found to be markedly elevated, consistent with hepatocellular necrosis commonly seen with fluoroquinolones. Screening for other causes of hepatotoxicity, including alcoholic or viral hepatitis, obstruction, or autoimmune-mediated processes, were negative. Other potential medication causes were less likely. The patients liver function steadily declined, eventually resulting in multiple organ failure. The patient died 25 days after completing the course of gatifloxacin. DISCUSSION: This case of hepatotoxicity was associated with gatifloxacin. Other fluoroquinolones, most notably trovafloxacin, have been observed to cause variable degrees of hepatotoxicity, ranging from asymptomatic elevations of liver enzymes to fulminant hepatic failure. Fluoroquinolones are thought to cause hepatocellular necrosis, which results in elevated ALT and AST concentrations with a normal alkaline phosphatase concentration. A variable degree of hyperbilirubinemia is often seen, with the presence and degree of jaundice often correlating to a poorer prognosis. Hepatic encephalopathy and coagulopathy are also commonly present. CONCLUSIONS: Fluoroquinolones, including trovafloxacin, ciprofloxacin, ofloxacin, enoxacin, norfloxacin, and, in this case report, gatifloxacin, have been associated with hepatotoxicity. It is important that these medications be considered a possible cause when the patient being treated has liver disease.

The Effect of β‐Blockers on Health‐Related Quality of Life in Patients with Heart Failure

β‐Blockers reduce the risk of death in patients with heart failure and are recommended in those with stable class II or III disease despite optimal standard therapy. Health‐related quality of life (HRQOL) is an increasingly important end point in clinical trials. We reviewed all studies that determined the effect of β‐blockers on HRQOL in patients with heart failure. In these trials, HRQOL was assessed by the Quality of Life Questionnaire in Severe Heart Failure and the Minnesota Living with Heart Failure Questionnaire. Three of the 10 studies that used either of these instruments reported significant improvements in scores. When HRQOL was determined by a single‐question global assessment, substantial improvements were observed by patients and physicians in five of the seven studies that used the instrument. Possible reasons for the lack of consistent effect on HRQOL include lack of responsiveness of currently available instruments, incomplete data collection, and true lack of effect of β‐blockers on HRQOL in these patients.

An Economic Analysis of Amiodarone versus Placebo for the Prevention of Atrial Fibrillation After Open Heart Surgery

Study Objective. To determine if the additional costs of oral amiodarone in patients undergoing open heart surgery would be offset by reductions in the frequency of atrial fibrillation.

Efficacy and Cost Analysis of Ibutilide

OBJECTIVE: To determine the efficacy and safety of ibutilide in atrial fibrillation (AF) and atrial flutter (AFl) in a clinical setting and to compare the cost of first-line ibutilide with that of projected first-line electrical cardioversion (EC) from a hospital and third-party payer perspective. METHODS: Medical records of all patients (n = 60) who received ibutilide from August 1996 to March 1998 were reviewed. Efficacy was defined as successful conversion to sinus rhythm within 60 minutes of the end of the infusion, and the maintenance of sinus rhythm until hospital discharge. Safety was evaluated by determining the incidence of torsade de pointes. Charges for EC and drug administration were obtained from the hospital database and converted to costs using cost/charge ratios. Hospital costs included drug, drug administration, cardiac intensive care laboratory fee, and the cost of managing torsade de pointes. The third-party payer calculation included all of the above plus the cardiologist and anesthesiologist fees. RESULTS: Fifty percent of patients with AF or AFl were successfully converted with ibutilide; 67% of these remained in sinus rhythm at hospital discharge. Three patients experienced nonsustained torsade de pointes; all resolved with pharmacologic management. From a hospital perspective, the cost of first-line ibutilide was greater than the cost of first-line EC (

Comparison of healthcare resource use between patients receiving ondansetron or palonosetron as prophylaxis for chemotherapy-induced nausea and vomiting

280 vs.