The effect of alternative summary statistics for communicating risk reduction on decisions about taking statins: a randomized trial. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Statin therapy for the prevention of atrial fibrillation trial (SToP AF trial). High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. How should the impact of different presentations of treatment effects on patient choice be evaluated? A pilot randomized trial. A randomized trial to improve early detection and prevention practices among siblings of melanoma patients. A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Tailored versus generic interventions for skin cancer risk reduction for family members of melanoma patients. Adjuvant interferon in high-risk melanoma: the AIM HIGH Study--United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon Alfa-2a in high-risk resected malignant melanoma.
While different ways of presenting treatment effects can affect health care decisions, little is known about which presentations best help people make decisions consistent with their own values. We compared six summary statistics for communicating coronary heart disease (CHD) risk reduction with statins: relative risk reduction and five absolute summary measures-absolute risk reduction, number needed to treat, event rates, tablets needed to take, and natural frequencies.
                We conducted a randomized trial to determine which presentation resulted in choices most consistent with participants' values. We recruited adult volunteers who participated through an interactive Web site. Participants rated the relative importance of outcomes using visual analogue scales (VAS). We then randomized participants to one of the six summary statistics and asked them to choose whether to take statins based on this information. We calculated a relative importance score (RIS) by subtracting the VAS scores for the downsides of taking statins from the VAS score for CHD. We used logistic regression to determine the association between participants' RIS and their choice. 2,978 participants completed the study. Relative risk reduction resulted in a 21% higher probability of choosing to take statins over all values of RIS compared to the absolute summary statistics. This corresponds to a number needed to treat (NNT) of 5; i.e., for every five participants shown the relative risk reduction one additional participant chose to take statins, compared to the other summary statistics. There were no significant differences among the absolute summary statistics in the association between RIS and participants' decisions whether to take statins. Natural frequencies were best understood (86% reported they understood them well or very well), and participants were most satisfied with this information.
                Presenting the benefits of taking statins as a relative risk reduction increases the likelihood of people accepting treatment compared to presenting absolute summary statistics, independent of the relative importance they attach to the consequences. Natural frequencies may be the most suitable summary statistic for presenting treatment effects, based on self-reported preference, understanding of and satisfaction with the information, and confidence in the decision.
                ISRCTN85194921. Atrial fibrillation (AF) after cardiac surgery is associated with increased risk of complications, length of stay, and cost of care. Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF. We tested this observation in a randomized, controlled trial.
                Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass, without previous statin treatment or history of AF, were enrolled. Patients were randomized to atorvastatin (40 mg/d, n=101) or placebo (n=99) starting 7 days before operation. The primary end point was incidence of postoperative AF; secondary end points were length of stay, 30-day major adverse cardiac and cerebrovascular events, and postoperative C-reactive protein (CRP) variations. Atorvastatin significantly reduced the incidence of AF versus placebo (35% versus 57%, P=0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9+/-1.4 versus 6.3+/-1.2 days, P=0.001). Peak CRP levels were lower in patients without AF (P=0.01), irrespective of randomization assignment. Multivariable analysis showed that atorvastatin treatment conferred a 61% reduction in risk of AF (odds ratio 0.39, 95% confidence interval 0.18 to 0.85, P=0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, P=0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms.
                Treatment with atorvastatin 40 mg/d, initiated 7 days before surgery, significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay. These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery. Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation (NCT00252967).
                In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n = 33) or placebo (n = 31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers (high-sensitivity C- reactive protein [hs-CRP], interleukin-6 [IL-6], interleukin-1β[IL-1β], tumor necrosis factor alpha [TNFα]) were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (P = 0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, P = 0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median [IR]: 29 [2-145] days versus 22 [7-70] days, P = 0.9). Although no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, P = 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, P = 0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (P = 0.03).
                High-dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress.
                © 2010 Wiley Periodicals, Inc. Pivotal trial E1684 of adjuvant high-dose interferon alfa-2b (IFNalpha2b) therapy in high-risk melanoma patients demonstrated a significant relapse-free and overall survival (RFS and OS) benefit compared with observation (Obs).
                A prospective, randomized, three-arm, intergroup trial evaluated the efficacy of high-dose IFNalpha2b (HDI) for 1 year and low-dose IFNalpha2b (LDI) for 2 years versus Obs in high-risk (stage IIB and III) melanoma with RFS and OS end points.
                A total of 642 patients were enrolled (608 patients eligible), of whom a majority (75%) had nodal metastasis (50% had nodal recurrence). Unlike E1684, E1690 allowed entry of patients with T4 (> 4 mm) deep primary tumors, regardless of nodal dissection, and 25% of the patients entered onto this trial had deep primary tumors (compared with 11% in E1684). At 52 months' median follow-up, HDI demonstrated an RFS benefit exceeding that of LDI compared with Obs. The 5-year estimated RFS rates for the HDI, LDI, and Obs arms were 44%, 40%, and 35%, respectively. The hazards ratio for the intent-to-treat analysis of HDI versus Obs was 1.28 (P(2) =.05); for LDI versus Obs, it was 1.19 (P(2) =.17). By Cox analysis, the impact of HDI on RFS achieved significance (P(2) =.03). The RFS benefit was equivalent for node-negative and node-positive patients. Neither HDI nor LDI has demonstrated an OS benefit compared with Obs at this time. A major improvement in the median OS of patients in the E1690 Obs arm was noted in comparison with E1684 (6 years v 2.8 years). An analysis of salvage therapy for patients who relapsed on E1690 demonstrated that a significantly larger proportion of patients in the Obs arm received IFNalpha-containing salvage therapy compared with the HDI arm; this therapy was unavailable to patients during E1684, and patients with undissected regional nodes were not included in E1684. This study did not specify therapy at recurrence. Analysis of treatments received at recurrence demonstrated significantly more frequent use of IFNalpha2b at relapse from Obs than from HDI, which may have confounded interpretation of the survival benefit of assigned treatments in E1690.
                The results of the intergroup E1690 trial demonstrate an RFS benefit of IFNalpha2b that is dose-dependent and significant for HDI by Cox multivariable analysis. Different presentations of treatment effects can affect decisions. However, previous studies have not evaluated which presentations best help people make decisions that are consistent with their own values. We undertook a pilot study to compare different methods for doing this.
                We conducted an Internet-based randomized trial comparing summary statistics for communicating the effects of statins on the risk of coronary heart disease (CHD). Participants rated the relative importance of treatment consequences using visual analogue scales (VAS) and category rating scales (CRS) with five response options. We randomized participants to either VAS or CRS first and to one of six summary statistics: relative risk reduction (RRR) and five absolute measures of effect: absolute risk reduction, number needed to treat, event rates, tablets needed to take, and natural frequencies (whole numbers). We used logistic regression to determine the association between participants' elicited values and treatment choices. 770 participants age 18 or over and literate in English completed the study. In all, 13% in the VAS-first group failed to complete their VAS rating, while 9% of the CRS-first group failed to complete their scoring (p = 0.03). Different ways of weighting the elicited values had little impact on the analyses comparing the different presentations. Most (51%) preferred the RRR compared to the other five summary statistics (1% to 25%, p = 0.074). However, decisions in the group presented the RRR deviated substantially from those made in the other five groups. The odds of participants in the RRR group deciding to take statins were 3.1 to 5.8 times that of those in the other groups across a wide range of values (p = 0.0007). Participants with a scientific background, who were more numerate or had more years of education were more likely to decide not to take statins.
                Internet-based trials comparing different presentations of treatment effects are feasible, but recruiting participants is a major challenge. Despite a slightly higher response rate for CRS, VAS is preferable to avoid approximation of a continuous variable. Although most participants preferred the RRR, participants shown the RRR were more likely to decide to take statins regardless of their values compared with participants who were shown any of the five other summary statistics.
                Controlled-Trials.com ISRCTN85194921. Identifying high-risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first-degree relatives of melanoma patients represent a risk group who may experience a 'teachable moment' for enhanced education and risk reduction.
                We report a randomized trial testing an intervention that provided personalized telephone counseling and individually tailored materials to siblings of recently-diagnosed melanoma patients. The purpose of this study was to test whether an intervention could lead to improvements in siblings' skin cancer risk reduction practices. Intervention condition participants received the following: (1) an initial motivational and goal-setting telephone intervention session delivered by the health educator; (2) three sets of computer-generated materials specifically tailored to individual responses from the baseline survey; (3) three telephone counseling sessions with the health educator, timed to follow receipt of the mailed materials; and (4) linkages to free screening programs. Families in the usual care arm received the suggestion from the physician that patients diagnosed with melanoma notify the family members about their diagnosis and encourage the family members to be screened.
                494 siblings were recruited to the study and 403 siblings remained in the study through at least 6 months. At 12 months, intervention siblings were more likely to examine all moles, including those on the back (OR, 1.76; 95% CI, 1.06-2.91). Compared with baseline, the number of participants in both groups that had received a skin cancer examination more than doubled, with no differences between groups. At 12 months, two-thirds of siblings in both groups reported routine use of sunscreen, but there were no differences in change over baseline between the two groups.
                This study is the one of the first, to our knowledge, to address skin cancer risk-reduction strategies in a sample of individuals who have a recent family diagnosis of melanoma. Diagnosis of melanoma in a family member provides an important opportunity to intervene with others in that family. The components of the intervention may provide a useful foundation for future efforts to target the more than half million siblings at risk for melanoma, a lethal but preventable disease. The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival. Improving strategies for risk reduction among family members of patients with melanoma may reduce their risk for melanoma.
                To evaluate the effects of two behavioral interventions designed to improve the frequency of total cutaneous skin examination by a health provider (TCE), skin self-examination (SSE), and sun protection among first degree relatives of patients with melanoma; and to evaluate whether increased intentions, increased benefits, decreased barriers, and improved sunscreen self-efficacy mediated the effects of the tailored intervention, as compared with the generic intervention on TCE, SSE, or sun protection.
                Four hundred forty-three family members (56 parents, 248 siblings, 239 children) who were nonadherent with these practices were randomly assigned to either a generic (N = 218) or a tailored intervention (N = 225) which included 3 print mailings and 1 telephone session. Participants completed measures of TCE, SSE, and sun protections at baseline, 6 months, and 1 year, and measures of intentions, benefits, barriers, and self-efficacy at baseline and 6 months.
                Those enrolled in the tailored intervention had almost a twofold increased probability of having a TCE ( p < .0001). Treatment effects in favor of the tailored intervention were also noted for sun protection habits ( p < .02). Increases in TCE intentions mediated the tailored intervention's effects on TCE. Increases in sun protection intentions mediated effects of the tailored intervention's effect on sun protection.
                Tailored interventions may improve risk reduction practices among family members of patients with melanoma.
                © 2010 APA, all rights reserved. To evaluate low-dose extended duration interferon alfa-2a as adjuvant therapy in patients with thick (> or = 4 mm) primary cutaneous melanoma and/or locoregional metastases.
                In this randomized controlled trial involving 674 patients, the effect of interferon alfa-2a (3 megaunits three times per week for 2 years or until recurrence) on overall survival (OS) and recurrence-free survival (RFS) was compared with that of no further treatment in radically resected stage IIB and stage III cutaneous malignant melanoma.
                The OS and RFS rates at 5 years were 44% (SE, 2.6) and 32% (SE, 2.1), respectively. There was no significant difference in OS or RFS between the interferon-treated and control arms (odds ratio [OR], 0.94; 95% CI, 0.75 to 1.18; P =.6; and OR, 0.91; 95% CI, 0.75 to 1.10; P =.3; respectively). Male sex (P =.003) and regional lymph node involvement (P =.0009), but not age (P =.7), were statistically significant adverse features for OS. Subgroup analysis by disease stage, age, and sex did not show any clear differences between interferon-treated and control groups in either OS or RFS. Interferon-related toxicities were modest: grade 3 (and in only one case, grade 4) fatigue or mood disturbance was seen in 7% and 4% respectively, of patients. However, there were 50 withdrawals (15%) from interferon treatment due to toxicity.
                The results from this study, taken in isolation, do not indicate that extended-duration low-dose interferon is significantly better than observation alone in the initial treatment of completely resected high-risk malignant melanoma.
The melanoma outcomes data collected in this review of RCTs of statins and fibrates does not exclude the possibility that these drugs prevent melanoma. There was a 10% and 42% reduction for participants on statins and fibrates, respectively, however these results were not statistically significant. Until further evidence is established, limiting exposure to ultraviolet radiation remains the most effective way to reduce the risk of melanoma.