major bleeds enrolled in five phase III trials comparing dabigatran with warfarin in 27,419 patients treated for 6 to 36 months. There were 627 of 16,755 patients on dabigatran who had major bleeds. These patients were older, had lower creatinine clearances, and more frequently used aspirin or nonsteroid anti-inflammatory agents than those on warfarin with major bleeds (n ¼ 407 of 10,002). Thirty-day mortality after the first major bleed tended to be lower in the dabigatran group (9.1%) than in the warfarin group (13.0%; pooled odds ratio, 0.68; 95% confidence interval, 0.46-1.01; P ¼ .057). With adjustments for sex, age, weight, renal function and concomitant antithrombotic therapy, the pooled odds ratio for 30-day mortality with dabigatran vs warfarin was 0.66 (95% confidence interval, 0.144-1.00; P ¼ .051). In dabigatran patients with major bleeds, the bleeding was more frequently treated with blood transfusions (61%) than bleeds in warfarin patients (42%; P < .001). Patients with major bleeds treated with dabigatran were less frequently treated with plasma compared to warfarin patients with major bleeds (19.8% vs 30.2%; P < .001). Patients with major bleeds had shorter stays in intensive care units if they had previously received dabigatran (mean,1.6 nights) compared with those who had received warfarin (mean, 2.7 nights; P ¼ .01).Comment: There is obviously no ideal anticoagulant agent. Despite the fact there is no reversal agent for dabigatran, outcomes of major bleeding on this drug appear no worse and are perhaps slightly better than outcomes for patients with major bleeding on warfarin. It does not appear overall resources needed to manage major bleeding on dabigatran are greater than to manage such bleeding on warfarin. It also does not appear that the prognosis after major bleeding is worse with dabigatran than with warfarin despite the lack of a reversal agent for dabigatran. Dabigatran is an alternative to warfarin with similar or superior efficacy and overall lower risk of major bleeding. Bleeding episodes can be managed satisfactorily with relatively simple measures such as drug discontinuation and transfusion of red cells. Thus, the overall safety profile of dabigatran compared to warfarin remains favorable. Nevertheless, it is still desirable to develop a specific antidote to dabigatran.

No abstract

When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12610000590066.).

This randomized study evaluated the efficacy and tolerability of continued treatment with protease inhibitor plus nucleoside-analogue combination regimens (n=79) or a change to the simplified regimen of abacavir-lamivudine-zidovudine (n=84) in patients with suppressed human immunodeficiency virus type 1 (HIV-1) RNA for > or = 6 months who did not have the reverse transcriptase 215 mutation. After a median follow-up of 84 weeks, virologic failure was 6% in the continuation and 15% in the simplified group (P=.081). Previous zidovudine monotherapy or dual therapy and archived reverse transcriptase resistance mutations in HIV-1 DNA at baseline were significant predictors of failure. Study treatment was discontinued because of adverse events in 20% of the continuation and 7% of the simplified group (P=.021). Simplification to abacavir-lamivudine-zidovudine significantly decreased nonfasting cholesterol and triglyceride levels; however, this switch strategy carries a risk of virologic failure when treatment history or resistance testing suggest the presence of archived resistance mutations to the simplified regimen.

Addition of very low nicotine content cigarettes to standard Quitline smoking cessation support may help some smokers to become abstinent.

Background and Purpose-Fish-derived omega-3 fatty acids have long been associated with cardiovascular protection. In this trial, we assessed whether treatment with a guideline-recommended moderate-dose fish oil supplement could improve cardiovascular biomarkers, mood-and health-related quality of life in patients with ischemic stroke. Methods-Patients with CT-confirmed stroke were randomized to 3 g/day encapsulated fish oil containing approximately 1.2 g total omega-3 (0.7 g docosahexaenoic acid; 0.3 g eicosapentaenoic acid) or placebo oil (combination palm and soy) taken daily over 12 weeks. Serum triglycerides, total cholesterol and associated lipoproteins, selected inflammatory and hemostatic markers, mood, and health-related quality of life were assessed at baseline and follow-up. The primary outcome was change in triglycerides. Compliance was assessed by capsule count and serum phospholipid omega-3 levels (Australian Clinical Trials Registration: ACTRN12605000207617). Results-One hundred two patients were randomized to fish oil or placebo. Intention-to-treat and per-protocol (Ͼ85% compliance) analyses showed no significant effect of fish oil treatment on any lipid, inflammatory, hemostatic, or composite mood parameters measured. Adherence to treatment based on pill count was good (89%) reflected by increased serum docosahexanoic acid (PϽ0.001) and eicosapentaenoic acid (Pϭ0.0006) in the fish oil group. Analysis of oil composition, however, showed some degradation and potentially adverse oxidation products at the end of the study. Conclusions-There was no effect of 12 weeks of treatment with moderate-dose fish oil supplements on cardiovascular biomarkers or mood in patients with ischemic stroke. It is possible that insufficient dose, short duration of treatment, and/or oxidation of the fish oils may have influenced these outcomes. (Stroke. 2009;40:3485-3492.)

In this, the largest pre-cessation NRT trial to date, using NRT 2 weeks before the target quit day was safe and well tolerated but offered no benefit over usual care. However, in conjunction with previous pre-cessation trials there appears to be a moderate benefit, but not as large as that seen in most smaller trials.

BackgroundElectronic cigarettes (e-cigarettes or electronic nicotine delivery systems [ENDS]) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and/or glycerol mist to the airway of users when drawing on the mouthpiece. Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device. People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids. However, to date there have been no adequately powered randomised trials investigating their cessation efficacy or safety. This paper outlines the protocol for this study.Methods/designDesign: Parallel group, 3-arm, randomised controlled trial. Participants: People aged ≥18 years resident in Auckland, New Zealand (NZ) who want to quit smoking. Intervention: Stratified blocked randomisation to allocate participants to either Elusion™ e-cigarettes with nicotine cartridges (16 mg) or with placebo cartridges (i.e. no nicotine), or to nicotine patch (21 mg) alone. Participants randomised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day, while participants randomised to patches will be told to use them daily for the same period. All participants will be offered behavioural support to quit from the NZ Quitline. Primary outcome: Biochemically verified (exhaled carbon monoxide) continuous abstinence at six months after quit day. Sample size: 657 people (292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarettes group) will provide 80% power at p = 0.05 to detect an absolute difference of 10% in abstinence between the nicotine e-cigarette and nicotine patch groups, and 15% between the nicotine and placebo e-cigarette groups.DiscussionThis trial will inform international debate and policy on the regulation and availability of e-cigarettes. If shown to be efficacious and safe, these devices could help many smokers as an alternative smoking cessation aid to standard nicotine products.Trial registrationAustralian NZ Clinical Trials Registry (ACTRN12610000866000).