DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis.

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE). We performed a systematic review and meta-analysis to compare the effects of direct oral anticoagulants (DOAC) versus LMWH for the treatment of CA-VTE. The primary efficacy and safety outcomes were VTE recurrence and major bleeding (MB). The secondary outcomes were clinically relevant non-MB (CRNMB), all-cause mortality and the net clinical benefit. We searched MEDLINE, EMBASE, CENTRAL and Web of Science (inception-December 2019) and abstracts of relevant conferences (2000-2019) to identify randomized controlled trials comparing DOAC and LMWH for the treatment of CA-VTE. Relative risks (RR) and 95% confidence intervals were estimated (Mantel-Haenszel method, random-effects models). A non-inferiority analysis with a margin of 1.3 for the upper boundary of the RR was conducted for the primary outcomes. From 637 references, we included four publications which encompass three trials (1756 patients). Compared to LMWH, DOAC were associated with a trend for decreased VTE recurrence (RR 0.51; 95%CI 0.25-1.03; p = 0.06; I2 = 51%), whereas MB (RR 1.64; 95%CI 1.00-2.69; p = 0.05; I2 = 0%) and CRNMB (RR 1.83; 95%CI 1.04-3.20; p = 0.03; I2 = 50%) were significantly more frequent with DOAC. Conversely, all-cause mortality (RR 1.06; 95%CI 0.83-1.35; p = 0.64; I2 = 36%) and net clinical benefit (RR 0.74; 95%CI 0.38-1.42; p = 0.36; I2 = 65%) were comparable. DOAC were non-inferior to LMWH in preventing CA-VTE recurrence, but were associated with an increased risk of MB and CRNMB. Further studies are required to confirm these results and inform on the risk/benefit ratio for specific populations.

Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial.

OBJECTIVES: To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. METHODS: We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed. RESULTS: Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9-13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45-0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels. CONCLUSIONS: Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.

Aids to quitting tobacco use: how important are they outside controlled trials?

BACKGROUND: Although there is good evidence that several pharmacotherapies and counseling can effectively facilitate smoking cessation, there is little information about the use or effectiveness of these or any other quit aids outside of controlled trials. METHODS: A mailed survey with phone follow-up documented the use of various quit aids among 3,122 health plan members who smoke. A multilevel statistical modeling technique controlled for potentially confounding variables. RESULTS: Nearly half (1,513) of these smokers reported a quit attempt during the preceding 6 months. Although 1,036 (33.2%) reported using some type of aid to quitting, primarily nicotine products or bupropion, 10-26% of these "users" did not report an actual quit attempt. Ninety percent of the medication users had a personal cost, averaging $53-$87. Fully 26.9% of those reporting a quit without any type of aid quit for at least 7 days. This rate equals that of users of all types of aids except for nicotine patches and bupropion, both of which had associated 7 or more day quit rates of about 46% (95% CI 39.3-52.2). CONCLUSIONS: Pharmacotherapeutic quit aids are being widely used, even in the absence of significant insurance coverage.

Patient satisfaction and discussion of smoking cessation during clinical visits.

OBJECTIVE: To learn whether patients who smoke and who receive smoking cessation information during medical office visits were less likely to be satisfied with the smoking cessation help they received than patients who smoke but who did not receive such information. PATIENTS AND METHODS: A total of 3703 current cigarette smokers were identified by a mailing in November 1998 to 163,596 members of 2 Minnesota health plans, and 2714 (77.3%) responses to a 44-item questionnaire were available for analysis. Using hierarchical analysis to control confounding variables, we assessed the relationship between patient-reported smoking cessation support actions at the last physician visit and satisfaction "with the help received from your doctor about quitting smoking." RESULTS: Smokers were very satisfied (12.0%), satisfied (25.3%), neutral (48.6%), and dissatisfied or very dissatisfied (13.5%) with physician help. After controlling for other characteristics, the 1898 patients who reported that they had been asked about tobacco use or advised to quit during the latest visit had 10 percentage point greater satisfaction ratings and 5 percentage point less dissatisfaction than those not reporting such discussions (P<.001). Smokers reporting no interest in quitting at the time of the latest visit also demonstrated greater satisfaction in association with these actions. CONCLUSION: Smoking cessation interventions during physician visits were associated with increased patient satisfaction with their care among those who smoke. This information should reduce concerns of physicians or nurses about providing tobacco cessation assistance to patients during office visits.

Simultaneous plasma levels determination of mexiletine and one of its metabolites by electron capture gas-liquid chromatography.

A sensitive and specific electron capture gas-liquid chromatographic method is developed for the determination in human plasma both of mexiletine and of one of its hydroxymethyl metabolites appearing progressively during the kinetics and the presence of which is characterized by mass spectrometry. This method involves the use of two internal standards and the extraction of the drug and of its metabolite from alkaline plasma with diethyl ether followed by back extraction into sulfuric acid (0.2 N) for clean-up procedure and re-extraction by diethyl ether. The limits of detection of the heptafluorobutyryl derivatives of mexiletine and of its metabolite are 20 and 7 ng/ml of plasma, respectively. The preliminary results of the pharmacokinetic study performed in a cardiological unit after single oral administration and during long-term oral maintenance therapy are described in this paper. The method makes it possible to get a better knowledge of the kinetic behaviour of mexiletine and of its metabolite and contributes to the understanding of the origins of the variable pharmacokinetics of mexiletine in patients.