Effect of Flibanserin Treatment on Body Weight in Premenopausal and Postmenopausal Women with Hypoactive Sexual Desire Disorder: A Post Hoc Analysis.

Background: Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the effect of flibanserin treatment on body weight in premenopausal and postmenopausal women with HSDD. Materials and Methods: This analysis included three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg each bedtime (qhs) in premenopausal women, a similarly designed study in postmenopausal women, and a 52-week, open-label extension study in premenopausal women. Results: In a pooled analysis of premenopausal women, mean baseline body mass index (BMI) was 27.0 kg/m2 in the flibanserin group (n = 1227) and 26.8 kg/m2 in the placebo group (n = 1238). Among patients who completed 24 weeks of treatment, least squares (LS) mean weight change was −1.4 kg in the flibanserin group (n = 1010) and −0.1 kg in the placebo group (n = 1066; p \u3c 0.0001). Weight loss ≥5% from baseline was reported in 21.0% of patients who received flibanserin and 7.8% of patients who received placebo; weight loss ≥10% was reported in 3.8% and 2.0% of patients, respectively. In postmenopausal women, mean baseline BMI was 27.7 kg/m2 in the flibanserin group (n = 467) and 27.3 kg/m2 in the placebo group (n = 480). LS mean weight change at week 24 was −1.8 kg in the flibanserin group (n = 385) and −0.1 kg in the placebo group (n = 425; p \u3c 0.0001), with weight loss ≥5% reported in 24.7% and 7.3% of patients, respectively, and weight loss ≥10% reported in 5.2% and 1.7%, respectively. In HSDD patients with \u3e12 months (n = 880) and \u3e18 months (n = 637) of exposure to flibanserin, mean weight change was −1.0 and −1.2 kg, respectively; 25.4% and 26.9% of patients, respectively, experienced weight loss ≥5% from baseline, and 7.8% and 8.4%, respectively, experienced weight loss ≥10%. Conclusions: Women treated with flibanserin for HSDD may experience weight loss

Higher occurrence of nausea and vomiting after total hip arthroplasty using general versus spinal anesthesia: an observational study.

BACKGROUND: Under the assumption that postoperative nausea and vomiting (PONV) may occur after total hip arthroplasty (THA) regardless of the anesthetic technique used, it is not clear whether general (GA) or spinal (SA) anesthesia has higher causal effect on this occurrence. Conflicting results have been reported. METHODS: In this observational study, we selected all elective THA interventions performed in adults between 1999 and 2008 in a Swiss orthopedic clinic under general or spinal anesthesia. To assess the effect of anesthesia type on the occurrence of PONV, we used the propensity score and matching methods, which allowed us to emulate the design and results of an RCT. RESULTS: Among 3922 procedures, 1984 (51 %) patients underwent GA, of which 4.1 % experienced PONV, and 1938 underwent SA, of which 3.5 % experienced PONV. We found that the average treatment effect on the treated, i.e. the effect of anesthesia type for a sample of individuals that actually received spinal anesthesia compared to individuals who received GA, was ATET = 2.00 % [95 % CI, 0.78-3.19 %], which translated into an OR = 1.97 [95 % CI 1.35; 2.87]. CONCLUSION: This suggests that the type of anesthesia is not neutral regarding PONV, general anesthesia being more strongly associated with PONV than spinal anesthesia in orthopedic surgery

An international multicenter protocol to assess the single and combined benefits of antiemetic interventions in a controlled clinical trial of a 2x2x2x2x2x2 factorial design (IMPACT).

For various diseases clinicians have to combine different drugs or interventions when a single drug or intervention does not lead to satisfactory results. However, quantifying the relative benefit of certain drugs or interventions when given alone and in combination under controlled conditions requires a complex factorial design. This paper describes such a method applied to a large multicenter trial for the prevention of postoperative nausea and vomiting (PONV), which may be of great interest for other specialties. Approximately 28 million operations are performed annually in the United States, mainly under general anesthesia with volatile anesthetics. Unfortunately, one-third of these patients suffer from PONV. This prompted extensive research of antiemetic and anesthetic drugs, but none of the interventions appeared to satisfactorily prevent PONV. Scuderi et al. were the first to almost eliminate PONV by combining various antiemetic interventions; however, the relative benefit of each intervention remained unclear. Accordingly, we have designed a large randomized controlled trial studying six different antiemetic interventions-three involving use of various antiemetic drugs and three involving choice of anesthetic drugs-to answer the following main questions: (1) What is the relative benefit of each of the antiemetic intervention? (2) Are certain combinations of antiemetic interventions more effective than others? Using a complete factorial design this leads to 2(3)=8 antiemetic combinations, which multiply with the 2(3)=8 combinations of anesthetic drugs, leading to a total of 2(6)=64 possible combinations. The six factors are the antiemetics ondansetron (versus control), dexamethasone (versus control), droperidol (versus control), and the intravenous anesthetic propofol (versus volatile anesthetics), air (versus nitrous oxide), and remifentanil (versus fentanyl). The primary outcome is freedom from PONV within the first 24 hours after anesthesia. Eligible patients are adults scheduled for elective surgery under general anesthesia with an increased risk for PONV so that the expected incidence in the control group (with none of the six antiemetic interventions) is approximately 60%. In order to allow analyses for up to three factor interactions, a sample size was estimated to be in the range of approximately 5000 patients. To the best of our knowledge this is the first randomized controlled trial of a six-way factorial design that may serve as an example for numerous other medical specialties

A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.

BACKGROUND: Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown. METHODS: We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly. RESULTS: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk. CONCLUSIONS: Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients