Effects of single-dose injectable paracetamolversus propacetamol in pain management after minor gynecologic surgery: A multicenter, randomized, double-blind, active-controlled, two-parallel-group study

AbstractBackground:Intravenous administration is the route of choice for drug therapy in the immediate postoperative period. Propacetamol (ProAPAP), an injectable prodrug of paracetamol requiring reconstitution, has demonstrated efficacy in managing acute pain and fever. However, it has been associated with pain at the injection site. A stable, ready-to-use formulation of paracetamol solution infused intravenously (IV-APAP) has been developed and might be associated with less pain at the injection site compared with ProAPARObjective:The objective of this study was to assess the tolerability and efficacy of a single dose of IV APAP 1 g compared with those of a single dose of ProAPAP 2 g in patients with moderate to severe pain after minor gynecologic surgery.Methods:This single-dose, randomized, double-blind, active-controlled,2-parallel-group study was conducted at 23 hospitals and outpatient clinics in France. After minor gynecologic surgery, patients reporting moderate to severe pain were randomized to receive a single 15-minute infusion of IV-APAP 1 g or ProAPAP 2 g (bioeyuivalent doses). Tolerability was monitored using local and systemic adverse event (AE) reporting, clinical examination including vital sign measurement, and patients' ratings of acceptability of the infusion. Efficacy end points included pain intensity at 0, 1, 2, 4, and 6 hours; median time to rescue medication (defined as the time at which 50% of patients requested rescue medication); and percentage of patients requesting rescue medication. Patients' satisfaction with the study drugs was assessed using patient's global evaluation (PGE) and the percentage of patients willing to receive the treatment again.Results:Of the 163 women who were randomized, 161 received the studymedication. The IV-APAP group comprised 80 patients (mean [SD] age, 38.3 [12.8] years [range, 18.0-69.0 years]; mean [SD] weight, 61.1 [11.0] kg [range, 49.0–90.0 kg]), and the ProAPAP group comprised 81 patients (mean [SD] age, 33.9 [12.0] years [range, 18.0–67.0 years]; mean [SD] weight, 61.6 [10.2] kg [range, 42.0–95.5 kg]); the difference in mean age between the 2 groups was statistically significant (P < 0.05). The incidence of local treatment-emergent AEs (TEAEs) was significantly lower in the IV-APAP group compared with that in the ProAPAP group (7.5% vs 38.3%; P < 0.001). No between-group differences in the incidence of systemic TEAEs was found. All patients in the IV-APAP group found the infusion tolerable, compared with 95% of patients in the ProAPAP group. The median time to rescue medication was not evaluated because <50% of the patients in each group requested it. No significant differences in mean pain intensity score or percentage of patients requesting rescue medication were found between the 2 groups at any time point. The percentages of patients in the IV-APAP and ProAPAP groups who rated the study medication as good or excellent on the PGE (83.6% vs 75.6%; P < 0.05) and who were willing to receive the same treatment again (96.0% vs 81.0%; P = 0.005) were significantly higher with IV-APAP compared with ProAPAPConclusion:In these patients with moderate to severe pain after minor gynecologic surgery, a single dose of IV-APAP was associated with better local tolerability, similar analgesic efficacy, and greater patient satisfaction compared with a single bioequivalent dose of ProAPAP

Intravenous buspirone for the prevention of postoperative nausea and vomiting

Rationale: Buspirone, a partial 5HT1A agonist and D2 and D3 antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown. Objective: To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV. Methods: A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable). Results: A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0% (90% confidence interval [CI] 37.5-60.5%). With buspirone, that incidence ranged from a mean of 40.8% (29.3-52.4%) in the 1mg arm to 58.0% (46.5-69.5%) in the 0.3mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures. Conclusion: We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PON

Estimating Attributable Mortality Due to Nosocomial Infections Acquired in Intensive Care Units

Background. The strength of the association between intensive care unit (ICU)-acquired nosocomial infections (NIs) and mortality might differ according to the methodological approach taken. Objective. TO assess the association between ICU-acquired NIs and mortality using the concept of population-attributable fraction (PAF) for patient deaths caused by ICU-acquired NIs in a large cohort of critically ill patients. Setting. Eleven ICUs of a French university hospital. Design. We analyzed surveillance data on ICU-acquired NIs collected prospectively during the period from 1995 through 2003. The primary outcome was mortality from ICU-acquired NI stratified by site of infection. A matched-pair, case-control study was performed. Each patient who died before ICU discharge was defined as a case patient, and each patient who survived to ICU discharge was denned as a control patient. The PAF was calculated after adjustment for confounders by use of conditional logistic regression analysis. Results. Among 8,068 ICU patients, a total of 1,725 deceased patients were successfully matched with 1,725 control Patients. The adjusted PAF due to ICU-acquired NI for patients who died before ICU discharge was 14.6% (95% confidence interval [CI], 14.4%—14.8%). Stratified by the type of infection, the PAF was 6.1% (95% CI, 5.7%-6.5%) for pulmonary infection, 3.2% (95% CI, 2.8%-3.5%) for central venous catheter infection, 1.7% (95% CI, 0.9%-2.5%) for bloodstream infection, and 0.0% (95% CI, -0.4% to 0.4%) for urinary tract infection. Conclusions. ICU-acquired NI had an important effect on mortality. However, the statistical association between ICU-acquired NI and mortality tended to be less pronounced in findings based on the PAF than in study findings based on estimates of relative risk. Therefore, the choice of methods does matter when the burden of NI needs to be assesse

Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study

ABSTRACT: BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission. METHODS: We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay &gt;=48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS: Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring [greater than or equal to]48 hours is considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Vichy and the Holy See : four years of diplomatic relations, July 1940-August 1944

Cette étude se propose de dresser un tableau des relations d’Etat à Etat qu’ont entretenues le régime de Vichy et le Saint-Siège entre juillet 1940 et août 1944, par l’intermédiaire de leurs représentants diplomatiques : le nonce apostolique en France, Mgr Valeri et les deux ambassadeurs qui se sont succédé dans la Cité du Vatican, Wladimir d’Ormesson et Léon Bérard. Elle insiste sur l’importance de la caution que représentait, pour un gouvernement de plus en plus contesté, la présence d’un nonce auprès du maréchal Pétain et de son ambassadeur auprès du Souverain Pontife. Elle met en parallèle les attentes que nourrissait l’Etat français d’une action plus visible et tangible de la diplomatie vaticane et sa déception devant la réserve qu’observe cette dernière. Elle décrit également, en dépit des avances faites par Vichy à l’Eglise, la méfiance croissante provoquée au Vatican par la politique du régime : dérives autoritaires, mesures anti juives, alignement sur le Reich. Elle relate enfin le rapprochement qui s’opère avec la France libre et aboutit, après l’effondrement du régime et le retrait de son ambassadeur, à la reconnaissance du Gouvernement provisoire de la République.This research study describes the interstate relations which the Vichy regime maintained with the Vatican between July 1940 and August 1944 on the diplomatic level : the apostolic nuncio in France , mgr Valeri, on one side and, on the other side, the French ambassadors accredited to the Holy See, Wladimir d’Ormesson followed by Léon Bérard in December 1940. It underlines how valuable were, for a more and more disputed and rejected government, the presences of a high ranked papal envoy close to marshal Pétain and conversely of a French plenipotentiary in the Vatican state. It worked as a voucher of legitimacy. The study points out the expectations of the “Etat français” towards a more visible and concrete action of Pius XII diplomacy and the disappointment prompted by its spinelessness. It emphasizes, in spite of the advances made in the direction of the Church, the growing mistrust created in Rome by the political line followed by the French leaders: authoritarian downward spiral, anti Jewish measures, submission to the 3rd Reich. It finally sketches out the gradual move of the Holy See towards the “France libre” which led, after the collapse of the regime and the forced resignation of its ambassador to the formal recognition of the de Gaulle government

Chronobiologie du sufentanil intrathécal dans l'analgésie du travail obstétrical

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF