Predicting the ovarian response: towards a determinant model and implications for practice.

Objective: To improve the reliability of prediction models for ovarian response to stimulation in ART.

Design: A multicenter retrospective cohort study.

Setting: Twelve reproductive centers.

Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase fusion sarcomas.

Background: Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas.

Methods: Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials.

Larotrectinib versus historical standard of care in patients with infantile fibrosarcoma: protocol of EPI-VITRAKVI.

The EPI VITRAKVI study is a retrospective study designed to place the results of the single-arm Phase I/II larotrectinib SCOUT trial into context by comparison with external historical controls. Its primary objective is to compare the time to medical treatment failure between larotrectinib and the historical standard of care (chemotherapy) in patients with infantile fibrosarcoma. External historical cohorts have been selected by using objective criteria.

Reliability of AMH and AFC measurements and their correlation: a large multicenter study.

Purpose: Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are correlated with the ovarian response, but their reliability and reproducibility are questionable. This large multicenter study describes their distribution, inter-cycle and inter-center variability, and their correlation.

Methods: A total of 25,854 IVF cycles among 15,219 patients were selected in 12 ART centers.

A large observational data study supporting the PROsPeR score classification in poor ovarian responders according to live birth outcome.

Study Question: Can the Poor Responder Outcome Prediction (PROsPeR) score identify live birth outcomes in subpopulations of patients with poor ovarian response (POR) defined according to the ESHRE Bologna criteria (female age, anti-Müllerian hormone (AMH), number of oocytes retrieved during the previous cycle (PNO) after treatment with originator recombinant human follitropin alfa?

Summary Answer: The PROsPeR score discriminated the probability of live birth in patients with POR using observational data with fair discrimination (AUC ≅ 70%) and calibration, and the AUC losing less than 5% precision compared with a model developed using the observational data.

What Is Known Already: Although scoring systems for the likelihood of live birth after ART have been developed, their accuracy may be insufficient, as they have generally been developed in the general population with infertility and were not validated for patients with POR. The PROsPeR score was developed using data from the follitropin alfa (GONAL-f; Merck KGaA, Darmstadt, Germany) arm of the Efficacy and Safety of Pergoveris in Assisted Reproductive Technology (ESPART) randomized controlled trial (RCT) and classifies women with POR as mild, moderate or severe, based upon three variables: female age, serum AMH level and number of oocytes retrieved during the previous cycle (PNO).

Effect of recombinant LH supplementation on cumulative live birth rate compared with FSH alone in poor ovarian responders: a large, real-world study.

Research Question: The benefit of LH supplementation (LHS) over sole use of FSH during controlled ovarian stimulation (COS) remains controversial. Meta-analyses have provided some evidence that the benefit of LHS is limited to women with poor ovarian response (POR). This study aimed to assess the effectiveness of LHS on cumulative live birth rate (CLBR) in POR using a large controlled study in a real-world context.

Long-term outcome of patients undergoing in-vitro fertilisation in France: The outcome study.

The Outcome study examines the fate of 4083 patients beginning IVF in 41 IVF centres, between January 2010 and December 2013. Cumulative live birth rate per patient (CLBR), the best reflection of IVF efficacy, is rarely presented in publications as it requires long-term follow-up, including all successive cycles, and pregnancies outcome. Analysis of international publications shows an average CLBR of 41.

Equivalent live-birth rate in antagonist IVF/ICSI protocol after oocyte triggering with GnRH agonist supplemented with 1500 r-hCG the day of oocyte retrieval vs r-hCG : A case-control study.

Objective: To compare live birth rate after fresh transfer and cumulative birth rates after vitrified embryo transfer in patients triggered by GnRHa, and 1500 r-hCG bolus on the day of the pick up to a selected population of patients triggered by r-hCG.

Design: Retrospective case-control study SETTING: Private hospital, Rennes, France PATIENTS: Patients with more than 18 follicles greater than 11 mm on the day of the triggering, or patients with a history of OHSS INTERVENTION: We triggered according to the European protocol by GnRHa and a bolus of 1500 UI of r-HCG on the day of the pick-up and performed if possible a fresh transfer on day 2, 3 or 5.

Main Outcome Measure: The live birth rate using fresh transfer (FT) and the cumulative birth rate by cycle of FT and frozen embryo transfer (FET) between patients triggered by GnRHa with a bolus injection of 1500 r-hCG and patients triggered by r-hCG.

Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles.

Research Question: Can previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed?

Design: Retrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor.

Results: In addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.

Determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease.

Purpose: Changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), including patterns of bacteriological relapse and superinfection are not well understood. Sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. Therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation.

Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD.

Background: Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood.

Efficacy and safety of moxifloxacin in hospitalized patients with secondary peritonitis: pooled analysis of four randomized phase III trials.

Background: Secondary peritonitis is an advanced form of complicated intra-abdominal infection (cIAI) requiring hospitalization, surgical source control, and empiric antibiotic therapy against causative aerobic and anaerobic bacteria.

Methods: This pooled analysis of four prospective, active-controlled randomized clinical trials compared the efficacy and safety of moxifloxacin with that of comparator antibiotics in patients with confirmed secondary peritonitis. The primary efficacy endpoint was clinical success rate at test-of-cure (TOC) between day 10 and 45 post-therapy in the per-protocol (PP) population.

[GnRH agonist triggering in IVF and luteal phase support in women at risk of ovarian hyperstimulation syndrome].

Objective: To evaluate the efficacy and safety of ovulation triggering by agonists in antagonists IVF cycles with fresh embryo transfer in modulating low HCG dose for luteal phase support in patients at risk of ovarian hyperstimulation syndrome (OHSS).

Patients And Methods: In an observational study from September 2011 to March 2013, we triggered with agonist 107 cycles with OHSS risk, we initially triggered 39 cycles with 2 doses of Triptorelin 0.1 mg.

Moxifloxacin in complicated skin and skin structure infections (cSSSIs): A prospective, international, non-interventional, observational study.

Introduction: ARTOS was an international, prospective, non-interventional, non-controlled observational study designed to determine the effectiveness, safety, and tolerability of moxifloxacin under daily-life conditions in patients with complicated skin and skin structure infections (cSSSIs) treated in Europe, the Middle East, and Asia-Pacific region.

Methods: Eligible patients included males and females who were hospitalized patients or outpatients requiring antibiotic therapy for cSSSIs and for whom the treating physician had elected to begin moxifloxacin therapy in accordance with its approved indications. Patients were assessed before therapy and then at one or two follow-up visits.

Characterisation of patients receiving moxifloxacin for acute bacterial rhinosinusitis in clinical practice: results from an international, observational cohort study.

Unlabelled: We conducted a prospective, non-controlled, multi-centre Phase IV observational cohort study of patients with acute bacterial rhinosinusitis who were treated with moxifloxacin in clinical practice in 19 countries in Asia Pacific, Europe and the Middle East. With the data collected we evaluated the presentation and course of the current disease episode, particularly in terms of the principal clinical signs and symptoms of acute rhinosinusitis and diagnostic procedures. A final assessment of moxifloxacin therapy was made to evaluate the impact of the sinusitis episode on activities of daily life and on sleep disturbance, and to evaluate the clinical outcome of treatment.

[Predictive models for ART].

A predictive model is a mathematical expression estimating the probability of pregnancy, by combining predictive variables, or indicators. Its development requires three successive phases: formulation of the model, its validation--internal then external--and the impact study. Its performance is assessed by its discrimination and its calibration.

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study.

Objective: The aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs).

Methods: Data of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems.

Randomised clinical trial of moxifloxacin versus ertapenem in complicated intra-abdominal infections: results of the PROMISE study.

Antibiotic therapy for complicated intra-abdominal infections (cIAIs) should provide broad-spectrum coverage both Gram-positive and Gram-negative microorganisms. The PROMISE study compared the clinical and bacteriological efficacy and safety of moxifloxacin versus ertapenem for the treatment of cIAIs. This randomised, prospective, double-dummy, double-blind, multicentre trial was designed as a non-inferiority study.

Acute right-sided heart failure caused by Neisseria meningitidis.

Meningococcal myocarditis is a rarely diagnosed infection and could be the consequence of primary invasive infection or late immunologic complications. An unusual presentation of meningococcemia in an immunocompetent adult is described, with Neisseria meningitidis identified as the cause of selective right-sided heart failure in a case of acute myocarditis.

A role for TLR1, TLR2 and NOD2 in cytokine induction by Bacteroides fragilis.

Bacteroides fragilis, an intestinal flora commensal microorganism, is frequently isolated from abscesses and soft tissue infections. This study aimed to identify pattern recognition receptors (PRRs) involved in B. fragilis recognition and to characterize the induced cytokine profile.

Update on the cardiac safety of moxifloxacin.

Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II-IV randomized active-controlled clinical trials. Moxifloxacin 400 mg once-daily monotherapy was administered orally (PO) or sequentially (intravenous/oral, IV/PO). Across 64 trials, 21,298 patients received PO therapy (10,613 moxifloxacin, 10,685 comparators) while 6846 received sequential IV/PO therapy (3431 moxifloxacin, 3415 comparators).

Simple adaptations to the Templeton model for IVF outcome prediction make it current and clinically useful.

Study Question: What is the validity of the Templeton model (TM) in predicting live birth (LB) for a couple starting an IVF/ICSI cycle?

Summary Answer: A centre-specific model based on the original predictors of the TM may reach a sufficient level of accuracy to be used in every day practice, with a few simple adaptations.

What Is Known And What This Paper Adds: The TM seems the best predictive model of LB in IVF. However, previous validations of the TM suggest a lack of discrimination and calibration which means that it is not used in regular practice.

Moxifloxacin safety: an analysis of 14 years of clinical data.

Background: Moxifloxacin, a fluoroquinolone antibiotic, is used for the treatment of respiratory tract, pelvic inflammatory disease, skin, and intra-abdominal infections. Its safety profile is considered favorable in most reviews but has been challenged with respect to rare but potentially fatal toxicities (e.g.

Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results.

Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study.