Comparison of serum progesterone levels on the day of frozen embryo transfers according to type of endometrial preparation: a single centre, retrospective study.

The live birth rate following embryo transfer is comparable between spontaneous, stimulated and artificial cycles. However, the pregnancy loss rate appears elevated with hormonal therapy, possibly due to luteal insufficiency. This study aimed to determine whether the serum progesterone level on transfer day differed according to the endometrial preparation method for frozen embryo transfer (FET). Twenty spontaneous cycles (SC), 27 ovarian stimulation cycles (OS) and 65 artificial cycles (AC) were retrospectively studied from May to December 2019 in a single French hospital. The primary endpoint was the level of serum progesterone on the day of FET between the three endometrial preparation methods. The mean serum progesterone level on transfer day was 29.47 ng/ml in the OS group versus 20.03 ng/ml in the SC group and 14.32 ng/ml AC group (P < 0.0001). Progesterone levels remained significantly different after logistic regression on age and anti-Müllerian hormone (AMH) level. There was no significant difference in demographic and hormone characteristics (age, body mass index, embryo stage of embryo, type of infertility, basal follicle stimulating hormone, luteinizing hormone, estradiol and AMH levels), endometrial thickness, number and type of embryos transferred, duration of infertility, pregnancy rate, live birth rate and pregnancy loss rate. No difference was found in serum progesterone levels between clinical pregnancy with fetal heartbeat and no clinical pregnancy (no pregnancy or pregnancy loss, 17.49 ng/ml vs 20.83 ng/ml, respectively, P = 0.07). The lower serum progesterone level found on FET day in the AC group should be further investigated to see whether this difference has a clinical effect on the live birth rate.

Violence against nurses in the emergency department: an observational study.

OBJECTIVE: This study aimed to evaluate the number and risk factors of violent events encountered in the emergency department. An observation grid was developed following interviews with emergency department staff to target the most pertinent information to collect in a prospective study design. DESIGN: Observational study. SETTING: Emergency department of a tertiary hospital in France. OUTCOME MEASURES: Number of violent events occurring during a single shift, recorded over 6 months by two observers. Information collected included time and date of incident; number of male/female staff; number of patients and accompaniers present in the service and the waiting room and length of staff debriefing. Perpetrator, victim and patient information were collected. Victims were followed-up 72 hours later. RESULTS: Eighty-two periods were observed between November 2015 and April 2016 recording 35 violent incidents affecting 37 perpetrators and 48 victims, equally distributed over the days of the week and months of the year. The median interval until violence was 0 [0-96] min from entry. Eight (23%) events were officially reported, with two (6%) resulting in charges being pressed. No risk factors were significantly associated with violent incidents in multivariate analysis, although there was a tendency towards significance for fewer senior female doctors present (p=0.0787) and a resulting longer debriefing session (p=0.0712). CONCLUSIONS: We confirm the high rate of violence in the emergency department and poor level of official reporting. Strategies should be implemented to anticipate and reduce incidence and encourage reporting by affected staff. TRIAL REGISTRATION NUMBER: NCT02116439.

Sutureless socket technique after removal of third molars: a multicentric, open, randomized controlled trial.

BACKGROUND: Although wisdom-tooth extraction is a routine intervention, the postoperative period remains marked by local inflammation classically manifesting as pain, edema and trismus. Furthermore, there is no consensus on the best operative techniques, particularly for the mucosal closure stage on impacted mandibular wisdom teeth. METHODS: This parallel, randomized, non-blinded study compared pain following removal of impacted third molars, with and without sutures. Patients were electronically allocated 1:1 to extraction with versus without sutures. Patients ≥ 14 years' old scheduled for extraction of four impacted wisdom teeth under general anesthesia at three French hospitals were eligible for inclusion. Exclusion criteria included taking antiplatelet agents or anticoagulants, coagulation disorders or immunosuppression, and planned orofacial surgical procedures or emergency pain/infection. The primary objective was pain evaluated by Visual Analogue Scale on Day 3. Secondary outcomes were edema, trismus, healing, complications, painkiller consumption and quality of life on Day 3 and 31. RESULTS: Between June 2016 and November 2018, 100 patients were randomized. Finally, 44 patients in the Suture group and 50 patients in the Without Suture group were analyzed. Mean age was 16.5 years and 66.6% of patients were female. After adjustment on center, age and smoking, no statistical difference was seen between groups for pain on Day 3 (p = 0.904). No differences were seen for swelling, trismus, consumption of painkillers, healing, complications or quality of life. Smokers had a 3.65 times higher complications rate (p = 0.0244). CONCLUSIONS: Sutureless removal of third molars is thus a reliable technique without negative consequence on outcomes, and allows shorter operating time. Smoking is a risk factor for postoperative complications. Trial registration www. CLINICALTRIALS: gov (NCT02583997), registered 22/10/2015.

Rehabilitation and lumbar surgery: the French recommendations for clinical practice.

BACKGROUND: Indications and techniques of rehabilitation differ widely across types of lumbar surgery, including timing (before or after surgery) and prescriptions (surgeons but also medical or paramedical professionals). OBJECTIVES: This project aimed to build consensual recommendations for practice in this context. METHODS: The SOFMER methodology was used to establish recommendations for physical medicine and rehabilitation: a steering committee defined the types of lumbar surgery involved and developed the main questions to be addressed; a scientific committee performed a literature review for grading evidence and proposed the first version of recommendations, which were discussed during a dedicated session at the national Physical and Rehabilitation Medicine congress; then an e-Delphi method with cross-professional experts was used to finalise recommendations and reach a multidisciplinary consensus. RESULTS: The main questions developed were the value of rehabilitation before and after surgery, timing and type of rehabilitation, benefit of supervision and instrumental rehabilitation, value of patient education, and complementary interventions concerning rehabilitation for discectomy, fusion, and disc prosthesis (excluding decompression for spinal stenosis). The literature review identified 60 articles, but for several of the questions, no article in the literature addressed the issue. The multidisciplinary scientific committee analysed the literature and addressed the questions to propose the first version of a set of 23 recommendations. The congress session failed to answer all questions or to reach consensus for all items. After a three-step e-Delphi, 20 recommendations were retained, for which consensus among experts was reached. The recommendations are applicable only to patients without a neurological lesion. CONCLUSIONS: These recommendations provide important and consensual knowledge to assist clinicians in decision-making for rehabilitation in lumbar surgery. Despite many of the recommendations relying exclusively on expert opinion rather than published evidence, this approach is an important advance to improve concordance among healthcare professionals.

A prospective cohort study of postpartum glucose metabolic disorders in early versus standard diagnosed gestational diabetes mellitus.

Early gestational diabetes mellitus (eGDM) is diagnosed when fasting plasma glucose before 24 weeks of gestation (WG) is ≥ 5.1 mmol/L, whilst standard GDM is diagnosed between 24 and 28 WG by oral glucose tolerance test (OGTT). eGDM seems to have worse obstetric outcomes than standard GDM. We compared the rates of postpartum glucose metabolism disorders between women with early versus standard GDM in this prospective study on women with GDM from three university hospitals between 2014 and 2016. Patients were included if they were < 24 WG with at least one risk factor for GDM and excluded if they had type 2 diabetes. Patients were assigned to Group 1 (G1) for eGDM according to IADPSG: fasting blood glucose < 24 WG between 5.1 and 7 mmol/L. Group 2 (G2) consisted of patients presenting a standard GDM at 24-28 WG on OGTT results according to IADPSG: T0 ≥ 5.1 mmol/L or T60 ≥ 10.0 mmol g/L or T120 ≥ 8.5 mmol/L. The primary outcome was postpartum OGTT result. Five hundred patients were analysed, with 273 patients undergoing OGTT at 4-18 weeks postpartum: 192 patients in G1 (early) and 81 in G2 (standard). Patients in G1 experienced more insulin therapy during pregnancy than G2 (52.2% versus 32.5%, p < 0.001), but no patients were taking insulin postpartum in either group. G1 patients experienced less preterm labour (2.6% versus 9.1%, p = 0.043), more induced deliveries (38% versus 25%, p = 0.049) and reduced foetal complications (29.2% versus 42.0%, p = 0.048). There was no significant difference in the rate of postpartum glucose metabolism disorders (type 2 diabetes, impaired glucose tolerance, impaired fasting glycaemia) between groups: 48/192 (25%) in G1 and 17/81 (21%) in G2, p = 0.58. Thus the frequency of early postpartum glucose metabolism disorders is high, without difference between eGDM and standard GDM. This supports measurement of fasting plasma glucose before 24 WG and the threshold of 5.1 mmol/L seems appropriate until verification in future studies.Trial registration: NCT01839448, ClinicalTrials.gov on 22/04/2013.

Quality of life determinants in older patients with cancer: Results from a French prospective monocenter cohort.

OBJECTIVES: The aim of this study is to describe determinants of quality of life (QOL) quoted by vulnerable older patients with cancer and compare them with domains included in cancer-specific QOL questionnaires. MATERIAL AND METHODS: This prospective, monocenter, observational study was performed in a French university hospital. Cancer patients Patients with cancer aged over 74 years were recruited when referred for an out-patient geriatric evaluation (n = 102). After geriatric assessment, they were invited to respond to open-ended questions, Q1: "For you, what is most important to have a good QOL?" Q2: "What could improve your QOL?" Q3: "What could worsen your QOL?" A Delphi process was conducted to categorize patient responses according to content analysis. RESULTS: The most frequently patient-reported determinants for high quality of life were maintaining close ties with family/friends or social relations, autonomy for decision and mobility without depending on others, being in good health, not suffering from pain and the absence of problems concerning relatives. Global health status, physical functioning/mobility, social functioning and worries about others were the more frequently mentioned QOL domains related to the EORTC QLQ-C30 and ELD14 questionnaires. Some determinants of QOL were not linked to pre-defined domains, some others without a 100% consensus after the Delphi process, illustrating the subjectivity of QOL analysis by a single practitioner. CONCLUSION: Patient interview with open-ended questions provides valuable supplementary information to QOL questionnaires, in order to personalize health related (cancer treatment, pain management…) and global (maintenance of autonomy and family/social relations…) assessment and intervention.

CT scan does not make a diagnosis of Covid-19: A cautionary case report.

Here, we report the clinical case of a 12-year-old girl presenting with flu-like symptoms, cough, anosmia, ageusia, breathing difficulties, and patchy ground glass opacities on TDM chest scan who turned out to be Coronavirus 229E-infected. This case draws attention to the risk of false COVID-19 diagnosis when over-relying on CT scan imaging.

Impact on quality of life 3 years after diagnosis of prostate cancer patients below 75 at diagnosis: an observational case-control study.

BACKGROUND: Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression. METHODS: Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients < 75 years old from the EPICAP cohort, newly diagnosed from 1 December 2011 to 31 March 2014 and 879 healthy controls. Participants were excluded if they experienced a relapse. Controls from the same geographical region were age-matched and were excluded if they were diagnosed with prostate cancer. Patients received one of the following treatments: active surveillance (AS), radical prostatectomy (RP), external beam radiotherapy (EBRT), High-intensity Focused Ultrasound (HIFU), chemotherapy (CT), or androgen deprivation therapy (ADT) as appropriate. The primary outcome was the quality of life as evaluated by the QLQ-C30 questionnaire. Scores were analyzed by multivariate analysis to adjust for predefined socio-demographic confounding effects. RESULTS: In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151). CONCLUSIONS: Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients < 75 years at diagnosis. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunction. TRIAL REGISTRATION: clinicaltrials.gov, NCT02854982 . Registered 4 August 2016, retrospectively registered.

Unilateral versus bilateral sacral neuromodulation test in the treatment of refractory idiopathic overactive bladder: A randomized controlled pilot trial.

AIM: To compare treatment success rate in terms of improvement of bladder overactivity between unilateral and bilateral sacral neuromodulation testing. METHODS: A multicentric, parallel, randomized, open pilot trial (October 2012-September 2017) was conducted. Participants presented primary overactive bladder resistant to first-line treatments. Patients were excluded in case of secondary bladder, pelvic, or neurological condition. Patients were randomized between bilateral testing (n = 28) or unilateral testing (n = 27), to determine the best functional response before final implantation. The primary outcome was the rate of patients presenting at least 50% of clinical improvement at 1 month on urinary frequency, number of urge incontinence episodes or number of urinary urgency episodes. Symptom severity, implantation success rate, uroflowmetry, device tolerance, complications, and quality of life were also assessed. RESULTS: Fifty-five patients have been included. The rate of patients presenting at least one significant clinical improvement at month 1 was 62% in the bilateral group versus 84% in the unilateral group (P = .0891), RR = 0.74 (0.51; 1.07). There was no significant difference between bilateral and unilateral groups in terms of improvement of urinary frequency (0% and 17%; P = .1115), number of urge incontinence episodes (52% and 63%; P = .4929) or number of urinary urgency episodes (57% and 74%; P = .2411). More complications were reported in the bilateral group than in the unilateral group (9 [47%] vs 4 [16%], respectively; P = .0239). CONCLUSION: Systematic bilateral sacral neuromodulation testing before final implantation did not appear to increase success rate compared with unilateral stimulation in the treatment of overactive bladder.

Impact of pharmacist-led multidisciplinary medication review on the safety and medication cost of the elderly people living in a nursing home: a before-after study.

Objectives: Adverse drug events (ADE) are a common cause of morbidity and mortality in elderly patients. In this study, we assessed the impact of multidisciplinary medication review (MMR) for nursing home residents on patient safety and costs incurred by the hospital and the national health service. Methods: Medical files of residents were retrospectively assessed for medications prescribed in the previous six months. A pharmacist reviewed the prescriptions and suggested modifications to the patient's medical team. Patients were followed for six months. Trivalle's ADE geriatric risk score was calculated before and after MMR, as were number of potentially inappropriate medications, and economic impact from the perspective of the health care system and the nursing home. Results: Forty-nine patients were recruited. ADE score dropped one risk level (median score of 4 before versus 1 after, p < 0.0001). The number of patients taking at least one potentially inappropriate medication decreased from 30.6% before to 6.1% after MMR (p = 0.005). A mean saving of €232 per patient was made from the nursing home perspective following MMR (p = 0.008). Conclusion: The MMR reduced the iatrogenic drug risk for elderly residents and costs from the nursing home perspective, particularly drug expenditure.

Impact of KIT exon 10 M541L allelic variant on the response to imatinib in aggressive fibromatosis: analysis of the desminib series by competitive allele specific Taqman PCR technology.

BACKGROUND: Aggressive fibromatosis (AF) is a rare fibroblastic proliferative disease with a locally aggressive behavior and no distant metastasis, characterized by driver mutations in CTNNB1 or the APC gene. When progressive and/or symptomatic AF is not amenable to local management, a variety of medical treatments may be efficient, including imatinib mesylate. The phase II "Desminib trial" included 40 patients with AF to evaluate the toxicity and efficacy of imatinib resulting in a 65% tumor control rate at 1 year. We investigated a potential predictive value of KIT exon 10 M541L variant (KITL541) on this prospective series. METHODS: DNA was extracted in sufficient quantity from 33 patients included in the Desminib trial. The detection of KITL541 was performed by Competitive Allele-Specific Taqman® PCR technology. Chi-2 analyses were performed to search for a correlation between KIT status and tumor response. Progression free (PFS) and overall survival (OS) were compared by log-rank test after Kaplan-Meier analysis. RESULTS: In 6 out of 33 cases (18%), the technique failed to determine the mutational status; 5 patients (19%) harboured KITL541 and 22 patients (81%) were classified as KIT wild type. Compared with total cohort, KITL541 frequency did not distinguish between different clinical characteristics. In the KITL541 and the KITWT subgroups, the tumor control rate at 1 year was 100% and 68%, respectively (p = 0.316). The median PFS of patients harboring KITL541 or not is 29.9 and 24.5 months, respectively (p = 0.616), and the median OS is not reached, in any of the groups. CONCLUSION: Our results do not support a predictive effect of KITL541 on the efficacy of imatinib for patients with AF.

Cell-cycle synchronisation of bloodstream forms of Trypanosoma brucei using Vybrant DyeCycle Violet-based sorting.

Studies on the cell-cycle of Trypanosoma brucei have revealed several unusual characteristics that differ from the model eukaryotic organisms. However, the inability to isolate homogenous populations of parasites in distinct cell-cycle stages has limited the analysis of trypanosome cell division and complicated the understanding of mutant phenotypes with possible impact on cell-cycle related events. Although hydroxyurea-induced cell-cycle arrest in procyclic and bloodstream forms has been applied recently with success, such block-release protocols can complicate the analysis of cell-cycle regulated events and have the potential to disrupt important cell-cycle checkpoints. An alternative approach based on flow cytometry of parasites stained with Vybrant DyeCycle Orange circumvents this problem, but is restricted to procyclic form parasites. Here, we apply Vybrant Dyecycle Violet staining coupled with flow cytometry to effectively select different cell-cycle stages of bloodstream form trypanosomes. Moreover, the sorted parasites remain viable, although synchrony is rapidly lost. This method enables cell-cycle enrichment of populations of trypanosomes in their mammal infective stage, particularly at the G1 phase.

Genome-wide expression profiling of in vivo-derived bloodstream parasite stages and dynamic analysis of mRNA alterations during synchronous differentiation in Trypanosoma brucei.

BACKGROUND: Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. RESULTS: In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T.brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. CONCLUSION: Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition.

Role for RAD18 in homologous recombination in DT40 cells.

RAD18 is an E3 ubiquitin ligase that catalyzes the monoubiquitination of PCNA, a modification central to DNA damage bypass and postreplication repair in both yeast and vertebrates. Although current evidence suggests that homologous recombination provides an essential backup in vertebrate rad18 mutants, we show that in chicken DT40 cells this is not the case and that RAD18 plays a role in the recombination reaction itself. Gene conversion tracts in the immunoglobulin locus of rad18 cells are shorter and are associated with an increased frequency of deletions and duplications. rad18 cells also exhibit reduced efficiency of gene conversion induced by targeted double-strand breaks in a reporter construct. Blocking an early stage of the recombination reaction by disruption of XRCC3 not only suppresses immunoglobulin gene conversion but also prevents the aberrant immunoglobulin gene rearrangements associated with RAD18 deficiency, reverses the elevated sister chromatid exchange of the rad18 mutant, and reduces its sensitivity to DNA damage. Together, these data suggest that homologous recombination is toxic in the absence of RAD18 and show that, in addition to its established role in postreplication repair, RAD18 is also required for the orderly completion of gene conversion.