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Objectives During normal menstrual cycles, serum levels of progesterone vary widely between cycles of same woman and between women. This study investigated the profiles of pregnanediol during the luteal phase. Methods Data stemmed from a previous multicenter prospective observational study and concerned 107 women (who contributed 326 menstrual cycles). The study analyzed changes in observed cervical mucus discharge, various hormones in first morning urine, and serum progesterone. Transvaginal ultrasonography and cervical mucus helped identifying the day of ovulation. Changes in pregnanediol glucuronide levels during the luteal phase were examined and classified according to the length of that phase, a location parameter, and a scale parameter. Associations between nine pregnanediol glucuronide profiles and other hormone profiles were examined. Results Low periovulatory pregnanediol glucuronide levels and low periovulatory luteinizing hormone levels were associated with delayed increases in pregnanediol glucuronide after ovulation. That ‘delayed increase profile’ was more frequently associated with cycles with prolonged high LH levels than in cycles with rapid pregnanediol glucuronide increases. A ‘plateau-like profile’ during the luteal phase was associated with longer cycles, cycles with higher estrone-3-glucuronide and pregnanediol glucuronide during the preovulatory phase, and cycles with higher periovulatory pregnanediol glucuronide levels. Conclusions Distinct profiles of urinary progesterone levels are displayed during the luteal phase. These profiles relate to early hormone changes during the menstrual cycle. In everyday clinical practice, these findings provide further evidence for recommending progesterone test seven days after the mucus peak day. The search for other correlations and associations is underway.

Poor vitamin D status and high parathyroid hormone (PTH) level are associated with impaired bone microarchitecture, but these data are mainly cross-sectional. We studied the association of the baseline PTH and 25-hydroxycholecalciferol (25OHD) levels with the prospectively assessed deterioration of bone microarchitecture and in estimated bone strength in older men. Distal radius and tibia bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, then after 4 and 8 years in 826 men aged 60-87 years. At distal radius, total bone mineral density (Tt.BMD), cortical thickness (Ct.Th

Context Determination of steroid levels in the amniotic fluid gives some insight on fetal adrenal and gonadal functions. Objective Our objectives were to establish reference ranges of 12 steroid levels throughout pregnancy and to compare them with steroid levels from pregnancies with fetuses presenting with 21-hydroxylase deficiency (21OHD). Methods Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was applied to 145 “control” amniotic fluid samples from gynecology activity (12 + 6 to 32 + 4 gestational weeks, GW). The following steroids were analyzed according to gestational age and compared to 23 amniotic fluid samples from fetuses with classic 21OHD confirmed by molecular studies: delta-4-androstenedione (D4), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (11OH), 21-deoxycortisol (21OH), corticosterone, deoxycorticosterone (DOC), testosterone, pregnenolone, 17-hydroxypregnenolone (17Pregn), cortisol, and cortisone. Chromosomal sex was determined by karyotype and gestational age by biometric measurements. Results Analysis of control samples showed a statistically significant difference for D4 and testosterone levels according to fetal sex. Cortisol, corticosterone, and DOC had lower concentrations before 20 GW than after 20 GW, whereas 17Pregn and pregnenolone had higher concentrations before 20 GW. This allowed us to establish age- and sex-dependent reference values. We observed higher 21OH, 17Pregn, D4, and testosterone levels in females with 21OHD than female controls. The ratios 17OHP/17Pregn, D4/DHEA, and 11OH/17OHP appeared discriminant for the diagnosis of 21OHD. Conclusion Our study provides information on fetal steroidogenesis and suggests reference values for 12 steroids during pregnancy. This allows a prenatal diagnosis of 21OHD within 24 hours and might be useful in the diagnosis of other variations of sex development.

STUDY QUESTION Should testicular sperm extraction (TESE) in non-mosaic 47,XXY Klinefelter syndrome (KS) patients be performed soon after puberty or could it be delayed until adulthood? SUMMARY ANSWER The difference in sperm retrieval rate (SRR) in TESE was not significant between the ‘Young’ (15–22 years old) cohort and the ‘Adult’ (23–43 years old) cohort of non-mosaic KS patients recruited prospectively in parallel. WHAT IS KNOWN ALREADY Several studies have tried to define predictive factors for TESE outcome in non-mosaic KS patients, with very heterogeneous results. Some authors have found that age was a pejorative factor and recommended performing TESE soon after puberty. To date, no predictive factors have been unanimously recognized to guide clinicians in deciding to perform TESE in azoospermic KS patients. STUDY DESIGN, SIZE, DURATION Two cohorts (Young: 15–22 years old; Adult: 23–43 years old) were included prospectively in parallel. A total of 157 non-mosaic 47,XXY KS patients were included between 2010 and 2020 in the reproductive medicine department of the University Hospital of Lyon, France. However 31 patients gave up before TESE, four had cryptozoospermia and three did not have a valid hormone assessment; these were excluded from this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Data for 119 patients (61 Young and 58 Adult) were analyzed. All of these patients had clinical, hormonal and seminal evaluation before conventional TESE (c-TESE). MAIN RESULTS AND THE ROLE OF CHANCE The global SRR was 45.4%. SRRs were not significantly different between the two age groups: Young SRR=49.2%, Adult SRR = 41.4%; P = 0.393. Anti-Müllerian hormone (AMH) and inhibin B were significantly higher in the Young group (AMH: P = 0.001, Inhibin B: P LIMITATIONS, REASONS FOR CAUTION c-TESE was performed in the whole study; we cannot rule out the possibility of different results if microsurgical TESE had been performed. Because of the limited sensitivity of inhibin B and AMH assays, a large number of patients had values lower than the quantification limits, preventing the definition a threshold below which negative TESE can be predicted. WIDER IMPLICATIONS OF THE FINDINGS In contrast to some studies, age did not appear as a pejorative factor when comparing patients 15–22 and 23–44 years of age. Improved accuracy of inhibin B and AMH assays in the future might still allow discrimination of patients with persistent foci of spermatogenesis and guide clinician decision-making and patient information. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by a grant from the French Ministry of Health D50621 (Programme Hospitalier de Recherche Clinical Régional 2008). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER NCT01918280.

BACKGROUND AND AIMS Although associated with better quality of life and potential economic advantages, home dialysis use varies greatly internationally and appears to be underused in many countries. This study aimed to estimate the dialysis-network variability in home dialysis use and identify factors associated with (i) the uptake in home dialysis, (ii) the proportion of time spent on home dialysis and (iii) home dialysis survival (patient and technique). METHOD All adults ≥18 years old who had dialysis treatment during 2017–9 in mainland France were included. Mixed-effects regression models were built to explore factors including patient characteristics or residence and dialysis network associated with outcomes. RESULTS: During 2017–9, 7728/78 757 (9.8%) patients underwent dialysis at least once at home for a total of 120 594/1 508 000 (8%) months. The heterogeneity in dialysis networks regarding the uptake or total time spent on home dialysis was marginally explained by patient characteristics or residence and dialysis-network factors. Heterogeneity was less for home dialysis survival. These results were similar when the analysis was restricted to home peritoneal dialysis or home hemodialysis. Income inequity and housing were associated with reduced home dialysis uptake and reduced proportion of time on home dialysis. Home dialysis use was not affected by the number of self-care HD units in the administrative district of residence. CONCLUSION Our results suggest that to increase home dialysis use in France, one should focus on home dialysis uptake rather than survival. Financial incentives and a quality improvement program should be implemented at the dialysis-network level to increase home dialysis use.

Objective: The outbreak of coronavirus disease 2019 (COVID-19) in South Kivu, Democratic Republic of Congo raised concerns regarding additional morbidity and mortality. Updating these indicators before a second wave is essential in order to prepare for additional help. Methods: From mid-May to mid-December 2020, weekly surveys were undertaken in sampled streets from 10 health areas to quantify the use of barrier measures, and interview pedestrians about sickness and deaths in their households. Crude death rates (CDRs) were estimated. Results: Minimal use or no use of face masks was observed in at least half of the streets. From May to December 2020, the number of suspected cases of COVID-19 increased six-fold (P < 0.05). Of deaths within 30 days preceding the interviews, 20% were considered to be related to COVID-19. The monthly CDRs at the beginning and end of the study were approximately 5 and 25 per 1000 population, respectively (P < 0.05); that is, annual CDRs of 60 and 260 per 1000 population, respectively. Thus, during the first wave, the estimated mortality rate increased by 50% compared with previous years, and increased at least four-fold by the end of 2020. Conclusion: Despite possible overestimations, the excess mortality in South Kivu is extremely concerning. This crisis calls for a rapid response and increased humanitarian assistance.

Depuis le debut de l’annee 2018, le langage non sexiste constitue l’une des principales polemiques qui ebranlent l’opinion publique en Allemagne. Outre les arguments linguistiques, cette polemique comporte de nombreuses references aux discours antifeministes et « antigenre ». Il semblerait donc que les debats sur le langage non sexiste soient bien plus etroitement lies qu’il n’y parait aux debats actuels sur les politiques d’egalite des sexes. Notre analyse d’une selection des principales prises de position contre le langage non sexiste, publiees principalement dans la presse ecrite liberale et conservatrice, souligne la necessite d’approfondir davantage les liens entre ces discours et l’antifeminisme actuel.

Objectives: The aim of the study was to assess the efficacy and safety of an enhanced recovery program (ERP) after robot-assisted partial nephrectomy (RAPN) for cancer. Methods: It was a monocentric, retrospective, comparative study. An ERP after RAPN was introduced at our institution in 2015 and proposed to all consecutive patients admitted for RAPN. The control group for this study was composed of patients managed immediately before the introduction of the ERP. We collected information on patient characteristics, tumor sizes, ischemia times, biology, hospital length of stays, postoperative (≤30 days) complications, and readmission rates. Group comparisons were made using the Pearson χ2 test for qualitative data and the Student t test for quantitative data. Results: Between 2015 and 2017, 112 patients were included in the ERP group. Fifty patients were included in the control group. Ninety patients in the ERP group (80.4%) were discharged at or before postoperative day (POD) 2 versus 10 patients (20%) in the control group (p < 0.001). There was no significant difference between the ERP and control groups for the urinary retention rate (respectively 3.6 vs. 2%; p = 0.593). Resumption of normal bowel function was significantly shorter in the ERP group (94.6% at POD1 vs. 69.6% in the control group, p < 0.001). There were no significant differences for postoperative complications (15.2% in the ERP group vs. 20% in the control group, p = 0.447) or readmissions within 30 days (8.04 vs. 0.2%, p = 0.140). Conclusions: ERP after RAPN seems to reduce postoperative length of stay without increasing postoperative complications or readmissions.

Des représentants de la commune de Sayat-Argnat ont souhaité redynamiser le moulin à farine ainsi que la blanchisserie au travers d’événements culturels réguliers. Afin de soumettre des idées, recueillir l’opinion de la population et aider à mettre en place des projets durables et satisfaisants pour le plus grand nombre, ils ont pris contact avec l’université Clermont-Auvergne, et cette redynamisation culturelle a fait l’objet de projets collectifs au sein des première et deuxième années de Master Direction de Projets ou Établissements Culturels.Notre groupe de deuxième année, constitué de Maëllia Bardinet, Clémence Ecochard, Sébastien Gallois, Louise Morel et Lisa Villebesseix, a pris en charge l’élaboration d’un événement culturel au moulin à farine. Ce rapport résume le développement du projet au cours de l’année universitaire 2021-2022.

We present the case of a four-year-old girl, who was hospitalized in intensive care unit for a coma resulting from metabolic acidosis with increased anion gap. The patient was treated for short bowel syndrome, following necrotising enterocolitis, which occurred 51 days after birth. In our initial evaluation of the patient's metabolic acidosis, we were unable to identify the cause of the increased anion gap. Urinary organic acids chromatography identified a large peak of lactate (quantified at 15 mmol/mol of creatiniuria), as well as its metabolites. The discrepancy between normal blood lactate concentration assayed by enzymatic assay, and the large amount of lactate found by gas-chromatography/mass spectrometry (GC/MS) in urine highlights the limit of the stereospecificity of enzymatic assays. Indeed, most lactates assay use enzymatic assays that are specific for L-lactate, whereas organic acids chromatography, whose column is mostly achiral, can detect both stereoisomers, D- and L-lactate. Organic acids in urine analysis, in addition to the clinical context, suggested a diagnosis of D-lactic acidosis. Following a review of the physiopathology and treatment of short bowel syndrome, we will discuss the mechanism and diagnosis of the D-lactic acidosis in our patient. This case highlights the need to perform an organic acid profile in urine in the presence of any unexplained increased anion gap to determine its cause.

Aim In PARADIGM-HF, sacubitril/valsartan demonstrated superiority to enalapril in reducing mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Several patient-centred outcomes like improved physical activity and quality of life have been emphasised as important treatment goals in HF management. OUTSTEP-HF has been designed to evaluate the effect of sacubitril/valsartan compared with enalapril on non-sedentary daytime physical activity in patients with HFrEF. Methods OUTSTEP-HF is a randomised, actively controlled, double-blind, double-dummy study that plans to enrol 600 ambulatory patients with symptomatic HFrEF in 19 European countries. Patients will be randomised 1:1 to receive sacubitril/valsartan 97/103 mg bid or enalapril 10 mg bid. The primary objective of the study is to assess changes from baseline (Week 0) to Week 12 in exercise capacity measured by the 6-min walk test and in daily non-sedentary daytime activity. Physical activity and objective sleep parameters will be measured by accelerometry using a wrist-worn device, worn continuously from screening (Week -2) until the end of study (Week 12). As a co-primary outcome, changes from baseline in sub-maximal exercise capacity will be assessed by the 6-min walk test. Patient- and physician-reported questionnaires will be used to assess quality of life, changes in signs and symptoms of HF and sleep parameters. Conclusion OUTSTEP-HF will be the largest randomised trial in HF to date to use non-invasive accelerometry to assess whether treatment with sacubitril/valsartan improves patients' daily physical activity and exercise capacity compared with enalapril.

Treatment selection markers are generally sought for when the benefit of an innovative treatment in comparison with a reference treatment is considered, and this benefit is suspected to vary according to the characteristics of the patients. Classically, such quantitative markers are detected through testing a marker-by-treatment interaction in a parametric regression model. Most alternative methods rely on modeling the risk of event occurrence in each treatment arm or the benefit of the innovative treatment over the marker values, but with assumptions that may be difficult to verify. Herein, a simple non-parametric approach is proposed to detect and assess the general capacity of a quantitative marker for treatment selection when no overall difference in efficacy could be demonstrated between two treatments in a clinical trial. This graphical method relies on the area between treatment-arm-specific receiver operating characteristic curves (ABC), which reflects the treatment selection capacity of the marker. A simulation study assessed the inference properties of the ABC estimator and compared them with other parametric and non-parametric indicators. The simulations showed that the estimate of the ABC had low bias, power comparable to parametric indicators, and that its confidence interval had a good coverage probability (better than the other non-parametric indicator in some cases). Thus, the ABC is a good alternative to parametric indicators. The ABC method was applied to data of the PETACC-8 trial that investigated FOLFOX4 versus FOLFOX4 + cetuximab in stage III colon adenocarcinoma. It enabled the detection of a treatment selection marker: the DDR2 gene.

International audience; Microhabitat selection models are frequently used in rivers to evaluate anthropogenic effects on aquatic organisms. Fish models are generally developed from few rivers, with debatable statistical treatments for coping with overdispersed abundance distributions. Analyses of data from multiple rivers are needed to test their transferability and increase their relevance for stakeholders. Using 3,528 microhabitats sampled in nine French rivers during 129 surveys, we developed models for 35 specific size classes of 22 fish species. We used mixed‐effects generalized linear models (accounting for multiple surveys), involving B‐spline transformations (accounting for nonlinear responses) and assuming a negative binomial distribution (accounting for abundance overdispersion). We compared models of increasing complexity: no selection (M1), an “average” selection similar in all surveys (M2), two models with different selection across surveys (M3–M4). Of 132 univariate cases (specific size classes by habitat), 63% indicated selection for depth, 71% for velocity, 45% for substratum size and 13% for substratum heterogeneity. A total of 50 models were retained, involving 26/35 specific size classes. Model fits indicated low explained deviance (R2MF

Resume Introduction L’information preoperatoire est determinante a l’adhesion du patient au traitement mais peut etre insuffisamment assimilee par le patient du fait de sa densite et de sa complexite. L’objectif de cette etude etait d’evaluer la comprehension et la satisfaction des patients de l’information preoperatoire de chirurgie de l’hypertrophie benigne de prostate (HBP). Les facteurs influencant la comprehension etaient egalement etudies. Methodes Il s’agissait d’une etude monocentrique sur questionnaire incluant tous les patients devant se faire operer d’une HBP quelle que soit la technique chirurgicale. Un questionnaire etait envoye a chaque patient, a domicile, apres la consultation urologique preoperatoire. Resultats Deux cent dix questionnaires ont ete envoyes et 106 patients (50,5 %) ont renvoye le questionnaire. L’information etait jugee excellente (cotee 9/10 et 10/10 sur l’echelle numerique) par 38,68 % (41/106) des patients et « tres bonne » (cotee 7–8) par 45,28 % des patients (48/106). Les complications postoperatoire les plus frequemment citees par les patients etaient l’ejaculation retrograde (39,6 % des patients, n = 42/106) et le saignement (29,2 %, n = 31/106). 57,6 % des patients (n = 61) se rappelaient avoir recu la fiche d’information ecrite. Apres rappel des complications eventuelles, 5,7 % des patients (n = 6/106) hesitaient a se faire operer. Seul l’âge des patients etait significativement associe a une difference de comprehension (p Conclusion L’information dispensee aux patients avant chirurgie d’HBP paraissait satisfaisante bien qu’elle semble mal comprise, notamment concernant les complications. Cette etude pourrait permettre de modifier notre vision de l’information du patient, en passant d’un modele paternaliste a un modele de « partenariat » avec le patient. Niveau de preuve 3.

Background Care goals are often implicit, although their identification is a key element of any prescription process. This study aimed to describe the clinical goals of drug prescriptions in general practice, their determinants and the agreement between physicians and patients. Methods This was a cross-sectional study conducted by 11 resident trainees acting as observers in 23 general practices. The residents recorded the indication and main physician’s goal for all drugs prescribed during five consultation days in each practice in December 2015, and the main patient’s goal for a sub-sample of consultations. We used an eight-category generic classification of prescription goals, including three specific (mortality, morbidity and cure), three non-specific (symptoms, quality of life, functioning) and two non-specified (other goal, no goal) categories. Analyses were based on a multivariable, multilevel model and on the kappa statistic applied to the sub-sample of consultations. Results The sample encompassed 2141 consultations and 5036 drugs. The main physicians’ goal of drug prescriptions was to relieve symptoms (43.3%). The other goals were to decrease the risk of morbidity (22.4%), to cure disease (11.7%), to improve quality of life (10.6%), to decrease the risk of mortality (8.5%) and to improve functioning (1.8%). The choice of a specific goal was more frequent in patients with the following characteristics: over 50 (OR [1.09;1.15]), of male gender (OR [1.09;1.39]), with full financial coverage for a long-term condition (OR [1.47;1.97]), known by the physician (OR [1.19;2.23]), or with a somatic health problem (OR [2.56;4.17]). Cohen’s kappa for drug prescription goals between the patients and the physicians was 0.26 (0.23–0.30). Conclusions Physicians’ goals are poorly shared with patients. It remains to be assessed whether it is possible to collect and discuss information on prescription goals on a daily basis.

Additional file 1: Supplementary Table 1. Definitions used in the study. Supplementary Table 2. Details of eligibility criteria. Supplementary Table 3. Patient reported outcome tool: mMIDAS. Supplementary Table 4. Change from baseline in MMD by visit, observed,mixed model repeated measures (full analysis set). Supplementary Table 5. Patientincidence rates of treatment-emergent SAEs in the study by primary SOC (Safety analysis set).

Background Although associated with better quality of life and potential economic advantages, home dialysis use varies greatly internationally and appears to be underused in many countries. This study aimed to estimate the dialysis-network variability in home dialysis use and identify factors associated with (i) the uptake in home dialysis, (ii) the proportion of time spent on home dialysis and (iii) home dialysis survival (patient and technique). Methods All adults ≥18 years old who had dialysis treatment during 2017–2019 in mainland France were included. Mixed-effects regression models were built to explore factors including patient or residence characteristics and dialysis network associated with variation in home dialysis use. Results During 2017–2019, 7728/78 757 (9.8%) patients underwent dialysis at least once at home for a total of 120 594/1 508 000 (8%) months. The heterogeneity at the dialysis-network level and to a lesser extent the regional level regarding home dialysis uptake or total time spent was marginally explained by patient characteristics or residence and dialysis-network factors. Between-network heterogeneity was less for patient and technique survival. These results were similar when the analysis was restricted to home peritoneal dialysis or home hemodialysis. Conclusions Variability between networks in the use of home dialysis was not fully explained by non-modifiable patient and residence characteristics. Our results suggest that to increase home dialysis use in France, one should focus on home dialysis uptake rather than survival. Financial incentives and a quality improvement programme should be implemented at the dialysis-network level to increase home dialysis use.

This paper examines the oxidation behavior of thin specimens of cast NiCoCrAlY alloys at 1150 $$^\circ {\rm C}$$ through successive stages, from $${\rm Al}_2{\rm O}_3$$ growth to complete alloy conversion to oxide. Five alloy compositions were used, with varying fractions and compositions of $$\gamma$$ and $$\beta$$ . The time evolution of the alloy composition during $${\rm Al}_2{\rm O}_3$$ growth was simulated using the DICTRA module of Thermo-Calc and calculated analytically in the approximation of flat profiles. Simulated and experimental profiles were found to be in good agreement, indicating that the phase equilibrium and mass balance were correctly reproduced in the simulations. Local variations of alloy composition were observed in thinner specimens and found to be comparable with the variations expected from the uncertainty on the initial specimen thickness. The variations observed in the time-to- $${\rm Al}_2{\rm O}_3$$ failure were greater than expected on this basis, suggesting that additional sources of variability were in effect. Alumina failure was followed by the growth of a $${\rm Cr}_2{\rm O}_3$$ layer at the alloy–scale interface. Similarly, Cr consumption eventually led to $${\rm Cr}_2{\rm O}_3$$ failure, and Ni- and Co-containing spinel oxide formed, converting the $${\rm Cr}_2{\rm O}_3$$ at the alloy–scale interface and the $${\rm Al}_2{\rm O}_3$$ at the scale–gas interface. The remaining NiCo alloy was then converted to (Ni,Co)O. This sequence occurred without abrupt increase in the mass gain, due to the continued presence of the remnant $${\rm Al}_2{\rm O}_3$$ layer, and to the small amount of metal left to oxidize when the (Ni,Co)O eventually broke through the scale. The evolution of the scale composition throughout the oxidation stages is discussed based on an analysis of the thermodynamic conditions at the alloy–scale interface.