Evidence that the woman's ovarian cycle is driven by an internal circamonthly timing system.

The ovarian cycle has a well-established circa-monthly rhythm, but the mechanisms involved in its regularity are unknown. Is the rhythmicity driven by an endogenous clock-like timer or by other internal or external processes? Here, using two large epidemiological datasets (26,912 cycles from 2303 European women and 4786 cycles from 721 North American women), analyzed with time series and circular statistics, we find evidence that the rhythmic characteristics of the menstrual cycle are more likely to be explained by an endogenous clock-like driving mechanism than by any other internal or external process. We also show that the menstrual cycle is weakly but significantly influenced by the 29.5-day lunar cycle and that the phase alignment between the two cycles differs between the European and the North American populations. Given the need to find efficient treatments of subfertility in women, our results should be confirmed in larger populations, and chronobiological approaches to optimize the ovulatory cycle should be evaluated.

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds.

STUDY QUESTION: Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? SUMMARY ANSWER: This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. WHAT IS KNOWN ALREADY: Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. STUDY DESIGN, SIZE, DURATION: This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. MAIN RESULTS AND THE ROLE OF CHANCE: The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24 h; u24LH = 0.035 or 0.08 IU/24 h). The combination of u24FSH > 1.1 IU/24 h and u24LH > 0.08 IU/24 h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS: The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used. All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER: In-house #23-5214 registered study.

The menstrual cycle is influenced by weekly and lunar rhythms.

OBJECTIVE: To study whether the menstrual cycle has a circaseptan (7 days) rhythm and whether it is associated with the lunar cycle (also defined as the synodic month, it is the cycle of the phases of the Moon as seen from Earth, averaging 29.5 days in length). DESIGN: Cross-sectional study. SUBJECTS: A total of 35,940 European and North American women aged 18-40 years. EXPOSURE: Data were collected in real-life conditions. INTERVENTION: No intervention was performed. MAIN OUTCOME MEASURE: The onset of menstruation was assessed in prospectively measured menstrual cycles (311,064 cycles) over 3 full years (2019-2021). Associations were calculated between the onset of menstruation and the day of the week, and between the onset of menstruation and the lunar phase. RESULTS: In this large data set, a circaseptan (7-day) rhythmicity of menstruation was observed, with a peak (acrophase) of menstrual onset on Thursdays and Fridays. This circaseptan rhythm was observed in every age group, in every phase of the lunar cycle, and in all seasons. This feature was most pronounced for cycle durations between 27 and 29 days. In winter, the circaseptan rhythm was found in cycles of 27-29 days, but not in other cycle lengths. A circalunar rhythm was also statistically significant, but not as clearly defined as the circaseptan rhythm. The peak (acrophase) of the circalunar rhythm of menstrual onset varied according to the season. In addition, there was a small but statistically significant interaction between the circaseptan rhythm and the lunar cycle. CONCLUSION: Although relatively small in amplitude, the weekly rhythm of menstruation was statistically significant. Menstruation occurs more often on Thursdays and Fridays than on other days of the week. This is particularly true for women whose cycles last between 27 and 29 days. Circalunar rhythmicity was also statistically significant. However, it is less pronounced than the weekly rhythm.

Relationship Between Steroid Hormone Profile and Premenstrual Syndrome in Women Consulting for Infertility or Recurrent Miscarriage.

To determine the relationships between luteal-phase steroidal hormonal profile and PMS for a large number of women attending a dedicated fertility clinic. This was a retrospective cross-sectional study on women attending a hospital-based clinic for fertility concerns and/or recurrent miscarriage. All participants were assessed with a women's health questionnaire which also included evaluation of premenstrual symptoms. Day of ovulation was identified based on the peak mucus symptom assessed by the woman after instruction in a fertility awareness-based method (FABM). This enabled reliable timing of luteal-phase serum hormone levels to be taken and analysed. Between 2011 and 2021, 894 of the 2666 women undertaking the women's health assessment had at least one evaluable serum luteal hormone test. Serum progesterone levels were up to 10 nmol/L lower for symptomatic women compared with asymptomatic women. This difference was statistically significant (p < 0.05) for the majority of PMS symptoms at ≥ 9 days after the peak mucus symptom. A similar trend was observed for oestradiol but differences were generally not statistically significant. ROC curves demonstrated that steroid levels during the luteal phase were not discriminating in identifying the presence of PMS symptoms. Blood levels for progesterone were lower throughout the luteal phase in women with PMS, with the greatest effect seen late in the luteal phase.

Anesthesia practices for management of labor pain and cesarean delivery in France (EPIDOL): A cross-sectional survey.

BACKGROUND: This study aimed to collect obstetric anesthesia practice and patient-reported outcomes as an update to the last French Obstetric Anesthesia survey from 1996. METHODS: Maternity units were randomly selected across France and surveyed for 7 consecutive days from February, 2016, to January, 2017. Data was gathered prospectively by questionnaires filled out by patients and anesthesia providers. RESULTS: There were 1885 questionnaires received from 56 units, with 379 cesarean delivery (CD) and 1506 vaginal delivery (VD) cases analyzed. The overall neuraxial labor analgesia (NLA) rate was 82.5% (95% CI [82.4-82.6]), with 70.3% (95% CI [71.4-71.6]) receiving automated administration (PCEA/PIEB). NLA was effective throughout labor in 68.2% of cases, however, severe pain was reported by 29.4% of patients. The overall rate of alternative approaches for labor analgesia was 19.5% (95%CI [19.2-19.7]). Obesity (OR 2.8; 95% CI [1.0-7.5], p < 0.04) and delivery in level I units (OR 0.6; 95% CI [0.5-0.9], p < 0.01) were associated with severe pain during VD. Satisfaction was found to be similar in patients delivering with or without NLA. The incidence of pain during CD was similar in scheduled versus non-scheduled CD. Failure of NLA during CD was associated with severe pain (OR 10.0; 95% CI [3.1-31.9], p < 0.01) and dissatisfaction (OR 26.2; 95% CI [3.0-225.1], p < 0.01). CONCLUSION: Despite the high NLA rate in France, a significant proportion of women experience severe pain during labor and delivery. This study emphasizes the need for further practice guidelines in obstetric anesthesia to ensure optimal pain management and improve patients' experience during childbirth. CLINICALTRIALS: govNCT02853890.

Clustering of trajectories with mixed effects classification model: Inference taking into account classification uncertainties.

Classifying patient biomarker trajectories into groups has become frequent in clinical research. Mixed effects classification models can be used to model the heterogeneity of longitudinal data. The estimated parameters of typical trajectories and the partition can be provided by the classification version of the expectation maximization algorithm, named CEM. However, the variance of the parameter estimates obtained underestimates the true variance because classification uncertainties are not taken into account. This article takes into account these uncertainties by using the stochastic EM algorithm (SEM), a stochastic version of the CEM algorithm, after convergence of the CEM algorithm. The simulations showed correct coverage probabilities of the 95% confidence intervals (close to 95% except for scenarios with high bias in typical trajectories). The method was applied on a trial, called low-cyclo, that compared the effects of low vs standard cyclosporine A doses on creatinine levels after cardiac transplantation. It identified groups of patients for whom low-dose cyclosporine may be relevant, but with high uncertainty on the dose-effect estimate.

Stronger Impact of COVID-19 in Nursing Homes of a French Region During the Second Pandemic Wave.

OBJECTIVES: Quantify the effects of characteristics of nursing homes and their surroundings on the spread of COVID-19 outbreaks and assess the changes in resident protection between the first 2 waves (March 1 to July 31 and August 1 to December 31, 2020). DESIGN: An observational study was carried out on data on COVID-19 outbreaks extracted from a database that monitored the spread of the virus in nursing homes. SETTING AND PARTICIPANTS: The study concerned all 937 nursing homes with >10 beds in Auvergne-Rhône-Alpes region, France. METHODS: The rate of nursing homes with at least 1 outbreak and the cumulative number of deaths were modeled for each wave. RESULTS: During the second (vs the first wave), the proportion of nursing homes that reported at least 1 outbreak was higher (70% vs 56%) and the cumulative number of deaths more than twofold (3348 vs 1590). The outbreak rate was significantly lower in public hospital-associated nursing homes than in private for-profit ones. During the second wave, it was lower in public and private not-for-profit nursing homes than in private for-profit ones. During the first wave, the probability of outbreak and the mean number of deaths increased with the number of beds (P < .001). During the second wave, the probability of outbreak remained stable in >80-bed institutions and, under proportionality assumption, the mean number of deaths was less than expected in >100-bed institutions. The outbreak rate and the cumulative number of deaths increased significantly with the increase in the incidence of hospitalization for COVID-19 in the surrounding populations. CONCLUSIONS AND IMPLICATIONS: The outbreak in the nursing homes was stronger during the second than the first wave despite better preparedness and higher availabilities of tests and protective equipment. Solutions for insufficient staffing, inadequate rooming, and suboptimal functioning should be found before future epidemics.

Diversity of the quality of data collection in a registry: proposal of an analysis approach and application to the REIN register / Diversité de la qualité de recueil des données dans un registre : proposition d'une démarche d'analyse et application au registre REIN

Missing data may lead to bias and loss of information in epidemiological research. In this article, we propose an approach to analyze missing data on comorbidity variables in a register with consideration of the territorialized organization of the collection. To illustrate this approach, we used the national REIN registry as an application case.

Les données manquantes peuvent introduire des biais et des pertes d'informations dans les études épidémiologiques. Dans cet article, nous proposons une démarche d'analyse des données manquantes sur des variables de comorbidités dans un registre, avec prise en compte de l'organisation territorialisée du recueil. Afin d'illustrer cette démarche, nous avons utilisé le registre national du Réseau épidémiologie et information en néphrologie (REIN) comme cas d'application.

Steroid Profiling in the Amniotic Fluid: Reference Range for 12 Steroids and Interest in 21-Hydroxylase Deficiency.

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.

Distinct urinary progesterone metabolite profiles during the luteal phase.

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.

Functional representation of the network organisation of dialysis activities in France: A novel level for assessing quality of care.

To assess quality of care, groups of care units that cared for the same patients at various stages of end-stage renal disease, might be more appropriate than the centre level. These groups constitute "communities" that need to be delineated to evaluate their practices and outcomes. In this article, we describe the use of an agglomerative (Fast Greedy) and a divisive (Edge Betweenness) method to describe dialysis activities in France. The validation was based on the opinion of the field actors at the regional level of the REIN registry. At the end of 2018, ESRD care in France took place in 1,166 dialysis units. During 2016-2018, 32 965 transfers occurred between dialysis units. With the Edge Betweenness method, the 1,114 French dialysis units in metropolitan France were classified into 156 networks and with the Fast Greedy algorithm, 167 networks. Among the 32 965 transfers, 23 168 (70%) were defined in the same cluster by the Edge Betweenness algorithm and 26 016 (79%) in the same cluster by the Fast Greedy method. According to the Fast Greedy method, during the study period, 95% of patients received treatment in only one network. According to the opinion of the actors in the field, the Fast Greedy algorithm seemed to be the best method in the context of dialysis activity modelling. The Edge Betweenness classification was not retained because it seemed too sensitive to the volume of links between dialysis units.

Delaying testicular sperm extraction in 47,XXY Klinefelter patients does not impair the sperm retrieval rate, and AMH levels are higher when TESE is positive.

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 < 0.001), and also higher in patients with a positive TESE than in those with a negative TESE (AMH: P = 0.001, Inhibin B: P = 0.036). The other factors did not differ between age groups or according to TESE outcome. AMH had a better predictive value than inhibin B. SRRs were significantly higher in the upper quartile of AMH plasma levels than in the lower quartile (or in cases with AMH plasma level below the quantification limit): 67.7% versus 28.9% in the whole population (P = 0.001), 60% versus 20% in the Young group (P = 0.025) and 71.4% versus 33.3% in the Adult group (P = 0.018). 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.

Association of Vitamin D and Parathyroid Hormone Status With the Aging-Related Decline of Bone Microarchitecture in Older Men: The Prospective Structure of Aging Men's Bones (STRAMBO) Study.

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.Thd ), cortical area (Ct.Ar), cortical BMD (Ct.BMD), and trabecular BMD (Tb.BMD) decreased, whereas trabecular area (Tb.Ar) increased more rapidly in men with 25OHD ≤20 ng/mL versus the reference group (>30 ng/mL). Men with 25OHD ≤10 ng/mL had faster decrease in reaction force and failure load than men with 25OHD >30 ng/mL. At the distal tibia, Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, failure load, and reaction force decreased, whereas Tb.Ar increased more rapidly in men with 25OHD between 10 and 20 ng/mL versus the reference group. The results were similar when 12 ng/mL was used as a threshold of severe vitamin D deficiency. At distal radius, men with PTH levels above the median (>44 pg/mL) had more rapid decrease in Tt.BMD, Ct.Ar, Ct.BMD, Ct.Thd , reaction force, and failure load, and more rapid increase in Tb.Ar versus the lowest quartile (≤34 pg/mL). At the distal tibia, men in the highest PTH quartile had faster decrease in Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, reaction force, and failure load and faster increase in Tb.Ar versus the lowest quartile. The results were similar in men with glomerular filtration rate >60 mL/min. The results were similar in men who took no vitamin D or calcium supplements for 8 years. In summary, vitamin D deficiency and secondary hyperparathyroidism are associated with more rapid prospectively assessed cortical and trabecular bone decline in older men. © 2022 American Society for Bone and Mineral Research (ASBMR).

Fertility in men with Klinefelter's syndrome.

Patients with a Klinefelter syndrome (KS), defined by a 47 XXY karyotype, were long considered infertile. Testicular sperm extraction (TESE) now allows them to access fatherhood. We will present the data of studies since first experiment of TESE. Several factors influencing TESE outcome were proposed in these different studies. Among them, clinical and hormonal parameters have reported by few studies, age has been one of the most discussed prognostic factor of positive sperm retrieval rate. Data seems to show that TESE carried out before an age greater than 30 has a poorer prognosis for positive sperm retrieval. In few studies performed in younger patient, before 20 years, SRR was closed to result for 20 to 30 year old patients. Offering a TESE before 16 years old does not improve positive sperm extraction rate. In fact, the few studies carried out before the age of 16 were of poorer prognosis, most often linked to insufficient maturation of the residual gametes. In addition, androgen therapy, frequently prescribed in case of Klinefelter syndrome, did not seem to show any effect on sperm retrieval but only few studies were interested in the possible impact of this treatment. In conclusion, further studies are necessary to determine the interest of new markers to predict the chance of sperm retrieval, taking into account age, hormonal therapy.

Dialysis-network variability in home dialysis use not explained by patient characteristics: a national registry-based cohort study in France.

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.

Descriptive analysis of the relationship between progesterone and basal body temperature across the menstrual cycle.

OBJECTIVE: Describe the relationship between basal body temperature (BBT) and pregnanediol-3 alpha-glucuronide (PDG, the urine metabolite of progesterone) across the menstrual cycle. DESIGN: Observational study. SETTING: Study carried out from 1996 to 1997 in eight European family planning clinics. PARTICIPANT(S): One hundred and seven normally fertile and cycling women. MAIN OUTCOME MEASURE(S): BBT and PDG level on each day of 283 cycles and ultrasound determination of the day of ovulation. RESULT: (s): In comparison with previous end-of-cycle levels, decreases in PDG and BBT on the first day of menses were seen in nearly 90% and 80% of cycles, respectively. In a non-negligible percentage of cycles, luteolysis would continue during menses: between the second and the third day after menses, small but significant decreases in PDG and BBT were seen in 76% and 48% of cycles, respectively. During the peri-ovulatory phase, between the third and the second day before ovulation, PDG and BBT began to rise in 56% and 41% of cycles, respectively. There was a medium degree of correlation between PDG levels and BBT (r = 0.53; 7,279 days with available measurements). The relationship between PDG levels and BBT was linear at low PDG levels but BBT increased no longer when PDG levels continued to rise above a threshold of nearly 10 mcg/mg Cr. CONCLUSION: (s): PDG and BBT had parallel increases at low PDG rates but diverged at higher rates.

COVID-19 outbreaks in nursing homes: A strong link with the coronavirus spread in the surrounding population, France, March to July 2020.

BACKGROUND: Worldwide, COVID-19 outbreaks in nursing homes have often been sudden and massive. The study investigated the role SARS-CoV-2 virus spread in nearby population plays in introducing the disease in nursing homes. MATERIAL AND METHODS: This was carried out through modelling the occurrences of first cases in each of 943 nursing homes of Auvergne-Rhône-Alpes French Region over the first epidemic wave (March-July, 2020). The cumulative probabilities of COVID-19 outbreak in the nursing homes and those of hospitalization for the disease in the population were modelled in each of the twelve Départements of the Region over period March-July 2020. This allowed estimating the duration of the active outbreak period, the dates and heights of the peaks of outbreak probabilities in nursing homes, and the dates and heights of the peaks of hospitalization probabilities in the population. Spearman coefficient estimated the correlation between the two peak series. RESULTS: The cumulative proportion of nursing homes with COVID-19 outbreaks was 52% (490/943; range: 22-70% acc. Département). The active outbreak period in the nursing homes lasted 11 to 21 days (acc. Département) and ended before lockdown end. Spearman correlation between outbreak probability peaks in nursing homes and hospitalization probability peaks in the population (surrogate of the incidence peaks) was estimated at 0.71 (95% CI: [0.66; 0.78]). CONCLUSION: The modelling highlighted a strong correlation between the outbreak in nursing homes and the external pressure of the disease. It indicated that avoiding disease outbreaks in nursing homes requires a tight control of virus spread in the surrounding populations.

Effect of age and care organization on sources of variation in kidney transplant waiting list registration.

Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016-2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log-linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between-transplant center variability (0.23 ± 0.08) was 1.8 higher than between-dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18-64, 65-74, and 75-84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access.

Trajectory clustering using mixed classification models.

Trajectory classification has become frequent in clinical research to understand the heterogeneity of individual trajectories. The standard classification model for trajectories assumes no between-individual variance within groups. However, this assumption is often not appropriate, which may overestimate the error variance of the model, leading to a biased classification. Hence, two extensions of the standard classification model were developed through a mixed model. The first one considers an equal between-individual variance across groups, and the second one considers unequal between-individual variance. Simulations were performed to evaluate the impact of these considerations on the classification. The simulation results showed that the first extended model gives a lower misclassification percentage (with differences up to 50%) than the standard one in case of presence of a true variance between individuals inside groups. The second model decreases the misclassification percentage compared with the first one (up to 11%) when the between-individual variance is unequal between groups. However, these two extensions require high number of repeated measurements to be adjusted correctly. Using human chorionic gonadotropin trajectories after curettage for hydatidiform mole, the standard classification model classified trajectories mainly according to their levels whereas the two extended models classified them according to their patterns, which provided more clinically relevant groups. In conclusion, for studies with a nonnegligible number of repeated measurements, the use, in first instance, of a classification model that considers equal between-individual variance across groups rather than a standard classification model, appears more appropriate. A model that considers unequal between-individual variance may find its place thereafter.

The COVID-19 pandemic is deepening the health crisis in South Kivu, Democratic Republic of Congo.

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.