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For various reasons, despite previous linguistic, formatting, and other checks, beginner-authored or multi-authored manuscripts may be rushed to submission while lacking consistency. This article provides a clear outline of the final round of checks for section consistency, subsection consistency, and overall coherence that a scientific manuscript should undergo before submission. Checks for consistency should target the following: consistency between full and short titles; the exact answer in conclusion to research objectives (questions) and matching between methods and results in the abstract; consistency from a comprehensive view of the research field to the announcement of a single specific objective in the introduction section; coherence between methods and results sections and between results and illustrations in the rest of the text; and, recalls of the objective, the results, and the conclusions in the discussion section. Finally, consistency should be ensured between the various sections of the abstract and those of the manuscript, with the ideal abstract being a true miniature of the manuscript. An original figure provides a handy visual checklist authors might use to implement and achieve manuscript drafting. This round of checks increases readability, comprehensibility, confidence in the results, and the credibility of the authors. Subsequently, confidence and credibility will increase the probability of publication and the visibility of a whole team’s work.

To assess the interrater reliability of the SOFMER Activity Score (SAS) (version 2 [v2], an 8-item [4 motor and 4 cognitive] and 5-level scale) and improve its scoring system before conducting further validation steps.Cross-sectional, prospective, observational, noninterventional, and multicentric study.The study was conducted between November 2018 and September 2019 in 4 French rehabilitation centers (2 public university hospitals for adults and 2 private not-for-profit rehabilitation centers for children).The study included 101 participants (N=101; mean age, 44.5±25.4 years; 28.7% younger than 18 and 18.8% older than 65 years). The female/male sex ratio was 0.6. The causes for admission to the center were mainly neurologic (65%) or orthopedic (24%).None.Activity limitation was rated with the SAS the same day by 2 independent multidisciplinary teams. The interrater reliabilities of the score items were assessed using weighted kappa coefficients.All weighted kappa coefficients ranged between 0.83 and 0.92, indicating "good" to "excellent" interrater reliability. Interteam score disagreements occurred in 227 of 808 scores (28%). The reason for most disagreements was unnoticed human or material aid during the observation period.The results demonstrate the high interrater reliability of the SASv2 and allow carrying out further validation steps after minor changes to item scoring instructions and clearer definitions of some items that help improving scoring standardization. The SASv2 may then become a consistent measure of activity level for clinical research or burden of care investigations.

To improve the performance of individual DNA sequencing results, researchers often use replicates from the same individual and various statistical clustering models to reconstruct a high-performance callset. Here, three technical replicates of genome NA12878 were considered and five model types were compared (consensus, latent class, Gaussian mixture, Kamila–adapted k-means, and random forest) regarding four performance indicators: sensitivity, precision, accuracy, and F1-score. In comparison with no use of a combination model, i) the consensus model improved precision by 0.1%; ii) the latent class model brought 1% precision improvement (97%–98%) without compromising sensitivity (= 98.9%); iii) the Gaussian mixture model and random forest provided callsets with higher precisions (both >99%) but lower sensitivities; iv) Kamila increased precision (>99%) and kept a high sensitivity (98.8%); it showed the best overall performance. According to precision and F1-score indicators, the compared non-supervised clustering models that combine multiple callsets are able to improve sequencing performance vs. previously used supervised models. Among the models compared, the Gaussian mixture model and Kamila offered non-negligible precision and F1-score improvements. These models may be thus recommended for callset reconstruction (from either biological or technical replicates) for diagnostic or precision medicine purposes.

International audience; The major economic and health consequences of COVID-19 called for various protective measures and mass vaccination campaigns. A previsional model was used to predict the future impacts of various measure combinations on COVID-19 mortality over a 400-day period in France. Calibrated on previous national hospitalization and mortality data, an agent-based epidemiological model was used to predict individual and combined effects of booster doses, vaccination of refractory adults, and vaccination of children, according to infection severity, immunity waning, and graded non-pharmaceutical interventions (NPIs). Assuming a 1.5 hospitalization hazard ratio and rapid immunity waning, booster doses would reduce COVID-19-related deaths by 50–70% with intensive NPIs and 93% with moderate NPIs. Vaccination of initially-refractory adults or children ≥5 years would half the number of deaths whatever the infection severity or degree of immunity waning. Assuming a 1.5 hospitalization hazard ratio, rapid immunity waning, moderate NPIs and booster doses, vaccinating children ≥12 years, ≥5 years, and ≥6 months would result in 6212, 3084, and 3018 deaths, respectively (vs. 87,552, 64,002, and 48,954 deaths without booster, respectively). In the same conditions, deaths would be 2696 if all adults and children ≥12 years were vaccinated and 2606 if all adults and children ≥6 months were vaccinated (vs. 11,404 and 3624 without booster, respectively). The model dealt successfully with single measures or complex combinations. It can help choosing them according to future epidemic features, vaccination extensions, and population immune status.

International audience; In epidemiology, left-truncated data may bias exposure effect estimates. We analyzed the bias induced by left truncation in estimating breast cancer risk associated with exposure to airborne dioxins. Simulations were run with exposure estimates from a Geographic Information System (GIS)-based metric and considered two hypotheses for historical exposure, three scenarios for intra-individual correlation of annual exposures, and three exposure-effect models. For each correlation/model combination, 500 nested matched case–control studies were simulated and data fitted using a conditional logistic regression model. Bias magnitude was assessed by estimated odds-ratios (ORs) versus theoretical relative risks (TRRs) comparisons. With strong intra-individual correlation and continuous exposure, left truncation overestimated the Beta parameter associated with cumulative dioxin exposure. Versus a theoretical Beta of 4.17, the estimated mean Beta (5%; 95%) was 73.2 (67.7; 78.8) with left-truncated exposure and 4.37 (4.05; 4.66) with lifetime exposure. With exposure categorized in quintiles, the TRR was 2.0, the estimated ORQ5 vs. Q1 2.19 (2.04; 2.33) with truncated exposure versus 2.17 (2.02; 2.32) with lifetime exposure. However, the difference in exposure between Q5 and Q1 was 18× smaller with truncated data, indicating an important overestimation of the dose effect. No intra-individual correlation resulted in effect dilution and statistical power loss. Left truncation induced substantial bias in estimating breast cancer risk associated with exposure with continuous and categorical models. With strong intra-individual exposure correlation, both models detected associations, but categorical models provided better estimates of effect trends. This calls for careful consideration of left truncation-induced bias in interpreting environmental epidemiological data.

Background In 2012, the World Health Organization (WHO) recommended seasonal malaria chemoprevention (SMC) in areas of high seasonal transmission. Though implemented since 2013, the effectiveness of SMC in Togo was never evaluated. Methods This study concerned routine data from 2013 to 2020 mass SMC campaigns for children under five in all health facilities of three Regions of Togo. Treatment coverage, reasons for non-treatment, and SMC-attributable adverse reactions were analysed per year and treatment round. Random effect logistic models estimated SMC effectiveness per health district, year, and treatment round. Results The overall coverage was 98% (7,971,877 doses for 8,129,668 children). Contraindication was the main reason for non-administration. Over the study period, confirmed malaria cases decreased from 11,269 (1st round of 2016) to 1395 (4th round of 2020). Only 2,398 adverse reactions were reported (prevalence: 3/10,000), but no severe Lyell syndrome or Stevens-Johnson-type skin reaction. Compared to 2016, malaria prevalence decrease was estimated at 22.6% in 2017 (p Conclusions SMC reduced significantly malaria cases among children under five. The results reassure all actors and call for effort intensification to reach the WHO goals for 2030.

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.

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.

Rationale: In cystic fibrosis, information on the efficacy of azithromycin past 12 months of treatment is still scarce.Objectives: The study sought to quantify the changes in lung function and the ...

International audience; The outbreak of the SARS-CoV-2 virus, enhanced by rapid spreads of variants, has caused a major international health crisis, with serious public health and economic consequences. An agent-based model was designed to simulate the evolution of the epidemic in France over 2021 and the first six months of 2022. The study compares the efficiencies of four theoretical vaccination campaigns (over 6, 9, 12, and 18 months), combined with various non-pharmaceutical interventions. In France, with the emergence of the Alpha variant, without vaccination and despite strict barrier measures, more than 600,000 deaths would be observed. An efficient vaccination campaign (i.e., total coverage of the French population) over six months would divide the death toll by 10. A vaccination campaign of 12, instead of 6, months would slightly increase the disease-related mortality (+6%) but require a 77% increase in ICU bed–days. A campaign over 18 months would increase the disease-related mortality by 17% and require a 244% increase in ICU bed–days. Thus, it seems mandatory to vaccinate the highest possible percentage of the population within 12, or better yet, 9 months. The race against the epidemic and virus variants is really a matter of vaccination strategy.

Background and Objectives: To test the long-term ability of human ovarian cortex cells to develop in unconventional culture conditions. Materials and Methods. Ovarian cortex cells from fetuses aged 23 to 39 weeks gestation were cultured for 90 days in hollow chitosan hydrogel micro-bioreactors and concurrently in traditional wells. Various cell-type counts were considered. Results: With intact follicles as a denominator, the percentage of growing intact follicles at Day 0 varied widely between ovaries (0 to 31.7%). This percentage tended to increase or stay relatively constant in bioreactor as in control cultures; it tended more toward an increase over time in bioreactor vs. control cultures. Modeled percentages showed differences (though not significant) in favor of bioreactor cultures (16.12% difference at D50 but only 0.12% difference at D90). With all follicles present as a denominator, the percentage of growing primary and secondary follicles at D0 varied widely between ovaries (0 to 29.3%). This percentage tended to increase over time in bioreactor cultures but to decrease in control cultures. Modeled percentages showed significant differences in favor of bioreactor cultures (8.9% difference at D50 and 11.1% difference at D90). At D50 and D90, there were only few and sparse apoptotic cells in bioreactor cultures vs. no apoptotic cells in control cultures. Conclusions: Over three months, bioreactor folliculogenesis outperformed slightly traditional culture. This is an interesting perspective for follicle preservation and long-term toxicological studies.

Assess the quality of dental restorations with simplified FDI criteria and examine its relationships with other general characteristics of restored teeth.The study involved 76 dentists from private and hospital practices. Assessments of successes and failures of previous restorations used a simplified rating with FDI criteria 3 to 8, 11, 12, and 14. The results were examined versus tooth location, number of restored surfaces, type of restoration, and filling material.The dentists examined 4,612 dental restorations, of which 4,185 direct fillings mainly with resin composite materials (2,555). Of all restorations, 2,048 (44.4%) were considered as failures, of which 1,489 had one or two criteria for 'clinically unsatisfactory/poor restoration'. As simplified, the esthetic criterion 'color match' was the most frequent criterion for failure (912 cases). The rate of restoration failures was found associated with the number of surfaces restored and the use of glass-ionomer cement. Results are not comparable with others obtained with original FDI criteria.Assessing dental restorations with the original FDI criteria leads generally to much more failure statements than practitioners' decisions to reintervene. Though requiring some adjustment (e.g., regarding 'color match'), the simplified assessment proved convenient and amenable to standardization.Regardless of the type of practice, selecting, understanding, and optimal interpreting of FDI criteria for failure is essential to help practitioners faced with daily dilemmas of replacement vs. repair of failed dental restorations. Standardization of simplified criteria is desirable to help comparing research data.

Aims This study determined whether the improvements in hypertension management over the last five decades have influenced subjects’ prognosis. Methods and results The study considered 5693 eligible subjects seen January 1969 to February 1991 (follow-up until December 2003) or January 1995 to October 2014 (follow-up until July 2016) in an all-grade hypertension reference centre. Missing data or incomplete follow-ups led to exclude 1036 subjects (18%). The outcome was all-cause death. An adjusted modelling of the excess mortality rate assessed subjects’ net survival over five inclusion periods to allow for the increase in life expectancy of the general population during the same periods. The analysis of 4657 records (mean age: 47 years; 43.2% women) showed that the proportion of subjects with grade 3 hypertension decreased significantly from 43.3% (1142) to only 6.3% (22) over the five periods and that the net survival improved in men and women regardless of the hypertension grade; i.e. the gain in net survival at 15 years was estimated at 12.3% (95% confidence interval: 8.1–22.3). The 15-year restricted mean survival was estimated at 13 years over the first period and 14.8 years over the last period, which is nearly a 2-year gain in life expectancy at 15 years. Conclusion Since the 70s and the advent of modern management, the excess mortality of hypertensive subjects (vs. the general population) was markedly reduced. Within a context of trivialization of blood pressure measurement and reluctance to long-term treatments, physicians should consider this advantage and use it to promote blood pressure control.

BackgroundCompartmental models help making public health decisions. They were used during the COVID-19 outbreak to estimate the reproduction numbers and predict the number of hospital beds required. This study examined the ability of closely related compartmental models to reflect equivalent epidemic dynamics.MethodsThe study considered three independently designed compartmental models that described the COVID-19 outbreak in France. Model compartments and parameters were expressed in a common framework and models were calibrated using the same hospitalization data from two official public databases. The calibration procedure was repeated over three different periods to compare model abilities to: i) fit over the whole lockdown; ii) predict the course of the epidemic during the lockdown; and, iii) provide profiles to predict hospitalization prevalence after lockdown. The study considered national and regional coverages.ResultsThe three models were all flexible enough to match real hospitalization data during the lockdown, but the numbers of cases in the other compartments differed. The three models failed to predict reliably the number of hospitalizations after the fitting periods at national as at regional scales. At the national scale, an improved calibration led to epidemic course profiles that reflected hospitalization dynamics and reproduction numbers that were coherent with official and literature estimates.ConclusionThis study shows that prevalence data are needed to further refine the calibration and make a selection between still divergent models. This underlines strongly the need for repeated prevalence studies on representative population samples.

Objectives The one-compartment iohexol plasma clearance has been proposed as a reliable alternative to renal inulin clearance. However, this method’s performance depends on the formula used to calculate glomerular filtration rate (GFR). This study reports on performance comparisons between various mathematical formulas proposed for iohexol plasma clearance vs. inulin urinary clearance. Methods GFR was simultaneously determined by inulin and iohexol clearance in 144 participants (age: 10–84 years; glomerular filtration rate: 15–169 mL/min/1.73 m2). A retrospective cross-sectional study evaluated the performance of four formulas proposed to calculate plasma iohexol clearance (Brøchner–Mortensen, Fleming et al., Jødal–Brøchner–Mortensen, and Ng–Schwartz–Munoz). The performance of each formula was assessed using bias, precision (standard deviation of the bias), accuracy (percentage iohexol within 5, 10, and 15%), root mean square error, and concordance correlation coefficient vs. renal inulin clearance as reference. Results Regarding accuracy, there was no difference in root mean square error (RMSE), P5, P10, or P15 between the four formulas. The four concordance correlation coefficients (CCC) between the value from each formula and in-GFR were high and not significantly different. At in-GFR ≥90 mL/min/1.73 m2, Ng–Schwartz–Munoz formula performed slightly better than other formulas regarding median bias (−0.5; 95% CI [−3.0 to 2.0] and accuracy P15 (95.0; 95% CI [88.0–100.0]). Conclusions The studied formulas were found equivalent in terms of precision and accuracy, but the Ng–Schwartz–Munoz formula improved the accuracy at higher levels of in-GFR.

Objective and Background: Men’s experiences of first-fatherhood discovery differ widely with various circumstances; they were examined according to the intended/unintended occurrence of partner’s p...

Describe the relationship between basal body temperature (BBT) and pregnanediol-3 alpha-glucuronide (PDG, the urine metabolite of progesterone) across the menstrual cycle.Observational study.Study carried out from 1996 to 1997 in eight European family planning clinics.One hundred and seven normally fertile and cycling women.BBT and PDG level on each day of 283 cycles and ultrasound determination of the day of ovulation.(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.(s): PDG and BBT had parallel increases at low PDG rates but diverged at higher rates.

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.

Background: With the increase of life expectancy, *On behalf of the REIN registry. end-stage renal disease (ESRD) is affecting a growing number of people. Simultaneously, renal replacement therapies (RRTs) have considerably improved patient survival. We investigated the way current RRT practices would affect patients' survival.Methods: We used a multi-state model to represent the transitions between RRTs and the transition to death. The concept of “crude probability of death” combined with this model allowed estimating the proportions of ESRD-related and ESRD-unrelated deaths. Estimating the ESRD-related death rate requires comparing the mortality rate between ESRD patients and the general population. Predicting patients' courses through RRTs and Death states could be obtained by solving a system of Kolmogorov differential equations. The impact of practice on patient survival was quantified using the restricted mean survival time (RMST) which was compared with that of healthy subjects with same characteristics.Results: The crude probability of ESRD-unrelated death was nearly zero in the youngest patients (18–45 years) but was a sizeable part of deaths in the oldest (≥70 years). Moreover, in the oldest patients, the proportion of expected death was higher in patient without vs. with diabetes because the former live older. In men aged 75 years at first RRT, the predicted RMSTs in patients with and without diabetes were, respectively, 61% and 69% those of comparable healthy men.Conclusion: Using the concept of “crude probability of death” with multi-state models is feasible and useful to assess the relative benefits of various treatments in ESRD and help patient long-term management.

Cancer survival trend analyses are essential to describe accurately the way medical practices impact patients’ survival according to the year of diagnosis. To this end, survival models should be able to account simultaneously for non-linear and non-proportional effects and for complex interactions between continuous variables. However, in the statistical literature, there is no consensus yet on how to build such models that should be flexible but still provide smooth estimates of survival. In this article, we tackle this challenge by smoothing the complex hypersurface (time since diagnosis, age at diagnosis, year of diagnosis, and mortality hazard) using a multidimensional penalized spline built from the tensor product of the marginal bases of time, age, and year. Considering this penalized survival model as a Poisson model, we assess the performance of this approach in estimating the net survival with a comprehensive simulation study that reflects simple and complex realistic survival trends. The bias was generally small and the root mean squared error was good and often similar to that of the true model that generated the data. This parametric approach offers many advantages and interesting prospects (such as forecasting) that make it an attractive and efficient tool for survival trend analyses.

Summary Background: Even in normally cycling women, hormone level shapes may widely vary between cycles and between women. Over decades, finding ways to characterize and compare cycle hormone waves was difficult and most solutions, in particular polynomials or splines, do not correspond to physiologically meaningful parameters. Objective: We present an original concept to characterize most hormone waves with only two parameters. Methods: The modelling attempt considered pregnanediol-3-alpha-glucuronide (PDG) and luteinising hormone (LH) levels in 266 cycles (with ultrasound-identified ovulation day) in 99 normally fertile women aged 18 to 45. The study searched for a convenient wave description process and carried out an extended search for the best fitting density distribution. Results: The highly flexible beta-binomial distribution offered the best fit of most hormone waves and required only two readily available and understandable wave parameters: location and scale. In bell-shaped waves (e.g., PDG curves), early peaks may be fitted with a low location parameter and a low scale parameter; plateau shapes are obtained with higher scale parameters. I-shaped, J-shaped, and U-shaped waves (sometimes the shapes of LH curves) may be fitted with high scale parameter and, respectively, low, high, and medium location parameter. These location and scale parameters will be later correlated with feminine physiological events. Conclusion: Our results demonstrate that, with unimodal waves, complex methods (e.g., functional mixed effects models using smoothing splines, second-order growth mixture models, or functional principal-component- based methods) may be avoided. The use, application, and, especially, result interpretation of four-parameter analyses might be advantageous within the context of feminine physiological events.

There is a growing interest in using health care (HC) data to produce epidemiological surveillance indicators such as incidence. Typically, in the field of cancer, incidence is provided by local cancer registries which, in many countries, do not cover the whole territory; using proxy measures from available nationwide HC databases would appear to be a suitable approach to fill this gap. However, in most cases, direct counts from these databases do not provide reliable measures of incidence. To obtain accurate incidence estimations and prediction intervals, these databases need to be calibrated using a registry-based gold standard measure of incidence. This article presents a calibration model for count data developed to predict cancer incidence from HC data in geographical areas without cancer registries. First, the ratio between the proxy measure and incidence is modeled in areas with registries using a Poisson mixed model that allows for heterogeneity between areas (calibration stage). This ratio is then inverted to predict incidence from the proxy measure in areas without registries. Prediction error admits closed-form expression which accounts for heterogeneity in the ratio between areas. A simulation study shows the accuracy of our method in terms of prediction and coverage probability. The method is further applied to predict the incidence of two cancers in France using hospital data as the proxy measure. We hope this approach will encourage sound use of the usually imperfect information extracted from HC data.

BackgroundUveitis is a frequent and early feature of sarcoidosis. As BTNL2 (butyrophilin-like 2) gene polymorphism was found linked with the susceptibility to sarcoidosis, we investigated whether a specific genotype of BTNL2 gene G16071A (or rs2076530) single-nucleotide polymorphism (SNP) would be associated with the risk of sarcoid uveitis in all patient subgroups.MethodsThe study compared the genotype frequencies of SNP G16071A of 135 patients with sarcoid uveitis (Sa+Uv+) with those of 196 patients with sarcoidosis without uveitis (Sa+Uv−), 81 patients with uveitis without sarcoidosis (Sa−Uv+), and 271 controls with no sarcoidosis nor uveitis (Sa−Uv−). Three hypothetical subgroups of patients with sarcoid uveitis (Sa+Uv+ cases) were considered: (1) subgroup I: patients aged 45 years; and (3) subgroup III: all other patients.ResultsA statistically significant difference in genotype frequencies was found between the groups Sa+Uv− and Sa−Uv− (p=3.2×10−6) and between the groups Sa+Uv+ and Sa+Uv− (p=7.1×10−3). There was no difference between the three subgroups of Sa+Uv+ patients. There was a statistically significant difference in genotype frequencies between Sa+Uv− and Sa+Uv+ subgroup II (p=0.005) but no difference between Sa+Uv− and Sa+Uv+ subgroup I.ConclusionNo association was found between G16071A and the susceptibility to sarcoid uveitis. BTNL2 gene G16071A SNP seems to be a predisposing factor for sarcoidosis except in Caucasian postmenopausal women with sarcoid uveitis in whom the GG genotype prevails. These and future results will help in understanding differences between particular subgroups of patients with sarcoid uveitis.

Objective: Explore potential relationships between preovulatory, periovulatory, and luteal-phase characteristics in normally cycling women. Design: Observational study. Setting: Eight European natural family planning clinics. Patient(s): Ninety-nine women contributing 266 menstrual cycles. Intervention(s): The participants collected first morning urine samples that were analyzed for estrone-3 glucuronide (E1G), pregnanediol-3- alpha-glucuronide (PDG), follicle stimulating hormone (FSH), and luteinizing hormone (LH). The participants underwent serial ovarian ultrasound examinations. Main Outcome Measure(s): Four outcome measures were analyzed: short luteal phase, low mid-luteal phase PDG level (mPDG), normal then low luteal PDG level, low then normal luteal PDG level. Results: A long preovulatory phase was a predictor of short luteal phase, with or without adjustment for other variables. A high periovulatory PDG level was a predictor for short luteal phase as well as normal then low luteal PDG level. A low periovulatory PDG level predicted low mPDG and low then normal luteal PDG level, with or without adjustment for other variables. A small maximum follicle predicted normal then low luteal PDG level, with or without adjustment for other variables. The relationship between small maximum follicle size and short luteal phase or small maximum follicle size and low mPDG was no longer present when the regression was adjusted for certain characteristics. A younger age at menarche and a high body mass index were both predictors of low mPDG. Conclusion: Luteal phase abnormalities exist over a spectrum where some ovulation disorders may exist as deviations from the normal ovulatory process.This study confirms the negative impact of a small follicle size on the quality of the luteal phase. The occurrence of normal then low luteal PDG level is confirmed as a potential sign of luteal phase abnormality.

Objective: ADHD is one of the most frequent neurodevelopmental disorders. In addition to clinical assessment, its diagnosis requires the use of validated and reliable behavior questionnaires such as the Conners’ Parent Rating Scale–Revised: Short Form (CPRS-R:S). Though various French versions of the CPRS-R:S have been already put to use in clinical practice and research, only a few have undergone a stringent validation process. After a previous validation of the factorial structure of Lausanne French version, we sought here for the analysis of its invariance across sex and age. Method: This validation step was carried out in a rather homogeneous French population of 365 boys and 374 girls from a single school. Two-age classes were considered: children (boys and girls) aged 9 to 11 years ( n = 258) and adolescents aged 12 to 15 years ( n = 481). Results: Regarding age, dimension Oppositional showed a strong invariance whereas dimensions Hyperactivity and Cognitive problems/Inattention showed a partially strong invariance. Regarding sex, dimensions Oppositional and Hyperactivity showed a partially strong invariance whereas dimension Cognitive problems/Inattention showed a partially weak invariance. The distribution of the CPRS-R:S scores is given by sex and age class. Conclusion: The Lausanne French version of the CPRS-R:S, already validated regarding its factorial structure, internal consistency, and reliability, is here validated regarding its invariance across sex and age. Caution should be taken in using dimension Cognitive problems/Inattention in comparisons between boys and girls.

Objective: The objective of this study was to examine measurement invariance and discriminant validity of the French Lausanne version (FLV) of the Conners’ Parent Rating Scale–Revised, Short Form (CPRS-R:S) and assess its convergent validity against the ADHD Symptoms Rating Scale (ADHD-SRS) and the Child Behavior Checklist (CBCL). Method: A confirmatory factor analysis and Tobit models were used in 108 ADHD children (aged 6-17) vs. 794 controls (aged 9-15) and score correlations were examined between FLV and ADHD-SRS then CBCL. Results: The factorial structure and reliability of the FLV is confirmed in ADHD children. The FLV showed configural invariance, metric invariance, and scalar invariance. FLV scores were significantly higher in ADHD than in control children in all three dimensions ( p < .001). There were strong correlations between FLV Hyperactivity and Cognitive problems/Inattention scores and ADHD-SRS scores of Impulsivity/Hyperactivity ( r = .90) and Inattention ( r = .68) and also strong correlations between FLV Opposition score and the CBCL scores of Aggressive behavior ( r = .84) and Rule-breaking behavior ( r = .66). Conclusion: The study brings support for validation of the FLV regarding invariance in ADHD children, discriminant validity, and convergent validity.

International audience; Background and objective The knowledge of renal function is crucial for the management of pediatric kidney transplant recipients. In this population, the most commonly used plasma creatinine (PCr) based or cystatin C (CystC) based GFR-predicting formulas may underperform (e.g., corticosteroids and trimethoprim may affect PCr concentration, whereas prednisone and calcineurin inhibitors may affect CystC concentration). This study evaluated the performance of six formulas in pediatric kidney transplant recipients.Design, setting, participants, & measurements The study used PCr-based formulas (bedside Schwartz, Schwartz-Lyon), CystC-based formulas (Hoek, Filler), and combined PCr-CystC based formulas (CKD in Children [CKiD] 2012 and Zappitelli). The performance of these formulas was compared using inulin dearance as reference and assessed according to CKD stages in a historical cohort that included 73 pediatric kidney transplant recipients (199 measurements). The ability of the formulas to identify GFRs= 90 ml/min per 1.73 m(2) (nine patients; 23 measurements), the Zappitelli formula had the highest 30% accuracy (P30) (95% [95% confidence interval (95% CI), 87% to 100%]) and the bedside Schwartz had the highest 10% accuracy (P10) (56% [95% CI, 32% to 72%]). At mGFR60 and 80%. However, only the CKiD 2012 formula had a P10 value >50%. At mGFR90% in discriminating patients with renal dysfunction at various CKD stages (GFR

Summary Purpose Despite recent diagnostic advances, a fever of unknown origin (FUO) remains a clinical challenge. Methods This study reports the clinical courses and outcomes of 103 cases of FUO and evaluates the places of 18F-Fluorodeoxyglucose positrons emission tomography (18FDG-PET) and molecular biology in the diagnostic approach. Results This retrospective study was carried out from 2002 to 2012 in two departments of internal medicine. The diagnosis of FUO was based on the updated criteria of Durack and Street. It included 54 men and 49 women (mean age: 57 years) in 52 of whom the final diagnosis could not be established. Among the 51 patients with final diagnosis, non-infectious inflammatory disorders were the most prevalent (61%). The other diagnoses were infectious diseases (23.5%), miscellaneous causes (10%) and malignancies (6%). 18FDG-PET was performed in 48 patients and was contributory in 10. Molecular biology techniques were performed in 28 patients and were contributory in only one case: detection of a cytomegalovirus infection by polymerase-chain-reaction assay. At study closure, eleven patients had died, of whom five died from the disease that caused the FUO. Only two deaths among the 52 patients without diagnosis could be attributed to the feverish illness. Conclusion As observed in the most recent case series, the rate of undiagnosed patients is increasing. The prognosis was good for undiagnosed FUO. Here, the yield of 18FDG-PET was 21% but that of molecular biology negligible. The recourse to molecular biology seems useless unless directed by a high degree of clinical suspicion.

Steroids are nowadays routinely used as a long-term treatment in Duchenne muscular dystrophy (DMD). Their effects on body composition were assessed using dual X-ray absorptiometry. The study followed over 2 years 29 genetically confirmed DMD patients: 21 in the steroid-treated group and 8 in the steroid-naïve group. After 2 years of steroid treatment, the lean tissue mass values increased significantly (p0.0001), the percentage of body fat mass remained practically constant (p=0.94) in comparison with the initial visit. In the steroid-naïve patients, there were no significant increases in the lean tissue mass but deterioration in body composition confirmed by a significant increase in the percentage of body fat mass. Besides, significant negative correlations were found between the percentage of body fat mass and the MFM total score (R=-0.79, n=76, p0.0001). A 2-year steroid treatment improves significantly body composition of boys with DMD through a significant increase in lean tissue mass. We suggest that a thorough check of body composition should be carried out before steroid treatment discontinuation in case of overweight gain.

Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFR-predicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4- and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score ≤ or >15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR

ObjectivesNitrous oxide (N2O) present in anesthetic mixtures (e.g., equimolar mix of oxygen and N2O, EMONO) has been found responsible for various toxicities, including genetic and reproductive toxicities. N2O-containing mixtures are widely used in pediatric care units where most healthcare providers (HCPs) are women of childbearing age. This motivated an investigation of occupational exposure to N2O in search for overexposure and overexposure factors in a pediatric hospital.MethodsThis observational study concerned seven different units. On each of 34 HCPs, air samples were extracted by portable pumps and collected in Tedlar® bags. N2O was quantified by gas chromatography coupled to pulsed discharge ionization detection and infrared spectrometry. The data allowed calculating mainly the instantaneous exposure and the 8 hour time-weighted average (8h-TWA).ResultsThe exposure was four times higher in closed than in open treatment rooms and two times higher in case of use vs. non-use of EMONO. The exposure was significantly higher in junior vs. senior HCPs (by 12%) and higher during presumably short vs. presumably long procedures (by 20%). The mean 8h-TWAs were rather higher than the recommended exposure limit (25 ppm/8 hour) in emergency unit and in day hospital for thoracic and abdominal diseases. Overexposures represented 11% of all measurements but reached substantial levels (up to 3.5 times the recommended threshold).ConclusionsOverexposures to N2O were frequent during short-duration procedures. The causes of overexposure were insufficient air renewal and inappropriate equipment use. This calls for dedicated rooms, more efficient medical/nursing practices, proper training, and regular checks of gas levels.

The off-label use of TNF antagonists in refractory sarcoidosis is increasingly reported but data on their efficacy and safety are still insufficient.To report on efficacy and safety of TNF antagonists in severe and refractory sarcoidosis.Examination of retrospective demographic, clinical, therapeutic, and adverse event data on 132 sarcoidosis patients (58% women; mean (min-max) age = 45.5 (14-78) years) given TNF antagonists (mainly infliximab, 91%) and investigation of response-linked factors.The overall clinical response (complete and partial) rate was 64%. TNF-antagonist efficacy (i.e., significant decrease of the ePOST score) was noted in cases with neurologic, heart, skin, and upper respiratory tract involvements. No significant difference in efficacy was found between anti-TNF used alone and TNF with immunosuppressant. The use of anti-TNF allowed reducing prednisone dosage at end of follow-up (p0.001). Adverse events were observed in 52% of the patients; they included infections (36%) and allergic reactions (8%) and required treatment interruption in 31 cases (23%). When TNF antagonists were interrupted, 13 patients experienced relapses within 14 months on average (median follow-up: 20.5 months).TNF antagonists were efficacious in about two-thirds of patients with severe/refractory sarcoidosis but their use led to a high rate of adverse events.

Background: The survival rates of renal transplant children are indeed on the rise, but it is still important to ensure that there is optimal renal function in these children in all their future growing years. The number of functioning nephrons and the graft ability to adapt to an increasing demand during body growth seem to be the most important factors for long-term allograft function. This study examined the long-term change in the glomerular filtration rate in a pediatric kidney transplant cohort and the importance of the recipient and donor ages in predicting transplant outcome. Methods: Data on 67 renal transplant children who underwent 278 inulin-clearance measurements between 2000 and 2010 were examined. A longitudinal latent class model was used to identify renal function trajectories and classify the children. Results: This model identified 3 trajectories of renal allograft function after pediatric kidney transplantation: ‘low and decreasing', ‘moderate and stable', and ‘high and sharply decreasing'. The probability of belonging to the low and decreasing trajectory - that is, the poorer outcome - was lower in recipients of grafts from living versus deceased donor (adjusted OR (aOR) 0.02; p = 0.03). This probability increased with recipient age (aOR 1.20 per year of recipient ageing; p = 0.07) and donor-recipient age-difference (aOR 1.13 per additional year; p = 0.07). Conclusion: This study suggests that donation from living donors and from younger donors are favorable factors for long-term allograft function.

Backgroung: This study investigated the efficacy and safety of TNF antagonists in sarcoid uveitis in unselected cases. Design: This is a multicentre study on patients with sarcoidosis who received TNF antagonists in pneumology and internal medicine departments in France. We present here the subgroup of patients with biopsy-proven sarcoid uveitis included in the nationwide registry STAT (Sarcoidosis treated with TNF AnTagonists). Results: Among the 132 patients included in this multicenter study, 18 patients with refractory uveitis were treated as a first-line TNF antagonist with infliximab (n=14), adalimumab (n=3) and certolizumab (n=1). Before anti-TNF initiation, the median duration of sarcoidosis was 42 months and 83% of the patients have been treated with at least one immunosuppressive drug. Six patients switched for a second-line TNF antagonist. After a mean time under treatment of 29 months, the treatment resulted in a significant decrease of the ophthalmic extrapulmonary Physician Organ Severity Tool (ePOST) (mean score: 4.2 vs. 2.6) scores and a steroid sparing effect (29.4±20.7 vs. 6.2±5.2 mg/d). Overall, the ophthalmic response, either complete or partial, was 67%. Nine patients (50%) presented adverse events, including severe infectious complications in 5 patients, which required anti-TNF treatment interruption in 6 cases (33%). Among the 7 responder patients who discontinued anti-TNF therapy, 71% relapsed. Finally, 12 patients (67%) could continue TNF antagonist treatment. Conclusions: TNF antagonists were efficient in 67% of biopsy-proven refractory sarcoid uveitis. Severe adverse events, mainly infectious complications, were frequent. The high frequency of relapses after anti-TNF-α discontinuation requires a close patient follow-up thereafter. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 74-80)

SUMMARY Preterm newborns are at high risk of neurological injury. In this population, we investigated the link between neurological complications and sleep architecture. At term-corrected gestational age, we studied retrospectively the polysomnography of 45 preterm infants born at < 28 weeks or weighting < 1 kg. These infants were followed-up by a neuropaediatrician (median age at last follow-up 50.4 months). Two groups of children were constituted: a group without neurological disorder and a second group with at least one of the following: cerebral palsy, language or mental retardation, visual or hearing disability or attention disorder. A Multiple Indicators and Multiple Causes model assessed the relationship between the neurological outcome and two sleep components: spontaneous arousability [number of awakenings and movements per hour of quiet sleep (QS) and active sleep] and QS characteristics (median duration of QS cycles and percentage of QS over total sleep time). Twenty-six infants had an impaired neurological outcome. There were no statistical differences between the two groups regarding clinical characteristics. Compared to preterm neonates with normal neurological outcome, those with impaired outcomes had a lower spontaneous arousability; i.e. 0.7 (0.5–1) times less awakenings and movements per hour of QS and 0.9 (0.8–1) times less per hour of active sleep than infants with normal outcomes (P = 0.05). The differences in QS characteristics did not reach statistical significance. These findings suggested that, in preterm infants, perinatal neurological injuries could be associated with an abnormal sleep architecture characterized by altered spontaneous arousability.

Objective. Use of cancer cases from registries and PMSI claims database to estimate Département-specific incidence of four major cancers.Methods. Case extraction used principal diagnosis then surgery codes. PMSI cases/registry cases ratios for 2004 were modelled then Département-specific incidence for 2007 estimated using these ratios and 2007 PMSI cases.Results. For 2007, only colon-rectum and breast cancer estimations were satisfactorily validated for infranational incidence not ovary and kidney cancers. For breast, the estimated national incidence was 50,578 cases and the incidence rate 98.6 cases per 100,000 person per year. For colon-rectum, incidence was 21,172 in men versus 18,327 in women and the incidence rate 38 per 100,000 versus 24.8. For ovary, the estimated incidence was 4,637 and the rate 8.6 per 100,000. For kidney, incidence was 6,775 in men versus 3,273 in women and the rate 13.3 per 100.000 versus 5.2.Conclusion. Incidence estimation using PMSI patient identifiers proved encouraging though still dependent on the assumption of uniform cancer treatments and coding.

Objective To examine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity. Design Observational cross-sectional multicenter study. Setting Twenty-three physical medicine departments, neurology departments, or reference centers for neuromuscular diseases. Participants Patients (N=911) aged 6 to 60 years with Charcot-Marie-Tooth disease (CMT), facioscapulohumeral dystrophy (FSHD), or myotonic dystrophy type 1 (DM1). Interventions None. Main Outcome Measure(s) Comparison of the goodness-of-fit of the confirmatory factor analysis (CFA) model vs that of a modified multidimensional Rasch model on MFM item scores in each considered disease. Results The CFA model showed good fit to the data and significantly better goodness of fit than the modified multidimensional Rasch model regardless of the disease ( P .001). Statistically significant differences in item standardized factor loadings were found between DM1, CMT, and FSHD in only 6 of 32 items (items 6, 27, 2, 7, 9 and 17). Conclusions For multidimensional scales designed to measure patient abilities in various diseases, a Rasch analysis might not be the most convenient, whereas a CFA is able to establish the scale construct validity and provide weights to adapt the item scores to a specific disease.

AimTo assess changes in motor function in patients with Duchenne muscular dystrophy using the Motor Function Measure (MFM).MethodThree studies were performed. Two studies included only physiotherapy-treated patients, with 13 patients (males mean age 11y 7mo, SD 1y 10mo, range 8-14y) in the 3-month study and 41 patients (males mean age 14y 1mo, SD 5y 5mo, range 6-32y) in the 1-year study. A third study compared 12 patients treated with steroids with 12 age- and motor-function-matched untreated patients (males mean age of treated patients 10y 2mo, SD 2y 2mo range 6-14) over a 12-month period.ResultsOver 3 months, the MFM D1 subscore (standing and transfers) decreased significantly (-4.7%; p < 0.01). Over 1 year, all MFM subscores decreased significantly: -4.9% for D1 (p < 0.01); -7.7% for D2 (axial and proximal motor capacity; p < 0.01); -4.3% for D3 (distal motor capacity; p=0.03); and -5.8% for the total score (p < 0.01). A threshold value for loss of ambulation and a predictive value 1 year before loss were estimated (total score 70% and D1 subscore 40%). Compared with the controls, patients treated with steroids had more stable total scores (-0.59 vs -5.87; p=0.02) and D2 subscores (0.98 vs -8.50; p < 0.01).InterpretationThese results support the use of the MFM in everyday patient management to prepare for loss of ambulation and in clinical trials to follow up patients receiving various treatments.

Little is known about quality of life of adolescents with neuromuscular diseases or the factors that influence it. We searched whether physical impairment, physical disability, and medical complications were predictors of low quality of life.Motor function, health, orthopedic status, and rehabilitation were assessed in 43 adolescents with neuromuscular diseases (mean age, 13.8 years, standard deviation 1.7 year; sex ratio 2.9/1). Quality of life was measured with the VSP-A ("Vécu Santé Perçu par l'Adolescent"; self-perceived health state in adolescents), a validated health-related quality of life self-perception test. A mixed linear regression related quality of life to impairment, disability, and respiratory status. Comparisons were made with results from an age/sex-matched nondisabled group.On the average, the VSP-A scores in physically disabled adolescents were: (1) similar to those of the nondisabled group with regard to vitality, body image, relationships with parents and friends, and physical and psychological well-being; (2) higher with regard to school performance (score 68 vs. 52.8) and relationships with teachers (67.4 vs. 43.2); and (3) lower with regard to leisure activities (43.9 vs. 60.9). Physical disability and physical impairment were not negatively associated with seven of the nine VSP-A dimensions, but physical impairment was negatively associated with leisure activities and vitality (p.001 and p.01, respectively). Adolescents with ventilatory support did not express lower scores than adolescents not requiring ventilatory support (67.7+/-11 vs. 62.9+/-15, p=.39).These surprising results should lead us question our medical, educational, and rehabilitation practices. Already well-managed disabled adolescents should benefit from less compassionate but more daring and dynamic interpersonal contacts.

International audience; One approach to estimate cancer incidence in the French D?rtements is to quantify the relationship between data in cancer registries and data obtained from the PMSI (Programme de M?calisation des Syst?s d'Information M?cale). This relationship may then be used in D?rtements without registries to infer the incidence from local PMSI data. We present here some methodological solutions to apply this approach. Data on invasive breast cancer for 2002 were obtained from 12 D?rtemental registries. The number of hospital stays was obtained from the National PMSI using two different algorithms based on the main diagnosis only (Algorithm 1) or on that diagnosis associated to a mention of "resection" (Algorithm 2). Considering registry data as gold standard, a calibration approach was used to model the ratio of the number of hospital stays to the number of incident cases. In D?rtements with registries, validation of the predictions was done through cross-validation. In D?rtements without registries, validation was done through a study of homogeneity of the mean number of hospital stays per patient. Cross-validation showed that the estimates predicted by the model were true with data extracted by Algorithm 1 but not by Algorithm 2. However, with Algorithm 1, there was an important heterogeneity between French D?rtements as to the mean number of hospital stays per patient, which had an important impact on the estimations. In the near future, the method will allow using medico-administrative data (after calibration with registry data) to estimate D?rtemental incidence of selected cancers.