Place of concordance-discordance model in evaluating NGS performance.

INTRODUCTION: Ideally, evaluating NGS performance requires a gold standard; in its absence, concordance between replicates is often used as substitute standard. However, the appropriateness of the concordance-discordance criterion has been rarely evaluated. This study analyzes the relationship between the probability of discordance and the probability of error under different conditions. METHODS: This study used a conditional probability approach under conditional dependence then conditional independence between two sequencing results and compares the probabilities of discordance and error in different theoretical conditions of sensitivity, specificity, and correlation between replicates, then on real results of sequencing genome NA12878. The study examines also covariate effects on discordance and error using generalized additive models with smooth functions. RESULTS: With 99% sensitivity and 99.9% specificity under conditional independence, the probability of error for a positive concordant pair of calls is 0.1%. With additional hypotheses of 0.1% prevalence and 0.9 correlation between replicates, the probability of error for a positive concordant pair is 47.4%. With real data, the estimated sensitivity, specificity, and correlation between tests for variants are around 98.98%, 99.996%, and 93%, respectively, and the error rate for positive concordant calls approximates 2.5%. In covariate effect analyses, the effects' functional form are close between discordance and error models, though the parts of deviance explained by the covariates differ between discordance and error models. CONCLUSION: With conditional independence of two sequencing results, the concordance-discordance criterion seems acceptable as substitute standard. However, with high correlation, the criterion becomes questionable because a high percentage of false concordant results appears among concordant results.

Screening for psychosocial risks among physicians in a pediatric hospital.

Over the past decades, productivity practices at hospital resulted in staff overload and burnout. Prompted by physicians' complaints, this study assessed the level of psychosocial risk among senior pediatricians in a university hospital. The survey used the checklist of Quebec's National Institute of Public Health that comprises two six-indicator parts: "Context" and "Key Components" of the Organization. The psychosocial risk level was evaluated by a physician-psychologist duo during interviews of homogeneous groups of workers. The indicators were scored, tabulated, and discussed. The survey led to a substantial qualitative and quantitative clarification of physicians' working conditions, claims, and needs. Regarding Context, the staff reported mainly: (a) cumbersome organization and norms vs. limited human resources (lack of stability, incentives, and promotions); (b) absenteeism and presenteeism; (c) reluctance to seek care or advice for fear of discredit; (d) presence of verbal violence; (e) self-imposed harsh returns-to-work; (f) work-life conflicts and difficult mental disconnection from work. Regarding the Key Components, the staff reported mainly: (a) work overload (physical, mental, psychological, and relational/social), continuous stress, and perceived exhaustion; (b) low job satisfaction and insufficient recognition; (c) inconstant support by their superiors; (d) poor job relationships and colleagues' support; (e) occasional participation and lack of real autonomy and/or strategy sharing. The survey succeeded in underlining concerning issues that required the immediate attention of occupational physicians and managers. It proved the method feasible and valuable in the medical context despite a high diversity of staff functions and degrees.

Disclosure of HIV status and adherence to antiretroviral treatment in children and adolescents from Lomé and Abidjan.

Introduction: in Africa, the proportion of minors with AIDS is ever increasing and adherence to treatment protocols is still suboptimal. The study investigated the conditions of HIV status disclosure and adherence to treatment in patients < 19 in two West African cities. Methods: in 2016, thirteen health professionals and four parents filled out questionnaires to identify problems and solutions relative to disclosure of HIV status and adherence to treatment in 208 children and adolescents seen at University Hospitals in Abidjan (Ivory Coast) and Lomé (Togo). Results: medians (extrema) of patients´ ages at start and end of status disclosure process were 10 (8-13) and 15 (13-17.5) years. In 61% of cases, disclosure was made individually after preparation sessions. The main difficulties were: parents´ disapproval, skipped visits, and rarity of psychologists. The solutions proposed were: recruiting more full-time psychologists, improving personnel training, and promoting patients´ "clubs". One out of three respondents was not satisfied with patients´ adherence to treatments. The major reasons were: intake frequencies, frequent omissions, school constraints, adverse effects, and lack of perceived effect. Nevertheless, 94% of the respondents confirmed the existence of support groups, interviews with psychologists, and home visits. To improve adherence, the respondents proposed increasing the number of support groups, sustaining reminder phone calls and home visits, and supporting therapeutic mentoring. Conclusion: despite persisting disclosure and adherence problems, appropriate measures already put into practice still need to be taken further, especially through engaging psychologists, training counsellors, and promoting therapeutic support groups.

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.

Performance comparisons between clustering models for reconstructing NGS results from technical replicates.

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.

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.

Predicted Impacts of Booster, Immunity Decline, Vaccination Strategies, and Non-Pharmaceutical Interventions on COVID-19 Outcomes in France.

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.

Effectiveness of seasonal malaria chemoprevention in three regions of Togo: a population-based longitudinal study from 2013 to 2020.

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 < 0.001) and 75% in 2020 (p < 0.001). SMC effectiveness ranged from 76.6% (2nd round) to 96.2% (4th round) comparison with the 1st round. 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.

Development and Survival of Human Ovarian Cells in Chitosan Hydrogel Micro-Bioreactor.

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.

Selected and simplified FDI criteria for assessment of restorations.

OBJECTIVES: Assess the quality of dental restorations with simplified FDI criteria and examine its relationships with other general characteristics of restored teeth. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL SIGNIFICANCE: 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.

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.

Exposure of paediatric healthcare personnel to nitrous oxide in paediatric care units.

Nitrous oxide (N2O) was found responsible for genetic and reproductive toxicities, whereas it is widely used in paediatric care units where most healthcare providers are women of childbearing age. This motivated investigating occupational overexposure and overexposure factors in several paediatric hospital units. A cross-sectional study was carried out in seven healthcare units. On each of 34 healthcare providers, air samples were extracted (portable pumps and Tedlar® bags) and N2O quantified (gas chromatography, pulsed discharge ionization detection, and infrared spectrometry). The data allowed calculating mean instantaneous exposures. The mean instantaneous exposure was: i) four times higher in closed vs. open treatment rooms; ii) two times higher in case of use vs. non-use of N2O; iii) significantly higher in junior vs. senior healthcare providers (by 12%); and, iv) higher during presumably short vs. presumably long procedures (by 20%). Overexposures to N2O were mainly seen in the emergency unit and in day hospitals for thoracic/abdominal diseases and nephrology. Overexposures were frequent during short-duration procedures; among 88 N2O measurements, 77 (87.5%) exceeded the 200 ppm threshold over 15 minutes. The overexposures call for dedicated treatment rooms (with adequate equipment and ventilation), more efficient anaesthetic practices, appropriate training, and regular checks.

The impact of left truncation of exposure in environmental case-control studies: evidence from breast cancer risk associated with airborne dioxin.

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.

Gain in net survival from hypertension control over the last half-century.

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.

Determining the Interrater Reliability of the SOFMER Activity Score (version 2) for Individuals in Rehabilitation Centers.

OBJECTIVE: 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. DESIGN: Cross-sectional, prospective, observational, noninterventional, and multicentric study. SETTING: 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). PARTICIPANTS: 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%). INTERVENTIONS: None. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Expected Evolution of COVID-19 Epidemic in France for Several Combinations of Vaccination Strategies and Barrier Measures.

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.

Protocol of controlled odorant stimulation for reducing apnoeic episodes in premature newborns: a randomised open-label Latin-square study with independent evaluation of the main endpoint (PREMODEUR).

INTRODUCTION: Apnoea affects 85% of premature infants under 34 weeks of age and would be an important risk factor for subsequent neuropsychological disorders. Currently, premature children with life-threatening apnoeas receive stimulants such as methylxanthines (mainly, caffeine) or doxapram (an analeptic unlicensed in children under 15). However, these products have undesirable effects (hyperarousal, irritability, sleep disorders, tachycardia) and are not always effective because apnoea does persist in some premature newborns. Previous studies have indicated that odorant stimulation, a non-invasive intervention, may stimulate the respiratory rhythm. The objective of the present protocol is to reduce the occurrence of apnoeic episodes in premature newborns by controlled odorant stimulation added to current pharmacological treatments. METHODS AND ANALYSIS: The project is a randomised open-label Latin-square trial with independent evaluation of the main endpoint. It will include 60 preterm neonates from two university hospital neonatal intensive care units over 2 years (2021-2023). Each newborn will receive no (S0), sham (S1) or real olfactory stimulation (S2) in random order. During S2, three distinct odorants (mint, grapefruit and vanilla) will be delivered successively, in puffs, over 24 hours. Mint and grapefruit odours stimulate the main and the trigeminal olfactory pathways, whereas vanilla odour stimulates only the main olfactory pathway. A statistical analysis will compare the incidence of apnoeic episodes during S1 versus S2 using a mixed effects Poisson model. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Comité de Protection des Personnes Île-de-France XI (# 2017-AO13-50-53). The results will be disseminated through various scientific meetings, specialised peer-reviewed journals and, whenever possible, posted on appropriate public websites. TRIAL REGISTRATION NUMBER: NCT02851979; Pre-results.

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.

Validation of the French Version of Conners' Parent Rating Scale-Revised, Short Form in ADHD-Diagnosed Children and Comparison With Control Children.

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.