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Abstract Background While patient safety incident reporting is of key importance for patient safety in primary care, the reporting rate by healthcare professionals remains low. This study aimed to assess the effectiveness of a risk management program in increasing the reporting rate within multiprofessional primary care facilities. Methods A nation-wide cluster-randomised controlled trial was performed in France, with each cluster defined as a primary care facility. The intervention included professional e-learning training, identification of a risk management advisor, and multidisciplinary meetings to address incident analysis. In the first observational period, a patient safety incident reporting system for professionals was implemented in all facilities. Then, facilities were randomised, and the program was implemented. Incidents were reported over the 15-month study period. Quasi-Poisson models were used to compare reporting rates. Results Thirty-five facilities (intervention, n = 17; control, n = 18) were included, with 169 and 232 healthcare professionals, respectively, involved. Overall, 7 out of 17 facilities carried out the entire program (41.2%), while 6 did not hold meetings (35.3%); 48.5% of professionals logged on to the e-learning website. The relative rate of incidents reported was 2.7 (95% CI = [0.84–11.0]; p = 0.12). However, a statistically significant decrease in the incident rate between the pre-intervention and post-intervention periods was observed for the control arm (HR = 0.2; 95% CI = [0.05–0.54]; p = 0.02), but not for the intervention arm (HR = 0.54; 95% CI = [0.2–1.54]; p = 0.23). Conclusion This program didn’t lead to a significant improvement in the patient safety incident reporting rate by professionals but seemed to sustain reporting over time. Considering that the program was fully implemented in only 41% of facilities, this highlights the difficulty of implementing such multidisciplinary programs in primary care despite its adaptation to the setting. A better understanding of how risk management is currently organized in these multiprofessional facilities is of key importance to improve patient safety in primary care. Trial registrations The study has been registered at clinicaltrials.gov (NCT02403388) on 30 March 2015.

Objectives Integrating malaria prediction models into malaria control strategies can help to anticipate the response to seasonal epidemics. This study aimed to explore the possibility of using routine malaria data and satellite-derived climate data to forecast malaria cases in Togo.Methods Generalised additive (mixed) models were developed to forecast the monthly number of malaria cases in 40 health districts and three target groups. Routinely collected malaria data from 2013 to 2016 and meteorological and vegetation data with a time lag of 1 or 2 months were used for model training, while the year 2017 was used for model testing. Two methods for selecting lagged meteorological and environmental variables were compared: a first method based on statistical approach (‘SA’) and a second method based on biological reasoning (‘BR’). Both methods were applied to obtain a model per target group and health district and a mixed model per target group and health region with the health district as a random effect. The predictive skills of the four models were compared for each health district and target group.Results The most selected predictors in the models per district for the ‘SA’ method were the normalised difference vegetation index, minimum temperature and mean temperature. The ‘SA’ method provided the most accurate models for the training period, except for some health districts in children ≥5 years old and adults and in pregnant women. The most accurate models for the testing period varied by health district and target group, provided either by the ‘SA’ method or the ‘BR’ method. Despite the development of models with four different approaches, the number of malaria cases was inaccurately forecasted.Conclusions These models cannot be used as such in malaria control activities in Togo. The use of finer spatial and temporal scales and non-environmental data could improve malaria prediction.

Abstract Objective: To determine the factors associated with the nutritional status of children under 5 years of age in Guinea between 2005 and 2018. Design: Data from the 2005, 2012 and 2018 Guinea Demographic and Health Surveys (DHS) were used for this study. Three anthropometric indicators (stunting, underweight and wasting) were assessed according to the 2006 WHO Child Growth Standards and analysed according to the year, the characteristics of the household, the child and the mother using multivariate logistic regression. Setting: Data were collected in the capital Conakry and in the seven administrative regions of Guinea. Participants: The study included children under 5 years of age for whom height and weight were available: 2765 (DHS-2005), 3220 (DHS-2012) and 3551 (DHS-2018). Results: Analysis of the data from the three surveys showed that children living in rural areas were more likely to be stunted than children living in urban areas (OR = 1·32, 95 % CI (1·08, 1·62)). Similarly, the children from middle, poor and the poorest households were more likely to be stunted and underweight than children from richest households. The chance to stunting increased with age in the first 3 years. However, the chance to wasting decreased with age. Children in all age groups were more likely of being underweight. Children of thin mothers were more likely to be both wasted (OR = 2·0, 95 % CI (1·5, 2·6)) and underweight (OR = 1·9, 95 % CI (1·5, 2·3)). Conclusion: The implementation of targeted interventions adapted to the observed disparities could considerably improve the nutritional status of children and mothers.

Key points 1. Juniors characterized aggressive cancers less well than experienced seniors on prostate MRI. 2. Agreement between readers remained moderate even for experienced readers. 3. As compared to version 2, PI-RADSv2.1 descriptors tended to show improved specificity.

Abstract 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

Abstract Background In the Lao People's Democratic Republic (Lao PDR), cervical cancer is the third leading cause of women cancer. Aims The objective of this cross‐sectional study was to compare the efficacy of careHPV™ test versus conventional Pap smear or Siriraj liquid‐based cytology in the detection of cervical cancer in women living with human immunodeficiency virus type 1 (HIV‐1). Materials & Methods Overall, 631 women consented to participate. Four cervical specimens were taken for the purpose of conventional Pap smear, Siriraj liquid‐based cytology, careHPV™ test, and HPV‐16 genotyping. The exact McNemar test was used to compare the efficacy and diagnostic performance of the tests. Results Of the 631 women with follow‐up, 331 were human papillomavirus (HPV) negative. High‐grade squamous intraepithelial lesions were found in 37 women, biopsy‐proven high‐grade cervical intraepithelial neoplasia in 50 women, and invasive carcinoma in seven women. The proportion of women with high‐grade cervical lesion or carcinoma detected after abnormal careHPV™ test was higher (6.02%; 95% confidence interval [CI]: 4.4–8.1) than that detected by conventional Pap smear (4.59%; 95% CI: 3.2–6.5). careHPV™ and HPV‐16 genotyping had, respectively, the highest sensitivity (80.8%; 95% CI: 67.4–89.5) and specificity (92.2%; 95% CI: 89.8–94.2). HPV‐16 was the most frequently detected genotype. Conclusions careHPV™ test represents a screening option in Lao PDR, particularly in women living with HIV‐1 because of higher prevalence of chronic HPV in this population.

Abstract Background Stroke affects many aspects of life in stroke survivors and their family, and returning home after hospital discharge is a key step for the patient and his or her relatives. Patients and caregivers report a significant need for advice and information during this transition period. Our hypothesis is that, through a comprehensive, individualised and flexible support for patients and their caregivers, a patient-centred post-stroke hospital/home transition programme, combining an Internet information platform and telephone follow-up by a case manager, could improve patients’ level of participation and quality of life. Methods An open parallel-group randomized trial will be conducted in two centres in France. We will recruit 170 adult patients who have had a first confirmed stroke, and were directly discharged home from the stroke unit with a modified Rankin score ≤3. Intervention content will be defined using a user-centred approach involving patients, caregivers, health-care professionals and social workers. Patients randomized to the intervention group will receive telephonic support by a trained case manager and access to an interactive Internet information platform during the 12 months following their return home. Patients randomized to the control group will receive usual care. The primary outcome is patient participation, measured by the “participation” dimension score of the Stroke Impact Scale 6 months after discharge. Secondary outcomes will include, for patients, quality of life, activation, care consumption, as well as physical, mental and social outcomes; and for caregivers, quality of life and burden. Patients will be contacted within one week after discharge, at 6 and 12 months for the outcomes collection. A process evaluation alongside the study is planned. Discussion Our patient-centred programme will empower patients and their carers, through individualised and progressive follow-up, to find their way around the range of available healthcare and social services, to better understand them and to use them more effectively. The action of a centralised case manager by telephone and the online platform will make it possible to disseminate this intervention to a large number of patients, over a wide area and even in cases of geographical isolation. Trial registration: ClinicalTrials NCT03956160 , Posted: May-2019 and Update: September-2021.

Abstract Introduction The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co‐occurrence of COVID‐19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia). Methods This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia. Results The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible. Conclusions Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research. Trial registration Trial registration number: ISRCTN-81915073 . Date of registration: 17/04/2020, 'Retrospectively registered'.

Objectives: We evaluated the contribution of lung lesion quantification on chest CT using a clinical Artificial Intelligence (AI) software in predicting death and intensive care units (ICU) admission for COVID-19 patients. Methods: For 349 patients with positive COVID-19-PCR test that underwent a chest CT scan at admittance or during hospitalization, we applied the AI for lung and lung lesion segmentation to obtain lesion volume (LV), and LV/Total Lung Volume (TLV) ratio. ROC analysis was used to extract the best CT criterion in predicting death and ICU admission. Two prognostic models using multivariate logistic regressions were constructed to predict each outcome and were compared using AUC values. The first model (“Clinical”) was based on patients’ characteristics and clinical symptoms only. The second model (“Clinical+LV/TLV”) included also the best CT criterion. Results: LV/TLV ratio demonstrated best performance for both outcomes; AUC of 67.8% (95% CI: 59.5 - 76.1) and 81.1% (95% CI: 75.7 - 86.5) respectively. Regarding death prediction, AUC values were 76.2% (95% CI: 69.9 - 82.6) and 79.9% (95%IC: 74.4 - 85.5) for the “Clinical” and the “Clinical+LV/TLV” models respectively, showing significant performance increase (+ 3.7%; p-value

Abstract Background This study aimed to assess the seasonality of confirmed malaria cases in Togo and to provide new indicators of malaria seasonality to the National Malaria Control Programme (NMCP). Methods Aggregated data of confirmed malaria cases were collected monthly from 2008 to 2017 by the Togo’s NMCP and stratified by health district and according to three target groups: children

Abstract Background Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34–50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg−1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation. Methods The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg−1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg−1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles. Discussion The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing. Trial registration ClinicalTrials.gov NCT04349618 . Registered on April 16, 2020

Abstract Background About 25% of patients experience adverse drug events (ADE) in primary care, but few events are reported by the patients themselves. One solution to improve the detection and management of ADEs in primary care is for patients to report them to their general practitioner. The study aimed to assess the effect of a booklet designed to improve communication and interaction between patients treated with anti-hypertensive drugs and general practitioners on the reporting of ADEs. Methods A cluster randomized controlled cross-sectional stepped wedge open trial (five periods of 3 months) was conducted. A cluster was a group of general practitioners working in ambulatory offices in France. Adults consulting their general practitioner to initiate, modify, or renew an antihypertensive prescription were included. A booklet including information on cardiovascular risks, antihypertensive treatments, and ADE report forms was delivered by the general practitioner to the patient in the intervention group. The primary outcome was the reporting of at least one ADE by the patient to his general practitioner during the three-month period after enrolment. Two clusters were randomised by sequence for a total of 8 to receive the intervention. An intention-to-treat analysis was conducted. A logistic mixed model with random intercept was used. Results Sixty general practitioners included 1095 patients (median: 14 per general practitioner; range: 1–103). More patients reported at least one ADE to their general practitioner in the intervention condition compared to the control condition (aOR = 3.5, IC95 [1.2–10.1], p = 0.02). The modification and initiation of an antihypertensive treatment were also significantly associated with the reporting of ADEs (aOR = 4.4, CI95 [1.9–10.0], p

Background and AimsIntracranial Hypertension (ICH) is a life-threatening complication of brain injury. The invasive measurement of intracranial pressure (ICP) remains the gold standard to diagnose ICH. Measurement of Optic Nerve Sheath Diameter (ONSD) using ultrasonography is a non-invasive method for detecting ICH. However, data on paediatric brain injury are scarce. The aim of the study was to determine the performance of the initial ONSD measurement to predict ICH occurring in children with severe brain injury and to describe the ONSD values in a control group.MethodsIn this cross-sectional study, ONSD was measured in children aged 2 months-17 years old with invasive ICP monitoring: before placement of ICP probe and within the 60 min after, and then daily during 3 days. ONSD was also measured in a control group.ResultsNinety-nine patients were included, of whom 97 were analysed, with a median (IQR) age of 8.7 [2.3–13.6] years. The median (IQR) PIM 2 score was 6.6 [4.4–9.7] and the median (IQR) PELOD score was 21 [12–22]. Aetiologies of brain injury were trauma (n = 72), infection (n = 17) and stroke (n = 8). ICH occurred in 65 children. The median (IQR) ONSD was 5.58 mm [5.05–5.85]. ONSD performed poorly when it came to predicting ICH occurrence within the first 24 h (area under the curve, 0.58). There was no significant difference between the ONSD of children who presented with ICH within the first 24 h and the other children, with a median (IQR) of 5.6 mm [5.1–5.9] and 5.4 mm [4.9–5.8], respectively. Infants aged less than 2 years had a median (IQR) ONSD of 4.9 mm [4.5–5.2], significantly different from children aged more than 2 years, whose median ONSD was 5.6 mm [5.2–5.9]. Age, aetiology or ICP levels did not change the results. Thirty-one controls were included, with a median age of 3.7 (1.2–8.8) years. The median (IQR) of their ONSD measurement was 4.5 mm [4.1–4.8], significantly lower than the patient group.ConclusionIn a paediatric severe brain injury population, ONSD measurement could not predict the 24 h occurrence of ICH. Severity of patients, timing and conditions of measurements may possibly explain these results.

Abstract Background In common with many South East Asian countries, Malaysia is endemic for dengue. Dengue control in Malaysia is currently based on reactive vector management within 24 h of a dengue case being reported. Preventive rather than reactive vector control approaches, with combined interventions, are expected to improve the cost-effectiveness of dengue control programs. The principal objective of this cluster randomized controlled trial is to quantify the effectiveness of a preventive integrated vector management (IVM) strategy on the incidence of dengue as compared to routine vector control efforts. Methods The trial is conducted in randomly allocated clusters of low- and medium-cost housing located in the Federal Territory of Kuala Lumpur and Putrajaya. The IVM approach combines: targeted outdoor residual spraying with K-Othrine Polyzone, deployment of mosquito traps as auto-dissemination devices, and community engagement activities. The trial includes 300 clusters randomly allocated in a 1:1 ratio. The clusters receive either the preventive IVM in addition to the routine vector control activities or the routine vector control activities only. Epidemiological data from monthly confirmed dengue cases during the study period will be obtained from the Vector Borne Disease Sector, Malaysian Ministry of Health e-Dengue surveillance system. Entomological surveillance data will be collected in 12 clusters randomly selected from each arm. To measure the effectiveness of the IVM approach on dengue incidence, a negative binomial regression model will be used to compare the incidence between control and intervention clusters. To quantify the effect of the interventions on the main entomological outcome, ovitrap index, a modified ordinary least squares regression model using a robust standard error estimator will be used. Discussion Considering the ongoing expansion of dengue burden in Malaysia, setting up proactive control strategies is critical. Despite some limitations of the trial such as the use of passive surveillance to identify cases, the results will be informative for a better understanding of effectiveness of proactive IVM approach in the control of dengue. Evidence from this trial may help justify investment in preventive IVM approaches as preferred to reactive case management strategies. Trial registration ISRCTN ISRCTN81915073 . Retrospectively registered on 17 April 2020.

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.

Objective: The WHO Malaria Report 2019 stated that “globally, the burden of malaria was lower than ten years ago, but, in the last few years, there has been an increase in the number of malaria cases around the world”. This study reported changes in malaria cases and deaths at the Togo national level (2008–2017) and presented anti-malaria fight results and eradication chances by 2030 in Togo. Methods: Cases and deaths were collected from medical records, monthly reports, and notes of 6000 health workers; then summarized by Region, District, year, and specific subpopulations. Estimates of annual trends of numbers of cases and deaths were obtained through generalized linear models. Results: The number of cases increased by four times, whereas the population increased by 1.3 times (2008–2017). Increases affected all regions and subpopulations; the mean annual relative increases in children

Abstract Background In most health areas, an information system is necessary for an effective fight against COVID-19. Current methods for surveillance of diseases with epidemic potential do not include monitoring the adherence to preventive measures. Furthermore, modern data collection methods depend often on technologies (e.g., cameras or drones) that are hardly available in low-income countries. Simpler solutions could be just as effective. Methods A dashboard was used over a whole week to monitor preventive measures in Bukavu (DRC) by mid-May 2020. It was designed to collect from street passers-by information on the adherence to barrier measures, the level of awareness of these measures, the opinion on their usefulness, and the health status of people in the households. Results Creating a dashboard and collecting the necessary data proved feasible. The use of barrier measures was very limited and that of masks practically nil despite repeated recommendations from the health authorities. The end of each day was the worst moment due to clearly insufficient distancing. Barrier measures were significantly more used in areas where they were best known and most acknowledged. At the time of the study, there were few sick people and only rare severe cases were attributed to COVID-19. Conclusions Creating COVID-19 situation dashboards in limited-resource metropoles is feasible. They give real-time access to data that help fight the epidemic. The findings of this pilot study call for a rapid community awareness actions to back national media-based prevention campaigns.

Abstract Background The “practice makes perfect” concept considers the more frequent a hospital performs a procedure, the better the outcome of the procedure. We aimed to study this concept by investigating whether patient outcomes improve in hospitals with a significantly increased volume of high-risk surgery over time and whether a learning effect existed at the individual hospital level. Methods We included all patients who underwent one of 10 digestive, cardiovascular and orthopaedic procedures between 2010 and 2014 from the French nationwide hospitals database. For each procedure, we identified three groups of hospitals according to volume trend (increased, decreased, or no change). In-hospital mortality, reoperation, and unplanned hospital readmission within 30 days were compared between groups using Cox regressions, taking into account clustering of patients within hospitals and potential confounders. Individual hospital learning effect was investigated by considering the interaction between hospital groups and procedure year. Results Over 5 years, 759,928 patients from 694 hospitals were analysed. Patients’ mortality in hospitals with procedure volume increase or decrease over time did not clearly differ from those in hospitals with unchanged volume across the studied procedures (e.g., Hazard Ratios [95%] of 1.04 [0.93–1.17] and 1.08 [0.97–1.21] respectively for colectomy). Furthermore, patient outcomes did not improve or deteriorate in hospitals with increased or decreased volume of procedures over time (e.g., 1.01 [0.95–1.08] and 0.99 [0.92–1.05] respectively for colectomy). Conclusions Trend in hospital volume over time did not appear to influence patient outcomes based on real-world data. Trial registration NCT02788331 , June 2, 2016.

BackgroundWorldwide, 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 methodsThis 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.ResultsThe 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]).ConclusionThe 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.

Abstract Background Insufficient elastin synthesis leads to vascular complications and arterial hypertension in children with Williams-Beuren syndrome. Restoring sufficient quantity of elastin should then result in prevention or inhibition of vascular malformations and improvement in arterial blood pressure. Methods The aim of this study was to assess the efficacy and safety of minoxidil on Intima Media Thickness (IMT) on the right common carotid artery after twelve-month treatment in patient with Williams-Beuren syndrome. We performed a randomized placebo controlled double blind trial. All participants were treated for 12 months and followed for 18 months. The principal outcome was assessed by an independent adjudication committee blinded to the allocated treatment groups. Results The principal outcome was available for 9 patients in the placebo group and 8 patients in the minoxidil group. After 12-month treatment, the IMT in the minoxidil group increased by 0.03 mm (95% CI -0.002, 0.06) compared with 0.01 mm (95%CI - 0.02, 0.04 mm) in the placebo group (p = 0.4). Two serious adverse events unrelated to the treatment occurred, one in the minoxidil and 1 in the placebo group. After 18 months, the IMT increased by 0.07 mm (95% CI 0.04, 0.10 mm) in the minoxidil compared with 0.01 mm (95% CI -0.02, 0.04 mm) in the placebo group (p = 0.008). Conclusion Our results suggest a slight increase after 12 and 18-month follow-up in IMT. More understanding of the biological changes induced by minoxidil should better explain its potential role on elastogenesis in Williams-Beuren syndrome. Trials registration US National Institutes of Health Clinical Trial Register (NCT00876200). Registered 3 April 2009 (retrospectively registered).

Introduction The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated.Methods and analysis We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions.Ethics and dissemination Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals.Trial registration number NCT04341142.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18–70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (

Abstract Background In randomized clinical trials or observational studies, it is common to collect biomarker values longitudinally on a cohort of individuals. The investigators may be interested in grouping individuals that share similar changes of biomarker values and use these groups for diagnosis or therapeutic purposes. However, most classical model-based classification methods rely mainly on empirical models such as splines or polynomials and do not reflect the physiological processes. Methods A model-based classification method was developed for longitudinal biomarker measurements through a pharmacokinetic model that describes biomarker changes over time. The method is illustrated using data on human Chorionic Gonadotrophic Hormone measurements after curettage of hydatidiform moles. Results The resulting classification was linked to the evolution toward gestational trophoblastic neoplasia and may be used as a tool for early diagnosis. The diagnostic accuracy of the pharmacokinetic model was more reproducible than the one of a purely mathematical model that did not take into account the biological processes. Conclusion The use of pharmacokinetic models in model-based classification approaches can lead to clinically useful classifications.

To assess the diagnostic weight of sequence-specific magnetic resonance features in characterizing clinically significant prostate cancers (csPCa).We used a prospective database of 262 patients who underwent T2-weighted, diffusion-weighted, and dynamic contrast-enhanced (DCE) imaging before prostatectomy. For each lesion, two independent readers (R1, R2) prospectively defined nine features: shape, volume (V_Max), signal abnormality on each pulse sequence, number of pulse sequences with a marked (S_Max) and non-visible (S_Min) abnormality, likelihood of extracapsular extension (ECE) and PSA density (dPSA). Overall likelihood of malignancy was assessed using a 5-level Likert score. Features were evaluated using the area under the receiver operating characteristic curve (AUC). csPCa was defined as Gleason ≥7 cancer (csPCa-A), Gleason ≥7(4+3) cancer (csPCa-B) or Gleason ≥7 cancer with histological extraprostatic extension (csPCa-C).For csPCa-A, the Signal1 model (S_Max+S_Min) provided the best combination of signal-related variables, for both readers. The performance was improved by adding V_Max, ECE and/or dPSA, but not shape. All models performed better with DCE findings than without. When moving from csPCa-A to csPCa-B and csPCa-C definitions, the added value of V_Max, dPSA and ECE increased as compared to signal-related variables, and the added value of DCE decreased. For R1, the best models were Signal1+ECE+dPSA (AUC = 0,805 [95%CI:0,757-0,866]), Signal1+V_Max+dPSA (AUC = 0.823 [95%CI:0.760-0.893]) and Signal1+ECE+dPSA [AUC = 0.840 (95%CI:0.774-0.907)] for csPCa-A, csPCA-B and csPCA-C respectively. The AUCs of the corresponding Likert scores were 0.844 [95%CI:0.806-0.877, p = 0.11], 0.841 [95%CI:0.799-0.876, p = 0.52]) and 0.849 [95%CI:0.811-0.884, p = 0.49], respectively. For R2, the best models were Signal1+V_Max+dPSA (AUC = 0,790 [95%CI:0,731-0,857]), Signal1+V_Max (AUC = 0.813 [95%CI:0.746-0.882]) and Signal1+ECE+V_Max (AUC = 0.843 [95%CI: 0.781-0.907]) for csPCa-A, csPCA-B and csPCA-C respectively. The AUCs of the corresponding Likert scores were 0. 829 [95%CI:0.791-0.868, p = 0.13], 0.790 [95%CI:0.742-0.841, p = 0.12]) and 0.808 [95%CI:0.764-0.845, p = 0.006]), respectively.Combination of simple variables can match the Likert score's results. The optimal combination depends on the definition of csPCa.

BackgroundEstimating kidney glomerular filtration rate (GFR) is of utmost importance in many clinical conditions. However, very few studies have evaluated the performance of GFR estimating equations over all ages and degrees of kidney impairment. We evaluated the reliability of two major equations for GFR estimation, the CKD-EPI and Schwartz equations, with urinary clearance of inulin as gold standard.Methods and findingsThe study included 10,610 participants referred to the Renal and Metabolic Function Exploration Unit of Edouard Herriot Hospital (Lyon, France). GFR was measured by urinary inulin clearance (only first measurement kept for analysis) then estimated with isotope dilution mass spectrometry (IDMS)-traceable CKD-EPI and Schwartz equations. The participants' ages ranged from 3 to 90 y, and the measured GFRs from 3 to 160 ml/min/1.73 m2. A linear mixed-effects model was used to model the bias (mean ratio of estimated GFR to measured GFR). Equation reliability was also assessed using precision (interquartile range [IQR] of the ratio) and accuracy (percentage of estimated GFRs within the 10% [P10] and 30% [P30] limits above and below the measured GFR). In the whole sample, the mean ratio with the CKD-EPI equation was significantly higher than that with the Schwartz equation (1.17 [95% CI 1.16; 1.18] versus 1.08 [95% CI 1.07; 1.09], p < 0.001, t-test). At GFR values of 60-89 ml/min/1.73 m2, the mean ratios with the Schwartz equation were closer to 1 than the mean ratios with the CKD-EPI equation whatever the age class (1.02 [95% CI 1.01; 1.03] versus 1.15 [95% CI 1.13; 1.16], p < 0.001, t-test). In young adults (18-40 y), the Schwartz equation had a better precision and was also more accurate than the CKD-EPI equation at GFR values under 60 ml/min/1.73 m2 (IQR: 0.32 [95% CI 0.28; 0.33] versus 0.40 [95% CI 0.36; 0.44]; P30: 81.4 [95% CI 78.1; 84.7] versus 63.8 [95% CI 59.7; 68.0]) and also at GFR values of 60-89 ml/min/1.73 m2. In all patients aged ≥65 y, the CKD-EPI equation performed better than the Schwartz equation (IQR: 0.33 [95% CI 0.31; 0.34] versus 0.40 [95% CI 0.38; 0.41]; P30: 77.6 [95% CI 75.7; 79.5] versus 67.5 [95% CI 65.4; 69.7], respectively). In children and adolescents (2-17 y), the Schwartz equation was superior to the CKD-EPI equation (IQR: 0.23 [95% CI 0.21; 0.24] versus 0.33 [95% CI 0.31; 0.34]; P30: 88.6 [95% CI 86.7; 90.4] versus 29.4 [95% CI 26.8; 32.0]). This study is limited by its retrospective design, single-center setting with few non-white patients, and small number of patients with severe chronic kidney disease.ConclusionsThe results from this study suggest that the Schwartz equation may be more reliable than the CKD-EPI equation for estimating GFR in children and adolescents and in adults with mild to moderate kidney impairment up to age 40 y.

BACKGROUND:In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. METHODS:The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. RESULTS:The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70. CONCLUSIONS:The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.

To evaluate in unselected patients imaged under routine conditions the co-registration accuracy of elastic fusion between magnetic resonance (MR) and ultrasound (US) images obtained by the Koelis Urostation™.We prospectively included 15 consecutive patients referred for placement of intraprostatic fiducials before radiotherapy and who gave written informed consent by signing the Institutional Review Board-approved forms. Three fiducials were placed in the prostate under US guidance in standardized positions (right apex, left mid-gland, right base) using the Koelis Urostation™. Patients then underwent prostate MR imaging. Four operators outlined the prostate on MR and US images and an elastic fusion was retrospectively performed. Fiducials were used to measure the overall target registration error (TRE3D), the error along the antero-posterior (TREAP), right-left (TRERL) and head-feet (TREHF) directions, and within the plane orthogonal to the virtual biopsy track (TRE2D).Median TRE3D and TRE2D were 3.8-5.6 mm, and 2.5-3.6 mm, respectively. TRE3D was significantly influenced by the operator (p = 0.013), fiducial location (p = 0.001) and 3D axis orientation (p

The present work intends to evaluate the use of immediate loaded orthodontic screws in a growing model, and to study the specific bone response. Thirty-two screws (half of stainless steel and half of titanium) were inserted in the alveolar bone of 8 growing pigs. The devices were immediately loaded with a 100 g orthodontic force. Two loading periods were assessed: 4 and 12 weeks. Both systems of screws were clinically assessed. Histological observations and histomorphometric analysis evaluated the percent of "bone-to-implant contact" and static and dynamic bone parameters in the vicinity of the devices (test zone) and in a bone area located 1.5 cm posterior to the devices (control zone). Both systems exhibit similar responses for the survival rate; 87.5% and 81.3% for stainless steel and titanium respectively (p = 0.64; 4-week period), and 62.5% and 50.0% for stainless steel and titanium respectively (p = 0.09; 12-week period). No significant differences between the devices were found regarding the percent of "bone-to-implant contact" (p = 0.1) or the static and dynamic bone parameters. However, the 5% threshold of "bone-to-implant contact" was obtained after 4 weeks with the stainless steel devices, leading to increased survival rate values. Bone in the vicinity of the miniscrew implants showed evidence of a significant increase in bone trabecular thickness when compared to bone in the control zone (p = 0.05). In our study, it is likely that increased trabecular thickness is a way for low density bone to respond to the stress induced by loading.

Purpose. To compare central macular thickness (CMT) measurement on healthy patient using 3 different OCT devices by two operators. Methods. Prospective, monocentricstudy. Right eye’s central macular thickness (CMT) of 30 healthy patients has been measured three times using a time-domain (TD) OCT (Stratus OCT, Carl Zeiss Meditec, Dublin, Ca) and two spectral domain (SD) OCTs (Cirrus HD-OCT, Carl ZeissMeditec, Dublin, Ca) and 3D-OCT 1000 (Topcon, Tokyo, Japan) by two operators. Six measurements were taken randomly for each patient the same day. Results. No significant difference between measurements obtained by the two operators has been observed, whatever the studied OCT. P value was 0.164, 0.193, and 0.147 for Stratus OCT, Cirrus HD-OCT and 3D-OCT, respectively. Mean CMT significantly differed from instrument to instrument (P

BACKGROUND/OBJECTIVE: Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population. PATIENTS/METHODS: We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort. RESULTS: In Schwartz-Lyon formula, k was estimated at 32.5 in boys