Profound Defect of Amphiregulin Secretion by Regulatory T Cells in the Gut of HIV-Treated Patients.

The persistence of a leaky gut in HIV-treated patients leads to chronic inflammation with increased rates of cardiovascular, liver, kidney, and neurological diseases. Tissue regulatory T (tTreg) cells are involved in the maintenance of intestinal homeostasis and wound repair through the IL-33 pathway. In this study, we investigated whether the persistence of gut mucosal injury during HIV infection might be explained in part by a flaw in the mechanisms involved in tissue repair. We observed an increased level of IL-33 in the gut of HIV-infected patients, which is associated with an increased level of fibrosis and a low peripheral reconstitution of CD4+ T cells. Our results showed that intestinal Treg cells from HIV-infected patients were enriched in tTreg cells prone to support tissue repair. However, we observed a functional defect in tTreg cells caused by the lack of amphiregulin secretion, which could contribute to the maintenance of intestinal damage. Our data suggest a mechanism by which the lack of amphiregulin secretion by tTreg may contribute to the lack of repair of the epithelial barrier.

Assessing a New Prescreening Score for the Simplified Evaluation of the Clinical Quality and Relevance of eHealth Apps: Instrument Validation Study.

BACKGROUND: In 2020, more than 250 eHealth solutions were added to app stores each day, or 90,000 in the year; however, the vast majority of these solutions have not undergone clinical validation, their quality is unknown, and the user does not know if they are effective and safe. We sought to develop a simple prescreening scoring method that would assess the quality and clinical relevance of each app. We designed this tool with 3 health care stakeholder groups in mind: eHealth solution designers seeking to evaluate a potential competitor or their own tool, investors considering a fundraising candidate, and a hospital clinician or IT department wishing to evaluate a current or potential eHealth solution. OBJECTIVE: We built and tested a novel prescreening scoring tool (the Medical Digital Solution scoring tool). The tool, which consists of 26 questions that enable the quick assessment and comparison of the clinical relevance and quality of eHealth apps, was tested on 68 eHealth solutions. METHODS: The Medical Digital Solution scoring tool is based on the 2021 evaluation criteria of the French National Health Authority, the 2022 European Society of Medical Oncology recommendations, and other provided scores. We built the scoring tool with patient association and eHealth experts and submitted it to eHealth app creators, who evaluated their apps via the web-based form in January 2022. After completing the evaluation criteria, their apps obtained an overall score and 4 categories of subscores. These criteria evaluated the type of solution and domain, the solution's targeted population size, the level of clinical assessment, and information about the provider. RESULTS: In total, 68 eHealth solutions were evaluated with the scoring tool. Oncology apps (22%, 20/90) and general health solutions (23%, 21/90) were the most represented. Of the 68 apps, 32 (47%) were involved in remote monitoring by health professionals. Regarding clinical outcomes, 5% (9/169) of the apps assessed overall survival. Randomized studies had been conducted for 21% (23/110) of the apps to assess their benefit. Of the 68 providers, 38 (56%) declared the objective of obtaining reimbursement, and 7 (18%) out of the 38 solutions seeking reimbursement were assessed as having a high probability of reimbursement. The median global score was 11.2 (range 4.7-17.4) out of 20 and the distribution of the scores followed a normal distribution pattern (Shapiro-Wilk test: P=.33). CONCLUSIONS: This multidomain prescreening scoring tool is simple, fast, and can be deployed on a large scale to initiate an assessment of the clinical relevance and quality of a clinical eHealth app. This simple tool can help a decision-maker determine which aspects of the app require further analysis and improvement.

Long-term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease.

AIM: The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short-term efficacy in a randomized controlled trial. No long-term data are available to assess the benefit of this treatment. METHODS: This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end-point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. RESULTS: In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti-tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow-up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end-point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. CONCLUSION: An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease.

Reciprocal association between voting and the epidemic spread of COVID-19: observational and dynamic modeling study.

BACKGROUND: Whether voting is a risk factor for epidemic spread is unknown. Reciprocally, whether an epidemic can deter citizens from voting has not been often studied. We aimed to investigate such relationships for France during the coronavirus disease 19 (COVID-19) epidemic. METHODS: We performed an observational study and dynamic modelling using a sigmoidal mixed effects model. All hospitals with COVID-19 patients were included (18 March 2020-17 April 2020). Abstention rate of a concomitant national election was collected. RESULTS: Mean abstention rate in 2020 among departments was 52.5% ± 6.4% and had increased by a mean of 18.8% as compared with the 2014 election. There was a high degree of similarity of abstention between the two elections among the departments (P < 0.001). Among departments with a high outbreak intensity, those with a higher participation were not affected by significantly higher COVID-19 admissions after the elections. The sigmoidal model fitted the data from the different departments with a high degree of consistency. The covariate analysis showed that a significant association between participation and number of admitted patients was observed for both elections (2020: ß = -5.36, P < 1e-9 and 2014: ß = -3.15, P < 1e-6) contradicting a direct specific causation of the 2020 election. Participation was not associated with the position of the inflexion point suggesting no effect in the speed of spread. CONCLUSIONS: Our results suggest that the surrounding intensity of the COVID-19 epidemic in France did not have any local impact on participation to a national election. The level of participation had no impact on the spread of the pandemic.

Comparison of 20-gauge Procore® and 22-gauge Acquire® needles for EUS-FNB of solid pancreatic masses: an observational study.

Background and Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) has been proposed to obtain high-quality tissue samples for pancreatic tumors. We performed an observational study to compare EUS-FNB with a 20-gauge Procore® needle versus a 22-gauge Acquire® needle. Our primary endpoint was the quantity of the obtained tissue, as defined by the mean cumulative length of tissue core biopsies per needle pass. Methods: Sixty-eight EUS-FNB were consecutively performed on patients with a pancreatic mass. The choice of needle depended on availability at the time of admission: 34 punctures were performed with each needle. Histological material was studied in a blinded manner with respect to the needle, and the cumulative length of tissue core biopsies per needle pass was determined. Intraobserver and interobserver variability of this criterion was then evaluated. Results: There were no between-group differences. Histological diagnosis was achieved and core biopsy specimens were obtained in 28 out of 34 patients (82%) in the 20-gauge Procore® group and in 33 out of 34 patients (97%) in the 22-gauge Acquire® group (p = .1). The mean cumulative length of tissue core biopsies per needle pass was significantly higher with the 22-gauge Acquire® needle with 8.2 ± 4.2 mm versus 4.2 ± 3.8 mm for the 20-gauge Procore® needle (p < .01). No intra and inter-observer variability of this criterion was observed. Conclusions: Our results suggest significant differences, with a mean cumulative length of tissue core biopsies per needle pass significantly higher with the 22-gauge Acquire® needle. This simple criterion seems reliable and reproducible.

Health as an independent predictor of the 2017 French presidential voting behaviour: a cross-sectional analysis.

BACKGROUND: It has been suggested that poor health has influenced vote for Brexit and the US presidential election. No such research has been published regarding the 2017 French presidential election. METHODS: We performed a cross-sectional analysis using a comprehensive set of socioeconomic and health indicators, to be compared with voting outcome at the first round of the 2017 French presidential election. The 95 French departments were selected as the unit of analysis. Data were obtained from publicly available sources. The linear model was used for both univariate and multivariate analysis to investigate the relation between voting patterns and predictors. Sensitivity analyses were done using the elastic-net regularisation. RESULTS: Emmanuel Macron and Marine Le Pen arrived ahead. When projected on the first factorial plane (~ 60% of the total inertia), Emmanuel Macron and Marine Le Pen tended to be in opposite directions regarding both socioeconomic and health factors. In the respective multivariate analyses of the two candidates, both socio-economic and health variables were significantly associated with voting patterns, with wealthier and healthier departments more likely to vote for Emmanuel Macron, and opposite departments more likely to vote for Marine Le Pen. Mortality (p = 0.03), severe chronic conditions (p = 0.014), and diabetes mellitus (p < 0.0001) were among the strongest predictors of voting pattern for Marine Le Pen. Sensitivity analyses did not substantially change those findings. CONCLUSIONS: We found that areas associated with poorer health status were significantly more likely to vote for the far-right candidate at the French presidential election, even after adjustment on socioeconomic criteria.

Post-marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross-sectional study.

Post-marketing research in oncology has rarely been described. We aimed to characterize post-marketing trials for a consistent set of anticancer agents over a long period. We performed a cross-sectional analysis of post-marketing trials registered at ClinicalTrials.gov through September 2014 for novel anticancer agents approved by both the US Food and Drug Administration and the European Medicines Agency between 2005 and 2010. All relevant post-marketing trials were classified according to indication, primary outcome, starting date, sponsors, and planned enrollment. Supplemental indications were retrieved from regulatory documents and publication rate was assessed by two different methods. Ten novel anticancer agents were eligible: five were indicated for hematologic malignancies and the remaining five for solid cancers (three for kidney cancer). We identified 2,345 post-marketing trials; 1,362 (58.1%) targeted an indication other than the originally approved one. We observed extreme variations among drugs in both number of post-marketing trials (range 8-530) and overall population to be enrolled per trial (1-8,381). Post-marketing trials assessed almost all types of cancers, the three most frequently studied cancers being leukemia, kidney cancer and myeloma. In all, 6.6% of post-marketing trials had a clinical endpoint as a primary outcome, and 35.9% and 54.1% had a safety or surrogate endpoint, respectively, as a primary outcome. Nine drugs obtained approval for supplemental indications. The publication rate at 10 years was 12.3 to 26.1% depending on the analysis method. In conclusion, we found that post-marketing research in oncology is highly heterogeneous and the publication rate of launched trials is low.

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn's Disease.

BACKGROUND & AIMS: Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. METHODS: We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29-40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. RESULTS: Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula-related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula-related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). CONCLUSIONS: In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula-related cancer, and a high risk of rectal cancer.

Readmissions After Surgery: A French Nationwide Cross-Sectional Study of 1,686,602 Procedures Performed in 2010.

BACKGROUND: Surgical readmissions have been extensively studied in North America, but very few data from other countries are available. We aimed to describe surgical readmissions in France and to assess their association with hospital status, surgical volume, and day surgery activity. METHODS: We performed a cross-sectional study encompassing all 1270 French hospitals, except for military hospitals and hospitals with very small volume. Data were retrieved from the national database regarding all patients undergoing surgery between January 1, 2010 and November 30, 2010. The main outcome measure was 30-day readmission rate. Association with hospital status, surgical volume, and the level of day surgery were assessed. Risk adjustment was performed based upon administrative categories. RESULTS: After exclusion of deaths and hospital transfers, there were 1,686,602 patients in the study cohort. Thirty-day readmission rate was 5.9 %. Distribution was skewed, with 21.5 % of procedures accounting for 33.5 % of all 30-day readmissions. Early readmissions (≤3 days) were associated with higher mortality as compared to those occurring later (>7 days) (3.2 vs. 2.6 %; p < 0.0001). After multivariate analysis, University hospitals were shown to be affected by a significantly greater risk of 30-day readmission as compared to private hospitals (odds ratio 1.46 [95 % CI 1.42-1.5]). Other independent factors were as follows: male gender, longer initial hospital stay, and comorbidities. CONCLUSIONS: Surgical 30-day readmission rate was low, with early readmissions being associated with higher mortality. Conversely to prior research, University hospitals were shown to be associated with significantly higher risk of 30-day readmissions, even after risk adjustment.

Impact of resident and fellow changeovers on patient outcomes: a nationwide cross-sectional study.

Background: Findings regarding the association of cohort changeovers with patient outcomes are mixed. We sought to examine the association of resident and fellow changeovers with a comprehensive set of indicators. Methods: We performed a cross-sectional comparative study including all French teaching and non-teaching hospitals. All-cause mortality and length of stay were assessed. Focused analysis for three medical conditions (myocardial infarction, intestinal hemorrhage, stroke) and three surgical procedures (colorectal, vascular and spine surgery) was performed regarding other quality and efficiency indicators (readmissions, intensive care unit admission, transfers). Results: Overall, 34 330 716 patients were admitted in 2011 and 2012. Within the month following cohort changeovers, no increase in mortality was observed in teaching hospitals. Length of stay was longer in May and November in teaching hospitals (P < 0.0001) whereas it was shorter in the private sector. When focusing on six selected causes of hospitalization, we observed significant differences associated with resident changeovers, suggesting a decreased efficiency. In particular, readmissions rates and lengths of stay were found to be significantly higher (P < 0.0005) after intestinal hemorrhage and with a trend toward worse efficiency (P < 0.005) after colorectal surgery and stroke in teaching hospitals. Conclusion: Our findings provide some reassurance regarding cohort changeover and mortality even if they suggest a loss of efficiency in some cases.

Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010.

IMPORTANCE: Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. OBJECTIVES: To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. DESIGN AND SETTING: Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. EXPOSURES: Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time. MAIN OUTCOMES AND MEASURES: A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. RESULTS: From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near-regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). CONCLUSIONS AND RELEVANCE: Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near-regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.

Automatic classification of registered clinical trials towards the Global Burden of Diseases taxonomy of diseases and injuries.

BACKGROUND: Clinical trial registries may allow for producing a global mapping of health research. However, health conditions are not described with standardized taxonomies in registries. Previous work analyzed clinical trial registries to improve the retrieval of relevant clinical trials for patients. However, no previous work has classified clinical trials across diseases using a standardized taxonomy allowing a comparison between global health research and global burden across diseases. We developed a knowledge-based classifier of health conditions studied in registered clinical trials towards categories of diseases and injuries from the Global Burden of Diseases (GBD) 2010 study. The classifier relies on the UMLS® knowledge source (Unified Medical Language System®) and on heuristic algorithms for parsing data. It maps trial records to a 28-class grouping of the GBD categories by automatically extracting UMLS concepts from text fields and by projecting concepts between medical terminologies. The classifier allows deriving pathways between the clinical trial record and candidate GBD categories using natural language processing and links between knowledge sources, and selects the relevant GBD classification based on rules of prioritization across the pathways found. We compared automatic and manual classifications for an external test set of 2,763 trials. We automatically classified 109,603 interventional trials registered before February 2014 at WHO ICTRP. RESULTS: In the external test set, the classifier identified the exact GBD categories for 78 % of the trials. It had very good performance for most of the 28 categories, especially "Neoplasms" (sensitivity 97.4 %, specificity 97.5 %). The sensitivity was moderate for trials not relevant to any GBD category (53 %) and low for trials of injuries (16 %). For the 109,603 trials registered at WHO ICTRP, the classifier did not assign any GBD category to 20.5 % of trials while the most common GBD categories were "Neoplasms" (22.8 %) and "Diabetes" (8.9 %). CONCLUSIONS: We developed and validated a knowledge-based classifier allowing for automatically identifying the diseases studied in registered trials by using the taxonomy from the GBD 2010 study. This tool is freely available to the research community and can be used for large-scale public health studies.

Pharmacogenomic biomarkers as inclusion criteria in clinical trials of oncology-targeted drugs: a mapping of ClinicalTrials.gov.

PURPOSE: The aim of this study was to describe pharmacogenomics-based inclusion criteria (enrichment) and the main characteristics of clinical trials involving oncology-targeted therapies. METHODS: Clinical trials of oncology-targeted therapies approved after 2005 with pharmacogenomic testing required or recommended in their label were retrieved from a mapping of the ClinicalTrials.gov database. RESULTS: We examined information for 12 drugs and 858 trials. Overall, 434 trials (51%) were enriched on the biomarker first mentioned in the label and 145 (17%) were enriched on another biomarker, whereas 270 trials (31%) included all patients. The median proportion of trials corresponding to both the drug's indication and drug's target was 35%. Of the 361 trials that tested drugs in another disease than the first one in the label, 219 (61%) were without enrichment and 87 (24%) were actually enriched but on another biomarker than the first one in the label. CONCLUSION: Several drugs have been tested in trials enriched on many different biomarkers. Nonetheless, most targeted therapies have been developed only using biomarker-positive patients; therefore, exclusion of biomarker-negative patients from treatment relies on only preclinical data and on biological understanding of the disease and target.Genet Med 18 8, 796-805.

Regulatory anticipation of postmarket safety problems for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study.

PURPOSE: The aim of the study is to describe preapproval safety concerns expressed by the European Medicines Agency (EMA) following regulatory review and to compare those concerns with subsequent issuance of postmarket safety communications. METHODS: All novel medicines approved by the EMA through the centralized authorization procedure from 2001 to 2010 were included. Preapproval safety concerns were identified through examination of information related to regulatory review publicly available on the EMA's website. Relevant postmarket safety events were identified through Dear Healthcare Professional Communications (DHPCs), including those resulting in a withdrawal, issued by at least one of four leading national regulators of the European Union. RESULTS: Among the 184 novel medicines included, the EMA had expressed at least one preapproval safety concern for 110 (59.8%) of them. Then, at least one safety communication was issued for 53 (28.8%) medicines within the postmarket period of study, totaling 90 DHPCs and 5 withdrawals. Overall, these 95 DHPCs and withdrawals were pertaining to 66 different clinical safety events. The EMA had expressed a preapproval concern consistent with the postmarket safety event for 22.7% (15 of 66). The rate of issuance of a postmarket safety communication was not statistically different between medicines with or without any preapproval safety concern (31.8% vs. 24%, p = 0.25). CONCLUSIONS: Preapproval safety concerns are frequently expressed by the EMA following regulatory review. However, when comparing postmarket safety communications with prior concerns, anticipation was low. Our findings emphasize the need to systematically conduct postmarket studies dedicated to safety evaluation. Copyright © 2015 John Wiley & Sons, Ltd.

Regulatory review time and post-market safety events for novel medicines approved by the EMA between 2001 and 2010: a cross-sectional study.

AIMS: Regulatory review time has been associated with post-market medication safety issues in the United States. Our objective was to evaluate whether regulatory review time and near deadline approval are associated with post-market safety events (PMSEs) for novel medicines approved by the European Medicines Agency (EMA). METHODS: We performed a cross-sectional analysis of all novel medicines approved by the EMA through the centralized authorization procedure between 2001 and 2010. PMSEs were defined as withdrawals and communications identified through Dear Healthcare Professional Communications (DHPCs). Regulatory review time was defined as the time that elapsed between the start of the assessment procedure and approval. Near regulatory deadline approval was defined as approval within the 30 days before the EMA's 210 day regulatory deadline. RESULTS: Among 161 eligible medicines, PMSEs were identified for 49 (30.4%), 44 of which were DHPCs, five of which were withdrawals. Median regulatory review time was 337 days (IQR 276-406) and was not associated with PMSEs (P = 0.57). However, when categorized by regulatory review speed tertile, there were differences in risk of PMSEs, with higher rates among medicines in the middle tertile (25 of 55, 45.4%; P = 0.01). Finally, 26 medicines were approved near the 210 day regulatory deadline, but were not more likely to have PMSEs (38.5% vs. 28.7%; P = 0.32). CONCLUSIONS: Neither faster EMA regulatory review speed nor approval near regulatory deadlines was associated with greater likelihood of PMSEs among recently approved novel medicines.

Early Detection of 5 Neurodevelopmental Disorders of Children and Prevention of Postnatal Depression With a Mobile Health App: Observational Cross-Sectional Study.

BACKGROUND: Delay in the diagnosis of neurodevelopmental disorders (NDDs) in toddlers and postnatal depression (PND) is a major public health issue. In both cases, early intervention is crucial but too rarely implemented in practice. OBJECTIVE: Our goal was to determine if a dedicated mobile app can improve screening of 5 NDDs (autism spectrum disorder [ASD], language delay, dyspraxia, dyslexia, and attention-deficit/hyperactivity disorder [ADHD]) and reduce PND incidence. METHODS: We performed an observational, cross-sectional, data-based study in a population of young parents in France with at least 1 child aged <10 years at the time of inclusion and regularly using Malo, an "all-in-one" multidomain digital health record electronic patient-reported outcome (PRO) app for smartphones. We included the first 50,000 users matching the criteria and agreeing to participate between May 1, 2022, and February 8, 2024. Parents received periodic questionnaires assessing skills in neurodevelopment domains via the app. Mothers accessed a support program to prevent PND and were requested to answer regular PND questionnaires. When any PROs matched predefined criteria, an in-app recommendation was sent to book an appointment with a family physician or pediatrician. The main outcomes were the median age of the infant at the time of notification for possible NDD and the incidence of PND detection after childbirth. One secondary outcome was the relevance of the NDD notification by consultation as assessed by health professionals. RESULTS: Among 55,618 children median age 4 months (IQR 9), 439 (0.8%) had at least 1 disorder for which consultation was critically necessary. The median ages of notification for probable ASD, language delay, dyspraxia, dyslexia, and ADHD were 32.5 (IQR 12.8), 16 (IQR 13), 36 (IQR 22.5), 80 (IQR 5), and 61 (IQR 15.5) months, respectively. The rate of probable ADHD, ASD, dyslexia, language delay, and dyspraxia in the population of children of the age included between the detection limits of each alert was 1.48%, 0.21%, 1.52%, 0.91%, and 0.37%, respectively. Sensitivity of alert notifications for suspected NDDs as assessed by the physicians was 78.6% and specificity was 98.2%. Among 8243 mothers who completed a PND questionnaire, highly probable PND was detected in 938 (11.4%), corresponding to a reduction of -31% versus our previous study without a support program. Suspected PND was detected a median 96 days (IQR 86) after childbirth. Among 130 users who filled in the satisfaction survey, 99.2% (129/130) found the app easy to use and 70% (91/130) reported that the app improved follow-up of their child. The app was rated 4.8/5 on Apple's App Store. CONCLUSIONS: Algorithm-based early alerts suggesting NDDs were highly specific with good sensitivity as assessed by real-life practitioners. Early detection of 5 NDDs and PNDs was efficient and led to a possible 31% reduction in PND incidence. TRIAL REGISTRATION: ClinicalTrials.gov NCT06301087; https://www.clinicaltrials.gov/study/NCT06301087.

Early Detection of Neurodevelopmental Disorders of Toddlers and Postnatal Depression by Mobile Health App: Observational Cross-sectional Study.

BACKGROUND: Delays in the diagnosis of neurodevelopmental disorders (NDDs) in toddlers and postnatal depression (PND) in mothers are major public health issues. In both cases, early intervention is crucial. OBJECTIVE: We aimed to assess if a mobile app named Malo can reduce delay in the recognition of NDD and PND. METHODS: We performed an observational, cross-sectional, data-based study in a population of young parents with a minimum of 1 child under 3 years of age at the time of inclusion and using Malo on a regular basis. We included the first 4000 users matching the criteria and agreeing to participate between November 11, 2021, and January 14, 2022. Parents received monthly questionnaires via the app, assessing skills on sociability, hearing, vision, motricity, language of their infants, and possible autism spectrum disorder. Mothers were also requested to answer regular questionnaires regarding PND, from 4-28 weeks after childbirth. When any patient-reported outcomes matched predefined criteria, an in-app notification was sent to the user, recommending the booking of an appointment with their family physician or pediatrician. The main outcomes were the median age of the infant at the time of notification for possible NDD and the median time of PND notifications after childbirth. One secondary outcome was the relevance of the NDD notification for a consultation as assessed by the physicians. RESULTS: Among 4242 children assessed by 5309 questionnaires, 613 (14.5%) had at least 1 disorder requiring a consultation. The median age of notification for possible autism spectrum, vision, audition, socialization, language, or motor disorders was 11, 9, 17, 12, 22, and 4 months, respectively. The sensitivity of the alert notifications of suspected NDDs as assessed by the physicians was 100%, and the specificity was 73.5%. Among 907 mothers who completed a PND questionnaire, highly probable PND was detected in 151 (16.6%) mothers, and the median time of detection was 8-12 weeks. CONCLUSIONS: The algorithm-based alert suggesting NDD was highly sensitive with good specificity as assessed by real-life practitioners. The app was also efficient in the early detection of PND. Our results suggest that the regular use of this multidomain familial smartphone app would permit the early detection of NDD and PND. TRIAL REGISTRATION: ClinicalTrials.gov NCT04958174; https://clinicaltrials.gov/ct2/show/NCT04958174.

Frequency and risk factors of severe postoperative bleeding after proctological surgery: a retrospective case-control study.

PURPOSE: The aim of this study was to assess frequency and risk factors of severe bleeding after proctological surgery requiring hemostatic surgery observed after publication of the French guidelines for anticoagulant and platelet-inhibitor treatment. METHODS: All patients who underwent proctological surgery between January 2012 and March 2017 in a referral center were included. Delay, severity of bleeding, and need for blood transfusion were recorded. Patients with severe postoperative bleeding were matched to controls at a 2:1 ratio adjusted on the operator, and the type of surgery. RESULTS: Among the 8,890 operated patients, 65 (0.7%) needed a postoperative hemostatic procedure in an operating room. The risk of a hemostatic surgery was significantly increased after hemorrhoidal surgery compared with other procedures (1.9% vs. 0.5%, P<10-4) and was most frequent after Milligan-Morgan hemorrhoidectomy (2.5%). Mean bleeding time was 6.2 days and no bleeding occurred after day 15. Blood transfusion rate was 0.1%. Treatment with anticoagulants and platelet inhibitors were managed according to recommendations and did not increase the severity of bleeding. The risk of severe bleeding was significantly lower in active smokers vs. non-smokers in univariate (16.9% vs. 36.2%, P=0.007) and multivariate (odds ratio, 0.31; 95% confidence interval, 0.14-0.65) analysis whereas sex, age, and body mass were not significantly associated with bleeding. CONCLUSION: Severe postoperative bleeding occurs in 0.7% of patients, but varies with type of procedure and is not affected by anticoagulant or antiplatelet treatment. These treatments given in accordance with the new guidelines do not increase the severity of postoperative bleeding.

Predicting the propagation of COVID-19 at an international scale: extension of an SIR model.

OBJECTIVES: Several epidemiological models have been published to forecast the spread of the COVID-19 pandemic, yet many of them have proven inaccurate for reasons that remain to be fully determined. We aimed to develop a novel model and implement it in a freely accessible web application. DESIGN: We built an SIR-type compartmental model with two additional compartments: D (deceased patients); L (individuals who will die but who will not infect anybody due to social or medical isolation) and integration of a time-dependent transmission rate and a periodical weekly component linked to the way in which cases and deaths are reported. RESULTS: The model was implemented in a web application (as of 2 June 2020). It was shown to be able to accurately capture the changes in the dynamics of the pandemic for 20 countries whatever the type of pandemic spread or containment measures: for instance, the model explains 97% of the variance of US data (daily cases) and predicts the number of deaths at a 2-week horizon with an error of 1%. CONCLUSIONS: In early performance evaluation, our model showed a high level of accuracy between prediction and observed data. Such a tool might be used by the global community to follow the spread of the pandemic.