Survival without severe neonatal morbidity after antenatal betamethasone dose reduction: a post hoc analysis of a randomized non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated. OBJECTIVE: This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes. STUDY DESIGN: We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia. RESULTS: After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial. CONCLUSION: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings.

Experiences Among Patients With Cystic Fibrosis in the MucoExocet Study of Using Connected Devices for the Management of Pulmonary Exacerbations: Grounded Theory Qualitative Research.

BACKGROUND: Early detection of pulmonary exacerbations (PEx) in patients with cystic fibrosis is important to quickly trigger treatment and reduce respiratory damage. An intervention was designed in the frame of the MucoExocet research study providing patients with cystic fibrosis with connected devices and educating them to detect and react to their early signs of PEx. OBJECTIVE: This study aims to identify the contributions and conditions of home monitoring in relation to their care teams from the users' point of view to detect PEx early and treat it. This study focused on the patients' experiences as the first and main users of home monitoring. METHODS: A qualitative study was conducted to explore patients' and professionals' experiences with the intervention. We interviewed patients who completed the 2-year study using semistructured guides and conducted focus groups with the care teams. All the interviews were recorded and transcribed verbatim. Their educational material was collected. A grounded analysis was conducted by 2 researchers. RESULTS: A total of 20 patients completed the study. Three main categories emerged from the patients' verbatim transcripts and were also found in those of the professionals: (1) task technology fit, reflecting reliability, ease of use, accuracy of data, and support of the technology; (2) patient empowerment through technology, grouping patients' learnings, validation of their perception of exacerbation, assessment of treatment efficacy, awareness of healthy behaviors, and ability to react to PEx signs in relation to their care team; (3) use, reflecting a continuous or intermittent use, the perceived usefulness balanced with cumbersome measurements, routinization and personalization of the measurement process, and the way data are shared with the care team. Furthermore, 3 relationships were highlighted between the categories that reflect the necessary conditions for patient empowerment through the use of technology. CONCLUSIONS: We discuss a theorization of the process of patient empowerment through the use of connected devices and call for further research to verify or amend it in the context of other technologies, illnesses, and care organizations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03304028; https://clinicaltrials.gov/ct2/show/results/NCT03304028.

Clinics dedicated to transition preparation for adolescents and young adults with chronic conditions: Factors influencing their use.

To pool resources and reduce inequalities in access to transition preparation for patients, transition clinics were created in France. They are places in hospitals, independent of the usual care departments, offering multiple resources and services for adolescents and their parents. Of the 24 physicians from care departments who were surveyed, half of them do not use transition clinics. The implementation of transition clinics in hospitals did not lead to their adoption by the care departments that needed the most support for transition preparation of their patients. A strategy improving adoption is needed to allow transition clinics to reduce inequalities.

Young people's proposals for a web-based intervention for sexual health promotion: a French qualitative study.

BACKGROUND: Promoting sexual health is key to improving the supportive behaviors and well-being of young people. With the advent of the Internet, web-based features for sexual health promotion may be attractive to a diverse range of young people. This study aims to assess young people's proposals regarding a web-based intervention for sexual health promotion. METHODS: Nineteen French young people aged 15-24 years participated to the study. In a semi-structured interview, they presented their views on a web-based intervention for sexual promotion. Data were coded with N'Vivo and subjected to qualitative thematic analysis to explore their proposals. RESULTS: The majority of participants (n = 18) thought that a web-based intervention for sexual health promotion would be attractive. Young people interviewed made 31 concrete proposals for sexual health promotion on the Internet. Participatory and interactive dimensions on the internet appeared essential, with the need for stimulating activities and interaction with peers, but also with competent professionals and moderation. Face to the risks of the internet, they expressed the need of a secure and confidential space, to generate trust and participation in intervention. For participants, sexual health should be addressed in all its dimensions, taking into account the relational, sexual, and gender dimensions, and by incrementing on the internet valid, credible and personalized content. CONCLUSIONS: In sexual health promotion, young people are indispensable stakeholders who can make concrete proposals and can also participate in content creation and research. More broadly, in health promotion, involving target audiences in decisions represents a promising perspective.

Construction of reference criteria to admit patients to intermediate care units in France: a Delphi survey of intensivists, anaesthesiologists and emergency medicine practitioners (first part of the UNISURC project).

OBJECTIVES: No consensus criteria describe the medical eligibility of the patients to intermediate care units (IMCUs). In this first part of the UNISURC project, we aimed to develop criteria based on a consensus of physicians from the main specialties involved in IMCU admission decisions. DESIGN: We selected criteria from IMCU literature, scoring systems and intensive care unit nursing workload. We submitted these criteria to a panel of experts in a Delphi survey. We used a two-round Delphi survey procedure to assess the validity and feasibility of each criterion. SETTING: Medical practitioners in either public or private French institutions and proposed by the national scientific societies of anaesthesiology, emergency medicine and intensive care. The Delphi rounds took place in 2015-2016. OUTCOME MEASURES: Validity and feasibility of the proposed criteria; uniformity of the judgement across the primary specialty and the hospital category of the responders. RESULTS: The criteria submitted to vote were classified as one of: chronic factor (CF); acute factor (AF); specific pathway (SP); nursing activity (NA) and hospital environment (HE). Of 189 experts invited, 81 (41%) responded to the first round and 62 of them (76%) responded to the second round. A definite selection of 63 items was made, distributed across 6 CF, 18 AF, 31 SP, 3 NA and 5 HE. Validity and feasibility were influenced by the specialty or the public/private status of the institution of the responders for a few items. CONCLUSION: We created a set of 63 consensus criteria with acceptable validity and feasibility to assess the medical eligibility of the patients to IMCUs. The second part of the UNISURC project will assess the distribution of each criterion in a prospective multicentre national cohort. TRIAL REGISTRATION NUMBER: NCT02590172.

Health Promotion in Popular Web-Based Community Games Among Young People: Proposals, Recommendations, and Applications.

BACKGROUND: Young people use digital technology on a daily basis and enjoy web-based games that promote social interactions among peers. These interactions in web-based communities can develop social knowledge and life skills. Intervening via existing web-based community games represents an innovative opportunity for health promotion interventions. OBJECTIVE: The aim of this study was to collect and describe players' proposals for delivering health promotion through existing web-based community games among young people, elaborate on related recommendations adapted from a concrete experience of intervention research, and describe the application of these recommendations in new interventions. METHODS: We implemented a health promotion and prevention intervention via a web-based community game (Habbo; Sulake Oy). During the implementation of the intervention, we conducted an observational qualitative study on young people's proposals via an intercept web-based focus group. We asked 22 young participants (3 groups in total) for their proposals about the best ways to carry out a health intervention in this context. First, using verbatim transcriptions of the players' proposals, we conducted a qualitative thematic analysis. Second, we elaborated on recommendations for action development and implementation based on our experiences and work with a multidisciplinary consortium of experts. Third, we applied these recommendations in new interventions and described their application. RESULTS: A thematic analysis of the participants' proposals revealed 3 main themes and 14 subthemes related to their proposals and process elements: the conditions for developing an attractive intervention within a game, the value of involving peers in developing the intervention, and the ways to mobilize and monitor gamers' participation. These proposals emphasized the importance of interventions involving and moderating a small group of players in a playful manner but with professional aspects. We established 16 domains with 27 recommendations for preparing an intervention and implementing it in web-based games by adopting the codes of game culture. The application of the recommendations showed their usefulness and that it was possible to make adapted and diverse interventions in the game. CONCLUSIONS: Integrated health promotion interventions in existing web-based community games have the potential for promoting the health and well-being of young people. There is a need to incorporate specific key aspects of the games and gaming community recommendations, from conception to implementation, to maximize the relevance, acceptability, and feasibility of the interventions integrated in current digital practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT04888208; https://clinicaltrials.gov/ct2/show/NCT04888208.

Postoperative analgesia after surgical repair of distal radius fracture: a randomized comparison between distal peripheral nerve blockade and surgical site infiltration.

BACKGROUND: Pain following open reduction and internal fixation of distal radius fracture (DRF) can be significant. This study compared the intensity of pain up to 48 hours after volar plating for DRF, associated to either an ultrasound guided distal nerve block (DNB) or surgical site infiltration (SSI). METHODS: In this prospective single blind randomized study, 72 patients scheduled for DRF surgery under 1.5% lidocaine axillary block were allocated to receive, at the end of surgery, either an ultrasound-guided median and radial nerves block with ropivacaine 0.375% (DNB) performed by the anesthesiologist or a SSI with the same drug regimen, performed by the surgeon. Primary outcome was the duration between analgesic technique (H0) and pain reappearance (Numerical Rating Scale (NRS 0-10)>3). Secondary outcomes were the quality of analgesia, the quality of sleep, the magnitude of motor blockade, and the patient satisfaction. The study was built on a statistical hypothesis of equivalence. RESULTS: Fifty-nine patients were included in the final per-protocol analysis (DNB=30, SSI=29). Time to reach NRS>3 was (in median [95%CI]) 267 min [155;727] and 164 min [120;181] respectively after DNB and SSI (difference=103 min [-22;594] - rejection of equivalence hypothesis). Pain intensity throughout the 48 hours, quality of sleep, opiate consumption, motor blockade and patient satisfaction was not significantly different between groups. CONCLUSIONS: Although DNB provides a longer analgesia than SSI, both techniques gave comparable level of pain control during the first 48 hours after surgery, without any difference in the incidence of side effects or patient satisfaction.

Riluzole for treating spasticity in patients with chronic traumatic spinal cord injury: Study protocol in the phase ib/iib adaptive multicenter randomized controlled RILUSCI trial.

BACKGROUND: Satisfactory treatment is often lacking for spasticity, a highly prevalent motor disorder in patients with spinal cord injury (SCI). Low concentrations of riluzole potently reduce the persistent sodium current, the post-SCI increase in which contributes to spasticity. The repurposing of this drug may therefore constitute a useful potential therapeutic option for relieving SCI patients suffering from chronic traumatic spasticity. OBJECTIVE: RILUSCI is a phase 1b-2b trial designed to assess whether riluzole is a safe and biologically effective means of managing spasticity in adult patients with traumatic chronic SCI. METHODS: In this multicenter double-blind trial, adults (aged 18-65 years) suffering from spasticity after SCI (target enrollment: 90 participants) will be randomly assigned to be given either a placebo or a recommended daily oral dose of riluzole for two weeks. The latter dose will be previously determined in phase 1b of the study by performing double-blind dose-finding tests using a Bayesian continuous reassessment method. The primary endpoint of the trial will be an improvement in the Modified Ashworth Score (MAS) or the Numerical Rating Score (NRS) quantifying spasticity. The secondary outcomes will be based on the safety and pharmacokinetics of riluzole as well as its impact on muscle spasms, pain, bladder dysfunction and quality of life. Analyses will be performed before, during and after the treatment and the placebo-controlled period. CONCLUSION: To the best of our knowledge, this clinical trial will be the first to document the safety and efficacy of riluzole as a means of reducing spasticity in patients with chronic SCI. TRIAL REGISTRATION: The clinical trial, which is already in progress, was registered on the ClinicalTrials.gov website on August 9, 2016 under the registration number NCT02859792. TRIAL SPONSOR: Assistance Publique-Hôpitaux de Marseille.

Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial.

Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE (VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 [13.7] years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 [0.60-1.48]; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 [0.07-0.86], P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).

A Smoking Prevention Intervention Among Young People in an Online Community Game: Results from a Pilot Randomized Controlled Trial.

Background: Innovative methods for smoking prevention interventions need to be investigated to increase attractiveness, access hard-to-reach populations, and increase effectiveness. We studied the feasibility and immediate effects of an intervention to reinforce norms and behaviors of young people related to antismoking, integrated into a popular online community game. Methods: A pilot randomized controlled trial was conducted through the HABBO online community. The intervention group was exposed to repeated discussion sessions with small groups of peer players and two facilitators once a week for 1 month (four sessions), inside the game. The control group had access to antismoking information websites. Process indicators (attractiveness, participation) and immediate outcomes (norms and intentions with regard to smoking) were assessed by questionnaire. Results: One hundred sixteen players were invited to participate in the intervention; 10 did not meet eligibility criteria, 30 were allocated to the intervention group, and 76 to the control group. Median age was 23. Twenty-four percent were not in education, employment, or training. A median of eight players attended each session and the median number of exchange chats by session was 399; 70% of chat time was occupied by the players. Twenty players attended all four sessions. Immediate norms, representations, and intentions were evaluated in 39 players and showed small differences between groups. Conclusion: Delivering and evaluating a smoking prevention intervention in an online game is feasible. In the targeted online community game, the intervention was attractive and allowed the delivery of innovative interventions to audiences with diverse social profiles. Long-term effects, sustainability, and evaluation methodology are discussed.

Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study.

BACKGROUND: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort. METHODS: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses. RESULTS: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11). CONCLUSIONS: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015.

Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial.

BACKGROUND: Betaine is an "alternate" methyl donor for homocysteine remethylation catalyzed by betaine homocysteine methyltransferase (BHMT), an enzyme mainly expressed in the liver and kidney. Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients. AIMS: We compared 2 betaine doses (100 mg/kg/day vs. 250 mg/kg/day) in children affected by pnrCBS or cblC deficiencies. We also measured the pharmacokinetics parameters after a single dose of betaine (100 or 250 mg/kg) in these patients. METHODS: We conducted a prospective, randomized, crossover clinical trial with blinded evaluation. The primary outcome was the equivalence of total plasma homocysteine (tHcy) concentrations upon one-month oral treatment with betaine at 100 versus 250 mg/kg/day. RESULTS: Eleven patients completed the study (5 pnrCBS and 6 cblC). tHcy concentrations were equivalent after a one-month treatment period for the two betaine dosages. Multivariate analysis showed a significant effect of betaine dose on methionine (Met) (p = 0.01) and S-adenosylmethionine (SAM) concentrations (p = 0.006). CONCLUSIONS: Our analysis shows that there is no overt benefit to increasing betaine dosage higher than 100 mg/kg/day to lower tHcy concentrations in pnrCBS and cblC deficiencies. However, increasing betaine up to 250 mg/kg/d could benefit cblC patients through the increase of methionine and SAM concentrations, as low Met and SAM concentrations are involved in the pathophysiology of this disease. In contrast, in pnrCBS deficiency, betaine doses higher than 100 mg/kg/day could be harmful to these patients with pre-existing hypermethioninemia. TRIAL REGISTRATION: Clinical Trials, NCT02404337. Registered 23 May 2015-prospectively registered, https://clinicaltrials.gov .

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. METHODS: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. FINDINGS: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. INTERPRETATION: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. FUNDING: French Ministry of Health.

Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France.

Importance: Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. Objective: To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. Design, Setting, and Participants: This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. Exposures: PCV13 implementation. Main Outcomes and Measures: Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. Results: Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period. Conclusions and Relevance: PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

Are transition preparation consultations for adolescents with chronic conditions valuable? A mixed-methods study.

Our objective was to assess the value of transition preparation consultations (TPC) offered by the AD'venir unit (R. Debré hospital, Paris) as a new service of transitional care, from the perspective of adolescents with chronic conditions (CCs) and their referring healthcare providers (RHCPs). TPCs included a face-to-face interview with pediatricians trained in adolescent medicine, exploring the adolescent's past (CC history), present (daily life, Treatment Burden Questionnaire, family/peer relationships, school, hobbies, sexuality, drugs), and future (global life project, transition, Good2Go questionnaire). The mixed-methods design included the following: a qualitative analysis within a multidisciplinary group (clinicians/sociologists/psychologist/public health researchers) of audio-recordings of TPCs (n = 27/girls = 56%/median age = 17.7 years) and phone interviews with adolescents 2 years post-TPC (n = 26); and a quantitative analysis of the Treatment Burden and Good2Go questionnaires and the benefits perceived by RHCPs (questionnaire 6 months post-TPC). TPCs were a form of training for adult care, adolescents meeting a practitioner alone often for the first time. Naming their CC was difficult. All complained of limitations experienced in social life (diet, fatigue, laboratory/medical appointments), but not the treatment itself; most adolescents willingly talked about sexuality. Adolescents' feelings about transition were various, with poor representations of adult healthcare. Transfer was frequently unplanned. After TPCs, RHCPs modified their practices. Transition in the 2 years post-TPC was usually successful. Conclusion What is Known: • In adolescents with chronic conditions, it is advocated to personalize transition care according to the clinical and social context, pointed out as potentially impacting. • Little is known about the most effective ways to prepare patients according to their needs. What is New: • Based on a global approach to adolescent health, transition preparation consultations are delivered by specially trained physicians. • They are a feasible and valuable way to highlight facilitators and barriers to successful transition and initiate the adolescents' own vision of their future.

Agreement between a regional pharmacovigilance centre and an adjudication committee regarding adverse drug reactions on a cohort of hospitalised children.

BACKGROUND AND PURPOSE: The EREMI project was set up to collect data on adverse drug reactions (ADRs) occurring due to off-label and/or unlicensed drugs prescribed to hospitalised children in France. These events were evaluated by a regional pharmacovigilance centre (RPC) and an adjudication committee (AC). The aim of this study was to assess the agreement between these two different entities on their evaluation of ADRs. EXPERIMENTAL APPROACH: The RPC first validated the ADRs and assessed their causality using the Naranjo scale. The AC assessed then ADRs using all available information, including the RPC evaluation. The agreement on severity and nature of ADRs, role of treatment (suspect or concomitant) and drug causality was calculated using Cohen's nonparametric kappa coefficient (k). KEY RESULTS: Three hundred and eighty-six events were reported in 219 children. The RPC excluded 65 events and validated 321 ADRs. Agreement was very good on nature of ADRs (k=0.85) and role of treatment (k=0.81), moderate on severity of ADRs (k=0.60) and very poor on drug causality (k=0.05). CONCLUSION AND IMPLICATIONS: Agreement between the RPC and the AC was not constant throughout this evaluation. They troubled to agree on severe ADRs and on drug causality.

Long-term health-related quality of life outcomes of adults with pediatric onset of frequently relapsing or steroid-dependent nephrotic syndrome.

BACKGROUND: Long-term psychosocial outcomes and health-related quality of life (HRQOL) in adults with pediatric onset of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome (FRNS or SDNS) remain to be determined. METHODS: In this prospective cohort study, 59 adults with pediatric onset of FRNS/SDNS and persistent active glomerular disease in adulthood completed the GEDEPAC-2 questionnaire exploring 11 well-being domains. Data were compared to the French general population (FGP) with standardized incidence ratio ([SIR]; adjusted for period, age, gender). Regression models were performed to identify predictive factors of psychosocial well-being. RESULTS: In 82% of cases, the questionnaire was completed while the participants (n = 59; 47 men; median age = 32 years; median number of relapses = 13) were in complete remission (under specific therapy in 76% of cases). Participants had higher educational degree than in the FGP (SIR = 6.3; p < 0.01) and more frequently a managerial occupation (SIR = 3.1; p < 0.01). Social integration was acceptable with regard to marital status and experience of sexual intercourse, but experiences of discrimination were far more frequent (SIR = 12.5; p < 0.01). The SF-12 mental component summary (MCS) score was altered (Z-score = - 0.6; p < 0.01) and mean multidimensional fatigue inventory (MFI-20) global fatigue score appeared high (12). Transfer from pediatric to adult healthcare was followed by a period of discontinued care for 33% of participants. Multivariate analysis revealed a close relationship between MFI-20, physical health, and MCS. CONCLUSIONS: This study shows that pediatric onset FRNS and SDNS may have a long-term negative impact on mental HRQOL and highlights the impact of fatigue, which is often not adequately considered in routine care.

Social inequalities in access to care at birth and neonatal mortality: an observational study.

OBJECTIVE: To look at the association of socioeconomic status (SES) with the suitability of the maternity where children are born and its association with mortality. DESIGN: Retrospective analysis of a prospective cohort constituted using hospital discharge databases. SETTING: France POPULATION: Live births in 2012-2014 in maternity hospitals in mainland France followed until discharge from the hospital. MAIN OUTCOME MEASURE: Unsuitability of the maternity to newborns' needs based on birth weight and gestational age, early transfers (within 24 hours of birth) and in-hospital mortality. RESULTS: 2 149 454 births were included, among which 155 646 (7.2%) were preterm. Preterm newborns with low SES were less frequently born in level III maternities than those with high SES. They had higher odds of being born in an unsuitable maternity (OR=1.174, 95% CI 1.114 to 1.238 in the lowest SES quintile compared with the highest), and no increase in the odds of an early transfer (OR=0.966, 95% CI 0.849 to 1.099 in the lowest SES quintile compared with the highest). Overall, newborns from the lowest SES quintile had a 40% increase in their odds of dying compared with the highest (OR=1.399, 95% CI 1.235 to 1.584). CONCLUSIONS: Newborns with the lowest SES were less likely to be born in level III maternity hospitals compared with those with the highest SES, despite having higher prematurity rates. This was associated with a significantly higher mortality in newborns with the lowest SES. Strategies must be developed to increase health equity among mothers and newborns.

Sexual health promotion messages for young people in Netflix most-watched series content (2015-2020): mixed-methods analysis study.

INTRODUCTION: Sexual health is a major issue for young people, and there is a need to promote it. Sexual health promotion messages may be included in Netflix series that are widely watched by young people, with important emotional dimensions in scenarios. OBJECTIVE: The aim of this study is to investigate the explicit sexual health promotion messages integrated in Netflix series popular among young people, and to describe them and how they are delivered. METHODS: We selected two types of Netflix series, aimed at young people: (1) series whose synopsis is mainly about sexual health and (2) all-subject series. We extracted data from 65 episodes of 6 of the most-watched Netflix series. We used a data extraction grid on EpiData. We analysed sexual health themes and sexual health promotion messages. We described the series and listed all the sexual health and other health themes discussed. For each promotion message, we described scene contents and extracted dialogues. RESULTS: We found 62 promotion messages in the 6 analysed series. The two series that highlight sexual health in their synopsis account for 81% (n=50/62) of these identified promotion messages. Messages mainly focus on sexual harassment and violence (19%), on sexually transmitted infections protection (18%) and on contraception (15%). Messages are mainly delivered as verbal information, and mostly feature 16-18 years old characters in school. Analysis highlighted four main points concerning scenarios in these series: (1) there are different ways to deliver sexual health promotion messages; (2) there is depiction of negative value judgements and gender norms; (3) some information may be incomplete or misleading and (4) risky behaviours are represented. CONCLUSION: Netflix series incorporate diverse sexual health promotion messages for young people. Further research could assess how these messages are perceived and whether they increase the knowledge, skills and positive health behaviours of young people.