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Abstract Background Self-harm presents a significant public health challenge. Emergency departments (EDs) are crucial healthcare settings in managing self-harm, but clinician uncertainty in risk assessment may contribute to ineffective care. Clinical Decision Support Systems (CDSSs) show promise in enhancing care processes, but their effective implementation in self-harm management remains unexplored. Methods PERMANENS comprises a combination of methodologies and study designs aimed at developing a CDSS prototype that assists clinicians in the personalized assessment and management of ED patients presenting with self-harm. Ensemble prediction models will be constructed by applying machine learning techniques on electronic registry data from four sites, i.e., Catalonia (Spain), Ireland, Norway, and Sweden. These models will predict key adverse outcomes including self-harm repetition, suicide, premature death, and lack of post-discharge care. Available registry data include routinely collected electronic health record data, mortality data, and administrative data, and will be harmonized using the OMOP Common Data Model, ensuring consistency in terminologies, vocabularies and coding schemes. A clinical knowledge base of effective suicide prevention interventions will be developed rooted in a systematic review of clinical practice guidelines, including quality assessment of guidelines using the AGREE II tool. The CDSS software prototype will include a backend that integrates the prediction models and the clinical knowledge base to enable accurate patient risk stratification and subsequent intervention allocation. The CDSS frontend will enable personalized risk assessment and will provide tailored treatment plans, following a tiered evidence-based approach. Implementation research will ensure the CDSS’ practical functionality and feasibility, and will include periodic meetings with user-advisory groups, mixed-methods research to identify currently unmet needs in self-harm risk assessment, and small-scale usability testing of the CDSS prototype software. Discussion Through the development of the proposed CDSS software prototype, PERMANENS aims to standardize care, enhance clinician confidence, improve patient satisfaction, and increase treatment compliance. The routine integration of CDSS for self-harm risk assessment within healthcare systems holds significant potential in effectively reducing suicide mortality rates by facilitating personalized and timely delivery of effective interventions on a large scale for individuals at risk of suicide.

Abstract Background The emergence of new problematic alcohol consumption practices among young people requires new dynamics in prevention strategies. In this context, the ADUC project (Alcohol and Drugs at the University of Caen) aims to develop a better understanding of alcohol consumption, and in particular the practice of binge drinking (BD) in students, in order to develop relevant and adapted prevention tools. The ALCOMEDIIT study (Rin Normandie and IRESP funding; Agreement 20II31-00 - ADUC part 3) is a randomized controlled trial that focuses on the specific determinant of impulsivity. The main objective of this experiment is to assess a program for the prevention of BD practices based on motivational interviewing (MI) associated with implementation intention (II) and mindfulness meditation (MBM) in a student environment. Methods This study will include 170 healthy subjects who will be students at the university, alcohol users, with a BD score > 1 in the month preceding the inclusion but not presenting any specific disorder. The trial will be proposed by e-mail and students who meet the inclusion criteria will join either a control group which will benefit from a MI or an experimental group which will additionally benefit from an initiation to MBM with II (initial visit T0). In order to measure the effectiveness of the prevention program in terms of BD decrease, a follow-up at 1 month (T1) as well as a follow-up at 6 months (T6; exploratory) will be proposed to all participants. The total duration of this research protocol is 21 months. Discussion The purpose of this study is to evaluate the interest of associating mindfulness meditation practices and implementation of self-regulation strategies to optimize their use, with a motivational interview in an innovative prevention program aiming at reducing alcohol use and BD practice in the student population. Trial registration ClinicalTrials.gov Identifier: NCT05565989, September 30, 2022. https://clinicaltrials.gov/study/NCT05565989 Protocol version 2.0 (September 2022) No. ID-RCB : 2022-A00983-40

With a rapidly increasing number of Latinx students in a special education system that requires parent advocacy, it is imperative to study the perspectives Latinx families have on how to improve family-school partnerships. In this research, semi-structured interviews with 10 Latinx mothers who have children with disabilities led to insights about stressors and barriers, how families can be empowered, and how trusting partnerships can be facilitated. Implications for the field of special education are discussed.

The purpose of this conceptual replication study was to investigate the efficacy of an early literacy intervention when it was implemented by special educators in general education classrooms with students in the class participating in the lessons. The study was conducted in 16 schools in three states. Eighty students with severe disabilities participated in the study. Students in the intervention group received Early Literacy Skills Builder (ELSB) instruction, and students in the "business-as-usual" control group received literacy instruction planned by special education teachers to address the students' individualized education program literacy goals. Literacy assessments were conducted in five waves scheduled across the school year. Results showed that students receiving ELSB instruction made greater gains in assessed literacy skills than students in the control group. These findings provide evidence that students with severe disabilities can benefit from comprehensive emergent literacy instruction when it is implemented in general education settings. [For the corresponding grantee submission, see ED601011.]

Although total neoadjuvant therapy (TNT) is a new standard of care for locally advanced rectal cancer (LARC), there are no data to confirm the safety and efficacy of this approach in older patients. SHAPERS is a multicentre, open-label, randomised pragmatic trial, aiming to assess whether neoadjuvant short-course radiotherapy (SCRT) is a better trade-off between safety and efficacy than TNT in LARC patients aged ≥70 years. Eligible patients are randomised in a 1 : 1 ratio to SCRT followed by surgery [or watch & wait (w&w)] ± adjuvant chemotherapy or TNT (either SCRT followed by 12-18 weeks of chemotherapy, or long-course chemoradiotherapy followed or preceded by 16 weeks of chemotherapy, based on the investigator’s choice) followed by surgery (or w&w). The primary endpoint is the net treatment benefit, a multicomponent measure of treatment effect based on generalised pairwise comparisons, and defined by four prioritised outcome measures: (i) overall survival at 3 years; (ii) progression-free survival at 3 years; (iii) increased-grade peripheral sensory neuropathy at 3 years; (iv) grade ≥3 toxicities during treatment. The study sample size includes 230 eligible patients, to be recruited at 15-20 centres in Belgium. The trial is registered with ClinicalTrials.gov (NCT06052332).

ABSTRACT Water contamination in dental unit waterlines (DUWLs) is a potential source of healthcare-associated infection during dental care. The aim of this study was to evaluate the microbiological quality of DUWLs water from newly installed dental chairs in a French University Hospital. The microbiological quality of water from 24 new DUWLs initially disinfected by ICX Renew—prior to use of the dental units for patient treatment—was assessed for total culturable aerobic bacteria at 22°C and 36°C, Legionella sp., Pseudomonas aeruginosa, and total coliforms. Among the 24 samples analyzed, 21 were compliant with the water quality levels: 19 had no bacteria, and 2 contained only 4 and 1 CFU/mL for total culturable aerobic bacteria at 22°C and 36°C, respectively. Three samples were non-compliant due to contamination by P. aeruginosa (4, 2, and 2 CFU/100 mL). Controlling and preventing the microbiological contamination of DUWLs, especially by pathogenic bacteria, at the time of the installation of the new dental chairs are crucial to prevent healthcare-associated infection in dentistry.IMPORTANCEDental unit waterlines (DUWLs) of new dental chairs may be contaminated before their first clinical use, so an initial shock disinfection is crucial at the time of their installation. The microbiological analyses are crucial to control the water quality of DUWLs before their first clinical use because their disinfection does not guarantee the elimination of all bacteria.

Summary: Background: No study has compared the virological and immunological status of young people with perinatally-acquired HIV infection (P-HIV) with that of people with HIV adulthood (A-HIV) having a similar duration of infection. Methods: 5 French cohorts of P-HIV and A-HIV patients with a known date of HIV-infection and receiving antiretroviral treatment (ART), were used to compare the following proportions of: virological failure (VF) defined as plasma HIV RNA ≥ 50 copies/mL, CD4 cell percentages and CD4:CD8 ratios, at the time of the most recent visit since 2012. The analysis was stratified on time since infection, and multivariate models were adjusted for demographics and treatment history. Findings: 310 P-HIV were compared to 1515 A-HIV (median current ages 20.9 [IQR:14.4–25.5] and 45.9 [IQR:37.9–53.5] respectively). VF at the time of the most recent evaluation was significantly higher among P-HIV (22.6%, 69/306) than A-HIV (3.3%, 50/1514); p ≤ 0.0001. The risk of VF was particularly high among the youngest children (2–5 years), adolescents (13–17 years) and young adults (18–24 years), compared to A-HIV with a similar duration of infection: adjusted Odds-Ratio (aOR) 7.0 [95% CI: 1.7; 30.0], 11.4 [4.2; 31.2] and 3.3 [1.0; 10.8] respectively. The level of CD4 cell percentages did not differ between P-HIV and A-HIV. P-HIV aged 6–12 and 13–17 were more likely than A-HIV to have a CD4:CD8 ratio ≥ 1: 84.1% vs. 58.8% (aOR = 3.5 [1.5; 8.3]), and 60.9% vs. 54.7% (aOR = 1.9 [0.9; 4.2]) respectively. Interpretation: P-HIV were at a higher risk of VF than A-HIV with a similar duration of infection, even after adjusting for treatment history, whereas they were not at a higher risk of immunological impairment. Exposure to viral replication among young patients living with HIV since birth or a very early age, probably because of lower adherence, could have an impact on health, raising major concerns about the selection of resistance mutations and the risk of HIV transmission. Funding: Inserm - ANRS MIE.

BackgroundPatient-accessible electronic health records (PAEHRs) are assumed to enhance the quality of care, expressed in terms of safety, effectiveness, timeliness, person centeredness, efficiency, and equity. However, research on the impact of PAEHRs on the perceived quality of care among parents, children, and adolescents is largely lacking. In the Netherlands, a PAEHR (Iuvenelis) was developed for preventive child health care and youth care. Parents and adolescents had access to its full content, could manage appointments, ask questions, and comment on written reports. ObjectiveThis study aims to assess whether and how using this PAEHR contributes to perceived quality of care from a client’s perspective. MethodsWe chose a qualitative design with a phenomenological approach to explore how parents and adolescents perceived the impact of using a PAEHR on quality of care. In-depth interviews that simultaneously included 1 to 3 people were conducted in 2021. In total, 20 participants were included in the study, representing parents and adolescents, both sexes, different educational levels, different native countries, and all participating municipalities. Within this group, 7 of 13 (54%) parents had not previously been informed about the existence of a client portal. Their expectations of using the client portal, in relation to quality of care, were discussed after a demonstration of the portal. ResultsParents and adolescents perceived that using Iuvenelis contributed to the quality of care because they felt better informed and more involved in the care process than before the introduction of Iuvenelis. Moreover, they experienced more control over their health data, faster and simpler access to their health information, and found it easier to manage appointments or ask questions at their convenience. Parents from a migratory background, among whom 6 of 7 (86%) had not previously been informed about the portal, expected that portal access would enhance their understanding of and control over their care processes. The parents expressed concerns about equity because parents from a migratory background might have less access to the service. Nevertheless, portal usability was regarded as high. Furthermore, both parents and adolescents saw room for improvement in the broader interdisciplinary use of Iuvenelis and the quality of reporting. ConclusionsUsing Iuvenelis can contribute to the client-experienced quality of care, more specifically to perceived person centeredness, timeliness, safety, efficiency, and integration of care. However, some quality aspects, such as equity, still need addressing. In general, client information about the portal needs to be improved, specifically focusing on people in vulnerable circumstances, such as those from migratory backgrounds. In addition, to maximize the potential benefit of using Iuvenelis, stimulating a person-centered attitude among professionals is important. Considering the small number of adolescent participants (n=7), adding quantitative data from a structured survey could strengthen the available evidence.

ABSTRACTIn vitro reverse transcription of full-length HIV-1 RNA extracted from the blood plasma of people living with HIV-1 remains challenging. Here, we describe the initiation of reverse transcription of plasma-derived viral RNA in the absence of an exogenous primer. Real-time PCR and Sanger sequencing were applied to identify the source and to monitor the outcome of this reaction. Results demonstrated that during purification of viral RNA from plasma, tRNA(Lys-3) is co-extracted in a complex with the viral RNA. In the presence of a reverse transcription enzyme, this tRNA(Lys-3) can induce reverse transcription, a reaction that is not confined to transcription of the 5’ end of the viral RNA. A range of cDNA products is generated, most of them indicative for the occurrence of in vitro strand transfer events that involve translocation of cDNA from the 5’ end to random positions on the viral RNA. This process results in the formation of cDNAs with large internal deletions. However, near full-length cDNA and cDNA with sequence patterns resembling multiple spliced HIV-1 RNA were also detected. Despite its potential to introduce significant bias in the interpretation of results across various applications, tRNA(Lys-3)-driven reverse transcription has been overlooked thus far. A more in-depth study of this tRNA-driven in vitro reaction may provide new insight into the complex process of in vivo HIV-1 replication.IMPORTANCEThe use of silica-based extraction methods for purifying HIV-1 RNA from viral particles is a common practice, but it involves co-extraction of human tRNA(Lys-3) due to the strong interactions between these molecules. This co-extraction becomes particularly significant when the extracted RNA is used in reverse transcription reactions, as the tRNA(Lys-3) then serves as a primer. Reverse transcription from tRNA(Lys-3) is not confined to cDNA synthesis of the 5’ end of the viral RNA but extends across various regions of the viral genome through in vitro strand transfer events. Co-extraction of tRNA(Lys-3) has been overlooked thus far, despite its potential to introduce bias in downstream, reverse transcription-related applications. The observed events in the tRNA(Lys-3)-induced in vitro reverse transcription resemble in vivo replication processes. Therefore, these reactions may offer a unique model to better understand the replication dynamics of HIV-1.

Abstract Background In 2018, the European Medicines Agency authorized adjuvant therapy for patients with resected stage III melanoma. Objectives The objective of the present study (performed in France) was to assess dermatologists' and oncologists' opinions and prescribing habits in this context. Methods From 28 May to 8 June 2021, we performed an online survey of members of the French Groupe de Cancérologie Cutanée (GCC) skin cancer interest group. Results Thirty‐eight practitioners replied to the survey. For BRAF‐mutant melanoma, 58% of the practitioners favoured immunotherapy (IT). If they themselves were to suffer from melanoma with a BRAFV600 mutation, 65% would choose IT for stage IIIB disease, and 72% would choose IT for stage IIID disease. For stage IIIA melanoma with a positive sentinel lymphatic node (SLN) biopsy

Abstract Introduction At first interim analysis of KEYNOTE-629, health-related quality of life (HRQoL) with pembrolizumab was stable or improved over 48 weeks in recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). HRQoL results from the second interim analysis in R/M or locally advanced (LA) cSCC are presented. Methods Patients received pembrolizumab 200 mg every 3 weeks for ≤ 2 years. Change in EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EQ-5D-5L scores were exploratory end points. Primary analysis was performed at week 12 to ensure adequate completion/compliance. Descriptive analyses were also conducted through weeks 48 and 75 for the LA and R/M cohorts, respectively. Results At data cutoff (29 July 2020), mean scores in the LA cohort (n = 47) were stable from baseline to week 12 for EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) (−0.27 points [95% confidence interval (CI) −10.93 to 10.39]), physical functioning (−1.29 points [95% CI −8.77 to 6.19]), and EQ-5D-5L visual analog scale (2.06 [95% CI −7.70 to 11.82]). HRQoL remained stable through week 48 in the LA cohort; 76.6% and 74.5% of patients had improved or stable GHS/QoL and physical functioning scores, respectively. HRQoL continued to show stability or improvement through week 75 in the R/M cohort (n = 99); 71.7% and 64.6% of patients had improved or stable GHS/QoL and physical functioning scores, respectively. Conclusions Pembrolizumab has demonstrated antitumor activity and manageable safety. The current analysis shows pembrolizumab treatment preserved HRQoL. Collectively, these results support pembrolizumab as standard of care for LA or R/M cSCC. Trial Registration ClinicalTrials.gov, NCT03284424—September 15, 2017.

Abstract Aims The endodontic literature reports a lot of comparative study on endodontic instruments, concerning as well their geometry, instrumental dynamics, material, mechanical behavior or heat treatment. However, to our knowledge, no study has focused on the influence of endodontic motors on the shaping abilities of endodontic instruments. Thus, the aim of this study was to analyze the influence of the endodontic motors on root canal shaping instruments. Method Dual Move (MICRO-MEGA, Besançon, France), Canal Pro CL2i (COLTENE, Alstätten, Suisse), Canal Pro Jeni Motor (COLTENE, Alstätten, Suisse), Ai Motor (WOODPECKER, Guilin, China), Wave One motor (VDW, Postfach, Munich) and Smart A (WOODPECKER, Guilin, China) were pre-clinically compared in continuous rotation and reciprocating motion on a traction/compression bench using resin blocks. Canal shaping in continuous rotation and reciprocating motion were performed with One Curve and One RECI instruments (MICRO-MEGA, Besançon, France), respectively. The penetration/removal forces, making it possible to objectify the cutting effect and screwing effect of the instruments during root canal shaping, were analyzed. Results The results showed (i) that endodontic motors influence the mechanical behavior of endodontic instruments, (ii) that the influence of the motors is essentially felt during reciprocating motion and (iii) that the reciprocating angles influence the mechanical behavior of endodontic instruments. Conclusion Only endodontic instruments are widely studied in literature while endodontic motors have a direct influence on root canal treatment. This study analyzes the influence of the endodontic motors on root canal shaping instruments. This study tends to demonstrate that Jeni Motor could optimize the mechanical behavior of endodontic instruments.

Abstract Background Laboratory results are influenced by presence and severity of disease, as well as preanalytical factors, analytical variation, and biological variation. Biological variation data for urinary protein: creatinine ratio (UPC) and urine specific gravity (USG) in cats are lacking. Objectives Determine the biological variation of UPC and USG in cats. Animals Eighty healthy client‐owned cats. Methods Prospective study. Urine was collected on days 0, 14, and 56 from all 80 cats to investigate the persistence of borderline or overt proteinuria or suboptimal urine concentration. In 15 of these cats, urine was collected weekly from day 0 to 42 to calculate the index of individuality (II) and reference change value (RCV), and on days 56 and 57 to evaluate day‐to‐day variability of UPC and USG. Results Borderline or overt proteinuria (UPC ≥0.2) was present in 18/80 (23%) cats at baseline and persisted on 3 occasions in 2 months in 8/18 (44%) cats. Urine concentration was suboptimal at inclusion (USG 82% increase in UPC in a healthy cat is not solely attributable to physiological and analytical variation. For USG, a decrease of >36% is considered clinically relevant.