Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre

Importance The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Objective To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. Design We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Findings Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Conclusions and relevance Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

Background Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. Methods We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (e.g., personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. Results We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. Conclusions Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

Importance Well-designed and properly executed randomized trials are considered the most reliable evidence on the benefits of health care interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomized trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Herein, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. Observations We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (harms, outcomes, nonpharmacological treatment), other related reporting guidelines (Template for Intervention Description and Replication [TIDieR]), and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, 3-round Delphi survey involving 317 participants and discussed at a 2-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added 7 new checklist items, revised 3 items, deleted 1 item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomized trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. Conclusions and Relevance Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomized trials to ensure that trial reports are clear and transparent.

Background Mixtures of food additives are daily consumed worldwide by billions of people. So far, safety assessments have been performed substance by substance due to lack of data on the effect of multiexposure to combinations of additives. Our objective was to identify most common food additive mixtures, and investigate their associations with type 2 diabetes incidence in a large prospective cohort. Methods and Findings Participants (n = 108,643, mean follow-up = 7.7 years (standard deviation (SD) = 4.6), age = 42.5 years (SD = 14.6), 79.2% women) were adults from the French NutriNet-Santé cohort (2009–2023). Dietary intakes were assessed using repeated 24h-dietary records, including industrial food brands. Exposure to food additives was evaluated through multiple food composition databases and laboratory assays. Mixtures were identified through nonnegative matrix factorization (NMF), and associations with type 2 diabetes incidence were assessed using Cox models adjusted for potential socio-demographic, anthropometric, lifestyle and dietary confounders. A total of 1,131 participants were diagnosed with type 2 diabetes. Two out of the five identified food additive mixtures were associated with higher type 2 diabetes incidence: the first mixture included modified starches, pectin, guar gum, carrageenan, polyphosphates, potassium sorbates, curcumin, and xanthan gum (hazard ratio (HR)per an increment of 1SD of the NMF mixture score = 1.08 [1.02, 1.15], p = 0.006), and the other mixture included citric acid, sodium citrates, phosphoric acid, sulphite ammonia caramel, acesulfame-K, aspartame, sucralose, arabic gum, malic acid, carnauba wax, paprika extract, anthocyanins, guar gum, and pectin (HR = 1.13 [1.08,1.18], p < 0.001). No association was detected for the three remaining mixtures: HR = 0.98 [0.91, 1.06], p = 0.67; HR = 1.02 [0.94, 1.10], p = 0.68; and HR = 0.99 [0.92, 1.07], p = 0.78. Several synergistic and antagonist interactions between food additives were detected in exploratory analyses. Residual confounding as well as exposure or outcome misclassifications cannot be entirely ruled out and causality cannot be established based on this single observational study. Conclusions This study revealed positive associations between exposure to two widely consumed food additive mixtures and higher type 2 diabetes incidence. Further experimental research is needed to depict underlying mechanisms, including potential synergistic/antagonist effects. These findings suggest that a combination of food additives may be of interest to consider in safety assessments, and they support public health recommendations to limit nonessential additives. Trial Registration The NutriNet-Santé cohort is registered at clinicaltrials.gov (NCT03335644). https://clinicaltrials.gov/study/NCT03335644.

Importance Digital health technologies (DHTs) aiming to monitor, treat, and manage diseases can be prescribed for patients with multimorbidity; yet most DHTs are designed for individual conditions or problems, while approximately half of patients with chronic conditions have multiple chronic conditions. Objectives To identify DHTs approved by the US Food and Drug Administration (FDA) or listed in the Organisation for the Review of Care and Health Apps (ORCHA) library and prescribable for a hypothetical patient with 5 conditions and to model the number of DHTs this patient should be prescribed to receive benefits health professionals considered important. Evidence Review The FDA databases (Premarket Notification 510(k), Premarket Approval, and De Novo) and the ORCHA App Library from National Health Service Somerset were systematically searched for DHTs registered or updated between January 1, 2019, and December 31, 2022, that could be prescribed to a hypothetical woman with 5 chronic conditions (type 2 diabetes, hypertension, chronic obstructive pulmonary disease, osteoporosis, and osteoarthritis). After abstracting each DHT’s elementary functions (ie, simple and delineated features to monitor, treat, and/or manage conditions), an assessment was undertaken to determine the fewest DHTs this hypothetical patient should be prescribed to receive benefit from digital functions health professionals considered important. Findings A total of 148 DHTs were identified (68 [46%] from FDA databases), of which 96 (65%) involved devices and 52 (35%) were standalone health apps. Only 5 DHTs (3.4%) were intended for 2 or more conditions. DHTs offered 140 elementary functions, ranging from recording, tracking, or visualizing health parameters to providing information to digital therapeutics with just-in-time interventions. The hypothetical patient would need to be prescribed up to 13 apps and 7 devices (a blood pressure monitor, a smartwatch, a pulse oximeter, a connected weight scale, a sensor-attached inhaler to monitor adherence, a lung function monitor, and a blood glucose sensor) to receive benefits from 28 functions at least 3 of 5 health professionals considered important. Conclusions and Relevance This systematic review found that almost all prescribable DHTs were developed for a single condition or problem. Thus, patients with multiple chronic conditions would have to routinize many DHTs concurrently in daily life to benefit from digital functions health professionals considered important.

Importance Retractions are rising in the scientific literature, increasing the risk of reusing unreliable results. Objectives To identify reports of systematic reviews that included retracted studies in their meta-analyses, and to assess the impact of these retracted studies on the results. Design, Setting, and Participants In this systematic review and meta-analysis the Feet of Clay Detector tool was searched to identify all systematic reviews that reported at least 1 meta-analysis including at least 1 retracted study and were published in the 25 highest impact factor journals in medicine, general and internal, from January 2013 to April 2024. All effect estimates where the retracted study contributed to the analysis were identified. For each meta-analysis, the summary effect, including all studies and excluding retracted studies was calculated. The search was conducted on April 8, 2024. Results Overall, 61 systematic reviews were identified that included retracted studies in their meta-analyses. Of these, 11 (18%) have been republished, retracted, or withdrawn. Data were extracted from 50 systematic reviews that included a total of 62 retracted studies. Retraction occurred after the publication in 37 systematic reviews (74%). Overall, 173 meta-analyses including the retracted study were identified; 70 of them (40%) were primary outcomes. One-hundred sixty-six meta-analyses were recalculated. Overall, 160 (96%) of the 166 recalculated effect estimates were within the CIs of the original effect. After exclusion of the retracted study, the statistical significance of the results changed in 18 meta-analyses (11%). The rate of evolution between effect estimates with and without retracted studies for 163 meta-analyses overall were calculated, including 64 addressing the primary outcomes of the systematic reviews. For primary outcomes (n = 64), the recalculated effect estimates changed by at least 10% in 27 meta-analyses (42%), 30% in 16 (25%), and 50% in 12 (19%). Overall (n = 163), effect estimates changed by at least 10% in 57 meta-analyses (35%), 30% in 31 (19%), and 50% in 23 (14%). Conclusions and Relevance This study found that retracted studies have been included in systematic reviews and meta-analyses, with retractions occurring mainly after the publication of the systematic review. The inclusion of retracted studies can impact the results and interpretation of reviews. Quality control measures should be implemented to prevent the dissemination of unreliable data in scientific literature.

Purpose We investigated total sleep time (TST) and sleep paradigms during schooldays and leisure days in teenagers, and compared the findings to results from 8 years before. Methods The EnCLASS epidemiological survey is a representative sample of thousands of French middle and high schoolers. Specific sleep questions allowed us to assess TST, sleep debt, too short sleep, and screen use. Sleep debt as was defined as a difference between the total sleep time (TST) during schooldays (TSTS) non-schooldays (weekends or vacations; TSTN) of over 2 hours. Too short sleep was assesses when TSTS was < 7 hours. We detailed results of the 2018 bivariable analysis and adjusted by sex, age, class level, academic delay and socio-economic level, allowing us to compare the 2018 and 2010 results. Results TST decreases constantly from the beginning of middle school (MS) to the end of high school (HS). In 2018, 26.7% of middle and 43.7% of high schoolers were in “sleep debt”. Additionally, 13.8% of middle and 29% of high schoolers reported too short sleep (less than 7 hours) on schooldays (vs. 7.8% in middle and 25.1% in high school in 2010). In 8 years, the TSTS of middle schoolers decreases by an average of 20 minutes of sleep per night on weekdays, dropping from 8 h 35 min to 8 h 14 min. Regarding screens at bedtime, an increase of 36.8 points was observed on schooldays in MS between 6th and 9th grade, with 13.9% more in HS, in 12th grade. This included 40.6% of middle and 60.6% of high schoolers using internet before sleep on schooldays. Conclusion Faced with this trend, teachers and parents need to take preventive action to avoid an inexorable decline in teenagers’ sleep.

To quantify the impact of the regular or irregular menstrual cycle (MC) or combined oral contraception (OC) on the time spent at the maximum effort exertion per training, assessed using latent effort states through a Hidden Markov chain Model (HMM). 6303 training sessions with heart rate (HR) and power output (PO) recorded every second were used to train HMM in order to determine latent effort states of 12 elite French cyclists followed up over 30 months. A total of 101 MC/OCs full cycles were analyzed. A calendar method was used to estimate regular MC phases (menstruation, estimated follicular phase, estimated luteal phase). Irregular MC was divided into menstruations/no menstruations and OC into break/active pill taking. Four latent effort states were identified: high, medium+, medium‐, and low. Focused on high intensity‐oriented training sessions, the proportion of time spent in high intensity effort state was significantly lower during menstruation (34.5%) compared to estimated follicular (65.2%, p = 0.0009) and luteal (55.4% p = 0.024) phases for regular MC, and during pills' break (43.7%) compared to active pill taking phase (62.6% p = 0.031) for OC cycles. During the high intensity‐oriented training sessions, the proportion of time spent in high effort state is almost twice higher in mid‐regular cycles whereas is lower during menstruation or pill's break in elite cyclists. These findings rely on repeated assessment of training loads in a real‐world context, analyzed using novel machine learning techniques that objectively quantify both internal and external training loads in elite female cyclists.

Polysomnography (PSG) is essential for diagnosing sleep disorders, but its manual interpretation is labor‐intensive. Automated sleep staging algorithms are promising, yet their utility in complex sleep disorders such as insomnia remains uncertain. This study evaluates five of the most recognised sleep staging classifiers—U‐Sleep, STAGES, GSSC, Luna and YASA—on PSG data from 904 patients with chronic insomnia. Performance was assessed using F1 scores, confusion matrices and predicted sleep metrics. The effect of demographics, sleepiness and PSG metrics on each classifier's performance was assessed using linear regression. Across all sleep stages, GSSC performed best (macro F1 score = 0.66), followed by U‐Sleep (0.62), Luna (0.56), STAGES (0.54) and YASA (0.52). GSSC achieved the highest F1 scores in Wake (0.83), N1 (0.22), N2 (0.80), N3 (0.71) and REM (0.76), while U‐Sleep matched its performance in N1 and REM and Luna in N3. STAGES performed poorest in N3 (0.39) and YASA in REM (0.35). Common misclassifications included N1 vs. Wake/N2 and N3 vs. N2, with REM misclassified as Wake/N1/N2 by STAGES, Luna and YASA. GSSC and U‐Sleep exhibited minimal demographic bias, while STAGES and Luna had more. No performance difference was observed between chronic insomnia patients with and without abnormal PSG. Sleep metric accuracy was highest for U‐Sleep (TST, R ² = 0.88), STAGES (SOL, R ² = 0.82) and GSSC (WASO, R ² = 0.82). These findings underscore the solid yet variable performance of the classifiers and highlight GSSC and U‐Sleep as leading tools for sleep staging in patients with chronic insomnia.

Background Researchers explore the biology of painful experiences not primarily felt in the body (‘non-physical pain’), sometimes referred to as mental, social or emotional pain. A critical challenge lies in how to operationalise this subjective experience for biological research, a crucial process for translating findings into clinical practice. Aims To map studies investigating biological features of non-physical pain, focusing on their conceptual features (i.e. terms and definitions of non-physical pain) and methodological characteristics (e.g. experimental paradigms and measures). Method This methodological systematic review searched reports of primary research on the biological features of non-physical pain across Embase, MEDLINE and Web of Science. Using a meta-research approach, we synthetised results on terms, definitions, populations, experimental paradigms, confounders, measures of non-physical pain and investigation methods (e.g. functional magnetic resonance imaging). Results We identified 92 human studies, involving 7778 participants. Overall, 59.1% of the studies did not report any definition of non-physical pain, and 82% of studies did not use a specific measure. Regarding the possibility of translating results to clinical settings, most of the human studies involved only healthy participants (71.7%) and the seven different experimental paradigms used to induce non-physical pain had unknown external validity. Confounders were not considered by 32.4% of the experimental studies. Animal studies were rare, with only four rodent studies. Conclusions Biomedical studies of non-physical pain use heterogeneous concepts with unclear overlaps and methods with unknown external validity. As has been done for physical pain, priority actions include establishing an agreed definition and measurement of non-physical pain and developing experimental paradigms with good external validity.

Background/Objectives: Cardiac amyloidosis (CA) is associated with amyloid infiltration of the extra-cardiac tissue, which may occur in the early stages of the disease. This study evaluates the diagnostic utility of thoracic fat pad biopsy obtained during a pacemaker or ICD implantation as an alternative to the standard diagnostic criteria for systemic amyloidosis. Methods: This exploratory, retrospective study included 27 patients with suspected or diagnosed CA who underwent pacemaker or defibrillator therapy. Results: Of these, 16 patients were confirmed to have CA (15 with technetium-labeled bisphosphonate bone scintigraphy and 1 with protein electrophoresis and echocardiographic findings) while 11 were confirmed to be CA-negative. The thoracic fat pad biopsy demonstrated a specificity of 100% but a sensitivity of only 31%. Among patients with transthyretin (ATTR)-CA, the sensitivity remained similarly low, at 27%. These results are consistent with prior findings on abdominal fat pad biopsy in ATTR-CA, highlighting the limited diagnostic yield of this method. Conclusions: Thoracic fat pad biopsy cannot be recommended as a standard diagnostic tool for CA, particularly in ATTR-CA, due to its poor sensitivity. However, in AL (amyloid light-chain) amyloidosis, this minimally invasive procedure may aid diagnosis without additional invasive interventions.

Purpose Insomnia represents a major issue in oncology, which can be successfully treated by online Cognitive-Behavioural Therapy for Insomnia, such as the Insomnet program. However, promoting its successful implementation in routine care requires healthcare providers’ involvement. This study aimed to explore healthcare professionals’ perceptions of this online program. Methods This qualitative study was a part of the French Sleep-4-All-2.0 multicentric study. It explored, through two focus groups including 19 healthcare professionals of three cancer centers, their perceptions regarding their role in patient referral, and the perceived barriers and facilitators in accessing this type of intervention. The content of the focus groups was subjected to a descriptive thematic analysis. Results Four major themes were identified: (1) ambivalent representations of online tools (including patients convinced by remote intervention, evolution of representations in relation to the health context, adapted to sleep disorders, professionals’ preconceptions of online tools), (2) barriers to implementation (including few perceived barriers, forgetting patients’ particularities, professionals’ lack of knowledge, a possible threat to the patient-caregiver relationship, financial cost), (3) levers for implementation (including real benefits for patients, professionals who feel confident, preserved patient-caregiver relationship, institutional innovations to remedy dysfunctions), and (4) professional involvement in implementation (what they need, what to avoid, what they already do, what they see themselves doing). Conclusion Online (healthcare) services were reported to help increase access to healthcare, but that should not replace the relationship between patients and healthcare professionals. All professionals must be informed and trained to refer patients to these programs.

Background Older adults with stroke and multimorbidity experience frequent care transitions, which are often poorly coordinated and fragmented. We conducted a pragmatic randomized controlled trial (RCT) to test the implementation and effectiveness of the Transitional Care Stroke Intervention (TCSI), a 6-month, multi-component, evidence-informed intervention to support older adults with stroke and multimorbidity using outpatient stroke rehabilitation services. The TCSI was designed to support self-management, improve health outcomes, and enhance the quality and experience of care transitions. Objective To explore the facilitators and challenges to implementing the TCSI, from the perspective of healthcare providers (HCPs) (n = 12) and Managers (n = 3). Methods Data collection and analysis were guided by the Consolidated Framework for Implementation Research (CFIR). Data were collected from study documents, individual and group interviews conducted with HCPs and a Care Coordinator, and surveys from managers. Data were analyzed using thematic analysis. Results Intervention implementation was facilitated by: a) strong collaborative and interdependent HCP team relationships, b) dedicated resources (funding, staffing) to support intervention delivery, c) training and ongoing support, customized to individual HCP needs, d) organizational readiness, strong leadership, and effective champions, e) structures to facilitate virtual information-sharing, and f) regular monitoring of intervention implementation. Implementation challenges included: a) COVID-19 related challenges (staff turnover, community service disruptions), b) poor communication with community service providers, c) documentation burden (intervention-related), and d) virtual care delivery. Conclusions This research enhances understanding of the diversity of factors influencing implementation of the TCSI, and the conditions under which implementation is more likely to succeed.

Introduction Estimating hypertension incidence and improving screening in general population could enhance blood pressure control and decrease cardiometabolic risks. Identifying those likely to develop hypertension is essential. Our study focused on predicting onset hypertension and its incidence based on initial characteristics. Methods We utilized data from the French prospective CONSTANCES cohort, including volunteers assessed twice over 5 years up to 31 December 2019, who were initially free from hypertension. Hypertension was defined as having a SBP at least 140 mmHg or DBP at least 90 mmHg during the second checkup or if antihypertensive medication was prescribed. We calculated annual incidence rates among subgroups and used machine learning models to identify predictors of hypertension. The impact of changes in BMI was analyzed using logistic regression. Results Of the 11 112 participants (average age 47.5 ± 12 years), 1929 (17.4%) developed hypertension within an average of 5.2 years, with 383 on medication. The incidence rate was 3.4 new cases per 100 person-years, rising with age and consistently higher in men (4.3 vs. 2.8). A blood pressure (BP) threshold of 130 mmHg predicted 70% of new cases. One-point BMI reduction significantly reduced hypertension risk by 16%, regardless of initial BMI and SBP levels. Conclusion The study reports a notable hypertension incidence of 3.4 new cases per 100 person-years, particularly among those with SBP over 130 mmHg, highlighting the need for regular screening. Early diagnosis and control can mitigate hypertension's adverse effects, emphasizing the crucial role of preventive measures like BMI reduction.

Background Scientific societies universally recommend evaluating the accuracy of electronic devices designed for blood pressure (BP) measurement using established validation protocols. Objective This study aimed to assess the accuracy of the Combei BP880W wrist device for BP measurement in the general population, according to the ISO 81060–2:2018/AMD 1:2020 Universal Standard. Methods The Combei BP880W is an oscillometric device designed to measure BP at the wrist. This study adhered to the ISO 81060–2:2018/AMD 1:2020 protocol and employed the same-arm sequential BP measurement method. A total of 85 participants, meeting protocol-specified age, gender, BP, and cuff distribution criteria, were included. The accuracy analysis utilized Criterion 1 (differences and standard deviations between reference and test device measurements) and Criterion 2 (intra-individual standard deviation of BP differences). Results Eighty-five participants were included. Mean BP differences between the simultaneous observer measurements were −0.2 ± 1.9 mmHg for systolic BP (SBP) and 0.1 ± 1.9 mmHg for diastolic BP (DBP). For Criterion 1, the mean difference ± standard deviation (SD) between the reference and test device measurements were −2.7 ± 5.9 mmHg (SBP) and −2.0 ± 3.9 mmHg (DBP), meeting the required threshold (≤ 5 ± 8 mmHg). For Criterion 2, intra-individual SDs were 4.6 mmHg (SBP) and 3.4 mmHg (DBP), both below the respective limits (≤ 6.39 mmHg for SBP and ≤ 6.65 mmHg for DBP). Conclusion The Combei BP880W wrist device meets the accuracy requirements of the ISO 81060–2:2018/AMD 1:2020 protocol, supporting its use for home BP monitoring in the general population.