Search Results for: Follow-up ottimale dopo embolia polmonare acuta

Introduction
Palliative care (PC) improves quality of life (QOL). However, PC is currently delivered ‘too little, too late’ in heart failure (HF). Timely interventions to enable and reach patients with HF and their caregivers, with PC (TIER-HF-PC) is a novel, nurse coach-led model of PC that integrates PC into HF care. We will compare the effectiveness of TIER-HF-PC against usual care for improving patient and caregiver health outcomes. We will also evaluate implementation outcomes (such as care experience) of TIER-HF-PC.

Methods and analysis
In TIER-HF-PC, patients undergo regular distress screening. The intensity of PC treatments will be tiered based on the severity of problems detected. Minimally, all patients will receive PC education resources. Patients with moderate-intensity needs will receive PC health coaching. Patients with high-intensity needs will receive a PC physician consultation, on top of PC health coaching. Patients in usual care are not screened but can be referred to a PC physician based on cardiologist discretion.
We will recruit 240 English- or Mandarin-speaking patients with HF and up to 240 caregivers from 3 sites across 2 cardiac centres. Patients will be randomised in a 1:1 ratio to TIER-HF-PC or usual care. We will use an intention-to-treat approach for data analysis. Our primary outcome is patient QOL on the Kansas City Cardiomyopathy Questionnaire at 24 weeks. Secondary outcomes include patient healthcare utilisation, caregiver QOL and cost-effectiveness. All participants who received PC treatments will receive a service evaluation survey. Additionally, a sample of these participants and their treating healthcare staff will be purposively recruited for in-depth semistructured interviews on their TIER-HF-PC experience. Interviews will be thematically analysed. We will evaluate protocol fidelity through case notes and study process audits.

Ethics and dissemination
This study was approved by the SingHealth Institutional Ethics Review Board—review number: 2024–2213. Results of the study will be disseminated when data analysis is complete.

Trial registration number
NCT06244953.

Background
Immunotherapies targeting the programmed death receptor-1/programmed death ligand-1(PD-1/PD-L1) checkpoint have a major impact on the treatment of both resectable and advanced non-small cell lung cancer (NSCLC). Additional blockade of the T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-receptor may synergistically foster the immune-related response. Several trials are currently investigating the combination of neoadjuvant platinum-based chemotherapy and dual checkpoint inhibition prior to curative surgery. The investigator-initiated NeoTRACK trial (EU CT number: 2022-501322-38-00; ClinicalTrials.gov identifier: NCT05825625; IKF056) aims to evaluate the feasibility and safety of perioperative anti-PD-L1 (by atezolizumab) and anti-TIGIT (by tiragolumab) treatment in combination with chemotherapy in patients with early stage NSCLC.

Methods and analysis
NeoTRACK is an open-label, single-arm, prospective, bicentric phase II trial. Patients with NSCLC in clinical stages II, IIIA and IIIB (only T3N2) will receive two cycles of standard platinum-based chemotherapy in combination with the anti-TIGIT antibody tiragolumab and the anti-PD-L1 antibody atezolizumab, followed by curative surgery. After surgery, patients without pathological complete response (pCR) will receive another two cycles of chemotherapy in combination with tiragolumab and atezolizumab, followed by tiragolumab/atezolizumab maintenance for up to 1 year (maximum 16 cycles). Patients with pCR will only receive dual immunotherapy. All patients will be followed-up for 30 months after the last study treatment. The clinical study will be aligned with a translational research programme to investigate treatment-naïve tumour tissues, surgical specimens and longitudinally collected blood samples. 35 patients are planned for enrolment. Patient recruitment started in August 2023, and treatment of the last patient is estimated to start 2.5 years thereafter.

Discussion
The NeoTRACK trial aims to assess the feasibility and efficacy of combining tiragolumab and atezolizumab as both neoadjuvant and adjuvant therapies in patients with resectable NSCLC. The concept of treatment personalisation based on postoperative pCR is of great clinical interest.

Ethics and dissemination
The trial obtained ethical and regulatory approval in Germany through the Clinical Trials Information System (CTIS, ID: 2022-501322-38-00) and the Paul Ehrlich Institute (PEI, competent authority for approval of clinical trials using medicinal products for human use in Germany, process number: PB00148) on 30 March 2023. A data safety and monitoring board will meet regularly to review ongoing treatment in terms of safety.
Study results will be published in peer-reviewed journals, presented at conferences and in the public registry of CTIS, following trial completion.

Trial registration number
NCT05825625.

Introduction
The prevalence of cancer in Canada is growing, leading to multiple lasting side effects in survivors. The physical and psychosocial benefits of regular physical activity (PA) during and after treatment for individuals with cancer are well established, however, not well implemented in a clinical setting. The overall aim of this project is to build on previous work and conduct a multicentred randomised controlled trial (RCT) and evaluate the effectiveness of a novel implementation strategy using PA and self-management versus usual care during cancer treatment.

Methods and analysis
Study design: a hybrid implementation–effectiveness RCT will occur at five cancer centres across Ontario, Canada. Participants: eligible participants include adults with a cancer diagnosis (any type or stage) who are receiving treatment and cleared for exercise by their oncology care team. Intervention: participants (n=129) will be randomised to one of three groups: (1) institution-based exercise and self-management (SM) (eight in-person sessions of aerobic exercise and eight SM modules), (2) SM alone (SM only: eight virtual modules) or (3) usual care (no intervention). Outcomes: the Reach, Effectiveness, Adoption, Implementation and Maintenance framework will assess implementation outcomes. The primary effectiveness outcome is self-report PA level postintervention. Data analysis: outcomes will be measured at four time points (baseline, postintervention, 6- and 12-month follow-up). Descriptive statistics will be used to present implementation outcomes. An analysis of covariance will assess change between groups over time.

Ethics and dissemination
Findings from this trial will build on previous work and inform the way PA services are provided within cancer institutions across Ontario, Canada, and inform decision-making on how to incorporate exercise evidence into real-world clinical practice in cancer care. The Hamilton Integrated Research Ethics Board (ID: 7673 & 17454) has approved this study. Results will be disseminated using a combination of peer-reviewed publications, conference presentations and community organisation presentations. Participants will contribute to dissemination by sharing ‘participant perspectives’, highlighting their experience in the project and thoughts on the implementation strategies used.

Trial registration number
The study is registered on clinicaltrials.gov (ID: NCT06323707).

Background
Immunotherapies targeting the programmed death receptor-1/programmed death ligand-1(PD-1/PD-L1) checkpoint have a major impact on the treatment of both resectable and advanced non-small cell lung cancer (NSCLC). Additional blockade of the T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-receptor may synergistically foster the immune-related response. Several trials are currently investigating the combination of neoadjuvant platinum-based chemotherapy and dual checkpoint inhibition prior to curative surgery. The investigator-initiated NeoTRACK trial (EU CT number: 2022-501322-38-00; ClinicalTrials.gov identifier: NCT05825625; IKF056) aims to evaluate the feasibility and safety of perioperative anti-PD-L1 (by atezolizumab) and anti-TIGIT (by tiragolumab) treatment in combination with chemotherapy in patients with early stage NSCLC.

Methods and analysis
NeoTRACK is an open-label, single-arm, prospective, bicentric phase II trial. Patients with NSCLC in clinical stages II, IIIA and IIIB (only T3N2) will receive two cycles of standard platinum-based chemotherapy in combination with the anti-TIGIT antibody tiragolumab and the anti-PD-L1 antibody atezolizumab, followed by curative surgery. After surgery, patients without pathological complete response (pCR) will receive another two cycles of chemotherapy in combination with tiragolumab and atezolizumab, followed by tiragolumab/atezolizumab maintenance for up to 1 year (maximum 16 cycles). Patients with pCR will only receive dual immunotherapy. All patients will be followed-up for 30 months after the last study treatment. The clinical study will be aligned with a translational research programme to investigate treatment-naïve tumour tissues, surgical specimens and longitudinally collected blood samples. 35 patients are planned for enrolment. Patient recruitment started in August 2023, and treatment of the last patient is estimated to start 2.5 years thereafter.

Discussion
The NeoTRACK trial aims to assess the feasibility and efficacy of combining tiragolumab and atezolizumab as both neoadjuvant and adjuvant therapies in patients with resectable NSCLC. The concept of treatment personalisation based on postoperative pCR is of great clinical interest.

Ethics and dissemination
The trial obtained ethical and regulatory approval in Germany through the Clinical Trials Information System (CTIS, ID: 2022-501322-38-00) and the Paul Ehrlich Institute (PEI, competent authority for approval of clinical trials using medicinal products for human use in Germany, process number: PB00148) on 30 March 2023. A data safety and monitoring board will meet regularly to review ongoing treatment in terms of safety.
Study results will be published in peer-reviewed journals, presented at conferences and in the public registry of CTIS, following trial completion.

Trial registration number
NCT05825625.

Objectives
Vitamin D deficiency is prevalent among the population. Previous studies have shown that vitamin D supplementation might be useful for treating COVID-19 infection. Therefore, we performed a meta-analysis to explore vitamin D supplementation efficacy in treating COVID-19 patients with vitamin D deficiency.

Design
Systematic review and meta-analysis

Data sources
PubMed, Cochrane Library, Embase and Web of Science.

Eligibility criteria
Randomised controlled trials exploring vitamin D supplementation for patients with COVID-19 and vitamin D deficiency.

Data extraction and synthesis
Two independent reviewers employed standardised methods to search, screen and code the included studies. The primary outcomes included mortality during follow-up, 28-day mortality, need for mechanical ventilation and intensive care unit (ICU). The secondary outcome included length of stay in hospital and ICU. The risk of bias was assessed using the Risk of Bias 2 tool. Depending on the level of heterogeneity, either a random-effects model or a fixed-effects model was applied. The findings were summarised using Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profiles and synthesised qualitatively.

Results
A total of nine studies, comprising 870 participants, were included in the analysis. The pooled results indicated that vitamin D supplementation was associated with a lower risk of mortality (risk ratio 0.76; 95% CI 0.60 to 0.97). However, this apparent benefit was not robust when examined through the leave-one-out method and trial sequential analysis. Regarding other outcomes, there was no statistically significant difference between vitamin D supplementation and no supplementation in terms of 28-day mortality, the need for mechanical ventilation and ICU admission. Vitamin D supplementation was associated with a 0.41 day shorter length of stay in the ICU (mean difference –0.41; 95% CI –1.09 to 0.28) and a 0.07 day shorter length of stay in the hospital (mean difference –0.07; 95% CI –0.61 to 0.46) compared with no supplementation; however, neither difference was statistically significant.

Conclusion
Based on evidence of low to moderate quality, vitamin D supplementation reduced the mortality rate during follow-up in COVID-19 patients with vitamin D deficiency. However, it did not improve 28-day mortality, nor did it reduce the need for mechanical ventilation and ICU admission, or the length of stay in the ICU and hospital.

PROSPERO registration number
CRD42024573791.

Introduction
Arm weakness after stroke is one of the leading causes of adult-onset disability. Invasive vagus nerve stimulation (VNS) paired with rehabilitation has been shown to improve arm recovery in chronic stroke. Small studies of non-invasive or transcutaneous VNS (tVNS) suggest it is safe and tolerable. However, it is not known whether tVNS paired with rehabilitation is effective in promoting arm recovery in chronic stroke and what the mechanisms of action are.

Methods and analysis
TRICEPS is a UK multicentre, double-blinded, superiority, parallel-group, three-arm two-stage with an option to select promising arm(s) at 50% accrual, individually randomised, sham-controlled trial. Up to 243 participants will be randomised (1:1:1) using minimisation via a restricted, web-based centralised system. tVNS will be delivered by a movement-activated tVNS system (TVNS Technologies), which delivers stimulation during repetitive task practice. Rehabilitation will consist of repetitive task training for 1 hour a day, 5 days per week for 12 weeks. Participants will be adults with anterior circulation ischaemic stroke between 6 months and 10 years prior with moderate-severe arm weakness. The primary outcome measure will be the change in Upper Limb Fugl-Meyer total motor score at 91 days after the start of treatment. Secondary outcome measures include the Wolf Motor Function Test, the Modified Ashworth Scale to assess spasticity in the affected arm and the Stroke-Specific Quality of Life Scale. A mechanistic substudy including 40 participants will explore the mechanisms of active versus sham tVNS using multimodal MRI and serum inflammatory cytokine levels. Participant recruitment started on 30 November 2023.

Ethics and dissemination
The study has received ethical approval from the Cambridge Central Research Ethics Committee (REC reference: 22/NI/0134). Dissemination of results will be via publications in scientific journals, meetings, written reports and articles in stakeholder publications.

Trial registration number
ISRCTN20221867.

Objectives
A previous cohort study of male Norwegian Navy submariners showed higher overall cancer incidence and lower all-cause mortality than the general Norwegian population. We have extended the follow-up and show more precise estimates through seven decades.

Design
Historical cohort study using outcome data from Norwegian cancer incidence and cause-of-death registries.

Setting
Linkage with the outcome registries was performed by means of unique national identification numbers given to all Norwegian citizens.

Participants
2663 military men who ever served aboard a Navy submarine between 1942 and 2005.

Outcome measures
Standardised incidence ratios for cancer and mortality ratios were calculated from national period-specific, gender-specific and age-specific rates. Poisson regression was used to compare cancer incidence in groups with different length of submarine service ( >2 years vs ≤2 years).

Results
The overall cancer incidence was 15% higher than expected from the national rates, with colon, lung, skin (melanoma and non-melanoma) and urinary tract contributing 90% of the excess number of cases. Most of the excess was confined to those with shorter-time service, who also showed elevated risk of alcohol-related cancers. Excess non-melanoma skin cancer was most clearly seen among submariners with >2 years of service. Mortality from all causes combined was lower among submariners than in the general population, due to a markedly low mortality from non-neoplastic diseases and external causes.

Conclusions
Increased risk of non-melanoma skin cancer was found among submariners with long-term service, and skin exposure to carcinogens in petroleum products was hypothesised as an explanation. Less support for occupational risks was found for other cancers, although the lack of specific exposure data and limited statistical power reduced the possibility of identifying such associations. A ‘healthy soldier effect’ appeared in the mortality data, mainly restricted to low mortality from non-neoplastic diseases and external causes.

Objective
To examine the current state of data-sharing practices in gastroenterology literature, focusing on data-sharing statements (DSS) and identifying influential factors on DSS inclusion.

Background
High-quality, reproducible research is crucial in addressing the widespread prevalence of gastrointestinal diseases. Data-sharing practices enable researchers to access studies more easily, enhancing reproducibility. Our study aims to analyse the inclusion and influence of DSS in top gastroenterology journals.

Methods
We conducted a cross-sectional analysis to examine the use and contents of DSS in gastroenterology clinical trials. Using Clarivate’s Journal Citation Reports, we selected five leading gastroenterology journals. Then, we searched MEDLINE (PubMed) for original research articles published between 1 January 2018 and 31 December 2023. In a double-blind, duplicate manner, data were extracted on DSS presence, funding source, study design and open-access status. We then conducted a thematic analysis of all DSS. Additionally, authors were contacted and given 14 days to respond or share data to investigate adherence to their DSS.

Results
Of the 953 articles that met inclusion criteria, 400 (400/953; 42.0%) contained a DSS. Open-access articles had a higher likelihood of containing DSS (estimate=0·413; p

Introduction
Target trial emulation is a framework for evaluating the effects of treatments using observational data. The trial emulation approach involves specifying key elements of a protocol for a target trial (a randomised controlled trial designed to address the question of interest) and then describing how best to emulate the trial using observational data. Recent years have seen an uptake of target trial emulation in several disease areas, although there are limited examples in cystic fibrosis (CF). This protocol describes a study which aims to assess the applicability of target trial emulation in CF. We aim to emulate an existing trial in CF and assess to what extent the results from the trial can be replicated using registry data.

Methods and analysis
The target trial is a published randomised controlled trial which found evidence for beneficial effects of azithromycin use on lung function in young adults with CF. Two emulated trials are planned: one using data from the UK CF Registry and one using data from the US CF Registry. The inclusion and exclusion criteria, treatment and outcome definitions, follow-up period, and estimand of interest are all designed to match the published trial as closely as possible. The analysis step of the trial emulations will use causal inference methods to control for confounding. Results obtained in the emulated trials using registry data will be compared with those from the target trial.

Ethics and dissemination
Ethical approval has been granted by the London School of Hygiene and Tropical Medicine Ethics Committee (Ref: 29609). This study has also been approved by the UK CF Registry Research Committee and the North Star Review Board. The results of this study will be published in a peer-reviewed journal and presented at relevant scientific conferences.

Stroke, Ahead of Print. BACKGROUND:Recent randomized trials demonstrated the beneficial effect of endovascular therapy in patients with low Alberta Stroke Program Early Computed Tomography Score. Despite large follow-up infarct volumes, a significantly increased rate of good functional outcomes was observed, challenging the role of infarct volume as a predictive imaging marker. This analysis evaluates the extent to which the effects of endovascular thrombectomy on functional outcomes are explained by (1) follow-up infarct volume and (2) early neurological status in patients with stroke with low Alberta Stroke Program Early Computed Tomography Score.METHODS:TENSION was a randomized trial conducted from February 2018 to January 2023 across 41 stroke centers. Two hundred fifty-three patients with ischemic stroke due to anterior circulation large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of 3 to 5 were randomized to endovascular thrombectomy plus medical treatment or medical treatment alone. All patients with the availability of relevant data points were included in this secondary as-treated analysis. The primary outcome was the 90-day modified Rankin Scale score. Confounder-adjusted mediation analysis was performed to quantify the proportion of the treatment effect on a 90-day modified Rankin Scale score explained by (1) 24-hour follow-up infarct volume and (2) 24-hour National Institutes of Health Stroke Scale scores.RESULTS:One hundred eighty-eight patients were included; thereof, 87 (46%) were females. Median age was 72 (interquartile range, 63–79) years. The endovascular thrombectomy cohort had a 20.5 (95% CI, 8.3–33.7) percentage points higher probability of achieving independent ambulation (modified Rankin Scale, 0–3) and a 24.2 (95% CI, 13.4–35.8) percentage points lower mortality at 90 days compared with medical treatment alone. The reduction in 24-hour follow-up infarct volume explained 30% of the treatment effect on functional outcomes, while the 24-hour National Institutes of Health Stroke Scale score explained 61%.CONCLUSIONS:In patients with low Alberta Stroke Program Early Computed Tomography Score, infarct volume demonstrated limited explanatory power for functional outcomes compared with the early neurological status, which may more effectively reflect factors such as the involvement of specific brain regions, disruption of structural networks, and selective neuronal loss.

Introduction
Smoking in pregnancy negatively impacts the mother’s and offspring’s health. Mobile health, especially mobile phone-based approaches, shows promise in supporting pregnant women to quit smoking. Our previous research indicated that support from laypersons, such as family, friends and coworkers, can increase smoking cessation. Building on these findings, we developed an innovative smartphone application (app) that combines the power of social support with artificial intelligence. The app leverages the unique functionality of smartphones and reinforcement learning (RL) to provide a deeply tailored intervention that continuously adapts while emphasising positive support through reciprocal interactions between the smoker and the support person. Herein, we report the methods used to develop, implement and test the feasibility and effectiveness of a novel adaptive mobile pregnancy tobacco cessation app-based intervention using deep tailoring and a self-nominated supporter.

Methods and analysis
The study is a type II hybrid effectiveness-implementation randomised controlled trial. In total, 300 pregnant smokers and their supporters will be randomised to (1) the SmokeFree Together 2.0 app and an RL-based intervention that continuously decides if a counselling call is needed using a fixed algorithm measuring motivation and craving or (2) a control group. The intervention will be administered throughout pregnancy up to 1 month after giving birth, with a 5-month follow-up period and outcome assessments at 3-month and 6-month post partum. Cessation (primary outcome) is defined as 7-day point biochemically verified prevalence of tobacco use and abstinence since birth, assessed at 6 months post partum. The central hypothesis is that the intervention will show evidence of feasibility and effectiveness in increasing social support, pregnancy cessation and postnatal abstinence.

Ethics and dissemination
The Institutional Review Board of Michigan State University (#IRB00000297) approved this trial. The findings will be disseminated through peer-reviewed publications and participation in scientific conferences.

Trial registration number
NCT05337722. Protocol version: 1.3 from 15.05.2024.

Objectives
Changes in poststroke heart rate variability (HRV) might be helpful for early identification of patients with neurological impairment and poor prognosis, which could allow for early intervention to reduce adverse outcomes. The aim of this study is to perform a scoping review to identify the influence of poststroke HRV on the neurological impairment severity and the prognosis among patients with ischaemic stroke (IS).

Design
The study design allows us to examine existing research, identify the research gaps and target the important areas for future research. In the search and report process, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines and checklist were used.

Data sources
Three databases (PubMed, Web of Science and Ovid MEDLINE (Ovid)) were searched before December 2023.

Eligibility criteria for selecting studies
The literature related to the topic of this study was mainly included, and the articles were excluded if they only focused on cerebral haemorrhage or were reviews, guidelines, books, etc.

Data extraction and synthesis
Descriptive analysis was used to display the distribution of the included studies and then the summary method was adopted for further analysing.

Results
3251 articles that may be related to the scoping review topic were screened. After title and abstract screening and full-text reading, 21 records were finally included. Whether at discharge (n=6) or after follow-up (n=11), it was found that when the SD of all normal-to-normal intervals (SDNN) or the SD of the averages of normal-to-normal intervals decreased, the neurological impairment severity would be increased, including dysarthria, aphasia and hemiplegia. The root mean square of successive differences, the ratio of low frequency to high frequency and the high frequency were valuable predictors for the occurrence of adverse cardiocerebrovascular events. And the poor prognosis among patients with IS might be influenced by SDNN.

Conclusion
This scoping review confirmed that post-IS HRV indicators can predict neurological impairment and prognosis of patients with stroke, highlighting a potential direction for early intervention. Large independent cohorts should be used to evaluate the predictive performance, reliability and potential limitations of these indicators in the future, and it will be important to explore interventions that make HRV change.

Introduction
Musculoskeletal disorders (MSDs) represent a significant global health burden that leads to substantial disability with socioeconomic impact. With the rise of artificial intelligence (AI), particularly large language model-driven conversational agents (chatbots), there is potential to enhance the management of MSDs. However, the application of AI-powered chatbots in this population has not been comprehensively synthesised. Therefore, this scoping review aims to explore the current and potential use of AI-powered chatbots in managing MSDs. The review will map out the targeted diseases, the purposes of chatbot interventions, the clinical tools or frameworks used in training these systems and the evaluated outcomes in clinical settings.

Methods and analysis
This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, with a comprehensive search across multiple databases, including Medline (Ovid Medline), Embase (Ovid), ISI Web of Science (Clarivate) and ClinicalTrials.gov. We will include studies involving adults with MSDs, regardless of publication status, language or year. The scoping review will exclude studies using non-AI chatbots or human health coaches. Data extraction and synthesis will focus on demographic characteristics, chatbot methods, outcomes and thematic analysis.

Ethics and dissemination
Formal ethical approval is not required as this study involves neither human participants nor unpublished secondary data. The findings of this scoping review will be disseminated through professional networks, conference presentations and publication in a scientific journal.

Introduction
Transition shock is a very common negative clinical practice experience for nursing students, which not only makes the adaptation to clinical practice difficult but also influences the smooth transition from nursing students to registered nurses and eventually could lead them to leave the nursing field. Therefore, transition shock of nursing students deserves attention. Recently, there has been a notable increase in research dedicated to transition shock experienced by nursing students. However, the overview of research done on this topic remains unclear. Therefore, we will conduct a scoping review to summarise assessment tools, influencing factors, the impacts and intervention strategies of transition shock among nursing students and identify knowledge gaps in this field to guide further research.

Methods and analysis
We will follow the Joanna Briggs Institute scoping review guidelines to conduct this scoping review. A comprehensive literature search will be conducted through 12 databases and grey literature sources. The search period will be restricted from May 2009 to December 2024, and this review will only incorporate publications in Chinese or English. Two researchers will independently screen the literature according to inclusion criteria, and then conduct data extraction. Any differences arising between the two researchers will be addressed by engaging in discussion with a third researcher. We will collate, summarise and analyse the extracted data and subsequently present the results by means of figures, tables and descriptive narratives. This review will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting checklist.

Ethics and dissemination
As this review does not involve patients or the public, there is no need for ethical approval. The results of this scoping review will be disseminated by means of conference presentations and publication in a peer-reviewed academic journal.

Registration
Open Science Framework (https://osf.io/2r6jn/).

Coming back once onto my son’s floor from a late evening break, a woman in the family room asked me to help look for her phone. We turned over cushions, looked under the couch, coffee table, retraced her steps in the hall. The desk attendant put down her book, brought up the lost and found box. Its sides were fingerpainted with smiley faces and names.

Circulation, Ahead of Print. BACKGROUND:Genetic variants in desmosomal cadherins, desmoglein 2 (DSG2) and desmocollin 2 (DSC2), cause a distinct form of arrhythmogenic right ventricular cardiomyopathy (ARVC), which remains poorly reported. In this study, we aimed to provide a comprehensive description of the phenotypic expression, natural history, and clinical outcomes of patients with this ARVC subset.METHODS:Genetic and clinical data ofDSG2andDSC2variant carriers were collected from 5 countries in Europe and Asia. We assessed the phenotypic profile of these patients and their clinical outcomes, focusing on heart failure and ventricular arrhythmia events.RESULTS:Overall, 271 subjects, 254 withDSG2variants, were included in this study (median age, 38 years [interquartile range, 25–52]; 62.7% male). Of these, 165 were probands, and 200 were diagnosed with definite ARVC. A total of 181 (66.8%) individuals carried missense variants, mainly distributed in the extracellular domains. Notably, we included 78 (28.8%) individuals with multiple variants. Of the 200 cases with diagnosed ARVC, 41 (20.5%) experienced premature cardiac death before the age of 65. Among the 81 individuals for whom both left ventricular ejection fraction and right ventricular fractional area change data were available at presentation, 29 (35.8%) had isolated right ventricular dysfunction, and 16 (19.8%) had biventricular dysfunction. Single-variant carriers who engaged in intense physical exercise were younger at disease onset compared with those who did not (P=0.001). Compared with single-variant carriers, those with multiple variants were more likely to be diagnosed with ARVC (96.2% versus 64.8%;P