Protocol for Health Risk Information Technology-Assisted Genetic Evaluation (HeRITAGE): a randomised controlled trial of digital genetic cancer risk assessment in a diverse underserved gynaecology clinic

Introduction
In the USA, up to 95% of individuals harbouring cancer-predisposing germline pathogenic variants have not been identified despite recommendations for screening at the primary care level.

Methods and analysis
Our primary objective is to use a two-arm, single-institution randomised controlled trial to compare the proportion of eligible patients that are recommended genetic testing for hereditary cancer syndromes using a digital tool versus clinician interview for genetic cancer risk assessment in an urban academic gynaecology clinic. New gynaecology patients will be consented and randomised 1:1 to either the intervention arm, in which a digital tool is used for genetic cancer risk assessment, or usual care, in which the clinician performs genetic cancer risk assessment. Individuals will be considered eligible for hereditary cancer syndrome genetic testing if criteria set forth by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology are met. Eligible patients are 18 years or older, speak and read English, have not yet undergone hereditary cancer genetic testing and have access to a smartphone. The study aims to enrol 50 patients in each arm to allow for 80% power with two-tailed alpha of 5% to detect a 20% difference in proportion of eligible patients recommended for genetic testing. The primary outcome is the proportion of eligible individuals recommended genetic testing in the digital tool arm versus usual care arm, analysed using the 2 or Fisher’s exact test as appropriate for sample size. The secondary outcome is completion of genetic testing, as well as exploration of patient factors, particularly social determinants of health, which may affect the receipt, utilisation and experience with genetic services.

Ethics and dissemination
This study has been approved by the Weill Cornell Institutional Review Board (Protocol No. 21-11024123). Participants will be informed of the benefits and risks of participation prior to consent. Dissemination of data will be deidentified and conducted through academic conferences and journals. Patients identified to be eligible for genetic testing who did not receive counselling from their providers will be contacted; participants will not receive direct notification of trial results.

Registration details
This trial is registered at clinicaltrials.gov (NCT05562778) in September 2022.

Protocol version
This is protocol version 1, as of 22 May 2024.

Countries of recruitment and recruitment status
USA, currently recruiting.

Health conditions/problems studied
Genetic predisposition to cancers such as breast, ovarian, uterine and pancreatic.

Deidentified individual clinical trial participant-level data (IDP) sharing statement
IDP will not be shared.

Trial registration number
NCT05562778.

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Empowering Portable Age-Related Macular Degeneration Screening: Evaluation of a Deep Learning Algorithm for a Smartphone Fundus Camera

Objectives
Despite global research on early detection of age-related macular degeneration (AMD), not enough is being done for large-scale screening. Automated analysis of retinal images captured via smartphone presents a potential solution; however, to our knowledge, such an artificial intelligence (AI) system has not been evaluated. The study aimed to assess the performance of an AI algorithm in detecting referable AMD on images captured on a portable fundus camera.

Design, setting
A retrospective image database from the Age-Related Eye Disease Study (AREDS) and target device was used.

Participants
The algorithm was trained on two distinct data sets with macula-centric images: initially on 108,251 images (55% referable AMD) from AREDS and then fine-tuned on 1108 images (33% referable AMD) captured on Asian eyes using the target device. The model was designed to indicate the presence of referable AMD (intermediate and advanced AMD). Following the first training step, the test set consisted of 909 images (49% referable AMD). For the fine-tuning step, the test set consisted of 238 (34% referable AMD) images. The reference standard for the AREDS data set was fundus image grading by the central reading centre, and for the target device, it was consensus image grading by specialists.

Outcome measures
Area under receiver operating curve (AUC), sensitivity and specificity of algorithm.

Results
Before fine-tuning, the deep learning (DL) algorithm exhibited a test set (from AREDS) sensitivity of 93.48% (95% CI: 90.8% to 95.6%), specificity of 82.33% (95% CI: 78.6% to 85.7%) and AUC of 0.965 (95% CI:0.95 to 0.98). After fine-tuning, the DL algorithm displayed a test set (from the target device) sensitivity of 91.25% (95% CI: 82.8% to 96.4%), specificity of 84.18% (95% CI: 77.5% to 89.5%) and AUC 0.947 (95% CI: 0.911 to 0.982).

Conclusion
The DL algorithm shows promising results in detecting referable AMD from a portable smartphone-based imaging system. This approach can potentially bring effective and affordable AMD screening to underserved areas.

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Vaping in Youth

This JAMA Insights reviews the health effects of vaping among youth in the US and current recommendations for screening and treatment.

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Randomized Invitation to Systematic NT-proBNP and ECG Screening in 75-Year Olds to Detect Atrial Fibrillation -STROKESTOP II

Circulation, Ahead of Print. Background:Guidelines have suggested screening for atrial fibrillation to enable early treatment and avoid downstream negative clinical events. We aimed to determine if atrial fibrillation screening potentially enhanced by NT-proBNP would reduce stroke or systemic embolism incidence as compared to in a control group and to determine if it was safe for those with low NT-proBNP concentrations to forfeit prolonged screening.Methods:In this randomized controlled trial all 75/76-year-old individuals in Stockholm Region, Sweden were randomized 1:1 to be invited to screening or serve as a control group. NT-proBNP concentration were measured and a single-lead-ECG registered only once if NT-proBNP

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Associations Between Prenatal Cannabis Use and Maternal Health Outcomes

With the legalization of cannabis in many states, the question of what effect it has on pregnant individuals has become more pressing. In this issue of JAMA Internal Medicine, Young-Wolff and colleagues examine the association between prenatal cannabis use and maternal health outcomes. Data were drawn from the Kaiser Permanente Northern California system, with prenatal cannabis use defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening when establishing prenatal care. Using a population-based cohort design, they examined outcomes of gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity during an 8-year period (2011-2019).

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Contralateral Breast Cancer Remains a Complex Biological Conundrum

Although contralateral breast cancer (CBC) is the most frequent second malignant tumor among women who have experienced a diagnosis of primary breast cancer, it is less frequent, and less ominous than recurrence of the initial cancer. Nevertheless, for many patients with newly diagnosed unilateral breast cancer, it can be a prominent source of worry as they navigate their treatment decisions. This worry is accentuated among young patients and those with early-stage disease. The most effective preventive solution for CBC is contralateral mastectomy, which was rarely used in the 20th century but has been increasingly used during the past 20 years, first in the US, and now in other countries with comparable resources. For women with a unilateral breast cancer, the consideration of contralateral mastectomy has many drivers, some undoubtedly patient-related, but others stemming from misconceptions among the medical community regarding the risks and benefits of contralateral mastectomy. To date, studies addressing the question of survival following contralateral phylactic mastectomy (CPM) have failed to provide evidence for improved survival. Although lack of survival benefit may seem counter-intuitive, a tenable explanation is that the dominant hazard to survival derives from the index primary tumor rather than the CBC. Because patients with breast cancer are diagnosed with the index primary tumor at a younger age (which increases the hazard of death) and are treated with older, less effective regimens, it is possible that the risk of death from CBC is subsumed by the risk from the index cancer, particularly if second cancers are diagnosed at earlier stages in survivors who tend to be more adherent to posttreatment screening. Consequently, surgical measures to prevent a second primary tumor do not extend survival.

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Screening ECGs for Cardiovascular Risk Assessment

In their article on routine electrocardiogram (ECG) screening and cardiovascular disease (CVD) events Yagi and colleagues report findings from a nationwide cohort study on screening electrocardiography in Japan between January 2015 and December 2021. Since 1989, an annual screening ECG has been mandatory for working-age people in Japan aged 35 years and older. The authors assessed claims and annual health screening data from the Japan Health Insurance Association that included 3 698 429 individuals registered in the database and who had a screening ECG in 2016. Electrocardiograms were classified as having 1 minor abnormality, 2 or more minor abnormalities, or major abnormalities. Using multivariable Cox proportional hazards models and adjusting for multiple clinical covariates, the authors found a greater risk of the composite outcome of overall death or hospital admission for CVD in people with 1 minor abnormality (hazard ratio [HR], 1.19; 95% CI, 1.18-1.20), 2 or more minor abnormalities (HR, 1.37; 95% CI, 1.34-1.39), and major ECG abnormalities (HR, 1.96; 95% CI, 1.92-2.02) compared with people with a normal ECG result. Cardiovascular events were observed across subgroups by age, sex, and low vs moderate to high CVD risk groups. The authors concluded that “further studies are needed to elucidate the role of routine ECG screening for early prevention of CVD events, along with optimal follow-up strategies for both major and minor ECG abnormalities.”

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AI and Big Data approaches to addressing the opioid crisis: a scoping review protocol

Introduction
This paper outlines the steps necessary to assess the latest developments in artificial intelligence (AI) as well as Big Data technologies and their relevance to the opioid crisis. Fatal opioid overdoses have risen to over 82 998 annually in the USA. This highlights the need for urgent and effective data-driven solutions. AI approaches, such as machine learning, deep learning and natural language processing, have been employed to analyse patterns and trends in overdose data and facilitate timely interventions. However, a comprehensive scoping review on the effectiveness of AI-driven technologies to detect, treat, prevent or respond to the opioid crisis remains absent. Thus, it is important to identify recent advancements in AI and Big Data technologies in addressing the opioid crisis.

Methods and analysis
We will electronically search four scientific databases (PubMed, Web of Science, Engineering Village and PsycInfo), including finding reference lists and grey literature from 2013 to 2023. Covidence will be used for screening and selecting papers. We will extract information such as citation details, study context, data used, AI/Big Data technologies, features, algorithms and evaluation metrics. This data will be synthesised, analysed and summarised to draw meaningful conclusions and identify future directions to tackle the opioid crisis.

Ethics and dissemination
Ethics approval is not required. Results will be disseminated via conference presentations and peer-reviewed publication.

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Opportunities for nurses aspiring to or undertaking clinical academic development globally: protocol for a scoping review

Introduction
Nurse researchers often lack awareness of how to start a clinical academic research career and often lack clear entry routes. This scoping review aims to identify the range and nature of clinical academic opportunities available for nurses. This will also identify the knowledge gaps and provide the basis for future research.

Methods and analysis
The review will be conducted using scoping review methodology and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the Extension for Scoping Reviews guidelines. We will search CINAHL (EBSCO), MEDLINE (Ovid), AMED (Ovid) and ProQuest using a search based on the facet’s ‘nurse’, ‘research’ and ‘clinical academic’. Grey literature and a hand search of the reference lists will be conducted for additional publications meeting the inclusion and exclusion criteria. We will include articles published in English, with a focus on registered nurses interested in undertaking clinical academic development within any healthcare system, with no restrictions regarding the date of publication. Following initial screening of titles and abstracts, relevant full-text papers will be screened for inclusion. Two independent reviewers will participate in an iterative process of screening the literature, paper selection and data extraction. We will use a prespecified form to extract data which will be charted and presented in a tabular form. Samples of data extraction and charting will be checked by a second reviewer. This will support a narrative summary structured around key identified variables agreed on iteratively by the review team.

Ethics and dissemination
No ethical or Health Research Authority approval is required to undertake this scoping review. The findings will inform future research exploring the opportunities supporting nurses aspiring to undertake clinical academic development and be disseminated via presentations at national conferences and publications in peer-reviewed journals.

Study registration
Open Science Framework, DOI:10.17605/OSF.IO/WVDXH.

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Psychological and pharmacological treatments of intermittent explosive disorder: a meta-analysis protocol

Introduction
Intermittent explosive disorder (IED) is characterised by recurrent, sudden episodes of impulsive aggression that are disproportionate to the provocation. The condition’s management remains challenging due to the variability in treatment efficacy and the absence of Food and Drug Administration-approved interventions specifically for IED. This meta-analysis aims to evaluate the effectiveness of existing treatments for IED.

Methods and analysis
Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive literature search was conducted in November 2023, yielding 17 randomised controlled trials after screening and eligibility assessments. Studies were included based on participants’ confirmed diagnosis of IED, sufficient statistical power and provision of data for effect size calculation. Interventions analysed included pharmacological treatments, psychotherapies and combination therapies, with an emphasis on cognitive–behavioural therapy and selective serotonin reuptake inhibitors. Quality assessment was performed using the Cochrane Risk of Bias Tool.

Ethics and dissemination
Given that our study is a synthesis of published data, ethical approval from a research ethics committee is not required. Nevertheless, the methodology of this review was designed to ensure full transparency and accountability. All efforts have been made to respect the confidentiality and intellectual property rights of the original data sources. Any ethical issues encountered during the data collection process were addressed in accordance with the guidelines of the Declaration of Helsinki. As this research involves the analysis of existing published data, there are no direct safety concerns related to patient interactions. Our primary focus has been on ensuring the secure handling and processing of data to uphold the ethical standards set by previous original studies. To ensure the findings of our meta-analysis reach both the academic community and the public effectively, we aim to submit our findings to peer-reviewed journals within the fields of psychology to ensure rigorous review and broad academic dissemination.

PROSPEO registration number
CRD42024497587.

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Comparison of outcomes of open, laparoscopic and robot-assisted laparoscopic pyeloplasty in children with ureteropelvic junction obstruction: protocol for a systematic review and meta-analysis

Introduction
The treatment of children with pelviureteric junction obstruction (PUJO) has naturally progressed from open, to minimally invasive approaches, including laparoscopic pyeloplasty and robot-assisted laparoscopic pyeloplasty (RALP). The RALP is now considered to be the gold standard for paediatric patients with PUJO, except for smaller infants due to size limitations. Our systematic review aims to synthesise all the available evidence regarding key postoperative outcomes for the three surgical approaches to pyeloplasties in children. Our outcomes of interest include, but are not limited to, the reoperation rate, length of hospital stay and postoperative complications as classified by the Clavien-Dindo grading system. A comprehensive assessment of all three methods in paediatric patients has yet to be conducted in the literature to date.

Methods and analysis
A systematic search of the MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included papers will be full-text manuscripts written between 1947 and March 2024, comparing the outcomes and complications of open, laparoscopic and RALP. Quality and study bias will be assessed using the Newcastle-Ottawa score and, if relevant, the Cochrane risk of bias tool for randomised trials. This present protocol is written in accordance with the PRISMA Protocol 2015 checklist, ensuring that the highest methodological standards are adhered to.

Ethics and dissemination
No ethical approval shall be required, as this is a review of already published literature. Findings will be disseminated through publications in peer-reviewed journals and presentations at international and national conferences.

PROSPERO registration number
CRD42023456779.

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