Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Purpose: ATM germline pathogenic variants (GPVs) are associated with a moderately increased risk of female breast cancer, pancreatic cancer, and prostate cancer. Resources for managing ATM heterozygotes in clinical practice are limited.

Methods: An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion.

Pediatric firearm injuries and socioeconomic vulnerability before and during the COVID-19 pandemic.

Background: Pediatric firearm injuries disproportionately affect groups experiencing socioeconomic disadvantage. Firearm injuries increased during the COVID-19 pandemic, but the impact on communities by degree of socioeconomic disadvantage is unknown. We examined the association between socioeconomic vulnerability and change in pediatric firearm injuries before versus during the pandemic.

The Impact of COVID-19 on Patterns of Fractures Presenting to Pediatric Emergency Departments.

Objective: To examine differences in pediatric fracture prevalence, severity, and mechanisms of injury before and during the COVID-19 pandemic.

Methods: This is a subanalysis of data from a multicenter, cross-sectional study of all injury-related visits to 40 urban pediatric emergency departments (EDs) for children younger than 18 years occurring January 2019-December 2020. ED visits for injuries including fractures were identified by International Classification of Diseases, Tenth Revision codes.

Classification of variants of reduced penetrance in high-penetrance cancer susceptibility genes: Framework for genetics clinicians and clinical scientists by CanVIG-UK (Cancer Variant Interpretation Group-UK).

Purpose: Current practice is to report and manage likely pathogenic/pathogenic variants in a given cancer susceptibility gene as though having equivalent penetrance, despite increasing evidence of intervariant variability in risk associations. Using existing variant interpretation approaches, largely based on full-penetrance models, variants in which reduced penetrance is suspected may be classified inconsistently and/or as variants of uncertain significance. We aimed to develop a national consensus approach for such variants within the Cancer Variant Interpretation Group UK (CanVIG-UK) multidisciplinary network.

'I Live With Lynch. Cancer Worry Ebbs Into the Background, Then Something Brings It to the Fore.' A Qualitative Interview Study Exploring How Lynch Syndrome Carriers Make Sense of Their Cancer Risks and Implications to Support Decision Making.

Background: Lynch syndrome carriers ('carriers') are presented with complex, emotionally laden choices regarding management of increased genetic cancer risks. Decision aids encourage active involvement in values-based health decisions. This paper aimed to address the research question: How do Lynch syndrome carriers make sense of their chances of developing cancer, and what are the implications for providing support with decision making about genetic cancer risk management?

Methods: Adult carriers were recruited through a genetics service or involvement with Lynch Syndrome UK.

Genitourinary cancer and family: The reverberating psychological and cardiovascular effects of a genitourinary cancer diagnosis on first-degree relatives and spouses.

Background: The psychological and cardiovascular health impacts on family members of patients who have been diagnosed with cancer have not been well characterized. The purpose of this study is to determine whether a family member's cancer diagnosis influences the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients affected by cancer.

Methods: This retrospective cohort analysis evaluated the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients diagnosed with a genitourinary cancer between 1990 and 2015 compared to relatives of those not diagnosed with a genitourinary cancer.

The PS4-likelihood ratio calculator: flexible allocation of evidence weighting for case-control data in variant classification.

Background: The 2015 American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant classification framework specifies that case-control observations can be scored as 'strong' evidence (PS4) towards pathogenicity.

Methods: We developed the PS4-likelihood ratio calculator (PS4-LRCalc) for quantitative evidence assignment based on the observed variant frequencies in cases and controls. Binomial likelihoods are computed for two models, each defined by prespecified OR thresholds.

A Randomized Controlled Comparison of Guardian-Perceived Cosmetic Outcome of Simple Lacerations Repaired With Either Dermabond, Steri-Strips, or Absorbable Sutures.

Objectives: The aim of this study was to compare the guardian-perceived 3-month cosmetic outcome for pediatric lacerations repaired with absorbable sutures, Dermabond, or Steri-Strips. Secondarily, pain and satisfaction with the procedure from both guardian and provider perspectives were compared.

Methods: In this randomized controlled trial, we enrolled a convenience sample of children aged 0 to <18 years who presented with simple linear lacerations (≤5 cm in length, ≤0.

Machine learning and deep learning tools for the automated capture of cancer surveillance data.

The National Cancer Institute and the Department of Energy strategic partnership applies advanced computing and predictive machine learning and deep learning models to automate the capture of information from unstructured clinical text for inclusion in cancer registries. Applications include extraction of key data elements from pathology reports, determination of whether a pathology or radiology report is related to cancer, extraction of relevant biomarker information, and identification of recurrence. With the growing complexity of cancer diagnosis and treatment, capturing essential information with purely manual methods is increasingly difficult.

Landscape analysis of environmental data sources for linkage with SEER cancer patients database.

One of the challenges associated with understanding environmental impacts on cancer risk and outcomes is estimating potential exposures of individuals diagnosed with cancer to adverse environmental conditions over the life course. Historically, this has been partly due to the lack of reliable measures of cancer patients' potential environmental exposures before a cancer diagnosis. The emerging sources of cancer-related spatiotemporal environmental data and residential history information, coupled with novel technologies for data extraction and linkage, present an opportunity to integrate these data into the existing cancer surveillance data infrastructure, thereby facilitating more comprehensive assessment of cancer risk and outcomes.

Mapping Quality Indicators to Assess Older Adult Health and Care in Community-, Continuing-, and Acute-Care Settings: A Systematic Review of Reviews and Guidelines.

Quality indicators (QIs) play a vital role in enhancing the care of older adults. This study aimed to identify existing QIs relevant to the health and care of older adults in community-care, continuing-care, and acute-care settings, along with available information such as definitions and calculation methods. A systematic review of published review studies, grey literature, and guidelines was undertaken, utilizing six electronic databases searched for materials dated from 2010 to 2 June 2023.

Modeling pediatric antibiotic use in an area of declining malaria prevalence.

In malaria-endemic areas of Sub-Saharan Africa, overlap of clinical symptoms between malarial and non-malarial febrile illnesses can lead to empiric use of antibiotics among children. Our study aimed to illustrate the potential impact of decreasing malaria prevalence from malaria control efforts on antibiotic use. We constructed a probabilistic decision tree model representing antibiotic prescription in febrile children < 5 years.

Environmental determinants of health: Measuring multiple physical environmental exposures at the United States census tract level.

Physical environment plays a key role in determining human health risks. Exposure to toxins, weather extremes, degraded air and water quality, high levels of noise and limited accessibility to green areas can negatively affect health. Furthermore, adverse environmental exposures are often correlated with each other and with socioeconomic status, thereby compounding disadvantages in marginalized populations.

Modelling the innate immune system in microphysiological systems.

This critical review aims to highlight how modeling of the immune response has adapted over time to utilize microphysiological systems. Topics covered here will discuss the integral components of the immune system in various human body systems, and how these interactions are modeled using these systems. Through the use of microphysiological systems, we have not only expanded on foundations of basic immune cell information, but have also gleaned insight on how immune cells work both independently and collaboratively within an entire human body system.

Digital innovation for cancer risk assessment allows large-scale service redevelopment of regional cancer genetics service delivery.

Family-history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention and Early Detection (SPED). The online patient-facing cancer Family History Questionnaire Service (cFHQS) is a digitalised, resource efficient tool for family history data capture to facilitate this. The capturing of digital data from cFHQS allows for data interrogation of patients referred to Clinical Genetics for the purposes of service improvement.

Joint ABS-UKCGG-CanGene-CanVar consensus regarding the use of CanRisk in clinical practice.

Background: The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice.

Methods: To address this gap, the UK Cancer Genetics Group in collaboration with the Association of Breast Surgery and the CanGene-CanVar programme held a workshop on 16 of May 2023, with the aim of establishing best practice guidelines.

Breast cancer risk assessment for prescription of menopausal hormone therapy in women with a family history of breast cancer: an epidemiological modelling study.

Background: Menopausal hormone therapy (MHT) can alleviate menopausal symptoms but has been associated with an increased risk of breast cancer. MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking.

Aim: To quantify the risks associated with MHT use in women with varying breast cancer family histories of developing and dying from breast cancer.