Mitochondrial trifunctional protein deficiency caused by a deep intronic deletion leading to aberrant splicing.

Trifunctional protein deficiency (TFP) is a disorder of fatty acid beta-oxidation associated with metabolic, cardiac, and liver dysfunction in severe forms. We present two siblings diagnosed by newborn screening and confirmed by biochemical testing at birth. Their clinical course was complicated by recurrent rhabdomyolysis, retinopathy, and hypoparathyroidism.

Heuristics Identified in Health Data-Sharing Preferences of Patients With Cancer: Qualitative Focus Group Study.

Background: Evaluating precision oncology outcomes requires access to real-world and clinical trial data. Access is based on consent, and consent is based on patients' informed preferences when deciding to share their data. Decision-making is often modeled using utility theory, but a complex decision context calls for a consideration of how heuristic, intuitive thought processes interact with rational utility maximization.

The impact of home-based call on sleep patterns and wellness in genetics and metabolism physicians compared with subspecialists.

Purpose: With increases in precision medicine initiatives and genetically defined rare diseases, the genetics and metabolism workforce is necessary to provide around-the-clock care for patients. Here, we describe the impact that home-based call has on the geneticist and metabolist workforce.

Methods: Physicians from 3 populations were self-identified (pediatric subspecialist, geneticist, metabolist) and completed a survey regarding the impact of home-based call service on their sleep and wellness.

Using Genomic Heterogeneity to Inform Therapeutic Decisions for Metastatic Colorectal Cancer: An Application of the Value of Heterogeneity Framework.

Background And Objective: Mutations in KRAS and NRAS are predictive of poor response to cetuximab and panitumumab, two anti-epidermal growth factor receptor (EGFR) monoclonal antibodies used in metastatic colorectal cancer (mCRC). Our objective was to explore the value of using KRAS and NRAS mutation status to inform third-line anti-EGFR therapy for mCRC using the value of heterogeneity (VOH) framework.

Methods: We used administrative data to identify mCRC patients who were potentially eligible for third-line therapy in 2006-2019 in British Columbia (BC), Canada.

Fifty Years of Psychiatric Classification and Epidemiology Interactions: What is a Mental Disorder?

Psychiatric clinical diagnostic formulation has evolved over time. The changes alter our understanding and our ability to provide a public health perspective on the epidemiology of mental disorders in large populations. Epidemiology is an important perspective and set of tools to assess prevalence, treated prevalence, untreated prevalence, individual risks for mental disorders, and possible links to the etiology of disorders by following the trails of environmental exposures, biological measures, interpersonal dynamics, and genetic risk factors.

Addressing immortal time bias in precision medicine: Practical guidance and methods development.

Objective: To compare theoretical strengths and limitations of common immortal time adjustment methods, propose a new approach using multiple imputation (MI), and provide practical guidance for using MI in precision medicine evaluations centered on a real-world case study.

Study Setting And Design: Methods comparison, guidance, and real-world case study based on previous literature. We compared landmark analysis, time-distribution matching, time-dependent analysis, and our proposed MI application.

"I Just Assumed This Was Already Being Done": Canadian Patient Preferences for Enhanced Data Sharing for Precision Oncology.

Purpose: In Canada, health data are siloed, slowing bioinnovation and evidence generation for personalized cancer care. Secured data-sharing platforms (SDSPs) can enable data analysis across silos through rapid concatenation across trial and real-world settings and timely researcher access. To motivate patient participation and trust in research, it is critical to ensure that SDSP design and oversight align with patients' values and address their concerns.

Next-generation sequencing in oncology: challenges in economic evaluations.

Introduction: Next-generation sequencing (NGS) identifies genetic variants to inform personalized treatment plans. Insufficient evidence of cost-effectiveness impedes the integration of NGS into routine cancer care. The complexity of personalized treatment challenges conventional economic evaluation.

Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis.

Costly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care.

Real-world cost-effectiveness of panel-based genomic testing to inform therapeutic decisions for metastatic colorectal cancer.

Background: Mutations in KRAS and NRAS are associated with a lack of response to cetuximab and panitumumab, two biologics used for third-line therapy of metastatic colorectal cancer (mCRC). In British Columbia, Canada, eligibility for cetuximab or panitumumab was first based on single-gene KRAS testing. OncoPanel, a multi-gene next-generation sequencing panel with both KRAS and NRAS, was introduced in 2016.

Health Care Costs After Genome-Wide Sequencing for Children With Rare Diseases in England and Canada.

Importance: Etiologic diagnoses for rare diseases can involve a diagnostic odyssey, with repeated health care interactions and inconclusive diagnostics. Prior studies reported cost savings associated with genome-wide sequencing (GWS) compared with cytogenetic or molecular testing through rapid genetic diagnosis, but there is limited evidence on whether diagnosis from GWS is associated with reduced health care costs.

Objective: To measure changes in health care costs after diagnosis from GWS for Canadian and English children with suspected rare diseases.

Paving the path for implementation of clinical genomic sequencing globally: Are we ready?

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse.

Development of a Value Assessment Framework for Pediatric Health Technologies Using Multicriteria Decision Analysis: Expanding the Value Lens for Funding Decision Making.

Objectives: A health technology assessment (HTA) does not systematically account for the circumstances and needs of children and youth. To supplement HTA processes, we aimed to develop a child-tailored value assessment framework using a multicriteria decision analysis approach.

Methods: We constructed a multicriteria-decision-analysis-based model in multiple phases to create the Comprehensive Assessment of Technologies for Child Health (CATCH) framework.

Hyperammonemia in the Pediatric Emergency Department.

Hyperammonemia is a serious clinical condition associated with significant morbidity and mortality. In the pediatric population, this is often caused by urea cycle disorders, acute liver failure, or other less common underlying etiologies. Children and teens with hyperammonemia can have a broad range of clinical findings, including vomiting, respiratory distress, and changes in mental status.

Case report: Early molecular confirmation and sodium polystyrene sulfonate management of systemic pseudohypoaldosteronism type I.

Introduction: Type 1 pseudohypoaldosteronism (PHA) consists of resistance to aldosterone. Neonatal presentation is characterized by salt wasting, hyperkalemia, and metabolic acidosis with high risk of mortality. Type 1 PHA can be autosomal dominant (renal type 1) or autosomal recessive (systemic type 1).

Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: Evidence from Canada.

Purpose: To determine real-world diagnostic rates, cost trajectories, and cost-effectiveness of exome sequencing (ES) and genome sequencing (GS) for children with developmental and/or seizure disorders in British Columbia, Canada.

Methods: Based on medical records review, we estimated real-world costs and outcomes for 491 patients who underwent standard of care (SOC) diagnostic testing at British Columbia Children's Hospital. Results informed a state-transition Markov model examining cost-effectiveness of 3 competing diagnostic strategies: (1) SOC with last-tier access to ES, (2) streamlined ES access, and (3) first-tier GS.

Palliative Emergency General Surgery.

Acute care surgeons encounter patients experiencing surgical emergencies related to advanced malignancy, catastrophic vascular events, or associated with multisystem organ failure. The acute nature is a factor in establishing a relationship between surgeon, patient, and family. Surgeons must use effective communication skills, empathy, and a knowledge of legal and ethical foundations.

"I just wanted more": Hereditary cancer syndromes patients' perspectives on the utility of circulating tumour DNA testing for cancer screening.

Hereditary cancer syndromes (HCS) predispose individuals to a higher risk of developing multiple cancers. However, current screening strategies have limited ability to screen for all cancer risks. Circulating tumour DNA (ctDNA) detects DNA fragments shed by tumour cells in the bloodstream and can potentially detect cancers early.