Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability.

The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria.

Innovative all-in-one exome sequencing strategy for diagnostic genetic testing in male infertility: Validation and 10-month experience.

Background: Current guidelines indicate that patients with extreme oligozoospermia or azoospermia should be tested for chromosomal imbalances, azoospermia factor (AZF) deletions and/or CFTR variants. For other sperm abnormalities, no genetic diagnostics are recommended.

Objectives: To determine whether exome sequencing (ES) with combined copy number variant (CNV) and single nucleotide variant (SNV) analysis is a reliable first-tier method to replace current methods (validation study), and to evaluate the diagnostic yield after 10 months of implementation (evaluation study).

46,XX males with congenital adrenal hyperplasia: a clinical and biochemical description.

Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males.

Detection of DNA Contamination in Prenatal Samples from Whole Exome Sequencing Data.

Background: Maternal cell contamination (MCC) in prenatal samples poses a risk for misdiagnosis, and therefore, testing for contamination is necessary during genetic analysis of prenatal specimens. MCC testing is currently performed as a method separate from the diagnostic method. With the increasing application of whole exome sequencing (WES) in prenatal diagnosis, we sought to develop a method to estimate the level of contamination from WES data, aiming to eliminate the need for a separate MCC test.

Exome sequencing in fetuses with congenital diaphragmatic hernia in a nationwide cohort.

Objective: To evaluate the diagnostic yield of exome sequencing (ES) in fetuses and neonates with prenatally detected congenital diaphragmatic hernia (CDH) and normal copy number variant (CNV) analysis.

Methods: We conducted a retrospective cohort study of prenatally diagnosed CDH cases seen between 2019 and 2022. All cases who underwent prenatal or postnatal genetic testing were reviewed.

Future of Dutch NGS-Based Newborn Screening: Exploring the Technical Possibilities and Assessment of a Variant Classification Strategy.

In this study, we compare next-generation sequencing (NGS) approaches (targeted panel (tNGS), whole exome sequencing (WES), and whole genome sequencing (WGS)) for application in newborn screening (NBS). DNA was extracted from dried blood spots (DBS) from 50 patients with genetically confirmed inherited metabolic disorders (IMDs) and 50 control samples. One hundred IMD-related genes were analyzed.

Newspaper Coverage of Hospitals During a Prolonged Health Crisis: Longitudinal Mixed Methods Study.

Background: It is important for health organizations to communicate with the public through newspapers during health crises. Although hospitals were a main source of information for the public during the COVID-19 pandemic, little is known about how this information was presented to the public through (web-based) newspaper articles.

Objective: This study aims to examine newspaper reporting on the situation in hospitals during the first year of the COVID-19 pandemic in the Netherlands and to assess the degree to which the reporting in newspapers aligned with what occurred in practice.

Toward a Theory of Organizational DNA: Routines, Principles, and Beliefs (RPBs) for Successful and Sustainable Organizational Change.

Organizational change is a key mechanism to ensure the sustainability of healthcare systems. However, healthcare organizations are persistently difficult to change, and literature is riddled with examples of failed change endeavors. In this chapter, we attempt to unravel the underlying causes for failed organizational change.

Back to the Future: What Healthcare Organizations Need to Thrive in the Face of Persistent Environmental Uncertainty.

While uncertainty has always been a feature of the healthcare environment, its pace and scope are rapidly increasing, fueled by myriad factors such as technological advancements, the threat and frequency of disruptive events, global economic developments, and increasing complexity. Contemporary healthcare organizations thus persistently face what is known as "deep uncertainty," which obscures their ability to predict outcomes of strategic action and decision-making, presenting them with novel challenges and threatening their survival. Persistent, deep uncertainty challenges us to revisit and reconsider how we think about uncertainty and the strategic actions needed by organizations to thrive under these circumstances.

Return to sender: Unraveling the role of structural and social network ties in patient sharing networks.

Healthcare is increasingly delivered through networks of organizations. Well-structured patient sharing networks are known to have positive associations with the quality of delivered services. However, the drivers of patient sharing relations are rarely studied explicitly.

A Delphi Survey Study to Formulate Statements on the Treatability of Inherited Metabolic Disorders to Decide on Eligibility for Newborn Screening.

The Wilson and Jungner (W&J) and Andermann criteria are meant to help select diseases eligible for population-based screening. With the introduction of next-generation sequencing (NGS) methods for newborn screening (NBS), more inherited metabolic diseases (IMDs) can technically be included, and a revision of the criteria was attempted. This study aimed to formulate statements and investigate whether those statements could elaborate on the criterion of for IMDs to decide on eligibility for NBS.

The impact of a multi-hospital network on the inequality in odds of receiving resection or ablation for synchronous colorectal liver metastases.

Background: This study investigates whether inequalities in the utilization of resection and/or ablation for synchronous colorectal liver metastases (SCLM) between patients diagnosed in expert and non-expert hospitals changed since a multi-hospital network started.

Materials And Methods: Patients diagnosed with SCLM between 2009 and 2020 were included. The likelihood of receiving ablation and/or resection was analyzed in the prenetwork (2009-2012), startup (2013-2016), and matured-network (2017-2020) periods.

Two sides of the same coin? Absolute income and perceived income inadequacy as social determinants of health.

Background: Absolute income is commonly used in studies of health inequalities, however it does not reflect spending patterns, debts, or expectations. These aspects are reflected in measures concerning perceived income inadequacy. While health inequities by absolute income or perceived income inadequacy are well established, few studies have explored the interplay of absolute income and perceived income inadequacy in relation to health.

A Social Network Analysis of Influences on Residents' Value-Based Decisions.

Purpose: To ensure a value-based health care system, it is becoming increasingly important that residents are trained in making value-based decisions. This study explored the social network influencing residents' value-based decisions.

Method: To explore the social network influencing residents' value-based decisions, the authors used a semistructured individual and mini-group interviewing approach and participatory visual mapping.

Involving Health Professionals in the Development of Quality and Safety Dashboards: Qualitative Study.

Background: Dashboards are an important tool for hospitals to improve quality and safety performance. However, implementing quality and safety dashboards often does not increase performance due to a lack of use by health professionals. Including health professionals in the development process of quality and safety dashboards can improve their use in practice.

Use it or lose it? Identifying reasons for the low use of psychosocial support by hospital staff.

Background: Psychosocial support programs are a way for hospitals to support the mental health of their staff. However, while support is needed, utilization of support by hospital staff remains low. This study aims to identify reasons for non-use and elements that are important to consider when offering psychosocial support.

Novel likely pathogenic variant in NR5A1 gene in a Tanzanian child with 46,XY differences of sex development, inherited from the mosaic father.

Summary: Pathogenic variants in the nuclear receptor subfamily 5 group A member 1 gene (NR5A1), which encodes steroidogenic factor 1 (SF1), result in 46,XY and 46,XX differences of sex development (DSD). In 46,XY individuals with a pathogenic variant in the NR5A1 gene a variable phenotype ranging from mild to severe is seen, including adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus and infertility. We report the clinical, endocrinological and genetic characteristics of a patient with 46,XY DSD with a novel likely pathogenic missense variant in the NR5A1 gene.

Getting our hopes up: How actors perceive network effectiveness and why it matters.

Health care's grand challenges, such as continuously increasing costs, challenge the sustainability of health systems. Purpose-oriented networks are considered a favorable mode of organization to address these grand challenges. Therefore, it is crucial that they are effective.

Through the looking glass: Confronting health care management's biggest challenges in the wake of a crisis.

Background: The challenges brought on by the pandemic triggered a renewed scholarly focus on managing during crises. Now, 3 years on, having covered the initial crisis response, it is important to reevaluate what the crisis has taught us about health care management more generally. In particular, it is useful to consider the persistent challenges that continue to face health care organizations in the wake of a crisis.

All-in-one whole exome sequencing strategy with simultaneous copy number variant, single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience.

Objective: We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods: After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

Let's Talk About it: The Utility of Formalized Support for Medical Residents.

Medical residents are significantly impacted by burnout and depression. Recent events have only further increased the pressure and demands on the healthcare sector, intensifying the burden facing residents and posing a threat to residents' well-being. As a result, significant efforts are being made to provide formalized support and well-being programs.

Charting a Course: A Research Agenda for Studying the Governance of Health Care Networks.

Networked forms of organizing in health care are increasingly viewed as an effective means of addressing "wicked", multifaceted health and societal challenges. This is because networks attempt to address these challenges via collaborative approaches in which diverse stakeholders together define the problem(s) and implement solutions. Consequently, there has been a sharp increase in the number and types of networks used in health care.