Unravelling undiagnosed rare disease cases by HiFi long-read genome sequencing.

Solve-RD is a pan-European rare disease (RD) research program that aims to identify disease-causing genetic variants in previously undiagnosed RD families. We utilised 10-fold coverage HiFi long-read sequencing (LRS) for detecting causative structural variants (SVs), single nucleotide variants (SNVs), insertion-deletions (InDels), and short tandem repeat (STR) expansions in extensively studied RD families without clear molecular diagnoses. Our cohort includes 293 individuals from 114 genetically undiagnosed RD families selected by European Rare Disease Network (ERN) experts.

The effect of air-free administration of intravenous drugs on microemboli during cardiopulmonary bypass.

Objective: During cardiopulmonary bypass (CPB), gaseous microemboli (GME) that originate from the extracorporeal circuit are released into the arterial blood stream of the patient. Gaseous microemboli may contribute to adverse outcome after cardiac surgery with CPB. Possibly, air may be collected in the right atrium during induction of anesthesia and released during CPB start.

encoding Shiga toxin subtype Stx2f causing human infections in England, 2015-2022.

Shiga toxin-producing (STEC) belong to a diverse group of gastrointestinal pathogens defined by the presence of Shiga toxin genes () of which there are at least ten subtypes (Stx1a-Stx1d and Stx2a-Stx2g). Initially thought to be associated with mild symptoms, more recently STEC encoding have been isolated from cases of haemolytic uraemic syndrome (HUS) and the clinical significance and public health burden require further investigation. We analysed clinical outcomes and genome-sequencing data linked to patients infected with STEC encoding- in England to assess the risk to public health.

Diagnostic analysis of the highly complex OPN1LW/OPN1MW gene cluster using long-read sequencing and MLPA.

Pathogenic variants in the OPN1LW/OPN1MW gene cluster are causal for a range of mild to severe visual impairments with color deficiencies. The widely utilized short-read next-generation sequencing (NGS) is inappropriate for the analysis of the OPN1LW/OPN1MW gene cluster and many patients with pathogenic variants stay underdiagnosed. A diagnostic genetic assay was developed for the OPN1LW/OPN1MW gene cluster, consisting of copy number analysis via multiplex ligation-dependent probe amplification and sequence analysis via long-read circular consensus sequencing.

The performance of genome sequencing as a first-tier test for neurodevelopmental disorders.

Genome sequencing (GS) can identify novel diagnoses for patients who remain undiagnosed after routine diagnostic procedures. We tested whether GS is a better first-tier genetic diagnostic test than current standard of care (SOC) by assessing the technical and clinical validity of GS for patients with neurodevelopmental disorders (NDD). We performed both GS and exome sequencing in 150 consecutive NDD patient-parent trios.

Long-read technologies identify a hidden inverted duplication in a family with choroideremia.

The lack of molecular diagnoses in rare genetic diseases can be explained by limitations of current standard genomic technologies. Upcoming long-read techniques have complementary strengths to overcome these limitations, with a particular strength in identifying structural variants. By using optical genome mapping and long-read sequencing, we aimed to identify the pathogenic variant in a large family with X-linked choroideremia.

The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports.

Proximal 6q (6q11-q15) deletions are extremely rare and little is known about their phenotypic consequences. Since parents and caregivers now use social media to seek information on rare disorders, the Chromosome 6 Project has successfully collaborated with a Facebook group to collect data on individuals worldwide. Here we describe a cohort of 20 newly identified individuals and 25 literature cases with a proximal 6q deletion.

Accuracy, Precision, and Trending Ability of Electrical Cardiometry Cardiac Index versus Continuous Pulmonary Artery Thermodilution Method: A Prospective, Observational Study.

Introduction: Evaluation of accuracy, precision, and trending ability of cardiac index (CI) measurements using the Aesculon™ bioimpedance electrical cardiometry (Aesc) compared to the continuous pulmonary artery thermodilution catheter (PAC) technique before, during, and after cardiac surgery.

Methods: A prospective observational study with fifty patients with ASA 3-4. At six time points (T), measurements of CI simultaneously by continuous cardiac output pulmonary thermodilution and thoracic bioimpedance and standard hemodynamics were performed.

Does public disclosure of quality indicators influence hospitals' inclination to enhance results?

Objective: The national guideline on oesophageal carcinoma's recommendation of a minimum number of 10 resections per year and the intervention of the Dutch Health Care Inspectorate have highlighted hospitals' 'need to score' on the public quality indicator for the annual number of oesophageal resections. To determine whether low-volume hospitals are inclined to adjust their numbers, we studied the difference between the reported and actual numbers of oesophageal resections in 2005 and 2006.

Design: A retrospective cohort study.

Obstetric interventions for babies born before 28 weeks of gestation in Europe: results of the MOSAIC study.

Objective: To describe obstetric intervention for extremely preterm births in ten European regions and assess its impact on mortality and short term morbidity.

Design: Prospective observational cohort study.

Setting: Ten regions from nine countries participating in the 'Models of Organising Access to Intensive Care for Very Preterm Babies in Europe' (MOSAIC) project.

[The usefulness of the hospital standardized mortality ratio as an indicator of hospital mortality].

In 2007, a patient safety programme was started to reduce hospital mortality in the Netherlands. The hospital standardized mortality ratio (HSMR) seems to be a promising indicator for monitoring the reduction of hospital mortality within hospitals. It is questionable, however, whether the HSMR can be used to compare the performance of hospitals.

[At the limits of viability: Dutch referral policy for premature birth too reserved].

Objective: Evaluation of policy and treatment of deliveries at the limits of viability in the Netherlands and resulting survival figures.

Design: Cohort study.

Method: Within the framework of the European 'Models of organising access to intensive care for very preterm births in Europe' (MOSAIC) study, data was collected on all 512 births in 2003 (terminations excluded) following 22-31 weeks gestation in the catchment areas of the perinatal centres in Nijmegen and Utrecht, the Netherlands.

Outcome of perinatal care for very preterm infants at 5 years of age: a comparison between 1983 and 1993.

Perinatal mortality in very preterm infants has decreased by up to 50% during the last decades. Studies of changes of long-term outcome are inconclusive. We studied the visual, auditory, neuromotor, cognitive and behavioural development of two geographically defined populations of very preterm, singleton infants, born in 1983 and in 1993, and analysed the relationship between perinatal risk factors and outcomes.

Lower mortality but higher neonatal morbidity over a decade in very preterm infants.

Better perinatal care has led to better survival of very preterm children, but may or may not have increased the number of children with cerebral and pulmonary morbidity. We therefore investigated the relationship between changes in perinatal care during one decade, and short-term outcome in very preterm infants. Perinatal risk factors and their effects on 28-day and in-hospital mortality, and on intraventricular haemorrhage and bronchopulmonary dysplasia (BPD) in survivors, were compared in two surveys of very preterm singleton infants in the Netherlands.

The compangle: a new goniometer for joint angle measurements of the hand. A technical note.

The accuracy of joint angle measurement of the hand may be negatively influenced by joint swelling, deformation and other obstacles. We developed an alternative goniometer with clear ergonomic advantages, especially for the measurement of small joints. This new concept of goniometry is described and preliminary results on the reliability of the measurements are presented.

Is attrition bias a problem in neonatal follow-up?

Aim: To assess whether attrition rate influences outcome in the follow-up of very preterm infants.

Study Design: In a national follow-up study of infants born alive in 1983 in the Netherlands with a gestational age less than 32 weeks and/or a birth weight less than 1500 g, outcome was assessed separately for adolescents who responded early or late to a follow-up invitation at age 14 years. Neonatal data and outcome results of earlier assessments from early and late responders were compared to those of non-responders by univariate and nominal (polytomous logistic) regression analysis.

Catch-up growth up to ten years of age in children born very preterm or with very low birth weight.

Background: Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth.

Ethnic differences in congenital malformations in the Netherlands: analyses of a 5-year birth cohort.

Congenital malformations are among the major causes of perinatal mortality and morbidity at present. Research into the ethnic diversity of congenital malformations can form a basis both for aetiological studies and for health care advice and planning. This study compared the overall prevalence of congenital malformations, the prevalence in different organ systems and of several specific malformations between different maternal ethnic groups in the Netherlands using a 5-year national birth cohort (1996-2000) containing 881 800 births.

Changes in neonatology: comparison of two cohorts of very preterm infants (gestational age <32 weeks): the Project On Preterm and Small for Gestational Age Infants 1983 and the Leiden Follow-Up Project on Prematurity 1996-1997.

Objective: To determine changes in peri- and neonatal care concerning neonatal mortality and morbidity by comparing 2 cohorts of very prematurely born infants (gestational age [GA] <32 weeks), 1 from the 1980s and 1 from the 1990s.

Methods: The Leiden Follow-Up Project on Prematurity (LFUPP-1996/97), a regional, prospective study, includes all infants who were born alive after a GA <32 weeks in 1996 and 1997 in the Dutch health regions Leiden, The Hague, and Delft. The Project On Preterm and Small for Gestational Age Infants (POPS-1983), a national, prospective study from the presurfactant era, includes all liveborn infants <32 weeks' GA and/or <1500 g from 1983 (n = 1338).

Development and evaluation of a follow up assessment of preterm infants at 5 years of age.

Background: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled.

Aims: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life.

Methods: A total of 431 very premature infants, mean gestational age 30.

Periconceptional folic acid use and the prevalence of neural tube defects in The Netherlands.

Objective: To study the effect of increased folic acid intake on the prevalence of neural tube defects (NTD) in The Netherlands.

Study Design: Using the capture-recapture method, the prevalence of NTD was estimated on the basis of five different registries on births affected by NTD.

Results: Total prevalence over the 1988-1998 period varied between 1.