Application of four pricing models for orphan medicines: a case study for lumasiran.

Background: The combination of high prices and uncertain effectiveness is a growing challenge in the field of orphan medicines, hampering health technology assessments. Hence, new methods for establishing price benchmarks might be necessary to support reimbursement negotiations. In this study, we applied several pricing models containing cost-based elements to the case of lumasiran for treating primary hyperoxaluria type 1.

Supporting the continuous development and use of a patient partnership framework in European rare disease networks (ERNs): a scoping review of frameworks in the scientific literature.

The European Reference Networks (ERNs) for rare and complex diseases offer significant potential for building, maintaining and evaluating patient partnership, for which the recently developed ERN Patient Partnership Framework may serve as guidance. This scoping review aims to identify and describe relevant frameworks published in scientific literature, capturing key learning points to inform future updates of the ERN Patient Partnership Framework and promote its use in practice. MEDLINE, Embase, and the Web of Science Core Collection were searched to identify recently published frameworks (2013-2023) focused on patient partnership and aligned with at least one core ERN activity.

Long-term risk and characteristics of cerebrovascular events after upper body radiotherapy among childhood cancer survivors in the DCCSS-LATER cohort.

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed View Article and Find Full Text PDF

Outcomes in early mobilisation research in critically ill children: A scoping review.

Objective: Early mobilisation in critically ill children is safe and feasible. However, the effectiveness of early mobilisation on short- and long-term outcomes is understudied. The aim of this scoping review was to generate an overview of outcomes used in previous research regarding early mobilisation in critically ill children.

Mapping challenges in the accessibility of treatment products for urea cycle disorders: A survey of European healthcare professionals.

Current management guidelines for urea cycle disorders (UCDs) offer clear strategies, incorporating both authorized and non-authorized medicinal products (including intravenous formulations and products regulated as food). These varying product categories are subject to specific accessibility challenges related to availability, reimbursement, and pricing. The aim of this study is to identify potential obstacles to optimal UCD treatment implementation in European clinical practice.

UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer.

Elevated de novo lipid synthesis is a remarkable adaptation of cancer cells that can be exploited for therapy. However, the role of altered lipid metabolism in the regulation of apoptosis is still poorly understood. Using thermal proteome profiling, we identified Manidipine-2HCl, targeting UGT8, a key enzyme in the synthesis of sulfatides.

Plasma Profiling of Acute Myeloid Leukemia With Fever- and Infection-Related Complications During Chemotherapy-Induced Neutropenia.

Background: Acute myeloid leukemia (AML) is a heterogenous and complex blood cancer requiring aggressive treatment. Early identification and prediction of the complications following treatment is vital for effective disease management.

Aims: We explored associations between plasma protein levels and fever- and infection-related complications in 26 AML patients during chemotherapy-induced neutropenia.

The Definition of Recurrence of Differentiated Thyroid Cancer: A Systematic Review of the Literature.

Recurrence is a key outcome to evaluate the treatment effect of differentiated thyroid carcinoma (DTC). However, no consistent definition of recurrence is available in current literature or international guidelines. Therefore, the primary aim of this systematic review was to delineate the definitions of recurrence of DTC, categorized by total thyroidectomy with radioactive iodine ablation (RAI), total thyroidectomy without RAI and lobectomy, to assess if there is a generally accepted definition among these categories.

Imaging the development of the human craniofacial arterial system - an experimental study.

Background: The process of vascular development is essential for shaping complex craniofacial structures. Investigating the interplay between vascular development and orofacial morphogenesis holds critical importance in clinical practice and contributes to advancing our comprehension of (vascular) developmental biology. New insights into specific vascular developmental pathways will have far-reaching implications across various medical disciplines, enhancing clinical understanding, refining surgical techniques, and elucidating the origins of congenital abnormalities.

Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

Study Question: Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives?

Summary Answer: Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives.

What Is Known Already: HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives.

Patient, Parental, and Health Professional Perspectives on Growth in Children With CKD.

Rationale & Objective: Growth failure is a common problem among children with chronic kidney disease (CKD). Reduced height is associated with psychosocial burden, social stigma, and impaired quality of life. This study describes the aspects of growth impairment that are most impactful from the perspectives of children with CKD, their parents, and health professionals.

Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up.

Introduction: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality.

Effect of probiotic supplementation on the gut microbiota in very preterm infants: a systematic review.

Objective: There is increasing evidence that probiotic supplementation in very preterm infants decreases the risk of necrotising enterocolitis (NEC), sepsis and mortality. The underlying mechanisms, including effects on the gut microbiota, are largely unknown. We aimed to systematically review the available literature on the effects of probiotic supplementation in very preterm infants on gut microbiota development.

Association between bronchopulmonary dysplasia severity and its risk factors and long-term outcomes in three definitions: a historical cohort study.

Objective: To compare the association of the severity categories of the 2001-National Institutes of Health (NIH), the 2018-NIH and the 2019-Jensen bronchopulmonary dysplasia (BPD) definitions with neurodevelopmental and respiratory outcomes at 2 and 5 years' corrected age (CA), and several BPD risk factors.

Design: Single-centre historical cohort study with retrospective data collection.

Setting: Infants born between 2009 and 2015 at the Amsterdam University Medical Centers, location Amsterdam Medical Center.

Analysis of genes differentially expressed in the cortex of mice with the Tbl1xr1 variant.

Transducin β-like 1 X-linked receptor 1 (mouse Tbl1xr1) or TBL1X/Y related 1 (human TBL1XR1), part of the NCoR/SMRT corepressor complex, is involved in nuclear receptor signaling. Variants in TBL1XR1 cause a variety of neurodevelopmental disorders including Pierpont syndrome caused by the p.Tyr446Cys variant.

Carboxylesterase 1 directs the metabolic profile of dendritic cells to a reduced inflammatory phenotype.

The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. The carboxylesterase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells; however, its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DC differentiation in inflammatory models.

PSMD11 loss-of-function variants correlate with a neurobehavioral phenotype, obesity, and increased interferon response.

Primary proteasomopathies have recently emerged as a new class of rare early-onset neurodevelopmental disorders (NDDs) caused by pathogenic variants in the PSMB1, PSMC1, PSMC3, or PSMD12 proteasome genes. Proteasomes are large multi-subunit protein complexes that maintain cellular protein homeostasis by clearing ubiquitin-tagged damaged, misfolded, or unnecessary proteins. In this study, we have identified PSMD11 as an additional proteasome gene in which pathogenic variation is associated with an NDD-causing proteasomopathy.