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.

Drug pricing models, no 'one-size-fits-all' approach: a systematic review and critical evaluation of pricing models in an evolving pharmaceutical landscape.

Access to new medicines is crucial for patients but increasingly sparks discussion due to high prices. Simultaneously, the growing emphasis on specialized products and uncertainty surrounding the long-term effectiveness of new drug classes brought to the market underscore the need for innovative pricing approaches. A systematic literature review of pharmaceutical pricing models, accompanied by a critical appraisal, was conducted to offer insights contributing to novel approaches balancing sustainable pharmaceutical innovation with affordability and accessibility for patients.

Characterization of heterozygous and homozygous mouse models with the most common hypertrophic cardiomyopathy mutation MYBPC3 in the Netherlands.

Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the cardiac myosin binding protein-C (cMyBP-C) encoding gene MYBPC3. In the Netherlands, approximately 25% of patients carry the MYBPC3 founder mutation. Most patients are heterozygous (MYBPC3) and have highly variable phenotypic expression, whereas homozygous (MYBPC3) patients have severe HCM at a young age.

EGFR/IGF1R Signaling Modulates Relaxation in Hypertrophic Cardiomyopathy.

Background: Diastolic dysfunction is central to diseases such as heart failure with preserved ejection fraction and hypertrophic cardiomyopathy (HCM). However, therapies that improve cardiac relaxation are scarce, partly due to a limited understanding of modulators of cardiomyocyte relaxation. We hypothesized that cardiac relaxation is regulated by multiple unidentified proteins and that dysregulation of kinases contributes to impaired relaxation in patients with HCM.

Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful tool for studying mutation-mediated changes in cardiomyocyte function and defining the effects of stressors and drug interventions. In this study, it is demonstrated that this optics-based system is a powerful tool to assess the functional parameters of hiPSC-CMs in 2D. By using this platform, it is possible to perform paired measurements in a well-preserved temperature environment on different plate layouts.

Super-resolution re-scan second harmonic generation microscopy.

Second harmonic generation microscopy (SHG) is generally acknowledged as a powerful tool for the label-free three-dimensional visualization of tissues and advanced materials, with one of its most popular applications being collagen imaging. Despite the great need, progress in super-resolved SHG imaging lags behind the developments reported over the past years in fluorescence-based optical nanoscopy. In this work, we demonstrate super-resolved re-scan SHG, qualitatively and quantitatively showing on collagenous tissues the available resolution advantage over the diffraction limit.

Relations Between BMI Trajectories and Habitual Physical Activity Measured by a Smartwatch in the Electronic Cohort of the Framingham Heart Study: Cohort Study.

Background: The prevalence of obesity is rising. Most previous studies that examined the relations between BMI and physical activity (PA) measured BMI at a single timepoint. The association between BMI trajectories and habitual PA remains unclear.

Organization and dynamics of the SpoVAEa protein and its surrounding inner membrane lipids, upon germination of Bacillus subtilis spores.

The SpoVA proteins make up a channel in the inner membrane (IM) of Bacillus subtilis spores. This channel responds to signals from activated germinant receptors (GRs), and allows release of Ca-DPA from the spore core during germination. In the current work, we studied the location and dynamics of SpoVAEa in dormant spores.

Comparison of Daily Routines Between Middle-aged and Older Participants With and Those Without Diabetes in the Electronic Framingham Heart Study: Cohort Study.

Background: Daily routines (eg, physical activity and sleep patterns) are important for diabetes self-management. Traditional research methods are not optimal for documenting long-term daily routine patterns in participants with glycemic conditions. Mobile health offers an effective approach for collecting users' long-term daily activities and analyzing their daily routine patterns in relation to diabetes status.

The Mirroring Dance: Synchrony and Interaction Quality of Five Adolescents and Adults on the Autism Spectrum in Dance/Movement Therapy.

Individuals on the autism spectrum are often described as having atypical social interactions. Ideally, interactional synchrony helps any interaction flow smoothly with each individual responding verbally, non-verbally, and/or emotionally within a short timeframe. Differences in interactional synchrony may impact how individuals on the autism spectrum experience social encounters.

Automatic detection of adult cardiomyocyte for high throughput measurements of calcium and contractility.

Simultaneous calcium and contractility measurements on isolated adult cardiomyocytes have been the gold standard for the last decades to study cardiac (patho)physiology. However, the throughput of this system is low which limits the number of compounds that can be tested per animal. We developed instrumentation and software that can automatically find adult cardiomyocytes.

Association of Habitual Physical Activity With Home Blood Pressure in the Electronic Framingham Heart Study (eFHS): Cross-sectional Study.

Background: When studied in community-based samples, the association of physical activity with blood pressure (BP) remains controversial and is perhaps dependent on the intensity of physical activity. Prior studies have not explored the association of smartwatch-measured physical activity with home BP.

Objective: We aimed to study the association of habitual physical activity with home BP.

In Vivo Visualization and Quantification of Mitochondrial Morphology in C. elegans.

Caenorhabditis elegans is a highly versatile model system, intensively used for functional, genetic, cytometric, and integrative studies. Due to its simplicity and large muscle cell number, C. elegans has frequently been used to study mitochondrial deficiencies caused by disease or drug toxicity.

Flap Closure of Spinal Defects in High-Risk Patients: A 10-Year Institutional Experience.

Background: Complication rates after spinal surgery are high, in part because of surgical advancements that have made procedures available to a broader range of medically complicated patients. The high rates of infection, hematoma, and dehiscence resulting in open wounds after spinal surgery often warrant plastic surgery involvement. In this study, we aim to examine the effects of preoperative and operative risk factors on complication rates, reoperation rates, and hospital length of stay after flap reconstruction of spinal defects.

Adherence of Mobile App-Based Surveys and Comparison With Traditional Surveys: eCohort Study.

Background: eCohort studies offer an efficient approach for data collection. However, eCohort studies are challenged by volunteer bias and low adherence. We designed an eCohort embedded in the Framingham Heart Study (eFHS) to address these challenges and to compare the digital data to traditional data collection.

Large-Scale Contractility Measurements Reveal Large Atrioventricular and Subtle Interventricular Differences in Cultured Unloaded Rat Cardiomyocytes.

The chambers of the heart fulfill different hemodynamic functions, which are reflected in their structural and contractile properties. While the atria are highly elastic to allow filling from the venous system, the ventricles need to be able to produce sufficiently high pressures to eject blood into the circulation. The right ventricle (RV) pumps into the low pressure pulmonary circulation, while the left ventricle (LV) needs to overcome the high pressure of the systemic circulation.

Association of Habitual Physical Activity With Cardiovascular Disease Risk.

Rationale: A sedentary lifestyle is associated with increased risk for cardiovascular disease (CVD). Smartwatches enable accurate daily activity monitoring for physical activity measurement and intervention. Few studies, however, have examined physical activity measures from smartwatches in relation to traditional risk factors associated with future risk for CVD.

Surgical Management of Hand Deformity in Epidermolysis Bullosa: Initial Experience and Technique.

Epidermolysis bullosa describes a rare group of genetic mucocutaneous disorders characterized by excessive epithelial fragility resulting in mechanically induced blistering and abnormal wound healing. Its prevalence and incidence are 8.2 and 19.

A Nomogram for the Rapid Prediction of Hematocrit Following Blood Loss and Fluid Shifts in Neonates, Infants, and Adults.

Introduction There is often a need for a simple means of predicting hematocrit (Hct) following blood loss, administration of intravenous fluids, or fluid shifts. The aim of this study is to introduce a nomogram for the rapid prediction of blood volume and packed red cell volume appropriate for a given patient's body weight and Hct in both the pediatric and adult populations. Methods A nomogram for prediction of Hct was created using the following variables: 1) blood volume determined from bodyweight, 2) estimated blood loss, and 3) initial Hct.