Non-adherence and non-persistence with antiretroviral treatment in Belgium: A real-world evaluation using a pharmacy database, 2018-2021.

Purpose: To evaluate the real-world rates of non-adherence and non-persistence to antiretroviral therapy (ART) among treatment-naïve adult patients with HIV after a 12-month follow-up period in Belgium.

Methods: A retrospective analysis of longitudinal pharmacy claims was conducted using the Pharmanet database from January 1, 2018, to December 31, 2021. Non-adherence was assessed over 12 months and reported as the proportion of days covered below the 80% threshold.

Analysis of admissions to intensive care units that could be supported on an intermediate care unit.

Background: Only one third of European countries use intermediate care units (IMCs). An IMC makes it possible to manage patients who do not require intensive care but who need a higher level of nursing care that cannot be provided on the general ward. In Belgium, there are no national criteria for ICU admission or discharge, and no policies regarding IMC care or for differentiating ICU intensity levels.

The impact of policy interventions to promote the uptake of biosimilar medicines in Belgium: a nationwide interrupted time series analysis.

Background: The Belgian government has taken several measures to increase the uptake of biosimilars in past years. However, no formal evaluation of the impact of these measures has been made yet. This study aimed to investigate the impact of the implemented measures on biosimilar uptake.

STAT3 Inhibition Attenuates MYC Expression by Modulating Co-Activator Recruitment and Suppresses Medulloblastoma Tumor Growth by Augmenting Cisplatin Efficacy In Vivo.

MB is a common childhood malignancy of the central nervous system, with significant morbidity and mortality. Among the four molecular subgroups, MYC-amplified Group 3 MB is the most aggressive type and has the worst prognosis due to therapy resistance. The present study aimed to investigate the role of activated STAT3 in promoting MB pathogenesis and chemoresistance via inducing the cancer hallmark MYC oncogene.

Discovery of -sulfonylated aminosalicylic acids as dual MCL-1/BCL-xL inhibitors.

The anti-apoptotic protein MCL-1, which is overexpressed in multiple cancers, is presently a focus for the development of targeted drugs in oncology. We previously discovered inhibitors of MCL-1 based on 1-sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acids ("1,6-THQs"). However, with the nitrogen atom constrained in the bicyclic ring, we were unable to modify the alkyl portion of the tertiary sulfonamide functionality.

Trends and regional variations in prescriptions dispensed to stimulate uterine contractions at the end of pregnancy in Belgium: A community-based study from 2003 to 2018.

Purpose: To investigate trends and regional variations in uterotonics dispensed around birth between 2003 and 2018 in Belgium.

Methods: Data, including outpatient and inpatient prescriptions were extracted from a nationally representative prescription database. The prevalence of uterotonics dispensed during a period including the 7 days before birth, the delivery day and the 7 days after birth was computed over three 4-year-long study periods from 2003 to 2018.

1-Sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acids as simple, readily-accessible MCL-1 inhibitors.

MCL-1 is a member of the BCL-2 family of proteins that regulates the mitochondrial pathway of apoptosis. Overexpression of MCL-1 is associated with the development and progression of a range of human cancers, and is also responsible for the onset of resistance to conventional chemotherapies. Although several MCL-1 inhibitors have now advanced to clinical trials, recent suspensions and terminations reveal the urgency with which new inhibitor chemotypes must be discovered.

Determinants of prescribing decisions for off-patent biological medicines in Belgium: a qualitative study.

Background: A competitive market for off-patent biologicals leads to more affordable and high-quality healthcare. In recent years, Belgium has been characterized by its low use of biosimilars and by its shifts from off-patent biologicals toward new alternative therapies. Yet, the prescribing decisions involved in these observations are poorly understood.

Scaffold hopping from indoles to indazoles yields dual MCL-1/BCL-2 inhibitors from MCL-1 selective leads.

Overexpression of the anti-apoptotic BCL-2 proteins is associated with the development and progression of a range of cancers. Venetoclax, an FDA-approved BCL-2 inhibitor, is fast becoming the standard-of-care for acute myeloid leukemia and chronic lymphocytic leukemia. However, the median survival offered by venetoclax is only 18 months (as part of a combination therapy regimen), and one of the primary culprits for this is the concomitant upregulation of sister anti-apoptotic proteins, in particular MCL-1 (and BCL-xL), which provides an escape route that manifests as venetoclax resistance.

Elevating SOX2 Downregulates MYC through a SOX2:MYC Signaling Axis and Induces a Slowly Cycling Proliferative State in Human Tumor Cells.

Slowly cycling/infrequently proliferating tumor cells present a clinical challenge due to their ability to evade treatment. Previous studies established that high levels of SOX2 in both fetal and tumor cells restrict cell proliferation and induce a slowly cycling state. However, the mechanisms through which elevated SOX2 levels inhibit tumor cell proliferation have not been identified.

Perceptions About Biosimilar Medicines Among Belgian Patients in the Ambulatory Care.

Biosimilar medicines have been on the European market for 15 years. Despite the extensive and positive experience with biosimilars across Europe, their uptake remains limited in Belgium. One of the possible factors limiting uptake in clinical practice is the inadequate understanding and lack of trust in biosimilars among patients.

Physiologically Relevant Free Ca Ion Concentrations Regulate STRA6-Calmodulin Complex Formation via the BP2 Region of STRA6.

The interaction of calmodulin (CaM) with the receptor for retinol uptake, STRA6, involves an α-helix termed BP2 that is located on the intracellular side of this homodimeric transporter (Chen et al., 2016 [1]). In the absence of Ca, NMR data showed that a peptide derived from BP2 bound to the C-terminal lobe (C-lobe) of Mg-bound CaM (CaM).

Cost-DALY comparison of hip replacement care in 12 Belgian hospitals.

Background: In view of the expected increase in expenditure on hip replacement treatment in Belgium, the complication rate and potential waste reduction, as estimated by the Organisation for Economic Cooperation and Development, we are not yet in a position to assess the efficiency of hip replacement treatment in Belgian hospitals. This objective study uses a cost-disability-adjusted life years (DALYs) ratio to propose a comparison of hip replacement surgery among 12 Belgian hospitals.

Methods: Our study seeks to innovate by proposing an interhospital comparison that simultaneously integrates the weighting of quality indicators and the costs of managing a patient.

The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.

S100B is frequently elevated in malignant melanoma. A regulatory mechanism was uncovered here in which elevated S100B lowers mRNA and secreted protein levels of interleukin-6 (IL6) and inhibits an autocrine loop whereby IL6 activates STAT3 signaling. Our results showed that S100B affects IL6 expression transcriptionally.

Off-Patent Biological and Biosimilar Medicines in Belgium: A Market Landscape Analysis.

Best-value biological medicines may generate competition in the off-patent biologicals market, resulting in having more resources available to provide patients with access to necessary medicines while maintaining high-quality care. Belgium is a country known to have low biosimilar market shares, suggesting a malfunctioning market for off-patent biologicals. This study aims to gain an in-depth understanding of the Belgian off-patent biologicals market, by looking at the evolution in volumes and costs of the relevant products in the market.

The Off-Patent Biological Market in Belgium: Is the Health System Creating a Hurdle to Fair Market Competition?

We investigated the off-patent biological market in Belgium from a policy maker's perspective, in light of the Belgian pharmaceutical health system. The main barriers relate to a short-term budgetary focus, to the overwhelming innovator's reach and to a concertation model with assessment and appraisal being mixed which results in poorly effective policy measures.

The impact of early phase price agreements on prices of orphan drugs.

Background: Innovative orphan drugs often have an incremental cost-effectiveness ratio (ICER) which is higher than the maximum threshold for reimbursement. Payers have limited budgets and often cannot pay the full price of a new product, but pharmaceutical and biotechnology companies require a minimum price to satisfy their investors. The objective of this study was to present a possible solution to bridge this pricing gap by having early phase price agreements, which reduce the risk for investors.

Immunoglobulin Replacement Therapy is critical and cost-effective in increasing life expectancy and quality of life in patients suffering from Common Variable Immunodeficiency Disorders (CVID): A health-economic assessment.

Background: Common variable immunodeficiency disorders (CVID), the most common form of primary antibody deficiency, are rare conditions associated with considerable morbidity and mortality. The clinical benefit of immunoglobulin replacement therapy (IgGRT) is substantial: timely treatment with appropriate doses significantly reduces mortality and the incidence of CVID-complications such as major infections and bronchiectasis. Unfortunately, CVID-patients still face a median diagnostic delay of 4 years.

Informing Patients about Biosimilar Medicines: The Role of European Patient Associations.

Biosimilar medicines support the sustainability of national healthcare systems, by reducing costs of biological therapies through increased competition. However, their adoption into clinical practice largely depends on the acceptance of healthcare providers and patients. Patients are different from health care professionals (HCPs), who are informing themselves professionally.

Economic Evaluation of Vaccines: Belgian Reflections on the Need for a Broader Perspective.

Objectives: The standard framework of economic evaluation of health programs, which is increasingly used for policy funding decisions, is insufficiently equipped to reflect the full range of health and economic benefits conferred by vaccines and thus undervalues vaccination.

Methods: In 2019, a group of Belgian health economic and clinical experts, supported by 2 senior international vaccination experts (1 American, 1 Belgian), convened 4 roundtable meetings to highlight which particular value elements of vaccination remain neglected in economic evaluations.

Results: They concluded that the standard economic evaluation framework fails to reflect the full value of vaccination with respect to prevention of complications linked to some vaccine-preventable diseases, health gains for caregivers, herd effects, changes in exposure to and distribution of serotypes, the effect on antimicrobial resistance, productivity gains for caregivers and patients, and the distributive implications of vaccination programs.

Tumor quiescence: elevating SOX2 in diverse tumor cell types downregulates a broad spectrum of the cell cycle machinery and inhibits tumor growth.

Background: Quiescent tumor cells pose a major clinical challenge due to their ability to resist conventional chemotherapies and to drive tumor recurrence. Understanding the molecular mechanisms that promote quiescence of tumor cells could help identify therapies to eliminate these cells. Significantly, recent studies have determined that the function of SOX2 in cancer cells is highly dose dependent.

Rationally Designed Polypharmacology: α-Helix Mimetics as Dual Inhibitors of the Oncoproteins Mcl-1 and HDM2.

Protein-protein interactions (PPIs), many of which are dominated by α-helical recognition domains, play key roles in many essential cellular processes, and the dysregulation of these interactions can cause detrimental effects. For instance, aberrant PPIs involving the Bcl-2 protein family can lead to several diseases including cancer, neurodegenerative diseases, and diabetes. Interactions between Bcl-2 pro-life proteins, such as Mcl-1, and pro-death proteins, such as Bim, regulate the intrinsic pathway of apoptosis.

Correction to: H, C, and N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A transporter (CaMBP2).

The article H, C, and N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A transporter (CaMBP2), written by Kristen M. Varney, Paul T. Wilder, Raquel Godoy-Ruiz, Filippo Mancia and David J.

Structure of the cell-binding component of the binary toxin reveals a di-heptamer macromolecular assembly.

Targeting infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent strains often have a binary toxin termed the toxin, in addition to the enterotoxins TsdA and TsdB. The toxin has an enzymatic component, termed CDTa, and a pore-forming or delivery subunit termed CDTb.