Ferring Pharmaceuticals (United Kingdom)

Some current prostate cancer (PCa) treatment regimens are known to have adverse effects on bone, for example androgen deprivation therapy (ADT), and on cardiovascular health, for example ADT and antiandrogen therapy. Strengthened recommendations for the practical assessment and management of bone and cardiovascular health in men with PCa are needed. This review aims to provide practical guidance for healthcare providers along the continuum of patient care on the management of bone and cardiovascular health in men with PCa undergoing ADT and antiandrogen therapy based on real-world evidence. Evidence was identified by searching PubMed for publications that reported the effects of PCa treatment on bone or cardiovascular health in a real-world setting and were published between January 2017 and August 2023. Review articles were excluded. The evidence identified indicates that ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis and fractures. Bone-protecting agents (BPAs) are effective at improving bone health in patients undergoing ADT and antiandrogen therapy at all stages of the PCa pathway. Despite this, the use and timing of initiation of BPAs are variable. Furthermore, real-world studies have confirmed an association between ADT and cardiovascular risk. As survival outcomes improve, maintenance of bone and cardiovascular health is increasingly important in men with PCa. Risk is a continuous variable that must be assessed throughout the continuum of PCa treatment. Therefore, all men starting ADT should be assessed for bone and cardiovascular risk. Lifestyle adjustments, dietary supplementation and pharmacological intervention may be advised.

PurposePersistence and adherence with subcutaneous growth hormone (GH; somatropin) therapy in children is widely acknowledged to be suboptimal. This study aimed to investigate how the use of a jet-delivery device, ZomaJet®, impacts on medication-taking behaviors compared to needle-based devices.Materials and methodsA retrospective cohort study of children aged ≤18 years was conducted using a UK-based, nationwide database of GH home-delivery schedules. Data were evaluated for the period between January 2010 and December 2012 for 6,061 children receiving either Zomacton® (somatropin) via the ZomaJet jet-delivery device or one of six brands of GH all administered via needle-based devices. Persistence was analyzed for patients with appropriate data, measured as the time interval between first and last home deliveries. An analysis of adherence was conducted only for patients using ZomaJet who had appropriate data, measured by proportion of days covered. Brand switches were identified for all patients.ResultsPersistence with GH therapy was significantly longer in patients using ZomaJet compared to needle-based devices (599 days versus 535 days, respectively, n=4,093; P<0.001); this association was observed in both sexes and across age subgroups (≤10 and 11–16 years). The majority (58%) of patients using ZomaJet were classed as adherent (n=728). Only 297 patients (5%) switched GH brand (n=6,061), and patients tended to use ZomaJet for longer than other devices before switching.ConclusionIt appears important that the choice of a jet-delivery device is offered to children prescribed daily GH therapy. These devices may represent a much-needed effective strategy for maintaining persistence with subcutaneous GH administration in children, potentially offering better clinical outcomes and greater cost-efficiency.

Active myofibroblast (MF) contraction contributes significantly to the increased intrahepatic vascular resistance that is the primary cause of portal hypertension (PHT) in cirrhosis. We sought proof of concept for direct therapeutic targeting of the dynamic component of PHT and markers of MF activation using short-term administration of the peptide hormone relaxin (RLN). We defined the portal hypotensive effect in rat models of sinusoidal PHT and the expression, activity, and function of the RLN-receptor signaling axis in human liver MFs. The effects of RLN were studied after 8 and 16 weeks carbon tetrachloride intoxication, following bile duct ligation, and in tissue culture models. Hemodynamic changes were analyzed by direct cannulation, perivascular flowprobe, indocyanine green imaging, and functional magnetic resonance imaging. Serum and hepatic nitric oxide (NO) levels were determined by immunoassay. Hepatic inflammation was assessed by histology and serum markers and fibrosis by collagen proportionate area. Gene expression was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting and hepatic stellate cell (HSC)-MF contractility by gel contraction assay. Increased expression of RLN receptor (RXFP1) was shown in HSC-MFs and fibrotic liver diseases in both rats and humans. RLN induced a selective and significant reduction in portal pressure in pathologically distinct PHT models, through augmentation of intrahepatic NO signaling and a dramatic reduction in contractile filament expression in HSC-MFs. Critical for translation, RLN did not induce systemic hypotension even in advanced cirrhosis models. Portal blood flow and hepatic oxygenation were increased by RLN in early cirrhosis. Treatment of human HSC-MFs with RLN inhibited contractility and induced an antifibrogenic phenotype in an RXFP1-dependent manner. We identified RXFP1 as a potential new therapeutic target for PHT and MF activation status.