Combined oral prolonged-release oxycodone and naloxone in chronic pain management

Introduction: The use of opioids is associated with unwanted adverse effects, particularly opioid-induced constipation (OIC). The adverse effects of opioids on gastrointestinal function are mediated by the interaction with opioid receptors in the gastrointestinal tract. The most common drugs used for relieving OIC are laxatives, which do not address the opioid receptor-mediated bowel dysfunction and do not provide sufficient relief. Areas covered: This paper discusses the role of a combination of prolongedrelease formulation of oxycodone (OX) and naloxone (N) in the prevention and management of OIC, reporting efficacy and safety outcome of controlled studies. In a therapeutic area of great unmet need, the combination tablet of prolonged release of OX and N (PR OXN) could offer patients effective analgesia, while improving opioid-induced bowel dysfunction. Expert opinion: PR OXN offers a unique and specific mechanism to control OIC in patients receiving chronic opioid therapy. This combination has the potential advantage of preventing OIC, particularly in subgroups of population, like elderly or advanced cancer patients. This approach can decrease the use of laxatives and additional medications, which represent a burden for patients presenting comorbidities requiring multiple medication

Cryogenic propellant venting under low pressure conditions Final report

Wall temperatures and heat transfer coefficients for solid-vapor mixtures of para hydrogen and nitrogen venting under low pressur

Is it time to combine untargeted antifungal strategies to reach the goal of 'early' effective treatment?

LETTER TO EDITO

Breakthrough pain in patients with abdominal cancer pain.

Abstract OBJECTIVE: Characterization of breakthrough cancer pain (BTcP) in patients with abdominal cancer is lacking. The aim of this study was to assess the characteristics of BTcP in patients with abdominal cancer pain. PATIENTS AND METHODS: In an observational cohort study, from a consecutive sample of patients admitted to a pain relief and supportive care unit for a period of 13 months, patients with abdominal disease due to cancer, including primary cancer or metastases, were assessed for the presence of chronic abdominal pain; its mechanism, intensity of background pain, and pain flares, which were distinguishable from the baseline pain, were recorded. Patients presenting with pain flares were assessed regarding the causes and the possible factors associated with it. Patients were reassessed when background pain control was considered optimal. RESULTS: From a sample of 522 patients admitted to an acute pain relief and palliative care unit in a period of 13 months, 100 patients with abdominal disease were available. The mean age was 65.3 years (SD\ub111.4); of the 100 patients, 45 (45%) were males. The mean Karnofsky status was 47.7 (SD\ub111.1). At admission (T0), 67 patients (67%) had background pain with mean pain intensity of 4.9 (SD\ub11.6). Sixty-one patients of those with background pain (91%) had superimposed and well-distinguished pain flares. After analgesic optimization (T1), the mean background pain intensity was 1.7 (SD\ub11.2), and 55.2% of patients had BTcP episodes. The difference with T0 was significant (P<0.0005). CONCLUSIONS: This preliminary study provides new insights on the characteristics of BTcP in a subclass of patients with abdominal disease. It has been estimated that about 55% of patients with well-controlled background pain will develop BTcP episodes. This percentage was higher (about 90%) in patients who presented with uncontrolled background pain, underlying the need to better characterize patients with BTcP, only after a careful optimization of basal pain, as considered by the definition of BTcP

Protein Aggregation Through Acoustic Cavitation

Therapeutic proteins represent an essential piece of a health management plan for diseases such as diabetes, cancer, hemophilia, Crohn\u27s Disease, and myocardial infarction. These proteins, however, must be maintained in their correct, biologically active conformation throughout processing, transportation, and delivery. This requirement poses serious engineering challenges because of a protein\u27s susceptibility to thermodynamic instabilities resulting from the weak bonds driving the tertiary structure of the molecule. A particularly problematic type of protein degradation is aggregation. Administration of aggregated proteins, a particularly problematic degradation form, can have dire consequences, including blocking a patient\u27s responsiveness to therapy, inducing immunogenicity, and even anaphylactic shock and death. Normal shipping and delivery methodologies are suspected of causing protein aggregation after the normal quality control process has been completed. This work investigates the effect of acoustic cavitation on protein aggregation as a function of impurity level, gas-liquid surface to value ratios, protein concentration, solution viscosity, density, surface tension, and nebulization time. A 0.2M and pH of 4.2 Glycine buffer solution was utilized with IVIg protein at 0.5, 1.0, 5.0, and 10.0 mg/ml and 20ºC. Protein aggregates were characterized using Microflow imaging and NanoSight tracking analysis. Transient cavitation and formation of radicals was monitored using classical iodine assays. Higher protein aggregation is observed in solutions that initially contain greater amounts of impurities or have a larger contact area with the gas interface. Aggregate production in hyper clean solutions, with no gas-liquid interface, initially increases with protein concentration, but eventually decreases at high concentrations. In contrast, aggregation rates in hyper clean solution with a gas-liquid interface continue to fall with increasing protein concentration. The size of the particulate in these two conditions suggests different degradation pathways. The small sizes when a gas interface is available are likely a result of the large area over which the process takes place. The effect of concentration is actually an effect of diffusion or availability for proteins at the surface. The large sizes found in conditions with no gas interface suggest a much more concentrated process consistent with an intense energy release at a single location. Moreover, monitoring of the formation of I3- from iodine as a function of nebulization time shows increasing production or radicals. All this supports the hypothesis that ultrasonic pressure waves in protein solutions cause transient cavitation which upon bubble implosion release hydroxyl radicals that can attack the protein in solution. In this circumstance, a rise in viscosity at higher protein concentration inhibits cavitation by elevating the lowest pressure region based on a specified pressure drop

Hungry Ghost

Hungry Ghost is a collection of poetry that examines the relationships between fathers and daughters, sisters, and one's selves