The Grizzly, September 17, 1982

New Ursinus Students Welcomed • Lantern Needs Associate Editor • Vandalism at Myrin • Administration Alterations • Committee Needs Chairmen • Folk Festival Summer Fun • Forum Preview • Lewis on Wall Street • Fencing Anyone? • Sendai Students at UC • Changes in Wismer • USGA Notes • Field Hockey Falls to Trenton State • The Bear Pack is in Top Form, Again • Volleyball Dumps Del Val • Grizzlies Drop Football Opener • Soccer Team Loses Two Close Oneshttps://digitalcommons.ursinus.edu/grizzlynews/1081/thumbnail.jp

Comparison of serious inhaler technique errors made by device-naïve patients using three different dry powder inhalers: a randomised, crossover, open-label study

Background: Serious inhaler technique errors can impair drug delivery to the lungs. This randomised, crossover, open-label study evaluated the proportion of patients making predefined serious errors with Pulmojet compared with Diskus and Turbohaler dry powder inhalers. Methods: Patients ≥18 years old with asthma and/or COPD who were current users of an inhaler but naïve to the study devices were assigned to inhaler technique assessment on Pulmojet and either Diskus or Turbohaler in a randomised order. Patients inhaled through empty devices after reading the patient information leaflet. If serious errors potentially affecting dose delivery were recorded, they repeated the inhalations after watching a training video. Inhaler technique was assessed by a trained nurse observer and an electronic inhalation profile recorder. Results: Baseline patient characteristics were similar between randomisation arms for the Pulmojet-Diskus (n = 277) and Pulmojet-Turbohaler (n = 144) comparisons. Non-inferiority in the proportions of patients recording no nurse-observed serious errors was demonstrated for both Pulmojet versus Diskus, and Pulmojet versus Turbohaler; therefore, superiority was tested. Patients were significantly less likely to make ≥1 nurse-observed serious errors using Pulmojet compared with Diskus (odds ratio, 0.31; 95 % CI, 0.19–0.51) or Pulmojet compared with Turbohaler (0.23; 0.12–0.44) after reading the patient information leaflet with additional video instruction, if required. Conclusions These results suggest Pulmojet is easier to learn to use correctly than the Turbohaler or Diskus for current inhaler users switching to a new dry powder inhaler

Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit

OBJECTIVES: Faecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact of colonic cleansing and transit time. DESIGN: Faecal samples were obtained from 30 healthy volunteers (HV) and 79 patients with IBS-D participating in a trial of ondansetron versus placebo. Colonic transit was measured using radio-opaque markers. Samples were also obtained from 24 HV before and after colonic cleansing with the osmotic laxative MoviPrep. FSPs were purified from faecal extracts using benzamidine-Sepharose affinity chromatography. SDS-PAGE profiled components were identified using trypsinolysis and tandem mass spectrometry. Functional protease activity in faecal extracts was measured using a colorimetric assay based on the proteolysis of azo-casein. RESULTS: Protein analysis identified the most abundant FSPs as being of human origin and probably derived from pancreatic juice. Functional assays showed increased faecal protease (FP) and amylase in patients with IBS-D compared with HV. Those with higher amylase had significantly higher FP and greater anxiety. FP activity correlated negatively with whole gut transit in patients with IBS-D (Spearman r=−0.32, p=0.005) and HV (r=−0.55, p=0.014). Colon cleansing caused a significant rise in FP activity in HV from a baseline of median (IQR) 253 (140–426) to 1031 (435–2296), levels similar to those seen in patients with IBS-D. FSP activity correlated positively with days/week with urgency. CONCLUSIONS: The most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. CLINICALTRIALS.GOV: NCT00745004

PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol

BACKGROUND: A "physiologically based pharmacokinetic" (PBPK) approach uses a realistic model of the animal to describe the pharmacokinetics. Previous PBPKs have been designed for specific solutes, required specification of a large number of parameters and have not been designed for general use. METHODS: This new PBPK program (PKQuest) includes a "Standardhuman" and "Standardrat" data set so that the user input is minimized. It has a simple user interface, graphical output and many new features: 1) An option that uses the measured plasma concentrations to solve for the time course of the gastrointestinal, intramuscular, intraperotineal or skin absorption and systemic availability of a drug – for a general non-linear system. 2) Capillary permeability limitation defined in terms of the permeability-surface area products. 4) Saturable plasma and tissue protein binding. 5) A lung model that includes perfusion-ventilation mismatch. 6) A general optimization routine using either a global (simulated annealing) or local (Powell) minimization applicable to all model parameters. RESULTS: PKQuest was applied to measurements of human propranolol pharmacokinetics and intestinal absorption. A meal has two effects: 1) increases portal blood flow by 50%; and 2) decreases liver metabolism by 20%. There is a significant delay in the oval propranolol absorption in fasting subjects that is absent in fed subjects. The oral absorption of the long acting form of propranolol continues for a period of more than 24 hours. CONCLUSIONS: PKQuest provides a new general purpose, easy to use, freely distributed and physiologically rigorous PBPK software routine

Cost Effectiveness of Raloxifene in the Treatment of Osteoporosis in Sweden: An Economic Evaluation Based on the MORE Study

Background: The Multiple Outcomes of Raloxifene Evaluation (MORE) study showed that treatment with raloxifene reduces the risk of vertebral fracture and breast cancer in postmenopausal women with osteoporosis. Objective: Based on the MORE study the aim of the present study was to assess the cost effectiveness of raloxifene (compared with no treatment) for the treatment of osteoporosis in postmenopausal women in Sweden. Design: A revised version of a previously developed computer simulation model was used. The impact of the risk-reducing effect of raloxifene on vertebral fractures and breast cancer on cost effectiveness was analysed using a clinical and a morphometric definition of vertebral fracture. Benefits of raloxifene treatment were measured in quality-adjusted life-years (QALYs) and life-years gained. The study estimated the cost effectiveness mainly from a healthcare perspective but the cost effectiveness taking a societal perspective was also analysed. Results: Intervention costs (in Swedish kronor [SEK] and euros [ Conclusions: In relation to accepted threshold values for cost per QALY in Sweden, this model indicates, with its underlying assumptions and data, that raloxifene (compared with no treatment) is cost effective for the treatment of postmenopausal women at an increased risk of vertebral fracture, from the Swedish healthcare and societal perspectives.Breast-cancer, Cost-utility, Menopause, Postmenopausal-osteoporosis, Raloxifene, Vertebral-fracture