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BUSINESS ENVIRONMENT Axcan's revenue has historically been and continues to be principally derived from sales of pharmaceutical products to large pharmaceutical wholesalers and large pharmacy chains. Axcan utilizes a "pull-through" marketing approach that is typical of pharmaceutical companies. According to this approach, Axcan's sales representatives demonstrate the features and benefits of its products to gastroenterologists, who may write their patients prescriptions for Axcan's products. The patients, in turn, take the prescriptions to pharmacies to be filled. The pharmacies then place orders with the wholesalers or, in the case of large pharmacy chains, their distribution centres, to which Axcan sells its products. The level of patient and physician acceptance of Axcan's products, as well as the availability of similar therapies, which may be less effective but also less expensive than some of Axcan's products, impact Axcan's revenues by driving the level and timing of prescriptions for its products. Axcan's expenses are comprised primarily of selling and administrative expenses including marketing expenses ; , cost of goods sold including royalty payments to those companies from which Axcan licenses some of its commercialized products ; , research and development expenses, as well as depreciation and amortization. Axcan's annual and quarterly operating revenues are primarily affected by three factors: the level of acceptance of Axcan's products by gastroenterologists and their patients; the ability of Axcan to convince practitioners to use Axcan's products for approved indications; and wholesaler buying patterns. Historically, wholesalers' business models in the United States were dependent on drug price inflation. Their profitability and gross margins were directly tied to the speculative purchasing of pharmaceutical products at pre-increase prices, and the selling of their product inventory to their customers at the increased price. This inventory price arbitrage accounted for a predominant portion of wholesalers' compensation for their distribution services and had a dramatic effect on wholesaler buying patterns, as they invested in inventories in anticipation of generating higher gross margins from manufacturer price increases. More recently, pharmaceutical manufacturers have not been increasing drug prices as frequently, and the percentage increases have been lower. For these and other reasons, some wholesalers have changed their business model to a fee-for-service arrangement, whereby manufacturers pay wholesalers a fee for inventory management and other services. These fees typically are a percentage of the wholesaler's purchases from the manufacturer or a fixed charge per item or per unit. The fee-for-service approach results in wholesalers' compensation being more stable, and volume-based as opposed to price-increase based. As a result of the move to a fee-for-service business model, many wholesalers are no longer investing in inventory ahead of anticipated price increases and are reducing their inventories from their historical levels. Under the new model, the consequence of manufacturers using wholesalers is that they now realize the benefit of price increases more rapidly in return for paying wholesalers for the services they provide, on a fee-for-service basis. This change in wholesalers' business models has affected Axcan's revenue since fiscal 2005, and the resulting distribution services agreement "DSA" ; fees are deducted from gross sales and fluticasone.
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In this study, another approach, classification and regression tree CART ; analysis was investigated. CART is a statistical method that explains the variation of a response variable using a set of explanatory variables, so-called predictors [14]. The method is based on a recursive binary splitting of the data into mutually exclusive subgroups containing objects with similar properties. CART is extensively used for modeling and classification in several areas, such as medical diagnosis and prognosis [1416], and ecology [17]. However, its use in analytical chemistry is very limited. A very interesting advantage of CART is the possibility to deal with large numbers of both categorical and numerical variables. Another advantage is that no assumption about the underlying distribution of the predictor variables is required even categorical variables can be used ; . Eventually, CART provides a graphical representation, which makes the interpretation of the results easy. Therefore, we felt that CART could be a very interesting method to select and relate molecular descriptors with the chromatographic retention of the molecules. The goal of this study was to explore the possibilities of CART to find relationships between chromatographic retention of solutes on a given chromatographic system and the selected molecular descriptors. Since, for a given molecule we are mainly interested in the prediction of a suitable chromatographic system, we focused on the ability of the methodology to distinguish between classes with respectively low, intermediate and high retention on the considered system, rather than on the exact retention prediction of the compounds. A physicochemical explanation of the selected descriptors is also given.
PROGNOSTIC VALUE OF ELECTROCARDIOGRAPHIC ABNORMALITIES IN PATIENTS WITH ACUTE PULMONARY EMBOLISM John A. Sallach, MD * ; Susan M. Sallach, MD; James D. Thomas, MD; Mario J. Garcia, MD; Michael P. Hudson, MD; James K. McCord, MD. Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Acute pulmonary embolism PE ; may affect cardiac rate, rhythm, conduction pattern and repolarization manifesting a variety of nonspecific abnormalities on 12-lead electrocardiogram ECG ; . No prior studies have examined the prognostic significance of these abnormalities. The purpose of this study was to determine the value of ECG abnormalities in predicting 30-day mortality in acute PE. METHODS: Between 1998 and 2000, 144 patients admitted with acute PE had an ECG and cardiac troponin I cTnI ; measurement within 24 hours of diagnosis. Medical records were abstracted for baseline characteristics, ECG findings and clinical outcomes. Patients were stratified according to 30-day mortality status. ECG findings and cTnI positivity a documented strong predictor of 30-day mortality ; were analyzed in order to determine the prognostic value of these indices. RESULTS: Eighteen percent 26 144 ; of patients died within 30 days of PE diagnosis. Table 1 displays ECG findings and cTnI positivity in patients alive mean age 68 16 years, 46% male ; and those dead mean age 71 15 years, 38% male ; at 30 days. ECG findings of PVCs, atrial fibrillation and low QRS voltage are significantly associated with increased mortality. CONCLUSIONS: In the setting of acute PE, the presence of PVCs, atrial fibrillation and low QRS voltage on the 12-lead ECG at the time of presentation are significantly associated with increased 30-day mortality. CLINICAL IMPLICATIONS: At the time of acute PE diagnosis, the 12-lead EKG offers important prognostic information. An electrocardiogram should therefore be performed on all patients presenting with acute PE. Table 1. Alive 30d n 118 ; PVCs A. Fib Low Volt QRS Positive cTnI S1S2S3 RBBB Anterior ST Depression Tachycardia Transition Zone V5 4% 6% 9% Death 30d n 26 ; 23% 27% OR 95% CI ; 6.8 4.8 4.0 ; 1.3-18.1 ; 1.2-13.3 ; 1.4-9.7 ; 0.6-21.6 ; 0.5-6.1 ; 0.4-6.8 ; P value 0.005 * 0.017 * 0.021 * 0.006 * 0.213 0.493 0.574 and
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4. Gronert GA, Tjhompson SL, Onofrio BM. Human malignant hyperthermia: Awake episodes and correction by Dantrolene. Anesthesia and Analgesia 1980; 59 5 ; : 377-378. 5. Britt BA. Combined anesthetic- and stress-induced malignant hyperthermia in two offspring of malignant hyperthermic-susceptible parents. Anesthesia and Analgesia 1988; 67: 393-399. Wingard DW, Gatz EE. Some observations on stress susceptible patients New York, 1978. 363-372 p. 7. Britt BA, Kalow W. Malignant hyperthermia: A statistical review. Canadian Anaesthetics Society Journal 1970; 17: 293 - 315. 8. Ording H. Incidence of malignant hyperthermia in Denmark. Anesthesia and Analgesia 1985; 64 700 - 704 ; . 9. Bell G, deMello W. Malignant hyperpyrexia in a serving officer. Journal of the Royal Army Medical Corps 1996; 142: 30 - 31. 10. Strazis KP, Fox AW. Malignant hyperpyrexia: A review of published cases. Anesthesia and Analgesia 1993; 77: 297 - 304. 11. Harrison GG. Dantrolene - Dynamics and kinetics. British Journal of Anaesthetics 1988; 60: 279 - 286. 12. Halsall PJ, Cain PA, Ellis FR. Retrospective analysis of anaesthetics received by patients before susceptibility to malignant hyperthermia was recognized. British Journal of Anaesthetics 1979; 51: 949 - 954. 13. 1996. Personal communication: Corkoran M. Malignant Hyperthermia incidence. December and
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Another aspect of R&D management is hiring the right sort of people for R&D. Ranbaxy is aggressively hiring senior scientists from overseas as well as other Indian companies with emphasis on hiring senior scientists working in MNC labs. DRL we noted targeted Indian doctoral and post-doctoral students in the US, while Wockhardt mainly recruits scientists working in Indian academia and research institutes who are conversant with Indian medical problems. In our interviews, we came across many scientists who had worked in Hoechst or in Ranbaxy prior to joining R&D departments of Wockhardt, DRL and NPIL. This transfer of personnel has and
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