Pharmaceutical prices 1999-2008: an exploration into global variation, comparative measures, and potential determinants

Despite globalization, major differences in access and affordability of pharmaceuticals remain across the countries of the world. This dissertation aims at quantifying the differences in the price of pharmaceuticals amongst countries, identifying the factors responsible for these differences, and examining the policy consequences. Paper 1 compares prices in a large set of middle-income countries to some high- and lowincome countries. It finds that prices of pharmaceuticals are inconsistently related to income, with many middle-income countries paying more than some high-income countries and some paying less than countries that are far poorer. Paper 2 confirms the belief that drug prices in United States are generally higher than in 20 other high-income countries, but shows that prices became more similar over the period 1999-2008. Using the values and the range of three price indices (Laspeyres, Paasche, and Fisher) calculated with multilaterally- and bilaterally-matched samples provides a nuanced understanding of these price differences and their evolution. Paper 3 combines price data from middle- and high-income countries to ascertain the social, economic and demographic factors that determine differences in pharmaceutical prices. It finds that prices in middle- and high-income countries are affected differently by competition and globalization and that the greater effect of demographic factors on prices in middle-income countries can give them an inherent disadvantage in early price negotiation. Paper 4 also examines possible determinants of price but in this case focusses on health system characteristics in OECD countries only. The study finds that whilst the overall health system type does not bear any significant relationship with price, governance structures do have a moderately strong relationship with the price and availability of pharmaceuticals. Based on these results, the Conclusion discusses the issue of horizontal and vertical equity in pricing across countries and highlights important policy themes emerging from this work overall

Occupational Science for Occupational Therapy. Un Livre de Doris Pierce

Sans résumé

L'importance de la prise en soin préventive de la constipation pour une meilleure qualité de vie en milieu hospitalier:: travail de Bachelor

Thème : La constipation est souvent un sujet tabou. Ce symptôme peut parfois susciter du dégoût, ce qui peut provoquer une sous-estimation de l’inconfort de la personne et une banalisation de la part du soignant. Faisant partie de la sphère intime, le besoin d’élimination, pourtant naturel, s’avère un sujet gênant pour la personne qui en souffre et reporte peu, voire pas, les symptômes. Pourtant, cet état peut influencer de manière négative la qualité de vie. Problématique : Cette revue de littérature tente d’identifier si des interventions préventives auraient un effet sur la qualité de vie des patients hospitalisés à risque de constipation

Prion protein in the cerebrospinal fluid of healthy and naturally scrapie-affected sheep

The aim of this study was to characterize the cerebrospinal fluid (CSF) prion protein (PrP) of healthy and naturally scrapie-affected sheep. The soluble form of CSF PrPC immunoblotted with an anti-octarepeat and an anti-C terminus mAb showed two isoforms of approximately 33 and 26 kDa, corresponding to the biglycosylated and unglycosylated isoforms of brain PrPC. Neither the mean concentration nor the electrophoretic profile of CSF PrP differed between healthy and scrapieaffected sheep, whereas a slightly increased resistance of CSF PrP to mild proteolysis by proteinase K was evident in the CSF of scrapie-affected sheep. No difference in susceptibility to proteolysis was observed between the two ARR and VRQ genetic variants of the purified prokaryote recombinant PrP. It was concluded that the physicochemical properties of PrPC in the CSF could be altered during scrapie and that these changes might reflect the physiopathological process of prion disease

Selective and Efficient Immunoprecipitation of the Disease-associated Form of the Prion Protein Can Be Mediated by Nonspecific Interactions between Monoclonal Antibodies and Scrapie-associated Fibrils

Transmissible spongiform encephalopathies are characterized by the accumulation in brain tissues of an abnormal isoform of the prion protein named PrPsc, which is the only direct marker known for transmissible spongiform encephalopathies. Here we show that PrPsc can be specifically immunoprecipitated by using several monoclonal antibodies (mAbs) of various specificities independently of the properties of their binding site (paratope). These results strongly suggest that a significant proportion of mAbs can interact with PrPsc aggregates through nonspecific paratope-independent interactions allowing selective immunoprecipitation of PrPsc when these mAbs are immobilized on a polydisperse solid phase like microbeads

Fabry disease with atypical phenotype identified by massively parallel sequencing in early-onset kidney failure

Background. The cause of chronic kidney disease (CKD) remains unknown in ∼20% of patients with kidney failure. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, with a diagnostic yield of 12%–56%. Here, we report the use of MPS to establish a genetic diagnosis in a 24-year-old index patient who presented with hypertension, nephrotic-range proteinuria and kidney failure of unknown origin. Additionally, we describe a second family with the same mutation presenting with early-onset CKD. Results. In Family 1, MPS identified a known pathogenic variant in GLA (p.Ile319Thr), and plasma globotriaosylsphingosine and α-galactosidase A activity were compatible with the diagnosis of Fabry disease (FD). Segregation analysis identified three other family members carrying the same pathogenic variant who had mild or absent kidney phenotypes. One family member was offered enzyme therapy. While FD could not be established with certainty as the cause of kidney failure in the index patient, no alternative explanation was found. In Family 2, the index patient had severe glomerulosclerosis and a kidney biopsy compatible with FD at the age of 30 years, along with cardiac involvement and a history of acroparesthesia since childhood, in keeping with a more classical Fabry phenotype. Conclusion. These findings highlight the large phenotypic heterogeneity associated with GLA mutations in FD and underline several important implications of MPS in the work-up of patients with unexplained kidney failure.</p

Fabry disease with atypical phenotype identified by massively parallel sequencing in early-onset kidney failure

Background. The cause of chronic kidney disease (CKD) remains unknown in ∼20% of patients with kidney failure. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, with a diagnostic yield of 12%–56%. Here, we report the use of MPS to establish a genetic diagnosis in a 24-year-old index patient who presented with hypertension, nephrotic-range proteinuria and kidney failure of unknown origin. Additionally, we describe a second family with the same mutation presenting with early-onset CKD. Results. In Family 1, MPS identified a known pathogenic variant in GLA (p.Ile319Thr), and plasma globotriaosylsphingosine and α-galactosidase A activity were compatible with the diagnosis of Fabry disease (FD). Segregation analysis identified three other family members carrying the same pathogenic variant who had mild or absent kidney phenotypes. One family member was offered enzyme therapy. While FD could not be established with certainty as the cause of kidney failure in the index patient, no alternative explanation was found. In Family 2, the index patient had severe glomerulosclerosis and a kidney biopsy compatible with FD at the age of 30 years, along with cardiac involvement and a history of acroparesthesia since childhood, in keeping with a more classical Fabry phenotype. Conclusion. These findings highlight the large phenotypic heterogeneity associated with GLA mutations in FD and underline several important implications of MPS in the work-up of patients with unexplained kidney failure.</p

Development and implementation of a new service delivery model for children with disabilities : implications for DCD

There is a general consensus that new service delivery models are needed for children with developmental coordination disorder (DCD). Emerging principles to guide service delivery include the use of graduated levels of intensity and evidence-based services that focus on function and participation. Interdisciplinary, community-based service delivery models based on best practice principles are needed. In this case report, we propose the Apollo model as an example of an innovative service delivery model for children with DCD. We describe the context that led to the creation of a program for children with DCD, describe the service delivery model and services, and share lessons learned through implementation. The Apollo model has 5 components: first contact, service delivery coordination, community-, group- and individual-interventions. This model guided the development of a streamlined set of services offered to children with DCD, including early-intake to share educational information with families, community interventions, inter-disciplinary and occupational therapy groups and individual interventions. Following implementation of the Apollo model, waiting times decreased and numbers of children receiving services increased, without compromising service quality. Lessons learned are shared to facilitate development of other practice models to support children with DCD