Cost effectiveness of a new combined immunosuppressive and antiviral regimen on the one-year follow-up of kidney transplant patients.

Background: Medical prescription after organ transplant must prevent both rejection and infectious complications. We assessed the 1-year effectiveness and cost of introducing a new combined regimen in kidney transplantation. Methods: Patients transplanted from January 2000 to March 2003 (Period 1) were compared to patients transplanted from April 2003 to July 2005 (Period 2). In period 1, patients were treated with Basiliximab, Cyclosporin, steroids and Mycophenolate (MMF) or Azathioprine. Prophylaxis with Valacyclovir was prescribed only in CMV D+/R- patients. In period 2, immunosuppressive drugs were Basiliximab, Tacrolimus, steroids and MMF. A 3-month universal CMV prophylaxis with Valganciclovir was used. Medical charts of outpatient visits allowed identifying drug, laboratory and radiological tests use, and hospital information system causes of hospitalisation and length of stay (LOS) over the first year after transplant. Patients with incomplete costs data were excluded. Results: 53 patients were analysed in period 1, and 60 in period 2. CMV serostatus patterns were not significantly different between the 2 periods. Over 12 months, acute rejection decreased from 22 patients (42%) in period 1 to 4 patients (7%) in period 2 (p<0.001), and CMV infection from 25 patients (47%) to 9 patients (15%, p<0.001). Average total rehospitalisation LOS decreased from 28±19 to 20±11 days (p<0.007). Average outpatient visits decreased from 49±10 to 39±8 (p<0.001). Average immunosuppression and CMV prophylaxis costs increased from US$ 18,362±6,546 to 24,637±5,457 (p<0.001), while average graft rejection costs decreased form US$ 4,135±9,164 to 585±2,850 (p=0.005), and average CMV treatment costs from US$ 2,043±5,545 to 91±293 (p=0.008). Average outpatient visits costs decreased from US$ 7,619±1,549 to 6,074±1,043 (p<0.001), and other hospital costs from US$ 3,801±6,519 to 1,196±3,146 (p=0.007). Altogether, average 1-year treatment costs decreased from US$ 35,961±14,916 to 32,584±6,211 (p=0.115). Cost-effectiveness ratios to avoid graft rejection and CMV infection decreased from US$ 61,482±9,292 to 34,911± 1,639 (p=0.006) and US$ 68,070±11,122 to 39,899±2,650 (p=0.015), respectively. Conclusion: The new combined regimen administered in period 2 was significantly more effective. Its additional cost was more than offset by savings linked with complications avoidance.

La charmeuse d'enfants / Jules Mary

Collection : Le livre national ; n° 25

Gastrointestinal malformations: impact of prenatal diagnosis on gestational age at birth.

The aim of the study was to analyse the degree to which gestational age (GA) has been shortened due to prenatal diagnosis of gastrointestinal malformations (GIM). The data source for the study was 14 population-based registries of congenital malformations (EUROCAT). All liveborn infants with GIMs and without chromosomal anomalies, born 1997-2002, were included. The 14 registries identified 1047 liveborn infants with one or more GIMs (oesophageal atresia, duodenal atresia, omphalocele, gastroschisis and diaphragmatic hernia). Median GA at birth was lower in prenatally diagnosed cases for all five malformations, although not statistically significant for gastroschisis. There was little difference in median birthweight by GA for the pre- and postnatally diagnosed infants. The difference in GA at birth between prenatally and postnatally diagnosed infants with GIMs is enough to increase the risk of mortality for the prenatally diagnosed infants. Clinicians need to balance the risk of early delivery against the benefits of clinical convenience when making case management decisions after prenatal diagnosis. Very few studies have been able to show benefits of prenatal diagnosis of congenital malformations for liveborn infants. This may be because the benefits of prenatal diagnosis are outweighed by the problems arising from a lower GA at birth.

Bureaucracy and the flypaper effect : Evidence from intercommunal fiscal equalisation in the canton of Vaud

Unlike classical theoretical expectations, our empirical study shows that financial transfers to decentralised governments increase local public expenditures much more than would be triggered by an equivalent rise in local income. This empirical evidence of the presence of a flypaper effect is achieved using panel data from 375 municipalities located in the Swiss canton of Vaud covering the period 1994 to 2005. During that time there was a major change in the financial equalisation scheme. Furthermore, our study confirms the analysis of the public choice theory: the effect depends partly on the degree of complexity of the municipal bureaucracy. These results show that local bureaucratic behaviour may impede the effectiveness of a financial equalisation scheme that aims to reduce disparities in local tax.

Chlamydiaceae and Chlamydia-like organisms in free-living small mammals in Europe and Afghanistan.

Few data are available on the occurrence of chlamydial infections in wild small mammals. We investigated the significance of free-living small mammals as reservoirs or transmission hosts for microorganisms of the phylum/class Chlamydiae. We obtained 3,664 tissue samples from 911 animals in Switzerland, Germany, Austria, the Czech Republic, and Afghanistan. Samples included internal organs (n = 3,652) and feces (n = 12) from 679 rodents (order Rodentia) and 232 insectivores (order Soricomorpha) and were tested by three TaqMan® real-time PCRs specific for members of the family Chlamydiaceae and selected Chlamydia-like organisms such as Parachlamydia spp. and Waddlia spp. Only one of 911 (0.11%) animals exhibited a questionable positive result by Chlamydiaceae-specific real-time PCR. Five of 911 animals were positive by specific real-time PCR for Parachlamydia spp. but could not be confirmed by quantitative PCR targeting the Parachlamydia acanthamoebae secY gene (secY qPCR). One of 746 animals (0.13%) was positive by real-time PCR for Waddlia chondrophila. This result was confirmed by Waddlia secY qPCR. This is the first detection of Chlamydia-like organisms in small wildlife in Switzerland. Considering previous negative results for Chlamydiaceae in wild ruminant species from Switzerland, these data suggest that wild small mammals are unlikely to be important carriers or transport hosts for Chamydiaceae and Chlamydia-like organisms.

Acvbp Versus Acvbp Plus Rituximab For Young Patients With Localized Low-Risk Diffuse Large B-Cell Lymphoma: A Study By The Groupe D'etude Des Lymphomes De L'adulte

Introduction: In a prior study, we demonstrated that ACVBP + consolidation was superior to 3 cycles of CHOP + radiotherapy in young patients (pts) with localized aggressive lymphoma (Reyes F et al. N Engl J Med 2005;352:1197). This randomized trial compared in these pts ACVBP vs. ACVBP + a short course of rituximab (R-ACVBP).Methods: untreated pts between 18 and 65y with stage I/II DLBCL and no adverse prognostic factors according to the aa-IPI were eligible. ACVBP consisted of 3 induction cycles given every 2 weeks: doxorubicin (75 mg/m2) day 1, cyclophosphamide (1.2g/m2) day 1, vindesine (2 mg/m2) day 1 and 5, bleomycin (10 mg) day 1 and 5, prednisone (60 mg/m2) day 1 to 5 followed by consolidation with metothrexate, ifosfamide, VP-16 and cytarabine. R-ACVBP consisted of the same regimen combined with 4 doses of rituximab (375 mg/m2) on day 1, 15, 29 and 43. Primary objective was EFS.Results: From 01/04 to 03/08, 223 pts were randomized, 113 in ACVBP and 110 in R-ACVBP arm. Characteristics were: median age 49y (18-65), stage I 63%, extranodal involvement 45%, bulky disease 4%. CR was 94% in ACVBP and 97% in ACVBP arm (ns). With a median follow-up of 43 months, the 3-y EFS was 82% (95% CI, 73% to 88%) in ACVBP and 93% (95% CI, 87% to 97%) in R-ACVBP group (P=0.0487). The 3-y PFS was 83% (95% CI, 74% to 89%) and 95% (95% CI, 89% to 98%) respectively (P=0.0205). OS did not significantly differ with a 3-y estimates of 97% (95% CI, 90% to 99%) for ACVBP and 98% (95% CI, 92% to 100%) for R-ACVBP (P=0.686). In multivariate analysis, a longer PFS was associated with R-ACVBP arm (P=0.0302) and lower b2-m level (P=0.0164). The same proportion of pts (27%) experienced at least 1 SAE in both groups. There were 4 deaths in each arm, with 1 treatment-related death in R-ACVBP (pneumocystis jiroveci pneumonia).Conclusion: the addition of only 4 doses of rituximab to ACVBP significantly improves EFS and PFS in younger pts with low-risk localized DLBCL.

Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice

The aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC - PK1) and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.


Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets.

Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2 D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases.

Pliensbachian magnetostratigraphy: new data from Paris Basin (France)

Sampling of an industrial drill string from the northeastern Paris Basin (Montcornet, France) provides early Jurassic magnetostratigraphic data coupled with biochronological control. About 375 paleomagnetic samples were obtained from a 145 m thick series of Pliensbachian rocks. A composite demagnetization thermal up to 300 C and an alternating field up to 80 mT were used to separate the magnetic components. A low unblocking temperature component (<250degreesC) with an inclination of about 64 is interpreted as a present-day field overprint. The characteristic remanent component with both normal and reversed antipodal directions was isolated between 5 and 50 mT. Twenty-nine polarity intervals were recognized. Correlation of these new results from the Paris Basin with data from the Breggia Gorge section (Ticino, southern Alps, Switzerland), which is generally considered as the reference section for Pliensbachian magnetostratigraphy, reveals almost identical patterns of magnetic polarity reversals. However, the correlation implies significant paleontological age discrepancies. Revised age assignments of biostratigraphic data of Breggia as well as an objective evaluation of the uncertainties on zonal boundaries in both Breggia and Moncornet resolve the initial discrepancies between magnetostratigraphic correlations and biostratigraphic ages. Hence, the sequence of magnetic reversals is significantly strengthened and the age calibration is notably improved for the Pliensbachian, a stage for which sections combining adequate magnetic signal and biostratigraphic constraints are still very few. (C) 2002 Elsevier Science B.V. All rights reserved.

UMA ANÁLISE COMPREENSIVA DA REFORMA DO SISTEMA DE SAÚDE DE CABO VERDE

Neste estudo adota-se o modelo de análise compreensiva de política de saúde para investigar a reforma do sistema de saúde de Cabo Verde, no período de 1991-2009, e identificar as perspectivas de futuro da reforma na opinião dos seus principais atores. Trata-se de uma pesquisa qualitativa do tipo estudo de caso baseada no modelo de Walt e Gilson (1994) para análise de política, operacionalizado por Araújo Júnior e Maciel Filho (2001). A reforma do sistema de saúde de Cabo Verde é examinada com base em quatro categorias: o macro contexto geográfico, histórico, político e socio-econômico em que a política de saúde caboverdiana é desenvolvida; o micro contexto enfocando a estrutura e características do sistema de saúde do país; o conteúdo da reforma desse sistema de saúde; o processo da sua formulação e implementação; e uma análise dos principais atores envolvidos no tocante a sua opinião sobre as perspectivas futuras. Durante o seu percurso o sistema de saúde de Cabo Verde tem sofrido importantes modificações que decorrem das mudanças no macro contexto observadas em escala mundial. A trajetória interna do sistema de saúde evidenciada aponta para inúmeros desafios para cumprir seu papel na sociedade, principalmente sob aspectos relevantes apontados pelo estudo que afetam na atualidade todos os sistemas nacionais de saúde. O estudo identifica a opinião dos principais atores sobre o futuro que consideram haver necessidade de aprofundamento da reforma do sistema de saúde cabo-verdiano. Em que pese a necessidade de investigação mais detalhada sobre essa questão, por se tratar de uma pesquisa de opinião considerando a diversidade dos atores da política, pode-se dizer que eles apontam para fatores cruciais para o Sistema de Saúde de Cabo Verde. Entre eles destaca-se a redefinição da forma de financiamento e da política de recursos humanos. Assim como, observa-se tendência para nova diretriz da saúde pública no sentido de reestruturação dos programas existentes. Evidencia-se ainda opiniões que apontam para descentralização e regionalização com atribuição de mais poderes, competências, e alocação de recursos financeiros e materiais aos municípios para a prestação de cuidados de saúde. A introdução do programa de saúde de família e uma melhor articulação entre os setores público e privado no setor saúde, com a introdução de prática de avaliação e regulação no sistema são temas recorrentes na opinião dos entrevistados. O estudo conclui que repensar o modelo de sistema de saúde cabo-verdiano, encarando como fragilidades, a qualidade dos cuidados de saúde prestados, a segurança dos pacientes e o combate ao desperdício, na base de responsabilidade partilhada por profissionais de saúde, gestores, políticos, setor privado, sociedade civil, usuários e agencias internacionais afigura-se como um debate oportuno para contribuir de alguma forma para melhorar o desempenho do sistema universal de saúde daquele pais.

Helsinki 24/7 1945

Kirje 24.7.1945