Evaluation des technologies médicales : travaux présentés pendant le Congrès TEKMED 87 = Assessment of medical technologies : the papers presented during the TEKMED 87 Congress

[Table des matières] Technology assessment in health care in the United States: an historical review / S. Perry. - The aims and methods of technology assessment / JH Glasser. - Evaluation des technologies de la santé / A. Griffiths. - Les données nécessaires pour l'évaluation des technologies médicales / R. Chrzanowski, F. Gutzwiller, F. Paccaud. - Economic issues in technology assessment/DR Lairson, JM Swint. - Two decades of experience in technology assessment: evaluating the safety, performance, and cost effectiveness of medical equipment / JJ Nobel. - Demography and technology assessment / H. Hansluwka. - Méthodes expérimentale et non expérimentale pour l'évaluation des innovations technologiques / R. Chrzanowski, F. Paccaud. - Skull radiography in head trauma: a successful case of technology assessment / NT Racoveanu. - Complications associées à l'anesthésie: une étude prospective en France / L. Tiret et al. - Impact de l'information publique sur les taux opératoires: le cas de l'hystérectomie / G. Domenighetti, P. Luraschi, A. Casabianca. - The clinical effectiveness of acupuncture for the relief of chronic pain / MS Patel, F. Gutzwiller, F. Paccaud, A. Marazzi. - Soins à domicile et hébergement à long terme: à la recherche d'un développement optimum / G. Tinturier. - Economic evaluation of six scenarios for the treatment of stones in the kidney and ureter by surgery or ESWL / MS Patel et al. - Technology assessment and medical practice / F. Gutzwiller. - Technology assessment and health policy / SJ Reiser. - Global programme on appropriate technology for health, its role and place within WHO / K. Staehr Johansen.

A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology.

BACKGROUND: Pathogen reduction of platelets (PRT-PLTs) using riboflavin and ultraviolet light treatment has undergone Phase 1 and 2 studies examining efficacy and safety. This randomized controlled clinical trial (RCT) assessed the efficacy and safety of PRT-PLTs using the 1-hour corrected count increment (CCI(1hour) ) as the primary outcome. STUDY DESIGN AND METHODS: A noninferiority RCT was performed where patients with chemotherapy-induced thrombocytopenia (six centers) were randomly allocated to receive PRT-PLTs (Mirasol PRT, CaridianBCT Biotechnologies) or reference platelet (PLT) products. The treatment period was 28 days followed by a 28-day follow-up (safety) period. The primary outcome was the CCI(1hour) determined using up to the first eight on-protocol PLT transfusions given during the treatment period. RESULTS: A total of 118 patients were randomly assigned (60 to PRT-PLTs; 58 to reference). Four patients per group did not require PLT transfusions leaving 110 patients in the analysis (56 PRT-PLTs; 54 reference). A total of 541 on-protocol PLT transfusions were given (303 PRT-PLTs; 238 reference). The least square mean CCI was 11,725 (standard error [SE], 1.140) for PRT-PLTs and 16,939 (SE, 1.149) for the reference group (difference, -5214; 95% confidence interval, -7542 to -2887; p<0.0001 for a test of the null hypothesis of no difference between the two groups). CONCLUSION: The study failed to show noninferiority of PRT-PLTs based on predefined CCI criteria. PLT and red blood cell utilization in the two groups was not significantly different suggesting that the slightly lower CCIs (PRT-PLTs) did not increase blood product utilization. Safety data showed similar findings in the two groups. Further studies are required to determine if the lower CCI observed with PRT-PLTs translates into an increased risk of bleeding.

Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods, [and] Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes

Rapport de synthèse1. Partie de laboratoireCette première étude décrit le développement et la validation, selon les standards internationaux, de deux techniques de mesure des concentrations sanguines de voriconazole, un nouvel agent antifongique à large spectre: 1) la chromatographic en phase liquide à haute pression et 2) le bio-essai utilisant une souche mutante de Candida hypersensible au voriconazole. Ce travail a aussi permis de mettre en évidence une importante et imprévisible variabilité inter- et intra-individuelle des concentrations sanguines de voriconazole malgré l'utilisation des doses recommandées par le fabriquant. Ce travail a été publié dans un journal avec "peer-review": "Variability of voriconazole plasma levels measured by new high- performance liquid chromatography and bioassay methods" by A. Pascual, V. Nieth, T. Calandra, J. Bille, S. Bolay, L.A. Decosterd, T. Buclin, P.A. Majcherczyk, D. Sanglard, 0. Marchetti. Antimicrobial Agents Chemotherapy, 2007; 51:137-432. Partie CliniqueCette deuxième étude a évalué de façon prospective l'impact clinique des concentrations sanguines de voriconazole sur l'efficacité et sécurité thérapeutique chez des patients atteints d'infections fongiques. Des concentrations sanguines élevées étaient significativement associés à la survenue d'une toxicité neurologique (encéphalopathie avec confusion, hallucinations et myoclonies) et des concentrations sanguines basses à une réponse insuffisante au traitement antifongique (persistance ou progression des signes cliniques et radiologiques de l'infection). Dans la majorité des cas, un ajustement de la dose de voriconazole, sur la base des concentrations mesurées, a abouti à une récupération neurologique complète ou à une résolution de l'infection, respectivement. Ce travail a été publié dans un journal avec "peer-review": " Voriconazole Therapeutic Drug Monitoring in Patients with Invasive Mycoses Improves Efficacy and Safety Outcomes" by A. Pascual, T. Calandra, S. Bolay, T. Buclin, J. Bille, and O. Marchetti. Clinical Infectious Diseases, 2008 January 15; 46(2): 201-11.Ces deux études, financées de façon conjointe par un "grant" international de la Société suisse d'infectiologie et la Société internationale de maladies infectieuses et par la Fondation pour le progrès en microbiologie médicale et maladies infectieuses (FAMMID, Lausanne), ont été réalisées au sein du Service des Maladies Infectieuses, Département de Médecine, au CHUV, en étroite collaboration avec la Division de Pharmacologie Clinique, Département de Médecine, au CHUV et l'Institut de Microbiologie du CHUV et de l'Université de Lausanne.

Multiplex ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, anidulafungin, and caspofungin.

Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.

Surgical safety and hospital volume across a wide range of interventions

OBJECTIVES:: For certain major operations, inpatient mortality risk is lower in high-volume hospitals than those in low-volume hospitals. Extending the analysis to a broader range of interventions and outcomes is necessary before adopting policies based on minimum volume thresholds. METHODS:: Using the United States 2004 Nationwide Inpatient Sample, we assessed the effect of intervention-specific and overall hospital volume on surgical complications, potentially avoidable reoperations, and deaths across 1.4 million interventions in 353 hospitals. Outcome variations across hospitals were analyzed through a 3-level hierarchical logistic regression model (patients, surgical interventions, and hospitals), which took into account interventions on multiple organs, 144 intervention categories, and structural hospital characteristics. Discriminative performance and calibration were good. RESULTS:: Hospitals with more experience in a given intervention had similar reoperation rates but lower mortality and complication rates: odds ratio per volume deciles 0.93 and 0.97. However, the benefit was limited to heart surgery and a small number of other operations. Risks were higher for hospitals that performed more interventions overall: odds ratio per 1000 for each event was approximately 1.02. Even after adjustment for specific volume, mortality varied substantially across both high- and low-volume hospitals. CONCLUSION:: Although the link between specific volume and certain inpatient outcomes suggests that specialization might help improve surgical safety, the variable magnitude of this link and the heterogeneity of hospital effect do not support the systematic use of volume-based referrals. It may be more efficient to monitor risk-adjusted postoperative outcomes and to investigate facilities with worse than expected outcomes.

Capturing diagnosis-timing in ICD-coded hospital data: recommendations from the WHO ICD-11 topic advisory group on quality and safety.

PURPOSE: To develop a consensus opinion regarding capturing diagnosis-timing in coded hospital data. METHODS: As part of the World Health Organization International Classification of Diseases-11th Revision initiative, the Quality and Safety Topic Advisory Group is charged with enhancing the capture of quality and patient safety information in morbidity data sets. One such feature is a diagnosis-timing flag. The Group has undertaken a narrative literature review, scanned national experiences focusing on countries currently using timing flags, and held a series of meetings to derive formal recommendations regarding diagnosis-timing reporting. RESULTS: The completeness of diagnosis-timing reporting continues to improve with experience and use; studies indicate that it enhances risk-adjustment and may have a substantial impact on hospital performance estimates, especially for conditions/procedures that involve acutely ill patients. However, studies suggest that its reliability varies, is better for surgical than medical patients (kappa in hip fracture patients of 0.7-1.0 versus kappa in pneumonia of 0.2-0.6) and is dependent on coder training and setting. It may allow simpler and more precise specification of quality indicators. CONCLUSIONS: As the evidence indicates that a diagnosis-timing flag improves the ability of routinely collected, coded hospital data to support outcomes research and the development of quality and safety indicators, the Group recommends that a classification of 'arising after admission' (yes/no), with permitted designations of 'unknown or clinically undetermined', will facilitate coding while providing flexibility when there is uncertainty. Clear coding standards and guidelines with ongoing coder education will be necessary to ensure reliability of the diagnosis-timing flag.