Meta-analytic estimation of measurement variability and assessment of its impact on decision-making: the case of perioperative haemoglobin concentration monitoring

Abstract Background As a part of a larger Health Technology Assessment (HTA), the measurement error of a device used to monitor the hemoglobin concentration of a patient undergoing surgery, as well as its decision consequences, were to be estimated from published data. Methods A Bayesian hierarchical model of measurement error, allowing the meta-analytic estimation of both central and dispersion parameters (under the assumption of normality of measurement errors) is proposed and applied to published data; the resulting potential decision errors are deduced from this estimation. The same method is used to assess the impact of an initial calibration. Results The posterior distributions are summarized as mean ± sd (credible interval). The fitted model exhibits a modest mean expected error (0.24 ± 0.73 (−1.23 1.59) g/dL) and a large variability (mean absolute expected error 1.18 ± 0.92 (0.05 3.36) g/dL). The initial calibration modifies the bias (−0.20 ± 0.87 (−1.99 1.49) g/dL), but the variability remains almost as large (mean absolute expected error 1.05 ± 0.87 (0.04 3.21) g/dL). This entails a potential decision error (“false positive” or “false negative”) for about one patient out of seven. Conclusions The proposed hierarchical model allows the estimation of the variability from published aggregates, and allows the modeling of the consequences of this variability in terms of decision errors. For the device under assessment, these potential decision errors are clinically problematic

Two cases of lymphoepithelial cyst of the pancreas

A 35-year-old man was found to have a cystic mass in the pancreatic body on a routine health examination ; high serum CA19-9 was also detected. The enucleated cyst was diagnosed as a lymphoepithelial cyst (LEC). A 74-year-old man found to have a cystic mass in the pancreatic head by computer tomography as well as high serum CA19-9 was suspected of a cystic neoplasm of the pancreas (IPMN), and pylorus-preserving pancreaticoduodenectomy (PPPD) was performed. Pathologically, the cyst was found to be LEC. It is often difficult to diagnose pancreatic cyst as LEC preoperatively. Care should be taken not to do over-surgery for benign disease LEC

ANCA-negative pauci-immune renal vasculitis: histology and outcome

Background. Pauci-immune renal vasculitis with focal glomerular necrosis and crescent formation is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, ANCA's are absent in up to 10% of cases, which constitutes a rarely studied variant of renal vasculitis. Methods. This retrospective multicentre cohort study analyzed the presenting features, renal histology and outcome in 20 patients with pauci-immune crescentic necrotizing renal vasculitis in whom indirect immunofluorescence did not detect ANCA. Results. Renal histology revealed a high percentage of active glomerular lesions (50%), mainly cellular crescents, 28% of them with glomerular necrosis. Chronic tissue damage with glomerulosclerosis (21%) and diffuse interstitial fibrosis (40%) was already present at diagnosis, more prominent than in historical PR3-positive patients. Infiltrates of polymorphonuclear neutrophils in glomerular capillary loops were observed in 40% of all biopsies, mainly in necrotic lesions. The subsets of interstitially infiltrating leukocytes similar to ANCA-associated disease. Microscopic polyangiitis was diagnosed in 17 patients, Wegener's granulomatosis in two and renal-limited vasculitis in one. The patients median disease extent index (DEI) of 5 (range 4-11) reflected a systemic vasculitis. ANCA-negative vasculitis was not associated with infection or malignancy. Renal outcome was correlated to DEI (P = 0.032) and serum creatinine at diagnosis (P = 0.04). The mortality rate was high (35%) and closely related to age above 65 years at diagnosis (P = 0.014). Conclusions. The histological findings and prognosis in ANCA-negative renal vasculitis are comparable with those of ANCA-positive disease. Our data underline the importance of the exact diagnosis in an active vasculitic disease process even in the absence of ANCA

Les 100 médicaments essentiels. Une approche de médecine interne = 100 essential drugs. An internal medicine approach

Déclaration d'intérêts : B. Grosbois : expert pour Actélion, Celgene, Octapharma, Shire. Recherche subventionnée par LFB, Janssen, Genzyme. L. Guillevin : conseiller scientifique Actélion, expert pour (et conférences rémunérées par) GSK, CSL, Roche. L. Guillevin estime cependant n'avoir pas de conflit d'intérêt concernant le présent travail. C. Le Jeunne : expert pour Roche, Sanofi, Novartis, BSM, UCB. Essais thérapeutiques en cours pour Bayer, Pfizer, BMS. P. Morlat : expert pour Gilead, ViiV Health Care, BMS, Abbott, MSD. Ph. Morlat estime cependant n'avoir pas de conflit d'intérêt concernant le présent travail. P. Arlet, O. Aumaitre, J. Cosserat, A. Kettaneh, C. Massot et M. Thomas : aucun conflit d'intérêt.International audiencePURPOSE: Up to 4600 drugs in about 15,000 pharmaceutical forms are available in France which may be a source of misuse with increased occurrence of side effects and costs. While the World Health Organization is encouraging each developed country to work out its own list of essential drugs. The list provided in 2008 by the French Office for the safety of health products has had so far limited impact on practice, so it became obvious to a group of internists to work out a "wise list" of 100 essential medicines covering 95% of the disorders observed in France. METHODS: In June 2011, 10 internists agreed to each provide a list of 100 essential medicines, according to individual experience. In December 2011, a meeting of the participants provided a list as initial consensus and mandated five among them to make proposals for those areas neglected by too many participants or in which needless dispersion of medicines was stated. After internet-facilitated exchanges, an additional list was validated in mild-January 2012. RESULTS: Fifty-four drugs were included in the list of initial consensus (including nine selected by all 10 participants), and 46 in the additional list. So the final "wise list" included 100 drugs. In June 2012, 56 of these drugs were available as generics. This list was compared to those lists set out by five countries in the European Union. CONCLUSION: Generating such a list is feasible. Undoubtedly still non-comprehensive, this list will benefit from the expertise of 14 general practitioners who are currently working out a similar list across France. The final list will be submitted for validation by the French associations of generalist teachers and Internists

Protective effect of A/H1N1 vaccination in immune-mediated disease—a prospectively controlled vaccination study

Objectives. To assess the 2009 influenza vaccine A/H1N1 on antibody response, side effects and disease activity in patients with immune-mediated diseases. Methods. Patients with RA, SpA, vasculitis (VAS) or CTD (n = 149) and healthy individuals (n = 40) received a single dose of adjuvanted A/H1N1 influenza vaccine. Sera were obtained before vaccination, and 3 weeks, 6 weeks and 6 months thereafter. A/H1N1 antibody titres were measured by haemagglutination inhibition (HAI) assay. Seroprotection was defined as specific antibody titre ≥ 1 : 40, seroconversion as 4-fold increase in antibody titre. Results. Titres increased significantly in patients and controls with a maximum at Week 3, declining to levels below protection at Month 6 (P < 0.001). Seroprotection was more frequently reached in SpA and CTD than in RA and VAS (80 and 82% and 57 and 47%, respectively). There was a significantly negative impact by MTX (P < 0.001), rituximab (P = 0.0031) and abatacept (P = 0.045). Other DMARDs, glucocorticoids and TNF blockers did not significantly suppress response (P = 0.06, 0.11 and 0.81, respectively). A linear decline in response was noted in patients with increasing age (P < 0.001). Disease reactivation possibly related to vaccination was suspected in 8/149 patients. No prolonged side effects or A/H1N1 infections were noted. Conclusions. The results show that vaccination response is a function of disease type, intensity and character of medication and age. A single injection of adjuvanted influenza vaccine is sufficient to protect a high percentage of patients. Therefore, differential vaccination recommendations might in the future reduce costs and increase vaccination acceptanc

Usefulness of Tc-99m Sestamibi studies for monitoring response to therapy in patients with high grade gliomas: a preliminary study

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM).National audienceEarly and late Sestamibi studies were acquired in addition to conventional MRI protocol in 14 patients with high-grade gliomas to monitor an antiangiogenic treatment. Global and local indices were deduced from these SPECT studies and were compared with progression free survival (PFS) and overall survival (OS). Variations of intensity in late studies were not correlated with PFS, but were related to OS. This suggests the possible role of Sestamibi for monitoring response to treatment

Virus-induced Systemic Vasculitides: New Therapeutic Approaches

The best therapeutic strategy in virus-induced vasculitides should take into account the etiology of the disease and be adapted to the pathogenesis. The combination of antiviral treatments and plasma exchanges has been proven effective in polyarteritis nodosa (PAN). In human immunodeficiency virus (HIV)-related vasculitis this strategy is also effective and does not jeopardize, like cytotoxic agents, the outcome of AIDS. In vasculitis related to HCV-associated cryoglobulinemia, plasma exchanges improve the outcome but the poor effectiveness of antiviral drugs is not able to favor, usually, a definite recovery of the patients and relapses are frequent

When a collective outcome triggers a rare individual event: a mode of metastatic process in a cell population

A model of early metastatic process is based on the role of the protein PAI-1, which at high enough extracellular concentration promotes the transition of cancer cells to a state prone to migration. This transition is described at the single cell level as a bi-stable switch associated with a subcritical bifurcation. In a multilevel reaction-diffusion scenario, the microenvironment of the tumor is modified by the proliferating cell population so as to push the concentration of PAI-1 above the bifurcation threshold. The formulation in terms of partial differential equations fails to capture spatio-temporal heterogeneity. Cellular-automata and agent-based simulations of cell populations support the hypothesis that a randomly localized accumulation of PAI-1 can arise and trigger the escape of a few isolated cells. Far away from the primary tumor, these cells experience a reverse transition back to a proliferative state and could generate a secondary tumor. The proposed role of PAI-1 in controlling this metastatic cycle is candidate to explain its role in the progression of cancer