Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis with multiple organ failure

OBJECTIVES: The aim of this study was to estimate the expected cost and clinical benefits associated with the use of drotrecogin alfa (activated) (Xigris; Eli Lilly and Company; Indianapolis, IN) in the French hospital setting. METHODS: The recombinant human activated PROtein C Worldwide Evaluation in Severe Sepsis (PROWESS) study results (1271 patients with multiple organ failure) were adjusted to 9,948 hospital stays from a database of Parisian area intensive-care units (ICUs)-the CubRea (Intensive Care Database User Group) database. The analysis features a decision tree with a probabilistic sensitivity analysis. RESULTS: The cost per life year gained (LYG) of drotrecogin treatment for severe sepsis with multiple organ failure (European indication) was estimated to be dollars 11,812. At the hospital level, the drug is expected to induce an additional cost of dollars 7545 per treated patient. The incremental cost-effectiveness ratio ranges from dollars 7873 per LYG for patients receiving three organ supports during ICU stay to dollars 17,704 per LYG for patients receiving less than two organ supports. CONCLUSIONS: Drotrecogin alfa (activated) is cost-effective in the treatment of severe sepsis with multiple organ failure when added to best standard care. The cost-effectiveness of the drug increases with baseline disease severity, but it remains cost-effective for all patients when used in compliance with the European approved indication.     

A study of interlaboratory influence on column evaluation

A liquid chromatography method for the characterization of base deactivated columns was investigated in a collaborative study involving six laboratories. This work was carried out on two chromatographic supports (Xterra RP 18 and Symmetry Shield). Different cooling systems, namely water bath and air oven, were tested and it was shown that column thermoregulation did not significantly influence chromatographic data. In order to control the mobile phase composition, the latter was prepared by weight rather than volume. Thanks to the injection of a set of selected neutral compounds, extra-column effects were evaluated in each of the participating laboratories. The results showed that chromatographic supports tested in different laboratories and following the same test protocol could be effectively compared.     

Clinical, electrophysiological and molecular genetic studies in a family with X-linked dominant Charcot-Marie-Tooth neuropathy presenting a novel mutation in GJB1 Promoter and a rare polymorphism in LITAF/SIMPLE

Charcot-Marie-Tooth disease is a genetically heterogeneous group of neuropathies. In the demyelinating form of Charcot-Marie-Tooth disease with dominant inheritance, five genes have been incriminated: PMP22, MPZ, LITAF/SIMPLE, EGR2 (CMT1A to D), and GJB1 (CMTX). Here, we report clinical, electrophysiological and molecular genetic studies in a family with a Charcot-Marie-Tooth disease variable phenotype, ranging from asymptomatic to moderately affected. The absence of male-to-male transmission as well as the results of systematic electrophysiological studies suggested a CMTX secondary to a GJB1 mutation. Screening for mutations in the coding regions of PMP22, MPZ, EGR2 and GJB1 was negative. We identified (1) a LITAF/SIMPLE substitution (T49M), absent in 1000 control chromosomes, but which was thought to be a polymorphism because of discrepancies of segregation when considering the results of electrophysiology; and (2) a novel substitution T>C in the P2 promoter of GJB1 at position -529, in the SOX10 binding site S2. The transmission of this second mutation was consistent with the electrophysiological data. We emphasise the role of electrophysiological studies that help to discriminate between asymptomatic subjects and that bring some additional valuable data to the genetic approach.     

Familial Creutzfeldt-Jakob disease with an R208H-129V haplotype and Kuru plaques

OBJECTIVE: To report the clinical and neuropathological features in the first patient seen, to our knowledge, with familial Creutzfeldt-Jakob disease and an R208H mutation associated with a Val/Val homozygosity at codon 129 in the prion protein gene (PRNP) and a type 2 protease-resistant prion protein. PATIENT AND RESULTS: A 61-year-old man with a long-standing history of memory loss and emotional disorders had an obvious behavioral change. Then he developed cerebellar ataxia, followed by cognitive decline. He had no myoclonus. Electroencephalography showed slow activity, and 14-3-3 protein detection was negative. Finally, the patient developed akinetic mutism and died 7 months after the onset of ataxia. Neuropathological examination showed severe spongiform changes in the frontal cortex and striatum and gliosis in the striatum and thalamus. Kuru plaques were noted in the cerebellum, notably in the molecular layer. Immunohistochemical findings showed granular, synaptic, perineuronal, and perivacuolar staining with antiprion antibodies. Kuru plaques were also stained. CONCLUSION: This study strengthens the linkage of the R208H mutation to Creutzfeldt-Jakob disease and points to some particular features such as Kuru plaques and long-standing psychiatric signs.     

Non-specific regulation of immune responsiveness to a thymus-independent antigen, TNP-LPS, in high and low responder lines of mice

Responsiveness to a thymus-independent (TI-1) antigen, TNP-LPS, was investigated in the high and low responder lines of mice resulting from four independent selective breedings carried out for antibody production to various complex natural immunogens (selections I, III, IV and V). The superiority of the high responder vs. the low responder line was generally observed, confirming that the genes accumulated through selective breeding can modify the responsiveness to unrelated antigens including TI antigens. Two special features were observed in selection III: (1) A secondary response to TNP-LPS: higher peak values and IgG isotype antibody production were obtained in the H line. (2) Pretreatment with LPS modified the responses to TNP in the L line only.     

Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial

Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve fibromyalgia symptoms, but the level of evidence is still poor. This study is a randomized, controlled, double-blind trial in fibromyalgia patients that compared once a day oral magnesium 100 mg (Chronomag^®, magnesium chloride technology formula) to placebo, for 1 month. The primary endpoint was the level of stress on the DASS-42 scale, and secondary endpoints were pain, sleep, quality of life, fatigue, catastrophism, social vulnerability, and magnesium blood concentrations. After 1 month of treatment, the DASS-42 score decreased in the magnesium and placebo groups but not significantly (21.8 ± 9.6 vs. 21.6 ± 10.8, respectively, p = 0.930). Magnesium supplementation significantly reduced the mild/moderate stress subgroup (DASS-42 stress score: 22.1 ± 2.8 to 12.3 ± 7.0 in magnesium vs. 21.9 ± 11.9 to 22.9 ± 11.9 in placebo, p = 0.003). Pain severity diminished significantly (p = 0.029) with magnesium while the other parameters were not significantly different between both groups. These findings show, for the first time, that magnesium improves mild/moderate stress and reduces the pain experience in fibromyalgia patients. This suggests that daily magnesium could be a useful treatment to improve the burden of disease of fibromyalgia patients and calls for a larger clinical trial.