Clinical and economic impact of drug eluting beads in transarterial chemoembolization for hepatocellular carcinoma.

WHAT IS KNOWN AND OBJECTIVE: Drug eluting beads (DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2). METHODS: All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system and from the analytic accountability. RESULTS AND DISCUSSION: One hundred and sixty-one patients were included. Median time to treatment failure and overall survival were 13.1 and 23.8 months in Period 1 vs. 14.1 and 30.2 months in Period 2 (P = 0.45 and P = 0.40). Mean hospital durations and tariffs were 14.9 ± 7.7 days and € 11 472 ± 5901 in Period 1 vs. 12.4 ± 8.4 days and € 7654 ± 4625 in Period 2 (P = 0.03 and P < 10(-4) ). WHAT IS NEW AND CONCLUSION: The possibility of using DEBs did not improve the prognosis in HCC patients treated by TACE. Nonetheless, it had a better medico-economic profile.

Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia.

UNLABELLED: Concerns have recently emerged about the quality of generic vancomycin products. Our aim is to analyze serum vancomycin concentrations measured 48 hours after the start of an empirical treatment regimen in patients with acute myeloid leukemia (AML) who received one of the two generic vancomycin products available in France. PATIENTS AND METHODS: Seventy-nine AML patients treated with vancomycin during two study periods were included in the study. Our vancomycin dosing regimen was based on the patients' total body weight adjusted for renal clearance. RESULTS: A total of 93 serum vancomycin concentrations were collected: 31 in period 1 and 62 in period 2. In bivariate analysis, the mean serum vancomycin concentrations were not significantly different (19.9 ± 11.2 mg/L in period 1 vs 18.9 ± 6.0 mg/L in period 2, P=0.64). In the final generalized estimating equations model, serum vancomycin concentrations correlated statistically with a positive coefficient for age (P<0.001) and with negative coefficients for male sex (P=0.001) and hemoglobin level (P=0.021). CONCLUSION: Serum vancomycin concentrations measured 48 hours after the start of an empirical treatment were not influenced by the nature of the generic product but correlated with age, sex and hemoglobin level in AML patients.

[Economic impact of strategies using ephedrine prefilled syringes]. / Impact économique des stratégies de recours à l'éphédrine en seringues préremplies.

OBJECTIVES: Ephedrine is an emergency drug available in ampules and syringes need to be prepared in advance according to one of two strategies in our establishment: strategy 1 (S1: 1 ampule per patient) and strategy 2 (S2: 1 ampule per operating room). There are also prefilled syringes. Because of their high cost and conflicting results in the literature, we assessed the economic interest of using prefilled syringes compared with strategies S1 and S2. TYPE OF STUDY: This was a prospective observational study. PATIENTS AND METHODS: The consumption of ephedrine was recorded over two periods of 14 days: P1 with syringes prepared in advance according to S1 or S2 and P2 with the on-demand use of prefilled syringes. RESULTS: The cost of a syringe of ephedrine prepared in advance (nurse time preparation included) was evaluated at €1.65 vs. €3.57 for a prefilled syringe. In operating rooms using S1, the use of prefilled syringes reduced overall the cost per patient about €1.22 and global annual costs by 72% (€2830), while the decrease was about €0.32 for the cost per patient and about 47% (€2760) for global annual costs for operating rooms using S2. CONCLUSION: The interest of our study is that we investigated different supply strategies for ephedrine within a large number of operating rooms. In our establishment, it was decided to use prefilled syringes in operating rooms that used S1. As well as the economic interest, prefilled syringes contributed to improved safety and saved nursing time.

Result and cost of hepatic chemoembolisation with drug eluting beads in 21 patients.

PURPOSE: The aim of our study was to assess the results and cost of a treatment strategy involving transarterial chemoembolisation with drug eluting beads (DEB-TACE) in patients with unresectable non-metastatic hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study included all patients treated with DEB-TACE in our hospital between January 2009 and December 2010. All patients received DEB-TACE on demand and were evaluated after each session. RESULTS: Twenty-one patients received an average of 1.3 sessions. The median time to treatment discontinuation and median progression-free survival was 181 days and 295 days, respectively. Toxicity caused treatment discontinuation in three patients (14%). For the hospital, the average direct cost of treatment was €6,033 according to the analytical accounting system vs. €4,558 according to the official tariffs from the new French Diagnosis-Related Group prospective payment system (P=0.002). CONCLUSION: In the treatment of HCC, on-demand DEB-TACE stabilises the disease in some patients but has not yet been thoroughly evaluated.

The P2-Na(2/3)Co(2/3)Mn(1/3)O2 phase: structure, physical properties and electrochemical behavior as positive electrode in sodium battery.

Manganese substituted sodium cobaltate, Na(2/3)Co(2/3)Mn(1/3)O(2), with a layered hexagonal structure (P2-type) was obtained by a co-precipitation method followed by a heat treatment at 950 °C. Powder X-ray diffraction analysis revealed that the phase is pure in the absence of long-range ordering of Co and Mn ions in the slab or Na(+) and vacancy in the interslab space. The oxidation states of the transition metal ions were studied by magnetic susceptibility measurements, electron paramagnetic resonance (ESR) and (23)Na magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. The charge compensation is achieved by the stabilization of low-spin Co(3+) and Mn(4+) ions. The capability of Na(2/3)Co(2/3)Mn(1/3)O(2) to intercalate and deintercalate Na(+) reversibly was tested in electrochemical sodium cells. It appears that the P2 structure is maintained during cycling, the cell parameter evolution versus the sodium amount is given. From the features of the cycling curve the formation of an ordered phase for the Na(0.5)Co(2/3)Mn(1/3)O(2) composition is expected.

[Impact of the angles and the age of the thrombus on efficacity of thromboaspiration device. A bench study]. / Impact du diamètre et de l'âge du thrombus sur la thromboaspiration. Étude expérimentale.

INTRODUCTION: Coronary thrombectomy is usually used to treat acute coronary syndrome. Many studies evaluated its benefit in this context however, it is still unknown if coronary characteristics are predictive of success or failure. The aim of our laboratory bench study was to evaluate the impact of angiographic characteristics on the thromboaspiration efficiency. METHODS: Glass tubes of 150 mm in the length were used, with five diameters: 2; 2.6; 3; 3.6 and 4 mm; and for each diameter, three angulations: no angulation; 90° and 120°. Blood sample were taken from healthy subject and thrombi of 3 and 6 hours old were performed, with a constant volume for each test. Thromboaspirations were performed with an Export(®) catheter (Medtronic). The primary endpoint was total thrombectomy. A total of 240 thromboaspirations were performed. RESULTS: A total thrombectomy was obtained for 71.2% of the tests. It was achieved more frequently with the smaller diameter, respectively: 100% for 2 mm, 81.3% for 2.6 mm, 89.6% for 3 mm vs 54.2% for 3.6 mm and 31.3% for 4 mm (P<0.001). No differences were observed between the 2 thrombi ages (73.3% for the 3 hours old thrombi and 69.2% for the 6 hours old thrombi, P = 0.476), nor between the three tube's angulations (77.5% for no angle, 66.3% for 90° and 70.0% for 120°, P = 0.278). RESULTS AND CONCLUSION: This study shows an impact of the coronary diameters on the rate of thromboaspiration success with an Export(®) catheter. Beyond 3 mm of diameter, the rate of success is divided by 2: for diameters less or equal to 3 mm, 90.3% of success vs 42.7% for diameters greater than 3 mm (P<0.001). There is no difference of efficiency between the 3 and 6 hours old thrombi, neither between the tube's angulations. However, this is a preliminary and further works are needed to clarify how to optimize the aspiration and the impact of other catheters.

Second-harmonic generation of thermally poled chalcogenide glass.

Second harmonic generation (SHG) has been obtained in a sample of Ga5Ge20Sb10S65 glass submitted to a thermal poling treatment. An original characterization method is used for the determination of the induced second-order nonlinear profile. A reproducible chi(2) susceptibility of 4.4 +/- 0.4 pm/Volt was achieved for specific poling conditions.

New oral formulation of cyclosporin A (Neoral) pharmacokinetics in allogeneic bone marrow transplant recipients.

Cyclosporin A (CsA) absorption is variable in bone marrow transplant (BMT) patients compromising the efficacy of graft-versus-host disease prevention. Neoral, a new microemulsion formulation of CsA which has an improved bioavailability, increases intestinal absorption of the drug with less variable pharmacokinetic parameters in non-BMT patients. In order to predict the best dosage of Neoral when patients are switched from i.v. to oral administration we performed a randomised study comparing two oral doses, either the same or twice the last i.v. dose used after BMT. Fourteen adults were randomised around day 25 after BMT. Whole blood CSA concentrations were measured 2 and 12 h after the oral administration of Neoral on days 0, 7 and 14 to determine residual and maximum concentration, and modified whenever necessary to maintain blood level CsA concentration within therapeutic range (150-250 ng/ml). We found that patients who received twice the last i.v. dose had better concentrations than patients from the other group while toxicity was identical in both groups. We conclude that doubling the last i.v. dose during the switch to oral administration of Neoral gives the best therapeutic range concentration and should be recommended for graft-versus-host prevention.

[Relation between plasma renin level and antihypertensive response to nicardipine]. / Relation entre la concentration de la rénine plasmatique et la réponse antihypertensive à la nicardipine.

The antihypertensive efficacy of calcium antagonists could depend on the concentration of circulating renin. To investigate this hypothesis, 102 hypertensive men or women were included in this study. After an initial 2 week placebo period, the patients were administered slow-release nicardipine, 50 mg twice a day for twelve weeks. The blood pressures were measured with a mercury sphygmomanometer at inclusion (S2) and after 12 weeks of treatment (S14), in addition to home automeasure during the week before inclusion and the two weeks preceding the final visit. The plasma renin activity (RA) was measured at S2 and S14. Its value at inclusion was used to differentiate patients with low renin (< or = 11 ng/l) from those with normal (> 11 < or = 17 ng/l) or high renin activity (> 17 ng/l). The blood pressure measured by sphygmomanometer or automeasure was significantly lower at the end of the active treatment period (SBP: -8 mmHg; DBP: -9.5 mmHg; and SBP: -5.8 mmHg; DBP: -5.7 mmHg respectively); the reduction in blood pressure was significantly higher in the group with low RA than in the group with high RA. The reductions in SBP measured in the morning and evening and in DBP measured in the morning were significantly greater in the group with low RA than in the group with high RA. The reduction of SBP measured in the morning at midday, and in the evening was correlated to the basal value of RA. Mild side effects were observed in 20 patients leading to the interruption of treatment in 11 cases because of headache. The best antihypertensive response is observed in patients with low plasma RA. This could explain the good response to calcium antagonists usually observed in elderly hypertensives.

Bone loss during gonadotropin releasing hormone agonist treatment and use of nasal calcitonin.

Gonadotropin releasing hormone (GnRH) agonists have shown to be effective in the treatment of several sex-hormone-dependent conditions. However, their use could be limited by the bone loss they induce. To evaluate the use of nasal salmon calcitonin (sCT) in preventing this bone loss, 40 patients with endometriosis were treated for 6 months with triptoreline (3.75 mg monthly) and calcium (1 g daily), and randomized in three groups-placebo, sCT 100 IU daily and sCT 200 IU daily-in a prospective double-masked study. Dual-energy X-ray absorptiometry and biochemical parameters were used to evaluate the benefit of the treatment. At baseline, there were no statistically significant differences between the groups. After 6 months, estradiol and biochemical markers of bone metabolism were at postmenopausal levels, with no difference between the groups. There was no difference in bone loss in the three groups, at all sites. Mean lumbar bone loss was 4.01 +/- 2.59% (mean +/- SD) in this population. In this study dosages of 100 IU and 200 IU daily of nasal sCT were insufficient to prevent bone loss during GnRH agonist treatment.

[Efficacy and tolerance of LA 50 mg nicardipine in hypertensive athletes]. / Efficacité et tolérance de la nicardipine LP 50 mg dans l'hypertension artérielle du sportif.

The beneficial effects of physical exercise on the blood pressure are widely recognised. Nevertheless, some athletes remain hypertensive and the treatment of this population makes special demands with respect to treatment efficacy and tolerability, the respect of athletic performance and problems of proscribed substances. For example, the Athletic Boards have prohibited betablockers and diuretics in competitive athletes. The aim of this study was to assess nicardipine LA 50 mg administered twice daily in the special context of hypertensive athletes. Thirty-eight athletes with mild or moderate hypertension undergoing endurance training were included in this double blind trial versus placebo. After two months treatment, the systolic and diastolic blood pressures were significantly lower at rest in the nicardipine than in the placebo group (delta SBP = -18.9 vs -4.1 mmHg, p less than 0.001; delta DBP = -15.7 vs -4.1 mmHg, p less than 0.01). In addition the maximum SBP on effort was significantly lower in the nicardipine group (200 vs 215 mmHg, p less than 0.05). On the other hand, no difference was observed between the two groups as regards the maximum oxygen consumption (delta VO2 max = 6.2 vs -0.4 ml/min/kg, NS) and duration of effort (13.75 vs 12.32 min, NS), showing that athletic performance was unchanged in the group treated by nicardipine LA. These results suggest that treatment with nicardipine LA fulfills the special criteria of hypertensive athletes.

Improvement of human ovulatory cervical mucus by alpha-amylase. Effect on spinability and crystallization in vitro.

Alpha-amylase can modify ovulatory cervical mucus in vitro, changing both its structure and an essential rheological parameter, spinability. After 5 min at alpha-amylase concentrations above 4.6 mg/ml, spinability was greatly reduced or even non-existent because of the total liquefaction of the mucus. These concentration levels also induced breakdown of the solid phase of the hydrogel, producing more or less marked abnormalities in mucus crystallization after air drying. In the presence of the highest alpha-amylase concentrations (greater than or equal to 37.5 mg/ml) dendrites could not be formed and only sodium chloride crystals were visible at high magnification under a scanning electron microscope. In the 75 to 1.2 mg/ml concentration range, where alpha-amylase has a significant action on cervical mucus, there was an overall decrease in average spinability as the enzyme concentration fell. The action of the enzyme was greater after 10 min than after 5 min reaction time. For the 10-min reaction time interval, the activity could be adjusted using a squared polynominal regression, whereas for the 5-min reaction time interval a linear regression was a suitable model of enzymatic activity. In the 4.6 to 1.2-mg/ml concentration range, adjustment on a linear model showed that there was a significant effect of alpha-amylase concentration and reaction time on mucus spinability. Statistical analysis of the dose-effect data was compatible with the structural changes in dried cervical mucus demonstrated by scanning electron microscopy.

Circadian rhythms in plasma levels of cortisol, dehydroepiandrosterone, delta 4-androstenedione, testosterone and dihydrotestosterone of healthy young men.

Three healthy males (18, 22 and 30 years of age; 85 kg/177 cm, 82 kg/181 cm and 75 kg/168 cm, respectively), synchronized with a diurnal activity (06.00 to 23.00 h) and nocturnal rest, volunteered for this study. Blood was sampled (venous catheter) hourly during a 24 h span. A radiocompetition method was used for cortisol determinations. Other steroids were first extracted (ethyl-ether) from each plasma sample, then chromatographed on a celite column to isolate 3 fractions: 1) delta 4-androstenedione (delta-4); 2) dihydrotestosterone (DHT) and dehydroepiandrosterone (DHA); 3) testosterone (T). A radioimmunological assay was used thereafter for the determination of androgenic steroids. Statistically significant (both conventional and cosinor methods) circadian rhythms were detected (P > 0.005). Acrophases (peak times) occurred in the following order: cortisol (07.28), DHA (08.43), delta-4 (09.54), T (11.15) and DHT (16.37). The respective circadian amplitudes of DHA and delta-4 were smaller than those of cortisol while the amplitudes T and DHT did not show differences statistically significant from each other.

Plasma variations in testicular and adrenal androgens during prolonged physical exercise in man.

The evolution of the relationship between cortisol and testicular androgens was verified on two teams of respectively 10 and 9 male subjects (average age 34) running 100 km races in an average time of 14 hours. When compared to a control population of the same age, these trained athletes exhibited reduced testicular androgen levels (T and DHT) and increased adrenal androgen (delta 4) and cortisol levels with no significant alteration of LH. The period of recovery is characterized by rapid return to normal of the hormonal parameters whereas testosterone levels continue to increase in the following days. This hormonal picture, which reappears under certain pathological situations or when subjects are exposed to heavy stresses, seems to prove that the testicular androgens could be, both by their metabolic and psychic action, one of the limiting factors of physical aptitude to sustained effort.

[Production of antihaptene antisera. Comparison of methods of immunisation (author's transl)]. / Production d'antisérums anti-haptènes. Comparaison de modes d'immunisation

Five immunogenic substances were injected to rabbits. The method of immunisation by the intradermal route at 30 to 50 different points, with low doses of immunogen, without booster, does not seem to lead to production of antiserum of great specificity. The choice of the dose of immunogen to be injected is difficult, owing to our ignorance of the immunogenic dose for a given immunogen. The method of immunisation by the subcutaneous route with high doses followed by a booster, leads to more constant results, comparable to those obtained by the first method to which one may associate boosters by the subcutaneous route. The titers, affinities and specificities of the antisera thus produced are sufficient for the development of radio-immunoassay. The characteristics of the antisera obtained, related to the quality of the immunogen, do not seem to depend on the method of immunisation.