Reduction of the use of antimicrobial drugs following the rapid detection of Streptococcus agalactiae in the vagina at delivery by real-time PCR assay.

OBJECTIVE: To assess whether the determination of the presence of group B streptococci (GBS) in the vagina using a rapid polymerase chain reaction (PCR) assay at delivery was able to spare useless antimicrobial treatments, as compared with conventional culture at 34-38 weeks of gestation. DESIGN: Practical evaluation and prospective cost-effectiveness analysis. SETTING: A university hospital in France. POPULATION: A cohort of 225 women in labour at the University-Hospital of Saint-Etienne. METHODS: Each woman had a conventional culture performed at 34-38 weeks of gestation. At the beginning of labour, two vaginal swabs were sampled for rapid PCR testing and culture. The decision to prescribe a prophylactic antimicrobial treatment or not was taken according to the result of the PCR test. A comparative cost-effectiveness analysis of the two diagnostic strategies was carried out. MAIN OUTCOME MEASURES: Number of women receiving inadequate prophylactic antimicrobial drugs following each testing strategy, costs of PCR testing and culture, frequency of vaginal GBS, and diagnostic performance of the PCR test at delivery. RESULTS: The percentage of unnecessarily treated women was significantly reduced using the rapid test versus conventional culture (4.5 and 13.6%, respectively; P < 0.001). The rate of vaginal GBS at delivery was 12.5%. The incremental cost-effectiveness ratio (ICER) for each inadequate management avoided was €36 and €173 from the point of view of the healthcare system and hospital, respectively. CONCLUSIONS: The PCR assay reduced the number of inadequate antimicrobial treatments aimed to prevent the early onset of GBS disease. However, this strategy generates extra costs that must be put into balance with its clinical benefits.

Cost-effectiveness of adjuvant docetaxel for node-positive breast cancer patients: results of the PACS 01 economic study.

BACKGROUND: Using data from the PACS 01 randomized trial, we evaluated the cost-effectiveness of anthracyclines plus docetaxel (Taxotere; FEC-D) versus anthracyclines alone (FEC100) in patients with node-positive breast cancer. PATIENTS AND METHODS: Costs and outcomes were assessed in 1996 patients and the incremental cost-effectiveness ratios (ICERs) were estimated, using quality-adjusted life years (QALYs) as outcome. To deal with uncertainty due to sampling fluctuations, confidence regions around the ICERs were calculated and cost-effectiveness acceptability curves were drawn up. Sensitivity analyses were also carried out to assess the robustness of conclusions. RESULTS: The mean cost of treatment was 33% higher with strategy FEC-D, but this difference decreased to 18% at a 5-year horizon. The ICER of FEC-D versus FEC100 was estimated to be 9665euro per QALY gained (95% confidence interval euro2372-euro55 515). The estimated probability that FEC-D was cost-effective reached >96% for a threshold of euro50 000 per QALY gained. If the price of taxane decreased slightly, the ICER would reach some very reasonable levels and this strategy would therefore be much more cost-effective. CONCLUSION: The sequential use of FEC100 followed by docetaxel appears to be a cost-effective alternative, even when uncertainty is taken into account.

Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908.

BACKGROUND: The present article reports the updated survival outcome of the 200 patients enrolled in the Southern Italy Cooperative Oncology Group 9908 trial, which compared 12 weekly cycles of cisplatin-epirubicin-paclitaxel (PET) with 4 triweekly (once every 3 weeks) cycles of epirubicin-paclitaxel (ET) in patients with locally advanced breast cancer (LABC). METHODS: The effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed. RESULTS: At a median follow-up of 74 (range 48-105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour. CONCLUSIONS: The PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.

Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer.

BACKGROUND: Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with triple-negative large operable breast cancer after the administration of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles. The safety and efficacy data of the initial population were updated, with inclusion of additional experience with the same therapy. METHODS: Patients with triple-negative large operable breast cancer (T2-T3 N0-1; T > 3 cm) received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel (Taxol) 120 mg/m2, with granulocyte colony-stimulating factor (5 microg/kg days 3-5) support. RESULTS: Overall 74 consecutive patients (T2/T3 = 35/39; N0/N+ = 26/48) were treated, from May 1999 to May 2008. At pathological assessment, 46 women (62%; 95% confidence interval 50-73) showed pCR in both breast and axilla. At a 41-month median follow-up (range 3-119), 13 events (nine distant metastases) had occurred, 5-year projected disease-free survival (DFS) and distant disease-free survival being 76% and 84%, respectively. Five-year DFS was 90% and 56% in pCRs and non-pCRs, respectively. Severe neutropenia and anemia occurred in 23 (31%) and eight (10.8%) patients, respectively. Severe non-hematological toxicity was recorded in <20% of patients. Peripheral neuropathy was quite frequent but never severe. CONCLUSIONS: Eight weekly PET cycles are a highly effective primary treatment in women with triple-negative large operable breast cancer. This approach results in a very promising long-term DFS in this poor prognosis population. This triplet regimen is worthy of evaluation in phase III trials.

Diurnal beta-endorphin changes in human cerebrospinal fluid.

Plasma and cerebrospinal fluid (CSF) beta-endorphin levels were determined by a RIA method in seven hydrocephalic male patients. The samples were simultaneously collected every two hours from 8 AM to 12 midnight and every hour from 1 AM to 7 AM. In both plasma and CSF beta-endorphin levels showed significant time-related variations during the 24 hour period. These results suggest the existence of diurnal CSF beta-endorphin variations analogous to those observed in plasma.

Variations of prolactin content in human cerebrospinal fluid after metoclopramide and morphine.

Serum and cerebrospinal fluid (CSF) prolactin (PRL) concentrations were determined in fourteen patients of both sexes suffering from hydrocephalus, in basal conditions and after i.m. administration of 10 mg metoclopramide or 10 mg morphine. A significant increase in both serum and CSF hormone values was found after administration of both drugs. Serum and CSF PRL values after metoclopramide administration increased earlier and to a greater extent than after morphine. Furthermore, the metoclopramide induced CSF PRL increase immediately followed the serum peak, whereas after morphine administration an evident delay in the CSF hormone peak with respect to the serum increase was found. These data suggest that PRL entry in the CSF compartment is subject to a controlling mechanism which acts at the blood/brain barrier.

Changes of CSF prolactin induced by metoclopramide in man.

A sharp increase in serum and CSF prolactin (PRL) values after acute metoclopramide (10 mg i.m.) administration was found in six male patients without endocrine diseases. Peak values occurred simultaneously in serum and in CSF. This finding suggests the possibility that CSF PRL content depends also on the retrograde transport from pituitary gland.

Portal vein pressure and graft oxygen consumption monitoring during liver transplantation.

UNLABELLED: Abnormal splanchnic circulation (ASC) is often detected too late, when hepatic circulation is already irreversibly compromised. If we could detect surgical or metabolic problems early after graft reperfusion, we might be able to correct them immediately before the damage becomes irreversible. The aim of this study was to determine if ASC can be predicted early after liver transplantation (LT) using portal vein pressure measurements and graft oxygen consumption monitoring. PATIENTS AND METHODS: Twenty-patients (13 men, 7 women of mean age 46 years) undergoing LT with the piggyback technique for hepatitis C virus (HCV)/hepatitis B virus (HBV)-related cirrhosis were retrospectively divided in two groups. Group A (16 patients), in which LT was successful, and group B (4 patients) in which LT was unsuccessful because of primary nonfunction (2 patients), infrahepatic portal vein thrombosis (1 patient), or hepatic vein kinking (1 patient). We then compared the portal blood pressure values and the prehepatic and posthepatic oxygen content difference (p-pDO(2)) before portal clamping; at the end of anhepatic phase; 5, 15, and 25 minutes after portal vein (PV) reperfusion; and 5, 20, 40, and 100 minutes after hepatic artery anastomosis. RESULTS: Early after graft reperfusion; portal pressure decreased to levels lower than that at baseline in group A, but remained high until the end of surgery in group B. At the end of surgery, p-pDO(2) increased more among group B than group A. CONCLUSION: ASC, specifically an increased PV resistance, can be predicted early after LT by portal vein pressure measurements and graft oxygen consumption monitoring.

Modifications of cerebral vascular resistance and autoregulation after graft reperfusion during human orthotopic liver transplantation.

We have studied cerebral blood flow velocity (CBFV) and cerebral autoregulation (CA) in 23 orthotopic liver transplantation (OLT) patients using transcranial doppler. CBFV was continuously recorded using a fixed (helmet) 2-Mz probe through the trans-temporal window. CA changes were studied using a linear regression analysis of percentile changes in CBFV and mean arterial blood pressure (MABP) after phenylephrine infusion compared with baseline. Pearson's "r" coefficient was considered an index of CA. In case of autoregulation is lost "r" tends to 1, thus representing complete dependence of CBFV on MABP. We regarded the slope coefficient parameter "S" as an index of cerebral vascular resistance (CVR), namely, the ratio of the corresponding variations of CBFV to MABP. Wilcoxon test showed a significant increase in both "r" and "S" between the anhepatic versus postreperfusion phases (within the first hour) and versus recovery in the neohepatic phase (end of surgery). A decreased CVR was observed within the first hour after graft reperfusion producing a loss of CA. These phenomena lead to an increase of CBFV and exposed the brain to hyperperfusion.

[The handling of uncertainty in economic evaluations of health care strategies]. / Le traitement de l'incertitude dans les évaluations économiques de stratégies sanitaires.

BACKGROUND: The recent development of prospective economic evaluations in association with randomized controlled clinical trials has provided clinical and economic data allowing a statistical analysis of uncertainty. Pertinent comparison of alternative medical strategies in the cost-effectiveness analysis requires analysis of the incremental cost-effectiveness ratio. In this work, we were interested in developing confidence regions of the cost-effectiveness ratio in order to take into consideration its uncertainty which creates a certain number of problems when the denominator approaches zero. Our objectives were to conduct a critical analysis of the different estimations used and examine their application in the decision making process. METHODS: There are two kinds of methods: those based on the density of the estimated ratio (Taylor method, parametric and non-parametric bootstrap methods such as percentile, percentile-t and bias-corrected and accelerated methods) and those based on the bivariate density of the variable pair: difference of average costs, difference of average effects (box method, ellipse method, and Fieller method). RESULTS: We showed that methods based on the density of the ratio become unstable and inapplicable when the statistical difference of average effects tends towards zero. In practice however, data often take on such a pattern. We give an example of an economic evaluation as an illustration. Bivariate density methods do not have this drawback. Moreover, the "mirror decision" phenomenon requires that the region of confidence be a directed single confidence sector for valid decision making. CONCLUSIONS: Uncertainty must be taken into account for all economic evaluations but the use of undirected confidence regions is inappropriate as a decision-making tool.

[Surgical treatment in day surgery of uncertain breast lesions]. / La terapia chirurgica in day surgery di lesioni mammarie dubbie.

AIM: New models of care are proposed to reduce the costs of traditional hospitalization and to improve the utilization of resources in surgery. Day surgery is widely employed in breast surgery. In this study we report the conversion rate and causes in ordinary hospitalization and we identify some contraindications related to breast surgery in day surgery. METHODS: A cohort study was performed on 306 patients operated on between July 1999 and December 2001 for breast lesions with uncertain interpretation at the clinical and/or instrumental examination. Those patients who lived at a distance of less than 50 km from the hospital, had a telephone, a suitable house, direct family support and, if necessary, could benefit from home health care in addition to hospitalization, were considered as eligible to day surgery. The kind of anesthesia and hospital admission were established after clinical, psycho-emotional, and socio-familiar evaluation of the patients by the surgeon and the anesthetist. RESULTS: A total of 250 excisional biopsies and 56 biopsies with a Mammotome were performed. Surgery was performed under local anesthesia in 278 patients and general anesthesia in 28 subjects. Observation exceeding 24 hours was only necessary in 10 patients reporting hypotension syndrome and anxiety. The conversion rate in ordinary hospitalization was 0.3%. Postoperative morbidity was 1%. CONCLUSION: Day surgery is an effective model of care in breast surgery for diagnostic and therapeutic purposes without axillary dissection. A good selection of patients, perfect interdisciplinary collaboration, and an efficient structural organization are necessary to control the complication and conversion rates of traditional hospitalization.

Electromanometric confirmation of needle position in haemopericardium with severe tamponade.

Simultaneous recording of the electrocardiogram and of the pressure transmitted through the drainage needle in patients with haemopericardium provided confirmation that the needle tip was in the pericardial cavity. Proper position was indicated by a positive pressure wave beginning before the QRS complex, reaching its maximum value in the first part of the ST segment and ending with the T wave. In contrast, ventricular penetration was signalled by a positive pressure wave beginning in the first part of the QRS complex, reaching its maximum during the T wave and ending between the T and P waves.

[Effects of the intravenous infusion of althesin on intracranial pressure and related functions]. / Effetti dell'infusione endovenosa di Althesin sulla pressione intracranica e su alcune funzioni correlate.

30-60 min after the i.m. administration of 0.5 mg atropine sulphate, 9 adult conscious neurosurgical patients on spontaneous ventilation were given a total of 12 i.v. infusions of Althesin at a rate of 0,25-0,60 ml/kg/h able to induce stable clinical and EEG levels of anaesthesia. PICm, PAm and PVCm respectively decreased in all, in ten and in six administrations. The PAm decreased below 60 mmHg in only one case, in another there was no change and in another still it increased in a stable manner. In all cases PICm, PAm and PVCm decreased by a mean of 3.88 +/- 1.22 (P < 0,05), 20,76 +/- 17,44 (P < 0,05) and 0,90 +/- 1,50 mmHg. The paCO2 generally increased and, in only one case, did it induce an intracranial hypertensive reaction; the paO2 was frequently reduced. The interruption in the infusion was followed by the regression of all effects. This appened for the PICm and PAm without dangerous rebound effects. The clinical use of Althesin in neurosurgical patients is discussed with regards to problems of anaesthesia and intensive care.

[Effects of an intravenous bolus of althesin on intracranial pressure and related functions]. / Effetti dell'althesin in bolo endovenoso sulla pressione intracranica e su alcune funzioni correlate.

30-40 min after i.m. administration of 0.5 mg atropine sulphate, 8 adult conscious neurosurgical patients on spontaneous ventilation were given a total of 10 rapid i.v. injections of Althesin at a dosage of 40-50 (45.5 +/- 4.33 as a mean) microliter/kg. Method was able to induce clinical and EEG signs of deep anaesthesia. PICm and PAm decreased in all cases by 6.82 +/- 3.91 (P < 0,05) and 20.18 +/- 9.30 mmHg respectively; PVCm decreased in only half of the cases. The intracranial hypotensive effect was positively correlated to the basal PICm (P < 0.05) and resulted proportionately more marked in cases with greater signs of EEG depression. The PAm never decreased below 60 mmHg. The paCO2 was generally increased and the paO2 was always decreased. The intracranial hypotensive effects regressed 12-23 min after the injection without dangerous rebound effects; recovery of the PAm was slower. The use of Althesin in the anaesthesia and in the intensive care of neurosurgical patients is discussed.

Metoclopramide increases plasma but not cerebrospinal fluid vasopressin levels in man: study in hydrocephalic patients.

Arginine vasopressin (AVP) concentrations were determined in plasma and in cerebrospinal fluid (CSF) in 8 adult male patients suffering from hydrocephalus of various etiologies, before and after intravenous administration of 10 mg metoclopramide. Metoclopramide was able to increase the plasma (2.6 +/- 0.2 ng/l in basal conditions and 6.1 +/- 0.6 ng/l at 30 min) but not the CSF AVP levels. The results suggest that the neurons which secrete AVP into the CSF may be functionally different from those secreting into the peripheral circulation.

Diurnal pattern of plasma and cerebrospinal-fluid vasopressin levels in hydrocephalic patients: absence of a circadian rhythm and of a correlation between plasma and cerebrospinal-fluid variations.

The arginine vasopressin (AVP) concentrations were determined in plasma and in cerebrospinal fluid (CSF) during a 24-hour period in 7 male patients suffering from hydrocephalus of differing etiologies. Blood and ventricular CSF samples were simultaneously collected every 2 h during the day (08.00-22.00) and every hour during the night (24.00-07.00). In both plasma and CSF, the AVP levels did not show significant time-related circadian variations. No significant correlation was found between the plasma and CSF AVP values during the 24-hour period. The data obtained indicate the absence of the plasma and CSF AVP circadian rhythm in hydrocephalic patients and suggest that in these patients, and possibly in healthy humans, physiological stimuli which are able to induce variations in the plasma AVP concentration during daily life do not alter the CSF AVP content.

Diurnal changes of plasma and cerebrospinal fluid somatostatin and 24-h growth hormone secretory pattern in man. A study in hydrocephalic patients.

Somatostatin concentration was determined in plasma and in cerebrospinal fluid during a 24-h period in 7 male patients suffering from hydrocephalus of differing aetiologies. Blood and ventricular cerebrospinal fluid samples were taken every 2 h during the day (08.00-22.00 h) and every hour during the night (24.00-07.00 h). Simultaneously, plasma growth hormone levels were also evaluated. Plasma SRIH levels showed significant circadian variations with highest values in the daytime and lowest values during the night. Cerebrospinal fluid SRIH did not show any significant time-related circadian changes. Plasma GH levels showed the well-known circadian pattern in the majority of patients. No significant correlation was found between the plasma GH and plasma or cerebrospinal fluid SRIH values recorded during the 24-h period. Results suggest that peripheral SRIH does not play any major role in the control of the 24-h GH secretory pattern in man.

[Analysis of EEG frequency in althesin anesthesia]. / Analisi di frequenza dell'EEG nell'anesthesia con althesin.

Twelve subjects were given Althesin until the EEG level of burst suppression was reached. The cerebral electrical activity was continuously monitored by the conventional EEG-tracing method and by a tracing compression technique (BFA), based on the time to-frequency domain conversion and the display of the spectra in prospectical array. The BFA computed in real time the power spectra of 64 frequencies (0,25-16 Hz) by means of the Fourier's transform. The depth of Althesin anesthesia proved to correlate with the EEG spectra.