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.

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.

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-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.

[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.

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.

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.

[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.

[Subarachnoid hemorrhage and pregnancy]. / ESA e gravidanza.

Intracranial haemorrhage from ruptured aneurysm or bleeding in arteriovenous malformation is rare, but may result in significant maternal and fetal mortality and serious neurological morbidity in survivors. Surgical intervention creates risks for the mother and her fetus, but is the best form of management. The anaesthetic procedure can present many clinical dilemmas, one of which is the role of induced hypotension. This review will focus on the diagnosis and management of this dramatic event.

[The recurrence of hepatitic C in orthotopic liver transplantation]. / La recidiva di epatite C nel trapianto ortotopico di fegato (OLT).

BACKGROUND: This study is a review of hepatitis C recurrence in patients undergoing an orthotopic liver transplantation (OLT); to verify how many patients HCV-positive before OLT confirm a persistent viremia after OLT and how many with viremia show hepatitis histological evidence. METHODS: Thirty consecutive patients, 24 males, median age 52.5 underwent OLT for posthepatitic C cirrhosis since January 1993 in the "Transplantation Center" of Genoa. Serology included anti-HCV search, HCV-RNA and HBV-DNA determinations, biopses were performed in the transplanted liver within the month after operation, subsequently at every hepatic enzymes increase. RESULTS: Twenty-one patients are currently alive, median follow-up of 14.5 months. Before OLT anti-HCV antibodies search was positive in all the patients while the HCV-RNA by PCR resulted positive in 17 and negative in 4. Before OLT the HBV-DNA in patients with associated hepatitis B was negative. After OLT 5 patients, of the 17 HCV-RNA positive before OLT, have turned negative then all became again positive from 6 to 12 months later; 2 of the 4 patients HCV-RNA negative before OLT have turned positive, and remained still negative two with hepatitis C associated with hepatitis B. Although viral replication was present in 95% of the patients, clinical and histological evidence of recurrence was ascertained only in 29%. CONCLUSIONS: It should be noted that the hepatitis histological picture doesn't correspond to a severe worsening of clinical conditions, an evolution justifying transplantation. The long-term results of this therapeutic choice are still uncertain due to the high incidence of recurrences.

[Severe infections after orthotopic hepatic transplant]. / Infezioni gravi dopo trapianto epatico ortotopico.

METHODS: The authors analysed severe infections in 43 consecutive patients undergoing orthotopic liver transplant. Prophylaxis and full anti-infection monitoring was performed in all cases. Immunosuppressive therapy was administered in the form of primary cyclosporine in 27 cases and primary OKT3 in 16 cases. RESULTS: Twenty-seven patients are still alive (median 8 months, range 2-40) and 16 died (median 22 days, range 10-92) of whom 4 without and 12 with infection, including two deaths owing to non-correlated causes with infection after recovery. Twenty-three patients underwent 33 episodes of severe infection (plus four with inconclusive positive cultures) without any case of protozoal or viral infection. All episodes occurred within two months of surgery and affected the lung (10), abdomen (7), lung + abdomen (1), urinary tract (1), lung + urinary tract (1), as well as two diffused cases and 7 cases of isolated bacteremia deriving from the donor (1), venous catheters (3), mild otorhinolaryngeal infection (1) and two unknown sources (2). Eighteen infective agents were identified in 45 cases. The bacteria involved in single-agent episodes were: 11 Gram+, 9 Gram- and five fungi. Polymicrobic and bacterial/fungal episodes were repeatedly observed in two and two cases. Postoperative renal insufficiency significantly influenced both the incidence of and mortality due to infection. Overall mortality was also influenced by early graft function, postoperative complications and reoperations, and the incidence of infections by the portal clamping stage, reject and prolonged coma. CONCLUSIONS: The absence of severe viral infections and the gradual reduction of mortality caused by infection appear to be parallel to the aggressive antiviral prophylaxis, the gradual improvement of intra- and postoperative management and primary immunosuppression with OKT3.

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.

[Evaluation of 2 modalities of use of propofol in cerebral angiography]. / Valutazione di due modalità di impiego del propofol nelle angiografie cerebrali.

Fifty eight adult patients suffering from different intracranial lesions and scheduled for cerebral angiography were given propofol. In the first group (38 patients) brief periods of anaesthesia were induced and reinduced by means of 1.5 mg/kg of propofol iv and sometimes extended with boluses of 25-50 mg of this anesthetic. The patients were premedicated with 0.5 mg atropine im 30-40 min before the induction. Fentanyl, droperidol and diazepam in various combinations and doses were injected, im together with the atropine and iv 1-2 min before the induction, to obtain long-lasting sedations. In the second group (20 patients) the induction of the anaesthesia started 20-35 min after 0.5 mg of atropine im and 1 min after 0.1 mg of fentanyl iv. The induction was based on a bolus of 2.5 mg/kg of propofol and it was followed by suxamethonium, tracheal intubation and mechanical ventilation with N2O 70% in O2. An adequate depth of anaesthesia was maintained with supplemental doses of 50 mg of propofol, frequently associated with 25 mg of suxamethonium. Both methods proved to be reliable and safe. Nevertheless, the second method provided a better stability as far as a number of physiologic variables is concerned.

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.