Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: a cost-effectiveness analysis in Greece.

BACKGROUND: Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival. OBJECTIVE: The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting. METHOD: A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective. RESULTS: Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting. CONCLUSIONS: The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.

Ethanol-like effects of thiopental and ketamine in healthy humans.

The gamma-aminobutyric acid-A (GABA(A)) and N-methyl-D-aspartate (NMDA) receptors mediate aspects of the behavioural effects of alcohol. Prior studies reported drugs that block NMDA receptors or facilitate GABA(A) receptor function produce ethanol-like effects in humans. The purpose of this study was to compare the ethanol-related effects of two pharmacological agents with known NMDA and GABA(A) receptor activity. As part of an ongoing, larger study, 28 subjects (age, 21-30) with no personal or family histories of alcoholism were administered subanesthetic doses of the GABA(A) receptor agonist thiopental, the NMDA receptor antagonist, ketamine and placebo on three separate test days. Various ethanol-related measures were administered. At doses of thiopental and ketamine that produced similar levels of sedation and cognitive effects, both agents produced significant ethanol-like effects and subjective intoxication. However, the intensity of the ethanol-like effects of ketamine was greater than that of thiopental. In addition, ketamine produced alterations in perception that were not produced by thiopental. These data provide further support for a model where GABA(A) receptor facilitation may contribute significantly to ethanol effects associated with social drinking, whereas NMDA receptor antagonism may contribute to relatively greater extent to features of ethanol 'intoxication'.

Major hepatectomy and right hemicolectomy at the time of primary cytoreductive surgery for advanced ovarian cancer: report of a case.

Major liver involvement at the time of diagnosis is a rare event in patients with ovarian cancer, and the issue of major hepatectomy at the time of primary cytoreductive surgery is controversial. A 61-year-old woman was admitted to our hospital with nonspecific abdominal pain of 2-month duration and weight loss of 5 kg during the last semester. A computed tomography scan demonstrated bilateral ovarian masses, extending to the right iliac fossa, pressing the cecum-ascending colon. In the liver parenchyma, three cystic lesions were found of about 6-cm maximum diameter each, along with pelvic lymphadenopathy. There was no ascites. The diagnosis of advanced ovarian cancer was clinically suspected; the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, right hemicolectomy, omentectomy, left lobectomy, deroofing, and draining of the cystic formation of the right liver lobe along with systematic pelvic and para-aortic lymphadenectomy. Systemic chemotherapy (six cycles of paclitaxel/carboplatin) was subsequently administered, and after 15 months of follow-up period, the patient is still in first remission and alive. Ovarian cancer with concomitant extensive right colon infiltration and hematogenous liver metastases can be successfully managed with aggressive surgical resection and postoperative chemotherapy in carefully selected patients.

Confirmation and fine mapping of the chromosome 1 alcohol dependence risk locus.

Two previous large genetic linkage studies in the US population have implicated an area in chromosome 1p to contain a susceptibility gene for alcohol dependence. The 1-LOD support interval of the linkage signal spans about 30 cM and contains >30000000 DNA base pairs (bp) and 700 predicted genes. In order to reduce the size of the candidate area and potentially identify novel candidate genes within this region, we fine-mapped this area using closely spaced short tandem repeat (STR) markers and the transmission disequilibrium test (TDT) in small nuclear families. The subjects were 87 European-American families including one or more alcohol-dependent offspring (93 children and 174 parents). The initial marker set consisted of 30 STR markers, spanning the Marshfield map interval between 101.48 and 130.73 cM. Using the TDTPHASE program, we identified three markers in the distal part of this region (125-126 cM), which showed evidence of transmission disequilibrium. On the basis of this result, an additional 12 STR markers were genotyped in this region; some of these markers provided additional evidence for linkage disequilibrium. The strongest evidence for transmission disequilibrium was obtained at the marker D1S406 (P=0.005, 126.16 cM), with supporting evidence from three neighboring STR markers D1S424 (126.16 cM, P=0.01), D1S2804 (126.16 cM, P=0.04), and D1S2776 (126.16 cM, P=0.02), which are all located within a <350000 bp interval. These findings suggest that a gene (or genes) causing susceptibility to alcohol dependence resides near location 126.16 cM on chromosome 1. In addition, these results provide independent confirmation of the linkage finding regarding the identification of at least one gene in this region increasing the risk for alcohol dependence.

Management of neglected giant omphalocele with Gore-tex in a child aged 8 years.

Omphalocele is a disease of neonatal age and its present management is successful in almost all specialized centers of Pediatric Surgery. A case of an 8-year-old girl who was managed with conservative treatment during her neonatal period with mercurochrome (Grob method) is presented. Due to very serious congenital cardiopathy, a corrective operative procedure of the omphalocele was not feasible during neonatal age. However, following successful heart surgery the child grew up with her initial disorder. The child was first seen in our clinic at the age of 5 years, presenting with a very large omphalocele. Following a staged pressure of the abdomen with a special belt an attempt was made to close the ventral hernia successfully using a Gore-tex sheet.

Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in healthy subjects.

BACKGROUND: Acute hyperglycemia has been associated with delayed gastric emptying of solid foods in healthy control subjects. Erythromycin has been found to be a gastrointestinal prokinetic agent in humans. We examined whether acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of a solid meal after a fasted state in healthy subjects. METHODS: Twelve healthy subjects ate standard solid meals that had been radiolabeled. Gastric emptying was measured by scintigraphy during normoglycemia (5-8.9 mmol/L glucose) and hyperglycemia induced by intravenous glucose (16-19 mmol/L glucose) after administration of placebo or 200 mg of erythromycin intravenously. Emptying was measured randomly on 4 different days. RESULTS: Administration of erythromycin during normoglycemia or induced hyperglycemia compared with placebo accelerated the gastric emptying of the solid meal but did not completely normalize the delay caused by hyperglycemia versus normoglycemia (p < 0.001). In both conditions, erythromycin versus placebo significantly reduced the lag-phase duration (9.7 +/- 2.3 min and 22.0 +/- 3.9 min vs. 38.3 +/- 5.7 min and 49.5 +/- 6.0 min, respectively; p < 0.001), gastric emptying of the half meal (39.2 +/- 4.0 min and 52.0 +/- 7.1 min vs. 75.7 +/- 11.8 min and 94.0 +/- 13.4 min, respectively; p < 0.001), and the percentage of meal retained in the stomach 120 min postprandially (p < 0.001). CONCLUSION: The erythromycin-induced acceleration effect on gastric emptying was related to the plasma glucose level. Hyperglycemia might have chosen a cholinergic antagonist pathway that delayed gastric emptying of solids. Even though induced hyperglycemia inhibited gastric emptying, erythromycin accelerated the gastric emptying rate through two distinct pathways: cholinergic and noncholinergic.

The role of video-assisted thoracoscopic surgery in the treatment of parapneumonic empyema after the failure of fibrinolytics.

BACKGROUND: Approximately 10% of patients treated with intrapleural instillation of fibrinolytics fail to respond and therefore need more invasive techniques, such as video-assisted thoracoscopic surgery (VATS). METHODS: During the period 1994-99, we treated 20 consecutive patients with complicated parapneumonic effusion (CPE) and pleural empyema (PE) that did not resolve with urokinase instillation given through the chest tube in a dose of 100,000 IU diluted in 100 ml of normal saline/daily for 3-5 days. The patients' ages ranged from 21 to 68 years (median, 46); 14 were male and six female. All patients had pleural fluid pH <7.1, LACTATE DEHYDRAGENASE (LDH) >1000, glucose <40 mg/dl and were submitted to VATS. RESULTS: Complete drainage was observed in 17 patients (85%), in the other three (15%), the procedure had to be converted to open thoracotomy due to a thickened visceral pleural peel. The mean operative time was 80.3 min (range, 55-140), and the mean duration of postoperative hospital stay was 7.5 days (range, 4-19). CONCLUSION: We found that VATS is a safe, effective, and well-tolerated surgical procedure in CPE and PE patients who have failed to resolve with initial treatment with fibrinolytics.

Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists.

Ketamine blocks the calcium channel associated with N-methyl-D-aspartate (NMDA) glutamate receptors. It has transient behavioral effects in healthy humans that resemble aspects of schizophrenia, dissociative disorders, and ethanol intoxication. Ethanol is an antagonist of both NMDA receptors and L-type voltage-sensitive calcium channels (VSCC) and it has minimal psychotogenic activity in humans. A double-blind placebo-controlled study was conducted that evaluated whether pretreatment with the L-type VSCC antagonist, nimodipine, 90 mg D, modulated ketamine response (bolus 0.26 mg/kg, infusion of 0.65 mg/kg/hr) in 26 ethanol-dependent inpatients who were sober for at least one month prior to testing. This study found that nimodipine reduced the capacity of ketamine to induce psychosis, negative symptoms, altered perception, dysphoria, verbal fluency impairment, and learning deficits. Nimodipine improved memory function, but had no other intrinsic behavioral activity in this patient group. Nimodipine pretreatment attenuated the perceived similarity of ketamine effects to ethanol as well as ketamine-induced euphoria and sedation. However, nimodipine did not reduce the stimulant effects of ketamine. These data suggest that antagonism of L-type VSCCs attenuates the behavioral effects of NMDA antagonists in humans. They support the continued evaluation of nimodipine in the treatment of neuropsychiatric disorders. They also suggest that drugs, such as ethanol, that combine NMDA and L-type VSCC antagonism may have enhanced tolerability without attenuation of their stimulant effects.

New perspectives in the management of sigmoid diverticulitis.

The sigmoid colon is the part of the large intestine, which most commonly involved in diverticular disease due to its anatomical properties. Diverticular disease of the colon is being seen with increasing frequency mostly in western countries. Diverticulitis results from inflammation and subsequent perforation of a colonic diverticulum. Mild forms of diverticulitis usually present with gradually increasing symptoms from the lower left quadrant of the abdomen, whereas acute complicated disease is characterised by dramatic onset of abdominal pain, followed by fever within a few hours. The standard treatment for uncomplicated diverticulitis is bowel rest, with liquid diet or intravenous fluids in combination with antibiotics. Prophylactic resection is not to be recommended for patients with diverticular disease, but a high-fibre diet may afford protection by preventing further complications. Patients not responding to conservative treatment within the first 24 hours require further evaluation by computed tomography or ultrasonography. Fistula formation and intestinal obstruction are indications for surgical intervention, although the frequent recurrent attacks, which commonly afflict these patients, are seldom associated with severe complications. Laparoscopic approach has been introduced in the diagnosis and definitive treatment of uncomplicated diverticulitis, with less morbidity and mortality rates, and hospitalisation of the patients and in these terms could be promising in the future.

Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients.

BACKGROUND: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol-dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue-induced craving for alcohol in recently abstinent alcoholic individuals. METHODS: Alcohol-dependent patients (n = 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue-exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. RESULTS: There were no significant changes in the magnitude of cue-induced craving with active tryptophan depletion compared with placebo. CONCLUSIONS: These data question the dependence of alcohol cue-induced craving in sober alcoholics on the ongoing synthesis of serotonin.

Upper extremities deep venous thrombosis: comparison of light reflection rheography and colour duplex ultrasonography for diagnosis and follow-up.

BACKGROUND: Non-invasive diagnosis of axillary-subclavian vein thrombosis or documentation of the post-thrombotic syndrome performing methods currently in use is not definitive. The purpose of this prospective study was to compare two methods for the diagnosis and follow-up of patients with primary and secondary axillary-subclavian vein thrombosis: light reflection rheography (LLR) which is a reflection of venous pressure changes in the extremity as record from the subdermal capillary plexus, and colour duplex ultrasonography (CDUS). METHODS: In 36 patients with primary and secondary axillary-subclavian vein thrombosis were used a 4006 GE (Milwaukee, USA) colour duplex ultrasonography and an AV-1000 Hemodynamics instrument for the light reflection rheography for diagnosis and follow-up. The LLR methodology that applied was simple, involving testing of the venous outflow in the upper extremities in response to exercise, and with normally respiratory variations of an open venous system that was also assessed by the non-invasive modalities. In the LLR application of venous congesting pressure, and measurement of the rate of venous outflow when the congesting pressure is released was also performed. RESULTS: Both methods were able to diagnose the axillary-subclavian thrombosis in the initial acute state. There were no cases of false-positive results in either method. The CDUS presented a lower sensitivity in comparison to LLR in the follow-up period of the patients. A positive study was confirmed by phlebography in each instance. CONCLUSIONS: The tracing obtained by LLR is easy to interpret and provides objective evidence of proximal venous occlusion. The test is easy to apply and the instrumentation is relatively inexpensive. Both LLR and CDUS, could prove to be an exciting development among non invasive diagnostic techniques for axillary-subclavian vein thrombosis, with major sensitivity of LLR in the follow-up.

Diagnosis and treatment of Barrett's oesophagus. A general survey.

Barrett's oesophagus is an acquired condition with columnar metaplasia of the distal oesophagus. This condition represents the most serious consequence of chronic gastro-oesophageal reflux as it is associated with an increased incidence of oesophageal adenocarcinoma. Since the exact pathophysiology is not known, prevention is not possible. The diagnosis of Barrett's oesophagus requires the presence of intestinal metaplasia in at least one biopsy specimen from the lower oesophagus. Barrett's oesophagus is considered a premalignant condition and some cases progress from dysplasia to invasive adenocarcinoma. Medical or surgical antireflux treatment controls symptoms and oesophagitis, but Barrett's oesophagus remains. Patients are usually followed up by endoscopy for detection of dysplasia or early cancer. Several reports in the literature have assessed the effects of H2-blocker and proton pump inhibitors treatment on Barrett's epithelium, but none has clearly documented a significant and consistent regression of the metaplastic epithelium. Even with high doses of proton pump inhibitors given for a prolonged period of time, it does not appear that a significant regression of Barrett's epithelium can be achieved. Various studies have assessed the effects of antireflux surgery on the regression of columnar epithelium and dysplasia and its potential protective effect on the subsequent development of carcinoma. Overall, it appears from these reports that antireflux surgery, despite adequate symptomatic results, does not significantly and consistently lead to a reduction in length or disappearance of the Barrett's mucosa, and does not prevent the development of dysplasia and its progression to carcinoma. Recently, numerous reports have documented the regression of Barrett's mucosa by using various experimental techniques: these thermal therapies focus on the removal of the columnar epithelium with restoration of the squamous epithelium. Technological advances including laser and especially photodynamic therapy have allowed for endoscopic mucosal ablation. Long-term results are more encouraging when this mucosal ablation is associated with antireflux medical or surgical therapy. Currently, none of these approaches can obviate the need for continued endoscopic surveillance; however the photodynamic therapy seems to be a promising alternative in the future.

Effects of cocaine prior to and during bupropion maintenance in cocaine-abusing volunteers.

The effects of cocaine were examined prior to and during bupropion maintenance in nonopioid-dependent cocaine abusers. Prior to bupropion maintenance, subjects underwent an experimental session during which repeated cocaine doses (0, 50, 100 mg/70 kg) were administered intranasally. Then subjects were maintained on bupropion (150 and 300 mg per day) and underwent experimental sessions as before. Cocaine, regardless of bupropion, produced dose-related increases in several stimulant-like self-reports, performance and cardiovascular measures. Bupropion decreased POMS ratings of friendliness and vigor, regardless of cocaine dose. Bupropion enhanced and attenuated cocaine-induced increases in ratings on the LSD and BG subscales of the ARCI, respectively. These results suggest that bupropion does not alter the acute subjective or cardiovascular effects of cocaine in a robust manner.

Solid pseudopapillary neoplasm of the pancreas: report of a case after a 10-year follow-up and review of the literature.

A solid pseudopapillary neoplasm (SPN) is an extremely rare tumour of the pancreas that frequently occurs in young females and is mostly benign. SPN is a low-grade malignant tumour that may evolve years before symptoms start. However, the pathogenesis of this tumour remains unclear and there are no adequate reports of long-term results to evaluate the management and the long-term surgical control. We describe a new case of SPN with a 10-year follow-up, and review the world literature that accounts for approximately 322 cases. Moreover, a review of the current management and surgical tendencies in the treatment of SPN is considered. An SPN pancreatic tumour occurred in a 24-year-old female who complained of episodic mild abdominal pain sustained by a palpable epigastric mass. The tumour mass was detected by ultrasound and computer tomography and was localised at the tail of the pancreas adherent to the spleen. The preoperative diagnosis was uncertain and en-block distal pancreatectomy and splenectomy were performed. The size of the mass which weighed 300 g was 11 x 12 x 8 cm, and the tumour was strictly adherent and invaded the splenic hilum. Histologic examination confirmed a complete resection of the primary SPN that locally invaded spleen. The postoperative period was uneventful and after a 10-year follow-up the patient is free of symptoms. SPN should be considered in the differential diagnosis of large pancreatic masses, especially in young females. Radical resection, where technically feasible, should be considered the therapy of choice as it is a safe and effective control of the disease.

Sex differences in self-reported and physiological response to oral cocaine and placebo in humans.

Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug.

Cocaine use and the mid-latency auditory evoked responses.

To examine the effects of chronic cocaine use on the mid-latency auditory evoked responses (MLAERs), we recorded the evoked responses of 15 cocaine-dependent subjects and 13 age-matched healthy control subjects. Two evoked response paradigms were used: a trains paradigm with four different inter-stimulus intervals (ISIs) and a paired-click paradigm. Our data suggest that cocaine-dependent subjects generate smaller P50 components when long ISIs are used with multiple repetitions (in the trains paradigm). In a single repetition paradigm (paired clicks), a significant decrease in the ability to attenuate the N100 component was seen in the cocaine-dependent subjects.

Experience with new techniques for extraanatomic arterial reconstruction of the lower limb.

The aim of this report is to present our experience with new techniques for extraanatomic lower limb arterial reconstruction. Two techniques are described here of construction of an extraanatomical bypass for lower limb revascularization either through the wing of the iliac bone or underneath the iliopsoas fascia through the muscular lacuna close to the anterior superior spine of the iliac crest. Both techniques are recommended for the treatment of a severely injured groin, such as in patients with pelvic malignancy and/or an acute groin bleeding due to postirradiation femoral artery erosion or an infected femoropopliteal bypass graft with severe upper medial thigh sepsis. These techniques were used in nine patients (five with malignancy and four with an infected femoropopliteal bypass graft). Our results showed that the transosseous route through the wing of the iliac bone or underneath the iliopsoas fascia through the muscular lacuna may be considered effective alternate routes for lower limb arterial extraanatomic reconstruction when the common femoral cannot be used for arterial inflow.