Assessment of clinical and economic benefits of weight management with sibutramine in general practice in Germany

Obesity is associated with major health risks and a high economic burden impacting on health care systems. This study utilises the latest evidence from randomised clinical trials (RCTs) to explore and to assess the cost effectiveness of sibutramine in combination with diet and lifestyle advice compared to diet and lifestyle advice alone for the treatment of obese subjects without comorbidities at baseline in Germany. New evidence from recently published RCTs and post-marketing surveillance studies, including health economic data as well as quality of life (QoL) data, were used to model the long-term outcomes of weight management with sibutramine in German practice. German healthcare costs and new data from over 8,000 patients were analysed based on a recently published model. These new RCT data were used to model weight losses, proportion of responders to treatment, utilities by weight loss and variability in weight regain post-treatment. Costs and QoL benefits associated with weight loss (using SF-36 data from sibutramine trials), reduced incidence of coronary heart disease (using Framingham equations) and diabetes were used to estimate the cost per quality adjusted life year of sibutramine treatment. For 1,000 patients treated with sibutramine for 1 year, extrapolating outcomes over 4 further years, sibutramine is estimated to save 4.18 CHD events, 2.58 diabetes incident cases and give 51.5 more quality-adjusted life years (QALYs). The cost-utility analysis (CUA) estimates €13,706 per QALY gained. Results are sensitive to changes in weight loss, rate of weight regain and discounting rate. Although the non-pharmacological weight management programme in the comparator arm yielded higher weight losses than generally observed in clinical practice, these results demonstrate that additional sibutramine treatment is a cost effective therapy for an obese population without comorbidities in Germany. The CUA results are within the range generally accepted as cost effective and should be viewed as conservative when generalizing to settings offering standard non-pharmacological treatment.     

Real-Time Three-Dimensional Echocardiography for Improved Evaluation of Diastolic Function Using Volume-Time Curves

Background: Accurate assessment of left ventricular function is of the greatest importance in clinical cardiology for decision making. Diastolic dysfunction is getting more concern as a cause of heart failure while, currently used non-invasive modalities for diagnosing diastolic abnormalities have significant limitations. Dynamic left ventricular volume change was applied for the evaluation of diastolic function by various techniques that have been demonstrated to be of diagnostic value. However, it has not been accepted into clinical practice because existing techniques are either invasive, inaccurate, expensive or time consuming. Real-Time Three-Dimensional Echocardiography: Real-time three-dimensional (3-D) echocardiography is a new ultrasound technique that provides transthoracic volumetric images of the heart in real time. Thereby, the acquired images are ideally suited for the assessment of dynamic left ventricular volume change. Generation and analysis of left ventricular volume-time curves by real-time 3-D echocardiography has been demonstrated to be feasible in normal subjects and patients and accuracy of volume-time curves was good compared to magnetic resonance imaging. We compare the new real-time 3-D echo approach with the advantages and limitations of existing noninvasive and invasive techniques. Hintergrund: Eine genaue Beurteilung der linksventrikulären Funktion ist von größter Bedeutung für die kardiologische Diagnostik und Therapie. Besonders diastolische Funktionsstörungen als Ursache für eine diastolische Herzinsuffizienz lassen sich jedoch mit nicht-invasiven Methoden nur eingeschränkt beurteilen. Die Methode der Volumen-Zeit-Kurven-Analyse erlaubt eine detailliertere Beurteilung der diastolischen Funktion. Sie ist jedoch nicht Bestandteil der Routinediagnostik, da die existierenden bildgebenden Verfahren entweder invasiv, ungenau, kostenintensiv oder zeitintensiv sind. Echtzeit-3-D-Echokardiographie: Die Echtzeit-3-D-Echokardiographie, ein neues Verfahren zur Gewinnung von dynamischen Volumendatensätzen des Herzens, ist jedoch besonders beeignet zur Akquisition von linksventrikulären Volumen-Zeit-Kurven. Im direkten Vergleich mit der Magnetresonanztomographie zeigen die Volumen-Zeit-Kurven mittels Echtzeit-3-D-Echokardiographie eine hohe Übereinstimmung bei Untersuchungen an Normalpersonen und Patienten. Die vorliegende Arbeit liefert einen Überblick über die Methode der Volumen-Zeit-Kurven-Analyse mittels Echtzeit-3-D-Echokardiographie sowie den Vorteilen und Limitationen im Vergleich mit anderen Verfahren.     

Candida-induced stomatopyrosis and its relation to diabetes mellitus

BACKGROUND: Glycaemic disorders and oral candidosis can be accompanied by burning mouth sensations. However, no clear relation between all three disorders is known. METHODS: Seventy-two native Upper-Austrians with burning mouth sensations were examined and smears for Candida estimation were taken from the spots where the sensations were felt. All patients with previously unknown diabetes mellitus (DM) were subjected to an oral glucose tolerance test (OGTT). Use of glucocorticoid-containing anti-asthmatic sprays and the body mass index (BMI) were determined. RESULTS: Of the examined non-inhalers of sprays, 52% had increased candidal density. A correlation between that increase and type 2 DM was found. The burning sensations in all patients with increased candidal density subsided completely after anti-mycotic therapy. CONCLUSION: The perception of burning sensations was hypothesised to occur via stimulation of the capsaicin (vanilloid) receptor by Candida metabolites. The Candida-induced stomatopyrosis should be regarded as a single symptom indicating (predisposition to or established) type 2 DM in non-inhalers of the concerned population.     

Treatment and reconstruction after disconnection of the failed cervical esophagogastric anastomosis

Reconstruction of the esophageal passage after severe complications of the esophagogastric anastomosis (disconnection, long stenosis) remains a surgical challenge. We describe the course of five patients with cervical defects (n = 4) or stenosis (n = 1) after complications of the cervical esophagogastric anastomosis and successful reconstruction by free jejunal transfer. Cause of failure of the anastomosis was ischemia in two, and compression, bleeding and unknown reasons in the other three patients respectively. In four patients, subsequent treatment consisted of disconnection of the anastomosis. In all cases, reconstruction by free jejunal transfer was done between 8 weeks and 12 months after primary surgery. A perforation of the graft was observed in one patient (decubital ulcer from the split sternum). All patients regained normal swallowing function. Free jejunal transfer is a safe method for reconstruction of short defects with a satisfactory functional result and minimal surgical trauma.     

Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer.

PURPOSE: The purpose of this study was to investigate the prognostic significance of assessment of human epidermal growth factor receptor (HER)-2 oncogene protein overexpression of breast cancer tissue by the United States Food and Drug Administration (FDA)-approved HercepTest and grading system (negative, 0 or 1+; weakly positive, 2+; strongly positive, 3+). Furthermore, results of the HercepTest were correlated with immunohistochemical results obtained using different antibodies and protocols and with HER-2 oncogene gene amplification assessed by fluorescence in situ hybridization (FISH). EXPERIMENTAL DESIGN: HER-2 status in 303 patients with lymph node-positive breast cancer was investigated by using a rabbit polyclonal antibody (DAKO) by conventional immunohistochemistry and by applying the HercepTest. Furthermore, the monoclonal antibody CB-11 was used in conventional immunohistochemistry and with the NexES automatic stainer, which is also under consideration for FDA approval for determination of eligibility for Herceptin therapy. Results were compared with FISH analysis performed in all 2+ and 3+ specimens (103 cases) and 104 HER-2-negative specimens. RESULTS: 3+ positive carcinomas were found in 8.9-15.7% of specimens. FISH revealed that almost exclusively 3+ positive cases were amplified, with the HercepTest and the NexES automatic stainer giving the best results. In univariate analysis, staining with the HercepTest revealed a significantly worse prognosis in 3+ cases. Also, 3+ cases were significantly associated with lower estrogen receptor levels and histological grade III tumors. CONCLUSIONS: This study shows that the results of the FDA-approved HER-2 grading and test system correlated strongly with findings in FISH. Furthermore, HercepTest proved to be of prognostic relevance. Strict adherence to the given protocols is critical.     

Efficacy of Silver Nanoparticles-Impregnated External Ventricular Drain Catheters in Patients with Acute Occlusive Hydrocephalus

Introduction  Catheter-associated infection of cerebrospinal fluid (CSF) is a potentially life-threatening complication of external ventricular drainage (EVD). The purpose of this pilot study was to address the efficacy of silver-impregnated EVD catheters in neurological and neurosurgical patients requiring external CSF drainage due to acute occlusive hydrocephalus. Methods  Nineteen consecutive patients were enrolled in the treatment arm of the study and data were prospectively recorded for these patients. The control group consisted of 20 patients for whom data were retrospectively assessed. CSF samples were drawn at least three times a week and routine bacterial cultures and CSF analyses were done according to standard protocols. The primary endpoint of the study was the occurrence of catheter-associated ventriculitis (CAV) proven by positive CSF culture. Secondary endpoints were bacterial colonization of the catheter tip and CSF pleocytosis. Results  In 20 control patients, 5 CAVs were microbiologically diagnosed. In contrast, no positive CSF cultures were found in the treatment group. This difference was statistically significant (P < 0.05). All CAVs occurred later than day 10 after catheter placement. Colonization of the catheter tip was found in 6 patients in the control group and in 5 patients in the treatment group (not significant). Conclusions  This pilot study indicates that EVD catheters impregnated with silver nanoparticles might be a new option for preventing CAV in neurocritical care patients, and therefore evaluation in a large prospective randomized study is warranted.     

Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock.

OBJECTIVE: To determine the early effects of therapy of endotoxin (ET) shock with epinephrine, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. SUMMARY BACKGROUND DATA: Conflicting concepts exist concerning the catecholamine therapy of septic shock, but little is known about the effects of catecholamine treatment on splanchnic circulation and mucosal integrity. METHODS: ET shock was induced in pigs by ET infusion over 30 minutes, and animals were studied for 4 hours. All animals were resuscitated with fluid. To mimic the treatment of septic shock in humans, mean arterial pressure was maintained in two groups at >70 mm Hg with the administration of epinephrine or norepinephrine. A third group of animals received dopexamine at 7 microg/kg per minute. Systemic and splanchnic blood flow and oxygen metabolism were studied, sigmoid colon mucosal pHi was obtained tonometrically, and bacterial translocation was determined by culture of portal venous blood, mesenteric lymph nodes, liver, spleen, and lung specimens. Histologic sections of ileal, colonic, and sigmoid mucosa were morphometrically examined for therapy effects. RESULTS: All investigated catecholamines increased cardiac output and systemic oxygen delivery, whereas intestinal blood flow and oxygen delivery remained unchanged. Sigmoid mucosal pHi decreased in all study animals, but the decrease was most pronounced in the epinephrine group. Pigs receiving epinephrine also showed >40% damage of the mucosa of the ileum and colon, whereas animals receiving ET alone, norepinephrine, or dopexamine showed only moderate lesions with signs of restitution. No animal showed bacterial translocation. CONCLUSIONS: Systemic hemodynamics and oxygen metabolism data do not reflect intestinal perfusion. Norepinephrine or dopexamine administration in ET shock causes no additional impairment of intestinal integrity. Epinephrine therapy, in contrast, is associated with a significant reduction of mucosal pHi and considerable early mucosal damage. Its application in septic shock is hazardous.