The cost-effectiveness of basiliximab induction in "old-to-old" kidney transplant programs: Bayesian estimation, simulation, and uncertainty analysis.

INTRODUCTION: Markov models are employed in economic analyses to evaluate all possible expectations in a dilemna. The introduction of a new clinical protocol (Basiliximab induction with calcineurin-sparing protocols) for a group of kidney transplant recipients receiving organs from marginal donors was validated with a Markov simulation model, demonstrating the usefulness of combining simulation with Bayesian estimation methods for analysis of cost-effectiveness data collected alongside a clinical trial. We sought to determine whether calcineurin-sparing protocols using anti-interleukin-2/antibody induction (Simulect) would show a beneficial effect on initial kidney function and reduce transplantation costs upon admission, clinical incidences, graft function, and complications during the first month after transplant. PATIENTS AND METHODS: A Markov Chain Monte Carlo (MCMC) was used to estimate a system of generalized linear models relating costs and outcomes to a kidney transplant process affected by treatment under alternative therapies. The Markov simulation model was established following three chains: a calcineurin-free regimen with Basiliximab induction (chain A); a calcineurin-sparing protocol with Basiliximab induction (chain B); and a conventional immunosuppressive regimen (chain C). The MCMC draws were used as parameters in simulations that yielded inferences about the relative cost-effectiveness of the novel therapy under a variety of scenarios. After designing the Markov chain and cohorts, 31 patients from the "old-to-old" program were assigned; eight to chain A; eight to chain B; and 15 to chain C. A year after transplantation a cost-benefit study was performed guided by the three branches of the Markov model. RESULTS: The Markov model showed a benefit of induction therapies in elderly patients. A cost-benefit model showed that after a year, there was a clear benefit from calcineurin-free plus Basiliximab induction therapies, with a slight benefit from calcineurin-sparing protocols. CONCLUSIONS: Markov models are extremely useful when introducing new clinical therapies. The approach allows flexibility in assessing treatment using various premises and quantifies the global effect of parametric uncertainty on a decision maker's confidence to adopt one therapy over another. In our transplant program, a cost-effective analysis of outcomes in old patients using the Markov model showed a clear benefit of calcineurin-sparing protocols with Basixilimab induction.

[Fulminant liver failure after administration of the herbal antidepressant Kava-Kava]. / Fulminantes Leberversagen nach Einnahme des pflanzlichen Antidepressivums Kava-Kava.

HISTORY AND CLINICAL FINDINGS: A 60 year-old woman was admitted to hospital because of jaundice, fatigue, weight loss over several months and icteric skin. Because of progressive liver failure, concomitant renal failure and progressive encephalopathy she was transferred to an intensive care unit. INVESTIGATIONS: Biochemical tests revealed acute liver failure with high levels of total and conjugated bilirubin (30 mg/dl) as well as aspartate aminotransferase (921 IU/l) and alanine aminotransferase (1350 IU/l) concentrations. Prothrombin time was less than 10 %. Serological tests could rule out viral hepatitis, metabolic or autoimmune causes of liver failure. On abdominal computed tomography and ultrasonography no pathological changes were detected. Above all portal vein thrombosis, ascites, focal lesions of the liver and extrahepatic cholestasis could be excluded. Liver histology showed extensive hepatocellular necrosis with intrahepatic cholestasis. TREATMENT AND CLINICAL COURSE: The patient's physical condition deteriorated. She had to be intubated because of respiratory insufficiency and encephalopathy stage IV. Because of progressive liver failure under conservative treatment the patient received an orthotopic liver transplant 11 days after admission. CONCLUSIONS: The exclusion of other causes and the histological diagnosis made Kava-Kava as the cause of acute liver failure most likely. This is the 18th case of Kava-Kava induced liver failure reported to the European regulatory authorities.

Outcome of surgical intervention for rectoneovaginal fistulas in Mayer-Rokitansky-Kuester-Hauser syndrome.

Creation of a neovagina to treat vaginal atresia or aplasia in Mayer-Rokitansky-Kuester-Hauser syndrome must always be followed by long-term application of dilators to avoid shrinkage. However, rectoneovaginal fistulas are caused by chronic alteration and consecutive necrosis of the posterior neovaginal wall. We evaluated retrospectively the postoperative outcome of rectal wall and neovaginal reconstruction using a standardized surgical technique in an exclusive collection of women. Eight women with a mean age of 28 years (range 22-31 years) were treated for rectoneovaginal fistulas in our clinic. Preoperatively, proctoscopy, sphincter manometry, endoluminal rectal ultrasonography, and colonoscopy were performed; and regular postoperative follow-up by digital examination and rectoscopy were obligate. The standard surgical procedure via a perineal approach included fistulectomy and closure of the mucosa and rectal wall followed by a levatorplasty. All but one woman had a temporary colostomy. After 2 weeks the patients were allowed to wear vaginal dilators of a smaller size. Within the mean follow-up period of 20 months, reintervention was necessary twice because of late fistula relapse detected by proctoscopy, barium enema, and subjective symptoms. Morbidity was 25% (n = 2) due to secondary superficial wound healing or urinary tract infection. The average time of the hospital stay was 13 days (10-14 days). One patient complained of vaginal shrinkage and underwent local estrogen therapy with a good functional result 3 months later. Proper fistulectomy and surgical reconstruction with interpositioning of well perfused muscle layers achieved good functional outcome with an acceptable number of minor morbidities. Local estrogen treatment is helpful for avoiding scarification and decreasing the neovaginal size.

Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis.

The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.

[Prognostic differences in primary malignancies of the small intestine]. / Prognoseunterschiede primärer Dünndarmmalignome.

Malignant small bowel tumours are rare, with about 320 deaths every year due to metastases. Tumours of differing histologic entitites (adenocarcinomas, leimyosarcomas, non-Hodgkin, lymphomas, carcinoids) are detected at late stages of the disease because of non-specific symptoms. Valuable diagnostic means are small bowel enema, intestinoscopy and abdominal CT/ultrasound. Five-year survival rates are poor for carcinomas (21%), for sarcomas (37%), lymphomas (44%) and best for carcinoids (100%). Surgical options are poor for carcinomas with a high number of R2 resections and bypass operations. Multivisceral surgery is beneficial for sarcomas and lymphomas, followed by local radiation therapy or chemotherapy.