Cost-effectiveness analysis of screening for abdominal aortic aneurysms based on five year results from a randomised hospital based mass screening trial.

BACKGROUND: The aim of this study was to estimate the cost effectiveness of screening for abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: All 12,639 men born in the years 1921-1933 (aged 64-73) living in Viborg County, Denmark, were randomly allocated either to receive an invitation to abdominal ultrasound scanning for AAA or to be controls. Costs for screening and surveillance were assessed prospectively. Diagnosis Related Group (DRG) costs from 1999 were used concerning admissions with uncomplicated and complicated operations. Admissions for AAA surgery were retrospectively classified according to complications in patient records. RESULTS: Mean follow-up time was 52 months. 76.6% of invited men attended screening, and 191 (4.0%) had an AAA. As previously reported, the cumulative 5-year AAA-specific mortality in the invited group was significantly reduced by 67% compared to the control group (P = 0.003). The costs were estimated to be Euro 11.23 per scan. The costs per life-year saved were Euro 9057 (Euro 5872-20,063) after 5 years, and were expected to decrease to Euro 2708 (Euro 1758-6031) after 10 years and to Euro 1825 (Euro 1185-4063) after 15 years. CONCLUSION: Screening of 64-73 years old males in Denmark seems cost effective.     

Ultrasound Examination and Localization of the Sciatic Nerve: A Volunteer Study

Background: Few studies have examined the use of ultrasound for sciatic nerve localization. The authors evaluated the usefulness of low-frequency ultrasound in identifying the sciatic nerve at three locations in the lower extremity and in guiding needle advancement to target before nerve stimulation.

Methods: In this prospective observational study, 15 volunteers underwent sciatic nerve examination using a curved ultrasound probe in the range of 2-5 MHz and a Philips-ATL 5000 unit (ATL Ultrasound, Bothell, WA) in the gluteal, infragluteal, and proximal thigh regions. Thereafter, an insulated block needle was advanced inline with the ultrasound beam to reach the nerve target, which was further confirmed by electrical stimulation. The quality of sciatic nerve images, ease of needle to nerve contact, threshold stimulating current, and resultant motor response were recorded.

Results: The sciatic nerve was successfully identified in the transverse view as a solitary predominantly hyperechoic structure on ultrasound in all of the three regions examined. The target nerve was visualized easily in 87% and localized within two needle attempts in all patients. Nerve stimulation was successful in 100% after two attempts with a threshold current of 0.42 +/- 0.12 (mean +/- SD) eliciting foot plantarflexion or dorsiflexion.     

Plasma thymulin and nerve growth factor levels in patients with primary open angle glaucoma and elevated intraocular pressure

Background The objective was to measure the plasma concentrations of thymulin and nerve growth factor (NGF) in a group of patients with primary open angle glaucoma (POAG) and compare them with age- and sex-matched normal controls.Methods Twenty-eight patients newly diagnosed with POAG who were not undergoing treatment were compared with the same number of age- and sex-matched healthy controls. Blood samples were drawn into heparinized tubes and plasma samples were collected for the determination of the concentrations of thymulin and NGF, using specific enzyme-linked immunosorbent assay (ELISA). The Student’s t test was used to perform the necessary statistical analysis of the results.Results Seventeen women and 11 men were enrolled in each of the two groups (study and control), with a mean age of 63.7 (SD 10.3) years in the former and 63.3 (SD 9.6) years in the latter. There was a highly significant (p<0.001) elevation in the thymulin levels in POAG patients compared with the control group. However, no significant difference was observed when comparing the plasma NGF levels.Conclusion This is the first report to measure plasma thymulin levels in glaucoma patients. The significant results point the possible role of this immunomodulator in the pathogenesis of primary open angle glaucoma. The potential role of NGF seems to be less likely. These findings warrant further investigation.     

Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.     

Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.

Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg x m(-2), primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.     

Expression of innate immune complement regulators on brain epithelial cells during human bacterial meningitis

Background  

In meningitis, the cerebrospinal fluid contains high levels of innate immune molecules (e.g. complement) which are essential to ward off the infectious challenge and to promote the infiltration of phagocytes (neutrophils, monocytes). However, epithelial cells of either the ependymal layer, one of the established niche for adult neural stem cells, or of the choroid plexus may be extremely vulnerable to bystander attack by cytotoxic and cytolytic complement components.     

Systematic overview of drug interactions with antidepressant medications.

OBJECTIVE: Antidepressants are commonly used drugs with potential for numerous drug interactions. This study aims to systematically review the literature on drug interactions with antidepressants. METHODS: We searched MEDLINE (1966 to November 2003) and EMBASE (1980 to 2003), using the heading drug interactions combined with individual antidepressant names. We restricted searches to English-language articles and human studies. We screened drug interaction texts and review articles for relevant studies. We included articles reporting original human data on drug interactions with antidepressants commonly used in North America. Articles were independently evaluated by 2 reviewers on clinical effect, clinical significance, and quality of evidence. Discrepancies were resolved by consensus. RESULTS: There were 904 eligible interactions, involving 9509 patients, for a total of 598 summary interactions. Of these, 439 (73%) demonstrated an interaction, 148 (25%) had no effect, and 11 (2%) had conflicting evidence. For 510 interactions (85%), the quality of evidence was poor. It was fair for 67 (11%) interactions and good for 10 (2%) interactions. There were no interactions with excellent quality of evidence. There were 145 (24%) interactions of major clinical significance. These were predominantly hypertensive emergencies and serotonin syndrome. Most interacting drugs had central nervous system (CNS) activity. As expected, monoamine oxidase inhibitors (MAOIs) appear to be the most problematic family in terms of potential for serious drug interactions. CONCLUSIONS: Drug interactions with antidepressants are an important cause for concern, but this concern is based primarily on poor evidence. We recommend caution when combining antidepressants with other CNS drugs, particularly when coadministering MAOIs with other substances.     

Women's access to modern methods of fertility regulation.

Preventing unintended pregnancies through access to modern family planning could avert 20-35% of maternal deaths, saving the lives of more than 100,000 women each year. Obstacles to wider access still exist, but they may be overcome by overt policy commitment to reproductive health services, partnership between stakeholders, community involvement and quality programs.