Prediction of psychosis onset in Alzheimer disease: The role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes.

BACKGROUND: Psychotic symptoms in Alzheimer disease (AD+P) identify a heritable phenotype associated with more rapid cognitive decline. The authors have proposed that AD+P is itself a composite of a misidentification and a paranoid subtype with increased cognitive impairment restricted to the misidentification type. Most prior studies of the clinical correlates of AD+P have been limited, however, by the inclusion of prevalent cases. METHODS: Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were assessed at the time of initial presentation and then annually. Psychotic symptoms were assessed using the CERAD Behavioral Rating Scale. Survival analyses used Cox proportional hazard models with time-dependent covariates to examine the predictors of psychosis onset. RESULTS: A total of 288 subjects completed at least one follow-up examination. Mean duration of follow-up was 22.1 months. The incidence of psychosis was 0.19 per person-year. Cognitive impairment was associated with onset of psychosis, largely as a result of its association with onset of the misidentification, but not the paranoid, subtype. Including psychotropic medication use in the model revealed an association of antidepressant use with the onset of psychosis. This latter association appeared to arise from an underlying association between depression and the risk of psychosis onset rather than from antidepressant treatment. CONCLUSION: These findings are consistent with the hypothesis that the misidentification and the paranoid subtypes each define a more biologically homogeneous group than AD+P as a whole. Further exploration of the relationship between depressive symptoms and psychosis in patients with AD is warranted.     

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.     

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.     

Decreased corpus callosum size in sickle cell disease: relationship with cerebral infarcts and cognitive functioning.

We assessed midsagittal corpus callosum size in sickle cell disease (SCD) and its relationship to lesion volume, lesion location, and cognitive functioning. Twenty-eight children with SCD and 16 demographic controls completed magnetic resonance imaging (MRI) and neuropsychological testing. Corpus callosum (CC) size was smaller for children with silent infarcts (n = 8) or overt stroke (n = 8) than for those without visible infarcts (n = 12) or control participants. Lesion volume was a robust predictor of IQ and other cognitive scores; total CC size did not typically add explanatory power for these measures. The size of the rostral body of the CC, however, independently predicted measures of distractibility, speeded production, and working memory. Posterior CC size was also decreased among many of the children with SCD, even in the absence of visible infarcts in this region. Brain morphology appears to provide additional information about SCD-related effects on the brain above and beyond visible infarcts.     

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.     

Perspectives on Health Among Adult Users of Illicit Stimulant Drugs in Rural Ohio

CONTEXT: Although the nonmedical use of stimulant drugs such as cocaine and methamphetamine is increasingly common in many rural areas of the United States, little is known about the health beliefs of people who use these drugs. PURPOSE: This research describes illicit stimulant drug users' views on health and health-related concepts that may affect their utilization of health care services. METHODS: A respondent-driven sampling plan was used to recruit 249 not-in-treatment, nonmedical stimulant drug users who were residing in 3 rural counties in west central Ohio. A structured questionnaire administered by trained interviewers was used to collect information on a range of topics, including current drug use, self-reported health status, perceived need for substance abuse treatment, and beliefs about health and health services. FINDINGS: Participants reported using a wide variety of drugs nonmedically, some by injection. Alcohol and marijuana were the most commonly used drugs in the 30 days prior to the interview. Powder cocaine was used by 72.3% of the sample, crack by 68.3%, and methamphetamine by 29.7%. Fair or poor health status was reported by 41.3% of the participants. Only 20.9% of the sample felt they needed drug abuse treatment. Less than one third of the sample reported that they would feel comfortable talking to a physician about their drug use, and 65.1% said they preferred taking care of their problems without getting professional help. CONCLUSIONS: Stimulant drug users in rural Ohio are involved with a range of substances and hold health beliefs that may impede health services utilization.