A Pilot Randomized Trial Comparing CD-34Selected Versus Unmanipulated Hemopoietic Stem Cell Transplantation for Severe, Refractory Rheumatoid Arthritis

Objective. Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. Methods. Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. Results. All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. Conclusion. HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.

Koala mortality on roads in south-east Queensland: the koala speed-zone trial

In 1995, the Queensland Parks and Wildlife Service, the Queensland Department of Main Roads and Redland Shire Council initiated the Koala Speed Zone Trial in the Koala Coast, south-east Queensland. The aim of the trial was to assess the effect of differential speed signs on the number of koalas ( Phascolarctos cinereus) hit by vehicles in the Koala Coast from 1995 to 1999. On the basis of information collected by the Queensland Parks and Wildlife Service 1407 koalas were hit by vehicles in the Koala Coast during the five-year study ( mean 281 koalas per year, range 251 - 315). Monitoring of vehicle speeds by the Queensland Department of Main Roads suggested that there was no significant reduction in vehicle speed during the trial period from August to December. Consequently, there was no evidence to suggest that a reduction in the number of koalas hit by vehicles occurred during the trial. Approximately 70% of koalas were hit on arterial and sub-arterial roads and approximately 83% did not survive. The location of each koala hit was recorded and the signed speed limit of the road was noted. Most koalas that were hit by vehicles were young healthy males. Pooling of data on koala collisions and road speed limits suggested that the proportion of koalas that survived being hit by vehicles was slightly higher on roads with lower speed limits. However, vehicle speed was not the only factor that affected the number of koalas hit by vehicles. It is suggested that habitat destruction, koala density and traffic volume also contribute to road-associated koala mortality in the Koala Coast.

A randomised controlled trial of methadone maintenance treatment versus wait list control in an Australian prison system

Objectives: The aim was to determine whether methadone maintenance treatment reduced heroin use, syringe sharing and HIV or hepatitis C incidence among prisoners. Methods: All eligible prisoners seeking drug treatment were randomised to methadone or a waitlist control group from 1997 to 1998 and followed up after 4 months. Heroin use was measured by hair analysis and self report; drugs used and injected and syringe sharing were measured by self report. Hepatitis C and HIV incidence was measured by serology. Results: Of 593 eligible prisoners, 382 (64%) were randomised to MMT (n = 191) or control (n = 191). 129 treated and 124 control subjects were followed up at 5 months. Heroin use was significantly lower among treated than control subjects at follow up. Treated subjects reported lower levels of drug injection and syringe sharing at follow up. There was no difference in HIV or hepatitis C incidence. Conclusions: Consideration should be given to the introduction of prison methadone programs particular where community based programs exist. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Are thiazide diuretics preferred as first-line therapy for hypertension? An appraisal of The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

No Abstract

Development of a quality use of medicines coding system to rate clinical pharmacists' medication review recommendations

Objective: To develop a 'quality use of medicines' coding system for the assessment of pharmacists' medication reviews and to apply it to an appropriate cohort. Method: A 'quality use of medicines' coding system was developed based on findings in the literature. These codes were then applied to 216 (111 intervention, 105 control) veterans' medication profiles by an independent clinical pharmacist who was supported by a clinical pharmacologist with the aim to assess the appropriateness of pharmacy interventions. The profiles were provided for veterans participating in a randomised, controlled trial in private hospitals evaluating the effect of medication review and discharge counselling. The reliability of the coding was tested by two independent clinical pharmacists in a random sample of 23 veterans from the study population. Main outcome measure: Interrater reliability was assessed by applying Cohen's kappa score on aggregated codes. Results: The coding system based on the literature consisted of 19 codes. The results from the three clinical pharmacists suggested that the original coding system had two major problems: (a) a lack of discrimination for certain recommendations e. g. adverse drug reactions, toxicity and mortality may be seen as variations in degree of a single effect and (b) certain codes e. g. essential therapy were in low prevalence. The interrater reliability for an aggregation of all codes into positive, negative and clinically non-significant codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the sample of 216 profiles showed that the most prevalent recommendations from the clinical pharmacists were a positive impact in reducing adverse responses (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive impact in reducing drug toxicity (11.1%). Most medications were assigned the clinically non-significant code (96.6%). In fact, the interventions led to a statistically significant difference in pharmacist recommendations in the categories; adverse response, toxicity and good clinical pharmacy practice measured by the quality use of medicine coding system. Conclusion: It was possible to use the quality use of medicine coding system to rate the quality and potential health impact of pharmacists' medication reviews, and the system did pick up differences between intervention and control patients. The interrater reliability for the summarised coding system was fair, but a larger sample of medication regimens is needed to assess the non-summarised quality use of medicines coding system.

Reproducibility of a laboratory-based 40-km cycle time-trial on a stationary wind-trainer in highly trained cyclists

The purpose of the present study was to examine the reproducibility of laboratory-based 40-km cycle time-trial performance on a stationary wind-trainer. Each week, for three consecutive weeks, and on different days, forty-three highly trained male cyclists ((x) over bar +/- SD; age = 25 +/- 6 y; mass = 75 +/- 7 kg; peak oxygen uptake [(V) over dot O-2 peak] = 64.8 +/- 5.2 ml x kg(-1) x min(-1)) performed: 1) a (V) over dot O-2 peak test, and 2) a 40-km time-trial on their own racing bicycle mounted to a stationary wind-trainer (Cateye - Cyclosimulator). Data from all tests were compared using a one-way analysis of variance. Performance on the second and third 40-km time-trials were highly related (r = 0.96; p < 0.001), not significantly different (57:21 +/- 2:57 vs. 57:12 +/- 3:14 min:s), and displayed a low coefficient of variation (CV) = 0.9 +/- 0.7%. Although the first 40-km time-trial (58:43 +/- 3:17min:s) was not significantly different from the second and third tests (p = 0.06), inclusion of the first test in the assessment of reliability increased within-subject CV to 3.0 +/- 2.9%. 40-km time-trial speed (km x h(-1)) was significantly (p < 0.001) related to peak power output (W; r = 0.75), (V) over dot O-2 peak (1 x min(-1); r = 0.53), and the second ventilatory turnpoint (1 x min(-1); r = 0.68) measured during the progressive exercise tests. These data demonstrate that the assessment of 40-km cycle time-trial performance in well-trained endurance cyclists on a stationary wind-trainer is reproducible, provided the athletes perform a familiarization trial.

Effect of central venous catheter type on infections: a prospective clinical trial

This study reports on a block clinical trial of two types of central venous catheters (CVCs): antiseptic-impregnated catheters (AIC) and non-impregnated catheters (non-AIC), on catheter tip colonization and bacteraemia. In total, 500 catheters were inserted in 390 patients over the 18 month study period, 260 (52.0%) AIC and 240 (48.0%) non-AIC. Of these, 460 (92.0%) tips (237 AIC and 223 non-AIC) were collected. While significantly fewer AIC, 14 (5.9%), than non-AIC, 30 (13.5%), catheters were colonized (P < 0.01), there was no difference in the rates of bacteraemias in the two groups (0.8% vs. 2.7%, respectively, P = 0.16). There were 6.87 (95% CI 3.38-14.26) and 16.92 (95% CI 10.61-27.12) colonized AIC and non-AIC catheters, respectively, per 1000 catheter days, a difference that was significant (P < 0.01). However, no difference emerged between bacteraemias in AIC and non-AIC catheters per 1000 catheter days measured at 0.98 (95% CI 0.24-5.54) and 3.38 (95% CI 1.29-9.34), respectively (P = 0.10). Of the 444 CVCs that were sited in the subclavian or jugular veins and had tips collected, significantly more catheters were colonized in the jugular group, 19 (20%), compared with the subclavian group, 24 (6.9%; P less than or equal to 0.01). Overall, the low rates of colonization and bacteraemia may be explained by the population studied, the policies used and the employment of a clinical nurse dedicated to CVC management. (C) 2003 The Hospital Infection Society. Published by Elsevier Science Ltd. All rights reserved.

Prevalence of periodontal disease in dogs and owners' level of awareness - a prospective clinical trial

Periodontal disease (PD) is widely known among veterinarians for its high prevalence and serious consequences to the dogs. The objective of this study was to assess the occurrence of PD in dogs that live in the micro-region of Viçosa, treated at the Veterinary Hospital of the Federal University of Viçosa (HVT - Hospital Veterinário da Universidade Federal de Viçosa), as well as to assess how aware of this disease dog owners are. In order to do so, all dogs treated at the HVT from March 10th, 2009 to November 30th, 2009, on alternate days, had their oral cavities examined. Medical history data, such as age, type of food, main complaint and owner consent, halitosis, presence of dental calculus, inflammation and gingival recession and tooth loss, were collected. A prevalence of 88.67% was found for PD in dogs referred to the HVT, and 2.67% were referred due to this disease. Of all the owners who participated in the study, 43.83% knew about periodontal disease and of these 17.46% made use of some type of prevention or treatment. Therefore, periodontal disease is highly prevalent and the owners are not aware of the disease. Thus, a dog owner clarification program on periodontal disease is needed in the area where HVT-UFV operates.

Preliminary clinical trial in percutaneous nephrolithotomy using a real-time navigation system for percutaneous kidney access

Background: Precise needle puncture of renal calyces is a challenging and essential step for successful percutaneous nephrolithotomy. This work tests and evaluates, through a clinical trial, a real-time navigation system to plan and guide percutaneous kidney puncture. Methods: A novel system, entitled i3DPuncture, was developed to aid surgeons in establishing the desired puncture site and the best virtual puncture trajectory, by gathering and processing data from a tracked needle with optical passive markers. In order to navigate and superimpose the needle to a preoperative volume, the patient, 3D image data and tracker system were previously registered intraoperatively using seven points that were strategically chosen based on rigid bone structures and nearby kidney area. In addition, relevant anatomical structures for surgical navigation were automatically segmented using a multi-organ segmentation algorithm that clusters volumes based on statistical properties and minimum description length criterion. For each cluster, a rendering transfer function enhanced the visualization of different organs and surrounding tissues. Results: One puncture attempt was sufficient to achieve a successful kidney puncture. The puncture took 265 seconds, and 32 seconds were necessary to plan the puncture trajectory. The virtual puncture path was followed correctively until the needle tip reached the desired kidney calyceal. Conclusions: This new solution provided spatial information regarding the needle inside the body and the possibility to visualize surrounding organs. It may offer a promising and innovative solution for percutaneous punctures.

Effects of a randomized trial of exercise on body composition of liver transplanted patients

Liver transplantation is used as a only therapy so far, that stop the progression of some aspects of familial amyloidotic polyneuropathy disease (FAP) an autossomic neurodegenerative disease. FAP often results in severe functional limitations. Transplantation requires aggressive medication which impairs bone and muscle metabolism. Malnutrition plus weight loss is already one feature of FAP patients. All this may produce negative consequences on body composition. The effect of exercise training in FAP patients after a liver transplant (FAPTX) is currently unknown. The purpose of this study is to evaluate the effects of a six months exercise training program on body composition in FAPTX patients.