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PubMed2006

Reduced 6-month resource use and costs associated with cilostazol in patients after successful coronary stent implantation: results from the Cilostazol for RESTenosis (CREST) trial.

BACKGROUND: The CREST trial demonstrated that after successful coronary stent implantation, the 6-month rate of target vessel revascularization (TVR) was similar (15.4% vs 16%, P = .90) for the 2 treatment groups, but restenosis rate was lower (22.0% vs 34.5%, P = .002) in cilostazol-treated patients. We sought to evaluate resource use, cost, and cost-effectiveness of cilostazol in CREST. METHODS: A total of 705 patients were randomized to cilostazol 100 mg twice daily (n = 354) versus placebo (n = 351) for 6 months. Resources included rehospitalizations, medications, and outpatient services. Costs were determined from the Medicare fee schedule. Cilostazol was priced at 1.64 dollars a day. Base-case cost and cost-effectiveness analysis was performed for the entire population using TVR as a measure of effectiveness. Sensitivity analysis was conducted among 526 patients because restenosis data were available only for this patient population. A bootstrap resample approach (5000 samples) was used to obtain confidence intervals for cost differences. RESULTS: For the entire population, costs of rehospitalizations, concomitant medications, outpatient tests, and physician or emergency department visits were lower during follow-up for cilostazol-treated patients. Overall, total 6-month follow-up costs remained 447 dollars lower for cilostazol (4178 dollars vs 4625 dollars), although this difference did not reach significance (95% CI -1458 dollars to 515 dollars). Cilostazol is likely a cost-saving strategy (similar rate of TVR and lower costs). Sensitivity analysis showed that cilostazol is likely a dominant strategy (lower restenosis rate and costs, 85% dominant, 88.9% <1000 dollars per restenosis averted). CONCLUSIONS: Treatment with cilostazol is likely a cost-saving or dominant strategy in patients with successful coronary bare metal stent implantation. Cilostazol may offer a low-cost alternative to restenosis prevention in patients who do not receive drug-eluting stents.

Adult↗
PubMed2001

Two-dimensional analysis of tear protein patterns of diabetic patients.

In diabetic patients, dry eye and other ocular surface diseases occur more often than in healthy subjects. The aim of this study was to analyze the tear protein patterns of patients suffering from diabetes mellitus type II (dia) and to compare them to the patterns of healthy volunteers (ctrl). Tear proteins of nonstimulated tears of 20 patients (ctrl n=10, dia n=10) were separated using two-dimensional electrophoretic techniques. The protein patterns of each group were analyzed by a multivariate analysis of discriminance. Furthermore, for all spots of each gel, a 50 x 50 variables pH/Mr (molecular weight) array was generated and subsequently analyzed by a multivariate analysis of discriminance. Additionally, an artificial neural network was trained using the matrix data as input and a sensitivity analysis was performed to figure out, which spots were the most important to differentiate between the tear protein patterns. In both groups a complex staining pattern could be obtained. In diabetic patients significantly more spots were detected compared to the control group (P<0.02). The analysis of discriminance found a highly significant difference between dia and ctrl (P<0.00001). Using the matrix data, the analysis of discriminance showed a significant difference between the two groups, too (P<0.0001). The sensitivity analysis by means of the artificial neural network revealed several spots that were more expressed or more frequently present in the diabetic group. Our findings reveal that the composition of tear proteins of diabetic patients is different from that of healthy subjects. The use of the two-dimensional electrophoretic technique could give more insight into the diabetic-related changes in the tear film composition.

Adult↗
PubMed2005

Persistence, switching, and discontinuation rates among patients receiving sertraline, paroxetine, and citalopram.

STUDY OBJECTIVE: To compare persistence, switching, and discontinuation rates among patients taking brand-name selective serotonin reuptake inhibitors (SSRIs). DESIGN: Retrospective cohort study. Data Source. Protocare Sciences managed care database. PATIENTS: A total of 14,933 patients with depression, posttraumatic stress disorder, or social anxiety disorder whose prescriptions for brand-name SSRIs were filled from January 1, 1999-June 30, 2002. MEASUREMENTS AND MAIN RESULTS: A total of 5598 patients received sertraline, 4131 citalopram, and 5204 paroxetine. Adherence status was categorized as persistence, switching (from one SSRI to another SSRI), and discontinuation. Persistence was determined based on the number of days' supply of the prescribed drug, with a minimum of 15 days to refill. Survival analyses using life-table survival curves and Cox proportional hazard models were conducted. Age, sex, and copayment were covariates in the Cox proportional models. Sensitivity analysis with a longer time to refill was performed to determine whether the results were sensitive to the algorithm for determining adherence. Compared with patients receiving sertraline and citalopram, those receiving paroxetine had lower rates of persistence (23.79% vs 25.96% for sertraline [p = 0.0093] and 26.56% for citalopram [p = 0.0022]) and higher rates of switching (3.55% vs 3.32% for sertraline [p = 0.5076] and 2.78% for citalopram [p = 0.0359]) and discontinuation (72.66% vs 70.72% for sertraline [p = 0.0258] and 70.66% for citalopram [p = 0.0334]). Survival curves showed that persistence rates with sertraline and citalopram were significantly greater than with paroxetine (p<0.05, log-rank and Wilcoxon tests). Age was an independent predictor of persistence; male sex and copayment were not. The comparisons across SSRIs were robust in the sensitivity analysis that varied the time to refill allowed. CONCLUSION: Differences in the persistence rates were noted among patients receiving three brand-name SSRIs, with patients receiving paroxetine having lower persistence than those receiving sertraline and citalopram. Observed differences in persistence across SSRIs were not sensitive to model specifications. Prescription of SSRIs that demonstrate better adherence would benefit both the patient and the health care system.

Adolescent↗
PubMed1999

Kinetic model of biosurfactant-enhanced hexadecane biodegradation by Pseudomonas aeruginosa.

Many sites of environmental concern contain groundwater contaminated with nonaqueous phase liquids (NAPL). In such sites interfacial processes may affect both the equilibrium and kinetic behavior of the system. In particular, insoluble hydrocarbon partitioning and microbial biodegradation of insoluble hydrocarbon are influenced by the physicochemical and interfacial characteristics of the system. A mechanistic model describing the influence of biological surfactants on microbial biodegradation of liquid-phase insoluble hydrocarbon and subsequent reduction of nonaqueous-phase liquid hydrocarbon is presented. The model consists of six coupled differential equations which use lumped kinetic parameters to describe surfactant micelle formation and diffusion to the microbial cell, nonlinear kinetic expressions for microbial growth and degradation of insoluble hydrocarbon, kinetic spatial descriptions of the change in NAPL-phase droplet size and the organic phase volume fraction with time, as well as equilibrium partitioning expressions for hydrophobic organic contaminant partioning into the surfactant micelle. The model is validated by comparison to data obtained for hexadecane degradation in a well-mixed batch system by the biosurfactant producing microorganism Pseudomonas aeruginosa strain PG201 as well as for nonproducing mutants' growth and hexadecane biodegradation in the presence of exogenously added biosurfactant. Experimentally determined biological growth parameters, as well as physical parameters such as hydrocarbon droplet size, were applied in the kinetic model. Parameter sensitivity analysis was performed on the physical and biological parameters in the model. The parameter sensitivity analysis indicates that for the biological system examined the rate of hydrocarbon solubilization and micellar transport to the cell controls the rate at which cellular uptake and biodegradation of insoluble hydrocarbon occurs. Practical aspects relating to use of the model for support of surfactant-based bioremediation efforts are discussed.

Alkanes↗
PubMed2000

Development of a microscale emission factor model for CO for predicting real-time motor vehicle emissions.

The U.S. Environmental Protection Agency's (EPA) National Exposure Research Laboratory has initiated a project to improve the methodology for modeling human exposure to motor vehicle emissions. The overall project goal is to develop improved methods for modeling the source through the air pathway to human exposure in significant microenvironments of exposure. This paper presents the technical description of a newly developed model for CO emissions. The sensitivity analysis and evaluation of this emission model is presented in a companion paper titled "Sensitivity Analysis and Evaluation of MicroFacCO: A Microscale Motor Vehicle Emission Factor Model for CO Emissions." The MOBILE models (used in the United States, except California) and EMFAC models (used in California only) used to estimate emissions are suitable for supporting mostly regional (county)-scale modeling and emission inventory because of their dependence on vehicle-miles-traveled aggregate data. These emission models are not designed to estimate real-time emissions needed for human exposure studies near roadways. A number of independent studies have found that current mobile source emission factor models are not very reliable at estimating microscale emissions and are, therefore, inappropriate for use with microscale modeling necessary to estimate human exposures near roadways. A microscale emission factor model for predicting real-world real-time motor vehicle CO emissions (MicroFacCO) has been developed. It uses available information on the vehicle fleet composition. The algorithm used to calculate emission factors in MicroFacCO is disaggregated based on the on-road vehicle fleet. The emission factors are calculated from a real-time fleet rather than from a fleet-wide average estimated by a vehicle-miles-traveled weighting of the emission factors for different vehicle classes. MicroFacCO uses the same database used to develop the MOBILE6 model. As compared with MOBILE emission models, MicroFacCO requires only a few input variables, which are necessary to characterize the real-time fleet being modeled. The main input variables required are on-road vehicle fleet, time and day of year, ambient temperature, and relative humidity.

Carbon Monoxide↗
PubMed2001

Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children.

BACKGROUND: Oral rehydration solution (ORS) has reduced childhood deaths from diarrhoea in many countries. Recent studies suggest that the currently recommended formulation of ORS recommended by the World Health Organization (WHO) may not be optimal, and solutions that contain lower concentrations of sodium and glucose may be more effective. OBJECTIVES: In children with acute diarrhoea, to compare reduced osmolarity glucose-based oral rehydration salt solution with international WHO formulation. SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional trials were identified by hand searching. Content experts were contacted. SELECTION CRITERIA: Randomised controlled trials comparing reduced osmolarity ORS solution with the WHO formulation. Outcomes sought were unscheduled intravenous fluid infusion therapy and measures of clinical illness. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers. We tested for heterogeneity using the chi-square statistic, conducted sensitivity analysis by allocation concealment, and the regression approach to assess funnel plot asymmetry from selective trial publication. MAIN RESULTS: The primary outcome was reported in 12 trials. In a meta-analysis of nine trials, reduced osmolarity ORS was associated with fewer unscheduled infusions compared with standard WHO ORS (Mantel Haenzel odds ratio 0.61, 95% confidence interval 0.47 to 0.81) with no evidence for heterogeneity between trials. No unscheduled intravenous fluid infusion therapy was required in any participant in three trials. Thirteen trials reported stool output, and data suggested less stool output in the reduced osmolarity ORS group. Vomiting was less frequent in the reduced osmolarity group in the six trials reporting this. Six trials sought hyponatraemia, with events in three studies, but no obvious difference between the two arms. REVIEWER'S CONCLUSIONS: In children admitted to hospital with diarrhoea, reduced osmolarity ORS when compared to WHO ORS is associated with fewer unscheduled intravenous infusions, smaller stool volume post randomisation, and less vomiting. No additional risk of developing hyponatraemia when compared with WHO ORS was detected.

Bicarbonates↗
PubMedDate not supplied

CT pulmonary angiography in the detection of pulmonary emboli: a meta-analysis of sensitivities and specificities.

OBJECTIVE: To determine the overall sensitivity and specificity for CT pulmonary angiography (CTPA) in the diagnosis of pulmonary emboli (PE) using a meta-analysis of the published literature. MATERIALS AND METHODS: A Medline search was constructed to include all English language publications indexed in the Index Medicus from 1990 to 2000, which included the terms CT, PE and pulmonary angiography. Studies selected were designed principally to compare CTPA in the overall detection of PE as confirmed by an abnormal fluoroscopic pulmonary angiogram or a high probability V:Q scan. Results were corrected for the patient sample size in the respective studies prior to pooling the data. In the absence of an accepted technique for calculating a ROC curve in the meta-analysis of imaging studies, a previously untested theoretical technique was used to obtain a composite ROC curve. RESULTS: Twelve studies of CTPA comprising a total of 1250 patients were analyzed. The overall sensitivity and specificity for CTPA after correction for study size was 74.1% and 89.5% with a range of 57-100% and 68-100%, respectively, for the detection of PE. No trend was detected with respect to the year of publication or sample size. CONCLUSIONS: CTPA has acceptable sensitivity and specificity with a strong ROC curve making it a good first line investigation for PE.

Angiography↗
PubMed1995

Highly sensitive chiral analysis in on-line combined chiral and achiral media by capillary zone electrophoresis.

A new approach is described for highly sensitive chiral analyses by capillary zone electrophoresis, based on using an on-line combination of two capillaries filled with either chiral selective or achiral background electrolytes (BGE). Thus, the BGEs are selected in such a way that the first capillary provides optimum chiral selectivity and the second one optimum detection sensitivity. Direct chiral separations of enantiomers of mandelic, m-methoxymandelic, 3-phenyllactic and 3-indolelactic acids served as a model example for testing the approach proposed. The analyses were performed in a BGE containing acetate as a coion and L-OH-proline or aspartame as a chiral selector. For high sensitive analyses, an arrangement containing on-line combined chiral and achiral media were tested in one or two capillaries coupled via a bifurcation block. A detection limit as low as 10(-18) moles was reached in the column-coupling system when the direct chiral separation was performed in the first capillary, filled with 20 mM acetate buffer, pH 4.4, containing 8 mM Cu (II) and 16 mM aspartame (L-aspartyl-L-phenylalanine methylester) and separated enantiomers were detected in the second capillary, filled with 20 mM acetate buffer, pH 3.1. The principle described is of general use in cases where the separation and detection of analytes in question require mutually different BGEs to reach the optimum selectivity and sensitivity, respectively.

Aspartame↗
PubMed1976

Automated amino acid analysis with sensitive fluorescence detection.

The fluorigenic o-phthalaldehyde-mercaptoethanol reagent gives good reproducibility with a very stable baseline when applied to the automated analysis of amino acids at the nanomole level. Determination of even smaller quantities is possible; basic amino acids are then preferably eluted separately at constant pH (for example pH 6.0); this eliminates the baseline irregularities that occur with single column systems at high sensitivity settings. The reagent gives excellent results in the assay of small quantities of biological fluids such as blood plasma.

Aldehydes↗
PubMed2001

Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials.

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

Anemia↗
PubMed2005

Orlistat for the treatment of obesity: cost utility model.

This study aimed to assess the cost utility of orlistat treatment based on (i) criteria from recent guidance from the National Institute for Clinical Excellence (NICE) for England and Wales (treatment discontinued if weight loss < 5% at 3 months; and < 10% at 6 months); and (ii) alternative criteria from the European Agency for the Evaluation of Medicinal Products (EMEA) licence for orlistat prescription in the European Community (treatment discontinued if weight loss < 5% at 3 months). Subjects were 1398 obese individuals who participated in three large European Phase III trials of orlistat treatment for adults (BMI: 28-47 kg m(-2)). Measures were: response to treatment in orlistat and placebo treatment groups; health benefit expressed as quality adjusted life years (QALYs) gained associated with weight loss; costs associated with orlistat treatment. In the cost utility model with multiway sensitivity analysis, the cost/QALY gained using the NICE criteria was estimated to be 24,431 pounds (sensitivity analysis range: 10,856 to 77,197 pounds). The cost/QALY gained using the alternative EMEA criteria was estimated to be 19,005 pounds (range: 8,840 to 57,798 pounds). In conclusion, NICE guidance for the continued use of orlistat was supported in this updated cost utility model, comparing favourably with a previously published estimate of 45,881 pounds per QALY gained. Moreover, the value for money of orlistat treatment is improved further if EMEA treatment criteria for continued orlistat treatment are applied. The EMEA criteria should be considered in any future changes to the NICE guidance or in guidance issued by similar agencies.

Anti-Obesity Agents↗
PubMed2000

Cost-effectiveness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy in older patients with myocardial infarction.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has proven efficacy in reducing the rate of coronary and cerebrovascular events in patients 75 years of age or younger with a history of myocardial infarction. However, in patients older than 75 years of age, the efficacy and potential cost-effectiveness of statins are unknown. OBJECTIVE: To estimate the incremental cost-effectiveness of statin therapy compared with usual care in patients 75 to 84 years of age with previous myocardial infarction. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Published data from cohort studies. TARGET POPULATION: Patients 75 to 84 years of age with a history of myocardial infarction. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Statin therapy. OUTCOME MEASURES: Life expectancy, quality-adjusted life expectancy, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: The incremental cost-effectiveness of statin therapy compared with usual care in patients 75 to 84 years of age with previous myocardial infarction was $18800 per quality-adjusted life-year (QALY). RESULTS OF SENSITIVITY ANALYSIS: On the basis of a probabilistic sensitivity analysis, there is a 75% chance that statin therapy costs less than $39800 per QALY compared with usual care. If the cost of statin therapy and efficacy of statin therapy at reducing myocardial infarction were set to their most favorable values, statin therapy cost $5400 per QALY; if cost and efficacy were set to their least favorable values, statin therapy cost $97800 per QALY. CONCLUSIONS: The cost-effectiveness ratios of statin therapy in older patients with previous myocardial infarction are reasonable under a wide variety of assumptions about drug efficacy, drug cost, and rates of cardiac and cerebrovascular events. Pending results of randomized, controlled trials of secondary prevention in patients in this age group, statin therapy seems to be as cost-effective as many routinely accepted medical interventions in this setting.

Aged↗
PubMed2006

Fast and sensitive environmental analysis utilizing microextraction in packed syringe online with gas chromatography-mass spectrometry: determination of polycyclic aromatic hydrocarbons in water.

A new sensitive, selective, fast and accurate technique for online sample preparation was developed. Microextraction in a packed syringe (MEPS) is a new miniaturised, solid-phase extraction (SPE) technique that can be connected online to GC or LC without any modifications. In MEPS approximately 1mg of the solid packing material is inserted into a syringe (100-250 ml) as a plug. Sample preparation takes place on the packed bed. The bed can be coated to provide selective and suitable sampling conditions. The new method is very promising. It is very easy to use, fully automated, of low cost and rapid in comparison with previously used methods. The determination of polycyclic hydrocarbons (PAHs) in water was performed using MEPS as sample preparation method online with gas chromatography and mass spectrometry (MEPS-GC-MS). The results from MEPS as sample preparation were compared with other techniques such as stir bar sorptive extraction (SBSE) and solid-phase microextraction (SPME). The method was validated and the standard curves were evaluated by the means of quadratic regression and weighted by inverse of the concentration: 1/x for the calibration range 5-1,000 ng/L. The MEPS applied polymer (silica-C8) could be used more than 400 times before the syringe was discarded. The extraction recovery was about 70%. The results showed close correlation coefficients (R>0.998) for all analytes in the calibration range studied. The accuracy of MEPS-GC-MS was between 90 and 113% and the inter-day precision (n=3 days), expressed as the relative standard deviation (RSD%), was 8-16%. MEPS reduced the handling time by 30 and 100 times compared to SPME and SBSE, respectively.

Gas Chromatography-Mass Spectrometry↗
PubMed2004

Azithromycin for acute lower respiratory tract infections.

BACKGROUND: The spectrum of acute lower respiratory tract infection ranges from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Annually approximately five million people die of acute respiratory tract infections. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Azithromycin is a new macrolide antibiotic, structurally modified from erythromycin and is noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae). OBJECTIVES: To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to January Week 3, 2004), and EMBASE (January 1988 to 2003). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials, which compared azithromycin to amoxycillin or amoxycillin/clavulanic acid in patients with clinical evidence of acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic bronchitis were studied. DATA COLLECTION AND ANALYSIS: The criteria for assessing study quality were generation of allocation sequence, concealment of treatment allocation, blinding, and completeness of the trial. All types of acute lower respiratory tract infections were initially pooled in the meta-analyses. Funnel plot was used to examine publication bias. The heterogeneity of results was investigated by the forest plot and Chi-square test. Index of I(2) was also used to measure inconsistency results among trials. Subgroup analysis was conducted for age, types of respiratory tract infection and types of antibiotic in control groups. Sensitivity analysis was conducted under the condition of trial size and concealment of treatment allocation. MAIN RESULTS: Fourteen trials with 2,521 enrolled patients used 2,416 patients in the analysis. A total of 1,350 patients received azithromycin and 1,066 received amoxicillin or amoxicillin-clavulanic acid. The pooled analysis of all trials showed that there was no significant difference in the incidence of clinical failure on about day 10 to 14 after therapy started between the two groups (relative risk (RR) (random effects) 0.96; 95% CI 0.58 to 1.57). Sensitivity analysis showed that a reduction of clinical failure in azithromycin-treated patients (RR 0.52; 95% CI 0.24 to 1.12) in three adequately concealed studies, compared to RR 1.14 (95% CI 0.62 to 2.08) in eleven studies with inadequate concealment. Eleven trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.98; 95% CI 0.91 to 1.07). The reduction of adverse events in azithromycin group was RR 0.75 (95% CI 0.56 to 1.00). REVIEWERS' CONCLUSIONS: There is unclear evidence that azithromycin is superior to amoxicillin or amoxicillin-clavulanic acid in treating acute LRTI. Future trials with high methodological quality are needed.

Acute Disease↗
PubMed1998

Application of micro-electrospray liquid chromatography techniques to FT-ICR MS to enable high-sensitivity biological analysis.

A microbore electrospray (ESI) injection system has been adapted to our 9.4-tesla ESI FT-ICR mass spectrometer, greatly enhancing the stability and sensitivity of the system. Spray was generated from micro-ESI needles made from sharply tapered, polished fused silica capillaries of 25 to 50 microns inner diameter. Micro-ESI permits low-level sample analysis by constant infusion at sub-microL/min flow rate over a wide range of solvent conditions in both positive- and negative-ion mode. The system is flexible and allows rapid conversion to allow routine LC/MS analysis on low-level mixtures presented in biological media. LC/MS analyses were accomplished by replacing micro-ESI needles with capillaries packed with reverse phase retention media to permit analyte concentration and purification prior to analysis (micro-ESI/LC). A unique nano-flow LC pumping system was developed, capable of producing a true unsplit solvent gradient at flow rates below 1 microL/min. The micro-ESI/LC FT-ICR system produces mass spectra from a mixture of three neuroactive peptides at a concentration of 500 amol/microL (5 fmol each total loaded) in biological salts with baseline separation, signal-to-noise ratio of > 10:1 and mass resolving power > 5000. These results represent a reduction in detection limit by a factor of approximately 2 x 10(6) over the best previously published LC/FT-ICR MS data.

Endorphins↗
PubMed2003

[Bacteremia due to Escherichia coli: epidemiological analysis and sensitivity to antibiotics in a county hospital].

BACKGROUND AND OBJECTIVE: There are few studies analyzing the epidemiological characteristics of Escherichia coli bacteremia including the susceptibility to antibiotics and outcome. PATIENTS AND METHOD: E. coli bacteremia episodes were recorded from January 1989 to December 1998. Clinical variables, setting acquisition, source of bacteremia, outcome and susceptibility to antibiotics were included. The study was prospective and comparative. Descriptive and univariate analysis were performed. RESULTS: 330 episodes of E. coli bacteremia were recorded: 117 in women. The most frequent source was the urinary tract (68%), followed by an abdominal and biliary focus. E. coli bacteremia appeared mostly in groups II and III of McCabe & Jackson. In 46 cases (14%), E. coli bacteremia was nosocomial. Crude and related mortality was 6.6 and 4.2%, respectively. A significant increase in the resistance to ciprofloxacin was observed. CONCLUSIONS: The epidemiological characteristics of E. coli bacteremia have not changed, yet the mortality was lower in our series. Preventive measures in the hospital and a rational use of antibiotics, principally quinolones, are necessary.

Anti-Bacterial Agents↗
PubMed2006

The long-term cost effectiveness of treatments for benign prostatic hyperplasia.

INTRODUCTION: Excellent treatment outcomes with long-term durability and few adverse effects are expectations of treatments for chronic conditions. The long-term cost effectiveness of newer treatments for benign prostatic hyperplasia (BPH), including high-energy transurethral microwave thermotherapy (TUMT) and combination pharmaceutical therapy, has not been sufficiently studied against existing alternatives. The objective of this study was to estimate the incremental cost effectiveness of BPH treatment alternatives. METHODS: We employed a Markov model over a 20-year time horizon and the payer's perspective to evaluate the cost effectiveness of watchful waiting (WW), pharmaceuticals (alpha-adrenoceptor antagonists [alpha-blockers], 5-alpha-reductase inhibitors [5-ARIs], combination therapy), TUMT and transurethral resection of the prostate (TURP) in treating BPH. Markov states included improvement in symptoms, no improvement in symptoms, adverse effects and death. We used data from the published literature for outcomes, including systematic reviews whenever possible. Costs were estimated using a managed-care claims database and Medicare fee schedules, and were reported in Dollars US, 2004 values. Costs and effectiveness outcomes were discounted at a rate of 3% per year. Men (aged > or =45 years) with moderate to severe lower urinary tract symptoms and uncomplicated BPH were included in the analysis, and results were stratified by age and BPH symptom levels. Outcomes included costs, QALYs, incremental cost-utility ratios and cost-effectiveness acceptability curves. Sensitivity analysis was performed on important parameters, with an emphasis on probabilistic sensitivity analysis. RESULTS: alpha-Blockers and TUMT were cost effective for treating moderate symptoms using the threshold of Dollars US 50,000 per QALY. For example, at 65 years of age, the cost per QALY was Dollars US 16,018 for alpha-blockers compared with WW and Dollars US 30,204 for TUMT versus alpha-blockers. TURP was the most cost-effective treatment for severe symptoms (Dollars US 5824 per QALY ) versus WW. Model results were robust to changes in costs and sensitive to the assumed probabilities, utility weights, extent of improvement and life expectancy. Nevertheless, acceptability curves consistently demonstrated the same alternatives as most likely to be cost effective. CONCLUSIONS: Our model suggests that alpha-blockers and TURP appear to be the most cost-effective alternatives, from a US payer perspective, for BPH patients with moderate and severe symptoms, respectively. TUMT was promising for patients with moderate symptoms and the oldest patients with severe symptoms, but otherwise was dominated. Value of information analysis could be used to determine the net benefit of additional research.

Adrenergic alpha-Antagonists↗