Assessing cost-effectiveness - Mental health: introduction to the study and methods

Objective: The Assessing Cost-Effectiveness - Mental Health (ACE-MH) study aims to assess from a health sector perspective, whether there are options for change that could improve the effectiveness and efficiency of Australia's current mental health services by directing available resources toward 'best practice' cost-effective services. Method: The use of standardized evaluation methods addresses the reservations expressed by many economists about the simplistic use of League Tables based on economic studies confounded by differences in methods, context and setting. The cost-effectiveness ratio for each intervention is calculated using economic and epidemiological data. This includes systematic reviews and randomised controlled trials for efficacy, the Australian Surveys of Mental Health and Wellbeing for current practice and a combination of trials and longitudinal studies for adherence. The cost-effectiveness ratios are presented as cost (A$) per disability-adjusted life year (DALY) saved with a 95% uncertainty interval based on Monte Carlo simulation modelling. An assessment of interventions on 'second filter' criteria ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') allows broader concepts of 'benefit' to be taken into account, as well as factors that might influence policy judgements in addition to cost-effectiveness ratios. Conclusions: The main limitation of the study is in the translation of the effect size from trials into a change in the DALY disability weight, which required the use of newly developed methods. While comparisons within disorders are valid, comparisons across disorders should be made with caution. A series of articles is planned to present the results.

Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective: To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to 'current practice'. Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria ('equity'; 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6-17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios. Results: Compared to current practice, CBT by public psychologists is the most cost-effective intervention for MDD in children and adolescents at A$9000 per DALY saved (95% UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders. Conclusions: Cognitive behavioural therapy provided by a public psychologist is the most effective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require 'start-up' costs and attention to ensuring an adequate workforce.

Cost-effectiveness of dexamphetamine and methylphenidate for the treatment of childhood attention deficit hyperactivity disorder

Objective: To analyze from a health sector perspective the cost-effectiveness of dexamphetamine (DEX) and methylphenidate (MPH) interventions to treat childhood attention deficit hyperactivity disorder (ADHD), compared to current practice. Method: Children eligible for the interventions are those aged between 4 and 17 years in 2000, who had ADHD and were seeking care for emotional or behavioural problems, but were not receiving stimulant medication. To determine health benefit, a meta-analysis of randomized controlled trials was performed for DEX and MPH, and the effect sizes were translated into utility values. An assessment on second stage filter criteria ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Simulation modelling techniques are used to present a 95% uncertainty interval (UI) around the incremental cost-effectiveness ratio (ICER), which is calculated in cost (in A$) per DALY averted. Results: The ICER for DEX is A$4100/DALY saved (95% UI: negative to A$14 000) and for MPH is A$15 000/DALY saved (95% UI: A$9100-22 000). DEX is more costly than MPH for the government, but much less costly for the patient. Conclusions: MPH and DEX are cost-effective interventions for childhood ADHD. DEX is more cost-effective than MPH, although if MPH were listed at a lower price on the Pharmaceutical Benefits Scheme it would become more cost-effective. Increased uptake of stimulants for ADHD would require policy change. However, the medication of children and wider availability of stimulants may concern parents and the community.

Electrocatalytic oxidation of ethanol on Sn((1-x))Ir((x))O(2) electrodes in acid medium

The electrochemical oxidation of ethanol at Sn((1-x))Ir (x) O(2) electrodes (with x = 0.01, 0.05, 0.1 and 0.3) was studied in 0.1 mol L(-1) HClO(4) solution. Electrolysis experiments were carried out and the reaction products were analyzed by Liquid Chromatography. It was found that the amounts of the reaction products depended on the composition of the electrode. In situ infrared reflectance spectroscopy measurements were performed to identify the adsorbed intermediates and to postulate a reaction mechanism for ethanol electrooxidation on these electrode materials. As evidence, acetaldehyde and acetic acid were formed through a successive reaction process. Carbon dioxide was also identified as the end product, showing that the cleavage of the carbon-carbon bond occurred. These results indicate that the synthesized catalysts are able to lead to the total combustion of organic compounds. Analysis of the water bending band at different potentials illustrated its role at the electrode interface.

Fast-convergent iterative scheme for filtering velocity signals and finding Kolmogorov scales

The present fundamental knowledge of fluid turbulence has been established primarily from hot- and cold-wire measurements. Unfortunately, however, these measurements necessarily suffer from contamination by noise since no certain method has previously been available to optimally filter noise from the measured signals. This limitation has impeded our progress of understanding turbulence profoundly. We address this limitation by presenting a simple, fast-convergent iterative scheme to digitally filter signals optimally and find Kolmogorov scales definitely. The great efficacy of the scheme is demonstrated by its application to the instantaneous velocity measured in a turbulent jet.

A dangerous entanglement

Entrapment of guidewires by inferior vena cava filters can occur during the blind insertion of a jugular or a subclavian central venous catheter. Recently, few case reports have been published in the radiology literature. In addition, others have described endovascular techniques aimed at removing entrapped guidewires, avoiding the possibility of vena cava rupture. Given that a temporary hemodialysis venous catheter is frequently used as a first access, the possibility of entrapping the dialysis catheter guidewire should not be neglected.

Image reconstruction affects computer tomographic assessment of lung hyperinflation

Objectives: Lung hyperinflation may be assessed by computed tomography (CT). As shown for patients with emphysema, however, CT image reconstruction affects quantification of hyperinflation. We studied the impact of reconstruction parameters on hyperinflation measurements in mechanically ventilated (MV) patients. Design: Observational analysis. Setting: A University hospital-affiliated research Unit. Patients: The patients were MV patients with injured (n = 5) or normal lungs (n = 6), and spontaneously breathing patients (n = 5). Interventions: None. Measurements and results: Eight image series involving 3, 5, 7, and 10 mm slices and standard and sharp filters were reconstructed from identical CT raw data. Hyperinflated (V-hyper), normally (V-normal), poorly (V-poor), and nonaerated (V-non) volumes were calculated by densitometry as percentage of total lung volume (V-total). V-hyper obtained with the sharp filter systematically exceeded that with the standard filter showing a median (interquartile range) increment of 138 (62-272) ml corresponding to approximately 4% of V-total. In contrast, sharp filtering minimally affected the other subvolumes (V-normal, V-poor, V-non, and V-total). Decreasing slice thickness also increased V-hyper significantly. When changing from 10 to 3 mm thickness, V-hyper increased by a median value of 107 (49-252) ml in parallel with a small and inconsistent increment in V-non of 12 (7-16) ml. Conclusions: Reconstruction parameters significantly affect quantitative CT assessment of V-hyper in MV patients. Our observations suggest that sharp filters are inappropriate for this purpose. Thin slices combined with standard filters and more appropriate thresholds (e.g., -950 HU in normal lungs) might improve the detection of V-hyper. Different studies on V-hyper can only be compared if identical reconstruction parameters were used.

An Inhalation Chamber Model for Controlled Studies of Tobacco Smoke Toxicity in Rodents

Introduction: Smoking is a serious worldwide public health problem. Animal models act as a bridge between laboratory and human studies. The models applied are difficult to reproduce because of the use of different types of inhalation chambers and mainly because of the lack of continuous monitoring of smoke concentration. Objective: To develop an inhalation chamber for rats (with only the nose exposed) in which the amount of carbon monoxide (CO) can be maintained and monitored constantly. Material and methods: Male Wistar rats weighing 250 g were exposed to 50 ppm CO produced by the smoke from a filter-free cigarette. The animals were submitted to a single 2-h exposure and then sacrificed at 0, 4, 24 and 48 h. The control group was left restrained inside the small perpendicular chambers, receiving only 5 L/min of compressed air. Results: The model was able to increase HbCO levels immediately after the end of exposure (p < 0.001). with a decrease being observed from 2 h onwards when compared to the levels of the control group. Plasma cotinine increased immediately after exposure, and showed still detectable levels at 2 and 4 h (p < 0.05). Conclusion: We conclude that the presented inhalation chamber system is able to maintain a controlled CO concentration in a model in which small animals are exposed to the inhalation of cigarette smoke, permitting well-controlled studies, as well as investigations involving other toxic gases and air pollutants. (C) 2008 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.

The time course of vasoconstriction and endothelin receptor A expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution

The present study aimed to verify the time course of the effects of environmental levels of urban air pollution toxicity on lung arterioles. BALB/c mice (n = 56) were continuously exposed to selective chambers equipped with (filtered, F) or without (non-filtered, NF) filter devices for particles and toxic gases for 24 h/day, over 14, 21, 30 or 45 days. After exposure, we evaluated the lumen-wall relationship (an estimator of arteriolar narrowing), endothelial nitric oxide synthase (eNOS) and endothelin type A receptor (ETAr) expression in the vascular wall and inflammatory influx of the peribronchiolar area. Concentrations of fine particulate matter (PM <= 2.5 mu g/m(3)), nitrogen dioxide (NO(2)), black smoke (BS), humidity and temperature in both the environment and inside the chambers were measured daily. Filters cleared 100% of BS and 97% of PM inside the F chamber. The arteriole wall of the lungs of mice from NF chamber had an increased ETAr expression (p <= 0.042) concomitant to a decrease in the lumen/wall ratio (p = 0.02) on the early days of exposure, compared to controls. They also presented a progressive increment of inflammatory influx in the peribronchiolar area during the study (p = 0.04) and decrement of the eNOS expression on the 45th day of exposure in both vascular layers (p <= 0.03). We found that after 14 days of exposure, the ambient levels of air pollutants in Sao Paulo induced vasoconstriction that was associated with an increase in ETAr expression. These vascular results do not appear to be coupled to the progressive inflammatory influx in lung tissue, suggesting a down-regulation of vasoconstrictive mechanisms through an imbalance in the cytokines network. It is likely that these responses are protective measures that decrease tissue damage brought about by continuous exposure to air pollutants. (C) 2010 Elsevier Inc. All rights reserved.

Applying linear time-varying constraints to econometric models: With an application to demand systems

When linear equality constraints are invariant through time they can be incorporated into estimation by restricted least squares. If, however, the constraints are time-varying, this standard methodology cannot be applied. In this paper we show how to incorporate linear time-varying constraints into the estimation of econometric models. The method involves the augmentation of the observation equation of a state-space model prior to estimation by the Kalman filter. Numerical optimisation routines are used for the estimation. A simple example drawn from demand analysis is used to illustrate the method and its application.

Measuring macromolecular diffusion using heteronuclear multiple-quantum pulsed-field-gradient NMR

We have previously shown that H-1 pulsed-field-gradient (PFG) NMR spectroscopy provides a facile method for monitoring protein self-association and can be used, albeit with some caveats, to measure the apparent molecular mass of the diffusant [Dingley et al. (1995) J. Biomol. NMR, 6, 321-328]. In this paper we show that, for N-15-labelled proteins, selection of H-1-N-15 multiple-quantum (MQ) coherences in PFG diffusion experiments provides several advantages over monitoring H-1 single-quantum (SQ) magnetization. First, the use of a gradient-selected MQ filter provides a convenient means of suppressing resonances from both the solvent and unlabelled solutes. Second, H-1-N-15 zero-quantum coherence dephases more rapidly than H-1 SQ coherence under the influence of a PFG. This allows the diffusion coefficients of larger proteins to be measured more readily. Alternatively, the gradient length and/or the diffusion delay may be decreased, thereby reducing signal losses from relaxation. In order to extend the size of macromolecules to which these experiments can be applied, we have developed a new MQ PFG diffusion experiment in which the magnetization is stored as longitudinal two-spin order for most of the diffusion period, thus minimizing sensitivity losses due to transverse relaxation and J-coupling evolution.

PM(2.5) and PM(10): The influence of sugarcane burning on potential cancer risk

In Brazil, sugarcane fields are often burned to facilitate manual harvesting, and this burning causes environmental pollution from the large amounts of soot released into the atmosphere. This material contains numerous organic compounds such as PAHs. In this study, the concentrations of PAHs in two particulate-matter fractions (PM(2.5) and PM(10)) in the city of Araraquara (SE Brazil, with around 200,000 inhabitants and surrounded by sugarcane plantations) were determined during the sugarcane harvest (HV) and non-harvest (NHV) seasons in 2008 and 2009. The sampling strategy included four campaigns, with 60 samples in the NHV season and 220 samples in the HV season. The PM(2.5) and PM(10) fractions were collected using a dichotomous sampler (10 L min(-1), 24 h) with Teflon (TM) filters. The filter sets were extracted (ultrasonic bath with hexane/acetone (1:1 v/v)) and analyzed by HPLC/Fluorescence. The median concentration for total PAHs (PM(2.5) in 2009) was 0.99 ng m(-3) (NHV) and 3.3 ng m(-3) (HV). In the HV season, the total concentration of carcinogenic PAHs (benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, and benzo(a)pyrene) was 5 times higher than in the NHV season. B(a)P median concentrations were 0.017 ng m(-3) and 0.12 ng m(-3) for the NHV and HV seasons, respectively. The potential cancer risk associated with exposure through inhalation of these compounds was estimated based on the benzo[a]pyrene toxic equivalence (BaP(eq)), where the overall toxicity of a PAR mixture is defined by the concentration of each compound multiplied by its relative toxic equivalence factor (TEF). BaP(eq) median (2008 and 2009 years) ranged between 0.65 and 1.0 ng m(-3) and 1.2-1.4 ng m(-3) for the NHV and HV seasons, respectively. Considering that the maximum permissible BaPeq in ambient air is 1 ng m(-3), related to the increased carcinogenic risk, our data suggest that the level of human exposure to PAHs in cities surrounded by sugarcane crops where the burning process is used is cause for concern. (C) 2010 Published by Elsevier Ltd.

Western blotting method (TESAcruzi) as a supplemental test for confirming the presence of anti-Trypanosoma cruzi antibodies in finger prick blood samples from children aged 0-5 years in Brazil

Some Latin American countries have plans for total control and/or eradication of Chagas disease by the main vector (Triatoma infestans) and by blood transfusion. To achieve this, patients with Chagas disease must be identified. A Western blotting test, TESAcruzi, is described as a supplemental test for diagnosis of Chagas disease using samples collected from children <5 years living in different states of Brazil. Blood samples collected by finger prick on filter paper were sent to the test laboratory by a central laboratory to confirm results obtained previously. Ten percent of negative samples, all doubtful and all positive samples were received. Commercial reagents, IgG indirect immunofluorescence, enzyme immunoassay, and a recently introduced TESAcruzi test were used. From 8788 samples, 163 (1.85%) were reactive by IgG-ELISA and 312 (3.55%) by IgG IIF. From these, 77 (0.87%) were reactive in the TESAcruzi test. The results had high clinical value to identify those truly infected. (C) 2010 Elsevier B.V. All rights reserved.

The Provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study

Objective. To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). Methods. In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordce in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. Results. The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician`s global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent`s global assessment of patient`s well-being, 5) functional ability, and 6) health-related quality of life. Conclusion. The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European Leauge Against Rheumatism, propose a core set of criteria for the evaluation of response of therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

Influence of gender on the vestibular evoked myogenic potential

There is no consensus on the relevance of factors that influence gender differences in the behavior of muscles. Some studies have reported a relationship between muscle tension and amplitude of the vestibular evoked myogenic potential; others, that results depend on which muscles are studied or on how much load is applied. Aims: This study aims to compare vestibular evoked myogenic potential parameters between genders in young individuals. Methods: Eighty young adults were selected - 40 men and 40 women. Stimuli were averaged tone-bursts at 500 Hz, 90 dBHL intensity, and a 10-1000 Hz bandpass filter with amplification of 10-25 microvolts per division. The recordings were made in 80 ms windows. Study type: An experimental and prospective study. Results: No significant gender differences were found in wave latency - p = 0.19 and p = 0.50 for waves P13 and N23, respectively. No differences were found in amplitude values - p = 0.28 p = 0.40 for waves P13 and N23, respectively. Conclusion: There were no gender differences in latency and amplitude factors; the sternocleidomastoid muscle strain was monitored during the examination.