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PubMed2000

Socioeconomic status and infant mortality in Australia: a national study of small urban areas, 1985-89.

This study uses small-area data for the period 1985-89 to examine the relationship between socioeconomic status and infant mortality in each of the mainland State capital cities of Australia. An unweighted OLS regression analysis based on 195 Statistical Local Areas (SLAs) that recorded five or more deaths over the reference period shows that standardised infant mortality ratios were significantly higher in areas with greater concentrations of low income families. This relationship was independent of the effects of low birthweight, Aboriginality, ethnicity and variability between each of the capital cities. To test for the robustness of this result a sensitivity analysis was undertaken. This involved (a) performing a Principal Components Analysis on a wide range of sociodemographic variables to derive factor scales that were subsequently included in a regression analysis, (b) using weighted least-squares regression and a Poisson generalised linear model and (c) including in the analysis all SLAs irrespective of the number of infant deaths. The sensitivity analysis supported the results of this study, thus validating the observed association between the socioeconomic characteristics of urban areas and their rate of infant mortality. Despite marked reductions in overall rates of infant mortality over the last century in Australia. socioeconomic disparities were still evident during the mid-to-late 1980s. Whether and to what extent this situation persisted during the early-to-mid 1990s will be known in the near future when the next collection of area-based data are publicly released. The results of this study, therefore, represent an important baseline against which more contemporary national trends can be monitored.

Australia↗
PubMed1999

Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation in coronary artery bypass surgery.

The cost-effectiveness of amiodarone prophylaxis of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) was determined. A decision analysis using current hospital data and values from the literature was conducted. Under the base-case scenario, CABG patients received usual care (no prophylaxis) or 2 g of oral amiodarone hydrochloride over one to three days before surgery and 400 mg daily for seven days after surgery. Costs of hospitalization in the intensive care unit (ICU) and the cardiac step-down unit (SDU), cardioversion costs, electrocardiogram costs, drug costs, nursing administration charges, and pharmacy i.v. admixture charges were included. A sensitivity analysis using a Monte Carlo simulation and a one-way sensitivity analysis were performed. The mean cost per AF event avoided was lower in the amiodarone group ($15,750, 95% confidence interval [CI]: $15,591-$15,999) than the control group ($17,426,95% CI: $17,252-$17,600). A majority of the cost difference was due to the cost of hospitalization for patients without AF, the frequency of AF, and the cost of hospitalization in the SDU for patients with AF. For patients treated with amiodarone who did not develop AF, the cost difference was sensitive to changes in the cost of hospitalization and the efficacy of amiodarone. For patients who did develop AF, the cost difference was robust. Prophylaxis of AF with amiodarone in CABG patients was more cost-effective than usual care in the short term from a hospital perspective; the results were sensitive to changes in the cost of hospitalization of patients who did not develop AF and the efficacy of amiodarone.

Amiodarone↗
PubMed2004

Metastases in mediastinal and hilar lymph nodes in patients with non-small cell lung cancer: quantitative and qualitative assessment with STIR turbo spin-echo MR imaging.

PURPOSE: To evaluate short inversion time inversion-recovery (STIR) turbo spin-echo (TSE) magnetic resonance (MR) imaging for detection of metastases in lymph nodes by using quantitative and qualitative analyses. MATERIALS AND METHODS: One hundred ten patients (68 men and 42 women) with non-small cell lung cancer who ranged in age from 36 to 82 years (mean age, 64 years) were examined with respiratory-triggered STIR TSE MR imaging. Ratios of signal intensity in a lymph node to that in a 0.9% saline phantom (lymph node-saline ratios [LSRs]) for all lymph nodes were classified into three groups according to nodal short-axis diameter. LSRs of each group were compared by using pathologic diagnosis as the standard of reference. For quantitative analysis, the LSR threshold value for a positive test was determined on a per-node basis and tested for ability to enable a correct diagnosis on a per-patient basis. For qualitative analysis, signal intensities of lymph nodes were assessed by using a five-point visual scoring system. Results of quantitative and qualitative analyses were compared on a per-patient basis with McNemar testing. RESULTS: In 110 patients, 92 of 802 lymph nodes were pathologically diagnosed as containing metastases, while 710 lymph nodes did not contain metastases. Mean LSR in the lymph node group with metastasis was higher than that in the group without metastasis (P <.05). When an LSR of 0.6 was used as the positive-test threshold at quantitative analysis, sensitivity was 93% (37 of 40 patients) and specificity was 87% (61 of 70 patients) on a per-patient basis. With a score of 4 as the positive-test threshold at qualitative analysis, sensitivity was 88% (35 of 40 patients) and specificity was 86% (60 of 70 patients) on a per-patient basis. There was no significant difference (P >.05) between results of quantitative and those of qualitative analysis. CONCLUSION: Quantitative and qualitative analyses of STIR TSE MR images enable differentiation of lymph nodes with metastasis from those without. Qualitative analysis can substitute for quantitative analysis of STIR TSE MR imaging data.

Adult↗
PubMed2005

Design and analysis of trials with rare outcomes: examples from trials in herpes transmission and influenza prophylaxis.

For trials with rare outcomes, the number of events to be observed drives the power of the study rather than the proportions of subjects with the event and this is an important consideration when determining sample size. The stratified version of Fisher's exact test was described by Cox as long ago as 1966, but it is only recently that computing power has allowed this to be performed routinely. The issue of stratified analysis can also be addressed through permutation tests and their implementation for multicentre trials where randomisation is stratified by site has potential value. Where the time to event is available, analysis using a proportional hazards model has a potentially valuable role but estimates of differences in proportions are often required particularly for non-inferiority studies and typical software employed for these analyses uses an asymptotic approximation rather than an exact analysis. It is important to assess the impact of missing data on such trials. This can be approached through examination of the pattern of missing data and the covariates predicting discontinuation as well as through sensitivity analysis. Sensitivity analyses need to be done carefully using realistic alternative assumptions and an appealing approach is to impute events for subjects with missing data using the observed placebo rate. Issues of design and analysis for trials with rare outcomes are discussed in the context of two examples-one from a trial designed to investigate transmission of herpes and one that studied prophylaxis of influenza.

Chemoprevention↗
PubMed2002

Economic evaluation of propofol for sedation of patients admitted to intensive care units.

BACKGROUND: The goal of the current study was to evaluate the economic impact of propofol as compared with midazolam for sedating patients in the intensive care unit (ICU). METHODS: A randomized, unblinded, multicenter pharmacoeconomic trial captured health resource utilization and outcome measurements associated with sedation and treatment of patients in four ICUs across Canada. Statistical analysis was performed to investigate the difference in sedation quality, ICU length of stay, and other health resources used. The authors compared the costs (1997 Canadian dollars) associated with the two treatments. Two types of sensitivity analyses were performed. RESULTS: Although overall sedation duration was similar, propofol patients spent more time at adequately sedated status (60.2% vs. 44%; P = 0.01) and were extubated faster (median extubation time, 2.5 vs. 7.1 h; P = 0.001). The ICU length of stay and health resource utilization did not differ. The total cost per patient, including drug cost and ICU stay cost, did not differ between groups (median, $5,718 for propofol vs. $5,950 for midazolam; P = 0.94). The first sensitivity analysis suggested that the incremental cost (per patient) of propofol varies from an extra cost of $114 to a savings of $2,709. Based on a hypothetical model, the second sensitivity analysis showed a potential saving of $479 per patient as a result of improved discharge planning. CONCLUSION: The analysis demonstrated that using propofol resulted in a reduction of time to extubation and higher sedative regimen costs. There was no difference in intensity of resource use or ICU length of stay and hence in costs. Issues regarding discharge delay among propofol-treated patients remain to be explored.

Drug Costs↗
PubMed2005

Retrospective economic evaluation of the Hellenic Air Force Teleconsultation Project.

Hellenic Air Force introduced its teleconsultation project in 2002 by the establishment of PC-based videoconference links between the Central Air Force Hospital in Athens, Greece and several remote camps in order to serve the personnel and their dependants. A retrospective cost-minimization analysis was conducted for 38 remote subjects that were telemedically examined, instead of being referred to the hospital. For the evaluation of the annual cost of both procedures (telemedicine and referral), the fixed and variable costs were estimated. Furthermore, a simplified sensitivity analysis was conducted. The telemedical system proved to be cost-effective even for the limited number of 38 enrollees. Sensitivity analysis suggested that upon upgrade of the service as an integral component of daily care with subsequent higher number of beneficiaries and users of the system, the cost of each session would decrease dramatically. Current technology indicates that telemedical systems could provide efficient and cost-effective care to eligible enrollees.

Cost Control↗
PubMed2000

Cost-of-illness of epilepsy in Italy. Data from a multicentre observational study (Episcreen).

OBJECTIVE: To investigate the impact of epilepsy in Italy on healthcare resources, producing an average cost per patient per year of follow-up. DESIGN AND SETTING: The Episcreen Project is a multicentre longitudinal Italian observational study; its methodology, organisational network and case report form have been reported in detail elsewhere. Using a subset of patients with epilepsy from this project, we conducted a retrospective cost-of-illness analysis based on clinical records. The analysis was performed from the societal (community) perspective, including both direct and indirect costs. Hospital admissions, day-hospital visits, specialist visits, instrumental examinations, drugs and productivity losses because of visits and hospitalisation were analysed. Each cost variable was valued in 1996 Italian liras (L) using published national tariffs (except for drugs for which published prices were used). A sensitivity analysis was conducted on indirect costs to test the robustness of the assumption that 1 working day lost for each day hospital visit would produce a change of 0.3% in the weight of indirect costs. PATIENTS AND PARTICIPANTS: Patients analysed in this study were registered in the Episcreen database as at 21 November 1996. They were diagnosed with epilepsy at the last visit, had at least 1 follow-up visit (i.e. at least 1 visit after the enrolment visit), and had at least 12 months of follow-up. RESULTS: The average cost per patient per year was L2,726,116 ($US1767). The average cost per patient was higher for children than for adults [L3,629,997 ($US2353) and L2,362,134 ($US1531), respectively), and for newly diagnosed patients for whom the first diagnosis of epilepsy was addressed at the first Episcreen visit [adults: old referrals L1,304,353 ($US845), new referrals L6,901,374 ($US4473); children: old referrals L2,810,504 ($US1822), new referrals L7,814,400 ($US5065)]. Direct costs represented 87.6% of total costs. The major cost driver was hospitalisation (63.7%), followed by drugs (10.5%), day-hospital visits (4.1%), out-patient visits (3.85%), other tests (3.1%) and electroencephalographs (2.3%). Indirect costs (lost productivity) represented 12.4% of total costs. Sensitivity analysis showed that the results are sensitive to the value attributed to lost productivity. CONCLUSIONS: The cost of managing a patient with epilepsy in Italy is influenced by age, syndrome and modality of referral to the centre for epilepsy.

Adolescent↗
PubMedDate not supplied

[Cost-effectiveness of drotrecogin alpha [activated] in the treatment of severe sepsis in Spain].

INTRODUCTION: The PROWESS clinical trial has shown that treatment with drotrecogin alpha (activated) in patients with severe sepsis is associated with a reduction in the absolute risk of death compared with standard treatment. The aim of the present study was to assess the cost-effectiveness of drotrecogin alpha (activated) versus that of standard care in the treatment of severe sepsis in Spain. PATIENTS AND METHODS: A decision analysis model was drawn up to compare costs to hospital discharge and the long-term efficacy of drotrecogin alpha (activated) versus those of standard care in the treatment of severe sepsis in Spain from the perspective of the health care payer. Most of the information for creating the model was obtained from the PROWESS clinical trial. A two-fold baseline analysis was performed: a) for all patients included in the PROWESS clinical trial and b) for the patients with two or more organ failures. The major variables for clinical assessment were the reduction in mortality and years of life gained (YLG). Cost-effectiveness was expressed as cost per YLG. A sensitivity analysis was applied using 3% and 5% discount rates for YLG and by modifying the patterns of health care, intensive care unit costs, and life expectancy by initial co-morbidity and therapeutic efficacy of drotrecogin alpha (activated). RESULTS: Treatment with drotrecogin alfa (activated) was associated with a 6.0% drop in the absolute risk of death (p = 0.005) when all of the patients from the PROWESS trial were included and with a 7.3% reduction (p = 0.005) when the analysis was restricted to patients with two or more organ failures. The cost-effectiveness of drotrecogin alfa (activated) was 13,550 euros per YLG with respect to standard care after analysing all of the patients and 9,800 euros per YLG in the group of patients with two or more organ failures. In the sensitivity analysis, the results ranged from 7,322 to 16,493 euros per YLG. The factors with the greatest impact on the results were the change in the efficacy of drotrecogin alfa (activated), adjustment of survival by initial co-morbidity and the application of discount rates to YLG. CONCLUSIONS: Treatment with drotrecogin alfa (activated) presents a favorable cost-effectiveness ratio compared with other health care interventions commonly used in Spain.

Anti-Infective Agents↗
PubMed1994

Sensitivity of physiologically based pharmacokinetic models to variation in model parameters: methylene chloride.

The parameters in a physiologically based pharmacokinetic (PBPK) model of methylene chloride were varied systematically, and the resulting variation in a number of model outputs was determined as a function of time for mice and humans at several exposure concentrations. The importance of the various parameters in the model was highly dependent on the conditions (concentration, species) for which the simulation was performed and the model output (dose surrogate) being considered. Model structure also had a significant impact on the results. For sensitivity analysis, particular attention must be paid to conservation equations to ensure that the variational calculations do not alter mass balance, introducing extraneous effects into the model. All of the normalized sensitivity coefficients calculated in this study ranged between -1.12 and 1, and most were much less than 1 in absolute value, indicating that individual input errors are not greatly amplified in the outputs. In addition to ranking parameters in terms of their impact on model predictions, time-dependent sensitivity analysis can also be used as an aid in the design of experiments to estimate parameters by predicting the experimental conditions and sampling points which will maximize parameter identifiability.

Animals↗
PubMed2005

Risk factors for primary liver carcinoma in Chinese population.

AIM: To evaluate the risk factors for primary liver carcinoma (PLC) in Chinese population. METHODS: Chinese Biomedical Literature Database, China Hospital Knowledge Database and MEDLINE were searched. All the related literatures were screened, and the risk factors for PLC in Chinese population were studied. Heterogeneity was evaluated by odds ratio (OR) q test. Combined OR and its 95% confidence interval (95%CI) were calculated, the association between the investigated risk factors and PLC was determined. Validity and bias of the findings were evaluated by sensitivity analysis and funnel plot analysis respectively. RESULTS: Fifty-five of one hundred and ninety identified studies were accepted according to the inclusive criteria. Ten factors related to PLC were demonstrated by sensitive analysis and funnel plot analysis. They were cirrhosis (OR = 11.97, P = 0.000), HBV infection (OR = 11.34, P = 0.000), HCV infection (OR = 4.28, P = 0.000), family history of liver cancer (OR = 3.49, P = 0.000), unstable emotion (OR = 2.20, P = 0.000), depressed characters (OR = 3.07, P = 0.000), aflatoxin (OR = 1.80, P = 0.000), alcoholic (OR = 1.88, P = 0.000), intake of musty food (OR = 1.87, P = 0.000) and drinking contaminated water from pond (OR = 1.77, P = 0.003). CONCLUSION: The main risk factors for PLC in China are liver diseases, family history of liver carcinoma, poor psychic status, aflatoxin, and some unhealthy behaviors.

Alcohol Drinking↗
PubMed1994

Genetic analysis of sensitization and tolerance to cocaine.

The present study investigated the effects of acute and repeated administration of cocaine (1.0-56.0 mg/kg) on locomotor activity in the genetically distinct DBA/2J and C57BL/6J inbred strains of mice. In addition, quantitative trait loci analysis of the effects of acute and repeated cocaine in 16 BXD recombinant inbred strains was used to provisionally detect and map minor gene loci which associate with cocaine responsiveness. Whereas locomotor activity was elevated maximally in both strains by 32 mg/kg of cocaine, DBA/2J mice were stimulated to a much greater extent than C57BL/6J mice. The stimulant effects of cocaine were diminished to control levels in DBA/2J mice after repeated daily injections, whereas cocaine-induced locomotion remained consistent in C57BL/6J mice throughout the 7-day testing period. Emergence of stereotyped behavior with repeated daily injections of 32 mg/kg of cocaine was observed in DBA/2J but not C57BL/6J mice. No differences in brain cocaine levels were found between the DBA/2J and C57BL/6J strains after acute or repeated injections. Quantitative trait loci analysis indicated significant associations of differences in cocaine responsiveness with marker loci on several chromosomes in the BXD recombinant inbred series. Those marker loci associated with the acute cocaine response were in most cases different from those markers associated with long-term responses. The current results demonstrate that genotype-dependent variation exists in behavioral responsiveness to cocaine in mice and suggest that the acute and long-term responses to cocaine may be under the control of separate sets of genes.

Animals↗
PubMed1997

A pharmacoeconomic analysis of patients with symptoms of benign prostatic hyperplasia.

A pharmacoeconomic analysis of therapies for patients with benign prostatic hyperplasia (BPH) was conducted. The therapies compared were androgenic hormone inhibition (finasteride) and alpha-blockade (doxazosin, prazosin and terazosin). This was a cost-effectiveness analysis from the perspective of the US military. The 36-month decision-tree model considered the aforementioned drugs as initial therapy for BPH following an unsuccessful period of watchful waiting. Therapy was continued toward a successful response. All patients who did not respond to therapy received secondary interventions, including transurethral resection of the prostate (TURP). The main outcome measures were clinical effectiveness and incurred costs. A Monte Carlo sensitivity analysis was performed on all cost-effectiveness ratios. The model and sensitivity analysis supported prazosin as the most cost effective alpha-blocker over finasteride: the mean difference was $US381.65 (1994 values) per successfully treated patient, with a range of $US57.83 to $US675.53, in favour of prazosin. If prazosin was used as initial drug therapy after watchful waiting for a man over 50 years of age with classical symptoms of prostatism and no other severe or confounding comorbid conditions, a cost of $US578.15 per treatment could be expected, with clinical effectiveness of 70.3%. Patients who cannot tolerate prazosin should be considered for terazosin therapy before moving on from alpha-blockers. Subsequent treatment with finasteride would cost $US1426.53, with an additional clinical effectiveness of 9.9%. For the small number of patients who fail both therapies, the cost effectiveness of a first TURP as 'third-line' intervention [$US4321.36 for an additional effectiveness of 8.62% and a repeat TURP as 'fourth-line' ($US7650.54 for 0.59%) interventional] was calculated in a similar manner. Costs were cumulative, and effectiveness was derived from the total number of patients who started prazosin therapy. Pharmacological therapy was more cost effective than surgical intervention, and alpha-blockers were more cost effective than finasteride. Among the alpha-blockers, prazosin was by far the most cost effective followed by terazosin, then doxazosin.

Cost-Benefit Analysis↗
PubMedDate not supplied

Potential clinical and economic effects of homocyst(e)ine lowering.

BACKGROUND: Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials. SUBJECTS AND METHODS: We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved. RESULTS: Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women. CONCLUSIONS: Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable costs. If homocyst-(e)ine lowering is considered, a screen and treat strategy is likely to be more cost-effective than universal supplementation. Arch Intern Med. 2000;160:3406-3412.

Coronary Disease↗
PubMedDate not supplied

[Cost-effectiveness analysis of ceftriaxone and cefotaxime in the treatment of community-acquired pneumonia].

OBJECTIVE: To assess the cost-effectiveness ratio of ceftriaxone and cefotaxime to treat moderate to severe community acquired pneumonia (CAP). METHODS: A clinical trial was done in five hospitals of the Instituto Mexicano del Seguro Social, at the metropolitan area of Mexico City. Ceftriaxone and cefotaxime were compared to treat moderate to severe CAP, and the costs of purchasing, preparation, administration, hospitalization, and therapeutic success were quantified. Cost-effectiveness ratio was calculated, and sensitivity analysis and incremental analysis were done. RESULTS: The main isolated germs were Streptococcus pneumoniae (23.6%) and Staphylococcus aureus (18.5%). Most of the microorganisms were sensitive to ceftriaxone, ceftazidime, and cefotaxime, and were resistant to penicillin, ampicillin, and erythromycin. Therapeutic success was 98% in the ceftriaxone group and 83% in the cefotaxime group (p = 0.0091). Cost-effectiveness ratio for per cent unit of success was $19,458.62 Mexican pesos in the ceftriaxone group and $29,218.08 in the cefotaxime group. Sensitivity analysis showed consistently a lower cost-effectiveness ratio in the ceftriaxone group. Incremental analysis based on the treatment of 55 patients showed that using ceftriaxone instead of cefotaxime resulted in saving $35,170.79 per each additional cured patient. CONCLUSIONS: Ceftriaxone has a lower cost-effectiveness ratio than cefotaxime to treat patients with CAP and bad prognosis criteria requiring hospitalization.

Cefotaxime↗
PubMed2006

Statistical analysis of longitudinal psychiatric data with dropouts.

Longitudinal studies are used in psychiatric research to address outcome changes over time within and between individuals. However, because participants may drop out of a study prematurely, ignoring the nature of dropout often leads to biased inference, and in turn, wrongful conclusions. The purpose of the present paper is: (1) to review several dropout processes, corresponding inferential issues and recent methodological advances; (2) to evaluate the impact of assumptions regarding the dropout processes on inference by simulation studies and an illustrative example using psychiatric data; and (3) to provide a general strategy for practitioners to perform analyses of longitudinal data with dropouts, using software available commercially or in the public domain. The statistical methods used in this paper are maximum likelihood, multiple imputation and semi-parametric regression methods for inference, as well as Little's test and index of sensitivity to nonignorability (ISNI) for assessing statistical dropout mechanisms. We show that accounting for the nature of the dropout process influences results and that sensitivity analysis is useful in assessing the robustness of parameter estimates and related uncertainties. We conclude that recording the causes of dropouts should be an integral part of any statistical analysis with longitudinal psychiatric data, and we recommend performing a sensitivity analysis when the exact nature of the dropout process cannot be discerned.

Antidepressive Agents↗
PubMed2003

Costs of medical services for patients with HIV/AIDS in Khon Kaen, Thailand.

OBJECTIVE: To estimate the savings and cost of providing highly active antiretroviral therapy (HAART) to adult patients with AIDS under Universal Coverage (UC) in Khon Kaen Province, Thailand. DESIGN: Micro-costing of outpatient and inpatient services of two referral hospitals, and cost modelling. SETTING: Khon Kaen Regional Hospital and Northeast Regional Infectious Hospital. PATIENTS: Adult patients who resided in Khon Kaen and made outpatient visits at and/or those who were discharged from those hospitals from 1 December 2001 to 28 February 2002. MAIN OUTCOME MEASURE: The average cost per outpatient visit and per inpatient day. Based on these figures, the savings and cost of providing HAART to adult patients with AIDS under UC at outpatient settings in this province were estimated. RESULTS: The average cost per outpatient visit with and without antiretroviral drugs (ARV) was US$294.2 and US$26.1, respectively. The average cost per inpatient day with and without ARV drugs was US$368.1 and US$43.8, respectively. The net annual cost of HAART was estimated to be US$5 674 629. This is equivalent to 20.0% of the annual UC budget for adults in this province in 2002. Sensitivity analysis and projection to the year 2006 were conducted. CONCLUSION: A large increase in the budget would be required to provide HAART to all adult patients with AIDS under UC. However, the sensitivity analysis showed it would be an affordable policy option if low-cost antiretroviral drugs were successfully introduced. This type of analysis would be useful to assess the financial implications of providing HAART in public health systems worldwide.

Adult↗
PubMed2006

Quantitative performance metrics for robustness in circadian rhythms.

MOTIVATION: Sensitivity analysis provides key measures that aid in unraveling the design principles responsible for the robust performance of biological networks. Such metrics allow researchers to investigate comprehensively model performance, to develop more realistic models, and to design informative experiments. However, sensitivity analysis of oscillatory systems focuses on period and amplitude characteristics, while biologically relevant effects on phase are neglected. RESULTS: Here, we introduce a novel set of phase-based sensitivity metrics for performance: period, phase, corrected phase and relative phase. Both state- and phase-based tools are applied to free-running Drosophila melanogaster and Mus musculus circadian models. Each metric produces unique sensitivity values used to rank parameters from least to most sensitive. Similarities among the resulting rank distributions strongly suggest a conservation of sensitivity with respect to parameter function and type. A consistent result, for instance, is that model performance of biological oscillators is more sensitive to global parameters than local (i.e. circadian specific) parameters. Discrepancies among these distributions highlight the individual metrics' definition of performance as specific parametric sensitivity values depend on the defined metric, or output. AVAILABILITY: An implementation of the algorithm in MATLAB (Mathworks, Inc.) is available from the authors. SUPPLEMENTARY INFORMATION: Supplementary Data are available at Bioinformatics online.

Animals↗