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PubMed2002

Cost-effectiveness of periconceptional supplementation of folic acid.

BACKGROUND: Supplementation of folic acid prior to and in the beginning of pregnancy may prevent neural tube defects (NTDs) in newborns--such as spina bifida--and possibly other congenital malformations. OBJECTIVE: To estimate cost effectiveness of periconceptional supplementation of folic acid using pharmaco-economic model calculation. METHOD: Probabilities for NTDs, risk reductions through periconceptional supplementation of folic acid and lifetime costs of care for children with spina bifida were estimated using Dutch registrations and international literature. MAIN OUTCOME MEASURE: Cost effectiveness was expressed in net costs per discounted life-year gained. Cost effectiveness was calculated in the baseline and in sensitivity analysis. RESULTS: Estimated cost effectiveness of periconceptional supplementation of folic acid amounts to NLG 3900 ([symbol: see text] 1800) in the base case. In sensitivity analysis cost effectiveness mostly remains below NLG 10,000 ([symbol: see text] 4500). CONCLUSION: Periconceptional supplementation of folic acid shows a favorable cost effectiveness. From pharmaco-economic point of view this justifies further stimulation of folic-acid supplementation prior to pregnancy. This can be done through targeted education by health-care workers, such as pharmacists.

Cost of Illness↗
PubMed1998

Cost-effectiveness of noninvasive testing and treatment strategies for H. pylori infection in children with dyspepsia.

OBJECTIVE: We sought to model the cost-effectiveness of endoscopy, noninvasive testing and treatment strategies for Helicobacter pylori infection in children with recurrent abdominal pain in two health care systems, those of the United States and Finland. METHODS: Initial serological testing and treatment was compared to empirical treatment with antimicrobials, endoscopy with rapid urease testing, and 13C urea breath testing. Key assumptions and ranges were obtained from the published literature. Costs were determined for the acquisition of various tests and actual reimbursement figures were used for procedural costs. RESULTS: The disease management costs were very similar for both endoscopy ($643.00) and serology ($646.00) in the United States. In Finland, endoscopy ($173.00) was less expensive than serology ($192.00). The 13C urea breath test was the most expensive procedure in the United States. Sensitivity analysis demonstrated that serological testing became the preferred path if its cost was < $42 in the United States. Empirical treatment of children with dyspepsia was not cost-effective in either country. Sensitivity analysis showed that when prevalence of infection was > 53% in children with recurrent abdominal pain, empirical therapy with endoscopy reserved for failures was the optimal path. CONCLUSIONS: In developed countries like the United States and Finland, significant cost savings are unlikely with an initial test and treat strategy based on serology. Noninvasive testing and treatment of H. pylori infection can be cost-effective in populations with highly prevalent rates of infection.

Anti-Bacterial Agents↗
PubMed2003

Medical costs of fourteen occupational illnesses in the United States in 1999.

OBJECTIVES: This study estimated the annual medical costs associated with 14 occupational illnesses in the United States in 1999. METHODS: National data sets collected by the National Center for Health Statistics, the Health Care Financing Administration, and the Agency for Healthcare Research and Quality were aggregated and analyzed. The cost assessment began with estimates of national health expenditures. These included categories for hospital care, professional services, nursing homes, and medical products, including drugs, administration, public health activities, research and construction. The total disease burden was assessed from estimates of hospital days and number of outpatient visits. The occupational disease burden was assessed by multiplying the total disease burden by a given percentage of the proportionate attributable risk for the disease in question. The occupational burden was then combined with costs for each disease. Adjustments were made for unique inpatient and outpatient costs. RESULTS: In the preferred model, the 14 diseases generated USD 14.5 billion in medical costs in 1999. Roughly USD 10.7 billion was attributed to men and USD 3.8 billion to women. The diseases generating the most costs were as follows: circulatory diseases in the age group 24-64 years (USD 4.7 billion), cancer (USD 4.3 billion), chronic obstructive pulmonary disease (USD 2.2 billion), and asthma (USD 1.5 billion). A sensitivity analysis generated alternative estimates. An upper age limit of 74 years increased the circulatory disease estimate by USD 3.7 billion. The range of the sensitivity analysis was USD 9.6-19.7 billion. CONCLUSION: This study significantly improves over the methodology of previous literature. Our methods were transparent. Occupational illnesses were a major contributor to the total cost of medical care.

Adult↗
PubMed2002

In vivo validation of the design rules of the coronary arteries and their application in the assessment of diffuse disease.

The conventional rationale that uses per cent diameter reduction to assess diffuse coronary artery disease is not appropriate because no normal reference segments exist. In a recent publication, we have proposed a theoretical model based on physical principles that relate the various morphological and haemodynamic parameters (cross-sectional area, length, volume and flow) of the normal coronary arterial tree. The model was validated using haemodynamic simulations based on detailed morphological data of the pig coronary arterial tree. This paper extends the model validation to in vivo swine studies. Coronary arteriography was performed in five swine (15-18 kg body weight) after power injection of contrast material into the coronary artery. Coronary arterial length was obtained using a 3D reconstruction technique. The arterial volume, cross-sectional area and blood flow were measured using videodensitometry. The proposed relationships between these quantities were validated. Furthermore, a sensitivity analysis was demonstrated based on a simulation of diffuse coronary artery disease (approximately 40% reduction in cross-sectional area). The results of a sensitivity analysis based on a simulation of diffuse coronary artery disease suggest that the relationships between arterial volume, cross-sectional area, blood flow and the distal arterial length can be utilized to quantify moderate levels of diffuse coronary artery disease.

Algorithms↗
PubMed2003

A sensitive transcriptome analysis method that can detect unknown transcripts.

We have developed an AFLP-based gene expression profiling method called 'high coverage expression profiling' (HiCEP) analysis. By making improvements to the selective PCR technique we have reduced the rate of false positive peaks to approximately 4% and consequently the number of peaks, including overlapping peaks, has been markedly decreased. As a result we can determine the relationship between peaks and original transcripts unequivocally. This will make it practical to prepare a database of all peaks, allowing gene assignment without having to isolate individual peaks. This precise selection also enables us to easily clone peaks of interest and predict the corresponding gene for each peak in some species. The procedure is highly reproducible and sensitive enough to detect even a 1.2-fold difference in gene expression. Most importantly, the low false positive rate enables us to analyze gene expression with wide coverage by means of four instead of six nucleotide recognition site restriction enzymes for fingerprinting mRNAs. Therefore, the method detects 70-80% of all transcripts, including non-coding transcripts, unknown and known genes. Moreover, the method requires no sequence information and so is applicable even to eukaryotes for which there is no genome information available.

Animals↗
PubMedDate not supplied

The benefit and cost of prostate cancer early detection. The Investigators of the American Cancer Society-National Prostate Cancer Detection Project.

Cost-effectiveness calculations of prostate cancer early detection have not been possible due to the lack of any data demonstrating reduction in mortality from any test or procedure. Prior analyses focused only on cost assessments without consideration of any possible benefits. We used current data from three consecutive years of the American Cancer Society-National Prostate Cancer Detection Project to assess different economic perspectives of test performance, marginal costs, and benefit-cost analysis. The marginal cost, or cost per cancer, of digital rectal examination (DRE) markedly increased by the third year relative to several proposed prostate-specific antigen (PSA) scenarios. Sensitivity analysis for average cost showed that at 4 ng/ml, pricing PSA below $30 would be the most potent factor in potentially lowering costs. Analysis of receiver operator characteristic curves suggested that optimal performance for PSA may be at 3 ng/ml when combined with DRE or between 2 to 3 ng/ml when used alone. Benefit-cost calculations demonstrated that DRE when performed by highly skilled examiners had the lowest cost. However, DRE became one of the most costly detection scenarios when a minor decrease in performance was assumed. Sensitivity analysis demonstrated that the three most determinant parameters of net benefit, in decreasing order, are: specificity, benefits from earlier therapy, and prevalence. If a slightly more specific PSA assay is developed, the higher prevalence of clinically detectable prostate cancer could also make screening less costly than breast cancer screening. Under the assumptions of these analyses, the combination of PSA and DRE appears to represent an ethical and economical detection choice for individual patients in consultation with their physicians. Additional research is needed to quantify the significance of differences between different screening strategies.

American Cancer Society↗
PubMed2004

Autonomously oscillating biochemical systems: parametric sensitivity of extrema and period.

This work addresses sensitivity analysis of autonomously oscillating biochemical systems. Building on results from the engineering literature, a general analysis is presented which addresses key features of oscillatory trajectories, namely the period and local maximum or minimum values of species concentrations and reaction rates. A discussion of sensitivity invariants generalises results from steady-state sensitivity analysis to this context. The results are illustrated by the application to a model of a circadian oscillator.

Biochemistry↗
PubMed1993

Cost-effectiveness of a smoking cessation program after myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of a smoking cessation program initiated after acute myocardial infarction. BACKGROUND: The value of allocating health care resources to smoking cessation programs after myocardial infarction has not been compared with the value of other currently accepted interventions. METHODS: A model was developed to examine the cost-effectiveness of a recently reported smoking cessation program after an acute myocardial infarction. The cost was estimated by considering the resources necessary to implement the program, and the effectiveness was expressed as discounted years of life saved. Years of life saved were estimated by modeling life expectancy using a single declining exponential approximation of life expectancy based on data from published reports. RESULTS: The cost-effectiveness of the nurse-managed smoking cessation program was estimated to be $220/year of life saved. In a one-way sensitivity analysis, the cost-effectiveness of the program remained < $20,000/year of life saved if the program decreased the smoking rate by only 3/1,000 smokers (baseline assumption 26/100 smokers), or if the program cost as much as $8,840/smoker (baseline assumption $100). In a two-way sensitivity analysis, even if the cost of the program were as high as $2,000/participant, the cost-effectiveness of the program would be < $10,000/year of life saved so long as the program helped an additional 12 smokers quit for every 100 enrolled. CONCLUSIONS: Over a wide range of estimates of costs and effectiveness, a nurse-managed smoking cessation program after acute myocardial infarction is an extremely cost-effective intervention. This program is more cost-effective than beta-adrenergic antagonist therapy after myocardial infarction.

Analysis of Variance↗
PubMed1997

Cost-effective analysis of mass screening for cervical cancer in Japan.

Cost-effectiveness analysis for cervical cancer screening in Japan was performed to estimate the cost per life-year saved by the screening; cost-effectiveness ratio (CER). The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. CER of cervical cancer screening was estimated to be US$ 40,604 which was 2.4 times more expensive than that for gastric cancer screening but was about the same as that for colorectal cancer screening. It was within the range of cost-effectiveness of other cancer screening programs financed under the Health and Medical Services Law for the Aged in Japan. We performed sensitivity analysis on the following seven estimates, the screening charge, the sensitivity and the specificity of the screening test, the frequency of carcinoma in situ (CIS) among cases detected in the screening program, the initial cost and the terminal cost for patients with invasive cancer, and the incidence rate of cervical cancer. The sensitivity analysis demonstrated that the screening charge was the most influential factor on CER. CER was fairly stable under various assumptions on the accuracy of the screening test, the frequency of carcinoma in situ (CIS), the treatment cost for patient, and the incidence of cervical cancer. CER was less sensitive to the changes in incidence, even to as low as a 50% decrease of the current figure. Then if the incidence rate becomes 85% of the current figure in 2015, CER would be US$ 48,176 and it was suggested that the cervical cancer screening would remain reasonably cost-effective until the year 2015.

Adult↗
PubMed2005

[Cost-effectiveness of screening for amblyopia].

BACKGROUND: The effectiveness of a screening program for amblyopia has been discussed controversely for several years. While the medical profit is obvious, little is known on the cost-effectiveness of such a screening program. METHODS: By literature research all important variables were determined: incidence of amblyopia, sensitivity of different screening modalities, effectiveness of therapy, costs as well as the loss of utility and life quality by an existing amblyopia. Based on those data in a simple model the costs of a screening program for amblyopia were determined per quality adjusted life year (QALY). The result was analyzed for its stability by sensitivity analysis and compared to the costs of other therapies. RESULTS: Amblyopia occurs with an incidence of approximately 2 % (1.3 - 12 %). Most Screening programs reach a sensitivity of 60 - 90 % and cause costs of 900 - 1400 Euro per detected case. By appropriate therapy with mean costs of 2300 Euro approx. 60 % of the cases obtain useful vision of > 20/40. However, therapy results vary considerably. After discounting the incremental cost-effectiveness ratio (ICER) reaches 7684 Euro/QALY for a screening and treatment program for amblyopia. This is well comparable with other therapies and accepted to be cost-efficient. Sensitivity analysis yielded 24 700 Euro/QALY and 57,633 Euro/QAL with higher discounting for worst case scenarios. CONCLUSION: Screening for amblyopia meets the basic requirements of cost-effectiveness.

Amblyopia↗
PubMed1977

[Spatial analysis of the electrophysiological changes in ventricular loading].

Space analysis methods of the changes in heart electromotive force are described (EMF). The size of the space vector in millivolts, azimuth and elevation are obtained by formula substitution in the mathematical analysis. The same values, in graphis analysis, are obtained by the "Circle for space vectors determination", proposed by the authors. Axial and space analysis of the changes in the electrogenesis of right ventricle was performed in 27 patients with pulmonary stenosis, confirmed by catheterization, on the base of the corrective orthogonal electrocardiogram according to Frank. The axial indices, indicating the size of the forces directed to the right (Sxmv) and forward (Qzmv) are compared as well as the size, elevation and azimuth of the maximal space vector, directed to the right (Vmax.sp-x) and forward (Vmax.sp-z). The index from the axial analysis (sensitivity 62%, r = 0.65) shows a priority for the forces, directed to the right. The priority is on the side of the indices from space analysis (sensitivity 33%, r = 0.78) in case of forces directed forward. There is no statistically significant difference in the diagnostic value of the two methods.

Adult↗
PubMed2001

Primate horizontal cell dynamics: an analysis of sensitivity regulation in the outer retina.

The human cone visual system maintains sensitivity over a broad range of illumination, from below 1 troland to 1,000,000 trolands. While the cone photoreceptors themselves are an important locus for sensitivity regulation-or light adaptation-the degree to which they contribute in primates remains unclear. To determine the range of sensitivity regulation in the outer retina, the temporal dynamics, neural gain control, and response range compression were measured in second-order neurons, the H1 horizontal cells, of the macaque retina. Situated at the first synapse in the retina, H1 cells receive input from a large population of cones. Lee et al. have previously shown that sensitivity regulation in H1 cells is both cone type-specific and spatially restricted. The sensitivity regulation seen in H1 cells at moderate illuminances thus takes place before the summation of cone signals in these cells, and the data establish the H1 cell as a convenient locus for analyzing cone signals. In the present study, cone-driven responses of primate H1 cells to temporally modulated sine-wave stimuli and to increment pulses were measured at steady levels of 1-1,000 trolands. The H1 cell gave a modulated response to sine-wave stimuli and hyperpolarized to increment pulses with overshoots at stimulus onset and offset. The temporal amplitude sensitivity function was primarily low-pass in shape, with a small degree of low-frequency roll off and a resonance shoulder near 40 Hz. A model incorporating a cascade of first-order filters together with an underdamped second-order filter could describe both temporal sinusoidal and pulse hyperpolarizations. Amplitude sensitivity was estimated from both pulse and sine-wave data as a function of the steady adaptation level. Sensitivity at low light levels (1 troland) showed a slowing in temporal dynamics, indicating time-dependent sensitivity regulation. Sensitivity was reduced at light levels above approximately 10 trolands, reflecting both response range compression and neural gain control. Thus the outer retina is a major locus for sensitivity regulation in primates.

Animals↗
PubMed1995

Radiation therapy: are we getting value for money?

The aim of this study was to examine the long term cost effectiveness of radiotherapy (RT) in the treatment of cancer at the Department of Radiation Oncology, Westmead Hospital, from its inception in 1980 to December 1993. A Kaplan-Meier survival curve was constructed for all patients treated by RT during the study period. The area under this curve represented the average survival. The total number of life years was calculated by multiplying the number of patients by the average survival. Costing for one RT treatment field had previously been derived. The cost included capital costs, building costs and overheads as well as labour, goods and services, and operating costs. The cost per field was multiplied by the total number of fields given each year and the yearly total summed to give the total cost. The total cost was divided by the number of life years to give a cost per life year. An overall percentage survival gain was estimated from departmental results and the literature. Cost per life year gained (LYG) was derived by dividing the cost per life year by the percentage survival gain. Sensitivity analysis was performed with best- and worst-case survival scenarios, and high and low cost per field estimates. A total of 9868 patients were treated by radiotherapy between January 1980 and December 1993. Median follow-up was 4.2 years. Median survival was 2 years. The 5- and 10-year survival rates were 35% and 22%, respectively. The area under the survival curve (the average survival) was 4.75 years. The total number of life years of survival was thus 4.75 x 9868 = 46,873. In 1993, the cost per field was $71.52 (Australian dollars). The total number of fields treated in the study period was 758,097. Hence, the total cost in 1993 dollars was $54,219,097. The survival gain (excluding skin cancer) with RT was 16.1% and the cost/LYG was $7186. Sensitivity analysis of best and worst case scenarios gave costs/LYG of $3920 and $15,632 respectively. Efficient resource allocation can be aided by examining the relative cost-effectiveness of different prevention and treatment strategies. RT is shown to have a lower cost/LYG than other accepted treatments in current practice. Other major treatment modalities should be subjected to the same scrutiny of cost effectiveness as has been applied to RT.

Australia↗
PubMed2004

Robustness properties of circadian clock architectures.

Robustness, a relative insensitivity to perturbations, is a key characteristic of living cells. However, the specific structural characteristics that are responsible for robust performance are not clear, even in genetic circuits of moderate complexity. Formal sensitivity analysis allows the investigation of robustness and fragility properties of mathematical models representing regulatory networks, but it yields only local properties with respect to a particular choice of parameter values. Here, we show that by systematically investigating the parameter space, more global properties linked to network structure can be derived. Our analysis focuses on the genetic oscillator responsible for generating circadian rhythms in Drosophila as a prototypic dynamical cellular system. Analysis of two mathematical models of moderate complexity shows that the tradeoff between robustness and fragility is largely determined by the regulatory structure. Rank-ordered sensitivities, for instance, allow the correct identification of protein phosphorylation as an influential process determining the oscillator's period. Furthermore, sensitivity analysis confirms the theoretical insight that hierarchical control might be important for achieving robustness. The complex feedback structures encountered in vivo, however, do not seem to enhance robustness per se but confer robust precision and adjustability of the clock while avoiding catastrophic failure.

Animals↗
PubMed2004

Cost-effectiveness of ramipril in patients at high risk for cardiovascular events: a Swiss perspective.

BACKGROUND: Ramipril may prevent cardiovascular death, myocardial infarction and stroke in patients without evidence of left ventricular dysfunction or heart failure who are at high risk for cardiovascular events. In the present study we assessed the cost-effectiveness of ramipril in patients with an increased risk of cardiovascular events from a third party payer's perspective in Switzerland. In addition, the cost-effectiveness of ramipril in the subgroup of diabetic patients was assessed. METHODS: We developed a decision analytic cost-effectiveness model to estimate the incremental costs (in 2001 in Swiss Francs [CHF]), incremental effects (in terms of life-years gained [LYG]) and incremental cost-effectiveness (CHF per LYG) of ramipril versus placebo. Clinical input parameters were derived from the Heart Outcomes Prevention Evaluation (HOPE) study. Cost data were extracted from the literature. Deterministic sensitivity analysis was used to assess the impact of varying the input parameters on the cost effectiveness of the intervention. In addition, first order Monte Carlo simulation was used to capture patient-to-patient variability, presented as cost-effectiveness acceptability curves. RESULTS: The incremental cost-effectiveness ratio of ramipril versus placebo was CHF 6,005 per life-year gained in the base case analysis. In diabetic patients the cost-effectiveness ratio was CHF 3,790 per life-year gained. Varying the price of ramipril in a deterministic sensitivity analysis only had a moderate impact on the cost-effectiveness ratio in the overall population (range: CHF 3,652-15,418 per LYG) as well as in diabetic patients (range: CHF 2,370-9,468 per LYG). CONCLUSION: Ramipril in patients at high risk for cardiovascular events represents an efficient use of scarce health care resources in Switzerland and is cost-effective under reasonable assumptions. Ramipril is even more cost-effective in the subgroup of diabetic patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Ambulatory care or home-based treatment? An economic evaluation of two physiotherapy delivery options for people with rheumatoid arthritis.

OBJECTIVE: To assess the difference in costs of home-based versus clinic-based physiotherapy (PT) for patients with rheumatoid arthritis (RA) from a societal perspective. METHODS: A cost analysis was performed using statistical and financial information provided by The Arthritis Society, Ontario Division, from April 1, 1997 to March 30, 1998. Cost estimates included treatment costs and costs borne by patients. A sensitivity analysis was conducted to examine the effect of altering the valuation of treatment time and patient employment status. RESULTS: Total costs per case were $210.87 for the home setting, and $183.87 for the clinic setting when patients were employed. Sensitivity analysis did not change the trend of the results. The estimated start-up costs for an arthritis clinic were between $302.90 and $652.40. From the perspective of the health care system, these costs would be recovered after serving 4 to 8 RA patients at a clinic. CONCLUSION: The findings suggest that ambulatory PT care is less costly than home-based services for people with RA based on The Arthritis Society model. Further studies should be conducted to examine the effectiveness and the possible adverse consequences of alternative settings for service delivery.

Aged↗
PubMed2005

The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis.

The association between retinopathy in type 2 diabetes [diabetic retinopathy (DR)] and the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been investigated in several case-control studies. These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of developing DR whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of developing DR was conducted. Four out of five identified studies included populations of East Asian descent, and only one involved samples from European descent (Caucasians). Overall, the meta-analysis suggested large heterogeneity between studies (p = 0.08, I(2) = 52%) and marginal association between C677T transition and the risk of developing DR: random effects odds ratio (OR) = 1.39 [95% CI (1.05, 1.83)]. The sensitivity analysis [exclusion of one East Asian study with the controls not in Hardy-Weinberg equilibrium (HWE)] showed no heterogeneity (p = 0.25, I(2) = 27%) and no significant association: fixed effects OR = 1.22 [95% CI (0.99, 1.51)] and random effects OR = 1.24 [95% CI (0.96, 1.60)]. The sub-group analysis for the East Asian population produced a significant association: fixed effects OR = 1.48 [95% CI (1.20, 1.83)] and random effects OR = 1.52 [95% CI (1.14, 2.03)]. However, sensitivity analysis in East Asians revealed that the association is marginal: fixed effects OR = 1.33 [95% CI (1.04, 1.70)] and random effects OR = 1.36 [95% CI (1.01, 1.83)]. There is a source of bias in the selected studies: the largest studies failed to show association while the smallest study claimed an association. The above findings reinforce the need for larger and more rigourous studies in this area.

Diabetes Mellitus, Type 2↗
PubMed1996

The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators.

OBJECTIVE: To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care. DESIGN: Prospective cohort study. SETTING: Five US teaching hospitals between 1989 and 1994. SUBJECTS: A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories. MAIN OUTCOME MEASURES: Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results. RESULTS: By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful. CONCLUSION: In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study.

APACHE↗