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PubMed1995

Economic evaluation using mathematical models: the case of misoprostol prophylaxis.

Using misoprostol prophylaxis as an example, many of the methods employed in economic analyses that incorporate mathematical models were described. These included: decision analysis, cost effectiveness analysis (including incremental cost effectiveness analysis), one-way, multi-way, and probabilistic sensitivity analysis, and the estimation of quality adjusted life years for use in cost utility analysis. In the case of misoprostol prophylaxis, the cost effectiveness analysis demonstrated that, compared to the no prophylaxis alternative, prophylaxis cost an extra $650, on average, for every additional ulcer prevented, and was potentially cost saving for some high risk groups. The cost utility analysis demonstrated that prophylaxis resulted (on average) in modest additional costs and no additional quality of life benefits. Sensitivity analysis demonstrated that, at worst, prophylaxis reduced quality of life; at best, the incremental cost effectiveness ratio was $9333 for each quality adjusted life-year gained by prophylaxis compared to no prophylaxis. The results of the cost utility analysis also showed that prophylaxis may be cost saving in high risk groups, confirming the results of the cost effectiveness analysis. Finally, and perhaps most importantly, this analysis illustrated the importance of incorporating measures of health related quality of life into economic evaluation.

Cost-Benefit Analysis↗
PubMed2000

Cost-effectiveness of universal compared with voluntary screening for human immunodeficiency virus among pregnant women in Chicago.

OBJECTIVES: To determine and compare the cost-effectiveness of implementing 3 screening strategies to detect human immunodeficiency virus (HIV) infection among pregnant women in Chicago, Illinois: no screening, voluntary screening, and universal screening. METHODS: A decision-analysis model was developed, using standard cost-effectiveness analysis from a societal perspective. Reference case estimates were derived from a surveillance project conducted by the Illinois Department of Public Health and studies were published in the medical literature. Costs included direct and indirect medical costs associated with identification of pregnant women infected with HIV and identification, prevention, and treatment of perinatally HIV-infected newborns. Specifically, for each screening option, the cost per pregnant woman screened, the resulting number of pediatric HIV infections, and the number of newborn life-years were calculated. All costs were adjusted to the 1997 dollar value and discounted at 3%. Sensitivity analyses were determined for all variables included in the decision model. RESULTS: The estimated prevalence of HIV infection among pregnant women in Chicago is .41%. For every 100,000 pregnant women, it is estimated that 104.6 children would be infected with HIV if no screening strategy were implemented and 44.8 children would be infected if voluntary HIV testing (assuming a 92.7% acceptance rate) were available. In comparison, if universal HIV testing was performed, the number of children infected with HIV would decrease to 40 cases. Sensitivity analysis across a maternal HIV prevalence rate of.01% to 2.2% found that universal screening would be cost-saving in communities where the seroprevalence is.21%. In Chicago, it would take an estimated 5. 2 months of screening pregnant women to avert 1 case of pediatric HIV. Taking into consideration the lifetime costs of treating a child with HIV infection, universal HIV testing of 100,000 pregnant women would result in a cost-savings of $3.69 million when compared with no screening, and $269,445 when compared with voluntary screening. We estimated that it would cost $11.1 million to screen 100,000 pregnant women in Chicago. The cost-savings produced with increased screening are the direct result of reduced cases of newborns infected with HIV. A 2-way sensitivity analysis was performed to examine how costs vary as a function of the voluntary rates for HIV-positive and HIV-negative women. When screening falls below 50% for HIV-positive mothers, universal screening becomes cheaper than voluntary screening even if no HIV-negative mothers were screened. CONCLUSION: Reference case analyses showed that universal HIV screening of pregnant women in Chicago would both decrease the number of HIV-infected newborns and save money in comparison to voluntary or no testing strategies. Sensitivity analysis was robust across all variables for the conclusion that universal screening was more effective than voluntary screening. For many communities that have HIV prevalence rates for mothers of >.21%, universal screening would also save money in comparison to voluntary screening. For communities with prevalence rates <.21%, the benefits of universal screening may outweigh the costs for screening as we found that desirable incremental cost-effectiveness ratios were found for prevalence rates as low as.0075%.

AIDS Serodiagnosis↗
PubMed2004

Cost-effectiveness analysis of total ankle arthroplasty.

BACKGROUND: There is renewed interest in total ankle arthroplasty as an alternative to ankle fusion in the treatment of end-stage ankle arthritis. Despite a lack of long-term data on the clinical outcomes associated with these implants, the use of ankle arthroplasty is expanding. The purpose of this cost-effectiveness analysis was to evaluate whether the currently available literature justifies the emerging use of total ankle arthroplasty. This study also identifies thresholds for the durability and function of ankle prostheses that, if met, would support more widespread dissemination of this new technology. METHODS: A decision model was created for the treatment of ankle arthritis. The literature was reviewed to identify possible outcomes and their probabilities following ankle fusion and ankle arthroplasty. Each outcome was weighted for quality of life with use of a utility factor, and effectiveness was expressed in units of quality-adjusted life years. Gross costs were estimated from Medicare charge and reimbursement data for the relevant codes. The effect of the uncertainty of estimates of costs and effectiveness was assessed with sensitivity analysis. RESULTS: The reference case of our model assumed a ten-year duration of survival of the prosthesis, resulting in an incremental cost-effectiveness ratio for ankle arthroplasty of $18,419 per quality-adjusted life year gained. This reflects a gain of 0.52 quality-adjusted life years at a cost of $9578 when ankle arthroplasty is chosen over fusion. This ratio compares favorably with the cost-effectiveness of other medical and surgical interventions. Sensitivity analysis determined that the cost per quality-adjusted life year gained with ankle arthroplasty rises above $50,000 if the prosthesis is assumed to fail before seven years. Treatment options with ratios above $50,000 per quality-adjusted life year are commonly considered to have limited cost-effectiveness. This threshold is also crossed when the theoretical functional advantages of ankle arthroplasty are eliminated in sensitivity analysis. CONCLUSIONS: The currently available literature has not yet shown that total ankle arthroplasty predictably results in levels of durability and function that make it cost-effective at this time. However, the reference case of this analysis does demonstrate that total ankle arthroplasty has the potential to be a cost-effective alternative to ankle fusion. This reference case assumes that the theoretical functional advantages of ankle arthroplasty over ankle fusion will be borne out in future clinical studies. Performance of total ankle replacement will be better justified if these thresholds are met in published long-term clinical trials.

Ankle Joint↗
PubMed1988

Covalent immobilization of proteins for high-sensitivity sequence analysis: electroblotting onto chemically activated glass from sodium dodecyl sulfate-polyacrylamide gels.

We report a new method for the preparation of proteins in a form suitable for high-sensitivity N-terminal amino acid sequence analysis. Proteins separated by polyacrylamide gel electrophoresis were electrophoretically transferred onto glass fiber filter paper chemically activated by the introduction of phenyl isothiocyanate functional groups. The proteins became covalently coupled to the matrix during the electrotransfer process. Bands containing transferred proteins were detected by fluorescent staining or autoradiography, cut out from the glass fiber filter, and directly loaded into the cartridge of a gas-phase sequenator. The covalent nature of the interactions between protein and glass fiber support permitted the use of more vigorous solid-phase sequencing protocols and of alternative sequencing reagents. This high-efficiency isolation and covalent coupling method provides the essential first step toward enhanced-sensitivity protein sequence analysis. The method has been successfully applied to the isolation of a wide variety of proteins from SDS-polyacrylamide gels, and was shown to be compatible with both the standard Edman reagent phenyl isothiocyanate and alternative sequencing reagents such as 4-(N,N'-dimethylamino)azobenzene-4'-isothiocyanate (DABITC).

Amino Acid Sequence↗
PubMed1984

Renal artery flow velocity analysis: a sensitive measure of experimental and clinical renovascular resistance.

Renal artery flow velocity analysis has recently been shown to be an indicator of renal parenchymal resistance. Noninvasive measurement of graded renovascular resistance is investigated with experimental models of canine gel microsphere embolization (n = 15), canine renal allografts (n = 4), and clinical renal allografts (n = 6). Intraoperative pulsed Doppler recordings were made on the canine renal artery simultaneous to pressure and flow measurements with sequentially increasing resistance. Transcutaneous echo-Doppler (Duplex) measurements were made on acute patient renal allografts following chemical estimation of renal function. Noninvasive prediction of renovascular resistance in the experimental canine gel microsphere and allograft models correlates with invasive recordings of volume flow (pressure nearly constant), r = 0.93 and r = 0.90, respectively. Duplex estimation of clinical renal allograft resistance and chemical prediction of renal function are similarly interdependent, r = 0.81. Directional arterial flow analysis may be a useful indicator of native and acute allograft renovascular resistance.

Animals↗
PubMed1998

High-sensitivity immunocytologic analysis of neuroblastoma cells in paired blood and marrow samples.

High-sensitivity immunocytochemistry was used to evaluate the relative frequency of neuroblastoma cells in bone marrow and peripheral blood in patients with neuroblastoma (NB). A total of 51 concomitant paired blood and marrow samples (102 total) from 35 patients with NB (age 4 months-31 years; stage 29 stage IV, 4 stage III, 2 stage IVS; 14 at diagnosis, 18 in relapse, 12 during treatment, and 7 off-therapy) were analyzed. Cytospins containing up to 10(6) cells each were prepared using the mononuclear cell (MNC) fraction. For immunocytologic staining, a primary mouse monoclonal anti-GD2 antibody (3F8), a secondary antimouse biotinylated antibody, and a streptavidin-alkaline phosphatase complex were used. A minimum of two cytospins containing a mean of 1.4 x 10(6) total MNCs was analyzed in addition to a negative and a positive control. No circulating tumor cells were detected when the concomitant marrow samples were negative or had <10 positive cells per 106 MNC (23 of 51 samples). Of the 18 marrow samples positive at 10-10,000 cells per 106 MNC, 6 had detectable NB cells in the corresponding blood sample, whereas for marrow samples with >10,000 NB cells per 10(6) MNC (1%), the concomitant blood sample was positive for 9 of the 10. When both marrow and blood samples were positive (15 BM-PB pairs), NB cell frequency was significantly lower in blood, with a mean difference of 2.14 logs (median 2.22, range -0.16-4.8, standard error 0.38). In patients with NB, circulating tumor cell frequencies seem to be substantially lower than in concomitant marrow samples, with a mean difference of >2 logs.

Adolescent↗
PubMed1977

High-sensitivity sequence analysis of peptides and proteins by 4-NN-dimethylaminoazobenzene 4'-isothiocyanate.

A manual high-sensitivity sequencing method is described, in which 4-NN-dimethylaminoazobenzene 4'-isothiocyanate is used for the stepwise degradation of amino acid residues from the peptides. The 4-NN-dimethylaminoazobenzene 4'-thiazolinones of amino acids that were released, after conversion into their thiohydantoin derivatives, were identified by t.l.c. on polyamide sheets. This new method is simple and sensitive, and requires only 2-10nmol of peptides or proteins for extended sequence analysis. The method was tested on the sequence analysis of a hexapeptide (Leu-Trp-Met-Arg-Phe-Ala), bradykinin, glucagon and native lysozyme. Results show that the proposed procedure is a sensitive method for the sequence determination of short peptides as well as for the partial sequence determination of intact proteins.

Amino Acid Sequence↗
PubMed1998

[Analysis of the clinical decision in the initial management of BPH].

RATIONALE: Diagnostic management of prostate benign hyperplasia remains a controversial issue subject to variations as made evident in surveys conducted in our country showing that 47.9% urologists regularly perform intravenous urography. The aim of this paper was to determine the preferred strategy from the standpoint of a more accurate diagnosis for evaluation of patients with prostate benign hyperplasia and no absolute indication for surgery. MATERIAL AND METHODS: The methodology used was an analysis of the decision taken by elucidation of the problem using a decision tree with three major choices: (a) to perform IPSS, flowmetry and ultrasound: (b) to perform IPSS and flowmetry, or (c) to perform IPSS alone. Basic analysis by estimation of the expected value and three sensitivity analysis, one-tailed and two-tailed, were used to see whether the dominant choice changed. RESULTS: The choice of performing IPSS alone, resulted in accurate diagnosis adjustment in 80.5% cases. When flowmetry was added from the beginning, this percentage declined to 66.2%; if ultrasound was also done, the decline reached down to 11.2%. The Odds Ratio (OR) for diagnosis imbalance was 15.52 and 33, in choice (a) versus choices (b) and (c), respectively. The OR for the IPSS and flowmetry choice to cause imbalance versus IPSS alone was 2, 12. Also, the choice with greater expected value was IPSS, and this result did not change with the sensitivity analysis. CONCLUSIONS: The choice that considers the possibility of symptom quantification in the IPSS scale and, based on the results, continuation of the diagnostic sequence is the one that should be followed, since it provides higher effectiveness from the standpoint of diagnosis adjustment.

Decision Trees↗
PubMed2004

Effect of Vitamin D on falls: a meta-analysis.

CONTEXT: Falls among elderly individuals occur frequently, increase with age, and lead to substantial morbidity and mortality. The role of vitamin D in preventing falls among elderly people has not been well established. OBJECTIVE: To assess the effectiveness of vitamin D in preventing an older person from falling. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Register from January 1960 to February 2004, EMBASE from January 1991 to February 2004, clinical experts, bibliographies, and abstracts. Search terms included trial terms: randomized-controlled trial or controlled-clinical trial or random-allocation or double-blind method, or single-blind method or uncontrolled-trials with vitamin D terms: cholecalciferol or hydroxycholecalciferols or calcifediol or dihydroxycholecalciferols or calcitriol or vitamin D/aa[analogs & derivates] or ergocalciferol or vitamin D/bl[blood]; and with accidental falls or falls, and humans. STUDY SELECTION: We included only double-blind randomized, controlled trials (RCTs) of vitamin D in elderly populations (mean age, 60 years) that examined falls resulting from low trauma for which the method of fall ascertainment and definition of falls were defined explicitly. Studies including patients in unstable health states were excluded. Five of 38 identified studies were included in the primary analysis and 5 other studies were included in a sensitivity analysis. DATA EXTRACTION: Independent extraction by 3 authors using predefined data fields including study quality indicators. DATA SYNTHESIS: Based on 5 RCTs involving 1237 participants, vitamin D reduced the corrected odds ratio (OR) of falling by 22% (corrected OR, 0.78; 95% confidence interval [CI], 0.64-0.92) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15 (95% CI, 8-53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. The inclusion of 5 additional studies, involving 10 001 participants, in a sensitivity analysis resulted in a smaller but still significant effect size (corrected RR, 0.87; 95% CI, 0.80-0.96). Subgroup analyses suggested that the effect size was independent of calcium supplementation, type of vitamin D, duration of therapy, and sex, but reduced sample sizes made the results statistically nonsignificant for calcium supplementation, cholecalciferol, and among men. CONCLUSIONS: Vitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%. Further studies examining the effect of alternative types of vitamin D and their doses, the role of calcium supplementation, and effects in men should be considered.

Accidental Falls↗
PubMed2006

The generalisability of pharmacoeconomic studies: issues and challenges ahead.

Developing from a previous review, this article revisits the generalisability theme to summarise recent advances in methodology and provide an update of challenges faced by producers and users of pharmacoeconomic data. Our original evaluative criteria encompassed technical issues, applicability and transferability. The technical elements of best practice are comparatively uncontroversial: choosing relevant alternatives; transparent reporting of methods and findings; accessing and applying the best-quality evidence; using best methods to synthesise data; and using deterministic sensitivity analysis to explore potential systematic bias whilst employing probabilistic sensitivity analysis to explore the influence of random error at the whole model level. The applicability of economic findings within their original policy context (e.g. national analyses based on generalisable within-country data) can be determined, provided that best practice guidelines for economic modelling are adhered to. The transferability of economic findings (from one policy setting to another, e.g. country, region, clinical setting or patient population) requires careful exploration of changes in resource implications, unit prices and outcomes, a process facilitated again by transparent reporting of methods, adjustment for baseline risk and potentially by recent statistical developments intended to deal with hierarchically structured data. Although there is considerable consensus in the published literature about these key issues, limitations remain for economic analysis as implemented because of its opaqueness of method, failure to reflect the opportunity cost of decisions and lack of societal mandate. If the primary purpose of health economic evaluation is to help society to obtain the best value from limited resources, then, at a time when most technologically advanced societies need to engage with the realities of limited healthcare funding, technocratic solutions alone appear insufficient. Making health economic findings accessible to patients, clinicians and society, in the form of relevant narratives, will help this essential debate and expose assumptions underpinning economic analysis to broader critical inspection.

Economics, Pharmaceutical↗
PubMed1991

[A highly sensitive immunoenzyme analysis using electrochemical detection].

The authors have developed a method for improving the sensitivity of electrochemical enzyme immunoassay, based on binding the enzymatic reaction volatile component to a complexone, followed by destruction of the complex in a flow-type amperometric detector. The lowest limit of the measured levels of blood serum antibodies and antigens is 10(-11)-10(-12) M. The method was tried in enzyme immunoassay of the blood serum IgE in patients with asthma and chronic obstructive bronchitis. Reduction of IgE level after therapy was found to be a regular feature; the authors claim that it may be considered as one of the criteria indicating the treatment efficacy.

Adult↗
PubMed1988

Extractive alkylation and gas chromatographic analysis of sulfide.

A sensitive analysis of sulfide in blood was established, using an extractive alkylation technique. Pentafluorobenzyl bromide was used as the alkylating agent, tetradecyldimethylbenzylammonium chloride as the phase-transfer catalyst, and potassium dihydrogenphosphate as the buffer to suppress the formation of sulfide. Mass fragmentography was used to identify the sulfide derivative and gas chromatography with an electron capture detector was used for quantitative determination, with the lowest limit of detection being about 0.01 microgram/g. The blood level of rats exposed to hydrogen sulfide was also determined.

Alkylation↗
PubMed2001

Decision analysis for small, asymptomatic intracranial arteriovenous malformations.

OBJECT: Asymptomatic intracranial arteriovenous malformations (AVMs) represent a clinically challenging problem because of the complex decision making that must be undertaken prior to beginning any type of treatment. In addition, the relative infrequency of these lesions means that there is relatively little experience reported in the literature. The authors use a decision-analysis technique to model the considerations that go into determining the treatment of these lesions in an effort to quantify the various risks and overall benefits conferred by the following three treatment strategies: observation/natural history, microsurgery, and stereotactic radiosurgery. METHODS: The authors conducted a thorough literature search to elucidate the risks and outcomes associated with each treatment option. These values were used to build and run a comprehensive Markov model to determine a base-case analysis. All of the input variables were also subjected to sensitivity analysis to identify the most influential input variables and the crossover points in which favored strategies changed. The base-case analysis suggested that microsurgery was the favored treatment option because this hypothetical cohort accumulated 21.53 quality-adjusted life years (QALYs) over the course of the model compared with the 16.97 QALYs and 16.40 QALYs for stereotctic radiosurgery and observation, respectively. Sensitivity analysis demonstrated that overall major neurological morbidity and mortality were the most influential input variables both perioperatively and during the radiosurgical "latent" period (that is, up to 2 years posttreatment). The maximum acceptable perioperative combined major neurological morbidity and mortality rate was 6.8%. The latent period combined major neurological morbidity and mortality would need to be 0.7% to make radiosurgery favorable in this analysis. CONCLUSIONS: Results of this decision analysis model suggest that microsurgery in the hands of experienced cerebrovascular surgeons, who can expect a less than 6.8% combined rate of major neurological morbidity and mortality, offers patients a greater overall quality of life over time.

Algorithms↗
PubMed2000

Decision analysis in dentistry--the last 30 years.

OBJECTIVES: To review publications in dentistry of decision analyses during the last 30 years. METHODS: A systematic review of the English literature from 1969 to 1998 was performed using specified indexing terms. The number of retrieved articles in dentistry was compared with the number of articles in medicine. The quality of articles in dentistry presenting a decision tree with utilities and a sensitivity analysis was judged using a published peer review process. We report weaknesses of the analyses together with selected applications. RESULTS: Sixty-seven articles were published on decision analysis in dentistry. Whilst the number of articles published in medicine has accelerated there has been a decline in the last four years in dental publications. Only 22 of the articles in dentistry presented a decision analysis with utilities and a sensitivity analysis. CONCLUSIONS: Current weaknesses of the decision analyses reported were: opaque basic assumptions in the description of the analysis, lack of data on patient preferences and of reliable data on the chances of the long-term effects and side effects of intervention together with an absence of sensitivity analyses. The decision analysis approach complements that of "evidence-based health care" by enabling the best empirical evidence to be used in clinical practice. Formal methods such as decision analysis will promote the rational use of existing knowledge. For it to do this the quality of research data will have to improve in dentistry. Furthermore decision analysis is important in education to demonstrate explicitly how decisions might be arrived at and improved.

Decision Support Techniques↗
PubMed2000

Intravascular ultrasound-guided interventions in coronary artery disease: a systematic literature review, with decision-analytic modelling, of outcomes and cost-effectiveness.

BACKGROUND: Intravascular ultrasound (IVUS) is the generic name for any ultrasound technology used in vivo within the blood vessels. More specifically, intracoronary ultrasound enables imaging of the coronary arteries from within the lumen. This review concentrates on the role of intracoronary ultrasound as an adjunct to interventional cardiology. OBJECTIVES: (1) To identify the literature on IVUS for guiding coronary interventions, and to synthesise evidence about outcomes compared with outcomes when IVUS guidance has not been used. (2) To use this evidence, together with other information about costs and outcomes, to model the cost effectiveness of IVUS guidance. (3) To synthesise the evidence on the reproducibility of measurements of cross-sectional area made using IVUS. METHODS DATA SOURCES: (1) Electronic searches of MEDLINE, EMBASE, Science Citation Index, Index to Scientific and Technical Proceedings, Engineering Compendex, Engineering Page One, Cochrane Library, Inside (British Library), 1990-98. (2) Contacting experts and centres of expertise, 1990-99. (3) Internet search, 1990-99. METHODS STUDY SELECTION: Studies of IVUS-guided coronary interventions performed on humans were included in the review. Non-English language studies were also included when they covered IVUS-guided stenting or angioplasty. Control evidence regarding outcomes without IVUS guidance was sought only from randomised controlled trials (RCTs). Studies investigating the reproducibility of measurements of cross-sectional area were included only if the results were expressed in terms of the mean and standard deviation of paired differences. METHODS DATA EXTRACTION: Checklists that covered study details, patient characteristics and results were completed independently by three reviewers. Consensus was reached on any disagreements. Local data were gathered on the costs of IVUS-guided stenting. METHODS DATA SYNTHESIS: Overall event rates were calculated by pooling patient results from the included studies. A decision-analytic model was used to combine information from the literature with cost estimates, in order to predict cost-effectiveness in terms of cost per restenosis event avoided by the use of IVUS guidance. The analysis was performed from the perspective of the healthcare provider. Sensitivity analysis was undertaken. A simple extrapolation was made to long-term outcome so that cost-utility (using quality-adjusted life years (QALYs)) could be estimated. The minimum detectable change in cross-sectional area was estimated from the reproducibility results. RESULTS: Only one study on IVUS-guided angioplasty satisfied the inclusion criteria, and there were no studies on IVUS-guided atherectomy or other IVUS-guided interventions that satisfied the inclusion criteria. Of the 15 articles on IVUS-guided stenting that satisfied the inclusion criteria, seven presented data on outcomes at 6 months post-intervention. The angiographic restenosis rate was 16 +/- 1%. This compared with 24 +/- 2% derived from five articles on stenting without IVUS guidance. Data for follow-up periods longer than 6 months were presented in only two studies. Data from a total of five studies were included in the decision-analytic model. The cost per restenosis event avoided was 1545 pound sterling. After extrapolation to long-term outcome, the calculated cost per QALY was 6438 pound sterling. The baseline QALY gain was only 0.03 years. Sensitivity analysis resulted in large differences between the best- and worst-case scenarios, for example, from a saving of 5000 pound sterling to a cost of 24,000 pound sterling restenosis event avoided. The smallest changes in cross-sectional area that could be measured were 1.6 mm2 by a single observer and 1.9 mm2 by different observers. CONCLUSIONS: Implications for healthcare: The evidence available is too weak for there to be any reliable implications for clinical practice. (ABSTRACT TRUNCATED)

Algorithms↗
PubMed2003

Measuring the hemodynamic response to primary pharmacoprophylaxis of variceal bleeding: a cost-effectiveness analysis.

OBJECTIVES: The hemodynamic response to ss-blockers alone or with nitrates is highly predictive of efficacy in prevention of variceal bleeding. Hemodynamic monitoring (HDM) requires catheterization of the hepatic vein and measurement of the hepatic venous pressure gradient, the difference between wedged and free hepatic venous pressure. The aim of this study was to compare HDM with no HDM in patients considered for primary pharmacoprophylaxis of esophageal variceal bleeding. METHODS: A decision model was constructed to compare HDM with no HDM in cirrhotic patients with moderate to large esophageal varices. Patients intolerant to beta-blocker therapy would undergo endoscopic variceal ligation; those with an inadequate hemodynamic response (HDR) to beta-blocker therapy could have nitrates added before ligation was considered. Variceal bleeding was treated with ligation, with transjugular intrahepatic portosystemic shunt (TIPS) reserved for refractory bleeding. Probabilities of treatment responses as well as risks of bleeding and mortality were based on published literature. Only direct costs were considered during the 5-yr time horizon. Outcomes were cost in United States dollars, survival length in life-years, and proportions of patients who experienced variceal bleeding, TIPS insertion, and mortality from any cause. RESULTS: In the base case analysis, HDM was either cost-saving ($2,523 US dollars /life-year gained) or cost-effective (incremental cost-effectiveness ratio of $5,200 US dollars/life-year saved) compared with no HDM, depending on whether nitrates were added to beta-blocker therapy. HDM reduced variceal bleeding by nearly 60% and had a small effect on all-cause mortality. In the sensitivity analysis, HDM was sensitive to the time horizon, as it was not cost-effective for a time horizon of <22 months and was not cost-saving before 49 months. The cost-effectiveness of HDM was not sensitive to reasonable variation in the probability of HDR to beta-blocker therapy, risk of bleeding, risk reduction with pharmacotherapy, or to the costs of HDM, bleeding, ligation, or TIPS. Probabilistic sensitivity analysis indicated that HDM was more effective and less costly 100% and 57% of the time, respectively. CONCLUSIONS: Compared with the current standard of no HDM, measuring the hemodynamic response of primary pharmacoprophylaxis substantially reduces the number of bleeding episodes and is cost-effective or cost-saving over a wide range of sensitivity analyses. A randomized trial of HDM is needed to verify its efficacy in clinical practice.

Adrenergic beta-Antagonists↗
PubMed2006

Cost-effectiveness of alternative treatments for women with osteoporosis in Canada.

BACKGROUND: During the years following menopause, estrogen levels decline leading to accelerated bone loss and an increased risk of osteoporosis and osteoporosis-related fractures. METHODS: Using a Markov model and decision analytic techniques, the long-term costs and outcomes of five treatment and secondary prevention strategies for osteoporosis were compared: 'no intervention', alendronate, etidronate, risedronate, and raloxifene. The base case analysis examined postmenopausal (65 year old) osteoporotic women without prior fracture. Probabilistic sensitivity analysis (PSA) was used to incorporate the impact of parameter uncertainty, and deterministic sensitivity analysis (DSA) was used to compare alternative patient populations and modeling assumptions. Life years and Quality Adjusted Life Years (QALYs) were used as measures of effectiveness. RESULTS: In the base case analysis, risedronate was dominated by etidronate and alendronate. Alendronate and etidronate were projected to have similar costs and QALYs, and the efficiency frontier was represented by 'no intervention', etidronate, alendronate, and raloxifene (Can$32 571, Can$38 623 and Can$114 070 per QALY respectively). Alternative assumptions of raloxifene's impact on CHD and breast cancer, alternative discount rates and alternative patient risk factors (e.g., starting age of therapy, CHD risk, and prior fracture risk) had significant impacts on the overall cost-effectiveness results for both the bisphosphonates and raloxifene. DISCUSSION: Using conventionally quoted benchmarks and compared to no therapy, alendronate, etidronate, and raloxifene would all be considered cost-effective alternatives for treating women with osteoporosis. Potential limitations of this study include the usual caveats and cautions associated with long-term projection models and the fact that not all inputs into the model are Canadian data sources.

Aged↗
PubMed1997

Signed rank statistics for coherent predictions.

A generalization of Wilcoxon's signed rank test is proposed for testing a dose-response relationship with one or more outcomes. The test is useful in matched observational studies or in nonrandomized experiments that use dose-response relationships and predictions about multiple outcomes in an effort to distinguish actual treatment effects from hidden biases. A sensitivity analysis indicating whether a dose-response relationship or multiple predictions are confirmed with sufficient strength to reduce sensitivity to hidden bias is performed. Together, the test and the sensitivity analysis help to quantify the degree to which a coherent pattern of associations is present or absent, and the degree to which this strengthens or fails to strengthen evidence of cause and effect. Formal properties of tests of this kind are examined. The form of the optimal test is determined, though this test is not usable because it depends upon the values of the unknown parameters under study. Also examined are the conditions under which the proposed test resembles the optimal test, as well as the impact of various violations of those conditions on power. An example involving matched pairs exposed to varying doses of cadmium is considered in detail.

Bias↗