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Biomedical subjects

A J Moskowitz

Publications and source records attributed to A J Moskowitz.

At least 19 recordsLinked to original sources
PubMed2001

Long-term use of a left ventricular assist device for end-stage heart failure.

BACKGROUND: Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. METHODS: We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. RESULTS: Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95) times that in the medical-therapy group, with a predominance of infection, bleeding, and malfunction of the device. The quality of life was significantly improved at one year in the device group. CONCLUSIONS: The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation.

Activities of Daily Living↗
PubMed2001

The cost of long-term LVAD implantation.

BACKGROUND: With increasing use of left ventricular assist devices (LVAD) worldwide, the economics of LVAD implantation have become an important focus of concern. Although these devices have high unit costs, they are the only hope for survival for a large group of terminally ill patients and are likely to have an expansion in indications for use. METHODS: We calculated the costs associated with long-term LVAD implantation. We used the ratio of cost-to-charges method to calculate hospital costs per resource category, market prices for drugs and device, and payments for physician services. RESULTS: Based on our experience with "bridge-to-transplantation" patients, we estimated average first-year costs to be $222,460 including professional fees and $192,154 excluding professional fees. The latter figure is comparable to average first-year costs for cardiac transplantation, which is $176,605 without professional fees at our institution. CONCLUSIONS: The costs of LVAD therapy will change after the first year of implantation, and device reliability and longevity will be important factors in determining these costs. Should the costs of LVAD therapy continue to track those of cardiac transplantation, devices will be cost-effective only if they offer similar efficacy to cardiac transplantation.

Ambulatory Care↗
PubMed2000

Hypoplastic left heart syndrome: valuing the survival.

OBJECTIVE: To examine the survival, developmental status, quality of life, and direct medical costs of children with hypoplastic left heart syndrome who have undergone stage I, II, and III reconstructive surgery. METHODS: A total of 106 children underwent staged repair for classic hypoplastic left heart syndrome between February 1990 and March 1999 (stage I: 106; stage II: 49; stage III: 25; 4 converted to heart transplantation). Survival was analyzed by the Kaplan-Meier method. In a cross-sectional study, parents assessed quality of life by completing the Infant/Toddler Child Health Questionnaire or Child Health Questionnaire Parent Format-28; they assessed developmental progress by completing the Ages and Stages Questionnaire. The ratio-of-costs-to-charges method was used to derive hospital costs, and payments were used to capture physician time and wholesale pricing for outpatient medications. RESULTS: Institutional 1-year and 5-year actuarial survivals were 58% and 54%. Birth weight, the need for preoperative inotropic drugs, and surgical experience were predictors of survival. Norwood I patients achieved fewer developmental benchmarks than those who survived to subsequent stages. Child Health Questionnaire Parent Format-28 mean summary scores for physical and psychosocial health were 48.5 +/- 6.3 and 42.8 +/- 9.9. The median inpatient costs for stage I, II, and III repairs were $51,000, $33,892, and $52,183, respectively. Monthly outpatient and readmission costs were less than 10% of total costs. CONCLUSION: A prospective, large-scale study of the comprehensive outcomes of staged repair and transplantation is needed. This study will need to address the longer-term developmental and quality-of-life outcomes, as well as the long-term cost effectiveness of these procedures.

Child Development↗
PubMed1999

Purine catabolism: links to mitochondrial respiration and antioxidant defenses?

Type I diabetes in rodents is associated with a spectrum of liver mitochondrial abnormalities ranging from evidence of oxidative stress and altered antioxidant defenses to frank defects in respiration rates and respiratory control ratios. To better address the myriad changes in redox metabolism in these mitochondria, we have applied new chromatographic techniques that enable simultaneous analysis of multiple components of pathways of interest (e.g., purine catabolites and oxidation by-products). We report here a portion of these results, which, in conjunction with other reported data, suggest that purine catabolism may contribute to mitochondrial antioxidant defenses by producing the antioxidant urate. In liver mitochondria from diabetic rats, increases in uric acid (threefold) and its direct precursor xanthine (sixfold) were observed in moderate diabetes, but levels fell essentially to normal in severe disease. Failure to maintain elevated xanthine and uric acid occurred contemporaneously with progressive mitochondrial dysfunction. Regression analysis revealed altered precursor-product relationships between xanthine, its precursors, and uric acid. An independent set of studies in isolated rat liver mitochondria showed that mitochondrial respiration was associated with essentially uniform decreases (approximately 30%) in all purine catabolites measured (urate, xanthine, hypoxanthine, guanine, guanosine, and xanthosine). That result suggests the potential for steady production of urate. Taken together, the two studies raise the possibility that purine catabolism may be a previously unappreciated component of the homeostatic response of mitochondria to oxidant stress and may play a critical role in slowing progressive mitochondrial dysfunction in certain disease states.

Animals↗
PubMed1999

Bayesian estimation of cost-effectiveness ratios from clinical trials.

Estimation of the incremental cost-effectiveness ratio (ICER) is difficult for several reasons: treatments that decrease both cost and effectiveness and treatments that increase both cost and effectiveness can yield identical values of the ICER; the ICER is a discontinuous function of the mean difference in effectiveness; and the standard estimate of the ICER is a ratio. To address these difficulties, we have developed a Bayesian methodology that involves computing posterior probabilities for the four quadrants and separate interval estimates of ICER for the quadrants of interest. We compute these quantities by simulating draws from the posterior distribution of the cost and effectiveness parameters and tabulating the appropriate posterior probabilities and quantiles. We demonstrate the method by re-analysing three previously published clinical trials.

Bayes Theorem↗
PubMed1999

The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure.

BACKGROUND: Because left ventricular assist devices have recently been approved by the Food and Drug Administration to support the circulation of patients with end-stage heart failure awaiting cardiac transplantation, these devices are increasingly being considered as a potential alternative to biologic cardiac replacement. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial is a multicenter study supported by the National Heart, Lung, and Blood Institute to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. METHODS: We discuss the rationale for conducting REMATCH, the obstacles to designing this and other randomized surgical trials, the lessons learned in conducting the multicenter pilot study, and the features of the REMATCH study design (objectives, target population, treatments, end points, analysis, and trial organization). CONCLUSIONS: We consider what will be learned from REMATCH, expectations for expanding the use of left ventricular assist devices, and future directions for assessing clinical procedures.

Heart Failure↗
PubMed1999

Volume-outcome relationships in cardiovascular operations: New York State, 1990-1995.

BACKGROUND: It has been known for nearly 20 years that, in cardiovascular operations, a significant inverse relationship exists between clinical outcomes and the volume of procedures performed. Interestingly, this relationship persists 2 decades after it was recognized. OBJECTIVE: The purpose of this study was to examine the relationship between hospital volume and in-hospital deaths in 3 cardiovascular procedures: coronary artery bypass grafting, elective repair of abdominal aortic aneurysms, and repair of congenital cardiac defects. METHODS: The database includes all patients who were hospitalized in New York State during the years 1990 to 1995. Using standard logistic regression techniques, we analyzed the relationship between hospital volume and outcome. RESULTS: No correlation exists between hospital volume and in-hospital deaths in coronary artery bypass grafting. Statewide, 31 hospitals performed 97,137 operations over the 6-year period (overall mortality rate, 2. 75%). By contrast, most of the hospitals statewide (195 of 230 hospitals) performed 9847 elective abdominal aortic aneurysm repairs with an overall mortality rate of 5.5%. In abdominal aortic aneurysm operations, a significant inverse relationship between hospital volume and in-hospital deaths was determined. Sixteen hospitals performed 7199 repairs for congenital cardiac defects. A significant inverse relationship (which was most pronounced for neonates) was found between volume and death. CONCLUSIONS: The importance of these findings lies in the rather striking difference between the volume-outcome relationship found for operations for abdominal aortic aneurysms and congenital cardiac defects and the lack of such a relationship for coronary artery bypass grafting. This observation may be largely explained by the quality improvement program in New York State for bypass operations since 1989. If so, these results have important implications for expanding the scope of quality improvement efforts in New York State.

Adolescent↗
PubMed1999

Probabilistic sensitivity analysis in cost-effectiveness. An application from a study of vaccination against pneumococcal bacteremia in the elderly.

OBJECTIVES: We explore the policy implications of probabilistic sensitivity analysis in cost-effectiveness analysis by applying simulation methods to a decision model. METHODS: We present the multiway sensitivity analysis results of a study of the cost-effectiveness of vaccination against pneumococcal bacteremia in the elderly. We then execute a probabilistic sensitivity analysis of the cost-effectiveness ratio by specifying posterior distributions for the uncertain parameters in our decision analysis model. In order to estimate probability intervals, we rank the numerical values of the simulated incremental cost-effectiveness ratios (ICERs) to take into account preferences along the cost-effectiveness plane. RESULTS: The 95% probability intervals for the ICER were generally much narrower than the difference between the best case and worst case results from a multiway sensitivity analysis. Although the multiway sensitivity analysis had indicated that, in the worst case, vaccination in the 85 and older age group was not acceptable from a policy standpoint, probabilistic methods indicated that the cost-effectiveness of vaccination was below $50,000 per quality-adjusted life-year in greater than 92% of the simulations and below $100,000 in greater than 95% of the simulations. CONCLUSIONS: Probabilistic methods can supplement multiway sensitivity analyses to provide a more comprehensive picture of the uncertainty associated with cost-effectiveness ratios and thereby inform policy decisions.

Aged↗
PubMed1998

The effectiveness of preoperative erythropoietin in averting allogenic blood transfusion among children undergoing scoliosis surgery.

Concerns about the transmission of the human immunodeficiency virus (HIV) have driven the evolution of surgical transfusion practices including the use of preoperative erythropoietin (rhEPO). Although there is significant experience documenting the efficacy of preoperative rhEPO in reducing transfusion requirements for adult patients, there is little experience in the pediatric population. With 178 pediatric patients who underwent surgery for spinal deformity, a retrospective cohort study was performed using patient charts, administrative records, and blood bank computer data. Of these patients, 44% received erythropoietin and 55% did not. From the entire population, 17.5% were in the rhEPO treatment group that received homologous blood transfusion compared with 30.6% in the untreated group (p < 0.05). Among the children with idiopathic scoliosis, this effect was more pronounced, with 3.9% of rhEPO patients receiving blood transfusion compared with 23.5% of nontreated patients (p = 0.006). Additionally, rhEPO treatment was associated with a significantly decreased length of stay only for patients in the idiopathic group (9.3 vs. 6.7, p = 0.02). Use of preoperative erythropoietin in pediatric patients undergoing scoliosis surgery resulted in higher preoperative hematocrit levels. Significantly lower rates of transfusion were noted only in the idiopathic group, however. Although there is a possibility of erythropoietin "resistance" in the neuromuscular and congenital patients, alternative explanations for the lack of effect on transfusion rates may include underdosing and biases existent in this nonrandomized retrospective study.

Adolescent↗
PubMed1997

Evolving costs of long-term left ventricular assist device implantation.

BACKGROUND: To examine the long-term costs of implanting a left ventricular assist device, we reviewed the initial hospitalization and outpatient costs for 12 patients who received a vented electric left ventricular assist device, and projected the first-year costs. METHODS: We used the ratio-of-cost-to-charges method to measure hospital costs and payments for physician time. We examined time trends in the resource use of 50 pneumatic left ventricular assist device recipients, using actuarial techniques and regression modeling. RESULTS: The average actual cost of left ventricular assist device support is $221,313 over an average of 9.5 months. If there had been no Food and Drug Administration regulatory policy precluding hospital discharge before 30 days, this value would have been $201,148. Based on this latter figure, the average predicted first-year cost is $219,139. The length of the intensive care unit stay, one of the most costly components of care, decreased significantly over time. CONCLUSIONS: The high costs of left ventricular assist device implantation are similar to those reported for cardiac transplantation. Given their success in supporting survival, we anticipate that these devices will be similarly cost-effective. However, further research is imperative to determine the cost-effectiveness of these devices beyond the introductory phase, when costs, benefits, and Food and Drug Administration requirements have stabilized.

Actuarial Analysis↗
PubMed1997

Quality of life with an implanted left ventricular assist device.

BACKGROUND: With the increasing use of left ventricular assist devices (LVADs) for longer-term support of patients awaiting cardiac transplantation, we must now consider whether to use these devices as alternatives to medical therapy when biologic hearts are needed but not forthcoming. This expansion of use depends as much on quality of life as it does on survival. To draw an inference about long-term quality of life with implanted LVADs, we studied "bridged" patients at our institution. METHODS: We elicited, by standard gamble, the utilities (preferences) of bridged patients at three points in their care: before LVAD implantation, during LVAD support, and after cardiac transplantation. RESULTS: Utility was 0.548 (+/-0.276) before implantation, 0.809 (+/-0.136) during LVAD support, and 0.964 (+/-0.089) after transplantation. For patients interviewed during all three states of health, the utilities were significantly different (p = 0.0009 by analysis of variance). CONCLUSIONS: The quality of life with an LVAD was substantially better than with medical therapy, on par with renal transplantation (as established by others), and not as good as after cardiac transplantation. These results portend an acceptable quality of life for long-term use of LVADs for patients with end-stage heart failure and contribute to the growing body of evidence supporting a clinical trial to test this new use.

Female↗
PubMed1989

A patient with new Q waves: methods for decision making in the individual patient.

Decision analysis, an analytic approach to making decisions when uncertainty is present, has its foundation in probability and utility theory. It provides insights into the trade-offs that are involved when a selection must be made among patient management strategies. In general, several broad steps are involved. The process begins by formulating the clinical problem as a well focused choice among a limited set of clinical etiologies. These strategies are then structured explicitly in a model that depicts the clinical events that may ensue from each option. By assigning probability values to each outcome, the weighted average outcome or expected utility can be calculated for each alternative strategy. The strategy with the highest expected utility is the optimal one. The methods of decision analysis offer a number of distinct advantages. These include: 1) providing a structure with which to simplify and focus clinical dilemmas; 2) providing a forum for discussing clinical reasoning; and 3) developing a consensus among groups of decision makers.

Aged↗
PubMed1988

Dealing with uncertainty, risks, and tradeoffs in clinical decisions. A cognitive science approach.

To generate hypotheses about how physicians make difficult clinical decisions, we analyzed transcripts of the "thinking aloud" behavior of expert clinicians making a testing or treatment decision with an uncertain diagnosis. We compared the clinicians' reasoning with a decision analysis of the same problem. The experts did not formulate a global outline of their decision, but chained together a sequence of decisions based on available and incomplete information. Despite effective and efficient problem solving, the clinicians used numeric terms only as symbolic representations of likelihood, used limited information in choosing among alternatives, and dismissed the possibility that a less conventional strategy, empiric therapy, might yield equivalent outcome. We describe cognitive problem-solving strategies and knowledge representations that permit persons to make successful decisions despite limited processing resources. The same cognitive procedures probably contribute to observed errors in decision-making under uncertainty.

Amphotericin B↗
PubMed1987

Decision analysis: a progress report.

Since its introduction into medicine 15 years ago, decision analysis has been applied to difficult clinical problems. Several important advances have made the process more practical and acceptable: computer programs that eliminate the need for burdensome calculations, improved techniques for designing analytic models, the ability to carry out sensitivity analyses over several dimensions simultaneously, and the elaboration of clinically relevant measures of utility. Using these techniques, analysts have addressed many important clinical issues including screening for and prevention of disease, tradeoffs among tests and treatments, and the interpretation of clinical data under conditions of uncertainty. Problems with the approach remain and applications have not been extensive, but decision analysis is evolving as a powerful clinical tool and gradually is gaining acceptance in medical practice.

Bayes Theorem↗
PubMed1986

Clinical decision analysis using microcomputers. A case of coexistent hepatocellular carcinoma and abdominal aortic aneurysm.

Many difficult medical decisions involve uncertainty. Decision analysis-an explicit, normative and analytic approach to making decisions under uncertainty-provides a probabilistic framework for exploring difficult problems in nondeterministic domains. As the methodology has advanced, clinical decision analysis has been applied to increasingly complex medical problems and disseminated widely in the medical literature. Unfortunately, this approach imposes a heavy computational burden on analysts. Microcomputer-based decision-support software can ease this burden.

Aged↗
PubMedDate not supplied

A peripartum neurologic event: shooting from the hip.

We have shown that a simplified model, generated quickly in response to an emergency consultation, may provide useful insights in certain situations. A more developed model was useful in verifying these insights. Because the more complex model considered a longer time horizon than the simple model, it allows us to consider questions regarding long-term benefits of aneurysm repair. When modeling any problem, the most important reason for performing decision analysis is to gain insight from analyzing the clinical setting and from constructing the model. The quantitative results are usually of only minor importance. However, our most important insights are sometimes gained by looking beyond the quantitative level to understand the interactions of various effects within the model. In this case, it was those insights that were of the greatest benefit to the patient in arriving at a decision to have cerebral arteriography.

Adult↗
PubMedDate not supplied

Problems with interval estimates of the incremental cost-effectiveness ratio.

The defining feature of a confidence interval is that it has a fixed minimum probability of covering the true value of the parameter being estimated, whatever the value of the parameter. The authors demonstrate by simulation that some recently proposed methods for interval estimation of the incremental cost-effectiveness ratio (ICER) either do not satisfy this definition or have other problems that limit their usefulness in applications. The problems are most prominent when the ICER is large and the true effectiveness difference is small relative to its standard error. A modification of the percentile bootstrap confidence interval that involves a reordering of the sample space provides a partial solution of the problem.

Confidence Intervals↗