Economic evaluation of DNA ploidy analysis vs liquid-based cytology for cervical screening.

BACKGROUND: DNA ploidy analysis involves automated quantification of chromosomal aneuploidy, a potential marker of progression toward cervical carcinoma. We evaluated the cost-effectiveness of this method for cervical screening, comparing five ploidy strategies (using different numbers of aneuploid cells as cut points) with liquid-based Papanicolaou smear and no screening. METHODS: A state-transition Markov model simulated the natural history of HPV infection and possible progression into cervical neoplasia in a cohort of 12-year-old females. The analysis evaluated cost in 2012 US$ and effectiveness in quality-adjusted life-years (QALYs) from a health-system perspective throughout a lifetime horizon in the US setting. We calculated incremental cost-effectiveness ratios (ICERs) to determine the best strategy. The robustness of optimal choices was examined in deterministic and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, the ploidy 4 cell strategy was cost-effective, yielding an increase of 0.032 QALY and an ICER of $18 264/QALY compared to no screening. For most scenarios in the deterministic sensitivity analysis, the ploidy 4 cell strategy was the only cost-effective strategy. Cost-effectiveness acceptability curves showed that this strategy was more likely to be cost-effective than the Papanicolaou smear. CONCLUSION: Compared to the liquid-based Papanicolaou smear, screening with a DNA ploidy strategy appeared less costly and comparably effective.

Real-time data acquisition and alerts may reduce reaction time and improve perfusionist performance during cardiopulmonary bypass.

Delayed perfusionist identification and reaction to abnormal clinical situations has been reported to contribute to increased mortality and morbidity. The use of automated data acquisition and compliance safety alerts has been widely accepted in many industries and its use may improve operator performance. A study was conducted to evaluate the reaction time of perfusionists with and without the use of compliance alert. A compliance alert is a computer-generated pop-up banner on a pump-mounted computer screen to notify the user of clinical parameters outside of a predetermined range. A proctor monitored and recorded the time from an alert until the perfusionist recognized the parameter was outside the desired range. Group one included 10 cases utilizing compliance alerts. Group 2 included 10 cases with the primary perfusionist blinded to the compliance alerts. In Group 1, 97 compliance alerts were identified and, in group two, 86 alerts were identified. The average reaction time in the group using compliance alerts was 3.6 seconds. The average reaction time in the group not using the alerts was nearly ten times longer than the group using computer-assisted, real-time data feedback. Some believe that real-time computer data acquisition and feedback improves perfusionist performance and may allow clinicians to identify and rectify potentially dangerous situations.

Managing the extracorporeal membrane oxygenation (ECMO) circuit integrity and safety utilizing the perfusionist as the "ECMO Specialist".

Extracorporeal membrane oxygenation (ECMO) is an extracorporeal technique of providing both cardiac and respiratory support to patients whose heart and lungs are so severely diseased or damaged that they can no longer serve their function. Neonatal and pediatric ECMO was accepted as practice in the early 1990s and according to the Extracorporeal Life Support Organization, ELSO; of the >50,000 patients registered, 73% have survived extracorporeal life support (ECLS). It is not uncommon to find initial cannulation of a patient receiving ECMO performed by a surgeon and then the maintenance of the patient being left in the hands of various others deemed as the "ECMO Specialists". The specialist has a broad base of professionals, including: nurses, respiratory therapists, perfusionists and physicians. Each institution, having its own unique training for these individuals, has provided a milieu for education, but does not share an established standard of care. From 2009, after the surge of the H1N1 epidemic, adult ECMO has been increasing; n=53 in 2010 to n=110 in 2012 at our institution. The perfusionist has been the "specialist" for ECMO at our institution since the early 1990s and remained at bedside during ECMO. We have now developed a safe circuit and fiscally responsible staffing model that utilizes a perfusionist and a telemetry-based electronic record keeper, permitting the perfusionist to leave the bedside and interact with the circuit when necessary. This has permitted an expansive growth of ECMO in our intensive care units at our facility incorporating a multidisciplinary collaboration system wide.

Case report: Remote monitoring using Spectrum Medical Live Vue allows improved response time and improved quality of care for patients on cardiopulmonary support.

Clinician rounding on bedside extracorporeal membrane oxygenation (ECMO) is a common coverage practice at many centers across the USA. Occasionally, clinical issues or concerns may go unnoticed for a considerable period of time during the intervals of clinician rounds. We report a case utilizing the LiveVue (Spectrum Medical, Fort Mill, SC) remote monitoring for care of a patient on ECMO. A patient was placed on veno-arterial (VA) ECMO in our intensive care unit, using a Rotaflow centrifugal pump and a Quadrox D polymethylpentene (PMP) fiber oxygenator (both Maquet, Fairfield, NJ). Following ECMO initiation and stabilization, a two-hour rounding schedule was established for the covering perfusionist. On day two, shortly after the perfusionist had rounded, the ECMO flow began fluctuating between 0.1 and 2.1 L/min. A compliance alert (i.e. red flashing notification) was recognized by the perfusion team on a large screen monitor installed in the perfusion pump room. Immediate response from the perfusion team identified venous inflow obstruction due to cannula malposition. The pump revolutions per minute (rpm) and, thus, the resulting flow were temporarily reduced to prevent vessel intimal damage and the surgical team was summoned to reposition the venous cannula. Later in that ECMO run, a steady rise in pre-oxygenator pressure was noted by the perfusionist. This increasingly concerning event was able to be trended and monitored with the LiveVue from a remote location. After a few hours, a compliance alert was noticed again on the LiveVue screen in the pump room. The pre-oxygenator pressure increased by 150 mmHg and the circuit flow decreased by half. Again, the perfusionist response was immediate and an oxygenator change-out ensued. Once more, a potentially dangerous clinical scenario was avoided with continuous critical parameter remote monitoring using the LiveVue system.

The cold thyroid nodule: an analysis of diagnostic and therapeutic options.

We applied decision analysis to the controversy over the management of the solitary nonfunctioning thyroid nodule. Three standard management plans were considered: immediate subtotal thyroidectomy; a six month trial of thyroid suppression with L-thyroxine, with non-suppressible lesions being removed surgically; and aspiration cytology followed by surgery or thyroid suppression based on the cytologic examination. The literature formed the basis for quantitative assumptions of the analysis, including the consequences of thyroidectomy, the probability of malignancy, the types and prognoses of cancers found at operation, the likelihood of successful suppression adn relapse, and the possible results of aspiration cytology. We used Bayes' rule to revise the probability of cancer on the basis of cytological results. The relative worths of the 59 possible diagnostic and therapeutic outcomes were expressed as quality-adjusted life expectancies. The expected utility of each management plan was determined by "folding back" the decision tree. Although we found that each possible approach yielded a quality-adjusted life expectancy very close to that of the healthy population, aspiration biopsy with cytologic examination appeared slightly superior. Extensive sensitivity analyses demonstrated that either aspiration biopsy or immediate thyroid suppression was the treatment of choice over a wide range of assumptions, although in no case did the benefit exceed 1 year of life. We conclude that all therapies for cold thyroid nodule are essentially equal, viewed in terms of mortality and morbidity. The decision to operate, suppress or aspirate is thus a " tossup ", dependent in the individual case upon such subjective factors as psychological disutility , relative cost, and attitudes toward operative risk and long-term medical therapy. The controversy concerning the "best" management of the cold thyroid nodule is an illusion: quantitative analysis shows the futility of pursuing the debate any further.

A computer-based Markov decision analysis of the management of symptomatic bifascicular block: the threshold probability for pacing.

This review illustrates the use of computer-based Markov models to estimate cost-effectiveness and prognosis in a complex problem in clinical cardiology. Decision analysis and cost-effectiveness analysis were used to assess whether to implant a permanent cardiac pacemaker, treat with drugs, perform electrophysiologic studies or observe patients who have two clinical features--syncope and bifascicular block--that may or may not be causally related. Using a Markov process model, a computer program simulated the prognosis of five cohorts of such patients--one treated conservatively, one given empiric antiarrhythmic drug therapy, one receiving a pacemaker, one treated with empiric drugs and pacing and one tested with electrophysiologic studies. On the basis of data from published reports and expert opinion, quality-adjusted life expectancy was calculated by summing the average time a member of each cohort would survive with and without symptoms for each initial treatment choice. The costs were estimated from 1985 hospital charges. For patients with normal left ventricular function, electrophysiologic testing provides a benefit of 14 quality-adjusted months of life over observation, at an additional cost of $24,200. Empiric pacing would add 2.5 additional months, at a further cost of $14,300. In patients with poor left ventricular function, empiric drug therapy offers 1.5 additional quality-adjusted months over observation, at a cost of $6,900. Electrophysiologic testing provides a further 16.5 months at an additional cost of $16,900. These results hold when the relation between symptoms and arrhythmia is not firmly established. Varying the probabilities of underlying ventricular tachyarrhythmias, bradyarrhythmic conduction defects or noncardiac causes of syncope affects the cost-effectiveness relative to the alternative treatments.

Chronic granulocyte leukemia with respiratory distress. Efficacy of emergency leukapheresis.

In the absence of preexisting pulmonary disease, progressive respiratory failure caused by leukostasis associated with uncontrolled chronic granulocytic leukemia developed in two patients. The conditions of both patients improved dramatically with aggressive leukapheresis. Clinical improvement correlated with decreased pulmonary wedge pressure, while vascular volume remained constant. Continuous-flow cell separation removed numerous immature myeloid cells, replaced them with oxygen-carrying erythrocytes, and maintained a constant blood volume. The course of these two patients demonstrates the use of continuous-flow leukapheresis in an intensive care unit to reduce leukocyte count and manifestations of leukostasis rapidly, while improving the oxygen-carrying capacity of blood, without exposing the patients to dangerously large shifts in fluid volume.

A convenient approximation of life expectancy (the "DEALE"). I. Validation of the method.

The physician developing a treatment plan for a particular patient often needs to know the life expectancy associated with the outcomes of therapeutic choices. Currently available methods for estimating life expectancy are cumbersome and of limited clinical use. We describe a simple approximation of life expectancy (the "DEALE") that is based on the assumption that survival follows a simple declining exponential function. In this approach, the reciprocal of the age-, sex-, and race-adjusted life expectancy is used to estimate the mortality rate of a healthy person. The life expectancy of a person who also has one or more diseases is obtained by adding disease-specific mortalities to the age-, sex-, and race-adjusted mortality rate and taking the reciprocal of that sum. In this paper we show that this approximation estimates life expectancy accurately for the great majority of clinical problems.

A convenient approximation of life expectancy (the "DEALE"). II. Use in medical decision-making.

We show how to use a bedside approximation of life expectancy in quantitative decision-making. This method, the declining exponential approximation of life expectancy (DEALE), enables the physician to collate various survival data with information on morbidity to determine a quality-adjusted expected survival for a potential management plan. The keystone in the DEALE approach is the approximation of survival by a simple exponential function. This approximation makes it possible to translate data from various literature sources (life expectancy tables, five-year survival rates, survival curves, median survival) into a single, unified mortality scale. In this paper, we use the DEALE method to obtain approximations of quality-adjusted life expectancy and illustrate the application of the method in a quantitative analysis of a clinical decision.

Comparative cost-effectiveness analysis of quinidine, procainamide and mexiletine.

Quinidine and procainamide have the potential for major organ toxicity, whereas mexiletine has been reported to have little risk of organ toxicity, serious proarrhythmia or congestive heart failure, but a relatively high incidence of nuisance side effects. In light of the potential adverse effects of all antiarrhythmic agents as highlighted by the Cardiac Arrhythmia Suppression Trial, the relative cost-effectiveness of these 3 agents was assessed. Based on a review of greater than 1,000 published reports, studies included in the analysis examined greater than or equal to 1 of these agents in adults, with adequate efficacy or safety data, or both. The majority of studies assessed patients with symptomatic or malignant arrhythmias, or both. Data were analyzed using a decision analysis/cost-effectiveness model. Probabilities were averaged using techniques of meta-analysis. Costs were obtained from a university medical center cost-accounting system and from expected follow-up visits to university clinics. Thirty-seven separate side effects were included in the analysis. In terms of overall cost, 12 months of mexiletine would engender $875, quinidine $1,239 and procainamide $1,911 of expenses. Mexiletine dominates the older agents in terms of cost per successful drug response, a result that holds over a wide range of efficacy and safety data. Analyses demonstrated no increase in all-cause mortality for quinidine and mexiletine over placebo, but a trend toward higher mortality with procainamide. The results suggest that mexiletine is a cost-saving alternative therapy for ventricular arrhythmias when adverse reactions are considered in addition to pharmaceutical costs and treatment efficacy.

Clinical and morphologic cardiac findings after anthracycline chemotherapy. Analysis of 64 patients studied at necropsy.

The relation between clinical evidence of and histologic signs of anthracycline cardiotoxicity was evaluated by reviewing the clinical and morphologic findings in 64 patients studied at necropsy, all of whom had received doxorubicin or daunorubicin chemotherapy during life. Of the 64 patients, 20 (31%) had documented clinical toxicity consisting of impaired left ventricular systolic performance; in 7 (35%) of these 20 patients, histologic signs of toxicity were absent. In the remaining 13 patients with clinical toxicity, histologic signs of toxicity ranged from mild to severe. Of the 44 (69%) patients without clinical signs of drug toxicity, 21 (48%) had no histologic sign of cardiotoxicity; in 23 (52%) of the patients without clinical toxicity, however, morphologic signs of cardiotoxicity were nevertheless present--mild in most patients, but extensive in 4. Signs of extensive histologic toxicity (19 [30%] of 64 patients) were associated with large doses (greater than 450 mg/m2) of the drug, mediastinal irradiation, and age greater than 70 years. This study suggests that attempts to monitor cardiotoxicity by serial evaluation of cardiac histology in patients undergoing anthracycline chemotherapy may be seriously limited by the fact that clinical evidence of toxicity may be present without histologic signs of toxicity; likewise, histologic signs of anthracycline toxicity may be present without clinical evidence of toxicity.

The "iron screen": modification of standard laboratory practice with data analysis.

Multivariate analysis was applied to iron deficiency anemia to generate an efficient sequence of diagnostic laboratory tests. A three step diagnostic system--serum ferritin level and mean corpuscular volume as a screen in all patients, followed by serum iron level and total iron binding capacity in some patients, and by erythrocyte sedimentation rate in a few patients--was constructed using a previously validated data reduction system. When compared to bone marrow iron stores, this system was found to have 96 per cent accuracy. In one year of clinical trial the "iron screen" classified 396 of 416 patients in a hospital setting. This sequential strategy shows how clinical laboratory data can be utilized to render diagnoses of defined probability.

Desaturated venous-to-arterial shunting reduces right-sided heart failure after cardiopulmonary bypass.

BACKGROUND: Right-sided circulatory failure is a major cause of morbidity in heart transplant and ventricular assist device recipients. METHODS: Several systems for managing right-sided circulatory failure with use of a right-to-left shunt without need for an oxygenator or systemic heparinization were designed and used clinically. RESULTS: A right-to-left shunt was successfully used to treat severe right-sided circulatory failure in both a transplant and a left ventricular assist device recipient. CONCLUSIONS: If constructed between the femoral vein and artery, such a shunt could (1) be easily inserted and removed, (2) selectively infuse the lower extremities with desaturated blood while maintaining cerebral and cardiac perfusion with saturated blood, (3) selectively reduce the risk of paradoxical emboli to the head and heart, and (4) provide a known and adjustable degree of shunting depending on the condition of the patient, a major advantage of this system compared with creation of an atrial septal defect.

Informatics. A subspecialty in pathology.

The emerging discipline of pathology informatics is reviewed, and its placement as a subspecialty within the broader field of pathology and laboratory medicine is proposed. Informatics concepts should guide the development of the next generation of laboratory information systems. Advanced laboratory systems will incorporate decision support leading to improvements in quality and in interpretive reporting providing support for clinical diagnosis and decision making. Training programs in pathology should take into account the need for expertise in informatics and develop fellowships in this area to adequately prepare junior faculty members for their future professional role.

A knowledge-based system for transfusion advice.

A knowledge-based system has been designed for evaluating the appropriateness of transfusion of non-red blood cell blood components. The goal of the system is to assist the blood bank physician in quality assurance efforts by automatically identifying cases of inappropriate transfusion before the blood is issued. Evaluation of a working prototype system shows that it is indeed capable of serving this function. The system identifies and summarizes cases, but it leaves consultation, education, and decision making to the blood bank physician. Small "expert systems" such as this may find use in quality assurance activities throughout the laboratory.

Workflow computing. Improving management and efficiency of pathology diagnostic services.

Traditionally, information technology in health care has helped practitioners to collect, store, and present information and also to add a degree of automation to simple tasks (instrument interfaces supporting result entry, for example). Thus commercially available information systems do little to support the need to model, execute, monitor, coordinate, and revise the various complex clinical processes required to support health-care delivery. Workflow computing, which is already implemented and improving the efficiency of operations in several nonmedical industries, can address the need to manage complex clinical processes. Workflow computing not only provides a means to define and manage the events, roles, and information integral to health-care delivery but also supports the explicit implementation of policy or rules appropriate to the process. This article explains how workflow computing may be applied to health-care and the inherent advantages of the technology, and it defines workflow system requirements for use in health-care delivery with special reference to diagnostic pathology.

Multivariate approach to predictive diagnosis of bone-marrow iron stores.

The authors constructed a computer-assisted multivariate data analysis system that finds the subset of a group of laboratory tests (i.e., experimental variables) best able to discriminate between previously identified subpopulations. A Bayesian decision-analysis algorithm was devised for predictive diagnosis by the use of sample means and standard deviations of those identified tests. This approach was used on a set of nine hematologic laboratory tests to find a subset capable of efficiently predicting the presence or absence of bone-marrow iron stores. This identified subset proved to have a diagnostic efficiency of 0.90. The success of this system suggests the feasibility of such an approach in finding a "best" subset of loosely related variables.

Hypermedia in pathology--the Dartmouth Interactive Medical Record project.

Hypermedia and hypertext are the focus of intense interest in multiple disciplines in medicine, particularly pathology. This communication provides explanation of theories and applications that serve as motivation for the expansion of use of these technologies. The Dartmouth Interactive Medical Record (IMR) project is discussed.