Leslie A. Lenert

A Rapid Bedside Test for B-Type Peptide Predicts Treatment Outcomes in Patients Admitted for Decompensated Heart Failure: A Pilot Study

OBJECTIVES The goal of this study was to determine if B-type natriuretic peptide (BNP) levels predict outcomes of patients admitted with decompensated heart failure. BACKGROUND Treatment of decompensated congestive heart failure (CHF) has often been based on titration of drugs to relieve patients symptoms, a case that could be made for attempting to also treat neurohormonal abnormalities. Because BNP reflects both elevated left ventricular pressure as well as neurohormonal modulation, we hypothesized that BNP might be useful in assessing outcomes in patients admitted with decompensated CHF. METHODS We followed 72 patients admitted with decompensated New York Heart Association class III to IV CHF, measuring daily BNP levels. We then determined the association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (death and 30-day readmission). RESULTS Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death: n = 13, readmission: n = 9). In these patients, BNP levels increased during hospitalization (mean increase, 233 pg/ml, p < 0.001). In patients without end points, BNP decreased (mean decrease 215 pg/ml). Univariate analysis revealed that the last measured BNP was strongly associated with the combined end point. In patients surviving hospitalization, BNP discharge concentrations were strong predictors of subsequent readmission (area under the receiver operator curve of 0.73). CONCLUSIONS In patients admitted with decompensated CHF, changes in BNP levels during treatment are strong predictors for mortality and early readmission. The results suggest that BNP levels might be used successfully to guide treatment of patients admitted for decompensated CHF.

Validity and Interpretation of Preference-based Measures of Health-related Quality of Life

Utilities are numeric measurements that reflect an individual’s beliefs about the desirableness of a health condition, willingness to take risks to gain health benefits, and preferences for time. This report discusses the approaches to assess and compare the validity of methods used to assign utilities for cost-utility analysis. Threats to validity include construct underrepresentation and construct-irrelevant variance. Construct underrepresentation occurs when a stimulus presented to a judge fails to fully represent the depth and complexity of information required in actual judgments. Construct-irrelevant variation occurs when factors irrelevant to preferences influence measurements of utilities. Among several factors that cause construct-irrelevant variation are cognitive abilities, numeracy skills, emotions and prejudices, and the elicitation procedure. Commonly used elicitation methods (visual-analog scales, time tradeoff, and standard gamble) capture different facets of utilities (desirableness of states, time preferences, and risk attitude) to different degrees. The validity of an elicitation protocol depends (1) on the degree to which its scaling method captures the relevant facets of utility and (2) on the degree to which measurements are influenced by construct-irrelevant variation. Discrete-state health index models provide an alternative to direct elicitation of utilities and work by attaching fixed preference weights to observable health states. The creation of discrete-state models with current technologies requires the adoption of strong assumptions about the scaling properties of utilities. Future research must refine methods of eliciting utilities and identify sources of construct-irrelevant variability that reduce the validity of utility assessments. Because of the impact of variation in techniques on measurements, we do not recommend the combination of utilities elicited with different protocols in cost-utility analysis and do not recommend the display of cost-utility ratios from different studies in comparison or “league” tables.

Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis.

OBJECTIVE To assess the practicality of an automated computer interview as a method to assess preferences for use in decision making. To assess preferences for outcomes of deep vein thrombosis (DVT) and its treatment. STUDY DESIGN A multimedia program was developed to train subjects in the use of different preference assessment methods, presented descriptions of mild post-thrombotic syndrome (PTS), severe PTS and stroke and elicited subject preferences for these health states. This instrument was used to measure preferences in 30 community volunteers and 30 internal medicine physicians. We then assessed the validity of subject responses and calculated the number of quality-adjusted life years (QALYs) for each individual for each alternative. RESULTS All subjects completed the computerized survey instrument without assistance. Subjects generally responded positively to the program, with volunteers and physicians reporting similar preferences. Approximately 26.5% of volunteers and physicians had preferences that would be consistent with the use of thrombolysis. Individualization of therapy would lead to the most QALYs. CONCLUSIONS Utilization of computerized survey instruments to elicit patient preferences appears to be a practical and valid approach to individualize therapy. Application of this method suggests that there may be many patients with DVT for whom treatment with a thrombolytic drug would be optimal.

Utilities for prostate cancer health states in men aged 60 and older

Purpose:We sought to measure utilities for prostate cancer health states in older men. Methods:A total of 162 men aged 60 years or older (52% of whom had been diagnosed with prostate cancer) provided standard gamble utilities for 19 health states associated with prostate cancer or its treatment using an interactive, computer-based utility assessment program. Demographics and experience with specific health states were examined as predictors of ratings using ordinary least squares regression analysis. Results:Mean utilities ranged from 0.67 to 0.84 for living with symptom-free cancer under conservative management (“watchful waiting”) and from 0.71 to 0.89 for symptoms occurring with treatment (prostatectomy, radiation, and hormone ablation). For long-term treatment complications, bowel problems (0.71) were rated as significantly worse than impotence (0.89), urinary difficulty (0.88), or urinary incontinence (0.83). Combinations of these conditions were rated as significantly worse than individual component states. Men who had experienced impotence or urinary incontinence rated these states as slightly better than men who had not experienced the specific problems. Conclusions:Both “watchful waiting” and treatment complications from prostate cancer treatments can have large impacts on quality of life. Mean ratings are important for use in policy-making and cost-effectiveness analyses. Variation in ratings across patients suggests that mean scores do not reflect individual preferences and that shared decision-making may be best for clinical decisions.

Public preferences for health states with schizophrenia and a mapping function to estimate utilities from positive and negative symptom scale scores

BACKGROUND Schizophrenia is a common severe syndrome with a highly variable pattern of symptoms. The medications used to treat this disorder are expensive and may cause severe adverse effects. Little is known about how the public perceives health outcomes in schizophrenia or the potential adverse effects of antipsychotic medication. This complicates the use of standard cost-effectiveness analysis to set priorities for health resource allocation. OBJECTIVE In this study, we measured utility weights for a set of health states derived from Positive and Negative Symptom Scale (PANSS) scores, and a set of health states that included the presence of common adverse effects of medication, thus creating utility mapping function for clinical data. METHODS We presented a convenience sample of members of a large commercial Internet survey panel with digital video materials portraying eight different patterns of schizophrenia with varying levels of positive, negative and cognitive symptoms, and five common adverse effects of antipsychotic medications. We then elicited their standard gamble (SG) and visual analog scale (VAS) ratings using iMPACT3 computer program, with an automated error repair feature, deliberately over-sampling minority ethnic groups in the panel. We censored subjects with uncorrected errors in ratings and estimated utilities for each state by re-weighting responses to match United States population demographics. SUBJECTS 620 well-educated, ethnically diverse volunteers (54% Caucasian), who spanned a broad range of age groups and geographical regions of the US participated in this study. RESULTS Because of evidence of bias in ratings, 175 (29%) subjects with internal inconsistencies in ratings were censored from estimates of mean population utilities. In the remaining 441 subjects, SG utilities, re-weighted to match US population demographic profiles, ranged from 0.88 for mild schizophrenia to 0.47 extremely severe schizophrenia. Variability in the types of symptoms exhibited (positive, negative or cognitive) was less important to participants than the overall severity of each state. Modest reductions in symptoms (for example, from severe to moderate or moderate to mild) were associated with relatively large changes in utility (0.12-0.19). Adverse effects decreased utilities for states by amounts ranging from 0.09 (pseudo-parkinsonism) to 0.05 (obesity). CONCLUSIONS The public views schizophrenia is a very disabling syndrome and treatments that reduce symptoms produce important gains in utility, even if they do not induce a complete remission. Adverse effects significantly reduce utilities for states; therefore, cost-effectiveness analyses for this disorder should take adverse effects of treatment into consideration.

Electronic Support for Public Health: Validated Case Finding and Reporting for Notifiable Diseases Using Electronic Medical Data

Health care providers are legally obliged to report cases of specified diseases to public health authorities, but existing manual, provider-initiated reporting systems generally result in incomplete, error-prone, and tardy information flow. Automated laboratory-based reports are more likely accurate and timely, but lack clinical information and treatment details. Here, we describe the Electronic Support for Public Health (ESP) application, a robust, automated, secure, portable public health detection and messaging system for cases of notifiable diseases. The ESP application applies disease specific logic to any complete source of electronic medical data in a fully automated process, and supports an optional case management workflow system for case notification control. All relevant clinical, laboratory and demographic details are securely transferred to the local health authority as an HL7 message. The ESP application has operated continuously in production mode since January 2007, applying rigorously validated case identification logic to ambulatory EMR data from more than 600,000 patients. Source code for this highly interoperable application is freely available under an approved open-source license at http://esphealth.org.

Differences in health values among patients, family members, and providers for outcomes in schizophrenia.

Objective.The objectives of this study were to determine whether there are important differences in how patients, family members, and health care providers (HCPs) value health outcomes in schizophrenia and to assess the degree to which such differences, if they exist, could adversely affect clinical and policy decision making. Methods.Participants viewed videotaped depictions of simulated patients with mild and moderate symptoms of schizophrenia, with and without a common adverse drug effect (pseudoparkinsonism), and then provided standard gamble and visual analog scale ratings of desirability of these states. Subjects.A convenience sample of unrelated patients (n = 148), family members of patients (n = 91), and HCPs (nurses, psychologists, doctors of pharmacy, and doctors of medicine; n = 99) was drawn from geographically and clinically diverse environments. Results.Patients’ and family members’ utilities for health states averaged 0.1 to 0.15 units higher than those of HCPs (P <0.002 for differences between groups, ANOVA for multiple observations). The disutility of adverse drug effects was less for health professionals than patients and family members (P = 0.008). Health professionals tended to prefer states with mild symptoms with extrapyramidal side effects to states with moderate symptoms. Patients and family members found these states equally preferable (P <0.007 for differences between groups). Conclusions.There are systematic differences in values for health outcomes between patients and HCPs with regard to states with adverse effects of antipsychotic drugs. Family members of patients in general had values that were more similar to those of patients than were those of health professionals. The results emphasize the importance of participation by patients (or family member proxies) in clinical decision making and guideline development.

Public Health Surveillance and Meaningful Use Regulations: A Crisis of Opportunity

The Health Information Technology for Economic and Clinical Health Act is intended to enhance reimbursement of health care providers for meaningful use of electronic health records systems. This presents both opportunities and challenges for public health departments. To earn incentive payments, clinical providers must exchange specified types of data with the public health system, such as immunization and syndromic surveillance data and notifiable disease reporting. However, a crisis looms because public healths information technology systems largely lack the capabilities to accept the types of data proposed for exchange. Cloud computing may be a solution for public health information systems. Through shared computing resources, public health departments could reap the benefits of electronic reporting within federal funding constraints.

Quality-of-Life Research on the Internet: Feasibility and Potential Biases in Patients with Ulcerative Colitis

Objective: The World Wide Web (WWW) is a new communications medium that permits investigators to contact patients in nonmedical settings and study the effects of disease on quality of life through self-administered questionnaires. However, little is known about the feasibility and, what is more important, the validity of this approach. An on-line survey for patients with ulcerative colitis (UC) and patients whose UC had been treated with surgical procedures was developed. To understand how patients on the WWW might differ from those in practice and the potential biases in conducting epidemiological research in volunteers recruited on the Internet, post-surgery patients who responded to the WWW survey were compared with those in a surgical practice. Setting: The Internet and private practice surgical clinic. Main outcomes: Scores from the Short form 36 (SF-36) Health Assessment Questionnaire and the Self-Administered Inflammatory Bowel Disease Questionnaire (IBDQ).

Adverse effects of medications and trade-offs between length of life and quality of life in human immunodeficiency virus infection

In the mid-1990s, the availability of enhanced “combination therapy” antiviral regimens revolutionized treatment of patients with the human immunodeficiency virus (HIV) (1,2). Although efficacious in controlling viral expression in many patients, combination therapy does not cure the infection. Furthermore, in contrast with advanced infection, there is little published evidence that early initiation of combination therapy influences the course of HIV disease (3). In response, several recent articles have called for delays in initiation of therapy and an “individualized” approach to treatment (3–5). We sought to determine which aspects of therapy physicians should discuss with patients, given the limitations of combination therapy. An important consideration, for example, may be a patient’s beliefs about adverse drug effects. A patient who believes that combination therapy poses a substantial threat to his or her quality of life might prefer to initiate treatment at a lower CD4 count, or to take an alternative, less effective, regimen. We examined the beliefs and preferences of patients with HIV disease about trade-offs between length of life and an aspect of quality of life that many persons value highly—physical appearance. We were concerned specifically about the lipodystrophy syndrome, a relatively common problem that is thought to be an adverse effect of combination antiretroviral therapy (6,7). Lipodystrophy syndrome can include loss of body fat in the face and extremities, deposition of fat in the central abdomen and the back of the neck, and, in women, enlargement of the breasts (7). Although not the only potential adverse effect of combination therapy regimens, the syndrome can be grossly disfiguring and is easily explained to patients. This makes it a potentially useful model to study HIV-infected patients’ willingness to trade length of life to avoid risks to quality of life from adverse drug effects. METHODS