Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders.At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.

Cardiovascular specialists have been leaders in medicine because of our willingness to study major clinical issues by means of randomized clinical trials. Consequently, the evidence supporting many cardiovascular treatments is substantial, especially when the results of multiple large clinical trials are consistent in showing strong benefits. Cardiovascular professional societies also have been at the forefront in forging consensus among clinical experts and codifying best practice into practice guidelines. It is reasonable to expect that a treatment demonstrated to be effective in clinical trials and strongly endorsed by professional guidelines will be adopted by practicing physicians and consistently used in day-to-day patient care.

Angiotensin-converting enzyme (ACE) inhibitors have followed this pathway of building evidence and professional consensus. Many randomized clinical trials have clearly shown that ACE inhibitors reduce mortality and morbidity rates among patients with heart failure and left ventricular systolic dysfunction. Pooled data from 5 large trials showed the odds of death of patients randomized to ACE inhibitors were reduced by 26% compared with placebo, translating into roughly 6 fewer deaths per 100 patients treated. The economic outcomes also are favorable because much of the cost of prescribing ACE inhibitors for heart failure is recouped by the reduced need for hospital admissions. Consequently, the use of ACE inhibitors for heart failure is quite cost-effective. The American College of Cardiology/American Heart Association Guidelines Committee has weighed the evidence and given ACE inhibitors for treatment of heart failure a Class I recommendation. Indeed, use of ACE inhibitors is so well accepted that it is part of the quality-of-care clinical performance measure for heart failure. There is little, if any, controversy that ACE inhibitors should be generally prescribed for patients with heart failure due to systolic dysfunction.

Use of ACE inhibitors increased progressively for heart failure through the early 1990s, but growth in use has stalled more recently, and a substantial number of patients with heart failure still do not receive ACE inhibitors. The data reported by Masoudi and associates in this issue of Circulation show a stubborn, persistent gap between ideal practice and actual use of ACE inhibitors for heart failure. These investigators found that between 1998 and 2001, only 68% of patients 65 years of age and older with heart failure, systolic dysfunction, and no contraindications to treatment received an ACE inhibitor. This percentage rose only to 76% of patients when either ACE inhibitor or angiotensin receptor blocker (ARB) use was counted. The percentage of patients receiving ACE inhibitors or ARBs was below 80% in all but 3 of the 55 subgroups examined by Masoudi and associates. The investigators found little explanation for this persistent and vexing gap between actual and ideal performance, inasmuch as the only strong predictor of ACE inhibitor use versus nonuse was the presence of preexisting renal dysfunction. The latest national report card on this important aspect of heart failure treatment shows a "D+" for ACE inhibitor use (68%), rising only to a "C" (76%) if extra credit is given for ARB use. Should we accept these grades?

Closing the Gap

Perhaps the most optimistic interpretation of the data reported by Masoudi and associates is that evidence from clinical trials, by itself, will only go so far in changing clinical practice. Evidence may be necessary to alter the knowledge and attitudes of physicians about treatment, but this may not be sufficient to change their management consistently. To close the gap between actual and ideal performance, additional, specific measures are probably needed. A variety of active interventions have been shown to improve use of evidence-based therapies. Masoudi and associates did not report any data on use of measures within the hospitals or physician practices that might improve quality of care, so there may be an opportunity to adopt such measures more widely. Reminder systems for physicians, either simple chart-based measures or more sophisticated computerized approaches, can be quite effective in improving use of medications when physicians agree that the medication is effective. Critical pathways, care maps, and other structured approaches to quality improvement also may work well within hospitals to increase adherence to evidence-based practice guidelines. Reorganization of care by use of heart failure care teams or nurse facilitators may be even more effective, but these approaches require a much greater commitment of resources. Nevertheless, multidisciplinary approaches are particularly attractive in the care of patients with chronic diseases such as heart failure, because management of multiple factors, including adherence to diet and medication recommendations, is needed for successful outcomes. The structure of our medical care system also may contribute to the gap between actual and ideal clinical management; paying for innovative practice improvement programs has been difficult because they are not readily reimbursed in the fee-for-service model (although they may be well suited to prepaid integrated healthcare systems).

We have paid a lot of attention to translation of novel therapies from the basic laboratory to proof of efficacy in clinical trials, yet we've not paid enough attention to the final steps of learning how to best deliver consistent, high-quality care. With more attention to the nitty-gritty details of practice improvement, the grade for ACE inhibitor use in patients with heart failure could (and should) be raised to an "A" on the next report card.

This issue of CHP/PCOR's quarterly newsletter covers news and developments from the spring 2004 quarter.

It features articles about: our new core faculty member Paul Wise, a children's health policy researcher who joins us from Boston University; a survey of patient safety culture now getting underway at hospitals nationwide; CHP/PCOR acting director Doug Owens' research findings on the cost-effectiveness of potential HIV vaccines; a wrap-up of the second annual Health Care Quality and Outcomes Research Conference, where CHP/PCOR faculty and trainees attended and presented research; and new CHP/PCOR assistant director Vandana Sundaram.

OBJECTIVE: To examine the effects of market-level managed care activity on the treatment, cost, and outcomes of care for Medicare fee-for-service acute myocardial infarction (AMI) patients.

DATA SOURCES/STUDY SETTING: Patients from the Cooperative Cardiovascular Project (CCP), a sample of Medicare beneficiaries discharged from nonfederal acute-care hospitals with a primary discharge diagnosis of AMI from January 1994 to February 1996.

STUDY DESIGN: We estimated models of patient treatment, costs, and outcomes using ordinary least squares and logistic regression. The independent variables of primary interest were market-area managed care penetration and competition. The models included controls for patient, hospital, and other market area characteristics.

DATA COLLECTION/EXTRACTION METHODS: We merged the CCP data with Medicare claims and other data sources. The study sample included CCP patients aged 65 and older who were admitted during 1994 and 1995 with a confirmed AMI to a nonrural hospital.

PRINCIPAL FINDINGS: Rates of revascularization and cardiac catheterization for Medicare fee-for-service patients with AMI are lower in high-HMO penetration markets than in low-penetration ones. Patients admitted in high-HMO-competition markets, in contrast, are more likely to receive cardiac catheterization for treatment of their AMI and had higher treatment costs than those admitted in low-competition markets.

CONCLUSIONS: The level of managed care activity in the health care market affects the process of care for Medicare fee-for-service AMI patients. Spillovers from managed care activity to patients with other types of insurance are more likely when managed care organizations have greater market power.

Variability in demand for hospital services may have important effects on hospital costs, but this has been difficult to examine because data on within-year variations in hospital use have not been available for large samples of hospitals. We measure daily occupancy in California hospitals and examine variation in hospital utilization at the daily level. We find substantial day-to-day variation in hospital utilization, and noticeable differences between hospitals in the amount of day-to-day variation in utilization. We examine the impact of variation on hospital costs, showing that increases in variance are associated with increases in hospital expenditures, but that the effects are qualitatively modest

OBJECTIVE: Positron emission tomography (PET) is a high-cost imaging tool primarily used in oncology, cardiology, and neuropsychiatry. Accurate estimates of the cost of PET are needed to assess its cost effectiveness and determine the appropriate role for this modality in clinical applications. We performed a survey-based cost analysis of PET with FDG by estimating direct, indirect, and capital costs from eight PET centers. A breakdown of the operational budget of PET centers and FDG-compounding facilities is presented along with the costs per scan. Differences in costs between sites that purchase FDG and those that manufacture FDG are also examined. MATERIALS AND METHODS: We sent surveys to managers of eight Veterans Affairs and two non-Veterans Affairs PET scanning and FDG-compounding facilities. The survey included questions about service volume and the direct costs of equipment, personnel, space, supplies, and repairs needed for FDG compounding and PET scanning and interpretation. We estimated the indirect costs associated with FDG compounding, PET scanning, and PET interpretation. RESULTS: Of the eight sites that responded to our survey, three sites manufacture FDG on-site, three sites purchase FDG, and two sites do both. The total mean cost per scan using manufactured FDG is 1885 US dollars, and it is 1898 US dollars using purchased FDG. CONCLUSION: PET is expensive. The cost is similar when FDG is manufactured or purchased. Because both PET and cyclotron facilities have high fixed costs, increasing the number of scans obtained and the number of FDG doses manufactured may lead to a decrease in unit costs.

Background: In recent years, there has been significant controversy over how institutional review board (IRB) procedures are structured, administered, and balanced against other concerns (for example, the feasibility of multicenter research). Formal economic analysis has been largely absent in these debates. With hospitals and research facilities under budgetary pressures, it is essential that cost-effective IRB systems be developed.

Objective: To estimate the cost of IRB procedures in an eight-site observational substance abuse treatment study.

Methods and Findings: We estimated the cost of each IRB "action" (initial reviews, continuing reviews, amendments, and adverse event reports) at each project site using a method that has been described in detail elsewhere. In brief, a national administrative database on IRBs was consulted to determine the estimated total cost of operating IRBs of various sizes. These total costs comprised personnel, space, supplies, and training. Dividing these total costs by the total number of actions conducted per year by an IRB yielded a cost per action. When these data were used as a reference point, each of the eight IRBs in our study was estimated to have a cost per action equal to that of IRBs of a comparable size in the national database.

All study procedures for the substance abuse treatment study were approved by our local university IRB. Nevertheless, the IRBs at each of the eight participating medical centers elected to conduct an independent, full-board review of the research protocol. The focus of our economic study was the costs of these "supplemental" IRB actions. In other words, how much money was expended on further reviewing the study after the home IRB had approved the project?

Expenditures for the supplemental IRB activities were estimated at $56 191 in 2001 dollars. This consumed 16.8% of the total research grant budget for all activities (recruiting sites, enrolling and interviewing participants, analyzing data) over the same period. Most of these costs ($29 824) reflected the IRBs' expenditures for 70 supplemental actions. Coordinating center personnel, space, and supply costs made up the second largest expense, at $16 951. The additional effort for the investigators at the eight participating sites totaled $9416.

Discussion: The high costs of IRBs were driven by several factors. First, our home IRB and committees at local sites frequently disagreed on the formatting of consent procedures and patient survey forms, and all expected final say on study implementation. This resulted in consent forms and patient survey instruments being reviewed and re-reviewed many times. Second, participating institutions required review both by hospital and affiliated university IRBs. We believe this redundancy was due to fear generated by recent high-profile cases in which research institutions were penalized for human subjects violations. Third, our coordinating center was often not allowed to directly contact IRB staff at the participating sites, nor would the nine IRBs involved (including our home IRB) communicate with each other. Coordinating center staff thus spent long periods translating and retransmitting information to IRB staff and local investigators scattered throughout the country, which slowed and sometimes garbled communication.

Conclusion: These extensive IRB procedures had no discernible impact on human subjects protection. The essential procedures of the study never changed substantially, despite exchanges of over 15 000 pages of material among the nine sites. In addition, as an empirical matter, no adverse incidents occurred among the participants. Researchers and policymakers should weigh the cost and benefits of multisite review for minimal-risk studies, such as observational health services research. The National Cancer Institute's centralized IRB for multisite phase III trials is an intriguing model. Other systems exist, although none has explicitly discussed minimal-risk studies. If costs such as those identified in this project continue to grow without consideration of the benefits of facilitating scientific projects, we worry that future research may be unjustly affected.

We compared results of safety climate survey questions from health care respondents with those from naval aviation, a high-reliability organization. Separate surveys containing a subset of 23 similar questions were conducted among employees from 15 hospitals and from naval aviators from 226 squadrons. For each question a "problematic response" was defined that suggested an absence of a safety climate. Overall, the problematic response rate was 5.6% for naval aviators versus 17.5% for hospital personnel (p0.0001). The problematic response was 20.9% in high-hazard domains such as emergency departments and operating room. Problematic response among hospital workers was up to 12 times greater than that among aviators on certain questions.

CONCLUSION: Although further research on safety climate in health care is warranted, hospitals may need to make substantial changes to achieve a safety climate consistent with the status of high-reliability organizations.