Costeffectiveness of diagnostic tests.

We review the principles underlying cost-effectiveness analysis of diagnostic tests and procedures. We use two clinical examples, diagnostic testing for early multiple sclerosis and for Helicobacter pylori to illustrate the methods of analysis and to show how the results can be useful for physicians or payers of health services in making decisions about provision and use of diagnostic services. Economic assessments of diagnostic tests are inherently more difficult than assessments of therapeutic interventions, mainly because of uncertainty about the relation between diagnosis and end results (outcomes) of care. Nonetheless, because of the increasing importance of diagnostic technology in medicine and healthcare, only with such assessments will the most value be gained from restricted medical resources.

Dedicated asthma center improves the quality of care and resource utilization for pediatric asthma: a multicenter study.

OBJECTIVES: To determine the relative effectiveness of pediatric asthma care among patients treated by a dedicated asthma center (AC) vs children who use the emergency department (ED) as a site of primary asthma care. METHODS: A retrospective case-control design was used. A random sample of AC cases was selected from a designated comprehensive AC over a 12-month period. Concurrent ED control patients were identified from all cases of pediatric asthma from five urban hospitals based on two or more ED visits. Cases and controls were matched (1:2) based on age and National Heart, Lung, and Blood Institute (NHLBI) asthma severity of illness classification. A telephone survey was administered to the caregivers of all enrolled patients in the study sample. RESULTS: Four elements of pediatric asthma care were examined: quality, access, hospital utilization, and functional impact of disease. Demographic data were similar between the ED cases and the AC controls. In terms of quality of care, the AC patients were more likely to use maintenance antiinflammatory medications, 60.2% vs 22.5% (OR = 5.3; 95% CI = 2.9 to 9.7) and more likely to be taking medications at school, 71.4% vs 48.1% (OR = 2.7; 95% CI = 1.5 to 4.7). In terms of access to care, the AC families were more likely to have a physician to call to assist with outpatient management, 98.2% vs 65.0% (OR = 25.3; 95% CI = 9.0 to 76.9). Frequent ED utilization (> or = 1 visit/month) was less likely in the AC patients, 9.2% vs 22.0% (OR = 0.35; 95% CI = 0.16 to 0.79) and school absenteeism was lower as well (9.5 +/- 6.7 days vs 16.6 +/- 10.3, p < 0.001). Additionally, the caregivers of the AC patients missed fewer workdays (4.7 +/- 2.8 vs 7.4 +/- 4.1; p = 0.03). CONCLUSIONS: Significant disparities in quality, access, resource utilization, and functional impact exist between AC and ED patients. Emergency physicians have a unique opportunity to improve the public health by directing ED patients toward pediatric AC treatment.

Reversibility of scrapie-associated prion protein aggregation.

During the course of the transmissible spongiform encephalopathy diseases, a protease-resistant ordered aggregate of scrapie prion protein (PrP(Sc)) accumulates in affected animals. From mechanistic and therapeutic points of view, it is relevant to determine the extent to which PrP(Sc) formation and aggregation are reversible. PrP(Sc) solubilized with 5 m guanidine hydrochloride (GdnHCl) was unfolded to a predominantly random coil conformation. Upon dilution of GdnHCl, PrP refolded into a conformation that was high in alpha-helix as measured by CD spectroscopy, similar to the normal cellular isoform of PrP (PrP(C)). This provided evidence that PrP(Sc) can be induced to revert to a PrP(C)-like conformation with a strong denaturant. To examine the reversibility of PrP(Sc) formation and aggregation under more physiological conditions, PrP(Sc) aggregates were washed and resuspended in buffers lacking GdnHCl and monitored over time for the appearance of soluble PrP. No dissociation of PrP from the PrP(Sc) aggregates was detected in aqueous buffers at pH 6 and 7.5. The effective solubility of PrP was <0.7 nm. Treatment of PrP(Sc) with proteinase K (PK) before the analysis did not enhance the dissociation of PrP from the PrP(Sc) aggregates. Treatment with 2.5 m GdnHCl, which partially and reversibly unfolds PrP(Sc), caused only limited dissociation of PrP from the aggregates. The PrP that dissociated from the aggregates over time was entirely PK-sensitive, like PrP(C), whereas all of the aggregated PrP was partially PK-resistant. PrP also dissociated from aggregates of protease-resistant PrP generated in a cell-free conversion reaction, but only if treated with GdnHCl. Overall, the results suggest that PrP aggregation is not appreciably reversible under physiological conditions, but dissociation and refolding can be enhanced by treatments with GdnHCl.

Wrapping hydroxyapatite orbital implants with posterior auricular muscle complex grafts.

PURPOSE: To report the use of posterior auricular muscle complex grafts as a wrapping material for hydroxyapatite orbital implants in enucleation surgery. METHOD: In a retrospective multicenter study, autogenous posterior auricular muscle complex grafts were used to cover hydroxyapatite orbital implants in 83 patients with a mean age of 38.6 years (range, 1 to 85 years), of whom 63 had primary unilateral enucleation and 20 had secondary orbital implants following enucleation. The mean follow-up period after posterior auricular muscle complex grafts was 36 months (range, 14 to 60 months). RESULTS: Of the 83 patients, two (2.4%) developed limited orbital implant exposure, which was treated with a second posterior auricular muscle complex "patch graft." No patient developed postoperative orbital infection or implant extrusion. All patients were fitted with an acceptable prosthesis and had satisfactory cosmetic and functional results. No patient developed vascular compromise or a wound defect associated with the posterior auricular donor site. CONCLUSION: Autogenous posterior auricular muscle complex grafts should be considered as an appropriate wrapping material for hydroxyapatite orbital implants for primary enucleation and for secondary orbital implants after enucleation.

Resident expectations of morning report: a multi-institutional study.

BACKGROUND: Morning report, a cornerstone of inter nal medicine residency programs for many years, involves a diverse group of teachers and learners with heterogeneous learning goals. METHODS: We distributed a self-administered, cross sectional survey to internal medicine residents to clarify the objectives of the learners at morning report. We selected a convenience sample of internal medicine residents at community- and university-based programs Questions were answered in a Likert scale or multiple-choice format. RESULTS: Residents from 13 residency programs in 7 states participated. We received 356 completed surveys, which represented a 63% response rate. The house staff in our sample preferred that half of the guest attending physicians be generalists. They indicated that the primary function of morning report should be educational, and preferred to discuss the management of a few interesting cases rather than review all patients admitted the previous day. The majority of respondents (60.8%) favored a stepwise presentation of cases to simulate the chronology of receiving information. Disease process, diagnostic workup, and evaluation of tests and procedures were all considered important topics for discussion, while medical ethics and research methods were viewed as less important. Responses varied little when stratified by sex, postgraduate year, type of residency program, subspecialty fellowship plans, or location of medical school. CONCLUSIONS: Residents from a diverse group of programs expressed remarkably similar opinions about morning report. Consistent with the recently increased emphasis on ambulatory care and general internal medicine in residency training, they expressed a desire for about 50% of the guest attending physicians to be generalists. In addition, they preferred a style in which challenging cases were presented in a stepwise manner.

Functional interaction of human immunodeficiency virus type 1 Vpu and Gag with a novel member of the tetratricopeptide repeat protein family.

Viral protein U (Vpu) is a protein encoded by human immunodeficiency virus type 1 (HIV-1) that promotes the degradation of the virus receptor, CD4, and enhances the release of virus particles from cells. We isolated a cDNA that encodes a novel cellular protein that interacts with Vpu in vitro, in vivo, and in yeast cells. This Vpu-binding protein (UBP) has a molecular mass of 41 kDa and is expressed ubiquitously in human tissues at the RNA level. UBP is a novel member of the tetratricopeptide repeat (TPR) protein family containing four copies of the 34-amino-acid TPR motif. Other proteins that contain TPR motifs include members of the immunophilin superfamily, organelle-targeting proteins, and a protein phosphatase. UBP also interacts directly with HIV-1 Gag protein, the principal structural component of the viral capsid. However, when Vpu and Gag are coexpressed, stable interaction between UBP and Gag is diminished. Furthermore, overexpression of UBP in virus-producing cells resulted in a significant reduction in HIV-1 virion release. Taken together, these data indicate that UBP plays a role in Vpu-mediated enhancement of particle release.

Informed decisions about protecting and promoting public health: rationale for a National Human Exposure Assessment Survey.

Accurate and reliable exposure-related information is essential for informed decisions about protecting and promoting public health. The need for more and better data on population exposures to environmental chemicals is discussed, with emphasis on the justification for collecting baseline data on exposure distributions for the general population and for important population subgroups. A rationale is provided for undertaking exposure surveillance in the U.S. population by means of a National Human Exposure Assessment Survey (NHEXAS). The knowledge and understanding generated by NHEXAS will contribute to more informed and more credible decisions in three ways: (1) by establishing a core set of approaches, methods, and data that will significantly advance the field of exposure analysis; (2) by developing a strong and direct connection between science (exposure research and surveillance) and policy (decisions about assessment, management, and communication of health risks); and (3) by creating a connected group of researchers and regulators who share a mutual appreciation and understanding of the value of exposure surveillance for well-reasoned decisions.

Overview of important design issues for a National Human Exposure Assessment Survey.

Exposure issues have important consequences for regulatory decisions. Reliable answers to exposure questions are critical for site cleanup, model validation, and cumulative risk issues, as well as giving perspective on our risk estimates. This paper discusses some of the important issues in designing the National Human Exposure Assessment Survey (NHEXAS) and, by implication, other exposure-monitoring-based studies as well. Sampling design issues are discussed in terms useful to exposure assessors. These issues include simple random sample designs versus more complex multistage designs, design efficiency, how to determine the sample size for the desired precision of the estimate, and the effects of stratification and oversampling on the needed sample size. This paper also discusses several important nonsampling issues such as population definition, response rates, and several potential sources of error in interpreting the monitoring results.

Estimating exposure and dose to characterize health risks: the role of human tissue monitoring in exposure assessment.

Exposure assessment is an integral part of health risk characterization. Exposure assessments typically address three critical aspects of exposure: the number of people exposed to the environmental toxicant, at specific concentrations, for the time period of interest; the resulting dose; and the relative contribution of important sources and pathways to exposure/dose. Because historically both "point-of-contact" measurements and information about dose and related pharmacokinetic processes have been lacking, exposure assessments have had to rely on construction of "scenarios" to estimate exposure and dose. This could change, however, as advances in development of biologic markers of exposure and dose make it possible to measure and interpret toxicant concentrations in accessible human tissues. The increasing availability of "biomarkers," coupled with improvements in pharmacokinetic understanding, present opportunities to estimate ("reconstruct") exposure from measurements of dose and knowledge of intake and uptake parameters. Human tissue monitoring, however, is not a substitute for more traditional methods of measuring exposure, but rather a complementary approach. A combination of exposure measurements and dose measurements provides the most credible scientific basis for exposure assessment.

Role of exposure databases in risk assessment.

Risk assessments have assumed an increasingly important role in the management of risks in this country. The determination of which pollutants or public health issues are to be regulated, the degree and extent of regulation, and the priority assigned to particular problems are all areas of risk assessment that influence the country's $100 billion annual investment in environmental protection. Recent trends in public policy have brought the practice of risk assessment under greater scrutiny. As policy makers increasingly insist that specific numerical risk levels (so-called bright lines) be incorporated into regulatory decisions, the stakes for good risk assessment practice, already high, are raised even further. Enhancing the scientific basis of risk assessments was a major goal of the Workshop on Exposure Databases. In this article, we present the Risk Assessment Work Group's evaluation of the use of exposurerelated databases in risk assessment and the group's recommendations for improvement. The work group's discussion focused on the availability, suitability, and quality of data that underly exposure assessments, a critical component of risk assessment. The work group established a framework for evaluation, based on exposure scenarios typically used in regulatory decisions. The scenarios included examples from Superfund, the Clean Air Act, the Toxic Substances Control Act, and other regulatory programs. These scenarios were used to illustrate current use of exposure data, to highlight gaps in existing data sources, and to discuss how improved exposure information can improve risk assessments. The work group concluded that many of the databases available are designed for purposes that do not meet exposure and risk assessment needs. Substantial gaps exist in measurements of actual human exposure and in the data necessary to model exposures, to characterize distributions of exposure, to identify high-risk groups, and to identify possible environmental inequities in exposure. The work group, on the basis of its findings, made both short-term and longer-term recommendations for improving the collection of exposure data in the future.

Mohs micrographic surgery for periorbital skin cancer.

The authors have illustrated the use of the Mohs technique on periorbital skin cancer. The indications for the technique are documented for eyelid and canthal neoplasia, and the case histories illustrate the potential danger of skin cancer in this area. It is the well balanced team of micrographic surgeons and reconstructive surgeons that will give the patient the best result.

Canthal fixation with a stainless steel screw: a report of ten patients.

During a period of six years (1981-1987) we have used the Nelson stainless steel screw for fixation of the medial canthal tissues to the medial orbital wall in nine patients and in the lateral wall in one. No complications have occurred in any of the patients, and we endorse its use.

Prevention of blindness after blepharoplasty.

As reported in the medical literature, approximately 68 patients have been blinded by complications of the blepharoplasty procedure. All cases have been associated with intraoperative or postoperative orbital hemorrhage. Those factors which will help blepharoplasty surgeons reduce the occurrence of orbital hemorrhage and subsequent blindness are reviewed.