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Background: Despite the prevalence of evidence-based interventions to improve quality in health care systems, there is a paucity of documented evidence of a financial return on investment (ROI) for these interventions from the perspective of the investing entity.Purposes: To report on a demonstration project designed to measure the business case for selected quality interventions in high-risk high-cost patient populations in 10 Medicaid managed care organizations across the United States.Methodology/Approach: Using claims and enrollment data gathered over a 3-year period and data on the costs of designing, implementing, and operating the interventions, ROIs were computed for 11 discrete evidence-based quality-enhancing interventions.Findings: A complex case management program to treat adults with multiple comorbidities achieved the largest ROI of 12.21:1. This was followed by an ROI of 6.35:1 for a program which treated children with asthma with a history of high emergency room (ER) use and/or inpatient admissions for their disease. An intervention for high-risk pregnant mothers produced a 1.26:1 ROI, and a program for adult patients with diabetes resulted in a 1.16:1 return. The remaining seven interventions failed to show positive returns, although four sites came close to realizing sufficient savings to offset investment costs.Practice Implications: Evidence-based interventions designed to improve the quality of patient care may have the best opportunity to yield a positive financial return if it is focused on high-risk high-cost populations and conditions associated with avoidable emergency and inpatient utilization. Developing the necessary tracking systems for the claims and financial investments is critical to perform accurate financial ROI analyses. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Balanced Budget Act of 1997 dramatically changed the way that Medicare pays skilled nursing facilities and also cut per-diem rates. Previous studies have found effects on facility-wide staffing but not on quality for short-stay residents. Because facilities may combine revenue streams to be used where needed, spillover effects on quality of care for long-stay residents are possible. OBJECTIVE: We sought to investigate effects of financial pressures from Medicare payment changes on quality of care for long-stay residents. METHODS: We investigated the effect of Medicare's Prospective Payment System for skilled nursing facilities on incidence of urinary tract infections and pressure sores among long-stay residents while controlling for resident severity. We conducted panel data analysis of nursing home residents in Ohio, Kansas, Maine, Mississippi, and South Dakota using Minimum Data Set data from 1995 to 2000. Each facility's Medicare dependence was used to separate effects of the policy from underlying industry trends. RESULTS: The probability of developing a urinary tract infection or pressure sore increased significantly among long-stay residents after Medicare's prospective payment system was implemented. Effects were roughly proportional to the percent of residents in a facility covered by Medicare. CONCLUSIONS: Although Medicare prospective payment and rate cuts were directly applicable only to Medicare (largely short-stay) residents in skilled nursing facilities, the resulting financial pressures lowered the quality of care experienced by long-stay residents, as measured by the likelihood of adverse outcomes. The observed quality decreases were likely due to decreases in nurse staffing prompted by the payment reductions. [ABSTRACT FROM AUTHOR]

There is a growing and increasingly compelling body of evidence that self-management interventions for persons with type 2 diabetes can be both effective and cost-effective from a societal perspective. Yet, the evidence is elusive that these interventions can produce a positive business case for a sponsoring provider organization in the short term. The lack of a business case limits the enthusiasm for provider organizations to implement these proven quality-enhancing interventions more widely. This article provides a case example of a self-management intervention in a community general hospital targeting an underserved population who have significant barriers to receiving regular health care. The 3-component program sought to improve meaningful access to care, increase health literacy related to type 2 diabetes, and partner with the enrollees to make long-term lifestyle changes. The intervention not only resulted in significant improvements in HbA1c levels (-0.77%) but saved the hospital an average of $551 per active patient per year, primarily by reducing hospital visits. With only 255 actively enrolled patients, the hospital can recover fully its total direct annual personnel and operating costs for the program. Because the program serves patients who would have been seen at other hospitals, it also enhanced care quality and reduced costs for the broader community in which the program is embedded.

Purpose: The purpose of this study is to estimate the cost-effectiveness of diabetes self-management programs in real-world community primary care settings. Estimates incorporated lifetime reductions in disease progression, costs of adverse events, and increases in quality of life., Methods: Clinical results and costs were based on programs of the Diabetes Initiative of the Robert Wood Johnson Foundation, implemented in primary care and community settings in disadvantaged areas with notable health disparities. Program results were used as inputs to a Markov simulation model to estimate the long-term effects of self-management interventions. A health systems perspective was adopted., Results: The simulation model estimates that the intervention does reduce discounted lifetime treatment and complication costs by $3385, but this is more than offset by the $15,031 cost of implementing the intervention and maintaining its effects in subsequent years. The intervention is estimated to reduce long-term complications, leading to an increase in remaining life-years and quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio is $39,563/QALY, well below a common benchmark of $50,000/QALY. Sensitivity analyses tested the robustness of the model's estimates under various alternative assumptions. The model generally predicts acceptable cost-effectiveness ratios., Conclusions: Self-management programs for type 2 diabetes are cost-effective from a health systems perspective when the cost savings due to reductions in long-term complications are recognized. These findings may justify increased reimbursement for effective self-management programs in diverse settings.

Objective: To describe the steps in developing a business case for quality-enhancing interventions (QEIs) in health care., Analysis: The development of a business case for QEIs in health care involves 11 steps. These steps include (1) describing the intervention, (2) determining perspective, (3) identifying the effects of the intervention on quality, (4) designing the study, (5) identifying and measuring cash flows, (6) considering the effects of capacity constraints, (7) selecting a measure of return on investment, (8) determining the time horizon for the analysis, (9) determining the discount rate, (10) adjusting costs and savings for inflation, and (11) determining organizational readiness for business case development. A checklist offers guidance on assessing readiness for the business case., Conclusion: The absence of a 'business case' for quality is frequently cited as the reason health care organizations do not implement QEIs, despite decades of careful research demonstrating their effectiveness. Our continuing commitment to advancing the discipline of business case analysis is based on a belief that delineating the cost and economic implications of investments in QEIs is a critical threshold issue to widespread adoption of evidence-based quality improvements. We believe it is appropriate and timely to consider how best to standardize approaches and move the field of business case analysis forward.

Purpose: To determine whether a positive financial return on investment for quality-enhancing interventions is more likely for particular health conditions, in specific organizational settings, or with the use of particular interventions., Data Sources: Electronic search of MEDLINE., Data Extraction: Search keywords included: business case, cost-effectiveness, cost-benefit, return on investment, costs, cost savings, quality, quality improvement, and program evaluation., Results: Only 15 of 1968 articles identified contained sufficient information on both the costs of implementing quality-enhancing interventions and the resultant changes in costs of care or revenues to permit the calculation of a return on investment., Conclusions: Scant attention is currently paid in the quality-of-care literature to the cost of implementing quality-enhancing interventions. To understand which quality-enhancing interventions are likely to produce positive returns on investments, data collection and analysis must include tracking the investment and operating costs of implementing the intervention as well as the changes in revenues and costs that result from the intervention.

Objective: To investigate the effects of Medicare's Prospective Payment System (PPS) for skilled nursing facilities (SNFs) and associated rate changes on quality of care as represented by staffing ratios and regulatory deficiencies., Data Sources: Online Survey, Certification and Reporting (OSCAR) data from 1996-2000 were linked with Area Resource File (ARF) and Medicare Cost Report data to form a panel dataset., Study Design: A difference-in-differences model was used to assess effects of the PPS and the BBRA (Balanced Budget Refinement Act) on staffing and deficiencies, a design that allows the separation of the effects of the policies from general trends. Ordinary least squares and negative binomial models were used., Data Collection Methods: The OSCAR and Medicare Cost Report data are self-reported by nursing facilities; ARF data are publicly available. Data were linked by provider ID and county., Principal Findings: We find that professional staffing decreased and regulatory deficiencies increased with PPS, and that both effects were mitigated with the BBRA rate increases. The effects appear to increase with the percent of Medicare residents in the facility except, in some cases, at the highest percentage of Medicare. The findings on staffing are statistically significant. The effects on deficiencies, though exhibiting consistent signs and magnitudes with the staffing results, are largely insignificant., Conclusions: Medicare's PPS system and associated rate cuts for SNFs have had a negative effect on staffing and regulatory compliance. Further research is necessary to determine whether these changes are associated with worse outcomes. Findings from this investigation could help guide policy modifications that support the provision of quality nursing home care.

Type II collagen binds to chondrocytes through integrins and annexin V. While the potential integrin binding sites have been identified, it is unclear which domains bind to annexin V. Proteolytic fragments of collagen are known to modulate cell signaling pathways resulting in degradation of articular cartilage; it is unknown whether annexin V binds to the fragments. The focus of our study was to determine the binding of type II collagen and its fragments to chondrocytes using flow cytometry and fluorescence microscopy. The N-telopeptide binds to annexin V, whereas the C-telopeptide and triple helical peptides do not. These data suggest that the binding of the N-telopeptide of type II collagen is through annexin V, whereas binding of the C-telopeptide and the triple helical peptide to the surface of chondrocytes are potentially facilitated through other collagen receptors, such as integrins or cell-associated matrix proteins.

Previously we demonstrated the rapid generation of affinity matured monoclonal antibody (MAb) producing cell lines following gene gun delivery of DNA using a mammalian expression vector (pAlpha/hFc), which enables the expression of human Fc-chimera proteins in vivo. Here we compare the pAlpha/hFc vector to modified vectors that replace human IgG(1) with either a Glutathione-S-Transferase (GST) fusion protein or a mouse IgG(2c) (mFc) fusion protein. We report that in vivo expression of a GST-chimera results in the rapid generation of affinity matured MAbs, comparable with antibodies raised using the pAlpha/hFc vector, that were reactive with annexin V. The mFc vector failed to induce early antigen-specific B-cell responses suitable for MAb development.

EphA2 is a transmembrane receptor tyrosine kinase that is up-regulated on many aggressive carcinoma cells. Despite its overexpression, the EphA2 on malignant cells fails to bind its ligand, ephrinA1, which is anchored to the membrane of adjacent cells. Unlike other receptor kinases, EphA2 demonstrates kinase activity that is independent of ligand binding. However, ligand binding causes EphA2 to negatively regulate tumor cell growth and migration. Herein, we translate knowledge of EphA2 into strategies that selectively target malignant cells. Using a novel approach to preserve extracellular epitopes and optimize antibody diversity, we generated monoclonal antibodies that identify epitopes on the extracellular domain of EphA2. EphA2 antibodies were selected for their abilities to inhibit behaviors that are unique to metastatic cells while minimizing damage to nontransformed cells. A subset of EphA2 monoclonal antibodies were found to inhibit the soft agar colonization by MDA-MB-231 breast tumor cells but did not affect monolayer growth by nontransformed MCF-10A breast epithelial cells. These EphA2 antibodies also prevented tumor cells from forming tubular networks on reconstituted basement membranes, which is a sensitive indicator of metastatic character. Biochemical analyses showed that biologically active antibodies induced EphA2 phosphorylation and subsequent degradation. Antisense-based targeting of EphA2 similarly inhibited soft agar colonization, suggesting that the antibodies repress malignant behavior by down-regulating EphA2. These results suggest an opportunity for antibody-based targeting of the many cancers that overexpress EphA2. Our studies also emphasize how tumor-specific cellular behaviors can be exploited to identify and screen potential therapeutic targets.

Objective: To assess the effect of new consumer information materials about the Medicare program on beneficiary knowledge of their health care coverage under the Medicare system., Data Source: A telephone survey of 2,107 Medicare beneficiaries in the 10-county Kansas City metropolitan statistical area., Study Design: Beneficiaries were randomly assigned to a control group and three treatment groups each receiving a different set of Medicare informational materials. The "handbook-only" group received the Health Care Financing Administration's new Medicare & You 1999 handbook. The "bulletin" group received an abbreviated version of the handbook, and the "handbook + CAHPS" group received the Medicare & You handbook plus the Consumer Assessment of Health Plans (CAHPS) survey report comparing the quality of health care provided by Medicare HMOs. Beneficiaries interested in receiving information were oversampled., Data Collection Methods: Data were collected during two separate telephone surveys of Medicare beneficiaries: one survey of new beneficiaries and another survey of experienced beneficiaries. The intervention materials were mailed to sample members in advance of the interviews. Knowledge for the treatment groups was measured shortly after beneficiaries received the intervention materials., Principal Findings: Respondents' knowledge was measured using a psychometrically valid and reliable 15-item measure. Beneficiaries who received the intervention materials answered significantly more questions correctly than control group members. The effect on beneficiary knowledge of providing the information was modest for all intervention groups but varied for experienced beneficiaries only, depending on the intervention they received., Conclusions: The findings suggest that all of the new materials had a positive effect on beneficiary knowledge about Medicare and the Medicare + Choice program. While the absolute gain in knowledge was modest, it was greater than increases in knowledge associated with traditional Medicare information sources.

In response to the Balanced Budget Act (BBA) of 1997, the Center for Medicare & Medicaid Services (CMS) initiated a massive information and education campaign to promote effective health plan decision-making. Early results suggest that the pilot version of the Medicare & You handbook and other new Medicare informational materials were viewed favorably overall. Despite their limitations, most beneficiaries found the information useful. The longer, more comprehensive materials were not perceived to be more useful than the shorter, less complicated version. Additional research is needed to determine which subgroups of beneficiaries may need more and, possibly less, information.

We report on the rapid generation of two monoclonal antibodies, ATM A16.35 and ATM D16.11, that bind to the kinase domain of mutated ataxia telangiectasia (ATM). These antibodies were generated against E. coli-expressed recombinant protein using the RIMMS strategy. We show that ATM A16.35 binds ATM by Western blot analysis, and ATM D16.11 forms immune complexes with native ATM in immunoprecipitations without neutralizing kinase activity.

Class-switched, affinity-matured murine monoclonal antibody (MAb) producing cell lines reactive with PED/PEA-15 were generated and isolated in less than 4 weeks following polynucleotide immunizations using only 5 microg of DNA in conjunction with the Powderject gene gun. Somatic fusions of peripheral lymph node cells were performed 13 days after initiating delivery of DNA encoding the target antigen. The data presented demonstrates the rapid production, identification, and characterization of class-switched, affinity-matured MAbs that bind PED/PEA-15. The reported strategy enabled the rapid development of MAbs that are useful in enzyme-linked immunoadsorbent assay (ELISA), Western blotting, and immunoprecipitations.

Adapter proteins such as Grb2 play a central role in the formation of signaling complexes through their association with multiple protein binding partners. These interactions are mediated by specialized domains such as the well-characterized Src homology SH2 and SH3 motifs. Using yeast three-hybrid technology, we have identified a novel adapter protein, expressed predominantly in T lymphocytes, that associates with the activated form of the costimulatory receptor, CD28. The protein is a member of the Grb2 family of adapter proteins and contains an SH3-SH2-SH3 domain structure. A unique glutamine/proline-rich domain (insert domain) of unknown function is situated between the SH2 and N-terminal SH3 domains. We term this protein GRID for Grb2-related protein with insert domain. GRID coimmunoprecipitates with CD28 from Jurkat cell lysates following activation of CD28. Using mutants of CD28 and GRID, we demonstrate that interaction between the proteins is dependent on phosphorylation of CD28 at tyrosine 173 and integrity of the GRID SH2 domain, although there are also subsidiary stabilizing contacts between the PXXP motifs of CD28 and the GRID C-terminal SH3 domain. In addition to CD28, GRID interacts with a number of other T cell signaling proteins, including SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa), p62dok, and RACK-1 (receptor for activated protein kinase C-1). These findings suggest that GRID functions as an adapter protein in the CD28-mediated costimulatory pathway in T cells.

Previously we reported making high-affinity monoclonal antibodies (MAbs) 13 days after the onset of Repetitive Immunizations Multiple Sites (RIMMS) strategy. The Ig subclass variety and affinity of these antibodies suggested that maturational processes had already begun within draining lymph nodes. We now demonstrate that this diversity can in fact be captured as early as Day 7. In the work reported here, somatic fusion of immune lymphocytes isolated from peripheral lymph nodes resulted in the isolation of affinity-matured MAbs reactive with cytosine deaminase. This model further demonstrates and substantiates at a cellular level the rapid development and maturation of T-cell-dependent B-cell responses occurring within draining lymph nodes following antigen challenge.

High affinity, specific murine monoclonal antibodies have been produced for ranitidine using the novel RIMMS (repetitive immunizations, multiple sites) technique. We demonstrate that this technique can be employed to produce high affinity monoclonal antibodies to drug haptens in approximately 1 month; whereas, conventional techniques typically require 3-9 months. Polyclonal antiserum development typically requires at least 6 months. Consequently, RIMMS has a clear impact allowing reagent antibodies to be available earlier in the drug development process. Isotyping studies demonstrated that the developed antibodies are either IgG1 or IgG2b immunoglobulins which confirms that the technique produces class-switched, affinity matured reagent antibodies. The most promising monoclonal antibody for quantitative applications afforded similar sensitivity, by competitive ELISA, to the established sheep polyclonal anti-ranitidine sera. The calibration range, estimated as the limits between the asymptotic regions of calibration graphs, is 0.5-41.2 ng ranitidine per well. Specificity studies indicated that the monoclonal antibody afforded superior selectivity, yielding only 4.1% cross-reactivity with the ranitidine sulphoxide metabolite; the corresponding value for the antiserum was 8.6%. Both reagents had similar cross-reactivities with the N-oxide metabolite.

Class-switched, affinity-matured murine monoclonal antibody (MAb)-producing cell lines were generated against the Flt-3 receptor in less than 4 weeks following polynucleotide immunizations, used in conjunction with repetitive immunizations, multiple sites (RIMMS). Plasmid DNA encoding Flt-3/Fc was coated onto gold particles, which were subsequently propelled into the epidermis of mice using biolistic particle bombardment using the Accell gene gun. Pools of immune peripheral lymph node cells were somatically fused 13 days after the onset of delivery of DNA encoding the target antigen. To determine if early responses could be augmented, DNA-encoding murine GM-CSF was delivered 3 days prior to the Flt-3/Fc DNA immunizations. The data presented demonstrates the successful identification and characterization of class-switched, affinity-matured MAbs that bind to the Flt-3 receptor. When compared to conventional methodologies or intramuscular targeted DNA-based immunization for the generation of MAbs, use of the gene gun in conjunction with RIMMS allows for a more rapid production of affinity-matured MAb-producing cell lines.

Tyrosine phosphorylation is a form of signal transduction that regulates cell growth, differentiation, migration, and survival. This knowledge has promoted much interest in the role of tyrosine kinases and phosphatases in regulating cell behavior during development and tumorigenesis. However, it is generally less well appreciated that tyrosine phosphorylated proteins are enriched within sites of cell adhesion, particularly in transformed cells. To identify these, we developed a panel of monoclonal antibodies specific for tyrosine phosphorylated proteins in breast cancer cells, using extensive modifications of existing technologies for immunization, somatic fusion, and antibody screening. Mice were immunized with a complex mixture of phosphotyrosine containing proteins using the newly developed RIMMS method. By increasing the sensitivity of antigen recognition, we isolated reagents specific for a wide diversity of tyrosine phosphorylated adhesion proteins in breast cancer cells.

Affinity matured murine monoclonal antibody producing cell lines can now be rapidly generated using a novel repetitive, multiple site immunization strategy designated RIMMS. RIMMS capitalizes on rapid hypermutation and affinity maturation events which occur in B cell populations localized within secondary lymphatic tissue early in response to antigenic challenges. A murine myeloma cell line, P3XBcl-2-13, stably transfected with Bcl-2, enhances the outgrowth of hybridomas following somatic fusion with immune lymphocytes isolated from pooled peripheral lymph nodes (PLN) 8-14 days after the initial immunization. Immunizations somatic fusion, screening and isolation of affinity matured IgG secreting monoclonal antibody cell lines occur within a one month time period. By using RIMMS, we have been able to expedite the isolation of affinity matured monoclonal antibodies to numerous antigens, including a drug hapten.

Tumor necrosis factor alpha (TNF alpha) is a polypeptide hormone with pleiotropic effects on cellular proliferation and differentiation. To investigate how TNF alpha inhibits and reverses adipocyte differentiation, we studied the expression of two factors involved in the adipocyte differentiation process. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a positive regulator of adipogenesis, whereas preadipocyte factor 1 (Pref-1) inhibits adipocyte differentiation. The expression patterns of both PPARgamma and Pref-1 change during early stages of adipocyte differentiation. Decreased expression of Pref-1 and increased expression of PPARgamma occur 1 day and 2 days, respectively, after 3T3-L1 cells reach confluence. During TNF alpha-mediated inhibition of adipocyte differentiation, PPARgamma messenger RNA (mRNA) expression stays at low levels. In contrast, TNF alpha treatment has no effect on the normal decrease in Pref-1 gene expression that occurs during adipogenesis. We observed that certain cytokine and growth factors [such as TNF alpha, basic fibroblast growth factor, transforming growth factor beta, and protein kinase C-activating agents plus calcium ionophore], when added to differentiated adipocytes, cause rapid down-regulation of PPARgamma mRNA expression with concomitant decrease in adipocyte-specific gene expression but fail to increase Pref-1 mRNA expression. Moreover, addition of TNF alpha to fully differentiated adipocytes results in the rapid disappearance of PPARgamma protein expression and the rapid loss of PPARgamma DNA-binding activity. Therefore, Pref-1 seems to function as a nonreversible molecular checkpoint whose expression is insensitive to TNF alpha-generated signals, whereas PPARgamma expression remains sensitive to TNF alpha at all stages of the adipogenesis program. Our results support the notion that dedifferentiated adipocytes and preadipocytes are not identical, though they share many similar morphological and gene expression patterns.

Numerous studies have demonstrated the importance of urokinase plasminogen activator (uPA) and its receptor, uPAR, in the processes of tumor progression and metastasis. Thus, the uPA/uPAR interaction may represent an important target for inhibiting metastatic disease. The baculovirus expression system was used to produce high levels of a secreted uPA-Immunoglobulin G fusion protein (uPA-IgG) which could then be used for displacing uPA from the surface of tumor cells. The recombinant uPA-IgG fusion protein was placed under the control of either the viral polyhedrin promoter or a copy of the viral basic protein promoter. Recombinant viruses were then used to infect Sf9 and BTI-Tn-5B1-4 cells. Infection of both cell types resulted in the production of secreted uPA-IgG. The molecular mass of the secreted protein as determined by SDS-PAGE was approximately 40 kDa. The highest level of secreted uPA-IgG, 444 microg/ml, was found in the culture medium of BTI-Tn-5B1-4 cells 72 h post-infection with the basic protein promoter-uPA-IgG virus. In the case of Sf9 cells, the highest level of secreted protein was 195 microg/ml. The amount of cell-associated uPA-IgG in infected BTI-Tn-5B1-4 cells was significantly less than that of infected Sf9 cells, reflecting the superior secretory capability of the BTI-Tn-5B1-4 cells. The uPA-IgG was readily purified using a combination of zinc chelate and sephacryl S-100 column chromatography. Routinely, greater than 100 mg of greater than 95% pure protein could be obtained per liter of culture medium collected at 72 h post-infection of BTI-Tn-5B1-4 cells with the basic protein promoter virus. BIAcore analysis and competition binding assays using LOX human malignant melanoma cells expressing uPAR indicated that the purified recombinant protein possessed similar ligand binding characteristics to that of human uPA.

In this article, the authors present a resident-based reimbursement system for intermediate care facilities for the mentally retarded (ICFs-MR), which represent a large and growing proportion of the medicaid budget. The statistical relationship between resident disability level and the expected cost of caring for the individual is estimated, allowing for the prediction of expected resource use across the population of ICF-MR residents. The system incorporates an indirect cost rate, a base direct care rate (constant across all providers), and an individual-specific direct care rate, based on the expected cost of care.

Health administration education in schools of public health has undergone a steady but remarkable evolution over the last five decades. What was once taught was simply an enumeration of statutory requirements and programs managed by public health agencies. This changed dramatically in the 1960s with the incorporation of both theoretical concepts and skills from the fields of public administration and business administration. In the 1990s, the differentiation between training required for public health administration and for health services administration has become increasingly blurred as institutional responsibility for the health of defined populations has necessitated the adoption of the community epidemiology perspective, long the centerpiece of public health programs, by all health services administration programs. The future challenge for programs located in schools of public health is to identify the unique characteristics of public health practice and to prepare graduates to assure that core public health functions are met adequately in the communities in which they will serve.

The production of two different murine monoclonal antibodies to human Gadd45, a protein that is induced in response to DNA damage, is reported. Antibodies were generated in a SJL mouse using a recombinant form of the human Gadd45 protein. Monoclonal antibody 4TCYA1, which recognizes the denatured form of human Gadd45 in Western blots, was selected based upon the recognition of Gadd45 induced by functional p53 in the human myeloid leukemia cell line, ML-1. A second monoclonal antibody, designated 30T.14, immunoprecipitates native human Gadd45 in lysates produced from RKO cells, a colorectal carcinoma cell line that expresses relatively high basal levels of Gadd45, as well as from cell lysates made from ML-1 cells after exposure to ionizing irradiation (IR). Since 4TCYA1 fails to immunoprecipitate Gadd45, and 30T.14 fails to bind to IR-induced Gadd45 in immunoblotting, these two monoclonal antibodies probably recognize different epitopes.

Objective: As part of a project to estimate physician requirements for the Department of Veterans Affairs, the Institute of Medicine (IOM) developed and tested empirically based models of physician staffing, by specialty, that could be applied to each VA facility., Data Source/study Setting: These analyses used selected data on all patient encounters and all facilities in VA's management information systems for FY 1989., Study Design: Production functions (PFs), with patient workload dependent on physicians, other providers, and nonpersonnel factors, were estimated for each of 14 patient care areas in a VA medical center. Inverse production functions (IPFs), with physician staffing levels dependent on workload and other factors, were estimated for each of 11 specialty groupings. These models provide complementary approaches to deriving VA physician requirements for patient care and medical education., Data Collection/extraction Methods: All data were assembled by VA and put in analyzable SAS data sets containing FY 1989 workload and staffing variables used in the PFs and IPFs. All statistical analyses reported here were conducted by the IOM., Principal Findings: Existing VA data can be used to develop statistically strong, clinically plausible, empirically based models for calculating physician requirements, by specialty. These models can (1) compare current physician staffing in a given setting with systemwide norms and (2) yield estimates of future staffing requirements conditional on future workload., Conclusions: Empirically based models can play an important role in determining VA physician staffing requirements. VA should test, evaluate, and revise these models on an ongoing basis.

GADD45 (growth arrest and DNA damage) is a DNA-damage-inducible gene regulated in part by the tumor suppressor p53. A role in negative growth control has recently been suggested based on significant (more than 75%) reduction of colony formation following over expression of Gadd45. To better understand the role of Gadd45, we have developed specific rabbit and murine antibodies raised against the human recombinant protein. Using these antibodies, we have found that in ML-1 cells Gadd45 is predominantly a nuclear protein. MyD118, a protein induced by terminal differentiation sharing 57% homology with Gadd45, does not cross-react with any of the antibodies produced. As expected, the induction of Gadd45 protein by ionizing radiation (IR) was also found to be dependent on a wild type p53 phenotype. Interestingly, WI-L2-NS, a human lymphoid cell line, showed very high basal levels of Gadd45 mRNA and protein in addition to a high constitutive level of a mutated p53 protein. In this cell line, the high levels of GADD45 did not inhibit cellular growth in spite of the fact that no mutations were found in GADD45 sequence. These results indicate that some cell line(s) can tolerate high levels of Gadd45 and abrogate its growth suppression function.

Results of a 1992 Medicaid cost-of-dispensing study among North Carolina pharmacies are presented. The estimated statewide weighted average cost incurred by pharmacies to dispense a prescription was $5.37 in 1991. The variation in dispensing costs found among pharmacies of various sizes, organizational types, and locations is identified. Higher average dispensing costs were reported for large chain pharmacies and those pharmacies in urban areas. Considering the potential for expanded prescription drug benefits under a reformed health care system, the implications of the study's findings for pharmacy payment policy are discussed.

While a great deal of attention has been paid in recent years to establishing the magnitude and characteristics of uncompensated care in hospitals, comparatively little research has been undertaken to study physician uncompensated care. This article reports the results of a prospective patient-specific study of uncompensated care in Florida. Of 4,042 cases examined, 26.2 percent had charges voluntarily reduced below the usual and customary charge at the time of service. However, only 13.5 percent of those reductions were attributed to charity. Overall, 10.4 percent of the total billed amount was left unresolved. When payment source was considered, it was found that self-pay patients accounted for 30.6 percent of the cases but accounted for 52.0 percent of the unresolved amounts. Further analysis indicated that the self-pay patients were 35.5 times more likely to leave an outstanding balance than individuals with some type of insurance coverage. Odds of unresolved balances were also calculated as a function of income, specialty type, practice size, and type of visit.

To determine the economic impact of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) cases on North Carolina hospitals, we collected inpatient data from all North Carolina hospitals on charges and number of patients discharged with these diagnoses. More than 97% of the state's hospitals responded to the survey for the study year (1987-1988). There were 540 AIDS/ARC discharges from 58 North Carolina general hospitals and 125 AIDS/ARC discharges from 13 other types of hospitals, for a statewide total of 665 patients. The total general hospital charges for AIDS/ARC inpatients in North Carolina were approximately $7.7 million per year, and almost $2 million of these charges were uncompensated by any insurance. The greatest burden of cost for this care was borne disproportionately by 15 of the 58 general hospitals, accounting for 82% of the discharges.

Forecasts of ophthalmology manpower depend on assumptions about future supply and requirements. The two factors that influence supply are the number of residents trained and the attrition of ophthalmologists in practice. The factors that influence requirements are the estimated amount of future ophthalmic services the public will demand and the productivity of ophthalmologists. Previous forecasts have produced widely differing results because of an inadequate data base and varying theoretical assumptions. A conservative approach is to use past ophthalmologist to population ratios as a guide, and to tailor the output of ophthalmologists accordingly. A yearly reduction from 1982 to 1990 between 5% and 10% in the number of residency positions will be necessary to bring supply in line with requirements within the next thirty years.

Forecasts of the requirements for and supply of ophthalmologists in 1990 have produced conflicting results because of varying assumptions about the future utilization of eye care services, incidence and prevalence of ophthalmic disease, physician productivity, and availability of residency training positions. A typical "utilization-based" models, founded on present consumer behavior, predicts a substantial 1990 surplus of ophthalmologists at current rates of residency training. Two "need-based" models, founded on ideal rather than actual use, reach different conclusions because of varying use of a fragile data base and the need to rely heavily on the subjective judgment of experts with regard to norms of care. The 1980 Graduate Medical Educational National Advisory Committee forecasted a surplus, while the 1978 American Academy of Ophthalmology predicted a deficit. Utilization-based models may slightly underestimate future ophthalmologist requirements. However, analysis of the factors that will influence future use suggests that need-based models are likely to overestimate the requirements. It is risky to accept the need-based model projections because of the high cost of a surplus, which include not only the expenses of training unneeded ophthalmologists but also the cost of their decreased exposure to disease and of declining physician morale, acumen, and thresholds for surgical procedures. Because free market mechanisms are ineffective in governing the supply of health providers, it will be necessary for the profession itself to review the current and projected supply and to set limits on the number of persons in training.

A model is described that predicts hospital census and computes, for each day, the number of elective admissions that will maximize the census over the short run, subject to constraints on the probability of overflow. Where a computer is available the model provides detailed predictions of census in units as small as 10 beds; used with manual computation the model allows production of tables of the recommended numbers of elective admissions to the hospital as a whole. The model has been tested in five hospitals and is part of the admissions system in two of them; implementation is described, and the results obtained are discussed.

This paper describes the evolution of a computerized support system for health care capacity planning within the Veterans Administration (VA) health care system. The VA's early attempts at computerization are described, along with the subsequent refinements made necessary by the deficiencies in those early attempts. The evolution of both the planning logic and the software configurations in set forth, along with some plans for future development.