Immunological function in marine invertebrates: responses to environmental perturbation.

The inception of ecological immunology has led to an increase in the number of studies investigating the impact of environmental stressors on host immune defence mechanisms. This in turn has led to an increased understanding of the importance of invertebrate groups for immunological research. This review discusses the advances made within marine invertebrate ecological immunology over the past decade. By demonstrating the environmental stressors tested, the immune parameters typically investigated, and the species that have received the greatest level of investigation, this review provides a critical assessment of the field of marine invertebrate ecological immunology. In highlighting the methodologies employed within this field, our current inability to understand the true ecological significance of any immune dysfunction caused by environmental stressors is outlined. Additionally, a number of examples are provided in which studies successfully demonstrate a measure of immunocompetence through alterations in disease resistance and organism survival to a realized pathogenic threat. Consequently, this review highlights the potential to advance our current understanding of the ecological and evolutionary significance of environmental stressor related immune dysfunction. Furthermore, the potential for the advancement of our understanding of the immune system of marine invertebrates, through the incorporation of newly emerging and novel molecular techniques, is emphasized.

Escherichia coli isolates' serotypes, genotypes, and virulence genes and clinical coliform mastitis severity.

Dairy cattle with clinical mastitis caused by Escherichia coli exhibit a wide range of disease severity, from mild, with only local inflammatory changes of the mammary gland, to severe, with significant systemic derangement. The present study was designed to examine the relationship between serotype and virulence genes of E. coli mastitis isolates, different levels of systemic disease severity, and farm from which the E. coli strain was obtained. One hundred twenty-three E. coli milk isolates were obtained from cows with clinical mastitis of varying systemic disease severity from 6 different farms. No predominant serotype was identified by farm or by systemic disease severity; however, the most frequent serotype, O158:NM (n = 3), was isolated from cows in the moderate severity group. Virulence genes evaluated were identified infrequently and were not associated with systemic disease severity. Evaluation of genetic similarity showed no clustering assigned by farm or mastitis severity based on systemic disease signs. We concluded that a high degree of genotypic variability is characteristic of E. coli strains causing clinical mastitis within and between different farms and systemic severity groups, and that specific cow factors probably play a more important role in determining systemic disease severity.

Comparison of the odds of isolation, genotypes, and in vivo production of major toxins by Clostridium perfringens obtained from the gastrointestinal tract of dairy cows with hemorrhagic bowel syndrome or left-displaced abomasum.

OBJECTIVE: To compare the frequency of isolation, genotypes, and in vivo production of major lethal toxins of Clostridium perfringens in adult dairy cows affected with hemorrhagic bowel syndrome (HBS) versus left-displaced abomasum (LDA). DESIGN: Case-control study. ANIMALS: 10 adult dairy cattle with HBS (cases) and 10 adult dairy cattle with LDA matched with cases by herd of origin (controls). PROCEDURE: Samples of gastrointestinal contents were obtained from multiple sites during surgery or necropsy examination. Each sample underwent testing for anaerobic bacteria by use of 3 culture methods. The genotype of isolates of C. perfringens was determined via multiplex polymerase chain reaction assay. Major lethal toxins were detected by use of an ELISA. Data were analyzed with multivariable logistic regression and chi2 analysis. RESULTS: C. perfringens type A and type A with the beta2 gene (A + beta2) were the only genotypes isolated. Isolation of C. perfringens type A and type A + beta2 was 6.56 and 3.3 times as likely, respectively, to occur in samples from cattle with HBS than in cattle with LDA. Alpha toxin was detected in 7 of 36 samples from cases and in 0 of 32 samples from controls. Beta2 toxin was detected in 9 of 36 samples from cases and 0 of 36 samples from controls. CONCLUSIONS AND CLINICAL RELEVANCE: C. perfringens type A and type A + beta2 can be isolated from the gastrointestinal tract with significantly greater odds in cattle with HBS than in herdmates with LDA. Alpha and beta2 toxins were detected in samples from cows with HBS but not from cows with LDA.

Creaming, skimping and dumping: provider competition on the intensive and extensive margins.

Reimbursement incentives influence both the intensity of services and who is treated when patients differ in severity of illness. The social optimum is compared to the private Cournot-Nash solution for three provider strategies: creaming--over-provision of services to low severity patients; skimping--under-provision of services to high severity patients; and dumping--the explicit avoidance of high severity patients. Cost-based reimbursement results in overprovision of services (creaming) to all types of patients. Prospectively paid providers cream low severity patients and skimp high severity ones. If there is dumping of high severity patients, then there will also be skimping.

Provider behavior under prospective reimbursement. Cost sharing and supply.

This paper develops a model in which physicians choose the level of services to be provided to their patients. We show that if physicians undervalue benefits to patients relative to hospital profits, prospective payment, a system in which hospitals receive a payment dependent on the diagnosis-related group within which a patient falls, can lead to too few services being provided. In contrast, a 'cost-based' reimbursement system is shown to result in too many services being provided. Competition between hospitals for physicians will tend to augment both of these problems. We also examine a mixed reimbursement system, in which hospital reimbursements are paid partly prospectively and partly cost-based. This system is shown under a variety of circumstances to be superior to the other two reimbursement systems by improving the incentives for the efficient level of services, reducing incentives to unnecessarily admit or reclassify patients, and reducing risk to providers.

Insurance principles and the design of prospective payment systems.

This paper applies insurance principles to the issues of optimal outlier payments and designation of peer groups in Medicare's case-based prospective payment system for hospital care. Arrow's principle that full insurance after a deductible is optimal implies that, to minimize hospital risk, outlier payments should be based on hospital average loss per case rather than, as at present, based on individual case-level losses. The principle of experience rating implies defining more homogenous peer groups for the purpose of figuring average cost. The empirical significance of these results is examined using a sample of 470,568 discharges from 469 hospitals.

Hospital response to prospective payment: moral hazard, selection, and practice-style effects.

In response to a change in reimbursement incentives, hospitals may change the intensity of services provided to a given set of patients, change the type (or severity) of patients they see, or change their market share. Each of these three responses, which we define as a moral hazard effect, a selection effect, and a practice-style effect, can influence average resource use in a population. We develop and implement a methodology for disentangling these effects using a panel data set of Medicaid psychiatric discharges in New Hampshire. We also find evidence for the form of quality competition hypothesized by Dranove (1987).

Optimal payment systems for health services.

Demand-side cost sharing and the supply-side reimbursement system provide two separate instruments that can be used to influence the quantity of health services consumed. For risk-averse consumers, optimal payment systems--pairs of insurance and reimbursement plans--are characterized by conflict rather than consensus between patient and provider about the quantity of treatment. A model of conflict resolution based on bargaining theory is used to represent the outcome when the payment system creates divergences between desired demand and desired supply. Using that model, we describe the optimal combination of insurance and reimbursement systems that maximize consumer welfare.

Setting capitation payments in markets for health services.

Health maintenance organizations (HMO's) are paid a capitated amount for enrolled Medicare beneficiaries that is 95 percent of what these enrollees would be expected to cost in the fee-for-service sector. However, it appears that HMO enrollees are less costly than other Medicare beneficiaries. With a simulation model, we demonstrate that with a 95-percent pricing rule, any significant degree of biased selection leads to increased cost to the payer, even when HMO's are cost effective compared with the fee-for-service sector. Optimal pricing percentages from the point of view of cost minimization are considerably less than 95 percent.

Using diagnoses to describe populations and predict costs.

The Diagnostic Cost Group Hierarchical Condition Category (DCG/HCC) payment models summarize the health care problems and predict the future health care costs of populations. These models use the diagnoses generated during patient encounters with the medical delivery system to infer which medical problems are present. Patient demographics and diagnostic profiles are, in turn, used to predict costs. We describe the logic, structure, coefficients and performance of DCG/HCC models, as developed and validated on three important data bases (privately insured, Medicaid, and Medicare) with more than 1 million people each.

Diagnosis-based risk adjustment for Medicare capitation payments.

Using 1991-92 data for a 5-percent Medicare sample, we develop, estimate, and evaluate risk-adjustment models that utilize diagnostic information from both inpatient and ambulatory claims to adjust payments for aged and disabled Medicare enrollees. Hierarchical coexisting conditions (HCC) models achieve greater explanatory power than diagnostic cost group (DCG) models by taking account of multiple coexisting medical conditions. Prospective models predict average costs of individuals with chronic conditions nearly as well as concurrent models. All models predict medical costs far more accurately than the current health maintenance organization (HMO) payment formula.

Principal inpatient diagnostic cost group model for Medicare risk adjustment.

The Balanced Budget Act (BBA) of 1997 required HCFA to implement health-status-based risk adjustment for Medicare capitation payments for managed care plans by January 1, 2000. In support of this mandate, HCFA has been collecting inpatient encounter data from health plans since 1997. These data include diagnoses and other information that can be used to identify chronic medical problems that contribute to higher costs, so that health plans can be paid more when they care for sicker patients. In this article, the authors describe the risk-adjustment model HCFA is implementing in the year 2000, known as the Principal Inpatient Diagnostic Cost Group (PIPDCG) model.

The revenue generating potential of user fees in Kenyan government health facilities.

This paper develops and implements a methodology for estimating the total revenue that would result from a system of user fees for health services provided by public facilities in a developing country. After setting out a set of principles based on efficiency, equity, and administrative goals upon which the user fees should be founded, a formula for estimating total revenue generated is presented which reflects six different factors affecting total revenues. These factors include reductions in demand due to imposing fees, exemption of selected services from any fees, forgiving fees from those unable to pay, and 'leakage' of revenue due to bribes, etc. Three specific fee structures are then examined for Kenya, and the total revenue to be generated is predicted. The revenue totals are large, on the order of 10-22% of the government's total recurrent health costs, suggesting that even modest user fees can make a significant contribution to public health costs.

Protection of rams against epididymitis by a Brucella ovis-vitamin E adjuvant vaccine.

Rams vaccinated at 7 and 8 months of age with a B. ovis-vitamin E adjuvant vaccine had increased antibody titers compared with Freund's incomplete adjuvant or commercial bacterin vaccinated rams. The percent overall infectivity in an experimental infection of B. ovis-vitamin E adjuvant vaccinated rams was 22% compared to 44% for B. ovis-Freund's incomplete adjuvant or bacterin vaccinated rams and 67% for control.

Prospective characterization of the clinicopathologic and immunologic features of an immunodeficiency syndrome affecting juvenile llamas.

The clinicopathologic and immunologic features of 15 llamas affected with juvenile llama immunodeficiency syndrome (JLIDS) are described. Healthy adult (n = 10) and juvenile (n = 10) llamas served as controls. JLIDS llamas were characterized by wasting, and clinically apparent, repeated infections were frequently observed. The median age at which a health problem was first perceived was 11.6 months. All 15 affected llamas died or were killed, and JLIDS was confirmed at necropsy. The median duration of illness was 3.5 months. Lymphocyte blastogenesis assays showed suppressed responses (particularly to Staphylococcus sp. Protein A) in JLIDS llamas. No evidence of retroviral infection was detected. Mild, normocytic, normochromic, non-regenerative anemia, low serum albumin concentration and low to low-normal globulin concentrations were typically found on initial clinical evaluation. Lymph node biopsies showed areas of paracortical depletion. All llamas affected with JLIDS had low serum IgG concentrations, pre-vaccination titers against Clostridium perfringens C and D toxoids of < or = 1:100, and no titer increase following vaccination.

Immune response in rams experimentally infected with Brucella ovis.

Cellular as well as humoral immune responses were detected in six rams experimentally infected with Brucella ovis. Specific antibodies were detectable by enzyme-linked immunosorbent assay by day 11 after infection in all the rams. The levels of IgM antibodies and total antibodies in the serum rose until 33 and 41 days after infection respectively, then levelled off. Antigen-induced blastogenic responses by lymphocytes developed as early as five days after infection in all rams but had decreased to low levels by day 63 in most. Blastogenesis induced by phytohaemagglutinin and concanavalin A varied among infected rams and did not differ significantly (P greater than 0.05) from control rams. All rams had developed delayed-type skin hypersensitivity by day 63 after infection. One ram which did not become infected as a result of exposure had low levels of B ovis serum antibodies and a detectable antigen-induced lymphocyte blastogenic response before infection, suggesting the involvement of cell-mediated immunity in protection against B ovis.

Formal risk adjustment by private employers.

This paper explores explanations for why few private employers have adopted formal risk adjustment. The lack of data, challenges of using highly imperfect signals, and absence of market power are not compelling explanations. Alternative strategies that reduce selection problems are clearly important. The central argument is that U.S. health markets are not in equilibrium, but rather are changing rapidly. Since many agents-consumers, employers, health plans, and providers--do not currently demand formal risk adjustment, it is not surprising that adoption has been slow. Recent changes in health plan markets may change the demand and accelerate future adoption.

Refinements to the Diagnostic Cost Group (DCG) model.

The Diagnostic Cost Group (DCG) model, originally developed by Ash et al. (1986, 1989), has been proposed as an alternative to the existing payment system for reimbursing Medicare health maintenance organizations, the Adjusted Average Per Capita Cost (AAPCC). The DCG model is a linear regression model that uses both demographic and diagnostic information to predict total plan payments for health care. This paper extends previous work by estimating the model using 1984-85 data and by developing a more thorough method for classifying hospitalizations by degrees of discretion. It also explores the loss of predictive power resulting from not using diagnoses for the most discretionary hospitalizations for calculating payments. The paper examines a number of extensions and refinements to the basic DCG model.

Alternative payment systems for hospital medical staffs.

This paper examines the implications of using a Medical Staff Payment System (MSPS) for reimbursing physicians for services provided to inpatients. Inpatient episodes are defined to include seven days before admission and 30 days postdischarge. Simulations are performed using Medicare Part A and B data from nine states in 1988. DRGs are strong predictors of expenditures on physician services during the inpatient episode, achieving an R2 of .61. Gains and losses for various types of facilities are simulated, and the characteristics of winning and losing hospitals under an MSPS are identified.

Provider response to Medicare's PPS: reductions in length of stay for psychiatric patients treated in scatter beds.

We used Medicare discharge data for the years 1984 and 1985 to analyze reductions in lengths of stay for psychiatric patients treated in general hospitals that did not have specialized psychiatric units. In response to Medicare's Prospective Payment System (PPS), not-for-profit hospitals experienced declines in lengths of stay averaging between 10% and 20% two years after they went onto PPS, while for-profit hospitals experienced a somewhat greater decline. Lengths of stay fell most rapidly during the months immediately surrounding the date on which a hospital began to be paid under PPS. This response included an anticipatory effect--hospital lengths of stay began shortening just before PPS payments started.