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BACKGROUND. Oncology services in a managed care organization may be defined by the structure of the provider network, coverage policies, and specific health plan programs for oncology services. METHODS. The policies and programs of Aetna U.S. Healthcare were reviewed to illustrate the approach of a large, national health benefits company in the provision of oncology services to its members. RESULTS. Standard oncology services are provided by a network of independent participating providers, paid fee-for-service. There are no capitated arrangements for oncology services. The process is driven by the participating providers. For patients requiring bone marrow transplant or therapy available in few medical centers, precertification and case management are provided by the health plan, through the National Medical Excellence Unit. Criteria are used to select facilities for these services and global case rates are negotiated. In the health maintenance organization, educational material is distributed by the health plan to physicians and members to encourage the use of cancer screening services. In addition, reimbursement to primary care physicians can be enhanced by the screening rate for their members. The overall policy of Aetna U.S. Healthcare is to cover Phase II and III clinical trials. Coverage for Phase I trials or use of non-Food and Drug Administration approved drugs is based on reported safety and efficacy and participation in an academic program. CONCLUSIONS. Through arrangements with participating providers, dedicated support for transplant and rare cases, programs encouraging the use of cancer screening, and member-focused policies on coverage issues, managed care companies can provide complete oncology services to its membership.

Managed care organizations must establish formal processes for the evaluation of new technology, procedures, and drugs to enhance the quality of health care delivered and to support coverage and utilization decision making. Evidence-based research and the results of controlled clinical trials are the preferred sources of outcomes data to support the safety and effectiveness of the technology, procedure, or drug under review. In addition to extensive literature review, the opinion of experts in the field and acceptance by the medical community are considered. Assessments of new technology and drugs are available for purchase from several vendors, and managed care organizations can adopt or modify such evaluations to develop medical coverage policies. The research community can assist third-party payers by conducting studies on practices that might lead to substantial, rather than marginal, improvement in health, pay particular attention to study design when randomized controlled studies are not possible, and include functional and behavioral measures in analysis of outcomes.

The extent of membrane invagination or endocytosis in intact erythrocytes was quantified by measuring the loss of acetylcholinesterase activity. Primaquine-induced endocytosis was completely inhibited in ATP-depleted cells. However, chlorpromazine and vinblastine were capable of inducing membrane invagination in depleted cells. With both drugs, the loss of enzyme activity was less than that measured in fresh cells. We conclude that drug-induced endocytosis is not necessarily an energy-dependent process.

The deoxythymidine diphosphate d-glucose oxidoreductase from Escherichia coli is a protein of molecular weight 78,000, containing 1 mole of firmly bound DPN per mole of enzyme. Treatment of the enzyme with p-hydroxymercuribenzoate followed by removal of the mercurial with dithiothreitol releases bound DPN, and dissociates the protein into subunits of molecular weight 40,000, as determined by gel chromatography. This process is fully reversible. Inactive dimeric protein (mole wt 78,000) can also be formed by allowing the apoenzyme to react with the DPN analogue adenosine diphosphate ribose. The kinetics of reactivation of the apoenzyme with DPN suggests that the apoenzyme binds DPN with a dissociation constant of approximately 5 x 10-6 at 16° and 5 x 10-4 at 37°, followed by a slow conformational change (measured in minutes) to yield active enzyme. The apoenzyme appears to retain the substrate-binding site. Deoxythymidine diphosphate (a substrate analogue) specifically inhibits the rate of apoenzyme reactivation, and this inhibition can be reversed by the substrate deoxythymidine diphosphate glucose. The substrate analogue deoxythymidine diphosphate 6-deoxy-d-glucose reacts with enzyme to yield enzyme-DPNH and deoxythymidine diphosphate 4-keto-6-deoxy-d-glucose, the normal product of the reaction. The release of this product from enzyme-DPNH is, however, slower by at least three orders of magnitude, depending on temperature, pH, and ionic strength, than the release of the same product from enzyme-DPN in the normal catalytic reaction. The role of DPN and DPNH in the structure of the enzyme is discussed in the light of these observations.

A method for the preparation of highly purified deoxythymidine diphosphate-d-glucose oxidoreductase is described. The purified enzyme gives a single band on disc gel electrophoresis, has a molecular weight of 78,000, and contains 1 mole of bound DPN per mole of enzyme. Spectral evidence is presented that is in accord with the formation of bound DPNH in the course of the reaction. The increase in fluorescence of the enzyme after substrate addition is inhibited by prior incubation with product and seems to represent a change in enzyme conformation rather than DPN reduction. DPN analogues with a modified pyridine ring are bound to the enzyme, but yield inactive enzyme, whereas, deamino-DPN and other analogues with a hypoxanthine ring do not bind tightly to the enzyme. Thus the tight binding of DPN is due in large part to the adenine portion of DPN.

Evidence is presented to show that in the dTDP-D-glucose oxidoreductase reaction, product is only released from enzyme containing DPN, and product release from enzyme containing DPNH does not occur at a significant rate. This result is interpreted to indicate that the conformation of the protein depends on the oxidation state of the bound pyridine nucleotide.

A case of lymphoma in an infant in whom the skin was the only apparent organ involved is reported. Response to combination chemotherapy was excellent and no recurrence has been observed in the 13 months since diagnosis.

Of 274 newborns with bacterial infections, only 16 were jaundiced, and in only six of the 16 was jaundice the initial single sign of the infection.

Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S pneumoniae in children with sickle cell anemia who were younger than 3 years of age at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84% reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients v 2 of 105; P = .0025). There were no deaths from pneumococcal septicemia in the penicillin-treated group but three deaths from the infection occurred in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by 4 months of age to decrease the morbidity and mortality [SEE FIGURE IN SOURCE PDF.] associated with pneumococcal septicemia. (Previously published in N Engl J Med 1986;314:1593-1599.

Hospitalization in a NICU averages 1 mo. but may extend to 8-9 mos. Voluminous amounts of data makes it difficult to systematically study disease processes with the conventional medical record. A computer system is being developed to aid in the analysis of the incidence, course, interrelationships and demographic features of the various newborn illnesses seen in a referral NICU averaging 600 admissions/year. How does this computer system provide information about newborn problems which would otherwise be difficult to acquire? Each infant's database is divided into 4 categories: 1) Admission history and physical exam 2) In-hospltal clinical events 3) Laboratory data 4) Outpatient follow-up. Complete information from each category is entered into separate computer files. Information is assessed via bit-mapped (inverted) files which allow acquisition of single or multiple pieces of data common to some subset of the total of patients. Laboratory data collected on a daily basis is available for analysis as an interface with clinical data. These file structures favor rapid searches of the entire database but will still permit display of all or part of an individual patient's complex hospital course. The major advantage of this system is that it permits the user to explore rapidly a large number of possibly significant relationships in a large population of newborn infants.