CEO/supplier dialogue on patient safety. Panel discussion.

Leaders and vendors candidly explore new opportunities for industry standards, work-force training, and patient-focused care.

Care management and technology enhance care delivery.

Many health care delivery organizations have experienced a flattening in the rate of their ability to decrease health care costs. Providers--if they are willing to take responsibility for care management and make appropriate investments to support the initiatives--are the logical party to take responsibility for improving care and cost control. Taking responsibility for care management, however, requires the tactical deployment of information technology to enhance care management. This article outlines what is required for information technology to improve care and cut costs.

Coagulation factor XIIIa undergoes a conformational change evoked by glutamine substrate. Studies on kinetics of inhibition and binding of XIIIA by a cross-reacting antifibrinogen antibody.

Coagulation factor XIIIa, plasma transglutaminase (endo-gamma-glutamine:epsilon-lysine transferase EC 2.3.2.13) catalyzes isopeptide bond formation between glutamine and lysine residues and rapidly cross-links fibrin clots. A monoclonal antibody (5A2) directed to a fibrinogen Aalpha-chain segment 529-539 was previously observed from analysis of end-stage plasma clots to block fibrin alpha-chain cross-linking. This prompted the study of its effect on nonfibrinogen substrates, with the prospect that 5A2 was inhibiting XIIIa directly. It inhibited XIIIa-catalyzed incorporation of the amine donor substrate dansylcadaverine into the glutamine acceptor dimethylcasein in an uncompetitive manner with respect to dimethylcasein utilization and competitively with respect to dansylcadaverine. Uncompetitive inhibition was also observed with the synthetic glutamine substrate, LGPGQSKVIG. Theoretically, uncompetitive inhibition arises from preferential interaction of the inhibitor with the enzyme-substrate complex but is also found to inhibit gamma-chain cross-linking. The conjunction of the uncompetitive and competitive modes of inhibition indicates in theory that this bireactant system involves an ordered reaction in which docking of the glutamine substrate precedes the amine exchange. The presence of substrate enhanced binding of 5A2 to XIIIa, an interaction deemed to occur through a C-terminal segment of the XIIIa A-chain (643-658, GSDMTVTVQFTNPLKE), 55% of which comprises sequences occurring in the fibrinogen epitope Aalpha-(529-540) (GSESGIFTNTKE). Removal of the C-terminal domain from XIIIa abolishes the inhibitory effect of 5A2 on activity. Crystallographic studies on recombinant XIIIa place the segment 643-658 in the region of the groove through which glutamine substrates access the active site and have predicted that for catalysis, a conformational change may accompany glutamine-substrate binding. The uncompetitive inhibition and the substrate-dependent binding of 5A2 provide evidence for the conformational change.

Lessons from the trenches in physician integration.

Beyond the theoretical basis for integration, three core considerations stand out as the primary reasons for pursuing integration from a physician's perspective. In the authors' experience, the ability to make a case for physician integration stands or falls based on the ability of the integrated delivery system to address these considerations: Gain greater access to capital; develop human resources with talents in managed care and the full spectrum of care services; and sustain an information infrastructure. This article explores the lessons learned in pursuing physician integration.

Coagulation assay with improved specificity to factor V mutants insensitive to activated protein C.

The prevalence of a new hereditary defect in the protein C anticoagulant pathway, the factor V-Leiden, has been reported to range between 20% to 60% in familial thrombophilia. In addition to differences in patient groups, these very divergent numbers might also be due to the detection method applied. In most studies a modified APTT was used, where activated protein C (APC) is added simultaneously with the start of the clotting reaction. However, this method is also influenced by other factors like protein S, factor VIII or lupus anticoagulants. Furthermore, heparin or oral anticoagulant therapy might interfere. We tried to develop a coagulation assay dependent only on those mutant forms of factor V stable against proteolytic attack by APC. For this purpose, samples were first diluted with a factor V deficient plasma (f.V-dp). Then, coagulation was initiated either on the intrinsic pathway (APTT) or on the extrinsic pathway (PT) or, by directly activating factor X (RVVT). Additionally, APC was added, which prolongation of the clotting time. Deficiencies in protein S or the presence of factor V-Leiden resulted in a less pronounced clotting time prolongation. Titration of protein S-deficient plasma samples with f.V-dp diminished this effect. In contrast, in samples with factor V-Leiden the difference to the clotting time obtained with normal plasma even increased in the order APTT>>RVVT>PT. In the APTT-based method high concentrations of factor VIII shortened the clotting times, thus mimicking a factor V-Leiden defect. This could be compensated for up to 4 U/ml factor VIII by using a f.V-dp containing factor VIII at physiological concentration. Neither unfractionated nor LMW-heparin (up to 2 U/ml) interfered with the determination. In a brief investigation on 16 plasma samples from patients under oral anticoagulation 5 (30%) showed a similar behaviour as observed with normal plasma from factor V-Leiden carriers. These results let us suggest that by simply mixing the patient sample with a factor V-deficient plasma factor V-Leiden might be detected also in patients under oral anticoagulant therapy. Inherited disorders of protein C or protein S are well known as thrombotic risk factors (1). The recent investigations by Dahlbäck et al. (2) led to the discovery of a new hereditary defect in the protein C anticoagulant pathway: the factor V-Leiden (3). This mutation renders activated factor V stable against proteolytic attack by activated protein C (APC). The reports on the prevalence of this mutation in thrombophilic patients show a considerable variation between 21% (4) and 64% (5).(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of an automated chromogenic substrate assay for the rapid determination of hirudin in plasma.

A fully mechanized chromogenic substrate assay method for the rapid and specific determination of recombinant hirudin (r-hirudin) in citrated plasma on clinical chemistry analyzers (Hitachi 911 and Cobas Mira) is described. In a first step, 12 microliters sample volume is mixed with the chromogenic substrate. Due to the almost immediate action of hirudin the inhibitory reaction and the cleavage of the substrate is started simultaneously when bovine thrombin is added in excess. This excludes interferences by antithrombin III or heparin cofactor II. The change in absorbance/min is recorded at 405 nm. The measuring range is about 0.2-4.0 mg/l r-hirudin on both analyzers. Precision is characterized by intraassay coefficients of variation between 0.63% and 2.78% on the Hitachi 911 and 1.51% and 7.84% on the Cobas Mira, respectively and interassay coefficients of variation of 3.57% to 9.15% (Hitachi 911) and 3.72% to 12.99% (Cobas Mira) for the same r-hirudin plasma concentrations. The described determination of r-hirudin correlates well with an enzyme linked immunosorbent assay method for r-hirudin (Hitachi 911: r = 0.964, y = 0.978x + 0.038, n = 323; Cobas Mira: r = 0.964, y = 0.959x-0.003, n = 323).

Elements and strategies of an effective provider integration strategy.

Regardless of the outcome of the debate in our nation's capitol, a health care revolution is sweeping the nation. In fact, if the debate lasts much longer, policy makers will be playing catch-up and responding to policies already in place in the trenches. Everywhere we turn as health care leaders, there is evidence of major change on the horizon. Reimbursement methodologies are undergoing radical alteration, traditionally stable institutions are being challenged, new organizational models are evolving, the types and roles of providers best suited to provide care are being questioned, and consumer expectations are being heightened. One of the basic strategies that is receiving attention throughout the country as a response to all this change relates to the development of integrated delivery organizations (IDO), integrated delivery systems (IDS), or integrated delivery networks (lDN). This article discusses these emerging systems in terms of health care reform, describes the rationale for their creation, and provides some strategies for their successful development.

The National Health Care Reform Debate.

Because of increasing costs and decreasing access, most policymakers agree with the public perception that the health care system in the United States is in need of change. This chapter summarizes the various proposals under consideration, which ranges from a single-payer model similar to the system in Canada to the less radical concept of managed competition.

Determination of factor XIII activity by a new photometric assay in plasma and platelets of healthy blood donors.

Crosslinking of fibrin monomers by activated factor XIII (F XIIIa) is a final event in blood coagulation. So the fibrin clot gains mechanical stability and resistance to plasmin degradation which is thought to be essential for normal blood clotting and wound healing (1-3). In addition, changes in plasma F XIII activity were found in several state of disease such as collagenoses, inflammatory bowel diseases, leukemias, subarachnoidal bleeding and delayed fracture healing (4-12). Because approximately 50% of the potential F XIII activity in plasma are present in platelets (1), the additional determination of F XIII activity in platelets is of clinical interest especially concerning platelet transfusions that may exert an additional benefit due to simultaneous substitution of platelet-bound F XIII. The latter differs from plasma F XIII as a dimer containing only a-chains (a2) compared to the plasmatic tetramer carrying additional b-chains (a2b2). We applied a recently described photometric assay suitable for the routine laboratory after adaption to an autoanalyser to determine F XIII activity in plasma and platelets of 64 healthy blood donors.

The rest of the spectrum: alternatives to managed competition.

In the November-December 1993 and January 1994 issues of Physician Executive, Kevin Fickenscher, MD, and David A. Kindig, MD, PhD, described the Clinton health reform plan and the Senate Republican Task Force proposals. At either end of the political spectrum are other proposals that are options to the managed competition model. This entry in the column is the last in a series that outlines the major proposals pending before Congress. It and the others are intended to highlight the major elements of the proposals, not their details. "A Matter of Policy" is jointly edited by Drs. Fickenscher and Kindig of the College's Forum on Health Policy.

The Republican task force health reform proposal: loyal opposition or bipartisan collaboration?

In the November-December issue of Physician Executive, Drs. Fickenscher and Kindig explored the major elements of the Clinton health reform initiative, the Health Security Act of 1993. Although the Clinton proposal represents one of the major health reform proposals presently before Congress, it is by no means the only proposal. Over the next several issues, this column will provide an overview of other major proposals pending before Congress that will receive serious consideration in the coming months.

Elements of the American Health Security Act of 1993.

Over the past several decades, there has been a plethora of proposals that were developed in response to the ongoing debate on how best to solve the problems of the American health care delivery system. In the past decade, calls for modification of our health system have become even more resonant, as measures to control rising costs were unsuccessful and access to basic services was diminished for many Americans. The most recent addition to the list of proposals for modifying the health care system is the American Health Security Act of 1993, introduced by President Clinton in September 1993. This article will examine the position of the Clinton Administration on health reform and the core elements of the reform package.

Health reform for small population areas.

There has been criticism of the managed competition model in terms of its impact on rural areas. It is suggested that the approach simply won't work for providers in rural areas and that an adjustment will be necessary. The author, acknowledging the flaw, proposes changes that will make competition work better for all providers. This column is jointly edited by Kevin M. Fickenscher, MD, and David A. Kindig, MD, PhD, chair and member, respectively, of the College's Forum on National Health Policy. Dr. Fickenscher is participating in various advisory capacities on health care in the Clinton Administration, and Dr. Kindig is Senior Advisor to HHS Secretary Donna Shalala.

A photometric assay for blood coagulation factor XIII.

An assay for a direct photometric determination of F XIII in untreated and undiluted plasma was developed. In a one-step procedure F XIII is activated by thrombin and Ca2+ and cross-links glycine-ethylester to a specific glutamine containing peptide substrate. The released ammonia is incorporated into alpha-ketoglutarate by glutamate dehydrogenase, and the NADH consumption of this reaction is measured photometrically at 340 nm. NADH-consumption is directly proportional to the F XIII activity. Fibrin polymerization and the corresponding turbidity is avoided by the use of a fibrin aggregation inhibitor. The procedure is rapid and simple and enables to measure within the range of 0 to 150% F XIII. It can be performed with automated analyzers as well as with common photometric equipment. The normal range of F XIII activity in 167 healthy donors was determined to be 70 to 140%.

Effects of an expanded medical curriculum on the number of graduates practicing in a rural state.

In 1973 the University of North Dakota School of Medicine (UNDSM), following the national trend toward four-year medical programs, expanded its previous two-year medical school curriculum to include all four years of medical education. It was hoped that this change, along with a renewed emphasis on primary care-oriented residency training within the state, would encourage medical students to establish practices within the state. In 1985 the UNDSM's Center for Rural Health mailed questionnaires to the 2,230 living graduates of the UNDSM to document a variety of their personal and practice characteristics. Based on the responses to the 924 completed questionnaires, the authors found that (1) the students from rural North Dakota were more likely than were urban students to practice in rural areas of the state, as were the students with primary care specialty training; and (2) the alumni completing residencies in North Dakota following the curriculum expansion (1976-1985) were more than twice as likely to establish practices in North Dakota. It was concluded that recruiting medical students (preferably in-state "natives") from rural areas, training them in primary care specialty areas, and enabling them to remain in North Dakota for the duration of their medical training (including residency training) combined to exert a considerable "retaining" effect on the UNDSM alumni.