Renormalization group analysis of polymer cyclization with non-equilibrium initial conditions.

We develop a renormalization group approach for cyclizing polymers for the case when chain ends are initially close together (ring initial conditions). We analyze the behavior at times much shorter than the longest polymer relaxation time. In agreement with our previous work (Europhys. Lett. 73, 621 (2006)) we find that the leading time dependence of the reaction rate k(t) for ring initial conditions and equilibrium initial conditions are related, namely k (ring)(t) proportional, variant t (-delta) and k (eq)(t) proportional, variant t (1-delta) for times less than the longest polymer relaxation time. Here delta is an effective exponent which approaches delta = 5/4 for very long Rouse chains. Our present analysis also suggests a "sub-leading" term proportional to (ln t)/t which should be particularly significant for smaller values of the renormalized reaction rate and early times. For Zimm dynamics, our RG analysis indicates that the leading time dependence for the reaction rate is k(t) approximately 1/t for very long chains. The leading term is again consistent with the expected relation between ring and equilibrium initial conditions. We also find a logarithmic correction term which we "exponentiate" to a logarithmic form with a Landau pole. The presence of the logarithm is particularly important for smaller chains and, in the Zimm case, large values of the reaction rate.

The total laboratory solution: a new laboratory E-business model based on a vertical laboratory meta-network.

Major forces are now reshaping all businesses on a global basis, including the healthcare and clinical laboratory industries. One of the major forces at work is information technology (IT), which now provides the opportunity to create a new economic and business model for the clinical laboratory industry based on the creation of an integrated vertical meta-network, referred to here as the "total laboratory solution" (TLS). Participants at the most basic level of such a network would include a hospital-based laboratory, a reference laboratory, a laboratory information system/application service provider/laboratory portal vendor, an in vitro diagnostic manufacturer, and a pharmaceutical/biotechnology manufacturer. It is suggested that each of these participants would add value to the network primarily in its area of core competency. Subvariants of such a network have evolved over recent years, but a TLS comprising all or most of these participants does not exist at this time. Although the TLS, enabled by IT and closely akin to the various e-businesses that are now taking shape, offers many advantages from a theoretical perspective over the current laboratory business model, its success will depend largely on (a) market forces, (b) how the collaborative networks are organized and managed, and (c) whether the network can offer healthcare organizations higher quality testing services at lower cost. If the concept is successful, new demands will be placed on hospital-based laboratory professionals to shift the range of professional services that they offer toward clinical consulting, integration of laboratory information from multiple sources, and laboratory information management. These information management and integration tasks can only increase in complexity in the future as new genomic and proteomics testing modalities are developed and come on-line in clinical laboratories.

Integrating laboratory processes into clinical processes, Web-based laboratory reporting, and the emergence of the virtual clinical laboratory.

References to integration occur frequently in the health-care literature. Integration in this context refers to the blending or merging of the separate components of a health-care organization to form a cohesive and seamless interoperating whole. The health-care industry is now in the process of reorganizing and consolidating through hospital mergers and the creation of provider networks. The stimulus for these activities, all integrative, has been the introduction of managed care as a replacement for fee-for-service reimbursement. Managed care was designed to introduce competition into health-care delivery, and it certainly has succeeded in this goal. The quest for integration in health care is thus a consequence of the shift to managed care and has been driven by the belief that integration will lead to greater efficiency and cost savings in the industry. The major vehicles for achieving integration in the clinical laboratories will be Web-based reporting and the emergence of the virtual clinical laboratory.

Orchestrating a unified approach to information management.

Articles in both business and healthcare literature make frequent reference to the need for integration in healthcare organizations. In healthcare, the term horizontal integration can refer to the purchase of one hospital by another in the same geographical area, particularly where the hospitals' services overlap. Services might be consolidated in this example or one hospital may totally shut down the acquired one. Vertical integration refers to a hospital exercising control of its inputs or outputs. In one sense, patients referred to a hospital can be considered inputs. A hospital that purchases physician practices or integrated delivery systems is an example. Purchasing a nursing facility by an integrated delivery system (IDS) is another. This article focuses on organizational or holographic integration, where an organization is understood and embedded--like a hologram--in each of its smaller components, and each operating unit has knowledge about the whole system in which it is embedded. Conceptually, a hospital can achieve organizational integration relatively easily. One way is to assign administrative responsibility for two departments, radiology and pathology, for example, to one person who will handle billing, budgeting and human resources issues. Organizational integration breaks down turf barriers between distinct functional areas (often known as stovepipes or the silo mentality) because the result is less energy expended to solve problems. Organizational integration must include the merging of information technology (IT) into a single computer system that can report results across several departments, for example, in order entry, result reporting, resource scheduling or billing. At the University of Michigan Health System, technical and organizational integration are taking place across the information systems of the radiology and pathology departments. Deployment of an intranet-based architecture for ancillary information systems will provide the means to achieve high level integration across previously heterogeneous and non-integrated department-based clinical information systems.

Using hub technology to facilitate information system integration in a health-care enterprise.

The deployment and maintenance of multiple point-to-point interfaces between a clinical information system, such as a laboratory information system, and other systems within a healthcare enterprise is expensive and time consuming. Moreover, the demand for such interfaces is increasing as hospitals consolidate and clinical laboratories participate in the development of regional laboratory networks and create host-to-host links with laboratory outreach clients. An interface engine, also called a hub, is an evolving technology that could replace multiple point-to-point interfaces from a laboratory information system with a single interface to the hub, preferably HL7 based. The hub then routes and translates laboratory information to other systems within the enterprise. Changes in application systems in an enterprise where a centralized interface engine has been implemented then amount to thorough analysis, an update of the enterprise's data dictionary, purchase of a single new vendor-supported interface, and table-based parameter changes on the hub. Two other features of an interface engine, support for structured query language and information store-and-forward, will facilitate the development of clinical data repositories and provide flexibility when interacting with other host systems. This article describes the advantages and disadvantages of an interface engine and lists some problems not solved by the technology. Finally, early developmental experience with an interface engine at the University of Michigan Medical Center and the benefits of the project on system integration efforts are described, not the least of which has been the enthusiastic adoption of the HL7 standard for all future interface projects.

The challenge of managing laboratory information in a managed care environment.

This article considers some of the major changes that are occurring in pathology and pathology informatics in response to the shift to managed care in the United States. To better understand the relationship between information management in clinical laboratories and managed care, a typology of integrated delivery systems is presented. Following this is a discussion of the evolutionary trajectory for the computer networks that serve these large consolidated healthcare delivery organizations. The most complex of these computer networks is a community health information network. Participation in the planning and deployment of community health information networks will be important for pathologists because information management within pathology will be inexorably integrated into the larger effort by integrated delivery systems to share clinical, financial, and administrative data on a regional basis. Finally, four laboratory information management challenges under managed care are discussed, accompanied by possible approaches to each of them. The challenges presented are (1) organizational integration of departmental information systems such as the laboratory information system; (2) weakening of the best-of-breed approach to laboratory information system selection; (3) the shift away from the centralized laboratory paradigm; and (4) the development of rule-based systems to monitor and control laboratory utilization.

Differentiating between marketing-driven and technology-driven vendors of medical information systems.

Buyers of medical information systems such as laboratory information systems need to recognize that the vendors of such systems may pursue corporate strategies emphasizing expenditures on marketing and client services, expenditures on technology and research and development (R&D), or a more balanced approach. The strategic goals and objectives of a vendor of an information system should align closely with those of a potential hospital client. A restless hospital client seeking cutting-edge technology will probably be dissatisfied with a system vendor who emphasizes slow ongoing incremental system development. Objective criteria for distinguishing between a marketing-driven vendor and a technology-driven vendor of medical information systems, and their variants, are presented based on the ratio of marketing expenditures to sales revenue compared with the ratio of research and development expenditures to sales revenue of the company. More subjective narrative criteria are also offered for making such distinctions.

The laboratory information float, time-based competition, and point-of-care testing.

A new term, the laboratory information float, should be substituted for turnaround-time when evaluating the performance of the clinical laboratory because it includes the time necessary to make test results both available (ready to use) and accessible (easy to use) to clinicians ordering tests. The laboratory information float can be greatly reduced simply by telescoping the analytic phase of laboratory testing into the preanalytic phase. Significant costs are incurred by such a change, some of which can be reduced by developing a mobile clinical laboratory (sometimes referred to as a "lab-on-a-slab" or "rolling thunder") to transport the analytic devices directly to patient care units. The mobile clinical laboratory should be equipped with an integrated personal computer that can communicate continuously with the host laboratory information system and achieve some semblance of continuous flow processing despite test performance in point-of-care venues. Equipping clinicians with palmtop computers will allow the mobile clinician to access test results and order tests on the run. Such devices can be easily configured to operate in a passive mode, accessing relevant information automatically instead of forcing clinicians to query the laboratory information system periodically for the test results necessary to render care to their patients. The laboratory information float of the year 2,000 will surely be measured in minutes through the judicious deployment of relevant technology such as mobile clinical laboratories and palmtop computers.

Selecting and managing a professional consultant to a clinical laboratory.

Managers of clinical laboratories, like those in other complex organizations, will often seek the advice of external professional consultants to provide solutions to current problems. Optimizing the process of selecting and managing consultants to clinical laboratories is the topic of this article. A number of practical tips are offered, including a discussion of the use of nontraditional consultants. Special emphasis is placed on developing a request for proposal and evaluating responses to the request for proposal by the various consulting firms bidding for the engagement. The use of consultants in the health-care arena in general and clinical laboratories in particular will undoubtedly increase as financial and organizational challenges to the industry continue to proliferate.

Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group.

OBJECTIVE: To determine the efficacy and safety of fluconazole treatment of coccidioidal meningitis. DESIGN: Uncontrolled clinical trial. SETTING: Four university-based treatment centers in California, Arizona, and Texas. Most therapy was conducted without hospitalization. PATIENTS: Fifty consecutive patients with active coccidioidal meningitis, of which 47 (94%) were evaluable. Twenty-five patients had received no previous treatment for their meningitis, and nine had coinfection with human immunodeficiency virus (HIV). INTERVENTION: Fluconazole was administered in an oral dose of 400 mg once per day for up to 4 years (median, 37 months) in responding patients. Concurrent therapy with another antifungal agent was prohibited. MEASUREMENTS: Predefined assessment of infection-related abnormalities was done at the time of enrollment and was repeated at least every 4 months during treatment. Elimination of 40% or more of baseline abnormalities was considered a response. RESULTS: Thirty-seven of 47 (79%; 95% CI, 61% to 90%) evaluable patients responded to treatment. Response rates were similar for patients with and without previous therapy, for patients with and without concomitant HIV infection, and for patients with and without pre-existing hydrocephalus. Most improvement occurred within 4 to 8 months after starting treatment. Patient symptoms resolved more quickly than did cerebrospinal fluid abnormalities. In 15 of 20 responding patients followed for 20 months or more, residual low-level cerebrospinal fluid abnormalities remained throughout therapy. No patient discontinued therapy because of drug-related side effects, although confusion developed in two patients that resolved when the dose of fluconazole was reduced. CONCLUSION: Fluconazole therapy is often effective in suppressing coccidioidal meningitis.

Integrating information from decentralized laboratory testing sites. The creation of a value-added network.

The decentralization of laboratory testing provides distinct advantages for clinicians and patients, such as the reduction of test turnaround time, but also promotes the development of scattered caches of results. This problem could be ameliorated by the creation of an integrated laboratory data base. Such an approach would provide clinicians with a patient view of laboratory information in addition to the functional view of it that is offered currently. Impressive technologic advances are being made in the development of a distributed computer architecture in which processing tasks and information are shared across multiple hardware platforms attached to a network. Such architecture could be used to create a regional value-added laboratory network to integrate test information generated in decentralized testing sites. Independent reference laboratories and tertiary-care referral hospitals are the most likely candidates to create distributed value-added networks. Pathologists should view themselves as health-care professionals responsible for the processing, storage, and transmission of information, as well as for its generation. In time, the partition of information along hospital geopolitical boundaries will appear archaic and will be replaced by an emphasis on local and regional integration of medical information similar to that advocated here.

Client-server design provides model for 'coopetition' alliances.

As healthcare organizations move from isolated departments to integrated information sharing, who will pilot this change? Both the director and manager of pathology data systems at the University of Michigan Hospitals in Ann Arbor suggest vendors, system integrators and hospital administrators put aside competition and try a new concept--"coopetition"--to solve the problem.

An analysis of the relationship between a pathology department and its laboratory information system vendor.

The ongoing collaborative relationship between a pathology department and the vendor of its laboratory information system is vitally important because of the strategic importance of the laboratory information system in managing the information product of the department. Laboratory information system vendors are value-added resellers in that they produce software and package it with hardware manufactured by another manufacturer. The success of laboratory information system value-added resellers in creating information systems that are highly functional depends on their forward vertical quasi-integration into pathology departments. Because of this relationship, laboratory information system value-added resellers exert a significant degree of control over departments, largely through the creation of switching costs. There are a number of strategies by which departments can exercise greater control over vendors, one of which is to serve as either an alpha- or beta-development site for the vendor's software. Such a strategy is not without risk, but it achieves the dual purpose of enhancing both the expertise of departmental personnel and the quality of the software product.

Comparison of susceptibility to beta-lactam antimicrobial agents among bacteria isolated from intensive care units.

Evaluating microbial isolation and susceptibility patterns from institutional settings is a well-established component of ongoing infection control activities. At the University of Michigan Hospitals, susceptibility profiles for selected bacteria tested from 1984 to 1989 were analyzed for major changes in the percentage of organisms susceptible to beta-lactam antimicrobials. Data on bacteria isolated from respiratory specimens obtained from 1433 patients in intensive care units (ICUs) during a 10-month interval were compared with like data obtained from 750 non-ICU patients. Antimicrobial agents studied were chosen based on hospital formulary availability and prevailing usage in the institution. Susceptible and moderately susceptible categories were combined for purposes of reporting, since empiric therapeutic doses would cover strains having both susceptibility levels. Antimicrobic susceptibilities were compared and differences analyzed among the ICUs. Major shifts in susceptibility were noted during the 5-year period. The incidence and susceptibility profiles of the microorganisms varied considerably between ICU and non-ICU patients. Pseudomonas aeruginosa isolates from individual ICUs showed large variations in prevailing susceptibilities, with the burn unit harboring the most resistant strains. However, the neurological, surgical, and critical care medicine units also showed large numbers of antimicrobial-resistant pseudomonads. Among Enterobacter cloacae isolates, only imipenem showed a high level of activity against both ICU and total hospital isolates. When examined by individual ICU, however, imipenem resistance was seen in the general medicine and burn units. The burn and pediatric ICUs showed increased rates of recovery of beta-lactam-resistant E. cloacae isolates, although significantly high resistance rates were seen throughout all ICUs. The surgical ICU was noted to have an abnormally high incidence of lower respiratory infections caused by P. aeruginosa. The antibiogram indicated that one possible epidemic strain was involved. However, when the isolates were subjected to fatty-acid profiling by gas-liquid chromatography, it was found that cross-contamination with five discernible strains had occurred among the ten patients tested. These preliminary data suggest that resistant pseudomonads can be harbored and spread within an ICU, and that the ICU can act as a reservoir of resistance that is spread to a "step-down" unit.

The deployment of information technology in clinical laboratories and its impact on professional roles.

New information technology is deployed in hospital clinical laboratories to increase both the quality and efficiency of laboratory operations. Although total laboratory expenses may rise as a result of technology deployment, the average cost per test may decline. S-curves can be used to illustrate the effects of new information technology--such as a laboratory information system (LIS)--on the useful output and use of resources in laboratories. Major changes are now occurring as a result of the deployment of information technology, most notably in the area of automated information management. The role of laboratory professionals must be modified in response to this new information environment. The generation of information within clinical laboratories should be considered as the beginning--not the end--of the responsibility of laboratory professionals.

Using the laboratory information system to achieve strategic advantage over the competitors of hospital-based clinical laboratories.

The competitors of hospital pathologists are commercial reference laboratories, hospital special function laboratories, pathology groups in neighboring hospitals, hospital mainframe computer personnel, and users of patient proximity testing systems. The laboratory information system can provide a strategic advantage over these competitors by matching, exceeding, or substituting for their capabilities and by creating switching costs for clinics, administrations, and patients. For example, the installation of microcomputers in clinicians' private offices provides them with ready access to the pathology data base, bonds them to the hospital, and capitalizes on the willingness of the hospital to invest in information technology.

Informatics as a separate section within a department of pathology.

Departments of pathology should be reorganized to include a separate section of pathology informatics (PI) in addition to the traditional sections of clinical pathology and anatomic pathology. PI is the discipline of medical informatics as practiced within pathology and encompasses a rich mix of activities. The primary role of specialists working in clinical pathology and anatomic pathology would be to create information, whereas that of informaticians in a section of PI would be to add value to the created information by processing it and communicating it to users. The four major benefits associated with a PI section would be as follows: (1) enhanced productivity and efficiency in the development of alignment and impact applications; (2) better management of the information product of pathology and the informaticians themselves; (3) increased political power and influence for pathology; and (4) increased awareness and sophistication on the part of departmental leaders about information processing. Departmental benefits from the proposed organizational change would thus be calibrated in terms of the ability of the revamped department to harness and exploit new information technology.