Yuzuru Takemura

Background: Excessive use of broad spectrum antibiotics is related to the spread of drug resistant bacterial strains in the community. Aim/methods: The effects of immediate testing for C reactive protein (CRP) and white blood cell count (WBC) on physicians’ choices of antibiotic was investigated in patients with acute infection. Acutely febrile new outpatients were randomised into two groups: group 1 (147 patients) underwent CRP and WBC testing before initial consultation (advance testing). Prescriptions were compared with those in group 2 (no advance testing; 154 patients). Results: In non-pneumonic acute respiratory tract infections, 61 (58%) and 122 (91%) of group 1 and 2 patients were prescribed antibiotics, respectively. Cefcapene pivoxil (third generation cephalosporin) and amoxicillin were the most frequently chosen drugs for group 1 and 2, respectively. Total prescriptions of newer, extended spectrum antibiotics (cefcapene pivoxil and clarithromycin (advanced macrolide)) were reduced by 25% in group 1, although they increased in rate (41 (67%) v 55 (45%) prescriptions) because of the decreased prescription of amoxicillin. In group 1, cefcapene pivoxil was preferentially selected when WBC values were greater than 9 × 10 ⁹ /litre. Prescription shifted to macrolides (mainly clarithromycin) in patients without leucocytosis. Patient treatment outcome did not significantly differ between the two groups. Conclusions: The availability of CRP and WBC data during initial consultation greatly reduced prescription of amoxicillin, but had a lesser effect on newer, potent, broad spectrum antibiotics.

Few studies have demonstrated the optimal usage of common inflammatory markers, alone or in combination, based on the cost-effectiveness. We analyzed the yield and cost of C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), sialic acid, and protein fractionation in 177 new primary care outpatients with inflammation-related symptoms. A useful result (UR) was assigned if tests contributed to a change in physician's diagnosis or decision-making. Costs of testing were calculated based on either single or simultaneous measurement. Five inflammatory markers generated 147 URs in 123 patients. CRP showed the best contribution to generation of UR, followed by sialic acid, protein fractionation, WBC, and ESR. CRP demonstrated poor correlation with WBC (r = 0.458), while sialic acid strongly correlated with total absolute amount of alpha1 and alpha2 fractions in protein fractionation (r = 0.855) and moderately with ESR (r = 0.651). The combination of CRP and WBC produced the best cost-effectiveness at a cost of Yen 1169 (US dollars 9.6 or Euro 9.7)/additional UR against CRP testing alone. Sialic acid, an automated multichannel analyzer-based test, demonstrated the favorable cost-effectiveness over ESR or protein fractionation when combined with CRP (and WBC). Our results indicate that the optimal usage of these inflammatory markers should involve careful cost-effectiveness considerations.

C-Reactive protein (CRP) is a well-known indicator of inflammation. Advances in laboratory technology have enabled its quantification at lower concentrations by an automated analyzer (1)(2)(3). Because an increase in serum CRP concentration, even within the reference intervals of conventional analytic methods, has been related to increases in the risk of atherothrombotic events (4)(5)(6)(7), efforts for CRP quantification are currently directed toward healthy, elderly individuals or populations at risk of atherosclerotic diseases. When measured with a high-sensitivity analytic method, CRP may have diagnostic value in neonatal infection because newborns are unable to produce sufficient amounts of acute-phase proteins (8) and respond to infection with a smaller increase in CRP compared with that in adults (9).

Background:Appropriate diagnostic testing involves considerations of cost-effectiveness. We examined the cost-effectiveness of individual tests in a panel of tests defined by the Japan Society of Clinical Pathology. Methods: We studied 540 new, symptomatic primary care outpatients with a set of 30 common diagnostic tests [the Essential Laboratory Tests (2); ELT(2) panel] for clinical evaluation and identification of occult disease. A useful result (UR) of testing was defined as a finding that contributed to a change in a physician’s diagnosis or decision-making relating to a “tentative initial diagnosis” obtained from history and physical examination alone. Results: The ELT(2) panel testing yielded 398 URs and uncovered 261 occult diseases among 540 patients. In total, 1592 tests contributed to either UR-generation or discovery of occult disease. The cost per effective test (cost required per test that contributed to either definition of effectiveness) ranged from ¥108 (∼US$0.92) for total cholesterol to ¥6200 (∼$52.50) for chest x-ray. Contribution rates and the cost per effective test varied among disease categories. We restructured panel components considering the effectiveness of each test. Subsets of the ELT(2) would have improved cost-effectiveness and achieved cost savings in five of eight disease categories. Conclusions: Assembly of tests based on cost-effectiveness can improve clinical efficiency and decrease total cost of panel testing for selected patient groups.

We have established human leukemia cell lines made resistant to various antifolate drugs and analyzed resistance mechanisms developed in these cells at the cellular and molecular levels. The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Each resistance mechanism was not necessarily induced at random, but appeared to relate to the biochemical and pharmacological properties of the drug exposed, biological dispositions of the cells, drug-exposure manners to, or culture conditions of the cells. Since it has been shown that a minor modification at the specified position of the folate structure resulted in a drastic change in its pharmacological properties, many new compounds have been rationally designed on the basis of the knowledge of relationships between structure modifications and pharmacological properties. The step-by-step approach to the development of new analogues led to the discoveries of several promising antifolate drugs such as trimetrexate and raltitrexed, which can overcome the acquired and natural resistance to methotrexate, a classical antifolate, and clinical trials of these newer classes of antifolate compounds are currently underway.

The uncontrolled escalation of total health care expenditure despite the government's endeavours during the past decades in the USA had led to the rapid infiltration of managed care organisations (MCOs). Traditional hospital based laboratories have been placed in a crucial situation with the advent of the managed care era. A massive reduction of in house testing urged them to develop strategies against financial difficulty. Consolidation and networking, participation in the outreach testing market, and emphasis on point of care/satellite laboratory testing in non-traditional, ambulatory settings are major strategies for the survival of hospital laboratories. Several physicians' office laboratories (POLS) have closed their doors in response both to regulatory restrictions imposed by the Clinical Laboratory Improvement Amendments of 1988 and to managed care infiltration. It seems likely that POLs and hospital laboratories will continue to reduce test volumes, whereas commercial reference laboratories will thrive through contracting with MCOs. In the current climate of managed care dominance in the USA, clinical laboratories are changing their basic operation focus and mission in response to the aggressively changing landscape.

Background: Diagnostic test panels have been advocated by the Japan Society of Clinical Pathology for evaluation of presenting complaints of new outpatients in primary care medicine. The tests have additional potential utility for opportunistic finding of asymptomatic diseases, but data are lacking on the number of new conditions identified by the test panels and on the cost per identified case. Methods: We studied 540 new, symptomatic patients at the Comprehensive Medicine Clinics of National Defense Medical College during 1991–1997. All underwent testing with the “Essential Laboratory Tests” panel (2) [ELT(2) panel]. This panel includes hematologic tests, urinalysis, total protein, C-reactive protein, albumin, cholesterol, triglycerides, glucose, urea nitrogen, creatinine, uric acid, serum protein fractionation, six enzymes, and optional tests, including x-rays, electrocardiogram, and fecal occult blood. Results: The ELT(2) panel uncovered 276 additional diagnoses of asymptomatic disease or abnormal health status. The most frequent occult condition was hyperlipidemia (100 cases) followed by liver dysfunction (53 cases). Clinical efficiency of the panel (occult diseases/patient) varied depending on the category of tentative initial diagnosis, with the highest efficiency in patients with cardiovascular disease. We created smaller panels by combining 11 basic tests [called the ELT(1) baseline panel] with one or more additional tests from the ELT(2) and analyzed their cost-effectiveness. Addition of four tests (total cholesterol, alanine aminotransferase, glucose, and uric acid) improved both clinical efficiency (0.41 occult disease/patient) and economic efficiency [¥2372 (∼$22.50 US)/occult disease] at a cost-effectiveness of ¥177 per incremental case of occult disease. Addition of further tests decreased cost-effectiveness. Conclusions: Although the ELT(2) panel has supplemental utility for opportunistic screening of some significant, occult diseases and conditions, universal utilization of the full panel is not supported by the cost-effectiveness found in this study.