RAPID3? Aptly named!

The RAPID3 score is the sum of three 0-10 patient self-report scores: pain, functional impairment on MDHAQ, and patient global estimate. It requires 5 seconds for scoring and can be used in all rheumatologic conditions, although it has mostly been used in rheumatoid arthritis where cutoffs for low disease activity (<6/30) or high disease activity (>12/30) have been set. A RAPID3 score of ≤ 3/30 with 1 or 0 swollen joints (RAPID3 ≤ 3 + ≤ SJ1) provides remission criteria comparable to Boolean, SDAI, CDAI, and DAS28 remission criteria, in far less time than a formal joint count. RAPID3 performs as well as the DAS28 in separating active drugs from placebos in clinical trials. RAPID3 also predicts subsequent structural disease progression. RAPID3 can be determined at short intervals at home, allowing the determination of the area under the curve of disease activity between two visits and flare detection. However, RAPID3 should not be seen as a substitute for DAS28 and face to face visits in routine care. Monitoring patient status with only self-report information without a rheumatologist's advice (including joints and physical examination, and consideration of imaging and laboratory tests) may indeed be as undesirable for most patients than joint examination without a patient questionnaire. Conversely, combining the RAPID3 and the DAS28 may consist in faster or more sensitive confirmation that a medication is effective. Similarly, better enquiring of most important concerns of patients (pain, functional status and overall opinion on their disorder) should reinforces patients' confidence in their rheumatologist and treatments.

Electrical excitation of surface plasmons by an individual carbon nanotube transistor.

We demonstrate here the realization of an integrated, electrically driven, source of surface plasmon polaritons. Light-emitting individual single-walled carbon nanotube field effect transistors were fabricated in a plasmonic-ready platform. The devices were operated at ambient conditions to act as an electroluminescence source localized near the contacting gold electrodes. We show that photon emission from the semiconducting channel can couple to propagating surface plasmons developing in the electrical terminals. Our results show that a common functional element can be operated for two different platforms emphasizing thus the high degree of compatibility between state-of-the-art nano-optoelectronics devices and a plasmonic architecture.

Electron-induced limitation of surface plasmon propagation in silver nanowires.

Plasmonic circuitry is considered as a promising solution-effective technology for miniaturizing and integrating the next generation of optical nano-devices. A key element is the shared metal network between electrical and optical information enabling an efficient hetero-integration of an electronic control layer and a plasmonic data link. Here, we investigate to what extent surface plasmons and current-carrying electrons interfere in such a shared circuitry. By synchronously recording surface plasmon propagation and electrical output characteristics of individual chemically-synthesized silver nanowires we determine the limiting factors hindering the co-propagation of an electrical current and a surface plasmon in these nanoscale circuits.

Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients.

OBJECTIVES: Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS: Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor α (TNFα) and IL-1ß. Wild-type, jnk1(-/-)-jnk2(-/-) and nemo(-/-) murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-κB) and JNK in that effect. RESULTS: IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNFα and IL-1ß stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-κB and JNK pathway. CONCLUSION: This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNFα and IL-1ß, may contribute to inflammation and bone erosions in RA.

Validation of a new fluidic device for mechanical stimulation and characterization of microspheres: A first step towards cartilage characterization.

Articular cartilage is made of chondrocytes surrounded by their extracellular matrix that can both sense and respond to various mechanical stimuli. One of the most widely used in vitro model to study cartilage growth is the model of mesenchymal stromal cells-derived cartilage micropellet. However, mechanical stimulation of micropellets has never been reported probably because of their small size and imperfect round shape. The objective of the study was to develop an original custom-made device allowing both the mechanical stimulation and characterization of cartilage micropellets. The fluidic-based device was designed for the concomitant stimulation or characterization of six microspheres placed into the conical wells of a tank. In the present study, the device was validated using alginate-, collagen- and crosslinked collagen-based microspheres. Different types and ranges of pressure signals (square, sinusoidal and constant) were applied. The mechanical properties of microspheres were equivalent to those determined by a conventional compression test. Accuracy, repeatability and reproducibility of all types of pressure signals were demonstrated even though square signals were less accurate and sinusoidal signals were less reproducible than the others. The interest of this new device lies in the reliability to mechanically stimulate and characterize microspheres with diameters in the range of 900 to 1500 µm. Mechanical stimulation can be performed on six microspheres in parallel allowing the mechanical and molecular characterization of the same group of cartilage micropellets. The device will be useful to evaluate the growth of cartilage micropellets under mechanical stimuli.

T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis.

Rheumatoid arthritis is a multistep disorder associated with autoimmune features of yet unknown etiology. Implication of viruses such as Epstein-Barr virus (EBV) in rheumatoid arthritis pathogenesis has been suspected on the basis of several indirect observations, but thus far, a direct link between EBV and rheumatoid arthritis has not been provided. Here we show that a large fraction of T cells infiltrating affected joints from a patient with chronic rheumatoid arthritis recognizes two EBV transactivators (BZLF1 and BMLF1) in a major histocompatibility complex-restricted fashion. Responses to these EBV antigens by synovial lymphocytes from several other chronic rheumatoid arthritis patients were readily detectable. Thus these results suggest a direct contribution of EBV to chronic rheumatoid arthritis pathogenesis. They also demonstrate for the first time the occurrence of T cell responses against EBV transactivating factors, which might be central in the control of virus reactivation.

Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry.

OBJECTIVE: To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare the risks for different anti-TNF agents. METHODS: A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case-control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference. RESULTS: 38 cases of lymphoma, 31 non-Hodgkin's lymphoma (NHL) (26 B cell and five T cell), five Hodgkin's lymphoma (HL) and two Hodgkin's-like lymphoma were collected. Epstein-Barr virus was detected in both of two Hodgkin's-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3-7.1) and 3.6 (2.3-5.6) versus 0.9 (0.4-1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case-control study: odds ratio 4.7 (1.3-17.7) and 4.1 (1.4-12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2). CONCLUSION: The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.

Validity of the polymyalgia rheumatica activity score in primary care practice.

OBJECTIVE: To evaluate the validity and reliability of the polymyalgia rheumatica (PMR) activity score (PMR-AS) for relapse diagnosis by general practitioners (GPs) who manage a large proportion of patients with PMR. METHODS: Seven clinical vignettes of PMR were used, for which 35 rheumatologists previously made a diagnosis of relapse or no relapse with greater than 80% agreement. These vignettes were submitted to 163 GPs, who were asked to assess disease activity using a visual analogue scale (VASph), this being the only physician-dependent component of the PMR-AS. The 1116 available vignette-GP combinations were used to assess differences in VASph assessed by GPs versus rheumatologists. Statistical associations linking a relapse diagnosis by the rheumatologists (the reference standard) to the value of the GP-assessed PMR-AS or its components (GP-assessed VASph, visual analogue scale pain score, C-reactive protein, morning stiffness and elevation of upper limbs) were evaluated. RESULTS: No significant differences were found between VASph scores by GPs versus rheumatologists for any of the vignettes. A relapse diagnosis was strongly associated with PMR-AS values of 7 or more (sensitivity 99.4%; specificity 93.3%; agreement 95.9% (95% CI 94.5% to 97.0%) with kappa = 0.92). Of the 590 GP-vignette combinations with PMR-AS values lower than 7, all but three (0.5%) had no relapse diagnosis. Of 510 combinations with PMR-AS values of 7 or more, only 42 (8%) had no flare diagnosis. CONCLUSIONS: This study supports the validity of the PMR-AS in primary care practice and provides evidence that a good scoring system can be useful to guide clinical and therapeutic decisions.

Characteristics and survival of 26 patients with paraneoplastic arthritis.

OBJECTIVE: To date, only a few series of patients with paraneoplastic arthritis have been published. The charts of patients with cancer-associated arthritis were collected in order to describe characteristics of this rheumatism. METHODS: A questionnaire was created for this study and validated by experts based on specific criteria of inclusion and exclusion. Histology of neoplasia was included. RESULTS: In all, 16 males and 10 females with a mean (range) age of 57.5 years (28-85) were recruited from 17 nationwide centres in France. Patients presented with symmetric polyarthritis involving wrists and hands (85%) and extra-articular symptoms were frequent (84%). There was no specific biologic or radiographic feature. The mean (range) delay between the diagnosis of rheumatism and neoplasia was 3.6 months (0-21.2). Tumours were usually diagnosed after articular symptoms occurred (88.5%). Twenty patients had a solid cancer, and six a haematological malignancy. Adenocarcinoma of the lungs was the most frequent type of solid cancer (60%). Tumours were diagnosed at an early stage, which may explain the good median survival of 1.21 years (range 0.64-present) with a mean follow-up of 1.9 years (range 0.16-10). The percentage of articular symptoms resolution was significantly higher in patients with solid tumours, as compared to patients with haemopathy (p = 0.007). In cases of tumour relapse, rheumatic symptoms did not recur for 75% of patients. CONCLUSIONS: Underlying neoplasia should be considered in male patients with new onset polyarthritis, smokers, and particularly in patients chronically ill. Additional investigations should then be performed to diagnose cancer at an early stage.

Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer.

BACKGROUND: Best supportive care has long been considered to be the standard therapy for metastatic non-small-cell lung cancer (NSCLC). There is now evidence from randomized trials that a number of chemotherapy regimens can palliate cancer-related symptoms and modestly improve survival. We show how cost-effectiveness analyses can be used to make choices between different (ambulatory) chemotherapy regimens. METHODS: Clinical algorithms describing the diagnosis, staging, and treatment of metastatic NSCLC were incorporated into Statistics Canada's Population Health Model. Using consistent methodology, we assessed the cost-effectiveness of several chemotherapeutic interventions: a combination of vindesine (VDS) plus cisplatin, etoposide (VP-16) plus cisplatin, vinblastine (VLB) plus cisplatin, vinorelbine (Navelbine; NVB) plus cisplatin, paclitaxel (Taxol) plus cisplatin, and gemcitabine (GEM) and NVB alone. We calculated the total chemotherapy costs in 1995 Canadian dollars, the cost per case, the average life-years saved, and the cost per life-year saved. Using the Population Health Model, we then constructed an advanced decision framework that rank-ordered the various treatment regimens so as to optimize benefit below various cost-effectiveness thresholds. RESULTS: One regimen (VLB plus cisplatin) appears to result in better survival and lower health care expenditures than best supportive care. By use of cost-effectiveness thresholds of $25,000 and $50,000 per life-year gained, NVB plus cisplatin is the preferred regimen. When quality of life is considered, however, GEM is preferred to NVB plus cisplatin at a threshold value of $50,000. At thresholds of $75 000 and $100,000, paclitaxel plus cisplatin at a dose of 135 mg/m(2) is the preferred regimen. At thresholds of $50,000 and above, best supportive care is the least preferred regimen. CONCLUSIONS: This decision framework allows the comparison of different treatment regimens based on various cost-effectiveness thresholds. Our analysis also supports the use of chemotherapy regimens and the abandonment of best supportive care as the standard of care for patients with advanced NSCLC. [J Natl Cancer Inst 2000;92:1321-9].

Cost of combined modality interventions for stage III non-small-cell lung cancer.

PURPOSE: To evaluate the cost-effectiveness (CE) of new combined modality strategies in patients with stage III non-small-cell lung cancer (NSCLC). METHODS: Recent studies suggest that combined modality therapy confers a survival advantage for patients with stage III NSCLC. Using the Statistics Canada (Ottawa, Canada) lung cancer costing model, we have evaluated the CE of these interventions using 1993 Canadian health care costs and the perspective of the government as payer in a universal health care system. RESULTS: We estimate that the cost to treat a stage IIIa NSCLC patient with preoperative and postoperative chemotherapy would increase by $15,886, and a similar combined modality approach with the addition of postoperative radiotherapy would increase the cost by $22,963. Chemoradiotherapy for stage IIIb NSCLC would produce a smaller incremental cost of approximately $8,912 per case. However, these approaches are remarkably cost-effective, with cost per life-year gained (LYG) ranging from $3,348 to $14,958. Administering all chemotherapy in the outpatient department would improve CE. For sensitivity analysis, we reduced the survival gain that resulted from the three interventions by 25% and 50%, and increased the hospital per diem rates by 10%, 20%, and 30%. CONCLUSION: Even with the most adverse assumptions, the CE estimates were all considered acceptable for new health care technologies in Canada. Overall, it appears that neoadjuvant therapy for stage IIIa NSCLC and combined modality therapy for stage IIIb NSCLC are cost-effective. Economic considerations should not be a barrier to their adoption.

[Management of phenylketonuria and hyperphenylalaninemia: the French guidelines]. / Consensus national sur la prise en charge des enfants dépistés avec une hyperphénylalaninémie.

Phenylketonuria (PKU) is an inherited metabolic disease affecting about one birth out of 15 000. From 1978, a national systematic neonatal screening was set up in France with a regional organisation. French rational and guidelines have been established by the national PKU group with the collaboration of all the physicians responsible for the regional centres. These guidelines specify the minimal diagnosis procedures leading to an optimal treatment of all patients. A low-phenylalanine diet must be started as soon as possible in the neonatal period for all newborns whose phenylalanine levels are above 10 mg/dl. The dietary control must keep the phenylalanine plasma levels between 2 and 5 mg/dl until 10 years of age. After this age, several data argue for a progressive and controlled relaxation of the diet, keeping the phenylalanine level below 15 mg/dl until the end of the adolescence and below 20 to 25 mg/dl in adulthood. All PKU patients must be followed up for life, in order to screen those who may not bear the diet relaxation and in order to strictly prevent maternal PKU deleterious consequences.

Canada's Population Health Model (POHEM): a tool for performing economic evaluations of cancer control interventions.

This paper describes the Population Health Model (POHEM) developed by Statistics Canada and shows its usefulness in the evaluation of cancer control interventions and policy decision-making. Models of the costs of diagnosis and treatment of lung and breast cancer were developed and incorporated into POHEM. Then, POHEM was used to evaluate the economic impact of chemotherapy for advanced non-small cell lung cancer; reduced length of hospital stay following breast cancer surgery; and the provision of preventive tamoxifen to women at high risk of breast cancer. A lung cancer chemotherapy treatment decision framework was developed to rank order currently available chemotherapy regimens according to relative cost-effectiveness and cost-utility. Reducing post-surgical breast cancer hospitalisation with optimal home care support could produce major healthcare savings. However, the provision of preventive tamoxifen was estimated to have no population health benefit. This paper demonstrates that POHEM is an effective tool for performing economic evaluations of cancer control interventions and to inform healthcare policy decisions.

Estimates of the lifetime costs of breast cancer treatment in Canada.

A comprehensive understanding of the cost components of common illnesses is a necessary first step towards ensuring optimal use of scarce healthcare resources. Since breast cancer is the commonest malignancy affecting Canadian women, we estimated the direct healthcare costs associated with the lifetime management of a cohort of 17700 women diagnosed in 1995. Using a multiplicity of data sources, treatment algorithms, follow-up and disease progression patterns were determined by age (<50; >/=50 years) for all four stages of breast cancer at diagnosis, as well as for the management of local and distant recurrence. Statistics Canada's Population Health Model (POHEM) was used to integrate the data from the different sources and to estimate the lifetime costs, discounted at 0, 3 and 5% rates. The average undiscounted lifetime cost per case of treating women diagnosed with breast cancer varied by stage, from $36,340 for stage IV or metastatic disease, to $23,275 for stage I patients. The total cost of treatment for the cohort diagnosed in 1995 was estimated to be over 454 million Canadian dollars. Hospitalisation (mainly for initial treatment and terminal care) represented 63% of the lifetime costs of care delivery. Disease costing models are valuable tools for optimising the use of scare resources without compromising the health status of individual patients. The breast cancer costing model has recently been used to assess the cost impact and cost-effectiveness of providing radiotherapy to all patients undergoing breast surgery, and of performing outpatient breast surgery.

Autosomal dominant Muckle-Wells syndrome associated with cystinuria, ichthyosis, and aphthosis in a four-generation family.

Muckle-Wells syndrome is a rare autosomal dominant disorder characterized by chronic recurrent urticaria, periodic arthritis, sensorineural deafness, general signs of inflammation, and secondary amyloidosis (AA type). We report on a 4-generation family with 7 persons sharing various signs of this syndrome associated with bipolar aphthosis in 5 cases and cystinuria in one. Two other relatives in the family had ichthyosis.

Rheumatoid arthritis as a bone marrow disorder.

Both the concept of rheumatoid arthritis (RA) as an autoimmune process restricted to joints and the major role of T cells in its pathogenesis have been challenged in the literature. Fibroblastlike and macrophagelike synoviocytes play an important role in RA pannus, and these cells originate in or have their counterpart in bone marrow (BM). Yet the B cell autoimmunity characteristic of RA occurs early, and synovial tissue, like BM, favors the B cell response. Because BM is abnormal in RA, and because germinal centers are unique to RA synovium, RA could be regarded as a disorder of the microenvironments able to sustain B cell response. In fact, RA could even begin in BM, with its onset facilitated by stem cell abnormalities. Moreover, most viruses suspected of playing a role in RA share a BM tropism. This may explain why RA frequently overlaps with other autoimmune disorders and benign lymphoproliferations, such as large granular T lymphocytosis. Because remissions from RA have been reported after BM transplantation, careful studies of the rheumatological outcome of RA patients undergoing such therapeutic procedures are needed. Although RA is a complex process, it can be considered initially as a stem cell disorder requiring treatment similar to that administered to transplant patients. Animal models have provided convincing evidence for these assumptions.

The nosology-taxonomy of recent-onset arthritis: the experience of early-arthritis clinics.

OBJECTIVE: To compare the conclusions of studies addressing the outcome of early-arthritis cohorts. METHODS: The methodologies of previous reports on early-arthritis cohorts were examined, and their results and conclusions were compared. RESULTS: Thirty-four reports on 23 cohorts of early arthritis were found. The methodology was poor in most studies, with numerous inclusion and exclusion biases, frequently short follow-up periods, and a lack of precision about the rationale for diagnosis. However, similar conclusions were reached on several points: a large number of cases of early arthritis remained undifferentiated and/or resolved spontaneously, about 80% of cases initially classified as undifferentiated or rheumatoid arthritis retained this diagnosis during follow-up, and the incidence of psoriatic arthritis in most studies was similar (2% to 4%). Conversely, there were striking discrepancies among studies concerning the frequency of crystal arthropathies (0% to 18%), spondyloarthropathy (1% to 33%) and rheumatoid arthritis (15% to 47%). CONCLUSIONS: There appears to be a lack of agreement among researchers about the nosology and/or taxonomy of many cases of mild arthritis, despite the existence of classification criteria. RELEVANCE: Recognition of cultural bias in the diagnosis of early arthritis could be a prerequisite for the optimization of new sets of criteria for the diagnosis of early rheumatoid arthritis and spondyloarthropathy.

Follow-up of bone mineral density in 27 cases of anorexia nervosa.

Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%, +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/- 1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0 +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4-10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.

Anti-Epstein-Barr virus-nuclear antigen-1, -2A and -2B antibodies in rheumatoid arthritis patients and their relatives.

We have examined serum antibodies to Epstein-Barr virus Nuclear Antigen (EBNA)-1, -2A and -2B, in addition to antibodies to viral capsid antigen and early antigen in 100 rheumatoid arthritis patients and 50 of their relatives. Using indirect immunofluorescence on transfected cells and Western-blot technique, we have found increased frequency and titres of antibodies to EBNA-2B in patients and, to a lesser degree, in their family members, whereas other anti-Epstein-Barr virus antibodies appeared to be similar to controls. Cross-inhibition experiments were carried out and show that antibodies to EBNA-2A are distinct from those to -2B, and vice versa.

The economics of lung cancer management in Canada.

Because lung cancer is a major health care problem in Canada, it is imperative to understand how resources are used to diagnose and treat this disease. This paper describes a method of modelling the direct patient care costs for lung cancer from the perspective of the government as payer in a universal health care system. Clinical algorithms were developed to describe the management of non-small cell (NSCLC) and small cell (SCLC) lung cancer. Patients were allocated to the treatment algorithms in the model based on a knowledge of their distribution by cell type and stage in Canadian cases. A microsimulation model developed by Statistics Canada was used to integrate the data on type of lung cancer, extent of disease, clinical management, survival and health care resource utilization. The direct care costs for diagnosis and treatment of NSCLC ranged from $Cdn 17 889 for the surgery/post-operative radiotherapy treatment of Stages I and II to $Cdn 6333 for supportive care for patients with Stage IV disease. The costs of determining relapse for NSCLC were estimated to be $Cdn 1528 and terminal care costs, made up largely of hospitalization charges and some palliative radiotherapy, were $Cdn 10 331. Direct care costs for the diagnosis and initial treatment of SCLC ranged from $Cdn 18 691 for management of limited stage disease to $Cdn 4739 for the supportive care of patients with extensive disease. The cost of determining relapse for SCLC was estimated to be $Cdn 1590 and terminal care costs averaged $Cdn 9966. For all 15 624 cases of lung cancer diagnosed in Canada in 1988, it was estimated that the total cost of providing treatment and follow-up, and managing relapse over 5 years was $Cdn 328 million. Despite the large total cost of lung cancer management, estimates of cost effectiveness of therapy showed that the cost per life year gained was approximately $Cdn 11 000 for NSCLC and $Cdn 19 560 for SCLC. These estimates of the direct health care costs assume that all patients have access to care, treatment is uncomplicated and practice is standard, and must be viewed as an idealized assessment of the cost of lung cancer management. The microsimulation model, however, does provide a useful framework for evaluating the costs of new diagnostic procedures, treatment strategies and new drugs.