Antithrombin III in patients admitted to intensive care units: a multicenter observational study

INTRODUCTION: The administration of antithrombin III (ATIII) is useful in patients with congenital deficiency, but evidence for the other therapeutic indications of this drug is still uncertain. In Italy, the use of ATIII is very common in intensive care units (ICUs). For this reason we undertook an observational study to determine the pattern of use of ATIII in ICUs and to assess the outcome of patients given this treatment. METHODS: From 20 May to 20 July 2001 all consecutive patients admitted to ICUs in 20 Italian hospitals and treated with ATIII were enrolled. The following information was recorded from each patient: congenital deficiency, indication for use of ATIII, daily dose and duration of ATIII treatment, outcome of hospitalization (alive or dead). The outcome data of our observational study were compared with those reported in previously published randomized controlled trials (RCTs). RESULTS: Two hundred and sixteen patients were enrolled in the study. The clinical indications for using ATIII were sepsis (25.9%), disseminated intravascular coagulation (23.1%), and other clinical conditions (46.8%). At the end of the study, 65.3% of the patients were alive, 24.5% died and 10.2% were still in the hospital. Among the patients with sepsis (n = 56), 19 died during the observation period (33.9%; 95% confidence interval 22.1–47.5%). DISCUSSION: Our study described the pattern of use of ATIII in Italian hospitals and provided information on the outcome of the subgroup treated with sepsis. A meta-analysis of current data from RCTs, together with our findings, indicates that there is no sound basis for using this drug in ICU patients with sepsis

Quality of Life and Utility in Patients with Non-Small Cell Lung Cancer

Background: Although several studies have determined quality of life in patients with lung cancer, there is still little information about the use of generic questionnaires [e.g. the 36-item Short Form health survey (SF-36)] and utility questionnaires [e.g. the EuroQOL instrument (EQ-5D)] in this disease. Objectives: To 1. measure quality of life and utility in patients with non-small cell lung cancer (NSCLC) using the SF-36 and the EuroQOL questionnaires; 2. to evaluate the impact of some clinical variables on quality of life and utility; 3. to assess the correlation between the measurements produced by the 2 questionnaires. Study design: Cross-sectional study. Participants: 95 patients from 15 Italian hospitals with NSCLC (93% male, mean age 62 years) completed both questionnaires. Results: The mean scores for the 8 domains of the SF-36 ranged from 20.8 (physical role) to 63.0 (social functioning). The mean physical and mental summed scores of the SF-36 were 36.8 [standard deviation (SD) 9.8] and 43.0 (SD 11.5), respectively. The EuroQOL mean score was 0.58 (SD 0.32) in the self-classifier (SC) version and 0.58 (SD 0.20) in the visual analogue scale (VAS) version. Among the clinical variables that affected quality of life and utility, the presence of metastasis had the greatest impact: patients with metastasis had statistically significantly lower scores for 2 domains of the SF-36 (physical functioning, p = 0.009; bodily pain, p = 0.016), for the physical component summed score of the SF-36 (p = 0.015) and for both utility estimates (EuroQOL-SC, p = 0.027; EuroQOL-VAS, p = 0.038) than patients without metastasis. Both the SC and VAS EuroQOL scores showed a statistically significant correlation with each of the 8 domains of the SF-36. The scores for both the SF-36 and the EuroQOL in patients with NSCLC were considerably worse (relative differences ranging from -8 to -73%) than the corresponding values (normative data) previously reported for healthy individuals. Conclusions: Our study quantified the degree to which quality of life is impaired in patients with NSCLC, showed that the presence of metastasis had an important role, and indicated a strong correlation between the measurements produced by the 2 questionnaires. The EuroQOL measurements obtained from these patients will aid evaluation of the cost-utility ratio for NSCLC therapies.Antineoplastics, Non small cell lung cancer, Pharmacoeconomics, Quality of life, Radiotherapy, Surgery

2001; 07

Background and Objectives. Although several studies have determined quality of life (QOL) in patients with hemophilia, generic questionnaires have rarely been used. The objectives of our study were; 1) to measure QOL and utility in patients with hemophilia using the Short Form 36 (SF-36) and the Euro-QOL questionnaires; 2) to evaluate the influence of some clinical variables on QOL and utility; 3) to assess the correlation between the two questionnaires. Design and Methods. All consecutive patients with hemophilia were asked to complete the SF-36 and the EuroQOL questionnaires. The following information was recorded from each patient: age, type of hemophilia, severity of disease, HCV and HIV infection, number of bleeding episodes and cumulative dose of coagulation factors over the previous year. These items were entered into a multivariate analysis to assess their effect on QOL. Correlation analyses were conducted to evaluate the relationship between the EuroQOL and SF-36. Results. Fifty-six patients completed the SF-36 and the EuroQOL questionnaires. The mean scores of the SF-36 ranged from 55.2 (general health) to 74.7 (social functioning). The EuroQOLself-classifier and the EuroQOLvas showed a mean score of 0.67 (SD=0.26) and 0.66 (SD=0.17), respectively. Among the clinical variables, age significantly influenced both the EuroQOL and the SF-36 scores. The EuroQOL indices showed a statistically significant correlation with each dimension of the SF-36. Interpretation and Conclusions. Our study quantified the degree to which QOL is impaired in patients with hemophilia by using both a generic questionnaire and a utility-based approach. ©2001, Ferrata Storti Foundation Key words: hemophilia, quality of life, utility T he research on quality of life (QOL) in hemophilia is still at an early stage of advancement. We used the SF-36 and the EuroQOL questionnaires to study QOL in the hemophilia patients referred to our regional Hemophilia Center in Tuscany. Our study had three objectives: 1) to measure QOL and utility in patients with hemophilia using a generic questionnaire (SF-36) and a utility questionnaire (EuroQOL); 2) to analyze the QOL and utility scores in the framework of a multivariate analysis for determining the influence of some clinical variables on these measurements; 3) to assess the correlation between the QOL and the utility measurements produced by the two questionnaires. Design and Methods Study design and data collection We studied all consecutive patients with hemophilia who were referred to our regional Hemophilia Center in Tuscany from 1 April, 2000 to 30 June, 2000. The study had a cross-sectional design; © F e r r a t a S t o r t i F o u n d a t i o n accordingly, patients were included in the study once only (i.e. on the occasion of their first contact with our Center during the study period). The eligibility criteria for patients' enrollment were the following: a) diagnosis of either hemophilia A or hemophilia B; b) age ≥ 16 years; c) referral as an in-patient or out-patient to the units of Hematology of the Careggi Hospital or to the Regional Hemophilia Center of Careggi; d) no measurable titer of inhibitors at the last visit (determined over the previous 12 months using the Bethesda assay); e) no regular administration of factor VIII or IX for prophylaxis (defined as at least two weekly prophylactic infusions of the deficient factor over the previous six months). The ineligibility of patients with inhibitors and those receiving a regular prophylaxis [criteria (d) and (e)] had the purpose of increasing the homogeneity of our QOL measurements. When the eligibility criteria were met, the inclusion criterion was simply written consent from the patient to participate in the study. All patients enrolled in the QOL study were asked to complete the SF-36 and the EuroQOL questionnaires. For the purpose of our study, the following information was obtained from each patient: or mild depending on whether the level of the deficient factor was less than 1%, between 1% and 5%, or greater than 5%, respectively); 6. presence of HCV infection determined by two criteria: a) anti-HCV antibody assayed by EIA (assay manufactured by Roche, Italy); and b) ALT more than 2.5 higher than upper limit of normal in at least two independent samples over a period of 6 months; 7. presence of HIV infection (determined by ELISA assay, Organon, Italy); 8. number of bleeding episodes over the previous year; 9. dosage of coagulation factors over the previous year. The information of items from 3 to 9 was used as clinical variables for our statistical analysis, and their influence was assessed on the results of both the SF-36 and the EuroQOL questionnaires. Questionnaires and scoring methods The SF-36 questionnaire measures 2 main health concepts (physical and mental health) with 36 items and 8 multi-item scales called dimensions or domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health). An additional 1-item measure assesses self-evaluated change in health status. Scores are assembled using the method of summated ratings; 10,13,14 the raw scores are then transformed to a 0 to 100 scale (with 0 and 100 assigned to the lowest and highest possible value, respectively). Highest transformed scores indicate better health. Two component summary scores, one concerning the physical dimension (physical component score or PCS) and the other concerning the mental dimension (mental component score or MCS), are also calculated as a result of a weighted combination of the 8 dimensions. The EuroQOL questionnaire 11,12 consists of 5 questions and contains a visual analog scale (VAS). Two separate utility estimates are calculated, the first (EuroQOLself-classifier) from the 5 questions [which are processed through a simple computation algorithm, In our study, the two questionnaires were used in the Italian version 9,11 and were self-administered in accordance with current recommendations. Normative data To assess the influence of hemophilia on QOL, the results obtained using the SF-36 in our patients were compared with those of 2,031 Italian normal subjects (normative data) reported previously by Apolone et al. 9 Since normative data from Italian subjects are lacking for the EuroQOL, no comparison with normative information is presented for this questionnaire. Statistical analysis The parameters estimated from the two questionnaires (namely: scores for each of the 8 dimensions of SF-36, summary physical score and summary mental score of SF-36, EuroQOL utility according to the self-classifier algorithm, EuroQOL utility according to the VAS) were presented as means with standard deviation (SD) inclusive of subgroup analyses where appropriate. To determine the influence of the clinical variables on the SF-36 and the EuroQOL measurements, a multivariate regression analysis (SPSS computer program for Windows, Version 8.0, SPSS Inc., 1997) was conducted to test the statistical association between each of the SF-36 and EuroQOL parameters and the clinical variables; this analysis estimated the significance level for each variable and calculated partial correlations and regression coefficients. Categorical variables stratified on more than two levels (e.g. disease severity stratified as severe, moderate, or mild) were handled as dummy variables. A backward stepwise method of variable elimination was used, wherein the variables with p<0.10 were eventually retained; the choice of using this p=0.10 limit was made to explore not only the associations with clear-cut statistical significance (p<0.05), but also those suggested in terms of statistical trends (0.05<p<0.10). A separate analysis tested the inter-relations between the SF-36 and the EuroQOL results (using Spearman's correlation); this analysis, too, was carried out using the SPSS computer program mentioned above. Results Our study recruited a total of 67 patients at their first contact with our Center over the study period. After excluding patients with inhibitors (n=7) and patients receiving prophylaxis (n=4), a total of 56 cases were enrolled in the QOL study; none of these patients refused to participate in the study. The main characteristics of this patient cohort are summarized in The administration of the SF-36 questionnaire to these patients gave the results shown in The results obtained with the EuroQOL questionnaire were the following: EuroQOLself-classifier = 0.68 (SD=0.26, valid cases=56), EuroQOLvas = 0.66 (SD=0.17, valid cases=55). Our comparison of the SF-36 results between hemophilia patients and normal subjects ( indicates that the 4 physical domains (physical functioning, role physical, bodily pain, general health) are all consistently affected by hemophilia. Among the mental-related domains, the role emotional dimension was worsened while the other 3 were unaffected. Among the clinical variables that influenced QOL and utility (multivariate regression analysis, HIV infection negatively influenced the mental health domain of the SF-36 and both EuroQOL measurements. Subgroup means (with SD) of all QOL and utility parameters are presented in In our multivariate analysis Discussion Two studies 6,7 have thus far utilized the SF-36 and/or the EuroQOL in patients with hemophilia ( *The cut-off for retaining a variable in the analysis was set at p=0.10. °A negative correlation coefficient indicates that the clinical variable worsens the QOL or the utility parameter and vice versa. † This symbol identifies paradoxical results in that the effect of the variable on QOL was opposite to that expected. © F e r r a t a S t o r t i F o u n d a t i o n In comparison with our results, Molho et al. 6 reported higher scores in the domains of physical functioning, role physical, general health, social functioning, and role emotional. On the other hand, the results of the two summary scores of the SF-36 were very similar to ours. In the case of Miners' investigation, 7 the average scores of the SF-36 (with the exception of the domain of physical functioning) and of the EuroQOL were higher than ours Quality of life in patients with hemophilia One limitation of our analysis is that its statistical power was probably insufficient to explore the effect on QOL of disease severity (split into 3 subgroups of 32 vs 15 vs 9 patients). For example, there was a paradoxical effect for moderate disease which had some scores lower than those found for severe disease. There is plenty of data in the literature on HCV in individuals without hemophilia that suggest HCV decreases QOL. Since in our study all individuals with severe hemophilia were HCV positive, it was impossible to rule this out. Because many advanced treatments for hemophilia have become available in the last 15 years, the impaired QOL level of our older patients might reflect the negative long-term effect of inadequate treatments received in young age; however, the decline that QOL indices generally show with age in normal subjects and in a variety of disease conditions might also have contributed to this finding. HIV infection ranked second in our multivariate analysis. As shown in The strong agreement between the two utility estimates and each of the 8 domains of the SF-36 In conclusion, the section of our study based on the SF-36 substantially confirmed the results of previous investigations and provided new information on the critical issue of which variables affect QOL in hemophilia. The section of our study based on the EuroQOL provided original data in terms of utility that could be useful for future cost-effectiveness studies evaluating this disease condition. Complete information about utility is the prerequisite to translate clinical outcome and cost of hemophilia patients into a cost/utility ratio (e.g. cost per QALY gained) and to place this latter parameter in the framework of those previously calculated for other medical interventions in other disease conditions. Finally, because relevant results were obtained Potential implications for clinical practice This study sheds light on the main factors that influence quality of life in hemophilia. This information can be of benefit to clinicians in order that they interact adequately with individual patients. © F e r r a t a S t o r t i F o u n d a t i o