Kawasaki disease: guidelines of the Italian Society of Pediatrics, part I - definition, epidemiology, etiopathogenesis, clinical expression and management of the acute phase.

The primary purpose of these practical guidelines related to Kawasaki disease (KD) is to contribute to prompt diagnosis and appropriate treatment on the basis of different specialists' contributions in the field. A set of 40 recommendations is provided, divided in two parts: the first describes the definition of KD, its epidemiology, etiopathogenetic hints, presentation, clinical course and general management, including treatment of the acute phase, through specific 23 recommendations.Their application is aimed at improving the rate of treatment with intravenous immunoglobulin and the overall potential development of coronary artery abnormalities in KD. Guidelines, however, should not be considered a norm that limits treatment options of pediatricians and practitioners, as treatment modalities other than those recommended may be required as a result of peculiar medical circumstances, patient's condition, and disease severity or complications.

Correction to: The Italian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The family name of author Francesco La Torre was incorrect in the published article. The correct family name should read as La Torre F.

The Italian version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Italian language.The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents.The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity).A total of 1296 JIA patients (7.2% systemic, 59.5% oligoarticular, 21.4% RF negative polyarthritis, 11.9% other categories) and 100 healthy children, were enrolled in 18 centres. The JAMAR components discriminated well healthy subjects from JIA patients except for the Health Related Quality of Life (HRQoL) Psychosocial Health (PsH) subscales. All JAMAR components revealed good psychometric performances.In conclusion, the Italian version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Development of a Low-Cost Stem-Loop Real-Time Quantification PCR Technique for EBV miRNA Expression Analysis.

MicroRNAs (miRNAs) are short, single stranded, non-coding RNA molecules. They are produced by many different species and are key regulators of several physiological processes. miRNAs are also encoded by the genomes of multiple virus families, such as herpesvirus family. In particular, miRNAs from Epstein Barr virus were found at high concentrations in different associated pathologies, such as Burkitt's lymphoma, Hodgkin disease, and nasopharyngeal carcinoma. Thanks to their stability, these molecules could possibly serve as biomarkers for EBV-associated diseases. In this study, a stem-loop real-time PCR for miR-BART2-5p, miR-BART15, and miR-BART22 EBV miRNAs detection and quantification has been developed. Evaluation of these miRNAs in 31 serum samples (12 from patients affected by primary immunodeficiency, 9 from X-linked agammaglobulinemia and 10 from healthy subjects) has been carried out. The amplification performance showed a wide dynamic range (10(8)-10(2) copies/reaction) and sensibility equal to 10(2) copies/reaction for all the target tested. Serum samples analysis, on the other hand, showed a statistical significant higher level of miR-BART22 in primary immunodeficiency patients (P = 0.0001) compared to other groups and targets. The results confirmed the potential use of this assay as a tool for monitoring EBV-associated disease and for miRNAs expression profile analysis.

Treatment quality and outcomes of African American versus white breast cancer patients: retrospective analysis of Southwest Oncology studies S8814/S8897.

PURPOSE: Women of African ancestry (AA) have lower WBC counts and are more likely to have treatment delays and discontinue adjuvant breast cancer therapy early compared with white women. We assessed the association between race and treatment discontinuation/delay, WBC counts, and survival in women enrolled onto breast cancer clinical trials. PATIENTS AND METHODS: AA and white women from Southwest Oncology Group adjuvant breast cancer trials (S8814/S8897) were matched by age and protocol. Only the treatment arms in which patients were scheduled to receive six cycles of chemotherapy were analyzed. RESULTS: A total of 317 pairs of patients (n = 634) were analyzed. At baseline, AA women had higher body-surface area (P < .0001) and lower WBC (P = .0009). AA women were more likely to have tumors that were > or = 2 cm (P = .01) and hormone receptor negative (P < .0001). AA women, versus white women, were marginally more likely to discontinue treatment early (11% v 7%, respectively; P = .07) or have one or more treatment delays (85% v 79%, respectively; P = .07) and were significantly more likely to experience the combined end point (discontinuation/delay; 87% v 81%, respectively; P = .04). The mean relative dose-intensity (RDI) was similar for both groups (87% in AA women v 86% in white women); however, overall, 43% had an RDI of less than 85%. After adjusting for baseline WBC and prognostic factors in a multivariate model, AA women had worse disease-free survival (hazard ratio [HR] = 1.56; 95% CI, 1.15 to 2.11; P = .005) and overall survival (HR = 1.95; 95% CI, 1.36 to 2.78; P = .0002). The inclusion of RDI and treatment delivery/quality in the regression had little impact on the results. CONCLUSION: On cooperative group breast cancer trials, AA and white women had similar RDIs, but AA women were more likely to experience early discontinuation or treatment delay. Despite correcting for these factors and known predictors of outcome, AA women still had worse survival.

Impact of the year 2000 Medicare policy change on older patient enrollment to cancer clinical trials.

PURPOSE: A prior analysis by the Southwest Oncology Group (SWOG) showed that women and African American patients were adequately represented on cancer clinical treatment trials but that older patients were substantially underrepresented. Twenty-five percent of patients > or = 65 years old were enrolled onto SWOG trials from 1993 to 1996, whereas 63% of all patients with cancer were > or = 65 years old. Recognition of this under-representation led to a change in Medicare policy in 2000 to include coverage of routine patient care costs of clinical trials. We conducted an updated analysis of accrual trends. METHODS: The proportions of enrollment onto SWOG treatment trials by sex, race/ethnicity, and age (> or = 65 years) were computed for the years 1997 to 2000; corresponding rates in the United States were derived from US Census and National Cancer Institute Surveillance, Epidemiology, and End results data. Additionally, method of payment data were analyzed over time (1993 to 2003) to assess whether patterns in method of payment changed with the new Year 2000 Medicare policy on clinical trials coverage. RESULTS: The results showed continued adequate representation by sex and race/ethnicity. Older patient accrual on SWOG trials increased significantly since 2000, with 31% of patients > or = 65 years old enrolled from 1997 to 2000 and 38% enrolled from 2001 to 2003 (v 25% from 1993 to 1996). The percentage of patients using Medicare plus supplemental insurance also increased beginning in 2000, whereas the percentage of patients using Medicare alone remained the same. CONCLUSION: Method of payment analyses provided evidence that the Year 2000 Medicare policy change had a positive impact, but only for those patients with supplemental private coverage of coinsurance costs. Improvements in the Medicare payment structure could further increase older patient participation in clinical trials.

Safety assessment of raloxifene over eight years in a clinical trial setting.

OBJECTIVE: Osteoporosis is a chronic disorder that warrants long-term therapy. If benefits are to outweigh risks, the long-term safety profiles of these therapies must be favorable. The aim of this study was to assess the safety of raloxifene over 8 years in 4011 postmenopausal women with osteoporosis in a clinical trial setting through adverse event reporting. METHODS: Data analyzed comprised all reported adverse events collected at each visit of both the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, and the subsequent Continuing Outcomes Relevant to Evista (CORE) trial. MORE was an international, 4-year double-blind, randomized, placebo-controlled study, designed to assess the effect of raloxifene on bone mineral density and vertebral fracture incidence in 7705 (placebo, 2576; raloxifene, 5129) postmenopausal women with osteoporosis. Breast cancer was a secondary endpoint. Based on the breast cancer findings of MORE, the CORE trial, a 4-year double-blind, placebo-controlled trial of a subset of MORE participants, was subsequently conducted. CORE enrolled 4011 (placebo, 1286; raloxifene, 2725) participants and was designed to examine raloxifene's effect on breast cancer incidence. Safety analyses were performed using the intention-to-treat principle, and comparison between therapies was analyzed using a two-sided Fisher's exact test. RESULTS: Over the 8 years of follow-up of 4011 women, there was no difference in all-cause mortality or hospitalization incidence between raloxifene and placebo groups (p > 0.1). Excluding breast cancer and non-melanoma skin cancer, cancer incidence was 4.6% and 6.3% in the raloxifene and placebo group, respectively (p = 0.027). Raloxifene was associated with a 1.7-fold increase in venous thromboembolism incidence (95% confidence interval 0.93-3.14), with an absolute risk difference of 0.9 per 1000 woman-years. There was no difference in the incidence of myocardial infarction, stroke, uterine cancer, endometrial hyperplasia, ovarian cancer or postmenopausal bleeding between the raloxifene and placebo treatment groups (p > 0.5). Uterine polyps, hot flushes and muscle cramps were more common in those receiving raloxifene versus placebo (p = 0.028, p < 0.001, and p = 0.008, respectively). CONCLUSION: These 8-year data support the known clinical safety profile of raloxifene, established in the MORE trial.

Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women.

PURPOSE: To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial. METHODS: Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL. RESULTS: Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001). CONCLUSION: Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.