A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting.

PURPOSE: Despite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV). METHODS: This multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1-4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events. RESULTS: 218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0-5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1-46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2-32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001). CONCLUSION: In patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer.

BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS: Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.

Canadian Cancer Trials Group (CCTG) IND215: A phase Ib study of Selumetinib in patients with untreated advanced or metastatic NSCLC who are receiving standard chemotherapy regimens.

Introduction Selumetinib (AZD6244, ARRY-142886) is a potent inhibitor of MEK1/2, thereby inhibiting phosphorylation of ERK2. We investigated the toxicity and the recommended phase II dose of the combination of selumetinib with two platinum based first line chemotherapy combinations in non-small cell lung cancer. Methods This was a phase I trial of escalating doses of selumetinib with carboplatin (AUC 6), paclitaxel (200 mg/m2) (cohort 1) or pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) (cohort 2) in patients with chemotherapy naïve, advanced or metastatic NSCLC. Patients enrolled on cohort 2 had non-squamous histology. Dose escalation of selumetinib proceeded using a 3 + 3 design: 50 mg b.i.d. days 2-19 (dose level 1); 75 mg b.i.d. days 2-19 (dose level 2); and 75 mg b.i.d. continuously. Adverse events were evaluated using CTC AE v4 and response by RECIST 1.1. Results Thirty-nine patients were enrolled (cohort 1 n = 16; cohort 2, n = 23). There were no dose limiting toxicities in either cohort and the recommended phase II dose for both regimens was standard doses of carboplatin, paclitaxel or pemetrexed and cisplatin with continuous selumetinib at a dose of 75 mg b.i.d. Most adverse events were grade 1 or 2 and were predominantly diarrhea, nausea, stomatitis, peripheral edema, neutropenia, and skin rash. Response rate was 37.5% for cohort 1 and 30.4% for cohort 2. Conclusion Selumetinib at a dose of 75 mg b.i.d continuously can be safely combined with paclitaxel and carboplatin or pemetrexed and cisplatin in patients with advanced or metastatic NSCLC. This trial provided the dose for the regimens used in a randomized phase II trial in NSCLC (CCTG IND.219).

Real-world patient- and caregiver-reported outcomes in advanced breast cancer.

Background: Advanced breast cancer (abc) represents a substantial burden for patients and caregivers. In the present study, we aimed to estimate quality of life (qol), utility, productivity loss, pain, health care resource utilization, and costs for patients with abc, and qol, utility, and productivity loss for their caregivers. Methods: This multicentre prospective non-interventional study was conducted in Canada. Eligible participants were postmenopausal women with estrogen receptor-positive, her2-negative unresectable abc and their caregivers. Validated questionnaires were used to measure qol, utility, productivity loss, and pain. Patients and caregivers were classified into 4 health states typically used in oncology economic modelling: first-line progression-free (1l-pf), first-line progressive disease (1l-pd), second- or subsequent-line progression-free (≥2l-pf), and second- or subsequent-line progressive disease (≥2l-pd). Results: Most patients and caregivers accepted to participate, with total recruitment of 202 patients and 78 caregivers. Compared with patients in pf, patients in pd had lower mean qol scores (52.9 ± 29.9 for 1l-pd vs. 68.2 ± 23.2 for 1l-pf, and 54.0 ± 23.6 for ≥2l-pd vs. 66.0 ± 22.1 for ≥2l-pf), lower mean utility values (0.64 ± 0.22 for 1l-pd vs. 0.73 ± 0.20 for 1l-pf, and 0.65 ± 0.25 for ≥2l-pd vs. 0.74 ± 0.18 for ≥2l-pf), and greater productivity loss (39.4 ± 27.7 for 1l-pd vs. 27.5 ± 30.1 for 1l-pf, and 37.6 ± 29.2 for ≥2l-pd vs. 32.0 ± 29.0 for ≥2l-pf). Compared with caregivers of patients in pf, caregivers of patients in pd had lower qol scores and utility values, and greater productivity loss. Conclusions: Study results indicate that, for patients and caregivers, pd health states are associated with a deterioration of qol and utility and a decrease in productivity in both 1l and ≥2l.

A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213.

BACKGROUND: Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and early clinical activity in breast cancer and synergistic cytotoxic activity with microtubule targeting agents. This multicentre, randomized, phase II trial was undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel for patients with metastatic breast cancer (mBC). METHODS: Following a safety run-in of 7 patients, 74 women with previously treated mBC were randomized either to paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 4 weeks plus pelareorep 3 × 1010 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4 weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate, overall survival (OS), circulating tumour cell counts, safety, and exploratory correlative analyses. All comparisons used a two-sided test at an alpha level of 20%. Survival analyses were adjusted for prior paclitaxel. RESULTS: Final analysis was performed after a median follow-up of 29.5 months. Pelareorep was well tolerated. Patients in Arm A had more favourable baseline prognostic variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80% CI 0.76-1.43, P = 0.87). There was no difference in response rate between arms (P = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46-0.91, P = 0.1). CONCLUSIONS: This first, phase II, randomized study of pelareorep and paclitaxel in previously treated mBC did not show a difference in PFS (the primary endpoint) or RR. However, there was a significantly longer OS for the combination. Further exploration of this regimen in mBC may be of interest.

Comparing effectiveness with efficacy: outcomes of palliative chemotherapy for non-small-cell lung cancer in routine practice.

INTRODUCTION: Randomized controlled trials (rcts) are the "gold standard" for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to □ describe outcomes of palliative platinum-doublet chemotherapy (ppdc) in non-small-cell lung cancer (nsclc) in routine practice, in terms of survival and well-being; and□ compare the effectiveness of ppdc in routine practice with its efficacy in rcts. METHODS: Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent ppdc for nsclc at Ontario's regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient's symptoms are recorded using the Edmonton Symptom Assessment System (esas). Score on the esas "well-being" item was used here as a proxy for quality of life (qol). Survival in the cohort was compared with survival in rcts, adjusting for differences in case mix. Changes in the esas score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable qol in relevant rcts. RESULTS: We identified 906 patients with pre-ppdcesas records. Median survival was 31 weeks compared with 28-48 weeks in rcts. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%-63% who had improved or stable qol in rcts. CONCLUSIONS: The effectiveness of ppdc for nsclc in routine practice in Ontario is consistent with its efficacy in rcts, both in terms of survival and improvement in well-being.

Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

BACKGROUND: This systematic review addresses the question "What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)-positive breast cancer?" METHODS: The medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched. RESULTS: Sixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47). CONCLUSIONS: Taking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.

Optimal systemic therapy for early breast cancer in women: a clinical practice guideline.

The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was "What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?" A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint. Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine therapy, and targeted therapy for her2-positive disease are reported in separate articles in this supplement. The full three-part 1-21 evidence-based series, including complete details of the development and consensus processes, can be found on the Cancer Care Ontario Web site at https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs.

Adjuvant chemotherapy for early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

BACKGROUND: The Program in Evidence-Based Care (pebc) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question "What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?" The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (her2)-directed therapy. METHODS: For the systematic review, the medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. RESULTS: Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists' Collaborative Group meta-analyses encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite-based regimens (for example, cyclophosphamide-methotrexate-5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline-taxane-based polychemotherapy regimens are, overall, considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and schedules are options; in general, paclitaxel given every 3 weeks is inferior. Evidence does not support the use of bevacizumab in the adjuvant setting; other systemic therapy agents such as metformin and vaccines remain investigatory. Adjuvant bisphosphonates for menopausal women will be discussed in later work. CONCLUSIONS: The results of this systematic review constitute a comprehensive compilation of the high-level evidence that is the basis for the 2014 pebc guideline on systemic therapy for early breast cancer. Use of cytotoxic chemotherapy is presented here; the results addressing endocrine therapy and her2-targeted treatment, and the final clinical practice recommendations, are published separately in this supplement.

Adjuvant endocrine therapy for early breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

BACKGROUND: Cancer Care Ontario's Program in Evidence-Based Care (pebc) recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question "What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?" The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and her2 (human epidermal growth factor receptor 2)-targeted therapy. METHODS: For the systematic review, the literature in the medline and embase databases was searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. RESULTS: Several hundred documents that met the inclusion criteria were retrieved. Meta-analyses from the Early Breast Cancer Trialists' Collaborative Group encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. SUMMARY: The results of the systematic review constitute a comprehensive compilation of high-level evidence, which was the basis for the 2014 pebc guideline on systemic therapy for early breast cancer. The review of the evidence for systemic endocrine therapy (adjuvant tamoxifen, aromatase inhibitors, and ovarian ablation and suppression) is presented here; the evidence for chemotherapy and her2-targeted treatment-and the final clinical practice recommendations-are presented separately in this supplement.

Real-world impact of granulocyte-colony stimulating factor on febrile neutropenia.

BACKGROUND: Primary prophylaxis with granulocyte colony-stimulating factors (pp-g-csf) is recommended in patients undergoing chemotherapy carrying a febrile neutropenia (fn) risk of 20% or more. In the present study, we examined clinical practice patterns and the impact of pp-g-csf on fn incidence in women with early-stage breast cancer (ebc) treated with modern adjuvant chemotherapy (act). METHODS: This single-centre retrospective cohort study of women with ebc, who were identified from the pharmacy database and who received at least 1 cycle of modern act from January 2009 to December 2011, was conducted at the Cancer Centre of Southeastern Ontario. Data on patient demographics, pathology, stage distribution, chemotherapy, pp-g-csf use, dose reductions, chemotherapy delays, treatment discontinuation, relative dose intensity, and fn events were collected. Chi-square tests, t-tests, univariate and multivariate logistic regression analyses, and nonparametric Mann-Whitney U-tests were used for data analysis. RESULTS: Of the 239 women eligible for analysis, 145 (61%) received pp-g-csf, and 50 (21%) developed at least 1 episode of fn. Use of pp-g-csf was associated with a significantly lower rate of fn (14% vs. 31%, p = 0.002) and trends to fewer dose delays (17% vs. 27%, p = 0.060) and dose reductions (19% vs. 25%, p = 0.28). Among women receiving pp-g-csf, higher fn rates were associated with an age of 65 years or older, taxane-based chemotherapy, and prophylaxis with filgrastim. CONCLUSIONS: Clinical practice patterns at our institution showed that more than 50% of ebc patients treated with modern act received pp-g-csf, which led to fewer fn episodes and increased delivery of planned act. The observed high fn risk despite pp-g-csf was linked to older age, taxane-based chemotherapy, and filgrastim.

[Deficits in lipid lowering therapy and achieving target lipid concentrations in patients with high risk of a cardiovascular event]. / Rezervy v hypolipidemické terapii a dosazení cílových koncentrací lipidu u pacientu s vysokým rizikem kardiovaskulárních príhod.

Lipid concentrations were analysed in 529 consecutive patients, 190 females (34%) and 339 males (66%) with mean age 66 years, at high cardiovascular risk, undergoing elective coronary angiography between 1st January and 31st May 2010. LDL-cholesterol level < 2,5 mmol/l was identified only in 36% of patients in primary prevention, LDL-cholesterol level < 2,0 mmol/l was identified only in 28% of subjects in secondary prevention of cardiovascular events. The study proves inadequate control of dyslipidaemia in patients at high cardiovascular risk.

Giant cell arteritis: intensity of the initial systemic inflammatory response and the course of the disease.

OBJECTIVE: Giant cell arteritis (GCA) has a variable course. We assessed whether intensity of initial systemic inflammatory response (ISIR) can predict the course of GCA. METHODS: Charts of 130 GCA patients were reviewed. ISIR intensity at presentation was determined by 5 parameters of inflammation: sedimentation rate >100 mm/h, thrombocytosis >400,000/microl, hemoglobin <11 g/dl, leukocytosis >11000/microl, and fever >37.5 degrees C. Patients were divided into 3 groups according to ISIR intensity: strong (4-5 parameters present, n=24), moderate (2-3 parameters, n=55) and weak ISIR (0-1 parameter, n=51). RESULTS: There were no significant differences between these groups regarding mean age, female:male ratio and the initial prednisone dose. At 1 year, 75% of patients in the strong ISIR group required >5 mg/d of prednisone, compared to 54% and 37% of patients with moderate or weak ISIR, respectively (p=0.015). Disease flares were more common in patients with strong ISIR during a 3-year period, compared to patients with moderate or weak ISIR (77%, 67% and 43%, respectively, p=0.013). Only 33% of patients with strong ISIR were able to discontinue steroids after 3 years, compared to 49% and 77% of patients with moderate and weak ISIR, respectively (p=0.003). CONCLUSION: GCA Patients with strong ISIR have prolonged disease course with more flares, requiring higher steroid doses. ISIR intensity should be taken into consideration when planning studies evaluating potential steroid-sparing agents, as response to treatment may vary in patients with different ISIR intensities.

[Management of autoimmune thrombocytopenic purpura: a prospective study of 147 children from the regional network RHémaP]. / Purpura thrombocytopénique auto-immun: à propos d'une cohorte prospective de 147 enfants pris en charge dans le réseau d'hématologie pédiatrique des régions PACA et Corse (RHémaP).

AIM: Assessment of the impact of guidelines from a regional pediatric network to standardize the management of childhood immune thrombocytopenic purpura (ITP). MATERIALS AND METHODS: Consensus guidelines were drawn up in centers of the pediatric network for hematological diseases, RHémaP, and a cohort of children referred for ITP in these centers was set up. A 1-year follow-up was recorded for each patient over a 43-month period. RESULTS: We report data from a cohort of 147 children. At diagnosis, we recorded severe thrombocytopenia (median=8G/l) and 141 children had hemorrhagic symptoms (96%). Only 23 children had a bone marrow aspiration (BMA) at diagnosis (16.3%), which meant a high level of implementation of the RHémaP recommendations (96%) since indications of BMA were limited to rare indications. For 135 children (91.8%), treatment fulfilled the RHémaP guidelines that were mainly based on the platelet count: 121 received intraveinous immunoglobulin (IVIG) and 14 were not treated. Among those who received IVIG, 110 were good responders (91%) at the 96-h evaluation (platelet count greater than 20G/l), nine (7.4%) were poor responders, and 1 died of intracranial hemorrhage. At 6 months, chronic ITP was observed in 40 children (32.8%). Chronic ITP was associated with a higher platelet count at diagnosis and an older age (p<10(-3) and p=10(-3), respectively). CONCLUSION: The practices recorded over a 43-month period in our cohort fulfilled the RhémaP guidelines and we conclude that we managed to standardize regional practices for children with ITP. We observed conventional epidemiological characteristics in this cohort. Older children and higher platelet count at diagnosis were significantly associated with higher frequency of chronic ITP.

The incidence of giant cell arteritis in Jerusalem over a 25-year period: annual and seasonal fluctuations.

OBJECTIVE: Giant-cell arteritis (GCA) incidence is reported to be rising. A cyclic pattern of annual incidence rates and seasonal variations were reported by several groups. However, such fluctuations were not observed by others. We examined both annual and seasonal rates of GCA over a period of 25 years in Jerusalem. METHODS: Charts of all patients diagnosed as GCA between 1980-2004 were reviewed. In 170 cases GCA was biopsy-proven. Thirty-six additional cases were included as they met the American College of Rheumatology GCA classification criteria. Data on the Jerusalem population throughout the study period was collected from the annual publications of the Israel Bureau of Statistics. Age- and sex-specific incidence rates per 100000 population aged>or=50 were calculated. RESULTS: For the whole period, the average age-adjusted incidence rate was 11.3 per 100000, and 9.5 for the biopsy-positive cases. The female: male ratio was 1.4:1. Cyclic fluctuations of GCA incidence with 3 distinctive peaks, 8-10 years apart, were observed. Altogether, there was no apparent increase in GCA incidence during this period. Seasonal variations were observed: in 192 patients we were able to estimate the time of onset of GCA symptoms. It showed a peak in the months of May and June, with the number of patients being twice as expected for this period (p<0.001). CONCLUSION: GCA onset was more common in late spring and early summer, and fluctuations in GCA annual incidence with 3 distinctive peaks were observed during a 25-year period. These suggest infectious or other environmental etiology, however thus far no such agents were proven.

Perceived efficacy among patients of various methods of complementary alternative medicine for rheumatologic diseases.

OBJECTIVE: The purpose of this cross-sectional survey was to obtain and analyze data on self-perceived efficacy of different types of complementary alternative medicine (CAM) by patients with various rheumatologic conditions. METHODS: Patients followed in rheumatology outpatient clinics were screened for the use of CAM. Patients reporting the use of CAM were asked to participate in face-to-face structured interviews, specifying the various CAM types they used, and grading their subjective impression of efficacy of each CAM type on a scale of 1-10. RESULTS: 350 consecutive patients were screened and 148 reported using CAM. In general, homeopathy and acupuncture were the most commonly used CAM types (44% and 41% of the CAM users, respectively). The mean number of different CAM methods used by a CAM user was 1.9 +/- 1.1. Patients with fibromyalgia used significantly more CAM methods (2.7 +/- 1.4, p = 0.005). On patients' self-perceived efficacy scale of 1-10, the mean score of the whole group was 5.3 +/- 3.2. Acupuncture and homeopathy achieved significantly higher self-perceived efficacy scores in CAM users with spondylo-arthropathies and osteoarthritis, respectively, when compared to some of the other disease groups. Satisfaction was lowest among CAM users with rheumatoid arthritis, vasculitis and connective tissue diseases. CONCLUSION: In general, CAM users were less than moderately satisfied with self-perceived-efficacy of CAM therapies. However efficacy of specific CAM methods differed significantly among patients in different disease groups.

[Cystic intrathoracic hemolymphangioma: a rare differential diagnosis of acute bronchiolitis in an infant]. / Hémolymphangiome kystique intrathoracique: un diagnostic différentiel rare de bronchiolite aiguë chez un nourrisson.

Hemolymphangioma is a benign malformation of the lymphatic vessels. Cervical localisation is the most frequent. Mediastinal localisation is rare, but may be life-threatening because of airway compression. We report on a four-month-old boy who presented, in a context of epidemics, with clinical signs of acute bronchiolitis requiring mechanical ventilation for several days. Chest X-rays showed an important mediastinal mass with airways compression. Diagnosis was evoked on CT-scan aspects and confirmed by histology. Surgery allowed complete resolution, but dysphonia and oropharyngeal disorders persisted for several months. This rare congenital malformation is reviewed.

[Deferral of coronary intervention based on measurement of myocardial fractional flow reserve]. / Osud nemocných po odlození koronární intervence na základe merení frakcní prutokové rezervy myokardu.

BACKGROUND: Myocardial fractional flow reserve (FFR) is a useful method in assessment of functional significance of coronary stenosis. Deferral of intervention of angiographically intermediate lesion based on FFR measurement is safe in selected patient population as previously described. The aim of the study was to assess mid-term results after deferring coronary intervention of intermediate lesion in a non-selected patient population with no respect to the extent of coronary artery disease and to the results of stress tests if performed. METHODS: A coronary intervention of angiographically intermediate lesion (40 - 70% according to QCA) was deferred in a group of 50 consecutive patients (33 men, mean age 60.8 +/- 10.2 y.) on the basis of FFR > or = 0.75 (mean FFR 0.89 +/- 0.06). FFR was measured in 62 lesions (mean stenosis diameter 55 +/- 7%, left anterior descending 34 lesions, circumflex artery 13 lesions, right coronary artery 15 lesions). One-vessel disease was presented in 14 pts (28%), 36 pts (72%) presented with multivessel disease (two-vessel disease in 27 pts - 54% and three-vessel disease in 9 pts - 18%). Stress test was positive in 15 pts, in 1 pts. negative, and in 3 pts. non-diagnostic. All-cause mortality, cardiac mortality, non-fatal myocardial infarction (MI) and ischemia driven target vessel revascularization (TLR) were recorded during follow-up. Severity of angina pectoris (CCS classification) and a need for antianginal treatment (beta-blockers, nitrates, calcium channel blockers) at the baseline and at the end of clinical follow-up was recorded. RESULTS: Follow-up was completed in 49 patients (98%). Mean time of follow-up is 15.4 +/- 2 months (range 12 - 22 months, median 15 months), two patients died (4 %)--one from colon cancer, the other patient died from lung cancer, there was not any cardiac death recorded, two patients (4%) had target vessel revascularization. Estimated 22 months event-free (all-cause death, MI, TLR) survival was (mean +/- SEM) 86 +/- 7%. There was a significant difference in symptom severity--mean grade of angina pectoris at baseline was 1.8 +/- 1.3, at follow-up 1.1 +/- 1.0 (p < 0.05). There was not difference in use of antianginal drugs was same at baseline and at follow-up (1.7 +/- 0.8 vs. 1.7 +/- 0.7). Thirty-five patients (71%) were treated by statins. CONCLUSIONS: Deferring of coronary interventions of intermediate stenosis based on FFR measurement is safe in a mid-term follow-up. Despite of the same intensity of antianginal treatment there was a significant decrease in symptom severity.

[Assessment of speed of an anti-platelet effect after two different doses of acetylsalicylic acid by flocculation]. / Stanovení rychlosti nástupu úcinku protidestickového vlivu dvou ruzných dávek kyseliny acetylsalicylové agregometrickou metodou.

UNLABELLED: Acetylsalicylic acid inhibits aggregation of blood platelets through affecting arachidon acid metabolism--a precursor of thromboxan which is a strong platelet aggregation inhibitor. A standard method for measurement of aggregation activity blockade (in percents) of platelet rich plasma is turbidimetric aggregomethry based on spectrophotometric principle. According to results of recent studies administration of acetylsalicylic acid is one of the basic pillars of prevention of thrombotic complications in atherosclerotic arterial disease. Acetylsalicylic acid doses differ from study to study. An aim of our work was to measure speed of two different doses of acetylsalicylic acid. RESULTS: Level of aggregation activity blockade in samples of platelet rich plasma was measured by aggregometry in 26 healthy volunteers after administration of four inductors of thrombocyte aggregation (arachidon acid, adenosindiphosphate, collagen, and ristocetin). The samples were taken before administration and 120, 240, and 360 minutes after single peroral administration of 100 or 400 mg of acetylsalicylic acid. Samples of plasma were analysed immediately after sampling. Before drug administration there was no aggregation activity in 27.7% of the sample after arachidon acid administration, 28.3% after ADP administration, 21.5% after collagen administration and 25.3% after ristocetin administration. After administration of 400 mg of acetylsalicylic acid and administration of arachidon acid as an inductor 89.9% of the aggregation activity of the sample was blocked after 120 minutes, 89.6% after 240 minutes, and 90.6% after 360 minutes. After administration of adenosindiphosphate as an inductor 71.7% of the aggregation activity of the sample was blocked after 120 minutes, 68.3% after 240 minutes, and 69.9% after 360 minutes. And, after administration of ristocetin as an inductor 64% of the aggregation activity of the sample was blocked after 120 minutes, 66.4% after 240 minutes, and 54% after 360 minutes. Blockade of aggregation activity after collagen administration was not statistically significant. After administration of 100 mg of acetylsalicylic acid and administration of arachidon acid 83.8% of the aggregation activity of the sample was blocked after 120 minutes, 89.2% after 240 minutes, and 89.6% after 360 minutes. After adenosindiphosphate administration statistically significant blockade of aggregation activity was achieved after 360 minutes in the 56.7% of the sample. Also after collagen administration 42.5% of aggregation activity of the sample was blocked significantly after 360 minutes while ristocetin has not proved to influence aggregation in a statistically significant manner. CONCLUSION: Both doses of acetylsalicylic acid influenced aggregation activity of platelets in a statistically significant manner as soon as after 120 minutes following their peroral administration. However, they had different ability to influence platelets response to alternative ways of activation--by adenosindiphosphate, collagen, and ristocetin. 400 mg dose blocked these ways while 100 mg dose was efficient in blocking these ways after 360 minutes and in case of ristocetin--an inductor used to monitor platelet adhesion ability--100 mg dose has not led to statistically significant blockade at all.

The interleukin-6 promoter polymorphism in Gaucher disease: a new modifier gene?

BACKGROUND: Individuals with Gaucher disease vary significantly with regard to degree of bone disease, but there are no predictive markers for severity of skeletal involvement. AIM: To determine the frequency of polymorphisms of interleukin-6 (IL-6) among patients with Gaucher disease, and the relationship to bone mineral density (BMD) and other markers of disease severity. DESIGN: Case-control study. METHODS: Genotyping for the 174G --> C promoter polymorphism of IL-6 was performed in adult patients with Gaucher disease for whom there was concurrent bone mineral density (BMD) data and in healthy Ashkenazi Jewish controls. RESULTS: The prevalence of allelic variants (58% G/G, 36% G/C, and 6% C/C) was similar in Ashkenazi Jewish adults with Gaucher disease as in Ashkenazi Jewish controls, but significantly different (p < 0.05) from that reported among Caucasians. No statistically significant correlation was found between IL-6 genotypes and BMD or markers of severity of Gaucher disease. Patients with the C/C genotype had relatively mild Gaucher disease. DISCUSSION: The IL-6 polymorphisms appear to be distributed differently in Ashkenazi Jews than among other Caucasians. In Gaucher disease, the C/C genotype may be associated with a milder Gaucher phenotype, and may serve as a mitigating genetic modifier.