OBJECTIVE: To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. METHODS: A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. RESULTS: At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. CONCLUSION: Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.
- MeSH
- difuzní sklerodermie * diagnóza MeSH
- intersticiální plicní nemoci * MeSH
- kožní vředy * MeSH
- lidé MeSH
- lokalizovaná sklerodermie MeSH
- průřezové studie MeSH
- systémová sklerodermie * diagnóza epidemiologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.
- MeSH
- časové faktory MeSH
- dávka záření * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfadenektomie * škodlivé účinky mortalita MeSH
- lymfatické metastázy MeSH
- mikrometastázy MeSH
- nádory vulvy mortalita patologie terapie MeSH
- prospektivní studie MeSH
- senioři MeSH
- sentinelová uzlina patologie účinky záření chirurgie MeSH
- staging nádorů MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- webové vysílání MeSH
Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA. The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA.MATERIALS AND METHODS: Included were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL). RESULTS: Elderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43-0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12-0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL. CONCLUSION: PR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.
- MeSH
- ANCA-asociované vaskulitidy terapie MeSH
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- registrace MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- separace krevních složek metody MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS: A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 ± 5 after the first and day 365 ± 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS: The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS: In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.
- MeSH
- časové faktory MeSH
- diabetes mellitus 1. typu farmakoterapie terapie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- imunosupresiva aplikace a dávkování MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- placeba MeSH
- pooperační období MeSH
- receptory interleukinu-8A antagonisté a inhibitory MeSH
- receptory interleukinu-8B antagonisté a inhibitory MeSH
- rozvrh dávkování léků MeSH
- sekrece inzulinu účinky léků MeSH
- senioři MeSH
- sulfonamidy aplikace a dávkování škodlivé účinky farmakologie MeSH
- transplantace Langerhansových ostrůvků * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is a standard of care for adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) and high risk of relapse. However, the stratification systems vary among study groups. Inadequate response at the level of minimal residual disease is the most commonly accepted factor indicating the need for alloHSCT. In this consensus paper on behalf of the European Working Group for Adult Acute Lymphoblastic Leukemia and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize available evidence and reflect current clinical practice in major European study groups regarding both indications for HSCT and particular aspects of the procedure including the choice of donor, source of stem cells and conditioning. Finally, we propose recommendations for daily clinical practice as well as for planning of prospective trials.
- MeSH
- akutní lymfatická leukemie terapie MeSH
- indukce remise MeSH
- lidé MeSH
- příprava pacienta k transplantaci metody MeSH
- prospektivní studie MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs. METHODS: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct. RESULTS: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. CONCLUSION: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.
- MeSH
- analýza nákladů a výnosů MeSH
- analýza přežití MeSH
- antitumorózní látky ekonomika terapeutické užití MeSH
- chronická myeloidní leukemie farmakoterapie ekonomika mortalita MeSH
- dospělí MeSH
- ekonometrické modely MeSH
- generika * ekonomika terapeutické užití MeSH
- imatinib mesylát ekonomika terapeutické užití MeSH
- inhibitory proteinkinas ekonomika terapeutické užití MeSH
- kvalitativně upravené roky života MeSH
- lékařská praxe - způsoby provádění * normy trendy MeSH
- lidé středního věku MeSH
- lidé MeSH
- Markovovy řetězce MeSH
- senioři MeSH
- tyrosinkinasy antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- srovnávací studie MeSH
- Geografické názvy
- Spojené státy americké MeSH