• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• toxikologie

• Publikační typ
• abstrakt z konference MeSH

INTRODUCTION: Few patients with type 2 diabetes mellitus (T2DM) achieve recommended glycemic control targets in the Czech Republic. Novel therapies, such as fixed-ratio combinations of basal insulin plus glucagon-like peptide-1 receptor agonists, may contribute to better glycemic control. In the analysis presented here, the present analysis assessed the long-term cost-effectiveness of two fixed-ratio combinations, IDegLira (insulin degludec/liraglutide) and iGlarLixi (insulin glargine/lixisenatide), for the treatment of patients with T2DM inadequately controlled with basal insulin from a healthcare payer perspective in the Czech Republic. METHODS: A cost-effectiveness analysis was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Treatment effects were obtained from an indirect treatment comparison as no head-to-head data for IDegLira versus iGlarLixi are currently available. IDegLira was compared with two iGlarLixi pens (100 U/mL insulin glargine + 33 μg/mL and 50 μg/mL of lixisenatide, respectively). Direct medical costs associated with pharmaceutical interventions, screening and diabetes-related complications were captured. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: IDegLira was associated with gains in life expectancy of 0.11 years and in quality-adjusted life expectancy of 0.14 quality-adjusted life-years (QALYs) versus iGlarLixi, due to a lower cumulative incidence and delayed onset of diabetes-related complications. IDegLira was also associated with higher projected costs due to higher acquisition costs; however, these were partially offset by cost savings from avoided complications. IDegLira was associated with incremental cost-effectiveness ratios of Czech Koruna (CZK) 695,998 and CZK 348,323 per QALY gained versus iGlarLixi pens containing 33 and 50 μg/mL of lixisenatide, respectively. These ratios were below the commonly used willingness-to-pay threshold of CZK 1,200,000 per QALY gained. CONCLUSION: The present analysis indicated that IDegLira was associated with clinical benefits relative to iGlarLixi over patient lifetimes and was likely to be cost-effective in the treatment of patients with T2DM uncontrolled on basal insulin in the Czech Republic. FUNDING: Novo Nordisk. Plain language summary is available for this article.

• Publikační typ
• časopisecké články MeSH

This study aimed to investigate the impact of Achilles tendon (AT) mechanical percussion massage (PM) on the passive stiffness of that tendon and subsequent drop jump kinematics. Eleven physically active participants performed two conditions in random order: (i) 60 s of PM applied to each AT (EXP) and (ii) no PM (CTRL). Measurements were performed 5 min before, immediately after, and 5 min following the completion of the PM. In the CTRL, measurements were performed at the same time point but no massage was applied. The two-way ANOVA indicated that there was no statistically significant interaction effect on contact time (p = 0.786), reactive strength index (p = 0.914), and relative peak power (p = 0.896). However, a statistically significant interaction on peak velocity (p = 0.046) and jump height (p = 0.03) was found. Despite that, there was no significant post-hoc comparisons for jump height, it slightly decreased 5 min post-PM (p = 0.136; ES = -0.25; Δ = -3.1%) compared with the CTRL condition (p = 1.00; ES = 0.11; Δ = +1.5%). Friedman's test did not show significant differences in dominant (p = 0.073) and non-dominant limb (p = 0.091) AT stiffness. Although not significant, numerically, the dominant limb AT (p = 0.126; ES = -0.64; Δ = -7.8%) had a larger reduction in stiffness immediately post-PM compared with the non-dominant limb (p = 0.294; ES = -0.26; Δ = -3.6%). The results of this study indicated the temporary effect of PM on the reduction in tissue stiffness. Moreover, these findings show that a mechanical PM might slightly hinder subsequent explosive athletic performance.

• MeSH
• Achillova šlacha * MeSH
• biomechanika MeSH
• lidé MeSH
• perkuse MeSH
• sportovní výkon * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• karcinogeny toxicita   MeSH
• myši MeSH
• nádorová transformace buněk účinky léků   MeSH
• papilom farmakoterapie   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• spermie abnormality   MeSH
• vitamin A MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

PURPOSE: Mantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned to be performed on the cohort of the two recently completed randomized trials of the European MCL Network. PATIENTS AND METHODS: Data of 958 patients with MCL (median age, 65 years; range, 32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were pooled to assess the prognostic value of MIPI with respect to overall survival (OS) and time to treatment failure (TTF). RESULTS: Five-year OS rates in MIPI low, intermediate, and high-risk groups were 83%, 63%, and 34%, respectively. The hazard ratios for OS of intermediate versus low and high versus intermediate risk patients were 2.1 (95% CI, 1.5 to 2.9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline characteristics constituting the MIPI, age, performance status, lactate dehydrogenase level, and WBC count, were confirmed as independent prognostic factors for OS and TTF. The validity of MIPI was independent of trial cohort and treatment strategy. CONCLUSION: MIPI was prospectively validated in a large MCL patient cohort homogenously treated according to recognized standards. As reflected in current guidelines, MIPI represents a generally applicable prognostic tool to be used in research as well as in clinical routine, and it can help to develop risk-adapted treatment strategies to further improve clinical outcome in MCL.

• MeSH
• chemoradioterapie MeSH
• cisplatina aplikace a dávkování   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• cytarabin aplikace a dávkování   MeSH
• dexamethason aplikace a dávkování   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk diagnóza   patologie   terapie   MeSH
• multicentrické studie jako téma MeSH
• myší monoklonální protilátky aplikace a dávkování   MeSH
• prednison aplikace a dávkování   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• transplantace periferních kmenových buněk metody   MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. PATIENTS AND METHODS: We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. RESULTS: The crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status >=2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of >=1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood cell count at diagnosis <10.9 x 109/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem cell transplant and achievement of complete response were all associated with improved survival. CONCLUSIONS: In MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.

• MeSH
• centrální nervový systém * patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk * farmakoterapie   MeSH
• nádory centrálního nervového systému farmakoterapie   prevence a kontrola   sekundární   MeSH
• počet leukocytů MeSH
• přežití MeSH
• protinádorové antimetabolity terapeutické užití   MeSH
• retrospektivní studie MeSH
• riziko MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Evropa MeSH

PURPOSE: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS: After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION: The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.

• MeSH
• čas MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• doxorubicin aplikace a dávkování   MeSH
• indukční chemoterapie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom z plášťových buněk farmakoterapie   MeSH
• následné studie MeSH
• prednison aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• rituximab aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• udržovací chemoterapie metody   MeSH
• vidarabin aplikace a dávkování   analogy a deriváty   MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH