Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Spatiotemporal analysis of drought by CHIRPS precipitation estimates

Drought is one of the most devastating natural hazards causing considerable losses in all climatic zones of the world. It is one of the most complex and the least understood hazards at the same time because of its spatially heterogeneous and temporally variable character. Spatially dense and uniformly distributed ground-based meteorological data are needed for proper spatial and temporal drought analysis. In practice, such data are lacking in general due either to the nonexistence of ground stations or their uneven and scarce distribution over a region. This creates a great potential in the use of satellite precipitation estimates (SPEs) such as the long-period high-resolution Climate Hazards Group Infrared Precipitation with Station (CHIRPS) data in drought analysis. In this study, we aim to analyze drought over the Kucuk Menderes River Basin in the western part of Turkey by using the CHIRPS data, which were found highly correlated with precipitation in the local ground stations. The analysis was performed by considering the spatial variability and temporal change in the drought characterization based on the Standardized Precipitation Index (SPI) calculated at the 3-month (seasonal) timescale. Drought in the river basin was found to have a within-year variability from month to month, and a spatial variability over the basin in any given month. Also, an over-year variability with a decreasing trend exists, which could be considered a signal for more strengthened droughts in the future. The study eventually demonstrates how the CHIRPS SPEs could be useful in the spatial and temporal drought analysis for regions with limited ground-based meteorological data

Spatiotemporal analysis of meteorological drought over Kucuk Menderes River Basin in the Aegean Region of Turkey

Eris, Ebru/0000-0003-0601-7666; CAVUS, Yonca/0000-0002-0528-284X; aksu, Hakan/0000-0003-4686-7446; Aksoy, Hafzullah/0000-0001-5807-5660; Burgan, Halil Ibrahim/0000-0001-6018-3521WOS: 000572602800001Meteorological drought is analyzed both in time and space by using drought indices based on site-specific precipitation and temperature data. Departure of precipitation from its normal called in this study as the Dimensionless Precipitation Anomaly Index (DPAI) is used at annual scale, while the Standardized Precipitation Index (SPI) using precipitation and the Standardized Precipitation Evapotranspiration Index (SPEI) using precipitation and temperature are considered at monthly time scale. Five meteorological stations over Kucuk Menderes River Basin in the western part of Turkey are selected for the case study. Results are presented in the forms of drought index time series, drought risk graphs, and drought severity maps. the prolonged severe historical dry periods of the river basin are correctly identified by the drought indices. It is seen that simple tools such as the drought indices used in this study based on easily available meteorological data could explain temporal variability at a site or spatial variability over a river basin. They are therefore important not only for the scientific community dealing with drought as a research problem but also for decision-makers, stakeholders, and end-users making practice about the drought through water allocation studies and drought management plans.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116Y425, 2219]; Research Fund of Istanbul Technical University (ITU) through the Undergraduate Contributed-Research Program, LOKAP [FLO-2019-42174]; Fulbright through the Academic Research Scholarship; Istanbul Technical University (ITU) through the International Research and Cooperation Program, UAIP [MUA-2019-42094]This study is based on findings of the project Hydrologic risks and water quality change for sustainable water management under the impact of climate change (IKLIM-RISK), Project number: 116Y425, funded by the Scientific and Technological Research Council of Turkey (TUBITAK). the study was also supported by the Research Fund of Istanbul Technical University (ITU) through the Undergraduate Contributed-Research Program, LOKAP, Project number: FLO-2019-42174. the final manuscript was written and submitted during the stay of H Aksoy at the University of Illinois, Urbana-Champaign, USA, supported by (1) Fulbright through the Academic Research Scholarship; (2) Istanbul Technical University (ITU) through the International Research and Cooperation Program, UAIP, Project number: MUA-2019-42094; and (3) the Scientific and Technological Research Council of Turkey (TUBITAK) through the 2219 Post-doctoral Research Program, all greatly appreciated

Heart-type, fatty-acid binding protein can be a diagnostic marker in acute coronary syndromes.

OBJECTIVES: Chest pain is one of the most common complaints among patients admitted to emergency departments. Cardiac troponins, CK-MB and myoglobin, which are used routinely in the diagnosis of acute coronary syndrome (ACS), are not elevated in the initial hours of ACS--precluding their usefulness in the early diagnosis. The aim of this study is to determine the efficacy of H-FABP compared to myoglobin and CK-MB in the early diagnosis of ACS. METHODS: Sixty-seven patients with ACS were enrolled in the study. An initial blood sample was obtained for CK-MB, cTnT, myoglobin and H-FABP. At the fourth, eighth, and 12th hours, repeat ECGs and cardiac enzyme samples were obtained. H-FABP test was repeated at the fourth hour. RESULTS: H-FABP has sensitivity equal to that of CK-MB and superior to that of myoglobin (97.6%, 96.7%, 85.4%, respectively) on the first hour. This trend extends to the fourth hour of myocardial injury as well. H-FABP was more specific than CK-MB, myoglobin and troponin T at the first hour (38.5%, 34.6%, 34.6%, 23.1%, respectively), whereas its specificity at the fourth hour was equal to those of CK-MB and troponin T and exceeded that of myoglobin. CONCLUSIONS: It can be suggested that in patients with an initial diagnosis of ACS and within 20 hours from symptom onset, H-FABP levels may be measured. For this purpose, point-of-care H-FABP test may be utilized, which has the advantage of bedside testing and rapid test results

Management of Brucella endocarditis: results of the Gulhane study

Brucella endocarditis (BE) is a rare but life-threatening complication of human brucellosis. The aim of this study was to investigate the course of BE along with the therapeutic interrelations. A total of 53 patients with BE hospitalised in 19 health institutions between 2006 and 2011 were included in the Gulhane study. Diagnosis of brucellosis was established by either isolation of Brucella sp. or the presence of antibodies, and the definition of endocarditis was made according to Duke's criteria. There were four treatment groups: ceftriaxone combined with oral antibiotics (Group 1); aminoglycosides combined with oral antibiotics (Group 2); oral antibiotic combinations (Group 3); and aminoglycoside plus ceftriaxone combined with an oral antibiotic (Group 4). Involvement rates of the aortic, mitral and tricuspid valves were 49.1%, 43.4% and 5.7%, respectively. Thirty-two patients (60.4%) had an underlying cardiac valvular problem, including previous prosthetic valve replacement (n = 18). Medical treatment was provided to 32 patients (60.4%), whilst concordant medical and surgical approaches were provided to 21 patients (39.6%). Mortality in Group 1 was 15% (3/20), whilst in Group 2 it was 5.3% (1/19). In Group 3, 25.0% (3/12) of the cases died, whereas none of the cases in Group 4 died. In conclusion, mortality increased 47-fold with pericardial effusion and 25-fold due to congestive heart failure that developed after BE. Although mortality was lower in the aminoglycoside-containing arm (Groups 2 and 4), statistical analysis could not be performed owing to the small number of patients. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved

Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real-world chronic hepatitis C patients cohort

WOS: 000469027000006PubMed ID: 30740820The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P<0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P=0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC. Ledipasvir and sofosbuvir with or without ribavirin is an effective and tolerable treatment in hepatitis C virus-infected patients with advanced liver disease. Eradication is associated with improvements in liver function and reduces the risk of developing a new occurrence of hepatocellular carcinoma

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Objective: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. Results: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. Interpretation: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis

Introduction: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy. Methods: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. Results: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001). Discussion: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019