Current Issue : July - September Volume : 2017 Issue Number : 3 Articles : 6 Articles
Background: Cerebellar ataxia (CA) is a frequent and often disabling condition that impairs motor functioning and impacts\non quality of life (QoL). No medication has yet been proven effective for the symptomatic or even causative treatment of\nhereditary or non-hereditary, non-acquired CA. So far, the only treatment recommendation is physiotherapy. Therefore, new\ntherapeutic options are needed. Based on three observational studies, the primary objective of the acetyl-DL-leucine on\nataxia (ALCAT) trial is to examine the efficacy and tolerability of a symptomatic therapy with acetyl-DL-leucine compared to\nplacebo on motor function measured by the Scale for the Assessment and Rating of Ataxia (SARA) in patients with CA.\nMethods/Design: An investigator-initiated, multicenter, European, randomized, double-blind, placebo-controlled, 2-\ntreatment 2-period crossover phase III trial will be carried out. In total, 108 adult patients who meet the clinical criteria\nof CA of different etiologies (hereditary or non-hereditary, non-acquired) presenting with a SARA total score of at least 3\npoints will be randomly assigned in a 1:1 ratio to one of two different treatment sequences, either acetyl-DL-leucine (up\nto 5 g per day) followed by placebo or vice versa. Each sequence consists of two 6-week treatment periods, separated by\na 4-week wash-out period. A follow-up examination is scheduled 4 weeks after the end of treatment. The primary efficacy\noutcome is the absolute change in the SARA total score. Secondary objectives are to demonstrate that acetyl-DL-leucine\nis effective in improving (1) motor function measured by the Spinocerebellar Ataxia Functional Index (SCAFI) and SARA\nsubscore items and (2) QoL (EuroQoL 5 dimensions and 5 level version, EQ-5D-5 L), depression (Beck Depression Inventory,\nBDI-II) and fatigue (Fatigue Severity Score, FSS). Furthermore, the incidence of adverse events will be investigated.\nDiscussion: The results of this trial will inform whether symptomatic treatment with the modified amino-acid acetyl-DLleucine\nis a worthy candidate for a new drug therapy to relieve ataxia symptoms and to improve patient care. If superiority\nof the experimental drug to placebo can be established it will also be re-purposing of an agent that has been previously\nused for the symptomatic treatment of dizziness....
Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia\nonset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue\nperfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research\nof pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from\nrestoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has\nbecome a promising approach, especially in animal research.The purpose of this article is to review completed and ongoing phases\nI and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and\nantineuroinflammatory drugs that may translate into more effective treatments....
Background: The clinical effect of bisphosphonate treatment has not been clearly evaluated by kidney function in\nJapanese Chronic Kidney Disease (CKD) patients with osteoporosis. This study analyzed the data from three risedronate\nJapanese phase III trials. The clinical effect of risedronate therapy was evaluated in CKD patients with osteoporosis.\nMethods: The Japanese clinical trials involved 852 subjects who received risedronate (2.5 mg once daily or 17.5 mg\nonce weekly) and whose estimated glomerular filtration rate (eGFR) were calculable and at � 30 mL/min. The subjects\nwere divided into subgroups according to the eGFR level: � 90 mL/min/1.73 m2, � 60 to < 90 mL/min/1.73 m2, � 30\nto < 60 mL/min/1.73 m2. Lumbar spine bone mineral density (BMD), bone turnover markers (BTMs) and adverse events\nwere evaluated at 48 weeks.\nResults: Adverse event incidence was similar among three subgroups. There was also no exacerbation of impaired\nkidney function associated with risedronate administration in the subjects with eGFR above 30 mL/min/1.73 m2.\nRisedronate administration induced a significant increase in lumbar spine BMD and significant inhibition of BTMs in\nthree subgroups.\nConclusions: The risedronate therapy showed similar clinical effects in CKD patients with osteoporosis compared to\nthose without CKD....
Background: To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR)\ninhibitor, in metastatic colorectal cancer (mCRC) patients.\nMethods: A phase Ib open-label study and phase II randomized, placebo-controlled trial compared the efficacy of\nfruquintinib plus best supportive care (BSC) with placebo plus BSC in mCRC patients with ââ?°Â¥2 lines of prior therapies.\nThe primary endpoint was progression-free survival (PFS).\nResults: In the phase Ib study, 42 patients took fruquintinib 5 mg for 3 weeks on/1 week off. The median PFS was 5.\n80 months, and the median overall survival (OS) was 8.88 months. In the phase II study, 71 patients were randomized\n(47 to fruquintinib, 24 to placebo). PFS was significantly improved with fruquintinib plus BSC (4.73 months; 95%\nconfidence interval [CI] 2.86ââ?¬â??5.59) versus placebo plus BSC (0.99 months; 95% CI 0.95ââ?¬â??1.58); (hazard ratio [HR] 0.30; 95%\nCI 0.15ââ?¬â??0.59; P < 0.001). The median OS was 7.72 versus 5.52 months (HR 0.71; 95% CI 0.38ââ?¬â??1.34). The most common\ngrade 3ââ?¬â??4 adverse events were hypertension and hand-foot skin reaction.\nConclusions: Fruquintinib showed a significant PFS benefit of 3.7 months in patients with treatment-refractory mCRC.\nThe safety profile was consistent with that of VEGFR tyrosine kinase inhibitors. A randomized phase III confirmatory\nstudy in mCRC is underway....
Background: Due to improvements in imaging and radiological techniques as well as the use of chemotherapy,\ndistant metastasis has become the predominant mode of treatment failure in patients with locally advanced\nnasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is\nnow the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum\nreagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal,\nhepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a\nfirst-line regimen in patients with LA-NPC are undetermined.\nMethods: Patients with stage IIIââ?¬â??IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined\nwith a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a\ndose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response\nrates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis\nwas used to calculate survival rates.\nResults: Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy.\nThe objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction\nchemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of\n44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8)\nand 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3ââ?¬â??4 toxicities were neutropenia (8.5%)\nand thrombocytopenia (40.7%) after ICT and CRT, respectively.\nConclusion: Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging\nanti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in\npatients with LA-NPC are warranted....
Background: Use of a reliable contraception method has become an inclusion criterion in prevention trials to\nminimize time off product. We report on hormonal contraceptive prevalence, uptake, sustained use and correlates\nof use in the Microbicides Development Programme (MDP 301) trial at the Masaka Centre in Uganda.\nMethods: HIV negative women in sero-discordant relationships were enrolled and followed-up for 52 to 104 weeks\nfrom 2005 to 2009. Contraceptive use data was collected through self-report at baseline and dispensing records\nduring follow-up. Hormonal contraceptives were promoted and provided to women that were not using a reliable\nmethod at enrolment. Baseline contraceptive prevalence, uptake and sustained use were calculated. Uptake was\ndefined as a participant who reported not using a reliable method at enrolment and started using a hormonal\nmethod at any time after. Logistic regression models were fitted to investigate predictors of hormonal\ncontraceptive uptake.\nResults: A total of 840 women were enrolled of whom 21 aged ââ?°Â¥50 years and 12 without follow-up data were\nexcluded; leaving 807 (median age 31 IQR 26ââ?¬â??38) in this analysis. At baseline, 228 (28%) reported using a reliable\ncontraceptive; 197 hormonal, 28 female-sterilisation, two IUCD and one hysterectomy. As such 579 were not using\na reliable contraceptive at enrolment, of whom 296 (51%) subsequently started using a hormonal contraceptive\nmethod; 253 DMPA, four oral pills, and two norplant. Overall 193 (98%) existing users and 262 (88%) new users\nsustained use throughout follow-up. Independent correlates of hormonal contraceptive uptake were: younger\nwomen ââ?°Â¤30 years, aOR = 2.5, 95% CI: 1.7ââ?¬â??3.6 and reporting not using contraceptives at baseline due to lack of\naccess or money, breastfeeding or other reasons, in comparison to women who reported using unreliable method.\nConclusion: Promotion and provision of hormonal contraception doubled the proportion of women using a\nreliable method of contraception. Uptake was pronounced among younger women and those not previously using\na reliable method because of lack of access or money, and breastfeeding. Promotion and provision of hormonal\ncontraceptives in trials that require the interruption or discontinuation of investigational products during pregnancy\nis important to reduce the time off product....
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