Matching-adjusted indirect comparison of bleeding outcomes in severe haemophilia A: Comparing valoctocogene roxaparvovec gene therapy, emicizumab prophylaxis, and FVIII replacement prophylaxis

INTRODUCTION: Head-to-head evaluation of valoctocogene roxaparvovec, the first gene therapy approved for haemophilia A, with emicizumab is not available. Therefore, phase 3 trial data were indirectly compared. AIM: To compare bleeding rates in trials evaluating 6 × 1013  vg/kg valoctocogene roxaparvovec (GENEr8-1; NCT03370913), 1.5 mg/kg emicizumab dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270-902) in participants with severe haemophilia A (FVIII ≤1 IU/dL). METHODS: Valoctocogene roxaparvovec versus emicizumab and FVIII prophylaxis as used in 270-902 versus emicizumab cross-trial comparisons were performed using matching-adjusted indirect comparison (MAIC). Individual participant data from GENEr8-1 and 270-902 were weighted to equalise aggregate participant baseline characteristics from HAVEN 3. After MAIC weighting, annualised bleeding rates (ABR) and proportions of participants without bleeds were compared for treated bleeds, all bleeds, treated joint bleeds, and treated spontaneous bleeds. RESULTS: After MAIC weighting, ABR for all bleeds was statistically significantly lower with valoctocogene roxaparvovec than emicizumab (rate ratio [95% CI], .55 [.33-.93]). Additionally, significantly higher proportions of participants had no treated joint bleeds (odds ratio [95% CI], 2.75 [1.20-6.31]) and no treated bleeds (3.25 [1.53-6.90]) with valoctocogene roxaparvovec versus emicizumab. When compared with the mainly standard half-life FVIII prophylaxis regimens in 270-902, mean ABRs (except for all bleeds) were significantly lower, and significantly higher proportions reported 0 bleeds for all outcomes with emicizumab. CONCLUSION: Valoctocogene roxaparvovec provided generally lower bleeding rates and higher probability of no bleeds, including treated joint bleeds, than emicizumab. Emicizumab was more effective than FVIII prophylaxis regimens used in 270-902

Aquilegia, Vol. 37 No. 2 - Special Issue, 2013, Newsletter of the Colorado Native Plant Society

https://epublications.regis.edu/aquilegia/1142/thumbnail.jp

Spinal intradural extraosseous Ewing's sarcoma

Extraosseous Ewing's sarcoma (EES) involving the central nervous system is rare, but can be diagnosed and distinguished from other primitive neuroectodermal tumors (PNET) by identification of the chromosomal translocation (11;22)(q24;q12). We report EES arising from the spinal intradural extramedullary space, based on imaging, histopathological, and molecular data in two men, ages 50 and 60 years old and a review of the literature using PubMed (1970–2009). Reverse transcriptase polymerase chain reaction (RT-PCR) identified the fusion product FL1-EWS. Multimodal therapy, including radiation and alternating chemotherapy including vincristine, cyclophosphamide, doxorubicin and ifosfamide and etoposide led to local tumor control and an initial, favorable therapeutic response. No systemic involvement was seen from the time of diagnosis to the time of last follow-up (26 months) or death (4 years). This report confirms that EES is not confined to the earliest decades of life, and like its rare occurrence as an extra-axial meningeal based mass intracranially, can occasionally present as an intradural mass in the spinal canal without evidence of systemic tumor. Gross total resection followed by multimodal therapy may provide for extended progression free and overall survival

Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance)

Background Patients with glioblastoma (GBM) have a poor prognosis and limited effective treatment options. Bevacizumab has been approved for treatment of recurrent GBM, but there is questionable survival benefit. Based on preclinical and early clinical data indicating that CD105 upregulation may represent a mechanism of resistance to bevacizumab, we hypothesized that combining bevacizumab with the anti-CD105 antibody TRC105 may improve efficacy in recurrent GBM.Methods Phase I dose-escalation/comparative randomized phase II trial in patients with GBM. During phase I, the maximum tolerated dose (MTD) of TRC105 in combination with bevacizumab was determined. In phase II, patients were randomized 1:1 to TRC105 and bevacizumab or bevacizumab monotherapy. Patients receivedTRC105 (10 mg/kg) weekly and bevacizumab (10 mg/kg) every 2 weeks. Efficacy, as assessed by progression-free survival (PFS), was the primary endpoint; safety, quality of life, and correlative outcomes were also evaluated.Results In total, 15 patients were enrolled in phase I and 101 in phase II; 52 patients were randomized to TRC105 with bevacizumab and 49 to bevacizumab monotherapy. The MTD was determined to be 10 mg/kg TRC105 weekly plus bevacizumab 10 mg/kg every 2 weeks. An increased occurrence of grade >= 3 adverse events was seen in the combination arm, including higher incidences of anemia. Median PFS was similar in both treatment arms: 2.9 months for combination versus 3.2 months for bevacizumab monotherapy (HR = 1.16, 95% CI = 0.75-1.78, P = .51). Quality of life scores were similar for both treatment arms.Conclusions TRC105 in combination with bevacizumab was well tolerated in patients with recurrent GBM, but no difference in efficacy was observed compared to bevacizumab monotherapy

Methylphenidate significantly improves declarative memory functioning of adults with ADHD

Contains fulltext : 87790.pdf (publisher's version ) (Closed access)BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory functioning of adults with ADHD. METHODS: Eighteen adults with ADHD who were clinical responders to methylphenidate participated in this randomized crossover trial. After 3 days of no treatment, patients received in random order either their usual methylphenidate dose (mean: 14.7 mg; range: 10-30 mg) or placebo, separated by a 6-7-day washout period. Patients performed an immediate word recall test 1 h after treatment administration. Three hours after intake, patients performed the second part of the memory test (delayed word recall and a recognition test). RESULTS: Delayed recognition and immediate recall was similar on treatment and on placebo. Delayed word recall was significantly better in the methylphenidate than in the placebo condition (F (1, 17) = 7.0, p < 0.017). A significant correlation was found between prestudy CES-D depression scores and difference scores on delayed recall (r = 0.602, p < 0.008). CONCLUSION: Methylphenidate improves declarative memory functioning in patients with ADHD. New studies should further examine whether subclinical depressive symptoms mediate the effect of methylphenidate on declarative memory.1 oktober 201

Successful and unsuccessful cannabis quitters: Comparing group characteristics and quitting strategies

<p>Abstract</p> <p>Background</p> <p>In order to improve treatments for cannabis use disorder, a better understanding of factors associated with successful quitting is required.</p> <p>Method</p> <p>This study examined differences between successful (<it>n </it>= 87) and unsuccessful (<it>n </it>= 78) cannabis quitters. Participants completed a questionnaire addressing demographic, mental health, and cannabis-related variables, as well as quitting strategies during their most recent quit attempt.</p> <p>Results</p> <p>Eighteen strategies derived from cognitive behavioral therapy were entered into a principal components analysis. The analysis yielded four components, representing (1) Stimulus Removal, (2) Motivation Enhancement, (3) (lack of) Distraction, and (4) (lack of) Coping. Between groups comparisons showed that unsuccessful quitters scored significantly higher on Motivation Enhancement and (lack of) Coping. This may indicate that unsuccessful quitters focus on the desire to quit, but do not sufficiently plan strategies for coping. Unsuccessful quitters also had significantly more symptoms of depression and stress; less education; lower exposure to formal treatment; higher day-to-day exposure to other cannabis users; and higher cannabis dependence scores.</p> <p>Conclusions</p> <p>The findings suggest that coping, environmental modification, and co-morbid mental health problems may be important factors to emphasize in treatments for cannabis use disorder.</p

The comparative effectiveness of decision aids in diverse populations with early stage prostate cancer: a study protocol for a cluster-randomized controlled trial in the NCI Community Oncology Research Program (NCORP), Alliance A191402CD

Abstract Background Treatments for localized prostate cancer present challenging tradeoffs in the face of uncertain treatment benefits. These options are best weighed in a process of shared decision-making with the patient’s healthcare team. Minority men experience disparities in prostate cancer outcomes, possibly due in part to a lack of optimal communication during treatment selection. Decision aids facilitate shared decision-making, improve knowledge of treatment options, may increase satisfaction with treatment choice, and likely facilitate long-term quality of life. Methods/design This study will compare the effect of two evidence-based decision aids on patient knowledge and on quality of life measured one year after treatment, oversampling minority men. One decision aid will be administered prior to specialist consultation, preparing patients for a treatment discussion. The other decision aid will be administered within the consultation to facilitate transparent, preference-sensitive, and evidence-informed deliberations. The study will utilize a four-arm, block-randomized design to test whether each decision aid alone (Arms 1 and 2) or in combination (Arm 3) can improve patient knowledge and quality of life compared to usual care (Arm 4). The study, funded by the National Cancer Institute’s Community Oncology Research Program (NCORP), will be deployed within select institutions that have demonstrated capacity to recruit minority populations into urologic oncology trials. Discussion Upon completion of the trial, we will have 1) tested the effectiveness of two evidence-based decision aids in enhancing patients’ knowledge of options for prostate cancer therapy and 2) estimated whether decision aids may improve patient quality of life one year after initial treatment choice. Trial registration Clinicaltrials.gov: NCT03103321 . The trial registration date (on ClinicalTrials.gov) was April 6, 2017