In a large, randomized trial involving patients undergoing knee or hip arthroplasty, aspirin was found to be noninferior to rivaroxaban in clot prevention and had a similar risk of serious bleeding.
There is evidence from observational studies that increasing physical activity may reduce the risk of cognitive decline in older adults. Exercise intervention trials have found conflicting results. A ...systematic review of physical activity and exercise intervention trials on cognition in older adults was conducted. Six scientific databases and reference lists of previous reviews were searched. Thirty studies were eligible for inclusion. Articles were grouped into intervention–outcome pairings. Interventions were grouped as cardiorespiratory, strength, and multicomponent exercises. Cognitive outcomes were general cognition, executive function, memory, reaction time, attention, cognitive processing, visuospatial, and language. An eight‐member multidisciplinary panel rated the quality and effectiveness of each pairing. Although there were some positive studies, the panel did not find sufficient evidence that physical activity or exercise improved cognition in older adults. Future research should report exercise adherence, use longer study durations, and determine the clinical relevance of measures used.
Summary Background Ixmyelocel-T is an expanded, multicellular therapy produced from a patient's own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ ...mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical, functional, symptomatic, and quality-of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy. We aimed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions. Methods In this randomised, double-blind, placebo-controlled phase 2B trial (ixCELL-DCM), patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy, who had left ventricular ejection fraction 35% or less, an automatic implantable cardioverter defibrillator, and who were ineligible for revascularisation procedures were randomly assigned (1:1) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months. Randomisation was done through an interactive (voice/web) response system. The pharmacist, treating physician, and coordinator at each site were unblinded, but the the follow-up team was completely blinded. The primary endpoint was a composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01670981. Findings Between April 2, 2013, and Jan 28, 2015, 126 participants were randomly assigned to receive either ixmyelocel-T (n=60) or placebo (n=66). 114 (90%) patients comprised the modified intention-to-treat population and 109 (87%) patients were included in the per-protocol primary efficacy analysis (58 in the ixmyelocel-T group and 51 in the placebo group). The primary efficacy endpoint was observed in 47 patients: 50 events in 25 (49%) of 51 patients in the placebo group and 38 events in 22 (38%) of 58 patients in the ixmyelocel-T group, which represents a 37% reduction in cardiac events compared with placebo (risk ratio 0·63 95% CI 0·42–0·97; p=0·0344). 41 (75%) of 51 participants in the placebo group had serious adverse events versus 31 (53%) of 58 in the ixmyelocel-T group (p=0·0197). Interpretation To the best of our knowledge, ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far. The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy resulted in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes. Funding Vericel Corporation.
Summary Background The goals of axillary-lymph-node dissection (ALND) are to maximise survival, provide regional control, and stage the patient. However, this technique has substantial side-effects. ...The purpose of the B-32 trial is to establish whether sentinel-lymph-node (SLN) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects. The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone. Methods 5611 women with invasive breast cancer were randomly assigned to receive either SLN resection followed by immediate conventional ALND (n=2807; group 1) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination (n=2804; group 2) in the B-32 trial. Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination. Primary endpoints, including survival, regional control, and morbidity, will be reported later. Secondary endpoints are accuracy and technical success and are reported here. This trial is registered with the Clinical Trial registry, number NCT00003830. Findings Data for technical success were available for 5536 of 5611 patients; 75 declined protocol treatment, had no SLNs removed, or had no SLN resection done. SLNs were successfully removed in 97·2% of patients (5379 of 5536) in both groups combined. Identification of a preincision hot spot was associated with greater SLN removal (98·9% 5072 of 5128). Only 1·4% (189 of 13171) of SLN specimens were outside of axillary levels I and II. 65·1% (8571 of 13 171) of SLN specimens were both radioactive and blue; a small percentage was identified by palpation only (3·9% 515 of 13 171). The overall accuracy of SLN resection in patients in group 1 was 97·1% (2544 of 2619; 95% CI 96·4–97·7), with a false-negative rate of 9·8% (75 of 766; 95% CI 7·8–12·2). Differences in tumour location, type of biopsy, and number of SLNs removed significantly affected the false-negative rate. Allergic reactions related to blue dye occurred in 0·7% (37 of 5588) of patients with data on toxic effects. Interpretation The findings reported here indicate excellent balance in clinical patient characteristics between the two randomised groups and that the success of SLN resection was high. These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control. Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate.
Age and acute myeloid leukemia Appelbaum, Frederick R.; Gundacker, Holly; Head, David R. ...
Blood,
05/2006, Letnik:
107, Številka:
9
Journal Article
Recenzirano
Odprti dostop
We conducted a retrospective analysis of 968 adults with acute myeloid leukemia (AML) on 5 recent Southwest Oncology Group trials to understand how the nature of AML changes with age. Older study ...patients with AML presented with poorer performance status, lower white blood cell counts, and a lower percentage of marrow blasts. Multidrug resistance was found in 33% of AMLs in patients younger than age 56 compared with 57% in patients older than 75. The percentage of patients with favorable cytogenetics dropped from 17% in those younger than age 56 to 4% in those older than 75. In contrast, the proportion of patients with unfavorable cytogenetics increased from 35% in those younger than age 56 to 51% in patients older than 75. Particularly striking were the increases in abnormalities of chromosomes 5, 7, and 17 among the elderly. The increased incidence of unfavorable cytogenetics contributed to their poorer outcome, and, within each cytogenetic risk group, treatment outcome deteriorated markedly with age. Finally, the combination of a poor performance status and advanced age identified a group of patients with a very high likelihood of dying within 30 days of initiating induction therapy. The distinct biology and clinical responses seen argue for age-specific assessments when evaluating therapies for AML.
This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype–guided antiplatelet therapy after percutaneous coronary intervention (PCI).
CYP2C19 ...loss-of-function alleles impair clopidogrel effectiveness after PCI.
After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.
Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).
These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
Display omitted
Parkinson’s disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, ...bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel
p
-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.
Abstract Background We aimed to evaluate health-related quality of life (QOL), dyspnea and functional exercise capacity during the year following the diagnosis of a first episode of pulmonary ...embolism. Methods Prospective multicenter cohort study of 100 patients with acute pulmonary embolism recruited at 5 Canadian hospitals from 2010-2013. We measured the outcomes QOL (by SF-36 and PEmb-QOL measures), dyspnea (by the University of California San Diego Shortness of Breath Questionnaire (SOBQ)) and six-minute walk distance at Baseline, 1, 3, 6, and 12 months after acute pulmonary embolism. CT pulmonary angiography was performed at baseline, echocardiogram was performed within 10 days, and cardiopulmonary exercise testing was performed at 1 and 12 months. Predictors of change in QOL, dyspnea, and six-minute walk distance were assessed by repeated measures mixed effects models analysis. Results Mean age was 50.0 years, 57% were male, and 80% were treated as out-patients. Mean scores for all outcomes improved during 1 year follow-up: from baseline to 12 months, mean SF-36 physical component score improved by 8.8 points, SF-36 mental component score by 5.3 points, PEmb-QoL by -32.1 points, and SOBQ by -16.3 points, and six-minute walk distance improved by 40 m. Independent predictors of reduced improvement over time were female sex, higher BMI and percent-predicted VO2 peak <80% on 1 month cardiopulmonary exercise test for all outcomes; prior lung disease and higher pulmonary artery systolic pressure on 10-day echocardiogram for the outcomes SF-36 physical component score and dyspnea score; and higher main pulmonary artery diameter on baseline CT pulmonary angiography for the outcome PEmb-QoL score. Conclusions On average, QOL, dyspnea, and walking distance improve during the year after pulmonary embolism. However, a number of clinical and physiological predictors of reduced improvement over time were identified, most notably female sex, higher BMI and exercise limitation on 1- month cardiopulmonary exercise test. Our results provide new information on patient-relevant prognosis after pulmonary embolism.
PDF
