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Query: UMLS:C0038454 (stroke)
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1. GENERAL: Here we updated our analysis of the UNOS Kidney Registry for the compound effects of 26 transplantation factors on graft survival within 2 consecutive posttransplantation risk periods. During the early risk period, 83,867 kidney-only recipients were followed through one year, and, in the second (chronic) risk period, 66,358 recipients whose grafts survived beyond one year were followed for 5 years after transplantation. 2. SHORT-TERM EFFECTS: From the analysis, the top (< 2% of assignable variation) factors influencing one-year graft survival rates were ranked as follows: 1) living-related and living-unrelated donor transplants were preferred; 2) some transplant centers had outstanding results; 3) kidneys from stroke victims displayed poor results; 4) recipients with PRA > 80% demonstrated poor survival; 5) patients transplanted before 1991 had poor results; 6) increasing numbers of HLA-ABDR mismatches decreased survival; 7) cold ischemia times beyond 24 hours diminished survival; 8) kidneys from younger and older donors impaired survival; 9) regrafting was detrimental, 10) Asians and Hispanics enjoyed superior results; 11) recipients with restricted activities pretransplantation were at higher risk of early graft failure; and 12) high (> 30 kg/m2) body mass recipients demonstrated lowered rates. 3. LONG-TERM EFFECTS: Fewer net factors influenced graft survival beyond 1 year through 5 years. The following 9 factors, each explaining > 2% of the assignable variation in conditional 5-year graft survival, were ranked and yielded poor results: 1) older (> 65) donors; 2) Black recipients; 3) poor transplant centers; 4) male recipients; 5) kidneys from cadaver or living parental donors; 6) transplantation prior to 1991; 7) stroke donors; 8) non-zero HLA-AB mismatched transplants; and 9) teenage recipients. 4. IMPACT ON KIDNEY ALLOCATION: This UNOS data analysis combined with other recent multi-center studies suggest that the criteria for kidney allocation need contain just 2 components in order to maximize long-term survival-an immunologic factor (avoiding HLA mismatches) and a non-immunologic factor (a senior citizens pool to receive older donor organs).
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PMID:A multi-factor analysis of kidney graft outcomes at one and five years posttransplantation: 1996 UNOS Update. 928 81

Aspirin protects from cardiovascular events because of its antiaggregant effect. The occurrence of new events in patients who take aspirin has been called clinical aspirin resistance. Many authors believe that aspirin resistance must be detected by biochemical tests, although there is no agreement on which is the best. Nor is there agreement on the term aspirin resistance. Tests used in research laboratories are aggregometry (turbidometric and impedance), tests based on activation-dependent changes in platelet surface, and tests based on activation-dependent release from platelets. Point-of-care tests are PFA-100, IMPACT and VerifyNow, which can detect platelet dysfunction that may be due to aspirin effect, but their use for this purpose is not yet recommended. Aspirin response may be modified by different factors: patient's compliance, dose, smoking, hyperlipidemia, hyperglucemia, acute coronary syndrome, percutaneous revascularization, recent stroke, extracorporeal circulation, heart failure, exercise, circadian rhythm, absorption, concomitant medications, polymorphisms. Patients with aspirin resistance may have an increased risk of cardiovascular events, and possible therapeutic options are to increase the dosage, to replace aspirin with another antiaggregant drug or to add another drug. In conclusion, there are many reasons that explain the variability in individual responsiveness to aspirin. The term resistance is probably not exact in describing this phenomenon.
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PMID:Variability in individual responsiveness to aspirin: clinical implications and treatment. 1822 Jul 26

Atrial fibrillation and atrial flutter are common cardiac arrhythmias associated with an increased risk of stroke in patients with additional risk factors. Anticoagulation ameliorates stroke risk, but because these arrhythmias may occur intermittently without symptoms, initiation of prophylactic therapy is often delayed until electrocardiographic documentation is obtained. The IMPACT study is a multicenter, randomized trial of remote surveillance technology in patients with implanted dual-chamber cardiac resynchronization therapy defibrillator (CRT-D) devices designed to test the hypothesis that initiation and withdrawal of oral anticoagulant therapy guided by continuous ambulatory monitoring of the atrial electrogram improve clinical outcomes by reducing the combined rate of stroke, systemic embolism, and major bleeding compared with conventional clinical management. For those in the intervention group, early detection of atrial high-rate episodes (AHRE) generates an automatic alert to initiate anticoagulation based on patient-specific stroke risk stratification. Subsequently, freedom from AHRE for predefined periods prompts withdrawal of anticoagulation to avoid bleeding. Patients in the control arm are managed conventionally, the anticoagulation decision prompted by incidental detection of atrial fibrillation or atrial flutter during routine clinical follow-up. The results will help define the clinical utility of wireless remote cardiac rhythm surveillance and help establish the critical threshold of AHRE burden warranting anticoagulant therapy in patients at risk of stroke. In this report, we describe the study design and baseline demographic and clinical features of the initial cohort (227 patients).
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PMID:Multicenter randomized study of anticoagulation guided by remote rhythm monitoring in patients with implantable cardioverter-defibrillator and CRT-D devices: Rationale, design, and clinical characteristics of the initially enrolled cohort The IMPACT study. 1969 58

Context High on-treatment platelet reactivity is associated with atherothrombotic events following coronary stent implantation. Objective To evaluate the capability of multiple platelet function tests to predict clinical outcome. Design, Setting, and Patients Prospective, observational, single-center cohort study of 1069 consecutive patients taking clopidogrel undergoing elective coronary stent implantation between December 2005 and December 2007. On-treatment platelet reactivity was measured in parallel by light transmittance aggregometry, Verify Now P2Y12 and Platelet works assays, and the IMPACT-R and the platelet function analysis system (PFA-100) (with the Dade PFA collagen/adenosine diphosphate (ADP) cartridge and Innovance PFA P2Y). Cutoff values for high on-treatment platelet reactivity were established by receiver operating characteristic curve (ROC) analysis. Main Outcome Measurement The primary end point was defined as a composite of all-cause death, nonfatal acute myocardial infarction, stent thrombosis, and ischemic stroke. The primary safety end point included TIMI (Thrombolysis In Myocardial Infarction) criteria major and minor bleeding. Results Kaplan-Meier analysis demonstrated that at 1-year follow-up, the primary end point occurred more frequently in patients with high on-treatment platelet reactivity when assessed by light transmittance aggregometry (52 [11.7%; 95% confidence interval {CI}, 8.9%-15.0%] vs 36 [6.0%;95%CI, 4.2%-8.2%] P.001; n=1049),Verify Now (54 [13.3%; 95% CI, 10.2%-17.0%] vs 37 [5.7%; 95% CI, 4.1%-7.8%]P.001; n=1052), Platelet works (33 [12.6%; 95% CI, 8.8%-17.2%] vs 21 [6.1%;95% CI, 3.8%-9.2%] P=.005; n=606), and Innovance PFA P2Y (18 [12.2%; 95%CI; 7.4%-18.6%] vs 28 [6.3%; 95% CI, 4.3%-8.9%] P=.02; n=588). ROC-curve analysis demonstrated that light transmittance aggregometry (area under the curve[AUC], 0.63; 95% CI, 0.58-0.68), Verify Now (AUC, 0.62; 95% CI, 0.57-0.67), and Platelet works (AUC, 0.61; 95% CI, 0.53-0.69) had modest ability to discriminate between patients with and without primary end point at 1-year follow-up. The IMPACT-R(n=905) and the Siemens PFA Collagen/ADP (n=812) were unable to discriminate between patients with and without the primary end point at 1-year follow-up (all AUCs included 0.50 in the CI). None of the tests identified patients at risk for bleeding. Conclusions Of the platelet function tests assessed, light transmittance aggregometry,Verify Now, Platelet works, and Innovance PFA P2Y were significantly associated with the primary end point. However, the predictive accuracy of these 4 tests was only modest. None of the tests provided accurate prognostic information to identify patients at higher risk of bleeding following stent implantation. Trial Registration clinical trials.gov Identifier: NCT00352014 [corrected].
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PMID:Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. 2156 4

People involved with development of health care policy must be appreciative of the social and economic challenges that will likely develop as a result of the rise in Alzheimer's disease (AD) as the 21st century progresses. Their attitudes, perceptions and understanding regarding AD were captured in the IMPACT survey, a 30-minute Web-based questionnaire. Fifty health policy managers and decision-makers (payors) were recruited, 10 each from 5 European countries--France, Germany, Italy, Spain and the United Kingdom. Most payors felt that AD was underdiagnosed and undertreated in their country (80% and 68%, respectively). Half of all payors felt that their government did not invest enough in treating AD, and 30% felt their government hindered access to drug therapy. Payors believed that treatment should be initiated as early as possible after a diagnosis of AD (82%), and that early treatment can delay progression of the disease (82%). Even more than caregivers, payors agreed that AD can have devastating effects on the family of the sufferer (90% vs 75%; P<0.05). Payors more often cited cancer, stroke and heart disease than AD as affecting their budgets, but cited AD more often than depression, diabetes, HIV/AIDs and arthritis. Cost savings were seen as the most important factor regarding policy decisions. These attitudes of the surveyed payors towards AD and the patients and caregivers affected by it suggest that they may advocate for national and international policies that will facilitate earlier diagnosis and improved access to treatment.
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PMID:Implications of the Impact Survey for payors across Europe. 2081 70

Device-detected atrial fibrillation (AF) episodes predict poor clinical outcome regardless of symptoms. Potential benefits of remote monitoring are early arrhythmia detection and patient continuous monitoring. Several studies of device remote monitoring consistently demonstrated that AF represents the most common clinical alert and that detailed information on arrhythmia onset, duration, and burden as well as on the ventricular rate may be early available for clinical evaluation. Reaction time to AF alerts was very short in all series involving either pacemakers or defibrillators and action ability of AF alerts was very high. In the Home Guide Registry, in which 1650 patients were enrolled, AF was detected in 16.3% of patients and represented 36% of all cardiovascular events during the follow-up. Timely anticoagulation introduction in asymptomatic patients may impact on the stroke rate. According to the results of repeated Monte Carlo simulations based on a real population of 166 patients, daily monitoring may reduce the 2-year stroke risk by 9-18% with an absolute reduction of 0.2-0.6%, compared with conventional inter-visit intervals of 6-12 months. In the COMPAS trial, the incidence of hospitalizations for atrial arrhythmias and related stroke was significantly higher in the control group than in the remote monitoring group. Major questions will be addressed by the ongoing IMPACT trial in which a remote monitoring guided anticoagulation strategy based on AF detection will be compared with a physician-directed standard strategy. In patients with heart failure, AF early detection combined with other indexes may help prevent hospitalizations.
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PMID:Disease management: atrial fibrillation and home monitoring. 2533 76

Research in traumatic brain injury (TBI) is challenging for several reasons; in particular, the heterogeneity between patients regarding causes, pathophysiology, treatment, and outcome. Advances in basic science have failed to translate into successful clinical treatments, and the evidence underpinning guideline recommendations is weak. Because clinical research has been hampered by non-standardised data collection, restricted multidisciplinary collaboration, and the lack of sensitivity of classification and efficacy analyses, multidisciplinary collaborations are now being fostered. Approaches to deal with heterogeneity have been developed by the IMPACT study group. These approaches can increase statistical power in clinical trials by up to 50% and are also relevant to other heterogeneous neurological diseases, such as stroke and subarachnoid haemorrhage. Rather than trying to limit heterogeneity, we might also be able to exploit it by analysing differences in treatment and outcome between countries and centres in comparative effectiveness research. This approach has great potential to advance care in patients with TBI.
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PMID:Advancing care for traumatic brain injury: findings from the IMPACT studies and perspectives on future research. 2413 79

Measurement of hemodynamic parameters such as stroke volume (SV) via impedance cardiography (ICG) is an easy, non-invasive and inexpensive way to assess the health status of the heart. We present a possibility to use this technology for monitoring risk patients at home. The IMPACT Shirt (IMPedAnce Cardiography Textile) has been developed with integrated textile electrodes and textile wiring, as well as with portable miniaturized hardware. Several textile materials were characterized in vitro and in vivo to analyze their performance with regard to washability, and electrical characteristics such as skin-electrode impedance, capacitive coupling and subjective tactile feeling. The small lightweight hardware measures ECG and ICG continuously and transmits wireless data via Bluetooth to a mobile phone (Android) or PC for further analysis. A lithium polymer battery supplies the circuit and can be charged via a micro-USB. Results of a proof-of-concept trial show excellent agreement between SV assessed by a commercial device and the developed system. The IMPACT Shirt allows monitoring of SV and ECG on a daily basis at the patient's home.
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PMID:The IMPACT shirt: textile integrated and portable impedance cardiography. 2484 72

Ischemia-reperfusion injuries occur when the blood supply to an organ or tissue is temporarily cut-off and then restored. Even though the restoration of blood flow is absolutely essential in preventing tissue death, the reperfusion of oxygenated blood to the oxygen-deprived areas may in itself augment the tissue damage in excess of that produced by the ischemia alone. The process of ischemia-reperfusion is multifactorial and there are several mechanisms involved in the pathogenesis. Ample evidence shows that the injury is in part caused by an excessive generation of reactive oxygen species or free radicals. The free radicals consequently initiate an inflammatory response, which in some cases may affect distant organs, thus causing remote organ injuries. Ischemia-reperfusion injuries are a common complication in many diseases (acute myocardial infarctions, stroke) or surgical settings (transplantations, tourniquet-related surgery) and they have potential detrimental and disabling consequences. The tolerance of ischemia-reperfusion has proven to be time-of-day-dependent and the size of myocardial infarctions has proven to be significantly higher when occurring in the dark-to-light period. This period is characterized by and coincides with a rapid decrease in the plasma levels of the hormone melatonin. Melatonin is the body's most potent antioxidant and is capable of both direct free radical scavenging and indirect optimization of other anti-oxidant enzymes. It also possesses anti-inflammatory properties and is known to inhibit the mitochondrial permeability transition pore during reperfusion. This inhibiting property has been shown to be of great importance in reducing ischemia-reperfusion injuries. Furthermore, melatonin is a relatively non-toxic molecule, which has proven to be safe for use in clinical trials. Thus, there is compelling evidence of melatonin's effect in reducing ischemia-reperfusion injuries in many experimental studies, but the number of human clinical trials is very limited. In this PhD thesis we set out to explore the oxidative and inflammatory biochemical markers of ischemia and reperfusion injuries and the possible effect of melatonin on these markers. We have reviewed the literature on the tourniquet-related oxidative damage and found that ischemic preconditioning and the use of propofol could significantly reduce the release of such markers. However, the relevance of this reduction in terms of clinical outcomes is still to be investigated (paper 1). We undertook the characterization of a human ischemia-reperfusion model without the influencing factors of surgery and anesthesia, and subsequently found ways to improve this model (paper 2). In order to apply an intracoronary melatonin administration, we investigated whether melatonin could be dissolved in non-ethanol based buffers and still activate the melatonin receptors (paper 3). We found this to be possible, and in a porcine closed-chest model of acute myocardial infarction (AMI) we randomized the pigs to intracoronary and systemic melatonin or placebo in order to test whether melatonin could attenuate the oxidative and inflammatory biomarkers following reperfusion (paper 4). The outcomes were not optimal for this model, and the effect of melatonin still remains to be explored in a large animal model. We are currently still awaiting the results of the IMPACT-trial - a randomized, placebo-controlled, clinical trial exploring the effect of intracoronary and systemic melatonin given to patients suffering from AMI and undergoing primary percutaneous coronary intervention (pPCI) (paper 5). Though pPCI is undisputedly life-saving, it holds a built-in consequence of aggravating the ischemic injury, paradoxically due to the reperfusion. The optimization of existing treatments and the exploring of new suitable interventions, such as melatonin, for minimizing the ischemia-reperfusion injuries is therefore of great interest.
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PMID:Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries. 2587 40

Atrial fibrillation (AF) is common, increasing as the population ages, and a major cause of embolic stroke. While oral anticoagulation (OAC) is highly effective at preventing stroke in patients with AF, it continues to be underused in eligible patients worldwide. The objective of this prospective, cluster randomized controlled trial (IMPACT-AF; ClinicalTrials.gov #NCT02082548) is to determine whether a comprehensive customized intervention will increase the rate and persistence of use of OAC in patients with AF. IMPACT-AF will be conducted in approximately 50 centers in 5 low- to middle-income countries. Before randomization, sites within countries will be paired to match in size, practice type and baseline rate of OAC use. Site pairs will be randomized to intervention versus control. In total, 40 to 70 patients with AF and at least 2 CHA2DS2-VASc risk factors will be enrolled at each site using a consecutive enrollment strategy, with the goal of capturing actual practice patterns. We aim for patients with a new diagnosis of AF to comprise at least 30% of the study cohort. Assuming an average baseline OAC use of 60% and a post-intervention use of 70% with a post-control rate of 60%, there will be roughly 94-98% power with 25 clusters per group (intracluster correlation coefficient of 0.02). While this trial focuses on improving treatment use and reducing preventable strokes, we also aim to better understand the reasons for OAC underuse. This will improve the intervention with the goal of creating educational recommendations to improve care for patients with AF.
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PMID:A clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AF): design and rationale. 2726 27


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