Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.)

Prognostic value of psychosocial factors for first and recurrent hospitalizations and mortality in heart failure patients: insights from the OPERA-HF study

Aims: Psychosocial factors are rarely collected in studies investigating the prognosis of patients with heart failure (HF), and only time to first-event is commonly reported. We investigated the prognostic value of psychosocial factors for predicting first or recurrent events after discharge following hospitalization for HF. Methods and results: OPERA-HF is an observational study enrolling patients hospitalized for HF. In addition to clinical variables, psychosocial variables are recorded. Patients provide the information through questionnaires which include social information, depression and anxiety scores, and cognitive function. Kaplan-Meier, Cox regression and the Andersen-Gill model were used to identify predictors of first and recurrent events (re-admissions or death). Of 671 patients (age 76±15 years, 66% men) with one-year follow-up, 291 had no subsequent event, 34 died without being readmitted, 346 had one or more unplanned readmissions and 71 patients died after a first readmission. Increasing age, higher urea and creatinine, the presence of co-morbidities (diabetes, history of MI, COPD), were all associated with increasing risk of first or recurrent event. Psychosocial variables independently associated with both the first and recurrent events were: presence of frailty, moderate to severe depression and moderate to severe anxiety. Living alone and the presence of cognitive impairment were independently associated only with an increasing risk of recurrent events. Conclusion: Psychosocial factors are strongly associated with unplanned recurrent readmissions or mortality following an admission to hospital for HF. Further research is needed to show whether recognition of these factors and support tailored to individual patients’ needs will improve outcomes

Successful Strategies for Promoting Self-Advocacy Among Students with LD: The LEAD Group

Students with learning disabilities (LD) often need to be taught self-determination skills to be better prepared for life after high school. This article describes the methods used by one school district to promote self-advocacy and self-awareness skills for students with LD. Through multicomponent group activities, students learned about their strengths and disabilities and how to advocate for their educational needs and rights. Advocacy skills were also applied to leadership roles, mentoring, and community education activities. Important features that contributed to the success of the program are described.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Equity in healthcare: status, barriers, and challenges

Global health provides a challenge for primary care and general practice which will become increasingly important in the future as the prevalence of multimorbidity increases. There is increasing likelihood of survival from acute illnesses and increase an in the elderly population. This literature review focuses on the health inequities, the role of family medicine and the factors that are essential in overcoming these inequalities. Health disparities refer to gaps in the quality of health and delivery of health care across racial, ethnic, gender and socioeconomic groups. The health disparities vary among different countries and the factors that lead to these disparities differ across the world. Family medicine plays a crucial role in bridging this gap and is an essential backbone of the society in developing nations as well as the wealthier nations in providing equity in health care to all people. There are many factors leading to inequity in health care. Family medicine should be recognized as a specialty across the world, as family medicine with its person centered care can bring about a global change in health care. This issue has to be taken up more seriously by the institutions like the WHO, UN and also individual governments along with the political parties to create uniformity in health care. In the current setting of the global economic and financial crisis, a truly global solution is needed. The WHO has come up with various strategies to solve the issue of financial crises and ensuring equity in health globally. This will ensure equal health care to all people especially the underprivileged in developing countries who do not have access to better healthcare due to lack of resources. This factor is a major contributor to the premature death of individuals at all stages of life from new born to the elderly and includes infant mortality and mortality due to chronic diseases. This is important in creating uniformity in health care across the world but has to be considered at a global level to have an impact

Sequential boundaries approach in clinical trials with unequal allocation ratios

BACKGROUND: In clinical trials, both unequal randomization design and sequential analyses have ethical and economic advantages. In the single-stage-design (SSD), however, if the sample size is not adjusted based on unequal randomization, the power of the trial will decrease, whereas with sequential analysis the power will always remain constant. Our aim was to compare sequential boundaries approach with the SSD when the allocation ratio (R) was not equal. METHODS: We evaluated the influence of R, the ratio of the patients in experimental group to the standard group, on the statistical properties of two-sided tests, including the two-sided single triangular test (TT), double triangular test (DTT) and SSD by multiple simulations. The average sample size numbers (ASNs) and power (1-β) were evaluated for all tests. RESULTS: Our simulation study showed that choosing R = 2 instead of R = 1 increases the sample size of SSD by 12% and the ASN of the TT and DTT by the same proportion. Moreover, when R = 2, compared to the adjusted SSD, using the TT or DTT allows to retrieve the well known reductions of ASN observed when R = 1, compared to SSD. In addition, when R = 2, compared to SSD, using the TT and DTT allows to obtain smaller reductions of ASN than when R = 1, but maintains the power of the test to its planned value. CONCLUSION: This study indicates that when the allocation ratio is not equal among the treatment groups, sequential analysis could indeed serve as a compromise between ethicists, economists and statisticians

Amino-acid PET versus MRI guided re-irradiation in patients with recurrent glioblastoma multiforme (GLIAA) – protocol of a randomized phase II trial (NOA 10/ARO 2013-1)

Background: The higher specificity of amino-acid positron emission tomography (AA-PET) in the diagnosis of gliomas, as well as in the differentiation between recurrence and treatment-related alterations, in comparison to contrast enhancement in T1-weighted MRI was demonstrated in many studies and is the rationale for their implementation into radiation oncology treatment planning. Several clinical trials have demonstrated the significant differences between AA-PET and standard MRI concerning the definition of the gross tumor volume (GTV). A small single-center non-randomized prospective study in patients with recurrent high grade gliomas treated with stereotactic fractionated radiotherapy (SFRT) showed a significant improvement in survival when AA-PET was integrated in target volume delineation, in comparison to patients treated based on CT/MRI alone. Methods: This protocol describes a prospective, open label, randomized, multi-center phase II trial designed to test if radiotherapy target volume delineation based on FET-PET leads to improvement in progression free survival (PFS) in patients with recurrent glioblastoma (GBM) treated with re-irradiation, compared to target volume delineation based on T1Gd-MRI. The target sample size is 200 randomized patients with a 1:1 allocation ratio to both arms. The primary endpoint (PFS) is determined by serial MRI scans, supplemented by AA-PET-scans and/or biopsy/surgery if suspicious of progression. Secondary endpoints include overall survival (OS), locally controlled survival (time to local progression or death), volumetric assessment of GTV delineated by either method, topography of progression in relation to MRIor PET-derived target volumes, rate of long term survivors (> 1 year), localization of necrosis after re-irradiation, quality of life (QoL) assessed by the EORTC QLQ-C15 PAL questionnaire, evaluation of safety of FET-application in AA-PET imaging and toxicity of re-irradiation. Discussion: This is a protocol of a randomized phase II trial designed to test a new strategy of radiotherapy target volume delineation for improving the outcome of patients with recurrent GBM. Moreover, the trial will help to develop a standardized methodology for the integration of AA-PET and other imaging biomarkers in radiation treatment planning. Trial registration: The GLIAA trial is registered with ClinicalTrials.gov (NCT01252459, registration date 02.12.2010), German Clinical Trials Registry (DRKS00000634, registration date 10.10.2014), and European Clinical Trials Database (EudraCT-No. 2012-001121-27, registration date 27.02.2012)

Optically Active Bimesogens Incorporating Branched Central Spacers

In the current fascination with liquid crystalline dimers, bimesogens and oligomers the role of the central spacer in these systems has perhaps been somewhat neglected. In compound 1, a phenyl 4-cyanobenzoate bimesogen, the central spacer incorporates a methyl group at the 2- position and is therefore chiral. The helical twisting power of 1, measured in both 5CB and E7, was found to be 0.36 and 0.35 μm-1 wt%-1 respectively. Compound 1 exhibited a monotropic chiral nematic phase, however no twist-bend modulated phase was observed. We prepared a number of analogues of 1 incorporating different mesogenic units and observe that those with a small aspect ratio are non mesogenic, whereas those with larger aspect ratios variously exhibit chiral nematic, TB, SmC and SmB phases

Clinical utility of remote platelet function measurement using P-selectin: assessment of aspirin, clopidogrel, and prasugrel and bleeding disorders

Vascular diseases such as myocardial infarction and ischemic stroke are associated with increased platelet function whilst the risk of recurrence is reduced by antiplatelet agents such as aspirin, clopidogrel, and prasugrel. However, some patients exhibit high platelet reactivity, especially with clopidogrel. Existing platelet function tests may not be ideal in that they can be expensive, are often time consuming, and measurements must be made near to the patient and within a few hours of blood collection. Platelet activation leads to translocation of P-selectin from alpha-granules to the cell surface. Following activation with arachidonic acid (which is blocked by aspirin) or adenosine diphosphate (inhibited by clopidogrel) and fixation, samples may be stored or posted to a laboratory performing flow cytometric quantification of platelet P-selectin expression. Acute myocardial infarction and ischemic stroke are associated with high platelet reactivity on clopidogrel in 6–58% of patients when assessed with P-selectin expression, and high reactivity was associated with an increased risk of recurrence after myocardial infarction. Use of P-selectin expression tests may also be of relevance to surgical and veterinary practice and the diagnosis of mild bleeding disorders. The present review explores this topic in further detail

Impact of diabetes on the predictive value of heart failure biomarkers

Altres ajuts: This study was funded by the Redes Temáticas de Investigación Cooperativa en Salud (RETICS); Red Cardiovascular (RD12/0042/0047) as part of the Plan Nacional de I+D+I.Patients with diabetes mellitus (DM) have an increased risk of developing heart failure (HF). Further, DM is associated with poor prognosis in patients with HF. Our aim was to determine whether DM has any impact on the predictive value of a multi-biomarker panel in patients with HF. We included 1069 consecutive ambulatory HF patients in the study: age 66.2 ± 12.8 years, 33.5 ± 13.3 left ventricular ejection fraction, 36% diabetic patients. We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST2, galectin-3, high-sensitivity C reactive protein (hs-CRP), cystatin-C, soluble transferrin receptor (sTfR), and neprilysin and followed patients for 4.9 ± 2.8 years. Primary endpoints were all-cause and cardiovascular death. During follow-up, 534 patients died; 283 died of cardiovascular causes. Diabetic subjects had higher mortality (57.7 vs. 45.6%, p < 0.001). NTproBNP (p = 0.07), hs-TnT (p < 0.001), galectin-3 (p < 0.001), and cystatin-C (p = 0.001) concentrations were higher in diabetic patients, whereas sTfR levels were lower (p = 0.005). There were no interactions between DM and NTproBNP, hs-TnT, galectin-3, hs-CRP, cystatin-C, sTfR, and neprilysin relative to risk prediction for all-cause or cardiovascular death. By contrast, ST2 significantly interacted with DM for all-cause (p = 0.02) and cardiovascular (p = 0.03) death. In diabetic patients, HRs for ST2 were 1.27 (95% CI 1.16-1.40, p < 0.001) and 1.23 (95% CI 1.09-1.39, p = 0.001) for all-cause and cardiovascular death, respectively. In nondiabetic patients, HRs for ST2 were 1.53 (95% CI 1.35-1.73, p < 0.001) and 1.64 (95% CI 1.31-2.05, p < 0.001) for all-cause and cardiovascular death, respectively. The multivariable Cox regression analysis showed that hs-TnT and ST2 were the only markers that were independently associated with both all-cause and cardiovascular mortality in patients with HF and diabetes. Moreover, in these patients, the combination of these two markers significantly increased discrimination as assessed by the area under the curve. Biomarkers used in the general population to predict the clinical course of heart failure are also useful in patients with diabetes. In these patients, among all the biomarkers analysed only hs-TnT and ST2 were independently associated with both all-cause and cardiovascular mortality