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The widespread use of pyridine‐based PNP pincer ligands has inspired the concept of metal‐ligand cooperation (MLC), in which the reactivity at the deprotonated CH2 (or NH) arm of the ligand is proposed to play an important role. Several groups developed a family of PNP‐type pincer ligands with methylated arms which were initially introduced to test the effect of blocking MLC in catalysis, but eventually led to unexpected consequences such as stabilization of unusual oxidation states, beneficial catalytic activity, or selectivity. Analysis of the sterics imposed by introducing Me groups revealed that arm protection can be an efficient tool to control sterics around the metal as an alternative to phosphine substitution, leading to much greater steric hinderance above and below pincer's coordination plane. This Concept will describe several illustrative examples which contrast the reactivity of classical CH2/NH‐arm PNP pincers with their CMe2/NMe‐armed counterparts, in particular related to Ru‐catalyzed alcohol dehydrogenative coupling, Fe‐catalyzed hydrogenation, hydroboration, and alkyne semihydrogenation. [ABSTRACT FROM AUTHOR]

Hydrogenation of substituted styrenes and unactivated aliphatic alkenes by molecular hydrogen has been achieved using a Mn catalyst with a non‐pincer, picolylphosphine ligand. This is the second reported example of alkene hydrogenation catalyzed by a Mn complex. Mechanistic studies showed that a Mn hydride formed by H2 activation in the presence of a base is the catalytically active species. Based on experimental and DFT studies, H2 splitting is proposed to occur via a metal‐ligand cooperative pathway involving deprotonation of the CH2 arm of the ligand, leading to pyridine dearomatization. [ABSTRACT FROM AUTHOR]

Introduction: Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. Our goal was to create and analyze a grading system for UNE electrodiagnostic severity. Methods: We retrospectively analyzed EMG reports with UNE. We then classified 112 limbs as having mild, moderate, or severe grade UNE based on electrodiagnostic findings. The association between presenting symptoms and signs, EMG findings, treatment type, and electrodiagnostic grade was statistically analyzed. Results: Seventeen limbs (15.2%) had mild, 80 (71.4%) had moderate, and 15 (13.4%) had severe UNE. Symptoms (P =.016), exam findings (P <.001), and treatment type (P =.043) were significantly associated with electrodiagnostic grade. Discussion Our UNE grading system was significantly related to symptoms, physical exam, and treatment selection and may be useful to measure electrodiagnostic severity. [ABSTRACT FROM AUTHOR]

A ligandless and solvent‐free copper‐catalyzed method for the regioselective C−H bond arylation of indoles and related heteroarenes is reported. The use of CuCl efficiently catalyzes the direct coupling of diverse heteroarenes with aryl iodides via chelation‐assistance. This reaction could tolerate sensitive and structurally diverse functionalities, including halides, ethers, thioethers, amines, indolyl, pyrrolyl and carbazolyl groups. The directing group, 2‐pyridinyl can be smoothly removed to generate C‐2 arylated free‐NH indoles, and the arylated indoles can further be functionalized into Tryptamine derivatives. Preliminary mechanistic study revealed a radical pathway for the arylation reaction. [ABSTRACT FROM AUTHOR]

People with epilepsy (PWE) from underserved populations face significant barriers to epilepsy management and therefore may lack knowledge about epilepsy and self-management (SM) of epilepsy. This paper evaluates SM practices, self-efficacy, outcome expectancy, quality of life, and personal impact of epilepsy in PWE from underserved populations as compared with all PWE. Recruitment for the Managing Epilepsy Well (MEW) Network PAUSE to Learn Your Epilepsy study occurred from October 2015 to March 2019. Participants were assessed at baseline; after SM education intervention; and 6-, 9-, and 15-month postbaseline assessment. Baseline data from 112 PWE were analyzed for this report. Study population was diverse: 63% were women, 47.3% were non-Hispanic black, 24.1% were Hispanic, and 57.4% had public healthcare coverage. Participants on average had epilepsy for 14 years, and 49.1% reported at least one seizure within the past month, but only 27% reported having used a seizure diary or calendar for seizure tracking. Self-management practices & behaviors were significantly lower among PWE from underserved populations than all PWE, though self-efficacy among PWE from underserved populations was significantly higher. This study identifies the unique epilepsy SM needs of PWE from underserved populations. We discuss the need for a personalized approach for developing SM skills and behaviors among these PWE. • People with epilepsy (PWE) from underserved populations have lower self-management (SM) practices as compared to all PWE. • PWE from underserved populations do not frequently utilize online epilepsy education resources. • Self-efficacy is highly correlated with quality of life, SM practices & behaviors, and personal impact of epilepsy. • Number of depressive symptoms, quality of life, and personal impact of epilepsy following seizures are highly correlated. [ABSTRACT FROM AUTHOR]

Introduction: Prior studies have demonstrated superiority of the combined sensory index (CSI) algorithm in diagnosing mild carpal tunnel syndrome (CTS) and have compared presenting symptoms to CTS grade. However, CTS symptoms, signs, and outcomes, including CSI-diagnosed cases, have not been compared with CTS grade.Methods: We retrospectively studied 294 CTS hands from 2010 to 2013; stratified them into mild, moderate, and severe grades; and analyzed the association between CTS grade and presenting symptoms/signs and outcomes.Results: Sensorimotor symptoms (P = 0.017) and signs (P < 0.001) were significantly associated with CTS grade. Regardless of CTS grade, 94% of hands improved with surgery compared with 42% with conservative treatment (P < 0.001). Even in mild CTS, 100% improved with surgery vs. 33% with conservative management (P = 0.011).Discussion: These results corroborate prior studies that compared symptoms to CTS grade and suggest that more objective signs associate even better. CTS grades associate with outcomes, but additional studies are required. Muscle Nerve 57: 45-48, 2018. [ABSTRACT FROM AUTHOR]

The quinoline-based pincer nickel(II) complexes κN,κN,κN-{R2N-C6H4-(μ-N)-C9H6N}NiX ((R2NNNQ)NiCl: R = Me, 2a; R = Et, 2b) were synthesized by the reaction of the ligand precursors (R2NNNQ)H (R = Me, 1a; R = Et, 1b) with (DME)NiCl2 in the presence of Et3N. Similarly, the pincer nickel(II) derivatives (R2NNNQ)NiX (R = Me, X = Br, 3a; R = Et, X = Br, 3b; R = Me, X = OAc, 4a) were obtained by treatment of the ligands (R2NNNQ)H with the nickel precursor (THF)2NiBr2 or Ni(OAc)2. All of these complexes were characterized by 1H and 13C NMR spectroscopy as well as by elemental analysis. Further, the molecular structures of 2a and 3a,b were elucidated by X-ray crystallography. Complex 2a is found to be an efficient catalyst for the direct C-H bond alkylation of substituted benzothiazoles and oxazoles with various unactivated alkyl halides containing β-hydrogens under mild reaction conditions. The catalyst 2a is very robust and was recycled and reused five times for the alkylation reaction without a decrease in its catalytic activity. Preliminary studies reveal that the catalyst 2a acts as an active catalyst and the alkylation reaction appears to operate via a radical pathway. [ABSTRACT FROM AUTHOR]

Objectives: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant drugs. The addition of low dose of 5-hydroxytryptamine type 2A enhances the therapeutic effect of SSRIs. The purpose of the present studies was to test the effects of combined treatment of a low dose of ketanserin (KET) and escitalopram (ESC) on behavioral anomalies occurring after olfactory bulbectomy (OBX). Materials and Methods: Chronic Depression was induced by OBX as shown in behavioral tests such as Open field, social interaction, and hyperemotionality tests. Acute and chronic treatment effect of KET, ESC, and combination was administered to the OBX rats. Results: Chronic (14 days) treatment with KET (1 mg/kg) or ESC (10 mg/kg) alleviated the behavioral anomalies of olfactory bulbectomized rats in modified open field exploration, social interaction, hyperemotionality. When KET treatment was combined with ESC, a short duration regimen (7 days) was sufficient to reverse the bulbectomy-induced anomalies. Conclusion: The combination therapy as a likely strategy to achieve an early-onset of antidepressant action. [ABSTRACT FROM AUTHOR]

There has been a movement to rename Hallervorden–Spatz disease to pantothenate kinase-associated neurodegeneration given Hallervorden and Spatz’s complicity in murderous Nazi programs. Similar controversy surrounds Reiter syndrome, and 2 studies demonstrated decreased unqualified use of that eponym in the literature, but not in textbooks. There have been no similar studies regarding Hallervorden–Spatz disease. The authors performed a MEDLINE search (1990-2010) looking for unqualified use of Hallervorden–Spatz disease and performed statistical analysis. They defined “unqualified” as having no reference to the eponym’s disfavored use. They then looked in 6 neurology textbooks. The authors identified 156 of 278 articles (56.1%) containing unqualified use of Hallervorden–Spatz disease. But there was a declining trend (P = .000), with 70/80 (87.5%) of articles from 1990 to 1999 and 86/198 (43.4%) from 2000 to 2010. There was also decreased unqualified use of the eponyms in textbooks, with all recent editions using pantothenate kinase-associated neurodegeneration instead. The significant decrease in unqualified use of Hallervorden–Spatz disease is reassuring. [ABSTRACT FROM PUBLISHER]

Hypertension is an important, modifiable risk for cardiovascular disease. The Women Take Heart study, a prospective, community-based cohort study of risk factors for heart disease, provides an opportunity to examine prevalence, awareness, and control of hypertension specifically in women. In 1992, 5932 women, age 35 and older (mean age, 52.9; 86% white, 9%African American, 5% other) and free of active heart disease symptoms for 3 months, were recruited through Chicago area public announcements, and their baseline examination data analyzed. Overall, 47.6% were hypertensive (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or self-report). Only 17.3% reported being hypertensive; in 63.2% of all hypertensive women, the hypertension was undetected or unacknowledged. Blood pressure was controlled to <140/90 mm Hg in 24.1% of self-reported hypertensives. Results from this study and national surveys indicate that hypertension detection and control remain major public health challenges in preventing cardiovascular disease in older women. [ABSTRACT FROM AUTHOR]

Assesses the validity of the use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD) codes to identify hospitalizations with clinical evidence of an episode of acute congestive heart failure in the United States. Data from the Corpus Christi Heart Project, a population-based surveillance program for hospitalized coronary heart disease.

People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy. Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8–12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points. The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2. This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE. • PAUSE is a personalized epilepsy self-management (SM) education program. • PAUSE was implemented in diverse and mostly underserved adults with epilepsy. • Self-efficacy, frequency of SM behaviors, and QOL significantly improved over time. • Personal negative impact of epilepsy significantly reduced over time. • Greater improvement was seen in those with lower scores at baseline. [ABSTRACT FROM AUTHOR]

The quinolinyl-based pincer nickel complex, κN,κN,κN-{C9H6N-(µ-N)-C6H4-NMe2}NiCl [(QNNNMe2)NiCl; (1)] has recently been demonstrated to be an efficient and robust catalyst for the alkylation of azoles with alkyl halides under copper-free conditions. Herein, we report the detailed mechanistic investigation for the alkylation of azoles catalyzed by (QNNNMe2)NiCl (1), which highlights an iodine-atom transfer (IAT) mechanism for the reaction involving a NiII/NiIII process. Deuterium labeling experiments indicate reversible cleavage of the benzothiazole C-H bond, and kinetic studies underline a fractional negative rate order with the substrate benzothiazole. The involvement of an alkyl radical during the alkylation is validated by radical clock and external additive experiments. An active intermediate species (QNNNMe2)Ni(benzothiazolyl) (5a) has been isolated and structurally characterized. The complex (QNNNMe2)Ni(benzothiazolyl) (5a) is found to be the resting state of catalyst 1. Kinetic analysis of electronically different intermediates suggests that the step involving the reaction of 5a with alkyl iodide is crucial and a rate-influencing step. DFT calculations strongly support the experimental findings and corroborate an IAT process for the alkylation reaction. [ABSTRACT FROM AUTHOR]

Background: Feedback on “quality indicators” collected from chart audit is a widely used quality-improvement strategy. Skeptics argue that temporal change in practice patterns or improvement of documentation as a result of implementation of chart audit can affect change in quality indicators rather than change in practice due to feedback. This study compared the effectiveness in quality improvement for stroke care of chart audit and feedback versus chart audit only. Methods: Data were examined on quality indicators constructed from the performance measures abstracted from chart audit for 1953 stroke patients admitted to 13 hospitals. Seven of the 13 hospitals were provided with feedback on quality indicators from baseline audit, and 6 hospitals had chart audit only. Results: Least-squares estimation was used to estimate the adjusted mean change in quality indicators between follow-up and baseline audits and differences in mean change between feedback and nonfeedback groups. Differences in adjusted mean change (with 90% confidence interval) were: deep vein thrombosis prophylaxis, 8.46 (−9.46 to 26.38); dysphagia screening, −3.78 (−21.37 to 13.81); antithrombotic therapy within 48 hours of hospitalization, 3.63 (−6.59 to 13.84); discharged on antithrombotic, −0.31 (−6.26 to 5.63); patients with atrial fibrillation discharged on warfarin/coumadin, 44.73 (−13.14 to 102.60); lipid screening, 19.93 (2.99 to 36.86); and smoking counseling, 17.47 (−12.13 to 47.08). Conclusions: Although not statistically significant, results suggest a potential for improvement with data feedback. There is a need for evaluation of the effectiveness of a multifaceted approach in a community setting. [Copyright &y& Elsevier]

Measurement of volume flow rates in major cerebral vessels can be used to evaluate the hemodynamic effects of cerebrovascular disease. However, both age and vascular anatomy can affect flow rates independent of disease. We prospectively evaluated 325 healthy adult volunteers using phase contrast quantitative magnetic resonance angiography to characterize these effects on cerebral vessel flow rates and establish clinically useful normative reference values. Flows were measured in the major intracranial and extracranial vessels. The cohort ranged from 18 to 84 years old, with 157 (48%) females. All individual vessel flows and total cerebral blood flow (TCBF) declined with age, at 2.6 mL/minute per year for TCBF. Basilar artery (BA) flow was significantly decreased in individuals with one or both fetal posterior cerebral arteries (PCAs). Internal carotid artery flows were significantly higher with a fetal PCA and decreased with a hypoplastic anterior cerebral artery. Indexing vessel flows to TCBF neutralized the age effect, but anatomic variations continued to impact indexed flow in the BA and internal carotid artery. Variability in normative flow ranges were reduced in distal vessels and by examining regional flows. Cerebral vessel flows are affected by age and cerebrovascular anatomy, which has important implications for interpretation of flows in the disease state. [ABSTRACT FROM AUTHOR]

Objective: To assess depressive symptom outcomes in a pooled sample of epilepsy self‐management randomized controlled trials (RCTs) from the Managing Epilepsy Well (MEW) Network integrated research database (MEW DB). Methods: Five prospective RCTs involving 453 adults with epilepsy compared self‐management intervention (n = 232) versus treatment as usual or wait‐list control outcomes (n = 221). Depression was assessed with the nine‐item Patient Health Questionnaire. Other variables included age, gender, race, ethnicity, education, income, marital status, seizure frequency, and quality of life. Follow‐up assessments were collapsed into a visit 2 and a visit 3; these were conducted postbaseline. Results: Mean age was 43.5 years (SD = 12.6), nearly two‐thirds were women, and nearly one‐third were African American. Baseline sample characteristics were mostly similar in the self‐management intervention group versus controls. At follow‐up, the self‐management group had a significantly greater reduction in depression compared to controls at visit 2 (P < .0001) and visit 3 (P = .0002). Quality of life also significantly improved in the self‐management group at visit 2 (P = .001) and visit 3 (P = .005). Significance: Aggregate MEW DB analysis of five RCTs found depressive symptom severity and quality of life significantly improved in individuals randomized to self‐management intervention versus controls. Evidence‐based epilepsy self‐management programs should be made more broadly available in neurology practices. [ABSTRACT FROM AUTHOR]

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year ofmarketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrelassociated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. [ABSTRACT FROM AUTHOR]

Life expectancy at birth has increased from 74 years in 1980 to 78 years in 2006. Older adults (aged 65 years and older) are living longer with cardiovascular conditions, which are leading causes of death and disability and thus an important public health concern. We describe several major issues, including the impact of comorbidities, the role of cognitive health, prevention and intervention approaches, and opportunities for collaboration to strengthen the public health system. Prevention can be effective at any age, including for older adults. Public health models focusing on policy, systems, and environmental change approaches have the goal of providing social and physical environments and promoting healthy choices. [ABSTRACT FROM AUTHOR]

The process of atherosclerosis may begin in youth and continue for decades, leading to both nonfatal and fatal cardiovascular events, including myocardial infarction, stroke, and sudden death. With primordial and primary prevention, cardiovascular disease is largely preventable. Clinical trial evidence has shown convincingly that pharmacological treatment of risk factors can prevent events. The data are less definitive but also highly suggestive that appropriate public policy and lifestyle interventions aimed at eliminating tobacco use, limiting salt consumption, encouraging physical exercise, and improving diet can prevent events. There has been concern about whether efforts aimed at primordial and primary prevention provide value (ie, whether such interventions are worth what we pay for them). Although questions about the value of therapeutics for acute disease may be addressed by cost-effectiveness analysis, the long time frames involved in evaluating preventive interventions make cost-effectiveness analysis difficult and necessarily flawed. Nonetheless, cost-effectiveness analyses reviewed in this policy statement largely suggest that public policy, community efforts, and pharmacological intervention are all likely to be cost-effective and often cost saving compared with common benchmarks. The high direct medical care and indirect costs of cardiovascular disease-approaching $450 billion a year in 2010 and projected to rise to over $1 trillion a year by 2030-make this a critical medical and societal issue. Prevention of cardiovascular disease will also provide great value in developing a healthier, more productive society. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions.Kidney International (2009) 75, S20–S24; doi:10.1038/ki.2008.613 [ABSTRACT FROM AUTHOR]

Objectives: We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background: The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods: Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results: Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions: Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. [Copyright &y& Elsevier]

Background: Little information is available regarding the risk factors for intracranial cerebral atherosclerosis (ICAS), particularly among asymptomatics. Methods: Data from a consecutive series of 1,208 subjects aged ≥40 years, with no history of stroke, and who had undergone transcranial Doppler ultrasonography (TCD) were collected prospectively. The role of classic risk factors was assessed in the presence and severity of asymptomatic ICAS, which was determined by TCD. Results: Regarding the presence of ICAS, the adjusted odds ratios (95% confidence intervals) were as follows: 1.22 (1.08–1.37) for every 10-year increase in age, 1.44 (1.08–1.91) for hypertension and 1.86 (1.33–2.59) for diabetes mellitus. No significant association was observed with regard to male sex, smoking or hyperlipidemia. Conclusion: The findings suggest that age, hypertension and diabetes mellitus are significant risk factors for ICAS in asymptomatic populations. [ABSTRACT FROM AUTHOR]

The Duke Treadmill Score (DTS) has been shown to predict mortality in women who have symptomatic heart disease, but its ability to do so in asymptomatic women is unknown, as is its comparative advantage to exercise capacity. We investigated whether a decreased DTS is associated with increased mortality in a prospective cohort of 5,636 asymptomatic women. A symptom-limited exercise treadmill test using Bruce’s protocol was performed at baseline. DTS was calculated using exercise time, exercise-induced angina, and ST-segment depression. Exercise capacity was measured in METs. Deaths and cause of death were identified from 1992 to 2000. After adjusting for the Framingham Risk Score, the risk of death decreased by 9% for each unit increase in DTS and by 17% for every 1-MET increase (p &#60;0.001). Those who had a DTS &#60;5 (moderate or high risk) had hazard ratios for death and cardiac death that were 2.2 and 2.5 times greater, respectively, than did those who had a DTS ≥5 (low risk), after adjusting for Framingham Risk Score (p &#60;0.001). Receiver-operating characteristic curves for the DTS model and the exercise capacity model were not significantly different. In conclusion, we have demonstrated that, although the DTS is an independent predictor of mortality and cardiac mortality in asymptomatic women, it does not appear to be a better predictor than exercise capacity alone. The role of ST-segment changes and symptoms with stress testing in asymptomatic women does not provide additional prognostic information. [Copyright &y& Elsevier]

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice. [ABSTRACT FROM AUTHOR]

Epilepsy, a complex spectrum of disorders, affects about 2.9 million people in the U.S. Similar to other chronic disorders, people with epilepsy face challenges related to management of the disorder, its treatment, co-occurring depression, disability, social disadvantages, and stigma. Two national conferences on public health and epilepsy (1997, 2003) and a 2012 IOM report on the public health dimensions of epilepsy highlighted important knowledge gaps and emphasized the need for evidence-based, scalable epilepsy self-management programs. The Centers for Disease Control and Prevention translated recommendations on self-management research and dissemination into an applied research program through the Prevention Research Centers Managing Epilepsy Well (MEW) Network. MEW Network objectives are to advance epilepsy self-management research by developing effective interventions that can be broadly disseminated for use in people's homes, healthcare providers' offices, or in community settings. The aim of this report is to provide an update on the MEW Network research pipeline, which spans efficacy, effectiveness, and dissemination. Many of the interventions use e-health strategies to eliminate barriers to care (e.g., lack of transportation, functional limitations, and stigma). Strengths of this mature research network are the culture of collaboration, community-based partnerships, e-health methods, and its portfolio of prevention activities, which range from efficacy studies engaging hard-to-reach groups, to initiatives focused on provider training and knowledge translation. The MEW Network works with organizations across the country to expand its capacity, help leverage funding and other resources, and enhance the development, dissemination, and sustainability of MEW Network programs and tools. Guided by national initiatives targeting chronic disease or epilepsy burden since 2007, the MEW Network has been responsible for more than 43 scientific journal articles, two study reports, seven book chapters, and 62 presentations and posters. To date, two programs have been adopted and disseminated by the national Epilepsy Foundation, state Epilepsy Foundation affiliates, and other stakeholders. Recent expansion of the MEW Network membership will help to extend future reach and public health impact. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 ( a d isintegrin a nd m etalloprotease, with t hrombo s pondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated that exercise capacity is an independent predictor of mortality in women. Normative values of exercise capacity for age in women have not been well established. Our objectives were to construct a nomogram to permit determination of predicted exercise capacity for age in women and to assess the predictive value of the nomogram with respect to survival. Methods: A total of 5721 asymptomatic women underwent a symptom-limited, maximal stress test. Exercise capacity was measured in metabolic equivalents (MET). Linear regression was used to estimate the mean MET achieved for age. A nomogram was established to allow the percentage of predicted exercise capacity to be estimated on the basis of age and the exercise capacity achieved. The nomogram was then used to determine the percentage of predicted exercise capacity for both the original cohort and a referral population of 4471 women with cardiovascular symptoms who underwent a symptom-limited stress test. Survival data were obtained for both cohorts, and Cox survival analysis was used to estimate the rates of death from any cause and from cardiac causes in each group. Results: The linear regression equation for predicted exercise capacity (in MET) on the basis of age in the cohort of asymptomatic women was as follows: predicted MET = 14.7 – (0.13 × age). The risk of death among asymptomatic women whose exercise capacity was less than 85 percent of the predicted value for age was twice that among women whose exercise capacity was at least 85 percent of the age-predicted value (P<0.001). Results were similar in the cohort of symptomatic women. Conclusions: We have established a nomogram for predicted exercise capacity on the basis of age that is predictive of survival among both asymptomatic and symptomatic women. These findings could be incorporated into the interpretation of exercise stress tests, providing additional prognostic information for risk stratification. N Engl J Med 2005;353:468-75. [ABSTRACT FROM AUTHOR]