The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Validity and reliability of the Swaymeter device for measuring postural sway

Abstract Background This study aimed to examine: 1) Swaymeter concurrent validity in discriminating between young and older adult populations; 2) Swaymeter convergent validity against a forceplate system; and 3) the immediate test-retest repeatability of postural sway measures obtained from the Swaymeter. Methods Twenty-nine older adults aged 71 to 83 years and 11 young adults aged 22 to 47 years had postural sway measured simultaneously with the Swaymeter and a forceplate for three repeat 30 second trials, under four conditions (floor eyes open, floor eyes closed, foam eyes open, foam eyes closed). Results Age-related differences in sway parameters across the four conditions were evident using the Swaymeter. Moderate-to-good correlations were found between Swaymeter and forceplate sway measures across conditions (r = 0.560-0.865). Good agreement between the Swaymeter and forceplate were found for anteroposterior and mediolateral sway displacement measures (average offset = 6 mm). Sway path length measures were longer for the forceplate compared to the Swaymeter (average offset = 376 mm), but these data showed good agreement following log-transformation. The Swaymeter was reliable across trials, with intraclass correlation coefficients ranging from 0.654 to 0.944. Conclusions The Swaymeter is a reliable tool for assessing postural sway and discriminates between performance of young and older people across multiple sensory conditions.</p

Mechanisms of axonal dysfunction in chronic kidney disease

This thesis examined the pathophysiology of peripheral neuropathy across the spectrum of chronic kidney disease (CKD) using nerve excitability techniques. The purpose of these studies was to establish the prevalence and impact of neuropathy in moderate severity CKD, to investigate the causative role of potassium in the development of axonal dysfunction and to provide an evidence base concerning the differential effects of various therapies on neuropathy in this patient group. Initial studies were undertaken in CKD patients receiving different forms of treatment, namely high-flux haemodialysis and haemodiafiltration. Compared to high-flux haemodialysis, patients who received haemodiafiltration demonstrated greater normality of nerve excitability prior to dialysis, across a single dialysis session and at long-term follow-up. In keeping with previous studies, pre-dialysis K+ was strongly correlated with measures of axonal depolarisation. Subsequent studies were undertaken to investigate whether potassium had a causal role in mediating axonal depolarisation using a modified dialysis intervention. This study demonstrated that axonal depolarisation remained unchanged for as long as serum potassium remained elevated, despite the significant removal of other dialysable uraemic toxins. Furthermore, mathematical modelling analysis revealed that nerve excitability abnormalities in dialysis patients were profoundly worse than that expected for normal axons exposed to similarly high potassium concentrations. Studies undertaken in renal transplant patients demonstrated differences in outcomes that were dependent on the form of post-transplant immunosuppression. Immunosuppressive regimens based on calcineurin inhibition were associated with a greater severity of neuropathy and nerve excitability abnormalities compared to patients receiving alternative immunosuppressive therapies. In the final set of studies nerve function was assessed in diabetic and non-diabetic CKD patients and a disease control group diabetic patients without CKD. Studies in the control group demonstrated nerve excitability abnormalities in type 1 diabetic patients prior to neuropathy onset. In CKD patients, peripheral neuropathy was highly prevalent and was strongly correlated with measures of physical function and quality of life. Additionally, this study revealed that diabetic-CKD is associated with a more severe neuropathy phenotype. In total these findings demonstrate the impact of neuropathy and highlight the need for early detection and management of this condition in all stages of CKD

Current and Emerging Pharmacotherapeutic Interventions for the Treatment of Peripheral Nerve Disorders

Peripheral nerve disorders are caused by a range of different aetiologies. The range of causes include metabolic conditions such as diabetes, obesity and chronic kidney disease. Diabetic neuropathy may be associated with severe weakness and the loss of sensation, leading to gangrene and amputation in advanced cases. Recent studies have indicated a high prevalence of neuropathy in patients with chronic kidney disease, also known as uraemic neuropathy. Immune-mediated neuropathies including Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy may cause significant physical disability. As survival rates continue to improve in cancer, the prevalence of treatment complications, such as chemotherapy-induced peripheral neuropathy, has also increased in treated patients and survivors. Notably, peripheral neuropathy associated with these conditions may be chronic and long-lasting, drastically affecting the quality of life of affected individuals, and leading to a large socioeconomic burden. This review article explores some of the major emerging clinical and experimental therapeutic agents that have been investigated for the treatment of peripheral neuropathy due to metabolic, toxic and immune aetiologies