Physical Activity and Risk of Bleeding in Elderly Patients Taking Anticoagulants.

BACKGROUND Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. OBJECTIVES To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. PATIENTS/METHODS In a prospective multicenter cohort study of 988 patients aged ≥65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically-relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years, and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95%-CI 0.22-0.72). There was no association between physical activity and non-major bleeding. CONCLUSIONS A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy. This article is protected by copyright. All rights reserved.

Immunoregulatory properties of ISG15, an interferon-induced cytokine.

ISG15 is a 15-kDa protein of unique primary amino acid sequence, which is transcriptionally regulated by interferon (IFN) alpha and IFN-beta. Because it is synthesized in many cell types and secreted from human monocytes and lymphocytes, we postulated that ISG15 might act to modulate immune cell function. ISG15 stimulated B-depleted lymphocyte proliferation in a dose-dependent manner with significant proliferation induced by amounts of ISG15 as low as 1 ng/ml (58 pM). Maximal stimulation of [3H]thymidine incorporation by B-depleted lymphocytes occurred at 6-7 days. Immunophenotyping of ISG15-treated B-depleted lymphocyte cultures indicated a 26-fold expansion of natural killer (NK) cells (CD56+). In cytotoxicity assays, ISG15 was a potent inducer of cytolytic activity directed against both K562 (100 lytic units per 10(6) cells) and Daudi (80 lytic units per 10(6) cells) tumor cell targets, indicating that ISG15 enhanced lymphokine-activated killer-like activity. ISG15-induced NK cell proliferation required coculturing of T and NK cells, suggesting that soluble factor(s) were required. Measurement of ISG15-treated cell culture supernatants for cytokines indicated production of IFN-gamma (> 700 units/ml). No interleukin 2 or interleukin 12 was detected. IFN-gamma itself failed to stimulate lymphocyte proliferation and lymphokine-activated killer cell activation. Further, induced expression of IFN-gamma mRNA was detected by reverse transcription-PCR in T lymphocytes after ISG15 treatment but not in NK cells. Enhancement of NK cell proliferation, augmentation of non-major histocompatibility complex-restricted cytotoxicity, and induction of IFN-gamma from T cells identify ISG15 as a member of the cytokine cascade and suggest that it may be responsible for amplifying and directing some of the immunomodulatory effects of IFN-alpha or IFN-beta.

Edoxaban versus enoxaparin–warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial

Background Edoxaban, an oral factor Xa inhibitor, is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy. Few safety data about edoxaban in patients undergoing electrical cardioversion are available. Methods We did a multicentre, prospective, randomised, open-label, blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin–warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. The dose of edoxaban was reduced to 30 mg per day if one or more factors (creatinine clearance 15–50 mL/min, low bodyweight [≤60 kg], or concomitant use of P-glycoprotein inhibitors) were present. Block randomisation (block size four)—stratified by cardioversion approach (transoesophageal echocardiography [TEE] or not), anticoagulant experience, selected edoxaban dose, and region—was done through a voice-web system. The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, analysed by intention to treat. The primary safety endpoint was major and clinically relevant non-major (CRNM) bleeding in patients who received at least one dose of study drug. Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety. This trial is registered with ClinicalTrials.gov, number NCT02072434. Findings Between March 25, 2014, and Oct 28, 2015, 2199 patients were enrolled and randomly assigned to receive edoxaban (n=1095) or enoxaparin–warfarin (n=1104). The mean age was 64 years (SD 10·54) and mean CHA2DS2-VASc score was 2·6 (SD 1·4). Mean time in therapeutic range on warfarin was 70·8% (SD 27·4). The primary efficacy endpoint occurred in five (<1%) patients in the edoxaban group versus 11 (1%) in the enoxaparin–warfarin group (odds ratio [OR] 0·46, 95% CI 0·12–1·43). The primary safety endpoint occurred in 16 (1%) of 1067 patients given edoxaban versus 11 (1%) of 1082 patients given enoxaparin–warfarin (OR 1·48, 95% CI 0·64–3·55). The results were independent of the TEE-guided strategy and anticoagulation status. Interpretation ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups. Funding Daiichi Sankyo provided financial support for the study. © 2016 Elsevier Ltd

Shopper Centric Category Management in Convenience Stores: a Qualitative Study

The literature shows that category management is an important concept and tool for retailers and suppliers, but that there is a trend to move to a more shopper-centric category management approach, linked to the shoppermarketing approach. However, the knowledge on this issue is scarce on some retailing sectors, like convenience stores. The present study is focused on convenience stores, with the main purpose of finding out to what extent non-major food retailers successfully adopt a shopper-centric category management. The study is relevant in order to evaluate if a more shopper-centric approach is adequate to smaller companies/stores. To accomplish that goal, an exploratory qualitative study was conducted among convenience store retailers and suppliers. Six semistructured face-to-face interviews were conducted with Commercial Directors and Trade Marketing Managers. This data was complemented with thirteen interviews with shopper marketing experts. The data was analyzed using thematic content analysis technique, identifying themes, categories, subcategories, units of meaning and relations. The results revealed that convenience store retailers use some of the principles and techniques of the shopper-marketing and shopper-centric category management approaches, which they do in a non-standardized and non-formal approach or process. Their suppliers (the manufacturers) do it in a more formal and structured manner, probably as a result of previous interaction with major supermarkets chains. Both direct and indirect evidences of a shopper-centric approach were found, which, however, were slight, discrete and not formal.

A comparison of motivation to learn English between English major and non-English major students in a Vietnamese university

Despite the plethora of literature examining higher education students’ motivation to learn a second language, it is not known if students who choose to study English as their major differ from those who are required to study English as the minor component of their wider degree. Drawing on self-determination theory, this paper reports on the findings of a quantitative study designed to investigate the types of motivation demonstrated by English major (n=180) and non-English major students (n=242), and their levels of effort expended in learning English in a Vietnamese university. The findings revealed that both groups demonstrated high levels of motivation to learn English to prepare for their future profession. English major students felt more intrinsically motivated and less obligated to learn English. In addition, for both groups, intrinsically motivated students invested the highest levels of effort in learning English. This paper argues that it is imperative for lecturers to foster students’ intrinsic aspirations to learn English to improve the quality of the teaching and learning of English in Vietnamese higher education.

Identifying major contributing sources to odour annoyance using a non-specific gas sensor array

Identification of major contributors to odour annoyance in areas with multiple emission sources is necessary to address and resolve odour disputes. In an effort to develop an appropriate tool for this task, odour samples were collected on-site at a piggery and an abattoir (the major odour sources in the area) and at surrounding off-site areas, then analysed using a commercial non-specific chemical sensor array to develop an odour fingerprint database. The developed odour fingerprint database was analysed using two pattern recognition algorithms including a partial least squares-discriminant analysis (PLS-DA) and a Kohonen self-organising map (KSOM). The KSOM model could identify odour samples sourced from the piggery shed 15, piggery pond 8, piggery pond 9, abattoir, motel and others with mean percentage values of 77.5, 65.0, 90.2, 75.7, 44.8 and 64.6%, respectively.

Characterization of Major Zinc Containing Myonecrotic and Procoagulant Metalloprotease `Malabarin' from Non Lethal Trimeresurus malabaricus Snake Venom with Thrombin Like Activity: Its Neutralization by Chelating Agents

A major myonecrotic zinc containing metalloprotease `malabarin' with thrombin like activity was purified by the combination of gel permeation and anion exchange chromatography from T. malabaricus snake venom. MALDI-TOF analysis of malabarin indicated a molecular mass of 45.76 kDa and its N-terminal sequence was found to be Ile-Ile-Leu-Pro(Leu)-Ile-Gly-Val-Ile-Leu(Glu)-Thr-Thr. Atomic absorption spectral analysis of malabarin raveled the association of zinc metal ion. Malabarin is not lethal when injected i.p. or i.m. but causes extensive hemorrhage and degradation of muscle tissue within 24 hours. Sections of muscle tissue under light microscope revealed hemorrhage and congestion of blood vessel during initial stage followed by extensive muscle fiber necrosis with elevated levels of serum creatine kinase and lactate dehydrogenase activity. Malabarin also exhibited strong procoagulant action and its procoagulant action is due to thrombin like activity; it hydrolyzes fibrinogen to form fibrin clot. The enzyme preferentially hydrolyzes A alpha followed by B beta subunits of fibrinogen from the N-terminal region and the released products were identified as fibrinopeptide A and fibrinopeptide B by MALDI. The myonecrotic, fibrinogenolytic and subsequent procoagulant activities of malabarin was neutralized by specific metalloprotease inhibitors such as EDTA, EGTA and 1, 10-phenanthroline but not by PMSF a specific serine protease inhibitor. Since there is no antivenom available to neutralize local toxicity caused by T. malabaricus snakebite, EDTA chelation therapy may have more clinical relevance over conventional treatment.

Characterization of major zinc containing myonecrotic and procoagulant metalloprotease 'malabarin' from non lethal trimeresurus malabaricus snake venom with thrombin like activity: its neutralization by chelating agents

A major myonecrotic zinc containing metalloprotease 'malabarin' with thrombin like activity was purified by the combination of gel permeation and anion exchange chromatography from T. malabaricus snake venom. MALDI-TOF analysis of malabarin indicated a molecular mass of 45.76 kDa and its N-terminal sequence was found to be Ile-Ile-Leu- Pro(Leu)-Ile-Gly-Val-Ile-Leu(Glu)-Thr-Thr. Atomic absorption spectral analysis of malabarin raveled the association of zinc metal ion. Malabarin is not lethal when injected i.p. or i.m. but causes extensive hemorrhage and degradation of muscle tissue within 24 hours. Sections of muscle tissue under light microscope revealed hemorrhage and congestion of blood vessel during initial stage followed by extensive muscle fiber necrosis with elevated levels of serum creatine kinase and lactate dehydrogenase activity. Malabarin also exhibited strong procoagulant action and its procoagulant action is due to thrombin like activity; it hydrolyzes fibrinogen to form fibrin clot. The enzyme preferentially hydrolyzes A? followed by B subunits of fibrinogen from the N-terminal region and the released products were identified as fibrinopeptide A and fibrinopeptide B by MALDI. The myonecrotic, fibrinogenolytic and subsequent procoagulant activities of malabarin was neutralized by specific metalloprotease inhibitors such as EDTA, EGTA and 1, 10-phenanthroline but not by PMSF a specific serine protease inhibitor. Since there is no antivenom available to neutralize local toxicity caused by T. malabaricus snakebite, EDTA chelation therapy may have more clinical relevance over conventional treatment.

Down-Regulating γ-gliadins in bread wheat leads to non-specific increases in other gluten proteins and has no major effect on dough gluten strength.

Background Gliadins are a major component of gluten proteins but their role in the mixing of dough is not well understood because their contribution to wheat flour functional properties are not as clear as for the glutenin fraction. Methodology/Principal Findings Transgenic lines of bread wheat with γ-gliadins suppressed by RNAi are reported. The effects on the gluten protein composition and on technological properties of flour were analyzed by RP-HPLC, by sodium dodecyl sulfate sedimentation (SDSS) test and by Mixograph analysis. The silencing of γ-gliadins by RNAi in wheat lines results in an increase in content of all other gluten proteins. Despite the gluten proteins compensation, in silico analysis of amino acid content showed no difference in the γ-gliadins silenced lines. The SDSS test and Mixograph parameters were slightly affected by the suppression of γ-gliadins. Conclusions/Significance Therefore, it is concluded that γ-gliadins do not have an essential functional contribution to the bread-making quality of wheat dough, and their role can be replaced by other gluten proteins

Correcting for bias when estimating the cost of hospital-acquired infection : an analysis of lower respiratory tract infections in non-surgical patients

Hospital acquired infections (HAI) are costly but many are avoidable. Evaluating prevention programmes requires data on their costs and benefits. Estimating the actual costs of HAI (a measure of the cost savings due to prevention) is difficult as HAI changes cost by extending patient length of stay, yet, length of stay is a major risk factor for HAI. This endogeneity bias can confound attempts to measure accurately the cost of HAI. We propose a two-stage instrumental variables estimation strategy that explicitly controls for the endogeneity between risk of HAI and length of stay. We find that a 10% reduction in ex ante risk of HAI results in an expected savings of £693 ($US 984).

Creating a therapeutic environment : a non-randomised controlled trial of a quiet time intervention for patients in acute care

Background: Noise is a significant barrier to sleep for acute care hospital patients, and sleep has been shown to be therapeutic for health, healing and recovery. Scheduled quiet time interventions to promote inpatient rest and sleep have been successfully trialled in critical care but not in acute care settings. Objectives: The study aim was to evaluate as cheduled quiet time intervention in an acute care setting. The study measured the effect of a scheduled quiet time on noise levels, inpatients’ rest and sleep behaviour, and wellbeing. The study also examined the impact of the intervention on patients’, visitors’ and health professionals’ satisfaction, and organisational functioning. Design: The study was a multi-centred non-randomised parallel group trial. Settings: The research was conducted in the acute orthopaedic wards of two major urban public hospitals in Brisbane, Australia. Participants: All patientsadmitted to the two wards in the5-month period of the study were invited to participate, withafinalsample of 299 participants recruited. This sample produced an effect size of 0.89 for an increase in the number of patients asleep during the quiet time. Methods: Demographic data were collected to enable comparison between groups. Data for noise level, sleep status, sleepiness and well being were collected using previously validated instruments: a Castle Model 824 digital sound level indicator; a three point sleep status scale; the Epworth Sleepiness Scale; and the SF12 V2 questionnaire. The staff, patient and visitor surveys on the experimental ward were adapted from published instruments. Results: Significant differences were found between the two groups in mean decibel level and numbers of patients awake and asleep. The difference in mean measured noise levels between the two environments corresponded to a ‘perceived’ difference of 2 to 1. There were significant correlations between average decibel level and number of patients awake and asleep in the experimental group, and between average decibel level and number of patients awake in the control group. Overall, patients, visitors and health professionals were satisfied with the quiet time intervention. Conclusions: The findings show that a quiet time intervention on an acute care hospital ward can affect noise level and patient sleep/wake patterns during the intervention period. The overall strongly positive response from surveys suggests that scheduled quiet time would be a positively perceived intervention with therapeutic benefit.