Macroeconomic Factors Influencing Cross-Border Merger & Acquisitions Value - An empirical study of UK acquirers on foreign targets

This thesis intends to contribute to research by evaluating how the market responds to the announcement of a CBM&A transaction for acquiring shareholders and examining the extent to which macroeconomic & cultural factors influence shareholder value creation as well as whether there are any differences between developed and developing countries

PERIODONTITIS AND EARLY MORTALITY IN ADULTS WITH KIDNEY FAILURE TREATED WITH HEMODIALYSIS: A MULTINATIONAL OBSERVATIONAL STUDY

Introduction and Aims: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases, however prognostic data for periodontitis in the setting of kidney failure are sparse. The aim of the study was to evaluate whether periodontitis was prognostic for all-cause and cardiovascular-related death in adults with kidney failure. Methods: ORALD is a multinational cohort study in adults with kidney failure treated with haemodialysis in Europe (France, Hungary, Italy, Poland, Portugal and Spain) and Argentina. Periodontitis was measured at baseline according to the World Health Organization Community Periodontal Index. The outcomes were all-cause and cardiovascular mortality. Analyses were conducted using a fixed-effect Cox proportional hazards analysis and additionally using a random effects model fitted using shared frailty to account for clustering within countries. Results: Periodontitis was evaluable in 3338 dentate participants of which 1355 (40.6%) had moderate to severe periodontitis. During 6150 person-years of follow-up, 650 deaths occurred of which 325 were cardiovascular. In multivariable analyses, moderate to severe periodontitis was associated with a lower hazard of all-cause (HR 0.76, 95% confidence interval 0.64 to 0.90) and cardiovascular (0.69, 0.54 to 0.87) mortality. There was evidence of decreasing mortality risks with more severe periodontal disease (P≤0.001 for trend). However, when analyses accounted for clustering of participants within countries, the associations between periodontitis and all-cause (0.92, 0.75 to 1.11) and cardiovascular (0.83, 0.63 to 1.09) mortality were not significant. Similar results were observed in analyses restricted to participants with 12 or more teeth and when competing risks for cardiovascular death were considered. Conclusions: Unlike in the general population, there is limited evidence that periodontitis is independently associated with increased all-cause or cardiovascular mortality in adults with kidney failure

CONVINCE in the context of existing evidence on haemodiafiltration

Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of ‘the comparison of high-dose HDF with high-flux HD’ (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis

BACKGROUND:Cardiovascular disease (CVD) is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), for whom the absolute risk of cardiovascular events is similar to people who have existing coronary artery disease. This is an update of a review published in 2009, and includes evidence from 27 new studies (25,068 participants) in addition to the 26 studies (20,324 participants) assessed previously; and excludes three previously included studies (107 participants). This updated review includes 50 studies (45,285 participants); of these 38 (37,274 participants) were meta-analysed.OBJECTIVE:To evaluate the benefits (such as reductions in all-cause and cardiovascular mortality, major cardiovascular events, MI and stroke; and slow progression of CKD to end-stage kidney disease (ESKD)) and harms (muscle and liver dysfunction, withdrawal, and cancer) of statins compared with placebo, no treatment, standard care or another statin in adults with CKD who were not on dialysis. METHODS:Search methods: We searched the Cochrane Renal Group's Specialised Register to 5 June 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on mortality, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD not on dialysis were the focus of our literature searches. Data collection and analysis: Two or more authors independently extracted data and assessed study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes (lipids, creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes (major cardiovascular events, all-cause mortality, cardiovascular mortality, fatal or non-fatal myocardial infarction (MI), fatal or non-fatal stroke, ESKD, elevated liver enzymes, rhabdomyolysis, cancer and withdrawal rates) with 95% confidence intervals (CI).MAIN RESULTS:We included 50 studies (45,285 participants): 47 studies (39,820 participants) compared statins with placebo or no treatment and three studies (5547 participants) compared two different statin regimens in adults with CKD who were not yet on dialysis. We were able to meta-analyse 38 studies (37,274 participants)

Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated with higher end-of-dialysis blood pressure, suggesting that intradialytic hypertension may play a role in generation of interdialytic hypertension

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival

A prospective observational study of iron isomaltoside in haemodialysis patients with chronic kidney disease treated for iron deficiency (DINO).

Iron deficiency is frequent in haemodialysis (HD) patients with chronic kidney disease (CKD), and intravenous iron is an established therapy for these patients. This study assessed treatment routine, effectiveness, and safety of iron isomaltoside (IIM) 5% (Diafer®) in a HD cohort.This article is freely available via Open Access. Click on the link to the publisher's site to access the full-text

Role of statins in preventing adverse cardiovascular outcomes in patients with chronic kidney disease

Purpose of review Cardiovascular disease accounts for the majority of deaths in chronic kidney disease (CKD). Dyslipidemia is a well established cardiovascular risk factor. We summarize key aspects of available evidence relating to beneficial effects of statins in nondialysis-dependent CKD, dialysis-dependent CKD and renal transplant recipients. Recent findings Previous trials and their meta-analyses suggested that statins reduce lipid levels, the risk of cardiovascular disease and all-cause mortality in nondialysis-dependent CKD. The Study of Heart and Renal Protection (SHARP) study that enrolled both dialysis-dependent and nondialysis-dependent CKD patients showed a 17% decrease in major atherosclerotic events with statins or ezetimibe. Similar cardiovascular benefits are observed in renal transplant recipients. However, such positive effects were not found in two recent clinical trials that enrolled hemodialysis patients alone. This lack of benefit might be attributed to differences in the cause of cardiovascular death seen in dialysis patients and smaller sample size. The overall benefits-harms tradeoff may benefit from meta-analysis and individual patient data meta-analysis in hemodialysis patients including the SHARP data. Summary Nondialysis-dependent CKD patients and renal transplant recipients benefit from statins. Statins have also been found to be beneficial in one of the three large trials in hemodialysis patients, a matter which may be further explored