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Background Some countries impose an upper age limit on whole blood and double RBC donation while others do not. We evaluated the safety of blood donation in older individuals (≥71 years), and their contribution to the blood supply of five countries. Study design and methods Twelve blood center members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative from four countries with no upper age limit for whole blood and double RBC donation (Canada, New Zealand, England, and the United States) or an upper age limit of 80 (Australia) provided 2016 data on donors and donations, deferral rates, and vasovagal reactions by donor age and sex. Donors under age 24 were included in the number of total donors and donations, but not in deferral and reaction rate comparisons. Results Older donors accounted for 1.0% (New Zealand) to 4.3% (United States) of donors, and 1.5% (New Zealand) to 5.6% (United States) of donations; most were between ages 71 and 76. The deferral rate was higher in older compared to 24- to 70-year-old males, but very similar between older and younger females. In contrast, vasovagal reaction rates were either lower (male donors) or similar (female donor for reactions with loss of consciousness) in older compared to 24- to 70-year-old donors. Conclusions Exclusion solely based on older age appears to be unwarranted based on safety concerns such as donor reactions. Healthy older individuals can continue to safely donate and make a significant contribution to the blood supply past arbitrary age limits.

BACKGROUND We compared donor and general population demographics over time to provide insight into current donation patterns and the future adequacy of the blood supply. STUDY DESIGN AND METHODS Seventeen blood center members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative from 12 countries provided the number of donors and people in the general population by demographic category for 2001 and 2011, changes in age criteria, and percentage of first-time donors. We calculated the median age of donors and the general population and determined the percentage of each group in age and sex cohorts. RESULTS Age criteria vary, with upper limits recently liberalized in several countries. In 2011, the percentage of first-time donors ranged from 10% to 41%. The median age of the donor and general population increased from 2001 to 2011 in most countries, as did the percentage of the general population over 60. The youngest donor cohort is overrepresented to a variable degree; this tendency increased over time. Although still underrepresented, older donors contributed more in 2011. A large middle-aged cohort is aging at a rate exceeding the progression of time, while 25- to 45-year-olds are relatively underrepresented. CONCLUSIONS All participating countries are experiencing aging of their general population. Donor demographics differ substantially between countries; this can be only partly explained by population demographics and age criteria. Many countries have an aging middle-aged donor and population cohort and are increasingly relying on their youngest donors to contribute disproportionately to the blood supply.

Purpose: Osteoporosis is a chronic disease of the bone, whose incidence increases progressively with aging. The main consequences of osteoporosis are fragility fractures, which have considerable medical, social, and economic implications. Adequate treatment of osteoporosis must be considered as a compelling public health intervention. Bisphosphonates (BPs) represent the most significant advance in this field in the past decade, and they are widely used in the treatment of osteoporosis. However, evidence for their effectiveness is limited to secondary prevention, whereas their effect in primary prevention is uncertain and needs further investigation. Methods: Using administrative data collected in the "Biphosphonates Efficacy-Safety Tradeoff" (BEST) study, a nested case-control study was conducted by including 56,058 participants, aged 55 years who were started on oral BPs from 2003 to 2005. Cases were the 1,710 participants who were hospitalized for osteoporotic fractures until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio of fracture associated with categories of treatment duration. Results: Compared with participants assuming BPs for less than 1 year, those who remained on therapy for at least 2 years had a 21 % (95 % confidence interval (CI) 7 to 33 %) fracture risk reduction. Conclusion: This study provides evidence that BPs, dispensed for primary prevention of osteoporotic fractures, are associated with a reduced risk of osteoporotic fractures after at least 2 years of treatment. © 2014 Springer-Verlag.

Background Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed. Aim To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases. Methods A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty. Results The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations. Conclusions No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.

Background Recent large randomized, controlled trials (BEST [β-blocker Evaluation of Survival Trial], CIBIS-II [Cardiac Insufficiency Bisoprolol Trial II], COPERNICUS [Carvedilol Prospective Randomized Cumulative Survival Study], and MERIT-HF [Metoprolol Randomized Intervention Trial in Congestive Heart Failure]) have addressed the usefulness of β-blockade in the treatment of advanced heart failure. CIBIS-II, COPERNICUS, and MERIT-HF have shown that β-blocker treatment with bisoprolol, carvedilol, and metoprolol XL, respectively, reduce mortality in advanced heart failure patients, whereas BEST found a statistically nonsignificant trend toward reduced mortality with bucindolol. We conducted a post hoc analysis to determine whether the response to β-blockade in BEST could be related to differences in the clinical and demographic characteristics of the study populations. We generated a sample from BEST to resemble the patient cohorts studied in CIBIS-II and MERIT-HF to find out whether the response to β-blocker therapy was similar to that reported in the other trials. These findings are further compared with COPERNICUS, which entered patients with more severe heart failure. Methods To achieve conformity with the entry criteria for CIBIS-II and MERIT-HF, the BEST study population was adjusted to exclude patients with systolic blood pressure 80 years (exclusion criteria employed in those trials). The BEST comparison subgroup (BCG) was further modified to more closely reflect the racial demographics reported for patients enrolled in CIBIS-II and MERIT-HF. The association of β-blocker therapy with overall survival and survival free of cardiac death, sudden cardiac death, and progressive pump failure in the BCG was assessed. Results In the BCG subgroup, bucindolol treatment was associated with significantly lower risk of death from all causes (hazard ratio (HR) = 0.77 [95% CI = 0.65, 0.92]), cardiovascular death (HR = 0.71 [0.58, 0.86]), sudden death (HR = 0.77 [0.59, 0.999]), and pump failure death (HR = 0.64 [0.45, 0.91]). Conclusions Although not excluding the possibility of differences resulting from chance alone or to different properties among β-blockers, this study suggests the possibility that different heart failure population subgroups may have different responses to β-blocker therapy.

Objectives This was a retrospective analysis to determine the effect of diabetes on outcome in patients with advanced heart failure (HF), and to determine the effect of beta-blockade in patients with HF with and without diabetes mellitus. Background In chronic HF the impact on clinical outcomes and therapeutic response of the prevalent comorbid condition diabetes mellitus has not been extensively investigated. Methods We assessed the impact of diabetes on prognosis and effectiveness of beta-blocker therapy with bucindolol in patients with HF enrolled in the Beta-Blocker Evaluation of Survival Trial (BEST). We conducted a retrospective analysis to examine the prognosis of patients with advanced HF with and without diabetes, and the effect of beta-blocker therapy on mortality and HF progression or myocardial infarction (MI). The database was the 2,708 patients with advanced HF (36% with diabetes and 64% without diabetes) who were randomized to the beta-blocker bucindolol or placebo in BEST and followed for mortality, hospitalization, and MI for an average of two years. Results Patients with diabetes had more severe chronic HF and more coronary risk factors than patients without diabetes. Diabetes was independently associated with increased mortality in patients with ischemic cardiomyopathy (adjusted hazard ratio 1.33, 95% confidence interval 1.12 to 1.58, p = 0.001), but not in those with a nonischemic etiology (adjusted hazard ratio 0.98, 95% confidence interval 0.74 to 1.30, p = 0.89). Compared with patients without diabetes, in diabetic patients beta-blocker therapy was at least as effective in reducing death or HF hospitalizations, total hospitalizations, HF hospitalizations, and MI. Ventricular function and physiologic responses to beta-blockade were similar in patients with and without diabetes. Conclusions Diabetes worsens prognosis in patients with advanced HF, but this worsening appears to be limited to patients with ischemic cardiomyopathy. In advanced HF beta-blockade is effective in reducing major clinical end points in patients with and without diabetes.

Thrombin- and plasmin-related indices were measured in peripheral blood of 50 patients at the onset of acute myocardial infarction (AMI) and 35 chronic stable angina (CSA) patients to establish which are most indicative of acute occlusive coronary thrombosis. AMI compared with CSA had significantly higher plasma prothrombin fragment F1.2, thrombin-antithrombin III (TAT) and plasmin-antiplasmin (PAP) complexes (direct indices), but similar soluble fibrin and D-dimer levels (indirect indices). F1.2, TAT and PAP were > the 90th percentile of CSA levels in 15, 10 and 29 AMI patients, respectively. Thus, direct indices of thrombin and plasmin formation appear more indicative of acute coronary thrombosis than indirect ones. In AMI, raised F1.2, TAT and PAP in only some patients is consistent with wide variability in the activity of the underlying thrombotic process.

Background Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of BPs in the setting of secondary prevention of osteoporotic fractures. Methods A nested case–control study was carried out within a cohort of 68,970 patients aged 45 years or older, who have been hospitalized for osteoporotic fracture from 2003 until 2005. Cases were the 804 patients who experienced hospitalization for UGIC until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current and past use of BPs (i.e. for drug dispensation within 30 days and over 31 days prior the outcome onset, respectively) after adjusting for several covariates. Results Compared with patients who did not use BPs, current and past users had OR (and 95% confidence interval) of 0.86 (0.60 to 1.22) and 1.07 (0.80 to 1.44) respectively. There was no difference in the ORs estimated according with BPs type (alendronate or risedronate) and regimen (daily or weekly), nor with co-therapies and comorbidities. Conclusions Further evidence that BPs dispensed for secondary prevention of osteoporotic fractures are not associated with increased risk of severe gastrointestinal complications is supplied from this study. Further research is required to clarify the role BPs and other drugs of co-medication in inducing UGIC.