Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Background: The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments. Methods: The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed. Findings: Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p<0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15–1·22] in men and 1·10 [1·06–1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval −0·84 g/L [95% CI −0·99 to −0·70] in men and −0·45 g/L [–0·59 to −0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval −6·5% [95% CI −7·6 to −5·5] in men and −5·3% [–6·5 to −4·2] in women; all p<0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p>0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p<0·0001). Interpretation: During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores. Funding: NHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Harmonia

" Harmonia is a multifaceted exhibition by Calgary based artist Yvonne Mullock. The artist’s various creative interests, including costuming, fashion, performance, sculpture, and textiles, interact harmoniously within the fifteen-hundred-square-foot installation. From afar, the viewer is teased and intrigued by an enlarged peephole in a massive floating wall, which offers a glimpse of a pillowy, hand-dyed, tandem garment, draped on two poised, headless mannequins. Through a large projection, Mullock introduces the garment’s unique utility in her video, which is cleverly repurposed through larger-than-life still shots plastered to the gallery’s walls. " -- Publisher's website

Carter-Ruck on libel and privacy

Carter Ruck on Libel and Privacy is the fully revised and renamed edition of this leading volume on the law governing publication and private interests. It offers comprehensive coverage of the substantive laws of defamation and privacy in England and Wales, details the legal practice and procedure in those areas, and gives an account of the comparable laws in over 60 other jurisdictions. Andrew Scott authored six chapters in the entirely new part on privacy law. These focus on the themes of 'privacy and publication'; 'misuse of private information: the reasonable expectation of privacy'; 'misuse of private information: the ultimate balancing test'; 'remedies for misuse of private information'; 'harassment', and 'data protection'

Oral Contraceptive Use and Breast Cancer in Indonesia

A hospital-based case-control study was conducted in Ujungpandang, Indonesia, to determine the association of breast cancer and current and former oral contraceptive (OC) use. This study included 119 newly diagnosed, histologically-confirmed, breast cancer cases who were admitted to the four largest referral hospitals in Ujungpandang from 1990–1991. Controls were 258 women admitted to these same four hospitals with diagnoses unrelated to breast cancer or OC use. Thirty cases (32%) and 55 (19%) controls reported having ever used OCs. The odds ratio for ever using OCs and breast cancer was 1.8 (95% confidence interval 1.2–3.0) after adjustment for age, age at first pregnancy, and family history of breast cancer. Increasing duration of OC use did not increase risk of breast cancer. No latency trend of increasing years since first OC use among cases was observed; however, a younger age at first OC use was associated with increasing breast cancer risk. A significant recency effect was observed; women last using OCs within five years of study enrollment were at greatest risk of breast cancer (OR = 4.9, 95% CI: 2.1–11.4). This first study of breast cancer and OC use in Indonesia does not provide consistent data to indicate an increased risk of breast cancer associated with OC use. Although breast cancer cases were 80% more likely to have ever used OCs, neither duration nor latency of OC use were associated with cancer risk. The significant recency effect suggests that a detection bias might explain the observed relationship between ever OC use and breast cancer. These results support the need for further studies which include population-based controls

The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake

Cannabinoid 1 receptor (CB1R) inverse agonists are emerging as a potential obesity therapy. However, the physiological mechanisms by which these agents modulate human energy balance are incompletely elucidated. Here, we describe a comprehensive clinical research study of taranabant, a structurally novel acyclic CB1 R inverse agonist. Positron emission tomography imaging using the selective CB1R tracer [F-18]MK-9470 confirmed central nervous system receptor occupancy levels (similar to 10%-40%) associated with energy balance/weight- loss effects in animals. In a 12-week weight-loss study, taranabant induced statistically significant weight loss compared to placebo in obese subjects over the entire range of evaluated doses (0.5, 2, 4, and 6 mg once per day) (p < 0.001). Taranabant treatment was associated with dose-related increased incidence of clinical adverse events, including mild to moderate gastrointestinal and psychiatric effects. Mechanism-of-action studies suggest that engagement of the CB1R by taranabant leads to weight loss by reducing food intake and increasing energy expenditure and fat oxidation

Comparison of the 2001 BRFSS and the IPAQ Physical Activity Questionnaires

Purpose: The 2001 Behavioral Risk Factor Surveillance System (BRFSS) physical activity module and the International Physical Activity Questionnaire (IPAQ) are used in population studies to determine the prevalence of physical activity. The comparability of the prevalence estimates has not been compared in U.S. adults. This study compares the physical activity prevalence estimates from the BRFSS and the IPAQ. Methods: A telephone survey was administered to a random sample of 11,211 U.S. adults aged 18-99 yr who were enrolled in the National Physical Activity and Weight Loss Survey. Data were analyzed from 9945 adults who provided complete data on the BRFSS and the IPAQ. Prevalence estimates were computed ( 1) applying the BRFSS scoring scheme for both questionnaires ( 2). Kappa statistics were used to compare prevalence estimates generated from the BRFSS and the IPAQ. Results: When scored using the BRFSS protocol, agreement between physical activity categories was fair ([kappa] = 0.34-0.49). Prevalence estimates were higher on the IPAQ than the BRFSS for the lowest category (inactive) by 0.1-3.9% and for the highest category (meets recommendations) by 0.2-9.7%. When scored using their own scoring, agreement between physical activity categories was lower ([kappa] = 0.26-0.39). The prevalence estimates on the IPAQ were higher than on the BRFSS for the lowest physical activity category by 0.2-13.3% and for the highest physical activity category by 0-16.4%. Differences in physical activity categories were observed for sex, age, income, education, and body mass index on both questionnaires. Conclusion: Because of differences in the physical activity prevalence estimates, direct comparison of the BRFSS and IPAQ prevalence estimates is not recommended

The Acyclic CB1R Inverse Agonist Taranabant Mediates Weight Loss by Increasing Energy Expenditure and Decreasing Caloric Intake

Cannabinoid 1 receptor (CB1R) inverse agonists are emerging as a potential obesity therapy. However, the physiological mechanisms by which these agents modulate human energy balance are incompletely elucidated. Here, we describe a comprehensive clinical research study of taranabant, a structurally novel acyclic CB1R inverse agonist. Positron emission tomography imaging using the selective CB1R tracer [(18)F]MK-9470 confirmed central nervous system receptor occupancy levels ( approximately 10%-40%) associated with energy balance/weight-loss effects in animals. In a 12-week weight-loss study, taranabant induced statistically significant weight loss compared to placebo in obese subjects over the entire range of evaluated doses (0.5, 2, 4, and 6 mg once per day) (p < 0.001). Taranabant treatment was associated with dose-related increased incidence of clinical adverse events, including mild to moderate gastrointestinal and psychiatric effects. Mechanism-of-action studies suggest that engagement of the CB1R by taranabant leads to weight loss by reducing food intake and increasing energy expenditure and fat oxidation.status: publishe