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

Acceptability of prison-based take-home naloxone programmes among a cohort of incarcerated men with a history of regular injecting drug use

Background: Take-home naloxone (THN) programmes are an evidence-based opioid overdose prevention initiative. Elevated opioid overdose risk following prison release means release from custody provides an ideal opportunity for THN initiatives. However, whether Australian prisoners would utilise such programmes is unknown. We examined the acceptability of THN in a cohort of male prisoners with histories of regular injecting drug use (IDU) in Victoria, Australia. Methods: The sample comprised 380 men from the Prison and Transition Health (PATH) Cohort Study; all of whom reported regular IDU in the 6 months prior to incarceration. We asked four questions regarding THN during the pre-release baseline interview, including whether participants would be willing to participate in prison-based THN. We describe responses to these questions along with relationships between before- and during-incarceration factors and willingness to participate in THN training prior to release from prison. Results: Most participants (81%) reported willingness to undertake THN training prior to release. Most were willing to resuscitate a friend using THN if they were trained (94%) and to be revived by a trained peer (91%) using THN. More than 10 years since first injection (adjusted odds ratio [AOR] 2.22, 95%CI 1.03-4.77), having witnessed an opioid overdose in the last 5 years (AOR 2.53, 95%CI 1.32-4.82), having ever received alcohol or other drug treatment in prison (AOR 2.41, 95%CI 1.14-5.07) and injecting drugs during the current prison sentence (AOR 4.45, 95%CI 1.73-11.43) were significantly associated with increased odds of willingness to participate in a prison THN programme. Not specifying whether they had injected during their prison sentence (AOR 0.37, 95%CI 0.18-0.77) was associated with decreased odds of willingness to participate in a prison THN training. Conclusion: Our findings suggest that male prisoners in Victoria with a history of regular IDU are overwhelmingly willing to participate in THN training prior to release. Factors associated with willingness to participate in prison THN programmes offer insights to help support the implementation and uptake of THN programmes to reduce opioid-overdose deaths in the post-release period

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

Surgical Management of Ulcerative Colitis in Children and Adolescents: A Systematic Review from the APSA Outcomes and Evidence-Based Practice Committee.

INTRODUCTION: The incidence of ulcerative colitis (UC) is increasing. Roughly 20% of all patients with UC are diagnosed in childhood, and children typically present with more severe disease. Approximately 40% will undergo total colectomy within ten years of diagnosis. The objective of this study is to assess the available evidence regarding the surgical management of pediatric UC as determined by the consensus agreement of the American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee (APSA OEBP). METHODS: Through an iterative process, the membership of the APSA OEBP developed five a priori questions focused on surgical decision-making for children with UC. Questions focused on surgical timing, reconstruction, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. A systematic review was conducted, and articles were selected for review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of Bias was assessed using Methodological Index for Non-Randomized Studies (MINORS) criteria. The Oxford Levels of Evidence and Grades of Recommendation were utilized. RESULTS: A total of 69 studies were included for analysis. Most manuscripts contain level 3 or 4 evidence from single-center retrospective reports, leading to a grade D recommendation. MINORS assessment revealed a high risk of bias in most studies. J-pouch reconstruction may result in fewer daily stools than straight ileoanal anastomosis. There are no differences in complications based on the type of reconstruction. The timing of surgery should be individualized to patients and does not affect complications. Immunosuppressants do not appear to increase surgical site infection rates. Laparoscopic approaches result in longer operative times but shorter lengths of stay and fewer small bowel obstructions. Overall, complications are not different using an open or minimally invasive approach. CONCLUSIONS: There is currently low-level evidence related to certain aspects of surgical management for UC, including timing, reconstruction type, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. Multicenter, prospective studies are recommended to better answer these questions and ensure the best evidence-based care for our patients. LEVEL OF EVIDENCE: Level of evidence III. STUDY TYPE: Systematic review

Evaluation and Management of Primary Spontaneous Pneumothorax in Adolescents and Young Adults: A Systematic Review From the APSA Outcomes & Evidence-Based Practice Committee.

INTRODUCTION: Controversy exists in the optimal management of adolescent and young adult primary spontaneous pneumothorax. The American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice Committee performed a systematic review of the literature to develop evidence-based recommendations. METHODS: Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL, Elsevier Scopus, and Wiley Cochrane Central Register of Controlled Trials databases were queried for literature related to spontaneous pneumothorax between January 1, 1990, and December 31, 2020, addressing (1) initial management, (2) advanced imaging, (3) timing of surgery, (4) operative technique, (5) management of contralateral side, and (6) management of recurrence. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Seventy-nine manuscripts were included. Initial management of adolescent and young adult primary spontaneous pneumothorax should be guided by symptoms and can include observation, aspiration, or tube thoracostomy. There is no evidence of benefit for cross-sectional imaging. Patients with ongoing air leak may benefit from early operative intervention within 24-48 h. A video-assisted thoracoscopic surgery (VATS) approach with stapled blebectomy and pleural procedure should be considered. There is no evidence to support prophylactic management of the contralateral side. Recurrence after VATS can be treated with repeat VATS with intensification of pleural treatment. CONCLUSIONS: The management of adolescent and young adult primary spontaneous pneumothorax is varied. Best practices exist to optimize some aspects of care. Further prospective studies are needed to better determine optimal timing of operative intervention, the most effective operation, and management of recurrence after observation, tube thoracostomy, or operative intervention. LEVEL OF EVIDENCE: Level 4. TYPE OF STUDY: Systematic Review of Level 1-4 studies

Biochemical and molecular studies using human autopsy brain tissue

The use of human brain tissue obtained at autopsy for neurochemical, pharmacological and physiological analyses is reviewed. RNA and protein samples have been found suitable for expression profiling by techniques that include RT-PCR, cDNA microarrays, western blotting, immunohistochemistry and proteomics. The rapid development of molecular biological techniques has increased the impetus for this work to be applied to studies of brain disease. It has been shown that most nucleic acids and proteins are reasonably stable post-mortem. However, their abundance and integrity can exhibit marked intra- and intercase variability, making comparisons between case-groups difficult. Variability can reveal important functional and biochemical information. The correct interpretation of neurochemical data must take into account such factors as age, gender, ethnicity, medicative history, immediate ante-mortem status, agonal state and post-mortem and post-autopsy intervals. Here we consider issues associated with the sampling of DNA, RNA and proteins using human autopsy brain tissue in relation to various ante- and post-mortem factors. We conclude that valid and practical measures of a variety of parameters may be made in human brain tissue, provided that specific factors are controlled

Digital Object Characterization: Document Conversion and Qualiity Assurance

Whether we are migrating document formats to achieve interoperability or ensure long term preservation, we are faced with the issue of assessing the quality of the digital object transformation. However, comparing two digital objects is not straightforward. It raises the issue of properties that are inherent to the digital objects and those that are dependent on the environment in which the objects are created, viewed, and compared to one another. That has implications for devising methods to extract document properties, interpret observed characteristics, and apply similarity metrics. Furthermore, in order to take actions based on collected measurements, we need to define or learn the significance of individual document properties from the perspective of human perception and usage scenarios. We illustrate the complexity of these issues by presenting a method for comparing converted office documents and discussing the challenges from the technical and methodology point of view