A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at a 5 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 85:403-408, 2010. V

SummaryBackgroundRemoval of adenomas reduces colorectal cancer incidence and mortality; however, the benefit of surveillance colonoscopy on colorectal cancer risk remains unclear. We examined heterogeneity in colorectal cancer incidence in intermediate-risk patients and the effect of surveillance on colorectal cancer incidence.MethodsWe did this retrospective, multicentre, cohort study using routine lower gastrointestinal endoscopy and pathology data from patients who, after baseline colonoscopy and polypectomy, were diagnosed with intermediate-risk adenomas mostly (>99%) between Jan 1, 1990, and Dec 31, 2010, at 17 hospitals in the UK. These patients are currently offered surveillance colonoscopy at intervals of 3 years. Patients were followed up through to Dec 31, 2014.We assessed the effect of surveillance on colorectal cancer incidence using Cox regression with adjustment for patient, procedural, and polyp characteristics. We defined lower-risk and higher-risk subgroups on the basis of polyp and procedural characteristics identified as colorectal cancer risk factors. We estimated colorectal cancer incidence and standardised incidence ratios (SIRs) using as standard the general population of England in 2007. This trial is registered, number ISRCTN15213649.Findings253 798 patients who underwent colonic endoscopy were identified, of whom 11 944 with intermediate-risk adenomas were included in this analysis. After a median follow-up of 7·9 years (IQR 5·6–11·1), 210 colorectal cancers were diagnosed. 5019 (42%) patients did not attend surveillance and 6925 (58%) attended one or more surveillance visits. Compared to no surveillance, one or two surveillance visits were associated with a significant reduction in colorectal cancer incidence rate (adjusted hazard ratio 0·57, 95% CI 0·40–0·80 for one visit; 0·51, 0·31–0·84 for two visits). Without surveillance, colorectal cancer incidence in patients with a suboptimal quality colonoscopy, proximal polyps, or a high-grade or large adenoma (≥20 mm) at baseline (8865 [74%] patients) was significantly higher than in the general population (SIR 1·30, 95% CI 1·06–1·57). By contrast, in patients without these features, colorectal cancer incidence was lower than that of the general population (SIR 0·51, 95% CI 0·29–0·84).InterpretationColonoscopy surveillance benefits most patients with intermediate-risk adenomas. However, some patients are already at low risk after baseline colonoscopy and the value of surveillance for them is unclear.FundingNational Institute for Health Research Health Technology Assessment, Cancer Research UK.

This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www.publicationethics.org/).Editorial contact: journals.library@nihr.ac.ukThe full HTA archive is freely available to view online at www.journalslibrary.nihr.ac.uk/hta. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www.journalslibrary.nihr.ac.uk Criteria for inclusion in the Health Technology Assessment journalReports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors.Reviews in Health Technology Assessment are termed 'systematic' when the account of the search appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others. HTA programmeThe HTA programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.The journal is indexed in NHS Evidence via its abstracts included in MEDLINE and its Technology Assessment Reports inform National Institute for Health and Care Excellence (NICE) guidance. HTA research is also an important source of evidence for National Screening Committee (NSC) policy decisions.For more information about the HTA programme please visit the website: http://www.nets.nihr.ac.uk/programmes/hta This reportThe research reported in this issue of the journal was funded by the HTA programme as project number 04/33/01. The contractual start date was in September 2006. The draft report began editorial review in March 2015 and was accepted for publication in December 2015. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health. Published by...

Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

The provision of some form of bereavement services is an integral part of any pediatric hospice program. The Canuck Place hospice program has offered bereavement services since it began in 1995. A mixedmethod evaluation of the impact of the Canuck Place program on the families it served during its first two-anda-half years of operation was conducted. The bereavement services reviewed included follow-up care for families, and bereavement support groups for children and their parents. Eight children were interviewed in the initial phase, and nine completed a survey questionnaire; 28 parents rated their level of satisfaction with various aspects of their experience with the parent support group. Findings indicated that the follow-up component of the program was well-received by family members. When assessing their group experiences, children and parents most appreciated the support and understanding they received, the freedom to express themselves, a diminished sense of isolation, and the normalization of their emotions. Practical considerations when offering bereavement support groups are discussed in this paper. Resume / L'accessibilite aun service de deuil est une partie integrante de tout programme de soins palliatifs pedlatrlques. Depuis ses debut en 1995, Canuck Place, une institution de soins palliatifs pediatriques, a toujours offert un service de soutien aux endeuilles. Afin d'en evaluer "impact et l'efficacite aupres des families y ayant eu recours, nous avons conduit une enquete selon la methode mixte d'evaluation. Les services de deuil comprennent Ie suivl aupres des families et les rencontres de groupes de soutien pour les enfants et leurs parents. Lors de la phase initiale du projet, huit enfants avaient ete lntervlewes alors que neuf enfants ont rempli un questionnaire d'enquete. D'autre part, vingt-huit parents ont exprlrne leur deqre de satisfaction sur les differents aspects des groupes de soutien pour les parents. Les resultats de notre enquete revelent que la partie du programme comportant Ie suivi apres-deces etait tres appreclee des families. Tant les parents que les enfants ont beneficie de "aide que les groupes de soutien leur ont apporte, lis ont souliqne Ie support et la comprehension qu'on leur a temolqne, la llberte qu'ils avaient de pouvoir s'exprimer, Ie fait de ne plus se sentir seuls et de pouvoir vivre un retour de leurs emotions ala normale. L'article conclut en offrant des conseils d'ordre pratique pour les groupes de soutien aux endeuilles.