Transfusion of red cells in hematopoietic stem cell transplantation (TRIST): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Insight regarding transfusion practices in Hematopoietic Stem cell Transplantation (HSCT) are lacking and the impact of red cell transfusion in this high risk group on outcomes following HSCT are not well appreciated. Red blood cell transfusion can be life-saving, however, liberal use of transfusion in critically ill patients failed to demonstrate significant clinical benefit. A large number of other observational studies have also demonstrated an association between red blood cell transfusions and increased morbidity such as infections and multi organ failure as well as increased mortality. The role of red cell transfusion on the clinical outcomes observed in patients undergoing HSCT remains poorly understood and a prospective randomized study of transfusion is required to gain insight and knowledge on best transfusion practices in this high risk population.</p> <p>Methods</p> <p>This report describes the design and methodological issues of a randomized pilot study evaluating red cell transfusion triggers in the setting of Hematopoietic Stem Cell Transplantation. This study has been funded by a peer review grant from the Canadian Blood Services and is registered on Clinicaltrials.gov NCT01237639.</p> <p>Results</p> <p>In 3 Canadian centres, 100 patients undergoing Hematopoietic Stem Cell Transplantation will be randomized to either a restrictive (target hemoglobin of 70-90 g/L) or liberal (target hemoglobin of 90-110 g/L) red cell transfusion strategy, based daily hemoglobin values up to 100 days post-transplant. The study will stratify participants by centre and type of transplant. The primary goal is to demonstrate study feasibility and we will collect clinical outcomes on 1) Transfusion Requirements, 2) Transplant Related Mortality, 3) Maximum grade of acute Graft versus Host Disease, 4) Veno-occlusive Disease, 5) Serious Infections, 6) Bearman Toxicity Score, 7) Bleeding, 8) Quality of Life, 9) Number of Hospitalizations and 10) Number of Intensive Care Unit (ICU) Admissions.</p> <p>Conclusion</p> <p>Upon completion, this pilot trial will provide preliminary insight into red cell transfusion practice and its influence in hematopoietic stem cell transplant outcomes. The results of this trial will inform the conduct of a larger study.</p

Batrachochytrium dendrobatidis Shows High Genetic Diversity and Ecological Niche Specificity among Haplotypes in the Maya Mountains of Belize

The amphibian pathogen Batrachochytrium dendrobatidis (Bd) has been implicated in amphibian declines around the globe. Although it has been found in most countries in Central America, its presence has never been assessed in Belize. We set out to determine the range, prevalence, and diversity of Bd using quantitative PCR (qPCR) and sequencing of a portion of the 5.8 s and ITS1-2 regions. Swabs were collected from 524 amphibians of at least 26 species in the protected areas of the Maya Mountains of Belize. We sequenced a subset of 72 samples that had tested positive for Bd by qPCR at least once; 30 samples were verified as Bd. Eight unique Bd haplotypes were identified in the Maya Mountains, five of which were previously undescribed. We identified unique ecological niches for the two most broadly distributed haplotypes. Combined with data showing differing virulence shown in different strains in other studies, the 5.8 s - ITS1-2 region diversity found in this study suggests that there may be substantial differences among populations or haplotypes. Future work should focus on whether specific haplotypes for other genomic regions and possibly pathogenicity can be associated with haplotypes at this locus, as well as the integration of molecular tools with other ecological tools to elucidate the ecology and pathogenicity of Bd

Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice

BACKGROUND: Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. METHODS: We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the ΔF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. RESULTS: In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-α and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation. CONCLUSION: Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Measuring eating concerns in Black and White adolescent girls

Objective: Few instruments exist to measure eating concerns in adolescent girls from diverse ethnic backgrounds. Methods: A Children's version of the Eating Disorder Inventory (EDI-C) has been under development for several years and was designed to be more appropriate for younger children with lower reading levels. However, little is known about the validity of this instrument. The current study reports on the factor structure of an early version of the EDI-C using nonclinical samples of 1,073 White and 1,155 Black girls (ages 11-12). Results: Factor analysis resulted in an eight-factor solution for each group that included a weight concerns factor and an emotional distress factor. For Black girls only, the positively worded items from the Body Dissatisfaction subscale loaded on a separate factor. Four of five factors were similar to the original EDI subscales (Bulimia, Interpersonal Distrust, Maturity Fears, and Perfectionism), although the latter was unique to White girls. Discussion: The factor structure was generally similar for Black and White girls, although the separate body satisfaction factor and lack of shared variance for the perfectionism factor for Black girls suggest that EDI data obtained from ethnic minority samples may need to be interpreted cautiously. (C) 2004 by Wiley Periodicals, Inc

Integrating global and national knowledge to select medicines for children: The Ghana National Drugs Programme

<p>Integrating Global and National Knowledge to Select Medicines for Children: The Ghana National Drugs Programme</p