scispace - formally typeset
Search or ask a question
Author

Tracey A. O'Brien

Bio: Tracey A. O'Brien is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Transplantation & Hematopoietic stem cell transplantation. The author has an hindex of 28, co-authored 131 publications receiving 2323 citations. Previous affiliations of Tracey A. O'Brien include Cardiff University & Royal Children's Hospital.


Papers
More filters
Journal ArticleDOI
TL;DR: Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, leading to clinical benefit in some patients.
Abstract: The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% in WGS only and 25.0% in RNAseq only). Of these patients, 93.7% had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 central nervous system tumors, methylome analysis confirmed diagnosis in 71.1% of patients and contributed to a change of diagnosis in two patients (2.6%). To date, 43 patients have received a recommended therapy, 38 of whom could be evaluated, with 31% showing objective evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, leading to clinical benefit in some patients.

156 citations

Journal ArticleDOI
TL;DR: The data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols.
Abstract: Background This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas β-lactams (noncarbapenems), carbapenems, and multidrug resistance. Results Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and β-lactam/β-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on β-lactam/β-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria. Conclusions Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial. Clinical Trials Registration NCT02257931.

149 citations

Journal ArticleDOI
03 Oct 2013-Blood
TL;DR: High-resolution genome-wide binding maps for a heptad of key transcription factors in human CD34(+) HSPCs are provided and the power of integrating multifactor sequencing of chromatin immunoprecipitates with coding and noncoding gene expression to identify regulatory circuits controlling cell identity is revealed.

121 citations

Journal ArticleDOI
TL;DR: Why the authors should be concerned about Australian health outcomes in this group is explored and how best they might respond to these concerns is considered.
Abstract: The optimal management of adolescent and young adult cancer has been the subject of vigorous debate in paediatric and adult cancer community for many years. This debate is rapidly coming to the boil. There is international recognition that not only is cancer in young people on the rise but also that improvements in outcomes of cancer in young people lag well behind the advances that have been achieved for both children and older adults in the past 30 years. The underlying problems appear to relate to a complex set of interactions between the health-care system and the prevalence of cancer in this age group and the unique psychosocial and educational needs of this population. This article explores why we should be concerned about Australian health outcomes in this group and considers how best we might respond to these concerns.

114 citations

Journal ArticleDOI
TL;DR: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials.

95 citations


Cited by
More filters
01 Jan 2011
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

2,187 citations

01 Jan 2011
TL;DR: The study concludes that understanding lags first requires agreeing models, definitions and measures, which can be applied in practice, and a second task would be to develop a process by which to gather these data.
Abstract: This study aimed to review the literature describing and quantifying time lags in the health research translation process. Papers were included in the review if they quantified time lags in the development of health interventions. The study identified 23 papers. Few were comparable as different studies use different measures, of different things, at different time points. We concluded that the current state of knowledge of time lags is of limited use to those responsible for R&D and knowledge transfer who face difficulties in knowing what they should or can do to reduce time lags. This effectively ‘blindfolds’ investment decisions and risks wasting effort. The study concludes that understanding lags first requires agreeing models, definitions and measures, which can be applied in practice. A second task would be to develop a process by which to gather these data.

1,429 citations

Journal ArticleDOI
01 May 2004-Cancer
TL;DR: An international multidisciplinary panel of experts assembled to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis.
Abstract: BACKGROUND A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis. METHODS The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines. RESULTS New evidence supports the view that oral mucositis is a complex process involving all the tissues and cellular elements of the mucosa. Other findings suggest that some aspects of mucositis risk may be determined genetically. GI proapoptotic and antiapoptotic gene levels change along the GI tract, perhaps explaining differences in the frequency with which mucositis occurs at different sites. Studies of mucositis incidence in clinical trials by quality and using meta-analysis techniques produced estimates of incidence that are presented herein for what to our knowledge may be a broader range of cancers than ever presented before. CONCLUSIONS Understanding the pathobiology of mucositis, its incidence, and scoring are essential for progress in research and care directed at this common side-effect of anticancer therapies. Cancer 2004;100(9 Suppl):1995–2025. © 2004 American Cancer Society.

1,282 citations