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1.  Metabolomic insights into system-wide coordination of vertebrate metamorphosis 
Background
After completion of embryogenesis, many organisms experience an additional obligatory developmental transition to attain a substantially different juvenile or adult form. During anuran metamorphosis, the aquatic tadpole undergoes drastic morphological changes and remodelling of tissues and organs to become a froglet. Thyroid hormones are required to initiate the process, but the mechanism whereby the many requisite changes are coordinated between organs and tissues is poorly understood. Metabolites are often highly conserved biomolecules between species and are the closest reflection of phenotype. Due to the extensive distribution of blood throughout the organism, examination of the metabolites contained therein provides a system-wide overview of the coordinated changes experienced during metamorphosis. We performed an untargeted metabolomic analysis on serum samples from naturally-metamorphosing Rana catesbeiana from tadpoles to froglets using ultraperformance liquid chromatography coupled to a mass spectrometer. Total and aqueous metabolite extracts were obtained from each serum sample to select for nonpolar and polar metabolites, respectively, and selected metabolites were validated by running authentic compounds.
Results
The majority of the detected metabolites (74%) showed statistically significant abundance changes (padj < 0.001) between metamorphic stages. We observed extensive remodelling of five core metabolic pathways: arginine and purine/pyrimidine, cysteine/methionine, sphingolipid, and eicosanoid metabolism and the urea cycle, and found evidence for a major role for lipids during this postembryonic process. Metabolites traditionally linked to human disease states were found to have biological linkages to the system-wide changes occuring during the events leading up to overt morphological change.
Conclusions
To our knowledge, this is the first wide-scale metabolomic study of vertebrate metamorphosis identifying fundamental pathways involved in the coordination of this important developmental process and paves the way for metabolomic studies on other metamorphic systems including fish and insects.
doi:10.1186/1471-213X-14-5
PMCID: PMC3928663  PMID: 24495308
Postembryonic development; Thyroid hormone; Metamorphosis; Metabolites; Serum; Ultra-performance liquid chromatography; Quadrupole time-of-flight; Mass spectrometry; Vertebrate
2.  A Pilot Program in Collaboration with African American Churches Successfully Increases Awareness of the Importance of Cancer Research and Participation in Cancer Translational Research Studies among African Americans 
African Americans are underrepresented in cancer research. We evaluate whether collaboration with African American churches can improve cancer awareness and increase participation in translational research protocols among African Americans. From February to April 2010, the Mayo Clinic partnered with African American Jacksonville churches to provide educational programs focused on cancer research and healthy behaviors. Education on multiple myeloma and on-site access to a translational cancer research pilot project evaluating the prevalence of monoclonal gammopathies and t(14,18) in African Americans was offered. Seventy-four percent, 236 out of 318 participants, returned the questionnaires. The majority of participants had never received information on multiple myeloma (67%), had never received clinical research study information (57%), and were enrolled in the translational research studies (55%). Partnerships with African American churches in community education projects that bring research to church venues are effective in improving cancer awareness and in increasing research participation among African Americans.
doi:10.1007/s13187-011-0288-x
PMCID: PMC3736846  PMID: 22072126
Healthcare disparities; Minority health; Cancer; Multiple myeloma; Monoclonal proteins; t(14,18); African Americans
3.  A Nurse Practitioner Directed Intervention Improves the Quality of Life of Patients with Metastatic Cancer: Results of a Randomized Pilot Study 
Journal of Palliative Medicine  2012;15(8):890-895.
Abstract
Background
There is a paucity of randomized studies evaluating the value of palliative interventions on a prospective basis in newly diagnosed oncology patients. We sought to prospectively evaluate quality of life (QoL) outcomes in advanced cancer patients who received discussion-based palliative care interventions from an advanced registered nurse practitioner (ARNP) integrated into the oncology team, and compare these outcomes with a control population.
Methods
Patients with metastatic cancer were randomized to standard care or an ARNP-directed intervention that included discussions of the benefits of hospice, discussions on living wills and advanced directives (Five Wishes document) along with an assessment of QoL. Relevant endpoints included change from baseline QoL and improvement in hospice knowledge.
Results
From November 13, 2008, through July 28, 2009, 26 patients were accrued at the Mayo Clinic in Jacksonville, Florida. The study closed early due to published data demonstrating the benefits of early palliative care interventions in the management of metastatic cancer patients. Statistically significant improvements from baseline were noted in emotional and mental QoL assessments in the intervention group that were not seen in the control group. Patients found it useful to have the living will and Five Wishes documents offered as part of the ARNP intervention.
Conclusions
An ARNP-directed intervention that explains the benefits of hospice and addresses advanced directives early in the course of metastatic cancer patients' treatment, is well received by the patients and their relatives and leads to measurable improvement in the patient's emotional and mental QoL.
doi:10.1089/jpm.2012.0014
PMCID: PMC3396133  PMID: 22559906
4.  Hospital-Onset Clostridium difficile Infection Rates in Persons with Cancer or Hematopoietic Stem Cell Transplant: A C3IC Network Report 
A multicenter survey of 11 cancer centers was performed to determine the rate of hospital-onset Clostridium difficile infection (HO-CDI) and surveillance practices. Pooled rates of HO-CDI in patients with cancer were twice the rates reported for all US patients (15.8 vs 7.4 per 10,000 patient-days). Rates were elevated regardless of diagnostic test used.
doi:10.1086/668023
PMCID: PMC3670420  PMID: 23041818
5.  Perceived Impact of Electronic Medical Records in Physician Office Practices: A Review of Survey-Based Research 
Background
Physician office practices are increasingly adopting electronic medical records (EMRs). Therefore, the impact of such systems needs to be evaluated to ensure they are helping practices to realize expected benefits. In addition to experimental and observational studies examining objective impacts, the user’s subjective view needs to be understood, since ultimate acceptance and use of the system depends on them. Surveys are commonly used to elicit these views.
Objective
To determine which areas of EMR implementation in office practices have been addressed in survey-based research studies, to compare the perceived impacts between users and nonusers for the most-addressed areas, and to contribute to the knowledge regarding survey-based research for assessing the impact of health information systems (HIS).
Methods
We searched databases and systematic review citations for papers published between 2000 and 2012 (May) that evaluated the perceived impact of using an EMR system in an office-based practice, were based on original data, had providers as the primary end user, and reported outcome measures related to the system’s positive or negative impact. We identified all the reported metrics related to EMR use and mapped them to the Clinical Adoption Framework to analyze the gap. We then subjected the impact-specific areas with the most reported results to a meta-analysis, which examined overall positive and negative perceived impacts for users and nonusers.
Results
We selected 19 papers for the review. We found that most impact-specific areas corresponded to the micro level of the framework and that appropriateness or effectiveness and efficiency were well addressed through surveys. However, other areas such as access, which includes patient and caregiver participation and their ability to access services, had very few metrics. We selected 7 impact-specific areas for meta-analysis: security and privacy; quality of patient care or clinical outcomes; patient–physician relationship and communication; communication with other providers; accessibility of records and information; business or practice efficiency; and costs or savings. All the results for accessibility of records and information and for communication with providers indicated a positive view. The area with the most mixed results was security and privacy.
Conclusions
Users sometimes were likelier than nonusers to have a positive view of the selected areas. However, when looking at the two groups separately, we often found more positive views for most of the examined areas regardless of use status. Despite limitations of a small number of papers and their heterogeneity, the results of this review are promising in terms of finding positive perceptions of EMR adoption for users and nonusers. In addition, we identified issues related to survey-based research for HIS evaluation, particularly regarding constructs for evaluation and quality of study design and reporting.
doi:10.2196/ijmr.2113
PMCID: PMC3626136  PMID: 23611832
Health care surveys; evaluation studies; ambulatory care information systems
6.  Randomized study evaluating testosterone recovery using short-versus long-acting luteinizing hormone releasing hormone agonists 
Introduction:
We sought to compare the rate of return of testosterone levels and sexual function in men with prostate cancer receiving longer acting, 3-month preparation of luteinizing hormone-releasing hormone agonist (L-LHRH-A) versus shorter acting, 1-month preparation of luteinizing hormone-releasing hormone agonist (S-LHRH-A).
Methods and Materials:
Men with low to intermediate risk localized prostate cancer were randomized to either L-LHRH-A (2–3 month duration LHRH-A) or S-LHRH-A (6-1 month duration LHRH-A) of androgen suppression therapy (AST) and prostate brachytherapy using iodine-125 radioisotopes. Serum total testosterone levels and PSA were recorded every 2 months for 2 years.
Results:
A planned target sample size of 100 was not achieved due to insufficient accrual. A total of 55 patients were randomized and 46 were used for analysis. The median time to recovery of testosterone to baseline levels (calculated from end of AST) was 8 and 4 months in the L-LHRH-A and S-LHRH-A arms, respectively (p = 0.268). The median time to testosterone recovery to lower limit of reference range was 4 and 2 months respectively (p = 0.087).
Interpretation:
This randomized study, which failed to reach accrual target, showed a trend towards more rapid recovery of testosterone levels using shorter acting LHRH-A. Another randomized study would be required to validate these findings. Currently, there is insufficient evidence to recommend the use of shorter acting LHRH-A as a means of providing more rapid recovery of testosterone levels.
doi:10.5489/cuaj.10102
PMCID: PMC3114026  PMID: 21672478
7.  Validation of a Web-Based Predictive Nomogram for Ipsilateral Breast Tumor Recurrence After Breast Conserving Therapy 
Journal of Clinical Oncology  2010;28(5):718-722.
Purpose
IBTR! version 1.0 is a web-based tool that uses literature-derived relative risk ratios for seven clinicopathologic variables to predict ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT). Preliminary testing demonstrated over-estimation in high-risk subgroups. This study uses two independent population-based datasets to create and validate a modified nomogram, IBTR! version 2.0.
Methods
Cox regression modeling was performed on 7,811 patients treated with BCT at the British Columbia Cancer Agency (median follow-up, 9.4 years). Population-based hazard ratios were generated for the seven variables in the original nomogram. A modified nomogram was then tested against 664 patients from Massachusetts General Hospital (median follow-up, 9.3 years). The mean predicted and observed 10-year estimates were compared for the entire cohort and for four groups predefined by nomogram-predicted risks: group 1: less than 3%; group 2: 3% to 5%; group 3: 5% to 10%; and group 4: more than 10%.
Results
IBTR! version 2.0 predicted an overall 10-year IBTR estimate of 4.0% (95% CI, 3.8 to 4.2), while the observed estimate was 2.8% (95% CI, 1.6 to 4.7; P = .10). The predicted and observed IBTR estimates were: group 1 (n = 283): 2.2% versus 1.3%, P = .40; group 2 (n = 237): 3.8% versus 3.5%, P = .80; group 3 (n = 111): 6.7% versus 3.2%, P = .05; and group 4 (n = 33): 12.5% versus 8.7%, P = .50.
Conclusion
IBTR! version 2.0 is accurate in the majority of patients with a low to moderate risk of in-breast recurrence. The nomogram still overestimates risk in a minority of patients with higher risk features. Validation in a larger prospective data set is warranted.
doi:10.1200/JCO.2009.22.6662
PMCID: PMC2834390  PMID: 20048188
8.  A reliability and validity study of the Palliative Performance Scale 
BMC Palliative Care  2008;7:10.
Background
The Palliative Performance Scale (PPS) was first introduced in1996 as a new tool for measurement of performance status in palliative care. PPS has been used in many countries and has been translated into other languages.
Methods
This study evaluated the reliability and validity of PPS. A web-based, case scenarios study with a test-retest format was used to determine reliability. Fifty-three participants were recruited and randomly divided into two groups, each evaluating 11 cases at two time points. The validity study was based on the content validation of 15 palliative care experts conducted over telephone interviews, with discussion on five themes: PPS as clinical assessment tool, the usefulness of PPS, PPS scores affecting decision making, the problems in using PPS, and the adequacy of PPS instruction.
Results
The intraclass correlation coefficients for absolute agreement were 0.959 and 0.964 for Group 1, at Time-1 and Time-2; 0.951 and 0.931 for Group 2, at Time-1 and Time-2 respectively. Results showed that the participants were consistent in their scoring over the two times, with a mean Cohen's kappa of 0.67 for Group 1 and 0.71 for Group 2. In the validity study, all experts agreed that PPS is a valuable clinical assessment tool in palliative care. Many of them have already incorporated PPS as part of their practice standard.
Conclusion
The results of the reliability study demonstrated that PPS is a reliable tool. The validity study found that most experts did not feel a need to further modify PPS and, only two experts requested that some performance status measures be defined more clearly. Areas of PPS use include prognostication, disease monitoring, care planning, hospital resource allocation, clinical teaching and research. PPS is also a good communication tool between palliative care workers.
doi:10.1186/1472-684X-7-10
PMCID: PMC2527603  PMID: 18680590
9.  In the absence of cancer registry data, is it sensible to assess incidence using hospital separation records? 
Background
Within the health literature, a major goal is to understand distribution of service utilisation by social location. Given equivalent access, differential incidence leads to an expectation of differential service utilisation. Cancer incidence is differentially distributed with respect to socioeconomic status. However, not all jurisdictions have incidence registries, and not all registries allow linkage with utilisation records. The British Columbia Linked Health Data resource allows such linkage. Consequently, we examine whether, in the absence of registry data, first hospitalisation can act as a proxy measure for incidence, and therefore as a measure of need for service.
Methods
Data are drawn from the British Columbia Linked Health Data resource, and represent 100% of Vancouver Island Health Authority cancer registry and hospital records, 1990–1999. Hospital separations (discharges) with principal diagnosis ICD-9 codes 140–208 are included, as are registry records with ICDO-2 codes C00-C97. Non-melanoma skin cancer (173/C44) is excluded. Lung, colorectal, female breast, and prostate cancers are examined separately. We compare registry and hospital annual counts and age-sex distributions, and whether the same individuals are represented in both datasets. Sensitivity, specificity and predictive values are calculated, as is the kappa statistic for agreement. The registry is designated the gold standard.
Results
For all cancers combined, first hospitalisation counts consistently overestimate registry incidence counts. From 1995–1999, there is no significant difference between registry and hospital counts for lung and colorectal cancer (p = 0.42 and p = 0.56, respectively). Age-sex distribution does not differ for colorectal cancer. Ten-year period sensitivity ranges from 73.0% for prostate cancer to 84.2% for colorectal cancer; ten-year positive predictive values range from 89.5% for female breast cancer to 79.35% for prostate cancer. Kappa values are consistently high.
Conclusion
Claims and registry databases overlap with an appreciable proportion of the same individuals. First hospital separation may be considered a proxy for incidence with reference to colorectal cancer since 1995. However, to examine equity across cancer health services utilisation, it is optimal to have access to both hospital and registry files.
doi:10.1186/1475-9276-5-12
PMCID: PMC1613240  PMID: 17026764

Results 1-9 (9)