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David Gifford

Publications and source records attributed to David Gifford.

12 recordsLinked to original sources
PubMed2006

A molecular correlate to the Gleason grading system for prostate adenocarcinoma.

Adenocarcinomas of the prostate can be categorized into tumor grades based on the extent to which the cancers histologically resemble normal prostate glands. Because grades are surrogates of intrinsic tumor behavior, characterizing the molecular phenotype of grade is of potential clinical importance. To identify molecular alterations underlying prostate cancer grades, we used microdissection to obtain specific cohorts of cancer cells corresponding to the most common Gleason patterns (patterns 3, 4, and 5) from 29 radical prostatectomy samples. We paired each cancer sample with matched benign lumenal prostate epithelial cells and profiled transcript abundance levels by microarray analysis. We identified an 86-gene model capable of distinguishing low-grade (pattern 3) from high-grade (patterns 4 and 5) cancers. This model performed with 76% accuracy when applied to an independent set of 30 primary prostate carcinomas. Using tissue microarrays comprising >800 prostate samples, we confirmed a significant association between high levels of monoamine oxidase A expression and poorly differentiated cancers by immunohistochemistry. We also confirmed grade-associated levels of defender against death (DAD1) protein and HSD17 beta4 transcripts by immunohistochemistry and quantitative RT-PCR, respectively. The altered expression of these genes provides functional insights into grade-associated features of therapy resistance and tissue invasion. Furthermore, in identifying a profile of 86 genes that distinguish high- from low-grade carcinomas, we have generated a set of potential targets for modulating the development and progression of the lethal prostate cancer phenotype.

Adenocarcinoma↗
PubMed2006

Influence of surgical manipulation on prostate gene expression: implications for molecular correlates of treatment effects and disease prognosis.

PURPOSE: Measurements of tissue gene expression are increasingly used for disease stratification, clinical trial eligibility, and assessment of neoadjuvant therapy response. However, the method of tissue acquisition alone could significantly influence the expression of specific transcripts or proteins. This study examines whether there are transcript alterations associated with surgical resection of the prostate gland by radical retropubic prostatectomy. MATERIALS AND METHODS: Twelve patients with clinically localized prostate cancer underwent immediate in situ prostate biopsy after induction of anesthesia for radical prostatectomy. Ex vivo prostate biopsies were performed immediately after surgical removal. Prostate epithelium was acquired by laser-capture microdissection, and transcript abundance levels were quantitated by cDNA microarray hybridization and confirmed by quantitative polymerase chain reaction. Data were analyzed by paired, two-sample t test using Statistical Analysis of Microarray algorithms, and linear models were fit as a function of clinical characteristics. RESULTS: Of 5,753 cDNAs with measurable expression in prostate epithelium, 88 (1.5%) were altered as a result of surgery (false-discovery rate < or = 10%), representing 62 unique genes. These included transcripts encoding acute phase response proteins, IER2 and JUNB, and regulators of cell proliferation, p21Cip1 and KLF6. Of the clinical characteristics examined, including patient age, prostate volume, serum prostate-specific antigen, blood loss, and operative time, only gland volume was significantly and negatively associated with the magnitude of gene expression difference between pre- and postsurgical specimens. CONCLUSION: Surgical manipulation results in significant gene expression changes. Molecular analyses of surgical samples should recognize that transcript alterations occur rapidly, and these results are important when designing and analyzing molecular correlates of clinical studies.

Aged↗
PubMed2005

Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma.

Prostate carcinogenesis is influenced by genetic alterations resulting in a biochemical condition that favors cell proliferation and survival. Studies of prostate carcinoma using comparative genomic hybridization and cDNA microarray analysis indicate that numerous biochemical processes may be affected during cellular transformation and progression to an invasive phenotype. Among the consistently observed tumor-associated changes are alterations in fatty acid metabolism that influence diverse cellular activities such as signaling, energy utilization, and membrane fluidity. Increases in fatty acid synthase (FAS) levels have been shown to be one of the earliest and most frequent molecular alterations in prostate carcinogenesis. We sought to identify tumor-associated changes in the expression of genes with functional roles associated with lipid metabolism. Defined populations of normal and neoplastic prostate epithelium were acquired by laser capture microdissection and transcript levels were measured by cDNA microarray hybridization. We determined that stearoyl-CoA desaturase (SCD) transcripts were downregulated in cancer relative to normal epithelium. These results were confirmed by quantitative PCR. Further analysis by immunohistochemical evaluation of radical prostatectomy samples employed a quantitative scoring system with a range of 0-300. The median SCD expression levels were 150, 45 and 10 for normal, PIN and carcinoma samples, respectively. Statistically significant differential SCD expression between normal and cancerous epithelium was determined at the p=0.001 level, and between PIN and prostate carcinoma at the p=0.03 level. Of these cases, 92% overexpressed fatty acid synthase (FAS) in cancerous cells and 84.7% exhibited the signature of FAS overexpression and SCD loss in prostate carcinoma as compared to normal prostate epithelium. These results indicate that loss of SCD expression is a frequent event in prostate adenocarcinoma, and further supports a role for altered lipid metabolism as a factor in the process of carcinogenesis.

Blotting, Northern↗
PubMed2005

The employment of nurse practitioners and physician assistants in U.S. nursing homes.

PURPOSE: Nursing facilities with nurse practitioners or physician assistants (NPs or PAs) have been reported to provide better care to residents. Assuming that freestanding nursing homes in urban areas that employ these professionals are making an investment in medical infrastructure, we test the hypotheses that facilities in states with higher Medicaid rates, and those in more competitive markets and markets with higher managed care penetration, are more likely to employ NPs or PAs. DESIGN AND METHODS: The Online Survey Certification and Reporting System (OSCAR) database, Area Resource File, and information from surveys of state policies from 1993 to 2002 are used to study the employment of NPs or PAs, using a cross-sectional time-series generalized estimating equation model with surveys nested within facilities, testing several market and state-policy effects while controlling for facility and market characteristics. RESULTS: Throughout the 1990s the proportion of nursing facilities with NPs or PAs doubled, from less than 10% to over 20%. Facilities in states in the upper quartile of Medicaid reimbursement rates were 10% more likely to employ NPs or PAs. Facilities in more competitive markets, and in markets with higher managed care penetration, were more likely to employ NPs or PAs (adjusted odds ratio = 1.27, 1.20 respectively). IMPLICATIONS: More generous state Medicaid nursing home reimbursement and higher competition may advance the investment in medical infrastructure, which in turn may positively affect the quality of care provided to nursing home residents.

Economic Competition↗
PubMed2005

Detection of delirium in the intensive care unit: comparison of confusion assessment method for the intensive care unit with confusion assessment method ratings.

OBJECTIVES: To compare the Confusion Assessment Method (CAM) and CAM for the Intensive Care Unit (CAM-ICU) methods for detecting delirium in alert, nonintubated older ICU patients. DESIGN: Comparison study. SETTING: Fourteen-bed medical ICU of an 800-bed university teaching hospital. PARTICIPANTS: Twenty-two patients aged 65 and older admitted to the ICU. MEASUREMENTS: Two blinded, trained clinician-researchers who had undergone interrater reliability testing interviewed patients separately, usually within 10 minutes of each other (up to 120 minutes). Each researcher examined patients for the four key CAM criteria: acuteness, inattention, disorganized thinking, and altered level of consciousness. One researcher used the CAM method with the Mini-Mental State Examination and Digit Span; the other researcher used the CAM-ICU method with nonverbal cognitive and attention tasks. RESULTS: Rates of delirium were 68% according to CAM and 50% according CAM-ICU. Comparing the two methods, agreement was 82%, with a kappa of 0.64. Using the CAM as the reference standard, the CAM-ICU had a sensitivity of 73% (95% confidence interval (CI)=60-86) and specificity of 100% (95% CI=56-100). There were four false-negative ratings using the CAM-ICU. Reasons for disparate results were that the CAM used more-detailed cognitive testing that detected more deficits (3 patients) and the time elapsed (90 minutes) between ratings in one patient with markedly fluctuating symptoms. CONCLUSION: CAM and CAM-ICU agreement was moderately high. Although the CAM-ICU is recommended for ICU patients because of its brevity and ease of use, the standard CAM method may detect more subtle cases of delirium in nonintubated, verbal ICU patients.

Aged↗
PubMed2005

Microbubble production in an in vitro cardiopulmonary bypass circuit ventilated with xenon.

Xenon, as an anaesthetic gas, has the potential to be used in an increasing range of applications. However, its use in cardiopulmonary bypass (CPB) has not yet progressed from the rat model due to concerns that its relative insolubility may cause microbubble formation and/or expansion in the micro-vasculature of the patient. An in vitro CPB circuit was designed to create and measure gaseous microbubbles over a range of temperature gradients, pressure drop and gas tensions. We were able to demonstrate that our test circuit did not produce any significant microbubbles and that, under normal physiological blood pressures, a fixed gas bubble in connection with the circuit did not grow in the presence of Xe.

Blood Gas Analysis↗
PubMed2003

Approaches to quality improvement in nursing homes: lessons learned from the six-state pilot of CMS's Nursing Home Quality Initiative.

BACKGROUND: In November 2002, the Centers for Medicare & Medicaid Services (CMS) launched a Nursing Home Quality Initiative that included publicly reporting a set of Quality Measures for all nursing homes in the country, and providing quality improvement assistance to nursing homes nationwide. A pilot of this initiative occurred in six states for six months prior to the launch. METHODS: Review and analysis of the lessons learned from the six Quality Improvement Organizations (QIOs) that led quality improvement efforts in nursing homes from the six pilot states. RESULTS: QIOs in the six pilot states found several key outcomes of the Nursing Home Quality Initiative that help to maximize the potential of public reporting to leverage effective improvement in nursing home quality of care. First, public reporting focuses the attention of all stakeholders in the nursing home industry on achieving good quality outcomes on a defined set of measures, and creates an incentive for partnership formation. Second, publicly reported quality measures motivate nursing home providers to improve in certain key clinical areas, and in particular to seek out new ways of changing processes of care, such as engaging physicians and the medical director more directly. Third, the lessons learned by QIOs in the pilot of this Initiative indicate that certain approaches to providing quality improvement assistance are key to guiding nursing home providers' desire and enthusiasm to improve towards a using a systematic approach to quality improvement. CONCLUSION: The Nursing Home Quality Initiative has already demonstrated the potential of public reporting to foster collaboration and coordination among nursing home stakeholders and to heighten interest of nursing homes in quality improvement techniques. The lessons learned from this pilot project have implications for any organizations or individuals planning quality improvement projects in the nursing home setting.

Journal Article↗
PubMed2003

The quality of quality measurement in U.S. nursing homes.

PURPOSE: This article examines various technical challenges inherent in the design, implementation, and dissemination of health care quality performance measures. DESIGN AND METHODS: Using national and state-specific Minimum Data Set data from 1999, we examined sample size, measure stability, creation of ordinal ranks, and risk adjustment as applied to aggregated facility quality indicators. RESULTS: Nursing home Quality Indicators now in use are multidimensional and quarterly estimates of incidence-based measures can be relatively unstable, suggesting the need for some averaging of measures over time. IMPLICATIONS: Current public reports benchmarking nursing homes' performances may require additional technical modifications to avoid compromising the fairness of comparisons.

Nursing Homes↗
PubMed2003

Reporting quality of nursing home care to consumers: the Maryland experience.

OBJECTIVE: To design and implement a reporting system for quality of long-term care to empower consumers and to create incentives for quality improvement. To identify a model to approach this technically and politically difficult task. APPROACH: Establishment of a credible and transparent decision process using a public forum. Development of the system based on: (1) review of the literature and existing systems, and discussions with stakeholders about strengths and weaknesses; (2) focus on consumer preferences in the design; and (3) responsiveness to industry concerns in the implementation. LESSONS LEARNED: None of the existing systems appeared to be a suitable model. We decided to develop an entirely new system based on three key design principles that allowed us to tailor the system to consumer needs: (1) designing a decision tool rather than a database; (2) summarizing rather than simplifying information; and (3) accounting for the target audience in the creative execution. Industry concerns focused on the burden of the system, the potential for errors, and the possible communication of a negative impression of the industry. As methodological and data limitations prevented us from resolving those concerns, we addressed them by using cautionary language in the presentation and by making a commitment to incorporate improvements in the future. All stakeholders regarded the final design as an acceptable compromise. CONCLUSIONS: Despite its potentially controversial nature and many methodological challenges, the system has been well received by both the public and the industry. We attribute this success to two key factors: a collaborative decision process, in which all critical design and execution choices were laid out explicitly and debated with stakeholders in a public forum, and realism and honesty regarding the limitations of the system.

Aged↗
PubMed2002

Bayesian network approach to cell signaling pathway modeling.

The modeling of cellular signaling pathways is an emerging field. Sachs et al. illustrate the application of Bayesian networks to an example cellular pathway involving the activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) in response to fibronectin binding to an integrin. They describe how to use the analysis to select from among proposed models, formulate hypotheses regarding component interactions, and uncover potential dynamic changes in the interactions between these components. Although the data sets currently available for this example problem are too small to definitively point to a particular model, the approach and results provide a glimpse into the power that these methods will achieve once the technology for obtaining the necessary data becomes readily available.

Bayes Theorem↗
PubMedDate not supplied

Access to postacute nursing home care before and after the BBA. Balanced Budget Act.

Anecdotal reports in the wake of the Balanced Budget Act (BBA) of 1997 raised concerns about restricted access to postacute nursing facility care for Medicare beneficiaries requiring costly, medically complex services. Using all Medicare Part A hospital and nursing facility claims for providers in the state of Ohio and a refined method of identifying hospitalized beneficiaries who were the most at risk, we observed only a small decrease in the proportion of the costliest patients discharged to nursing facilities in 1999 compared with pre-BBA years. Average hospital length-of-stay increased only slightly in 1999, and there were no changes in rehospitalization rates for the costliest patient types. However, reduced rates of admission were concentrated in specific types of nursing facilities, suggesting a need to closely monitor the effects of ongoing post-BBA policy updates.

Aged↗