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David Atkins

Publications and source records attributed to David Atkins.

31 records · Page 2Linked to original sources

Quantitative gene expression profiling in formalin-fixed, paraffin-embedded tissues using universal bead arrays.

We recently developed a sensitive and flexible gene expression profiling system that is not dependent on an intact poly-A tail and showed that it could be used to analyze degraded RNA samples. We hypothesized that the DASL (cDNA-mediated annealing, selection, extension and ligation) assay might be suitable for the analysis of formalin-fixed, paraffin-embedded tissues, an important source of archival tissue material. We now show that, using the DASL assay system, highly reproducible tissue- and cancer-specific gene expression profiles can be obtained with as little as 50 ng of total RNA isolated from formalin-fixed tissues that had been stored from 1 to over 10 years. Further, tissue- and cancer-specific markers derived from previous genome-wide expression profiling studies of fresh-frozen samples were validated in the formalin-fixed samples. The DASL assay system should prove useful for high-throughput expression profiling of archived clinical samples.

Algorithms↗

The cost-effectiveness of screening mammography beyond age 65 years: a systematic review for the U.S. Preventive Services Task Force.

PURPOSE: There are few data on the effects of disease biology and competing mortality on the effectiveness of screening women for breast cancer after age 65 years. The authors performed a review to determine the costs and benefits of mammography screening after age 65 years. DATA SOURCES: Cost-effectiveness articles published between January 1989 and March 2002. STUDY SELECTION: Studies were identified by using MEDLINE and the National Health Service Economic Evaluation Database. The authors included research on screening after age 65 years conducted from a societal or government perspective; reviews and analyses of other technologies were excluded. DATA SYNTHESIS: 115 studies were identified and 10 met inclusion criteria. One study modeled age-dependent assumptions of disease biology. No study fully captured the potential harms of screening, including anxiety associated with false-positive results, overdiagnosis, and previous knowledge of cancer or living longer with the consequences of treatment. Studies differed in the specific strategies compared and in analytic approaches. On average, extending biennial screening to age 75 or 80 years was estimated to cost 34 000 dollars to 88 000 dollars (2002 U.S. dollars) per life-year gained, compared with stopping screening at age 65 years. Two studies suggested that it was more cost-effective to target healthy women than those with several competing risks for death. CONCLUSIONS: Current estimates suggest that biennial breast cancer screening after age 65 years reduces mortality at reasonable costs for women without clinically significant comorbid conditions. More data are needed on disease biology and preferences for benefits and harms in older women.

Age Factors↗

Genetic test evaluation: information needs of clinicians, policy makers, and the public.

Growing knowledge about gene-disease associations will lead to new opportunities for genetic testing. Many experts predict that genetic testing will become increasingly important as a guide to prevention, clinical management, and drug treatment based on genetic susceptibilities. As part of a Human Genetic Epidemiology workshop convened by the Centers for Disease Control and Prevention, a group of experts evaluated the evidence needed when considering the appropriate use of new genetic tests. Because new tests are likely to vary in their predictive value, their potential to direct prevention or treatment efforts, and their personal and social consequences, the task of determining appropriate use will require careful consideration of a variety of factors, including the analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications of the test. Standardized formats are needed to summarize what is known and not known about new genetic tests with respect to each of these features. Following criteria for the objective assessment of test properties, reports should be structured to enable policy makers, clinicians, and the public to identify the available evidence, so that uncertainties can be taken into account when considering test use and planning future research.

Decision Making↗

Principles of preventive care.

Clinicians who wish to ensure that their prevention practices are current and appropriate should follow the following steps: Identify a source of prevention recommendations that is evidence-based and which has a perspective that matches that of your practice. Periodically review current recommendations to keep up with changing science. When a new screening test is introduced, ask whether it has been proven to improve important health outcomes or simply been shown to detect more disease. Consider what potential harms might be associated with screening. Acknowledge the role of the patient in decisions in areas of uncertainty. At the same time, educate patients that additional tests carry risks as well as benefits. Approach prevention as a package of important services. Educate patients of the need to address all important health issues rather than focusing on a single issue. Examine how well you are delivering high priority services.

Evidence-Based Medicine↗

Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.

BACKGROUND: Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer. METHODS: We analysed, with Affymetrix Human U133a GeneChips, the expression of 22000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment. FINDINGS: In a training set of 115 tumours, we identified a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years (hazard ratio 5.67 [95% CI 2.59-12.4]), even when corrected for traditional prognostic factors in multivariate analysis (5.55 [2.46-12.5]). The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients (9.60 [2.28-40.5]), 87 postmenopausal patients (4.04 [1.57-10.4]), and 79 patients with tumours of 10-20 mm (14.1 [3.34-59.2]), a group of patients for whom prediction of prognosis is especially difficult. INTERPRETATION: The identified signature provides a powerful tool for identification of patients at high risk of distant recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.

Adult↗

Making policy when the evidence is in dispute.

Policymakers often struggle with medical issues that are the subject of fierce scientific debate. On closer examination, many of these debates are manifestations of conflicting perspectives and values as much as disagreements over the evidence. We summarize common factors underlying recent debates and outline a series of questions that can help disentangle questions of evidence from those of values. These questions focus on identifying the most important outcomes, evaluating the quality of evidence, and assessing the trade-offs involved. We then use four recent policy debates-involving prostate-specific antigen (PSA) screening, high-dose chemotherapy for breast cancer, antibiotic therapy for otitis media, and newborn hearing screening-to illustrate how this approach can help clarify areas of agreement and disagreement of the opposing sides.

Anti-Bacterial Agents↗

Employer coverage of clinical preventive services in the United States.

PURPOSE: To characterize employers' coverage of clinical preventive services. DESIGN: Mercer Human Resource Consulting Inc. included questions on clinical preventive services as part of its National Survey of Employer-Sponsored Health Plans, 2001. SETTING: A national sample of employers of a large, medium, and small number of employees, including governments. SUBJECTS: Respondents self-identified as most knowledgeable about the organization's health benefits. MEASURES: Weighted analyses of responses to eight survey questions on health promotion. RESULTS: The survey was completed by 2180 employers, and the response rate was 21%. More than 90% of employers included increased productivity and decreased health care costs among their most important reasons for coverage of clinical preventive services. Within health insurance, coverage of physical examinations, immunizations, and screenings generally exceeded 50%, but coverage of lifestyle modification services was less than 20%. Only 20% of employers covered tobacco cessation services, and only 4% of employers provided an "optimal" benefit. We compared employers' offerings with a published ranking, by impact and value, of clinical preventive services. We found the biggest discrepancy in tobacco cessation services and alcohol problem prevention, which ranked high in terms of impact and value but are offered by only 20% and 18% of employers, respectively. CONCLUSIONS: Employers seek financial return from their offerings of clinical preventive services to employees, but they are least likely to offer the services most likely to provide this return.

Health Benefit Plans, Employee↗