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Biomedical subjects

William Lawrence

Publications and source records attributed to William Lawrence.

14 recordsLinked to original sources
PubMed2006

Psychological distress in U.S. women who have experienced false-positive mammograms.

BACKGROUND: In the United States, approximately 10.7% of all screening mammograms lead to a false-positive result, but the overall impact of false-positives on psychological well-being is poorly understood. MATERIALS AND METHODS: Data were analyzed from the 2000 U.S. National Health Interview Survey (NHIS), the most recent national survey that included a cancer control module. Study subjects were 9,755 women who ever had a mammogram, of which 1,450 had experienced a false-positive result. Psychological distress was assessed using the validated K6 questionnaire and logistic regression was used to discern any association with previous false-positive mammograms. RESULTS: In a multivariate analysis, women who had indicated a previous false-positive mammogram were more likely to report feeling sad (OR = 1.18, 95% CI, 1.03-1.35), restless (OR = 1.23, 95% CI, 1.08-1.40), worthless (OR = 1.27, 95% CI, 1.04-1.54), and finding that everything was an effort (OR = 1.27, 95% CI, 1.10-1.47). These women were also more likely to have seen a mental health professional in the 12 months preceding the survey (OR = 1.28, 95% CI, 1.03-1.58) and had a higher composite score on all items of the K6 scale (P < 0.0001), a reflection of increased psychological distress. Analyses by age and race revealed that, among women who had experienced false-positives, younger women were more likely to feel that everything was an effort, and blacks were more likely to feel restless. CONCLUSION: In a random sampling of the U.S. population, women who had previously experienced false-positive mammograms were more likely to report symptoms of anxiety and depression.

Adult↗
PubMed2006

NKG2D splice variants: a reexamination of adaptor molecule associations.

NKG2D is a homodimeric C-type lectin-related receptor expressed on natural killer (NK) cells and T cells. In mice, alternative deoxyribonucleic acid (DNA) splicing generates two isoforms of NKG2D that differ in the length of their cytoplasmic domains. Their ability to induce cellular activation is mediated via association with two membrane-bound, signaling adaptor molecules, DAP10 and DAP12. It has been reported that the long form of NKG2D associates exclusively with DAP10, whereas the short variant can interact with either adaptor. The short isoform was reported to be almost undetectable in naive NK cells. Using two distinct cell types, we demonstrate that like the short isoform, the long variant of NKG2D also associates not only with DAP10 but also with DAP12. Using reporter cells (70Z/3), we demonstrate that DAP12 can compete equally with DAP10 for association with both variants of NKG2D when DAP10 and DAP12 are coexpressed. Cross-linking either isoform of NKG2D induces a calcium flux when associated exclusively with DAP10 or DAP12. Moreover, using quantitative polymerase chain reaction (PCR), we also show that the short isoform of NKG2D is expressed in naive NK cells. Our data suggest that signaling via mouse NKG2D isoforms is more complex than originally presented.

Adaptor Proteins, Signal Transducing↗
PubMed2006

The SPECTRUM population model of the impact of screening and treatment on U.S. breast cancer trends from 1975 to 2000: principles and practice of the model methods.

OBJECTIVE: This stochastic simulation model was developed to estimate the impact of screening and treatment diffusion on U.S. breast cancer mortality between 1975 and 2000. MODELING APPROACH: We use an event-driven continuous-time state transition model. Women who are destined to develop breast cancer may be screen detected, present with symptoms, or die of other causes before cancer is diagnosed. At presentation, the cancer has a stage assigned on the basis of mode of detection. Cancers are assumed to be estrogen receptor (ER) positive or negative. Data on screening and treatment diffusion are based on national datasets; other parameters are based on a synthesis of the evidence available in the literature. MODEL METHODS: The model is calibrated to predict incidence and stage distribution (in situ, local, regional, and distant). Other than screening or treatment, background events that affect mortality are not explicitly modeled but are captured in the deviation between model projections of mortality trends and actual trends. We assume that: 1) tumors progress more slowly in older age groups, 2) screen- and clinically detected disease have the same survival conditional on age and stage, 3) women do not die of breast cancer within the "lead time" period, 4) screening benefits are captured by shifts in stage at diagnosis, 4) tamoxifen benefits only ER-positive women, and 5) preclinical sojourn time and dwell times in each of the clinical stages are stochastically independent. MODEL RESULTS: Dissemination of screening and therapeutic advances had a substantial impact on mortality trends. We estimate that, by the year 2000, diffusion of screening lowered mortality by 12.4% and treatment improvements and dissemination lowered mortality by 14.6%. CONCLUSIONS: Models such as this one can be useful to translate clinical trial findings to general populations. This model can also be used inform policy debates about how to best achieve targeted reductions in breast cancer morbidity and mortality.

Adult↗
PubMed2005

Chronic myeloid leukemia after treatment of lymphoid malignancies: response to imatinib mesylate and favorable outcomes in three patients.

Recent improved treatments for lymphoid malignancies produce more long-term survivors, yet increase the risk for secondary malignancies. Therapy-related myelodysplasia and acute myeloid leukemia are well described, but secondary chronic myeloid leukemia (CML) has only rarely been reported. We report three patients with CML diagnosed 8, 10 and 2.5 years following Hodgkin's disease, non-Hodgkin's lymphoma and chronic lymphocytic leukemia therapy, respectively. BCR-ABL transcripts were not detected after completion of primary therapy in two cases. All three patients received imatinib therapy, with one patient subsequently undergoing allogeneic hematopoietic stem cell transplantation. All three patients have ongoing favorable responses to CML therapy.

Adult↗
PubMed2005

Toward optimal screening strategies for older women. Costs, benefits, and harms of breast cancer screening by age, biology, and health status.

CONTEXT: Optimal ages of breast cancer screening cessation remain uncertain. OBJECTIVE: To evaluate screening policies based on age and quartiles of life expectancy (LE). DESIGN AND POPULATION: We used a stochastic model with proxies of age-dependent biology to evaluate the incremental U.S. societal costs and benefits of biennial screening from age 50 until age 70, 79, or lifetime. MAIN OUTCOME MEASURES: Discounted incremental costs per life years saved (LYS). RESULTS: Lifetime screening is expensive (151,434 dollars per LYS) if women have treatment and survival comparable to clinical trials (idealized); stopping at age 79 costs 82,063 dollars per LYS. This latter result corresponds to costs associated with an LE of 9.5 years at age 79, a value expected for 75% of 79-year-olds, about 50% of 80-year-olds, and 25% of 85-year-olds. Using actual treatment and survival patterns, screening benefits are greater, and lifetime screening of all women might be considered (114,905 dollars per LYS), especially for women in the top 25% of LE for their age (50,643 dollars per LYS, life expectancy of approximately 7 years at age 90). CONCLUSIONS: If all women receive idealized treatment, the benefits of mammography beyond age 79 are too low relative to their costs to justify continued screening. However, if treatment is not ideal, extending screening beyond age 79 could be considered, especially for women in the top 25% of life expectancy for their age.

Age Factors↗
PubMed2004

Benefits and costs of interventions to improve breast cancer outcomes in African American women.

PURPOSE: Historically, African American women have experienced higher breast cancer mortality than white women, despite lower incidence. Our objective was to evaluate whether costs of increasing rates of screening or application of intensive treatment will be off-set by survival benefits for African American women. METHODS: We use a stochastic simulation model of the natural history of breast cancer to evaluate the incremental societal costs and benefits of status quo versus targeted biennial screening or treatment improvements among African Americans 40 years of age and older. Main outcome measures were number of mammograms, stage, all-cause mortality, and discounted costs per life year saved (LYS). RESULTS: At the current screening rate of 76%, there is little incremental benefit associated with further increasing screening, and the costs are high: 124,053 US dollars and 124,217 US dollars per LYS for lay health worker and patient reminder interventions, respectively, compared with the status quo. Using reminders would cost 51,537 US dollars per LYS if targeted to virtually unscreened women or 78,130 US dollars per LYS if targeted to women with a two-fold increase in baseline risk. If all patients received the most intensive treatment recommended, costs increase but deaths decrease, for a cost of 52,678 US dollars per LYS. Investments of up to 6,000 US dollars per breast cancer patient could be used to enhance treatment and still yield cost-effectiveness ratios of less than 75,000 US dollars per LYS. CONCLUSION: Except in pockets of unscreened or high-risk women, further investments in interventions to increase screening are unlikely to be an efficient use of resources. Ensuring that African American women receive intensive treatment seems to be the most cost-effective approach to decreasing the disproportionate mortality experienced by this population.

Adult↗
PubMed2004

Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients.

PURPOSE: Approximately 5% to 10% of newly diagnosed breast cancer patients carry a BRCA1 or BRCA2 mutation. Given these patients' high risk for contralateral breast cancer, bilateral mastectomy is increasingly considered a treatment option for newly diagnosed BRCA1/2 carriers. In the present study, we prospectively evaluated the impact on surgical decision-making of pretreatment genetic counseling and BRCA1/BRCA2 testing among breast cancer patients at high-risk for carrying a mutation. PATIENTS AND METHODS: Participants were 194 newly diagnosed breast cancer patients who had not yet received definitive surgical treatment and who had at least a 10% prior probability of carrying a BRCA1/2 mutation. Participants were offered free genetic counseling and rapid BRCA1/2 testing. Primary analyses focused on the impact of BRCA1/2 test result on subsequent breast cancer surgical treatment. RESULTS: Forty-eight percent of patients who were found to carry a BRCA1/2 mutation chose bilateral mastectomy as their definitive breast cancer surgery. In contrast, 24% of patients in whom no mutation was detected and 4% of test decliners opted for bilateral mastectomy. Additional predictors of bilateral mastectomy included patients' self-reports of physician recommendations for BRCA1/2 testing and bilateral mastectomy. CONCLUSION: This study highlights patient interest in and the technical feasibility of offering presurgery BRCA1/2 testing to high-risk patients. Most importantly, these results demonstrate that BRCA1/2 test results significantly affect patients' surgical decision-making. The availability of genetic counseling and testing could serve as a valuable aid to patient decision-making for newly diagnosed breast cancer patients at high-risk for carrying a mutation.

Adult↗
PubMed2004

Descriptive review of the literature on breast cancer outcomes: 1990 through 2000.

BACKGROUND: There is increasing interest in the incorporation of nonbiomedical outcomes into cancer research. OBJECTIVE: Our goal was to review the use of nonbiomedical outcomes in research on breast cancer care. DATA SOURCES: We conducted a MEDLINE search of all studies on breast cancer quality of life, preferences, satisfaction, and economics that were published during the period from January 1, 1990, through December 31, 2000. We also searched bibliographies of published articles. STUDY SELECTION: We included original primary research and excluded reviews, methods papers, studies conducted outside the United States and Western Europe, or studies with fewer than 100 subjects. DATA ABSTRACTION: Data were abstracted by using a structured tool. DATA SYNTHESIS: There were 1089 articles identified; 230 were included. The greatest proportion of research focused on survivorship followed by screening. The most frequently reported outcomes were health-related quality of life (54%) followed by economic analyses (38%) and patient satisfaction (14%); only 9% measured patient preferences. Few studies included more than 10% nonwhite populations or focused on the elderly. No single instrument was used in more than 10% of the studies, and many authors developed de novo tools for use in their study. Methodologic flaws were prevalent and included use of nonstandard economic methods, insufficient power, low or differential response rates, and lack of control for baseline status. CONCLUSION: At present, outcomes measurement is variable in its approach and application to breast cancer care. More research is needed to develop practical approaches that are reliable, valid, and feasible in routine practice, that are applicable to diverse populations, and that can inform interventions to improve the quality of care across the full spectrum of services.

Breast Neoplasms↗
PubMed2002

Is outcomes research on cancer ready for prime time?

Contemporary treatment of patients with cancer has been challenged by the same influences that have stimulated broad interest among stakeholders in assessing the outcomes or "results" of medical care. These interrelated external forces include growing awareness of practice variations, increased recognition of the patient's central role in decision making, acknowledgment that treatment decisions for situations where cure is not possible require explicit metrics to assess trade-offs between length and quality of life, strong interest in cost containment, and broad public concern that efforts to rationalize spending may have led to decreases in quality of care. Clinical and health services researchers interested in cancer diagnosis and treatment have striven to address these issues and have been in the forefront of efforts to develop and use valid measures of health-related quality of life. However, the current challenges to the field of outcomes research are equally applicable to those applying its tools and methods to the study of cancer: lack of standardization of outcomes measures, limited evidence that assessing outcomes of care is followed by improved outcomes in practice, and development of a research infrastructure that links the products of outcomes research with informed, shared decision making in routine practice. The purpose of this article is to provide a brief overview of lessons learned from the first decade of outcomes research sponsored by the Agency for Healthcare Research and Quality that will inform suggested directions for future directions for cancer outcomes research.

Decision Making↗
PubMed2002

Diagnosis of community-acquired pertussis infection: comparison of both culture and fluorescent-antibody assays with PCR detection using electrophoresis or dot blot hybridization.

Diagnosis of Bordetella pertussis infection has been difficult due to the low sensitivity of culture. PCR tests have been shown to be more sensitive than culture, but the reported sensitivity of PCR is variable. We evaluated PCR product detection by using either agarose gel electrophoresis (PCR-gel) or dot blot hybridization with (32)P-labeled oligonucleotide probes, and we compared these methods to both culture and direct fluorescent-antibody (DFA) assays with microscopy for the detection of pertussis. This was done with 225 nasopharyngeal swab specimens collected in community clinic settings. The multiplexed PCR amplified the multiply repeated IS481 B. pertussis sequence and a sequence from the human globin gene as a positive control for specimen adequacy. Of 225 specimens, 179 were judged to be adequate for PCR analysis. Among the adequate specimens, 9, 4, and 10 were culture, DFA, and PCR-gel positive, respectively. The sensitivity of PCR-gel versus culture was 89% while the sensitivity of culture versus PCR-gel was 80%. DFA had the lowest sensitivity. Thirty specimens were positive by PCR with dot blot hybridization; no negative control specimens showed a signal above the background. Among the 79 (44%) adequate specimens with clinical data available, the rates of reported cough or persistent cough were similar for persons who were pertussis positive by each assay. The IS481 PCR, with either electrophoresis or dot blot hybridization, is a sensitive assay; however, at this time it cannot completely replace culture without an overall loss in sensitivity for the detection of pertussis. Further study is required to understand the clinical significance of B. pertussis PCR products detected by dot blot hybridization alone.

Bacteriological Techniques↗
PubMed2002

Feasibility of mobile cancer screening and prevention.

Many areas have high cancer mortality rates and medically underserved populations. This study describes the feasibility (acceptability and costs) of an urban multiphasic (multiple cancers) screening van. Feasibility was evaluated by literature review and informant interviews. Costs were estimated by resource use from urban mobile screening units; decision analysis estimated the costs per cancer detected for breast, cervix, colorectal, and prostate cancer screening. Acceptability of a multiphasic van varied by the informant's perspective. Feasibility and costs were most sensitive to four parameters: age, prior screening history, risk factors, and volume of simultaneous examinations. Subsidized mobile screening facilities may have the potential to reduce cancer morbidity and mortality if they target hard-to-reach underscreened groups, maintain high volume, coordinate with primary care providers, and build on an infrastructure that provides diagnostic and treatment services regardless of ability to pay. It is unclear whether the investment required will translate into a reasonable cost per year of life saved.

Cost-Benefit Analysis↗
PubMedDate not supplied

Characterization of long-term outcomes after Toupet fundoplication: symptoms, medication use, and health status.

GOALS AND BACKGROUND: Fundoplication is increasingly used for the treatment of gastroesophageal reflux disease (GERD). Few studies have tracked patient outcomes of the Toupet method for more than 1 year. Further clinical, physiologic, and patient-based outcome measures have not been well characterized for this method. The current study conducts a long-term, comprehensive outcome evaluation in patients receiving Toupet fundoplication. STUDY: Fifty-five patients who had previously undergone fundoplication were examined. In a subset of 24 patients, esophagogastroduodenoscopy was used to assess the severity of reflux esophagitis. Manometry and ambulatory pH monitoring also were performed. RESULTS: Patients were studied 2.9 (+/- 0.7) years after surgery. Sixty-seven percent of the sample reported heartburn, 51% reported postoperative bloating, 33% reported regurgitation, and 20% reported dysphagia. Thirty-three percent reported the use of prescription medications for GERD-related symptoms. Health status was diminished relative to population norms. Degree of GERD severity was associated with symptom reports and medication use. CONCLUSIONS: Although fundoplication is thought to be a curative procedure, the current findings suggest that many patients take symptomatic therapies and report symptoms and diminished health status up to 2 years after the procedure. These outcomes are associated with physiologic findings. Thus, these findings suggest that symptom-free status and absence of medication use cannot be assumed for all patients after Toupet fundoplication.

Endoscopy, Digestive System↗