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Biomedical subjects

K A Phillips

Publications and source records attributed to K A Phillips.

At least 37 records · Page 2Linked to original sources

Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study.

BACKGROUND: Research on the pharmacotherapy of body dysmorphic disorder (BDD) is limited. No placebo-controlled, continuation, maintenance, or discontinuation studies have been published. Only one augmentation study has been published. METHOD: In this chart-review study of 90 patients with DSM-IV BDD treated for up to 8 years by the first 2 authors (K.A.P., R.S.A.) in their clinical practice, response to a variety of medications, including augmentation strategies, was assessed. The relapse rate with medication discontinuation was also determined. RESULTS: All subjects received a serotonin reuptake inhibitor (SRI), with 63.2% (55/87) of adequate SRI trials resulting in improvement in BDD symptoms; similar response rates were obtained for each type of SRI. Discontinuation of an effective SRI resulted in relapse in 83.8% (31/37) of cases. Response rates to selective SRI augmentation were clomipramine, 44.4% (4/9) of trials; buspirone, 33.3% (12/36) of trials; lithium, 20.0% (1/5); methylphenidate, 16.7% (1/6); and antipsychotics, 15.4% (2/13) of trials. CONCLUSION: These findings from a clinical setting suggest that a majority of BDD patients improve with an SRI and that all SRIs appear effective. Certain SRI augmentation strategies may be beneficial. The high relapse rate with SRI discontinuation suggests that long-term treatment is often necessary. These preliminary findings require confirmation in placebo-controlled efficacy studies and effectiveness studies.

Adolescent↗

Health and economic benefits of increased beta-blocker use following myocardial infarction.

CONTEXT: beta-blockers are underused in patients who have myocardial infarction (MI), despite the proven efficacy of these agents. New evidence indicates that beta-blockers can have benefit in patients with conditions that have been considered relative contraindications. Understanding the consequences of underuse of beta-blockers is important because of the implications for current policy debates over quality-of-care measures and Medicare prescription drug coverage. OBJECTIVE: To examine the potential health and economic impact of increased use of beta-blockers in patients who have had MI. DESIGN AND SETTING: We used the Coronary Heart Disease (CHD) Policy Model, a computer-simulation Markov model of CHD in the US population, to estimate the epidemiological impact and cost-effectiveness of increased beta-blocker use from current to target levels among survivors of MI aged 35 to 84 years. Simulations included 1 cohort of MI survivors in 2000 followed up for 20 years and 20 successive annual cohorts of all first-MI survivors in 2000-2020. Mortality and morbidity from CHD were derived from published meta-analyses and recent studies. This analysis used a societal perspective. MAIN OUTCOME MEASURES: Prevented MIs, CHD mortality, life-years gained, and cost per quality-adjusted life-year (QALY) gained in 2000-2020. RESULTS: Initiating beta-blocker use for all MI survivors except those with absolute contraindications in 2000 and continuing treatment for 20 years would result in 4300 fewer CHD deaths, 3500 MIs prevented, and 45,000 life-years gained compared with current use. The incremental cost per QALY gained would be $4500. If this increase in beta-blocker use were implemented in all first-MI survivors annually over 20 years, beta-blockers would save $18 million and result in 72,000 fewer CHD deaths, 62,000 MIs prevented, and 447,000 life-years gained. Sensitivity analyses demonstrated that the cost-effectiveness of beta-blocker therapy would always be less than $11,000 per QALY gained, even under unfavorable assumptions, and may even be cost saving. Restricting beta-blockers only to ideal patients (those without absolute or relative contraindications) would reduce the epidemiological impact of beta-blocker therapy by about 60%. CONCLUSIONS: Our simulation indicates that increased use of beta-blockers after MI would lead to impressive gains in health and would be potentially cost saving. JAMA. 2000;284:2748-2754.

Adrenergic beta-Antagonists↗

Immunophenotypic and pathologic differences between BRCA1 and BRCA2 hereditary breast cancers.

Morphologically and clinically, breast cancer is a heterogeneous group of diseases. This heterogeneity may be a manifestation of differences in the molecular genetic events underlying distinct breast cancer pathogenesis pathways. Examination of hereditary breast cancers (HBC), which have in common an underlying germline mutation in BRCA1 or BRCA2, may provide further insight into this concept. Multiple studies have confirmed that BRCA1-associated HBC (BRCA1-HBC) generally exhibit a specific phenotype that is characterized by high tumor grade and estrogen receptor negativity. Conversely, discrepancies exist between the findings of studies that have examined BRCA2-HBC, and a specific phenotype has not been consistently described. The characteristic phenotype of BRCA1-associated tumors may prove a useful additional tool in selecting individuals with breast cancer who should be offered BRCA1 mutation testing, although further studies are required. Lastly, evidence is emerging to suggest that BRCA1 might be involved in the pathogenesis of a subgroup of non-HBC (by gene underexpression rather than mutation) and that these tumors may exhibit the same phenotype as their hereditary counterparts.

BRCA2 Protein↗

The cost-effectiveness of expanded HIV counselling and testing in primary care settings: a first look.

OBJECTIVE: To estimate the cost-effectiveness of approaches to expanded HIV counselling and testing. DESIGN: A cost-effectiveness analysis. SETTING: Primary care practices in the USA. PARTICIPANTS: New patient visits. INTERVENTIONS: Two approaches were examined: (i) requesting all patients to complete an HIV-risk screening instrument, with counselling as well as testing offered only to patients disclosing risk factors ('risk histories' option); and (ii) routine offering of voluntary testing to all patients, with consent obtained but no pre-test counselling ('routine testing'). MAIN OUTCOME MEASURES: The primary outcome was the cost per infection identified. We also examined: (i) the costs and numbers of infections averted if individuals change their risk behaviours; and (ii) the additional years of life and quality-adjusted life years (QALY) gained as a result of earlier HIV testing and treatment for infected individuals. RESULTS: Routine testing is the most cost-effective approach to identifying infected individuals at an incremental cost of US$4200 per infection identified. Although using risk histories is more costly and less effective than routine testing, it becomes similarly cost-effective using plausible ranges for sensitivity analyses. If at least 10% of HIV-positive individuals change their behavior, both routine testing and using risk histories would save money. If testing identifies infected individuals one year earlier than they otherwise would have been diagnosed, routine testing would cost US$22000 per QALY gained. CONCLUSION: Routine testing is the most cost-effective approach to identifying new HIV infections. However, using risk histories may be similarly cost-effective under various assumptions. Both routine testing and using risk histories are more cost-effective than current practices.

AIDS Serodiagnosis↗

Implications of stroke risk criteria on the anticoagulation decision in nonvalvular atrial fibrillation: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study.

BACKGROUND: Warfarin dramatically reduces the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) but increases the likelihood of bleeding. Accurately identifying patients who need anticoagulation is critical. We assessed the potential impact of prominent stroke risk classification schemes on this decision in a large sample of patients with NVAF. METHODS AND RESULTS: We used clinical and electrocardiographic databases to identify 13 559 ambulatory patients with NVAF from July 1996 through December 1997. We compared the proportion of patients classified as having a low enough stroke risk to receive aspirin using published criteria from the Atrial Fibrillation Investigators (AFI), American College of Chest Physicians (ACCP), and the Stroke Prevention in Atrial Fibrillation Investigators (SPAF). In this cohort, AFI criteria classified 11% as having a low stroke risk, compared with 23% for ACCP and 29% for SPAF (kappa range, 0.44 to 0.85). This 2- to-3-fold increase in low stroke risk patients by ACCP and SPAF criteria primarily resulted from the inclusion of many older subjects (65 to 75 years+/-men >75 years) with no additional clinical stroke risk factors. CONCLUSIONS: The age threshold for assigning an increased stroke risk has a dramatic impact on whether to recommend warfarin in populations of patients with NVAF. Large, prospective studies with many stroke events are needed to precisely determine the relationship of age to stroke risk in AF and to identify which AF subgroups are at a sufficiently low stroke risk to forego anticoagulation.

Aged↗

Rate of body dysmorphic disorder in dermatology patients.

BACKGROUND: Dermatologists appear to be the physicians most often seen by patients with the psychiatric condition body dysmorphic disorder (BDD), a distressing or impairing preoccupation with a nonexistent or slight defect in appearance. The frequency of BDD among patients seeking dermatologic treatment is unknown, however. OBJECTIVE: This study determined the percentage of patients seeking dermatologic treatment who screened positive for BDD. METHODS: A validated self-report questionnaire and a reliable defect severity scale were used to determine the rate of BDD in 268 patients seeking dermatologic treatment. RESULTS: A total of 11.9% (95% confidence interval [CI], 8.0%-15.8%) of patients screened positive for BDD. Rates were similar in a community general dermatology setting (14.4% [95% CI, 8.5%-20.3%]) and a university cosmetic surgery setting (10. 0% [95% CI, 6.1%-13.9%]). CONCLUSION: BDD appears relatively common among patients seeking dermatologic treatment. Further research is needed to confirm these findings and to assist dermatologists in identifying these potentially high-risk patients.

Adolescent↗

Characteristics of memory dysfunction in body dysmorphic disorder.

Although body dysmorphic disorder (BDD) is receiving increasing empirical attention, very little is known about neuropsychological deficits in this disorder. The current study investigated the nature of memory dysfunction in BDD, including the relationship between encoding strategies and verbal and nonverbal memory performance. We evaluated 17 patients with BDD and 17 healthy controls using the Rey-Osterrieth Complex Figure Test (RCFT) and the California Verbal Learning Test (CVLT). BDD patients differed significantly from healthy controls on verbal and nonverbal learning and memory indices. Multiple regression analyses revealed that group differences in free recall were statistically mediated by deficits in organizational strategies in the BDD cohort. These findings are similar to patterns previously observed in obsessive-compulsive disorder (OCD), suggesting a potential relationship between OCD and BDD. Studies in both groups have shown that verbal and nonverbal memory deficits are affected by impaired strategic processing.

Adult↗

Perceptions of Ashkenazi Jewish breast cancer patients on genetic testing for mutations in BRCA1 and BRCA2.

The perceived benefits and risks of genetic testing may vary between groups of individuals with different cultural, demographic, and family history features. This multicentre study examined the factors that influenced the decision to undergo genetic testing for BRCA1 and BRCA2 in Canadian Jewish women with breast cancer. A self-administered questionnaire was developed and distributed to 134 individuals enrolled in a research-based testing program for Ashkenazi women. The questionnaire assessed demographic, social, and family history parameters, and the influence of medical, family, social, psychological, and cultural/religious factors on decision making about genetic testing. Seventy-six percent of women completed the questionnaire. Forty-one percent of study participants had no family history of breast or ovarian cancer. The most important factors influencing the decision to undergo testing were a desire to contribute to research, potential benefit to other family members, curiosity, and the potential for relief if not found to be a carrier (endorsed by 87, 78, 70, and 60% of participants, respectively). The main perceived risks of undergoing genetic testing related to insurance discrimination, confidentiality, accuracy and interpretability of results, potential impact on marriage prospects for family members, and focus on the Jewish community (endorsed by 28, 24, 30, 17, and 14% of participants, respectively). This study provides novel information on the motivating factors for BRCA1 and BRCA2 mutation testing in Canadian women of Ashkenazi Jewish descent. The focus on altruistic factors and those related to perceived psychological benefits of testing is notable.

Adult↗

Quality of life for patients with body dysmorphic disorder.

Body dysmorphic disorder (BDD) is a relatively common, distressing, and impairing disorder. Quality of life in BDD, however, has not been investigated. In this study, 62 consecutive outpatients with BDD were evaluated with the self-report Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and other scales. SF-36 scores were descriptively compared to published norms for several populations. Physical health-related quality of life scores were generally worse than general U.S. population norms and better than norms for outpatients with a medical illness or depression. However, in all mental health domains, BDD subjects' scores were notably worse than norms for the general U.S. population and for patients with depression, diabetes, or a recent myocardial infarction. More severe BDD symptoms and greater delusionality were associated with poorer mental health-related quality of life. These results indicate that patients with BDD have notably poor mental health status and mental health-related quality of life.

Adolescent↗

Cognitive function in breast cancer patients receiving adjuvant chemotherapy.

PURPOSE: Breast cancer patients receiving chemotherapy have complained of difficulties in their ability to remember, think, and concentrate. This study assessed whether there are differences in cognitive function between breast cancer patients treated with standard-dose adjuvant chemotherapy compared with healthy controls. PATIENTS AND METHODS: The High Sensitivity Cognitive Screen and the Profile of Mood States (POMS) were used to assess cognitive function and mood in a group of 107 women. The women consisted of 31 breast cancer patients receiving adjuvant chemotherapy (group A), 40 breast cancer patients who had completed adjuvant chemotherapy a median of 2 years earlier (group B), and 36 healthy controls (group C). RESULTS: Univariate analysis showed statistically significant differences (P =.009) in overall cognitive function scores between groups A and C, with poorer function in patients receiving adjuvant chemotherapy. These differences remained significant (P =.046) when controlling for age, education level, and menopausal status. More patients had moderate or severe cognitive impairment in groups A and B than in controls (P </=.002). There were no significant differences in POMS scores between the groups, suggesting that the differences seen in cognitive scores were unlikely to be because of mood disturbance. CONCLUSION: Cognitive differences were observed in breast cancer patients receiving adjuvant chemotherapy compared with healthy controls. These differences did not seem to be caused by significant differences in mood disturbance between the two groups. If confirmed, these results have substantial implications for informed consent, counseling, and psychosocial support of patients receiving adjuvant chemotherapy for breast cancer.

Adult↗

Assessing the cost-effectiveness of pharmacogenomics.

The use of pharmacogenomics to individualize drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide cost-effective pharmaceutical care. However, the combinations of disease, drug, and genetic test characteristics that will provide clinically useful and economically feasible therapeutic interventions have not been clearly elucidated. The purpose of this paper was to develop a framework for evaluating the potential cost-effectiveness of pharmacogenomic strategies that will help scientists better understand the strategic implications of their research, assist in the design of clinical trials, and provide a guide for health care providers making reimbursement decisions. We reviewed concepts of cost-effectiveness analysis and pharmacogenomics and identified 5 primary characteristics that will enhance the cost-effectiveness of pharmacogenomics: 1) there are severe clinical or economic consequence that are avoided through the use of pharmacogenomics, 2) monitoring drug response using current methods is difficult, 3) a well-established association between genotype and clinical phenotype exists, 4) there is a rapid and relatively inexpensive genetic test, and 5) the variant gene is relatively common. We used this framework to evaluate several examples of pharmacogenomics. We found that pharmacogenomics offers great potential to improve patients' health in a cost-effective manner. However, pharmacogenomics will not be applied to all currently marketed drugs, and careful evaluations are needed on a case-by-case basis before investing resources in research and development of pharmacogenomic-based therapeutics and making reimbursement decisions.

Anticholesteremic Agents↗

HIV-1 drug resistance genotyping. A review of clinical and economic issues.

The development of mutations associated with resistance to antiretroviral therapy (ART) has been shown to be a major cause of treatment failure in patients infected with HIV-1. These resistance mutations can be assessed by a genotyping test that probes for specific mutations within the HIV genome or sequences specific genes, at a cost $US500/test (2000 prices). The stated goal of HIV-1 genotyping is to target HIV therapy effectively. This, as shown in the preliminary research, should result in better clinical outcomes and a lower incidence of virological failure and may be associated with lower costs of treatment. Failure of ART may result in an increase in costs of at least $US250 per patient per month, as assessed in 1 study, with costs rising further as patients experience multiple virological failures. Therefore, there is an economic as well as a therapeutic premium on the prevention of ART failure. The actual economic cost of genotyping has been preliminarily explored in the context of the antiretroVIRal ADAPTation (VIRADAPT) trial, which found no significant difference in the 1-year treatment cost of patients with and without genotyping. There is some evidence of cost neutrality or savings with genotypic testing but it needs to be further explored within the context of carefully framed prospective trials.

Anti-HIV Agents↗

Body dysmorphic disorder: diagnostic controversies and treatment challenges.

Body dysmorphic disorder (BDD) is a distressing, impairing, and relatively common yet underrecognized disorder. This clinically focused article discusses the following diagnostic controversies and challenges associated with BDD: the underdiagnosis and misdiagnosis of BDD, the relationship between BDD and obsessive-compulsive disorder, the relationship between BDD and depression, the delusionality controversy, and whether BDD can be diagnosed in children and adolescents. This article also discusses treatment controversies and challenges associated with serotonin reuptake inhibitors, antipsychotics, cognitive-behavioral therapy, approaches to treatment-resistant BDD, and getting reluctant patients to accept psychiatric treatment.

Adult↗

Implications of the genetics revolution for health services research: pharmacogenomics and improvements in drug therapy.

OBJECTIVE: To review the societal and economic implications of the use of genetic information to individualize drug therapies. Although studies have begun to address the ethical issues raised by the use of genetic information , few have examined the implications of pharmacogenomics f rom the perspective of health services research. PRINCIPAL FINDINGS: We propose a research agenda for health services research in three areas: (1) to evaluate the effectiveness and cost-effectiveness of pharmacogenomics; (2) to evaluate the effect of pharmacogenomics from the perspective of patients, providers, insurers, industry, and government ; and (3) to evaluate the ethical and societal implications of pharmacogenomics. Throughout the article we use the example of HIV genotyping as an illustration of how genetic technology is disseminated and used. CONCLUSION: More research is needed on the societal and economic implications of pharmacogenomics to inform the clinical and policy decisions about its use that will be increasingly urgent in the future.

Cost-Benefit Analysis↗

Warfarin use among ambulatory patients with nonvalvular atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study.

BACKGROUND: Warfarin dramatically reduces the risk for ischemic stroke in nonvalvular atrial fibrillation, but its use among ambulatory patients with atrial fibrillation has not been widely studied. OBJECTIVE: To assess the rates and predictors of warfarin use in ambulatory patients with nonvalvular atrial fibrillation. DESIGN: Cross-sectional study. SETTING: Large health maintenance organization. PATIENTS: 13428 patients with a confirmed ambulatory diagnosis of nonvalvular atrial fibrillation and known warfarin status between 1 July 1996 and 31 December 1997. MEASUREMENTS: Data from automated pharmacy, laboratory, and clinical-administrative databases were used to determine the prevalence and determinants of warfarin use in the 3 months before or after the identified diagnosis of atrial fibrillation. RESULTS: Of 11082 patients with nonvalvular atrial fibrillation and no known contraindications, 55% received warfarin. Warfarin use was substantially lower in patients who were younger than 55 years of age (44.3%) and those who were 85 years of age or older (35.4%). Only 59.3% of patients with one or more risk factors for stroke and no contraindications were receiving warfarin. Among a subset of "ideal" candidates to receive warfarin (persons 65 to 74 years of age who had no contraindications and had previous stroke, hypertension, or both), 62.1% had evidence of warfarin use. Among our entire cohort, the strongest predictors of receiving warfarin were previous stroke (adjusted odds ratio, 2.55 [95% CI, 2.23 to 2.92]), heart failure (odds ratio, 1.63 [CI, 1.51 to 1.77]), previous intracranial hemorrhage (odds ratio, 0.33 [CI, 0.21 to 0.52]), age 85 years or older (odds ratio, 0.35 [CI, 0.31 to 0.40]), and previous gastrointestinal hemorrhage (odds ratio, 0.47 [CI, 0.40 to 0.57]). CONCLUSIONS: In a large, contemporary cohort of ambulatory patients with atrial fibrillation who received care within a health maintenance organization, warfarin use was considerably higher than in other reported studies. Although the reasons why physicians did not prescribe warfarin could not be elucidated, many apparently eligible patients with atrial fibrillation and at least one additional risk factor for stroke, especially hypertension, did not receive anticoagulation. Interventions are needed to increase the use of warfarin for stroke prevention among appropriate candidates.

Aged↗

Continuing screening mammography in women aged 70 to 79 years: impact on life expectancy and cost-effectiveness.

CONTEXT: Mammography is recommended and is cost-effective for women aged 50 to 69 years, but the value of continuing screening mammography after age 69 years is not known. In particular, older women with low bone mineral density (BMD) have a lower risk of breast cancer and may benefit less from continued screening. OBJECTIVE: To compare life expectancy and cost-effectiveness of screening mammography in elderly women based on 3 screening strategies. DESIGN: Decision analysis and cost-effectiveness analysis using a Markov model. PATIENTS: General population of women aged 65 years or older. INTERVENTIONS: The analysis compared 3 strategies: (1) Undergoing biennial mammography from age 65 to 69 years; (2) undergoing biennial mammography from age 65 to 69 years, measurement of distal radial BMD at age 65 years, discontinuing screening at age 69 years in women in the lowest BMD quartile for age, and continuing biennial mammography to age 79 years in those in the top 3 quartiles of distal radius BMD; and (3) undergoing biennial mammography from age 65 to 79 years. MAIN OUTCOME MEASURES: Deaths due to breast cancer averted, life expectancy, and incremental cost-effectiveness ratios. RESULTS: Compared with discontinuing mammography screening at age 69 years, measuring BMD at age 65 years in 10000 women and continuing mammography to age 79 years only in women with BMD in the top 3 quartiles would prevent 9.4 deaths and add, on average, 2.1 days to life expectancy at an incremental cost of $66773 per year of life saved. Continuing mammography to age 79 years in all 10000 elderly women would prevent 1.4 additional breast cancer deaths and add only 7.2 hours to life expectancy at an incremental cost of $117689 per year of life saved compared with only continuing mammography to age 79 years in women with BMD in the top 3 quartiles. CONCLUSIONS: This analysis suggests that continuing mammography screening after age 69 years results in a small gain in life expectancy and is moderately cost-effective in those with high BMD and more costly in those with low BMD. Women's preferences for a small gain in life expectancy and the potential harms of screening mammography should play an important role when elderly women are deciding about screening.

Aged↗

Frequency of p53 mutations in breast carcinomas from Ashkenazi Jewish carriers of BRCA1 mutations.

BACKGROUND: Breast carcinomas occurring in carriers of BRCA1 gene mutations may have a distinctly different pathway of molecular pathogenesis from those occurring in noncarriers. Data from murine models implicate loss of p53 (also known as TP53) gene function as a critical early event in the malignant transformation of cells with a BRCA1 mutation. Therefore, breast tumors from BRCA1 mutation carriers might be expected to exhibit a high frequency of p53 mutations. This study examined the frequency of p53 mutations in the breast tumors of Ashkenazi Jewish carriers and noncarriers of BRCA1 mutations. METHODS: Tumor DNA from carriers and noncarriers of BRCA1 mutations was screened for mutations in exons 4 through 10 of the p53 gene by use of the polymerase chain reaction and single-strand conformation polymorphism (SSCP) analysis of the amplified DNA. Direct sequencing was performed on gene fragments that showed altered mobility in SSCP analysis. RESULTS: Mutations in the p53 gene were detected in 10 of 13 tumors from BRCA1 mutation carriers versus 10 of 33 tumors from non-carriers (two-sided P = .007). The p53 mutations were distributed throughout exons 4 through 10 and included both protein-truncating and missense mutations in both groups. CONCLUSIONS: A statistically significantly higher frequency of p53 mutations was found in breast tumors from carriers of BRCA1 mutations than from noncarriers, which adds to the accumulating evidence that loss of p53 function is an important step in the molecular pathogenesis of BRCA1 mutation-associated breast tumors. This finding may have implications for understanding phenotypic differences and potential prognostic differences between BRCA1 mutation-associated hereditary breast cancers and sporadic cancers.

Adult↗