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Biomedical subjects

K A Phillips

Publications and source records attributed to K A Phillips.

At least 19 recordsLinked to original sources
PubMed2001

Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review.

CONTEXT: Adverse drug reactions are a significant cause of morbidity and mortality. Although many adverse drug reactions are considered nonpreventable, recent developments suggest these reactions may be avoided through individualization of drug therapies based on genetic information, an application known as pharmacogenomics. OBJECTIVE: To evaluate the potential role of pharmacogenomics in reducing the incidence of adverse drug reactions. DATA SOURCES: MEDLINE English-language only searches for adverse drug reaction studies published between January 1995 and June 2000 and review articles of variant alleles of drug-metabolizing enzymes published between January 1997 and August 2000. We also used online resources, texts, and expert opinion. STUDY SELECTION: Detailed inclusion criteria were used to select studies. We included 18 of 333 adverse drug reaction studies and 22 of 61 variant allele review articles. DATA EXTRACTION: All the investigators reviewed and coded articles using standardized abstracting forms. DATA SYNTHESIS: We identified 27 drugs frequently cited in adverse drug reaction studies. Among these drugs, 59% are metabolized by at least 1 enzyme with a variant allele known to cause poor metabolism. Conversely, only 7% to 22% of randomly selected drugs are known to be metabolized by enzymes with this genetic variability (range, P =.006-P<.001). CONCLUSIONS: Our results suggest that drug therapy based on individuals' genetic makeups may result in a clinically important reduction in adverse outcomes. Our findings serve as a foundation for further research on how pharmacogenomics can reduce the incidence of adverse reactions and on the resulting clinical, societal, and economic implications.

Anticoagulants↗
PubMed2001

Deciding where and how to be tested for HIV: what matters most?

This study examined preferences for specific types of HIV tests as well as for test attributes such as cost, counseling, and privacy. A survey was administered to 354 clients of public testing services. Nonparametric tests and logistic regression were used to compare test preferences and attribute ratings, and to assess differences by demographic and risk groups. Nearly two thirds of respondents chose a public clinic test as their first choice, whereas 24% chose a home self-test, 12% chose a test at a doctor's office, and 1% chose a home specimen-collection test. Three attributes (accuracy/timeliness, privacy of test disclosure, and linking of test results) were rated equally-and most-important. In-person counseling was endorsed as the fourth most important attribute. Availability of in-person counseling was the strongest predictor of "loyalty" to public clinic tests-a consistent preference for that type of test even when the other tests were offered as additional no-cost options. There was also substantial interest in home self-tests. The results suggest specific attributes of testing that may be particularly important to individuals from diverse demographic and risk backgrounds.

AIDS Serodiagnosis↗
PubMed2001

Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.

CONTEXT: Atrial fibrillation is the most common arrhythmia in elderly persons and a potent risk factor for stroke. However, recent prevalence and projected future numbers of persons with atrial fibrillation are not well described. OBJECTIVE: To estimate prevalence of atrial fibrillation and US national projections of the numbers of persons with atrial fibrillation through the year 2050. DESIGN, SETTING, AND PATIENTS: Cross-sectional study of adults aged 20 years or older who were enrolled in a large health maintenance organization in California and who had atrial fibrillation diagnosed between July 1, 1996, and December 31, 1997. MAIN OUTCOME MEASURES: Prevalence of atrial fibrillation in the study population of 1.89 million; projected number of persons in the United States with atrial fibrillation between 1995-2050. RESULTS: A total of 17 974 adults with diagnosed atrial fibrillation were identified during the study period; 45% were aged 75 years or older. The prevalence of atrial fibrillation was 0.95% (95% confidence interval, 0.94%-0.96%). Atrial fibrillation was more common in men than in women (1.1% vs 0.8%; P<.001). Prevalence increased from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older. Among persons aged 50 years or older, prevalence of atrial fibrillation was higher in whites than in blacks (2.2% vs 1.5%; P<.001). We estimate approximately 2.3 million US adults currently have atrial fibrillation. We project that this will increase to more than 5.6 million (lower bound, 5.0; upper bound, 6.3) by the year 2050, with more than 50% of affected individuals aged 80 years or older. CONCLUSIONS: Our study confirms that atrial fibrillation is common among older adults and provides a contemporary basis for estimates of prevalence in the United States. The number of patients with atrial fibrillation is likely to increase 2.5-fold during the next 50 years, reflecting the growing proportion of elderly individuals. Coordinated efforts are needed to face the increasing challenge of optimal stroke prevention and rhythm management in patients with atrial fibrillation.

Adult↗
PubMed2001

An online educational facility for medical oncology trainees: www.vmotg.org.

PURPOSE: To design, implement, and evaluate a comprehensive educational Web site for medical oncology trainees. METHODS: The Web site was designed with three main areas (termed Journal Club, Key Papers, and Oncology Links) and compiled from articles presented at the Victorian Medical Oncology Trainees' Group journal club from the preceding 3 years. The Key Papers section was then reviewed by 30 academic medical oncologists. The site was advertised by mail and at the Annual Meeting of the Medical Oncology Group of Australia. Evaluation was by mail survey. RESULTS: The Web site, which may be accessed at www.vmotg.org, comprises more than 170 pages and 30,000 words of text. Journal club sessions are summarized with presented articles linked to abstracts from PubMed. Key Papers lists from five to 25 pivotal articles in each of 35 categories. Oncology Links is an extensive list of links in 10 categories including organizations, journals, and practice guidelines. Twenty-six of 45 trainees and 82 of 190 oncologists responded to the survey. Eighty-one percent of these trainees and 28% of oncologists have used the Web site. Ninety-six percent consider the Web site easy to use and "a useful medical oncology resource." All trainees rated the site good to excellent in terms of relevance and 94% considered the site beneficial to their education. CONCLUSION: The Web site www.vmotg.org is a relevant and useful educational resource for Australian medical oncology trainees and oncologists. As far as the authors are aware, this is the only educational site specifically for medical oncology trainees throughout the world. It may be a valuable oncology education resource for trainees in other countries, particularly those in isolated areas.

Humans↗
PubMed2001

The effect of risk factor reductions between 1981 and 1990 on coronary heart disease incidence, prevalence, mortality and cost.

OBJECTIVES: We sought to estimate the impact and cost-effectiveness of risk factor reductions between 1981 and 1990. BACKGROUND: Coronary heart disease (CHD) mortality rates have declined dramatically, partly as a result of reductions in CHD risk factors. METHODS: We used the CHD Policy Model, a validated computer-simulation model, to estimate the effects of actual investments made to change coronary risk factors between 1981 and 1990, as well as the impact of these changes on the incidence, prevalence, mortality and costs of CHD during this period and projected to 2015. RESULTS: Observed changes in risk factors between 1981 and 1990 resulted in a reduction of CHD deaths by approximately 430,000 and overall deaths by approximately 740,000, with an estimated cost-effectiveness of about $44,000 per year of life saved during this period, based on the estimated actual costs of the interventions used. However, because much of the benefit of risk factor reductions is delayed, the estimated reductions for the 35-year period of 1981 to 2015 were 3.6 million CHD deaths and 1.2 million non-CHD deaths, at a cost of only about $5,400 per year of life saved. CONCLUSIONS: Aggregate efforts to reduce risk factors between 1981 and 1990 have led to substantial reductions in CHD and should be well worth the cost, largely because of population-wide changes in life-style and habits. Some interventions are much better investments than others, and attention to such issues could lead to better use of resources and better outcomes in the future.

Adult↗
PubMed2001

Breast conservation in BRCA1 or BRCA2 mutation carriers with early stage breast cancer.

The role of breast conservation therapy (limited surgery and irradiation of the breast with/without axilla) in the approximately 5% of breast cancer patients who harbour a germline mutation in BRCA1 or BRCA2, is a largely unexplored area and is seen by some as controversial. The relatively high cumulative risk of second primary cancers in such patients and concern about a possible decreased ability of mutation carriers to repair DNA damage caused by radiation has fuelled this controversy. Published studies of breast conservation therapy in carriers of a mutation in BRCA1 or BRCA2 are reviewed, with particular attention to their methodology. These studies have not demonstrated any increase in radiation sensitivity of normal tissues in mutation carriers, either in terms of increased early or late toxicity or tumourigenesis. Likewise, tumour sensitivity to radiotherapy, which might be expected based on the known functions of the BRCA1 and BRCA2 genes, has not been documented to date in mutation carriers. Further, methodologically rigorous studies of large numbers of breast cancer patients who carry a mutation in BRCA1 or BRCA2 are required to fully elucidate these issues.

BRCA2 Protein↗
PubMed2001

Current perspectives on BRCA1- and BRCA2-associated breast cancers.

The identification of two breast cancer predisposition genes, BRCA1 and BRCA2, in the mid-1990s has led to a better understanding of the molecular pathogenesis of hereditary breast cancer and to a new era in breast cancer research. The present article reviews the current state of knowledge regarding the biology of BRCA1 and BRCA2, the cancer risks associated with carrying a pathogenic mutation in either of these genes and the possible genetic and environmental risk modifiers. The phenotypes of BRCA1- and BRCA2-associated hereditary breast cancers are reviewed. Research into BRCA1- and BRCA2-associated breast cancer is in its infancy and much remains to be learned, particularly about modifiers of genetic risk and the clinical implications of carrying a mutation in one of these two genes. Australia has an excellent research infrastructure in place, through the Australian Breast Cancer Family Study and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, to contribute substantially to future research in this area.

Animals↗
PubMed2001

A screening questionnaire for body dysmorphic disorder in a cosmetic dermatologic surgery practice.

BACKGROUND: Dermatologic surgeons frequently see patients with body dysmorphic disorder, a distressing or impairing preoccupation with a nonexistent or slight defect in appearance. Recognition of this disorder is essential to avoid unnecessary and generally unsatisfying surgical outcomes, but no screening tools are available for use in a dermatology setting. OBJECTIVE: To develop and validate a brief self-report questionnaire to screen for body dysmorphic disorder in dermatology settings. METHODS: A questionnaire was developed and its sensitivity and specificity determined in 46 subjects, using a reliable clinician-administered diagnostic interview for body dysmorphic disorder. The interrater reliability of a defect severity scale was also determined (n = 50). RESULTS: The self-report questionnaire had a sensitivity of 100% and a specificity of 93%. The interrater reliability (ICC) of the defect rating scale was.88. CONCLUSIONS: This brief questionnaire was a highly effective screening tool for body dysmorphic disorder in a cosmetic dermatology setting. Use of this questionnaire may help identify patients with this syndrome.

Adolescent↗
PubMed2001

Patterns of personality pathology in patients with generalized anxiety disorder, panic disorder with and without agoraphobia, and social phobia.

The relationship between co-occurring personality disorders and anxiety disorders (panic disorder with or without agoraphobia, social phobia, and generalized anxiety disorder) was examined, taking into account the effect of major depression. This article describes findings for 622 participants in the Harvard/Brown Anxiety Research Project, a longitudinal follow-up study of DSM-III-R-defined anxiety disorders. A total of 24% of participants had at least one personality disorder, with avoidant, obsessive compulsive, dependent, and borderline most common. Generalized anxiety disorder, social phobia, and major depression were positively associated with the occurrence of one or more personality disorders, whereas panic disorder with agoraphobia was not associated. Major depression was associated in particular with dependent, borderline, histrionic, and obsessive compulsive personality disorders and social phobia was associated with avoidant personality disorder. Whereas some of our findings confirm results from earlier studies, others are somewhat inconsistent with previous results and indicate the need for further investigation.

Adult↗
PubMed2001

The relationship between comorbid personality disorders and treatment received in patients with anxiety disorders.

Few studies have addressed the relationship between the presence of a comorbid personality disorder and the amount of psychiatric treatment received by patients with an Axis I disorder. This issue has not been studied in patients with anxiety disorders. In a prospective, naturalistic, longitudinal study of anxiety disorders, 526 subjects were assessed with the Personality Disorder Examination, and types of treatment received in 1991 and 1996 were identified. In 1991, compared to subjects without a personality disorder, subjects with a personality disorder were as likely to receive medication and they received a greater number of medications. Subjects with borderline personality disorder were more likely to receive heterocyclic antidepressants and interventions characteristic of psychodynamic psychotherapy and cognitive therapy; they also reported receiving a greater number of medications and types of psychosocial treatment than other subjects. In 1996, subjects with borderline personality disorder were more likely to receive psychodynamic interventions. These findings suggest that in patients with an anxiety disorder, the presence of a comorbid personality disorder is associated with receiving a greater number of medications but not with a greater likelihood of receiving pharmacologic or psychosocial treatment. However, the presence of borderline personality disorder is associated with a greater likelihood of receiving, and receiving a greater number of, certain types of somatic and psychosocial treatments.

Adult↗
PubMed2001

Delusionality and response to open-label fluvoxamine in body dysmorphic disorder.

BACKGROUND: Available data suggest that the delusional variant of body dysmorphic disorder (BDD), a type of delusional disorder, may respond to serotonin reuptake inhibitors (SRIs) and that delusionality (lack of insight) in BDD may improve with SRI treatment. However, this research has been hampered by the lack of a reliable and valid scale to assess delusionality. METHOD: Thirty subjects (21 women, 9 men; mean age = 33.3 +/- 9.0 years) with DSM-IV BDD were prospectively treated with open-label fluvoxamine for 16 weeks. Subjects were assessed at regular intervals with the Brown Assessment of Beliefs Scale (BABS), the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS; a measure of BDD severity), and other instruments. The BABS is a reliable and valid 7-item, semistructured, clinician-administered scale that assesses current delusionality. RESULTS: In this prospective, open-label study, 63% of BDD subjects responded to fluvoxamine. Delusional and nondelusional subjects had similar improvement in BDD symptoms. In addition, insight significantly improved in both delusional and nondelusional subjects. Baseline BABS scores did not contribute significantly to endpoint BDD-YBOCS scores in a regression analysis. CONCLUSION: Degree of delusionality did not predict fluvoxamine response, and delusionality significantly improved. These findings are preliminary and require confirmation in controlled trials. The implications of these findings for other types of delusions requires investigation.

Adult↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗