Determining the effects and challenges of incorporating genetic testing into primary care management of hypertensive patients with African ancestry.

People of African ancestry (Blacks) have increased risk of kidney failure due to numerous socioeconomic, environmental, and clinical factors. Two variants in the APOL1 gene are now thought to account for much of the racial disparity associated with hypertensive kidney failure in Blacks. However, this knowledge has not been translated into clinical care to help improve patient outcomes and address disparities. GUARDD is a randomized trial to evaluate the effects and challenges of incorporating genetic risk information into primary care. Hypertensive, non-diabetic, adults with self-reported African ancestry, without kidney dysfunction, are recruited from diverse clinical settings and randomized to undergo APOL1 genetic testing at baseline (intervention) or at one year (waitlist control). Providers are educated about genomics and APOL1. Guided by a genetic counselor, trained staff return APOL1 results to patients and provide low-literacy educational materials. Real-time clinical decision support tools alert clinicians of their patients' APOL1 results and associated risk status at the point of care. Our academic-community-clinical partnership designed a study to generate information about the impact of genetic risk information on patient care (blood pressure and renal surveillance) and on patient and provider knowledge, attitudes, beliefs, and behaviors. GUARDD will help establish the effective implementation of APOL1 risk-informed management of hypertensive patients at high risk of CKD, and will provide a robust framework for future endeavors to implement genomic medicine in diverse clinical practices. It will also add to the important dialog about factors that contribute to and may help eliminate racial disparities in kidney disease.

Genetic and lifestyle causal beliefs about obesity and associated diseases among ethnically diverse patients: a structured interview study.

BACKGROUND: New genetic associations with obesity are rapidly being discovered. People's causal beliefs about obesity may influence their obesity-related behaviors. Little is known about genetic compared to lifestyle causal beliefs regarding obesity, and obesity-related diseases, among minority populations. This study examined genetic and lifestyle causal beliefs about obesity and 3 obesity-related diseases among a low-income, ethnically diverse patient sample. METHODS: Structured interviews were conducted with patients attending an inner-city hospital outpatient clinic. Participants (n=205) were asked how much they agreed that genetics influence the risk of obesity, type 2 diabetes, heart disease, and cancer. Similar questions were asked regarding lifestyle causal beliefs (overeating, eating certain types of food, chemicals in food, not exercising, smoking). In this study, 48% of participants were non-Hispanic Black, 29% Hispanic and 10% non-Hispanic White. RESULTS: Over two-thirds (69%) of participants believed genetics cause obesity 'some' or 'a lot', compared to 82% for type 2 diabetes, 79% for heart disease and 75% for cancer. Participants who held genetic causal beliefs about obesity held more lifestyle causal beliefs in total than those who did not hold genetic causal beliefs about obesity (4.0 vs. 3.7 lifestyle causal beliefs, respectively, possible range 0-5, p=0.025). There were few associations between causal beliefs and sociodemographic characteristics. CONCLUSIONS: Higher beliefs in genetic causation of obesity and related diseases are not automatically associated with decreased lifestyle beliefs. Future research efforts are needed to determine whether public health messages aimed at reducing obesity and its consequences in racially and ethnically diverse urban communities may benefit from incorporating an acknowledgement of the role of genetics in these conditions.

Physician-patient discussions of controversial cancer screening tests.

BACKGROUND: Screening mammography for younger women and prostate-specific antigen (PSA) measurement have controversial benefits and known potential adverse consequences. While providing informed consent and eliciting patient preference have been advocated for these tests, little is known about how often these discussions take place or about barriers to these discussions. METHODS: We administered a survey to medical house staff and attending physicians practicing primary care. The survey examined physicians' likelihood of discussing screening mammography and PSA testing, and factors influencing the frequency and quality of these discussions. RESULTS: For the three scenarios, 16% to 34% of physicians stated that they do not discuss the screening tests. The likelihood of having a discussion was significantly associated with house staff physicians' belief that PSA screening is advantageous; house staff and attending physicians' intention to order a PSA test, and attending physicians' intention to order a mammogram; and a controversial indication for screening. The most commonly identified barriers to discussions were lack of time, the complexity of the topic, and a language barrier. CONCLUSIONS: Physicians report they often do not discuss cancer screening tests with their patients. Our finding that physicians' beliefs and intention to order the tests, and extraneous factors such as time constraints and a language barrier, are associated with discussions indicates that some patients may be inappropriately denied the opportunity to choose whether to screen for breast and prostate cancer.

Disclosing doctors' incentives: will consumers understand and value the information?

As part of a broader movement toward accountability in health care, federal and state governments have required health plans to disclose physicians' financial incentives. Available data suggest that patients have poor comprehension of the incentives and significant barriers to learning, including high trust in their physicians, reluctance to think of the physician/patient relationship in financial terms, and failure to understand the relevance of the information to their health care choices and treatment. Disclosure that conveys clearly what is at stake will increase the salience of incentive information but is also more likely to erode trust.

Approaches to eliminating sociocultural disparities in health.

The recent flurry of studies documenting the presence of racial, ethnic, and socioeconomic disparities in health care and health have outpaced articles that describe effective strategies to eliminate disparities. Through literature review and informal interviews with research, policy, and program experts, we developed a framework of programs that address disparities through targeting clinicians, patients and communities, and health systems. We found that the lack of technical expertise, resources, and sensitive tools are all common barriers to evaluating programs. To stimulate more effective programs and rigorous evaluations, we describe specialized implementation and evaluation techniques programs can use, and make recommendations for future efforts.

Musings on using evidence to guide CQI efforts toward success: the computerized firm system as primary care microunit.

BACKGROUND: The attempt to transfer classic industrial CQI (continuous quality improvement) theory into the clinical arena has proved to be more difficult than originally promised. A new "computerized firm system" approach to incorporating CQI efforts into mainstream practice settings, which has been able to obviate many of these shortcomings, is described. METHODS: To make it easier for CQI efforts to be successful, the scope of activities undertaken in completing the Shewhart cycle popularly referred to as PDSA (plan change, do change, study results, act on results) was delimited. Rather than plan the intervention themselves, staff worked with experts on tailoring a preselected change idea with already established efficacy--a computerized reminder system. Because the clinic was divided into two small group practices known as firms, a controlled time-series trial (CTST) design was used by initially turning the reminders on for one firm but not the other. The clinic was thereby also relieved of the responsibility of conducting a study to determine whether the intended improvement in quality had been achieved. In essence, one clinic was asked to do just DA (that is, do-act). RESULTS: This approach engendered the successful completion of a streamlined Shewhart cycle in a busy clinic setting at remarkably low cost. The compelling nature of controlled evaluation results aided leadership in rapidly disseminating the reminder system to the remaining 11 primary care clinics associated with the university's 2 academic medical centers. CONCLUSION: Computerized firm systems can be developed to conduct CTSTs as part of streamlined CQI cycles guided by both published and local evidence, and they are worth developing.

A randomized controlled trial of CQI teams and academic detailing: can they alter compliance with guidelines?

BACKGROUND: The availability of clinical guidelines in isolation has generally failed to promote voluntary change in practice patterns. Accordingly, a randomized controlled trial was conducted to determine the effectiveness of academic detailing (AD) techniques and continuous quality improvement (CQI) teams in increasing compliance with national guidelines for the primary care of hypertension and depression. METHODS: Fifteen small group practices at four Seattle primary care clinics were assigned to one of three study arms--AD alone, AD plus CQI teams, or usual care. The activity of 95 providers and 4,995 patients was monitored from August 1, 1993, through January 31, 1996. Twelve-month baseline and study periods were separated by a six-month "wash-in" period during which training sessions were held. Changes in hypertension prescribing, blood pressure control, depression recognition, use of older tricyclics, and scores on the Hopkins Symptom Checklist depression scale were examined. RESULTS: Clinics varied considerably in their implementation of both the AD and the CQI team interventions. Across all sites, AD was associated with change in a single process measure, a decline in the percentage of depressives prescribed first-generation tricyclics (-4.7 percentage points versus control, p = 0.04). No intervention effects were demonstrated for CQI teams across all sites for either disease condition. Within the clinic independently judged most successful at implementing both change strategies, the use of CQI teams and AD in combination did increase the percentage of hypertensives adequately controlled (17.3 percentage points versus control, p = 0.03). SUMMARY AND CONCLUSIONS: The AD techniques and the CQI teams evaluated were generally ineffective in improving guideline compliance and clinical outcomes regarding the primary care of hypertension and depression.

Conducting a randomized controlled trial of CQI and academic detailing to implement clinical guidelines.

BACKGROUND: A multisite, randomized controlled trial was conducted from August 1994 through January 1996 to compare the impact of two strategies-academic detailing (AD) and continuous quality improvement (CQI) teams-on the implementation of national guidelines for the primary care of hypertension and depression. STUDY: Twelve small groups of providers at four clinics-two at Group Health Cooperative of Puget Sound (Seattle) and two at academic medical centers-were randomized in blocks along with their primary care patients to receive AD alone, AD plus CQI, or usual care. A detailing session conducted by a physician and two follow-up sessions conducted by a pharmacist lasted an average of 8-9 minutes. Each CQI team, which met, on average, 14 times in nine months, devised at least one intervention (for example, weight loss counseling for hypertensives by nurse practitioners). RESULTS: The detailing endeavors differed greatly across organizations. Although all teams generally worked well together, organizational factors such as staff layoffs and reorganizations competed for the teams' attention. Team leaders differed in their ability to inspire members to "run with" ideas and to motivate personnel outside the team to implement interventions. SUMMARY AND CONCLUSIONS: Surveys and semi-structured interviews suggest that both the AD and CQI interventions involved complex social interactions that resulted in varied implementation across the different organizations. Final analyses will need to focus on identifying factors associated with the relative success or failure of both clinical change techniques.

Local and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy.

Evidence that interferon-gamma may be a physiologic macrophage-activating factor, and that macrophage activation may be defective in lepromatous leprosy, led us to test the effects of intradermal injection of low doses of recombinant interferon-gamma in six patients with this disease. Interferon-gamma, 1 or 10 micrograms, was administered daily by jet gun for three days into a single cutaneous lesion. A biopsy specimen was taken from the injection site on the sixth study day and compared with specimens obtained previously from a site where no injection had been made or where excipient alone had been injected in the same way as the interferon. Interferon-gamma elicited local effects similar to certain features of delayed-type hypersensitivity reactions or tuberculoid leprosy, including induration, T-cell and monocyte infiltration, keratinocyte proliferation, diminution of epidermal Langerhans cells, and dermal and epidermal cell HLA-DR (Ia) antigen expression. At some of the sites of interferon-gamma injection, there was also an apparent decrease in acid-fast bacilli. Before treatment, monocytes from patients with lepromatous leprosy released 48 percent as much hydrogen peroxide as did monocytes from controls in response to phorbol myristate acetate, and 36 percent as much as those from controls in response to Mycobacterium leprae. When recombinant interferon-gamma was injected, these responses became normal. No toxic effects were observed. These observations suggest that interferon-gamma can mediate certain manifestations of delayed-type hypersensitivity or cell-mediated immunity in vivo, and that recombinant interferon-gamma should be tested for possible therapeutic effects in certain nonviral infectious diseases.

Administration of recombinant interferon gamma to cancer patients enhances monocyte secretion of hydrogen peroxide.

Recombinant interferon gamma (rIFN-gamma) activates macrophage antimicrobial and antitumor functions and related metabolic processes, including secretion of reactive oxygen intermediates in mice and in cultured mouse and human macrophages. To look for similar actions in man, we monitored the H2O2 secretory capacity of monocytes from cancer patients receiving intravenous rIFN-gamma at 0.1, 0.5, or 1.0 mg/m2 of body area over 6 hr daily or over 1 hr on alternate days. Monocytes taken just before the first infusion served as controls and were comparable to normal donor monocytes in secretion of H2O2. Monocytes from 11 of the 13 subjects (85%) studied through 20 treatment cycles responded to rIFN-gamma with elevation in H2O2 secretion in greater than or equal to 67% of the tests conducted greater than 1 hr after the start of treatment. Five of the five subjects tested had monocytes with diminished H2O2 secretory capacity when tested immediately after a 1-hr infusion of rIRN-gamma, at which time the amount of adherent mononuclear cell protein recovered from the blood averaged only 24% of the control. At all other times tested (from 6 hr to 5 days after infusion) combined results for all subjects showed enhancement of H2O2 releasing capacity. Statistically significant mean increases ranged from 1.4- to 2.8-fold above the control and included the sets in which monocytes collected 24 hr following a single infusion were assayed the same day or the next. By the criterion of enhanced H2O2 secretory capacity, the ability of rIFN-gamma to activate mononuclear phagocytes is manifest upon its administration to patients with advanced malignancy.