JAMA. 2008;300(13):1532-1543.
Context In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA). Objective To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (SQ) to intramuscular (IM) and omitting the week 2 dose from the licensed schedule. Design, Setting, and Participants Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002). Intervention Healthy adults received AVA by the SQ (reference group) or IM route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals. Main Outcome Measures Noninferiority at week 8 and month 7 of anti–protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4xR). Reactogenicity outcomes were proportions of injection site and systemic AEs. Results At week 8, the 4-IM group (GMC, 90.8 µg/mL; GMT, 1114.8; %4xR, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 µg/mL; GMT, 1315.4; %4xR, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4xR (GMC, 52.2 µg/mL; GMT, 650.6; %4xR, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs. Conclusions The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067
JAMA. 2005;293:1367-1373.
The discovery of RNA interference (RNAi), an endogenous cellular gene-silencing mechanism, has already provided a powerful tool for basic science researchers to study gene function. The subsequent finding that RNAi also operates in mammalian cells has generated excitement regarding potential therapeutic applications. In this article we discuss the basic mechanism of RNAi and the therapeutic opportunities and obstacles for harnessing RNAi for therapy of human disease.
JAMA. 2002;288:1097-1101.
Since family practice was first recognized as a specialty in the late 1960s, considerable intellectual and organizational change has occurred in medicine, especially during the 1990s. To reflect on and reconsider the role of family practice in US health care, this article reviews the development of family practice as a specialty, provides a current assessment of the status of family medicine in the United States, and comments on issues that are of ongoing importance to family practice.
JAMA. 2002;288:1775-1779.
The chronic care model is a guide to higher-quality chronic illness management within primary care. The model predicts that improvement in its 6 interrelated components—self-management support, clinical information systems, delivery system redesign, decision support, health care organization, and community resources—can produce system reform in which informed, activated patients interact with prepared, proactive practice teams. Case studies are provided describing how components of the chronic care model have been implemented in the primary care practices of 4 health care organizations.
JAMA. 2002;287:2114-2119.
Objectives The Bethesda 2001 Workshop was convened to evaluate and update the 1991 Bethesda System terminology for reporting the results of cervical cytology. A primary objective was to develop a new approach to broaden participation in the consensus process. Participants Forum groups composed of 6 to 10 individuals were responsible for developing recommendations for discussion at the workshop. Each forum group included at least 1 cytopathologist, cytotechnologist, clinician, and international representative to ensure a broad range of views and interests. More than 400 cytopathologists, cytotechnologists, histopathologists, family practitioners, gynecologists, public health physicians, epidemiologists, patient advocates, and attorneys participated in the workshop, which was convened by the National Cancer Institute and cosponsored by 44 professional societies. More than 20 countries were represented. Evidence Literature review, expert opinion, and input from an Internet bulletin board were all considered in developing recommendations. The strength of evidence of the scientific data was considered of paramount importance. Consensus Process Bethesda 2001 was a year-long iterative review process. An Internet bulletin board was used for discussion of issues and drafts of recommendations. More than 1000 comments were posted to the bulletin board over the course of 6 months. The Bethesda Workshop, held April 30-May 2, 2001, was open to the public. Postworkshop recommendations were posted on the bulletin board for a last round of critical review prior to finalizing the terminology. Conclusions Bethesda 2001 was developed with broad participation in the consensus process. The 2001 Bethesda System terminology reflects important advances in biological understanding of cervical neoplasia and cervical screening technology.
JAMA. 2002;288:889-893.
This article—the first in a series on primary care—outlines the daunting challenges facing primary care today. Most people in the United States desire a primary care "home" to provide for and coordinate their health care needs. Yet primary care is endangered by physician stress, inadequate performance in managing chronic illness, and inability to provide prompt access and reliable continuity of care. Fundamental redesign is needed to improve access to and quality of care while easing physicians' workload without causing major increases in health care costs.
JAMA. 2003;289:1042-1046.
The advanced access model of patient scheduling is based on the core principle that if the capacity to provide patient appointments balances the demand for appointments, patients calling to see their physician are offered an appointment the same day. The accompanying article in the series "Innovations in Primary Care" presents the theory behind advanced access scheduling. In this article we describe 4 case studies of primary care practices that successfully implemented advanced access and 3 examples of practices that were unable to achieve advanced access despite considerable efforts. The lessons of these case studies should be useful for primary care practices desiring to improve timely access to care and wishing to avoid the pitfalls that can derail this innovation.
JAMA. 2000;283:2417-2426.
Objective Assays for drug resistance testing in human immunodeficiency virus type 1 (HIV-1) infection are now available and clinical studies suggest that viral drug resistance is correlated with poor virologic response to new therapy. The International AIDS Society–USA sought to update prior recommendations to provide guidance for clinicians regarding indications for HIV-1 resistance testing. Participants An International AIDS Society–USA 13-member physician panel with expertise in basic science, clinical research, and patient care involving HIV resistance to antiretroviral drugs was reconvened to provide recommendations for the clinical use of drug resistance testing. Evidence and Consensus Process The full panel met regularly between January and October 1999. Resistance and resistance testing data appearing in the last decade through April 2000 and presentations at national and international research conferences were reviewed. Recommendations and considerations were developed by 100% group consensus, acknowledging that definitive data to support final recommendations are not yet available. Conclusions Emerging data indicate that despite limitations, resistance testing should be incorporated into patient management in some settings. Resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women. It should be considered in treatment-naive patients with established infection, but cannot be firmly recommended in this setting. Testing also should be considered prior to initiating therapy in patients with acute HIV infection, although therapy should not be delayed pending the results. Expert interpretation is recommended given the complexity of results and assay limitations.
JAMA. 1998;280:78-86.
Objective.— To provide recommendations for antiretroviral therapy based on information available in mid-1998. Participants.— An international panel of physicians with expertise in antiretroviral research and care of patients with human immunodeficiency virus (HIV) infection, first convened by the International AIDS Society–USA in December 1995. Evidence. —The panel reviewed available clinical and basic science study results (including phase 3 controlled trials; clinical, virologic, and immunologic end point data; data presented at research conferences; and studies of HIV pathophysiology); opinions of panel members were also considered. Recommendations were limited to drugs available in mid-1998. Consensus Process. —Panel members monitor new clinical research reports and interim results. The full panel meets regularly to discuss how the new information may change treatment recommendations. Updated recommendations are developed through consensus of the entire panel at each stage of development. Conclusions. —Accumulating data from clinical and pathogenesis studies continue to support early institution of potent antiretroviral therapy in patients with HIV infection. A variety of combination regimens show potency, expanding choices for initial regimens for individual patients. Plasma HIV RNA assays with increased sensitivity are important in monitoring therapeutic response; however, more data are needed to determine precisely the HIV RNA levels that define treatment failure. Long-term adverse drug effects are beginning to emerge, requiring ongoing attention. Some issues regarding optimal long-term approaches to antiretroviral management are unresolved. The increased complexity in HIV management requires ongoing monitoring of new data for optimal treatment of HIV infection.
JAMA. 2002;288:1909-1914.
This article reviews research evidence showing to what extent the chronic care model can improve the management of chronic conditions (using diabetes as an example) and reduce health care costs. Thirty-two of 39 studies found that interventions based on chronic care model components improved at least 1 process or outcome measure for diabetic patients. Regarding whether chronic care model interventions can reduce costs, 18 of 27 studies concerned with 3 examples of chronic conditions (congestive heart failure, asthma, and diabetes) demonstrated reduced health care costs or lower use of health care services. Even though the chronic care model has the potential to improve care and reduce costs, several obstacles hinder its widespread adoption.