Editorials
Genomics and the Family Physician: Realizing the Potential
The dawning of the genome era is changing the scope of care for family physicians, with significant implications for the design of future health care delivery systems. Many consider the imminent introduction of genomics into clinical medicine to be the most significant advance in health care since antibiotics were introduced. Being able to build on the strengths of the physician-patient-family relationship enhances the potential for family physicians to realize the benefits of genomic technology. Knowledge of the individual patient across his or her lifespan provides an excellent foundation from which to begin integrating genomics information to improve health outcomes.
For example, a 43-year-old woman is concerned about her possible risk of cancer. She has been your patient for many years. You also cared for her mother before she was diagnosed with colon cancer at age 49. The patient reveals that her 45-year-old sister was diagnosed recently with colon cancer. Recognizing that a two-generation family history of colon cancer at a young age may indicate that your patient is at increased risk of developing colorectal cancer (http://www.cancer.gov), you gather more family history and consider the possibility of hereditary nonpolyposis colorectal cancer (HNPCC).1 Based on U.S. Preventive Services Task Force guidelines,2 you recommend a colonoscopy. Recognizing the potential implications of this information for your patient and her family, you ask if she is interested in learning more about genetic counseling and genetic testing for HNPCC. Ultimately, the patient and her sister test positive for a mutation in the MLH1 gene. Your patient is found to have three small polyps, which are excised. She agrees to a program of an annual colonoscopy that has an excellent chance of keeping her healthy.
This type of diagnostic testing, coupled with counseling and carefully designed programs of individualized prevention, will be feasible for an increasing number of common diseases in the next decade. The opportunity to integrate genomic biologic, clinical, and behavioral tools into your current scope of practice can make a difference in the care of patients whom you already are seeing.
Another application of genomics that will be increasingly common in family practice is pharmacogenomics. Variability in drug response can be a vexing problem, and often may be caused by genetic differences in individual patients, either with regard to drug metabolism or the targeted pathway.3,4 The objective of pharmacogenomics based on a patient's molecular genomic profile is to predict responsiveness to treatment, and then to improve results. This improvement in outcomes can occur only with sufficient understanding and appropriate use of genetically based testing in clinical practice.
In another example, a male patient and his wife come to you with some questions. Recently diagnosed with lung cancer, he has heard about a new drug called gefitinib. His female cousin died last year from lung cancer following treatment with that same drug. He and his wife wonder if it would be worth going through the chemotherapy. You are aware of a research study in which patients with certain somatic mutations in the epidermal growth-factor-receptor gene of the lung cancer tissue responded well to gefitinib. This molecular information was helpful in predicting improved clinical response and selecting those patients who would benefit from this specific drug intervention.5,6 You explain to your patient and his wife why he may respond differently than his cousin did to the treatment, and then make arrangements for DNA testing of his tumor specimen.
It also is likely that genomics will be the driving force behind new therapeutics during the next few decades. The molecular information about disease pathology generated by the genomics approach provides the opportunity for truly rational drug development. Such drug development is happening already in the oncology field, with the development of imatinib7 and gefitinib. The same type of drug development can be expected to happen in a few years for diseases such as diabetes, Alzheimer's disease, and osteoporosis. Options of care eventually will include genomic information along the pathway for care of all diseases, including prevention, screening, diagnostics, prognostics, selection of treatment, and monitoring of treatment effectiveness.
The rate of progress for applying a genomic approach throughout the continuum of care depends not only on technologic advances but also on physician expertise. The complexity of adopting this knowledge into practice includes an awareness of the science, provision of explanations to ensure informed patient decision making, and evaluation of the physical and psychologic ramifications of those decisions. Use of genomic information to meet the needs of patients in a changing health care environment requires a focus on reimbursement issues, informed resource access, and evaluation of the family practice environment to ensure confidentiality of collected genetic information (http://www.aafp.org/x24762.xml). Many of these topics will be highlighted in the monthly Web-based modules available through the American Academy of Family Physicians' (AAFP's) 2005 Annual Clinical Focus on genomics.
Genomic medicine is evolving rapidly. Even greater promise exists for the future. We do not yet have all the answers. A particularly important challenge is identifying the interaction of genes with other factors, such as environment and behavioral choices.8 Ongoing research will provide much needed data that will assist in translation into practice. However, translation of genomic research discoveries to improved clinical outcomes can occur only with an informed professional workforce. An informed family physician can be an active contributor to the design of future health care services, systems, tools, and resources that integrate genomic information. As genomic scientific knowledge rapidly advances, family physicians can assume a proactive role in learning about and realizing the potential of genomics in clinical care. Integration of genomics into medical curricula already has been recommended for family practice residents (http://www.aafp.org/x16547.xml). The AAFP, through the initiation of the Genomics Year in 2005, has made a statement about the importance of genomics competency for family physicians. Realizing the potential value of genomics in clinical care will be enhanced greatly through this educational effort.
The Author
Francis Collins, M.D., Ph.D., is the director of the National Human Genome Research Institute at the National Institutes of Health, Washington, D.C.
Address correspondence to Jean Jenkins, Ph.D., R.N., National Human Genome Research Institute, National Institutes of Health, 31 Center Dr., Bldg. 31 4B09, Bethesda, MD 20892-2152 (e-mail: jean.jenkins@nih.gov). Reprints are not available from the author.
REFERENCES
1. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003;348:919-32.
2. U.S. Preventive Services Task Force. Screening for colorectal cancer: recommendations and rationale. Rockville, Md.: Agency for Healthcare Research and Quality, July 2002. Accessed online July 2004 at: http://www.ahrq.gov/clinic/3rduspstf/colorectal/colorr.htm.
3. Evans WE, McLeod HL. Pharmacogenomics-drug disposition, drug targets, and side effects. N Engl J Med 2003;348:538-49.
4. Green MR. Targeting targeted therapy. N Engl J Med 2004;350:2191-3.
5. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39.
6. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500.
7. Wong S, Witte ON. The BCR-ABL story: bench to bedside and back. Annu Rev Immunol 2004;22:247-306.
8. Collins FS. The case for a U.S. prospective cohort study of genes and environment. Nature 2004;429:475-7.
Rhinosinusitis: What Is the Desired Outcome?
See articles on pages 1685 and
1697.
Antibiotics are no longer first-line treatment for many upper respiratory tract infections. Currently, the American Academy of Pediatrics and the American Academy of Family Physicians are promoting new guidelines for treatment of acute otitis media, proposing that antibiotics not always be used.1,2 Similarly, acute bronchitis, which in the past was almost always treated with antibiotics, is now recognized as a viral disease that generally should be treated with only supportive methods.3
In this issue, Scheid and Hamm present two excellent articles on acute bacterial rhinosinusitis (ABRS).4,5 They correctly state that most patients with upper respiratory infections do not have ABRS but, instead, have viral sinusitis. The question is, how should physicians manage this condition? At this time, physicians are still prescribing antibiotics for most patients whom they diagnose with sinusitis.
As described in Scheid and Hamm's articles, there are numerous methodologically rigorous clinical prediction rules that physicians may use for guidance when examining patients. The problem with these guidelines is that they are drawn from studies of patients in subspecialty clinics, and they measure disease-oriented findings documented by sinus radiographs, computed tomography, and bacterial growth from sinus puncture. What family physicians and patients truly need to provide guidance is practical or pragmatic clinical trials that test prediction rules under clinical conditions similar to what actually occurs in the primary care outpatient setting.6
During the office visit, the problem family physicians face is deciphering which patients will benefit from antibiotics and which ones have viral infections and need only symptomatic treatment. Any treatment ultimately is based on the precept of doing more good than harm. Family physicians are familiar with this struggle because it is at the root of what they do every day while treating patients, but for some reason this strategy has not been applied consistently in the treatment of upper respiratory infections.
If our goal in treating ABRS was to prevent serious complications, such as brain abscesses, then we would be willing to treat many patients unnecessarily to prevent even one brain abscess. Scheid and Hamm never mention such unlikely complications, and I applaud them for this. This omission on their part implicitly tells the reader that this is not the true worry of patients and physicians-that, generally, symptomatic improvement is the true goal of treatment in patients with ABRS. If our goal is to cure something as common and self-limited as purulent nasal discharge, we may not be willing to treat as many patients to help one because we know that antibiotics will help very few of them and that nearly two thirds of patients will continue having symptoms such as cough and nasal discharge for up to three weeks.7
In conjunction with our patients, we need to decide (1) what our goals are when we encounter patients with sinusitis-like symptoms and (2) why we continue to treat these patients with antibiotics if that treatment does not accomplish our goals. Patient-oriented clinical trials still are needed to identify a subset of patients that are likely to benefit from antibiotic treatment. Meanwhile, it is likely that physicians soon will approach the treatment of ABRS in a fashion similar to that of acute otitis media and bronchitis, and that antibiotics will no longer be the first-line treatment option.
The Author
Dan Merenstein, M.D., is Robert Wood Johnson Clinical Scholar at Johns Hopkins University in Baltimore.
Address correspondence to Dan Merenstein, M.D., Fellow, Dept. of Medicine, Robert Wood Johnson Clinical Scholars Program, 600 N. Wolfe St., Carnegie 291, Baltimore, MD 21287-6220 (e-mail: dmerenstein@jhu.edu). Reprints are not available from the author.
References
1. American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 2004;113:1451-65.
2. Neff MJ. AAP, AAFP release guideline on diagnosis and management of acute otitis media. Am Fam Physician 2004;69:2713-5.
3. Snow V, Mottur-Pilson C, Gonzales R. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann Intern Med 2001;134:518-20.
4. Scheid DC, Hamm RM. Evaluation of suspected acute bacterial rhinosinusitis in adults: part I. Am Fam Physician 2004;70:1685-92.
5. Scheid DC, Hamm RM. Evaluation of suspected acute bacterial rhinosinusitis in adults: part II. Am Fam Physician 2004;70:1697-704, 1711-12.
6. Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA 2003;290:1624-32.
7. Scott J, Orzano AJ. Evaluation and treatment of the patient with acute undifferentiated respiratory tract infection. J Fam Pract 2001;50:1070-7.
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