Frits Hommes Human Genetics Program, Department of Pediatrics New York University Medical Center New York, New York
Proficiency testing for biochemical genetics laboratories started in 1985 in SERGG and has, over the years, developed into a national program. The results of this program have been published (AJHG 46(1990) 1001) while an update will appear shortly in the Evv. J. Pediatr. The results have not changed since the first report. There is some improvement over time, especially for those laboratories that have participated a long time.
The dominant issue is presently the implementation of CLIA'88 for genetic testing, which will make proficiency testing mandatory. A proficiency testing program must, therefore, be prepared for legal implications, which requires a buffer of a large and financially strong organization. From this perspective, the alliance between the ACMG and the CAP is a good one.
Fulfilling legal requirements and meeting educational needs are distinctively different objectives. Continuation of the SERGG PT program for educational purposes is, therefore, meaningful. This touches on current issues of certification within the framework of CLIA'88. Biochemical genetics will, apparently, not be recognized as an independent discipline, but will be in the category clinical chemistry. Although those currently active as lab directors will be grandfathered in, the failure to recognize the ABMG will prevent new ABMG diplomats to become lab directors and, consequently, the involvement of professionally trained geneticists in laboratory biochemical genetics will be phased out, unless all of genetics is placed in a category of its own and the ABMG strengthens its training programs to become acceptable to government agencies.
Biochemical genetics has traditionally concerned itself with major metabolic pathways and has been mostly of a qualitative nature. There is an increasing need for quantitative data to differentiate between normal and mutations leading to a more subtle derangement of metabolism and to explore biochemical individuality. SERGG could play a central role in making available reference compounds, especially for isotope dilution assays.
RESULTS and INSIGHTS from 5-YEARS of PROSTATE CANCER SCREENING AND SCREENING POLICY RECOMMENDATIONS for ADULT CANCERS BASED on an EXTENSION of the PROSTATE CANCER SCREENING MODEL. Sanda Clejan, PhD, Professor of Pathology and Biochemistry, Tulane University Medical Center, New Orleans, Louisiana 70112-2699
Making recommendations about screening is one of the most difficult and complicated problems in clinical medicine, but progress in this direction is primarily due to a 5-year screening-study program of the Prostate Cancer Education Council in which 600,000 men over the age of 45 were enrolled and screened. One of the tenants of this program was that testing and screening is efficient only when counseling is given within specialized genetic counseling units, knowledgeable about molecular genetic issues, preferably within a university department and/or regional cancer center. The attributes needed for adult screening are: 1) there is a condition that we want to detect or interrupt; 2) the condition is changing within time; 3) one or more tests can be used to detect the condition; 4) the chance that a test will detect the condition is a function of the condition state of the development at the time of evaluation; and 5) there are positive outcomes related to state of the condition at the time of detection or interruption. The method found by our study to have the best positive predictive value for the screening of prostate cancer is prostate specific antigen (PSA). In tandem with digital rectal examination (DRE), the screening resulted in a detection rate of 6% in the general population. 43% of the cancers were identified in digitally normal glands with elevated PSA. Patterns of PSA elevation were developed for other benign prostate diseases (BPH, prostatitis), and a method of separation from prostate cancer was worked out. A cost effective program with PSA as a primary test for screening and lower screening intervals, for members of families with cancer and ethnic groups at higher risk, was set up, and follow-up was stratified as a result of this program. The sequence of actions and outcomes was developed with the confirmation of cancer and changes in the ti * 'treatment (earliness of detection, lead time, patient interval shortened). Estimation of the benefits, harms, and costs determined that the screening program was effective and worth the resources put into it, and especially can be applied in many other adult cancers. For other adult cancers, we propose to use the available tumor markers to the population at risk because of family history, environmental exposure, geographic prevalence, or clinical profile. In addition, we suggest enhancement of clinical utility of tumor markers by: a) shift with the diagnostic decision threshold; b) panels of molecular and biochemical markers; and c) sequential testing. Molecular diagnostic testing methods for tumor markers especially fluorescence in situ hybridization, PCR, and single stranded conformational polymorphism are recommended for detection of point mutations. Usefulness of such methods was demonstrated with p53 tumor suppressor gene detection in prostate cancer.
In summary, the overview of the model we propose is: 1) provide different programs for people in different age categories; 2) provide different programs for people in different risk categories; 3) use various screening techniques in various orders; 4) have the screening done at various frequencies; 5)change the detection capabilities of screening techniques. We learned that: 1) there was a difference between the relationship of prevalence cases and incidence cases; 2) lead time was gained in diagnosis through screening; 3) there was a relationship between the timing of tests and the proportion of cancers detected by various combinations of tests; 4) the effect of a person's past history of screening on the chance that a cancer will be detected; 5) there was a relationship between the method of detection, the rate of development of diagnostic clues, and the rate of patient response to the signs and symptoms.
Source: George Phillips, Jr.
Duke University Medical Center
Box 3523
Durham, North Carolina 27710
(919) 684-3147
NEW THERAPIES IN THE TREATMENT OF SICKLE CELL DISEASE
Sickle cell anemia is a disorder that has been extremely well characterized at the molecular biological, cellular biological and physiologic levels. However, presently there are no proven prophylactic or intervention therapies for sickle cell disease.
Potential new therapies for sickle cell disease include agents that enhance fetal hemoglobin synthesis, bone marrow transplantation, and gene therapy. There are several clinical trials that are in place at this time designed to determine the safety and efficacy of these therapies.
Amongst the fetal hemoglobin enhancing agents, hydroxyurea is the agent with which there is the most clinical experience. This agent can enhance fetal hemoglobin production and appears to be reasonably safe when the therapy is monitored closely. However, the benefit of hydroxyurea at preventing vaso-occlusion in sickle cell disease remains to be determined. Other agents that enhance fetal hemoglobin production include erythropoietin and butyrate. There is much less clinical experience with these agents and their benefit in the treatment of sickle cell disease is far from established.
Gene therapy is a possible treatment for sickle cell disease that continues to be developed. It is possible that the defective hemoglobin gene could be removed and a normal gene inserted which would cure the sickle cell disease. Several technical obstacles must be surmounted before this therapy becomes a reality.
Bone marrow transplantation is a curative therapy that is available today. This therapy has been used successfully in the treatment of sickle cell disease. There are ongoing trials of bone marrow transplantation in sickle cell disease.
New therapies for the treatment of sickle cell disease offer hope that in the near future we will have therapies that will significantly impact this disorder. Fetal hemoglobin synthesis enhancers may decrease severity of the disease and marrow transplantation and gene therapy offer hope for a cure.
FUTURE DIRECTIONS OF EDUCATION IN HUMAN AND MEDICAL GENETICS
Arno G. Motulsky, MD, DSc, University of Washington, Seattle
New developments in human and medical genetics require extensive and novel educational efforts. As genetics moves from an esoteric specialty to being part of medicine, physicians and other health professionals need better education and training. At the same time, sufficient facilities need to be available to train clinical geneticists, laboratory geneticists, and genetic counselors. In 1990, the American Board of Medical Genetics had licensed about 2,000 diplomats with about 40% being clinical geneticists and 40% genetic counselors. Future needs in these areas are difficult to predict, particularly in clinical genetics where currently almost all practice is carried out in University medical centers or in institutional settings.
Medical school instruction in genetics requires much improvement. There needs to be more emphasis on genetics in the clinical years, and genetic courses should be offered in all medical schools. The National Board of Medical Examiners and state boards need to incorporate more genetic questions in their tests. While some residencies in obstetrics/gynecology and in pediatrics already include genetics in their programs, more needs to be done since practitioners in these fields frequently encounter genetic problems. However, as genetic susceptibility factors in many common adult diseases become apparent, residency training in family medicine and internal medicine needs to incorporate more genetics into their programs. Continuing Medical Education courses need to provide more coverage of genetics. "Theme" issues of professional journals dealing with genetics have already appeared in the Journal of the American Medical Association and various AMA specialty journals.
PhD's working in diagnostic laboratories need to get more exposure to clinical genetics and should be able to provide clear explanations of genetic tests which can be understood by non-specialists. Better and effective group counseling using video tapes needs to be developed for prenatal diagnosis and for newborn testing. Nurses, social workers, nutritionists as well as public health workers require more exposure to human and medical genetics since the new scientific developments impact on their activities.
Public education at all levels should be encouraged. Decision-making on genetic and reproductive issues by the public and its representatives based on ignorance and misinformation is undesirable. Public education should start at the grade school level and should be particularly emphasized in high schools. Much of biology can be taught using examples from human biology and human genetics. More and better science teachers are needed. At the college level, we need more human biology and genetics courses offered to non-science majors.
Better reporting by commercial TV - not just public TV- needs to be fostered. Newspapers and magazines should be encouraged to cover current genetic topics in human and medical genetics and avoid "sensationalism". To achieve optimal public education, opinion leaders in the professions, media, and schools as well as on school boards and in the state and federal legislature must be reached. The emphasis on public education may be somewhat utopian when an increasing proportion of the population is illiterate and school drop-out rates are high. Yet, even though not everyone can be influenced, more and better educational efforts are likely to have effects.
Title: Education Regarding National Strategies for Nutrition in Health Care Reform Presented by: Rachel K. Johnson, PhD, MPH, RD Assistant Professor Department of Nutritional Sciences University of Vermont
Almost 17 million people each year are treated for illness or injury that place them at high risk of being malnourished. Whether in hospitals, long-term care institutions or scattered throughout the community, medical professionals recognize the need to provide medical nutrition therapy as a key factor to help improve outcome and speed recovery.
Medical nutrition therapy can help save health care costs. The need for long-term drug therapies for many chronic illnesses, such as diabetes and cardiovascular disease, is reduced through diet planning and control. Treatment needs for those with renal failure and with disease exacerbated by obesity or severe weight loss are reduced or eliminated by balancing nutrient intake (for example, proteins, calories, electrolytes). In addition, hospital stays are reduced or prevented by improving the patient's nutrition status. Research shows that for every dollar ($1) spent on nutrition therapy, between $3.25 and $600 in later medical costs is saved, depending on the severity of the condition. Multiplied by the 17 million patients in the medical system suffering diseases treatable by medical nutrition therapy, the benefit for the economy and the cost of health care is enormous.
No consistent policy or approach exists for covering the costs or charges of nutrition services. While medical protocols for many acute diseases include medical nutrition therapy, it is seldom reimbursed by insurance companies. Reimbursement for medical nutrition services is sporadic at best, resulting in reater use of costly high-tech procedures and longer hospitalizations.
The inclusion of medical nutrition therapy in the basic benefits package would help guarantee that patients receive the services they need to improve or maintain their health. Some of the wide range of patients in need of nutrition services include:
In summary, medical nutrition therapy is an integral part of medical
treatment. It improves outcomes and speeds recovery resulting in health care
cost savings. The American Dietetic Association strongly believes that the
coverage of medical nutrition therapy, when medically necessary and appropriate,
needs to be in the basic benefits package.
