Genomic-based tools for the risk assessment, management, and prevention of type 2 diabetes.

Type 2 diabetes (T2D) is a common and serious disorder and is a significant risk factor for the development of cardiovascular disease, neuropathy, nephropathy, retinopathy, periodontal disease, and foot ulcers and amputations. The burden of disease associated with T2D has led to an emphasis on early identification of the millions of individuals at high risk so that management and intervention strategies can be effectively implemented before disease progression begins. With increasing knowledge about the genetic basis of T2D, several genomic-based strategies have been tested for their ability to improve risk assessment, management and prevention. Genetic risk scores have been developed with the intent to more accurately identify those at risk for T2D and to potentially improve motivation and adherence to lifestyle modification programs. In addition, evidence is building that oral antihyperglycemic medications are subject to pharmacogenomic variation in a substantial number of patients, suggesting genomics may soon play a role in determining the most effective therapies. T2D is a complex disease that affects individuals differently, and risk prediction and treatment may be challenging for health care providers. Genomic approaches hold promise for their potential to improve risk prediction and tailor management for individual patients and to contribute to better health outcomes for those with T2D.

Pharmacogenomic knowledge gaps and educational resource needs among physicians in selected specialties.

BACKGROUND: The use of pharmacogenomic testing in the clinical setting has the potential to improve the safety and effectiveness of drug therapy, yet studies have revealed that physicians lack knowledge about the topic of pharmacogenomics, and are not prepared to implement it in the clinical setting. This study further explores the pharmacogenomic knowledge deficit and educational resource needs among physicians. MATERIALS AND METHODS: Surveys of primary care physicians, cardiologists, and psychiatrists were conducted. RESULTS: Few physicians reported familiarity with the topic of pharmacogenomics, but more reported confidence in their knowledge about the influence of genetics on drug therapy. Only a small minority had undergone formal training in pharmacogenomics, and a majority reported being unsure what type of pharmacogenomic tests were appropriate to order for the clinical situation. Respondents indicated that an ideal pharmacogenomic educational resource should be electronic and include such components as how to interpret pharmacogenomic test results, recommendations for prescribing, population subgroups most likely to be affected, and contact information for laboratories offering pharmacogenomic testing. CONCLUSION: Physicians continue to demonstrate pharmacogenomic knowledge gaps, and are unsure about how to use pharmacogenomic testing in clinical practice. Educational resources that are clinically oriented and easily accessible are preferred by physicians, and may best support appropriate clinical implementation of pharmacogenomics.

The promise and challenges of next-generation genome sequencing for clinical care.

With increased speed and decreased costs, next-generation gene sequencing has the potential to improve medical care by making possible widespread evaluation of patients' genomes in clinical settings. The entire genome of an individual can now be sequenced in less than 1 week at a cost of $5000 to $10,000; the cost will continue to decline. Analyses based on next-generation sequencing include whole-genome sequencing and whole-exome sequencing; DNA sequences that encode proteins are collectively known as the exome. In some instances, whole genome and whole-exome sequencing have already helped to accurately diagnose diseases with atypical manifestations, that are difficult to diagnose using clinical or laboratory criteria alone, or that otherwise require extensive or costly evaluation. For some patients with malignant neoplasms, next-generating sequencing can improve tumor classification, diagnosis, and management. Many challenges remain, however, such as the storage and interpretation of vast amounts of sequence data, training physicians and other health care professionals whose knowledge of genetics may be insufficient, effective genetic counseling and communication of results to patients, and establishing standards for the appropriate use of the technology. Rigorous studies are needed to assess the utility of whole-genome and whole-exome sequencing in large groups of patients, including comparative studies with other approaches to screening and diagnosis, and the evaluation of clinical end points and health care costs. The successes to date have been in single cases or in very small groups of patients. At present, although whole-genome or whole-exome sequencing show great promise, they should be incorporated into patient care only in limited clinical situations.

NCCN Biosimilars White Paper: regulatory, scientific, and patient safety perspectives.

Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval.

Maldynia: pathophysiology and management of neuropathic and maladaptive pain--a report of the AMA Council on Science and Public Health.

BACKGROUND: Because of disparate taxonomic arrays for classification, the American Academy of Pain Medicine has proposed categorizing pain on a neurobiologic basis as eudynia (nociceptive pain), Greek for "good pain," or maldynia (maladaptive pain), Greek for "bad pain." The latter has been viewed as maladaptive because it may occur in the absence of ongoing noxious stimuli and does not promote healing and repair. OBJECTIVE: To address recent findings on the pathogenesis of pain following neural injury and consider whether the development of maladaptive pain justifies its classification as a disease and to briefly discuss the scope of pharmacologic and non-pharmacologic approaches employed in patients with such pain. METHODS: English language reports on studies using human subjects were selected from a PubMed search of the literature from 1995 to August 2010 and from the Cochrane Library. Further information was obtained from Internet sites of medical specialty and other societies devoted to pain management. RESULTS: Neural damage to either the peripheral or central nervous system provokes multiple processes including peripheral and central sensitization, ectopic activity, neuronal cell death, disinhibition, altered gene expression, and abnormal sprouting and cellular connectivity. A series of neuro-immune interactions underlie many of these mechanisms. Imaging studies have shown that such damage is characterized by functional, structural, and chemical changes in the brain. Such pain is maladaptive in the sense that it occurs in the absence of ongoing noxious stimuli and does not promote healing and repair. CONCLUSION: As defined, maldynia is a multidimensional process that may warrant consideration as a chronic disease not only affecting sensory and emotional processing but also producing an altered brain state based on both functional imaging and macroscopic measurements. However, the absolute clinical value of this definition is not established.

Male breast cancer: risk factors, diagnosis, and management (Review).

Male breast cancer (MBC) is extremely rare, with an incidence in the general US population of <1%. It tends to be diagnosed at later stages than breast cancer in females, likely because of low awareness on the part of the patient and low suspicion by the physician. Risk factors include genetic predisposition, alterations to the estrogen-testosterone ratio, radiation exposure, and occupational hazards. Because of the rarity of MBC, mammography in men is more often utilized as a diagnostic tool to evaluate breast symptoms rather than as a tool for widespread screening. While clinical breast examinations are effective at evaluating breast symptoms, mammography also may be beneficial in separating malignant from benign breast disease. This study reviews MBC and its risk factors, recommendations for screening and diagnosis, the roles of mammography and genetic testing in surveillance, and management of patients with MBC. Heightened awareness of the increased risk in certain men by both physicians and patients, and adherence to guidelines recommended for the surveillance of men at increased risk, may result in earlier detection.

Reducing the population burden of cardiovascular disease by reducing sodium intake: a report of the Council on Science and Public Health.

Across populations, the level of blood pressure, the incremental rise in blood pressure with age, and the prevalence of hypertension are directly related to sodium intake. Observational studies and randomized controlled trials document a consistent effect of sodium consumption on blood pressure. The majority of sodium consumption in the United States is derived from amounts added during food processing and preparation. Leading scientific organizations and governmental agencies advise limiting sodium intake to 2400 mg or less daily (approximately 6000 mg of salt). Substantial public health benefits accrue from small reductions in the population blood pressure distribution. A 1.3-g/d lower lifetime sodium intake translates into an approximately 5-mm Hg smaller rise in systolic blood pressure as individuals advance from 25 to 55 years of age, a reduction estimated to save 150,000 lives annually. With an appropriate food industry response, combined with consumer education and knowledgeable use of food labels, the average consumer should be able to choose a lower-sodium diet without inconvenience or loss of food enjoyment. In the continued absence of voluntary measures adopted by the food industry, new regulations will be required to achieve lower sodium concentrations in processed and prepared foods.

The neurocognitive effects of alcohol on adolescents and college students.

BACKGROUND: Adolescents and college students are at high risk for initiating alcohol use and high-risk (or binge) drinking. There is a growing body of literature on neurotoxic and harmful cognitive effects of drinking by young people. On average, youths take their first drink at age 12 years. METHODS: MEDLINE search on neurologic and cognitive effects of underage drinking. RESULTS: Problematic alcohol consumption is not a benign condition that resolves with age. Individuals who first use alcohol before age 14 years are at increased risk of developing alcohol use disorders. Underage drinkers are susceptible to immediate consequences of alcohol use, including blackouts, hangovers, and alcohol poisoning and are at elevated risk of neurodegeneration (particularly in regions of the brain responsible for learning and memory), impairments in functional brain activity, and the appearance of neurocognitive deficits. Heavy episodic or binge drinking impairs study habits and erodes the development of transitional skills to adulthood. CONCLUSIONS: Underage alcohol use is associated with brain damage and neurocognitive deficits, with implications for learning and intellectual development. Impaired intellectual development may continue to affect individuals into adulthood. It is imperative for policymakers and organized medicine to address the problem of underage drinking.

Gender verification of female Olympic athletes.

Gender verification of female athletes has long been criticized by geneticists, endocrinologists, and others in the medical community. Problems include invalid screening tests, failure to understand the problems of intersex, the discriminatory singling out of women based only on laboratory results, and the stigmatization and emotional trauma experienced by individuals screened positive. Genuine sex-impostors have not been uncovered by laboratory-based genetic testing; however, gender verification procedures have resulted in substantial harm to a number of women athletes born with relatively rare genetic abnormalities. Individuals with sex-related genetic abnormalities raised as females have no unfair physical advantage and should not be excluded or stigmatized, including those with 5-alpha-steroid-reductase deficiency, partial or complete androgen insensitivity, and chromosomal mosaicism. In 1990, the International Amateur Athletics Federation (IAAF) called for ending genetic screening of female athletes and in 1992 adopted an approach designed to prevent only male impostors from competing. The IAAF recommended that the "medical delegate" have the ultimate authority in all medical matters, including the authority to arrange for the determination of the gender of the competitor if that approach is judged necessary. The new policy advocated by the IAAF, and conditionally adopted by the International Olympic Committee, protects the rights and privacy of athletes while safeguarding fairness of competition, and the American Medical Association recommends that it become the permanent approach.