Molecular testing for cystic fibrosis carrier status practice guidelines: recommendations of the National Society of Genetic Counselors.

PURPOSE: To provide practice recommendations for genetic counselors whose clients are considering cystic fibrosis (CF) carrier testing or seeking information regarding CF molecular test results. The goals of these recommendations are to: 1) Provide updated information about the natural history, diagnosis, and treatment of CF and related conditions. 2) Supplement genetic counselors' knowledge and understanding of the available carrier screening and diagnostic testing options. 3) Describe the current state of genotype/phenotype correlations for CFTR mutations and an approach to interpreting both novel and previously described variants. 4) Provide a framework for genetic counselors to assist clients' decision-making regarding CF carrier testing, prenatal diagnosis, and pregnancy management. Disclaimer The practice guidelines of the National Society of Genetic Counselors (NSGC) are developed by members of the NSGC to assist genetic counselors and other health care providers in making decisions about appropriate management of genetic concerns; including access to and/or delivery of services. Each practice guideline focuses on a clinical or practice-based issue, and is the result of a review and analysis of current professional literature believed to be reliable. As such, information and recommendations within the NSGC practice guidelines reflect the current scientific and clinical knowledge at the time of publication, are only current as of their publication date, and are subject to change without notice as advances emerge.In addition, variations in practice, which take into account the needs of the individual patient and the resources and limitations unique to the institution or type of practice, may warrant approaches, treatments and/or procedures that differ from the recommendations outlined in this guideline. Therefore, these recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. Genetic counseling practice guidelines are never intended to displace a health care provider's best medical judgment based on the clinical circumstances of a particular patient or patient population.Practice guidelines are published by NSGC for educational and informational purposes only, and NSGC does not "approve" or "endorse" any specific methods, practices, or sources of information.

Genetic testing insurance coverage trends: a review of publicly available policies from the largest US payers.

AIM: Health plan coverage policies can influence utilization of genetic tests. Our goal was to characterize the current state of test-related policies from US private payers. METHODS: We searched the public websites of 206 insurers for coverage policies. We documented the number of policies, tests mentioned, coverage determination and policy effective dates. RESULTS: Approximately one-third of insurers had at least one genetic testing policy. Moderate consistency was seen between payers. Tests in oncology and personalized medicine were most frequently addressed. Half of the policies specifically excluded coverage of a particular genetic service. Nearly half of insurers had at least one out-of-date policy. CONCLUSION: Genetic services are addressed by many large health plans. Challenges remain in ensuring consistency and currency of payer policy for genetic tests.

The soluble guanylate cyclase stimulator BAY 41-2272 inhibits vascular smooth muscle growth through the cAMP-dependent protein kinase and cGMP-dependent protein kinase pathways.

Vascular smooth muscle (VSM) proliferation and migration are key components in vessel remodeling. Cyclic nucleotide signaling is protective and has long-served as a therapeutic target against undesired VSM growth. The present work analyzed the effects of the soluble guanylate cyclase (sGC) stimulator 3-(4-amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine [BAY 41-2272 (BAY)] on VSM growth, and we hypothesize that BAY has the capacity to reduce proliferation and migration via cyclic nucleotide-driven kinase signaling. Perivascular BAY postballoon injury reduced neointimal growth by ∼ 40% compared with vehicle controls after 2 weeks. In VSM cells, BAY (10 µM) reduced proliferation by ∼ 40% after 72 h and migration by ∼ 40% after 6 h and ∼ 60% after 18 h without deleterious effects on cell viability. cGMP content peaked (248 ×) 20 min after BAY treatment and remained elevated (140 ×) through 60 min; however, BAY did not affect cAMP levels compared with controls. Conventional and In-Cell Western analyses showed increases in vasodilator-stimulated phosphoprotein (VASP) phosphorylation (pVASP) at serines 239 (3 ×) and 157 (2 ×), respective markers of cGMP- and cAMP-directed protein kinases (PKG and PKA, respectively). The PKG inhibitor YGRKKRRQRRRPPLRKKKKKH peptide (DT-2) completely reversed BAY-mediated increases in pVASPSer(239) and BAY-mediated inhibition of migration. In comparison, the PKA inhibitor peptide PKI further potentiated BAY-stimulated pVASPSer(157) and pVASPSer(239) and partially reversed the antiproliferative effects of BAY. This is the first report demonstrating the effectiveness of BAY in reducing neointimal growth with direct evidence for PKG-specific antimigratory and PKA-specific antiproliferative mechanisms. Conclusively, the sGC stimulator BAY reduces VSM growth through cGMP-dependent PKG and PKA processes, providing support for continued evaluation of its clinical utility.

Analysis of insurance preauthorization requests for BRCA1 and BRCA2 genetic testing: experience of the Humana Genetic Guidance Program.

Published evidence-based guidelines help healthcare providers identify appropriate individuals for BRCA1/2 genetic testing. Health plans often use these guidelines to help make coverage and reimbursement decisions. Humana, a major health plan, launched the Humana Genetic Guidance Program to further facilitate the appropriate use of genetic testing through education. AIM: Identify opportunities to improve medical appropriateness for BRCA1/2 test requests by providing genetic education to providers. MATERIALS & METHODS: BRCA1/2 insurance preauthorization requests submitted to the program were evaluated against guideline-based coverage criteria. RESULTS: In total, 22% of the requests did not meet criteria, and in approximately a quarter of those requests, the clinical history suggested testing for a different cancer syndrome or another affected relative. CONCLUSION: This report demonstrates the program's effectiveness and illustrates the need for additional provider education regarding genetic testing from a payer's perspective.

HLA-B*5701 clinical testing: early experience in the United States.

HLA-B*5701 testing to provide risk stratification for abacavir hypersensitivity has the potential to reduce incidence of hypersensitivity reactions in susceptible individuals. Early experience with clinical HLA-B*5701 testing of the first 100 specimens, from a large clinical reference laboratory in the United States, is presented. Patient samples were tested using a two-step approach. The first step allowed rapid identification of most HLA-B*5701-negative samples in a high throughput mode. The second step involved resolution of putative positives by DNA sequencing to identify B*5701 specifically as well as other B57 subtypes. Test reporting included a phone call from a genetic counselor to obtain the ethnic background and indication for testing and to provide a patient-specific interpretation. The patients population was comprised of Caucasians, 84%; Hispanics, 13%; and African Americans, 3%. Among the 100 samples tested, 92% were HLA-B*5701-negative and 8% were positive for the HLA-B*5701 allele. All HLA-B*5701 allele positives were identified in Caucasian patients. Where the indication for testing was obtainable (57 patients), pre-abacavir therapy screening was the indication 67% of the time. Clarification of previous suspected history of hypersensitivity was the indication 33% of the time. Among samples tested to help clarify a previous history of hypersensitivity, 16/19 or 84% did not carry the HLA-B*5701 allele whereas 3/19 (16%) were carriers of the HLA-B*5701 allele. Early utilization of HLA-B*5701 testing in community practice was not always consistent with the clinical indications for testing. Post-test communication assisted in providing physician education and interpretation of patient-specific results.

Colorectal cancer screening using stool DNA analysis in clinical practice: early clinical experience with respect to patient acceptance and colonoscopic follow-up of abnormal tests.

BACKGROUND: Stool-based DNA screening for colorectal cancer (CRC) was recently made available for use in daily clinical practice (PreGen-Plus). The main objectives of this study were to examine patients' screening experiences with stool DNA testing in routine clinical practice and the results of diagnostic colonoscopy in patients with an antecedent abnormal stool DNA test. PATIENTS AND METHODS: Patients undergoing stool-based DNA testing were asked to complete and return via mail an anonymous 10-item questionnaire inquiring about their test-related experiences. Colonoscopy findings for all abnormal stool-based DNA tests were ascertained via a telephone survey of the ordering primary care clinicians' offices. RESULTS: Patient survey responses were collected between August 2003 and July 2005 and reflect an 18% (1211 of 6730) response rate. The majority reported that the specimen collection process was very easy/easy to perform (87%), that they were very likely/likely to use the test again (91%), and that they had never been screened for CRC previously by any method (52%). Tests were ordered predominantly by the patient's primary care clinician (90%), including obstetrician/gynecologist providers. Colonoscopy findings from 69 of 159 patients with an antecedent abnormal stool DNA test screened with PreGen-Plus between August 2003 and July 2004 were available for review. An abnormal stool DNA test correlated with a colonoscopically demonstrable abnormality in 49% of cases (34 of 69). Abnormal findings, including CRC in 3 patients (4%; 1 with Dukes A and 2 with Dukes B disease), single or multiple adenomatous polyps in 23 patients (33%), hyperplastic polyps in 3 patients (4%), and colitis in 5 patients (7%). Colonoscopy was reported as negative in 51% of patients (35 of 69), including 2 cases (3%) with an altered BAT-26 microsatellite caused by a normal polymorphism. CONCLUSION: Stool DNA testing provides an acceptable noninvasive alternative for CRC screening that can identify early-stage CRCs and adenomatous polyps in routine clinical practice. Ongoing and broader surveys are indicated to support these early findings.

Cystic fibrosis prenatal screening in genetic counseling practice: recommendations of the National Society of Genetic Counselors.

For over a decade, prenatal screening for cystic fibrosis (CF) has been considered a model for the integration of genetic testing into routine medical practice. Data from pilot studies and public policy discourse have led to recommendations by some professional organizations that CF screening should be offered or made available to pregnant women and their partners, and to couples planning a pregnancy. It is crucial that genetic counselors gain thorough understanding of the complexities of CF and the implications of positive test results, so that they may serve as a reliable, educated referral base and resource for health care providers and their patients. While not all pregnant women will be referred for genetic counseling prior to CF carrier testing, genetic counselors often will be asked to counsel clients after they have a positive test result, or who are found to be at increased risk. Genetic counselors can play an important role in providing accurate and current information as well as support for patients' informed decisions. These recommendations were created by a multicenter working group of genetic counselors with expertise in CF and are based on personal clinical experience, review of pertinent English language medical articles, and reports of expert committees. The recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a particular client.