Molecular Diagnostic Services Research Articles

Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates

Management of breast cancer in limited-resource settings is hindered by a lack of low-cost, logistically sustainable approaches toward molecular and cellular diagnostic pathology services that are needed to guide therapy. To address these limitations, we have developed a multimodal cellphone-based platform—the EpiView-D4—that can evaluate both cellular morphology and molecular expression of clinically relevant biomarkers directly from fine-needle aspiration (FNA) of breast tissue specimens within 1 h. The EpiView-D4 is comprised of two components: (1) an immunodiagnostic chip built upon a “non-fouling” polymer brush-coating (the “D4”) which quantifies expression of protein biomarkers directly from crude cell lysates, and (2) a custom cellphone-based optical microscope (“EpiView”) designed for imaging cytology preparations and D4 assay readout. As a proof-of-concept, we used the EpiView-D4 for assessment of human epidermal growth factor receptor-2 (HER2) expression and validated the performance using cancer cell lines, animal models, and human tissue specimens. We found that FNA cytology specimens (prepared in less than 5 min with rapid staining kits) imaged by the EpiView-D4 were adequate for assessment of lesional cellularity and tumor content. We also found our device could reliably distinguish between HER2 expression levels across multiple different cell lines and animal xenografts. In a pilot study with human tissue (n = 19), we were able to accurately categorize HER2-negative and HER2-positve tumors from FNA specimens. Taken together, the EpiView-D4 offers a promising alternative to invasive—and often unavailable—pathology services and may enable the democratization of effective breast cancer management in limited-resource settings.

External quality assessment (EQA) and alternative assessment procedures (AAPs) in molecular diagnostics: findings of an international survey.

Quality management for clinical laboratories requires the establishment of internal procedures including standard operating procedures (SOPs), internal quality control (QC), validation of test results and quality assessment. External quality assessment (EQA) and alternativeassessment procedures (AAPs) are part of the quality hierarchy required for diagnostic testing. The International Organization for Standardization (ISO) document with requirements for conformance ISO 15189 and the Clinical and Laboratory Standards Institute document (CLSI) QMS24 require participation in EQA schemes and AAPs where applicable. The purpose of this study was to perform a global survey of EQA and AAPs for key procedures in molecular diagnostic laboratories. The Committee for Molecular Diagnostics of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC C-MD) conducted a survey of international molecular laboratories that covered specific topics of molecular diagnostic services as well as methods for EQA and AAPs. The survey addressed the following aspects: (1) usage of laboratory-developed test (LDT), (2) participation in EQA schemes and (3) performance of AAPs. A total of 93 responses from laboratories located in Asia, Europe, the Middle East, North America and South America were received. The majority of the participating laboratories (65.9%) use LDTs and 81.3% stated that it is mandatory for them to participate in EQA programs, while 22% of the laboratories reported not performing AAPs. Thirty-one percent of the laboratories use EQAs for fewer than 50.0% of their reported parameters/analytes. While the majority of laboratories perform EQA and AAPs to improve their quality in molecular diagnostics, the amount of AAPs as quality procedures differs within the laboratories. Further surveys are necessary to clarify the existing needs in additional EQAs and standardized AAPs. The survey will also guide future efforts of the IFCC C-MD for identifying quality practices in need to improve harmonization and standardization within molecular diagnostics.

Implementation of Novel Molecular Biomarkers for Non-small Cell Lung Cancer in the Netherlands: How to Deal With Increasing Complexity.

The diagnostic landscape of non-small cell lung cancer (NSCLC) is changing rapidly with the availability of novel treatments. Despite high-level healthcare in the Netherlands, not all patients with NSCLC are tested with the currently relevant predictive tumor markers that are necessary for optimal decision-making for today's available targeted or immunotherapy. An expert workshop on the molecular diagnosis of NSCLC involving pulmonary oncologists, clinical chemists, pathologists, and clinical scientists in molecular pathology was held in the Netherlands on December 10, 2018. The aims of the workshop were to facilitate cross-disciplinary discussions regarding standards of practice, and address recent developments and associated challenges that impact future practice. This paper presents a summary of the discussions and consensus opinions of the workshop participants on the initial challenges of harmonization of the detection and clinical use of predictive markers of NSCLC. A key theme identified was the need for broader and active participation of all stakeholders involved in molecular diagnostic services for NSCLC, including healthcare professionals across all disciplines, the hospitals and clinics involved in service delivery, healthcare insurers, and industry groups involved in diagnostic and treatment innovations. Such collaboration is essential to integrate different technologies into molecular diagnostics practice, to increase nationwide patient access to novel technologies, and to ensure consensus-preferred biomarkers are tested.

Gridlock from diagnosis to treatment of multidrug-resistant tuberculosis in Tanzania: low accessibility of molecular diagnostic services and lack of healthcare worker empowerment in 28 districts of 5 high burden TB regions with mixed methods evaluation

BackgroundMultidrug-resistant tuberculosis (MDR-TB) outcomes are adversely impacted by delay in diagnosis and treatment.MethodsMixed qualitative and quantitative approaches were utilized to identify healthcare system related barriers to implementation of molecular diagnostics for MDR-TB. Randomly sampled districts from the 5 highest TB burden regions were enrolled during the 4th quarter of 2016. District TB & Leprosy Coordinators (DTLCs), and District AIDS Coordinators (DACs) were interviewed, along with staff from all laboratories within the selected districts where molecular diagnostics tests for MDR-TB were performed. Furthermore, the 2015 registers were audited for all drug-susceptible but retreatment TB cases and TB collaborative practices in HIV clinics, as these patients were in principal targeted for drug susceptibility testing by rapid molecular diagnostics.ResultsTwenty-eight TB districts from the 5 regions had 399 patients reviewed for retreatment with a drug-susceptible regimen. Only 160 (40%) had specimens collected for drug-susceptibility testing, and of those specimens only 120 (75%) had results communicated back to the clinic. MDR-TB was diagnosed in 16 (13.3%) of the 120 specimens but only 12 total patients were ultimately referred for treatment. Furthermore, among the HIV/AIDS clinics served in 2015, the median number of clients with TB diagnosis was 92 cases [IQR 32–157] yet only 2 people living with HIV were diagnosed with MDR-TB throughout the surveyed districts. Furthermore, the districts generated 53 front-line healthcare workers for interviews. DTLCs with intermediate or no knowledge on the clinical application of XpertMTB/RIF were 3 (11%), and 10 (39%), and DACs with intermediate or no knowledge were 0 (0%) and 2 (8%) respectively (p = 0.02). Additionally, 11 (100%) of the laboratories surveyed had only the 4-module XpertMTB/RIF equipment. The median time that XpertMTB/RIF was not functional in the 12 months prior to the investigation was 2 months (IQR 1–4).ConclusionsUnderutilization of molecular diagnostics in high-risk groups was a function of a lack of front-line healthcare workforce empowerment and training, and a lack of equipment access, which likely contributed to the observed delay in MDR-TB diagnosis in Tanzania.

The West African Ebola emergency and reconstruction; lessons from Public Health England.

West African governments, the WHO and wider international community were caught unprepared for the world's largest Ebola outbreak of 2014-16. This was an unprecedented challenge to local services and international agencies, since the emergency required high-tech molecular diagnostic services operated by specialist staff and a coordinated emergency response in addition to humanitarian support, which was not available at the beginning of the outbreak. Public Health England (PHE), as a new national public health agency was well placed to provide support for these needs. After the outbreak, PHE supported reconstruction to ensure diagnostic and emergency planning capability remained in place in the immediate aftermath of the outbreak and build necessary public health infrastructure for the future. The article describes the role PHE played as a national public health agency supporting reconstruction and long-term development through the UK Government (Department for International Development) programme called 'Resilient Zero'. Public Health England (PHE), UK Government's Department for International Development, WHO, US Centers for Communicable Diseases (CDC), China Centre for Communicable Diseases (China CDC). The need for reliable, sustainable, in country molecular diagnostics, together with a programme to strengthen in country Emergency Planning, Preparedness and Response (EPRR). Providing high tech molecular capability in a resource-poor West African country with variable provision of basic diagnostic equipment, intermittent power supply, ineffective supply chains and maintaining training capacity for emergency planning in the long term. Emergency planning models from the West needed to be adapted for the countries' context. Short term aid projects as a model did not suite this development requirement. PHE had strong local and international political support to reconstruct three Government regional laboratories and deploy molecular technology. Significant learning by PHE as a national public health agency and sharing this will be of benefit to other national public health agencies. UK staff reported increased levels of satisfaction and experience relevant to public health practice. The Sierra Leonean Government and officials requested long-term levels of commitment. It is important for agencies such as PHE to constantly learn, develop long-term institutional partnerships and play a bigger role with other similar agencies internationally. How best to support sustainable high-tech molecular technology in West Africa and modules for emergency planning relevant to the context; evidence for long term versus short-term support for highly complex diagnostic capabilities; relevance to maintaining individual country public health infrastructure to ensuring global health security; benefits of overseas work for employee of a national agency.

Medical genetics services in VenezuelaServiços de genética médica na Venezuela

RESUMENObjetivo.Caracterizar los servicios de genética médica de Venezuela con el fin de conocer la distribución de sus recursos, servicios, tecnologías y formación profesional.Métodos.Se realizó una investigación descriptiva, de tipo documental, entre febrero y noviembre de 2016 de los servicios de genética, mediante la revisión de fuentes documentales primarias y el uso de una ficha de recolección de datos en las instituciones de investigación para información referente a disponibilidad de recursos humanos, servicios de atención y diagnóstico, así como formación profesional, y la base de datos de la Sociedad Venezolana de Genética Humana, que permitió identificar los recursos humanos en centros de genética. El criterio de inclusión fue instituciones con recursos humanos formados en genética.Resultados.Los criterios fueron cumplidos por cuatro instituciones de investigación, siete universidades y cuatro hospitales, todos del sector público. En estas instituciones trabajan 124 profesionales, 56 son médicos y 68 se desempeñan en el área de laboratorio. Sesenta y dos por ciento de los profesionales pertenecen a las instituciones de investigación; estas cuentan con servicios de atención clínico, diagnóstico molecular, bioquímico y, con menos frecuencia, los análisis citogenéticos, prenatales y forenses. Cinco regiones del país tienen entre dos y cuatro médicos genetistas por millón de habitantes. El 96% de los profesionales de laboratorio se localizan en dos regiones (Capital y Zuliana), cinco regiones carecen de ellos. Las instituciones de investigación han formado en genética el 40% de los recursos humanos actuales del país.Conclusiones.Los servicios de genética presentan gran variabilidad de opciones diagnósticas, un acceso limitado y grandes aportes en formación profesional; se requieren políticas coordinadas que los integre y disminuya las brechas.

Analysis of CTG repeat length variation in the DMPK gene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia

ObjectiveThe lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to...

Health Technology Assessment for Molecular Diagnostics: Practices, Challenges, and Recommendations from the Medical Devices and Diagnostics Special Interest Group

BackgroundHealth technology assessments (HTAs) are increasingly used to inform coverage, access, and utilization of medical technologies including molecular diagnostics (MDx). Although MDx are used to screen patients and inform disease management and treatment decisions, there is no uniform approach to their evaluation by HTA organizations. ObjectivesThe International Society for Pharmacoeconomics and Outcomes Research Devices and Diagnostics Special Interest Group reviewed diagnostic-specific HTA programs and identified elements representing common and best practices. MethodsMDx-specific HTA programs in Europe, Australia, and North America were characterized by methodology, evaluation framework, and impact. Published MDx HTAs were reviewed, and five representative case studies of test evaluations were developed: United Kingdom (National Institute for Health and Care Excellence’s Diagnostics Assessment Programme, epidermal growth factor receptor tyrosine kinase mutation), United States (Palmetto’s Molecular Diagnostic Services Program, OncotypeDx prostate cancer test), Germany (Institute for Quality and Efficiency in Healthcare, human papillomavirus testing), Australia (Medical Services Advisory Committee, anaplastic lymphoma kinase testing for non–small cell lung cancer), and Canada (Canadian Agency for Drugs and Technologies in Health, Rapid Response: Non-invasive Prenatal Testing). ResultsOverall, the few HTA programs that have MDx-specific methods do not provide clear parameters of acceptability related to clinical and analytic performance, clinical utility, and economic impact. The case studies highlight similarities and differences in evaluation approaches across HTAs in the performance metrics used (analytic and clinical validity, clinical utility), evidence requirements, and how value is measured. Not all HTAs are directly linked to reimbursement outcomes. ConclusionsTo improve MDx HTAs, organizations should provide greater transparency, better communication and collaboration between industry and HTA stakeholders, clearer links between HTA and funding decisions, explicit recognition of and rationale for differential approaches to laboratory-developed versus regulatory-approved test, and clear evidence requirements.

Sequence Variant Interpretation 2.0: Perspective on New Guidelines for Sequence Variant Classification.

Diagnostic tests based on next-generation sequencing (NGS),5 including gene-panel, exome, and whole-genome sequencing, are routinely performed worldwide. Although the technical validity of NGS-based tests continues to improve rapidly, the community is working to demonstrate the clinical validity and utility of these methods, which largely depend on our ability to interpret all sequence variants in a thorough, reproducible, timely, and clinically relevant manner. Accurately interpreting variants is challenging. The large volume of variants; the lack of curated information regarding the relationship between variants, gene functions, and clinical consequences; and the lack of consistent roles that capture all aspects of a variant's impact on the normal functions of a gene product are some of the challenges faced by medical geneticists, genetic counselors, and molecular pathologists specializing in molecular diagnostic services. The American College of Medical Genetics and Genomics (ACMG), the Association for Molecular Pathology, and the College of American Pathologists recently jointly released standards and guidelines for the interpretation of sequence variants (1). This collective effort by society leadership groups and the whole genetics community aims to address the above challenges and represents a milestone in NGS-based diagnostic testing. The first set of ACMG variant interpretation guidelines was released in 2008, at a time when Sanger sequencing was the main method of single gene variant detection and molecular diagnostic testing (2). In the 2008 version of these guidelines (referred to here as guidelines 1.0), the decision tree for interpreting a sequence variant started with whether a variant was previously reported as causative of the disease and followed with a prediction based on the nature or type of a variant. Because NGS-based tests often detect numerous previously unreported variants, a classification system based on previously reported variants is of very limited use. Furthermore, population-based exome and whole-genome sequencing projects suggest that many …

Roadblocks preventing personalized medicine from reaching its potential.

Biomarkers in MedicineVol. 9, No. 1 CommentaryRoadblocks preventing personalized medicine from reaching its potentialJoshua P CohenJoshua P CohenTufts Center for the Study of Drug Development, 75 Kneeland Street, Suite 1100, Boston, MA 02111, USA E-mail Address: joshua.cohen@tufts.eduSearch for more papers by this authorPublished Online:21 Jan 2015https://doi.org/10.2217/bmm.14.66AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: biomarkersclinical utilitypersonalized medicinereimbursementReferences1 President's Council of Advisors on Science and Technology. Priorities for personalized medicine (2008). www.whitehouse.gov Google Scholar2 US FDA. Guidance for Industry and Food and Drug Administration Staff: in vitro companion diagnostic devices (2011). www.fda.gov Google Scholar3 US FDA. Paving the way for personalized medicine: FDA's role in a new era of medical product development (2013). www.fda.gov Google Scholar4 Cohen J. Overcoming regulatory and economic challenges facing pharmacogenomics. N. Biotechnol. 29(6), 751–756 (2012).Crossref, Medline, CAS, Google Scholar5 US FDA. Table of pharmacogenomic biomarkers in drug labeling (2014). www.fda.gov Google Scholar6 Reinke T. Targeted medications: new focus on companion tests. Manag. Care 21(2), 35–38 (2012).Medline, Google Scholar7 Milne C-P, Garafalo S, Bryan C et al. Trial watch: Personalized medicines in late-stage development. Nat. Rev. Drug Discov. 13, 324–325 (2014).Crossref, Medline, CAS, Google Scholar8 Cohen J, Felix A. Personalized medicine's bottleneck: diagnostic test evidence and reimbursement. J. Pers. Med. 4, 163–175 (2014).Crossref, Medline, Google Scholar9 Ansari M. The regulation of companion diagnostics: a global perspective. Ther. Innovat. Reg. Sci. 47, 405–415 (2013).Crossref, Medline, Google Scholar10 US FDA. FDA approves Xalkori with companion diagnostic for a type of late-stage lung cancer (2011). www.fda.gov Google Scholar11 Centers for Medicare and Medicaid Services. Pharmacogenomic testing to predict warfarin responsiveness. www.cms.gov Google Scholar12 Eisenberg A. Variations on a gene, and tools to find them. New York Times 27 April 2013.Google Scholar13 Tunis S, Pearson S. Coverage options for promising technologies: Medicare's ‘coverage with evidence development’. Health Aff. 25(5), 1218–1230 (2006).Crossref, Medline, Google Scholar14 NIH. Reimbursement models to promote evidence generation and innovation for genomic tests (2012). www.genome.gov Google Scholar15 Twachtman G. With personalized medicine, payers want a role in early development. The Pink Sheet (2013). www.pharmamedtechbi.comGoogle Scholar16 Edlin M. Drug manufacturers seek payer feedback. Managed Care Executive (2013). http://managedhealthcareexecutive.modernmedicine.comlGoogle Scholar17 Palmetto's Molecular Diagnostic Services Program (MolDx) program. www.palmettogba.com Google Scholar18 Usdin S. Coding for utility. BioCentury 15 July 2013.Google Scholar19 Quinn B, Hoag F. Current issues and options: coverage and reimbursement for molecular diagnostics: Department of Health and Human Services (HHS) ASPE Workgroup (2011). http://aspe.hhs.govGoogle ScholarFiguresReferencesRelatedDetailsCited ByFundamentally low reproducibility in molecular genetic cancer research30 July 2016 | Russian Journal of Genetics, Vol. 52, No. 7Companion diagnostics at the intersection of personalized medicine and healthcare deliveryScott A Waldman & Andre Terzic21 January 2015 | Biomarkers in Medicine, Vol. 9, No. 1 Vol. 9, No. 1 Follow us on social media for the latest updates Metrics Downloaded 81 times History Published online 21 January 2015 Published in print January 2015 Information© Future Medicine LtdKeywordsbiomarkersclinical utilitypersonalized medicinereimbursementFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Clinical applications and implications of common and founder mutations in Indian subpopulations.

South Asian Indians represent a sixth of the world's population and are a racially, geographically, and genetically diverse people. Their unique anthropological structure, prevailing caste system, and ancient religious practices have all impacted the genetic composition of most of the current-day Indian population. With the evolving socio-religious and economic activities of the subsects and castes, endogamous and consanguineous marriages became a commonplace. Consequently, the frequency of founder mutations and the burden of heritable genetic disorders rose significantly. Specifically, the incidence of certain autosomal-recessive disorders is relatively high in select Indian subpopulations and communities that share common recent ancestry. Although today clinical genetics and molecular diagnostic services are making inroads in India, the high costs associated with the technology and the tests often keep patients from an exact molecular diagnosis, making more customized and tailored tests, such as those interrogating the most common and founder mutations or those that cater to select sects within the population, highly attractive. These tests offer a quick first-hand affordable diagnostic and carrier screening tool. Here, we provide a comprehensive catalog of known common mutations and founder mutations in the Indian population and discuss them from a molecular, clinical, and historical perspective.

K13 First Middle Eastern Focus On Research And Assistance On Huntington Disease In Oman

<h3>Background</h3> Huntington disease (HD) was sporadically described in the Arabic population, so far. Since Arabic people frequently marry within the same family, the mutation risk is reiterating in offspring. In Oman, only few and anecdotal reports, are known. <h3>Aims</h3> To set a HD Centre in the Middle East. <h3>Methods</h3> A Neurogenetic Centre with outpatient and molecular diagnostic services focused on HD, was inaugurated by Ministry of Health at Royal Hospital, Oman, in November 2013. We analysed clinical, genetic and demographic features of affected and at risk subjects from a large and inbred family from Muscat and surroundings. <h3>Results</h3> In this six generations family we have visited 23 alive symptomatic subjects of 42 reported by genealogical retrospective analysis. We counted about 84, 50% and 86, 25%, at risk individuals. We found 18 people with a theoretical risk &gt;50%, due to intermarriages and four with a risk of homozygousity for CAG mutation. DNA testing was provided, after informed consent, with the support of genetic counselling, and clinical data were collected by the Unified HD Rating Scale. Age at onset ranged between 2 and 79 years, (CAG)n between 39 (oldest onset) and over 80 (earliest onset) repeats. By careful interview of family members, we deduced that the ancestor carrying the HD mutation to Oman immigrated from Tanzania, Africa. <h3>Conclusions</h3> Our collaborative effort aims to improve medical assistance and social awareness on HD and related diseases in Middle East. Accordingly, we have now contributed to set the first HD family association in Middle East (www.hdom.org), in strict collaboration with Italian LIRH (www.lirh.it).

The Detection of Heterozygous Familial Hypercholesterolemia in Ireland

Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant condition with a population prevalence of 1 in 500, and is associated with significant cardiovascular morbidity and mortality. It may be caused by mutations in the low-density lipoprotein (LDL) receptor, apolipoprotein B100 (Apo B100), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes, with over 1,000 causative mutations described. Statin therapy in HeFH is considered effective and safe. Audit data suggest that approximately 80% of the putative HeFH population remains unidentified and, therefore, there is a need to develop a strategy for the identification of affected individuals so that early lipid-lowering treatment may be offered. There is good evidence showing the effectiveness and acceptability of HeFH screening programs in Europe. The authors describe a protocol for an all island approach to HeFH detection in the Republic of Ireland/Northern Ireland. Index cases will be identified by opportunistic screening using the Simon Broome, or Make Early Diagnosis to Prevent Early Death (MedPed) and World Health Organization (WHO) criteria. Patients identified as "definite," "probable," or "possible" HeFH criteria will be offered genetic testing. The authors expect causative mutations to be identified in approximately 80% of patients with "definite" HeFH but in only approximately 20% of patients with "possible" HeFH. Cascade screening will be undertaken in first-degree relatives of the index case using genetic testing (where a causative mutation has been identified), or otherwise using LDL cholesterol concentration. The establishment of a HeFH screening program on an all-island basis will require: expansion of the existing molecular genetics diagnostic services, the establishment of a cohort of nurses/genetic counselors, a HeFH database to support cascade testing, the development of a network of lipid clinics (in a primary or secondary care setting), and an educational initiative to raise awareness of HeFH among healthcare professionals and the general population.

The effect of mret treatment on human astrocyte cells post exposed to ionizing radiation of 2gy and 8 gy

The effect of mret treatment on human astrocyte cells post exposed to ionizing radiation of 2gy and 8 gy

Diagnosing sarcomas: the role of experience

Soft tissue sarcomas are rare but have numerous subtypes, and both benign and malignant soft tissue tumours can show considerable morphological variation. With increasing subspecialization, histopathologists become less skilled outside their areas of practice, and it can be difficult for an inexperienced pathologist to assess malignancy, subtype and grade of a sarcoma as required for management. In different clinicopathological settings, there is a consistent discrepancy rate between referring and expert diagnoses of approximately 25% for diagnosis and grading, with about a 5% malignant-benign change.Soft tissue tumour specimens should therefore be reported by specialist pathologists, within a multidisciplinary team. Furthermore, outcomes are better in specialized centres with dedicated multidisciplinary teams bringing together expertise in imaging, histopathology, surgery and oncology. This should include access to cytogenetic and molecular genetic diagnostic services. Ideally, patients with soft tissue masses suspected to be malignant should be referred to a specialist unit before biopsy.

A daganatos betegellátás innovatív fejlesztése genomikai módszerekkel. Beszámoló a Nemzeti Onkológiai Konzorcium 2008. évi tevékenységéről

In the 3rd year of the program 8 new molecular diagnostic services have been introduced to clinic in the management of breast-, lung-, colorectal cancers as well as in GIST and melanoma. Two patents have been filed for innovative modulation of mito/motogenic signaling pathways in cancer cells. In preclinical models of human cancer a functional imaging technique was developed to detect vascular eff ects of erythropoietin. Using a genomic approach, the sequential changes in human melanoma during systemic dissemination were determined revealing several novel potential prognostic factors and some interesting novel targets for therapy.

Vita Genomics, Inc.

Vita Genomics, Inc., centered in Taiwan and China, aims to be a premier genomics-based biotechnological and biopharmaceutical company in the Asia-Pacific region. The company focuses on conducting pharmacogenomics research, in vitro diagnosis product development and specialty contract research services in both genomics and pharmacogenomics fields. We are now initiating a drug rescue program designed to resurrect drugs that have failed in the previous clinical trials owing to low efficacies. This program applies pharmacogenomics approaches using biomarkers to screen subsets of patients who may respond better or avoid adverse responses to the test drugs. Vita Genomics, Inc. has envisioned itself as an important player in the healthcare industry offering advanced molecular diagnostic products and services, revolutionizing thedrug-development process and providing pharmacogenomic solutions.

A national audit of the laboratory diagnosis of tuberculosis and other mycobacterial diseases within the United Kingdom.

In order to audit United Kingdom laboratory diagnostic and reference services including novel molecular methods for tuberculosis, a questionnaire was sent to laboratories submitting specimens to the PHLS Mycobacterium Reference...

Molecular pathology and managed care: challenges and opportunities.

The inherent costs of sophisticated molecular-based diagnostic tests are of significant importance to managed care organizations. Providers of molecular diagnostic services have emphasized that these tests can provide a reduced length of stay for hospitalized patients resulting from earlier definitive diagnosis, a reduction in the use of less expensive nondefinitive tests, a reduction in expensive ancillary diagnostic services such as radiologic imaging and endoscopies, an enhanced ability to predict disease outcome and responses to various expensive therapies, and new programs in detecting disease risk and maintaining patient wellness. In order for these newer molecular-based tests to be included in the list of covered services by the health maintenance organizations (HMOs), the clinical value and potential cost-benefit ratios must be articulated to the medical directors, administrative officials, and subscribers of the HMOs by the molecular diagnostic test providers.

Physician knowledge and attitudes towards molecular genetic (DNA) testing of their patients.

To better define the knowledge and attitudes of practicing physicians about genetics; specifically molecular genetics. Further, to examine differences between four practice specialties and to assess variables that affect both knowledge and attitudes. A mail-in survey was sent to a random sample of non-geneticist physicians, with a second copy sent to non-responders. Questions included sociodemographic variables, sources of current knowledge and education in genetics, clinical experience with genetic disease, self-confidence in providing genetic counseling, attitudes towards referring patients to a genetic center, awareness of molecular genetic testing and attitudes towards its use in clinical practice and population screening. Responses were obtained from over 900 practicing physicians in the Canadian province of Ontario (population 10 million). Genetic services are provided through nine major and several outreach centers. Molecular diagnostic services are provided through six provincially funded laboratories. There are no direct costs to the patient for any genetic service. A random sample of family physicians, obstetricians, pediatricians and internists was surveyed from both private and hospital based practices. Responses varied by specialty, years from graduation, gender, and type of practice. Pediatricians and obstetricians were more knowledgeable about genetics, had more interaction with genetic services and were more supportive of their utility. A major proportion of physicians continue to rely upon undergraduate and medical school courses for knowledge, and the specialties showed different preferences for seeking information. A majority of physicians considered their knowledge of genetics to be adequate, but a minority were confident to provide genetic counseling for simple genetic scenarios. Relatively few had actually made use of DNA diagnostic services and there was relatively poor knowledge of what services were available.