Follow-up Of Positive Results Research Articles

Biochemical Assessment of Pheochromocytoma and Paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumors or in patients with an asymptomatic presentation. Additional measurements of plasma methoxytyramine can be important for some tumors, such as paragangliomas, and for surveillance of patients at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimization of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the test results, which can also suggest likely size, adrenal vs extra-adrenal location, underlying biology, or even metastatic involvement of a suspected tumor. Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.

A Collaborative Intervention Between Emergency Medicine and Infectious Diseases to Increase Syphilis and HIV Screening in the Emergency Department.

Sexually transmitted infections (STIs) are a common reason for evaluation in the emergency department (ED). Given the overlapping risk factors for STIs, patients screened for gonorrhea and chlamydia should be tested for syphilis and HIV. Syphilis and HIV testing rates in the ED have been reported to be low. The study objective was to examine whether collaboration between emergency medicine (EM) and infectious disease (ID) providers improved syphilis and HIV testing in the ED. A multidisciplinary team of EM and ID providers was formed to identify and address barriers to syphilis and HIV testing in the ED. Syphilis, HIV, chlamydia, and gonorrhea testing and infection rates were calculated and compared during 2 time periods: preintervention (January 1, 2012-December 30, 2017) and postintervention (November 1, 2018-November 30, 2019). We also extracted clinical and laboratory data from patients with positive syphilis and HIV results during the study period. The most commonly cited barrier to syphilis and HIV testing was concern about follow-up of positive results. Compared with the preintervention period, syphilis and HIV testing rates increased significantly in the postintervention period (incidence rate ratios, 30.70 [P < 0.0001] and 28.99 [P < 0.0001] for syphilis and HIV, respectively). The postintervention period was also associated with a significant increase in the identification of patients with positive syphilis and HIV results (incidence rate ratios, 7.02 [P < 0.0001] and 2.34 [P = 0.03], respectively). Collaboration between EM and ID providers resulted in a significant increase in syphilis and HIV testing and diagnosis in the ED.

Weight of evidence approach using a TK gene mutation assay with human TK6 cells for follow-up of positive results in Ames tests: a collaborative study by MMS/JEMS

BackgroundConflicting results between bacterial mutagenicity tests (the Ames test) and mammalian carcinogenicity tests might be due to species differences in metabolism, genome structure, and DNA repair systems. Mutagenicity assays using human cells are thought to be an advantage as follow-up studies for positive results in Ames tests. In this collaborative study, a thymidine kinase gene mutation study (TK6 assay) using human lymphoblastoid TK6 cells, established in OECD TG490, was used to examine 10 chemicals that have conflicting results in mutagenicity studies (a positive Ames test and a negative result in rodent carcinogenicity studies).ResultsTwo of 10 test substances were negative in the overall judgment (20% effective as a follow-up test). Three of these eight positive substances were negative after the short-term treatment and positive after the 24 h treatment, despite identical treatment conditions without S9. A toxicoproteomic analysis of TK6 cells treated with 4-nitroanthranilic acid was thus used to aid the interpretation of the test results. This analysis using differentially expressed proteins after the 24 h treatment indicated that in vitro specific oxidative stress is involved in false positive response in the TK6 assay.ConclusionsThe usefulness of the TK6 assay, by current methods that have not been combined with new technologies such as proteomics, was found to be limited as a follow-up test, although it still may help to reduce some false positive results (20%) in Ames tests. Thus, the combination analysis with toxicoproteomics may be useful for interpreting false positive results raised by 24 h specific reactions in the assay, resulting in the more reduction (> 20%) of false positives in Ames test.

Experience With Pretravel Testing for SARS-CoV-2 at an Academic Medical Center

International travel has been a significant factor in the coronavirus disease 2019 pandemic. Many countries and airlines have implemented travel restrictions to limit the spread of the causative agent, severe acute respiratory syndrome coronavirus-2. A common requirement has been a negative reverse-transcriptase polymerase chain reaction performed by a clinical laboratory within 48 to 72 hours of departure. A more recent travel mandate for severe acute respiratory syndrome coronavirus-2 immunoglobulin M serology testing was instituted by the Chinese government on October 29, 2020. Pretravel testing for severe acute respiratory syndrome coronavirus-2 raises complications in terms of cost, turnaround time, and follow-up of positive results. In this report, we describe the experience of a multidisciplinary collaboration to develop a workflow for pretravel severe acute respiratory syndrome coronavirus-2 reverse-transcriptase polymerase chain reaction and immunoglobulin M serology testing at an academic medical center. The workflow primarily involved self-payment by patients and preferred retrieval of results by the patient through the electronic health record patient portal (Epic MyChart). A total of 556 unique patients underwent pretravel reverse-transcriptase polymerase chain reaction testing, with 13 (2.4%) having one or more positive results, a rate similar to that for reverse-transcriptase polymerase chain reaction testing performed for other protocol-driven asymptomatic screening (eg, inpatient admissions, preprocedural) at our medical center. For 5 of 13 reverse-transcriptase polymerase chain reaction positive samples, the traveler had clinical history, prior reverse-transcriptase polymerase chain reaction positive, and high cycle thresholds values on pretravel testing consistent with remote infection and minimal transmission risk. Severe acute respiratory syndrome coronavirus-2 immunoglobulin M was performed on only 24 patients but resulted in 2 likely false positives. Overall, our experience at an academic medical center shows the challenge with pretravel severe acute respiratory syndrome coronavirus-2 testing.

Effect of Mailed Human Papillomavirus Test Kits vs Usual Care Reminders on Cervical Cancer Screening Uptake, Precancer Detection, and Treatment

In the United States, more than 50% of cervical cancers are diagnosed in underscreened women. Cervical cancer screening guidelines now include primary human papillomavirus (HPV) testing as a recommended strategy. Home-based HPV self-sampling is a viable option for increasing screening compliance and effectiveness; however, US data are needed to inform health care system implementation. To evaluate effectiveness of mailed HPV self-sampling kits vs usual care reminders for in-clinic screening to increase detection and treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and uptake of cervical cancer screening. Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Women aged 30 to 64 years with health plan enrollment for 3 years and 5 months or more, a primary care clinician, no Papanicolaou test within 3 years and 5 months, and no hysterectomy were identified through electronic medical records and enrolled from February 25, 2014, to August 29, 2016, with follow-up through February 26, 2018. The control group received usual care (annual patient reminders and ad hoc outreach from primary care clinics). The intervention group received usual care plus a mailed HPV self-sampling kit. Two primary outcomes were (1) CIN2+ detection within 6 months of screening and (2) treatment within 6 months of CIN2+ detection. Screening uptake within 6 months of randomization was a secondary outcome. A total of 19 851 women (mean [SD] age, 50.1 [9.5] years) were included, with 9960 randomized to the intervention group and 9891 randomized to the control group. All women randomized were included in analysis. In the intervention group, 12 participants with CIN2+ were detected compared with 8 in the control group (relative risk, 1.49; 95% CI, 0.61-3.64) and 12 cases were treated vs 7 in the control group (relative risk, 1.70; 95% CI, 0.67-4.32). Screening uptake was higher in the intervention group (2618 participants [26.3%] vs 1719 participants [17.4%]; relative risk, 1.51; 95% CI, 1.43-1.60). Mailing HPV kits to underscreened women increased screening uptake compared with usual care alone, with no significant differences in precancer detection or treatment. Results support the feasibility of mailing HPV kits to women who are overdue for screening as an outreach strategy to increase screening uptake in US health care systems. Efforts to increase kit uptake and follow-up of positive results are warranted to maximize detection and treatment of CIN2+. ClinicalTrials.gov identifier: NCT02005510.

Cervical cancer subtype less detectable by Papanicolaou testing.

An increasingly common cervical cancer subtype is less detectable by Papanicolaou testing, and this makes human papillomavirus (HPV) testing and vaccination more important than ever according to an American Cancer Society study in Preventive Medicine.1 The squamous cell carcinoma subtype of cervical cancer, which accounts for 80% to 90% of cases, has been on the decline, as have cervical cancers overall. However, adenocarcinomas, the second most common type of the disease, which Papanicolaou testing is less likely to detect, have become more common over the past 20 to 30 years, researchers note. As a result of these findings, investigators emphasized the importance of increasing screening utilization and ensuring appropriate follow-up of positive results. Because HPV infection is the cause of most of these cancers, increasing screening uptake is essential, Dr. Islami says. He adds that at the same time, researchers need to explore strategies to reduce overdiagnosis, which frequently occurs with HPV testing.

Current Practice in the Management of Pulmonary Nodules Detected on Computed Tomography Chest Scans.

Lung cancer is associated with high mortality. It can present as one or more pulmonary nodules identified on computed tomography (CT) chest scans. The National Lung Screening Trial has shown that the use of low-dose CT chest screening can reduce deaths due to lung cancer. High adherence to appropriate follow-up of positive results, including imaging or interventional approaches, is an important aspect of pulmonary nodule management. Our study is one of the first to evaluate the current practice in managing pulmonary nodules and to explore potential causes for nonadherence to follow-up. This is a retrospective analysis at St. Paul's Hospital, a tertiary healthcare center in Vancouver, British Columbia, Canada. We first identified CT chest scans between January 1 to June 30, 2014, that demonstrated one or more pulmonary nodules equal to or greater than 6 mm in diameter. We then looked for evidence of interventional (surgical resection or biopsy, or bronchoscopy for transbronchial biopsy and cytology) and radiological follow-up of the pulmonary nodule by searching on the province-wide CareConnect eHealth Viewer patient database. A total of 1614 CT reports were analyzed and 139 (8.6%) had a positive finding. Out of the 97 patients who received follow-up, 54.6% (N = 53) was referred for a repeat CT chest scan and 36.1% (N = 35) and 9.3% (N = 9) were referred for interventional biopsy and surgical resection, respectively. In our study, 30.2% (N = 42) of the patients with pulmonary nodules were nonadherent to follow-up. Despite the radiologist's recommendation for follow-up within a certain time interval, only 36% had repeat imaging in a timely manner. Our findings reflect the current practice in the management of pulmonary nodules and suggest that there is a need for improvement at our academic center. Adherence to follow-up is important for the potentially near-future implementation of lung cancer screening.

Standardized cell sources and recommendations for good cell culture practices in genotoxicity testing

Good cell culture practice and characterization of the cell lines used are of critical importance in in vitro genotoxicity testing. The objective of this initiative was to make continuously available stocks of the characterized isolates of the most frequently used mammalian cell lines in genotoxicity testing anywhere in the world (‘IVGT’ cell lines). This project was organized under the auspices of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing.First, cell isolates were identified that are as close as possible to the isolate described in the initial publications reporting their use in genotoxicity testing. The depositors of these cell lines managed their characterization and their expansion for preparing continuously available stocks of these cells that are stored at the European Collection of Cell Cultures (ECACC, UK) and the Japanese Collection of Research Bioresources (JCRB, Japan). This publication describes how the four ‘IVGT’ cell lines, i.e. L5178Y TK+/− 3.7.2C, TK6, CHO-WBL and CHL/IU, were prepared for deposit at the ECACC and JCRB cell banks. Recommendations for handling these cell lines and monitoring their characteristics are also described. The growth characteristics of these cell lines (growth rates and cell cycles), their identity (karyotypes and genetic status) and ranges of background frequencies of select endpoints are also reported to help in the routine practice of genotoxicity testing using these cell lines.

P008 An audit of time to treatment for bacterial STIs, and time to provision of HIV diagnosis, in a large urban sexual health clinic

Background The time from testing to treatment of STIs, and the provision of a new HIV diagnosis* , is a marker of quality of care. The follow-up of positive results is undertaken by nurses according to predetermined protocols. In April 2015 gonococcal NAAT superseded the relatively insensitive gonococcal culture test. Aims The aims were to determine the time to treatment for HIV*, syphilis, gonorrhoea and chlamydia; and if the introduction of gonorrhoea NAAT affected the time to treatment. Methods This observational study compared the median time (days) to treatment for HIV* and STIs in two time periods (P1: April-June 2014 and P2: April-June 2015). For gonorrhoea, the median time from testing to result complete and median follow-up time to treatment were also compared. The Mann-Whitney U Test for two independent samples was used to compare medians. Results The median time to treatment for all STIs, including HIV*, was 8 days or less in P1 and P2 (all p ≥ 0.08). The time to result complete for gonorrhoea was significantly less in P2 (n = 189, median = 3) compared to P1 (n = 50, median = 5) (p = 0.000). However, the median follow-up time to treatment was not significantly different between P1 (median = 3) and P2 (median = 4) (p = 0.4). Discussion/Conclusion The median time to treatment for HIV*, syphilis, gonorrhoea and chlamydia was not significantly different between P1 and P2. Despite gonorrhoea NAAT results being available significantly earlier, the overall time to treatment was not different. This likely relates to the nearly fourfold increase in the detection of gonorrhoea and the additional burden of work for follow-up nurses.

Opportunities to integrate new approaches in genetic toxicology: an ILSI-HESI workshop report.

Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided.

Ovarian Cancer Screening and Mortality

To the Editor: Dr Buys and colleagues assessed the effect of ovarian cancer screening on mortality. The study had adequate power, defined end points, extensive follow-up, comprehensive outcome review, and minimal contamination in the control group. However, there are important limitations to the study design. First, there was significant dilution of the screening effect. Women were screened for 4 to 6 years with a median follow-up of 12.4 years. This resulted in 86 of 212 cancers (40.6%) in the study group being diagnosed after screening ended, with those diagnosed more than 2 years after screening unlikely to have been affected by screening. The lower-than-expected adherence added to this dilution effect. Despite lack of power, a useful analysis would be to limit follow-up to 2 years after screening and compare deaths 8 years after randomization. Second, serum cancer antigen 125 (CA-125) was interpreted using an absolute cut-off. More recent refinements of CA-125 interpretation include serial change with time using the Risk of Ovarian Cancer Algorithm. This has led to improved specificity and higher sensitivity for detection of ovarian cancer at CA-125 values less than 35 U/mL. Third, one of the major determinants of the effect of screening on mortality is the quality of the screening process and follow-up of positive results. For example, in England, despite availability of cervical screening from the mid 1960s, a substantial fall in cervical cancer rates occurred only after introduction of organized screening in 1988. In the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, women underwent a primary screen with evaluation and follow-up of positive results at the discretion of their physicians. The lack of protocol-driven management and clearly defined timelines makes it difficult to draw conclusions about screening efficacy. In 73 of 212 screendetected ovarian cancers (34%) in the study group, a surrogate would be time from screen-detected abnormality to treatment. Fourth, quality assessment of ultrasound findings is essential given the difficulties in scanning postmenopausal women, the subjective nature of ultrasound, and the number of sonographers involved. Although some quality assessment was undertaken in a sample of participants, there was no systematic process involving training, accreditation, definition, and ongoing monitoring of quality markers. We agree that ovarian cancer screening cannot currently be recommended, but the limitations of the PLCO trial make it difficult to assess the effect on mortality. Usha Menon, MD, FRCOG Aleksandra Gentry-Maharaj, PhD Ian Jacobs, MD, FRCOG

Need and potential value of the Pig‐ain vivo mutation assay—A hesi perspective

The Health and Environmental Sciences Institute (HESI), a global branch of the International Life Sciences Institute (ILSI), initiated a project committee entitled "Relevance and Follow-up of Positive Results from In Vitro Genetic Toxicity Testing (IVGT)" with the overall objective of improving the scientific basis for the interpretation of results from genetic toxicology testing. The IVGT committee has also recognized the need to develop follow-up strategies for determining the relevance of in vitro test results to human health, and moving genetic toxicology testing from the sole purpose of hazard identification toward a more quantitative risk assessment approach. In this context, a group of experts evaluated the potential utility of the emerging in vivo mutational assessment model commonly known as the Pig-a gene mutation assay to follow-up positive in vitro genetic toxicology findings and to generate robust dose-response data for quantitative assessment of the in vivo mutagenicity. The IVGT experts participating in this effort represented academia, industry, and government agencies from across the globe and addressed such issues as the optimal sample size and experimental design for generating robust dose-response data. This expert group concluded that the emerging Pig-a gene mutation assay holds great promise as an in vivo mutagenicity assay, either as a stand-alone study or integrated into repeat-dose toxicology studies, and therefore supports further validation of the model.

ILSI-HESI IVGTプロジェクト：In Vitro遺伝毒性試験における陽性結果の妥当性と検証

ILSI-HESI IVGTプロジェクト：In Vitro遺伝毒性試験における陽性結果の妥当性と検証

Follow‐up actions from positive results of in vitro genetic toxicity testing

Appropriate follow-up actions and decisions are needed when evaluating and interpreting clear positive results obtained in the in vitro assays used in the initial genotoxicity screening battery (i.e., the battery of tests generally required by regulatory authorities) to assist in overall risk-based decision making concerning the potential effects of human exposure to the agent under test. Over the past few years, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing developed a decision process flow chart to be applied in case of clear positive results in vitro. It provides for a variety of different possibilities and allows flexibility in choosing follow-up action(s), depending on the results obtained in the initial battery of assays and available information. The intent of the Review Subgroup was not to provide a prescriptive testing strategy, but rather to reinforce the concept of weighing the totality of the evidence. The Review Subgroup of the IVGT committee highlighted the importance of properly analyzing the existing data, and considering potential confounding factors (e.g., possible interactions with the test systems, presence of impurities, irrelevant metabolism), and chemical modes of action when analyzing and interpreting positive results in the in vitro genotoxicity assays and determining appropriate follow-up testing. The Review Subgroup also examined the characteristics, strengths, and limitations of each of the existing in vitro and in vivo genotoxicity assays to determine their usefulness in any follow-up testing.

New and emerging technologies for genetic toxicity testing

The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow-up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans.

Strategies for the follow‐up of positive results in the in vitro genotoxicity assays—An international collaborative initiative

Strategies for the follow‐up of positive results in the in vitro genotoxicity assays—An international collaborative initiative

Perspectives for Early Genetic Screening of Lactose Intolerance: - 13910C/T Polymorphism Tracking in the MCM6 Gene

Introduction: For many years Lactose intolerance has been, considered as a universal problem in many children and adults. Objective: The aim is to investigate the prevalence of polymorphism -13910C/T, in a neonatal tracking, for early diagnosis of lactose tolerance/intolerance. Materials and Methods: In a cross-sectional study of 310 Brazilian newborns, DNA was extracted from leukocyte umbilical cord and specific primers were used to amplify the region that encloses the -13910C/T polymorphism of the MCM6 gene, using the polymerase chain reaction and the restriction fragment length polymorphism tests. Results: One hundred and sixty (52%) male newborns and 150 (48%) female new borns were evaluated. Out of these, 191 (62%) presented CC genotype (lactose intolerant), 95 (31%) CT genotype, and 24 (7%) TT genotype, comprising a total of 119 (38%) lactose tolerant newborns. Accordingly the newborns´ gender distribution in relation to the phenotypes has been found; 97 (32%) of male gender and 94 (30%) of female gender lactose intolerant, and 63 (20%) male and 56 (18%) female lactose tolerant newborns, not being such distribution statistically significant (p = 0.801). Conclusions: The molecular analysis made possible the identification of the presence or absence of lactase persistence variant in the Brazilian newborns. The neonatal molecular diagnosis can optimize the follow-up of positive results in newborn screening for lactose intolerance.

Relevance and follow-up of positive results in in vitro genetic toxicity assays: An ILSI-HESI initiative

In vitro genotoxicity assays are often used to screen and predict whether chemicals might represent mutagenic and carcinogenic risks for humans. Recent discussions have focused on the high rate of positive results in in vitro tests, especially in those assays performed in mammalian cells that are not confirmed in vivo. Currently, there is no general consensus in the scientific community on the interpretation of the significance of positive results from the in vitro genotoxicity assays. To address this issue, the Health and Environmental Sciences Institute (HESI), held an international workshop in June 2006 to discuss the relevance and follow-up of positive results in in vitro genetic toxicity assays. The goals of the meeting were to examine ways to advance the scientific basis for the interpretation of positive findings in in vitro assays, to facilitate the development of follow-up testing strategies and to define criteria for determining the relevance to human health. The workshop identified specific needs in two general categories, i.e., improved testing and improved data interpretation and risk assessment. Recommendations to improve testing included: (1) re-examine the maximum level of cytotoxicity currently required for in vitro tests; (2) re-examine the upper limit concentration for in vitro mammalian studies; (3) develop improved testing strategies using current in vitro assays; (4) define criteria to guide selection of the appropriate follow-up in vivo studies; (5) develop new and more predictive in vitro and in vivo tests. Recommendations for improving interpretation and assessment included: (1) examine the suitability of applying the threshold of toxicological concern concepts to genotoxicity data; (2) develop a structured weight of evidence approach for assessing genotoxic/carcinogenic hazard; and (3) re-examine in vitro and in vivo correlations qualitatively and quantitatively. Conclusions from the workshop highlighted a willingness of scientists from various sectors to change and improve the current paradigm and move from a hazard identification approach to a “realistic” risk-based approach that incorporates information on mechanism of action, kinetics, and human exposure..

Endoscopic Follow-Up of Positive Fecal Occult Blood Testing in the Ontario FOBT Project

The Ontario FOBT Project is a pilot study of fecal occult blood testing (FOBT) for colorectal cancer screening conducted among age-eligible volunteers (50 to 75 years) in 12 of 37 public health regions in Ontario. Volunteers responded to invitations from primary care practitioners (PCPs) in six regions, and from public health programs in the remaining regions. FOBT collection kits were distributed from routine laboratory specimen collection sites, to which completed kits were returned. Results were sent to PCPs in all 12 regions, with copies sent to the study office at Cancer Care Ontario (Toronto, Ontario). Follow-up of positive results was at the discretion of the PCPs. The study files contained the unique Ontario Health Insurance Numbers, the date of the analyses, the number of satisfactory slides and the results for each slide. The Ontario Health Insurance Numbers were encrypted for each participant, and along with the study file, were linked to medical billing claims, hospital records and aggregate demographic data. Among participants with positive results (men 3.5% and women 2.2%), the median time from date of FOBT analysis to date of colonoscopy was 121 days among men and 202 days among women. At the end of follow-up, after positive FOBT (six to 17 months), 73% of men and 56% of women had proceeded to colonoscopy. Although colonoscopy appeared to be acceptable to the majority of participants with positive FOBT, accessibility problems was the likely explanation for lengthy intervals between the date of positive FOBT and its performance. Differences between the experiences of men and women require further investigation.

In Vitro遺伝毒性試験陽性結果の妥当性と検証：産官学の研究者によるリスク評価向上のための取組み

In Vitro遺伝毒性試験陽性結果の妥当性と検証：産官学の研究者によるリスク評価向上のための取組み