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    <recommendedItem id="20100101_19_425"
                     title="AAN: Industrial Cleaner Again Tied to Parkinson Risk (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAN/tb/18338?impressionId=1265801185666"
                     
      TORONTO  --  The degreasing agent trichloroethylene (TCE) has been linked to increased rates of Parkinson&apos;s disease among industrial workers in yet another study, this time involving a large, well-studied group of World War II veterans.&lt;br&gt;
&lt;br&gt;Parkinson&apos;s disease developed in individuals with occupational exposure to TCE at more than five times the rate seen in those without such exposure (odds ratio 5.5, 95% CI 1.02 to 30), reported Samuel Goldman, MD, of the Parkinson&apos;s Institute in Sunnyvale, Calif.&lt;br&gt;
&lt;br&gt;Goldman described the research in a phone interview with &lt;em&gt;MedPage Today&lt;/em&gt;. It&apos;s scheduled for presentation here in April at the American Academy of Neurology&apos;s annual meeting.&lt;br&gt;
&lt;br&gt;A previous study in 2008 had fingered TCE as the most likely culprit behind a cluster of Parkinson&apos;s disease cases afflicting workers at a single industrial plant. (See &lt;a href=&quot;http://www.medpagetoday.com/Geriatrics/ParkinsonsDisease/7894&quot; mce_href=&quot;http://www.medpagetoday.com/Geriatrics/ParkinsonsDisease/7894&quot; target=&quot;_blank&quot;&gt;Trichloroethylene Implicated as Risk for Parkinsonism&lt;/a&gt;)&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Also, Goldman said, animal studies have found that TCE is selectively toxic to nigral dopaminergic neurons, the same type of nerve cell that progressively dies off in Parkinson&apos;s disease. He said the chemical&apos;s activity in rodent brains is very similar to that of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a dopaminergic neurotoxin commonly used to simulate Parkinson&apos;s disease in preclinical research.&lt;/p&gt;
&lt;p&gt;Goldman said the new study was the first population-based analysis to link TCE to the disease.&lt;/p&gt;
&lt;p&gt;It focused on 198 twin pairs in the National Academy of Sciences-National Research Council&apos;s World War II Twins Cohort, which comprises some 16,000 twin pairs overall.&lt;/p&gt;
&lt;p&gt;Members of the all-male cohort, who were born from 1917 to 1927 and served in the war, have been followed since the 1960s. Occupational histories for participants are available along with medical records from the VA healthcare system.&lt;/p&gt;
&lt;p&gt;In those pairs chosen for the current study, records showed that one twin had developed Parkinson&apos;s disease and the other had not. This design largely eliminates genetics as a confounding factor in the analysis.&lt;/p&gt;
&lt;p&gt;Goldman explained that occupational histories for each participant were reviewed by a blinded industrial hygienist and a preventive medicine physician to identify likely exposures to TCE and four other industrial chemicals: xylene, toluene, carbon tetrachloride, and tetrachloroethylene.&lt;/p&gt;
&lt;p&gt;As a single source of exposure, only TCE was significantly associated with development of Parkinson&apos;s disease, Goldman said.&lt;/p&gt;
&lt;p&gt;People working as aircraft mechanics, machinists, plumbers, and electricians likely had regular exposure to TCE, Goldman said. The chemical was commonly used as a &quot;spot&quot; cleaner to remove grease and oils from metal surfaces. It was also used for a time as a dry cleaning solvent, although tetrachloroethylene was more common for that purpose.&lt;/p&gt;
&lt;p&gt;Goldman said no increased risk was seen with xylene or toluene, but there were near-significant trends toward increased Parkinson&apos;s disease risk from carbon tetrachloride and tetrachloroethylene: &lt;ul&gt; &lt;li&gt;Carbon tetrachloride: OR 2.8 (95% CI 0.97 to 7.8)&lt;/li&gt; &lt;li&gt;Tetrachloroethylene: OR 9.0 (95% CI 0.78 to 103)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Twins exposed to either TCE or tetrachloroethylene were at significantly increased risk, with an odds ratio of 8.1 (95% CI 1.43 to 43) relative to individuals with no exposure to either chemical.&lt;/p&gt;
&lt;p&gt;Goldman said the analysis also examined whether duration of exposure was associated with increased risk. He said the results were in the same pattern as for the yes-no exposure analysis, but the findings were very uncertain because of the relatively small sample size.&lt;/p&gt;
&lt;p&gt;Occupational histories were available for only 99 of the 198 discordant twin pairs and some of the information was obtained by proxy rather than from the participant himself.&lt;/p&gt;
&lt;p&gt;Because of the wide confidence intervals even for the yes-no exposure analysis, the findings need confirmation in a larger study, he said, noting that the best approach would be a cohort study involving people with known, long-term exposure to TCE, compared with well-chosen controls.&lt;/p&gt;
&lt;p&gt;&quot;The study wouldn&apos;t have to be large,&quot; Goldman said. He estimated that 1,000 to 2,000 participants would be adequate to determine if the connection to Parkinson&apos;s disease is real.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the National Institute of Neurological Disorders and Stroke, the Valley Foundation, and the James and Sharron Clark Family Fund.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_377"
                     title="Advisory Panel Rates Genomic Cancer Tests"
                     score="0.01"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/Medicare/tb/18269?impressionId=1265801185666"
                     
      &lt;p&gt;Some genomic tests aimed at identifying patients most likely to respond to cancer drugs won a thumbs-up from a Medicare advisory panel, but others didn&apos;t make the grade.&lt;/p&gt;
&lt;p&gt;As part of a national coverage determination under way at the Centers for Medicare and Medicaid Services, members of the Medicare Evidence Development &amp;amp; Coverage Advisory Committee (MEDCAC) last week rated the clinical value of several pharmacogenomic cancer tests now available.&lt;/p&gt;
&lt;p&gt;The tests would be used to select patients for treatment with drugs including tamoxifen, irinotecan (Camptosar), trastuzumab (Herceptin), and imatinib (Gleevec).&lt;/p&gt;
&lt;p&gt;CMS has not previously decided whether such tests should be reimbursed by Medicare, although testing is already routine for some of these treatments.&lt;/p&gt;
&lt;p&gt;The FDA-approved labeling for trastuzumab requires such testing. Imatinib&apos;s approvals include chronic myeloid leukemia featuring the BCR-ABL &quot;Philadelphia chromosome&quot; mutation, although the label doesn&apos;t explicitly mention testing.&lt;/p&gt;
&lt;p&gt;&quot;CMS is aware that the body of evidence on the role of pharmacogenomic testing in cancer continues to evolve,&quot; according to the agency&apos;s notice of the meeting.&lt;/p&gt;
&lt;p&gt;&quot;Recognizing the rapid accumulation of such evidence, CMS seeks guidance from the panel to inform future coverage determinations. We want to ensure that Medicare beneficiaries have access to any demonstrated improved health outcomes of pharmacogenomic testing, and are protected from inaccurate or inappropriate pharmacogenomic testing that could compromise therapy or increase the risks of adverse events during therapy.&quot;&lt;/p&gt;
&lt;p&gt;MEDCAC panelists were asked to rate their confidence in the clinical utility of five tests and in the scientific evidence available for review.&lt;/p&gt;
&lt;p&gt;The five tests cover: &lt;ul&gt; &lt;li&gt;Polymorphisms in the CYP2D6 drug-metabolizing enzyme for breast cancer patients who are candidates for tamoxifen&lt;/li&gt; &lt;li&gt;Polymorphisms in the UGT1A1 gene for colon cancer patients considered for irinotecan treatment&lt;/li&gt; &lt;li&gt;Presence of HER/neu epidermal growth factor receptor expression in patients with breast cancer, indicating suitability for trastuzumab&lt;/li&gt; &lt;li&gt;Presence of the BCR-ABL mutation in patients with chronic myeloid leukemia who would be candidates for imatinib&lt;/li&gt; &lt;li&gt;Mutations in the K-ras gene for metastatic colorectal cancer patients eligible for cetuximab (Erbitux) or panitumumab (Vectibix)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The 15 panel members assigned values of one to five, reflecting low to high confidence, to each test. A score of two reflected medium-low confidence, while a four meant medium-high confidence.&lt;/p&gt;
&lt;p&gt;Most of the panelists agreed that the evidence underlying the tests for CYP2D6 and UGT1A1 polymorphisms was still too scant for an assessment of their clinical value. Mean scores for these tests were 2.07 and 1.83, respectively, with nearly all votes either a one or two.&lt;/p&gt;
&lt;p&gt;But MEDCAC members were more confident that the usefulness of the other three tests for diagnostic and monitoring purposes could be evaluated. Mean scores for those tests were all well above four.&lt;/p&gt;
&lt;p&gt;For the HER/neu, BCR-ABL, and K-ras tests, since members believed the evidence was adequate for assessment, MEDCAC also voted on whether their use actually would improve health outcomes in cancer patients.&lt;/p&gt;
&lt;p&gt;A third ranking provided the committee&apos;s views on whether the conclusions could be generalized to the Medicare population and patients in the community.&lt;/p&gt;
&lt;p&gt;Mean scores for those rankings were all also above four, indicating the panel&apos;s support for these tests as clinically beneficial.&lt;/p&gt;
&lt;p&gt;On the other hand, when asked whether there was enough evidence to assess the utility of the BCR-ABL test in detecting treatment failure, panelists didn&apos;t think so. Most of those votes were twos, and the mean was 2.47.&lt;/p&gt;
&lt;p&gt;CMS has not given a time line for deciding whether to approve Medicare coverage for the tests.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_250"
                     title="Cancer Research &quot;Giant&quot; Lawrence Garfinkel Dies at 88"
                     score="-0.001"
                     href="http://www.medpagetoday.com/Pulmonology/Smoking/tb/18108?impressionId=1265801185666"
                     
      &lt;p&gt;Epidemiologist Lawrence Garfinkel, MA, a legendary researcher for the American Cancer Society whose work helped establish a link between cancer and smoking and other activities, died of cardiovascular disease Thursday in Seattle, Washington at 88.&lt;/p&gt;
&lt;p&gt;&quot;The American Cancer Society today mourns the loss of one of its most important historical figures,&quot; said John R. Seffrin, PhD, the society&apos;s chief executive officer.&lt;/p&gt;
&lt;p&gt;&quot;Larry Garfinkel joined the American Cancer Society as a young scientist in 1947, and for more than four decades played an instrumental role in expanding knowledge of and reducing death from smoking.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel&apos;s 1982 Cancer Prevention Study-II (CPS-II) is the largest contemporary study of tobacco and mortality, with 1.2 million participants and 77,000 data-compiling volunteers across 50 states, the District of Columbia, and Puerto Rico.&lt;/p&gt;
&lt;p&gt;CPS-II uncovered the effects of lifestyle factors, such as obesity, alcohol consumption, medications, genetic elements, that affect cancer and other chronic diseases, the analysis of which still reveals important clues about cancer today.&lt;/p&gt;
&lt;p&gt;The study also found lung cancer mortality rates in women increased five-fold from data collected in the original Cancer Prevention Study, while cancer rates among non-smoking women remained the same. This information provided strong evidence that lung cancer was almost exclusively a disease found in smokers.&lt;/p&gt;
&lt;p&gt;Garfinkel was born on January 11, 1922 in Manhattan&apos;s Lower East Side and was raised in the South Bronx.&lt;/p&gt;
&lt;p&gt;He served in the army during World War II, where he was seriously injured in northern France in August, 1944.&lt;/p&gt;
&lt;p&gt;Ultimately, Garfinkel graduated from the City College of New York and received a Masters Degree from Columbia University. He also received several honorary doctorates.&lt;/p&gt;
&lt;p&gt;Garfinkel began work for the ACS in 1947.&lt;/p&gt;
&lt;p&gt;He assisted E. Cuyler Hammond, MD, and Daniel Horn, MD, in the first ACS prospective mortality study of 187,783 males in the late 1940&apos;s by coordinating much of the field work, including training thousands of ACS volunteers in data collection techniques.&lt;/p&gt;
&lt;p&gt;Garfinkel acted as the co-principal investigator of the larger Cancer Prevention Study I (CPS-I) in 1959. The study enrolled 1 million participants across 25 states and required over 68,000 volunteers to collect data.&lt;/p&gt;
&lt;p&gt;In the 1960s, he contributed to more than two dozen major papers on the relation between smoking and health. He was co-author of one of the first reports combining epidemiology with pathology and provided some of the first direct evidence of lung damage related to smoking.&lt;/p&gt;
&lt;p&gt;Garfinkel also contributed to issuance of the landmark 1964 Surgeon General&apos;s report on smoking and health.&lt;/p&gt;
&lt;p&gt;He was appointed director of ACS research in 1979 after Hammond&apos;s retirement.&lt;/p&gt;
&lt;p&gt;Garfinkel retired from the ACS in 1989. Over the course of his career, he had contributed to more than 100 journal articles.&lt;/p&gt;
&lt;p&gt;Richard D. Klausner, MD, then-director of the National Cancer Institute, said at the time: &quot;Few individuals have contributed as much to our present-day knowledge about the disease consequences of smoking.&lt;/p&gt;
&lt;p&gt;&quot;His remarkable achievement is an important reminder what a tremendous impact an individual can make, and inspires all of us to continue the fight against cancer.&quot;&lt;/p&gt;
&lt;p&gt;Garfinkel continued to volunteer with the ACS after his retirement and taught biostatistics at the New York University Dental School.&lt;/p&gt;
&lt;p&gt;He is survived by his brothers, Harold and Melvin; his sons, Martin and Herb; a daughter-in-law, Margaret Cary, and two grandchildren.&lt;/p&gt;

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