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    <recommendedItem id="20100101_19_425"
                     title="AAN: Industrial Cleaner Again Tied to Parkinson Risk (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAN/tb/18338?impressionId=1265736580994"
                     
      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_357"
                     title="Targeted Therapy Disappoints in Recurrent Brain Tumors (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/HematologyOncology/BrainCancer/tb/18237?impressionId=1265736580994"
                     
      &lt;p&gt;High hopes for treating recurrent glioblastoma with the novel, targeted antiangiogenic enzastaurin have been diminished by disappointing phase III results.&lt;/p&gt;
&lt;p&gt;The study failed its primary endpoint with a median progression-free survival of 1.5 months compared with 1.6 months on conventional lomustine (CeeNu, &lt;em&gt;P&lt;/em&gt;=0.08).&lt;/p&gt;
&lt;p&gt;Nor were there any other significant benefits, despite generally good tolerability, Wolfgang Wick, MD, of the University of Heidelberg, Germany, and colleagues reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;In an earlier &lt;a href=&quot;http://www.medpagetoday.com/HematologyOncology/BrainCancer/1062&quot; mce_href=&quot;http://www.medpagetoday.com/HematologyOncology/BrainCancer/1062&quot; target=&quot;_blank&quot;&gt;phase II study&lt;/a&gt;, the drug shrank tumors in 22% of heavily pretreated patients with recurrent glioblastoma, a heavily vascular cancer and one of the toughest to treat.&lt;/p&gt;
&lt;p&gt;The experimental agent is a potent and selective inhibitor of protein kinase C-beta, which mediates the most important regulator of vessel growth in glioma.&lt;/p&gt;
&lt;p&gt;Even so, jumping directly into a phase III study before the final results of a phase II study might have been premature, even with a strong preclinical rationale, the authors and an accompanying editorial said.&lt;/p&gt;
&lt;p&gt;Evanthia Galanis, MD, DSc, and Jan C. Buckner, MD, both of the Mayo Clinic in Rochester, Minn., wrote in an editorial that response rate &quot;can be particularly misleading as an indicator of antitumor activity of antiangiogenic agents.&quot;&lt;/p&gt;
&lt;p&gt;Reduced vascular permeability can appear as improvement on enhanced MRI, without true antitumor effect, the editorialists noted. Nor does response rate correlate well with progression-free or overall survival in this type of cancer, they wrote.&lt;/p&gt;
&lt;p&gt;Still, they cautioned, these negative phase III results aren&apos;t the final word on the drug whose modest activity was comparable to standard treatment  --  and with satisfactory tolerability.&lt;/p&gt;
&lt;p&gt;&quot;It would therefore still be worth incorporating enzastaurin in rationally designed combinatorial regimens, especially if based on a strong mechanistic rationale or preclinical demonstration of synergistic activity,&quot; Galanis and Buckner wrote.&lt;/p&gt;
&lt;p&gt;The study randomized patients with World Health Organization grade 4 glioblastoma to receive six-week cycles of open-label enzastaurin 500 mg/d (1,125-mg loading dose on day one) or lomustine (100 to 130 mg/m&lt;sup&gt;2&lt;/sup&gt; on day one).&lt;/p&gt;
&lt;p&gt;It was stopped at the planned interim futility analysis after enrollment of 266 patients.&lt;/p&gt;
&lt;p&gt;The researchers had powered the study for a 45% improvement in median progression-free survival, but found it actually tended to be 28% better with lomustine (HR 1.28, 95% CI 0.97 to 1.70).&lt;/p&gt;
&lt;p&gt;Six-month progression-free survival rates were 11.1% with the experimental treatment, compared with 19.0% among controls (&lt;em&gt;P&lt;/em&gt;=0.13).&lt;/p&gt;
&lt;p&gt;Overall survival, too, was similar at 6.6 and 7.1 months, respectively (HR 1.20, &lt;em&gt;P&lt;/em&gt;=0.25). Objective response rate showed no differences either (&lt;em&gt;P&lt;/em&gt;=0.501).&lt;/p&gt;
&lt;p&gt;Patient-reported time to deterioration  --  measured on the Functional Assessment of Cancer Therapy&amp;#8211;Brain questionnaire  --  was 2.27 months with enzastaurin compared with 2.33 months for lomustine (&lt;em&gt;P&lt;/em&gt;=0.54).&lt;/p&gt;
&lt;p&gt;Results likewise were similar between the groups for physical and functional well-being and for brain tumor&amp;#8211;specific concerns (&lt;em&gt;P&lt;/em&gt;&amp;gt;0.05).&lt;/p&gt;
&lt;p&gt;Adverse event rates were not different between groups, although more were drug-related in the lomustine group (62% versus 44%, &lt;em&gt;P&lt;/em&gt;=0.008).&lt;/p&gt;
&lt;p&gt;Enzastaurin did have the advantage of less hematologic toxicity overall (&lt;em&gt;P&lt;/em&gt;&amp;#8804;0.001), and specifically for grade 3 to 4 adverse events (one versus 46 events, &lt;em&gt;P&lt;/em&gt;&amp;#8804;0.001).&lt;/p&gt;
&lt;p&gt;Study deaths in the enzastaurin group totaled 11, including four due to adverse events and one drug-related; while the four deaths in lomustine-treated patients were disease-related.&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 supported by Eli Lilly, including writing and editorial support.&lt;/p&gt;&lt;p&gt;Wick and co-authors reported financial conflicts of interest with Eli Lilly, including employment and stock ownership for some.&lt;/p&gt;&lt;p&gt;Co-authors also reported financial conflicts of interest with Merck, Genentech, Enzon, Schering-Plough, and AstraZeneca.&lt;/p&gt;&lt;p&gt;Galanis reported conflicts of interest with Merck, Bristol-Myers Squibb, Gradalis, Genetech, and Bayer Pharmaceuticals.&lt;/p&gt;&lt;p&gt;Buckner reported conflicts of interest with Merck Serono, Genentech, Excelixis, Bayer Pharmaceuticals, Bristol-Myers Squibb, and Anti-Sense Pharma.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_343"
                     title="U.S. Marshals Seize Unapproved Ozone Generators"
                     score="0.007"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/EnvironmentalHealth/tb/18228?impressionId=1265736580994"
                     
      &lt;p&gt;WASHINGTON  --  U.S. Marshals have seized 77 unapproved ozone generators, valued at almost $76,000 from a California device manufacturer, the FDA announced.&lt;/p&gt;
&lt;p&gt;The devices were advertised as treatments for various conditions, including cancer, AIDS, hepatitis, herpes, and other diseases, but lacked approval or efficacy data to support the claims made on their behalf, an FDA release said.&lt;/p&gt;
&lt;p&gt;The raid came after the company, Applied Ozone Systems (AOS) of Auburn, Calif., failed to respond to a voluntary recall request last December, the agency said.&lt;/p&gt;
&lt;p&gt;The FDA raised concerns that patients using AOS-IM and AOS-IMD devices will consider it an appropriate treatment for an affliction and delay or stop FDA-approved and proven medical treatments. Patients using the devices may risk infection from contamination of the applicator or catheter, the release said.&lt;/p&gt;
&lt;p&gt;The FDA recommended that healthcare professionals and consumers cease use of the devices.&lt;/p&gt;
&lt;p&gt;The agency said it obtained an inspection warrant for the company&apos;s manufacturing facilities after the owner refused to admit FDA inspectors. It said the inspection revealed several breaches of the FDA&apos;s good manufacturing practice requirements for medical devices, which had never been approved in the first place.&lt;/p&gt;
&lt;p&gt;Ozone is an unstable allotrope of oxygen with three atoms, instead of the normal two. Ozone generators produce ozone from oxygen and have consumer and industrial applications, but ozone itself is harmful to the respiratory system, even at relatively low concentrations.&lt;/p&gt;
&lt;p&gt;Instructions with the Applied Ozone Systems devices suggest blowing ozoned air into the rectal and vaginal areas.&lt;/p&gt;
&lt;p&gt;Friday&apos;s seizure was part of a joint effort of the FDA and the California Department of Public Health to remove or prevent unapproved or unsafe medical devices from entering the market.&lt;/p&gt;
&lt;p&gt;A statement on the company&apos;s Web site said the two ozone generator models, which sold for $750 and $1,200 respectively, were no longer available by order of the FDA and California authorities.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_298"
                     title="FDA Updates Myeloma Drug Label for New Risks"
                     score="0.002"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18158?impressionId=1265736580994"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has revised dosage and safety information for bortezomib (Velcade), the myeloma and mantle cell lymphoma drug, to reflect an increased toxicity risk.&lt;/p&gt;
&lt;p&gt;The new labeling includes a warning for patients with moderate-to-severe hepatic impairment and now recommends at-risk patients start at a lower dosage of 0.7 mg for the first cycle of treatment and escalate to 1.0 mg, or reduce further to 0.5 mg, in subsequent cycles.&lt;/p&gt;
&lt;p&gt;The label has also been updated to include clinical study data showing a higher median survival rate in patients using a combination of bortezomib, melphalan, and prednisone versus a regiment of just melphalan and prednisone (&lt;em&gt;P&lt;/em&gt;=0.00084).&lt;/p&gt;
&lt;p&gt;The drug is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. The FDA also warns that women should avoid becoming pregnant while undergoing treatment with bortezomib.&lt;/p&gt;
&lt;p&gt;The drug is manufactured by Millennium: The Takeda Oncology Company of Cambridge, Mass.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_296"
                     title="FDA Okays Morphine for Tolerant Patients"
                     score="0.002"
                     href="http://www.medpagetoday.com/PainManagement/PainManagement/tb/18157?impressionId=1265736580994"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has approved the first high-concentration, oral morphine sulfate solution as part of its unapproved drugs initiative.&lt;/p&gt;
&lt;p&gt;The drug is indicated for opioid-tolerant patients with moderate-to-severe acute and chronic pain, as well as end-of-life care.&lt;/p&gt;
&lt;p&gt;Opioid tolerance was defined as a patient using 60 mg of an opioid per day, Sharon Hertz, MD, deputy director of the Division of Anesthesia, Analgesics, and Rheumatoid Products at the Center for Drug Evaluation and Research, said in a conference call.&lt;/p&gt;
&lt;p&gt;The new solution is available in 100 mg per 5 mL and 20 mg per 1 mL concentrations.&lt;/p&gt;
&lt;p&gt;Although morphine use in pain management has been a common practice, this form and concentration of the drug was not previously FDA approved.&lt;/p&gt;
&lt;p&gt;Approval for the new drug was based on efficacy and safety data already available, which applicants can use when seeking approval for unapproved formulations of drugs with a known safety profile, Hertz said.&lt;/p&gt;
&lt;p&gt;The FDA initiated the unapproved drugs initiative in March, 2009, when it sent warning letters to nine companies requesting they pull a number of morphine sulfate, oxycodone, and hydromorphone products from the market. (See &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/13526&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/13526&quot; target=&quot;_blank&quot;&gt;FDA Acts Against Unapproved Narcotic Drugs&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Seven of the warned companies produced unapproved concentrated morphine sulfate, but the FDA granted a reprieve from the initiative when it could not find a suitable approved replacement for the drug without disrupting patient care. (See &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/13682&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/13682&quot; target=&quot;_blank&quot;&gt;FDA Gives Temporary Reprieve to Unapproved Morphine Elixir&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The agency worked with manufacturer Roxane Laboratories to ensure that a sufficient supply of the drug was available and to develop a prescription and use guide for the medication.&lt;/p&gt;
&lt;p&gt;As part of the approval, the manufacturer needed to establish a safety profile prior to approval to address the risks of morphine misuse, abuse, and overdose.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>