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    <recommendedItem id="20100101_19_461"
                     title="Limited Benefit Seen in CML Drug, FDA Says"
                     score="0.01"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/18390?impressionId=1265735590536"
                     
      &lt;p&gt;WASHINGTON  --  Chronic myeloid leukemia (CML) patients who are resistant to imatinib (Gleevec) had a low response rate to treatment with omacetaxine (Omapro), according to Food and Drug Administration (FDA) reviewers.&lt;/p&gt;
&lt;p&gt;The FDA released its assessment of omacetaxine, made by ChemGenex Pharmaceuticals, in advance of Wednesday&apos;s meeting of an outside panel of oncology experts who will recommend whether the agency should approve the drug for imanitib-resistant CML patients with a Bcr-Abl T3151 mutation.&lt;/p&gt;
&lt;p&gt;The agency does not have to follow the advice of its advisory panels, but it usually does.&lt;/p&gt;
&lt;p&gt;The Oncologic Drugs Advisory Committee will look at data from manufacturer ChemGenex&apos;s lone trial, which tested the safety and efficacy of subcutaneously administered omacetaxine in the target population.&lt;/p&gt;
&lt;p&gt;The trial divided 66 patients into disease stage cohorts of &quot;chronic phase,&quot; &quot;accelerated phase,&quot; or &quot;blast phase,&quot; and gave them 1.25 mg/m&lt;sup&gt;2&lt;/sup&gt; subcutaneous omacetaxine twice daily for 14 days every 28 days until hematologic response for induction therapy.&lt;/p&gt;
&lt;p&gt;If a patient achieved a complete hematologic response, hematologic improvement, or any cytogenetic response, the patient was transitioned to a maintenance does twice daily for seven days every 28 days.&lt;/p&gt;
&lt;p&gt;Researchers found: &lt;ul&gt; &lt;li&gt;For the chronic phase cohort of 40 patients, the major cytogenetic response rate was 15%, and the median duration of response was 7.7 months. &lt;/li&gt; &lt;li&gt;After a mean of nine months, 86% of the 49 chronic patients who were no longer controlling their diseases with imatinib had achieved a complete hematological response. &lt;/li&gt; &lt;li&gt;For the &quot;accelerated phase&quot; cohort of 16 patients, the major cytogenetic response rate was 6%, and the complete hematological response rate was 31%, with a median of duration of response of 22 weeks. &lt;/li&gt; &lt;li&gt;No patients responded in the more severe &quot;blast&quot; group, indicating omacetaxine works best among patients who are not as sick.&lt;/li&gt; &lt;li&gt;Overall, about 27% of patients achieved a major cytogenetic response, defined as absence of Bcr-Abl mutation in at least 35% of cells. About 18% of the patients had achieved a complete cytogenetic response, defined as all cells appearing to have lost the Bcr-Abl mutation.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;&quot;The response rate observed in the efficacy study was low,&quot; FDA reviewers concluded in documents released in advance of Wednesday&apos;s meeting.&lt;/p&gt;
&lt;p&gt;However, ChemGenex researchers said, &quot;These results demonstrate that omacetaxine is an effective and durable therapy with rapid onset of action for CML patients with the Bcr-Abl T315I mutation.&quot;&lt;/p&gt;
&lt;p&gt;The most common adverse events in the trial were thrombocytopenia, anemia, diarrhea, and neutropenia.&lt;/p&gt;
&lt;p&gt;The FDA reviewers cited a number of concerns with the ChemGenex study, noting that the company planned to enroll 100 patients but submitted efficacy data from only 66, and then continued to enroll additional patients after the prespecified data cutoff.&lt;/p&gt;
&lt;p&gt;Also, the reviewers said there is no commercially available test to detect the T3151 mutation. And, although it was a requirement of the study that the patients have a confirmed T3151 mutation, the mutation status of 35% of the patients in the trial was not confirmed.&lt;/p&gt;
&lt;p&gt;There are currently no approved drugs that have been found to be effective at treating CML patients with the T315I mutation.&lt;/p&gt;
&lt;p&gt;&quot;Omacetaxine offers an important therapeutic option for the treatment of CML patients who have the T315I mutation, a population that has a clear unmet medical need and no proven treatment options,&quot; ChemGenex researchers wrote in the company&apos;s briefing document.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_460"
                     title="Black Mothers at Increased Risk for Cardiomyopathy (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Cardiology/Prevention/tb/18389?impressionId=1265735590536"
                     
      &lt;p&gt;African-American women have an increased risk of peripartum cardiomyopathy, researchers have found in a small, single-center Georgia study.&lt;/p&gt;
&lt;p&gt;Compared with healthy controls of other races, black women had a 15.7-fold increased risk of the dangerous heart condition (95% CI 3.5 to 70.6, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), Mindy B. Gentry, MD, of the Medical College of Georgia Cardiovascular Center in Augusta, and colleagues reported online in the &lt;em&gt;Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The researchers said that the findings &quot;could not be explained by several other factors,&quot; including hypertension and smoking.&lt;/p&gt;
&lt;p&gt;&quot;We are unable to determine in this study whether genetic factors of race, or other complex environmental, social, economic, or other factors that are linked to race, account for the increased risk,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;Peripartum cardiomyopathy is a major cause of heart failure and cardiovascular mortality among women of child-bearing age, and can occur in women without preexisting heart disease.&lt;/p&gt;
&lt;p&gt;However, its risk factors have not yet been established, the researchers said.&lt;/p&gt;
&lt;p&gt;So they conducted a single-center case-control study involving 28 women diagnosed with peripartum cardiomyopathy. Each case was matched with three healthy controls: all delivered babies within the same month.&lt;/p&gt;
&lt;p&gt;The researchers found that case incidence was 24 in 100,000 deliveries for non-blacks and 340 in 100,000 for African Americans.&lt;/p&gt;
&lt;p&gt;That relationship remained significant in multivariate analyses, controlling for other factors (OR 31.5, 95% CI 3.6 to 277.6).&lt;/p&gt;
&lt;p&gt;Other significant risk factors included hypertension (OR 10.8, 95% CI 2.6 to 44.4), being unmarried (OR 4.2, 95% CI 1.4 to 12.3), and having had more than two previous pregnancies (OR 2.9, 95% CI 1.1 to 7.4).&lt;/p&gt;
&lt;p&gt;It wasn&apos;t significant in the univariate analysis, but smoking during pregnancy was a significant risk factor in the multivariate analysis, the researchers said.&lt;/p&gt;
&lt;p&gt;Yet in a stratified analysis, &quot;none of these risk factors could explain solely the increased risk for this disorder among African-American women,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;They noted that the frequency of cardiomyopathy was higher at their center than in previous reports, although it was comparable to the frequency in countries with more women of African descent (100 to 980 in 100,000 deliveries).&lt;/p&gt;
&lt;p&gt;&quot;These data and an analysis of previous reports provide strong, consistent evidence that the risk of peripartum cardiomyopathy is increased among women of African descent,&quot; they concluded. &quot;It is important to consider whether the increased risk is due to genetic factors, environmental factors, or both.&quot;&lt;/p&gt;
&lt;p&gt;The authors noted that the study was limited by a relatively small sample size.&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 researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_459"
                     title="Murtha Dead at 77"
                     score="0.01"
                     href="http://www.medpagetoday.com/Washington-Watch/Washington-Watch/tb/18388?impressionId=1265735590536"
                     
      &lt;p&gt;Representative John P. Murtha (D-Pa.), 77, long-time chairman of the House Appropriations Subcommittee on Defense, died yesterday afternoon from complications following a planned laparoscopic cholecystectomy, according to a statement from the congressman&apos;s office.&lt;/p&gt;
&lt;p&gt;He had been admitted to the intensive care unit at Virginia Hospital Center in Arlington on Jan. 31, days after surgeons at the National Naval Medical Center in Bethesda, Md., accidentally nicked his intestine during the operation, according to a report in &lt;em&gt;The Washington Post&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;In that same report, Rep. Bob Brady (D-Pa.), a close friend of Murtha&apos;s, said the congressman developed an infection and fever.&lt;/p&gt;
&lt;p&gt;Citing a request for privacy from the Murtha family and patient privacy laws, a spokesperson for the National Naval Medical Center declined to provide information on the operation.&lt;/p&gt;
&lt;p&gt;In a statement, Virginia Hospital Center said Murtha died &quot;despite aggressive critical care interventions.&quot;&lt;/p&gt;
&lt;p&gt;According to the American College of Surgeons, risks of laparoscopic cholecystectomy include bleeding, infection, injury to the bile duct, liver injury, numbness, hernia at the incision site, anesthesia complications, and puncture of the intestine.&lt;/p&gt;
&lt;p&gt;Death is extremely rare in healthy individuals, occurring in no more than 1 per 1,000 patients, according to the college.&lt;/p&gt;
&lt;p&gt;A 2009 Cochrane Review comparing laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis found no difference in mortality in 38 trials. No patients died in the laparoscopic group and only 0.09% died in the open group.&lt;/p&gt;
&lt;p&gt;Severe complications were reported in 2.2% of the laparoscopic patients and 6.8% of the open patients.&lt;/p&gt;
&lt;p&gt;Murtha had recently become the longest serving member of Congress in Pennsylvania state history.&lt;/p&gt;
&lt;p&gt;First elected in 1974, Murtha, a former Marine, was the first Vietnam War combat veteran to serve in Congress, and he served as an advocate for the military throughout his career. He was also a prominent critic of the Iraq War.&lt;/p&gt;
&lt;p&gt;Murtha is survived by his wife, Joyce, and three children.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_458"
                     title="Calcium Scoring Misses 20% of CAD Cases (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/tb/18387?impressionId=1265735590536"
                     
      &lt;p&gt;Contrary to guidelines, the absence of coronary artery calcium doesn&apos;t rule out coronary artery disease in symptomatic patients, researchers found in a new study.&lt;/p&gt;
&lt;p&gt;In a multicenter clinical trial, 19% of patients with a coronary calcium score of 0 had stenosis of at least 50% in one or more coronary artery segments, according to Carlos E. Rochitte, MD, of the University of S&amp;#227;o Paulo, Brazil, and colleagues.&lt;/p&gt;
&lt;p&gt;Likewise, 20% of vessels seen to be totally occluded on revascularization had no calcium on scans, they reported in the Feb. 16 &lt;em&gt; Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;The absence of coronary calcification should not be used as a gatekeeper and should not prevent a symptomatic patient from undergoing angiography,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;Currently, American Heart Association/American College of Cardiology guidelines suggest that excluding measurable coronary calcium could serve as an effective filter for sending patients on to invasive testing or admitting them.&lt;/p&gt;
&lt;p&gt;One systematic review of 18 studies had indicated that a zero calcium score had a negative predictive value of 93% for stenosis and a positive predictive value of 68% in symptomatic patients.&lt;/p&gt;
&lt;p&gt;However, in Rochitte&apos;s trial  --  CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors)  --  the negative predictive value of a coronary calcium score of 0 was 68%, while the positive predictive value was 81%.&lt;/p&gt;
&lt;p&gt;Overall sensitivity to predict the absence of significant (at least 50%) stenosis was 45%, while specificity was 91%.&lt;/p&gt;
&lt;p&gt;&quot;This apparent lack of predictive value of a calcium scan should be enough to give a clinician pause,&quot; Rita F. Redberg, MD, of the University of California San Francisco, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Whatever the reason for the discrepancy, neither the trial nor the review provided any information on how coronary calcium scans add incrementally to traditional predictors of coronary artery disease, such as clinical assessment and stress testing, she said. Nor would she rule out their use entirely for patients with chest pain.&lt;/p&gt;
&lt;p&gt;&quot;Given the significant &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/12732&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/12732&quot; target=&quot;_blank&quot;&gt;radiation risks&lt;/a&gt; of coronary artery calcium scans, however, clinicians must use extreme caution when ordering such scans,&quot; Redberg cautioned.&lt;/p&gt;
&lt;p&gt;The prospective &lt;a href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/11927&quot; mce_href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/11927&quot; target=&quot;_blank&quot;&gt;CORE64 study&lt;/a&gt; was originally designed to compare diagnostic performance of CT and invasive angiography in symptomatic patients with suspected coronary artery disease. But it also included a coronary calcium scan up to 30 days prior to conventional angiography.&lt;/p&gt;
&lt;p&gt;Of the 291 patients included in the calcium score analysis (73% male, mean age 59.3), 56% had at least 50% coronary stenosis by conventional angiography and 45% had at least 70% stenosis.&lt;/p&gt;
&lt;p&gt;Calcium score only weakly correlated with the highest degree of coronary stenosis found in a patient. Its ability to predict presence of significant lesions was &quot;moderate&quot; (area under the receiver-operating characteristic curve 0.77, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;A non-zero score was associated with 8.1-fold likelihood of having at least 50% coronary stenosis (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) after adjusting for age, sex, hypertension, dyslipidemia, family history of premature heart disease, diabetes, race, and hospitalization.&lt;/p&gt;
&lt;p&gt;Among the 100 patients who went on to revascularization within 30 days of angiography, 13% had a coronary calcium score of 0, 25% had a score of 1 to 10, and 44% had a score over 10 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for trend).&lt;/p&gt;
&lt;p&gt;The fact that significant coronary artery disease occurred in the absence of calcification in almost 20% of patients should not be surprising, since coronary calcification is thought to occur late in the atherosclerotic process, while obstruction can occur earlier, Redberg asserted.&lt;/p&gt;
&lt;p&gt;The researchers also cautioned that the results would not apply to asymptomatic patients with intermediate risk for events, a group in which a score of 0 has been consistently shown to indicate low risk.&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 grants from Toshiba Medical Systems, the Doris Duke Charitable Foundation, the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Donald W. Reynolds Foundation.&lt;/p&gt;&lt;p&gt;Rochitte reported no conflicts of interest. Coauthors reported financial relationships with Toshiba Medical Systems, Bayer, Schering, GE Healthcare, Bracco, Bristol-Myers Squibb, sanofi-aventis, and Vital Images.&lt;/p&gt;&lt;p&gt;Redberg provided no information on conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_457"
                     title="Long-Term Safety of Drug-Eluting Stents Affirmed (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Cardiology/Atherosclerosis/tb/18374?impressionId=1265735590536"
                     
      &lt;p&gt;Using sirolimus-eluting stents for the treatment of in-stent restenosis appears safe and effective over four years of follow-up, a study of an Italian registry showed.&lt;/p&gt;
&lt;p&gt;Through four years, there were low rates of target lesion revascularization (11.1%) and stent thrombosis (2.8%), according to Francesco Liistro, MD, of San Donato Hospital in Arezzo, Italy, and colleagues.&lt;/p&gt;
&lt;p&gt;About one in 10 patients (9.8%) died, and 3.2% had a nonfatal myocardial infarction.&lt;/p&gt;
&lt;p&gt;Survival free from a major adverse cardiac event was 80.3% at the end of follow-up, the researchers reported in the Feb. 16 issue of the&lt;em&gt; Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Although drug-eluting stents have been shown to be safe and better than balloon angioplasty and vascular brachytherapy for in-stent restenosis in the short term, most previous studies have had limited follow-up.&lt;/p&gt;
&lt;p&gt;Reports of late stent thrombosis following implantation with drug-eluting stents have raised some concern about the long-term safety of these devices in unselected patient groups, according to Liistro and his colleagues.&lt;/p&gt;
&lt;p&gt;To explore the issue, the researchers turned to the Tuscany Registry of Unselected In-Stent Restenosis (TRUE), a prospective, two-center registry.&lt;/p&gt;
&lt;p&gt;All 244 patients included in the analysis underwent antiplatelet therapy with aspirin and either ticlopidine or clopidogrel (Plavix) for at least six months after the sirolimus-eluting stent was implanted.&lt;/p&gt;
&lt;p&gt;An earlier, nine-month analysis of this registry showed safety and effectiveness for the stent. This study confirmed the benefits through four years.&lt;/p&gt;
&lt;p&gt;Of 24 recorded deaths, 11 were from cardiac causes.&lt;/p&gt;
&lt;p&gt;Definite stent thrombosis occurred in five patients, four of whom had stopped taking clopidogrel more than a month before the event.&lt;/p&gt;
&lt;p&gt;Another two patients who were taking aspirin and clopidogrel had probable stent thrombosis.&lt;/p&gt;
&lt;p&gt;Patients who had diabetes were significantly more likely to have target lesion revascularization (OR 0.32, 95% CI 0.14 to 0.71) and major adverse cardiac events (OR 0.38, 95% CI 0.20 to 0.71) through four years.&lt;/p&gt;
&lt;p&gt;A left ventricular ejection fraction less than 50% was associated with higher odds of major adverse cardiac events (OR 0.32, 95% CI 0.13 to 0.80), as was creatinine greater than 1.5 mg/dL (OR 0.23, 95% CI 0.11 to 0.48).&lt;/p&gt;
&lt;p&gt;And patients with peripheral or carotid arterial disease were more likely to need target lesion revascularization (OR 0.35, 95% CI 0.14 to 0.88).&lt;/p&gt;
&lt;p&gt;The authors noted that the registry study was limited by the lack of valid control groups.&lt;/p&gt;
&lt;p&gt;In addition, in patients with a late occurrence of target lesion revascularization, the researchers could not determine whether a stenotic lesion inside the stented segment was a new atherosclerotic lesion or a restenosis.&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 authors did not make any financial disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>