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    <recommendedItem id="20100101_19_384"
                     title="Few Surprises in Warning Signs for Infections in Kids (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18276?impressionId=1265774952667"
                     
      &lt;p&gt;Cyanosis, rapid breathing, poor peripheral perfusion, and petechial rash are red flags for serious childhood infection, a systematic review affirmed.&lt;/p&gt;
&lt;p&gt;Parental concern and physician instinct were also strong warning signs of serious illness in children in developed countries, but only in the primary care setting, Ann Van den Bruel, MD, of Katholieke Universiteit Leuven, Belgium, and colleagues reported online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The researchers also looked for &quot;rule-out&quot; signs, with a negative likelihood ratio of less than 0.2, but found none, highlighting the difficulties facing clinicians.&lt;/p&gt;
&lt;p&gt;Nor were any of the red flags consistent at presentation in serious cases, suggesting that effective safeguards are needed, they said.&lt;/p&gt;
&lt;p&gt;&quot;There should be more emphasis on parental concern in the diagnostic process,&quot; they wrote. &quot;However, we now need to identify the level of risk at which clinical action should be taken.&quot;&lt;/p&gt;
&lt;p&gt;While the warning signs will be no surprise to most physicians, the poor evidence base should be shocking, Martin Dawes, MBBS, MD, of McGill University in Montreal, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Only one of the 30 studies included in the review was conducted in a primary setting, but that&apos;s the most common environment in which sick children are seen, he said.&lt;/p&gt;
&lt;p&gt;&quot;What is clear is that in 2010 we do not know how to effectively recognize or rule out severe disease in ill children and, what is more, we do not even have a cohesive national or even global research strategy to address this problem,&quot; he wrote.&lt;/p&gt;
&lt;p&gt;The World Health Organization has sponsored large scale studies to address these issues in resource-poor countries, Van den Bruel&apos;s group noted, but the range of diseases is different in developed countries, so that evidence doesn&apos;t generalize.&lt;/p&gt;
&lt;p&gt;The investigators reviewed studies of diagnostic accuracy or prediction rules for serious infection (mostly sepsis, bacteremia, meningitis, pneumonia, or urinary tract infection) in otherwise healthy children ages 1 month to 18 years, using features assessable in an ambulatory care setting.&lt;/p&gt;
&lt;p&gt;The studies had generally modest quality and were predominantly conducted in emergency departments.&lt;/p&gt;
&lt;p&gt;Fever of 104&amp;#176;F or more increased the likelihood of serious infection from 0.8% to 5.0% in the lowest prevalence setting.&lt;/p&gt;
&lt;p&gt;In the one primary care study where there was a low prevalence of disease (under 5%), a parent&apos;s concern that her child&apos;s illness was different from prior illnesses had a positive likelihood ratio of 14.40 for serious infection, while the clinician&apos;s instinct that something is wrong had a 23.50 positive likelihood ratio.&lt;/p&gt;
&lt;p&gt;Other predictors of the presence of serious infection and their positive likelihood ratios were: &lt;ul&gt; &lt;li&gt;Turning blue (52.20)&lt;/li&gt; &lt;li&gt;Poor peripheral circulation (4.71 to 38.80 in the low-to-intermediate prevalence setting and 2.39 to 17.70 in the high-prevalence setting)&lt;/li&gt; &lt;li&gt;Rapid breathing (1.26 to 9.78)&lt;/li&gt; &lt;li&gt;Shortness of breath (1.11 to 9.30)&lt;/li&gt; &lt;li&gt;Meningeal irritation (2.57 to 275)&lt;/li&gt; &lt;li&gt;Petechial rash (6.18 to 83.70)&lt;/li&gt; &lt;li&gt;Unconsciousness (19.80 to 155)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Changed crying pattern was a potential red flag in a low prevalence setting with a positive likelihood ratio of 10.50, but actually was associated with reduced probability of serious disease in a high prevalence setting (positive likelihood ratio 0.49 to 0.74).&lt;/p&gt;
&lt;p&gt;Sending all children with a probability of serious infection greater than 5% to the hospital would overwhelm services there, although parents would &quot;probably be unhappy to know that their child was not being referred despite a 1 in 20 risk of serious infection,&quot; the researchers observed.&lt;/p&gt;
&lt;p&gt;The most widely studied decision rule, the Yale Observation Scale, had disappointingly little value in confirming the possibility of serious infection, they noted (positive likelihood ratio range 1.10 to 6.70, negative likelihood ratio range 0.16 to 0.97).&lt;/p&gt;
&lt;p&gt;The best performing clinical decision rule for excluding serious infection was a five-stage system with a negative likelihood ratio of 0.04.&lt;/p&gt;
&lt;p&gt;The researchers noted that these findings largely fit with those identified by WHO for developing countries, with the exception of difficulty feeding. The current review found that wasn&apos;t helpful in developed areas.&lt;/p&gt;
&lt;p&gt;They cautioned that their review was only as strong as the studies included and was particularly limited by the paucity of studies in the initial presentation primary care setting and difficulties of knowing how reproducible the findings were.&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 Health Technology Assessment and National Institute for Health Research National School for Primary Care Research. The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;Dawes 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_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265774952667"
                     
      &lt;p&gt;Researchers say they can now grow liver cells that maintain their functions long enough to test potential treatments for hepatitis C.&lt;/p&gt;
&lt;p&gt;The method uses so-called &quot;micropatterned co-cultures&quot; of primary human hepatocytes and supportive stroma, according to Sangeeta N. Bhatia, MD, PhD, of MIT, and colleagues.&lt;/p&gt;
&lt;p&gt;The co-cultures were able to support the entire life cycle of hepatitis C, including infection and replication, Bhatia and colleagues reported online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Coupled with reporter systems, the co-cultures have &quot;potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity&quot; of antiviral drugs, the researchers said.&lt;/p&gt;
&lt;p&gt;The lack of such a system has been a roadblock to testing potential treatments for the virus, which affects 130 million people around the world, the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;Recently, they added, researchers have been able to propagate the virus in human hepatoma cells, but those cells, among other issues, proliferate abnormally and have disturbed gene expression.&lt;/p&gt;
&lt;p&gt;To overcome those obstacles, the researchers turned to primary hepatocytes, which would make a better test system, except that they are notoriously hard to maintain in culture.&lt;/p&gt;
&lt;p&gt;To form the co-cultures, Bhatia and colleagues seeded multi-well plates with human hepatocytes, followed several hours later by murine fibroblasts.&lt;/p&gt;
&lt;p&gt;&quot;If you just put cells on a surface in an unorganized way, they lose their function very quickly,&quot; Bhatia said in a statement. &quot;If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.&quot;&lt;/p&gt;
&lt;p&gt;In a series of experiments, Bhatia and colleagues found:&lt;ul&gt; &lt;li&gt;Pseudoparticles bearing the hepatitis C glycoproteins E1 and E2 were able to infect between 1% and 3% of the hepatocytes, but did not infect the fibroblasts.&lt;/li&gt; &lt;li&gt;A hepatitis C virus modified to express a fluorescent protein persistently replicated over a two-week period.&lt;/li&gt; &lt;li&gt;Infectious virus was found in the co-culture supernatant from four through 12 days after initial infection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers also tested some possible therapeutics, including antibodies against viral entry factors and viral protease inhibitors, and were able to show effects on replication of hepatitis C.&lt;/p&gt;
&lt;p&gt;They were also able to test two or more drugs simultaneously to show the feasibility of combination drug studies using the system.&lt;/p&gt;
&lt;p&gt;Although the system is &quot;an important step forward,&quot; Bhatia and colleagues said, the co-cultures have some limitations, including the relatively inefficient uptake of virus.&lt;/p&gt;
&lt;p&gt;But they concluded that the co-cultures have the potential to be a &quot;highly valuable system for studies of (hepatitis C) biology.&quot;&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;This study had support from the Greenberg Medical Research Institute, the Ellison Medical Foundation, the Starr Foundation, the Ronald A. Shellow Memorial Fund, the Richard Salomon Family Foundation, and the NIH. The researchers said they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_226"
                     title="ASCO GI: Blood Test Detects Colorectal Cancer"
                     score="-0.003"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18079?impressionId=1265774952667"
                     
      &lt;p&gt;ORLANDO  --  A novel blood test that measures CD24 protein levels may detect early colorectal cancer and precancerous adenomas, researchers found.&lt;/p&gt;
&lt;p&gt;The investigational assay had 78.4%% sensitivity and 86.8% specificity for distinguishing patients with colorectal adenoma or cancer from healthy controls in a study led by Sarah Kraus, PhD, of Tel Aviv Souraski Medical Center in Israel.&lt;/p&gt;
&lt;p&gt;Further validation for the biomarker would be needed before considering clinical use in surveillance, they cautioned here at the ASCO Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;But the results were exciting and could represent &quot;a very significant advance,&quot; commented Robert P. Sticca, MD, of the University of North Dakota in Grand Forks.&lt;/p&gt;
&lt;p&gt;&quot;It looks like it may be a very reliable marker for not only the early detection of colon cancer and even precancerous conditions, but also could be used for follow-up for patients who previously had cancer for recurrence,&quot; he said as moderator of a press briefing at which the results were discussed.&lt;/p&gt;
&lt;p&gt;Colorectal cancer screening is effective, with early detection and treatment shown to improve survival.&lt;/p&gt;
&lt;p&gt;However, colorectal cancer is often diagnosed at a late stage with poor prognosis, in part because of &lt;a href=&quot;http://www.medpagetoday.com/Gastroenterology/ColonCancer/10115&quot; mce_href=&quot;http://www.medpagetoday.com/Gastroenterology/ColonCancer/10115&quot; target=&quot;_blank&quot;&gt;poor uptake of colonoscopy&lt;/a&gt;, Kraus said at the press briefing.&lt;/p&gt;
&lt;p&gt;Unfortunately, there are no sufficiently accurate blood-based screening tests, he noted, although there have been &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ECCO-ESMO/16057&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ECCO-ESMO/16057&quot; target=&quot;_blank&quot;&gt;attempts&lt;/a&gt; to develop them.&lt;/p&gt;
&lt;p&gt;Her group had previously found that the CD24 protein  --  expressed on the cell surface, where it plays a role in cell adhesion and metastasis  --  was associated with development of colorectal cancer in a gene expression study.&lt;/p&gt;
&lt;p&gt;So, with two independent cohorts, they tested whether CD24 could be a good biomarker for colorectal cancer.&lt;/p&gt;
&lt;p&gt;The first cohort included 63 patients with colorectal cancer, 19 with adenoma, and 68 controls with a clean bill of health on colonoscopy. Of these 150 individuals, 143 were externally evaluated by a blinded investigator.&lt;/p&gt;
&lt;p&gt;CD24 expression was nearly six-fold higher among adenoma and colorectal cancer cases than among controls, a significant difference. Levels were similar between the cancer and adenoma groups.&lt;/p&gt;
&lt;p&gt;The second cohort included 73 subjects: 38 normal controls, 24 with colorectal adenoma, and 11 with colorectal cancer.&lt;/p&gt;
&lt;p&gt;The test could distinguish colorectal cancer cases from controls with &quot;relatively high&quot; sensitivity and specificity (92.3% and 83.8%, respectively), Kraus said.&lt;/p&gt;
&lt;p&gt;Its performance in detecting adenoma versus normal colonoscopy results was lower, 75.0% sensitivity and 89.2% specificity.&lt;/p&gt;
&lt;p&gt;Kraus said her group is now testing this CD24 approach in a larger sample and developing an enzyme-linked immunosorbent assay (ELISA) that could be more widely used.&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="20090101_2_771"
                     title="AASLD: Proton Pump Inhibitors May Be Problematic for Cirrhosis Patients"
                     score="-0.005"
                     href="