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    <recommendedItem id="20100101_19_344"
                     title="FDA Revises HIV Drug Label for Liver Complication"
                     score="0.008"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18229?impressionId=1265794714421"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has updated labels of the HIV drug didanosine (Videx and Videx EC) to include warnings for potentially serious liver damage.&lt;/p&gt;
&lt;p&gt;Although these cases are rare, the drug may cause noncirrhotic hypertension in patients, a potentially fatal complication which the FDA discovered through 42 postmarket, adverse event reports.&lt;/p&gt;
&lt;p&gt;Of those patients, three required liver transplant and four died. Two deaths were caused by esophageal hemorrhage, while two more were caused by progressive liver failure.&lt;/p&gt;
&lt;p&gt;One patient suffered multiorgan failure, cerebral hemorrhage, sepsis, and lactic acidosis.&lt;/p&gt;
&lt;p&gt;The FDA said in a statement that it chose not to recall the drug because it believes its benefits outweigh potential risks, but advised that treatment decisions be made on an individual basis between healthcare professionals and patients.&lt;/p&gt;
&lt;p&gt;The agency added that causal association is difficult to determine in postmarket reports, but that alternative causes of the hypertension were ruled out in well-documented cases.&lt;/p&gt;
&lt;p&gt;Healthcare professionals who determine didanosine is effective in treating a patient should monitor that patient for the development of portal hypertension and esophageal varices, the agency said.&lt;/p&gt;
&lt;p&gt;Didanosine is used in combination with other HIV medications to help maintain CD4 cells in patients.&lt;/p&gt;
&lt;p&gt;The drug already has a black box warning for lactic acidosis and hepatomegaly with steatosis.&lt;/p&gt;
&lt;p&gt;Like the antiretroviral agents hydroxyurea and ribavirin, didanosine has been associated with the development of liver toxicity.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_201"
                     title="Viral Cause of Appendicitis Called Unlikely (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/Surgery/GeneralSurgery/tb/18048?impressionId=1265794714421"
                     
      &lt;p&gt;The cause of appendicitis remains a mystery, according to a study that discounts flu and intestinal infection as candidates.&lt;/p&gt;
&lt;p&gt;Influenza&apos;s distinctive seasonal variations don&apos;t match appendicitis hospitalization rates, according to researchers led by Edward H. Livingston, MD, of the University of Texas Southwestern Medical Center in Dallas.&lt;/p&gt;
&lt;p&gt;Enteric infections and rotavirus showed trends that were likewise dissimilar to those of perforating and nonperforating appendicitis, the researchers reported in the January issue of the &lt;em&gt;Archives of Surgery&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Most theories regarding the underlying causes of appendicitis rely on the notion that the appendix becomes obstructed,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;However, a more complex explanation appears necessary, they said, citing studies suggesting that blockage by hard pieces of stool called fecaliths is rare and that intraluminal pressures become elevated only in late-stage disease as inflammation progresses.&lt;/p&gt;
&lt;p&gt;Viral infection has been proposed as one explanation.&lt;/p&gt;
&lt;p&gt;And apparent &quot;outbreaks&quot; of appendicitis have been described in epidemiologic studies, suggesting an infectious etiology, Livingston&apos;s group noted.&lt;/p&gt;
&lt;p&gt;&quot;Viral infection of the appendix could cause mucosal ulceration followed by secondary bacterial infection of the appendix,&quot; they wrote. &quot;Alternatively, viral disease could result in lymphoid hyperplasia of the appendix with resultant obstruction and mucosal injury followed by bacterial infection.&quot;&lt;/p&gt;
&lt;p&gt;To explore the viral etiology scenario, the researchers used the National Hospital Discharge Survey to measure disease incidence trends from 1970 to 2006 based on admissions for appendicitis, flu, rotavirus, and enteric infections.&lt;/p&gt;
&lt;p&gt;They found a decline in overall annual incidence of both nonperforating appendicitis and influenza until 1995, after which the incidence for both rose in parallel.&lt;/p&gt;
&lt;p&gt;Perforating appendicitis, on the other hand, slowly rose in incidence over the years without a U-shaped curve.&lt;/p&gt;
&lt;p&gt;The incidence of perforating appendicitis, in fact, did not correlate with that of nonperforating appendicitis or any infectious disease studied.&lt;/p&gt;
&lt;p&gt;This suggested that &quot;perforated appendicitis has causative factors that are more complex than the simple delay in treating acute appendicitis,&quot; the researchers said.&lt;/p&gt;
&lt;p&gt;Rebecca C. Britt, MD, of Eastern Virginia Medical School in Norfolk, Va., commented that this was perhaps the most important implication of the study  --  that perforating and nonperforating appendicitis may be separate entities.&lt;/p&gt;
&lt;p&gt;Her critique accompanying the &lt;em&gt;Archives&lt;/em&gt; paper cautioned that further investigation is &quot;definitely warranted.&quot;&lt;/p&gt;
&lt;p&gt;But if confirmed, management patterns could shift, the researchers said.&lt;/p&gt;
&lt;p&gt;&quot;This has important clinical ramifications since appendectomy is generally performed as an emergency operation for fear of causing a perforation if treatment is delayed,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;For nonperforating appendicitis, the year-to-year association with influenza was discounted by the lack of within-year correlation.&lt;/p&gt;
&lt;p&gt;Appendicitis occurred throughout the year, with a &quot;slight tendency&quot; to occur more often in summer months whereas the flu was largely limited to winter.&lt;/p&gt;
&lt;p&gt;Furthermore, appendicitis is predominantly a disease of the young, while influenza disproportionately affects the older population, &quot;which goes against influenza as a proximate agent,&quot; Britt added.&lt;/p&gt;
&lt;p&gt;&quot;While perhaps influenza plays a role in the development of appendicitis by sensitizing the immune system to another viral agent, there remains no clear evidence that it is a causative agent for appendicitis,&quot; she wrote.&lt;/p&gt;
&lt;p&gt;Rotavirus infection also peaked in the winter months, without an apparent association with appendicitis incidence.&lt;/p&gt;
&lt;p&gt;Intestinal infection incidence matched the fairly even distribution of appendicitis throughout the year, but had a propensity to be higher in winter months rather than during the summer as was the case with appendicitis.&lt;/p&gt;
&lt;p&gt;Overall and peak hospital admission rates for intestinal infection began a yearly rise in 1989 and have been steadily increasing, which also did not match trends in appendicitis.&lt;/p&gt;
&lt;p&gt;Britt cautioned that the study relied on hospital discharge data, which is not likely to be a complete picture of incidence for viral illness because the vast majority of cases do not require hospitalization and many are not treated at all.&lt;/p&gt;
&lt;p&gt;&quot;Certainly this makes comparison onerous,&quot; she said.&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. Britt 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_19_3536"
                     title="AASLD: Antibiotics Top Cause of Drug-Induced Liver Failure (CME/CE)"
                     score="-0.006"
                     href="http://www.medpagetoday.com/MeetingCoverage/AASLD/tb/16791?impressionId=1265794714421"
                     
      BOSTON  --  Antimicrobial agents are the most common cause of drug-induced liver failure, with most cases ending in death or transplant, a researcher said here.&lt;br&gt;
&lt;br&gt;A prospective analysis of some 1,200 cases of acute liver failure found that half of those caused by drugs were associated with antituberculosis, antifungal, sulfa drugs, and other antibiotics, according to Adrian Reuben, MBBS, of the Medical University of South Carolina in Charleston.&lt;br&gt;
&lt;br&gt;Herbal supplements, anticonvulsants, and statins also were relatively common causes of drug-induced liver injury (DILI), Reuben told attendees here at the American Association for the Study of Liver Diseases&apos; annual meeting.&lt;/p&gt;
&lt;p&gt;Only 27% of DILI patients in acute liver failure recovered spontaneously, Reuben said. About 40% had successful transplants, while another 30% died either waiting for transplant or were too ill to be wait-listed.&lt;/p&gt;
&lt;p&gt;Overall, 66% of patients with DILI-associated liver failure survived.&lt;/p&gt;
&lt;p&gt;Reuben said this was the first study of DILI-associated liver failure and its outcomes to use prospectively collected data. Prior to this study, he said, everything known about severe DILI has come from retrospective case series.&lt;/p&gt;
&lt;p&gt;The current study involved data collected at 23 centers participating in the Acute Liver Failure Study Group from 1998 to 2007, a total of 1,198 cases. These centers supplied detailed information for each case on prior drug use, presenting symptoms, laboratory findings, and outcomes.&lt;/p&gt;
&lt;p&gt;Causality from drugs was determined on the basis of three separate expert reviews, which were combined to assign probability of DILI for each proposed case.&lt;/p&gt;
&lt;p&gt;A total of 132 were ultimately identified as DILI, of which 107 were likely, 21 were probable, and four were possible. Acetaminophen reactions were excluded.&lt;/p&gt;
&lt;p&gt;&quot;Likely&quot; cases were those where the putative culprit drug was the only one taken or was taken only with other drugs with low liver-injury potential, and the timing of drug administration was consistent with DILI.&lt;/p&gt;
&lt;p&gt;At the other end of the spectrum, &quot;possible&quot; cases involved drugs with high DILI potential but temporal details were unknown, or there were other drugs or comorbidities present which could also account for liver failure.&lt;/p&gt;
&lt;p&gt;Women accounted for more than 70% of the DILI cases. About 57% of patients were white, suggesting over-representation of blacks, Hispanics, and Asians.&lt;/p&gt;
&lt;p&gt;Some 70% of patients had coma scores of 2 or more. Ascites was&lt;strong&gt; &lt;/strong&gt;present in 25%, Reuben said.&lt;/p&gt;
&lt;p&gt;Deep jaundice and coagulopathy were common, but liver enzyme elevations were relatively modest, he reported. Mean levels of alanine and aspartyl aminotransferases were both less than 600 U/L. Alkaline phosphatase levels averaged 165 U/L.&lt;/p&gt;
&lt;p&gt;Predictors of spontaneous survival, versus transplant or death, included relatively mild coma, smaller elevations in bilirubin, less extensive coagulopathy (as measured by international normalized ratio) and lower scores in the Model for End-Stage Liver Disease.&lt;/p&gt;
&lt;p&gt;Serum creatinine also was much higher in patients who died, compared with those who survived with or without transplant.&lt;/p&gt;
&lt;p&gt;Such factors as age, gender, body mass index, blood pressure, type of drug involved, and stoppage of the culprit drug did not appear to affect outcomes, Reuben said.&lt;/p&gt;
&lt;p&gt;He noted that use of N-acetyl-cysteine was common in patients who survived, but this effect was confounded by coma grade and MELD score.&lt;/p&gt;
&lt;p&gt;Of the 132 cases, the following drug classes were most commonly represented: &lt;ul&gt; &lt;li&gt;Antituberculosis: 25&lt;/li&gt; &lt;li&gt;Antibiotics: 18&lt;/li&gt; &lt;li&gt;Sulfa drugs: 12&lt;/li&gt; &lt;li&gt;Antifungals: 6&lt;/li&gt; &lt;li&gt;Herbal and folk medicine products: 14&lt;/li&gt; &lt;li&gt;Epilepsy drugs: 13&lt;/li&gt; &lt;li&gt;Statins: 10&lt;/li&gt; &lt;li&gt;NSAIDs: 7&lt;/li&gt; &lt;li&gt;abolite agents (e.g., disulfiram): 11&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Within these categories, the tuberculosis drug isoniazid and the antibiotic agent nitrofurantoin were involved in 21 and 11 cases, respectively, according to Reuben.&lt;/p&gt;
&lt;p&gt;Although the liver-toxicity potential for these agents is recognized, he said some aspects of these cases remained mysterious. For example, duration of nitrofurantoin treatment leading up to acute liver failure ranged from one month to three years.&lt;/p&gt;
&lt;p&gt;Similarly, Reuben reported, the median duration of isoniazid therapy was five months, with 30% of cases involving treatment of six to eight months.&lt;/p&gt;
&lt;p&gt;He said the latency period between drug initiation and DILI onset was a critical area for future research, for these and other drugs. He suggested that statins may be a drug class for which acute toxicity after long-term use has been overlooked.&lt;/p&gt;
&lt;p&gt;Reuben also called for more research on the reasons underlying the predominance of antimicrobial agents as causes of DILI.&lt;/p&gt;
&lt;p&gt;Scott Friedman, MD, president of the AASLD and a hepatologist at Mount Sinai School of Medicine in New York City, said the study shed important new light on the course of DILI-associated liver failure.&lt;/p&gt;
&lt;p&gt;&quot;Drug-induced liver injury is a huge problem in the U.S.,&quot; he noted, adding that it may be the single biggest reason for cancellation of drugs in late-stage development.&lt;/p&gt;
&lt;p&gt;The study, he said, &quot;characterizes in much greater detail and accuracy the features of drug-induced liver injury&quot; than has been available in the literature.&lt;/p&gt;
&lt;p&gt;&quot;We need much better genetic predictors of the risk for drug-induced liver injury,&quot; Friedman said.&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;No corporate funding for the study was reported.&lt;/p&gt;&lt;p&gt;Reuben said he had no financial disclosures. One co-author reported relationships with Eli Lilly, Gilead, Novartis, Schering-Plough, Bristol-Myers Squibb, Roche, Siemens, Vertex, and Globimmune.&lt;/p&gt;&lt;p&gt;Friedman reported relationships with Exalenz, sanofi-aventis, Axcan, Angion, Intercept, 7TM, Stromedix, and Celera.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_712"
                     title="IDSA: Link Between Tequin (gatifloxacin) and Hypoglycemia Strengthened"
                     score="-0.006"
                     href="