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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_407"
                     title="ICU Catheter Infections Can Be Virtually Eliminated (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/CriticalCare/InfectionControl/tb/18308?impressionId=1265806440980"
                     
      Catheter-related infections aren&apos;t inevitable in the ICU, according to a quality initiative that maintained rates at nearly zero for three years in Michigan hospitals.&lt;br&gt;
&lt;br&gt;The maintenance phase, after initial implementation of low-tech measures such as handwashing and removal of unneeded catheters, saw no rebound in catheter-related infections, Peter J. Pronovost, MD, PhD, of Johns Hopkins, and colleagues reported online in &lt;em&gt;BMJ&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The first 18 months of their &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/4771&quot; mce_href=&quot;http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/4771&quot; target=&quot;_blank&quot;&gt;Keystone ICU initiative&lt;/a&gt; dropped catheter-related interventions from a mean of 7.7 and median of 2.2 per 1,000 catheter days down to 1.3 and 0, respectively.&lt;br&gt;
&lt;br&gt;At the 36 month mark, infection rates remained almost nil, at a mean of 1.1 and median of 0 per 1,000 catheter days.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;For the most part, hospitals view these infections as inevitable, as the cost of doing business, that patients are too sick, that these can&apos;t be prevented,&quot; Pronovost told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;That&apos;s just not true.&quot;&lt;/p&gt;
&lt;p&gt;Catheter-related infections are the number one cause of preventable death in hospitals and ICUs, ahead of even ventilator-related pneumonia, he noted.&lt;/p&gt;
&lt;p&gt;The changes seen at the 90 Michigan ICUs that stayed with the catheter-related infection initiative were impressive, representing one of the largest and longest improvements the field has seen.&lt;/p&gt;
&lt;p&gt;Often, quality initiatives fail on durability after the study funding and resources disappear, and hospitals are left on their own, Pronovost noted.&lt;/p&gt;
&lt;p&gt;&quot;If you push you might get some effect, but then you stop pushing  --  in other words the external control goes away  --  and the performance goes right back down,&quot; he said in an interview. &quot;It can&apos;t just be the stick that drives it.&quot;&lt;/p&gt;
&lt;p&gt;The intervention started with 103 ICUs that implemented strategies to reduce rates of catheter-related bloodstream infections rates over 18 months, with measurement and feedback of infection rates.&lt;/p&gt;
&lt;p&gt;The strategies aimed at improving execution of five evidence-based recommendations, as follows: &lt;ul&gt; &lt;li&gt;Hand washing before insertion of the catheter&lt;/li&gt; &lt;li&gt;Using gowns and full barrier precautions at catheter insertion&lt;/li&gt; &lt;li&gt;Cleaning the skin with chlorhexidine before catheter insertion&lt;/li&gt; &lt;li&gt;Avoiding the femoral site when possible&lt;/li&gt; &lt;li&gt;Removing unnecessary catheters&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Then, over the subsequent 18-month maintenance period, ICU teams were instructed to integrate this intervention into staff orientation, to collect monthly data from hospital infection control staff, and to report infection rates to physicians and others.&lt;/p&gt;
&lt;p&gt;Along with the sustained reduction in overall catheter-related infections, the researchers found a prolonged reduction in bloodstream infections that was significant during all study periods, compared to baseline.&lt;/p&gt;
&lt;p&gt;Rates decreased from a mean of 7.7 and median 2.7 of per 1,000 catheter days at baseline to 1.3 and 0, respectively, at 16 to 18 months after implementation. They remained at 1.1 and 0 at months 34 to 36 (-1% versus 18 months, 95% CI -9% to +7%).&lt;/p&gt;
&lt;p&gt;ICU teams interviewed attributed the continuously low rates to five factors: &lt;ul&gt; &lt;li&gt;Continued feedback on infection data&lt;/li&gt; &lt;li&gt;Improvements in safety culture as part of the project&lt;/li&gt; &lt;li&gt;An &quot;unremitting belief in the preventability of bloodstream infections&quot;&lt;/li&gt; &lt;li&gt;Involvement of senior leaders&lt;/li&gt; &lt;li&gt;A noncompetitive, shared goal to reduce infection rates throughout the state&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Of these, Pronovost called culture change in the ICUs the key factor to sustainability, although the researchers cautioned that which aspects contributed were not formally evaluated.&lt;/p&gt;
&lt;p&gt;They said they could not determine the impact incentive payments from Blue Cross Blue Shield of Michigan to hospitals that continued their participation  --  payments that were based on performance thresholds in subsequent years.&lt;/p&gt;
&lt;p&gt;Pronovost&apos;s team is now working to implement the quality initiative state-by-state nationwide, supported by the Agency for Healthcare Research and Technology.&lt;/p&gt;
&lt;p&gt;&quot;It seems absurd that this wouldn&apos;t be in every hospital in the country,&quot; he said in an interview. &quot;It&apos;s worked on a large scale, it&apos;s exceedingly cheap, there&apos;s no fancy technology.&quot;&lt;/p&gt;
&lt;p&gt;Success isn&apos;t only for community hospitals, Pronovost emphasized.&lt;/p&gt;
&lt;p&gt;Large, often academic, medical centers frequently express the conviction that their sicker, more complex ICU population wouldn&apos;t produce the same results, that their infections truly are inevitable, he said.&lt;/p&gt;
&lt;p&gt;&quot;To them I say, Not so,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;We have shown at Johns Hopkins, at the University of Michigan, at Pittsburgh, using a similar but different approach, at Tufts  --  many large academic medical centers have had dramatic reductions of these infections.&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;The project was supported, for the period from October 2003 to September 2005, by the Agency for Healthcare Research and Quality and the Michigan Health &amp;amp; Hospital Association.&lt;/p&gt;&lt;p&gt;Pronovost and a co-author reported receiving received lecture fees from various healthcare organizations and grant support from the Agency for Healthcare Research and Quality, the Robert Wood Johnson Foundation, the National Patient Safety Agency, and the World Health Organization to study and improve quality of care, including catheter-related bloodstream infections.&lt;/p&gt;&lt;p&gt;Co-authors reported conflicts of interest with government agencies, Cubist, Astellas, Merck, Forrest, Cadence, the Robert Wood Johnson Foundation, Lilly, Edward Life Sciences, and Sage.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_384"
                     title="Few Surprises in Warning Signs for Infections in Kids (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18276?impressionId=1265806440980"
                     
      &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_379"
                     title="Novel Compound Blocks Many Viruses (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18273?impressionId=1265806440980"
                     
      A search for a drug that would block one virus has yielded a compound that prevents infection by viral pathogens ranging from Ebola to HIV, researchers said.&lt;br&gt;
&lt;br&gt;The compound, dubbed LJ001, emerged when researchers were hunting for ways to block infection by Nipah virus, an emerging zoonosis identified only in 1999, according to Benhur Lee, MD, of the University of California Los Angeles, and colleagues.&lt;br&gt;
&lt;br&gt;Testing showed that it renders an entire class of viruses  --  those surrounded by a lipid envelope  --  unable to infect cells, they wrote online in &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;In the lab, the compound blocked infection by more than 20 viruses, including Ebola, HIV, hepatitis C, influenza A, West Nile, Rift Valley fever, and yellow fever virus.&lt;/p&gt;
&lt;p&gt;That property raises the possibility that the compound  --  or others like it  --  can act as broad-spectrum antivirals, Lee and colleagues wrote.&lt;/p&gt;
&lt;p&gt;But clinical experts cautioned that the study is only a first step. &quot;There are a lot of ifs,&quot; said Aaron Glatt, MD, of New Island Hospital in Bethpage, N.Y., speaking for the Infectious Diseases Society of America.&lt;/p&gt;
&lt;p&gt;&quot;This is a very interesting  --  and very early  --  study,&quot; Glatt told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The study &quot;revved my motor, I liked reading it,&quot; said William Schaffner, MD, of Vanderbilt University in Nashville. But like Glatt, he told &lt;em&gt;MedPage Today&lt;/em&gt; he wants to see much more research.&lt;/p&gt;
&lt;p&gt;&quot;There are lots of starts and relatively few finishes&quot; in the hunt for new medications, Schaffner said. The next step, he said, is for the investigators to show the compound  --  or one of its chemical relatives  --  is safe and effective in animals.&lt;/p&gt;
&lt;p&gt;Lee and colleagues reported that the compound did not appear to have any overt toxicity in mice, other than a slight elevation in cholesterol levels.&lt;/p&gt;
&lt;p&gt;But a challenge test  --  in which mice were infected with Ebola after being treated once daily with the compound  --  did not show any benefit, they said.&lt;/p&gt;
&lt;p&gt;Analysis of the compound&apos;s behavior in serum showed that it did not reach a useful level for two hours after injection and that its half-life in the body was only about four hours.&lt;/p&gt;
&lt;p&gt;&quot;Clearly, once-daily dosing was not sufficient to maintain therapeutic steady-state plasma concentrations of LJ001,&quot; Lee and colleagues wrote.&lt;/p&gt;
&lt;p&gt;The compound appears to act by disrupting the lipid envelope of the virus, while leaving the viral particles themselves largely intact, the researchers said. The disruption prevents the virus from entering its target cells.&lt;/p&gt;
&lt;p&gt;Once the researchers realized LJ001 targeted enveloped viruses, &quot;we followed up and determined that it was somehow changing the lipid envelope to prevent the fusion of the virus particle with the host cell,&quot; according to Alexander Freiberg, PhD, director of the University of Texas Medical Branch at Galveston laboratory where much of the cell-culture work was done, as well as mouse studies with Ebola and Rift Valley fever viruses.&lt;/p&gt;
&lt;p&gt;&quot;It was, of course, very exciting,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The researchers showed that viruses  --  once treated with the compound  --  could not infect cells. The concentration needed to yield the effect was roughly similar for all of the tested viruses, they found.&lt;/p&gt;
&lt;p&gt;In a parallel experiment, the researchers treated viral particles of Rift Valley fever virus or a mouse version of Ebola-Zaire virus with LJ001 and then administered them to mice.&lt;/p&gt;
&lt;p&gt;Viral particles treated with inert compounds led to death from the viruses with a few days, the researchers said, but 100% of animals given the treated Rift Valley virus survived the challenge as did 80% of those given the LJ001-treated Ebola.&lt;/p&gt;
&lt;p&gt;Although the compound appears to perturb the viral membrane, it had no effect on cell-cell fusion, perhaps because mammalian cells can repair lesions to their membranes while viruses cannot, the researchers 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 study was supported by the NIH, the UCLA Center for Aids Research, the Burroughs Wellcome Fund, the March of Dimes, the California NanoSystems Institute (R.D.), a UCLA Microbial Pathogenesis Training Grant, a Warsaw Fellowship Endowment, and a Rheumatology Training Grant.&lt;/p&gt;&lt;p&gt;The authors said they had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_310"
                     title="Rotavirus Vaccine Effective in Third World Nations (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/Pediatrics/Vaccines/tb/18174?impressionId=1265806440980"
                     
      &lt;p&gt;Vaccination against rotavirus appears to be highly effective in reducing death and serious gastrointestinal disease among young children in developing countries, according to two&lt;strong&gt; &lt;/strong&gt;publications in the Jan. 28 &lt;em&gt;New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;In Malawi and South Africa, a vaccination program significantly reduced infantile gastroenteritis associated with the pathogen, researchers said.&lt;/p&gt;
&lt;p&gt;In a companion paper, investigators reported that a rotavirus vaccination program in Mexico appears to have been the cause of a marked reduction in deaths from diarrhea among young children.&lt;/p&gt;
&lt;p&gt;Taken together, the two studies suggest that physicians have &quot;another powerful weapon&quot; to help prevent death from diarrhea among young children, according to Mathuram Santosham, MD, of the Johns Hopkins Bloomberg School of Public Health, who was not involved in the research.&lt;/p&gt;
&lt;p&gt;&quot;It is time to act to combat the 1.8 million unnecessary deaths from diarrhea that continue to occur each year,&quot; Santosham wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Two oral, live attenuated vaccines against rotavirus have been shown to prevent the associated gastroenteritis  --  GlaxoSmithKline&apos;s Rotarix and Merck&apos;s RotaTeq, according to Nigel Cunliffe, MBChB, PhD, of the University of Liverpool in England, and colleagues.&lt;/p&gt;
&lt;p&gt;But trials of those drugs mainly occurred in more developed countries, the researchers noted, so the World Health Organization  --  fearing they might not work as well among the very poor  --  suggested additional trials in the Third World.&lt;/p&gt;
&lt;p&gt;To fill the knowledge gap, Cunliffe and colleagues conducted a randomized, placebo-controlled trial in Malawi and South Africa, enrolling 4,939 healthy infants.&lt;/p&gt;
&lt;p&gt;They were assigned to get either three doses of placebo (at six, 10, and 14 weeks of age), two doses of the Rotarix vaccine and one of placebo to maintain blinding, or three doses of the vaccine.&lt;/p&gt;
&lt;p&gt;The researchers found: &lt;ul&gt; &lt;li&gt;Severe gastroenteritis caused by rotavirus occurred in 4.9% of the placebo group and in 1.9% of the pooled vaccine group, yielding a vaccine efficacy of 61.2%, which was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001. &lt;/li&gt; &lt;li&gt;Vaccine efficacy was lower in Malawi than in South Africa  --  49.4% versus 76.9%. But the vaccine prevented more cases of severe rotavirus gastroenteritis in Malawi  --  6.7 cases prevented per 100 infants vaccinated yearly versus 4.2.&lt;/li&gt; &lt;li&gt;Efficacy against all-cause severe gastroenteritis was 30.2%.&lt;/li&gt; &lt;li&gt;At least one serious adverse event was reported in 9.7% of the vaccinated infants and 11.5% of the placebo group, but only three were judged to be related to the vaccine.&lt;/li&gt; &lt;li&gt;There was a single case of intussusception -- a 6-month-old child in the three-dose vaccine group, who recovered after bowel resection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The findings have led WHO to recommend that rotavirus vaccination be included in all national immunization programs, Cunliffe and colleagues noted.&lt;/p&gt;
&lt;p&gt;Mexico phased in rotavirus vaccination over slightly more than a year, from February 2006 through May 2007, according to Manish Patel, MD, of the CDC, and colleagues.&lt;/p&gt;
&lt;p&gt;To estimate the effect of the program, Patel and colleagues compared annual deaths from diarrhea before and after the immunization program began.&lt;/p&gt;
&lt;p&gt;Over the four years before the program started, the median annual number of diarrhea-related deaths among children younger than five was 1,793, the researchers found, for a mortality rate of 18.1 deaths per 100,000.&lt;/p&gt;
&lt;p&gt;In 2008, by contrast, there were 1,118 deaths, a reduction of 765, which yielded a mortality rate of 11.8 per 100,000 children, they reported in the journal.&lt;/p&gt;
&lt;p&gt;The rate reduction of 35% was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, Patel and colleagues said.&lt;/p&gt;
&lt;p&gt;The findings come with some caveats, the researchers said. Among them: &lt;ul&gt; &lt;li&gt;It was not possible to pin down the reduction in deaths attributable to vaccination because precise vaccine coverage information is lacking. &lt;/li&gt; &lt;li&gt;Other changes, such as hygiene improvements, might also have affected the trend.&lt;/li&gt; &lt;li&gt;Because of difficulty obtaining fecal specimens, it wasn&apos;t possible to study trends in rotavirus deaths specifically.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;While the studies suggests that rotavirus vaccination would prevent much disease and many deaths, there are obstacles to introducing the vaccine to poorer countries, Santosham noted in the editorial.&lt;/p&gt;
&lt;p&gt;A key obstacle, he said, is that the vaccine requires more refrigeration  --  so-called &quot;cold-chain&quot; storage  --  than typical childhood vaccines.&lt;/p&gt;
&lt;p&gt;Also problematic, he said, is the current recommendation that the vaccines be given early in life to avoid age-dependent occurrence of intussusception, which led to an earlier vaccine being taken off the market.&lt;/p&gt;
&lt;p&gt;In many of the poorest countries, on-time vaccination is rare, which may impede the use of a rotavirus vaccine unless the time window for administration can be opened wider, he 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 African study was supported by GlaxoSmithKline and the PATH Rotavirus Vaccine Program, a collaboration with the World Health Organization and the CDC with support from the Global Alliance for Vaccines and Immunization (GAVI). Cunliffe reported financial links with Sanofi Pasteur and GlaxoSmithKline.&lt;/p&gt;&lt;p&gt;For the Mexican study, the researchers did not report any external support or any conflicts.&lt;/p&gt;&lt;p&gt;Santosham reported financial links with GlaxoSmithKline and Merck, both of which make rotavirus vaccines.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_301"
                     title="Tight Glucose Control Fails in Septic Shock (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/CriticalCare/Sepsis/tb/18160?impressionId=1265806440980"
                     
      Septic shock patients treated with a corticosteroid get no survival advantage from tight glucose control or addition of a second corticosteroid to provide more mineralocorticoid activity, according to results of a randomized trial.&lt;br&gt;
&lt;br&gt;Aiming for normoglycemia at 80 to 110 mg/dL rather than the standard 150 mg/dL had no impact on inhospital mortality rates (45.9% versus 42.9%, &lt;em&gt;P&lt;/em&gt;=0.50), Djillali Annane, MD, of H&amp;#244;pital Raymond Poincar&amp;#233; in Garches, France, and colleagues found.&lt;br&gt;
&lt;br&gt;Inhospital mortality was likewise similar whether patients got hydrocortisone (Solu-Cortef) alone or with the addition of fludrocortisone ([Florinef] 42.9% versus 45.8%, &lt;em&gt;P&lt;/em&gt;=0.50), they reported in the Jan. 27 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;This aggressive treatment strategy should not be routine, the researchers recommended.&lt;/p&gt;
&lt;p&gt;These findings largely match the general lack of benefit seen with tight glycemic control in recent studies with ICU patients overall.&lt;/p&gt;
&lt;p&gt;The prematurely terminated &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/SCCM/5096&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/SCCM/5096&quot; target=&quot;_blank&quot;&gt;European Glucontrol Trial&lt;/a&gt; found no mortality benefit but a seven-fold higher risk of hypoglycemia with an 80 to 110 mg/dL target in the ICU.&lt;/p&gt;
&lt;p&gt;In the &lt;a href=&quot;http://www.medpagetoday.com/CriticalCare/Intensivists/13397&quot; mce_href=&quot;http://www.medpagetoday.com/CriticalCare/Intensivists/13397&quot; target=&quot;_blank&quot;&gt;NICE-SUGAR&lt;/a&gt; study, 90-day mortality was actually higher in the tight glucose control group (27.9% versus 24.9%, &lt;em&gt;P&lt;/em&gt;=0.02), although there was a trend for benefit in patients who got corticosteroids (&lt;em&gt;P&lt;/em&gt;=0.06).&lt;/p&gt;
&lt;p&gt;Glucose targets are being re-evaluated across medicine as the &quot;lower is better&quot; paradigm has had a safety asterisk added everywhere from diabetes care to the ICU, noted Richard Bergenstal, MD, American Diabetes Association president for medicine and science.&lt;/p&gt;
&lt;p&gt;&quot;All of a sudden it&apos;s becoming more than a single number,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;Now be it inpatient or outpatient, we&apos;re realizing that ... you have to do it while you&apos;re minimizing hypoglycemia.&quot;&lt;/p&gt;
&lt;p&gt;A more nuanced and &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; target=&quot;_blank&quot;&gt;individualized&lt;/a&gt; strategy is prudent, Bergenstal agreed.&lt;/p&gt;
&lt;p&gt;The current clinical uncertainty underscores the need for large-scale international cooperation to get adequately powered trials, according to an accompanying editorial.&lt;/p&gt;
&lt;p&gt;In it, Greet Van den Berghe, MD, PhD, of the Catholic University of Leuven, Belgium, cautioned that Annane&apos;s Corticosteroids and Intensive Insulin Therapy for Septic Shock (COIITSS) study was grossly underpowered.&lt;/p&gt;
&lt;p&gt;The initial studies that led to rapid adoption of intensive insulin therapy in ICUs around the world had suggested an absolute reduction in mortality of only 3%, whereas the COIITSS study projected a 12.5% absolute benefit.&lt;/p&gt;
&lt;p&gt;More importantly, the study achieved mean glucose levels of only between 120 and 130 mg/dL in the intervention group for whom the aim was 80 to 110 mg/dL, which resulted in considerable overlap with the standard care group for whom mean levels were about 145 mg/dL.&lt;/p&gt;
&lt;p&gt;This could account for the lack of difference in outcome, Van den Berghe said.&lt;/p&gt;
&lt;p&gt;But the intensive insulin group did have &quot;markedly&quot; lower blood glucose levels for the duration of their ICU stay and spent more time in the 80 to 110 mg/dL range compared with the standard care group (both &lt;em&gt;P&lt;/em&gt;&amp;lt;0.00001), the researchers noted.&lt;/p&gt;
&lt;p&gt;Because corticosteroids further aggravate the &quot;diabetes of injury&quot; seen with septic shock, Annane&apos;s group undertook a multicenter trial of 509 adults treated for septic shock with multiple organ dysfunction over a three year period at 11 ICUs in France.&lt;/p&gt;
&lt;p&gt;Patients were randomly assigned to tight glucose control using continuous intravenous insulin infusion to target a glucose level of 80 to 110 mg/dL or conventional insulin therapy targeted to guidelines-recommended 150 mg/dL or under. They were additionally randomized to receive hydrocortisone alone (50-mg bolus every six hours) or in combination with fludrocortisone (50-&amp;#956;g tablets once daily) for seven days.&lt;/p&gt;
&lt;p&gt;Aside from the lack of inhospital mortality advantage, tight glucose control also failed to produce a benefit for the following secondary endpoints: &lt;ul&gt; &lt;li&gt;Overall survival (hazard ratio 1.04, &lt;em&gt;P&lt;/em&gt;=0.78) &lt;/li&gt; &lt;li&gt; ICU length of stay for survivors (median 10 versus nine days, &lt;em&gt;P&lt;/em&gt;=0.68)&lt;/li&gt; &lt;li&gt;Duration of hospital stay overall (24 versus 22 days, &lt;em&gt;P&lt;/em&gt;=0.87)&lt;/li&gt; &lt;li&gt;Median vasopressor-free days (four for both, P=0.58)&lt;/li&gt; &lt;li&gt;Median mechanical ventilation-free days (10 versus 13, &lt;em&gt;P&lt;/em&gt;=0.51)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Nor was there evidence for interaction with fludrocortisone in the primary endpoint (relative risk 0.89 versus 0.91 hydrocortisone alone, &lt;em&gt;P&lt;/em&gt;=0.31) or benefit in any other endpoint.&lt;/p&gt;
&lt;p&gt;The one effect of intensive insulin appeared to be an increase in episodes of severe hypoglycemia, defined by glucose falling below 40 mg/dL (mean 0.29 versus 0.14 episodes per patient, &lt;em&gt;P&lt;/em&gt;=0.003).&lt;/p&gt;
&lt;p&gt;However, having hypoglycemia did not increase the risk of death in intervention group patients compared with controls (45.2% versus 50%).&lt;/p&gt;
&lt;p&gt;The researchers cautioned that the study did not rule out a benefit from some degree of glucose control compared with none.&lt;/p&gt;
&lt;p&gt;They also noted that healthcare providers were not blinded to administration of fludrocortisone, for which no placebo was available.&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 Assistance Publique&amp;#8211;H&amp;#244;pitaux de Paris. The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;Van den Berghe, through the Catholic University of Leuven, reported receiving structural research financing from the Methusalem program, funded by the Flemish government.&lt;/p&gt;&lt;p&gt;Bergenstal reported receiving research funding and serving on advisory boards for various pharmaceutical companies related to novel diabetes drugs but without any personal financial compensation.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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