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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_384"
                     title="Few Surprises in Warning Signs for Infections in Kids (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18276?impressionId=1265735448227"
                     
      &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_349"
                     title="Motavizumab Reduces Preemie Lung Infections (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Pediatrics/Vaccines/tb/18232?impressionId=1265735448227"
                     
      &lt;p&gt;Premature babies who received preventative treatment with motavizumab (Medi-524) suffered fewer outpatient respiratory infections than those taking palivizumab (Synagis), the current standard of treatment, a large new trial found.&lt;/p&gt;
&lt;p&gt;Compared with children who received palivizumab, those treated with motavizumab had similar rates of hospitalization for respiratory syncytial virus, or RSV (RR 0.74; 95% CI 0.503 to 1.083) and a 50% reduction in outpatient, RSV-specific, medically attended lower respiratory tract infection, or MALRI (2.0% vs 3.9%; &lt;em&gt;P&lt;/em&gt;=0.005), according to a report in the January issue of &lt;em&gt;Pediatrics&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Although not better than palivizumab in reducing RSV-associated hospitalizations, motavizumab did demonstrate a significant reduction in outpatient MALRI compared with palivizumab,&quot; Xavier Carbonell-Estrany, MD, PhD, of Hospital Cl&amp;#237;nic, in Barcelona, Spain, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;As such, motavizumab may offer an improved alternative for preventing serious RSV disease in high-risk infants and children.&quot;&lt;/p&gt;
&lt;p&gt;Most otherwise healthy patients recover within a week or two from RSV, which infects the lungs and breathing passages. However, the infection can be severe in people who are vulnerable, including premature infants and older children who were born prematurely. It&apos;s the most common cause of bronchiolitis and pneumonia in U.S. children in their first year of life, researchers noted.&lt;/p&gt;
&lt;p&gt;Palivizumab is a humanized monoclonal antibody recommended for prevention of RSV in children at high risk. Monthly treatments of high-risk youngsters have been found to reduce RSV-related hospitalizations by 50%, compared with placebo.&lt;/p&gt;
&lt;p&gt;Motavizumab, an investigational monoclonal antibody related to palivizumab, proved more potent at neutralizing the RSV virus in animal studies. Early trials indicated the drug was well-tolerated at treatment doses and reduced viral counts in the nasal aspirates of children hospitalized with RSV.&lt;/p&gt;
&lt;p&gt;Both drugs are manufactured by MedImmune, the sponsor of this phase III clinical trial.&lt;/p&gt;
&lt;p&gt;In the double-blind, multinational study, Carbonell-Estrany and colleagues randomly assembled 6,635 preterm infants (6 months and younger) and children (2 years and younger) suffering from chronic lung disease resulting from premature birth.&lt;/p&gt;
&lt;p&gt;They were randomized to five 15 mg/kg monthly doses of palivizumab or motavizumab between November 2004 and May 2006. The trial was conducted in 24 countries.&lt;/p&gt;
&lt;p&gt;The primary objective was to compare the efficacy of the two drugs at preventing a child from being hospitalized due to respiratory symptoms from an RSV infection, preventing a child already hospitalized from contracting a new infection, and preventing deaths from RSV.&lt;/p&gt;
&lt;p&gt;Of the 6,513 children who received full treatment with the drugs, 43 (1.4%) of those who received motavizumab and 59 (1.9%) of those who received palivizumab were hospitalized for RSV infections (95% CI 0.490 to 1.081).&lt;/p&gt;
&lt;p&gt;The study also compared the drugs&apos; efficacy at preventing RSV-specific outpatient MALRIs. Of the 2,283 outpatients who received full treatment with the drugs, 23 (2%) who received motavizumab and 45 (3.9%) who received palivizumab contracted RSV infections (&lt;em&gt;P&lt;/em&gt;=0.005).&lt;/p&gt;
&lt;p&gt;The authors noted that while the drugs had similar overall safety profiles, participants who took motavizumab had more cutaneous reactions.&lt;/p&gt;
&lt;p&gt;&quot;In this large, multinational, well controlled trial, motavizumab was shown to be noninferior to palivizumab for prevention of RSV hospitalization (primary end point) and was superior to palivizumab for reduction of RSV-specific outpatient MALRI (a secondary end point),&quot; the authors wrote.&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 MedImmune, the manufacturer of motavizumab.&lt;/p&gt;&lt;p&gt;Several of the authors reported being employees of MedImmune or receiving consulting and research services fees from MedImmune and Abbott International.&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="0.007"
                     href="http://www.medpagetoday.com/Pediatrics/Vaccines/tb/18174?impressionId=1265735448227"
                     
      &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="20090101_10_565"
                     title="RSV Moves from the Nursery to the Geriatric Set"
                     score="-0.005"
                     href="