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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="0.012"
                     href="http://www.medpagetoday.com/CriticalCare/InfectionControl/tb/18308?impressionId=1265806815047"
                     
      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_373"
                     title="Protein in Urine Presages More Severe Problems (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Nephrology/ESRD/tb/18265?impressionId=1265806815047"
                     
      &lt;p&gt;The three-year risk of death, heart attack, and kidney failure was markedly increased in patients with baseline proteinuria, regardless of their estimated glomerular filtration rate (eGFR), researchers said.&lt;/p&gt;
&lt;p&gt;In a population-based study of nearly 1 million people, mortality was approximately doubled with heavy proteinuria among individuals stratified according to their eGFR, reported Brenda R. Hemmelgarn, MD, PhD, of the University of Calgary in Canada, and colleagues.&lt;/p&gt;
&lt;p&gt;Rates of myocardial infarction were increased by about 50% with heavy proteinuria, and end-stage renal disease and doubled levels of serum creatinine were as much as 30 times more common, the researchers reported in the Feb. 3 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Prognosis associated with a given level of eGFR varies substantially based on the presence and severity of proteinuria,&quot; Hemmelgarn and colleagues concluded.&lt;/p&gt;
&lt;p&gt;&quot;In fact, patients with heavy proteinuria but without overtly abnormal eGFR appeared to have worse clinical outcomes than those with moderately reduced eGFR but without proteinuria.&quot;&lt;/p&gt;
&lt;p&gt;They added that the findings were important because current recommendations for managing chronic kidney disease rely on eGFR for staging purposes without consideration of proteinuria.&lt;/p&gt;
&lt;p&gt;&quot;Future revisions of the classification system for chronic kidney disease should incorporate information from proteinuria,&quot; the researchers urged.&lt;/p&gt;
&lt;p&gt;The results emerged from a laboratory registry covering some 921,000 adults in the province of Alberta who had had measurements of eGFR, serum creatinine, and urinary protein from 2002 to 2007.&lt;/p&gt;
&lt;p&gt;Proteinuria was measured with a urine dipstick or the albumin-creatinine ratio. Dipstick readings of at least 2 points were considered heavy proteinuria. Readings showing at least trace protein but less than 2 points were classed as mild; negative readings were considered normal.&lt;/p&gt;
&lt;p&gt;The stratifications of albumun-creatinine ratio were greater than 300 mg/g, 30 to 300 mg/g, and less than 30 mg/g for heavy, mild, and normal, respectively.&lt;/p&gt;
&lt;p&gt;Other registry data for the province provided outcomes in these individuals, with median follow-up of 35 months.&lt;/p&gt;
&lt;p&gt;Among individuals with eGFR rates of at least 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, death rates were 7.2 per 1,000 for those with dipstick-measured heavy proteinuria (95% CI 6.6 to 7.8) and 5.8 per 1,000 for mild proteinuria (95% CI 5.5 to 6.0) compared with 2.7 per 1,000 for those with normal urine protein (95% CI 2.6 to 2.8).&lt;/p&gt;
&lt;p&gt;At the other end of the eGFR spectrum  --  those with levels of 15 to 29.9 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;  --  proteinuria remained an independent predictor of death: Mortality rates were 10.4 per 1,000 with heavy proteinuria (95% CI 9.3 to 11.6) and 9.1 per 1,000 with mild proteinuria (95% CI 8.2 to 10.0) versus 6.7 per 1,000 with normal urine protein (95% CI 6.2 to 7.3).&lt;/p&gt;
&lt;p&gt;These death rates reflected adjustments for a host of potential confounding factors and comorbidities, including age, sex, diabetes, hypertension, liver disease, and cardiovascular conditions.&lt;/p&gt;
&lt;p&gt;Proteinuria also predicted myocardial infarction in patients stratified by eGFR, but not as strongly. In the group with eGFR above 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, rates of MI were 1.6 per 1,000 (95% CI 1.3 to 2.0) and 0.9 (95% CI 0.9 to 1.0) for heavy and normal urinary protein, respectively, as measured by dipstick.&lt;/p&gt;
&lt;p&gt;MI rates were also increased with proteinuria in participants with eGFR below 30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, the researchers reported.&lt;/p&gt;
&lt;p&gt;End-stage renal disease was enormously more common with dipstick-measured heavy proteinuria, independent of baseline eGFR.&lt;/p&gt;
&lt;p&gt;Individuals with eGFR above 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; were diagnosed with the condition at a rate of 1.0 per 1,000 (95% CI 0.7 to 1.4) if they had heavy proteinuria, compared with 0.03 per 1,000 (95% CI 0.02 to 0.09) among those with normal urine protein.&lt;/p&gt;
&lt;p&gt;A five-fold difference in rates of end-stage renal disease was still apparent among those with eGFR below 30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;: 65.9 (95% CI 52.3 to 82.9) versus 12.7 per 1,000 (95% CI 9.3 to 17.3) for heavy versus normal protein, respectively.&lt;/p&gt;
&lt;p&gt;These results were confirmed when cross-checked against the more accurate albumin-creatinine ratio, Hemmelgarn and colleagues indicated.&lt;/p&gt;
&lt;p&gt;Each 10-fold increase in albumin-creatinine ratio was associated with the following relative rates of the major study outcomes, after adjusting for eGFR:&lt;ul&gt; &lt;li&gt;Death: 1.22 (95% CI 1.21 to 1.24)&lt;/li&gt; &lt;li&gt;MI: 1.18 (95% CI 1.14 to 1.21)&lt;/li&gt; &lt;li&gt;Doubling of serum creatinine: 1.76 (95% CI 1.70 to 1.82)&lt;/li&gt; &lt;li&gt;End-stage renal disease: 1.92 (95% CI 1.81 to 2.04)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Hemmelgarn and colleagues noted several limitations to the study including the fact that the sample was restricted to outpatients undergoing laboratory evaluations for kidney function and urinary protein, and the data were based on single measurements. Missing were data on alcohol, tobacco, and antihypertensive drug use, which might have affected the findings.&lt;/p&gt;
&lt;p&gt;The researchers also indicated that the follow-up period may have been too short to fully evaluate risks of progression to kidney failure.&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;Support for the study came from the Alberta Heritage Foundation for Medical Research, the Canadian Institutes of Health Research, Alberta Health and Wellness, and internal funds.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_329"
                     title="Nixing Routine ICU Sedation Improves Outcomes (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/CriticalCare/Intensivists/tb/18199?impressionId=1265806815047"
                     
      A protocol of no sedation in the ICU may get patients off the ventilator and back home sooner, Danish researchers found.&lt;br&gt;
&lt;br&gt;Unsedated patients spent 4.2 fewer days on mechanical ventilators than those treated under a more conventional protocol for daily interruption of sedation (mean 13.8 versus 9.6 days without ventilation, &lt;em&gt;P&lt;/em&gt;=0.0191) in a randomized trial led by Thomas Str&amp;#248;m, MD, of Odense University Hospital.&lt;br&gt;
&lt;br&gt;Length of stay in the ICU and in the hospital were significantly shorter as well, the researchers reported in the Feb. 6 issue of &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The strategy appeared safe, with no increase in accidental extubation or other complications, Str&amp;#248;m&apos;s group said.&lt;/p&gt;
&lt;p&gt;Although simpler than daily interruption of sedation, a no-sedation protocol could mean extra work for ICU staff, according to an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Laurent Brochard, MD, of the Centre Hospitalier Albert Chenevier&amp;#8211;Henri Mondor in Cr&amp;#233;teil, France, wrote that the protocol would call for &quot;more frequent individual assessment of the patient&apos;s pain, fear, anxiety, agitation, or confusion, and adaption to the ventilator.&quot;&lt;/p&gt;
&lt;p&gt;It would also likely impose an increased workload in reassurance and patient mobilization, he said. Still, he called the results &quot;impressive and promising.&quot;&lt;/p&gt;
&lt;p&gt;Sedation is often overused in the ICU, particularly since drugs can accumulate in critically ill patients, Brochard asserted, and daily interruption of sedation was a major breakthrough in patient care because it was shown to &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ATS/5713&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ATS/5713&quot; target=&quot;_blank&quot;&gt;reduce duration of ventilation&lt;/a&gt;.&lt;/p&gt;
&lt;p&gt;Other benefits of the current study included reductions in &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/SCCM/8240&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/SCCM/8240&quot; target=&quot;_blank&quot;&gt;post-traumatic stress disorder&lt;/a&gt; and &lt;a href=&quot;http://www.medpagetoday.com/EmergencyMedicine/EmergencyMedicine/7931&quot; mce_href=&quot;http://www.medpagetoday.com/EmergencyMedicine/EmergencyMedicine/7931&quot; target=&quot;_blank&quot;&gt;complications&lt;/a&gt; such as ventilator-associated pneumonia, Str&amp;#248;m and colleagues added.&lt;/p&gt;
&lt;p&gt;In an effort to further reduce the negative effects of ICU sedation, their hospital adopted a routine protocol of no sedation for intubated medical and surgical ICU patients receiving mechanical ventilation.&lt;/p&gt;
&lt;p&gt;Given the lack of randomized data on the benefits of this strategy, the researchers randomized 140 critically ill adults expected to need more than 24 hours of ventilation to unblinded treatment without sedation or with an infusion of propofol (Diprivan) for 48 hours, then an infusion of midazolam (Versed) as needed for sedation with daily interruption until awake.&lt;/p&gt;
&lt;p&gt;Both groups got bolus doses of morphine (2.5 or 5 mg) as needed and daily mobilization to a chair if possible.&lt;/p&gt;
&lt;p&gt;Along with the reduction in ventilated days, the researchers found that patients on the no-sedation protocol left the ICU 9.7 days sooner on average and were discharged from the hospital 24 days earlier than those routinely sedated.&lt;/p&gt;
&lt;p&gt;After adjustment for baseline variables, sedation remained significantly associated with increased ICU stay (HR 1.86, 95% CI 1.05 to 3.23).&lt;/p&gt;
&lt;p&gt;The effect on hospital stay duration, though, was limited to the first 30 days (HR 3.57 for sedation, 95% CI 1.52 to 9.09).&lt;/p&gt;
&lt;p&gt;For days 31 to 90, sedation protocol had no impact (&lt;em&gt;P&lt;/em&gt;=0.54), likely because other factors, such as comorbidities, were more important when patients couldn&apos;t be weaned from ventilation, the researchers said.&lt;/p&gt;
&lt;p&gt;Complications were similar between no-sedation and sedation protocol groups as follows: &lt;ul&gt; &lt;li&gt;Accidental removal of endotracheal tube (seven versus six cases, &lt;em&gt;P&lt;/em&gt;=0.69)&lt;/li&gt; &lt;li&gt;Need for CT or MRI brain scans (five versus eight cases, &lt;em&gt;P&lt;/em&gt;=0.43)&lt;/li&gt; &lt;li&gt;Ventilator-associated pneumonia (six versus seven cases, &lt;em&gt;P&lt;/em&gt;=0.85)&lt;/li&gt; &lt;li&gt;Need for reintubation within 24 hours (seven versus 11 cases, &lt;em&gt;P&lt;/em&gt;=0.37)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Mortality in the ICU tended to be higher with sedation (38% versus 22%, P=0.06), but there was no significant difference in overall inhospital mortality between the groups (47% with sedation versus 36% without, &lt;em&gt;P&lt;/em&gt;=0.27).&lt;/p&gt;
&lt;p&gt;Overall, 18% of patients in the no-sedation group couldn&apos;t tolerate it and had to receive continuous sedation on more than two occasions, typically to permit sufficient oxygenation in severe acute respiratory distress syndrome.&lt;/p&gt;
&lt;p&gt;The one negative impact of the no-sedation strategy appeared to be an increase in agitated delirium (20% versus 7%, &lt;em&gt;P&lt;/em&gt;=0.04) resulting in more frequent use of haloperidol (Haldol, &lt;em&gt;P&lt;/em&gt;=0.0100).&lt;/p&gt;
&lt;p&gt;Morphine, which does have a sedative effect, was used at a low level in both groups without a significant difference.&lt;/p&gt;
&lt;p&gt;But it&apos;s likely that delirium went undetected in some sedation group patients, given the difficulty of assessing the condition even when patients are awakened routinely, Str&amp;#248;m&apos;s group said. Assessing confusion rather than hyperactive delirium might be a better strategy, they suggested.&lt;/p&gt;
&lt;p&gt;They said they plan to follow patients at one year to assess long-term psychological effects.&lt;/p&gt;
&lt;p&gt;The researchers and editorialist agreed that further confirmation of these results are needed in multicenter research to determine whether the strategy is generalizable.&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 Danish Society of Anesthesiology and Intensive Care Medicine, the Fund of Danielsen, the Fund of Kirsten Jensa la Cour, and the Fund of Holger og Ruth Hess.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;Brochard reported that his research laboratory has received research grants from several ventilator companies (Maquet, Dr&amp;#228;ger, Philips Respironics, General Electric) but no personal relationship to disclose for the use of sedation in intensive care.&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="0.005"
                     href="http://www.medpagetoday.com/CriticalCare/Sepsis/tb/18160?impressionId=1265806815047"
                     
      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;
    </recommendedItem>
    <recommendedItem id="20100101_19_280"
                     title="Better Overall Diabetes Care Lowers Nephropathy Risk (CME/CE)"
                     score="-0"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18136?impressionId=1265806815047"
                     
      &lt;p&gt;Simultaneously achieving tight glucose control and other targets in diabetes reduces the risk of kidney complications, researchers found.&lt;/p&gt;
&lt;p&gt;An aggressive multifactorial intervention appeared to delay diabetic nephropathy better when more targets were achieved (&lt;em&gt;P&lt;/em&gt;=0.002 for trend) in a longitudinal study of Chinese patients led by Ming-Chia Hsieh, MD, PhD, of Kaohsiung Medical University Hospital in Kaohsiung, Taiwan.&lt;/p&gt;
&lt;p&gt;The risk of new-onset microalbuminaria dropped 27.1% for those who met the American Diabetes Association-recommended goal of less than 7% glycosylated hemoglobin (&lt;em&gt;P&lt;/em&gt;=0.03), the researchers reported in the Jan. 25 &lt;em&gt;Archives of Internal Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Reaching the systolic blood pressure goal of less than 130 mm Hg reduced this risk 35.5% (&lt;em&gt;P&lt;/em&gt;=0.002). Achieving the HDL cholesterol goal  --  over 50 mg/dL for women and 40 mg/dL for men  --  reduced the risk by 28.5% (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;&quot;The control of microalbuminuria may halt progress to overt nephropathy and reduce occurrence of cardiovascular events in these patients,&quot; Hsieh&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;They suggested that this type of intensive intervention &quot;can be used at the very early stages of diabetic renal disease.&quot;&lt;/p&gt;
&lt;p&gt;Prior studies had suggested that intensive therapy could prevent nephropathy in patients who had already started showing signs of progression.&lt;/p&gt;
&lt;p&gt;So to see if starting earlier would be as effective, Hsieh and colleagues initiated a longitudinal cohort study of 1,290 patients with type 2 diabetes and normoalbuminuria in which participants received intensified treatment to meet ADA-recommended goals on glucose, blood pressure, cholesterol, and triglycerides.&lt;/p&gt;
&lt;p&gt;To this end, patients got the combined efforts of a physician, nurse, and dietitian working together on counseling and patient education to modify behavior.&lt;/p&gt;
&lt;p&gt;By the end of the intervention patients were more likely to have switched from single agent glucose-lowering treatment to insulin plus an oral hypoglycemic agent and to have gone on an antihypertensive (74% versus 48% baseline), statin (58.1% versus 28.0% baseline), and fibrate (14.0% versus 3.0% baseline).&lt;/p&gt;
&lt;p&gt;By the end of the study period, the mean glycosylated hemoglobin was 7.3%, while blood pressure averaged 129.3/74.4 mm Hg. Mean LDL cholesterol was 98.6 mg/dL, triglycerides were at 116.0 mg/dL, and mean HDL cholesterol was 53.6 mg/dL.&lt;/p&gt;
&lt;p&gt;Over the 4.5 years of follow-up, 16.4% of patients developed new-onset microalbuminuria.&lt;/p&gt;
&lt;p&gt;Unlike attainment of HDL cholesterol, glycosylated hemoglobin, and systolic blood pressure goals, reaching those for LDL cholesterol, diastolic blood pressure, and triglycerides appeared to have little impact on kidney function.&lt;/p&gt;
&lt;p&gt;But the more targets patients reached, the less likely they were to develop microalbuminuria (&lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;The majority of participants in the study reached one or two of the treatment targets (71.4%) and 8.1% achieved three.&lt;/p&gt;
&lt;p&gt;Those who did reach two or three of the goals were at significantly lower risk of new-onset microalbuminuria than the 20.5% who didn&apos;t reach any of the goals (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Those who reached one target tended to be at lower risk as well, but the effect was not significant compared with reaching none of the goals (&lt;em&gt;P&lt;/em&gt;=0.35).&lt;/p&gt;
&lt;p&gt;One of the concerns with the tight glucose control goal has been hypoglycemia. In the study, 217 patients had at least one episode. Four cases involved major hypoglycemia, though without clinical morbidity or mortality.&lt;/p&gt;
&lt;p&gt;Overall, 37 patients died from any cause during the study period.&lt;/p&gt;
&lt;p&gt;A &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;review&lt;/a&gt; of recent large trials of aggressive glycemic control  --  U.K. Prospective Diabetes Study (UKPDS) and the U.S.-based ACCORD, ADVANCE, and VA Diabetes trials  --  suggested a two- to threefold increased risk of severe hypoglycemia without macrovascular benefits.&lt;/p&gt;
&lt;p&gt;In the recent &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; target=&quot;_blank&quot;&gt;ACCORD&lt;/a&gt; trial, tight glucose control that brought hemoglobin A1c close to 6%, with a target of less than the standard 7.0%, resulted in 22% excess mortality risk.&lt;/p&gt;
&lt;p&gt;The search for a reason behind this risk has yet to turn up a culprit. &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; target=&quot;_blank&quot;&gt;Analyses&lt;/a&gt; have suggested that hypoglycemia isn&apos;t to blame and that the lower A1c levels themselves aren&apos;t a problem.&lt;/p&gt;
&lt;p&gt;In the wake of the negative findings from ACCORD, ADVANCE, and the VA trials, leading diabetologists had suggested that pushing too hard in people who couldn&apos;t reach the targets might have been at fault.&lt;/p&gt;
&lt;p&gt;Rather than a one-size-fits all approach, the ADA guidelines suggest individualizing treatment targets.&lt;/p&gt;
&lt;p&gt;Hsieh&apos;s group acknowledged that &quot;even with close attention, not all our patients could achieve the ADA-recommended goals,&quot; but re-emphasized that for patients who could achieve targets, there were benefits.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that their study was limited by lack of a comparison group, no data on genetic factors, and use of potentially arbitrary treatment target cutoff points.&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>
</recommendedContent>