<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3249"
                     title="ESC: Novel Agent Blocks Hyperkalemia in Heart Failure (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/22009?impressionId=1283456811143"
                     
      STOCKHOLM  --  An investigational potassium binder prevented hyperkalemia in at-risk patients with heart failure, a randomized, placebo-controlled trial showed.&lt;br&gt;
&lt;br&gt;Through four weeks, the compound  --  RLY5016  --  resulted in a drop in mean serum potassium levels from 4.69 to 4.48 mEq/L (a change of -0.22), Bertram Pitt, MD, of the University of Michigan in Ann Arbor, reported at the European Society of Cardiology congress here.&lt;br&gt;
&lt;br&gt;In the placebo group, potassium levels increased from 4.65 to 4.93 mEq/L (a change of +0.23). The between-group difference at the end of treatment was 0.45 mEq/L (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;br&gt;
&lt;br&gt;The drug was generally well tolerated; the most common side effects were gastrointestinal.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Because of three cases of hypokalemia in the treatment group, Pitt said additional studies are needed to determine whether a lower dose retains the benefits without dropping potassium too low. Ongoing studies suggest a lower dose does just that, he added.&lt;/p&gt;
&lt;p&gt;The drug could alleviate some of the concern clinicians have had regarding the use of renin-aldosterone-angiotensin-system (RAAS) blockers, which have been shown to reduce mortality in patients with heart failure but have been associated with hyperkalemia.&lt;/p&gt;
&lt;p&gt;&quot;If future studies bear out what we&apos;ve seen over the longer term... then we think we have the opportunity of taking a number of very high-risk patients and a relatively large number of them and making available to them life-saving therapy with multiple RAAS blockers, including aldosterone blockers, which we think will have tremendous effect on outcome,&quot; Pitt said at a press briefing.&lt;/p&gt;
&lt;p&gt;The PEARL-HF trial randomized 55 patients to receive 30 g a day of the new drug and 49 to receive placebo for four weeks.&lt;/p&gt;
&lt;p&gt;Most of the patients (about 98%) had relatively mild heart failure  --  New York Heart Association class II or III.&lt;/p&gt;
&lt;p&gt;In addition to heart failure, patients were also required to have stage 3 or 4 chronic kidney disease or a recent history of hyperkalemia that resulted in the discontinuation of RAAS blocker therapy. At baseline, all had a serum potassium level of 4.3 to 5.1 mEq/L.&lt;/p&gt;
&lt;p&gt;Use of RAAS blocker therapy was similar in the placebo and treatment groups at baseline, with indications that numerous patients were undertreated.&lt;/p&gt;
&lt;p&gt;All patients were given spironolactone 25 mg/day at the beginning of the study. At day 15, the dose was increased to 50 mg/day in patients whose serum potassium level was below 5.1 mEq/L.&lt;/p&gt;
&lt;p&gt;In addition to the significant drop in serum potassium in the treatment group, there was also a significant reduction with the new compound in the number of patients who had hyperkalemia at any point in the study (7% versus 25%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05). The benefit was seen across all levels of kidney function.&lt;/p&gt;
&lt;p&gt;Bertram noted that only 19% of patients with normal kidney function in the placebo group (and who entered the study because of a history of hyperkalemia resulting in stopping RAAS inhibitors) developed hyperkalemia during the study, which suggests that they should retry recommended doses of RAAS inhibitors before abandoning use or reducing the doses.&lt;/p&gt;
&lt;p&gt;The number of patients who were able to increase th spironolactone dose to 50 mg/day was greater in the treatment group (91% versus 74%, &lt;em&gt;P&lt;/em&gt;=0.019).&lt;/p&gt;
&lt;p&gt;There were few serious adverse events (two in each group), and one death (in the placebo group).&lt;/p&gt;
&lt;p&gt;The gastrointestinal adverse effects were all mild and transient, except for one case of severe flatulence, according to Pitt.&lt;/p&gt;
&lt;p&gt;Serving as a discussant at Pitt&apos;s presentation, Henry Dargie, a consultant cardiologist at Golden Jubilee National Hospital in Glasgow, Scotland, said the risks and benefits of the new compound need to be carefully explored in future studies.&lt;/p&gt;
&lt;p&gt;He noted that the patient population in PEARL-HF likely had milder heart failure and renal impairment than would be expected in patients taking RAAS inhibitors, which are indicated for severe heart failure.&lt;/p&gt;
&lt;p&gt;&quot;So the target population perhaps isn&apos;t exactly the one we would be using in clinical practice,&quot; he said.&lt;/p&gt;
&lt;p&gt;Future studies should target those with more severe heart failure and renal impairment, and should be able to evaluate the effect on mortality, considering the seriousness of hypokalemia, 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;Pitt reported serving as a consultant to and holding stock options in Relypsa, which is developing the compound evaluated in this study. He reported additional relationships with Abbott, AstraZeneca, AuraSense, Bayer, BG Medicine, Boehringer Ingelheim, Forest Labs, GE Healthcare, Medtronic, Merck, Novartis, Pfizer, and Takeda.&lt;/p&gt;&lt;p&gt;Dargie said he had 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_3245"
                     title="Spoonful of Sugar Debunked as Baby Painkiller (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/PainManagement/PainManagement/tb/22005?impressionId=1283456811143"
                     
      &lt;p&gt;Sugar given to blunt pain in newborns undergoing invasive procedures may only mask signs of distress, researchers found.&lt;/p&gt;
&lt;p&gt;In a randomized trial, a dose of sucrose significantly cut down on visible behaviors and facial expressions indicating pain compared with placebo, but the reaction in the brain and spinal cord was no different.&lt;/p&gt;
&lt;p&gt;Thus, sugar might not be effective as an analgesic at all, Rebeccah Slater, of University College London, and colleagues reported online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The results, &quot;together with uncertainty over the long-term benefits of repeated sucrose administration, suggest that sucrose should not be used routinely for procedural pain in infants without further investigation,&quot; they recommended in the paper.&lt;/p&gt;
&lt;p&gt;International guidelines recommend an oral dose of sucrose to relieve neonatal procedural pain, but that&apos;s based on studies that used observational signs of a pain response.&lt;/p&gt;
&lt;p&gt;&quot;The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief,&quot; Slater&apos;s group warned in the paper.&lt;/p&gt;
&lt;p&gt;Immaturity, neurological damage, maternal drug misuse, and other conditions can cause a disconnect with behavior but not necessarily the sensation of pain, they explained.&lt;/p&gt;
&lt;p&gt;However, that conclusion may be premature, warned Robert E. Lasky, PhD, of the University of Texas Medical School at Houston, and Wim van Drongelen, PhD, of the University of Chicago, in an editorial accompanying the &lt;em&gt;Lancet&lt;/em&gt; paper.&lt;/p&gt;
&lt;p&gt;Aside from statistical power to detect only a &quot;very large&quot; effect size, the methods used likely weren&apos;t a complete picture of activation of the neural pain pathway, they noted.&lt;/p&gt;
&lt;p&gt;&quot;Evolving measurement methodologies and small sample sizes are not the basis for definitive evaluations of treatments,&quot; the editorialists wrote.&lt;/p&gt;
&lt;p&gt;The trial included 59 healthy infants less than eight days old at a single hospital randomized to double-blind administration of 0.5 mL of 24% sucrose solution or the same amount of sterile water two minutes before a clinically-required heel lance to draw a blood sample.&lt;/p&gt;
&lt;p&gt;As seen in prior studies, behavioral and physiological signs of pain subjectively recorded using the premature infant pain profile (PIPP) indicated lower pain scores in response to the heel stick in infants given sucrose compared with those given placebo (mean 5.8 versus 8.5, &lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;Sucrose was also associated with zero change in facial expression in significantly more infants (seven of 20 [35%] versus none of 24, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;However, neonatal electroencephalography (EEG) indicated the same spike in brain activity in response to the heel lance in both groups compared with a control stimulus in which the lancet was sprung away from the foot before dosing to provide only tactile sensation and the click of the blade without the pain.&lt;/p&gt;
&lt;p&gt;Nociceptive brain activity after the heel lance averaged 0.10 in infants who received sucrose and 0.08 in those who received sterile water (&lt;em&gt;P&lt;/em&gt;=0.46).&lt;/p&gt;
&lt;p&gt;Infants&apos; reflex to pull their leg back after the heel lance  --  measured as spinal nociceptive reflex withdrawal in the femoral leg muscle  --  likewise did not differ significantly between groups in either magnitude of response or latency to start.&lt;/p&gt;
&lt;p&gt;In adults, activity in the brain and spinal sensory circuits evoked by pain are directly linked to perceived intensity of pain, Slater&apos;s group noted.&lt;/p&gt;
&lt;p&gt;But the researchers cautioned that even these electrophysiological measures can&apos;t be proven to indicate the conscious pain experience of a newborn since any measure of pain in this pre-verbal group is necessarily indirect.&lt;/p&gt;
&lt;p&gt;The study might have been underpowered to detect subtle effects based on the small sample size, they acknowledged.&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 Medical Research Council.&lt;/p&gt;&lt;p&gt;The researchers reported having no conflicts of interest to disclose.&lt;/p&gt;&lt;p&gt;Lasky and van Drongelen reported having no conflicts of interest to disclose.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3244"
                     title="ESC: Pre-Procedure Statins May Cut MI Risk (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/22001?impressionId=1283456811143"
                     
      &lt;p&gt;STOCKHOLM  --  Statins delivered before invasive procedures appear to reduce the occurrence of cardiovascular events, a meta-analysis showed.&lt;/p&gt;
&lt;p&gt;In pooled data from 21 trials, giving statins before percutaneous coronary intervention (PCI), CABG, or noncardiac surgery resulted in a reduction in post-procedural MI (RR 0.57, 95% CI 0.46 to 0.70), according to Anthony Bavry, MD, MPH, of the University of Florida, in Gainesville.&lt;/p&gt;
&lt;p&gt;The reduction in MI was significant only after PCI (7.5% versus 13.3%) and noncardiac surgical procedures (3.5% versus 7.6%; &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for both).&lt;/p&gt;
&lt;p&gt;Bavry reported the findings, which were also published online in the &lt;em&gt;Journal of the American College of Cardiology&lt;/em&gt;, at the European Society of Cardiology Congress here.&lt;/p&gt;
&lt;p&gt;&quot;The routine use of statins before invasive procedures should be considered,&quot; he and his colleagues wrote in their paper.&lt;/p&gt;
&lt;p&gt;Current guidelines for CABG, elective PCI, and acute coronary syndrome recommend statins only for use after such procedures.&lt;/p&gt;
&lt;p&gt;&quot;None of these guidelines specifically recommend the use of statins before invasive procedures for the express purpose of preventing periprocedural complications such as MI and atrial fibrillation,&quot; the researchers wrote. &quot;Our analysis adds strength to current recommendations and potentially expands the use of these agents before PCI and surgical procedures.&quot;&lt;/p&gt;
&lt;p&gt;Bavry and his colleagues conducted a meta-analysis of 21 randomized controlled trials involving 4,805 patients in which statins were administered one to seven days before PCI, CABG, or noncardiac surgery. The control interventions included placebo, usual care, or lower doses of statins.&lt;/p&gt;
&lt;p&gt;PCI was usually elective, although four studies included patients with acute coronary syndrome.&lt;/p&gt;
&lt;p&gt;Most of the patients had never received statins before, but one study included patients on long-term statin therapy.&lt;/p&gt;
&lt;p&gt;The reduction in post-procedural MI observed with pre-procedural statins was strengthened when only placebo-controlled trials were considered (RR 0.43).&lt;/p&gt;
&lt;p&gt;Pre-procedural statins also reduced post-CABG atrial fibrillation (19% versus 37%; RR 0.54, 95% CI 0.43 to 0.68), although they did not affect all-cause mortality (RR 0.66, 95% CI 0.37 to 1.17).&lt;/p&gt;
&lt;p&gt;The researchers noted in their paper that the optimal dose, statin type, and timing were unclear.&lt;/p&gt;
&lt;p&gt;&quot;Only a dedicated trial specifically exploring the relationship of dose and type of statin therapy before invasive procedures can answer this question,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;The studies included in the meta-analysis did not report adverse effects, so the researchers could not perform a formal analysis of potential drawbacks to pre-procedural statin use. They noted, however, that statins have a well-established safety record.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Kim Eagle, MD, and Vineet Chopra, MD, of the University of Michigan, in Ann Arbor, wrote that the benefits of statins in this context likely came from their pleiotropic effects  --  the enhancement of endothelial function, stabilization of vulnerable plaque, and reduction in adhesion molecules and circulating biomarkers.&lt;/p&gt;
&lt;p&gt;&quot;Therefore, before endothelial injury during coronary procedures, statin treatment likely mitigates the inflammatory cascade by decreasing vascular reactivity and stabilizing plaque, both at the site of intervention and at other &apos;vulnerable&apos; lesions,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Eagle and Chopra said that it appears statins should be routinely given to patients before undergoing coronary procedures, although questions remain regarding optimal dose and type of statin and whether such a strategy&lt;strong&gt; &lt;/strong&gt;would work in all patient subgroups. Also, they said the possibility of adverse effects still needs to be explored.&lt;/p&gt;
&lt;p&gt;Nevertheless, they wrote, &quot;Given the strong biological rationale and the sum of the clinical data, no patient should undergo coronary procedures without statin therapy unless clear contraindications exist. Indeed, it is time to consider a new indication for an old friend.&quot;&lt;/p&gt;
&lt;p&gt;Bavry and his colleagues acknowledged some limitations of the analysis, including the use of a control group mixing placebo, usual care, and lower statin doses, the fact that some of the surgical trials did not include MI as a primary outcome, and the lack of information on some of the methodological characteristics of the trials, like blinding or randomization technique.&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 an unrestricted grant from the Florida Heart Research Institute.&lt;/p&gt;&lt;p&gt;The study authors and the editorialists reported that they did not have any 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_3241"
                     title="&apos;Brain Exercise&apos; May Worsen Existing Alzheimer&apos;s (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/Neurology/AlzheimersDisease/tb/21998?impressionId=1283456811143"
                     
      &lt;p&gt;Keeping mentally active may help stave off Alzheimer&apos;s disease, but once patients are diagnosed with the condition, &quot;brain exercise&quot; may actually speed up cognitive decline, researchers said  --  adding that that may not be a bad thing.&lt;/p&gt;
&lt;p&gt;Among more than 1,000 older individuals in a large, longitudinal cohort study, scores on a measure of cognitive activity were significantly correlated with the rate of worsening in global cognitive function, according to Robert S. Wilson, PhD, of Rush University in Chicago, and colleagues.&lt;/p&gt;
&lt;p&gt;For each one-point increase in cognitive activity scores in Alzheimer&apos;s disease patients, the rate of cognitive decline increased 42% (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), they reported online in &lt;em&gt;Neurology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;But in patients with no cognitive impairment, each point in cognitive activity scores was associated with a 52% reduction in the rate of cognitive decline (&lt;em&gt;P&lt;/em&gt;=0.003), confirming &lt;a href=&quot;http://www.medpagetoday.com/PrimaryCare/Geriatrics/4735&quot; mce_href=&quot;http://www.medpagetoday.com/PrimaryCare/Geriatrics/4735&quot; target=&quot;_blank&quot;&gt;previous studies&lt;/a&gt; indicating that mental activity reduces the risk of dementia.&lt;/p&gt;
&lt;p&gt;&quot;More frequent cognitive activity was related to slower cognitive decline in those without cognitive impairment and more rapid cognitive decline in Alzheimer&apos;s disease, with no effect in mild cognitive impairment,&quot; Wilson and colleagues wrote.&lt;/p&gt;
&lt;p&gt;They argued that such an effect should not be a total surprise.&lt;/p&gt;
&lt;p&gt;Other researchers have suggested that mental activity maintains cognitive abilities even as the underlying pathologic burden continues to grow with age.&lt;/p&gt;
&lt;p&gt;But, Wilson and colleagues noted, &quot;cognitively active people do develop dementia,&quot; presumably when the pathologic burden becomes overwhelming.&lt;/p&gt;
&lt;p&gt;&quot;If cognitive activity does somehow allow the brain to tolerate more pathologic changes, those with high premorbid cognitive activity are likely to have a higher pathologic burden than those with low premorbid activity at the time of dementia onset and therefore to experience a more rapidly progressive dementia course,&quot; they theorized.&lt;/p&gt;
&lt;p&gt;&quot;In effect, these results suggest that the benefit of delaying the initial appearance of cognitive impairment comes at the cost of more rapid dementia progression.&quot;&lt;/p&gt;
&lt;p&gt;Wilson and colleagues analyzed data from the Chicago Health and Aging Project, an ongoing cohort study that began in 1993. At baseline, participants were 65 or older and were free of cognitive impairment.&lt;/p&gt;
&lt;p&gt;The current analysis focused on 1,157 of the participants with 12 years of follow-up. After six years in the study, participants had been tested for cognitive impairment and categorized as cognitively normal, mildly impaired, or having Alzheimer&apos;s disease. They were then followed for another six years, undergoing periodic mental status evaluations.&lt;/p&gt;
&lt;p&gt;At baseline, participants also rated how often they participated in seven cognitive activities: watching television, listening to the radio, reading newspapers, reading magazines, reading books, playing card or board games, and going to museums.&lt;/p&gt;
&lt;p&gt;Cognitive function was evaluated periodically with four brief assessments including the Mini-Mental State Exam, tests of immediate and delayed word recall, and the Symbol Digit Modalities Test.&lt;/p&gt;
&lt;p&gt;Wilson and colleagues calculated that the interaction of baseline cognitive activity score with changes in cognitive function scores and time was -0.075 in the Alzheimer&apos;s disease patients (SE 0.022), whereas in the participants with no cognitive impairment at follow-up the interaction estimate was 0.029 (SE 0.010).&lt;/p&gt;
&lt;p&gt;&quot;These observational data suggest that interventions designed to enhance cognitive plasticity may prove beneficial in compressing the cognitive morbidity of Alzheimer&apos;s disease,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;In other words, &quot;brain exercise&quot; may shorten the period of time in which patients must live with a diagnosis of Alzheimer&apos;s disease, as they remain mentally healthy deeper into old age and then decline quickly.&lt;/p&gt;
&lt;p&gt;They also noted that, to be effective, cognitive enrichment interventions may need to be initiated before the development of cognitive impairment,&quot; since any degree of cognitive deficit probably means an already substantial pathological burden.&lt;/p&gt;
&lt;p&gt;Wilson and colleagues cited several limitations to their analysis: the possibility of unmeasured differences between the diagnostic subgroups, the lack of detail in the cognitive function tests used, and a relatively small number of follow-up evaluations.&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 commercial funding for the study was reported.&lt;/p&gt;&lt;p&gt;Wilson serves as consulting editor for two other neurology journals and reported several NIH grants. Other authors reported consulting or other relationships with pharmaceutical companies including Pfizer and Eli Lilly.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3235"
                     title="ESC: New Anticoagulants Create Buzz"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21988?impressionId=1283456811143"
                     
      &lt;p&gt;STOCKHOLM  --  After years of waiting for an alternative to warfarin (Coumadin), there are now three wending their way through the regulatory process. In this exclusive InFocus video report we review each of these new agents.&lt;/p&gt;
&lt;p&gt;Two factor Xa inhibitors  --  apixiban and rivaroxaban  --  along with the direct thrombin inhibitor, dabigatran, are competing to be the first warfarin alternatives to gain FDA approval and that is good news according to Fausto Pinto, MD, PhD, the program chair at this year&apos;s European Society of Cardiology congress, where the new agents were featured in a number of sessions.&lt;/p&gt;
&lt;p&gt;Ralph L. Sacco, MD, president of the American Heart Association agreed that the news was good, but noted that, as the agents come to market, developing new guidelines for their use will be a critical task for the AHA and the ESC.&lt;/p&gt;
&lt;p&gt;Pinto and Sacco discussed the potential benefits  --  and challenges  --  of the new agents with &lt;em&gt;MedPage Today&lt;/em&gt; executive editor Peggy Peck.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>