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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_314"
                     title="Overall Mortality Down in Pediatric Rheumatology (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18179?impressionId=1265745251274"
                     
      &lt;p&gt;Overall mortality for children with rheumatologic diseases is down, although the risk of death remains elevated in certain inflammatory disorders, analysis of data from a large registry found.&lt;/p&gt;
&lt;p&gt;The overall standardized mortality ratio was 0.65 (95% CI 0.53 to 0.78, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), Philip J. Hashkes, MD, of the Cleveland Clinic, and colleagues reported in the February issue of &lt;em&gt;Arthritis &amp;amp; Rheumatism&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;But the mortality ratio for systemic lupus erythematosus was 3.06 (95% CI 1.78 to 4.90, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and that for dermatomyositis was 2.64 (95% CI 0.86 to 6.17, &lt;em&gt;P&lt;/em&gt;=0.030), they wrote.&lt;/p&gt;
&lt;p&gt;In contrast, the standardized mortality ratio was significantly decreased in pain syndromes, at 0.41 (95% CI 0.21 to 0.72, &lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;Earlier studies had identified increased mortality in a number of rheumatologic conditions. For example, estimates for systemic lupus erythematosus ranged from 83% to 95% for five-year survival and 76% to 95% for 10-year survival.&lt;/p&gt;
&lt;p&gt;However, most of those studies were limited in size and follow-up time and were conducted before the 1990s when new treatments became available.&lt;/p&gt;
&lt;p&gt;To get an updated picture, Hashkes and colleagues performed a systematic study of mortality outcomes using data from the Indianapolis Pediatric Rheumatology Disease Registry, which is the largest of its kind.&lt;/p&gt;
&lt;p&gt;They identified 110 deaths among 47,449 patients (0.23%, 95% CI 0.19 to 0.27), which is significantly lower than in the expected age- and sex-adjusted U.S. population.&lt;/p&gt;
&lt;p&gt;With a mean follow-up of 7.9 years, the five-year survival rates in all diagnoses were 99% or above.&lt;/p&gt;
&lt;p&gt;Ten-year survival rates were: &lt;ul&gt; &lt;li&gt;Entire cohort, 99.7% (95% CI 99.6 to 99.8)&lt;/li&gt; &lt;li&gt;Systemic lupus erythematosus, 98.2% (95% CI 97.2 to 99.2)&lt;/li&gt; &lt;li&gt;All connective tissue diseases, 98.8% (95% CI 98.2 to 99.3)&lt;/li&gt; &lt;li&gt;Systemic juvenile rheumatoid arthritis, 99.1% (95% CI 98.3 to 99.8)&lt;/li&gt; &lt;li&gt;Primary vasculitis, 96.7% (95% CI 93.2 to 100)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;In 35% of cases, the rheumatologic disease and its complications was the cause of death. Treatment complications was the cause in 10% of cases, non-natural causes in 23%, background disease in 21%. In 11% the cause of death was unknown.&lt;/p&gt;
&lt;p&gt;In a univariable survival analysis, the following disorders were significant predictors of increased risk of mortality: &lt;ul&gt; &lt;li&gt;All connective tissue diseases, HR 4.5 (95% CI 2.9 to 6.9)&lt;/li&gt; &lt;li&gt;Primary vasculitis, HR 9.2 (95% CI 3.4 to 25)&lt;/li&gt; &lt;li&gt;Genetic/chromosomal/metabolic diseases, HR 6.2 (95% CI 2 to 19.5)&lt;/li&gt; &lt;li&gt;Systemic lupus erythematosus, HR 6 (95% CI 3.6 to 10.1)&lt;/li&gt; &lt;li&gt;Dermatomyositis, HR 3.3 (95% CI 1.3 to 8)&lt;/li&gt; &lt;li&gt;Systemic juvenile rheumatoid arthritis, HR 2.5 (95% CI 1.1 to 5.7&lt;strong&gt;)&lt;/strong&gt;&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Other significant predictors of mortality included older age at the time of first visit to a rheumatologist and the use of systemic steroids and methotrexate.&lt;/p&gt;
&lt;p&gt;In a multivariable model, only connective tissue disease, other nonrheumatic diagnosis, male sex, and older age remained significantly predictive of mortality.&lt;/p&gt;
&lt;p&gt;A total of 58% of the deaths were in patients whose primary diagnosis was an inflammatory condition, and 41% were in patients whose primary diagnosis was noninflammatory. (The primary diagnosis was uncertain in one patient.)&lt;/p&gt;
&lt;p&gt;&quot;As expected, most of the patients with inflammatory disease died of their disease or disease complications. With longer follow-up this proportion may change, given the possibility of secondary malignancies or an increased rate of infections related to prolonged immunosuppression,&quot; the investigators cautioned.&lt;/p&gt;
&lt;p&gt;The study has limitations and may have underestimated mortality, the researchers acknowledged. Their ability to detect deceased patients in the registry was hampered by the limited identification (only birth date and initials were recorded).&lt;/p&gt;
&lt;p&gt;Also, identifying deaths through the Social Security Death Index may have missed some cases of children who had never received a Social Security number.&lt;/p&gt;
&lt;p&gt;The data also may not be entirely generalizable, because not all U.S. centers participate in the registry, and reporting compliance even in participating centers was variable.&lt;/p&gt;
&lt;p&gt;The study also had a relatively short follow-up, so it was unable to capture the complete extent of mortality, especially in early adulthood when premature cardiovascular disease develops in many patients with lupus and rheumatoid arthritis.&lt;/p&gt;
&lt;p&gt;&quot;While the results of our study are encouraging, with the mortality rate of our entire cohort similar to that of the age- and sex-matched U.S. population, it is important to follow up this cohort in the future for mortality trends, especially later deaths seen as sequelae in many rheumatic diseases,&quot; the investigators concluded.&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 Northeast Ohio Chapter of the Arthritis Foundation.&lt;/p&gt;&lt;p&gt;No disclosures were provided.&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="0.001"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18136?impressionId=1265745251274"
                     
      &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>
    <recommendedItem id="20090101_19_1160"
                     title="Lupus Nephritis Therapies Battle to a Draw"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Rheumatology/Lupus/tb/13745?impressionId=1265745251274"
                     
       HOUSTON, April 15 -- A randomized comparison of two therapies for lupus nephritis ended in a draw, as mycophenolate mofetil failed to demonstrate superiority to cyclophosphamide. 
              &lt;p&gt;&lt;p&gt;Both drugs achieved responses in about half of the patients treated, Neil Solomons, M.D., of Aspreva Pharmaceuticals Corp. in Victoria, British Columbia, and colleagues reported online in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt;. 
              &lt;p&gt;Similar rates of adverse events, serious adverse events, and infections occurred in similar proportions of patients in each group. 
              &lt;p&gt;&quot;Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that mycophenolate mofetil was superior to intravenous cyclophosphamide as induction treatment for lupus nephritis,&quot; the authors concluded.
              
              &lt;p&gt;
              &lt;p&gt;As many as 60% of adults with systemic lupus erythematosus develop lupus nephritis. Induction therapy with intravenous cyclophosphamide has been the standard of care for the better part of three decades. 
              &lt;p&gt;However, patients require monthly infusions and their response to therapy often is slow. The treatment also fails to provide complete control and predisposes patients to potentially serious adverse effects, the authors noted. 
              &lt;p&gt;Results of recent studies suggested that mycophenolate mofetil is at least as effective and and might offer advantages over the current standard. However, the two agents had not been compared in an international, randomized controlled trial. 
              &lt;p&gt;The authors reported findings from a multinational study involving 370 patients with class III-V lupus nephritis. 
              &lt;p&gt;The patients were randomized to open label mycophenolate mofetil dosed to a target of 3 g/d or to intravenous cyclophosphamide administered in monthly pulses of 0.5 to 1.0 g/m&lt;sup&gt;2&lt;/sup&gt;. All patients also received corticosteroids. 
              &lt;p&gt;The primary endpoint was response to therapy at 24 weeks. The protocol defined response as a decrease in the urinary protein/creatinine ratio to &lt;3 in patients with a baseline ratio of ?3 or a decrease ?50% in patients with a baseline ratio &lt;3, plus stabilization or improvement in serum creatinine. 
              &lt;p&gt;When the trial ended, 56.2% of the mycophenolate mofetil group met criteria for response, as did 53% of patients in the cyclophosphamide arm. 
              &lt;p&gt;The treatment groups also did not differ significantly with respect to any of the secondary endpoints, which included complete renal remission, systemic disease activity and damage, and safety. There were no differences in the rates of adverse events. 
              &lt;p&gt;The authors reported that 70% of patients had normalization of serum creatinine with mycophenolate mofetil compared with 67.6% of the cyclophosphamide group. 
              &lt;p&gt;Nine deaths occurred in the mycophenolate mofetil arm and five in the cyclophosphamide arm. 
              &lt;p&gt;Although it didn&apos;t turn out to be superior, mycophenolate mofetil may be considered an alternative to intravenous cyclophosphamide, the authors concluded. 
              &lt;p&gt;They based the conclusion on the convenience of twice-daily oral doses with mycophenolate mofetil and the potential for ovarian dysfunction with intravenous cyclophosphamide. 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt; The study was funded by F Hoffmann-LaRoche as part of Aspreva&apos;s rare disease program. 
              &lt;p&gt;Dr. Solomons is an employee of Aspreva. Co-author Gerald B. Appel has received honoraria from Aspreva, served as a consultant for Aspreva, and received grants for the Aspreva Lupus Management Study. Co-author Gabriel Contreras has received honoraria for from Roche. 
              &lt;p&gt;Co-author Mary Ann Dooley has served as a consultant for Teva and Aspreva, received honoraria from Aspreva, provided expert testimony for UCB, and received grants from Bristol-Myers Squibb, Aspreva, Amgen, and Roche. 
              &lt;p&gt;Co-author Ellen M. Ginzler has received honoraria and grants from Aspreva. Co-author David Jayne has received grants from Aspreva.
          &lt;tr&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_452"
                     title="CellCept Outdoes Cytoxan for Lupus Nephritis"
                     score="-0.005"
                     href="