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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="0.005"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/18179?impressionId=1265801872640"
                     
      &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"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18136?impressionId=1265801872640"
                     
      &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_662"
                     title="Rituximab Effective for Lupus Nephritis"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Nephrology/GeneralNephrology/tb/13123?impressionId=1265801872640"
                     
      PARIS, March 4 -- Rituximab may be an effective option for patients with lupus nephritis who are resistant to conventional therapy, researchers here said. 
              &lt;p&gt; 
              &lt;p&gt;About 60% of patients in a small trial showed a decrease in renal inflammation when treated with the B-cell antibody, Fadi Fakhouri, M.D., of Imperial College London, and colleagues reported online in the &lt;em&gt;Clinical Journal of the American Society of Nephrology&lt;/em&gt;.
              &lt;p&gt; 
              &lt;p&gt;Those who achieved B-cell depletion within a month were more likely to go into remission. 
              &lt;p&gt; 
              &lt;p&gt;&quot;Rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis when early B-cell depletion is obtained,&quot; the researchers said. 
              &lt;p&gt; 
              &lt;p&gt;Lupus nephritis occurs frequently in patients with systemic lupus erythematosus, and many are treated with corticosteroids and cyclophosphamide. However, a significant percentage of patients do not respond to these treatments, or have toxic side effects, the researchers said. 
              &lt;p&gt; 
              &lt;p&gt;Because the disease seems to be caused at least in part by hyperreactive B cells, targeting those cells with rituximab -- which induces long-lasting B-cell depletion -- could be a potential therapeutic option for lupus nephritis patients, the researcher theorized.
              &lt;p&gt; 
              &lt;p&gt;To test the treatment, they studied 20 patients (19 women, one man) with severe lupus nephritis treated in eight French nephrology centers between October 2003 and December 2006. 
              &lt;p&gt; 
              &lt;p&gt;The majority of enrolled patients had already experienced at least one relapse and were already on at least one line of therapy.
              &lt;p&gt; 
              &lt;p&gt;Rituximab was administered weekly for four weeks at a dose of 375 mg/m&lt;sup&gt;2&lt;/sup&gt; of body surface area, and patients were followed for 22 months.
              &lt;p&gt; 
              &lt;p&gt;Three patients received cyclophosphamide concomitantly with rituximab.
              &lt;p&gt; 
              &lt;p&gt;Improvement was seen in 12 patients, or 60% of the study sample. Seven had complete remission of nephritis and five had partial remission. 
              &lt;p&gt; 
              &lt;p&gt;&quot;Considering that response to first-line treatment is 81% at the very best, 60% response in severe lupus nephritis seems quite promising,&quot; the researchers said. 
              &lt;p&gt; 
              &lt;p&gt;Patients who didn&apos;t achieve B-cell depletion within a month were less likely to go into remission. Only one patient in whom B-cell depletion was obtained did not have a positive renal outcome. 
              &lt;p&gt; 
              &lt;p&gt;&quot;Even though these data need to be confirmed, B-cell depletion failure after one month should urge clinicians to use another therapy,&quot; they said.
              &lt;p&gt; 
              &lt;p&gt;Deep hypoalbuminuria, black ethnicity, and presence of human antichimeric antibodies were associated with depletion failure, the researchers said. 
              &lt;p&gt; 
              &lt;p&gt;They added that patients who received cyclophosphamide concomitantly with rituximab did not have a better outcome than those treated with rituximab alone. 
              &lt;p&gt; 
              &lt;p&gt;Side effects included five infections and four moderate neutropenias. 
              &lt;p&gt; 
              &lt;p&gt;The mechanism of action of rituximab in lupus nephritis is not fully understood, although the findings suggest that it works by modulating the complex role of B cells on the immune system, including the B-cell/T-cell cross talk, the researchers said. 
              &lt;p&gt; 
              &lt;p&gt;They concluded that rituximab may be beneficial in refractory or relapsing lupus nephritis, and that B-cell depletion after a month &quot;is a useful and early predictor of response.&quot;
              &lt;p&gt; 
               
              &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 researchers reported no conflicts of interest.&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="