<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3059"
                     title="Bone Loss Seen Early in Inflammatory Disorders (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/Rheumatology/Arthritis/tb/21733?impressionId=1283458810663"
                     
      &lt;p&gt;Half of patients with early spondylarthropathy  --  and particularly men with active ankylosing spondylitis  --  also have low bone mineral density (BMD), a cross-sectional Dutch study found.&lt;/p&gt;
&lt;p&gt;In the study of 130 patients diagnosed with early spondylarthropathies, multivariate logistic regression analysis found that male gender was significantly associated with low BMD in patients recently diagnosed with one of these inflammatory disorders (OR 4.18, 95% CI 1.73 to 10.09, &lt;em&gt;P&lt;/em&gt;=0.002), according to M.A.C. van der Weijden, MD, of VU University in Amsterdam, and colleagues.&lt;/p&gt;
&lt;p&gt;This was despite the fact that patients&apos; mean age was only 38 years, van der Weijden and co-authors wrote online in the journal &lt;em&gt;Clinical Rheumatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The spondylarthropathies  --  ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and undifferentiated spondylarthropathy  --  are characterized by inflammation of the axial joints, asymmetrical oligoarthritis, and enthesitis.&lt;/p&gt;
&lt;p&gt;Low BMD is recognized as an important complication of longstanding ankylosing spondylitis, which can increase patients&apos; risk for vertebral fractures, loss of function, and neurologic abnormalities.&lt;/p&gt;
&lt;p&gt;But little is known about bone loss in earlier ankylosing spondylitis or in other spondylarthropathies, so van der Weijden and colleagues enrolled 130 consecutive patients with a recent diagnosis of one of these conditions.&lt;/p&gt;
&lt;p&gt;Almost three-quarters of the patients had ankylosing spondylitis, 12% had undifferentiated spondylarthropathy, 8% had psoriatic arthritis, and small numbers had other diagnoses.&lt;/p&gt;
&lt;p&gt;Two-thirds of patients were men. Time since diagnosis was a median of 6.6 months, and time since the first symptoms appeared was a median of 6.3 years.&lt;/p&gt;
&lt;p&gt;In the literature, the mean duration of symptoms before formal diagnosis in ankylosing spondylitis ranges from eight to ten years.&lt;/p&gt;
&lt;p&gt;Dual x-ray absorptiometry scans at baseline revealed osteopenia in 38% and osteoporosis in 9% of the patients.&lt;/p&gt;
&lt;p&gt;Osteoporosis was seen in the femur in 2.3% of the patients, in the lumbar spine in 7.7%, and at both sites in 8.5%.&lt;/p&gt;
&lt;p&gt;In a univariate logistic regression analysis, the following characteristics were significantly associated with low BMD: &lt;ul&gt; &lt;li&gt;Male gender, OR 4.72 (95% CI 2.10 to 10.78, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;li&gt;Diagnosis of ankylosing spondylitis, OR 2.48 (95% CI 1.09 to 5.60, &lt;em&gt;P&lt;/em&gt;=0.030)&lt;/li&gt; &lt;li&gt;Elevated C-reactive protein, OR 1.04 (95% CI 1.01 to 1.08, &lt;em&gt;P&lt;/em&gt;=0.018)&lt;/li&gt; &lt;li&gt;High score on the Bath Ankylosing Spondylitis Functional Index (BASFI), OR 1.24 (95% CI 1.07 to 1.44, &lt;em&gt;P&lt;/em&gt;=0.004)&lt;/li&gt; &lt;li&gt;High score on the Bath Ankylosing Spondylitis Metrology Index (BASMI), OR 1.72 (95% CI 1.32 to 2.25, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;On multivariate logistic regression analysis, male gender remained associated with low BMD, as did high BASFI and BASMI scores, which reflect high disease severity and impaired physical function: &lt;ul&gt; &lt;li&gt;BASFI, OR 1.18 (95% CI 1 to 1.39, &lt;em&gt;P&lt;/em&gt;=0.053)&lt;/li&gt; &lt;li&gt;BASMI, OR 1.54 (95% CI 1.14 to 2.07, &lt;em&gt;P&lt;/em&gt;=0.005)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The multivariate analysis clearly showed that men with spondylarthropathies were more likely than women to have low BMD early on in the disease. Only 41% of men had normal BMD, 47% had osteopenia, and 12% already had osteoporosis, whereas the corresponding numbers for women were 77%, 21%, and 2%, respectively.&lt;/p&gt;
&lt;p&gt;Possible explanations for the gender differences included higher disease activity among men and the protective effects of estrogen in women, almost all of whom were premenopausal, van der Weijden and colleagues suggested.&lt;/p&gt;
&lt;p&gt;In the general population, factors associated with lower BMD typically include female gender, older age, low body mass index, and the presence of chronic inflammatory disease, the authors noted.&lt;/p&gt;
&lt;p&gt;In comparison, in spondylarthropathy patients  --  particularly those with ankylosing spondylitis  --  factors that contribute to bone loss include inflammation and spinal rigidity, which can lead to problems with mobility and reduced physical activity, the researchers added.&lt;/p&gt;
&lt;p&gt;Pro-inflammatory cytokines may also play a contributory role, as suggested in earlier studies that found elevated levels of tumor necrosis factor-alpha in patients with ankylosing spondylitis and that disease activity correlates with markers of increased bone metabolism.&lt;/p&gt;
&lt;p&gt;&quot;This supports the hypothesis that increased inflammatory activity in [ankylosing spondylitis] will lead to increased bone resorption and decreased bone density,&quot; van der Weijden and colleagues wrote.&lt;/p&gt;
&lt;p&gt;They concluded, &quot;We would like to emphasize the need for more alertness for osteoporosis and osteopenia in spondylarthropathy patients at an early stage of the disease.&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 authors declared that they had no financial ties to disclose.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2917"
                     title="HAE Drug Data See Peer-Reviewed Light of Day (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/tb/21554?impressionId=1283458810663"
                     
      &lt;p&gt;Results of phase III trials of two approved drugs for hereditary angioedema (HAE) and another in the late-stage pipeline have finally emerged from the gauntlet of peer review.&lt;/p&gt;
&lt;p&gt;Reports on a pasteurized and nanofiltered form of human C1 esterase inhibitor (Cinryze) and the synthetic agents ecallantide (Kalbitor) and icatibant (Firazyr)  --  the latter still in development  --  appeared in the Aug. 4 issue of the &lt;em&gt;New England Journal of Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Much of the data in all three papers had already been reported at meetings in &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/8810&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/8810&quot; target=&quot;_blank&quot;&gt;2008&lt;/a&gt; and &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ACAAI/11703&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ACAAI/11703&quot; target=&quot;_blank&quot;&gt;2009&lt;/a&gt;, but this is the first publication of full reports in a peer-reviewed journal.&lt;/p&gt;
&lt;p&gt;HAE, a rare disorder, is the result of a genetic defect in a regulatory protein that keeps C1 complement in check. Patients suffer frequent, unpredictable attacks marked by swelling and acute pain in various parts of the body.&lt;/p&gt;
&lt;p&gt;The C1 esterase inhibitor Cinryze, as well as a similar agent (Berinert) already FDA approved for acute attacks, are straight replacement products, derived from human plasma and treated to eliminate viral contaminants. The synthetic drugs come at HAE a different way, targeting bradykinin activity to block the downstream inflammatory effects of overactive complement.&lt;/p&gt;
&lt;p&gt;Icatibant is an antagonist of the bradykinin B2 receptor, whereas ecallantide inhibits plasma kallikrein to reduce bradykinin availability. Both drugs are given by subcutaneous injection, whereas the C1 esterase inhibitor proteins require intravenous delivery.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Icatibant Trials Disappointing&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Aleena Banerji, MD, of Massachusetts General Hospital in Boston, and colleagues reported data from two phase III trials of icatibant, FAST-1 and FAST-2. The results explain why the FDA in 2008 rejected a marketing application submitted by its manufacturer, the German firm Jerini AG.&lt;/p&gt;
&lt;p&gt;Paradoxically, the placebo-controlled FAST-1 trial failed to meet its primary endpoint, a significant reduction in median time to clinically significant relief of acute HAE attacks, whereas FAST-2 did show a significant advantage versus an active comparator.&lt;/p&gt;
&lt;p&gt;In the 56-patient FAST-1 study, the median time to meaningful symptom relief was 2.5 hours compared with 4.6 hours in the placebo group (&lt;em&gt;P&lt;/em&gt;=0.14).&lt;/p&gt;
&lt;p&gt;In FAST-2, a similar effect was seen for icatibant, but patients receiving the active comparator, tranexamic acid, had far worse outcomes than the placebo patients in FAST-1. Median response times in FAST-2 were 2.0 hours for icatibant versus 12.0 hours with tranexamic acid (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Differences between the two studies in the use of rescue medications likely accounted for the different outcomes, Banerji and colleagues indicated, not any action of tranexamic acid.&lt;/p&gt;
&lt;p&gt;Nearly half the placebo group in FAST-1 required rescue medication with C1 esterase inhibitor or other treatments because of inadequate relief or worsening symptoms. In FAST-2, on the other hand, only about 20% of patients assigned to tranexamic acid received rescue medications.&lt;/p&gt;
&lt;p&gt;Data from patients receiving rescue medication were not censored. Also, the primary endpoint in FAST-1 was judged only for the &quot;index symptom,&quot; the patient&apos;s primary complaint at the start of treatment, and not for other symptoms.&lt;/p&gt;
&lt;p&gt;This &quot;stringent definition&quot; of the primary endpoint and inclusion of placebo patients who received early rescue medication explained the relatively small difference in outcomes in FAST-1, Banerji and colleagues concluded.&lt;/p&gt;
&lt;p&gt;Nevertheless, Jerini is now sponsoring another trial, FAST-3, in hopes of allaying the FDA&apos;s doubts about the drug&apos;s efficacy.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Ecallantide Report Has No Mention of Anaphylaxis&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;The ecallantide report, from Marco Cicardi, MD, of the University of Milan, and colleagues, covered the drug&apos;s 72-patient, placebo-controlled pivotal trial called EDEMA3 in patients with acute attacks.&lt;/p&gt;
&lt;p&gt;Median time to significant improvement  --  defined as the patient&apos;s first report that overall symptoms were &quot;a lot better or resolved&quot;  --  was 2.75 hours with ecallantide compared with more than four hours for placebo.&lt;/p&gt;
&lt;p&gt;That was not the study&apos;s primary endpoint, however, which was a so-called treatment outcome score at four hours after treatment. Scores could range from -100 to +100, reflecting significant worsening or significant improvement, respectively.&lt;/p&gt;
&lt;p&gt;The mean four-hour score was 46.8 (SD 59.3) with ecallantide versus 21.3 (SD 69) in the placebo group (&lt;em&gt;P&lt;/em&gt;=0.004), Cicardi and colleagues reported.&lt;/p&gt;
&lt;p&gt;The report sidestepped mention of hypersensitivity or anaphylactic reactions that have &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/18843&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/18843&quot; target=&quot;_blank&quot;&gt;previously been reported&lt;/a&gt; with the drug. Cicardi and colleagues indicated that no such reactions occurred in EDEMA3.&lt;/p&gt;
&lt;p&gt;But a total of 16 such reactions had been seen in other trials, leading the FDA to require a boxed warning indicating that the drug should be administered by health professionals prepared to manage serious reactions.&lt;/p&gt;
&lt;p&gt;The problem has dashed hopes, at least for the present, that patients could carry ecallantide self-injectors to treat acute HAE attacks themselves.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Cinryze Looking for Acute Tx Indication&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;The piece of the &lt;em&gt;NEJM&lt;/em&gt; package included a report from Bruce Zuraw, MD, of the University of California San Diego, and colleagues on the nanofiltered C1 esterase inhibitor Cinryze. It covered two studies, a 68-patient placebo-controlled trial of the drug as a treatment for acute attacks, and a 22-patient study of twice-weekly Cinryze treatments for preventing attacks.&lt;/p&gt;
&lt;p&gt;Cinryze won FDA approval in October 2008 for preventing HAE attacks, and the &lt;em&gt;NEJM&lt;/em&gt; report includes data from a trial for that purpose. But its manufacturer is also seeking approval for the drug as a treatment for acute attacks; data from a study intended to support that indication were also included in the &lt;em&gt;NEJM&lt;/em&gt; paper&lt;/p&gt;
&lt;p&gt;The acute-attack trial had time to &quot;unequivocal&quot; symptom relief as its primary outcome. The median was 2.0 hours for Cinryze versus more than 4.0 hours for placebo (&lt;em&gt;P&lt;/em&gt;=0.02), according to Zuraw and colleagues.&lt;/p&gt;
&lt;p&gt;On the other hand, 40% of Cinryze patients failed to achieve unequivocal relief within four hours, the researchers indicated, a lower success rate than seen in earlier studies.&lt;/p&gt;
&lt;p&gt;Zuraw and colleagues also reported that open-label treatment resulted in improvement 93% of the time. They suggested this finding might be a better representation of real-life clinical responses, as &quot;fear of receiving placebo&quot; would not be a factor.&lt;/p&gt;
&lt;p&gt;Nevertheless, the FDA last year told the drug&apos;s manufacturer, ViroPharma, that &lt;a href=&quot;http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/14578&quot; mce_href=&quot;http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/14578&quot; target=&quot;_blank&quot;&gt;another acute-treatment trial&lt;/a&gt; would be needed before approval for an acute-treatment indication would be granted. The agency indicated that the existing data &quot;lacked robustness,&quot; according to the company.&lt;/p&gt;
&lt;p&gt;Berinert was approved last year as a treatment for acute attacks, but Cinryze is currently the only drug approved for preventing them.&lt;/p&gt;
&lt;p&gt;The prophylaxis trial, which used a placebo-controlled crossover design, found that only two of the 22 patients had more HAE attacks during the 12-week active-treatment period relative to a 12-week placebo period.&lt;/p&gt;
&lt;p&gt;The mean number of attacks in the Cinryze group was 6.26, compared with 12.73 for placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Choosing One Agent Over Another&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;An accompanying editorial by B. Paul Morgan, MB, PhD, of Cardiff University in Wales, noted that clinicians now need studies to help them sort through the trade-offs involved with using one of these agents versus another.&lt;/p&gt;
&lt;p&gt;Noting that C1 esterase inhibitors have been marketed in Europe for many years, he wrote that this class &quot;has proved to be safe and effective during decades of use.&quot;&lt;/p&gt;
&lt;p&gt;But the other agents have advantages as well, he pointed out. &quot;Newer agents eliminate the perceived risk of infection; some provide additional target specificity,&quot; Morgan wrote.&lt;/p&gt;
&lt;p&gt;&quot;Head-to-head comparisons are needed to guide the choice of agents for the treatment of acute attacks and prophylaxis,&quot; according to Morgan. &quot;Practical matters, particularly the stability of the drug and the route of administration, are likely to be critical, because optimal therapy requires prompt self-administration at the first hint of an attack.&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 C1 esterase inhibitor study was funded by Lev Pharmaceuticals, now owned by ViroPharma Biologics.&lt;/p&gt;&lt;p&gt;The ecallantide study was funded by Dyax.&lt;/p&gt;&lt;p&gt;The icatibant studies were funded by Jerini AG, now part of Shire, with partial National Institutes of Health support for FAST-1.&lt;/p&gt;&lt;p&gt;Zuraw reported consulting relationships with Lev, CSL Behring, Jerini, and Dyax; travel expenses from Lev, Shire, and Dyax; expert witness fees from Lev; and grant support from Lev, Shire, and Pharming. One co-author was an employee of Lev.&lt;/p&gt;&lt;p&gt;Cicardi reported consulting relationships with Dyax, Jerini, and Pharming; board membership at Jerini, Shire, and CSL Behring; travel reimbursements from Dyax, Jerini, Shire, CSL Behring, and Pharming; honoraria and speaking fees from Jerini, Shire, Pharming, CSL Behring, and ViroPharma; and manuscript preparation fees from Jerini. Two co-authors were Dyax employees.&lt;/p&gt;&lt;p&gt;Banerji reported consulting relationships with Shire and Dyax. Seven co-authors were Jerini employees.&lt;/p&gt;&lt;p&gt;Morgan reported giving expert testimony on behalf of Shire, with fees paid to his university.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2853"
                     title="Small Cancer Risk Seen in Children on TNF Blockers (CME/CE)"
                     score="-0.007"
                     href="http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/tb/21469?impressionId=1283458810663"
                     
      &lt;p&gt;The use of tumor necrosis factor (TNF)-alpha blockers in children may increase the risk of malignancy, particularly when these drugs are given for inflammatory bowel disease rather than for rheumatic conditions, a study found.&lt;/p&gt;
&lt;p&gt;A total of 48 cases of malignancy have been reported among children and young adults taking infliximab (Remicade), etanercept (Enbrel), or adalimumab (Humira), Peter Diak, PharmD, and colleagues from the Food and Drug Administration (FDA) in Silver Spring, Md., wrote in the August issue of &lt;em&gt;Arthritis &amp;amp; Rheumatism.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;But a clear causal relationship could not be established between TNF blockade and cancer in the study, because most of the children were on multiple immunosuppressive drugs, and the underlying risk for malignancy with autoimmune disease was unclear.&lt;/p&gt;
&lt;p&gt;In the FDA&apos;s Adverse Event Reporting System database, Diak and colleagues identified 31 cases of malignancy in children taking infliximab out of a total of 14,837 who have received the drug.&lt;/p&gt;
&lt;p&gt;There were nine cases of hepatosplenic T-cell lymphoma, five of non-Hodgkin&apos;s lymphoma, three of Hodgkin&apos;s lymphoma, and three of leukemia. The remaining cases consisted of one case each of 11 different cancers, including malignant melanoma, basal cell carcinoma, thyroid cancer, and colon cancer.&lt;/p&gt;
&lt;p&gt;A total of 24 of the malignancies, including all the cases of hepatosplenic T-cell lymphoma, developed in children receiving infliximab for inflammatory bowel disease, while five were in patients with rheumatic diseases.&lt;/p&gt;
&lt;p&gt;Median time from the start of treatment to the diagnosis of cancer was 30 months, and in 94% of cases other immunosuppressants were being used.&lt;/p&gt;
&lt;p&gt;Eleven children died, nine from hepatosplenic T-cell lymphoma.&lt;/p&gt;
&lt;p&gt;Among the 9,200 children treated with etanercept, there were 15 reported malignancies, with five cases of lymphoma, four of leukemia, two cases each of malignant melanoma and thyroid cancer, and one case each of myelodysplasia, yolk sac tumor, and bladder cancer.&lt;/p&gt;
&lt;p&gt;In 73% of those cases the indication for treatment was juvenile idiopathic arthritis (JIA), with most others being ankylosing spondylitis and psoriatic arthritis. Almost two-thirds were reported from foreign countries that have established registries for patients receiving biologic drugs.&lt;/p&gt;
&lt;p&gt;The median time from the start of etanercept treatment to the diagnosis of cancer was 28 months, and in 73% of cases additional immunosuppressives were being used.&lt;/p&gt;
&lt;p&gt;There were no deaths reported.&lt;/p&gt;
&lt;p&gt;Two cases of malignancy were reported among the 2,636 children given adalimumab, one of Hodgkin&apos;s lymphoma in a child with severe juvenile idiopathic arthritis and the other in young man with ulcerative colitis who died of hepatosplenic T-cell lymphoma.&lt;/p&gt;
&lt;p&gt;Both patients had received numerous immunosuppressive drugs, including other TNF blockers.&lt;/p&gt;
&lt;p&gt;The FDA investigators calculated that the reporting rate of malignancy in children on infliximab was 66 per 100,000 patient-years, which is about four times the estimated pediatric background rate; and the reporting rate for lymphoma specifically, at 44 per 100,000 patient-years, approximated 18 times the background rate.&lt;/p&gt;
&lt;p&gt;For etanercept, the overall reporting rate was 22 per 100,000 patient-years, which was similar to the background rate, while for lymphoma the rate was 11 per 100,000 patient-years, which was about five times the background rate.&lt;/p&gt;
&lt;p&gt;Reporting rates were not calculated for adalimumab because of small numbers and confounding.&lt;/p&gt;
&lt;p&gt;&quot;The number and the rare types of malignancies reported in these cases are worrisome given the under-reporting of adverse events in the AERS database, the long latency period of malignancy, and the relatively small number of pediatric patients treated with TNF blockers,&quot; the FDA investigators stated.&lt;/p&gt;
&lt;p&gt;They further cautioned that the under-reporting is considered to be substantial.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Thomas J.A. Lehman, MD, of Cornell University in New York City observed that the risk of lymphoma in children with juvenile idiopathic arthritis receiving etanercept was only 0.011%, and asked if that was sufficient to deny the remaining 99.98% of patients a treatment that has dramatically reduced the morbidity of this disease.&lt;/p&gt;
&lt;p&gt;&quot;Given the absence of convincing data that TNF-alpha blockers increase the risk of lymphoma over the background risk seen with the prior standard of methotrexate therapy, every clinician must think long and hard before denying TNF-alpha blockers to a child with JIA,&quot; he stated.&lt;/p&gt;
&lt;p&gt;And while pediatric rheumatologists cannot promise complete safety with any medication, they can educate parents and help provide perspective for the risks, Lehman explained.&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 disclosures were reported by the FDA authors.&lt;/p&gt;&lt;p&gt;Editorialist Lehman disclosed receiving speaking fees from Abbott, Amgen, Pfizer, and Wyeth.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2720"
                     title="Joint Replacement Registry Improves Quality of Care (CME/CE)"
                     score="-0.01"
                     href="http://www.medpagetoday.com/Surgery/Orthopedics/tb/21310?impressionId=1283458810663"
                     
      A total joint replacement registry begun in California in 2001 has enhanced patient safety and quality of care by tracking implant performance and outcomes, according to a new report.&lt;br&gt;
&lt;br&gt;For instance, registry data have shown that the cumulative five-year survival of both primary total hip and knee replacements currently is 97.3%, reported Elizabeth W. Paxton, MD, from Kaiser Permanente in San Diego, and colleagues.&lt;br&gt;
&lt;br&gt;Analysis of data from the registry also has determined that the main reasons for hip revisions are instability and infections, the researchers wrote online in &lt;em&gt;Clinical Orthopedics and Related Research.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;In the U.S., some 600,000 total joint replacement surgeries are performed each year, a number that is expected to rise markedly in the coming decades, with projected hospital costs increasing by more than 300% by 2015.&lt;/p&gt;
&lt;p&gt;Despite the volume and costs associated with joint arthroplasty, no national system exists that can compare devices and surgical techniques.&lt;/p&gt;
&lt;p&gt;To fill this gap, Kaiser Permanente surgeons undertook the development of a registry modeled after one in Sweden to track and monitor surgical revisions, infections, thromboembolic events, and mortality.&lt;/p&gt;
&lt;p&gt;A total of 350 surgeons from 43 medical centers participated voluntarily.&lt;/p&gt;
&lt;p&gt;They developed standardized forms that were integrated into the clinical workflow at the point of care. These included preoperative variables such as patient comorbidities and prior surgeries, procedure details including the approach used and prophylaxis given, and postoperative factors such as readmissions, revisions, and deaths.&lt;/p&gt;
&lt;p&gt;Among the keys to success in the development of the registry, according to the authors, was an effort to leverage existing administrative databases to reduce the data collection and processing burden on staff.&lt;/p&gt;
&lt;p&gt;&quot;Leveraging existing data sources provided the registry with enormous power to increase its data quality and validation,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Moreover, having the registry initiated, developed, and maintained by surgeons themselves has been essential to success, Paxton and colleagues observed.&lt;/p&gt;
&lt;p&gt;A crucial aspect of improving the quality of care has been the identification of patient risk factors.&lt;/p&gt;
&lt;p&gt;For example, it has become apparent that younger patients and those with diabetes are at higher risk for revisions, patients with higher body mass index are at risk of surgical site infections, and the types of prophylactic medication and anesthesia can influence thrombotic events.&lt;/p&gt;
&lt;p&gt;Multivariate statistical analyses are conducted at least once every year to reevaluate patient risk factors, with the results being reported annually to participating surgeons.&lt;/p&gt;
&lt;p&gt;Feedback on surgical techniques and implant characteristics has shown that there are higher revision rates with unicompartmental knees, uncemented total knee fixations, femoral head sizes less than 28 mm, and minimally invasive surgical procedures.&lt;/p&gt;
&lt;p&gt;The registry also has had an impact on cost, with data on device utilization and performance being used in decision-making on purchasing. Cost-effectiveness also is expected to further improve with long-term reduction in rates of revision, according to the researchers.&lt;/p&gt;
&lt;p&gt;As the registry has increased in scope, an additional important function has been to serve as an early warning system of potential device problems.&lt;/p&gt;
&lt;p&gt;The registry &quot;has been instrumental in investigating more than 15 recalls, advisories, and concerns with implants in 2009 alone,&quot; the authors noted.&lt;/p&gt;
&lt;p&gt;Strengths of the registry include its large volume, data that are representative of community-based practice, and extent of surgeon involvement.&lt;/p&gt;
&lt;p&gt;Limitations include the fact that the registry has not yet been fully integrated into the system&apos;s electronic health records, although efforts continue.&lt;/p&gt;
&lt;p&gt;A key future direction, the researchers stated, will be collaboration with other initiatives with the goal of establishing a national registry for total joint replacements, which will require cooperation among manufacturers, insurance providers, patient advocacy groups, and surgeons.&lt;/p&gt;
&lt;p&gt;&quot;Surgeons will need to take the lead, driving the development, implementation, and reporting of a national effort,&quot; they 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;All authors declared that they have 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_2669"
                     title="Varicella Vaccine Safe for Rheumatic Patients (CME/CE)"
                     score="-0.01"
                     href="http://www.medpagetoday.com/Pediatrics/Vaccines/tb/21245?impressionId=1283458810663"
                     
      &lt;p&gt;Varicella vaccine appears to be safe and relatively immunogenic for use in children with rheumatic diseases being treated with immunosuppressive drugs, a small prospective study has found.&lt;/p&gt;
&lt;p&gt;Positive varicella-zoster virus IgG titers were detected in 10 of 20 previously seronegative patients with juvenile idiopathic arthritis, dermatomyositis, scleroderma, or vasculitis and in 13 of 18 healthy matched controls (&lt;em&gt;P&lt;/em&gt;=0.2) four to six weeks after immunization, according to Gecilmara Salviato Pileggi, MD, of the University of S&amp;#227;o Paulo in Brazil.&lt;/p&gt;
&lt;p&gt;During the three months following receipt of the vaccine, no overt varicella episodes or severe adverse reactions were seen among children who seroconverted, the researchers reported in the July &lt;em&gt;Arthritis Care &amp;amp; Research.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Children with altered immune systems, such as can occur with the use of antirheumatic drugs, are at increased risk of severe disease should they be exposed to varicella, and there have been case reports of affected patients having serious and even fatal infections.&lt;/p&gt;
&lt;p&gt;But evidence has been lacking on the safety of live vaccines in children with rheumatic diseases receiving immunosuppressive therapy, so Pileggi and colleagues conducted an open-label study that included 25 patients whose median age was 7.2 years. All patients received a single dose of varicella vaccine.&lt;/p&gt;
&lt;p&gt;All participants were receiving methotrexate, at a mean dosage of 16.4 mg/m&lt;sup&gt;2&lt;/sup&gt;/week, and 13 also were receiving prednisone in doses of 0.1 to 0.7 mg/kg/day.&lt;/p&gt;
&lt;p&gt;Among the total cohort of 25 patients, five had equivocal pre-immunization virus titers and were excluded from the vaccine response analysis.&lt;/p&gt;
&lt;p&gt;Low-grade fever lasting a single day was seen in one patient and one control, and three patients had mild varicella-like rashes during the first two weeks.&lt;/p&gt;
&lt;p&gt;During a median follow-up period of 32 months, 16 patients reported exposure to wild varicella zoster virus, with eight of the exposures involving a household or classmate contact.&lt;/p&gt;
&lt;p&gt;Two of those eight, both of whom were nonresponders to the vaccine, developed chickenpox, with one having a severe case complicated by pneumonia and probable macrophage activation syndrome.&lt;/p&gt;
&lt;p&gt;That patient was receiving anti-tumor necrosis factor therapy at the time of the exposure, the investigators noted.&lt;/p&gt;
&lt;p&gt;Vaccination was not associated with worsening of the underlying disease, and, in fact, among the subgroup of 17 patients with juvenile idiopathic arthritis, a significant improvement was seen in the number of joints with active arthritis in the three months following vaccination, decreasing from a mean of 3.2 (95% CI 1.4 to 5) to 1.8 (95% CI 0.8 to 2.8, &lt;em&gt;P&lt;/em&gt;=0.009).&lt;/p&gt;
&lt;p&gt;The investigators noted that the overall seroconversion rate to the vaccine was lower in this study than was seen in an earlier large study, where response rates exceeded 90%.&lt;/p&gt;
&lt;p&gt;However, a more recent study found rates of seroconversion of 76% after one dose of the vaccine, and the Advisory Committee on Immunization Practices recommends the use of two doses in healthy children.&lt;/p&gt;
&lt;p&gt;An editorial accompanying the study concurred.&lt;/p&gt;
&lt;p&gt;&quot;Based on the results of the current study, if a decision was made to immunize children with rheumatic diseases against varicella, a two-dose regimen would be preferable,&quot; wrote Robert W. Frenck, MD, of Cincinnati Children&apos;s Hospital and Jane F. Seward, MBBS, of the Centers for Disease Control and Prevention in Atlanta.&lt;/p&gt;
&lt;p&gt;&quot;Of note, in countries using varicella vaccine (one- or two-dose policy) in their universal childhood immunization program, most children will receive varicella vaccine before developing juvenile rheumatic diseases,&quot; the editorialists pointed out.&lt;/p&gt;
&lt;p&gt;A limitation of the study was the small number of patients from a single center, and multicenter studies with larger numbers of patients are clearly needed to more fully estimate responsiveness to the vaccine in children with rheumatic diseases, Pileggi and colleagues noted.&lt;/p&gt;
&lt;p&gt;&quot;More research in this field is necessary for the development of specific immunization guidelines for patients with rheumatic and other autoimmune diseases receiving treatment with immunosuppressive agents who are still susceptible to preventable infectious disease,&quot; they 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 lead author&apos;s work was supported by the University of S&amp;#227;o Paulo, and another author was supported by the Conselho Nacional de Desenvolvimento Cient&amp;#237;fico e Technol&amp;#243;gico.&lt;/p&gt;&lt;p&gt;Editorialist Frenck has received consultant and speaking fees from the Data Safety Monitoring Boards of Novartis Vaccines.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>