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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_406"
                     title="AAPM: Opioid Gains Long-Term Control of Neuropathic Cancer Pain (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18316?impressionId=1265805584465"
                     
      &lt;p&gt;SAN ANTONIO  --  Patients with neuropathic cancer pain obtained consistent, long-term pain control with extended-release oxymorphone (Opana), according to results of a one-year, open-label extension study.&lt;/p&gt;
&lt;p&gt;Patients reported pain in the mild range throughout most of the follow-up, and only 11% discontinued because of lack of efficacy, Errol Gould, PhD, of Endo Pharmaceuticals in Chadds Ford, Pa., reported here at the American Academy of Pain Medicine meeting. The company manufactures Opana.&lt;/p&gt;
&lt;p&gt;No unexpected adverse events occurred.&lt;/p&gt;
&lt;p&gt;&quot;Current clinical guidelines recommend opioids as second- or third-line treatment for chronic neuropathic pain,&quot; Gould said in an interview. &quot;These results suggest that oxymorphone extended release may be a viable long-term option for patients with neuropathic pain.&quot;&lt;/p&gt;
&lt;p&gt;The findings came from a one-year extension of a multicenter, open-label, noncontrolled short-term study of patients with cancer-related chronic pain.&lt;/p&gt;
&lt;p&gt;Of 44 patients who entered the extension phase, 27 had pain that was primarily neuropathic in origin. The diagnosis of neuropathic pain was based on clinician judgment, with no prespecified diagnostic criteria for guidance.&lt;/p&gt;
&lt;p&gt;Patients began treatment in the extension phase with their ending dose from the short-term study. Dose adjustments to improve pain control or tolerability were allowed throughout the 52-week extension phase.&lt;/p&gt;
&lt;p&gt;Ten of the 27 patients completed the extension study. Principal reasons for withdrawal were adverse events, patient request, loss of effectiveness, and nonadherence.&lt;/p&gt;
&lt;p&gt;The median duration from initiation of long-term maintenance to final visit was 22 weeks. Baseline pain intensity averaged 32.9 on a 100-point scale and 32.6 at final visit. Mean least pain intensity was 13.8 at baseline and 16.2 at final visit, and worst pain intensity averaged 76.3 at baseline and 66.5 at final visit.&lt;/p&gt;
&lt;p&gt;&quot;Regression analysis showed that pain intensity changed very little throughout follow-up,&quot; Gould said.&lt;/p&gt;
&lt;p&gt;The median oxymorphone dose increased from 80 mg at baseline to 160 mg at 52 weeks.&lt;/p&gt;
&lt;p&gt;Eleven (41%) patients reported at least one treatment-related adverse event. The most common events were dry mouth, constipation, and fatigue. The only serious adverse event was an episode of depressed consciousness.&lt;/p&gt;
&lt;p&gt;&quot;Patients required some gradual increases in dosage over time, but that&apos;s consistent with the nature of the disease,&quot; said Gould.&lt;/p&gt;
&lt;p&gt;Not long ago opioids were considered ineffective for neuropathic pain, he added. This study provided additional evidence in support of opioids&apos; effectiveness in controlling neuropathic pain.&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 Endo Pharmaceuticals, which manufactures Opana.&lt;/p&gt;&lt;p&gt;Gould and another co-author are employees of Endo Pharmaceuticals.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_373"
                     title="Protein in Urine Presages More Severe Problems (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/Nephrology/ESRD/tb/18265?impressionId=1265805584465"
                     
      &lt;p&gt;The three-year risk of death, heart attack, and kidney failure was markedly increased in patients with baseline proteinuria, regardless of their estimated glomerular filtration rate (eGFR), researchers said.&lt;/p&gt;
&lt;p&gt;In a population-based study of nearly 1 million people, mortality was approximately doubled with heavy proteinuria among individuals stratified according to their eGFR, reported Brenda R. Hemmelgarn, MD, PhD, of the University of Calgary in Canada, and colleagues.&lt;/p&gt;
&lt;p&gt;Rates of myocardial infarction were increased by about 50% with heavy proteinuria, and end-stage renal disease and doubled levels of serum creatinine were as much as 30 times more common, the researchers reported in the Feb. 3 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Prognosis associated with a given level of eGFR varies substantially based on the presence and severity of proteinuria,&quot; Hemmelgarn and colleagues concluded.&lt;/p&gt;
&lt;p&gt;&quot;In fact, patients with heavy proteinuria but without overtly abnormal eGFR appeared to have worse clinical outcomes than those with moderately reduced eGFR but without proteinuria.&quot;&lt;/p&gt;
&lt;p&gt;They added that the findings were important because current recommendations for managing chronic kidney disease rely on eGFR for staging purposes without consideration of proteinuria.&lt;/p&gt;
&lt;p&gt;&quot;Future revisions of the classification system for chronic kidney disease should incorporate information from proteinuria,&quot; the researchers urged.&lt;/p&gt;
&lt;p&gt;The results emerged from a laboratory registry covering some 921,000 adults in the province of Alberta who had had measurements of eGFR, serum creatinine, and urinary protein from 2002 to 2007.&lt;/p&gt;
&lt;p&gt;Proteinuria was measured with a urine dipstick or the albumin-creatinine ratio. Dipstick readings of at least 2 points were considered heavy proteinuria. Readings showing at least trace protein but less than 2 points were classed as mild; negative readings were considered normal.&lt;/p&gt;
&lt;p&gt;The stratifications of albumun-creatinine ratio were greater than 300 mg/g, 30 to 300 mg/g, and less than 30 mg/g for heavy, mild, and normal, respectively.&lt;/p&gt;
&lt;p&gt;Other registry data for the province provided outcomes in these individuals, with median follow-up of 35 months.&lt;/p&gt;
&lt;p&gt;Among individuals with eGFR rates of at least 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, death rates were 7.2 per 1,000 for those with dipstick-measured heavy proteinuria (95% CI 6.6 to 7.8) and 5.8 per 1,000 for mild proteinuria (95% CI 5.5 to 6.0) compared with 2.7 per 1,000 for those with normal urine protein (95% CI 2.6 to 2.8).&lt;/p&gt;
&lt;p&gt;At the other end of the eGFR spectrum  --  those with levels of 15 to 29.9 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;  --  proteinuria remained an independent predictor of death: Mortality rates were 10.4 per 1,000 with heavy proteinuria (95% CI 9.3 to 11.6) and 9.1 per 1,000 with mild proteinuria (95% CI 8.2 to 10.0) versus 6.7 per 1,000 with normal urine protein (95% CI 6.2 to 7.3).&lt;/p&gt;
&lt;p&gt;These death rates reflected adjustments for a host of potential confounding factors and comorbidities, including age, sex, diabetes, hypertension, liver disease, and cardiovascular conditions.&lt;/p&gt;
&lt;p&gt;Proteinuria also predicted myocardial infarction in patients stratified by eGFR, but not as strongly. In the group with eGFR above 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, rates of MI were 1.6 per 1,000 (95% CI 1.3 to 2.0) and 0.9 (95% CI 0.9 to 1.0) for heavy and normal urinary protein, respectively, as measured by dipstick.&lt;/p&gt;
&lt;p&gt;MI rates were also increased with proteinuria in participants with eGFR below 30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;, the researchers reported.&lt;/p&gt;
&lt;p&gt;End-stage renal disease was enormously more common with dipstick-measured heavy proteinuria, independent of baseline eGFR.&lt;/p&gt;
&lt;p&gt;Individuals with eGFR above 60 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; were diagnosed with the condition at a rate of 1.0 per 1,000 (95% CI 0.7 to 1.4) if they had heavy proteinuria, compared with 0.03 per 1,000 (95% CI 0.02 to 0.09) among those with normal urine protein.&lt;/p&gt;
&lt;p&gt;A five-fold difference in rates of end-stage renal disease was still apparent among those with eGFR below 30 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;: 65.9 (95% CI 52.3 to 82.9) versus 12.7 per 1,000 (95% CI 9.3 to 17.3) for heavy versus normal protein, respectively.&lt;/p&gt;
&lt;p&gt;These results were confirmed when cross-checked against the more accurate albumin-creatinine ratio, Hemmelgarn and colleagues indicated.&lt;/p&gt;
&lt;p&gt;Each 10-fold increase in albumin-creatinine ratio was associated with the following relative rates of the major study outcomes, after adjusting for eGFR:&lt;ul&gt; &lt;li&gt;Death: 1.22 (95% CI 1.21 to 1.24)&lt;/li&gt; &lt;li&gt;MI: 1.18 (95% CI 1.14 to 1.21)&lt;/li&gt; &lt;li&gt;Doubling of serum creatinine: 1.76 (95% CI 1.70 to 1.82)&lt;/li&gt; &lt;li&gt;End-stage renal disease: 1.92 (95% CI 1.81 to 2.04)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Hemmelgarn and colleagues noted several limitations to the study including the fact that the sample was restricted to outpatients undergoing laboratory evaluations for kidney function and urinary protein, and the data were based on single measurements. Missing were data on alcohol, tobacco, and antihypertensive drug use, which might have affected the findings.&lt;/p&gt;
&lt;p&gt;The researchers also indicated that the follow-up period may have been too short to fully evaluate risks of progression to kidney failure.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Support for the study came from the Alberta Heritage Foundation for Medical Research, the Canadian Institutes of Health Research, Alberta Health and Wellness, and internal funds.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_325"
                     title="MRI Reveals Risk for Kidney Failure in Diabetic Patients (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18195?impressionId=1265805584465"
                     
      So-called silent strokes, visible on cerebral MRI scans, predict kidney failure in patients with type 2 diabetes, Japanese researchers said.&lt;br&gt;
&lt;br&gt;After an average follow-up of 7.5 years, diabetic patients with evidence of small cerebral infarctions at baseline later suffered death or kidney failure at more than twice the rate seen in patients who had not had silent strokes, reported Takashi Uzu, MD, of Shiga University of Medical Sciences in Shiga, Japan, and colleagues.&lt;br&gt;
&lt;br&gt;Silent strokes are a consequence of cerebral microvascular disease and thus may logically accompany the development of similar abnormalities in renal blood vessels, ultimately leading to kidney failure, the researchers explained online in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;It is important to identify individuals who are at risk of progression of diabetic renal disease,&quot; Uzu and colleagues wrote.&lt;/p&gt;
&lt;p&gt;The current standard prognostic test is the albumin-creatinine ratio, but it is not entirely adequate for the purpose, they suggested: &quot;Recent clinical studies have shown that renal insufficiency can occur in the absence of microalbuminuria in patients with type 2 diabetes.&quot;&lt;/p&gt;
&lt;p&gt;But they acknowledged that brain MRI scans would be too expensive and inconvenient for routine prognostic testing.&lt;/p&gt;
&lt;p&gt;&quot;New strategies are needed to determine the presence of renal and/or extrarenal microvascular diseases,&quot; Uzu and colleagues wrote.&lt;/p&gt;
&lt;p&gt;Their study involved 608 patients with type 2 diabetes who had no clinical signs of cerebrovascular or cardiovascular disease or overt nephropathy. Their mean age at baseline was about 60 and the average glycated hemoglobin level was about 8.6%.&lt;/p&gt;
&lt;p&gt;Participants underwent cerebral MRI scans at baseline, with 177 showing evidence of silent cerebral infarctions, defined as focal lesions of at least 3 mm in diameter with low signal intensity on T1-weighted images and high intensity with T2 weighting. Dilated perivascular spaces were distinguished from infarcts with proton density scans. Patients with positive findings who had a history of stroke or transient ischemic attack were excluded.&lt;/p&gt;
&lt;p&gt;Those with silent infarctions at baseline differed significantly from other participants according to several parameters. Not surprisingly, patients with cerebral infarcts on average were somewhat older (63 versus 57), had had diabetes for a longer period of time (9.8 years versus 7.6), had higher blood pressure (146.8 mm Hg systolic versus 136.5 ), and were more likely to have a history of smoking (58% versus 46%). All differences were significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01.&lt;/p&gt;
&lt;p&gt;On the other hand, baseline fasting plasma glucose and glycated hemoglobin levels were both significantly lower in the patients who&apos;d had silent infarctions: mean 163 mg/dL versus 176 for glucose and 8.3% versus 8.7% for HbA1c (&lt;em&gt;P&lt;/em&gt;&amp;#8804;0.01 for both).&lt;/p&gt;
&lt;p&gt;Patients were followed for up to 10 years, with a mean of 7.5. The primary outcome was end-stage renal disease or death, and Uzu and colleagues chose a secondary outcome combining dialysis with doubling of serum creatinine.&lt;/p&gt;
&lt;p&gt;Kaplan-Meier curves for the patients with and without silent infarctions at baseline indicated that the primary outcome occurred at equal rates through the first four years of follow-up, but then the curves diverged abruptly.&lt;/p&gt;
&lt;p&gt;At year eight, approximately 6% of the noninfarcted group had experienced the primary outcome, compared with 21% of those who&apos;d had silent strokes (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), according to Uzu and colleagues.&lt;/p&gt;
&lt;p&gt;Curves for the secondary outcome began diverging by year three. At year eight, about 6% of the noninfarct participants had gone to dialysis or had serum creatinine levels double, whereas these endpoints occurred in nearly 30% of the infarct group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;Overall, the hazard ratio associated with baseline silent cerebral infarctions for the primary outcome during follow-up was 2.44 (95% CI 1.36 to 4.38).&lt;/p&gt;
&lt;p&gt;The hazard ratio for death alone was somewhat smaller (1.61, 95% CI 0.71 to 3.62), indicating that most of the risk measured by the primary outcome was actually in end-stage renal disease.&lt;/p&gt;
&lt;p&gt;For the secondary outcome, the hazard ratio was 4.79 (95% CI 2.72 to 8.46).&lt;/p&gt;
&lt;p&gt;All the hazard ratios reflected adjustments for age, sex, duration of diabetes, body mass index, smoking status, HbA1c, blood pressure, serum lipids, and standard lab indices of kidney function at baseline.&lt;/p&gt;
&lt;p&gt;Estimated glomerular filtration rate (eGFR) during follow-up also decreased faster in patients with silent strokes. After five years, mean eGFR had fallen by 8 ml/min/m&lt;sup&gt;2&lt;/sup&gt; in the patients without silent infarcts at baseline compared with 10.5 ml/min/m&lt;sup&gt;2&lt;/sup&gt; in those with cerebral microvascular disease.&lt;/p&gt;
&lt;p&gt;The researchers noted that the study was conducted at two clinical sites, which used somewhat different MRI procedures. But they also indicated that the prevalence of silent infarctions did not differ between the sites.&lt;/p&gt;
&lt;p&gt;Other limitations included use of an older creatinine assay, inclusion of larger silent infarcts which could reflect macrovascular disease, and more patients in the cerebral infarct group who were taking renin-angiotensin system blocking drugs, which have renal impairment as an adverse effect.&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;External funding for the study was not reported.&lt;/p&gt;&lt;p&gt;No potential conflicts of interest were reported.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265805584465"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors 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 authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_298"
                     title="FDA Updates Myeloma Drug Label for New Risks"
                     score="0.002"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18158?impressionId=1265805584465"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has revised dosage and safety information for bortezomib (Velcade), the myeloma and mantle cell lymphoma drug, to reflect an increased toxicity risk.&lt;/p&gt;
&lt;p&gt;The new labeling includes a warning for patients with moderate-to-severe hepatic impairment and now recommends at-risk patients start at a lower dosage of 0.7 mg for the first cycle of treatment and escalate to 1.0 mg, or reduce further to 0.5 mg, in subsequent cycles.&lt;/p&gt;
&lt;p&gt;The label has also been updated to include clinical study data showing a higher median survival rate in patients using a combination of bortezomib, melphalan, and prednisone versus a regiment of just melphalan and prednisone (&lt;em&gt;P&lt;/em&gt;=0.00084).&lt;/p&gt;
&lt;p&gt;The drug is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. The FDA also warns that women should avoid becoming pregnant while undergoing treatment with bortezomib.&lt;/p&gt;
&lt;p&gt;The drug is manufactured by Millennium: The Takeda Oncology Company of Cambridge, Mass.&lt;/p&gt;

    </recommendedItem>
</recommendedContent>
