<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_397"
                     title="AAPM: Nerve Growth Factor Antibody  May Reduce Pain (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18300?impressionId=1265786327469"
                     
      &lt;p&gt;SAN ANTONIO  --  A humanized monoclonal antibody against nerve growth factor provided relief in three chronic pain syndromes, according to a summary of small studies reported as an abstract here.&lt;/p&gt;
&lt;p&gt;Treatment with tanezumab led to statistically or clinically significant reductions in pain for patients with osteoarthritis, chronic lower back pain, and interstitial cystitis. The most common adverse events were transient abnormal peripheral sensations, which generally occurred only after the first infusion.&lt;/p&gt;
&lt;p&gt;&quot;Patients with these three different pain syndromes all had significant improvement when treated with tanezumab,&quot; Leslie Tive, PhD, of Pfizer, said in an interview at the American Academy of Pain Medicine meeting. &quot;The pain relief was sustained over time, and patient acceptance was good.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Nerve growth factor is increased in many types of chronic pain and therefore represents an attractive target for therapy,&quot; she added. &quot;Tanezumab is being evaluated in some of these other conditions in ongoing studies.&quot;&lt;/p&gt;
&lt;p&gt;A small phase I study showed that the humanized monoclonal antibody resulted in significant pain improvement in patients with osteoarthritis (&lt;em&gt;Arthritis Rheum&lt;/em&gt; 2005; 52: S461). Tive presented data from a phase II trial involving 400 patients with osteoarthritis of the knee. They were randomized to placebo or to one of five tanezumab doses, administered on day one and day 56.&lt;/p&gt;
&lt;p&gt;All five doses of tanezumab resulted in significant reductions (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) versus placebo after one week and were sustained through 16 weeks. As assessed by a visual analog scale, the mean change in pain on walking from baseline to week 16 ranged from 30 to 45 points (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), a two- to threefold difference compared with placebo.&lt;/p&gt;
&lt;p&gt;The trial in chronic low back pain involved 217 adults with Quebec Task Force on Spinal Disorders category 1 or 2 pain for at least three months. The primary location of the pain was between the 12th thoracic vertebra and the lower gluteal folds.&lt;/p&gt;
&lt;p&gt;Eligibility criteria included a score of at least 4 on an 11-point pain scale on at least four occasions in the five days before randomization, as indicated by entries in an electronic pain diary.&lt;/p&gt;
&lt;p&gt;Patients were randomized 2:2:1 to a single infusion of tanezumab, to oral naproxen, or to placebo. The primary endpoint was the change in mean Lower Back Pain Index score from baseline to six weeks, averaged over the last seven days.&lt;/p&gt;
&lt;p&gt;Beginning at week one and continuing through week six, patients who were randomized to either dose of tanezumab had significantly greater improvement in pain than those who took the placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), and compared with the naproxen group beginning at week two (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01).&lt;/p&gt;
&lt;p&gt;The interstitial cystitis study included 64 men and women who had a score &amp;#8805;13 on Pelvic Pain Symptom/Frequency questionnaire, &amp;#8805;7 score on the O&apos;Leary-Sant Interstitial Cystitis index, and micturition frequency &amp;#8805;8 times a day, as recorded in an electronic diary for at least five consecutive days prior to randomization.&lt;/p&gt;
&lt;p&gt;Patients were randomized to intravenous tanezumab or matching placebo. The primary efficacy endpoint was change from baseline to six weeks in the 11-point pain scale. A difference of at least one point from placebo was considered clinically significant. Statistical significance was not evaluated.&lt;/p&gt;
&lt;p&gt;The mean difference between tanezumab and placebo was -0.7 at week two, increasing to -1.1 at week four and -1.4 at week six. The advantage versus placebo was maintained at week 10 (-0.9) and week 16 (-0.5).&lt;/p&gt;
&lt;p&gt;Adverse events were evaluated for all patients combined in the three studies. Adverse events were reported by 66.3% of tanezumab patients, 61.4% of naproxen patients, and 59.3% of placebo patients. Serious and severe adverse events occurred in 1.6% to 3.4% of patients and 4.8% to 5.7%, respectively.&lt;/p&gt;
&lt;p&gt;Tive said 14.4% of tanezumab patients reported abnormal peripheral sensations, the most common being paresthesia (7.1%), hyperesthesia (4.1%), and hypoesthesia (3.9%).&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 studies included in the summary were funded by Pfizer.&lt;/p&gt;&lt;p&gt;Investigators included several Pfizer employees.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_376"
                     title="Stress of Prostate Cancer Diagnosis May Be Deadly (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/HematologyOncology/ProstateCancer/tb/18268?impressionId=1265786327469"
                     
      Men have a slightly, but statistically significant, increased risk of dying from cardiovascular disease in the year after learning they have prostate cancer, researchers found.&lt;br&gt;
&lt;br&gt;The risk was greatest in the first month after diagnosis (standardized mortality ratio 2.05, 95% CI 1.89 to 2.22), Lorelei Mucci, PhD, of Brigham and Women&apos;s Hospital in Boston, and colleagues reported online in the &lt;em&gt;Journal of the National Cancer Institute&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;The study, which covered diagnoses made from 1979 through 2004, also found an overall increased risk of suicide in the year following a prostate cancer diagnosis (SMR 1.4, 95% CI 1.2 to 1.6), although the association was not significant after screening for prostate specific antigen (PSA) became widespread.&lt;br&gt;
&lt;br&gt;The findings&lt;em&gt;&lt;/em&gt; are &quot;one additional piece in weighing the pros and cons of PSA screening,&quot; Mucci said in an interview.&lt;br&gt;
&lt;br&gt;She also said that, &quot;not only do [clinicians] need to be treating the cancer, but they need to be thinking about the social support and other support that men may need to deal with this stressful event.&quot;&lt;p&gt;&lt;/p&gt;
&lt;p&gt;A previous study by Mucci&apos;s group that looked at a Swedish population found similarly increased risks of suicide and cardiovascular death following a prostate cancer diagnosis.&lt;/p&gt;
&lt;p&gt;Because PSA testing is more extensive in the U.S., increasing the number of early-stage and indolent cancers detected, the researchers wanted to see whether the results would carry over.&lt;/p&gt;
&lt;p&gt;Using the Surveillance, Epidemiology, and End Results (SEER) Program, they looked at data from 342,497 men who were diagnosed with prostate cancer from 1979 through 2004.&lt;/p&gt;
&lt;p&gt;The number of diagnoses steadily increased throughout the study period  --  from 6,106 in 1979 to 17,688 in 2004.&lt;/p&gt;
&lt;p&gt;But the percentage of cancers that were metastatic dropped from 18.2% in the pre-PSA period (1979 to 1986) to 5% in the period of widespread testing (1993 to 2004).&lt;/p&gt;
&lt;p&gt;During the study, 148 men committed suicide within one year of learning their diagnosis, higher than the 105.2 that would be expected in the general U.S. male population.&lt;/p&gt;
&lt;p&gt;The elevated risk was only evident prior to 1993, when PSA testing became more widely used. The authors suggested that this was likely because of the potentially lower degree of stress associated with the diagnosis of indolent prostate cancer.&lt;/p&gt;
&lt;p&gt;&quot;So that&apos;s reassuring,&quot; Mucci said.&lt;/p&gt;
&lt;p&gt;However, another 6,845 men died of cardiovascular disease, which was also higher than the expected 6,282.9.&lt;/p&gt;
&lt;p&gt;Contrary to the findings regarding suicide, the risk of cardiovascular death in the first month after hearing a diagnosis was significantly increased throughout the study period.&lt;/p&gt;
&lt;p&gt;Prostate cancer patients who were not married at the time of diagnosis had higher relative risks of both suicide and cardiovascular death than married patients.The authors suggested that this may be because &quot;having someone close to confide in might alleviate the psychological stress experienced from receiving a cancer diagnosis.&quot;&lt;/p&gt;
&lt;p&gt;They also observed a clear trend between higher relative risks for suicide and cardiovascular death among patients diagnosed with a metastatic tumor, which clearly would be more stressful than diagnosis of a clinically localized tumor.&lt;/p&gt;
&lt;p&gt;&quot;This finding might further explain the decreasing excess risks that have been observed in the PSA era, in which the proportion of advanced tumors was small (i.e., 18.2% metastatic tumors in the pre-PSA era and 5.0% in the PSA era),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Risk of cardiovascular death was magnified for patients with metastatic tumors (SMR 3.22, 95% CI 2.68 to 3.84) compared with those with local or regional tumors (SMR 1.57, 95% CI 1.42 to 1.74)(&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Prostate cancer patients who were not married at the time of diagnosis had higher relative risks of both suicide and cardiovascular death than married patients.&lt;/p&gt;
&lt;p&gt;The authors acknowledged some limitations of the study, including the lack of a cancer-free group as reference and the lack of information on physical or mental health status, other prevalent disorders or comorbid illness at diagnosis, and prostate cancer treatment.&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 received funding from the Swedish Council for Working Life and Social Research.&lt;/p&gt;&lt;p&gt;The authors 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="20100101_19_364"
                     title="ADT for Prostate Cancer Raises Heart Risks"
                     score="0.007"
                     href="http://www.medpagetoday.com/Urology/ProstateCancer/tb/18250?impressionId=1265786327469"
                     
      &lt;p&gt;Androgen deprivation therapy (ADT) for prostate cancer can exacerbate cardiac risk factors and may increase the risk of heart attack and cardiac death, according to an advisory supported by four medical organizations.&lt;/p&gt;
&lt;p&gt;However, the groups did not offer specific guidelines for clinicians on when to employ ADT therapy or avoid it.&lt;/p&gt;
&lt;p&gt;Clinical trials have shown that ADT increases body weight, decreases lean mass and increases fat mass, reduces insulin sensitivity, and triggers or worsens dyslipidemia.&lt;/p&gt;
&lt;p&gt;Several studies have demonstrated a significant increase in cardiovascular death in prostate cancer patients treated with hormonal therapy or bilateral orchiectomy, although some studies have shown no association between ADT and increased cardiovascular risk, according to a report that will appear in the Feb. 16 issue of &lt;em&gt;Circulation: Journal of the American Heart Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Some evidence also suggests ADT may predispose men to metabolic syndrome.&lt;/p&gt;
&lt;p&gt;&quot;Based on current data, it was appropriate to conclude that there may be a relationship between ADT therapy in patients with prostate cancer and future cardiovascular risk,&quot; Glenn N. Levine, MD, of Baylor College of Medicine in Houston and chair of the advisory writing committee, said in a statement.&lt;/p&gt;
&lt;p&gt;The writing committee comprised representatives of the American Heart Association, American Urological Association, and American Cancer Society. Additionally, the American Society for Radiation Oncology endorsed the advisory.&lt;/p&gt;
&lt;p&gt;The authors&apos; review of literature showed that ADT increased cardiovascular risk in 1% to 6% of various studies&apos; patient populations. With that in mind, &quot;the decision about whether to initiate ADT should be based on weighing the benefits of therapy with this potential modest risk,&quot; Levine said.&lt;/p&gt;
&lt;p&gt;The decision to initiate ADT should remain with the physician who has responsibility for treating a patient with prostate cancer, the authors wrote. That includes patients with known cardiac disease.&lt;/p&gt;
&lt;p&gt;&quot;It is the consensus of the writing group that there is no clear indication for patients for whom ADT is believed to be beneficial to be referred to internists, endocrinologists, or cardiologists for evaluation before initiation of ADT,&quot; the authors said.&lt;/p&gt;
&lt;p&gt;&quot;The decision as to whether or not to initiate ADT in patients with cardiac disease, in whom the benefits of therapy would be weighed against any possible risks, is most appropriately made by the physician treating the patient for prostate cancer.&quot;&lt;/p&gt;
&lt;p&gt;However, the potential adverse metabolic effects warrant periodic evaluation by a patient&apos;s primary care physician, they added.&lt;/p&gt;
&lt;p&gt;Noting a lack of clinical guidance for follow-up of patients treated with ADT, the advisory authors concluded that at least an annual assessment of blood glucose and lipids seems reasonable. They also called for prospective assessment of cardiovascular risk factors before and after ADT is begun in future clinical trials.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_336"
                     title="In Prostate CA, Sexual Decline After Radiation Has Limit (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/HematologyOncology/ProstateCancer/tb/18214?impressionId=1265786327469"
                     
      &lt;p&gt;Sexual function declines in the first two years after external beam radiation therapy for prostate cancer but stabilizes thereafter, according to data from a prospective cohort study.&lt;/p&gt;
&lt;p&gt;All parameters of sexual function declined significantly (&lt;em&gt;P&lt;/em&gt;&lt;0.05) in the first two years after external-beam radiation therapy (EBRT), Richard Valicenti, MD, of the University of California Davis, and colleagues found.&lt;/p&gt;
&lt;p&gt;But for years two through six of follow-up, none of the evaluated parameters of sexual function changed significantly.&lt;/p&gt;
&lt;p&gt;Pretreatment sexual function was the strongest predictor of sexual function at any time after EBRT, the investigators reported in the January issue of the &lt;em&gt;International Journal of Radiation Oncology*Biology*Physics&lt;/em&gt;&lt;em&gt;&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Their findings debunk the perception that sexual function declines continually after radiation therapy for prostate cancer.&lt;/p&gt;
&lt;p&gt;&quot;The results of this study allow patients and their partners to have a fuller understanding of the long-term sexual side effects of EBRT, and what they can expect after treatment should aid in deciding on a treatment course,&quot; Valicenti said in a statement.&lt;/p&gt;
&lt;p&gt;Reported rates of impotency after EBRT for prostate cancer have ranged from 8% to 85%, a variation the authors attributed to the different instruments used to assess sexual function. Moreover, many studies included men who received androgen deprivation therapy in addition to EBRT, possibly masking the contributions of radiation therapy to changes in sexual function.&lt;/p&gt;
&lt;p&gt;Several recent studies have suggested that rates of sexual dysfunction increase with follow-up. However, few studies included pretreatment assessment of sexual function or conducted serial assessments of sexual function after EBRT, the authors wrote.&lt;/p&gt;
&lt;p&gt;To shed more light on the question, the investigators prospectively followed 143 men who completed a sexual function questionnaire prior to EBRT for prostate cancer and at each follow-up visit. The questionnaire assessed four domains of sexual function: sexual drive, erectile function, ejaculatory function, and overall satisfaction.&lt;/p&gt;
&lt;p&gt;The mean age of the patients was 69, median Gleason score was 6, and median total radiation dose was 73.8 Gy (range of 66.6 to 79.2 Gy).&lt;/p&gt;
&lt;p&gt;During a median four-years of follow-up, the study participants completed a total of 1,187 questionnaires. Some patients were followed for as long as eight years after EBRT.&lt;/p&gt;
&lt;p&gt;Baseline scores for sexual drive and erectile function were significantly associated with patient age (&lt;em&gt;P&lt;/em&gt;=0.003 and &lt;em&gt;P&lt;/em&gt;=0.004, respectively). Ejaculatory function was significantly associated with age, race, and marital status (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05).&lt;/p&gt;
&lt;p&gt;Scores on all four domains of sexual function, as well as the total score, declined significantly in the first two years after EBRT (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) compared with baseline values.&lt;/p&gt;
&lt;p&gt;Investigators grouped the patients according to baseline sexual function. Analysis of scores for patients above and below the median sexual function value showed that differences in sexual function persisted over time. Regression analysis showed that baseline score was the best predictor of later scores for all of the domains assessed (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;A separate analysis of scores from years two through six showed no significant changes in any of the domains: sexual drive, &lt;em&gt;P&lt;/em&gt;=0.067; erectile function, &lt;em&gt;P&lt;/em&gt;=0.5; ejaculatory function, &lt;em&gt;P&lt;/em&gt;=0.6; and overall satisfaction, &lt;em&gt;P&lt;/em&gt;=0.44.&lt;/p&gt;
&lt;p&gt;Baseline scores indicated that 74.1% of the study participants were sexually potent before EBRT. Among those who were potent before treatment, 74.4% remained potent at one year and 70.4% at two years after EBRT. The one- and two-year potency rates differed significantly from baseline, but the investigators found no statistically significant change in potency from years two through six.&lt;/p&gt;
&lt;p&gt;&quot;Our data have indicated that the widely held opinion that sexual function has a slow, progressive decline after EBRT might be incorrect,&quot; the authors wrote in conclusion. &quot;Most sexual function decline in men undergoing EBRT for prostate cancer occurred in the first two years after treatment and all domains of sexual function, including erectile dysfunction, then appeared to stabilize.&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 reported 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_288"
                     title="SSRIs Affect Breast Milk Production (CME/CE)"
                     score="0.001"
                     href="http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/tb/18149?impressionId=1265786327469"
                     
      &lt;p&gt;Women taking selective serotonin reuptake inhibitor (SSRI) antidepressants may experience delays in postpartum breast milk production, researchers said.&lt;/p&gt;
&lt;p&gt;Delayed secretory activation occurred in 87.5% of a small group of women taking SSRIs, compared with 43.5% of those not taking the drugs (RR 2, 95% CI 1.51 to 2.67, &lt;em&gt;P&lt;/em&gt;=0.02), according to Aaron M. Marshall, PhD, of the University of Cincinnati.&lt;/p&gt;
&lt;p&gt;The relative risk of delayed activation remained significantly higher (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) among SSRI users after adjustment for maternal age, obesity, cesarean delivery, infant gestational age, and infant breastfeeding behavior, the researchers reported online in the &lt;em&gt;Journal of Clinical Endocrinology and Metabolism&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;An early breastfeeding difficulty faced by many women, particularly those who are primiparous, is milk secretion delayed beyond 72 hours postpartum.&lt;/p&gt;
&lt;p&gt;These women also are at risk of early cessation of breastfeeding. In fact, only 11% of mothers in the U.S. breastfeed exclusively for the recommended six months.&lt;/p&gt;
&lt;p&gt;Studies in animal models and cell cultures suggested that serotonin (5-HT) is an important local regulator of lactation homeostasis, and the 5-HT transporter is expressed in mammary tissue at the apical membrane of epithelial cells.&lt;/p&gt;
&lt;p&gt;Serotonin is controlled intracellularly by a balance between synthesis and degradation, while extracellularly its availability is controlled through recycling by the 5-HT transporter.&lt;/p&gt;
&lt;p&gt;The 5-HT transporter also is the target for the most commonly prescribed class of antidepressants in the U.S. and other developed countries. These SSRI antidepressants are typically used to treat postpartum depression.&lt;/p&gt;
&lt;p&gt;The investigators conducted in vitro and animal studies to establish that the 5-HT transporter is expressed in breast tissue, particularly in the apical membranes of mammary epithelial cells, and that pharmacologic inhibition of the transporter disrupts tight junctures leading to a local involution-like effect.&lt;/p&gt;
&lt;p&gt;To examine the potential effect of SSRI inhibition on milk production in women, Marshall and colleagues enrolled 431 mothers as part of a longitudinal cohort study examining barriers to early lactation success.&lt;/p&gt;
&lt;p&gt;All were expecting their first live-born infants, had no known absolute contraindication to breastfeeding, and were at least 19 years old.&lt;/p&gt;
&lt;p&gt;Women taking SSRIs were more likely to have scored higher on a depressive symptom scale (as expected), and were somewhat more likely to be obese or to have had a cesarean delivery.&lt;/p&gt;
&lt;p&gt;Participating mothers were visited between 72 and 96 hours after giving birth to assess their breastfeeding experience and to determine the timing of secretory activation, and then seen again one week later.&lt;/p&gt;
&lt;p&gt;Delayed secretory activation was defined as initiation more than 72 hours postpartum.&lt;/p&gt;
&lt;p&gt;Median onset of secretory activation among the SSRI-treated mothers was 85.8 hours compared with 69.1 hours in mothers not using the drugs (&lt;em&gt;P&lt;/em&gt;=0.004).&lt;/p&gt;
&lt;p&gt;Eight women reported regular use of an SSRI medication. Seven experienced definite delayed secretory activation, and the eighth reported activation at 72 hours and therefore did not meet the defined cutoff for delayed activation.&lt;/p&gt;
&lt;p&gt;All women taking SSRIs had experienced secretory activation by their second visit a week after the first interview.&lt;/p&gt;
&lt;p&gt;The researchers noted that most studies on the effects of SSRI use during pregnancy and lactation have focused on the risks for developmental defects or whether the drugs passed into milk during lactation.&lt;/p&gt;
&lt;p&gt;This study, they said, is the first to report data on another important aspect of SSRI use during the peripartum, the effect on milk production.&lt;/p&gt;
&lt;p&gt;They concluded that the risk of delayed secretory activation was twice as great among primiparous women using an SSRI medication, and although the fraction of women taking the drugs was small, the risk was significant and remained so after adjustment for potential confounding factors.&lt;/p&gt;
&lt;p&gt;Further examination of this relationship is needed in larger groups of mothers, the researchers said, and in studies to determine if there are differences among the antidepressant medications.&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;This work was supported by the National Institutes of Health, the USDA Cooperative State Research, Education, and Extension Service, and the Department of Health and Human Services.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>