<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_463"
                     title="AAPM: Online Program Helps Manage Pain (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18393?impressionId=1265791625609"
                     
      &lt;p&gt;SAN ANTONIO  --  A personalized, online self-management program helped patients with pain syndromes improve coping skills and reduce stress and depression in two studies reported here.&lt;/p&gt;
&lt;p&gt;Patients randomized to the self-management program demonstrated significant improvement in multiple social, emotional, and behavioral outcomes after six months (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01). Improvement in some parameters occurred within one month. A control group that was not exposed to the program showed no significant improvement.&lt;/p&gt;
&lt;p&gt;&quot;Our goal is to help people communicate better with providers, understand better how they can use social support, understand the comorbid conditions, like anxiety and depression, and develop cognitive skills to help get them through their pain episodes,&quot; said Emil Chiauzzi, PhD, of Inflexxion, the Newton, Mass. company that developed the program.&lt;/p&gt;
&lt;p&gt;Although the studies involved patients with migraine or low-back pain, programs are being developed for other types of pain condition, including several forms of neuropathic pain.&lt;/p&gt;
&lt;p&gt;The online program, demonstrated at &lt;a href=&quot;http://www.painACTION.com&quot; mce_href=&quot;http://www.painACTION.com&quot; target=&quot;_blank&quot;&gt;www.painACTION.com&lt;/a&gt;, employs patient-specific information to generate individualized self-management strategies.&lt;/p&gt;
&lt;p&gt;Patient responses to assessments are analyzed by a &quot;recommendation engine,&quot; which produces content recommendations designed to address each patient&apos;s informational and self-management needs.&lt;/p&gt;
&lt;p&gt;Elements on the Web site include multimedia education units, a pain inventory, interactive tools that provide information based on patient-provider communication, and medication risk management.&lt;/p&gt;
&lt;p&gt;&quot;The content on the Web site is focused on teaching people practical skills to manage the behavioral side of pain,&quot; Jonas Bromberg, PsyD, also of Inflexxion, said in an interview.&lt;/p&gt;
&lt;p&gt;Bromberg presented results of a randomized study involving 210 patients, all of whom met International Headache Society diagnostic criteria for migraine, with or without aura.&lt;/p&gt;
&lt;p&gt;Patients assigned to the online program completed at least eight 30-minute session during the first month of the study and at least five more 30-minute sessions during the five-month follow-up period. Patients in the control group continued to receive usual care without exposure to the Web site.&lt;/p&gt;
&lt;p&gt;Participants assigned to the online program had a minimum set of requirements for each session, which were provided at log-in. Follow-up assessments occurred at one, three, and six months.&lt;/p&gt;
&lt;p&gt;The two groups were balanced with respect to sex and headache frequency and severity, the researchers said.&lt;/p&gt;
&lt;p&gt;Bromberg reported that patients assigned to the self-management program demonstrated significant improvement in: &lt;ul&gt; &lt;li&gt;Headache self-efficacy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 compared with baseline)&lt;/li&gt; &lt;li&gt;Use of relaxation (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Use of social support (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Pain catastrophizing (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Depression (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Stress (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Chiauzzi presented results from a randomized study of 209 patients with low-back pain. The design was similar to that of the migraine study, except results were analyzed for between-group differences.&lt;/p&gt;
&lt;p&gt;The results showed significant improvement in the study group versus control group with respect to: &lt;ul&gt; &lt;li&gt;Stress (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Coping (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01)&lt;/li&gt; &lt;li&gt;Social supports (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The data showed significant effects of both treatment (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) and time (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01) favoring the Web site versus control. Chiauzzi said patients assigned to the Web site had greater mean improvement at posttest, three months, and six months.&lt;/p&gt;
&lt;p&gt;Qualitative analysis suggested that Web site participants had clinically meaningful improvement in depression, anxiety, and stress.&lt;/p&gt;
&lt;p&gt;Additionally, patients in the self-management program reported a 12.3% decrease in pain from baseline, versus 7% in the control group.&lt;/p&gt;
&lt;p&gt;Access to the Web site did not improve physical functioning.&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 were funded by the National Institutes of Health.&lt;/p&gt;&lt;p&gt;Chiauzzi and Bromberg are employees of Inflexxion, developer of the online program.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_419"
                     title="AAPM: Help for Pain and Mood in Fibromyalgia (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18334?impressionId=1265791625609"
                     
      &lt;p&gt;SAN ANTONIO  --  Patients with fibromyalgia and comorbid depression had significant improvement in both conditions when treated with duloxetine (Cymbalta), according to pooled data from four clinical trials presented here at the American Academy of Pain Medicine meeting.&lt;/p&gt;
&lt;p&gt;The magnitude of improvement in pain was consistent across all severity levels of depression. Conversely, patient mood improved to a similar extent across the range of pain severity.&lt;/p&gt;
&lt;p&gt;Analysis of treatment effect showed that 60% to 70% of the benefit for pain and mood resulted from a direct effect of the drug. The remaining 30% to 40% of improvement arose from an indirect effect.&lt;/p&gt;
&lt;p&gt;&quot;Improvement in pain and improvement in major depressive disorder are positively correlated,&quot; Lauren B. Marangell, MD, of Eli Lilly &amp;amp; Co. in Indianapolis, and colleagues reported in a poster presentation.&lt;/p&gt;
&lt;p&gt;&quot;Improvement in pain reflected greater direct treatment effect with an indirect effect of improved mood, indicating that the improvement seen with duloxetine in fibromyalgia is not solely a mood effect. Improvement in mood was found to reflect a greater direct treatment effect, with an indirect effect of pain improvement.&quot;&lt;/p&gt;
&lt;p&gt;&quot;These data support the independent analgesic properties of duloxetine in the treatment of fibromyalgia.&quot;&lt;/p&gt;
&lt;p&gt;As many as a third of patients with fibromyalgia have comorbid major depression, and as many as 70% have a history of major depression. Sorting out the association between the two conditions is complicated by the fact that the pain can obscure the depression and lead to underdiagnosis and undertreatment, the researchers wrote.&lt;/p&gt;
&lt;p&gt;On the other hand, major depression can intensify as pain interferes with daily activities, and comorbid depression can lead to increased pain complaints, intensity, and duration among patients with fibromyalgia, they noted.&lt;/p&gt;
&lt;p&gt;In an effort to clarify the clinical course of patients with both conditions, Marangell and colleagues analyzed data from four placebo-controlled clinical trials of duloxetine in patients with fibromyalgia. They limited the analysis to patients who had comorbid major depression at enrollment and who received 60 to 120 mg of duloxetine.&lt;/p&gt;
&lt;p&gt;The investigators performed two path analyses to determine the direct and indirect treatment effects on pain and on depression.&lt;/p&gt;
&lt;p&gt;The study involved 350 patients with fibromyalgia and comorbid depression, 147 randomized to placebo, and 203 to duloxetine. Baseline characteristics included a median Hamilton depression (HAMD) score of 15 and a Brief Pain Inventory (BPI) average of 6 to 7.&lt;/p&gt;
&lt;p&gt;The analysis showed that about half of the patients with a HAMD score above or below the median had &amp;#8805;30% improvement in pain score.&lt;/p&gt;
&lt;p&gt;Moreover, 35% to 40% of patients treated with duloxetine had &amp;#8805;50% improvement in pain score whether they had a low (HAMD &amp;lt;15) or high (HAMD &amp;#8805;15) depression scores.&lt;/p&gt;
&lt;p&gt;All of the differences from placebo were statistically significant (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05) except for &amp;#8805;30% improvement in patients with a low depression score at baseline.&lt;/p&gt;
&lt;p&gt;Patients&apos; depression improvement by baseline pain severity did not differ significantly between patients treated with duloxetine or placebo.&lt;/p&gt;
&lt;p&gt;Response was defined as a 50% reduction in the HAMD or Beck Depression Inventory. Moderate pain was defined as a BPI score &amp;#8804;4 to &amp;lt;7, and a score of 7 or higher was severe.&lt;/p&gt;
&lt;p&gt;About 35% to 40% of duloxetine patients met depression response criteria, regardless of baseline pain severity. About 25% to 30% of placebo-treated patients also met response criteria for depression.&lt;/p&gt;
&lt;p&gt;Path analysis showed that 68.7% of pain improvement was attributable to a direct treatment effect of duloxetine and 31.3% to an indirect effect on major depression.&lt;/p&gt;
&lt;p&gt;A direct treatment effect of duloxetine accounted for 59.9% of mood improvement, and the remaining 40.1% of improvement was related to the drug&apos;s effect on 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 Eli Lilly and Boehringer Ingelheim.&lt;/p&gt;&lt;p&gt;Marangell and several co-investigators are employees of Eli Lilly.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_415"
                     title="AAPM: Drug for Fibromyalgia Boosts Multiple Outcomes (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18327?impressionId=1265791625609"
                     
      &lt;p&gt;SAN ANTONIO  --  The fibromyalgia drug milnacipran (Savella) achieved clinically meaningful reductions in pain throughout almost four months of randomized therapy, a post-hoc analysis of daily pain control showed.&lt;/p&gt;
&lt;p&gt;Half of patients treated with the serotonin/norepinephrine reuptake inhibitor had at least a 30% improvement in pain scores at 15 weeks, and 35% to 40% had at least a 50% improvement, according to analyses reported here at the American Academy of Pain Medicine meeting.&lt;/p&gt;
&lt;p&gt;Two different doses of milnacipran led to at least 30% improvement in pain on almost half of the days during the randomized trial. Patients treated with milnacipran had at least 50% improvement during 30% of the days.&lt;/p&gt;
&lt;p&gt;&quot;A 30% improvement in pain is clinically significant, and half the patients treated with milnacipran attained that level of pain relief,&quot; Aroon Datta, MD, of Forest Laboratories in Jersey City, N.J., said in an interview. &quot;Even when the more stringent criteria of 50% improvement were applied, significantly more patients in the milnacipran groups achieved that threshold compared with placebo.&quot;&lt;/p&gt;
&lt;p&gt;&quot;By any measure, it is fair to say that patients treated with milnacipran had significantly better pain control,&quot; he added.&lt;/p&gt;
&lt;p&gt;Milnacipran is chemically similar to the antidepressant venlafaxine (Effexor). However, milnacipran has three times the power to inhibit norepinephrine reuptake. The drug was approved in 2009 for treatment of fibromyalgia.&lt;/p&gt;
&lt;p&gt;Datta reported results of a post-hoc analysis of data from two randomized, placebo-controlled clinical trials. One lasted 27 weeks, and the other had a 15-week follow-up.&lt;/p&gt;
&lt;p&gt;In the 27-week trial, approximately 900 patients were randomized 1:1:2 to placebo, milnacipran 100 mg/d (50 mg BID), or milnacipran 200 mg/d (100 mg BID). In the 15-week trial, 1,200 patients were randomized in equal proportion to placebo and the two doses of milnacipran.&lt;/p&gt;
&lt;p&gt;Patients recorded their pain level several times a day by means of an electronic diary. They rated their pain according to a visual analog scale (VAS) with a range of 0 to 100.&lt;/p&gt;
&lt;p&gt;The post-hoc analysis centered on outcomes at 15 weeks in both trials. The primary outcomes were change from baseline in weekly 24-hour VAS pain score, the proportion of patients who achieved &amp;#8805;30% and &amp;#8805;50% improvement in the VAS pain score, and the proportion of days with &amp;#8805;30% and &amp;#8805;50% improvement in pain.&lt;/p&gt;
&lt;p&gt;In the longer trial, the change in the weekly average of 24-hour recall of VAS scores differed significantly in both milnacipran groups within two weeks, and the difference was maintained through 15 weeks (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Significant differences emerged within the first week in the second trial and persisted through week 15 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;In both trials, 52% of patients assigned to 100 mg of milnacipran and 56% of those assigned to 200 mg had &amp;#8805;30% improvement in pain scores, compared with 40% to 42% of placebo-treated patients (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;When the more stringent criterion of &amp;#8805;50% improvement was used, 31% to 35% of the 100-mg milnacipran patients achieved that goal, as did 36% to 37% of patients treated with 200 mg.&lt;/p&gt;
&lt;p&gt;About 25% of placebo patients had &amp;#8805;50% improvement. Only the 200-mg dose differed significantly from placebo (&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;A similar pattern emerged in evaluation of the proportion of days with threshold pain reductions. Milnacipran-treated patients had &amp;#8805;30% improvement on 44% to 47% of days in the trial and &amp;#8805;50% improvement on 25% to 30% of days.&lt;/p&gt;
&lt;p&gt;For both thresholds, milnacipran was significantly better than placebo, whose patients had &amp;#8805;30% pain improvement on about a third of days and &amp;#8805;50% improvement on fewer than 20% of days (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.01 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Datta also reported findings from a randomized, placebo-controlled clinical trial evaluating the pain relief afforded by the 100-mg daily dose of milnacipran. The study involved 1,025 patients with fibromyalgia randomized to placebo or active therapy.&lt;/p&gt;
&lt;p&gt;The trial had two principal 12-week efficacy outcomes: the composite of &amp;#8805;30% improvement in pain and the Patient Global Impression of Change (PGIC), and the composite of the same two outcomes plus improvement &amp;#8805;6 points on the physical function component of the SF-36 health assessment survey.&lt;/p&gt;
&lt;p&gt;The principal efficacy analysis used baseline observation carried forward (BOCF) for patients with missing data. By that statistical method, 29% of milnacipran patients were responders compared with 18% of the placebo group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;An analysis that employed last observation carried forward (LOCF) showed response rates of 33% with milnacipran and 19&lt;strong&gt;%&lt;/strong&gt; with placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;An analysis of observed cases resulted in response rates of 42% versus 26% (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Similar results emerged from analyses of the three-measure outcome. Milnacipran led to significantly higher (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) response rates by BOCF (20% versus 11%), by LOCF (28% versus 12%), and by observed cases (30% versus 16%).&lt;/p&gt;
&lt;p&gt;Milnacipran therapy also led to significantly higher (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) response rates for each component of the composite outcomes: &amp;#8805;30% improvement in pain (45% versus 31%), PGIC (42% versus 26%), and &amp;#8805;6-point improvement in physical function (40% versus 31%).&lt;/p&gt;
&lt;p&gt;The results indicate that milnacipran 100 mg (50 mg BID) could offer an alternative for patients who cannot tolerate the FDA-approved 200-mg dose, said Datta. If physicians choose to start patients on 100 mg and then titrate up to the approved dose, that also would appear feasible, he 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;The studies were supported by Forest Laboratories and Cypress Bioscience.&lt;/p&gt;&lt;p&gt;All but two of the authors are employees of the study sponsors.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_397"
                     title="AAPM: Nerve Growth Factor Antibody  May Reduce Pain (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18300?impressionId=1265791625609"
                     
      &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="20090101_2_647"
                     title="Exercise and Education a Boost to Women With Fibromyalgia"
                     score="-0.005"
                     href="