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    <recommendedItem id="20100101_19_341"
                     title="Doctor&apos;s Orders: Brain&apos;s Wiring Makes Change Hard"
                     score="0.009"
                     href="http://www.medpagetoday.com/Psychiatry/Addictions/tb/18207?impressionId=1265738432162"
                     
      &lt;p&gt;Doctor&apos;s Orders&lt;em&gt; is a feature in the collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;. In this monthly segment we explore medical issues of interest to physicians and their patients alike. This month, we look at addiction and addictive behaviors, and what neuroimaging studies have revealed about why it&apos;s so hard to break bad habits. &lt;/em&gt;&lt;/p&gt;&lt;hr&gt;

&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;

&lt;p&gt;By the end of January, many New Year&apos;s resolutions have been tossed out with the leftover holiday cookies. That&apos;s because change is hard  --  and neuroscientists are learning why.&lt;br&gt;
&lt;br&gt;Advances in neuroimaging have enabled researchers to peer inside the brains of addicts and patients with addictive behaviors. They can see in real-time what gets patients hooked: how the brain&apos;s reward system  --  based largely on the neurotransmitter dopamine  --  thirsts for more, while inhibitory control centers experience a system failure.&lt;br&gt;
&lt;br&gt;The pattern is similar across all kinds of behaviors  --  from cocaine and tobacco addiction to overeating. That&apos;s why changing your mind may be the first step toward breaking a habit, but altering the brain&apos;s neural machinery is the real challenge.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Hijacked Pathways&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Drug-taking and other addictive behaviors &quot;hijack&quot; the brain&apos;s reward system, says Petros Levounis, MD, director of the Addiction Institute of New York at St. Luke&apos;s and Roosevelt Hospitals in Manhattan.&lt;/p&gt;
&lt;p&gt;In normal patients, dopamine plays a major role in motivation and reward, surging before and during a pleasurable activity  --  say, eating or sex  --  to make patients want to repeat a behavior that&apos;s crucial to the survival of the species.&lt;/p&gt;
&lt;p&gt;Dopaminergic pathways connect the limbic system, responsible for emotion, with the hippocampus, etching rewarding behaviors into the brain by creating strong, salient memories.&lt;/p&gt;
&lt;p&gt;The problem arises when the memory and the craving to recapture it takes over a person&apos;s life.&lt;/p&gt;
&lt;p&gt;&quot;Imagine what a strong hold these hijacked reward pathways take on our brains and our whole existence when they&apos;re so closely connected, geographically and anatomically speaking, with our memories and our emotions,&quot; Levounis says.&lt;/p&gt;
&lt;p&gt;As the dopamine surge repeats and repeats, it gains speed, but the brakes begin to fail: Normal function in the brain&apos;s frontal lobes, responsible for inhibitory control and executive functioning (read: willpower), tends to decrease in addicts.&lt;/p&gt;
&lt;p&gt;&quot;Ultimately,&quot; Levounis says, &quot;the war on drugs is a war between the hijacked reward pathways that push the person to want to use, and the frontal lobes, which try to keep the beast at bay. That is the essence of addiction.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Similar Patterns&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;These neural pathways have been well studied in the brains of hardcore addicts. Now, researchers say they see similar pathways involved in other bad behaviors.&lt;/p&gt;
&lt;p&gt;Gene-Jack Wang, MD, of Brookhaven National Laboratory on New York&apos;s Long Island, has conducted several brain imaging studies of obese patients using PET-CT scans.&lt;/p&gt;
&lt;p&gt;The scans have revealed similarities in brain activity  --  or a lack thereof  --  between patients addicted to cocaine or alcohol, and those &quot;addicted&quot; to eating. Normally, the PET scan lights up when a contrast of radioactive glucose is metabolized, revealing an area of red activity in the center of the brain.&lt;/p&gt;
&lt;p&gt;But in both drug-addicted and obese patients, the scans show very little red activity, because there aren&apos;t enough receptors to which the radioactive glucose can bind. Wang says the decreased availability of dopamine receptors is the brain&apos;s way of coping with a constant dopamine overload.&lt;/p&gt;
&lt;p&gt;&quot;If a person constantly has an excess of dopamine, the brain will down-regulate,&quot; Wang says, explaining the principle commonly referred to as tolerance. &quot;Once the system is down-regulated, we have to do more in order to get the same amount of feeling in our normal state.&quot;&lt;/p&gt;
&lt;p&gt;Thus, obese patients &quot;will want to eat more in order to compensate for their down-regulated system.&quot;&lt;/p&gt;
&lt;p&gt;In other experiments, Wang and his colleagues have also found that a higher body mass index (BMI) correlated with lower prefrontal cortex function  --  the area associated with inhibitory control.&lt;/p&gt;
&lt;p&gt;&quot;If they&apos;re obese,&quot; Wang said, &quot;they have a problem controlling their eating behaviors.&quot;&lt;/p&gt;
&lt;p&gt;Those studies also revealed that a higher BMI was linked to a decrease in memory and executive functioning.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Out of Control&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Ed Susman was 293 pounds when he decided to join a clinical trial for an investigational weight-loss drug and chronicle his year-long experience for &lt;em&gt;MedPage Today&lt;/em&gt;. (See &lt;a href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; mce_href=&quot;http://www.medpagetoday.com/PrimaryCare/Diabetes/8125&quot; target=&quot;_blank&quot;&gt;Journalist Participant to Present Insider View of Weight-Loss Trial&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Eating, to him, was a &quot;compulsion&quot;  --  as was biting his nails, a habit he picked up at age 4.&lt;/p&gt;
&lt;p&gt;Over the course of the trial, not only did Susman lose 52 pounds, he also stopped his nail-biting.&lt;/p&gt;
&lt;p&gt;He doesn&apos;t yet know if he was in the drug arm of the trial, but he strongly suspects he wasn&apos;t experiencing a placebo effect.&lt;/p&gt;
&lt;p&gt;&quot;I believe I was on the drug because it controlled a compulsion that I had had for 50 years,&quot; Susman says of the nail-biting. &quot;This stopped it cold.&quot;&lt;/p&gt;
&lt;p&gt;Unfortunately, he says, the same didn&apos;t happen with his eating habits, but he&apos;s gained back only 10 of those 52 pounds in the year since his participation in the trial ended.&lt;/p&gt;
&lt;p&gt;The still-investigational drug is lorcaserin  --  a combination of benzazepine and hydrochloride, two neurological agents. Susman says it is &quot;supposed to improve your willpower, your ability to overcome compulsions.&quot;&lt;/p&gt;
&lt;p&gt;Lorcaserin is a selective 5-HT&lt;sub&gt;2C&lt;/sub&gt; receptor agonist, working through the serotonin system, which regulates appetite, mood, and motor behavior.&lt;/p&gt;
&lt;p&gt;Two other investigational obesity drugs target the dopamine reward system  --  Contrave, which is a combination of bupropion and naltrexone, and Qnexa, which combines phentermine and topiramate.&lt;/p&gt;
&lt;p&gt;&quot;Some medications that have used similar dopamine modulation, until now, have failed,&quot; Wang said. &quot;These two companies are using the command of the modulation of the dopamine system with other neurological systems, such as the opiate or norepinephrine system. According to the trials, they&apos;ve been very effective.&quot;&lt;/p&gt;
&lt;p&gt;Wang called the new medications &quot;a bright light for the treatment of obesity.&quot;&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Kicking the Habit&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Basically, the idea of medications that act on the dopamine system is &quot;to cool down those reward pathways,&quot; Levounis says. There are two strategies for doing so: an agonist strategy, or an antagonist strategy.&lt;/p&gt;
&lt;p&gt;The agonist strategy is &quot;feeding the beast, providing activity in the cell so that the cravings go down,&quot; Levounis said. Classic examples are nicotine patches, or methadone for opioid dependence.&lt;/p&gt;
&lt;p&gt;On the other hand, the antagonist strategy is to block the receptors. Naltrexone, for example, will block opioid receptors so that the drug addict won&apos;t feel anything if he or she attempts to get high.&lt;/p&gt;
&lt;p&gt;&quot;After a while, you say, &apos;This is not worth my time, my money, my trouble,&apos; so you stop using,&quot; Levounis explains.&lt;/p&gt;
&lt;p&gt;These have been the two main strategies in addiction pharmacotherapy, but there&apos;s now a &quot;third avenue&quot;  --  the partial agonist approach.&lt;/p&gt;
&lt;p&gt;The partial agonist is one molecule that blocks most receptors while still providing just a little bit of an &quot;oomph&quot; to calm cravings. That&apos;s how varenicline (Chantix) helps smokers quit, and how buprenorphine gets junkies off heroin or other opioids.&lt;/p&gt;
&lt;p&gt;But what about inhibitory control? What if medications could ramp up will power?&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s an area of active research,&quot; Levounis says. &quot;There are some medications proposed, but nothing to write home about.&quot;&lt;/p&gt;
&lt;p&gt;He said treatment is typically twofold. For addicts, psychiatrists will try to &quot;cool down&quot; the reward pathways, often with medication. Then, they target the diminished frontal lobes.&lt;/p&gt;
&lt;p&gt;&quot;We try to beef up the frontal lobes as much as we can, and we do that with psychotherapy,&quot; Levounis said.&lt;/p&gt;
&lt;p&gt;Researchers agree that psychotherapy is key to regaining self-control, and it&apos;s the predominant treatment used in patients with addictive behaviors.&lt;/p&gt;
&lt;p&gt;Mark Smaller, PhD, a psychoanalyst in private practice in Chicago, said psychotherapy often reveals an underlying cause for an addiction or compulsive behavior. Usually, it&apos;s anxiety or depression.&lt;/p&gt;
&lt;p&gt;Acknowledging those problems may help change behaviors. Once they&apos;re realized, a patient can start working against them, with the help of the brain&apos;s own neuroplasticity. Essentially, neurons can disconnect and reconnect, or loosen their connections and tighten them, which often manifests in noticeable change.&lt;/p&gt;
&lt;p&gt;&quot;[Psychological] insights can actually begin to change brain chemistry and diffuse compulsions,&quot; he said. &quot;If you address those issues, you can have a positive impact on your life that can change the chemistry of your brain.&quot;&lt;/p&gt;
&lt;p&gt;Smaller said it &quot;creates a new psychological  --  if not neurological  --  structure that can help regulate behavior.&quot;&lt;/p&gt;
&lt;p&gt;Although research on neuroplasticity is relatively young, the concept of &quot;rewiring&quot; the brain is not new.&lt;/p&gt;
&lt;p&gt;In fact, too often, the electrician metaphor has been employed as an excuse for indulging, an explanation for a New Year&apos;s resolution deferred: &quot;I can&apos;t stop eating chocolate, I&apos;m just not wired that way.&quot;&lt;/p&gt;

&lt;hr&gt;
&lt;p&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/30/16717.jpg&quot; alt=&quot;&quot;&gt;&lt;em&gt; is a collaboration between &lt;/em&gt;MedPage Today &lt;em&gt;and&lt;/em&gt; ABC News&lt;em&gt;.&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_183"
                     title="Gastric Bypass Extends Life for Most Patients (CME/CE)"
                     score="-0.003"
                     href="http://www.medpagetoday.com/PrimaryCare/Obesity/tb/18020?impressionId=1265738432162"
                     
      &lt;p&gt;For most patients in most categories, bariatric surgery increases life expectancy, according to a new mathematical model.&lt;/p&gt;
&lt;p&gt;Only when short-term mortality following bariatric surgery is expected to be high or the likelihood of success is low will the procedure fail to improve life expectancy, researchers reported in the January &lt;em&gt;Archives of Surgery&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Computer modeling predicted that a hypothetical &quot;base case&quot; patient  --  a 42-year-old woman with a body mass index of 45  --  would gain 2.95 years of additional survival following bariatric surgery, according to Daniel P. Schauer, MD, of the University of Cincinnati, and colleagues.&lt;/p&gt;
&lt;p&gt;Surgery failed to be beneficial in the model only when 30-day mortality reached 9.5% or the likelihood that surgery would not add life-years was 2% or less, they found.&lt;/p&gt;
&lt;p&gt;Baseline 30-day mortality in the model was 0.2%, and the baseline efficacy of surgery in extending life expectancy was 53%.&lt;/p&gt;
&lt;p&gt;&quot;While not all patients are guaranteed a good outcome, our model indicates that gastric bypass increases life expectancy for most patient subgroups,&quot; they concluded.&lt;/p&gt;
&lt;p&gt;Their analysis was based on a Markov decision model using published data to estimate 30-day mortality following bariatric surgery and the efficacy of surgery in reducing long-term death rates.&lt;/p&gt;
&lt;p&gt;The latter had two components: reduction in excess mortality associated with obesity, and research data on long-term mortality following bariatric surgery.&lt;/p&gt;
&lt;p&gt;Excess mortality estimates came from National Health Interview Survey data on some 400,000 participants from 1991 to 1996 linked to the National Death Index. Inputs on surgery efficacy were derived from a 2007 study of nearly 8,000 patients who had undergone gastric bypass and the same number of medically treated or untreated obese controls.&lt;/p&gt;
&lt;p&gt;That study found that the procedure cut death rates by half during about seven years of follow-up. (See &lt;a href=&quot;http://www.medpagetoday.com/PrimaryCare/Obesity/6480&quot; mce_href=&quot;http://www.medpagetoday.com/PrimaryCare/Obesity/6480&quot; target=&quot;_blank&quot;&gt;Missing Link Found: Bariatric Surgery Reduces Mortality&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Schauer and colleagues obtained rates of inhospital mortality following bariatric surgery from the 2005 National Inpatient Survey, then multiplied them by three to estimate 30-day mortality.&lt;/p&gt;
&lt;p&gt;The researchers explained that according to earlier research, inhospital death rates typically underestimate 30-day mortality by a factor of two to three.&lt;/p&gt;
&lt;p&gt;Their threefold correction factor represents &quot;a conservative estimate that biases the model against gastric bypass surgery,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Schauer and colleagues tested this correction factor and other aspects of the model in sensitivity analyses.&lt;/p&gt;
&lt;p&gt;The biggest gains in life expectancy occurred in younger women with relatively high BMI values, the model showed.&lt;/p&gt;
&lt;p&gt;The age effect was less important than BMI at the time of surgery. A 35-year-old woman with BMI of 45 would gain about 3.2 years of extra life, whereas at 55, a similarly obese woman would gain about 2.5 extra years.&lt;/p&gt;
&lt;p&gt;But a 35-year-old woman with BMI of 55 could expect to live five more years with surgery, the model indicated.&lt;/p&gt;
&lt;p&gt;Men in general derived less survival benefit from bariatric surgery, particularly with advancing age at the time of the procedure.&lt;/p&gt;
&lt;p&gt;At 35, the difference in life expectancy gained was roughly 10%, but by age 75 it had grown to about 50%.&lt;/p&gt;
&lt;p&gt;The sensitivity analyses found that relatively large changes in most parameters used in the model did not affect the overall results substantially.&lt;/p&gt;
&lt;p&gt;The effect of 30-day mortality on whether or not surgery was beneficial for long-term survival was related to BMI and gender.&lt;/p&gt;
&lt;p&gt;For women with a BMI of 40, 30-day mortality of more than 5% would mean surgery was not helpful, but short-term mortality had to exceed 15% for surgery not to be preferable for those with BMI of 55 or more. These thresholds were about 10% higher for men.&lt;/p&gt;
&lt;p&gt;The efficacy of surgery in reducing mortality was less important for older men, the analysis also showed. A 75-year-man with a BMI of 35 could expect only a very slight gain in life span  --  perhaps one or two months.&lt;/p&gt;
&lt;p&gt;&quot;Younger patients have lower surgical risk and more time over which to realize the benefits of surgery. For older patients, the gain is smaller, and for some, gastric bypass surgery will decrease life expectancy,&quot; Schauer and colleagues wrote.&lt;/p&gt;
&lt;p&gt;However, they identified several potentially serious limitations to the analysis.&lt;/p&gt;
&lt;p&gt;The study of long-term mortality following bariatric surgery was conducted at a single center and was not randomized. Additionally, long-term complications, such as need for repeat surgery, were not addressed in the model. Certain other risks that might be heightened after bariatric surgery were excluded as well, and quality of life was not modeled.&lt;/p&gt;
&lt;p&gt;&quot;The decision analysis presented here is a step forward in understanding optimal patient selection but also highlights some of the areas for which better data are needed,&quot; the researchers wrote.&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 National Institute of Diabetes and Digestive and Kidney Diseases funded the study.&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="20090101_9_431"
                     title="Early Bariatric Surgery Mortality Rate Low at Academic Centers"
                     score="-0.005"
                     href="