{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nznogp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nznogp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;13\\\/10\\\/14\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;13\\\/10\\\/14\u0022}],\u0022ac\u0022:{\u0022spmdc;13\\\/10\\\/14\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;13\\\/10\\\/14\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EObesity drugs have eluded the United States Food and Drug Administration (FDA) approval process for 13 years, but with mechanisms of action identified and obesity recognized as a disease, that is changing. This article reviews the history of obesity pharmacology, present options in obesity pharmacotherapy, as well as the discovery of peptide-based mixed agonists based on glucagon.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObesity\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EObesity drugs have eluded the United States Food and Drug Administration (FDA) approval process for 13 years, but with mechanisms of action identified and obesity recognized as a disease, that is changing. Caroline M. Apovian, MD, Boston University School of Medicine, Boston, Massachusetts, USA, reviewed the history of obesity pharmacology.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EWhile there are more than 200 medications to treat hypertension and over 100 drugs for diabetes, those who suffer from obesity have few choices (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). One reason is safety, which is of paramount importance due to the need for long-term management. Another is the number of people needing obesity treatment: 33% of American adults were considered obese (body mass index [BMI]\u226530 kg\/m\u003Csup\u003E2\u003C\/sup\u003E) in 2009 to 2010 [Ogden CL et al. \u003Cem\u003ENCHS Data Brief Number 82\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13313\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13313\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13313\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EObesity Medications Available Prior to 2012\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EA third factor is the time and cost involved in the FDA approval process. It takes an average of 10 to 15 years for an experimental drug to travel from the lab to patients; 5 in 5000 compounds that enter preclinical testing make it to human testing; and it costs a company approximately $802 million to bring a new medicine to the market [How New Drugs Move through the Development and Approval Process. Tufts Center for the Study of Drug Development, Nov 2001].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ESince 1997, four obesity medications\u2014fenfluramine, dexfenfluramine, rimonabant, and sibutramine\u2014have been withdrawn from the market for reasons that range from heart valve damage and pulmonary hypertension to increased risk of heart attack and stroke in high-risk cardiac patients [Kang JG, Park CY. \u003Cem\u003EDiabetes Metab J\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThere are three newcomers, all originally denied FDA approval, that have struggled to gain approval. The FDA rejected lorcaserin in October 2010 citing potential cancer risks. These were addressed, and the drug has been available in the United States since June 2013. Qsymia, a combination of phentermine and topiramate, was rejected by the FDA in 2010 due to numerous side effects, including raised heart rate, psychiatric problems, and a potential for birth defects. Ultimately, the FDA approved it in 2012 due to impressive weight loss results and commitments to a postmarketing program to mitigate these risks. Contrave, a combination of buproprion and naltrexone, is pending approval based on the results of a cardiovascular outcomes trial.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe need for new ways to treat obesity is critical. By 2030, an estimated 10% of Americans will have a BMI \u0026gt;40 kg\/m\u003Csup\u003E2\u003C\/sup\u003E (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Finkelstein EA et al. \u003Cem\u003EAm J Prev Med\u003C\/em\u003E 2012]. Steven R. Smith, MD, Sanford Burnham Medical Research Institute, Orlando, Florida, USA, reviewed present options in obesity pharmacotherapy to address this dangerous trend.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/14\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Actual and Predicted Prevalence of Severe Obesity (BMI \u0026#x2265;40kg\/m2)\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1755363832\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Actual and Predicted Prevalence of Severe Obesity (BMI \u0026#x2265;40kg\/m\u0026amp;lt;sup\u0026amp;gt;2\u0026amp;lt;\/sup\u0026amp;gt;)\u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/14\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/14\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/10\/14\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13311\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EActual and Predicted Prevalence of Severe Obesity (BMI \u226540kg\/m\u003Csup\u003E2\u003C\/sup\u003E)\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced from Finkelstein EA et al. Obesity and Severe Obesity Forecasts Through 2030. \u003Cem\u003EAm J Prev Med\u003C\/em\u003E 2012;42(6):563\u2013570. With permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EAlthough other anthropometric measures (eg, waist circumference, and waist-to-hip-ratio) could add extra information to patient workups, BMI, in and of itself, is a strong predictor of overall mortality both above and below the apparent optimum of approximately 22.5 to 25.0 kg\/m\u003Csup\u003E2\u003C\/sup\u003E. At 30 to 35 kg\/m\u003Csup\u003E2\u003C\/sup\u003E, median survival is reduced by 2 to 4 years; at 40 to 45 kg\/m\u003Csup\u003E2\u003C\/sup\u003E, the figure is 8 to 10 years, which is comparable to the effects of smoking [Whitlock G et al. \u003Cem\u003ELancet\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003ELorcaserin is a selective 5-HT\u003Csub\u003E2C\u003C\/sub\u003E receptor agonist that increases satiety and reduces food intake at a dose of 10 mg BID [Martin \u003Cem\u003EC. Obesity\u003C\/em\u003E 2011]. It is indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of 30 kg\/m\u003Csup\u003E2\u003C\/sup\u003E or 27 kg\/m\u003Csup\u003E2\u003C\/sup\u003E in the presence of \u22651 weight-related comorbid condition (eg, hypertension or type 2 diabetes).\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EData from the BLOOM study show that at 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost \u22655% of their body weight (p\u0026lt;0.001), corresponding to an average weight loss of 5.8\u00b10.2 kg with lorcaserin and 2.2\u00b10.1 kg with placebo (p\u0026lt;0.001) [Smith SR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010]. In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss compared with placebo.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EFindings from the BLOOM-DM study also found that lorcaserin was associated with a significant improvement in glycemic control in patients with type 2 diabetes: 50.4% of patients treated with lorcaserin versus 26.3% on placebo achieved an HbA1C \u0026lt;7.0% from a baseline mean of 8.1% (p\u0026lt;0.001) [O\u0027Neil PM et al. \u003Cem\u003EObesity (Silver Spring)\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003ESome of today\u0027s obesity drugs are combinations of existing pharmaceuticals. Tomorrow\u0027s will most likely be derived from such novel sources as peptide-based mixed agonists and co-agonists. Richard D. DiMarchi, PhD, Indiana University, Bloomington, Indiana, USA, discussed the discovery of peptide-based mixed agonists based on glucagon, a hormone that when given alone stimulates an increase in blood concentration of glucose.\u003C\/p\u003E\u003Cp id=\u0022p-15\u0022\u003EThe glucagon-GLP-1 co-agonist hypothesis is that chronic glucagon action will decrease fat mass by increasing energy expenditure via the glucagon receptor; GLP-1 will decrease fat mass by reducing food intake via the GLP-1 receptor; a GLP-1\/glucagon co-agonist might potently decrease fat mass by synergistically affecting both components via 2 receptors; and a GLP-1\/glucagon co-agonist should minimize the diabetogenic risk of a pure glucagon analog.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EPreclinical testing in rodents and non-human primates of glucagon-based single molecule co-agonists showed high potency, balanced activity that was enhanced compared with pure GLP-1 agonists. The peptides decreased body weight and fat mass; improved blood glucose and insulin; and reduced blood lipid and liver fat content. Human clinical study is ongoing.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EOther physiologically active components of interest include estrogen, incretins and adipokines (peptide\/protein combination treatment), leptin, and extendin-4. To date, GLP-1 agonists provide significant clinical benefits, and glucagon\/GLP-1 and GIP\/GLP-1 co-agonists deliver significantly greater activity than GLP-1 in animal studies. The addition of leptin or estrogen provides additional efficacy and broadens the therapeutic index.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EThe door to medications for the treatment of obesity and metabolic disorders has opened just slightly, enough to let a few drugs through. However, great promise exists in the work on peptide-based mixed agonists.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/10\/14.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznogp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznogp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nznogp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}