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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\u003Cp id=\u0022p-1\u0022\u003EThe age-adjusted incidence of a new diagnosis of heart failure (HF) has not changed over the past decades and, in some patient populations, is actually decreasing. However, because our society is aging and mortality from HF has been reduced, the prevalence of people living with a diagnosis of HF has increased and is currently fueling a cycle of hospitalization for HF. This article discusses the impact of HF drugs in patients with diabetes, the impact of new glucose-lowering drugs on HF, sodium glucose cotransporter 2 (SGLT-2) inhibitors.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eheart failure\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EThe age-adjusted incidence of a new diagnosis of heart failure (HF) has not changed over the past decades and, in some patient populations, is actually decreasing. However, because our society is aging and mortality from HF has been reduced, the prevalence of people living with a diagnosis of HF has increased and is currently fueling a cycle of hospitalization for HF, stated Veronique L. Roger, MD, MPH, Mayo Clinic, Rochester, Minnesota, USA. There has been an increase in the proportion of HF patients with preserved ejection fraction (HFpEF \u2265 50%) when compared to reduced ejection fraction (HFrEF \u0026lt; 50%). At the Mayo Clinic, the proportion of HF patients diagnosed with HFpEF increased from 38% in the 1986-to-1990 period to 54% in the 1998-to-2001 period [Owan TE et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2006]. In Olmsted County, Minnesota, the proportion of HFpEF patients is estimated to be 55% [Bursi et al. \u003Cem\u003EJAMA.\u003C\/em\u003E 2006], with 53% of new cases categorized as HFpEF over the last decade [Gerber Y et al. AHA 2014 (abstr 15685)].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe increase in diabetes mellitus (DM) is associated with the increasing prevalence of HFpEF. The population-attributable risk for HF associated with DM was 9% in 2000 [Dunlay SM et al. \u003Cem\u003EAm J Med.\u003C\/em\u003E 2009], based on a 2.65-fold increased risk for developing HF with diabetes. As the prevalence of DM increases, the population-attributable risk is expected to increase, especially as other causes of HF (eg, coronary artery disease) are becoming less impactful.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EAn effect of diabetes on HF may be mediated by subclinical myocardial injury and non-atherosclerotic mechanisms. For instance, studies have shown a positive-graded relationship between categories of diabetes (no diabetes, prediabetes, and diabetes) and detectable levels of high-sensitivity troponin elevation [Selvin E et al. \u003Cem\u003ECirculation.\u003C\/em\u003E 2014]. Categories of diabetes were positively associated with the risk of HF and all-cause mortality, in those with and without troponin elevation. The association of elevated troponins with HF was stronger than that for coronary events, leading the authors to suggest that the risk of HF is unlikely to be mediated by myocardial infarction or microvascular disease.\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EIMPACT OF HF DRUGS IN PATIENTS WITH DIABETES\u003C\/h2\u003E\u003Cp id=\u0022p-5\u0022\u003EIn patients with HFrEF, with or without DM, there is a similar relative risk reduction in morbidity and mortality with all the evidence-based, guideline-recommended pharmacologic and device therapies, according to data reviewed by John J. V. McMurray, University of Glasgow, Glasgow, Scotland, United Kingdom. However, in patients with DM, similar relative risk reductions translate to greater absolute risk reductions because of their higher absolute risk. Although DM itself is associated with more adverse events, available evidence-based therapies for HFrEF are safe and well tolerated in patients with DM, he stated.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe SOLVD-Treatment trial in the 1990s found that the angiotensin-converting enzyme inhibitor enalapril was equally effective regardless of DM status in reducing cardiovascular (CV) death or hospitalization for HF (\u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003EInteraction\u003C\/sub\u003E = .54). Regarding \u03b2-blockers, HF and CV hospitalization was reduced with metoprolol in MERIT-HF [Deedwania PC et al. \u003Cem\u003EAm Heart J.\u003C\/em\u003E 2005], and all-cause mortality was reduced with carvedilol in COPERNICUS [Mohacsi P et al. \u003Cem\u003ECirculation.\u003C\/em\u003E 2001]. A similar reduction in mortality in patients with or without diabetes was found in an analysis of the \u03b2-blocker trials [Deedwania PC et al. \u003Cem\u003EAm Heart J.\u003C\/em\u003E 2005].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003E\u03b2-Blockers are safe and well tolerated in patients with HF and DM, although there are misperceptions regarding their safety, leading to suboptimal use. Data from MERIT-HF showed that study drug discontinuation was similar for placebo and metoprolol regardless of DM status. Hypoglycemia was rare with metoprolol and placebo (0.8% and 0.6%, respectively).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EMineralocorticoid receptor antagonists are also underused in patients with DM and HFrEF, stated Prof McMurray. In patients with severe HFrEF, there was a similar reduction in CV death or HF hospitalization with spironolactone in those with DM (HR, 0.68; 95% CI, 0.52 to 0.90) and without DM (HR, 0.64; 95% CI, 0.54 to 0.75; \u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003EInteraction\u003C\/sub\u003E =.67) in the RALES study. Eplerenone had a trend toward a greater effect on CV death or HF hospitalization in patients with DM (HR, 0.54; 95% CI, 0.42 to 0.70) than without DM (HR, 0.71; 95% CI, 0.58 to 0.88; \u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003EInteraction\u003C\/sub\u003E = .09) in the EMPHASIS-HF study [Zannad F et al. \u003Cem\u003EHeart Failure.\u003C\/em\u003E 2012]. Mineralocorticoid receptor antagonists are also safe and well tolerated in this patient group, with a low rate of hyperkalemia (K\u003Csub\u003E+\u003C\/sub\u003E \u0026gt; 6.0 mmoL\/L) in all patients taking eplerenone and those with diabetes (2.5% vs 3.8%) [Pitt B et al. ESC 2011] and with a similar change in estimated glomerular filtration rate (\u22123.2 and \u22124.9 mL\/min\/1.73 m\u003Csup\u003E2\u003C\/sup\u003E, respectively).\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EUnpublished data show that the reduction in CV death or HF hospitalization was similar in patients with or without DM with digoxin in the DIG trial (HR, 0.90 vs 0.83; \u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003EInteraction\u003C\/sub\u003E = .27) and the novel angiotensin receptor blocker\/neprilysin inhibitor LCZ696 (HR, 0.84 vs 0.77; \u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003EInteraction\u003C\/sub\u003E = .40) in the PARADIGM-HF study. Ivabradine was favorable regardless of diabetes history in the SHIFT study (HR, 0.81 vs 0.83; \u003Cem\u003EP\u003C\/em\u003E\n            \u003Csub\u003EInteraction\u003C\/sub\u003E = .86) [Swedberg K et al. \u003Cem\u003ELancet.\u003C\/em\u003E 2010]. In the A-HeFT trial [Taylor AL et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2004], unpublished subgroup analysis showed that the improvement in survival with hydralazine plus isosorbide dinitrate was similar in African-American patients regardless of diabetes status.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EIn SCD-HeFT\u2014the only large trial of an implantable cardioverter defibrillator in HF\u2014a subgroup analysis suggested that patients with DM did not receive the same benefit as those without DM (HR, 0.95 vs 0.67) [Bardy GH et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2005]. However, there was no suggestion of this in the MADIT II study of postinfarct patients with a low ejection fraction, suggesting a false-positive finding, stated Prof McMurray. Cardiac resynchronization therapy was beneficial regardless of DM status in reducing death or CV hospitalization and death or HF hospitalization in the CARE-HF trial, with a similar \u223c 7% improvement in left ventricular ejection fraction and NYHA class (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E) [Hoppe UC et al. \u003Cem\u003EDiabetes Care.\u003C\/em\u003E 2007].\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\/15168\/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\/15168\/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\/15168\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 \u003Cp id=\u0022p-11\u0022 class=\u0022first-child\u0022\u003EImprovements With Cardiac Resynchronization Therapy in Patients With and Without Diabetes\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\u003Ch2 class=\u0022\u0022\u003EIMPACT OF NEW GLUCOSE-LOWERING DRUGS ON HF\u003C\/h2\u003E\u003Cp id=\u0022p-15\u0022\u003ENo glucose-lowering drug or regimen has been shown to improve HF outcomes in patients with DM, stated Benjamin M. Scirica, MD, MPH, Brigham and Women\u0027s Hospital, Boston, Massachusetts, USA. Notably, signals of HF exacerbation and increased hospitalization for HF have been seen in randomized clinical trials of thiazolidinediones (TZD), dual peroxisome proliferator-activated receptor (PPAR) agonists with alpha-gamma activity, and dipeptidyl peptidase 4 (DPP-4) inhibitors.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003EOne meta-analysis showed an increased risk of HF with TZDs vs standard glucose management [Castagno D et al. \u003Cem\u003EAm Heart J.\u003C\/em\u003E 2011]. Data from the PROACTIVE study not only demonstrated a higher HF rate but also found an increased rate of edema with pioglitazone vs placebo (27.4% vs 15.9%; \u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001) [Erdmann E et al. \u003Cem\u003EDiabetes Care.\u003C\/em\u003E 2007]. Edema from PPAR agonists is thought to be due to fluid retention, decreased glycosuria, and increased adiposity. However, whether this is a nuisance side effect that can be managed or a bad prognostic marker of worsening HF is unclear, stated Dr Scirica. A signal of an increase in incident HF with pioglitazone and rosiglitazone (greater with the latter) was seen in another meta-analysis [Lago RM et al. \u003Cem\u003ELancet.\u003C\/em\u003E 2007].\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003ESimilarly, increased hospitalization for HF (HR, 1.22; 95% CI, 0.94 to 1.59; \u003Cem\u003EP\u003C\/em\u003E = .14) and risk for HF-related serious adverse events (HR, 1.24; 95% CI, 0.99 to 1.66; \u003Cem\u003EP\u003C\/em\u003E = .06) and edema (\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .001) have been found with the dual PPAR agonist aleglitazar versus placebo, although with no ischemic effects, in the AleCardio trial [Lincoff AM et al. \u003Cem\u003EJAMA.\u003C\/em\u003E 2014]. As with TZDs, for dual PPAR agonists, it remains unclear to what extent these signals translate into absolute rate increases in HF risk.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EThe DPP-4 inhibitors saxagliptin and alogliptin, when compared with placebo, had no effect on the primary CV end point in the SAVOR and EXAMINE trials, respectively [Scirica BM et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2013; White WB et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2013]. In SAVOR, there was an absolute increased risk of hospitalization for HF with saxagliptin vs placebo (3.5% vs 2.8%; HR, 1.27; 95% CI, 1.07 to 1.51; \u003Cem\u003EP\u003C\/em\u003E = .007); however, no increase in peripheral edema was found. Although not enough end points were available to achieve statistical significance, EXAMINE suggested a similar relative increase. SAVOR found that the HF risk was higher early, with fairly similar rates after 12 months in both arms (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Scirica BM et al. \u003Cem\u003ECirculation.\u003C\/em\u003E 2014]. More evidence from other trials is needed to determine whether this HF signal was a chance observation, whether the effect is specific to DPP-4 inhibitors or occurs with all incretin drugs, or whether it is a general effect of all glucose-lowering drugs that can exacerbate the disease process in patients at high risk of HF.\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\/14\/52\/33\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Time to Hospitalization for Heart Failure in the SAVOR Trial\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1864286674\u0022 data-figure-caption=\u0022Time to Hospitalization for Heart Failure in the SAVOR Trial\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\/14\/52\/33\/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\/14\/52\/33\/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\/14\/52\/33\/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\/15213\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 \u003Cp id=\u0022p-19\u0022 class=\u0022first-child\u0022\u003ETime to Hospitalization for Heart Failure in the SAVOR Trial\u003C\/p\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ECVD\/HF post hoc composite: 5.9% vs 5.0%; HR, 1.15; \u003Cem\u003EP\u003C\/em\u003E = .039. Black vertical lines indicate landmark analysis at 12 months: 1.7% vs 1.5%; HR, 1.09; \u003Cem\u003EP\u003C\/em\u003E = .51; time-varying interaction, \u003Cem\u003EP\u003C\/em\u003E = .017.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EAdapted from Scirica BM et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. \u003Cem\u003ECirculation.\u003C\/em\u003E 2014;130:1579\u20131588. With permission from American Heart Association, Inc.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-4\u0022\u003E\u003Ch2 class=\u0022\u0022\u003ESGLT-2 INHIBITORS\u003C\/h2\u003E\u003Cp id=\u0022p-20\u0022\u003EThe sodium glucose cotransporter 2 (SGLT-2) inhibitors have effects on sodium metabolism, fluid volume, and blood pressure (BP) that have the potential to be beneficial in regard to HF, stated Bruce Neal, MD, The George Institute for Global Health, Sydney, Australia. Although no data on HF outcomes have been reported, ongoing large-scale trials with SGLT-2 inhibitors should provide clear evidence of the effect on HF.\u003C\/p\u003E\u003Cp id=\u0022p-21\u0022\u003EA systematic review of studies of SGLT-2 inhibitors in patients with type 2 DM (45 studies vs placebo; 13 studies vs active comparator) showed a mean reduction in\nHbA\u003Csub\u003E1c\u003C\/sub\u003E of 0.79%, systolic BP of 3.8 mm Hg, diastolic BP of 1.8 mm Hg, and body weight of 1.74 kg [Vasilakou D et al. \u003Cem\u003EAnn Intern Med.\u003C\/em\u003E 2013]. Prof Neal noted that there was a 30% to 40% reduced risk of albuminuria found with SGLT-2 inhibition in patients with type 2 DM and chronic kidney disease in a randomized trial [Yale JF et al. \u003Cem\u003EDiabetes Obes Metab.\u003C\/em\u003E 2013].\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 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\/14\/52\/33.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?nzodp2\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?nzodp2\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?nzodp2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}