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Original article
Extrahepatic causes of death in cirrhosis compared to other chronic conditions in the United States, 1999-2017
Nagasri Shankara, Azaan Ramania, Connor Griffina, Uchenna Agbimb, Donghee Kimc, Aijaz Ahmedc, Sumeet K. Asrania,
Corresponding author
Sumeet.Asrani@BSWHealth.org

Corresponding author.
a Baylor University Medical Center, Dallas, TX, USA
b The University of Tennessee Health Science Center, Saint Louis University, MO, USA
c Stanford University School of Medicine, Stanford, CA, USA
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="cesectitle0009">Introduction</span><p id="para0012" class="elsevierStylePara elsevierViewall">Worldwide&#44; cirrhosis accounts for approximately two million deaths yearly and the burden may be underestimated and increasing <a class="elsevierStyleCrossRefs" href="#bib0001">&#91;1&#8211;10&#93;</a>&#46; Like congestive heart failure &#40;CHF&#41; and chronic obstructive pulmonary disease &#40;COPD&#41;&#44; cirrhosis can cause multi-organ damage and may be subject to similar precipitants of mortality&#46; Although deaths in cirrhosis are traditionally considered to be liver-related&#44; there may be a substantial impact from extrahepatic causes including cardiovascular disease &#40;CVD&#41;&#44; extrahepatic infections&#44; or non-hepatocellular carcinoma malignancies&#46; <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a></p><p id="para0013" class="elsevierStylePara elsevierViewall">If deaths are also driven by extrahepatic causes in the current era&#44; then a change in management is needed beyond the historically singular focus of preventing portal hypertension &#40;PH&#41;- related complications&#46; Further&#44; if extrahepatic causes differentially impact cirrhosis compared to other chronic diseases&#44; a realignment of healthcare policy may be required&#46; There is also limited understanding of how demographic and regional disparities affect mortality across cirrhosis&#44; COPD and CHF populations&#46;</p><p id="para0014" class="elsevierStylePara elsevierViewall">We hypothesized that trends in cirrhosis mortality over the last two decades have skewed towards extrahepatic causes which may contribute to excess deaths when compared to other chronic diseases&#46; Additionally&#44; certain demographic subgroups with cirrhosis may have excess mortality compared to other chronic disease populations&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="cesectitle0010">Methods</span><p id="para0015" class="elsevierStylePara elsevierViewall">We used national death data to describe trends in annual mortality within a cohort of US decedents with cirrhosis stratified by liver-related or extrahepatic causes of death&#46; Trends in cirrhosis mortality were also compared to trends among decedents with CHF and COPD&#46;</p><p id="para0016" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Data source</span>&#58;</span> The Multiple Cause of Death database is a public-use data file generated by the National Center for Health Statistics to enumerate deaths in the US <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&#46; The data set extracts de-identified death certificate data for &#62; 99&#37; of all deceased residents in all 50 states and the District of Columbia from 1999 to 2017&#46; Part I of the death certificates contain the single condition leading to death&#44; the underlying cause of death&#46; Certificates also contain additional causes occurring at the time of death&#44; referred to as multiple causes of death&#46; Diagnosis listed on death certificates are coded based on the <span class="elsevierStyleItalic">International Classification of Diseases&#44; Tenth Revision &#40;ICD-10&#41;</span>&#46;</p><p id="para0017" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Liver related and extrahepatic causes of death&#58;</span></span> The methods used in this study are like those previously described &#40;&#91;<a class="elsevierStyleCrossRefs" href="#bib0001">1-6</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0008">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0009">9</a>&#93;&#41;&#46; The underlying cause of death was classified as cirrhosis&#44; CHF&#44; or COPD&#46; Additional causes occurring at the time of death were classified as liver-related or extrahepatic&#46; Liver-related causes included those due to PH &#40;i&#46;e&#46; variceal bleeding&#44; hepatic encephalopathy &#91;HE&#93;&#44; hepatorenal syndrome &#91;HRS&#93;&#44; ascites&#44; peritonitis&#41;&#44; hepatocellular carcinoma &#40;HCC&#41;&#44; and sepsis&#46; Extrahepatic causes were national drivers of mortality defined as the top 15 leading causes of death in the US by the CDC&#58; cardiovascular diseases &#40;CVD&#41; &#40;i&#46;e&#46; myocardial infarction&#44; strokes&#44; CHF&#44; and hypertension&#41;&#44; malignancy &#40;non-HCC&#44; hepatobiliary&#44; other&#41;&#44; accidents &#40;unintentional injuries including motor vehicle collisions&#44; accidental drug overdose&#41;&#44; diabetes&#44; and influenza and pneumonia&#46; Extrahepatic causes outside of this list were not assessed&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Case ascertainment</span>&#58;</span> We first identified decedents with cirrhosis of all ages &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 1</span></a>&#41; using validated ICD-10 codes with positive predictive value of 93&#37; for predicting underlying cirrhosis in the medical record <a class="elsevierStyleCrossRef" href="#bib0007">&#91;7&#93;</a>&#46; To preserve coding accuracy&#44; other coding definitions of cirrhosis &#40;e&#46;g K70&#46;4&#44; K74&#46;0&#44; K74&#46;1&#44; K74&#46;2&#41; were excluded from this study&#46; Next&#44; within the cirrhosis cohort&#44; we identified decedents with liver-related causes of death also with validated codes &#40;positive predictive value approaching 90&#37;&#41; <a class="elsevierStyleCrossRef" href="#bib0007">&#91;7&#93;</a>&#46; Following this&#44; we identified decedents with extrahepatic causes of death&#46; Cirrhosis was categorized as the underlying cause of death while liver-related or extrahepatic manifestations were categorized as additional causes occurring at the time of death&#46; We then identified decedents with various etiologies of cirrhosis related to hepatitis C &#40;HCV&#41; or hepatitis B virus &#40;HBV&#41; infection&#44; alcohol associated liver disease &#40;ALD&#41;&#44; or non-alcoholic fatty liver disease &#40;NAFLD&#41; using diagnostic coding as previously described &#91;<a class="elsevierStyleCrossRef" href="#bib0002">2</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0006">6</a>&#93;&#46; We then identified decedents with CHF and COPD using coding definitions like those used in recent studies <a class="elsevierStyleCrossRefs" href="#bib0012">&#91;12&#8211;14&#93;</a>&#46; Within the CHF and COPD cohort&#44; we next identified decedents with extrahepatic causes of death and used the approach as described above&#46; We performed several sensitivity analyses&#58; 1&#41; using various definitions of liver disease 2&#41; considering each extrahepatic or liver-related manifestation as the underlying cause&#44; 3&#41; calculating rates standardized to the 2010 US population and 4&#41; considering sepsis as an extrahepatic cause of death &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 2</span></a> and <a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">3</span></a>&#41;&#46; Trends in mortality did not differ considerably between various methods of data acquisition&#46; Due to limitations of death certificate dataset&#44; it was difficult to parse out individuals with compensated versus decompensated cirrhosis&#46; However&#44; we defined decompensated cirrhosis using codes for cirrhosis and portal hypertension-related complications &#40;varices&#44; peritonitis&#44; ascites&#44; hepatic encephalopathy&#44; hepatorenal syndrome&#41; and sepsis as the underlying cause of death&#46; Compensated cirrhosis was defined using validated codes for cirrhosis as the underlying cause of death &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 1</span></a>&#41;&#46; Patients with overlapping chronic conditions &#40;i&#46;e cirrhosis as the underlying cause of death and CHF as additional&#44; comorbid cause occurring at the time of death&#41; were considered&#59; overall&#44; less than 10&#37; of total cirrhosis deaths occurred in decedents with both cirrhosis and other chronic disease listed on death certificates and these were excluded from the overall analysis&#46; Additional consideration was given for individuals &#60;18 years&#59; given that deaths in this subgroup account of 0&#46;03&#37; of all cirrhosis deaths&#44; they were included in the overall analysis&#46;</p><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0011">Statistical analysis</span><p id="para0019" class="elsevierStylePara elsevierViewall">Age-specific mortality rate per 100&#44;000 persons was calculated by dividing the number of liver-related or extrahepatic deaths by the total US census population for each calendar year&#46; Similar to previously published studies&#44; <a class="elsevierStyleCrossRef" href="#bib0006">&#91;6&#93;</a> rates were standardized to the age distribution of the 2000 US standard population using the direct method&#46; We also conducted a sensitivity analysis by repeating the analysis standardized to the 2010 US standard population&#46; We analyzed mortality in the year 2017 as well as annual trends from 1999-2017&#46; Trends were stratified by demographic subgroups of the population&#46; We used the 2013 National Center for Health Statistics Urban-Rural classification scheme to categorize deaths as urban or rural deaths <a class="elsevierStyleCrossRef" href="#bib0015">&#91;15&#93;</a>&#46; First&#44; trends in liver-related and extrahepatic causes of death were analyzed in the cirrhosis cohort&#46; Next&#44; extrahepatic causes were compared across cirrhosis&#44; CHF and COPD cohorts&#46; Lastly&#44; extrahepatic causes were compared among demographic subgroups across each chronic disease cohort&#46;</p><p id="para0020" class="elsevierStylePara elsevierViewall">Joinpoint regression analysis &#40;National Cancer Institute&#39;s Joinpoint regression software version 4&#46;7&#46;0&#46;0&#59; <a href="http://surveillance.cancer.gov/joinpoint">http&#58;&#47;&#47;surveillance&#46;cancer&#46;gov&#47;joinpoint</a>&#41; was utilized to assess changes in trends over time <a class="elsevierStyleCrossRef" href="#bib0016">&#91;16&#93;</a>&#46; Changes in age-standardized mortality rates &#40;ASMR&#41; were plotted over time and points of significant breaks in trend &#40;joinpoints&#41; were identified&#46; Statistically distinct trend segments were fitted with a log-linear model&#46; We calculated annual percentage change &#40;APC&#41; to describe the slope of each trend segment and average APC &#40;AAPC&#41; to describe trends from 1999-2017 <a class="elsevierStyleCrossRef" href="#bib0017">&#91;17&#93;</a>&#46; A maximum of three jointpoints were allowed&#46; At least two years were required from a joinpoint to either end of the data and in between consecutive jointpoints&#46; Statistically significant differences between trend segments were tested using 95&#37; confidence intervals &#40;CIs&#41; and t-test using a p-value of &#60;0&#46;05 <a class="elsevierStyleCrossRef" href="#bib0018">&#91;18&#93;</a>&#46; The study was approved by the institutional review board&#46;</p></span></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="cesectitle0012">Results</span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0013">Cirrhosis related all-cause mortality&#44; 2017</span><p id="para0021" class="elsevierStylePara elsevierViewall">Age-standardized mortality from all causes in the cirrhosis cohort was 9&#46;3&#47;100&#44;000 &#40;n&#61; 35&#44;960&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0001"><span class="elsevierStyleBold">Table 1</span></a>&#41;&#46; Rates were similar when standardized to the age distribution of the 2010 US standard population &#40;9&#46;3&#47;100&#44;000 vs 10&#46;3&#47;100&#44;000&#41;&#46; Among liver-related causes of death&#44; sepsis &#40;1&#46;1&#47;100&#44;000&#41;&#44; varices &#40;0&#46;5&#47;100&#44;000&#41; ascites &#40;0&#46;5&#47;100&#44;000&#41;&#44; and HRS &#40;0&#46;5&#47;100&#44;000&#41; had the highest ASMR followed by peritonitis &#40;0&#46;3&#47;100&#44;000&#41;&#44; HE &#40;0&#46;1&#47;100&#44;000&#41;&#44; and HCC &#40;0&#46;1&#47;100&#44;000&#41;&#46; Among extrahepatic causes&#44; ASMR was highest for CVD &#40;2&#46;5&#47;100&#44;000&#41; followed by diabetes &#40;0&#46;6&#47;100&#44;000&#41; influenza and pneumonia &#40;0&#46;5&#47;100&#44;000&#41;&#44; non-HCC malignancies &#40;0&#46;2&#47;100&#44;000&#41; and accidents &#40;0&#46;1&#47;100&#44;000&#41;&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2</span><span class="elsevierStyleSectionTitle" id="cesectitle0014">Annual trends in liver-related vs extrahepatic mortality in cirrhosis&#44; 1999-2017</span><p id="para0022" class="elsevierStylePara elsevierViewall">When examining trends over time&#44; both liver-related &#40;AAPC 1&#46;3&#37;&#44; 95&#37; CI 0&#46;7-1&#46;9&#41; and extrahepatic &#40;AAPC 1&#46;0&#37; 95&#37;CI 0&#46;7-1&#46;2&#41; mortality increased in the cirrhosis cohort from 1999-2017 &#40;<a class="elsevierStyleCrossRef" href="#tbl0001"><span class="elsevierStyleBold">Table 1</span></a><span class="elsevierStyleBold">and</span><a class="elsevierStyleCrossRef" href="#fig0001"><span class="elsevierStyleBold">Fig&#46; 1</span></a><span class="elsevierStyleBold">&#41;</span>&#46; Mortality related to CVD &#40;AAPC 1&#46;3&#37;&#44; 95&#37; CI 1&#46;1-1&#46;5&#41;&#44; influenza and pneumonia &#40;AAPC 1&#46;1&#37;&#44; 95&#37; CI 0&#46;3-1&#46;8&#41;&#44; diabetes &#40;AAPC 0&#46;9&#37;&#44; 95&#37; CI 0&#46;2-1&#46;7&#41; and accidents &#40;AAPC 1&#46;7&#37;&#44; 95&#37; CI 0&#46;3-3&#46;2&#41; rose&#46; Mortality related to non-HCC malignancy declined in the cirrhosis cohort &#40;AAPC -1&#46;1&#37;&#44; 95&#37; CI -1&#46;1- 0&#46;6&#41;&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0023" class="elsevierStylePara elsevierViewall">Within the cirrhosis cohort&#44; changes in mortality in compensated cirrhosis were driven by extrahepatic causes of death&#44; especially cardiovascular disease &#40;AAPC 1&#46;3&#37;&#44; 95&#37; CI 1&#46;1-1&#46;5&#41;&#44; accidents &#40;AAPC 1&#46;7&#37;&#44; 95&#37; CI 0&#46;3-3&#46;2&#41;&#44; and influenza and pneumonia &#40;AAPC 1&#46;1&#37;&#44; 95&#37; CI 0&#46;3-1&#46;8&#41;&#46; Non-HCC malignancy related mortality declined in this group &#40;AAPC -1&#46;1&#37;&#44; 95&#37; CI -1&#46;5- -0&#46;6&#41;&#46; By comparison&#44; decedents with decompensated cirrhosis had stable changes in annual mortality related to CVD &#40;AAPC -0&#46;1&#37;&#44; 95&#37; CI -0&#46;3- 0&#46;2&#41;&#44; non-HCC malignancy &#40;AAPC -0&#46;1&#37;&#44; 95&#37; CI -0&#46;4- 0&#46;3&#41;&#44; diabetes &#40;AAPC -0&#46;2&#37;&#44; 95&#37; -10&#46;0- 0&#46;5&#41; and influenza pneumonia &#40;AAPC 0&#46;3&#37;&#44; 95&#37; CI -0&#46;3- 1&#46;0&#41; &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 4</span></a>&#41;&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall">When examining etiology-based differences in cirrhosis mortality&#44; a greater proportion of deaths were attributed to extrahepatic causes compared to liver-related causes across all etiologies of cirrhosis &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 5</span></a>&#41;&#46; Among decedents with HCV-related cirrhosis&#44; both liver-related &#40;AAPC 1&#46;1&#37;&#44; 95&#37; CI 0&#46;6-1&#46;6&#41; and extrahepatic mortality increased &#40;AAPC 0&#46;8&#37;&#44; 95&#37; CI 0&#46;5- 1&#46;2&#41;&#46; Similar trends were observed in cirrhosis related to HBV &#40;liver-related&#58; AAPC 1&#46;1&#37;&#44; 95&#37; CI 0&#46;6- 1&#46;7&#59; extrahepatic&#58; AAPC 0&#46;8&#37;&#44; 95&#37; CI 0&#46;6-1&#46;1&#41; and ALD &#40;liver-related AAPC 1&#46;0&#37;&#44; 95&#37; CI 0&#46;6-1&#46;5&#59; extrahepatic&#58; AAPC 0&#46;7&#37;&#44; 95&#37; CI 0&#46;4- 1&#46;0&#41;&#46; In cirrhosis related to NAFLD&#44; both liver-related &#40;AAPC 1&#46;6&#37;&#44; 95&#37; CI 0&#46;7-2&#46;6&#41; and extrahepatic mortality &#40;AAPC 1&#46;3&#37;&#44; 95&#37; CI 1&#46;1-1&#46;5&#41; increased substantially&#46;</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;3</span><span class="elsevierStyleSectionTitle" id="cesectitle0015">Cirrhosis&#44; CHF and COPD related all-cause mortality&#44; 2017</span><p id="para0025" class="elsevierStylePara elsevierViewall">As expected&#44; ASMR in 2017 was higher in the CHF &#40;n&#61;80&#44;480&#44; 20&#46;4&#47;100&#44;000&#41; and COPD cohorts &#40;n&#61;155&#44;621&#44; 39&#46;7&#47;100&#44;000&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0002"><span class="elsevierStyleBold">Table 2</span></a>&#41;&#46; In the CHF cohort&#44; ASMR was highest for CVD &#40;1&#46;3&#47;100&#44;000&#41; followed by diabetes &#40;1&#46;1&#47;100&#44;000&#41;&#44; influenza and pneumonia &#40;0&#46;9&#47;100&#44;000&#41;&#44; malignancy &#40;0&#46;4&#47;100&#44;000&#41; and accidents &#40;0&#46;2&#47;100&#44;000&#41;&#46; In the COPD cohort&#44; ASMR was highest for CVD &#40;19&#46;3&#47;100&#44;000&#41;&#44; followed by diabetes &#40;3&#46;2&#47;100&#44;000&#41;&#44; malignancy &#40;1&#46;8&#47;100&#44;000&#41;&#44; accidents &#40;0&#46;5&#47;100&#44;000&#41; and influenza and pneumonia &#40;0&#46;4&#47;100&#44;000&#41;&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;4</span><span class="elsevierStyleSectionTitle" id="cesectitle0016">Annual trends in cirrhosis&#44; CHF and COPD related all-cause mortality&#44; 1999-2017</span><p id="para0026" class="elsevierStylePara elsevierViewall">Annual trends in all-cause mortality were higher in the cirrhosis cohort &#40;AAPC 1&#46;0&#37;&#44; 95&#37; CI 0&#46;7-1&#46;4&#41; than in CHF &#40;AAPC 0&#46;1&#37;&#44; 95&#37; CI -0&#46;5-0&#46;8&#41; or COPD &#40;AAPC -0&#46;4&#37;&#44; -0&#46;6- -0&#46;2&#41; cohorts <span class="elsevierStyleBold">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0002"><span class="elsevierStyleBold">Table 2</span></a><span class="elsevierStyleBold">&#44;</span><a class="elsevierStyleCrossRef" href="#fig0002"><span class="elsevierStyleBold">Figs&#46; 2</span></a><span class="elsevierStyleBold">&#44;</span><a class="elsevierStyleCrossRef" href="#fig0003"><span class="elsevierStyleBold">3</span></a><span class="elsevierStyleBold">&#41;</span>&#46; In recent years&#44; cirrhosis-related mortality increased &#40;2008-2017&#58; APC 2&#46;4&#37;&#44; 95&#37; CI 1&#46;8-3&#46;0&#41; and exceeded annual changes in CHF &#40;2008-2017&#58; APC 1&#46;6&#37;&#44; 95&#37; CI 0&#46;9-2&#46;4&#41; and COPD &#40;2008-2017&#58; APC -0&#46;4&#37;&#44; 95&#37; CI -0&#46;6- -0&#46;2&#41; related mortality&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;5</span><span class="elsevierStyleSectionTitle" id="cesectitle0017">Annual trends in extrahepatic mortality in cirrhosis&#44; CHF and COPD&#44; 1999-2017</span><p id="para0027" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Cardiovascular&#58;</span></span> Cardiovascular-related mortality increased in the cirrhosis cohort &#40;AAPC 1&#46;3&#37;&#44; 95&#37; CI 1&#46;1- 1&#46;5&#41; <span class="elsevierStyleBold">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0002"><span class="elsevierStyleBold">Table 2</span></a><span class="elsevierStyleBold">&#44;</span><a class="elsevierStyleCrossRef" href="#fig0004"><span class="elsevierStyleBold">Fig&#46; 4</span></a><span class="elsevierStyleBold">&#41;</span>&#46; Mortality declined in CHF &#40;AAPC -2&#46;0&#37;&#44; 95&#37; CI -5&#46;3- 1&#46;3&#41; and was unchanged in COPD &#40;AAPC 0&#46;1&#37;&#44; 95&#37; CI -0&#46;2- 0&#46;4&#41;&#46; Among decedents &#62; 65 years within the cirrhosis cohort &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 6</span></a>&#41;&#44; cardiovascular mortality increased &#40;AAPC 0&#46;8&#37;&#44; 95&#37; CI 0&#46;5- 1&#46;1&#41;&#46; In contrast&#44; mortality declined in CHF &#40;AAPC -1&#46;1&#37;&#44; 95&#37; CI -1&#46;1- -1&#46;7&#41; and was unchanged COPD &#40;AAPC 0&#46;0&#37;&#44; 95&#37; CI -0&#46;3- 0&#46;3&#41;&#46; Differences were more pronounced among women &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 7</span></a>&#41;&#58; Cardiovascular mortality increased among women in the cirrhosis cohort &#40;AAPC 1&#46;2&#37;&#44; 95&#37;CI 0&#46;8- 1&#46;7&#41;&#44; declined in CHF &#40;AAPC -1&#46;3&#37;&#44; 95&#37; CI -2&#46;4- -0&#46;3&#41; and increased minimally in COPD &#40;AAPC 0&#46;6&#37;&#44; 95&#37; CI 0&#46;3- 0&#46;9&#41;&#46; Cardiovascular mortality increased markedly in rural populations with cirrhosis &#40;AAPC 2&#46;6&#37;&#44; 95&#37; CI 1&#46;4- 3&#46;9&#41; &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 8</span></a>&#41;&#46; In contrast&#44; mortality declined among rural populations within the CHF cohort &#40;AAPC -0&#46;7&#37;&#44; 95&#37; CI -2&#46;8- 1&#46;5&#41; and increased minimally in the COPD cohort &#40;AAPC 1&#46;6&#37;&#44; 95&#37; CI 1&#46;2- 2&#46;0&#41;&#46;</p><elsevierMultimedia ident="fig0004"></elsevierMultimedia><p id="para0028" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Influenza &#38; pneumonia&#58;</span></span> Influenza and pneumonia-related mortality increased in the cirrhosis cohort &#40;AAPC 1&#46;1&#37;&#44; 95&#37; CI 0&#46;3- 1&#46;8&#41; while declining in CHF &#40;AAPC -4&#46;9&#37;&#44; 95&#37; CI -6&#46;1- -3&#46;7&#41; and COPD &#40;AAPC -15&#46;9&#37;&#44; 95&#37; CI -19&#46;0- -12&#46;7&#41; cohorts&#46; Among decedents &#62;65 years&#44; influenza and pneumonia-related mortality remained stable in the cirrhosis cohort &#40;AAPC -0&#46;2&#37; 95&#37; CI -0&#46;7-1&#46;1&#41; with significant rise in recent years &#40;APC 2009-2017 3&#46;5&#37;&#41;&#46; By comparison&#44; mortality declined in both CHF &#40;AAPC -5&#46;1&#37;&#44; 95&#37; CI -6&#46;3- -4&#46;0&#41; and COPD &#40;AAPC -16&#46;4&#37;&#44; 95&#37; CI -19&#46;7- -12&#46;9&#41; cohorts&#46; Influenza and pneumonia-related mortality increased among women in the cirrhosis cohort &#40;AAPC 1&#46;9&#37;&#44; 95&#37; CI 1&#46;0- 2&#46;9&#41; compared to declining rates among women in CHF &#40;AAPC -5&#46;2&#37;&#44; 95&#37; CI -6&#46;6- -3&#46;8&#41; and COPD &#40;AAPC -15&#46;2&#37; 95&#37; CI -18&#46;8- 11&#46;5&#41; cohorts respectively&#46; Influenza and pneumonia-related mortality increased among rural populations in the cirrhosis cohort &#40;AAPC 1&#46;9&#37;&#44; 95&#37; CI 0&#46;9- 2&#46;8&#41; while declining in CHF &#40;AAPC -5&#46;2&#37;&#44; 95&#37; CI -5&#46;8- -4&#46;5&#41; or COPD &#40;AAPC -14&#46;7&#37;&#44; 95&#37; CI -20&#46;7- -8&#46;3&#41; cohorts&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Accidents &#40;unintentional injuries&#41;&#58;</span></span> Accident-related mortality increased in the cirrhosis cohort &#40;AAPC 1&#46;7&#37;&#44; 95&#37; CI 0&#46;3- 3&#46;2&#41; while declining in CHF &#40;AAPC -2&#46;9&#37;&#44; 95&#37; CI -4&#46;6- -1&#46;2&#41; and COPD &#40;AAPC -1&#46;8&#37;&#44; 95&#37; CI -1&#46;8- -0&#46;2&#41; cohorts<span class="elsevierStyleBold">&#46;</span></p><p id="para0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Malignancy&#58;</span></span> Non-HCC malignancy-related mortality declined in the cirrhosis cohort &#40;AAPC -1&#46;1&#37;&#44; 95&#37; CI -1&#46;5- -0&#46;6&#41;&#46; Steeper declines were observed in CHF &#40;AAPC -3&#46;3&#37;&#44; 95&#37; CI -4&#46;8- -1&#46;8&#41; and COPD &#40;AAPC -2&#46;1&#37;&#44; 95&#37; CI -2&#46;3- -1&#46;9&#41; cohorts&#46;</p><p id="para0031" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Diabetes&#58;</span></span> Diabetes-related mortality increased in the cirrhosis cohort &#40;AAPC 0&#46;9&#37;&#44; 95&#37; CI 0&#46;2- 1&#46;7&#41; while declining in CHF &#40;AAPC -0&#46;7&#37;&#44; 95&#37; CI -1&#46;7- 0&#46;3&#41; and increasing in COPD &#40;AAPC 1&#46;9&#37;&#44; 95&#37; CI 1&#46;4- 2&#46;4&#41; cohort&#46;</p><p id="para0032" class="elsevierStylePara elsevierViewall">Further details of trends among women&#44; decedents &#62;65 years and rural populations are provided in <span class="elsevierStyleBold">Supplemental Table 6-8</span>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;6</span><span class="elsevierStyleSectionTitle" id="cesectitle0018">Annual trends in sepsis related mortality in cirrhosis&#44; CHF and COPD&#44; 1999-2017</span><p id="para0033" class="elsevierStylePara elsevierViewall">In the cirrhosis cohort&#44; sepsis related mortality rose markedly throughout the study period &#40;AAPC 3&#46;6&#37;&#44; 95&#37; CI 3&#46;2-4&#46;1&#41; and was especially high in recent years &#40;APC 2009-2017&#58; 6&#46;4&#37;&#41; <span class="elsevierStyleBold">&#40;</span><a class="elsevierStyleCrossRef" href="#tbl0001"><span class="elsevierStyleBold">Table 1</span></a><span class="elsevierStyleBold">&#41;&#46;</span> Sepsis was a major driver of liver-related mortality&#46; Liver related mortality was markedly increased &#40;AAPC 1&#46;3&#37;&#44; 95&#37; CI 0&#46;7-1&#46;9&#41; with sepsis considered as a liver-related cause of death&#46; On sensitivity analysis&#44; when sepsis was considered as an extrahepatic cause&#44; annual increases in liver-related mortality were not as high &#40;AAPC 0&#46;7&#37; -0&#46;2- 1&#46;5&#41; &#40;<a class="elsevierStyleCrossRef" href="#sec0014"><span class="elsevierStyleBold">Supplemental&#160;Table 3</span></a>&#41;&#46; When compared to other chronic diseases&#44; sepsis-related mortality increased more rapidly in the cirrhosis cohort &#40;AAPC 3&#46;6&#37;&#44; 95&#37; CI 3&#46;2- 4&#46;1&#41; while rates were unchanged in the CHF cohort &#40;AAPC 0&#46;6&#37;&#44; 95&#37; CI -0&#46;5- 1&#46;7&#41; and increased minimally in the COPD cohort &#40;AAPC 0&#46;8&#37;&#44; 95&#37; CI 0&#46;5- 1&#46;2&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0002"><span class="elsevierStyleBold">Table 2</span></a><span class="elsevierStyleBold">&#44;</span><a class="elsevierStyleCrossRef" href="#fig0005"><span class="elsevierStyleBold">Fig&#46; 5</span></a><span class="elsevierStyleBold">&#41;</span>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="cesectitle0019">Discussion</span><p id="para0034" class="elsevierStylePara elsevierViewall">From 1999-2017&#44; annual changes in cirrhosis mortality attributed to extrahepatic causes &#40;namely CVD and extrahepatic infections&#41; rose in the cirrhosis cohort&#46; The proportion of extrahepatic deaths exceeded liver-related deaths in all etiologies of cirrhosis&#46; Annual increases in extrahepatic mortality were larger in cirrhosis compared to other chronic diseases&#46; Additionally&#44; women&#44; decedents &#62; 65 years&#44; and rural populations with cirrhosis had disproportionately higher rates of extrahepatic mortality&#46;</p><p id="para0035" class="elsevierStylePara elsevierViewall">Multiple studies have demonstrated increases in all-cause mortality in cirrhosis over the last decade &#91;<a class="elsevierStyleCrossRefs" href="#bib0001">1-6</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0008">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0009">9</a>&#93;&#46; However&#44; our study highlights the need to shift focus towards also considering extrahepatic causes&#46; The rising impact of extrahepatic causes of death on cirrhosis mortality may reflect &#40;1&#41; an aging liver population with increasing comorbidities&#44; &#40;2&#41; improved care of PH- related complications&#44; or &#40;3&#41; certain manifestations &#40;e&#46;g&#46; infection&#41; being the penultimate expression of decompensated cirrhosis <a class="elsevierStyleCrossRef" href="#bib0019">&#91;19&#93;</a>&#46;</p><p id="para0036" class="elsevierStylePara elsevierViewall">Overall&#44; extrahepatic causes of death were significant drivers of mortality in compensated cirrhosis when compared to decompensated cirrhosis in our study&#46; Additionally&#44; liver-related mortality rose among all etiologies of cirrhosis&#46; In the last 10 years&#44; liver-related mortality was highest among decedents with ALD and NAFLD&#46; Rising incidence of hepatic encephalopathy may be a contributing factor &#91;<a class="elsevierStyleCrossRef" href="#bib0020">20</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0021">21</a>&#93;&#46; Alcohol-related cirrhosis may be associated with higher risk of developing HE when compared to NAFLD cirrhosis <a class="elsevierStyleCrossRef" href="#bib0022">&#91;22&#93;</a>&#46; We also observed that HCC-related mortality was an important contributor to liver-related mortality in our study&#46; Growing evidence suggests that alcohol consumption and related cirrhosis&#44; NAFLD&#44; and NASH may directly contribute to the development of HCC and are becoming increasingly common causes of HCC-related mortality at a national level <a class="elsevierStyleCrossRef" href="#bib0023">&#91;23&#93;</a>&#46; Lastly&#44; sepsis was a predominant driver of liver related mortality in our study among all etiologies of sepsis&#46; Rise in multidrug resistant bacteria likely contributes to the increased rates of mortality related to sepsis&#44; peritonitis&#44; and ascites&#46; However&#44; while liver-related mortality remains high because of these entities&#44; a greater proportion of cirrhosis deaths in our study were attributed to extrahepatic causes of death&#46; This further lends support to the fact that equal attention needs to be paid towards extrahepatic causes of death&#46;</p><p id="para0037" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Extrahepatic mortality in cirrhosis compared to other chronic diseases</span>&#58; The absolute number of deaths attributed to CHF and COPD were expectedly higher than deaths attributed to cirrhosis in our study&#46; However&#44; overall trends in mortality remained stable or declined in CHF and COPD while increasing in cirrhosis&#46; CVD remains a major contributor to mortality across <span class="elsevierStyleBold">all</span> chronic diseases&#46; However&#44; there has been an overall decline in cardiovascular mortality due to nationwide initiatives aimed at improving public awareness about reducing cardiometabolic risk factors &#91;<a class="elsevierStyleCrossRef" href="#bib0012">12</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0024">24</a>&#93;&#46; For example&#44; primary CHF admissions have declined over the years and deaths are more likely to be related to non-CHF causes &#40;e&#46;g&#46; atrial fibrillation&#41; or extra-cardiac causes &#40;e&#46;g&#46; malignancy&#44; diabetes&#44; COPD&#44; or kidney disease&#41; <a class="elsevierStyleCrossRef" href="#bib0014">&#91;14&#93;</a>&#46;</p><p id="para0038" class="elsevierStylePara elsevierViewall">Sepsis related mortality was higher in cirrhosis than in CHF or COPD in our study&#46; In the cirrhosis cohort&#44; increase in liver-related mortality&#44; especially within the last decade&#44; was predominantly driven by sepsis&#46; Peritonitis and ascites-related mortality did not fully account for the robust increase in liver-related mortality in the cirrhosis population and mortality in the cirrhosis population was strongly driven by other infections including influenza and pneumonia&#46; Therefore&#44; increased vigilance for non-liver sources of sepsis including respiratory&#44; urinary&#44; or viral causes is needed&#46;</p><p id="para0039" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cirrhosis mortality in demographic subgroups&#58;</span> Extrahepatic causes differentially impacted key demographic subgroups with cirrhosis&#46; For example&#44; rural populations with cirrhosis had higher rates of CVD and infection-related mortality compared to CHF and COPD populations in our study&#46; One explanation may be that the cirrhosis population consists of fewer insured patients and Medicare beneficiaries compared to CHF or COPD populations <a class="elsevierStyleCrossRef" href="#bib0008">&#91;8&#93;</a>&#46; Rates of cardiovascular-related mortality were also higher among women with cirrhosis while rates declined in women with CHF and minimally increased in women with COPD&#46; Interestingly&#44; diabetes-related mortality did not increase alongside cardiovascular mortality among women with cirrhosis suggesting that there may be non-traditional risk factors for CVD in cirrhosis beyond metabolic syndrome&#46; While female gender may be protective in multiple cardiovascular diseases resulting in longer survival compared to males&#44; drivers may be different in cirrhosis and merits further investigation <a class="elsevierStyleCrossRef" href="#bib0025">&#91;25&#93;</a>&#46;</p><p id="para0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Clinical and policy implications&#58;</span> Steps to improve cirrhosis mortality should begin with a shift in focus towards early intervention and reduction of modifiable risk factors&#46; This includes frequent monitoring of lipid profiles&#44; hemoglobin A1C&#44; and administration of age-specific vaccinations&#44; cancer screening&#44; and mood screening&#46; Healthcare models such as the patient-centered medical home may be useful in coordinating care across a multidisciplinary team and multiple health care systems <a class="elsevierStyleCrossRef" href="#bib0026">&#91;26&#93;</a>&#46; Additionally&#44; women&#44; individuals age &#62;65 years&#44; and rural populations with cirrhosis require targeted resource allocation and outreach programs to reduce mortality&#46;</p><p id="para0041" class="elsevierStylePara elsevierViewall">Exploring risk reduction strategies utilized in patients with HIV may be informative&#46; Deaths in this population are increasingly CVD-related not only due to traditional cardiometabolic risk factors &#40;e&#46;g age&#44; sex&#44; smoking status&#44; total cholesterol level&#41;&#44; but also HIV-related factors such chronic inflammation mediated by viral infection and side effects of antiretrovirals&#44; specifically protease inhibitors <a class="elsevierStyleCrossRef" href="#bib0027">&#91;27&#93;</a>&#46; As a result&#44; commonly used risk prediction models&#44; such as the atherosclerotic CVD &#40;ASCVD&#41; score&#44; have shown to underestimate CVD risk in HIV-infected individuals and potentially exclude them from receiving lipid lowering therapies or additional screening &#40;e&#46;g&#46;&#44; coronary artery calcium score&#41; <a class="elsevierStyleCrossRef" href="#bib0028">&#91;28&#93;</a>&#46; Differences in practice patterns of physicians treating HIV infected individuals are also a contributory factor&#59; one analysis <a class="elsevierStyleCrossRef" href="#bib0029">&#91;29&#93;</a> noted that physicians were less likely to prescribe guideline-recommended aspirin and statins to HIV-infected compared to HIV-uninfected patients&#46; This may reflect an uncertainty of statin efficacy in the HIV population&#44; concern for interactions with antiretroviral therapies&#44; or side effects with long term use&#46; To address these issues&#44; large scale trials investigating long term safety and efficacy of statin therapy in HIV- infected patients are currently underway <a class="elsevierStyleCrossRef" href="#bib0028">&#91;28&#93;</a>&#46; Similar analysis of CVD risk models and statin use in cirrhosis populations may be useful&#46;</p><p id="para0042" class="elsevierStylePara elsevierViewall">CVD risk reduction is also the focus in patients with rheumatoid arthritis &#40;RA&#41;&#44; where CVD accounts for nearly 40&#37; of deaths <a class="elsevierStyleCrossRef" href="#bib0030">&#91;30&#93;</a>&#46; Emerging data on benefits of physical activity in RA also warrant attention&#46; In one study&#44; six months of individualized aerobic and resistance training three times per week led to marked improved aerobic capacity &#40;measured by VO<span class="elsevierStyleInf">2</span> max&#41;&#44; blood pressure&#44; lipids levels and 10-year CVD event probability when compared to a group receiving education on exercise only <a class="elsevierStyleCrossRef" href="#bib0031">&#91;31&#93;</a>&#46; These data merit consideration for use in the cirrhosis population&#46;</p><p id="para0043" class="elsevierStylePara elsevierViewall">Our study has several strengths&#46; We examined a national database for cause-specific mortality in cirrhosis to capture recent trends compared to other major chronic conditions&#46; We used validated ICD-10 coding to define chronic diseases and completed sensitivity analysis using various coding algorithms to ensure consistency of results &#40;&#91;<a class="elsevierStyleCrossRef" href="#bib0001">1</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0002">2</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0006">6</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0007">7</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0010">10</a>&#93;&#41;&#46; Additionally&#44; while changes in coding practices over time may result in increased physician use of cirrhosis codes with ICD-10 compared to previous ICD versions&#44; <a class="elsevierStyleCrossRef" href="#bib0010">&#91;10&#93;</a> our analysis of death records begins in 1999&#44; which ensures that death certificate data was coded with a single &#40;ICD-10&#41; coding system&#46;</p><p id="para0044" class="elsevierStylePara elsevierViewall">Several limitations exist&#46; First&#44; death certificate data alone is insufficient to estimate the national disease burden <a class="elsevierStyleCrossRef" href="#bib0010">&#91;10&#93;</a>&#46; Healthcare data from other sources &#40;e&#46;g hospital and VA databases&#41; used in combination with death certificate data may provide additional information&#46; Second&#44; causes of death are subject misclassification among physicians leading to under or overestimation of mortality <a class="elsevierStyleCrossRef" href="#bib0032">&#91;32&#93;</a>&#46; Misclassification of death data may occur between 13-30&#37; of death certificates in published studies &#40;&#91;<a class="elsevierStyleCrossRef" href="#bib0033">33</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0034">34</a>&#93;&#41;&#46; Physicians may be more likely to code for a liver-related cause of death in a decedent known to have cirrhosis compared to a decedent without cirrhosis <a class="elsevierStyleCrossRef" href="#bib0035">&#91;35&#93;</a>&#46; Additionally&#44; increasing prevalence of cirrhosis in the US population may contribute to increased coding on death certificates because of rising awareness&#46; <a class="elsevierStyleCrossRef" href="#bib0006">&#91;6&#93;</a> While absolute number of deaths may be impacted by these limitations&#44; the overall rate of change in annual mortality&#44; which was the focus of this study&#44; may be less affected&#46; Third&#44; liver-related&#44; extrahepatic&#44; and disease-specific causes of death in cirrhosis&#44; CHF and COPD did not account for all deaths occurring between 1999-2017&#46; While 60&#37; of deaths in the cirrhosis population were attributed to extrahepatic and liver-related causes&#44; causes of death in the remaining population were not evaluated&#46; This is because we did not explore deaths attributed to other top 15 causes of national mortality &#40;such as renal diseases&#44; Alzheimer&#39;s&#44; Parkinson&#39;s&#44; or aspiration pneumonitis&#41; and deaths occurring outside of the top 15 causes were also not assessed&#46; However&#44; the intent of our study was to assess the leading causes of extrahepatic deaths across various chronic conditions&#46; Fourth&#44; when determining the impact of cardiovascular related mortality&#44; we did not account for differences in baseline cardiovascular risk factors among each chronic disease cohort&#46; Risk factors are not generally captured on death certificates as underlying or additional causes of death&#46; Future investigations using prospective data can allow for a better understanding and interpretation of these mortality trends&#46;</p><p id="para0045" class="elsevierStylePara elsevierViewall">In summary&#44; annual mortality in cirrhosis is increasingly driven by extrahepatic causes of death such as cardiovascular disease and extrahepatic infections&#46; The impact on mortality is larger in cirrhosis as compared to other chronic diseases&#46; Mitigating these trends may require a shift from how we currently define drivers of mortality in cirrhosis and further lends support to the need for an integrated model of cirrhosis care&#46;</p></span></span>"
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              "titulo" => "Cirrhosis related all-cause mortality&#44; 2017"
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              "titulo" => "Annual trends in liver-related vs extrahepatic mortality in cirrhosis&#44; 1999-2017"
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              "titulo" => "Cirrhosis&#44; CHF and COPD related all-cause mortality&#44; 2017"
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              "titulo" => "Annual trends in cirrhosis&#44; CHF and COPD related all-cause mortality&#44; 1999-2017"
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              "titulo" => "Annual trends in extrahepatic mortality in cirrhosis&#44; CHF and COPD&#44; 1999-2017"
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              "titulo" => "Annual trends in sepsis related mortality in cirrhosis&#44; CHF and COPD&#44; 1999-2017"
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            0 => "Chronic liver disease"
            1 => "National center for health statistics"
            2 => "CHF"
            3 => "COPD"
            4 => "Mortality"
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            6 => "burden"
            7 => "liver disease"
            8 => "morbidity"
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        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Introduction and objectives</span><p id="spara023" class="elsevierStyleSimplePara elsevierViewall">Cirrhosis-related mortality is underestimated and is increasing&#59; extrahepatic factors may contribute&#46; We examined trends in cirrhosis mortality from 1999-2017 in the United States attributed to liver-related &#40;varices&#44; peritonitis&#44; hepatorenal syndrome&#44; hepatic encephalopathy&#44; hepatocellular carcinoma&#44; sepsis&#41; or extrahepatic &#40;cardiovascular disease&#44; influenza and pneumonia&#44; diabetes&#44; malignancy&#41; causes&#44; and compared mortality trends with congestive heart failure &#40;CHF&#41; and chronic obstructive pulmonary disease &#40;COPD&#41; populations&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Materials and methods</span><p id="spara024" class="elsevierStyleSimplePara elsevierViewall">A national mortality database was used&#46; Changes in age-standardized mortality over time were determined by joinpoint analysis&#46; Average annual percentage change &#40;AAPC&#41; was estimated&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Results</span><p id="spara025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Cirrhosis cohort</span>&#58; From 1999-2017&#44; both liver-related &#40;AAPC 1&#46;3&#37;&#59; 95&#37; confidence interval &#91;CI&#93; 0&#46;7-1&#46;9&#41; and extrahepatic mortality &#40;AAPC 1&#46;0&#37;&#59; 95&#37; CI 0&#46;7-1&#46;2&#41; increased&#46; <span class="elsevierStyleBold">Cirrhosis vs other chronic disease cohorts</span>&#58; changes in all-cause mortality were higher in cirrhosis &#40;AAPC 1&#46;0&#37;&#59; 95&#37; CI 0&#46;7-1&#46;4&#41; than CHF &#40;AAPC 0&#46;1&#37;&#59; 95&#37; CI -0&#46;5- 0&#46;8&#41; or COPD &#40;AAPC -0&#46;4&#37;&#59; 95&#37; CI -0&#46;6- -0&#46;2&#41;&#46; Sepsis mortality was highest in cirrhosis &#40;AAPC 3&#46;6&#37;&#44; 95&#37; 3&#46;2- 4&#46;1&#41; compared to CHF &#40;AAPC 0&#46;6&#37;&#44; 95&#37; CI -0&#46;5- 1&#46;7&#41; or COPD &#40;AAPC 0&#46;8&#37;&#44; 95&#37; CI 0&#46;5- 1&#46;2&#41;&#46; Cardiovascular mortality increased in cirrhosis &#40;AAPC 1&#46;3&#37;&#44; 95&#37; CI 1&#46;1- 1&#46;5&#41;&#44; declined in CHF &#40;AAPC -2&#46;0&#37;&#44; 95&#37; CI -5&#46;3- 1&#46;3&#41; and remained unchanged in COPD &#40;AAPC 0&#46;1&#37;&#44; 95&#37; CI -0&#46;2- 0&#46;4&#41;&#46; Extrahepatic mortality was higher among women&#44; rural populations&#44; and individuals &#62;65 years with cirrhosis&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusions</span><p id="spara026" class="elsevierStyleSimplePara elsevierViewall">Extrahepatic causes of death are important drivers of mortality and differentially impact cirrhosis compared to other chronic diseases&#46;</p></span>"
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Annual changes in age-standardized mortality in cirrhosis cohort attributed to liver-related causes &#40;varices&#44; peritonitis&#44; ascites&#44; hepatic encephalopathy&#44; hepatorenal syndrome&#44; hepatocellular carcinoma&#44; and sepsis&#41;&#44; and extrahepatic causes &#40;cardiovascular disease&#44; non-hepatocellular carcinoma malignancy&#44; accidents&#44; diabetes&#44; influenza and pneumonia&#41;&#46; Asterix indicates statistically significant trend &#40;p&#60;&#46;05&#41;</p> <p id="spara002" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">ASMR&#58;</span> age-standardized mortality rate</p> <p id="spara003" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">APC&#58;</span> annual percent change</p>"
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                  \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">AAPC &#40;1999-2017&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">L95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">U95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0007"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0008"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">APC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0009"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">504&#44;192&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;0&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20092009-20152015-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;3&#37;&#42;3&#46;5&#37;0&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="8" align="left" valign="top"><span class="elsevierStyleBold">Liver-related</span></td></tr><tr title="table-row"><a name="en0018"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top"><span class="elsevierStyleBold">All liver-related</span><a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">130&#44;954</span>&#40;26&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">2&#46;7</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">1&#46;3&#37;&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;7</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">1&#46;9</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">1999-2007</span><span class="elsevierStyleBold">2007-2012</span><span class="elsevierStyleBold">2012-2017</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">-2&#46;5&#37;&#42;</span><span class="elsevierStyleBold">2&#46;7&#37;&#42;</span><span class="elsevierStyleBold">6&#46;1&#37;&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0026"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Varices&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">29&#44;942 &#40;5&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-1&#46;3&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20062006-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-6&#46;9&#37;&#42;2&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0034"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Peritonitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#44;743 &#40;2&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;5&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20072007-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-3&#46;6&#37;&#42;5&#46;9&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0042"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Ascites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&#44;006 &#40;4&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;9&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20092009-20142014-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-3&#46;0&#37;&#42;2&#46;8&#37;25&#46;6&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">HE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&#44;402 &#40;1&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;0&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0058"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">HRS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30&#44;688 &#40;6&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;3&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20092009-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-3&#46;2&#37;&#42;3&#46;5&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0066"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">HCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&#44;362 &#40;1&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&#46;2&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2008 2008-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;9&#37;5&#46;5&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0074"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&#44;759 &#40;9&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&#46;6&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20092009-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;4&#37;&#42;6&#46;4&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0082"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="8" align="left" valign="top"><span class="elsevierStyleBold">Extrahepatic</span></td></tr><tr title="table-row"><a name="en0083"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top"><span class="elsevierStyleBold">All extrahepatic</span><a class="elsevierStyleCrossRef" href="#tb1fn3"><span class="elsevierStyleSup">&#167;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">177&#44;303 &#40;35&#46;2&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">3&#46;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">1&#46;0&#37;&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">0&#46;7</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">1&#46;2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">1999-2008</span><span class="elsevierStyleBold">2008-2017</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">-0&#46;8&#37;&#42;</span><span class="elsevierStyleBold">2&#46;8&#37;&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0091"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">CVD<a class="elsevierStyleCrossRef" href="#tb1fn4"><span class="elsevierStyleSup">&#182;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">129&#44;377 &#40;25&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;3&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2008 2008-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;7&#37;&#42;3&#46;3&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Non-HCC Malignancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11&#44;124 &#40;2&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-1&#46;1&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0107"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Accidents &#40;unintentional injuries&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&#44;363 &#40;1&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;7&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0115"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Diabetes Mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33&#44;821 &#40;6&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;9&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20032003-20102010-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;4&#37;-1&#46;0&#37;2&#46;0&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0123"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Influenza and pneumonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&#44;684 &#40;5&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;1&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-20102010-2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;94&#46;2&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:4 [
            0 => array:3 [
              "identificador" => "tb1fn1"
              "etiqueta" => "&#8224;"
              "nota" => "<p class="elsevierStyleNotepara" id="notep0003">&#58; Total number of deaths from 1999-2017&#46; The denominator for &#8216;proportion&#8217; is total number of cirrhosis deaths&#44; 1999-2017&#44; from all causes</p>"
            ]
            1 => array:3 [
              "identificador" => "tb1fn2"
              "etiqueta" => "&#8225;"
              "nota" => "<p class="elsevierStyleNotepara" id="notep0004">&#58; Liver-related causes includes codes for varices&#44; peritonitis&#44; ascites&#44; hepatic encephalopathy&#44; hepatorenal syndrome&#44; HCC&#44; and sepsis</p>"
            ]
            2 => array:3 [
              "identificador" => "tb1fn3"
              "etiqueta" => "&#167;"
              "nota" => "<p class="elsevierStyleNotepara" id="notep0005">&#58; Extrahepatic causes include codes for CVD&#44; non-HCC malignancy&#44; accidents&#44; diabetes and influenza and pneumonia</p>"
            ]
            3 => array:3 [
              "identificador" => "tb1fn4"
              "etiqueta" => "&#182;"
              "nota" => "<p class="elsevierStyleNotepara" id="notep0006">&#58; Cardiovascular causes includes codes for myocardial infarction&#44; strokes&#44; congestive heart failure&#44; and hypertension&#44; and excludes codes for esophageal and gastric varices</p> <p class="elsevierStyleNotepara" id="notep0007">ASMR&#58; age-standardized mortality rate</p> <p class="elsevierStyleNotepara" id="notep0008">AAPC&#58; average annual percent change</p> <p class="elsevierStyleNotepara" id="notep0009">HRS&#58; hepatorenal syndrome</p> <p class="elsevierStyleNotepara" id="notep0010">HE&#58; hepatic encephalopathy</p> <p class="elsevierStyleNotepara" id="notep0011">HCC&#58; hepatocellular carcinoma</p> <p class="elsevierStyleNotepara" id="notep0012">CVD&#58; Cardiovascular disease</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara017" class="elsevierStyleSimplePara elsevierViewall">Age-standardized mortality from liver-related and extrahepatic causes of death in cirrhosis&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0007"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spara021" class="elsevierStyleSimplePara elsevierViewall">Asterix &#40;&#42;&#41; indicates significant &#40;p&#60;&#46;05&#41; trend</p><p id="spara022" class="elsevierStyleSimplePara elsevierViewall">No significant joinpoint trends were identified in deaths related to malignancy or accidents in cirrhosis and all-cause mortality&#44; cardiovascular disease&#44; malignancy&#44; or accidents in COPD</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0131"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0132"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">Deaths &#40;proportion&#41; <a class="elsevierStyleCrossRef" href="#tb2fn1"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0133"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">ASMR 2017&#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0134"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">AAPC 1999-2017&#40;95&#37;CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0135"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">Trend Segments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><a name="en0136"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0137"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0138"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Cirrhosis Mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0139"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0140"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0141"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">All causes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">504&#44;192&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9&#46;3 &#40;9&#46;2 to 9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0144"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;0&#37;&#42; &#40;0&#46;7 to 1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2009&#58; 0&#46;3&#37;&#42;2009-2015&#58; 3&#46;5&#37;&#42;2015-2017&#58; 0&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0146"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Liver-related<a class="elsevierStyleCrossRef" href="#tb2fn2"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">130&#44;954 &#40;26&#46;0&#37;&#41;<a class="elsevierStyleCrossRef" href="#tb2fn3"><span class="elsevierStyleSup">&#167;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0148"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;7 &#40;2&#46;7 to 2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;3&#37;&#42; &#40;0&#46;7-1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2007&#58; -2&#46;5&#37;&#42;2007-2012&#58; 2&#46;7&#37;&#42;2012-2017&#58; 6&#46;1&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0151"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cardiovascular disease <a class="elsevierStyleCrossRef" href="#tb2fn4"><span class="elsevierStyleSup">&#182;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">129&#44;377 &#40;25&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0153"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;5 &#40;2&#46;4 to 2&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;3&#37;&#42;&#40;1&#46;1 to 1&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2008&#58; -0&#46;7&#37;&#42;2008-2017&#58; 3&#46;3&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0156"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Non-HCC Malignancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11&#44;124 &#40;2&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0158"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;2 &#40;0&#46;16 to 0&#46;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0159"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-1&#46;1&#37;&#42; &#40;-1&#46;5 to -0&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0160"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0161"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Accidents &#40;unintentional injuries&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0162"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5&#44;363 &#40;1&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0163"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;1 &#40;0&#46;10 to 0&#46;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0164"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;7&#37;&#42; &#40;0&#46;3 to 3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0165"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0166"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33&#44;821 &#40;6&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0168"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;6 &#40;0&#46;56 to 0&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0169"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;9&#37;&#42; &#40;0&#46;2 to 1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0170"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2003&#58; 2&#46;4&#37;2003-2010&#58; -1&#46;0&#37;2010-2017&#58; 2&#46;0&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0171"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Influenza and pneumonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0172"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&#44;684 &#40;5&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0173"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;51 &#40;0&#46;49 to 0&#46;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0174"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;1&#37;&#42; &#40;0&#46;3 to 1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0175"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2010&#58; -0&#46;9&#37;2010- 2017&#58; 4&#46;2&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0176"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0177"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&#44;759 &#40;9&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0178"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;1 &#40;1&#46;0 to 1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0179"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&#46;6&#37;&#42; &#40;3&#46;2 to 4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0180"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2009&#58; 1&#46;4&#37;&#42;2009-2017&#58; 6&#46;4&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0181"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="5" align="left" valign="top"><span class="elsevierStyleBold">CHF Mortality</span></td></tr><tr title="table-row"><a name="en0182"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">All causes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0183"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#44;171&#44;928&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0184"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">20&#46;4 &#40;20&#46;3 to 20&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0185"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;1&#37; &#40;-0&#46;5 to 0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0186"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2005-2011&#58; -2&#46;6&#37;&#42;2011-2017&#58; 3&#46;9&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0187"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cardiovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0188"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">92&#44;476 &#40;7&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0189"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;3 &#40;1&#46;2 to 1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0190"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-2&#46;0&#37; &#40;-5&#46;3 to 1&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0191"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2003&#58; -5&#46;2&#37;2003-2006&#58; 10&#46;3&#37;2006-2017&#58; -4&#46;0&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0192"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Malignancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0193"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28&#44;123 &#40;2&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0194"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;4 &#40;0&#46;35 to 0&#46;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0195"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-3&#46;3&#37;&#42; &#40;-4&#46;8 to -1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0196"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2014&#58; -5&#46;0&#37;&#42;2014-2017&#58; 5&#46;4&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0197"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Accidents &#40;unintentional injuries&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0198"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11&#44;396 &#40;1&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0199"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;2 &#40;0&#46;14 to 0&#46;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0200"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-2&#46;9&#37;&#42; &#40;-4&#46;6 to -1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0201"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2012&#58; -4&#46;7&#37;&#42;2012-2017&#58; 1&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0202"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0203"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">69&#44;330 &#40;5&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0204"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;1 &#40;1&#46;05 to 1&#46;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0205"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;7&#37; &#40;-1&#46;7 to 0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0206"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2006-2009&#58; -7&#46;4&#37;&#42;2009-2014&#58; -1&#46;22014-2017&#58; 3&#46;5&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0207"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Influenza and pneumonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0208"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">83&#44;742 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0209"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;93 &#40;0&#46;90 to 0&#46;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0210"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-4&#46;9&#37;&#42; &#40;-6&#46;1 to -3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0211"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2005&#58; -4&#46;8&#37;&#42;2005-2009&#58; -10&#46;4&#37;&#42;2009-2018&#58; -2&#46;2&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0212"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0213"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">32&#44;255 &#40;2&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0214"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;60 &#40;0&#46;58 to 0&#46;62&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0215"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;6&#37; &#40;-0&#46;5 to 1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0216"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1999-2013&#58; -1&#46;1&#37;2013- 2017&#58; 6&#46;8&#37;&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0217"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead colgroup " colspan="5" align="left" valign="top"><span class="elsevierStyleBold">COPD Mortality</span></td></tr><tr title="table-row"><a name="en0218"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">All cause&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0219"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#44;504&#44;845&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0220"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39&#46;7 &#40;39&#46;46-39&#46;97&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0221"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-0&#46;4&#42; &#40;-0&#46;6 to - 0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0222"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0223"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cardiovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0224"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#44;160&#44;462&#40;46&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0225"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&#46;3 &#40;19&#46;2 to 19&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0226"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;1&#37; &#40;0&#46;2 to 0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0227"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0228"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Malignancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0229"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#44;233 &#40;0&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0230"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;8 &#40;1&#46;7 to 1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0231"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-2&#46;1&#37;&#42; &#40;-2&#46;3 to -1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Accidents &#40;unintentional injuries&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Diabetes&nbsp;\t\t\t\t\t\t\n
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ISSN: 16652681
Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos