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of psoriatic patients are associated with ischaemic heart disease&#44; 12&#37; associated with diabetes mellitus&#44; and 36&#37; associated with arterial hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> There are meta-analyses about psoriasis with single diseases&#44; e&#46;g&#46; Chronic Obstructive Pulmonary Disease &#40;COPD&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> However&#44; there is no comorbidity data at levels of organs&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Although the close relationship between psoriasis and concomitant diseases has been commonly accepted&#44; and the risk of a single specific disease in psoriasis has been intensively studied&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;23&#44;24</span></a> However&#44; a comprehensive analysis of comorbidities in terms of organs in psoriasis is still lacking&#46; In this study&#44; the authors aimed to investigate the differences between psoriasis and the general population in terms of different organ-based comorbidities&#46; The analysis was not limited to purely merger values and tried to find association patterns between them&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Literature review and search strategy</span><p id="par0015" class="elsevierStylePara elsevierViewall">This meta-analysis was registered in PROSPERO &#40;CRD 42020211821&#41;&#44; following the PRISMA 2020 checklist&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The authors searched Pubmed&#44; EMBASE&#44; and Cochrane Library databases&#44; including all studies from the respective inception of these databases to October 14&#44; 2020&#46; The investigator performed the literature retrieval&#44; research selection&#44; data extraction&#44; and quality assessment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The search strategy included a variety of terms related to psoriasis and organ-based comorbidities&#46; The detailed search strategies of Pubmed&#44; Embase&#44; and Cochrane Library were put in the supplementary material&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Selection of studies</span><p id="par0025" class="elsevierStylePara elsevierViewall">According to the PECO strategy&#44; articles that met the following criteria would be included&#46; Population&#58; the authors included studies that contained both psoriasis and the general population&#59; Exposure&#58; psoriasis with regular diagnosis &#40;no age limit&#41;&#59; Comparative&#58; the people without psoriasis and from the same research environment as psoriasis&#59; Outcome&#58; the record results were organ-based comorbidities &#40;cardiovascular diseases&#44; kidney diseases&#44; liver diseases&#44; respiratory diseases&#44; spleen diseases&#44; and cerebrovascular system-related diseases&#41;&#46; Publications with insufficient and reduplicated data were excluded&#46; The restriction of study type and language were not considered in the initial search&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Data extraction and assessment of study quality</span><p id="par0030" class="elsevierStylePara elsevierViewall">Full text of articles meeting the eligibility criteria was selected for data extraction&#46; Data was extracted by the first author&#44; year of publication&#44; country&#44; demographic&#44; number of patients&#44; and follow-up time&#46; For example&#44; 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pRRs were subjected to Z-test and sensitivity analysis and used to assess the combined stability effect&#46; Publication bias was measured by constructing funnel plots&#46; A symmetrical inverted funnel indicated that there is no high likelihood of publication bias&#46; Finally&#44; a study was removed to assess its impact on the merger&#46; The similarity of combined RRs before and after removing the study indicated that there was a high certainty in the results&#46; When heterogeneity existed between studies&#44; the authors applied the random-effect model and used the Mantel-Haenszel analysis method&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study selection</span><p id="par0040" class="elsevierStylePara elsevierViewall">The search strategy &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; produced 7&#44;412 potentially relevant references &#40;3&#44;862 in Pubmed&#44; 2&#44;984 in EMBASE&#44; and 566 in the Cochrane Library&#41;&#46; Finally&#44; fifteen retrospective cohort studies remained&#44; containing 216&#44;348 psoriatic patients and 9&#44;896&#44;962 general people&#46; All studies were based on a managed database&#44; relied on diagnostic codes to identify and verify the diagnosis of psoriasis and organ-based comorbidities&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study characteristics</span><p id="par0045" class="elsevierStylePara elsevierViewall">The main clinical characteristics and quality evaluation of the included studies were summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; These studies were conducted in seven countries&#58; the United States&#44; the United Kingdom&#44; Germany&#44; Denmark&#44; Italy&#44; Taiwan&#44; and South Korea&#46; The mean age of psoriatic patients ranged from 12&#46;0 to 69&#46;5 years&#44; and females accounted for 32&#46;58&#37; to 59&#46;19&#37;&#46; For the general population&#44; the mean age ranged from 12&#46;0 to 70&#46;6 years&#44; and females accounted from 22&#46;14&#37; to 67&#46;42&#37;&#46; Only two studies did not report the average age&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> and one study mainly investigated children with psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> So&#44; the span of age characteristics was large after synthesizing data&#46; There was little specific organ-based comorbidities data of race&#46; Therefore&#44; no subgroup analysis was conducted on race&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Psoriasis and all organ-based comorbidities</span><p id="par0055" class="elsevierStylePara elsevierViewall">The risks all included organ-based comorbidities between psoriatic patients and the general population were described in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; The authors mainly studied the involvements of the heart&#44; kidneys&#44; lung&#44; brain&#44; and liver&#46; In 15 studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;40</span></a> they contained 216&#44;348 psoriatic patients and 9&#44;896&#44;962 control subjects&#46; It showed that psoriatic patients had a significantly increased risk of these organ-based comorbidities&#44; and pRR was 1&#46;20 &#40;95&#37; CI 1&#46;11&#8210;1&#46;31&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; After removing the study involving mainly children&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> pRR became to 1&#46;17 &#40;95&#37; CI 1&#46;08&#8210;1&#46;27&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Psoriasis and specific organ-based comorbidities</span><p id="par0060" class="elsevierStylePara elsevierViewall">In 14 studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;34&#44;36&#8211;40</span></a> summing 210&#44;856 psoriatic patients and 9&#44;891&#44;470 controls&#46; The pRR for cardiovascular events was 1&#46;20 &#40;95&#37; CI 1&#46;11&#8210;1&#46;30&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>97&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; significantly increased comparing the general population&#46; In 9 studies<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;29&#8211;31&#44;34&#8211;36&#44;38&#44;40</span></a> involved 135&#44;345 psoriatic patients and 9&#44;699&#44;285 control subjects&#44; pRR for renal diseases was 1&#46;08 &#40;95&#37; CI 0&#46;87&#8210;1&#46;33&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>83&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In 8 studies<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27&#44;31&#8211;33&#44;35&#44;37&#44;40</span></a> with 103&#44;300 psoriatic patients and 4&#44;729&#44;963 control subjects&#44; pRR of cerebrovascular disease events was 1&#46;56 &#40;95&#37; CI 1&#46;20&#8210;2&#46;04&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>94&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In 9 studies<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;30&#8211;32&#44;35&#44;36&#44;38</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> with 132&#44;791 psoriatic patients and 9&#44;689&#44;831 control subjects&#44; pRR for the occurrence of pulmonary disease events was 1&#46;05 &#40;95&#37; CI 0&#46;89&#8210;1&#46;23&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>92&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In 5 studies<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28&#44;35&#44;38</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> involved 46&#44;469 psoriatic patients and 131&#44;154 control subjects&#44; pRR for the occurrence of liver diseases was 1&#46;75 &#40;95&#37; CI 1&#46;33&#8210;2&#46;29&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>88&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and it was remarkably higher than general population &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Psoriasis and multiple organ-based comorbidities</span><p id="par0065" class="elsevierStylePara elsevierViewall">Psoriatic patients had been reported to suffer from two or more comorbidities simultaneously&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#8211;46</span></a> Hence&#44; the authors extracted data of two organs from included studies and calculated pRRs &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; pRR for renal diseases <span class="elsevierStyleItalic">plus</span> cardiovascular events was 1&#46;09 &#40;95&#37; CI 1&#46;01&#8210;1&#46;18&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>85&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; pRR for renal diseases <span class="elsevierStyleItalic">plus</span> cerebrovascular events was 1&#46;28 &#40;95&#37; CI 0&#46;99&#8210;1&#46;66&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; pRR for renal diseases <span class="elsevierStyleItalic">plus</span> liver diseases were 1&#46;46 &#40;95&#37; CI 1&#46;10&#8210;1&#46;94&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; pRR for cardiovascular events <span class="elsevierStyleItalic">plus</span> liver diseases were 1&#46;41 &#40;95&#37; CI 1&#46;11&#8210;1&#46;80&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>95&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Organ-based comorbidity risks in mild and moderate&#47;severe psoriasis</span><p id="par0070" class="elsevierStylePara elsevierViewall">Three studies were subdividing psoriatic patients into mild and moderate&#47;severe subgroups&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;32&#44;36</span></a> They included 97&#44;285 patients with mild psoriasis and 15&#44;016 patients with moderate&#47;severe psoriasis in total&#46; pRR of organ-based comorbidity risk was 0&#46;61 &#40;95&#37; CI 0&#46;46&#8210;0&#46;81&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>94&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; for mild psoriasis&#44; which was lower than that of moderate&#47;severe psoriatic patients &#40;Supplementary Fig&#46; S1&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Sensitivity analyses</span><p id="par0075" class="elsevierStylePara elsevierViewall">Sensitivity is an important indicator of literature quality and heterogeneity&#46; One study was excluded to estimate the effect of pRRs at a time&#46; There was no obvious change and a significant decrease in heterogeneity&#46; Sensitivity analyses were performed to assess which study provided greater heterogeneity in the data by the Galbraith plot&#46; All studies showed stable and reliable results &#40;Supplementary Fig&#46; S2&#41;&#46; After careful evaluation&#44; it was concluded that every study was not sensitive to pRRs and could not be arbitrarily excluded&#46; As the score results were assessed by Newcastle-Ottawa Quality Assessment Scale for all included studies in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; All studies scored at least 6 points&#44; which was in line with the requirements for continuing study&#46; Meanwhile&#44; Stata&#39;s Metaninf command was used to assess the impact of a single study&#46; After excluding one study at a time&#44; the point of estimate did not fall out of 95&#37; CI &#40;Supplementary Fig&#46; S3&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Publication bias</span><p id="par0080" class="elsevierStylePara elsevierViewall">The funnel plot was utilized to analyze the publication bias of 15 studies&#46; The outcome of the graph showed a certain degree of publication bias&#46; The authors further used the Egger method to check and quantify the funnel plot&#46; The p-value was checked to determine whether there was publication bias&#46; The T-value in bias &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;854&#41; meant that there was no publication bias &#40;Supplementary Fig&#46; S4&#41;&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Study quality</span><p id="par0085" class="elsevierStylePara elsevierViewall">Regarding the quality of all studies&#44; the NOS score ranged from 6 to 8&#46; The authors determined that 6 studies had a low risk of bias&#44; 7 studies had a medium risk of bias&#44; and 2 studies had a high risk of bias &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Subgroup analysis</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors conducted the subgroup analyses&#44; including regions &#40;Western vs&#46; Asian countries&#41;&#44; study period &#40;covering 2000 vs&#46; after 2000&#41;&#44; and funding &#40;with vs&#46; without&#41;&#46; The research region of the three studies was Asia&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27&#44;34</span></a> the rest was the West&#46; The outcomes showed that Asian countries with pRR of 1&#46;09 &#40;95&#37; CI 0&#46;95&#8210;1&#46;24&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and 1&#46;24 &#40;95&#37; CI 1&#46;12&#8210;1&#46;37&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; for Western countries&#46; The I&#178; was 55&#46;5&#37; and p-value was 0&#46;13 between the subgroups &#40;Supplementary Fig&#46; S5&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Two studies had not clearly pointed out the study duration&#44;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;40</span></a> and the rest studies were divided into two groups for further discussion&#46; Four researches&#8217; periods were over the year of 2000&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;33&#44;34&#44;36</span></a> and pRR was 1&#46;04 &#40;95&#37; CI 0&#46;89&#8210;1&#46;21&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>97&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; pRR of the rest researches &#40;after 2000&#41; was 1&#46;31 &#40;95&#37; CI 1&#46;17&#8210;1&#46;47&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>99&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The I&#178; was 82&#46;7&#37; and the p-value was 0&#46;02 between the subgroups &#40;Supplementary Fig&#46; S6&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">There was some research that had no funding&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;32</span></a> while the rest of the studies were funded&#46; The analysis showed that pRR of unfunded research was 1&#46;33 &#40;95&#37; CI 1&#46;10&#8210;1&#46;62&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>99&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and pRR of funded ones was 1&#46;18 &#40;95&#37; CI 1&#46;09&#8210;1&#46;29&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; The I&#178; was 18&#46;7&#37; and p-value was 0&#46;27 between the subgroups &#40;Supplementary Fig&#46; S7&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">These results of subgroup analyses&#44; including regions &#40;Western vs&#46; Asian countries&#41;&#44; study period &#40;covering 2000 vs&#46; after 2000&#41;&#44; and funding &#40;with vs&#46; without&#41;&#44; had not provided any specific source of heterogeneity&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Meta-regression</span><p id="par0110" class="elsevierStylePara elsevierViewall">According to the characteristics of included studies&#44; new concomitant variables were generated after dummy variables were assigned according to regions &#40;Western vs&#46; Asian countries&#41;&#44; study period &#40;covering 2000 vs&#46; after 2000&#41;&#44; and funding &#40;with vs&#46; without&#41;&#46; The logarithmic LogRR of each study effect indicator RR was the dependent variable&#46; The meta regressions were all carried out &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; but there was no source of heterogeneity&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">The present study is the first meta-analysis of comorbidity risk in terms of organs in psoriatic patients&#46; These risks of organ-based comorbidity were consistent with the previously published data at single-disease level&#46; For example&#44; previous studies showed that psoriatic patients had a higher risk of hypertension &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;58&#44; 95&#37; CI 1&#46;42&#8210;1&#46;76&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> end-stage renal disease &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;29&#44; 95&#37; CI 1&#46;05&#8210;1&#46;60&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> stroke &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;08&#44; 95&#37; CI 1&#46;00&#8210;1&#46;16&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> non-alcoholic fatty liver disease &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;15&#44; 95&#37; CI 1&#46;57&#8210;2&#46;94&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and COPD &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;90&#44; 95&#37; CI 1&#46;36&#8210;2&#46;65&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The authors found that psoriatic patients had a significantly higher risk of organ-based comorbidities than the general population&#46; For example&#44; comorbidity pRR was 1&#46;20 for the overall cardiovascular organ&#44; 1&#46;75 for the whole liver&#44; 1&#46;56 for the whole cerebrovascular organ&#44; 1&#46;08 and 1&#46;05 for the entire kidney organ and lung organs&#44; respectively&#46; In the cardiovascular&#44; liver&#44; and cerebrovascular&#44; organ-based comorbidity risks of psoriasis were remarkably higher than in the general population&#46; Although there was no significant difference between psoriasis and controls in relation to renal and pulmonary diseases&#44; the results can also provide some reference for future research&#46; In addition&#44; compared with mild psoriatic patients&#44; the authors demonstrated that moderate&#47;severe psoriatic patients had a more notably increased risk of organ-based comorbidities&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Previous studies had shown that psoriatic patients may suffer from two or more comorbidities simultaneously&#44; e&#46;g&#46;&#44; heart failure combined with chronic kidney disease&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> gout or acute kidney injury combined with hypertension&#44; liver cirrhosis&#44; or cerebrovascular disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#8211;46</span></a> To find out these combined comorbidity risks in psoriasis&#44; the authors pooled data from multiple organs&#46; The authors found that pRR for renal diseases <span class="elsevierStyleItalic">plus</span> cardiovascular events in the same psoriatic patient was 1&#46;09 &#40;95&#37; CI 1&#46;01&#8210;1&#46;18&#41;&#44; 1&#46;28 &#40;95&#37; CI 0&#46;99&#8210;1&#46;66&#41; for renal diseases <span class="elsevierStyleItalic">plus</span> cerebrovascular events&#44; 1&#46;46 &#40;95&#37; CI 1&#46;10&#8210;1&#46;94&#41; for renal diseases <span class="elsevierStyleItalic">plus</span> liver diseases&#44; and 1&#46;41 &#40;95&#37; CI 1&#46;11&#8210;1&#46;80&#41; for cardiovascular events <span class="elsevierStyleItalic">plus</span> liver diseases&#46; These values showed that psoriatic patients had significantly higher risks of multiple organ-based comorbidities&#44; not only single organ-based comorbidities&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In order to further analyze the relationship between organ-based comorbidity risks of psoriasis and study year and patients&#8217; region&#44; the authors compared several sets of data&#46; Due to the diverse characteristics of the years included in the studies&#44; the authors took the year 2006 as the demarcation point&#44; based on the principle of pursuing maximum similarity&#46; Six groups of meaningful data were selected&#44;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;30&#8211;32&#44;35&#44;37</span></a> and pRR was 0&#46;23 &#40;95&#37; CI 0&#46;05&#8210;1&#46;00&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; after merging data &#40;Supplementary Fig&#46; S8&#41;&#46; This suggested that psoriatic patients after the year of 2006 were more likely to suffer from organ-based comorbidities&#46; As few studies were included in the East&#44; three groups matched with the characteristics of studies in East were used for comparative study&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27&#44;32&#8211;34&#44;39</span></a> After merging data&#44; pRR was 1&#46;73 &#40;95&#37; CI 1&#46;07&#8210;2&#46;77&#44; I&#178;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#37;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;Supplementary Fig&#46; S9&#41;&#46; The result suggested that Asian psoriatic patients were more likely to suffer from organ-based comorbidities&#46; These conclusions need more data for further confirmation&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The pathogenesis of psoriasis and organ-based comorbidities may be mediated by certain representative cytokines&#44; e&#46;g&#46;&#44; Interleukin-17 &#40;IL-17&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">50&#8211;53</span></a> Interleukin-23 &#40;IL-23&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> and Tumour Necrosis Factor-&#593; &#40;TNF-&#593;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;56</span></a> They can reach the body anywhere through the blood circulation and may mediate systemic inflammatory responses in psoriasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">57&#8211;61</span></a> Whether the inflammatory cytokines act on each system together or singly&#63; Whether the effects are generated by the same molecular mechanism and immune-inflammatory pathway&#63; These questions are unclear and still need further study&#46; Actually&#44; the cytokines behind the pathogenesis of each organ may be the same or absolutely different&#46; The existing research has shown that main inflammation cytokine behind psoriasis with joints or diabetes is TNF-&#593;&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">62&#8211;66</span></a> However&#44; the cytokine in psoriasis involving the cardiovascular system may be IL-17 or IL-23&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">67&#8211;69</span></a> All these still need further investigation&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The present study can provide a reference for effective clinical treatments&#46; Lately&#44; biological antibody therapy plays a promising role in the control of psoriatic morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">70&#8211;75</span></a> If molecular mechanisms and dysregulated target cytokines in involved organs are different&#44; then the choice of biological antibody should be totally different&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">76&#8211;80</span></a> No biological antibody is a panacea&#44;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">81&#8211;84</span></a> and the authors should try to provide patients with more individualized treatment plan according to organ-based comorbidities that psoriasis involved&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">There are several limitations in the meta-analysis&#46; First&#44; there is heterogeneity&#46; It was considered that heterogeneity was normally distributed and acceptable&#46; The statistical heterogeneity did not affect the outcome&#46; It was observed that the rate of heterogeneity in meta-analysis of general prevalence was always high&#46; It was related to a huge number of study objects and the nature of observational studies&#46; In this study&#44; subgroup analysis and meta-regression were conducted to try to find the source of heterogeneity&#46; The authors also used a random-effects model to address potential heterogeneity&#46; However&#44; each study was qualitatively similar to the analysis of all organ-based comorbidities and individual organ-based comorbidities&#46; Secondly&#44; some systematic analyses&#44; meta-regression&#44; and subgroup analyses lacked high statistical power because of the small number of included studies&#46; Care should be taken when analyzing these data&#46; Thirdly&#44; the topic of the present study is novel&#44; and there is no study on organ-based comorbidities of psoriasis&#46; For the PECO approach&#44; it is different from the traditional PECO expression and may cause confusion&#46; The study population included the exposure group plus the control group&#44; i&#46;e&#46;&#44; the Population contains Exposure and Comparative&#46; However&#44; the present study&#8217;s results can still provide a reference for clinicians in the management of psoriasis comorbidities&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors show that psoriatic patients have increased risks of both single and multiple organ-based comorbidities&#46; None of these has been reported in published literature&#46; These results suggest that systemic inflammation control should be observed in the treatment&#44; especially for moderate&#47;severe patients&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Financial support</span><p id="par0150" class="elsevierStylePara elsevierViewall">This study was supported in part by the <span class="elsevierStyleGrantSponsor" id="gs0005">National Natural Science Foundation of China</span> &#40;n&#186; <span class="elsevierStyleGrantNumber" refid="gs0005">81771783</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs0005">82073444</span>&#41;&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Authors&#8217; contributions</span><p id="par0155" class="elsevierStylePara elsevierViewall">Xuemei Tang&#58; Approval of the final version of the manuscript&#59; critical literature review&#59; data collection&#44; analysis&#44; and interpretation&#59; effective participation in research orientation&#59; intellectual participation in propaedeutic and&#47;or therapeutic&#59; management of studied cases&#59; manuscript critical review&#59; preparation and writing of the manuscript&#59; statistical analysis&#59; study conception and planning&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Conflicts of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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              "titulo" => "Background"
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          "titulo" => "Introduction"
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          "titulo" => "Material and methods"
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              "titulo" => "Psoriasis and all organ-based comorbidities"
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              "titulo" => "Organ-based comorbidity risks in mild and moderate&#47;severe psoriasis"
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    "fechaRecibido" => "2021-07-05"
    "fechaAceptado" => "2021-10-04"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Comorbidity"
            1 => "Meta-analysis"
            2 => "Psoriasis"
            3 => "Risk"
            4 => "Systematic review"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The close relationship between psoriasis and concomitant diseases is widely accepted&#46; However&#44; a comprehensive analysis of organ-based comorbidities in psoriasis is still lacking&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The authors aimed to present the risk of organ-based comorbidities in psoriasis by comparing the general population&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The authors retrieved a search of Pubmed&#44; EMBASE&#44; and Cochrane databases for studies reporting organ-based comorbidities in psoriasis versus the general population&#46; Observational studies that met the following criteria were assessed&#58; 1&#41; Psoriasis diagnosis&#59; 2&#41; Cardiovascular or kidney or liver or respiratory or cerebrovascular outcomes&#59; 3&#41; Comparison group of individuals without psoriasis&#46; Pooled Relative Risks &#40;pRRs&#41; and 95&#37; Confidence Intervals &#40;CIs&#41; were calculated by using the random-effect model&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Fifteen observational studies with 216&#44;348 psoriatic patients and 9&#44;896&#44;962 individuals from the general population were included&#46; Psoriasis showed a greater risk of organ-based comorbidities&#46; Compared to the general population&#44; pRR for all organ-based comorbidities was 1&#46;20 &#40;95&#37; CI 1&#46;11&#8210;1&#46;31&#41; in psoriasis&#44; and pRR was lower in mild 0&#46;61 &#40;95&#37; CI 0&#46;46&#8210;0&#46;81&#41; than in moderate&#47;severe patients&#46; pRR was 1&#46;20 &#40;95&#37; CI 1&#46;11&#8210;1&#46;30&#41; for cardiovascular&#44; 1&#46;56 &#40;95&#37; CI 1&#46;20&#8210;2&#46;04&#41;&#44; and 1&#46;75 &#40;95&#37; CI 1&#46;33&#8210;2&#46;29&#41; for cerebrovascular and liver diseases&#44; respectively&#46; pRR for coexisting renal and cardiovascular events was 1&#46;09 &#40;95&#37; CI 1&#46;01&#8210;1&#46;18&#41;&#46; pRR for coexisting renal and cerebrovascular events was 1&#46;28 &#40;95&#37; CI 0&#46;99&#8210;1&#46;66&#41;&#46; pRR for coexisting renal and liver diseases was 1&#46;46 &#40;95&#37; CI 1&#46;10&#8210;1&#46;94&#41;&#46; pRR for coexisting cardiovascular and liver diseases was 1&#46;41 &#40;95&#37; CI 1&#46;11&#8210;1&#46;80&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Study limitations</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">There is heterogeneity&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusion</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Psoriasis has a higher risk of single and multiple organ-based comorbidities than the general population&#46; The present study will further improve attention to psoriasis as a systemic inflammatory disease&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study conducted at the Southwest Medical University&#44; Luzhou&#44; Sichuan&#44; China&#46;</p>"
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            "apendice" => "<p id="par0170" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flow diagram of study selection&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Forest plot of the risks of comorbidities in psoriatic patients comparing the general population&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Forest plot of specific comorbidity risk in psoriatic patients compared with the general population &#40;cardiovascular&#44; renal&#44; cerebrovascular&#44; lung&#44; liver diseases&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">NR&#44; Not Reported&#59; NOS&#44; Newcastle&#8211;Ottawa Quality Assessment Scale&#59; CVD&#44; Cardiovascular Disease&#59; CD&#44; Cerebrovascular Disease&#59; KD&#44; Kidney Disease&#59; PD&#44; Pulmonary Disease&#59; LD&#44; Liver Disease&#59; US&#44; United States&#59; UK&#44; United Kingdom&#46;</p>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Region&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Study period&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">Data sources&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean age&#44; &#40;y&#41;&#59; Female &#40;&#37;&#41;</th><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#176; of psoriatic patients</th><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#176; of Control</th><th class="td" title="\n
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                  \t\t\t\t" scope="col">Specific comorbidities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">NOS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Psoriasis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">All&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comorbidities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">All&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comorbidities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" 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"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ahlehoff O&#44; 2011<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Danish&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2002&#8211;2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The Danish National Patient Register&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&#46;5 &#40;12&#46;1&#41;&#59; 36&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#46;6 &#40;13&#46;5&#41;&#59; 38&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">462&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">199&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48935&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20356&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; KD&#44; PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ahlehoff O&#44; 2012<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Danish&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1997&#46;01&#8211;2006&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The Danish National Patient Register&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;9&#59; 49&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;7&#59; 49&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39558&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">530&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4478926&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55660&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; KD&#44; CD&#44; PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Armstrong AW&#44; 2013<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">US&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2004&#8211;2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">University of California Davis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53 &#40;40&#8210;63&#41;&#59; 59&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53 &#40;40&#8210;63&#41;&#59; 51&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2078&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1776&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3616&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; CD&#44; PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Charlton R&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1998&#46;01&#8211;2014&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The UK Clinical Practice Research Datalink&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;39&#8210;59&#41;&#59; 50&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;39&#8210;59&#41;&#59; 50&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27132&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8444&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27132&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7051&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; CD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chiang CH&#44; 2011<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Taiwan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Before 2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Longitudinal Health Insurance Database 2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;4&#59; 43&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;4&#59; 22&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2783&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13910&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5145&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; KD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Feldman SR&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">US&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007&#46;01&#8211;2012&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The OptumHealth Reporting and Insights claims database&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;62&#59; 44&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;62&#59; 44&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5492&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">881&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5492&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">499&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KD&#44; CD&#44; PD&#44; LD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Khalid U&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Danish&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1997&#46;01&#8211;2011&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The Danish National Patient Register&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;3 &#40;15&#46;8&#41;&#59; 51&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#46;9 &#40;19&#46;9&#41;&#59; 5 0&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70665&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1292&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5036959&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">105321&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; KD&#44; PD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>Lee S&#44; 2017<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">US&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2010&#46;11&#8211;2015&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The US Department of Defense population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;1&#59; 51&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;1&#59; 51&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7249&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2932&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72490&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22367&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; CD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Min C&#44; 2019<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Korean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2002&#8210;2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The Korean National Health Insurance Service-National Sample Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&#59; 43&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&#59; 43&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11071&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44284&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20298&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; CD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prasada S&#44; 2020<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">US&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2000&#46;01&#8211;2019&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The Northwestern Medicine Enterprise Data Warehouse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;72 &#40;15&#46;95&#41;&#59; 51&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;60 &#40;16&#46;65&#41;&#59; 57&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5365&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1536&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19358&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5241&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; KD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Schell C&#44; 2015<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">German&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eberhard Karls University T&#252;bingen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;6&#59; 43&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;6&#59; 60&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">158&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CVD&#44; KD&#44; PD&#44; LD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tollefson MM&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">US&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2004&#46;01&#8211;2013&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Optum Laboratories Data Warehouse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&#46;0 &#40;4&#46;4&#41;&#59; 53&#46;52&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">29957&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1200&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">646&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">CVD&#44; LD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Italy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2001&#8210;2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">The Health Search&#47;Thales Database&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">52&#46;5 &#40;16&#46;5&#41;&#59; 47&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">52&#46;4 &#40;16&#46;4&#41;&#59; 52&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3516&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">399&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17580&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">CVD&#44; PD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Yang YW&#44; 2011<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2006&#46;01&#8211;2007&#46;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Longitudinal Health Insurance Database2000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NR&#44; &#62;18&#59; 32&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NR&#44; &#62;18&#59; 67&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1685&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1471&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">CVD&#44; KD&#44; CD&#44; PD&#44; LD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Yeung H&#44; 2013<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1945&nbsp;\t\t\t\t\t\t\n
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