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lives and affects physical health&#44; psychological state&#44; social relationships&#44; and work&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> The disorder is frequently associated with a range of comorbidities&#44; including inflammatory bowel disease&#44; heart disease&#44; and obesity&#44; thus complicating management and negatively impacting mental and emotional health&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Psoriasis has been reported to have a similar or even greater effect on quality of life than other chronic diseases such as ischemic heart disease or diabetes mellitus&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;9</span></a> Quality of life in psoriasis has been reported to be directly related to disease severity<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;10</span></a> and appears to be influenced&#44; to varying degrees&#44; by a wide range of physical and psychosocial factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Given the chronic nature of psoriasis&#44; patients often require long-term treatment&#44; which varies according to multiple factors such as the extent and severity of disease and the presence of psoriatic arthritis or other comorbidities&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Conventional treatment can be very effective in the short term&#44; but cumulative toxicity is often a problem in the long-term management of psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> New biologic agents that act more selectively on key inflammatory components are now considered a therapeutic alternative in this disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In view of the scant information available on the management of psoriasis in routine clinical practice in Spain&#44; we designed a study to describe the clinical characteristics and treatment of patients with moderate to severe psoriasis in Spain and to assess the impact of the disease on their quality of life&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We performed a multicenter&#44; epidemiological&#44; observational&#44; cross-sectional study in which the investigators were dermatology specialists treating patients with psoriasis at hospitals&#44; specialist centers&#44; or private offices&#46; The patients were enrolled consecutively during scheduled visits&#46; All the data required for the study were collected during a single visit&#44; which coincided with enrolment&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The inclusion criteria were an age of 18 years or older and a diagnosis of moderate or severe psoriasis&#44; defined as a Psoriasis Area and Severity Index &#40;PASI&#41; score of 10 or higher and&#47;or a body surface area affected by psoriasis &#40;BSA&#41; of 10&#37; or more&#46; Those enrolled were also required to have started treatment with systemic drugs&#44; phototherapy&#44; and&#47;or topical treatment between 2004 and 2006&#46; Written informed consent was obtained from all patients prior to inclusion and confidentiality of data was guaranteed&#46; The study was approved by the clinical research ethics committee at Hospital Nuestra Se&#241;ora de Sonsoles in &#193;vila&#46; Patients were recruited from 90 centers between March and November&#44; 2009&#46; Following enrolment at a scheduled visit&#44; each patient was interviewed and his or her medical record reviewed&#44; with collection of sociodemographic and clinical data&#44; including general clinical information&#44; clinical characteristics specific to psoriasis&#44; and information regarding treatment&#46; Disease severity was also assessed &#40;BSA or PASI&#41; at this visit&#44; as was quality of life using the patient-assessed Dermatology Life Quality Index &#40;DLQI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> A score of 5 or less on the DLQI was considered to indicate good or satisfactory quality of life while one of 6 or higher was considered to indicate poor or unsatisfactory quality of life&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">The data for all evaluable patients were analyzed&#46; Qualitative variables were described as absolute and relative frequencies while quantitative variables were described using means &#40;SD&#41; and CIs when they were normally distributed&#44; or medians &#40;range and interquartile range &#91;IQR&#93;&#41; when they were not&#46; This analysis was performed for the sample as a whole and for subgroups of patients classified according to disease severity &#40;moderate or severe&#41; and quality of life &#40;good&#47;satisfactory or poor&#47;unsatisfactory&#41;&#46; To analyze statistically significant differences between independent quantitative variables&#44; we used the <span class="elsevierStyleItalic">t</span> test for parametric variables and the Mann-Whitney U test for nonparametric variables&#46; The Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test for 2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2 contingency tables and the likelihood ratio test for m<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>n contingency tables were used for qualitative variables&#46; To investigate factors potentially associated with quality of life&#44; we performed multivariate logistic regression analysis&#44; where the dependent variable was quality of life according to the DLQI &#40;good or poor&#41; and the independent variables were factors identified as significant in the univariate analysis&#46; Estimates were expressed with a confidence level of 95&#37;&#46; SPSS version 17&#46;0 was used for all analyses&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Demographic and Clinical Variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 442 evaluable patients were included in the study&#46; The mean &#40;SD&#41; age was 46&#46;7 &#40;13&#46;9&#41; years and 62&#46;2&#37; of the group &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>275&#41; were men&#46; At the time of inclusion&#44; 76&#46;2&#37; of the patients &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>337&#41; had moderate psoriasis while 23&#46;8&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>105&#41; had severe psoriasis&#46; The mean BSA and PASI scores were&#44; respectively&#44; 12&#46;7<span class="elsevierStyleMonospace">&#40;</span>11&#46;9&#41; and 9&#46;0 &#40;9&#46;6&#41; for those with moderate disease and 29&#46;5<span class="elsevierStyleMonospace">&#40;</span>25&#46;2&#41; and 17&#46;7<span class="elsevierStyleMonospace">&#40;</span>12&#46;9&#41; for those with severe disease &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>001 in both cases&#41;&#46; A family history of psoriasis was reported in 51&#37; of patients &#40;214&#47;420&#41; but no significant differences were detected between those with moderate and severe disease &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>076&#41;&#46; Duration of disease&#44; calculated as the number of years from the time of diagnosis to inclusion of the patient in the study&#44; was significantly longer in the severe disease group &#40;15&#46;1&#91;11&#46;1&#93; years&#59; 95&#37; CI&#44; 13&#46;0-17&#46;3&#41; than in the moderate disease group &#40;12&#46;4 &#91;10&#46;9&#93; years&#59; 95&#37; CI&#44; 11&#46;2-13&#46;6&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; Of the patients with severe psoriasis&#44; 7&#46;6&#37; were on sick leave&#59; the corresponding proportion in the moderate psoriasis group was significantly lower at 2&#46;4&#37; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#46; The prevalence of concomitant conditions&#44; such as hypertension&#44; hormonal or metabolic disorders&#44; and gastrointestinal disorders&#44; was significantly higher in patients with severe disease &#40;26&#46;7&#37;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; 27&#46;6&#37;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#59; and 9&#46;5&#37;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#44; respectively&#41; than in those with moderate disease &#40;17&#46;2&#37;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>58&#59; 18&#46;1&#37;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>61&#59; and 4&#46;5&#37;&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#44; respectively&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>05 in all cases&#41; The percentage of patients who consumed alcohol was higher in the moderate psoriasis group &#40;13&#46;8&#37; vs 9&#46;8&#37; in the severe psoriasis group&#41; but mean consumption was lower &#40;19&#46;6 &#91;23&#46;6&#93; g&#47;d vs 28&#46;6 &#91;30&#46;6<span class="elsevierStyleHsp" style=""></span>g&#47;d&#93;&#41;&#44; although the differences were not significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>398&#41;&#46; Approximately 30&#37; of the sample were smokers&#44; but the differences between those with moderate and severe disease were not significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>567&#41;&#46; The main sociodemographic and clinical characteristics at inclusion in the study are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Those with severe psoriasis had greater skin involvement&#44; nail involvement&#44; and joint symptoms&#46; Specifically&#44; 82&#46;9&#37; &#40;87&#47;105&#41; had skin lesions with marked scaling&#44; 61&#37; &#40;64&#47;105&#41; had nail alterations&#44; and 34&#46;3&#37; &#40;36&#47;105&#41; had joint pain&#46; In the moderate disease group&#44; 54&#46;5&#37; &#40;183&#47;336&#41; had marked scaling&#44; 39&#46;6&#37; &#40;133&#47;336&#41; had nail alterations&#44; and 24&#46;7&#37; &#40;83&#47;336&#41; had joint pain&#46; The differences were statistically significant for the presence of marked scaling and nail involvement &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>001 in both cases&#41;&#46; Patients with severe psoriasis also had greater skin involvement in the following areas&#58; scalp&#44; flexures&#44; palms and soles&#44; and genital area &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>001 in all cases&#41;&#46; In total&#44; 17&#46;5&#37; of the group &#40;77&#47;441&#41; had a diagnosis of psoriatic arthritis at inclusion in the study&#44; but no significant differences in prevalence were detected between those with severe disease &#40;24&#46;6&#37;&#41; and those with moderate disease &#40;15&#46;1&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>076&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Quality of Life Variables</span><p id="par0050" class="elsevierStylePara elsevierViewall">The mean DLQI score for the whole group was 6&#46;7 &#40;6&#46;6&#41;&#44; with those with severe psoriasis scoring significantly higher &#40;9&#46;2 &#91;7&#46;8&#93;&#41; &#40;worse quality of life&#41; than those with moderate psoriasis &#40;5&#46;9 &#91;6&#46;0&#93;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Patients with severe psoriasis also had a significantly higher score in the 6 domains of the DLQI&#58; symptoms and feelings&#44; daily activities&#44; leisure&#44; work&#47;school&#44; personal relationships&#44; and treatment &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>01 for personal relationships and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001 for the rest&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Sixty percent &#40;63&#47;105&#41; of those with severe disease and 39&#46;8&#37; &#40;134&#47;337&#41; of those with moderate psoriasis had a poor or unsatisfactory quality of life &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>001&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Regardless of psoriasis severity&#44; those with a better quality of life according to the DLQI were significantly older &#40;48&#46;0 &#91;13&#46;9&#93; vs 44&#46;9 &#91;13&#46;8&#93; years&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41; and had longer disease duration &#40;14&#46;1 &#91;11&#46;8&#93; vs 11&#46;8 &#91;9&#46;7&#93; years&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41; than those with a worse quality of life&#46; Poor quality of life was significantly associated with greater involvement of the scalp &#40;74&#46;1&#37; vs 48&#46;5&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; nails &#40;48&#46;7&#37; vs 34&#46;0&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; genital area &#40;24&#46;9&#37; vs 11&#46;9&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; and flexures &#40;25&#46;9&#37; vs 14&#46;9&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#44; and a higher prevalence of psychiatric comorbidity &#40;15&#46;7&#37; vs 4&#46;5&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; Regression analysis of factors significantly associated with quality of life showed that age was a protective factor &#40;odds ratio &#91;OR&#93;&#44; 0&#46;973&#59; 95&#37; CI&#44; 0&#46;957-0&#46;989&#41;&#44; while scalp involvement &#40;OR&#44; 2&#46;260&#59; 95&#37; CI&#44; 1&#46;401-3&#46;645&#41;&#44; psychiatric comorbidity &#40;OR&#44; 5&#46;105&#59; 95&#37; CI&#44; 2&#46;177-11&#46;972&#41;&#44; and higher PASI score &#40;OR&#44; 1&#46;067&#59; 95&#37; CI&#44; 1&#46;037-1&#46;098&#41; were associated with a higher odds of low quality of life &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Treatment of Moderate to Severe Psoriasis</span><p id="par0060" class="elsevierStylePara elsevierViewall">All of the patients enrolled in this study had started systemic treatment&#44; phototherapy&#44; and&#47;or topical treatment for their psoriasis between 2004 and 2006&#46; In the 5 years before the start of the study&#44; 68&#37; had received conventional systemic agents&#44; 64&#46;1&#37; topical treatments&#44; 39&#46;1&#37; biologic agents&#44; 22&#46;3&#37; phototherapy&#44; and 24&#46;6&#37; &#40;n<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#61;</span><span class="elsevierStyleHsp" style=""></span>107&#41; another type of treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The mean duration of treatment was 28&#46;6<span class="elsevierStyleMonospace">&#40;</span>37&#46;6&#41; months &#40;95&#37; CI&#44; 22&#46;9-34&#46;3&#41; for topical treatments&#44; 15&#46;8<span class="elsevierStyleMonospace">&#40;</span>20&#46;8&#41; months &#40;95&#37; CI&#44; 13&#46;2-18&#46;4&#41; for conventional systemic treatment&#44; 10&#46;4<span class="elsevierStyleMonospace">&#40;</span>15&#46;9&#41; months &#40;95&#37; CI&#44; 7&#46;0-13&#46;8&#41; for phototherapy&#44; and 14&#46;4<span class="elsevierStyleMonospace">&#40;</span>12&#46;6&#41; months &#40;95&#37; CI&#46; 12&#46;3-16&#46;3&#41; for the first biologic agent received &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; The mean time from the start of systemic treatment or phototherapy to administration of the first biologic agent was 28&#46;0 &#40;49&#46;3&#41; months &#40;95&#37; CI&#44; 23&#46;4-33&#46;5&#41;&#46; The first biologic agent used in over 90&#37; of the patients was efalizumab or etanercept&#46; The specific percentages were 48&#46;8&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>83&#41; for efalizumab&#44; 45&#46;3&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>77&#41; for etanercept&#44; 3&#46;5&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; for adalimumab&#44; and 2&#46;4&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41; for infliximab&#46; The mean duration of treatment was 15&#46;6<span class="elsevierStyleMonospace">&#40;</span>13&#46;3&#41; months in the case of efalizumab&#44; 13&#46;8<span class="elsevierStyleMonospace">&#40;</span>12&#46;1&#41; months in the case of etanercept&#44; 5&#46;5<span class="elsevierStyleMonospace">&#40;</span>3&#46;6&#41; months in the case of adalimumab&#44; and 6&#46;6<span class="elsevierStyleMonospace">&#40;</span>4&#46;3&#41; months in the case of infliximab&#46; In total&#44; 77&#46;6&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>132&#41; of the patients who had been treated with a biologic agent before the start of the study did not need to be switched to another biologic agent&#46; Of the 38 patients who did&#44; 73&#46;7&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41; switched just once&#44; while 26&#46;3&#37; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41; switched twice&#46; All but 4 &#40;0&#46;9&#37;&#41; were being treated for their psoriasis at the study inclusion visit&#58; 57&#46;5&#37; &#40;252&#47;438&#41; were receiving a biologic agent &#40;55&#46;3&#37; &#91;184&#47;438&#93; of those with moderate psoriasis and 64&#46;8&#37; &#91;68&#47;438&#93; of those with severe psoriasis&#41;&#44; 32&#46;6&#37; &#40;143&#47;438&#41; were receiving conventional systemic treatment&#44; 11&#46;0&#37; &#40;48&#47;438&#41; were receiving phototherapy&#44; 27&#46;2&#37; &#40;119&#47;438&#41; were receiving concomitant topical treatment&#59; and 10&#46;3&#37; &#40;45&#47;438&#41; were receiving other drugs &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">The findings of the present study highlight the considerable impact that psoriasis has on patient quality of life&#44; the importance of determining disease severity before initiating treatment&#44; and the need for a multidimensional approach to management&#44; as has been mentioned by other authors&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> All the patients in our study had moderate to severe plaque psoriasis&#44; diagnosed according to clinical criteria based on BSA and PASI scores&#44; and they had all started specific psoriasis treatment with systemic agents&#44; phototherapy&#44; and&#47;or topical drugs between 2004 and 2006&#46; The characteristics of our patients are similar to those described in other epidemiological studies of moderate to severe plaque psoriasis in Europe&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#8211;17</span></a> In our series&#44; most of the patients had moderate disease &#40;76&#46;2&#37;&#41;&#44; there was a predominance of male patients &#40;62&#46;2&#37;&#41;&#44; and the mean duration of disease was 13 years&#46; As was to be expected&#44; there was a high prevalence of concomitant disease&#44; and 17&#46;5&#37; of the patients had associated arthritic psoriasis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Severe psoriasis &#40;present in 23&#46;8&#37; &#91;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>105&#93; of our patients&#41; was significantly associated with longer disease duration and a higher prevalence of concomitant disease&#44; nail alterations&#44; and lesions with marked scaling&#46; The areas most significantly affected were the scalp&#44; flexures&#44; palms and soles&#44; and the genital area&#46; While psoriatic arthritis appears to be more common in patients with more extensive disease&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> it can also run an aggressive course in patients with less severe psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Like other authors&#44;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;20</span></a> we did not detect any differences in the prevalence of psoriatic arthritis according to disease severity&#46; We also did not observe any significant differences in the prevalence of severe disease in men compared to women or detect a relationship with smoking&#44; contrasting with reports from an earlier epidemiological study published in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Psoriasis is significantly associated with a variety of physical and psychological dimensions that affect patient quality of life&#44; hence the consideration that dermatologists need to manage this disorder from a multidimensional approach&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;9&#44;10&#44;20&#44;21</span></a> A recent study of psoriasis patients in hospital and outpatients settings in Spain reported that the disease had a considerable impact on quality of life&#44; particularly with regard to emotional status&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In our study&#44; 60&#37; of patients with severe psoriasis but just 39&#46;8&#37; of those with moderate disease had a poor or unsatisfactory quality of life&#59; furthermore&#44; in those with severe disease&#44; all 6 domains of the DLQI were significantly affected&#46; Regardless of disease severity&#44; we observed a significant association between poor quality of life and the presence of concomitant psychiatric conditions and greater scalp involvement&#46; Age&#44; by contrast&#44; was a protective factor&#46; Psychiatric morbidity was the strongest predictor of poor quality of life in our patients&#44; with an OR of 5&#46;105&#44; contrasting with PASI score&#44; which was the weakest predictor&#44; with an OR of 1&#46;067&#46; This finding is consistent with those of previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;15</span></a> Our findings with regard to age are consistent with those reported in a systemic review of quality of life in psoriasis in that higher age was correlated with a better quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In agreement with other reports&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> we did not detect significant differences in quality of life between patients with psoriasis and psoriatic arthritis and those with psoriasis alone&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In an epidemiological study of severe psoriasis in Spain and Portugal conducted between 2004 and 2005&#44; approximately only half of the patients surveyed were receiving conventional systemic treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> The authors&#44; like others&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> concluded that psoriasis was inadequately treated in many of these patients&#46; One of the most relevant aspects of the present study is that we analyzed the prescribing habits of Spanish dermatologists in a retrospective analysis of up to 5 years &#40;2004-2009&#41;&#46; During this period&#44; 68&#37; of the patients in our series had been treated with conventional systemic agents&#44; 39&#46;1&#37; with biologic therapy&#44; 22&#46;3&#37; with phototherapy&#44; and 64&#46;1&#37; with concomitant topical drugs&#46; The mean duration of treatment was approximately 2 years for topical treatment&#44; approximately a year and a half for conventional systemic agents and the first biologic agent received&#44; and less than a year for phototherapy&#46; Although all the patients in our study had moderate to severe psoriasis&#44; just 39&#46;1&#37; had received biologics during this period&#59; this is probably related to the gradual introduction of biologic drugs starting in 2005&#44; which is when efalizumab&#44; infliximab&#44; and etanercept were marketed for the first time&#46; When enrolled in the study in 2009&#44; 57&#46;5&#37; of the patients were on biologic agents&#44; indicating an increasing tendency to use these drugs in moderate to severe psoriasis&#46; Nevertheless&#44; considering the centers that were selected to participate in the study&#44; it should be noted that this figure may possibly be higher than the average for Spain&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Despite the availability of international guidelines on the treatment of psoriasis&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> which include recommendations on the use of conventional systemic agents&#44; and despite the fact that these drugs have known beneficial effects&#44; questions remain about the optimal use of these drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;15</span></a> Current guidelines&#44; for example&#44; do not recommend how long systemic drugs should be ideally administered before switching to biologics in those cases where it is necessary&#46; In our series&#44; the mean duration of treatment&#44; including conventional systemic treatment and phototherapy&#44; before a switch to the first biologic agent&#44; was over 2 years&#44; providing new data on the therapeutic management of psoriasis in Spanish clinics&#46; New guidelines with recommendations on how long patients should receive systemic treatment before switching to biologic agents would certainly help to improve the management of psoriasis&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">When interpreting the findings of the present study and extrapolating them to a national level or drawing comparisons with populations with similar characteristics&#44; it is important to note that certain biases may have been introduced&#44; mostly related to the retrospective design of the study and the selection of participating centers&#46; Nonetheless&#44; the observational nature of the study is its main strength as it allowed us to provide a descriptive analysis of the clinical characteristics and treatment profile of patients with moderate to severe psoriasis in routine clinical practice in Spain&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">To conclude&#44; based on our findings&#44; severe psoriasis is significantly associated with longer disease duration&#59; a higher prevalence of comorbidity&#44; nail alterations&#44; and lesions with marked scaling&#59; greater involvement of the scalp&#44; flexures&#44; palms and soles&#44; and genital area&#59; and considerably impaired quality of life&#46; The strongest predictor of poor or unsatisfactory quality of life was the presence of psychiatric comorbidity&#44; regardless of disease severity&#46; The mean duration of treatment&#44; including conventional systemic treatment and phototherapy&#44; before switching to the first biologic agent&#44; was over 2 years&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">Dr Jos&#233; Manuel Hern&#225;nz&#44; Dr Manuel S&#225;nchez-Rega&#241;a&#44; and Dr Rosa Izu participated in clinical trials sponsored by Pfizer Spain and received consultancy and speakers&#8217; fees for activities sponsored by Pfizer Spain&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Dr Victoria Mendiola has participated in clinical trials sponsored by Pfizer Spain&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Dr Carmen Garc&#237;a-Calvo works in the Medical Department of Pfizer&#44; S&#46;L&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">This study was financed by Pfizer Spain&#46; The authors did not receive fees for contributing to the writing or publication of this manuscript&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Publishing support was provided by UBC Scientific Solutions and financed by Pfizer Spain&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evaluation of disease severity is considered essential in the optimal management of psoriasis&#46;</p> <span class="elsevierStyleSectionTitle">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To describe the clinical characteristics and therapeutic profile of patients with moderate to severe psoriasis in Spain and to assess the impact of the disease on the patients&#8217; quality of life&#46;</p> <span class="elsevierStyleSectionTitle">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This was an observational&#44; cross-sectional study carried out in 90 dermatology units in Spain in 2009&#46; We included 442 patients diagnosed with moderate to severe psoriasis who had started treatment with systemic agents&#44; phototherapy&#44; and&#47;or topical treatments between 2004 and 2006&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">More severe psoriasis was significantly associated with the following&#58; longer disease duration&#59; higher prevalence of concomitant disease&#59; greater involvement of the nails&#44; scalp&#44; flexures&#44; palms&#44; and soles&#59; and poorer quality of life&#46; In the 5 years before the start of the study&#44; 68&#37; of the patients had received conventional systemic treatments&#44; 39&#46;1&#37; biologic agents&#44; and 22&#46;3&#37; phototherapy&#46; At present&#44; 57&#46;5&#37; of the patients are being treated with biologic agents&#44; 32&#46;6&#37; with conventional systemic treatments&#44; and 11&#37; with phototherapy&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Severity of psoriasis was associated with a marked impact on quality of life&#46; Regardless of disease severity&#44; psychiatric comorbidity was the strongest predictor of poor quality of life&#46; On average&#44; patients had received other treatments&#44; such as conventional systemic treatments or phototherapy&#44; for more than 2 years before switching to biologic agents for the first time&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La evaluaci&#243;n de la gravedad de la psoriasis se considera esencial en el manejo terap&#233;utico &#243;ptimo de los pacientes&#46;</p> <span class="elsevierStyleSectionTitle">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Descripci&#243;n de las caracter&#237;sticas cl&#237;nicas y perfil terap&#233;utico de los pacientes con psoriasis moderada a grave en el &#225;mbito espa&#241;ol&#44; evaluando su impacto en la calidad de vida de los pacientes&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional&#44; de corte transversal&#44; realizado en 90 unidades dermatol&#243;gicas en Espa&#241;a en 2009&#46; Se incluyeron 442 pacientes diagnosticados de psoriasis moderada a grave que hab&#237;an iniciado tratamiento con f&#225;rmacos sist&#233;micos&#44; fototerapia y&#47;o tratamientos t&#243;picos entre 2004 y 2006&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con psoriasis m&#225;s grave presentaron de forma significativa un mayor tiempo de evoluci&#243;n de la enfermedad&#44; mayor prevalencia de enfermedades concomitantes y mayor afectaci&#243;n ungueal&#44; del cuero cabelludo&#44; de las flexuras y de la zona palmo-plantar&#44; as&#237; como peor calidad de vida&#46; Durante los 5 a&#241;os previos al inicio del estudio el 68&#37; de los pacientes recibieron tratamientos sist&#233;micos convencionales&#44; el 39&#44;1&#37; f&#225;rmacos biol&#243;gicos y el 22&#44;3&#37; fototerapia&#46; En la actualidad el 57&#44;5&#37; estaban siendo tratados con alg&#250;n f&#225;rmaco biol&#243;gico&#44; el 32&#44;6&#37; recib&#237;an f&#225;rmacos sist&#233;micos convencionales y el 11&#37; fototerapia&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La gravedad de la psoriasis se asoci&#243; en nuestro estudio con una marcada afectaci&#243;n de la calidad de vida&#46; Independientemente de la gravedad de la psoriasis&#44; el mayor predictor de mala calidad de vida fue la comorbilidad psiqui&#225;trica&#46; El tiempo medio de permanencia en otros tratamientos&#44; incluyendo sist&#233;micos convencionales o fototerapia&#44; hasta el cambio a un primer biol&#243;gico fue superior a los 2 a&#241;os&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Hern&#225;nz JM&#44; et al&#46; Evaluaci&#243;n cl&#237;nica y terap&#233;utica de los pacientes con psoriasis moderada o grave en Espa&#241;a&#46; Estudio Secuence&#46; Actas Dermosifiliogr&#46; 2012&#59;103&#58;897&#8211;904&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Impact of psoriasis severity on quality of life&#46; Mean &#40;SD&#41; scores for the 6 domains of the Dermatology Life Quality Index&#46;</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>01 personal relationships&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>001&#44; other domains&#59; severe vs moderate&#46;</p>"
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; BSA&#44; body surface area affected by psoriasis&#59; PASI&#44; Psoriasis Area and Severity Index&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Total Population &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>442&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#61;<span class="elsevierStyleHsp" style=""></span>&#46;124&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mean &#40;SD&#41; duration of disease&#44; y</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Lesion site&#44; &#37; &#40;No&#46;&#41;</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Scalp&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">54&#46;9 &#40;184&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">76&#46;7 &#40;79&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">60&#46;0 &#40;263&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nails&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">37&#46;9 &#40;127&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">49&#46;5 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40&#46;6 &#40;178&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Flexures&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#46;4 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40&#46;8 &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#46;9 &#40;87&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&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"><span class="elsevierStyleHsp" style=""></span>Palms and soles&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">11&#46;3 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27&#46;2 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&#46;1 &#40;66&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&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"><span class="elsevierStyleHsp" style=""></span>Genital area&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">13&#46;4 &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">31&#46;4 &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17&#46;7 &#40;78&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&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"><span class="elsevierStyleHsp" style=""></span>Other sites&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">94&#46;0 &#40;315&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">93&#46;2 &#40;96&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">93&#46;8 &#40;411&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#61;<span class="elsevierStyleHsp" style=""></span>&#46;474&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Concomitant disease&#44; &#37; &#40;No&#46;&#41;</span></td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Respiratory&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6&#46;2 &#40;21&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&#46;6 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6&#46;8 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#61;<span class="elsevierStyleHsp" style=""></span>&#46;405&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypertension&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">17&#46;2 &#40;58&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26&#46;7 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">19&#46;5 &#40;86&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&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"><span class="elsevierStyleHsp" style=""></span>Neoplastic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3&#46;3 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;8 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;6 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#61;<span class="elsevierStyleHsp" style=""></span>&#46;473&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"><span class="elsevierStyleHsp" style=""></span>Infectious&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#46;4 &#40;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;8 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2&#46;7 &#40;12&#41;&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="char" valign="\n
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                  \t\t\t\t">&#61;<span class="elsevierStyleHsp" style=""></span>&#46;429&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hormonal-metabolic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">18&#46;1 &#40;61&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27&#46;6 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">20&#46;4 &#40;90&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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