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Original article
Diagnostic accuracy and predictive validity of combined use of Fototest and Mini-Cog in cognitive impairment
Utilidad diagnóstica y validez predictiva del uso conjunto de Fototest y Mini-Cog en deteriorocognitivo
C. Carnero-Pardoa,
Corresponding author
ccarnero@neurocenter.es

Corresponding author.
, S. López-Alcaldea, M. Florido-Santiagob, M. Espinosa-Garcíaa, I. Rego-Garcíac, R. Calle-Callec, I. Carrera-Muñozc, R. de la Vega-Cotarelod
a FIDYAN Neurocenter, Granada, Spain
b Hospital Vithas Parque San Antonio, Málaga, Spain
c Servicio de Neurología, Hospital Universitario Virgen de las Nieves, Granada, Spain
d Servicio de Medicina Interna, Hospital Punta de Europa, Algeciras, Cádiz, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The purpose of cognitive assessment is to detect and measure impairment in any cognitive domain &#40;attention&#44; memory&#44; language&#44; executive function&#44; praxis&#44; visuospatial skills&#41;&#44; using these findings in the diagnostic and treatment process&#46; In some cases &#40;for instance in consultations due to cognitive complaints&#44; which are increasingly frequent<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#41; this assessment is a fundamental part of neurological examination&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Cognitive assessment may be informal&#58; during medical history taking&#44; the physician may detect disorientation&#44; impaired language expression&#44; marked memory problems&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> the &#8220;don&#8217;t know&#8221; sign&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> or the head turning sign&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> all of which suggest cognitive impairment &#40;CI&#41;&#46; However&#44; assessment is usually performed with validated instruments for structured evaluation of the patient&#8217;s cognitive function&#46; Like such other instruments as the ophthalmoscope or the reflex hammer&#44; these cognitive instruments and tests must meet certain technical requirements&#44; and the physician must be proficient in their use and the interpretation of results&#46; In clinical practice&#44; given the unavoidable limitations on consultation times&#44; these instruments must necessarily be quick and simple to administer&#46; Furthermore&#44; these instruments should evaluate all the cognitive domains currently considered in the diagnostic criteria for different constructs of CI &#40;attention&#44; memory and learning&#44; language&#44; executive function&#44; praxis&#44; and visuospatial skills&#41;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8</span></a> and&#44; needless to say&#44; present good psychometric properties&#44; like any other diagnostic tool&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> These multi-domain brief cognitive tests &#40;BCT&#41; should be validated specifically for the diagnosis of CI &#40;and not only for dementia&#41;&#59; otherwise&#44; the tool would be unable to detect cognitive problems at a stage when the appropriate intervention may either revert the problem or delay or halt dementia progression&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Normative data applicable to the population of interest should also be available for these BCTs&#44; and these tools should ideally be available free of charge&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Among the multi-domain BCTs validated in Spain for CI &#40;Supplementary material&#44; Table 1&#41;&#44; only the MoCA<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> and the ACE-III<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a> evaluate all cognitive domains&#46; However&#44; these tests require 10&#8211;15 and 15&#8211;20 minutes to administer&#44; respectively&#59; these administration times are excessive for general neurology consultations&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and impracticable in primary care&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Although the Mini-Mental State Examination&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Eurotest&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Fototest&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Mini-Cog&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and Clock Drawing Test<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> present shorter administration times&#44; they do not assess all cognitive domains&#46; Furthermore&#44; the Mini-Mental State Examination presents many other limitations that have led to a decline in its use in recent years&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Physicians frequently administer several BCTs to evaluate more cognitive domains&#44; increasing the sensitivity and diagnostic accuracy of these tests in cases of CI&#46; The most widely known examples are the 7 Minute Screen&#44; which combines an orientation task&#44; a cued recall task&#44; a semantic verbal fluency task&#44; and the Clock Drawing Test<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#59; and the Mini-Cog&#44; which includes a delayed recall task and the Clock Drawing Test&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The Fototest<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and the Mini-Cog<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> are 2 very short tests &#40;administration times of 3 and 2 minutes&#44; respectively&#41; that are widely used in Spain and have been validated specifically for CI&#46; The former evaluates language&#44; executive function&#44; and episodic visual memory with free and cued recall&#44; whereas the latter assesses attention&#44; verbal memory&#44; and visuospatial skills and visuoconstructive praxis&#46; This study explores the hypothesis that the combination of the Fototest and the Mini-Cog&#44; which together evaluate all the cognitive domains that should be included in a cognitive assessment&#44; improves the diagnostic accuracy of either test alone while requiring very little time to administer &#40;&#60; 5 minutes&#41;&#44; a particularly interesting feature in our setting&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our objective was to evaluate the diagnostic accuracy and predictive validity of the combination of Fototest plus Mini-Cog in detecting CI in everyday clinical practice&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0035" class="elsevierStylePara elsevierViewall">We conducted a phase III study for the evaluation of diagnostic tests&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> with a cross-sectional&#44; prospective&#44; naturalistic&#44; pragmatic design&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> The study included new patients attended between 21 February 2018 and 25 September 2018 &#40;inclusive&#41; at a neurology consultation specialising in cognitive-behavioural neurology&#44; at Hospital Universitario Virgen de las Nieves&#44; a tertiary-level hospital in Granada&#44; Spain &#40;study sample&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">For the purposes of external validation&#44; we also included an independent sample of patients attended due to cognitive complaints at a cognitive-behavioural neurology clinic at a private hospital in Malaga&#44; Spain&#44; from February 2019 &#40;external sample&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In both instances&#44; recruitment was consecutive and systematic&#44; only excluding individuals who had not completed primary education&#44; since previous studies have shown that the Mini-Cog is not recommended for this population&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Cognitive assessment</span><p id="par0050" class="elsevierStylePara elsevierViewall">All individuals&#44; regardless of their age&#44; the reason for consultation&#44; or the sample in which they were included&#44; underwent a brief cognitive assessment &#40;index assessment&#41; consisting of the administration of the Fototest<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and the Spanish-language version of the Mini-Cog&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The tests were administered consecutively&#44; and in that order&#44; by a neurologist &#40;CCP&#44; IRG&#44; RCC&#44; or ICM&#41;&#46; The administration time for both BCTs was measured with a digital stopwatch&#44; with a precision of one-hundredth of a second&#46; Times were rounded up to the next whole number&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">All individuals attended due to cognitive complaints or behavioural alterations&#44; or with Fototest scores equal to or lower than the 10th percentile&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> also underwent a formal cognitive assessment &#40;reference assessment&#41;&#44; including tests of orientation &#40;time&#44; space&#44; and person&#41;&#44; attention &#40;forward and backward digit span&#44; Trail Making Test A &#91;TMT-A&#93;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#41;&#44; memory &#40;learning&#44; free recall&#44; and recognition of the CERAD word list&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> for patients from Granada&#44; or the Free and Cued Selective Reminding Test &#91;FCSRT&#93;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> for patients from Malaga&#41;&#44; language &#40;short version of the Boston Naming Test&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> semantic verbal fluency&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> and understanding of commands&#41;&#44; motor praxis &#40;gesture imitation from the EULA test<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#41;&#44; executive function &#40;short-form version of the WAIS similarities subtest&#44; coin test from the Eurotest&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> semantic verbal fluency&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> and TMT-B<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#41;&#44; and visuospatial function &#40;copy and drawing tasks from the CERAD<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a>&#41;&#46; Scores equal to or below the 5th percentile&#44; with z-score &#61; &#8211;1&#46;5&#44; or scaled scores &#8804; 6&#44; depending on the norms for each test&#44; were considered pathological&#46; This assessment was performed by a researcher &#40;SLA&#44; MFS&#44; or MEG&#41; blinded to the results of the BCTs&#46; These individuals also underwent functional assessment &#40;Barthel Index<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> and Lawton-Brody IADL scale<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#41;&#46; The reference assessment and the BCTs were administered on the same day in both samples&#44; except in 9 individuals from the external sample&#44; who underwent these tests within a maximum of 8 days&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Diagnosis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Regardless of the reason for consultation and the final diagnosis&#44; all individuals were classified according to their cognitive and functional status using the Global Deterioration Scale<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> &#40;Supplementary material&#44; Table 2&#41;&#59; scores 1 and 2 were classified as &#8220;no CI&#8221; and scores &#8805; 3 as &#8220;CI&#46;&#8221; This diagnosis was established by a neurologist with experience in cognitive and behavioural neurology &#40;CCP&#41;&#44; based solely on the results from the formal cognitive assessment&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Models evaluated</span><p id="par0065" class="elsevierStylePara elsevierViewall">We calculated diagnostic accuracy for the Fototest and Mini-Cog independently&#44; and for the following combinations of both instruments&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Combined use&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Simple</span> &#40;Comb-simple&#41;&#58; single score resulting from the sum of the Fototest score and the Mini-Cog score&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Logistic regression model</span> &#40;Comb-LR&#41;&#58; includes Fototest and Mini-Cog scores as predictors&#44; with sex&#44; age&#44; and level of education as covariates&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Random decision tree</span> &#40;Comb-DT&#41;&#58; we developed a classification model using a machine learning technique&#44; applying the algorithm &#8220;classification and regression tree&#8221; &#40;CART&#41; for supervised learning with automatic Bayesian optimisation of accuracy &#40;percentage of correct predictions&#41; using the OptiML feature<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> of the free-access BigML platform&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> Models were trained with a total of 9 predictors&#44; including sociodemographic variables &#40;age&#44; sex&#44; and level of education&#41;&#44; Fototest scores &#40;total score and scores for naming&#44; free recall&#44; total recall&#44; and naming fluency&#41;&#44; and Mini-Cog scores &#40;total score and scores for recall and the clock-drawing task&#41;&#59; the response variable was &#8220;CI&#46;&#8221;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Stepped use&#58;</span> 2-step evaluation&#46; In the first step&#44; we considered 2 cut-off points for the Fototest&#46; The lower cut-off point &#40;Fototest &#8804; 25&#41; maximises the positive predictive value or precision&#44; minimising or even eliminating false positives&#46; The higher cut-off point &#40;Fototest &#8805; 40&#41; maximises the negative predictive value&#44; minimising or eliminating false negatives&#46; Individuals scoring &#8804; 25 on the Fototest were classified as CI and those scoring &#8805; 40 as no CI&#44; without the Mini-Cog being administered&#46; The second step considers Mini-Cog results&#44; only in patients with Fototest scores 26&#8211;39&#44; applying the previously mentioned combined models &#40;Step-simple&#44; Step-LR&#44; Step-DT&#41;&#46;</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">We conducted a descriptive study of sociodemographic variables and results&#59; comparisons were performed using the <span class="elsevierStyleItalic">t</span> test and the chi-square test&#44; according to whether variables were continuous or categorical&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The analysis was performed in the study sample&#59; to prevent overadjustment and&#44; consequently&#44; overestimation of diagnostic accuracy&#44; we randomly divided the study sample into 2 datasets&#46; The first &#40;base dataset&#41; included 80&#37; of participants and was used to create the different models and to perform an exploratory analysis enabling selection of the optimal cut-off points and criteria&#44; whereas the second &#40;test dataset&#41;&#44; including the remaining 20&#37;&#44; was used for independent validation of the different models and criteria selected in the base dataset&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The diagnostic accuracy of the different models in the base dataset was evaluated with the area under the curve &#40;AUC&#41; and the corresponding standard error &#40;SE&#41; for CI vs no CI&#59; AUCs were compared according to the method proposed by Hanley and McNeil&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> The optimal cut-off point was that which maximised the accuracy of the test &#40;percentage of correct classifications&#41;&#46; To select the Comb-DT model&#44; given that many of the 98 models created presented similar accuracy values&#44; we decided to maximise the phi coefficient &#40;Matthew&#8217;s correlation coefficient&#41; and&#44; according to the principle of parsimony&#44; to select the model with the smallest number of nodes&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The assessment and internal validation of the models and criteria selected in the base dataset were performed independently on the test dataset&#44; and the external validation was performed on the external sample&#44; using a pre-specified analysis of diagnostic accuracy with the parameters sensitivity&#44; precision&#44; phi coefficient&#44; and accuracy&#59; these parameters are frequently used in the validation of prediction models&#46; These data enabled the calculation of classical measures of the diagnostic accuracy of a test &#40;specificity&#44; predictive values&#44; likelihood ratios&#41;&#44; and the creation of the corresponding contingency table&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Statistical analysis was performed with SPSS&#44; version 19&#46;0&#46;0&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> and MedCalc&#44; version 18&#46;9&#46;1&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Formal considerations</span><p id="par0120" class="elsevierStylePara elsevierViewall">Study design and manuscript drafting followed the recommendations of the STARD 2015 guidelines<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> for reporting diagnostic accuracy studies&#44; the STARDdem statement<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> for reporting the diagnostic accuracy of studies into cognitive disorders&#44; and the guidelines for the development of predictive models in biomedicine&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The study complies with the ethical principles for medical research established in the latest revision of the World Medical Association&#8217;s Declaration of Helsinki &#40;Edinburgh&#44; 2000&#41;&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0130" class="elsevierStylePara elsevierViewall">The study sample included 448 individuals with a mean age &#40;SD&#41; of 60&#46;5 &#40;17&#46;7&#41; years&#44; with a slight predominance of women &#40;53&#46;8&#37;&#41; and individuals with more than primary education &#40;52&#46;2&#37;&#41;&#59; the prevalence of CI in this sample was 46&#46;4&#37;&#46; The 2 randomly generated datasets &#40;base and test&#44; including 358 and 90 individuals&#44; respectively&#41; showed no significant differences in any of the sociodemographic variables studied&#44; in the prevalence of CI&#44; or in Fototest and Mini-Cog results&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The external sample&#44; in contrast&#44; presented a much higher prevalence of CI &#40;77&#46;0&#37;&#41;&#44; an older mean age &#40;71&#46;7 &#91;10&#46;0&#93; years&#41;&#44; a higher education level &#40;60&#46;7&#37; of individuals had at least secondary education&#41;&#44; and a lower prevalence of women &#40;47&#46;5&#37;&#41;&#44; although differences were not significant in the latter 2 variables&#46; Fototest and Mini-Cog results were significantly lower in the external sample than in the study sample&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises the sociodemographic characteristics&#44; prevalence of CI&#44; and Fototest and Mini-Cog results of the 2 samples and the 2 datasets&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">The random decision tree model selected &#40;among the 98 models generated by the platform&#41; had an accuracy of 92&#46;2&#37; and a phi coefficient of 0&#46;84 in the test sample&#44; with a total of 7 levels &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; &#40;Supplementary Material&#44; Table 3&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarises the diagnostic parameters of the different models in the different samples and datasets&#46; The diagnostic accuracy of the Fototest was moderate&#44; but significantly higher than that of the Mini-Cog &#40;0&#46;93 &#177; 0&#46;01 &#91;AUC &#177; SE&#93; vs 0&#46;89 &#177; 0&#46;02&#59; <span class="elsevierStyleItalic">t</span> &#61; 2&#46;06&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;04&#41;&#44; while the diagnostic accuracy of the Comb-simple &#40;0&#46;95 &#177; 0&#46;01&#41; and Comb-LR models &#40;0&#46;98 &#177; 0&#46;01&#41; was significantly higher than that of either test alone &#40;<span class="elsevierStyleItalic">t</span> &#62; 4&#46;00 and <span class="elsevierStyleItalic">P</span> &#60; &#46;0001 for all comparisons&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The Comb-DT model does not have an AUC&#44; since it only includes one alternative for classification&#59; however&#44; its accuracy &#40;95&#46;2&#37;&#41; was significantly higher than that of the Mini-Cog &#40;81&#46;6&#37;&#59; &#967;<span class="elsevierStyleSup">2</span> &#61; 32&#46;24&#59; <span class="elsevierStyleItalic">P</span> &#60; &#46;0001&#41;&#44; the Fototest &#40;84&#46;9&#37;&#59; &#967;<span class="elsevierStyleSup">2</span> &#61; 21&#46;16&#59; <span class="elsevierStyleItalic">P</span> &#60; &#46;001&#41;&#44; and the Comb-simple &#40;88&#46;3&#37;&#59; &#967;<span class="elsevierStyleSup">2</span> &#61; 11&#46;2&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;001&#41; and Comb-LR models &#40;91&#46;6&#37;&#59; &#967;<span class="elsevierStyleSup">2</span> &#61; 3&#46;76&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;05&#41;&#46; Stepped models present the exact same diagnostic accuracy as the combined models they include&#44; with the added benefit of significantly shorter administration times &#40;197&#46;3 &#91;56&#46;7&#93; vs 233&#46;9 &#91;45&#46;2&#93;&#59; <span class="elsevierStyleItalic">t</span> &#61; 8&#46;8&#59; <span class="elsevierStyleItalic">P</span> &#60; &#46;0001&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">The validation of the models in the test dataset largely replicates the predictions of the models generated in the base dataset&#44; except for the models using random decision trees&#44; which present a slightly lower diagnostic accuracy&#44; as may be expected due to the overadjustment effect&#46; The models also showed a very high diagnostic accuracy in the external sample&#44; with accuracy values ranging from 86&#46;9&#37; to 91&#46;8&#37; &#40;except for the Mini-Cog&#44; at 78&#46;7&#37;&#41;&#44; although the difference between the external sample and the base dataset was not statistically significant &#40;81&#46;6&#37;&#59; &#967;<span class="elsevierStyleSup">2</span> &#61; 0&#46;29&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;59&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The Supplementary Material &#40;Tables 4&#8211;11&#41; presents the contingency tables and classical measures of diagnostic accuracy &#40;sensitivity&#44; specificity&#44; predictive values&#44; likelihood ratios&#41; for each model and in each sample for the selected cut-off points and criteria&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">The results of this prospective study&#44; which was conducted under conditions of routine clinical practice&#44; clearly show that the combined use of the Fototest and Mini-Cog surpasses the diagnostic accuracy of either instrument alone&#46; These results are consistent&#44; as they were replicated in 2 independent samples&#58; one with the same sociodemographic and clinical characteristics as the sample used to develop the models&#44; and another sample that was completely different in terms of sociodemographic and clinical characteristics &#40;drawn from a cognitive-behavioural neurology consultation&#44; older age&#44; higher prevalence of CI&#44; and different geographical location&#41;&#46; The greater diagnostic accuracy of the combined models is probably due to greater comprehensiveness of the cognitive assessment&#44; as these models evaluate more cognitive domains&#46; This&#44; in turn&#44; facilitates the identification of different profiles of CI&#44; which could enhance diagnostic studies&#46; However&#44; our study did not address this issue&#44; which should be explored in future research&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Our results are also consistent with and support the available data from Spain regarding the diagnostic accuracy of the instruments used&#46; The only previous study of Mini-Cog in Spain reported an AUC of 0&#46;88 &#40;SE&#58; 0&#46;01&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> which is practically identical to that found in our study &#40;0&#46;89 &#91;0&#46;02&#93;&#41;&#59; one study reconstructed the Mini-Cog score from the Clock-Drawing Test and the Mini&#8211;Mental State Examination&#44; so we do not consider it comparable&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Similarly&#44; the diagnostic accuracy of the Fototest in the present study &#40;0&#46;93 &#91;0&#46;01&#93;&#41; is very similar to that reported in previous studies in Spain &#40;0&#46;86 &#91;0&#46;02&#93;&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> 0&#46;93 &#91;0&#46;02&#93;&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> 0&#46;95 &#91;0&#46;01&#93;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#41; and even in Argentina &#40;0&#46;93 &#91;0&#46;03&#93;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a>&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The complex models &#40;Comb-LR and Comb-DT&#41; provide higher diagnostic accuracy than the Comb-simple model&#44; probably due to the weighting of diagnostic contributions from each test and the inclusion of sociodemographic variables &#40;sex&#44; age&#44; education level&#41; in these models&#46; These variables can be especially relevant&#44; particularly in the case of the Mini-Cog&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> These complex models have the disadvantage that they involve a computational process that may be difficult to apply during consultations&#46; The simple model&#44; in contrast&#44; is more practical for use in the clinical setting&#44; as it simply requires adding the scores from both instruments&#46; However&#44; one of the authors &#40;RVC&#41; developed a program to facilitate the application of these instruments&#44; incorporating a calculator that performs these computations automatically&#44; providing a report that includes all results &#40;Supplementary Material&#44; Fig&#46; 1&#41;&#46; This application&#44; Predi-Cog<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> &#40;<a href="https://www.hipocampo.org/Predi-Cog.asp">https&#58;&#47;&#47;www&#46;hipocampo&#46;org&#47;Predi-Cog&#46;asp</a>&#41;&#44; is available online&#44; free of cost&#44; at <a href="http://www.hipocampo.org">www&#46;hipocampo&#46;org</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Based on our results&#44; we recommend applying the tests in a stepped manner &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#44; which allows direct classification of a substantial percentage of individuals&#44; without compromising diagnostic accuracy&#44; using only the Fototest &#40;base dataset&#44; 36&#46;6&#37;&#59; test dataset&#44; 37&#46;8&#37;&#59; external sample&#44; 42&#46;6&#37;&#41;&#44; saving time &#40;197 &#91;56&#46;7&#93; vs 233&#46;9 &#91;45&#46;2&#93; seconds&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall">Our study has some limitations&#44; such as the exclusion of individuals without at least primary education&#44; which limits the possibility of extrapolating our results to the population with lower education levels&#46; In any case&#44; our previous data already recommended avoiding the use of Mini-Cog in this population&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> Another Fototest weakness is that only 63&#46;9&#37; of the individuals in the study sample underwent formal cognitive assessment&#46; However&#44; we only excluded individuals without cognitive complaints and with Fototest scores above the 10th percentile&#44; which makes it unlikely that these individuals would have CI&#44; thus minimising the risk of partial verification bias&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> Lastly&#44; while the index and reference assessments were performed by different professionals who were blinded to other results&#44; and diagnosis was based on reference test results&#44; the professional who issued the diagnosis was not blinded to the results of the BCTs&#46; Our study also has several strengths&#44; such as its naturalistic&#44; pragmatic nature&#44; the large sample size&#44; and&#44; most importantly&#44; the double validation of the results in 2 independent samples with very different characteristics&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In conclusion&#44; the combined use of the Fototest and Mini-Cog&#44; 2 very brief tests that are simple to administer and that evaluate all the cognitive functions that should be addressed in a brief cognitive assessment&#44; enhances the already high diagnostic accuracy of both instruments&#46; Stepped use of these tests is more efficient than their combined use&#44; since it achieves a significant decrease in mean administration time &#40;&#60; 200 seconds&#41; while maintaining accuracy&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Data availability statement</span><p id="par0195" class="elsevierStylePara elsevierViewall">The data that support the findings of this study are available upon reasonable request&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">C&#46; Carnero Pardo is the creator of the Fototest&#46; Under the terms of its Creative Commons licence&#44; the Fototest may be used and distributed for non-commercial purposes provided that it is not modified and its authorship is explicitly acknowledged&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">The Fototest and Mini-Cog include all the domains that are necessary in a cognitive assessment&#46; This study aims to evaluate the diagnostic accuracy of the combined use of both instruments for detecting cognitive impairment&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">We performed a phase III diagnostic accuracy study with 2 independent samples&#58; STUDY&#44; which included 448 participants randomly allocated to 2 datasets &#40;BASE &#91;80&#37;&#93; and TEST &#91;20&#37;&#93;&#41;&#59; and EXTERNAL&#44; which included 61 participants&#46; The index test was consecutive administration of the Fototest and Mini-Cog&#44; and the reference test was formal cognitive assessment&#46; We evaluated the diagnostic accuracy of two-step vs consecutive application of the tests and simple &#40;Comb-Simple&#41;&#44; logistic regression &#40;Comb-LR&#41;&#44; and random decision tree &#40;Comb-RDT&#41; models of their combined use for detecting cognitive impairment &#40;Global Deterioration Scale score &#8805; 3&#41;&#46; We performed an exploratory analysis of the BASE dataset&#44; selecting criteria that maximise accuracy&#59; a pre-specified analysis was used to evaluate the selected criteria in the TEST and EXTERNAL datasets&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">The diagnostic accuracy &#40;95&#37; confidence interval&#41; of the combined models in the BASE dataset &#40;Comb-Simple&#58; 88&#46;3 &#91;88&#46;5&#8722;91&#46;4&#93;&#59; Comb-LR&#58; 91&#46;6 &#91;88&#46;2&#8722;94&#46;3&#93;&#59; Comb-RDT 95&#46;2 &#91;92&#46;5&#8722;97&#46;2&#93;&#41; was significantly higher than the individual values observed for the Mini-Cog and Fototest &#40;81&#46;6 &#91;77&#46;1&#8722;85&#46;4&#93; and 84&#46;9 &#91;80&#46;8&#8722;88&#46;5&#93;&#44; respectively&#41;&#46; These results were replicated in the TEST &#40;Comb-Simple&#58; 88&#46;9&#59; Comb-LR&#58; 95&#46;6&#59; Comb-RDT&#58; 92&#46;2&#41; and EXTERNAL datasets &#40;Comb-Simple&#58; 91&#46;8&#59; Comb-LR&#58; 90&#46;2&#59; Comb-RDT&#58; 88&#46;5&#41;&#46; Two-step application had the same diagnostic accuracy than consecutive application but required less time &#40;mean &#91;SD&#93; of 197&#46;3 s &#91;56&#46;7&#93; vs 233&#46;9 s &#91;45&#46;2&#93;&#59; <span class="elsevierStyleItalic">P</span> &#60; &#46;0001&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Combined application of the Fototest and Mini-Cog takes less than 4 minutes and improves the diagnostic accuracy of both instruments&#46; Two-step application is more efficient as it requires less time while maintaining the same diagnostic accuracy&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">El Fototest y el Mini-Cog incluyen todos los dominios que debieran formar parte de una evaluaci&#243;n cognitiva&#46; Nuestro objetivo es evaluar la utilidad diagn&#243;stica del uso conjunto de ambos instrumentos para el diagn&#243;stico de deterioro cognitivo &#40;DC&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Estudio Fase III de evaluaci&#243;n de pruebas diagn&#243;sticas con dos muestras independientes&#44; ESTUDIO &#40;448 sujetos&#41;&#44; dividida aleatoriamente en dos dataset &#40;BASE 80&#37;&#44; TEST 20&#37;&#41;&#44; y EXTERNA &#40;61 sujetos&#41;&#46; Prueba index&#58; Fototest y Mini-Cog aplicados consecutivamente&#59; prueba de referencia&#58; evaluaci&#243;n cognitiva formal&#46; Se eval&#250;a la UD del uso combinado y escalonado de los modelos Simple &#40;Comb-Simple&#41;&#44; Regresi&#243;n Log&#237;stica &#40;Comb-RL&#41; y &#193;rbol Aleatorio &#40;Comb-AA&#41; para identificar DC &#40;GDS &#8805; 3&#41;&#46; Se realiza un an&#225;lisis exploratorio en BASE seleccionando los criterios que maximizan la Exactitud&#59; la evaluaci&#243;n se realiza en las muestras TEST y EXTERNA mediante un an&#225;lisis preespecificado con los criterios seleccionados&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">La UD de los modelos combinados en BASE &#40;Comb-Simple 88&#46;3 &#40;88&#46;5&#8722;91&#46;4&#41; &#91;Exactitud &#40;LI95&#37;-LS95&#37;&#41;&#93;&#44; Comb-RL 91&#46;6 &#40;88&#46;2&#8722;94&#46;3&#41; y Comb-AA 95&#46;2 &#40;92&#46;5&#8722;97&#46;2&#41;&#41; es significativamente superior a la de Mini-Cog y Fototest &#40;81&#46;6 &#40;77&#46;1&#8722;85&#46;4&#41; y 84&#46;9 &#40;80&#46;8&#8722;88&#46;5&#41; respectivamente&#41;&#59; estos resultados son replicados en TEST &#40;Comb-Simple 88&#46;9 &#40;Exactitud&#41;&#44; Comb-RL 95&#46;6 y Comb-AA 92&#46;2&#41; y EXTERNA &#40;Comb-Simple 91&#46;8&#44; Comb-RL 90&#46;2 y Comb-AA 88&#46;5&#41;&#46; La aplicaci&#243;n escalonada mantiene la misma UD pero requiere menos tiempo &#40;197&#46;3 &#177; 56&#46;7 vs 233&#46;9 &#177; 45&#46;2&#44; p &#60; 0&#46;0001&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">El uso conjunto del Fototest y el Mini-Cog requiere menos de cuatro minutos y mejora la UD de ambos instrumentos&#46; El uso escalonado es m&#225;s eficiente porque manteniendo la misma UD requiere menos tiempo de aplicaci&#243;n&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Random decision tree model&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CI&#58; cognitive impairment&#59; FR&#58; Fototest free recall score&#59; LR&#58; logistic regression&#59; MC&#95;rec&#58; Mini-Cog recall score&#59; no CI&#58; no cognitive impairment&#59; TR&#58; Fototest total recall score&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study sample&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">External sample&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"><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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"><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&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">No&#46; subjects&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">358&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&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">448&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">61&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">&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleItalic">CI</span>&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">166 &#40;46&#46;4&#37;&#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\ttop\n
                  \t\t\t\t">42 &#40;46&#46;7&#37;&#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\ttop\n
                  \t\t\t\t">208 &#40;46&#46;4&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;77&#46;0&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;03 &#40;0&#46;96&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;14 &#40;0&#46;0001&#41;&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"><span class="elsevierStyleItalic">Age &#40;years&#41;</span>&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">60&#46;7 &#40;17&#46;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\ttop\n
                  \t\t\t\t">60&#46;1 &#40;18&#46;7&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#46;7 &#40;17&#46;7&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#46;7 &#40;10&#46;0&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;08 &#40;0&#46;78&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;28 &#40;0&#46;0001&#41;&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"><span class="elsevierStyleItalic">Sex &#40;women&#41;</span>&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">193 &#40;53&#46;9&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;53&#46;3&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">241 &#40;53&#46;8&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;47&#46;5&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;01 &#40;0&#46;92&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;84 &#40;0&#46;36&#41;&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"><span class="elsevierStyleItalic">Education level</span>&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  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\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"><span class="elsevierStyleHsp" style=""></span>Primary education&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">171 &#40;47&#46;8&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46 &#40;51&#46;1&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">217 &#40;48&#46;4&#37;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;39&#46;3&#37;&#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  " rowspan="2" align="left" valign="middle">0&#46;31 &#40;0&#46;57&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="middle">1&#46;78 &#40;0&#46;18&#41;</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"><span class="elsevierStyleHsp" style=""></span>&#62; Primary education&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">187 &#40;52&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44 &#40;48&#46;9&#37;&#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">37 &#40;60&#46;7&#37;&#41;&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 " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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 " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">GDS</span></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"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">130 &#40;36&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;35&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">162 &#40;36&#46;2&#37;&#41;&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">&#8211;&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  " rowspan="5" align="left" valign="middle">4&#46;30 &#40;0&#46;51&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="middle">37&#46;78 &#40;0&#46;0001&#41;</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"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">62 &#40;17&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16 &#40;17&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">78 &#40;17&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;23&#46;0&#37;&#41;&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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">75 &#40;20&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19 &#40;21&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">94 &#40;21&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\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"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">71 &#40;19&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16 &#40;17&#46;8&#37;&#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">87 &#40;19&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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            ]
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                  \t\t\t\t">0&#46;036 &#40;0&#46;02&#41; &#40;2&#46;06&#59; 0&#46;04&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;024 &#40;0&#46;004&#41; &#40;5&#46;59&#59; &#60; 0&#46;0001&#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">0&#46;017 &#40;0&#46;018&#41; &#40;5&#46;04&#59; &#60;0&#46;0001&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;060 &#40;0&#46;015&#41; &#40;4&#46;04&#59; &#60; 0&#46;0001&#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">0&#46;080 &#40;0&#46;014&#41; &#40;5&#46;73&#59; &#60;0&#46;0001&#41;&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">&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 ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Comb-LR&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">&#8211;&nbsp;\t\t\t\t\t\t\n
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        "tipo" => "MULTIMEDIAECOMPONENTE"
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          "identificador" => "bibs0005"
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            0 => array:3 [
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              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analisis de la demanda asistencial neurologica generada por la atencion primaria en un area geografica de las comarcas de Girona"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Lopez-Pousa"
                            1 => "S&#46; Monserrat-Vila"
                            2 => "O&#46; Turro-Garriga"
                            3 => "M&#46; Aguilar-Barbera"
                            4 => "C&#46; Caja-Lopez"
                            5 => "J&#46; Vilalta-Franch"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Neurol"
                        "fecha" => "2009"
                        "volumen" => "49"
                        "paginaInicial" => "288"
                        "paginaFinal" => "294"
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Article information
ISSN: 21735808
Original language: English
DOI:10.1016/j.nrleng.2023.10.002
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