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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">Osteoarthritis is the most common joint disease and a major cause of functional disability and impaired quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is one of the most common reasons for visits to primary care and has a high socioeconomic impact<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> with an estimated annual cost of &#8364; 1502 per patient&#44; resulting in a total expense of 511<span class="elsevierStyleHsp" style=""></span>billion euros a year in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It occurs in all populations and its incidence increases with age&#46; It is estimated to affect 85&#37; of the elderly population and disables 10&#37; of people over 60 years&#44; mainly women&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The prevalence of knee and hands osteoarthritis in the Spanish population was estimated at 10&#46;2&#37; and 6&#46;2&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The goals of osteoarthritis treatment are to relieve pain&#44; improve joint function and delay disease progression in terms of structural joint damage&#44; preventing the toxic effects of treatment&#46; In choosing the therapeutic strategy&#44; clinicians can turn to the recommendations of the <span class="elsevierStyleItalic">European League Against Rheumatism</span> &#40;EULAR&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and the <span class="elsevierStyleItalic">American College of Rheumatology</span> &#40;ACR&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> as well as the consensus documents of the Spanish Society of Rheumatology &#40;SER&#41;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> or to the guidelines of the <span class="elsevierStyleItalic">Osteoarthritis Research Society International</span> &#40;OARSI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Most of the therapeutic goals can be achieved by treatment with various non-selective nonsteroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#46; However&#44; NSAID use is frequently associated with gastrointestinal disorders &#40;GI&#41; which can range from mild discomfort to severe adverse events such as perforations and bleeding&#59; this is associated with a high consumption of health resources&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Concomitant administration of proton pump inhibitors &#40;PPIs&#41; has shown an inverse relationship with the development of GI episodes&#44; strongly influenced by the adherence to PPIs&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The introduction of selective cyclooxygenase inhibitors 2 &#40;ICOX-2&#41; of similar efficacy provided an interesting alternative for improving the toxicity profile in terms of GI events compared to traditional NSAIDs&#46; However&#44; their widespread use has been associated to an increase of cardiovascular events &#40;CV&#41;&#44; some of which also involve traditional NSAIDs&#44; with the possible exception of naproxen&#44; which has not been associated with increased cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Therefore&#44; strategies can be employed with NSAID use&#44; both traditional and ICOX-2 of similar efficacy but different safety profiles&#44; which affect the quality of life related to the health of patients with osteoarthritis&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The fact that health care resources are limited requires that prescription be an act that considers the most effective among the available drugs and selects the most effective in treating the disease in question&#44; prescribing that which enables a lower incremental cost per additional unit of effectiveness&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The fixed dose combination of naproxen and esomeprazole<a class="elsevierStyleCrossRef" href="#fn0005"><span class="elsevierStyleSup">a</span></a> &#40;naproxen&#47;esomeprazole&#41; combines the efficiency of naproxen as an NSAID&#44; with a lower incidence of NSAID-associated ulcers and better tolerated in the upper digestive tract&#44; due to its association to esomeprazole&#44; a PPI&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Its efficacy in osteoarthritis is equivalent to ICOX-2 and has proven to maintain its profile of GI and CV safety&#44; even in the long term&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The objective of this analysis was to conduct an assessment of the efficiency of naproxen&#47;esomeprazole as an alternative therapy in patients with osteoarthritis compared to other NSAIDs available in Spain&#44; both traditional and ICOX-2&#44; alone or administered with a PPI&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Model Structure</span><p id="par0045" class="elsevierStylePara elsevierViewall">We used a Markov model&#44; developed in Microsoft Excel 2007&#44; to simulate the course of the disease in a hypothetical cohort of patients passing through different states of health&#46; These models are commonly used in simulations of chronic diseases&#46; The health states should be mutually exclusive&#44; so the patient at all times can only be in one of these states&#44; remaining for a uniform period of time&#44; called a cycle&#46; At the end of each cycle the patient may pass or <span class="elsevierStyleItalic">move</span> to another state according to transition probabilities&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In this case eight health states were created among which patients could move in defined cycles of 3 months&#46; From the initial &#8220;without incident&#8221; state&#44; the patient evolves to the &#8220;death&#8221; state or 6 other states derived from the appearance of a clinical event&#58; GI-dyspepsia&#44; symptomatic or complicated ulcer or ulcer-CV-myocardial infarction &#40;MI&#41;&#44; stroke&#44; or congestive heart failure &#40;CHF&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Except for dyspepsia&#44; the remaining episodes were considered serious&#46; After a severe episode&#44; the patient remained in the corresponding post-episode state for the rest of the simulation or until transition to the absorbing health state &#40;death&#41;&#46; However&#44; to consider the fact that&#44; in clinical practice&#44; a patient may experience later episodes&#44; and that the probability of occurrence of these events is highest in patients who have had a previous episode&#44; the cost and the associated usefulness of each severe postepisode state were weighted to take into account other possible future episodes&#46; Patients with dyspepsia could remain in this state for the rest of the simulation&#44; resulting in a serious episode with the implications described&#44; or die&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The profile of the population sampled in this model reflects a patient over 65 years of age with osteoarthritis and increased GI risk&#44; defined as a history of ulcer &#40;complicated or uncomplicated&#41; in the upper GI tract&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In a time horizon of one year&#44; total costs &#40;including the cost of drug treatment and the cost of managing clinical events&#41; and health outcomes at 6 months of treatment with any of the following strategies were estimated&#58; celecoxib&#44; PPI&#43;celecoxib&#44; diclofenac&#43;PPI&#44; etoricoxib&#44; etoricoxib&#43;PPI&#43;PPI ibuprofen&#44; naproxen&#43;PPI or naproxen&#47;esomeprazole&#46; The PPI of choice was omeprazole&#44; being the most used and the least costly&#44; at doses of 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; The duration and dosage considered for each alternative represented the most frequently used treatment by me in clinical practice for the treatment of patients with the profile described &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">After 6 months of treatment&#44; or if severe episode occurred&#44; involving permanent discontinuation of the NSAIDs&#44; the model assumed that patients went on to receive treatment with paracetamol <span class="elsevierStyleMonospace">&#40;</span>3000<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; for the rest of the simulation&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In the absence of evidence to the contrary&#44; it was assumed that the effect of the treatment received did not persist after its end&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The development of GI symptoms &#40;dyspepsia&#41; involved incorporating PPI to the treatment received in cases of therapeutic strategies which did not include PPI &#40;celecoxib and etoricoxib&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Adherence to established strategies were evaluated in terms of adherence to PPI&#46; This analysis found that within 6 months of treatment&#44; adherence was 69&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Type of Analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The efficiency of naproxen&#47;esomeprazole was established by its incremental cost effectiveness &#40;ICER&#41; for each of the other relation strategies evaluated according to the following formula&#58;<elsevierMultimedia ident="eq0005"></elsevierMultimedia></p><p id="par0085" class="elsevierStylePara elsevierViewall">The unit of effectiveness used were adjusted life years &#40;QALYs&#41;&#46; QALYs combine into a single value&#44; quantity&#44; and quality of life&#44; and are calculated by multiplying survival by the usefulness value&#46; The usefulness is a parameter representing the preference of patients for a given health condition&#44; taking into account the effect on their quality of life&#46; The value of 1 means a state of perfect health&#44; and the value of 0 equals death&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Model Parameters</span><p id="par0090" class="elsevierStylePara elsevierViewall">The probability of moving to any of the states considered are derived from the risk of GI and CV events and associated mortality&#46; The odds of each episode appearing were obtained from the evaluation conducted by the <span class="elsevierStyleItalic">National Institute for Health and Care Excellence</span> &#40;NICE&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> using the same premise to adjust the dosages to&#58; a reduction of 50&#37; of the dose involved a 25&#37; reduction in risk of developing an episode&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> For this analysis it was assumed that the risk of GI episodes with naproxen&#47;esomeprazole is equivalent to naproxen&#43;PPI separately if there is 100&#37; adherence to the PPI&#44; and that the risk of CV events is equivalent to naproxen&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> lists the probabilities used for development of the first episode&#46; PPI administration along with the therapeutic alternatives involved reduced the probability of GI episodes compared to monotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> This model considers that patients with a history of GI episodes have an increased risk of a new GI episode&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Similarly&#44; the existence of previous episodes of MI&#44; stroke or heart failure was associated with an increased likelihood of having a CV event&#46; Relationship between the level of adherence and the risk of GI events was determined using the same methodology as that used by other authors<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> calculating the increased risk of GI episodes per 10&#37; loss of adhesion &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The model considered both overall mortality by age of the Spanish population&#44; obtained from the tables of the National Statistics Institute &#40;INE&#41; and the mortality associated with GI complicated &#40;complicated ulcers&#41;&#44; MI&#44; stroke or congestive heart failure episodes&#44; whose values were obtained from the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Different values were considered useful&#44; depending on the age&#44; the underlying pathology and clinical events&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In the absence of specific data for Spanish population&#44; earnings by age were obtained from a health survey performed in the UK&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> As an item associated with osteoarthritis in the absence of clinical episodes&#44; a meta-analysis results of the WOMAC scale showed no differences between NSAIDs and ICOX-2&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> Earnings per development of clinical events were obtained from the literature<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The analysis was conducted from the perspective of the Spanish National Health System&#44; including only the costs associated with pharmacological treatment and management derived from clinical episodes&#46; The cost of drug therapies for each 3 months&#44; 91 established in days&#44; was calculated taking into account the doses of study&#44; from the retail price &#40;RRP-IVA&#41; and applying the appropriate 7&#46;5&#37; deduction established in the Royal Decree-Law 8&#47;2010&#46; For generic drugs and in which this deduction does not apply&#44; we chose the lowest-priced generic&#46; The costs of drugs were obtained from the Books of General Council of Official Colleges of Pharmacists&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The costs of managing clinical episodes&#44; and those associated with the state of health after each episode&#44; were obtained from Diagnosis Related Groups &#40;DRGs&#41; national aggregates<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> or the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a> In the absence of published data on the costs associated with symptomatic postulcer and complicated postulcer states considered that these were equivalent to the cost of management of dyspepsia&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> For the post-congestive heart failure state&#44; the cost was assumed to be<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> equivalent to the post-MI state&#44; consistent with the premise adopted by NICE in previous assessments&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> includes the costs used in the analysis&#46; All costs in euros are presented as 2012 euros&#44; after correction of cost data with the consumer price index &#40;CPI&#41; provided by the INE in appropriate cases&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">As the horizon of the analysis was one year&#44; no discount rate was applied to costs or health effects&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Sensitivity Analysis</span><p id="par0110" class="elsevierStylePara elsevierViewall">Deterministic sensitivity analyzes were performed to identify the influence on the results of variations in the following parameters&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Duration of treatment&#58; 3 months&#44; since there is variability in the length&#44; being sometimes shorter &#40;intermittent symptoms&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall">Dosage of ibuprofen&#58; due to increased variety in relation to the dose used in clinical practice for this population&#44; and since some guidelines recommend dosages reaching even 2400<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; an analysis was performed based on the maximum dose&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">Price of celecoxib&#58; due to the possible availability of celecoxib generic version throughout 2013&#44; its price was reduced by 40&#37;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall">Costs of managing events &#40;&#177;10&#37;&#41;&#59; because these parameters were susceptible to change&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">Earnings per episode&#58; modified with the upper and lower ends of the 95&#37; CI &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p></li></ul></p><p id="par0140" class="elsevierStylePara elsevierViewall">Additionally&#44; a probabilistic sensitivity analysis &#40;PSA&#41; was performed to change randomly and multivariate the values of the parameters&#44; thus retaining the possibility of extreme variations from the baseline case and allowing to estimate&#44; due to the high number of simulations&#44; the robustness of the results based on those considered outliers&#46; 10<span class="elsevierStyleHsp" style=""></span>000 Monte Carlo simulations were performed where the values of the parameters are changed simultaneously according to the following functions&#58; beta probability distribution&#44; adherence&#44; mortality and utilities&#44; log normal distribution and gamma distribution risks relating to episode cost management and cost of health states&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0145" class="elsevierStylePara elsevierViewall">At the end of the 12-month simulation and 6 months of treatment&#44; naproxen&#47;esomeprazole resulted in a &#40;more effective and less associated cost&#41; than the celecoxib&#44; etoricoxib and diclofenac&#43;PPI dominant strategy&#46; Whereas an efficiency threshold &#8364; 30<span class="elsevierStyleHsp" style=""></span>000&#47;QALY is an acceptable additional value of willingness to pay&#44; naproxen&#47;esomeprazole would be cost-effective regarding ibuprofen&#43;PPI and naproxen&#43;PPI strategy&#46; Celecoxib&#43;PPI and etoricoxib&#43;PPI were more effective than naproxen&#47;esomeprazole strategies&#44; which prevented the calculation of the ICER of naproxen&#47;esomeprazole with respect to them with the proposed formula for this calculation&#46; These results are detailed in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">In all deterministic sensitivity analysis performed &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#41;&#44; the results of naproxen&#47;esomeprazole remained&#58; dominant vs celecoxib and etoricoxib&#44; cost-effective compared to ibuprofen&#43;PPI and naproxen&#43;PPI and showing no change vs diclofenac&#43;PPI&#44; becoming cost-effective in reducing treatment to 3 months and reducing the costs of episodes by 10&#37;&#46; We performed two separate PSA vs the options for naproxen&#47;esomeprazole and that proved cost-effective in the baseline case&#44; ibuprofen&#43;PPI and naproxen&#43;PPI&#46; In the PSA&#44; after 10<span class="elsevierStyleHsp" style=""></span>000 simulations&#44; the average ICER&#44; naproxen&#47;esomeprazole stood at 18<span class="elsevierStyleHsp" style=""></span>436 and &#8364; 6367&#47;additional QALY vs&#43;ibuprofen&#43;PPI and naproxen&#43;PPI respectively&#44; 66&#46;4&#37; and 98&#46;3&#37; of cases were considered cost-effective &#40;below the threshold of &#8364; 30<span class="elsevierStyleHsp" style=""></span>000&#47;additional QALY&#41;&#44; respectively for each strategy &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">NSAIDs&#44; both non-selective as well as those selective for inhibition of COX-2&#44; are effective therapeutic alternative in the treatment of osteoarthritis&#46; However&#44; tolerability and GI and CV safety factors associated with its use in certain populations contraindicate their use or require appraisal of the individual profile of benefit&#47;risk for each patient&#46; Thus&#44; although ICOX-2 reduces the risk of gastrointestinal complications&#44; they have not shown&#44; on occasion&#44; a suitable CV safety profile&#46; Conversely&#44; naproxen is a therapeutic agent with a good CV safety profile at doses of 500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; but does not have this profile regarding the digestive tract&#46; It seems logical that the latter risk reduction &#40;with the addition of esomeprazole&#41; would give naproxen a role in the symptomatic treatment of osteoarthritis&#44; and that this would be an efficient therapeutic choice&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The many potential variables in the GI and CV risk for each patient makes assignment of the best therapeutic strategy based on existing resources difficult&#44; so that an indicator such as ICER&#44; which combines clinical and economic outcomes relative to different therapies&#44; is very interesting&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The ICER of naproxen&#47;esomeprazole was favorable&#44; even in the analysis of sensitivity compared to other options&#44; except for the treatment ICOX-2&#43;PPI&#46; The initial advantage of ICOX-2 came from the lack of need&#44; due to their lower rate of GI events&#44; of concomitant use of a PPI&#44; although in recent times there has been a change in clinical practice&#44; with the recommendation of using ICOX-2&#43;PPI in elderly patients with a history of gastrointestinal bleeding and the presence of multiple risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The results are important from the point of view of clinical practice&#46; The patient with osteoarthritis is usually elderly and has chronic multiple comorbidities including pathologies&#44; usually CV and include gastrointestinal manifestations&#46; Numerous studies have stratified these risks in said population and have established indication for NSAIDs in order to minimize the impact of adverse events&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> The availability of a fixed combination of a highly effective NSAID with excellent CV profile&#44; such as naproxen&#44; along with a powerful PPI&#44; might be able to mitigate its digestive impact by itself&#44; according to the authors&#44; becoming a good alternative&#46; The analysis performed in this study further corroborates&#44; from the pharmacoeconomic point of view&#44; its favorable clinical medicine perspective&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">This work is not without some limitations&#44; some inherent to the theoretical association or to the use of decision analytic models&#44; simulations that may not be an accurate reflection of clinical practice&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The validity and quality of decision analytical studies lie in their programming&#44; as well as in the assumptions made and the values for the parameters included under consideration&#46; In the development of economic evaluations it is crucial that the model has clinical sense and that the data comes from reliable and verifiable&#44; preferably published sources&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">This model was developed with the baseline assumption of equivalence in terms of efficacy of all treatments included&#44; so that the differences between the evaluated strategies lie in the differences in costs and rates of adverse events&#46; The decision on inclusion of clinical episodes was made considering the clinically relevant and data availability required<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> for the episodes&#46; The equivalence in efficacy&#44; if not exact&#44; could be a bias of the design&#44; but in the absence of proven evidence from controlled <span class="elsevierStyleItalic">head-to-head</span> trials it has to be understood as a reasonable premise&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The adjustment made in relation to the dose and the occurrence of clinical events that are handled in the model represents a limitation&#44; although the methodology is consistent with that used in other studies which concluded that the uncertainty associated with this parameter did not influence the<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> results&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In the absence of specific data concerning Spanish population it was necessary to use utility values per age obtained from the UK population&#46; Utilities&#44; associated with cultural factors&#44; may differ even between countries in the same environment&#44; but the sensitivity analysis&#44; changing the values of earnings per episode&#44; showed no influence of this parameter on the results&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Additionally&#44; the fact that in each 3 month cycle the patient may only experience one GI or CV episode must be considered&#46; This assumption may not be entirely realistic&#44; but its adoption was necessary to build the model&#44; also considering the generation of no significant impact on the results&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The limitations described were offset by conservative assumptions and tested in sensitivity analyzes&#44; showing no significant influence on the meaning of the results&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">There are several publications on economic evaluations of treatments used in osteoarthritis&#44; both internationally and in the<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Spanish context&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;28&#44;29</span></a> although&#44; to the authors&#8217; knowledge&#44; this is the first cost-utility analysis of naproxen&#47;esomeprazole over other ICOX-2 NSAIDs or adapted to Spain&#44; also individualized for each NSAID&#44; instead of treating all NSAIDs as a group&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The results obtained from the analysis of a hypothetical cohort of patients with a decision analytic model suggest that naproxen&#47;esomeprazole is an appropriate therapeutic option that is dominant over other strategies available&#44; such as celecoxib&#44; etoricoxib and diclofenac&#43;PPI&#59; and also using the standard reference threshold &#8364; 30<span class="elsevierStyleHsp" style=""></span>000&#47;additional QALY&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a> showing it as a cost-effective strategy against both the option prescribed in clinical practice &#40;ibuprofen&#43;PPI&#41; compared to the option of separate single-components &#40;naproxen&#43;PPI&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical Responsibilities</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Protection of human subjects and animals in research</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors declare that experiments have not been done on humans or animals&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Confidentiality of data</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors state that no patient data appears in this article&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Right to privacy and informed consent</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors state that no patient data appears in this article&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of Interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">IO and MAC are PORIB employees&#44; a consultant agency specialized in the area of economic evaluation of health technologies&#44; have received unconditional funding for this analysis from AstraZeneca&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">JSC and MC are employees of AstraZeneca&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">JT&#44; AL and JLZ have worked as clinical experts in the validation of the values of the parameters used in the analysis&#44; and therefore claim to have received unconditional funding from AstraZeneca&#44; which never influenced the participation and results obtained&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Materials and Methods"
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            0 => array:2 [
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          "titulo" => "Ethical Responsibilities"
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              "identificador" => "sec0050"
              "titulo" => "Protection of human subjects and animals in research"
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              "identificador" => "sec0055"
              "titulo" => "Confidentiality of data"
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              "titulo" => "Right to privacy and informed consent"
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          "identificador" => "xack85925"
          "titulo" => "Acknowledgments"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-06-18"
    "fechaAceptado" => "2013-11-20"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:3 [
            0 => "Osteoarthrosis"
            1 => "Nonsteroidal anti-inflammatory drugs"
            2 => "Cost-utility"
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          "clase" => "keyword"
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          "palabras" => array:3 [
            0 => "Artrosis"
            1 => "Antiinflamatorios no esteroideos"
            2 => "Coste-utilidad"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess&#44; from the perspective of the National Healthcare System&#44; the efficiency of a fixed-dose combination of naproxen and esomeprazole &#40;naproxen&#47;esomeprazole&#41; in the treatment of osteoarthritis &#40;OA&#41; compared to other NSAID&#44; alone or in combination with a proton pump inhibitor &#40;PPI&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A Markov model was used&#59; it included different health states defined by gastrointestinal &#40;GI&#41; events&#58; dyspepsia&#44; symptomatic or complicated ulcer&#59; or cardiovascular &#40;CV&#41; events&#58; myocardial infarction&#44; stroke or heart failure&#46; The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The total costs &#40;&#8364;&#44; 2012&#41;&#44; including drug and event-related costs&#44; and the health outcomes expressed in quality-adjusted life years &#40;QALY&#41; were estimated in patients with increased GI risk&#44; aged 65 or over&#44; for a 1-year time horizon and a 6-month treatment with celecoxib &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; celecoxib&#43;PPI&#44; diclofenac &#40;150<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#43;PPI&#44; etoricoxib &#40;60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; etoricoxib&#43;PPI&#44; ibuprofen &#40;1800<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#43;PPI&#44; naproxen &#40;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#43;PPI or naproxen&#47;esomeprazole &#40;naproxen 1000<span class="elsevierStyleHsp" style=""></span>mg&#47;esomeprazole 40<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; The selected PPI was omeprazole &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Naproxen&#47;esomeprazole was a dominant strategy &#40;more effective and less costly&#41; compared to celecoxib&#44; etoricoxib and diclofenac&#43;PPI&#46; Celecoxib&#43;PPI and etoricoxib&#43;PPI were more effective&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Considering a cost-effectiveness threshold of &#8364; 30<span class="elsevierStyleHsp" style=""></span>000 per additional QALY&#44; naproxen&#47;esomeprazole was cost-effective compared to ibuprofen&#43;PPI and naproxen&#43;PPI with incremental cost-effectiveness ratios &#40;ICER&#41; of &#8364; 15<span class="elsevierStyleHsp" style=""></span>154 and &#8364; 5202 per additional QALY&#44; respectively&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A fixed-dose combination of naproxen and esomeprazole is a cost-effective&#44; and even dominant&#44; alternative compared to other options in OA patients with increased GI risk&#46;</p>"
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        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluar&#44; desde la perspectiva del Sistema Nacional de Salud&#44; la eficiencia de la combinaci&#243;n a dosis fija de naproxeno y esomeprazol &#40;naproxeno&#47;esomeprazol&#41; en artrosis frente a otros AINE en monoterapia o combinados con un inhibidor de la bomba de protones &#40;IBP&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se emple&#243; un modelo de Markov con estados de salud definidos por episodios gastrointestinales &#40;GI&#41;&#58; dispepsia&#44; &#250;lcera p&#233;ptica sintom&#225;tica o complicada&#59; o cardiovasculares &#40;CV&#41;&#58; infarto agudo de miocardio&#44; ictus o insuficiencia cardiaca&#46; El modelo es semejante al utilizado por el NICE en su evaluaci&#243;n de AINE en artrosis publicada en 2008&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se estimaron&#44; en un horizonte temporal de 1 a&#241;o &#40;ciclos de 3 meses&#41;&#44; los costes totales &#40;&#8364;&#44; 2012&#41;&#44; incluyendo coste farmacol&#243;gico y de manejo de episodios&#44; y los resultados en salud&#44; expresados en a&#241;os de vida ajustados por calidad &#40;AVAC&#41;&#44; en pacientes mayores de 65 a&#241;os con riesgo GI aumentado&#44; tras 6 meses de tratamiento con celecoxib &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#44; celecoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; diclofenaco &#40;150<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; etoricoxib &#40;60<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#44; etoricoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; ibuprofeno &#40;1&#46;800<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; naproxeno &#40;1&#46;000<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP o naproxeno&#47;esomeprazol &#40;naproxeno 1&#46;000<span class="elsevierStyleHsp" style=""></span>mg&#47;esomeprazol 40<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#46; El IBP fue omeprazol &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Naproxeno&#47;esomeprazol result&#243; dominante &#40;m&#225;s efectivo y menor coste&#41; respecto a celecoxib&#44; etoricoxib y diclofenaco<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#46; Celecoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP y etoricoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP fueron m&#225;s efectivos&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Considerando un umbral de 30&#46;000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;AVAC adicional&#44; naproxeno&#47;esomeprazol result&#243; coste-efectivo respecto a ibuprofeno<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP y naproxeno<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP con valores de relaci&#243;n coste-efectividad incremental de 15&#46;154<span class="elsevierStyleHsp" style=""></span>&#8364; y 5&#46;202<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;AVAC adicional&#44; respectivamente&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La combinaci&#243;n a dosis fijas de naproxeno y esomeprazol en pacientes con artrosis y riesgo GI aumentado es una alternativa coste-efectiva e incluso dominante frente a otras opciones&#46;</p>"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0045">Please cite this article as&#58; Capel M&#44; Tornero J&#44; Zamorano JL&#44; Oyag&#252;ez I&#44; Casado M&#193;&#44; S&#225;nchez-Covisa J&#44; et al&#46; Eficiencia de la combinaci&#243;n naproxeno&#47;esomeprazol para el tratamiento de la artrosis en Espa&#241;a&#46; Reumatol Clin&#46; 2014&#59;10&#58;210&#8211;217&#46;</p>"
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      1 => array:2 [
        "etiqueta" => "a"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0050">This fixed dose combination is marketed in Spain as modified-release tablets containing naproxen with enteric coating and film-coated esomeprazole &#40;as magnesium trihydrate&#41;&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Markov diagram&#46; GI&#44; gastrointestinal&#59; MI&#44; myocardial infarction&#59; CHF&#44; congestive heart failure&#46; The balloons represent the possible health states&#44; and arrows&#44; the allowed transitions between them&#46;</p>"
        ]
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        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Plot of cost-effectiveness of naproxen&#47;esomeprazole&#46; The cost-effectiveness plane represents the results of the PSA&#46; Each point represents a value of ICER&#44; of each of the 10<span class="elsevierStyleHsp" style=""></span>000 Monte Carlo simulations performed&#46;</p>"
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        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
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        "figura" => array:1 [
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Acceptability curve of naproxen&#47;esomeprazole&#46; The acceptability curve reflects certain thresholds for willingness to pay &#40;from 0 to 50<span class="elsevierStyleHsp" style=""></span>000 &#8364; represented on the horizontal axis&#41;&#44; the proportion &#40;on the vertical axis&#41; of the 10<span class="elsevierStyleHsp" style=""></span>000 ICER values obtained in the PSA that would be less than that determined threshold&#44; considered cost effective&#46;</p>"
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Therapeutic alternatives&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" style="border-bottom: 2px solid black">Mode of administration&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">PVP-tax cost &#40;container&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><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">Celecoxib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">200<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 34&#46;35<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> &#40;30 tablets&#44; 200<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diclofenac&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 1&#46;65<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 50<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&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<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 30&#46;06<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> &#40;28 tablets&#44; 60<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibuprofen&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">1800<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 1&#46;97<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 600<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&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">1000<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 4&#46;34<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 500<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&#47;esomeprazole&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">1000&#47;40<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 23&#46;71<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> &#40;60 tablets&#44; 500&#47;20<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paracetamol&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">3000<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 2&#46;79<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 1000<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omeprazole&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<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 2&#46;42<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;28 tablets&#44; 20<span class="elsevierStyleHsp" style=""></span>mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab520510.png"
              ]
            ]
          ]
          "notaPie" => array:4 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Artilog<span class="elsevierStyleSup">&#174;</span>&#44; Celebrex<span class="elsevierStyleSup">&#174;</span> with 7&#46;5&#37; deduction provided for in Royal Decree 8&#47;2010&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Lowest price&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Acoxxel<span class="elsevierStyleSup">&#174;</span>&#44; Arcoxia<span class="elsevierStyleSup">&#174;</span>&#44; Exxiv<span class="elsevierStyleSup">&#174;</span> with 7&#46;5&#37; deduction provided for in Royal Decree 8&#47;2010&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Vimovo<span class="elsevierStyleSup">&#174;&#44;</span> with 7&#46;5&#37; deduction provided for in Royal Decree 8&#47;2010&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Dosage and Cost of Therapeutic Alternatives&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">MI&#44; acute myocardial infarction&#59; PPI&#44; proton pump inhibitor&#59; CHF&#44; congestive heart failure&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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">Therapeutic alternatives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="6" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Clinical episodes</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Dyspepsia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Complicated ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Congestive heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Celecoxib&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12450&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00090&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00050&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00150&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00020&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00040&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Celecoxib &#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;03113&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00023&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00013&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00150&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00020&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00040&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diclofenac&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;10991&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00062&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00039&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00108&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00072&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00024&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;16307&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00120&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00093&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00133&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00093&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00053&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;04077&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00030&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00023&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00133&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00093&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00053&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibuprofen&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;06564&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00089&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00044&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00180&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00072&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00108&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;07352&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00118&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00037&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00069&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00091&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00103&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&#47;esomeprazole&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;07352&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00118&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00037&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00069&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00091&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00103&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paracetamol<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12720&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00040&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00020&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00060&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00030&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab520509.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">As rescue therapy&#44; or at the end of 6 months of treatment with the study alternatives&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Probability of Development of the First Clinical Episode&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">NSAIDs&#44; nonsteroidal anti-inflammatory drugs&#59; PPI&#44; proton pump inhibitor&#59; GI&#44; gastrointestinal&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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">Therapeutic strategies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Increase &#40;&#37;&#41; in the risk of GI episode for every 10&#37; loss of adherence to PPI level</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Dyspepsia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Symptomatic ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Complicated ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">With COX-2 inhibitors &#40;celecoxib&#43;PPI or etoricoxib&#43;PPI&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;8&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;5&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;1&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nonselective NSAID &#40;diclofenac&#43;PPI or ibuprofen&#43;PPI or naproxen&#43;PPI&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;9&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;9&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab520506.png"
              ]
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Relationship Between PPI Adherence and Risk of GI Episodes&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">GI&#44; gastrointestinal&#59; DRG&#44; diagnostic related group&#59; MI&#44; acute myocardial infarction&#59; CI&#44; confidence interval&#59; CHF&#44; congestive heart failure&#59; NA&#44; not applicable&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Health status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Utilities mean &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Cost of episode management&#47;cost of state&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">No episode&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GI symptoms &#40;dyspepsia&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;73 &#40;0&#46;63&#8211;0&#46;84&#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">&#8364; 324&#46;96<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Symptomatic ulcer&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;55 &#40;0&#46;47&#8211;0&#46;65&#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">&#8364; 2884&#46;98 &#40;average DRG177 and 178&#41;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postulcer symptomatic&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;98&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">Equivalent to dyspepsia&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complicated ulcer&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;46 &#40;0&#46;37&#8211;0&#46;56&#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">&#8364; 3430&#46;30 &#40;average DRG174&#44; 175 and 176&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postulcer complicated&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;98&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">Equivalent to dyspepsia&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;37 &#40;0&#46;28&#8211;0&#46;47&#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">&#8364; 5595&#46;63 &#40;average DRG121 and 122&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-MI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;88 &#40;0&#46;78&#8211;0&#46;98&#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">&#8364; 259&#46;53<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stroke&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;35 &#40;0&#46;25&#8211;0&#46;45&#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">&#8364; 4964&#46;48 &#40;DRG14 and 810&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Poststroke&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;71 &#40;0&#46;61&#8211;0&#46;80&#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">&#8364; 107&#46;44<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CHF&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;71 &#40;0&#46;61&#8211;0&#46;80&#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">3575&#46;43 &#40;DRG127&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-CHF&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Equivalent post-MI&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Death&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">NA&#44; not applicable&#46;</p>"
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            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Therapeutic strategies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">QALY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Total cost &#40;&#8364;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">ICER &#40;&#8364;&#47;QALY additional naproxen&#47;esomeprazole vs&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Naproxen&#47;esomeprazole&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5911&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 662&#46;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Celecoxib&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5765&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 843&#46;35&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">Naproxen&#47;esomeprazole is dominant&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5635&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 960&#46;06&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">Naproxen&#47;esomeprazole is dominant&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diclofenac&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5708&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 674&#46;67&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">Naproxen&#47;esomeprazole is dominant&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibuprofen&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5870&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 599&#46;49&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">&#8364; 15<span class="elsevierStyleHsp" style=""></span>154&#46;20&#47;QALY<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5843&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 627&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 5201&#46;65&#47;QALY<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Celecoxib&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5996&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 659&#46;42&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">NA<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5946&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 699&#46;55&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">NA<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab520507.png"
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Naproxen&#47;esomeprazole would be cost-effective against these alternatives considering an additional acceptability threshold of &#8364; 30<span class="elsevierStyleHsp" style=""></span>000&#47;QALY&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Failure to implement the proposed formula for calculating the ICER of naproxen&#47;esomeprazole faced with this alternative because it is a more effective strategy&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Results of the Baseline Case&#46; Years of Quality-adjusted Life Years &#40;QALY&#41;&#44; Costs and Incremental Cost-effectiveness Ratio &#40;ICER&#41; of Naproxen&#47;Esomeprazole vs Other Alternatives&#46;</p>"
        ]
      ]
      8 => array:7 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0130" class="elsevierStyleSimplePara elsevierViewall">QALY&#44; quality-adjusted life years&#59; ICER&#44; incremental cost-effectiveness ratio&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Therapeutic strategies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Incremental QALY &#40;naproxen&#47;esomeprazole vs&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Total incremental cost &#40;&#8364;&#41; &#40;naproxen&#47;esomeprazole vs&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">ICER &#40;additional &#8364;&#47;QALY naproxen&#47;esomeprazole vs&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Duration of treatment&#58; 3 months</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Celecoxiba<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;99&#46;97&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">Naproxen&#47;esomeprazole is dominant&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Etoricoxiba<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;156&#46;58&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">Naproxen&#47;esomeprazole is dominant&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diclofenac&#43;PPI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46;83&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">&#8364; 1342&#46;63&#47;QALY&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ibuprofen&#43;PPI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">48&#46;31&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8364; 28<span class="elsevierStyleHsp" style=""></span>353&#46;52&#47;QALY&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>Naproxen&#43;PPI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33&#46;17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8364; 11<span class="elsevierStyleHsp" style=""></span>169&#46;24&#47;QALY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Cost of episode handling&#58; 10&#37; increase</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>Celecoxiba<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Naproxen&#47;esomeprazole is dominant&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Etoricoxib<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Naproxen&#47;esomeprazole is dominant&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diclofenac&#43;PPI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Naproxen&#47;esomeprazole is dominant&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Naproxen&#43;PPI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8364; 4175&#46;96&#47;QALY&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Episodes handling costs&#58; 10&#37; off</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>Celecoxib<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Naproxen&#47;esomeprazole is dominant&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Naproxen&#43;PPI&nbsp;\t\t\t\t\t\t\n
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Original Article
Efficiency of Naproxen/Esomeprazole in Association for Osteoarthrosis Treatment in Spain
Eficiencia de la combinación naproxeno/esomeprazol para el tratamiento de la artrosis en España
Margarita Capela, Jesús Tornerob, José Luis Zamoranoc, Itziar Oyagüezd,
Corresponding author
ioyaguez@porib.com

Corresponding author.
, Miguel Ángel Casadod, Joaquín Sánchez-Covisaa, Ángel Lanase
a Health Economics & Outcomes Research, AstraZeneca Farmacéutica Spain, Madrid, Spain
b Servicio de Reumatología, Hospital General Universitario de Guadalajara, Guadalajara, Spain
c Servicio de Cardiología, Hospital Ramón y Cajal, Madrid, Spain
d Pharmacoeconomics and Outcomes Research Iberia, Madrid, Spain
e Servicio de Aparato Digestivo, Hospital Clínico, CIBERehd, IIS Aragón, Universidad de Zaragoza, Zaragoza, 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">Osteoarthritis is the most common joint disease and a major cause of functional disability and impaired quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is one of the most common reasons for visits to primary care and has a high socioeconomic impact<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> with an estimated annual cost of &#8364; 1502 per patient&#44; resulting in a total expense of 511<span class="elsevierStyleHsp" style=""></span>billion euros a year in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It occurs in all populations and its incidence increases with age&#46; It is estimated to affect 85&#37; of the elderly population and disables 10&#37; of people over 60 years&#44; mainly women&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The prevalence of knee and hands osteoarthritis in the Spanish population was estimated at 10&#46;2&#37; and 6&#46;2&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The goals of osteoarthritis treatment are to relieve pain&#44; improve joint function and delay disease progression in terms of structural joint damage&#44; preventing the toxic effects of treatment&#46; In choosing the therapeutic strategy&#44; clinicians can turn to the recommendations of the <span class="elsevierStyleItalic">European League Against Rheumatism</span> &#40;EULAR&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and the <span class="elsevierStyleItalic">American College of Rheumatology</span> &#40;ACR&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> as well as the consensus documents of the Spanish Society of Rheumatology &#40;SER&#41;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> or to the guidelines of the <span class="elsevierStyleItalic">Osteoarthritis Research Society International</span> &#40;OARSI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Most of the therapeutic goals can be achieved by treatment with various non-selective nonsteroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#46; However&#44; NSAID use is frequently associated with gastrointestinal disorders &#40;GI&#41; which can range from mild discomfort to severe adverse events such as perforations and bleeding&#59; this is associated with a high consumption of health resources&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Concomitant administration of proton pump inhibitors &#40;PPIs&#41; has shown an inverse relationship with the development of GI episodes&#44; strongly influenced by the adherence to PPIs&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The introduction of selective cyclooxygenase inhibitors 2 &#40;ICOX-2&#41; of similar efficacy provided an interesting alternative for improving the toxicity profile in terms of GI events compared to traditional NSAIDs&#46; However&#44; their widespread use has been associated to an increase of cardiovascular events &#40;CV&#41;&#44; some of which also involve traditional NSAIDs&#44; with the possible exception of naproxen&#44; which has not been associated with increased cardiovascular events&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Therefore&#44; strategies can be employed with NSAID use&#44; both traditional and ICOX-2 of similar efficacy but different safety profiles&#44; which affect the quality of life related to the health of patients with osteoarthritis&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The fact that health care resources are limited requires that prescription be an act that considers the most effective among the available drugs and selects the most effective in treating the disease in question&#44; prescribing that which enables a lower incremental cost per additional unit of effectiveness&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The fixed dose combination of naproxen and esomeprazole<a class="elsevierStyleCrossRef" href="#fn0005"><span class="elsevierStyleSup">a</span></a> &#40;naproxen&#47;esomeprazole&#41; combines the efficiency of naproxen as an NSAID&#44; with a lower incidence of NSAID-associated ulcers and better tolerated in the upper digestive tract&#44; due to its association to esomeprazole&#44; a PPI&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Its efficacy in osteoarthritis is equivalent to ICOX-2 and has proven to maintain its profile of GI and CV safety&#44; even in the long term&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The objective of this analysis was to conduct an assessment of the efficiency of naproxen&#47;esomeprazole as an alternative therapy in patients with osteoarthritis compared to other NSAIDs available in Spain&#44; both traditional and ICOX-2&#44; alone or administered with a PPI&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Model Structure</span><p id="par0045" class="elsevierStylePara elsevierViewall">We used a Markov model&#44; developed in Microsoft Excel 2007&#44; to simulate the course of the disease in a hypothetical cohort of patients passing through different states of health&#46; These models are commonly used in simulations of chronic diseases&#46; The health states should be mutually exclusive&#44; so the patient at all times can only be in one of these states&#44; remaining for a uniform period of time&#44; called a cycle&#46; At the end of each cycle the patient may pass or <span class="elsevierStyleItalic">move</span> to another state according to transition probabilities&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In this case eight health states were created among which patients could move in defined cycles of 3 months&#46; From the initial &#8220;without incident&#8221; state&#44; the patient evolves to the &#8220;death&#8221; state or 6 other states derived from the appearance of a clinical event&#58; GI-dyspepsia&#44; symptomatic or complicated ulcer or ulcer-CV-myocardial infarction &#40;MI&#41;&#44; stroke&#44; or congestive heart failure &#40;CHF&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Except for dyspepsia&#44; the remaining episodes were considered serious&#46; After a severe episode&#44; the patient remained in the corresponding post-episode state for the rest of the simulation or until transition to the absorbing health state &#40;death&#41;&#46; However&#44; to consider the fact that&#44; in clinical practice&#44; a patient may experience later episodes&#44; and that the probability of occurrence of these events is highest in patients who have had a previous episode&#44; the cost and the associated usefulness of each severe postepisode state were weighted to take into account other possible future episodes&#46; Patients with dyspepsia could remain in this state for the rest of the simulation&#44; resulting in a serious episode with the implications described&#44; or die&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The profile of the population sampled in this model reflects a patient over 65 years of age with osteoarthritis and increased GI risk&#44; defined as a history of ulcer &#40;complicated or uncomplicated&#41; in the upper GI tract&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In a time horizon of one year&#44; total costs &#40;including the cost of drug treatment and the cost of managing clinical events&#41; and health outcomes at 6 months of treatment with any of the following strategies were estimated&#58; celecoxib&#44; PPI&#43;celecoxib&#44; diclofenac&#43;PPI&#44; etoricoxib&#44; etoricoxib&#43;PPI&#43;PPI ibuprofen&#44; naproxen&#43;PPI or naproxen&#47;esomeprazole&#46; The PPI of choice was omeprazole&#44; being the most used and the least costly&#44; at doses of 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; The duration and dosage considered for each alternative represented the most frequently used treatment by me in clinical practice for the treatment of patients with the profile described &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">After 6 months of treatment&#44; or if severe episode occurred&#44; involving permanent discontinuation of the NSAIDs&#44; the model assumed that patients went on to receive treatment with paracetamol <span class="elsevierStyleMonospace">&#40;</span>3000<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; for the rest of the simulation&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In the absence of evidence to the contrary&#44; it was assumed that the effect of the treatment received did not persist after its end&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The development of GI symptoms &#40;dyspepsia&#41; involved incorporating PPI to the treatment received in cases of therapeutic strategies which did not include PPI &#40;celecoxib and etoricoxib&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Adherence to established strategies were evaluated in terms of adherence to PPI&#46; This analysis found that within 6 months of treatment&#44; 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The value of 1 means a state of perfect health&#44; and the value of 0 equals death&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Model Parameters</span><p id="par0090" class="elsevierStylePara elsevierViewall">The probability of moving to any of the states considered are derived from the risk of GI and CV events and associated mortality&#46; The odds of each episode appearing were obtained from the evaluation conducted by the <span class="elsevierStyleItalic">National Institute for Health and Care Excellence</span> &#40;NICE&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> using the same premise to adjust the dosages to&#58; a reduction of 50&#37; of the dose involved a 25&#37; reduction in risk of developing an episode&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> For this analysis it was assumed that the risk of GI episodes with naproxen&#47;esomeprazole is equivalent to naproxen&#43;PPI separately if there is 100&#37; adherence to the PPI&#44; and that the risk of CV events is equivalent to naproxen&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> lists the probabilities used for development of the first episode&#46; PPI administration along with the therapeutic alternatives involved reduced the probability of GI episodes compared to monotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> This model considers that patients with a history of GI episodes have an increased risk of a new GI episode&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Similarly&#44; the existence of previous episodes of MI&#44; stroke or heart failure was associated with an increased likelihood of having a CV event&#46; Relationship between the level of adherence and the risk of GI events was determined using the same methodology as that used by other authors<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> calculating the increased risk of GI episodes per 10&#37; loss of adhesion &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The model considered both overall mortality by age of the Spanish population&#44; obtained from the tables of the National Statistics Institute &#40;INE&#41; and the mortality associated with GI complicated &#40;complicated ulcers&#41;&#44; MI&#44; stroke or congestive heart failure episodes&#44; whose values were obtained from the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Different values were considered useful&#44; depending on the age&#44; the underlying pathology and clinical events&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In the absence of specific data for Spanish population&#44; earnings by age were obtained from a health survey performed in the UK&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> As an item associated with osteoarthritis in the absence of clinical episodes&#44; a meta-analysis results of the WOMAC scale showed no differences between NSAIDs and ICOX-2&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> Earnings per development of clinical events were obtained from the literature<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The analysis was conducted from the perspective of the Spanish National Health System&#44; including only the costs associated with pharmacological treatment and management derived from clinical episodes&#46; The cost of drug therapies for each 3 months&#44; 91 established in days&#44; was calculated taking into account the doses of study&#44; from the retail price &#40;RRP-IVA&#41; and applying the appropriate 7&#46;5&#37; deduction established in the Royal Decree-Law 8&#47;2010&#46; For generic drugs and in which this deduction does not apply&#44; we chose the lowest-priced generic&#46; The costs of drugs were obtained from the Books of General Council of Official Colleges of Pharmacists&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The costs of managing clinical episodes&#44; and those associated with the state of health after each episode&#44; were obtained from Diagnosis Related Groups &#40;DRGs&#41; national aggregates<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> or the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a> In the absence of published data on the costs associated with symptomatic postulcer and complicated postulcer states considered that these were equivalent to the cost of management of dyspepsia&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> For the post-congestive heart failure state&#44; the cost was assumed to be<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> equivalent to the post-MI state&#44; consistent with the premise adopted by NICE in previous assessments&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> includes the costs used in the analysis&#46; All costs in euros are presented as 2012 euros&#44; after correction of cost data with the consumer price index &#40;CPI&#41; provided by the INE in appropriate cases&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">As the horizon of the analysis was one year&#44; no discount rate was applied to costs or health effects&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Sensitivity Analysis</span><p id="par0110" class="elsevierStylePara elsevierViewall">Deterministic sensitivity analyzes were performed to identify the influence on the results of variations in the following parameters&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Duration of treatment&#58; 3 months&#44; since there is variability in the length&#44; being sometimes shorter &#40;intermittent symptoms&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall">Dosage of ibuprofen&#58; due to increased variety in relation to the dose used in clinical practice for this population&#44; and since some guidelines recommend dosages reaching even 2400<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; an analysis was performed based on the maximum dose&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">Price of celecoxib&#58; due to the possible availability of celecoxib generic version throughout 2013&#44; its price was reduced by 40&#37;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall">Costs of managing events &#40;&#177;10&#37;&#41;&#59; because these parameters were susceptible to change&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">Earnings per episode&#58; modified with the upper and lower ends of the 95&#37; CI &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p></li></ul></p><p id="par0140" class="elsevierStylePara elsevierViewall">Additionally&#44; a probabilistic sensitivity analysis &#40;PSA&#41; was performed to change randomly and multivariate the values of the parameters&#44; thus retaining the possibility of extreme variations from the baseline case and allowing to estimate&#44; due to the high number of simulations&#44; the robustness of the results based on those considered outliers&#46; 10<span class="elsevierStyleHsp" style=""></span>000 Monte Carlo simulations were performed where the values of the parameters are changed simultaneously according to the following functions&#58; beta probability distribution&#44; adherence&#44; mortality and utilities&#44; log normal distribution and gamma distribution risks relating to episode cost management and cost of health states&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0145" class="elsevierStylePara elsevierViewall">At the end of the 12-month simulation and 6 months of treatment&#44; naproxen&#47;esomeprazole resulted in a &#40;more effective and less associated cost&#41; than the celecoxib&#44; etoricoxib and diclofenac&#43;PPI dominant strategy&#46; Whereas an efficiency threshold &#8364; 30<span class="elsevierStyleHsp" style=""></span>000&#47;QALY is an acceptable additional value of willingness to pay&#44; naproxen&#47;esomeprazole would be cost-effective regarding ibuprofen&#43;PPI and naproxen&#43;PPI strategy&#46; Celecoxib&#43;PPI and etoricoxib&#43;PPI were more effective than naproxen&#47;esomeprazole strategies&#44; which prevented the calculation of the ICER of naproxen&#47;esomeprazole with respect to them with the proposed formula for this calculation&#46; These results are detailed in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">In all deterministic sensitivity analysis performed &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>&#41;&#44; the results of naproxen&#47;esomeprazole remained&#58; dominant vs celecoxib and etoricoxib&#44; cost-effective compared to ibuprofen&#43;PPI and naproxen&#43;PPI and showing no change vs diclofenac&#43;PPI&#44; becoming cost-effective in reducing treatment to 3 months and reducing the costs of episodes by 10&#37;&#46; We performed two separate PSA vs the options for naproxen&#47;esomeprazole and that proved cost-effective in the baseline case&#44; ibuprofen&#43;PPI and naproxen&#43;PPI&#46; In the PSA&#44; after 10<span class="elsevierStyleHsp" style=""></span>000 simulations&#44; the average ICER&#44; naproxen&#47;esomeprazole stood at 18<span class="elsevierStyleHsp" style=""></span>436 and &#8364; 6367&#47;additional QALY vs&#43;ibuprofen&#43;PPI and naproxen&#43;PPI respectively&#44; 66&#46;4&#37; and 98&#46;3&#37; of cases were considered cost-effective &#40;below the threshold of &#8364; 30<span class="elsevierStyleHsp" style=""></span>000&#47;additional QALY&#41;&#44; respectively for each strategy &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">NSAIDs&#44; both non-selective as well as those selective for inhibition of COX-2&#44; are effective therapeutic alternative in the treatment of osteoarthritis&#46; However&#44; tolerability and GI and CV safety factors associated with its use in certain populations contraindicate their use or require appraisal of the individual profile of benefit&#47;risk for each patient&#46; Thus&#44; although ICOX-2 reduces the risk of gastrointestinal complications&#44; they have not shown&#44; on occasion&#44; a suitable CV safety profile&#46; Conversely&#44; naproxen is a therapeutic agent with a good CV safety profile at doses of 500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; but does not have this profile regarding the digestive tract&#46; It seems logical that the latter risk reduction &#40;with the addition of esomeprazole&#41; would give naproxen a role in the symptomatic treatment of osteoarthritis&#44; and that this would be an efficient therapeutic choice&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The many potential variables in the GI and CV risk for each patient makes assignment of the best therapeutic strategy based on existing resources difficult&#44; so that an indicator such as ICER&#44; which combines clinical and economic outcomes relative to different therapies&#44; is very interesting&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The ICER of naproxen&#47;esomeprazole was favorable&#44; even in the analysis of sensitivity compared to other options&#44; except for the treatment ICOX-2&#43;PPI&#46; The initial advantage of ICOX-2 came from the lack of need&#44; due to their lower rate of GI events&#44; of concomitant use of a PPI&#44; although in recent times there has been a change in clinical practice&#44; with the recommendation of using ICOX-2&#43;PPI in elderly patients with a history of gastrointestinal bleeding and the presence of multiple risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The results are important from the point of view of clinical practice&#46; The patient with osteoarthritis is usually elderly and has chronic multiple comorbidities including pathologies&#44; usually CV and include gastrointestinal manifestations&#46; Numerous studies have stratified these risks in said population and have established indication for NSAIDs in order to minimize the impact of adverse events&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> The availability of a fixed combination of a highly effective NSAID with excellent CV profile&#44; such as naproxen&#44; along with a powerful PPI&#44; might be able to mitigate its digestive impact by itself&#44; according to the authors&#44; becoming a good alternative&#46; The analysis performed in this study further corroborates&#44; from the pharmacoeconomic point of view&#44; its favorable clinical medicine perspective&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">This work is not without some limitations&#44; some inherent to the theoretical association or to the use of decision analytic models&#44; simulations that may not be an accurate reflection of clinical practice&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The validity and quality of decision analytical studies lie in their programming&#44; as well as in the assumptions made and the values for the parameters included under consideration&#46; In the development of economic evaluations it is crucial that the model has clinical sense and that the data comes from reliable and verifiable&#44; preferably published sources&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">This model was developed with the baseline assumption of equivalence in terms of efficacy of all treatments included&#44; so that the differences between the evaluated strategies lie in the differences in costs and rates of adverse events&#46; The decision on inclusion of clinical episodes was made considering the clinically relevant and data availability required<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> for the episodes&#46; The equivalence in efficacy&#44; if not exact&#44; could be a bias of the design&#44; but in the absence of proven evidence from controlled <span class="elsevierStyleItalic">head-to-head</span> trials it has to be understood as a reasonable premise&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The adjustment made in relation to the dose and the occurrence of clinical events that are handled in the model represents a limitation&#44; although the methodology is consistent with that used in other studies which concluded that the uncertainty associated with this parameter did not influence the<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> results&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In the absence of specific data concerning Spanish population it was necessary to use utility values per age obtained from the UK population&#46; Utilities&#44; associated with cultural factors&#44; may differ even between countries in the same environment&#44; but the sensitivity analysis&#44; changing the values of earnings per episode&#44; showed no influence of this parameter on the results&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Additionally&#44; the fact that in each 3 month cycle the patient may only experience one GI or CV episode must be considered&#46; This assumption may not be entirely realistic&#44; but its adoption was necessary to build the model&#44; also considering the generation of no significant impact on the results&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The limitations described were offset by conservative assumptions and tested in sensitivity analyzes&#44; showing no significant influence on the meaning of the results&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">There are several publications on economic evaluations of treatments used in osteoarthritis&#44; both internationally and in the<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Spanish context&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;28&#44;29</span></a> although&#44; to the authors&#8217; knowledge&#44; this is the first cost-utility analysis of naproxen&#47;esomeprazole over other ICOX-2 NSAIDs or adapted to Spain&#44; also individualized for each NSAID&#44; instead of treating all NSAIDs as a group&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The results obtained from the analysis of a hypothetical cohort of patients with a decision analytic model suggest that naproxen&#47;esomeprazole is an appropriate therapeutic option that is dominant over other strategies available&#44; such as celecoxib&#44; etoricoxib and diclofenac&#43;PPI&#59; and also using the standard reference threshold &#8364; 30<span class="elsevierStyleHsp" style=""></span>000&#47;additional QALY&#44;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a> showing it as a cost-effective strategy against both the option prescribed in clinical practice &#40;ibuprofen&#43;PPI&#41; compared to the option of separate single-components &#40;naproxen&#43;PPI&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Ethical Responsibilities</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Protection of human subjects and animals in research</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors declare that experiments have not been done on humans or animals&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Confidentiality of data</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors state that no patient data appears in this article&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Right to privacy and informed consent</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors state that no patient data appears in this article&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of Interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">IO and MAC are PORIB employees&#44; a consultant agency specialized in the area of economic evaluation of health technologies&#44; have received unconditional funding for this analysis from AstraZeneca&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">JSC and MC are employees of AstraZeneca&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">JT&#44; AL and JLZ have worked as clinical experts in the validation of the values of the parameters used in the analysis&#44; and therefore claim to have received unconditional funding from AstraZeneca&#44; which never influenced the participation and results obtained&#46;</p></span></span>"
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        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess&#44; from the perspective of the National Healthcare System&#44; the efficiency of a fixed-dose combination of naproxen and esomeprazole &#40;naproxen&#47;esomeprazole&#41; in the treatment of osteoarthritis &#40;OA&#41; compared to other NSAID&#44; alone or in combination with a proton pump inhibitor &#40;PPI&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A Markov model was used&#59; it included different health states defined by gastrointestinal &#40;GI&#41; events&#58; dyspepsia&#44; symptomatic or complicated ulcer&#59; or cardiovascular &#40;CV&#41; events&#58; myocardial infarction&#44; stroke or heart failure&#46; The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The total costs &#40;&#8364;&#44; 2012&#41;&#44; including drug and event-related costs&#44; and the health outcomes expressed in quality-adjusted life years &#40;QALY&#41; were estimated in patients with increased GI risk&#44; aged 65 or over&#44; for a 1-year time horizon and a 6-month treatment with celecoxib &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; celecoxib&#43;PPI&#44; diclofenac &#40;150<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#43;PPI&#44; etoricoxib &#40;60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; etoricoxib&#43;PPI&#44; ibuprofen &#40;1800<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#43;PPI&#44; naproxen &#40;1000<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#43;PPI or naproxen&#47;esomeprazole &#40;naproxen 1000<span class="elsevierStyleHsp" style=""></span>mg&#47;esomeprazole 40<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46; The selected PPI was omeprazole &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Naproxen&#47;esomeprazole was a dominant strategy &#40;more effective and less costly&#41; compared to celecoxib&#44; etoricoxib and diclofenac&#43;PPI&#46; Celecoxib&#43;PPI and etoricoxib&#43;PPI were more effective&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Considering a cost-effectiveness threshold of &#8364; 30<span class="elsevierStyleHsp" style=""></span>000 per additional QALY&#44; naproxen&#47;esomeprazole was cost-effective compared to ibuprofen&#43;PPI and naproxen&#43;PPI with incremental cost-effectiveness ratios &#40;ICER&#41; of &#8364; 15<span class="elsevierStyleHsp" style=""></span>154 and &#8364; 5202 per additional QALY&#44; respectively&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A fixed-dose combination of naproxen and esomeprazole is a cost-effective&#44; and even dominant&#44; alternative compared to other options in OA patients with increased GI risk&#46;</p>"
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      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluar&#44; desde la perspectiva del Sistema Nacional de Salud&#44; la eficiencia de la combinaci&#243;n a dosis fija de naproxeno y esomeprazol &#40;naproxeno&#47;esomeprazol&#41; en artrosis frente a otros AINE en monoterapia o combinados con un inhibidor de la bomba de protones &#40;IBP&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se emple&#243; un modelo de Markov con estados de salud definidos por episodios gastrointestinales &#40;GI&#41;&#58; dispepsia&#44; &#250;lcera p&#233;ptica sintom&#225;tica o complicada&#59; o cardiovasculares &#40;CV&#41;&#58; infarto agudo de miocardio&#44; ictus o insuficiencia cardiaca&#46; El modelo es semejante al utilizado por el NICE en su evaluaci&#243;n de AINE en artrosis publicada en 2008&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se estimaron&#44; en un horizonte temporal de 1 a&#241;o &#40;ciclos de 3 meses&#41;&#44; los costes totales &#40;&#8364;&#44; 2012&#41;&#44; incluyendo coste farmacol&#243;gico y de manejo de episodios&#44; y los resultados en salud&#44; expresados en a&#241;os de vida ajustados por calidad &#40;AVAC&#41;&#44; en pacientes mayores de 65 a&#241;os con riesgo GI aumentado&#44; tras 6 meses de tratamiento con celecoxib &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#44; celecoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; diclofenaco &#40;150<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; etoricoxib &#40;60<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#44; etoricoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; ibuprofeno &#40;1&#46;800<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#44; naproxeno &#40;1&#46;000<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP o naproxeno&#47;esomeprazol &#40;naproxeno 1&#46;000<span class="elsevierStyleHsp" style=""></span>mg&#47;esomeprazol 40<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#46; El IBP fue omeprazol &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Naproxeno&#47;esomeprazol result&#243; dominante &#40;m&#225;s efectivo y menor coste&#41; respecto a celecoxib&#44; etoricoxib y diclofenaco<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP&#46; Celecoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP y etoricoxib<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP fueron m&#225;s efectivos&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Considerando un umbral de 30&#46;000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;AVAC adicional&#44; naproxeno&#47;esomeprazol result&#243; coste-efectivo respecto a ibuprofeno<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP y naproxeno<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IBP con valores de relaci&#243;n coste-efectividad incremental de 15&#46;154<span class="elsevierStyleHsp" style=""></span>&#8364; y 5&#46;202<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;AVAC adicional&#44; respectivamente&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La combinaci&#243;n a dosis fijas de naproxeno y esomeprazol en pacientes con artrosis y riesgo GI aumentado es una alternativa coste-efectiva e incluso dominante frente a otras opciones&#46;</p>"
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0045">Please cite this article as&#58; Capel M&#44; Tornero J&#44; Zamorano JL&#44; Oyag&#252;ez I&#44; Casado M&#193;&#44; S&#225;nchez-Covisa J&#44; et al&#46; Eficiencia de la combinaci&#243;n naproxeno&#47;esomeprazol para el tratamiento de la artrosis en Espa&#241;a&#46; Reumatol Clin&#46; 2014&#59;10&#58;210&#8211;217&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "a"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0050">This fixed dose combination is marketed in Spain as modified-release tablets containing naproxen with enteric coating and film-coated esomeprazole &#40;as magnesium trihydrate&#41;&#46;</p>"
      ]
    ]
    "multimedia" => array:10 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1486
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Markov diagram&#46; GI&#44; gastrointestinal&#59; MI&#44; myocardial infarction&#59; CHF&#44; congestive heart failure&#46; The balloons represent the possible health states&#44; and arrows&#44; the allowed transitions between them&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Plot of cost-effectiveness of naproxen&#47;esomeprazole&#46; The cost-effectiveness plane represents the results of the PSA&#46; Each point represents a value of ICER&#44; of each of the 10<span class="elsevierStyleHsp" style=""></span>000 Monte Carlo simulations performed&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Acceptability curve of naproxen&#47;esomeprazole&#46; The acceptability curve reflects certain thresholds for willingness to pay &#40;from 0 to 50<span class="elsevierStyleHsp" style=""></span>000 &#8364; represented on the horizontal axis&#41;&#44; the proportion &#40;on the vertical axis&#41; of the 10<span class="elsevierStyleHsp" style=""></span>000 ICER values obtained in the PSA that would be less than that determined threshold&#44; considered cost effective&#46;</p>"
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      3 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Therapeutic alternatives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Mode of administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">PVP-tax cost &#40;container&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Celecoxib&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">200<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 34&#46;35<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> &#40;30 tablets&#44; 200<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diclofenac&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 1&#46;65<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 50<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&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<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 30&#46;06<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> &#40;28 tablets&#44; 60<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibuprofen&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">1800<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 1&#46;97<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 600<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&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">1000<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 4&#46;34<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 500<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&#47;esomeprazole&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">1000&#47;40<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 23&#46;71<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> &#40;60 tablets&#44; 500&#47;20<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Paracetamol&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">3000<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 2&#46;79<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;40 tablets&#44; 1000<span class="elsevierStyleHsp" style=""></span>mg&#41;&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omeprazole&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<span class="elsevierStyleHsp" style=""></span>mg daily&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">&#8364; 2&#46;42<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;28 tablets&#44; 20<span class="elsevierStyleHsp" style=""></span>mg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Artilog<span class="elsevierStyleSup">&#174;</span>&#44; Celebrex<span class="elsevierStyleSup">&#174;</span> with 7&#46;5&#37; deduction provided for in Royal Decree 8&#47;2010&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Lowest price&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Acoxxel<span class="elsevierStyleSup">&#174;</span>&#44; Arcoxia<span class="elsevierStyleSup">&#174;</span>&#44; Exxiv<span class="elsevierStyleSup">&#174;</span> with 7&#46;5&#37; deduction provided for in Royal Decree 8&#47;2010&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Vimovo<span class="elsevierStyleSup">&#174;&#44;</span> with 7&#46;5&#37; deduction provided for in Royal Decree 8&#47;2010&#46;</p>"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Dosage and Cost of Therapeutic Alternatives&#46;</p>"
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        "etiqueta" => "Table 2"
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        "mostrarFloat" => true
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">MI&#44; acute myocardial infarction&#59; PPI&#44; proton pump inhibitor&#59; CHF&#44; congestive heart failure&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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">Therapeutic alternatives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="6" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Clinical episodes</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Dyspepsia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Ulcer&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Complicated ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Congestive heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Celecoxib&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12450&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00090&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00050&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00150&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00020&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00040&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Celecoxib &#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;03113&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00023&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00013&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00150&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00020&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00040&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diclofenac&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;10991&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00062&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00039&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00108&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;00072&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">0&#46;00024&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
                  \t\t\t\t">Etoricoxib&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;16307&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">0&#46;00093&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00133&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00093&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="char" valign="\n
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                  \t\t\t\t">0&#46;00053&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&#43;PPI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;04077&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">0&#46;00030&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00023&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00133&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
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                  \t\t\t\t">0&#46;00053&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibuprofen&#43;PPI&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">0&#46;06564&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">0&#46;00089&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">0&#46;00044&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">0&#46;00180&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;00108&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">Naproxen&#43;PPI&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">0&#46;00037&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">0&#46;00069&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;00091&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">0&#46;00103&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&#47;esomeprazole&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  " align="left" valign="\n
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                  \t\t\t\t">Paracetamol<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&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">0&#46;00010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab520509.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0025"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">As rescue therapy&#44; or at the end of 6 months of treatment with the study alternatives&#46;</p>"
            ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Probability of Development of the First Clinical Episode&#46;</p>"
        ]
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      5 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">NSAIDs&#44; nonsteroidal anti-inflammatory drugs&#59; PPI&#44; proton pump inhibitor&#59; GI&#44; gastrointestinal&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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">Therapeutic strategies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Increase &#40;&#37;&#41; in the risk of GI episode for every 10&#37; loss of adherence to PPI level</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Dyspepsia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Symptomatic ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Complicated ulcer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">With COX-2 inhibitors &#40;celecoxib&#43;PPI or etoricoxib&#43;PPI&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;8&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;5&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;1&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nonselective NSAID &#40;diclofenac&#43;PPI or ibuprofen&#43;PPI or naproxen&#43;PPI&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;9&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;9&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab520506.png"
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          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Relationship Between PPI Adherence and Risk of GI Episodes&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">GI&#44; gastrointestinal&#59; DRG&#44; diagnostic related group&#59; MI&#44; acute myocardial infarction&#59; CI&#44; confidence interval&#59; CHF&#44; congestive heart failure&#59; NA&#44; not applicable&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Health status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Utilities mean &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Cost of episode management&#47;cost of state&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">No episode&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GI symptoms &#40;dyspepsia&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;73 &#40;0&#46;63&#8211;0&#46;84&#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">&#8364; 324&#46;96<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Symptomatic ulcer&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;55 &#40;0&#46;47&#8211;0&#46;65&#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">&#8364; 2884&#46;98 &#40;average DRG177 and 178&#41;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postulcer symptomatic&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;98&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">Equivalent to dyspepsia&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complicated ulcer&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;46 &#40;0&#46;37&#8211;0&#46;56&#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">&#8364; 3430&#46;30 &#40;average DRG174&#44; 175 and 176&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postulcer complicated&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;98&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">Equivalent to dyspepsia&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;37 &#40;0&#46;28&#8211;0&#46;47&#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">&#8364; 5595&#46;63 &#40;average DRG121 and 122&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-MI&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;88 &#40;0&#46;78&#8211;0&#46;98&#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">&#8364; 259&#46;53<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stroke&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;35 &#40;0&#46;25&#8211;0&#46;45&#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">&#8364; 4964&#46;48 &#40;DRG14 and 810&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Poststroke&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;71 &#40;0&#46;61&#8211;0&#46;80&#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">&#8364; 107&#46;44<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CHF&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;71 &#40;0&#46;61&#8211;0&#46;80&#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">3575&#46;43 &#40;DRG127&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-CHF&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Equivalent post-MI&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
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Death&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 0&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Utilities and Costs per Episode and Health State&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">NA&#44; not applicable&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Therapeutic strategies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">QALY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Total cost &#40;&#8364;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">ICER &#40;&#8364;&#47;QALY additional naproxen&#47;esomeprazole vs&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">Naproxen&#47;esomeprazole&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5911&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364; 662&#46;71&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 21735743
Original language: English
DOI:10.1016/j.reumae.2014.03.002
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