Gout: Diagnosis and treatment

Sivera, Francisca; Andrés, Mariano; Quilis, Neus
doi:10.1016/j.medcle.2017.03.009
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Synovial fluid microscopy at 600-magnification with ordinary light &#40;top image&#41;&#44; where a needle-shape crystal is shown inside a leucocyte&#46; Under simple polarized light &#40;middle image&#41;&#44; the glass shows strong birefringence which&#44; after applying the first order red compensator &#40;below&#41;&#44; is confirmed as negative birefringence&#8211;as it is yellow in colour and is positioned parallel to the compensator&#39;s axis &#40;arrow&#41;&#8211;&#46; Photographs courtesy of Prof&#46; Eliseo Pascual&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Gout is a disease caused by the deposition of monosodium urate &#40;MSU&#41; crystals in and around the joints as a result of persistent hyperuricemia&#46; It is a chronic process&#44; although its clinical manifestations may occur intermittently at onset &#40;episodes of acute inflammation&#41;&#46; Without a uric acid lowering treatment&#44; the frequency of episodes and the number of joints affected increase&#46; Any gout that does not receive adequate treatment is associated with significant morbidity&#44; disability and reduced quality of life&#46; However&#44; despite numerous guidelines and recommendations&#44; treatment of these patients is often poor&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Diagnosis</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Identification of crystals &#40;gold standard&#41;</span><p id="par0010" class="elsevierStylePara elsevierViewall">The identification of MSU crystals in synovial fluid or tophi aspirate remains the gold standard for the diagnosis of gout&#44; as specified by the recommendations and clinical practice guidelines<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#8211;3</span></a>&#59; this also comes from understanding gout as a MSU crystal deposition disease&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Their identification is simple and reliable after a short training&#46; An optical microscope equipped with 400&#8211;600 magnification is required&#46; This allows adequate visualization of crystals both under ordinary light as well as with single polarization&#46; The MSU crystals are acicular&#44; variable in size and can be located both in the cytoplasm of leukocytes and extracellularly &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; A very intense birefringence is observed with polarized light&#44; which facilitates identification even in very cellular samples&#44; mixed with blood or with few crystals&#46; Its negative birefringence can be determined using a first order red compensator&#44; a fact seldom necessary in clinical practice&#46; In the absence of a uric acid lowering treatment&#44; the crystals remain in the synovial fluid of previously inflamed joints&#44; which allows diagnosis during the intercritical stage&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">MSU crystal deposition precedes the first attack of gout&#44; over a not-well-defined period of time&#44; but presumably long&#46; In subjects with asymptomatic hyperuricemia &#40;AHU&#41;&#44; &#8211; i&#46;e&#46;&#44; without gout attacks or other manifestation attributable to the disease &#8211; crystals may be occasionally found in the synovial fluid of joints evaluated for another reason&#46; Using techniques such as ultrasound<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> or <span class="elsevierStyleItalic">dual-energy computed tomography</span> &#40;DECT&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> it has been estimated that such silent MSU crystal deposition occurs in about 25&#8211;30&#37; of subjects with AHU&#44; although not all patients with AHU develop gout&#46; The possible impact of such deposition in those who do not develop clinical inflammation is unknown&#59; recent data show a possible detrimental cardiovascular effect&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The use of Raman spectroscopy for the detection of the crystals&#44; both as synovial fluid and <span class="elsevierStyleItalic">in vivo</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> has been proposed&#44; but only very recently&#46; The results look very promising&#44; but so far&#44; they are preliminary and must be properly substantiated in the future&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Diagnosis without crystal identification</span><p id="par0030" class="elsevierStylePara elsevierViewall">To date&#44; no technique can replace the synovial fluid analysis to diagnose gout&#46; However&#44; in clinical practice&#44; it is common to establish the diagnosis when compatible clinical symptoms occur in a hyperuricaemic subject&#44; disregarding microscopy as a diagnostic method&#46; This occurs even in specialized care consultations&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> The clinical diagnosis is wrong in one out of every 4 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> Given the simplicity and reliability of synovial fluid microscopy&#44; this should not be disregarded even in situations of high probability &#40;e&#46;g&#46;&#44; recurrent podagra in a hyperuricaemic patient&#41;&#46; Incorporating arthrocentesis and synovial fluid analysis to the evaluation of all patients with arthritis or joint effusion in clinical practice&#8211;something that has been&#44; in fact&#44; formally recommended<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a>&#8211;allows&#44; on one hand&#44; to maintain proper caution in cases of just a clinical diagnosis&#44; and on the other&#44; diagnose cases of less typical forms of disease presentation&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A new set of classification criteria for gout has been recently validated&#46; It has shown excellent sensitivity and specificity using clinical&#44; laboratory and imaging data&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> However&#44; they are mean to be classification criteria and&#44; as specified by the authors themselves&#44; their aim is to select patients for clinical trials&#44; and therefore should not be used for diagnosis in clinical practice&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Ultrasound and DECT &#40;the latter with limited availability&#41; are imaging techniques that can be helpful to diagnose and evaluate patients with gout&#44; while others such as plain radiography&#44; conventional CT or MRI have a more marginal and specific use&#46; MSU crystal deposition is hyperechogenic&#44; resulting in lines parallel to the cortical bone <span class="elsevierStyleItalic">&#40;double contour sign&#41;</span> given its deposition on the cartilage surface&#44; or aggregates in joints&#44; tendon or periarticular areas&#44; occasionally surrounded by a hypoechoic halo<span class="elsevierStyleItalic">&#40;Tophi&#41;&#46;</span> These findings show remarkable results in experienced operators&#44; but&#44; for the moment&#44; they should not replace the synovial fluid analysis&#44; and they do not show sufficient sensitivity&#44; probably because a remarkable crystal load is required for proper ultrasound visualization&#46; An advantage of ultrasound is that it serves as a guide for conducting arthrocentesis on deep joints or punctures of possible deposition areas&#46; On the other hand&#44; DECT allows to characterize almost unequivocally the presence of urate crystals&#44; but needs a crystal load even higher than ultrasound for their visualization&#44; which hampers its sensitivity&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Differential diagnosis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Gout should be included in the differential diagnosis of all patients with acute arthritis&#44; along with arthritis caused by calcium pyrophosphate crystals&#44; septic arthritis and other less common&#44; such as reactive arthritis or psoriatic arthritis&#46; Mechanical joint problems &#40;e&#46;g&#46;&#44; arthritis&#44; hemarthrosis&#41; may be occasionally considered as gout attacks&#46; Sometimes&#44; especially in long-progression patients that are not being adequately treated and with extensive deposition&#44; gout can affect several joints &#40;oligo or polyarthritis&#41; and more in a more persistent way&#44; therefore&#44; it should be distinguished from other forms of chronic arthritis&#44; such as rheumatoid arthritis or spondyloarthritis&#46; As mentioned above&#44; the systematic analysis of all synovial fluid extracted greatly facilitates diagnosis of the less typical cases&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Comorbidities</span><p id="par0050" class="elsevierStylePara elsevierViewall">Patients with gout have a high frequency of cardiovascular and renal type comorbidities&#44; linked to the very pathogenesis of the disease&#58; hyperuricemia associated with metabolic syndrome&#44; renal hypoexcretion of uric acid caused by chronic kidney disease and&#47;or use of diuretics&#44; etc&#46; These comorbidities&#44; whose prevalence is significantly higher than in the general population&#44; affect patient prognosis and treatment&#44; therefore&#44; their adequate care is necessary when evaluating patients with gout&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Cardiovascular risk</span><p id="par0055" class="elsevierStylePara elsevierViewall">The association of gout with atherosclerosis and its complications is jointly related to the metabolic syndrome and the disease itself&#44; which is a proven independent risk factor for all forms of cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> This has been associated with MSU crystal-induced inflammation&#44; both the acute form related to the attacks as well as the subclinical form which persists during intercritical stages&#44; as evident in the fact that patients with tophaceous gout&#8211;with greater deposition extension and inflammatory state&#8211;have an increased risk of developing Q wave infarction and increased mortality&#46; Other factors&#44; such as a hyperuricaemic state or taking anti-inflammatories&#44; could also contribute to increased cardiovascular risk in gout&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Nephropathy</span><p id="par0060" class="elsevierStylePara elsevierViewall">The presence of renal failure in patients with gout is common in clinical practice&#44; although figures vary widely in different published series &#40;3&#8211;72&#37;&#41;&#46; Kidney disease is primarily due to prevalent processes like nephroangiosclerosis or diabetic nephropathy&#44; although microtophi have been described in the renal medulla which&#44; in long-term untreated patients&#44; could contribute to renal failure&#46;</p></span></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Gout treatment</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objectives</span><p id="par0065" class="elsevierStylePara elsevierViewall">MSU crystal deposition in patients with gout is reversible&#46; Therefore&#44; the treatment strategy objective &#40;non-negotiable&#41; is to remove MSU deposition &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Without crystals&#44; there is no inflammation &#40;or acute attacks&#44; or maintained subclinical inflammation&#41;&#44; therefore&#44; gout can be considered cured&#46; The only known method to dissolve deposition is to reduce uric acid levels below their saturation point in a sustained manner&#46; Uric acid reduction in gouty patients determines the decrease in tophi volume until their complete disappearance<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> and the absence of crystals in synovial fluid samples examined microscopically&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> The crystal dissolution rate is slow&#8211;usually&#44; years&#8211;and is conditioned by the magnitude of existing deposition and by the uric acid level reached with treatment&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">While crystals persist in the joints&#44; the patient may have episodes of acute inflammation&#44; mainly articular&#44; but also in bursae or tendons&#46; Hypouricemic treatment initiation contributes to the appearance of inflammatory episodes&#44; therefore&#44; patients should receive prophylactic treatment &#40;e&#46;g&#46;&#44; colchicine&#41;&#46; If&#44; despite prophylaxis&#44; inflammatory episodes occur&#44; the patient should receive early and appropriate anti-inflammatory treatment&#44; often self-initiated&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Finally&#44; gout is associated with comorbidities such as cardiovascular risk factors or kidney failure&#46; A gout related medical visit is an opportunity to detect and treat these comorbidities&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Reducing uricemia</span><p id="par0080" class="elsevierStylePara elsevierViewall">To be effective&#44; uric acid must be reduced below the saturation point&#44; although the optimal threshold is still under discussion&#46; Most guidelines recommend reducing uric acid levels below 6<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;16</span></a> Under certain circumstances &#40;e&#46;g&#46;&#44; tophi&#44; structural damage&#44; etc&#46;&#41; a stricter target is usually recommended &#40;&#60;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#46; It is worth mentioning that lower uric acid levels equal faster deposition dissolution&#46; Therefore&#44; the uric acid target will also determine the speed with which the patient will dissolve tophi and deposition&#46; There is no solid evidence to link the reduction of uric acid with unwanted side effects&#46; The proportion of gouty patients who can benefit from tighter uric acid controls can therefore be greater than that expressed in the recommendations &#40;e&#46;g&#46;&#44; patients with cardiovascular risk factors&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Treatment initiation should be considered in all patients with a clear diagnosis of gout from the outset&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> In patients with recurrent episodes of inflammation&#44; tophi&#44; nephrolithiasis or structural damage&#44; the hypouricemic treatment is clearly indicated&#46; Since the magnitude of the deposition is directly linked to gout progression time&#44; early treatment allows for a speedier recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> Also&#44; if the presence of crystals&#8211;and its associated subclinical inflammation&#8211;proves to be an independent risk factor for cardiovascular events and mortality&#44; early treatment may be advisable&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Currently there are different treatment options for reducing uricemia&#58; allopurinol&#44; febuxostat or benzbromarone&#44; among others &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The incorporation of a new drug is expected soon&#58; lesinurad&#46; However&#44; knowing the treatment objective is more important than the choice of drug itself&#58; reducing uric acid below the saturation point&#46; Some drugs can increase serum uric acid levels &#40;such as diuretics&#41; and should be avoided as far as possible&#59; others may offer some uricosuric effect &#40;losartan&#44; fenofibrate&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Xanthine oxidase inhibitors</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Allopurinol</span><p id="par0095" class="elsevierStylePara elsevierViewall">Allopurinol is the most widely used hypouricemic treatment<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> and enjoys an extensive experience&#46; The emergence of new molecules has increased the number of studies on allopurinol&#46; In clinical trials&#44; allopurinol at fixed-doses of 300<span class="elsevierStyleHsp" style=""></span>mg &#40;100&#8211;200<span class="elsevierStyleHsp" style=""></span>mg in patients with mild to moderate renal insufficiency&#41; gets uric acid concentration levels &#60;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dl in only 20&#8211;40&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;18</span></a> However&#44; the use of a fixed and relatively low but frequent dose of allopurinol makes the interpretation of these data difficult&#46; In Spain&#44; allopurinol is authorized to maximum doses of 900<span class="elsevierStyleHsp" style=""></span>mg daily with normal renal function&#46; A study in patients who did not achieve an adequate control of uric acid with 300<span class="elsevierStyleHsp" style=""></span>mg daily of allopurinol showed that increasing the dose to 600<span class="elsevierStyleHsp" style=""></span>mg daily was effective<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a>&#59; doses higher than 600<span class="elsevierStyleHsp" style=""></span>mg daily did not received critical attention&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The main limitation with allopurinol is the potential occurrence of adverse effects&#46; Most are mild and reversible &#40;such as elevated transaminases&#41;&#44; but occasionally they may be severe and even fatal &#40;as some hypersensitivity reactions&#41;&#46; The occurrence of allergic reactions is associated with the initial dose of allopurinol and the coexistence of renal failure&#46; Therefore&#44; starting with small doses &#40;&#60;1&#46;25<span class="elsevierStyleHsp" style=""></span>mg&#47;day per ml&#47;min of estimated glomerular filtration rate&#41; is recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> Gradual dose increases until reaching the therapeutic goal seems safe&#46; This strategy is known as <span class="elsevierStyleItalic">start low</span>&#44; <span class="elsevierStyleItalic">go slow</span>&#46; Despite these recommendations&#44; most patients never receive doses higher than 300<span class="elsevierStyleHsp" style=""></span>mg daily&#44; especially in primary care&#46; Desensitization regimens have been tested in patients with allergic reactions to allopurinol&#44; but given the availability of alternatives&#44; their use is limited&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Febuxostat</span><p id="par0105" class="elsevierStylePara elsevierViewall">Febuxostat is a non-purine xanthine oxidase inhibitor and is administered in a single daily dose of 80&#8211;120<span class="elsevierStyleHsp" style=""></span>mg&#46; In its pivotal studies&#8211;where gouty patients with uric acid concentrations above 8<span class="elsevierStyleHsp" style=""></span>mg&#47;dl were included&#8211;it achieved the therapeutic target in 45&#8211;70&#37; of patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;18</span></a> a substantially greater percentage than that obtained with a fixed dose of allopurinol&#46; Usually&#44; the starting dose is 80<span class="elsevierStyleHsp" style=""></span>mg &#40;40<span class="elsevierStyleHsp" style=""></span>mg dose is not sold in Europe&#41; and is increased to 120<span class="elsevierStyleHsp" style=""></span>mg after 2&#8211;4 weeks if the therapeutic goal is not achieved&#46; In addition&#44; febuxostat is effective and safe in patients with mild and moderate renal impairment&#44; not requiring dose adjustment&#59; there is anecdotal evidence on the use of febuxostat in patients with severe renal impairment &#40;creatinine clearance &#60;30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The safety profile is similar to that of allopurinol&#44; with diarrhoea as the main side effect in controlled studies&#46; Transaminase elevation occurs in one out of 10 patients and may require dose adjustment&#46; In case of hypersensitivity reaction to allopurinol&#44; febuxostat has emerged as a safe alternative&#46; However&#44; several studies &#40;retrospective&#41; show that a small proportion of patients with reaction to allopurinol may develop a further reaction when exposed to febuxostat<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>&#59; more data are needed to substantiate the safety of subsequent treatment with febuxostat after a severe reaction to allopurinol&#46; Currently&#44; caution is recommended in patients with ischaemic heart disease or congestive heart failure&#44; given the increase in adverse events in pivotal studies&#59; there are studies underway to test the drug&#39;s safety in this patient group&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">At present&#44; febuxostat is an effective alternative in patients intolerant or refractory to allopurinol&#46; In addition&#44; it is a first-line drug in patients with renal impairment or with very high uric acid concentrations&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Uricosurics</span><p id="par0120" class="elsevierStylePara elsevierViewall">The pathogenesis of most patients with gout is based on decreased renal excretion of uric acid&#44; so increasing its renal clearance is conceptually appealing&#46; Benzbromarone&#44; probenecid and sulfinpyrazone are uricosuric drugs&#44; with different accessibility in each country&#46; In Spain&#44; benzbromarone is accessible but restricted to certain indications and subject to prescription by a rheumatologist or nephrologist&#46; Benzbromarone inhibits tubular reabsorption of uric acid by the URAT-1 transporter and produces a significant reduction in uric acid levels at least as important as that achieved with allopurinol&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19&#44;22</span></a> Although there is risk of hepatotoxicity&#8211;severe in some cases&#8211;&#44; this seems very limited in patients of European descent<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a>&#59; the most common side effect is gastrointestinal intolerance&#46; Since it is a drug that facilitates renal excretion of uric acid&#44; benzbromarone should be avoided in previous cases of uric acid nephrolithiasis or excessive renal excretion of uric acid &#40;&#62;700<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41;&#46; Hydration and urine alkalinization hinder the appearance of uric acid lithiasis&#46; As with other potent uric-acid-lowering drugs&#44; it is advisable to start at low doses &#40;e&#46;g&#46;&#44; 50<span class="elsevierStyleHsp" style=""></span>mg daily&#41; and then increase the dose gradually until achieving the therapeutic goal&#44; with a maximum of 200<span class="elsevierStyleHsp" style=""></span>mg daily&#46; Given its different mechanism of action&#44; adding moderate doses of benzbromarone to standard doses of allopurinol or febuxostat has demonstrated an additive effect in reducing uric acid levels and can be a strategy in refractory patients&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Lesinurad is a selective inhibitor of uric acid absorption&#44; inhibiting the URAT-1 transporter&#46; It has been approved at doses of 200<span class="elsevierStyleHsp" style=""></span>mg daily in combination with a xanthine oxidase inhibitor&#46; Clinical trials in combination with allopurinol or febuxostat show an increase in the proportion of patients achieving the therapeutic goal&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> There has been a creatinine increase in patients receiving lesinurad&#44; sometimes significant&#44; and more studies are needed to determine its relevance&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">There are several drugs used in other diseases with small or moderate uricosuric properties &#40;fenofibrate&#44; losartan&#44; atorvastatin&#44; leflunomide&#41;&#46; Although not indicated in gout&#44; they can help control uric acid levels&#44; provided that the patient has comorbidities for which they are approved&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Uricases</span><p id="par0135" class="elsevierStylePara elsevierViewall">Uricase &#40;or urate oxidase&#41; catalyses the degradation of uric acid to allantoin&#44; an easy renal excretion molecule&#46; As a result of these mutations&#44; humans and some primates have no active uricase&#46; The development of recombinant techniques has enabled the production of uricases for human treatment &#40;rasburicase&#44; pegloticase&#41;&#46; Rasburicase is marketed for the prevention of tumour lysis syndrome and there are anecdotal cases of its use for refractory gout&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> Pegloticase &#40;a PEGylated uricase&#41; is not currently marketed in Spain&#44; although it has been approved by the FDA&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment of acute episodes</span><p id="par0140" class="elsevierStylePara elsevierViewall">Gouty inflammatory episodes occur with acute arthritis in one or more joints&#59; tend to be self-limiting&#44; but in the absence of treatment last for days or even weeks&#46; Non-pharmacological measures are not usually sufficient for their resolution&#46; NSAIDs &#40;including COX-2 selective inhibitors&#41;&#44; glucocorticoids&#44; colchicine and interleukin &#40;IL&#41;-1 inhibitors have proven effective for treatment&#46; The choice of one or the other will be individualized according to their associated comorbidities and preferences&#46; In any case&#44; the chosen treatment effectiveness depends on its early establishment&#44; since this is associated with a faster resolution of the attack&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">NSAIDs are widely used in the absence of contraindications&#46; Available studies do not show an anti-inflammatory superiority over others&#46; The use of maximum doses is recommended&#46; Both classic NSAIDs as well as COX-2 are effective in treating acute episodes&#44; the latter with better digestive tolerance&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Glucocorticoids can be used orally&#44; parenterally or intra-articularly&#46; Although there is little published data&#44; intra-articular injection &#40;e&#46;g&#46;&#44; triamcinolone acetonide&#41; is a quick and effective option for patients with monoarthritis&#46; The infiltration should be performed after having reasonably ruled out an infectious aetiology&#46; Orally&#44; a brief treatment with glucocorticoids &#40;prednisone 30&#8211;35<span class="elsevierStyleHsp" style=""></span>mg for 5&#8211;7 days&#41; may be as effective as NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> These guidelines may be accompanied by a rebound effect after suspension&#44; so colchicine should be started simultaneously&#46; Available data regarding intramuscular administration of corticosteroids are rare&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Colchicine at low doses &#40;1&#46;8<span class="elsevierStyleHsp" style=""></span>mg over one hour&#41;&#44; established early&#44; is effective and well tolerated&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> High doses should be avoided as gastrointestinal adverse effects are common&#44; with no improvement in efficacy&#46; The dose of colchicine should be reduced in patients with impaired renal or hepatic function&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Inflammation is mediated by IL-1&#946; in gouty arthritis&#44; therefore&#44; blocking the same has therapeutic implications both for the treatment of acute attack as well as for prophylaxis&#44; especially in patients where traditional options are contraindicated&#46; IL-1&#946; inhibitors are well tolerated&#44; although we must pay attention to the potential risk of infection resulting from their use&#46; Canakinumab was approved by the EMA in 2013 for the treatment of acute attacks in patients with recurrent attacks &#40;3 or more in the previous year&#41; and with contraindication or intolerance to NSAIDs&#44; colchicine and glucocorticoids&#46; Two randomized&#44; parallel&#44; double-blind&#44; compared with intramuscular triamcinolone acetonide trials show that the control of acute attacks is achieved faster with canakinumab&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Prophylaxis of acute attack</span><p id="par0165" class="elsevierStylePara elsevierViewall">When the hypouricemic treatment begins&#44; patients maintain&#8211;and even transiently increase&#8211;the risk of acute attacks&#46; The appearance of inflammatory episodes can negatively affect the confidence and adherence of patients&#44; so the implementation of an appropriate attack prophylaxis is important&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">The only drug approved for prophylaxis is colchicine &#40;0&#46;5&#8211;1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d with dose reduction in case of renal failure&#41;&#46; In refractory cases or where colchicine is contraindicated&#44; anti-inflammatories may be used &#40;e&#46;g&#46;&#44; indomethacin 25<span class="elsevierStyleHsp" style=""></span>mg&#47;d or naproxen 250&#8211;500<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41;&#44; low-dose prednisone &#40;&#60;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41; or new anti-IL-1 drugs&#46; There is no clear time limit in which prophylaxis should be maintained&#59; one option is to establish it 1&#8211;2 weeks prior to hypouricemic treatment initiation&#44; and hold it for 6 months&#46; However&#44; it is not recommended to suspend it in case of recurrent or persistent inflammation&#44; evidence of tophi or if the desired levels of uric acid have not been reached&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Lifestyle</span><p id="par0175" class="elsevierStylePara elsevierViewall">Numerous studies have evaluated the relationship between different foods and uric acid levels&#46; Alcoholic beverages&#44; mainly beer and spirits&#44; are related to increased uric acid&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> Foods rich in animal proteins as well as sugary drinks &#40;soft drinks&#41; and foods rich in fructose have been linked to increased uric acid levels&#44; while foods such as dairy products&#44; vegetable proteins &#40;legumes&#44; nuts&#41; coffee and low-fat products are associated with lower levels of uric acid&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> It is advisable to minimize the intake of alcohol &#40;especially beer&#41;&#59; however&#44; the impact that restrictive diets could have has not been critically evaluated&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The coexistence of cardiovascular risk factors such as obesity&#44; hypertension&#44; dyslipidaemia&#44; etc&#46;&#44; is common in patients with gout&#46; Therefore&#44; recommendations for a heart-healthy diet&#44; regular exercise&#44; weight control and smoking cessation should be incorporated into medical consultations of patients with gout&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0185" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall">The diagnosis of gout should be performed based on the identification of MSU crystals in a sample of synovial fluid or tophus aspirate&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall">The therapeutic goal in gout is the dissolution of crystal deposition&#46; To achieve this&#44; we must reduce uric acid levels &#60;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; In selected patients&#44; more stringent treatment goals should be considered &#40;&#60;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; as a lower uricemia means quicker crystal dissolution&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Initial treatment options include xanthine oxidase inhibitors&#58; allopurinol and febuxostat&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0205" class="elsevierStylePara elsevierViewall">If the therapeutic goal is not achieved&#44; the dose can be increased or combined with a uricosuric drug&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0210" class="elsevierStylePara elsevierViewall">Cardiovascular risk factor screening should be conducted in all patients diagnosed with gout&#46;</p></li></ul></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0215" class="elsevierStylePara elsevierViewall">FS has received fees from Menarini regarding educational programmes and presentations and has participated in AstraZeneca&#39;s <span class="elsevierStyleItalic">advisory board</span>&#46; MA has received fees from Menarinin associated with presentations and has participated in AstraZeneca&#39;s <span class="elsevierStyleItalic">advisory board</span>&#46; NQ declares no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Identification of crystals &#40;gold standard&#41;"
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              "titulo" => "Diagnosis without crystal identification"
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              "titulo" => "Treatment of acute episodes"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Sivera F&#44; Andr&#233;s M&#44; Quilis N&#46; Diagn&#243;stico y tratamiento de la gota&#46; Med Clin &#40;Barc&#41;&#46; 2017&#59;148&#58;271&#8211;276&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Synovial fluid microscopy at 600-magnification with ordinary light &#40;top image&#41;&#44; where a needle-shape crystal is shown inside a leucocyte&#46; Under simple polarized light &#40;middle image&#41;&#44; the glass shows strong birefringence which&#44; after applying the first order red compensator &#40;below&#41;&#44; is confirmed as negative birefringence&#8211;as it is yellow in colour and is positioned parallel to the compensator&#39;s axis &#40;arrow&#41;&#8211;&#46; Photographs courtesy of Prof&#46; Eliseo Pascual&#46;</p>"
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            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multinational evidence-based recommendations for the diagnosis and management of gout&#58; Integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Sivera"
                            1 => "M&#46; Andr&#233;s"
                            2 => "L&#46; Carmona"
                            3 => "A&#46;S&#46; Kydd"
                            4 => "J&#46; Moi"
                            5 => "R&#46; Seth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2013-203325"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2014"
                        "volumen" => "73"
                        "paginaInicial" => "328"
                        "paginaFinal" => "335"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23868909"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "Epub ahead of print&#46; Available from&#58; <span class="elsevierStyleInterRef" id="intr0010" href="http://ard.bmj.com/content/early/2016/07/25/annrheumdis-2016-209707.long">http&#58;&#47;&#47;ard&#46;bmj&#46;com&#47;content&#47;early&#47;2016&#47;07&#47;25&#47;annrheumdis-2016-209707&#46;long</span> &#91;accessed 16&#46;11&#46;16&#93;"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2016 updated EULAR evidence-based recommendations for the management of gout"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Richette"
                            1 => "M&#46; Doherty"
                            2 => "E&#46; Pascual"
                            3 => "V&#46; Barskova"
                            4 => "F&#46; Becce"
                            5 => "J&#46; Casta&#241;eda-Sanabria"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2016-209707"
                      "Revista" => array:2 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "American College of Rheumatology guidelines for management of gout&#46; Part 1&#58; Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Khanna"
                            1 => "J&#46;D&#46; Fitzgerald"
                            2 => "P&#46;P&#46; Khanna"
                            3 => "S&#46; Bae"
                            4 => "M&#46; Singh"
                            5 => "T&#46; Neogi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Care Res &#40;Hoboken&#41;"
                        "fecha" => "2012"
                        "volumen" => "64"
                        "paginaInicial" => "1431"
                        "paginaFinal" => "1446"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Synovial fluid analysis for diagnosis of intercritical gout"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Pascual"
                            1 => "E&#46; Batlle-Gualda"
                            2 => "A&#46; Mart&#237;nez"
                            3 => "J&#46; Rosas"
                            4 => "P&#46; Vela"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "1999"
                        "volumen" => "131"
                        "paginaInicial" => "756"
                        "paginaFinal" => "759"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10577299"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis of gout in patients with asymptomatic hyperuricaemia&#58; a pilot ultrasound study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; De Miguel"
                            1 => "J&#46;G&#46; Puig"
                            2 => "C&#46; Castillo"
                            3 => "D&#46; Peiteado"
                            4 => "R&#46;J&#46; Torres"
                            5 => "E&#46; Mart&#237;n-Mola"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2011.154997"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2012"
                        "volumen" => "71"
                        "paginaInicial" => "157"
                        "paginaFinal" => "158"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21953340"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout&#58; a dual energy CT study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Dalbeth"
                            1 => "M&#46;E&#46; House"
                            2 => "O&#46; Aati"
                            3 => "P&#46; Tan"
                            4 => "C&#46; Franklin"
                            5 => "A&#46; Horne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2014-206397"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2015"
                        "volumen" => "74"
                        "paginaInicial" => "908"
                        "paginaFinal" => "911"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25637002"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Silent monosodium urate crystal deposits are associated with severe coronary calcification in asymptomatic hyperuricemia&#58; an exploratory study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Andr&#233;s"
                            1 => "M&#46;A&#46; Quintanilla"
                            2 => "F&#46; Sivera"
                            3 => "J&#46; S&#225;nchez-Pay&#225;"
                            4 => "E&#46; Pascual"
                            5 => "P&#46; Vela"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.39581"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2016"
                        "volumen" => "68"
                        "paginaInicial" => "1531"
                        "paginaFinal" => "1539"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26748935"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleItalic">In vivo</span> detection of monosodium urate crystal deposits by Raman spectroscopy&#8212;a pilot study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Abhishek"
                            1 => "D&#46;J&#46; Curran"
                            2 => "F&#46; Bilwani"
                            3 => "A&#46;C&#46; Jones"
                            4 => "M&#46;R&#46; Towler"
                            5 => "M&#46; Doherty"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/kev339"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rheumatology"
                        "fecha" => "2016"
                        "volumen" => "55"
                        "paginaInicial" => "379"
                        "paginaFinal" => "380"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26342227"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An audit of the variability of diagnosis and management of gout in the rheumatology setting&#58; the gout evaluation and management study"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Perez-Ruiz"
                            1 => "L&#46; Carmona"
                            2 => "M&#46;J&#46; Yebenes"
                            3 => "E&#46; Pascual"
                            4 => "E&#46; de Miguel"
                            5 => "I&#46; Ure&#241;a"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/RHU.0b013e3182314d40"
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                        "tituloSerie" => "J Clin Rheumatol"
                        "fecha" => "2011"
                        "volumen" => "17"
                        "paginaInicial" => "349"
                        "paginaFinal" => "355"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21946457"
                            "web" => "Medline"
                          ]
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                    0 => array:2 [
                      "titulo" => "Clinical diagnostic criteria for gout&#58; Comparison with the gold standard of synovial fluid crystal analysis"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Malik"
                            1 => "H&#46;R&#46; Schumacher"
                            2 => "J&#46;E&#46; Dinnella"
                            3 => "G&#46;M&#46; Clayburne"
                          ]
                        ]
                      ]
                    ]
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                      "doi" => "10.1097/RHU.0b013e3181945b79"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Rheumatol"
                        "fecha" => "2009"
                        "volumen" => "15"
                        "paginaInicial" => "22"
                        "paginaFinal" => "24"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19125136"
                            "web" => "Medline"
                          ]
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                          "pii" => "S1470204510701467"
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                          "issn" => "14702045"
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                    0 => array:2 [
                      "titulo" => "EULAR&#47;EFORT recommendations for the diagnosis and initial management of patients with acute or recent onset swelling of the knee"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;B&#46; Landewe"
                            1 => "K&#46;P&#46; Gunther"
                            2 => "C&#46; Lukas"
                            3 => "J&#46; Braun"
                            4 => "B&#46; Combe"
                            5 => "P&#46;G&#46; Conaghan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2008.104406"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2010"
                        "volumen" => "69"
                        "paginaInicial" => "12"
                        "paginaFinal" => "19"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19147613"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0210"
              "etiqueta" => "12"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gout classification criteria&#58; an American College of Rheumatology&#47;European League Against Rheumatism collaborative initiative"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Neogi"
                            1 => "T&#46;L&#46; Jansen"
                            2 => "N&#46; Dalbeth"
                            3 => "J&#46; Fransen"
                            4 => "H&#46;R&#46; Schumacher"
                            5 => "D&#46; Berendsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2015-208237"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2015"
                        "volumen" => "74"
                        "paginaInicial" => "1789"
                        "paginaFinal" => "1798"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26359487"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            12 => array:3 [
              "identificador" => "bib0215"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gout as a risk factor for myocardial infarction and stroke in England&#58; evidence from record linkage studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "O&#46;O&#46; Seminog"
                            1 => "M&#46;J&#46; Goldacre"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rheumatology &#40;Oxford&#41;"
                        "fecha" => "2013"
                        "volumen" => "52"
                        "paginaInicial" => "2251"
                        "paginaFinal" => "2259"
                      ]
                    ]
                  ]
                ]
              ]
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            13 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "14"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of urate-lowering therapy on the velocity of size reduction of tophi in chronic gout"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "F&#46; Perez-Ruiz"
                            1 => "M&#46; Calabozo"
                            2 => "J&#46;I&#46; Pijoan"
                            3 => "A&#46;M&#46; Herrero-Beites"
                            4 => "A&#46; Ruibal"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.10511"
                      "Revista" => array:7 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2002"
                        "volumen" => "47"
                        "paginaInicial" => "356"
                        "paginaFinal" => "360"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12209479"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S030228381000905X"
                          "estado" => "S300"
                          "issn" => "03022838"
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                  ]
                ]
              ]
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            14 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Time required for disappearance of urate crystals from synovial fluid after successful hypouricaemic treatment relates to the duration of gout"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46; Pascual"
                            1 => "F&#46; Sivera"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2006.060368"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2007"
                        "volumen" => "66"
                        "paginaInicial" => "1056"
                        "paginaFinal" => "1058"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17223663"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "American College of Rheumatology guidelines for management of gout&#46; Part 2&#58; Therapy and antiinflammatory prophylaxis of acute gouty arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Khanna"
                            1 => "P&#46;P&#46; Khanna"
                            2 => "J&#46;D&#46; Fitzgerald"
                            3 => "M&#46;K&#46; Singh"
                            4 => "S&#46; Bae"
                            5 => "T&#46; Neogi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Care Res &#40;Hoboken&#41;"
                        "fecha" => "2012"
                        "volumen" => "64"
                        "paginaInicial" => "1447"
                        "paginaFinal" => "1461"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Febuxostat compared with allopurinol in patients with hyperuricemia and gout"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;A&#46; Becker"
                            1 => "H&#46;R&#46; Schumacher Jr&#46;"
                            2 => "R&#46;L&#46; Wortmann"
                            3 => "P&#46;A&#46; MacDonald"
                            4 => "D&#46; Eustace"
                            5 => "W&#46;A&#46; Palo"
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                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa050373"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2005"
                        "volumen" => "353"
                        "paginaInicial" => "2450"
                        "paginaFinal" => "2461"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16339094"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0240"
              "etiqueta" => "18"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout&#58; a 28-week&#44; phase <span class="elsevierStyleSmallCaps">iii</span>&#44; randomized&#44; double-blind&#44; parallel-group trial"
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                        0 => array:2 [
                          "etal" => true
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                            1 => "M&#46;A&#46; Becker"
                            2 => "R&#46;L&#46; Wortmann"
                            3 => "P&#46;A&#46; MacDonald"
                            4 => "B&#46; Hunt"
                            5 => "J&#46; Streit"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.24209"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2008"
                        "volumen" => "59"
                        "paginaInicial" => "1540"
                        "paginaFinal" => "1548"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18975369"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A randomised-controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300&#8211;600<span class="elsevierStyleHsp" style=""></span>mg&#47;day versus benzbromarone 100&#8211;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day in patients with gout"
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                        0 => array:2 [
                          "etal" => true
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                            1 => "C&#46; Haagsma"
                            2 => "T&#46;L&#46; Jansen"
                            3 => "E&#46;N&#46; van Roon"
                            4 => "J&#46; Delsing"
                            5 => "M&#46;A&#46; van de Laar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ard.2008.091462"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2009"
                        "volumen" => "68"
                        "paginaInicial" => "892"
                        "paginaFinal" => "897"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18633127"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0250"
              "etiqueta" => "20"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Starting dose is a risk factor for allopurinol hypersensitivity syndrome&#58; a proposed safe starting dose of alopurinol"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;K&#46; Stamp"
                            1 => "W&#46;J&#46; Taylor"
                            2 => "P&#46;B&#46; Jones"
                            3 => "J&#46;L&#46; Dockerty"
                            4 => "J&#46; Drake"
                            5 => "C&#46; Frampton"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.34488"
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                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "2012"
                        "volumen" => "64"
                        "paginaInicial" => "2529"
                        "paginaFinal" => "2536"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22488501"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0255"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
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                      ]
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                  "host" => array:1 [
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                      "doi" => "10.3899/jrheum.110092"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol"
                        "fecha" => "2011"
                        "volumen" => "38"
                        "paginaInicial" => "1957"
                        "paginaFinal" => "1959"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21724706"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0260"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia&#46; A pathogenic approach to the treatment of primary chronic gout"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46; Perez-Ruiz"
                            1 => "A&#46; Alonso-Ruiz"
                            2 => "M&#46; Calabozo"
                            3 => "A&#46; Herrero-Beites"
                            4 => "G&#46; Garcia-Erauskin"
                            5 => "E&#46; Ruiz-Lucea"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "1998"
                        "volumen" => "57"
                        "paginaInicial" => "545"
                        "paginaFinal" => "549"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9849314"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0265"
              "etiqueta" => "23"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A benefit-risk assessment of benzbromarone in the treatment of gout&#46; Was its withdrawal from the market in the best interest of patients&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;H&#46; Lee"
                            1 => "G&#46;G&#46; Graham"
                            2 => "K&#46;M&#46; Williams"
                            3 => "R&#46;O&#46; Day"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Drug Saf"
                        "fecha" => "2008"
                        "volumen" => "31"
                        "paginaInicial" => "643"
                        "paginaFinal" => "665"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18636784"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lesinurad in combination with allopurinol&#58; results of a phase 2&#44; randomised&#44; double-blind study in patients with gout with an inadequate response to allopurinol"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "RDEA594-203 Study Group"
                          "etal" => false
                          "autores" => array:5 [
                            0 => "F&#46; Perez-Ruiz"
                            1 => "J&#46;S&#46; Sundy"
                            2 => "J&#46;N&#46; Miner"
                            3 => "M&#46; Cravets"
                            4 => "C&#46; Storgard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/annrheumdis-2015-207919"
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Rheum Dis"
                        "fecha" => "2016"
                        "volumen" => "75"
                        "paginaInicial" => "1074"
                        "paginaFinal" => "1080"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26742777"
                            "web" => "Medline"
                          ]
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                        "itemHostRev" => array:3 [
                          "pii" => "S1470204507702851"
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                          "issn" => "14702045"
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                  ]
                ]
              ]
            ]
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              "etiqueta" => "25"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rasburicase for tophaceous gout not treatable with allopurinol&#58; an exploratory study"
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                          "etal" => false
                          "autores" => array:5 [
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                            1 => "C&#46; Bri&#232;re"
                            2 => "V&#46; Hoenen-Clavert"
                            3 => "D&#46; Loeuille"
                            4 => "T&#46; Bardin"
                          ]
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                        0 => array:2 [
                          "etal" => false
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                            3 => "P&#46;L&#46; van Riel"
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                        "paginaFinal" => "1860"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18514729"
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                      "titulo" => "High versus low dosing of oral colchicine for early acute gout flare&#58; twenty-four-hour outcome of the first multicenter&#44; randomized&#44; double-blind&#44; placebo-controlled&#44; parallel-group&#44; dose-comparison colchicine study"
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                        "paginaInicial" => "1060"
                        "paginaFinal" => "1068"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20131255"
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                    ]
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                        "fecha" => "2012"
                        "volumen" => "71"
                        "paginaInicial" => "1839"
                        "paginaFinal" => "1848"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22586173"
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                        "fecha" => "2004"
                        "volumen" => "363"
                        "paginaInicial" => "1277"
                        "paginaFinal" => "1281"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15094272"
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                    0 => array:2 [
                      "titulo" => "Effects of skim milk powder enriched with glycomacropeptide and G600 milk fat extract on frequency of gout flares&#58; a proof-of-concept randomised controlled trial"
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                            4 => "S&#46; Wong"
                            5 => "B&#46; Kuhn-Sherlock"
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                    ]
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