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Clinical Science
Effectiveness of Radiation Synovectomy with Samarium-153 Particulate Hydroxyapatite in Rheumatoid Arthritis Patients with Knee Synovitis: A Controlled Randomized Double-Blind Trial
Marla Francisca dos SantosI, Rita Nely Vilar FurtadoI, Monique Sayuri KonaiI, Mario Luiz Vieira CastiglioniII, Renata Rosa MarchettiII, Jamil NatourI,
Corresponding author
jnatour@unifesp.br

Tel. : 55 11 5576.4239
I Division of Rheumatology, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP) - São Paulo/SP, Brazil
II Department of Radiology, Division of Nuclear Medicine, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP) - São Paulo/SP, Brazil.
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis &#40;RA&#41; is a chronic disease that is mainly characterized by asymmetric erosive synovitis&#44; particularly affecting peripheral joints&#46;<a class="elsevierStyleCrossRef" href="#bib1">1</a> Functional disability in patients with RA is the consequence of joint deformity&#44; which is the result of pannus invasion of the articular cartilage&#44; capsule&#44; ligaments and subchondral bone&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a> Current treatment for RA is based on a pharmacological approach&#44;<a class="elsevierStyleCrossRef" href="#bib3">3</a> physical therapy&#44;<a class="elsevierStyleCrossRef" href="#bib4">4</a> and patient education&#46;<a class="elsevierStyleCrossRef" href="#bib5">5</a> Synovectomy through chemical&#44; radioisotopic&#44; or surgical means has been adopted as a therapeutic option in RA&#46;<a class="elsevierStyleCrossRefs" href="#bib6">6&#44;7</a> Most chemical synovectomy is performed using intra-articular injection &#40;IAI&#41; of glucocorticosteroids&#44; the most effective of which has been shown to be triamcinolone hexacetonide &#40;TH&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib8">8</a></p><p id="para20" class="elsevierStylePara elsevierViewall">Radiation synovectomy &#40;RS&#41; &#40;also called radio-synoviorthesis or radiosynovectomy&#41; is a local IAI of radionuclides in colloidal form for radiotherapy&#46; First used by Fellinger et al&#46;<a class="elsevierStyleCrossRef" href="#bib9">9</a> in 1952&#44; the technique has been applied for over 50 y in the treatment of resistant synovitis in individual joints after the failure of long-term systemic pharmacotherapy and intra-articular steroid injections&#46; Radioisotopes with emission of &#946; radiation have the capacity to diminish the inflammatory process and ablate the inflamed synovial membrane &#40;pannus&#41; with subsequent fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib10">10</a> Three radionuclides are currently in use&#58; Yttrium-90 &#40;<span class="elsevierStyleSup">90</span>Y-silicate&#47;citrate&#41;&#44; Rhenium-186 &#40;<span class="elsevierStyleSup">186</span>Re-sulfide&#41;&#44; and Erbium-169 &#40;<span class="elsevierStyleSup">169</span>Er citrate&#41;&#44; which have been indicated for large&#44; medium&#44; and small joints&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib10">10</a> These radionuclides are indicated for treatment of joint pain arising from arthropathies&#44; including RA&#44; spondyloarthropathy&#44; other inflammatory joint diseases &#40;Lyme disease&#44; Beh&#231;et&#8217;s disease&#41;&#44; persistent synovial effusion&#44; hemophilic arthritis&#44; calcium pyrophosphate dihydrate arthritis&#44; pigmented villonodular synovitis&#44; and undifferentiated arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;12</a></p><p id="para30" class="elsevierStylePara elsevierViewall">In clinical practice&#44; RS is a procedure that has been widely used for several decades&#44; mainly in European countries&#44; Australia&#44; and Canada&#44;<a class="elsevierStyleCrossRef" href="#bib11">11</a> especially for patients with refractory synovitis&#44; &#40;synovitis that fails to respond to at least one intra-articular injection with corticosteroids&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib12">12</a></p><p id="para40" class="elsevierStylePara elsevierViewall">Despite the established use of RS in clinical practice&#44; there are few randomized&#44; controlled studies using this technique in relation to the most often used radioisotopes&#58; <span class="elsevierStyleSup">186</span>Re&#44; <span class="elsevierStyleSup">169</span>Er and <span class="elsevierStyleSup">90</span>Y&#46;<a class="elsevierStyleCrossRefs" href="#bib7">7&#44;10&#44;12</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib24">24</a> Samarium<span class="elsevierStyleSup">153</span>-hydroxyapatite &#40;<span class="elsevierStyleSup">153</span>SmPHYP&#41; is considered another option for RS<a class="elsevierStyleCrossRefs" href="#bib25">25&#44;26</a>&#59; however&#44; there are few well-conducted studies in the literature using <span class="elsevierStyleSup">153</span>SmPHYP for the treatment of chronic synovitis&#46; Therefore&#44; we decided to develop a randomized controlled double-blinded study that aimed to investigate the effectiveness of <span class="elsevierStyleSup">153</span>SmPHYP in RS for chronic knee synovitis in patients with RA&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">PATIENTS AND METHODS</span><p id="para50" class="elsevierStylePara elsevierViewall">A controlled&#44; randomized&#44; double-blind prospective study was carried out comparing RS to <span class="elsevierStyleSup">153</span>SmPHYP associated with TH versus IAI with TH alone for the treatment of knee synovitis in patients with RA&#46;</p><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Patients</span><p id="para60" class="elsevierStylePara elsevierViewall">This study included 58 consecutive patients &#40;60 joints&#41; with RA and chronic knee synovitis&#46; Patients were recruited from the Rheumatology Outpatient Clinics at the Universidade Federal de S&#227;o Paulo &#40;UNIFESP&#41;&#44; S&#227;o Paulo&#44; Brazil&#46; The following were the inclusion criteria&#58; diagnosis of RA &#40;according to the ACR criteria&#41; at least 6 mo prior to recruitment&#59;<a class="elsevierStyleCrossRef" href="#bib27">27</a> chronic monoarticular knee synovitis or oligoarticular arthritis with the knee being the more symptomatic joint for over 6 wks&#59; age between 18 and 60 y&#59; use of stable doses of oral corticosteroids for the previous 30 d and use of stable doses of DMARDs &#40;disease modifying antirheumatic drugs&#41; for the previous 3 mo&#59; a score between 5 and 10 on a visual analog scale for pain &#40;VAS&#44; range 0&#8211;10 cm&#41;&#59; reading and writing skills&#59; and no risk of pregnancy &#40;women with a history of hysterectomy&#44; tubal ligation&#44; or menopause&#41;&#46; Written informed consent was obtained from all subjects&#44; and the Ethics Committee approved the study&#46; Exclusion criteria were as follows&#58; patients with collagen diseases other than RA&#59; pregnant or breast-feeding women&#59; intra-articular knee injection in the previous 3 mo &#40;or other joints&#41;&#59; prior knee surgery or skin lesion&#59; suspected septic arthritis or ruptured popliteal cyst &#40;knee&#41;&#59; urinary incontinence&#59; any intervention in the knee in the previous 3 mo&#46; Radiographs were performed with loads on the knees submitted to the procedure at the beginning of the study and later classified through &#8220;blinded&#8221; radiographic analysis according to the Kellgren-Lawrence scale for secondary osteoarthritis&#46;<a class="elsevierStyleCrossRef" href="#bib28">28</a></p><p id="para70" class="elsevierStylePara elsevierViewall">After a period of 3 mo of follow-up&#44; the patients could have their DMARDs modified&#46; We opted for that flexibility in order to provide better clinical control of the disease and to increase the adherence of the patients&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Intervention</span><p id="para80" class="elsevierStylePara elsevierViewall">Lots with opaque sealed envelopes were used to randomly and equally allocate patients into two intervention groups&#58; TH group&#44; in which 30 patients &#40;30 knees&#41; received an IAI in the knee with 40 mg triamcinolone hexacetonide &#40;TH&#41; alone&#59; and Sm&#47;TH group&#44; in which 28 patients &#40;30 knees&#41; received 40 mg TH combined with 15 mCi <span class="elsevierStyleSup">153</span>SmPHYP&#46; Both procedures were performed by the same researcher&#44; and assessments were carried out by a blinded evaluator&#46; In the case of bilateral synovitis&#44; the knee with the higher visual analogue score &#40;VAS&#41; for pain was infiltrated&#46; Inclusion of the same patient in the study for a second time was permitted if he&#47;she fulfilled the inclusion criteria after three months from the initial intervention and exhibited arthritis in the contralateral knee&#46; Inclusion a second time for the same knee was not permitted&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">153</span>SmPHYP was provided by the &#8220;Instituto de Pesquisas Energ&#233;ticas e Nucleares do Brasil&#8221; &#40;IPEN&#41;&#46; Both types of intervention were performed in the Nuclear Medicine Section following the bio-safety rules <a class="elsevierStyleCrossRef" href="#bib10">10</a> for the use of radioactive material&#46; Procedures were always performed in the same fluoroscopy room&#46; Threaded syringes were connected to a three-way tap and 50 &#215; 8 mm needles were used to avoid reflux of the injected medication&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Procedure</span><p id="para100" class="elsevierStylePara elsevierViewall">Each patient underwent IAI guided by fluoroscopy while lying comfortably on their back&#46; The knee was positioned at maximum extension with the needle entry point two centimeters from the upper-lateral angle of the patella subjected to eversion&#46; Lidocaine &#40;3 ml&#44; 2&#37;&#41; with no vasoconstrictor was injected into the intra-articular region&#46; Then&#44; 3 to 5 ml of non-ionic iodated contrast medium was also injected&#46; Distribution in the intra-articular recesses of the knee was viewed continuously by fluoroscopy&#46; The Sm&#47;TH group received 15 mCi injections of <span class="elsevierStyleSup">153</span>SmPHYP diluted with 5 ml of 0&#46;9&#37; saline solution followed by 40 mg of TH&#46; The TH group received 40 mg of TH alone&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">A small amount of air was maintained in the syringe upon terminating infiltration so as to hinder subcutaneous reflux of the drugs&#46; Systematic joint aspiration was performed prior to the injections in patients with synovial effusion&#46; No patient had visual access to the procedure or preparation of the syringes&#46;</p><p id="para120" class="elsevierStylePara elsevierViewall">All patients&#44; regardless of group&#44; remained at rest for four hours in a wheelchair in the Nuclear Medicine Section&#44; and the knee was extended with the help of a splint&#46;<a class="elsevierStyleCrossRef" href="#bib26">26</a> Patients were then transported to their homes and were told to remain at rest with a splint on the infiltrated knee for 48 h&#44; only getting up from the bed to attend to their physiological needs&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Evaluation</span><p id="para130" class="elsevierStylePara elsevierViewall">Patients were evaluated by a blinded physician at baseline &#40;T0&#41; as well as 1&#44; 4&#44; 12&#44; 32&#44; and 48 weeks after intervention &#40;T1&#44; T4&#44; T12&#44; T32&#44; and T48&#44; respectively&#41;&#46; The following instruments were applied during all assessment sessions&#58; VAS for joint pain and swelling &#40;range&#58; 0&#8211;10 cm&#41;&#44; knee goniometry &#40;flexion and extension&#41;&#44; morning stiffness&#44; knee circumference &#40;cm&#41;&#44; Likert scale of improvement &#40;a lot of improvement&#44; little improvement&#44; unchanged&#44; a little worse&#44; much worse&#41; according to the patient and the evaluator&#44; percentage of improvement&#44; Lequesne index&#44;<a class="elsevierStyleCrossRef" href="#bib29">29</a> calls to the physician&#44; hospital visits&#44; and adverse effects and events&#46;</p><p id="para140" class="elsevierStylePara elsevierViewall">The following assessment instruments were applied through T12&#58; Brazilian version of the Functional subscale of the Stanford Health Assessment Questionnaire &#40;HAQ&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib30">30</a> Brazilian version of the SF-36 generic quality of life questionnaire&#44;<a class="elsevierStyleCrossRef" href="#bib31">31</a> Lequesne index&#44;<a class="elsevierStyleCrossRef" href="#bib29">29</a> and use of non-steroidal anti-inflammatory drugs and oral corticosteroids&#46;</p><p id="para150" class="elsevierStylePara elsevierViewall">The number of sodium diclofenac tablets and oral prednisone doses were counted at each time point&#44; and average daily doses for these drugs were assessed&#46; Patients were considered withdrawals if they interrupted the follow-up in the first month of the study&#59; had altered DMARDs&#59; or experienced an interruption of their disease for a period of two weeks or more&#46; During the three-month follow-up period&#44; the DMARDs were maintained stable&#44; whereas prednisone and diclofenac doses could be altered according to need&#46; After this period&#44; there was flexibility for the following items&#58; physiotherapy&#44; acupuncture&#44; infiltrations&#44; and change in DMARDs according to the needs and activity of the disease&#46;</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Statistical Analysis</span><p id="para160" class="elsevierStylePara elsevierViewall">Data are presented as mean &#177; standard deviation&#46; Chi-square analysis was used to evaluate differences between categorical variables&#46; The Mann-Whitney test was used for analysis of non-parametric numerical variables&#46; ANOVA analysis was performed to compare numerical variables repeated over time&#46; The significance level was set at p&#60;0&#46;05&#46; The Tukey multiple comparison test was performed for intra-group analysis&#46; ANOVA with non-parametric repeated measurements was used in the analysis of ordinal data of the Likert scale&#46; Data were analyzed according to the intention-to-treat principle and patients with missing data had the previous evaluation data repeated&#46;</p></span></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">RESULTS</span><p id="para170" class="elsevierStylePara elsevierViewall">The sample was made up of 58 patients &#40;60 knees&#41;&#46; Two patients participated in the study twice and were randomized twice &#40;once for each knee&#41;&#46; The second randomization was for the contralateral knee and occurred three months after the intervention for the first knee&#46; The data displayed in the tables refer to the number of knees and not the number of patients&#46; There was no statistically significant difference between groups regarding joint&#44; functional class&#44; demographic&#44; or disease-related variables at baseline &#40;T0&#41; &#40;<a class="elsevierStyleCrossRef" href="#t1-cln64_12p1187">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="t1-cln64_12p1187"></elsevierMultimedia><p id="para180" class="elsevierStylePara elsevierViewall">The radiological assessment was done according to the Kellgren-Lawrence scale<a class="elsevierStyleCrossRef" href="#bib28">28</a> and no difference was found between the groups&#44; even when the groups were stratified into five degrees &#40;0 to 4&#41; according to this scale &#40;<a class="elsevierStyleCrossRef" href="#t1-cln64_12p1187">Table 1</a>&#41;&#46;</p><p id="para190" class="elsevierStylePara elsevierViewall">Three patients were absent from the T32 reevaluation &#40;2 from the Sm&#47;TH group and 1 from the TH&#41; and four were absent from the T48 reevaluation &#40;1 from the Sm&#47;TH Group and 3 from the TH group&#41;&#46;</p><p id="para200" class="elsevierStylePara elsevierViewall">In the <span class="elsevierStyleBold">intra-group</span> analysis in relation to T0 &#40;initial time&#41;&#44; there was a statistically significant improvement at all evaluation times for the VAS for pain and swelling&#59; at T1 for morning stiffness&#59; at T1&#44; T4&#44; and T12 for joint flexion&#59; at T1 and T4 for joint extensions&#59; and from T4 to T48 for knee circumference in both groups &#40;<a class="elsevierStyleCrossRef" href="#t2-cln64_12p1187">Table 2</a>&#41;&#46; In the <span class="elsevierStyleBold">inter-group</span> analysis throughout the evolution of the study&#44; no differences were observed between groups regarding the local variables &#40;VAS for pain and swelling&#44; morning stiffness&#44; knee flexion&#44; extension&#44; and circumference&#41; &#40;<a class="elsevierStyleCrossRef" href="#t2-cln64_12p1187">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="t2-cln64_12p1187"></elsevierMultimedia><p id="para210" class="elsevierStylePara elsevierViewall">There were no statistical differences between the groups for the following variables&#58; Likert scale of improvement according to patient and evaluator&#44; percentage of improvement&#44; HAQ &#40;<a class="elsevierStyleCrossRef" href="#t3-cln64_12p1187">Table 3</a>&#41; and SF-36 questionnaires&#44; Lequesne index &#40;<a class="elsevierStyleCrossRef" href="#t3-cln64_12p1187">Table 3</a>&#41;&#44; use of non-steroidal anti-inflammatory drugs and oral corticosteroids &#40;<a class="elsevierStyleCrossRef" href="#t4-cln64_12p1187">Table 4</a>&#41;&#44; calls to the physician and hospital visits&#46;</p><elsevierMultimedia ident="t3-cln64_12p1187"></elsevierMultimedia><elsevierMultimedia ident="t4-cln64_12p1187"></elsevierMultimedia><p id="para220" class="elsevierStylePara elsevierViewall">Side effects were divided into two groups&#58; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">adverse effects</span></span> were those cited by either the patient or evaluator as likely related to the procedure&#59; <span class="elsevierStyleBold"><span class="elsevierStyleItalic">events</span></span> were situations of any nature cited by either the patient or evaluator&#46; Twenty-two adverse effects were registered in the evolution of the patients&#44; the most frequent of which was post-injection flare &#40;6&#46;7&#37; of the initial sample&#41; with an average duration of 2&#46;25 d &#40;1 to 4 d&#41; after infiltration that did not persist through to the T1 evaluation&#46; The Sm&#47;TH group exhibited more adverse effects 1190 than the TH group at T1 &#40;<span class="elsevierStyleItalic">p&#60;0&#46;015</span>&#41;&#44; but in the evaluations T4 to T48 the number of adverse effects was similar in both groups&#46; Three of the five adverse effects &#40;60&#37;&#41; in the TH group occurred before the T1 evaluation&#46;</p><p id="para230" class="elsevierStylePara elsevierViewall">A femur fracture occurred in one patient from the Sm&#47;TH group with risk factors for osteoporosis&#46; This fracture was considered a casual event and occurred after 11 mo of follow-up&#46; There were no statistically significant differences between groups regarding events throughout the study &#40;<a class="elsevierStyleCrossRef" href="#t5-cln64_12p1187">Table 5</a>&#41;&#46;</p><elsevierMultimedia ident="t5-cln64_12p1187"></elsevierMultimedia><p id="para240" class="elsevierStylePara elsevierViewall">One patient from the Sm&#47;TH group required re-infiltration of the knee with TH after 8 mo&#44; and 2 patients from the TH group required re-infiltration of the knee after three and eight months from the intervention due to the recurrence of arthritis &#40;<span class="elsevierStyleItalic">p</span>&#61; 1&#46;00&#41;&#46; After three months&#44; 27 patients &#40;14 from the Sm&#47;TH group and 13 from the TH group&#59; <span class="elsevierStyleItalic">p&#61;</span> 0&#46;795&#41; modified the use of DMARDs due to activity of their disease&#46;</p></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">DISCUSSION</span><p id="para250" class="elsevierStylePara elsevierViewall">The effectiveness and cost benefit of RS for patients with chronic synovitis have not yet reached a consensus in the medical literature&#46; Despite the fact that RS has a higher cost than IAI with GC&#44; the benefit of its use is the impression of a greater response&#44; longer duration of response in comparison to chemical synovectomy through corticosteroid use&#44; and its use as an option for treatment of refractory synovitis&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;12</a> In our study&#44; <span class="elsevierStyleSup">153</span>SmPHYP was chosen because it is available for use in our country and for its properties&#46; <span class="elsevierStyleSup">153</span>SmPHYP is a radionuclide with a half-life of 46&#46;3 h and &#946;<span class="elsevierStyleSup">-</span> energy of 0&#46;29 MeV&#44; resulting in a maximum penetration of 3&#46;1 mm and therapeutic penetration of 0&#46;7 mm into soft tissue&#46;<a class="elsevierStyleCrossRefs" href="#bib25">25&#44;26</a> The <span class="elsevierStyleSup">153</span>SmPHYP compound emits a small amount of gamma radiation&#44; which is suitable for imaging by gamma camera equipment and is associated with low levels of leakage after injection&#44; safe&#44; and good tolerance&#46;<a class="elsevierStyleCrossRefs" href="#bib25">25&#44;26&#44;34</a> There is also a possible fibrotic action of this compound on the pannus&#44; enabling more lasting control over inflammation&#46; Therefore&#44; use of this radioisotope is theoretically superior to the use of TH alone&#46;</p><p id="para260" class="elsevierStylePara elsevierViewall">There are few controlled&#44; randomized trials in the literature comparing RS with IAI of glucocorticosteroids&#46; <span class="elsevierStyleSup">186</span>Re is used for synovectomy of medium-sized joints and has been assessed in controlled&#44; randomized prospective and retrospective trials that demonstrate its superiority to IAI of glucocorticosteroids&#46;<a class="elsevierStyleCrossRefs" href="#bib19">19&#44;20&#44;24</a> So far&#44; there is no consensus about the superiority of RS with <span class="elsevierStyleSup">169</span>Er &#40;used in small joints&#41; over IAI of glucocorticosteroids&#46;<a class="elsevierStyleCrossRefs" href="#bib21">21&#44;22</a> Synovectomy by <span class="elsevierStyleSup">90</span>Y has been studied in some controlled trials and has been shown to be superior to IAI of saline solution&#44;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;13</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib15">15</a> but studies comparing it to IAI of glucocorticosteroids have had conflicting results&#46;<a class="elsevierStyleCrossRef" href="#bib16">16</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib18">18</a> A systematic review regarding RS with <span class="elsevierStyleSup">90</span>Y concluded that there is no clear evidence of greater efficacy of <span class="elsevierStyleSup">90</span>Y over IAI of glucocorticosteroids despite its frequent use in cases of refractory synovitis&#46;<a class="elsevierStyleCrossRef" href="#bib7">7</a> New radioisotopes such as Dysprosium-165 Ferric Hydroxide Macroaggregate &#40;<span class="elsevierStyleSup">165</span>Dy&#41; and Holmium-166 &#40;<span class="elsevierStyleSup">166</span>Ho&#41; have been developed&#44; but their effectiveness and superiority have not yet been proven in clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib32">32&#44;33</a></p><p id="para270" class="elsevierStylePara elsevierViewall">The only controlled&#44; double-blinded study of <span class="elsevierStyleSup">153</span>SmPHYP similar to the present study was carried out by O&#8217; Duffy et al&#46; &#40;1999&#41;&#44; who found no difference between the groups studied&#46;<a class="elsevierStyleCrossRef" href="#bib26">26</a> However&#44; sixty patients with different inflammatory arthropathies participated in this study and few assessment instruments were used&#46;<a class="elsevierStyleCrossRef" href="#bib26">26</a> In the present study&#44; only patients with RA participated and more objective instruments were used&#44; rather than just scores&#44; including those that assess inflammation&#44; function&#44; quality of life&#44; subjective improvement&#44; and adverse effects and events&#46; The present study also found no statistically significant differences between groups for the diverse variables studied&#46;</p><p id="para280" class="elsevierStylePara elsevierViewall">A trial with the same experimental design as the present study demonstrated through magnetic resonance a statistically greater reduction in synovitis of the knee in the group using IAI of TH alone in a three-month follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib34">34</a> However&#44; it only analyzed evolution through an imaging method and for a much shorter follow-up period&#46; Nonetheless&#44; the findings of that study corroborate the impression that the addition of <span class="elsevierStyleSup">153</span>SmPHYP to TH does not increase the effectiveness of the glucocorticosteroids when injected into the intra-articular region&#46;<a class="elsevierStyleCrossRef" href="#bib34">34</a></p><p id="para290" class="elsevierStylePara elsevierViewall">Studies on <span class="elsevierStyleSup">153</span>SmPHYP for RS describe no side effects attributed to the radioisotope&#46;<a class="elsevierStyleCrossRef" href="#bib25">25</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib26">26</a> The present study found more adverse effects in the Sm&#47;TH group than in the TH group&#44; but the difference was only significant in the T1 evaluation <span class="elsevierStyleItalic">&#40;p</span>&#60;<span class="elsevierStyleItalic">0&#46;015&#41;</span> and the effects were mild with a short duration and spontaneous remission&#46; Most of the side effects were systemic and were also described for IAI of glucocorticosteroids&#46;<a class="elsevierStyleCrossRef" href="#bib6">6</a> Post-injection flare occurred at an equal frequency in both groups&#44; with an average duration of 2&#46;25 d &#40;1 to 4 d&#41;&#44; and these effects did not persist until T1 evaluation&#46;</p><p id="para300" class="elsevierStylePara elsevierViewall">In the present comparison study of RS with <span class="elsevierStyleSup">153</span>SmPHYP associated with TH and IAI of TH alone&#44; no difference was found&#44; which confirms the results of the study by O&#8217; Duffy et al&#46;<a class="elsevierStyleCrossRef" href="#bib26">26</a>&#46;</p><p id="para310" class="elsevierStylePara elsevierViewall">The results show that RS with <span class="elsevierStyleSup">153</span>SmPHYP associated with TH is not superior to IAI of HT alone&#44; and that the positive effects may be attributed to the concomitant use of HT&#46;<a class="elsevierStyleCrossRef" href="#bib13">13</a>&#8211;<a class="elsevierStyleCrossRefs" href="#bib16">16&#44;18</a></p><p id="para320" class="elsevierStylePara elsevierViewall">Some theories may explain the similar results between the groups studied&#58; <span class="elsevierStyleSup">153</span>SmPHYP penetration may not have been effective for the knee&#44; which is a large joint&#44; or its dosage may have been too small&#46;</p><p id="para330" class="elsevierStylePara elsevierViewall">We conclude that IAI of <span class="elsevierStyleSup">153</span>SmPHYP at a dosage of 15 mCi associated with TH was not superior to administration of TH alone for the treatment of synovitis of the knee in RA patients with a one-year follow-up&#46; There is a need for studies with longer follow-up periods in order to more completely evaluate the benefit of <span class="elsevierStyleSup">153</span>SmPHYP in these patients&#8217; knees&#46; <span class="elsevierStyleSup">153</span>SmPHYP may be useful in medium-size joint&#44; such as wrists&#44; elbows&#44; and ankles&#44; because it exhibits tissue penetration similar to <span class="elsevierStyleSup">186</span>Re&#44; which is also used in these joints&#46;<a class="elsevierStyleCrossRef" href="#bib35">35</a> Thus&#44; further studies assessing higher doses in the knees and similar doses in medium-sized joints are important for determination of the true effectiveness of RS through <span class="elsevierStyleSup">153</span>SmPHYP&#46;</p></span></span>"
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          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
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          "titulo" => "PATIENTS AND METHODS"
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              "titulo" => "Patients"
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            1 => array:2 [
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              "titulo" => "Intervention"
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              "titulo" => "Procedure"
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            3 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Evaluation"
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              "titulo" => "Statistical Analysis"
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        3 => array:2 [
          "identificador" => "cesec80"
          "titulo" => "RESULTS"
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        4 => array:2 [
          "identificador" => "cesec90"
          "titulo" => "DISCUSSION"
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        5 => array:2 [
          "identificador" => "xack640441"
          "titulo" => "Acknowledgments"
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        6 => array:1 [
          "titulo" => "REFERENCES"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2009-06-28"
    "fechaAceptado" => "2009-09-17"
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          "clase" => "keyword"
          "titulo" => "KEYWORDS&#58;"
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          "palabras" => array:5 [
            0 => "Rheumatoid arthritis"
            1 => "Intra-articular injection"
            2 => "Radiosynoviorthesis"
            3 => "Radiation synovectomy"
            4 => "Samarium"
          ]
        ]
      ]
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    "resumen" => array:1 [
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVES&#58;</span><p id="spara110" class="elsevierStyleSimplePara elsevierViewall">The aim of the present study was to investigate the effectiveness of Samarium<span class="elsevierStyleSup">153</span>-particulate hydroxyapatite radiation synovectomy in rheumatoid arthritis patients with chronic knee synovitis&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara120" class="elsevierStyleSimplePara elsevierViewall">Fifty-eight rheumatoid arthritis patients &#40;60 knees&#41; with chronic knee synovitis participated in a controlled double-blinded trial&#46; Patients were randomized to receive either an intra-articular injection with 40 mg triamcinolone hexacetonide alone &#40;TH group&#41; or 40 mg triamcinolone hexacetonide combined with 15 mCi Samarium<span class="elsevierStyleSup">153</span>-particulate hydroxyapatite &#40;Sm&#47;TH group&#41;&#46; Blinded examination at baseline &#40;T0&#41; and at 1 &#40;T1&#41;&#44; 4 &#40;T4&#41;&#44; 12 &#40;T12&#41;&#44; 32 &#40;T32&#41;&#44; and 48 &#40;T48&#41; weeks post-intervention were performed on all patients and included a visual analog scale for joint pain and swelling as well as data on morning stiffness&#44; flexion&#44; extension&#44; knee circumference&#44; Likert scale of improvement&#44; percentage of improvement&#44; SF-36 generic quality of life questionnaire&#44; Stanford Health Assessment Questionnaire &#40;HAQ&#41;&#44; Lequesne index&#44; use of non-steroidal anti-inflammatory drugs or oral corticosteroids&#44; events and adverse effects&#44; calls to the physician&#44; and hospital visits&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara130" class="elsevierStyleSimplePara elsevierViewall">The sample was homogeneous at baseline&#44; and there were no withdrawals&#46; Improvement was observed in both groups in relation to T0&#44; but no statistically significant differences between groups were observed regarding all variables at the time points studied&#46; The Sm&#47;TH group exhibited more adverse effects at T1 &#40;p&#60;0&#46;05&#41;&#44; but these were mild and transitory&#46; No severe adverse effects were reported during follow-up&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSION&#58;</span><p id="spara140" class="elsevierStyleSimplePara elsevierViewall">Intra-articular injection of Samarium<span class="elsevierStyleSup">153</span>-particulate hydroxyapatite &#40;15 mCi&#41; with 40 mg of triamcinolone hexacetonide is not superior to triamcinolone hexacetonide alone for the treatment of knee synovitis in patients with rheumatoid arthritis at 1 y of follow-up&#46;</p></span>"
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          "leyenda" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">TH group&#58; triamcinolone hexacetonide &#40;TH&#41;&#59; Sm&#47;TH group&#58; <span class="elsevierStyleSup">153</span>SmPHYP &#43; TH&#59; SD&#61;standard deviation&#59;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">Sm&#47;TH Group &#40;n&#61;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">TH Group &#40;n&#61;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">p<a class="elsevierStyleCrossRef" href="#tfn2-cln64_12p1187"><span class="elsevierStyleSup">&#35;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">Age&#44; years &#40;Mean&#177;SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">54&#46;8 &#40;&#177;8&#46;04&#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="top">54&#46;4 &#40;&#177;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">0&#46;491&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="top">Gender &#40;Women&#47; Men&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="top">25&#58;5&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="top">27&#58;3&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="top">0&#46;447&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  " align="left" valign="top">Race &#40;White&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">20&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="top">0&#46;11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">Disease duration&#44; years &#40;Mean&#177;SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">12&#46;07 &#40;<span class="elsevierStyleBold">&#177;</span>9&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">13&#46;2 &#40;<span class="elsevierStyleBold">&#177;</span>12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="top">0&#46;677&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="top">Rheumatoid Factor &#40;positive&#41; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">19 &#40;63&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">20 &#40;66&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;787&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="top">Functional class II&#58; III&nbsp;\t\t\t\t\t\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="top">9&#58;21&nbsp;\t\t\t\t\t\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="top">13&#58;17&nbsp;\t\t\t\t\t\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="top">0&#46;284&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="top">DMARDS &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">28 &#40;93&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">27 &#40;90&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;640&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="top">Methotrexate &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">24 &#40;80&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">23 &#40;76&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;754&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="top">Chloroquine diphosphate &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">4 &#40;13&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">4 &#40;13&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1&#46;000&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="top">Sulfasalazine &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1 &#40;3&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">2 &#40;6&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;554&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="top">Leflunomide &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">6 &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">8 &#40;26&#46;7&#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="top">0&#46;542&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="top">Infliximab &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1 &#40;3&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;313&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="top">Time from past infiltration of the knee &#40;months&#41; Mean&#177;SD&nbsp;\t\t\t\t\t\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="top">12&#46;4 &#40;<span class="elsevierStyleBold">&#177;</span>15&#46;4&#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="top">15&#46;4 &#40;<span class="elsevierStyleBold">&#177;</span>16&#46;9&#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="top">0&#46;954&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  " colspan="4" align="left" valign="top">Kellgren-Lawrence Classification</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="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Grade 0&nbsp;\t\t\t\t\t\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="top">1&nbsp;\t\t\t\t\t\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="top">3&nbsp;\t\t\t\t\t\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="top">0&#46;269&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="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Grade 1&nbsp;\t\t\t\t\t\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="top">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="left" valign="top">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="left" valign="top">&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="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Grade 2&nbsp;\t\t\t\t\t\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="top">6&nbsp;\t\t\t\t\t\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="top">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="left" valign="top">&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="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Grade 3&nbsp;\t\t\t\t\t\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="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">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="left" valign="top">&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="top" style="border-bottom: 2px solid black"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Grade 4&nbsp;\t\t\t\t\t\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="top" style="border-bottom: 2px solid black">4&nbsp;\t\t\t\t\t\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="top" style="border-bottom: 2px solid black">1&nbsp;\t\t\t\t\t\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="top" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="left" valign="top" scope="col">Time Points &#40;weeks&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top" scope="col">Sm&#47;TH Group &#40;n&#61;30&#41; Mean&#177;SD&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="top" scope="col">TH Group &#40;n&#61;30&#41; Mean&#177;SD&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top" scope="col">Inter-group p<a class="elsevierStyleCrossRef" href="#tfn4-cln64_12p1187">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="top">&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  " colspan="2" align="left" valign="top">VAS for pain &#40;0&#8211;10 cm&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;607&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  " colspan="4" align="left" valign="top"></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="top"><span class="elsevierStyleBold">T0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">6&#46;8 &#40;1&#46;4&#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="top">6&#46;8 &#40;1&#46;4&#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="center" valign="top">&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="top"><span class="elsevierStyleBold">T1</span>&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="top"><span class="elsevierStyleBold">2&#46;3 &#40;2&#46;4&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">2&#46;0 &#40;2&#46;1&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">2&#46;9 &#40;2&#46;6&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">2&#46;6 &#40;2&#46;6&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="top">&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="top"><span class="elsevierStyleBold">T12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">3&#46;4 &#40;2&#46;8&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">3&#46;0 &#40;2&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="top">&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="top"><span class="elsevierStyleBold">T32</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">4&#46;5 &#40;3&#46;0&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">4&#46;3 &#40;3&#46;2&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T48</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">3&#46;8 &#40;3&#46;2&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">3&#46;8 &#40;3&#46;3&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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  " colspan="4" align="left" valign="top"></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="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">VAS for swelling &#40;0&#8211;10 cm&#41;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;179&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  " colspan="4" align="left" valign="top"></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="top"><span class="elsevierStyleBold">T0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">3&#46;9 &#40;2&#46;0&#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="top">3&#46;8 &#40;1&#46;8&#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="center" valign="top">&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="top"><span class="elsevierStyleBold">T1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">1&#46;6 &#40;1&#46;7&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">1&#46;0 &#40;1&#46;4&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1&#46;1 &#40;1&#46;1&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;9 &#40;1&#46;4&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1&#46;3 &#40;1&#46;3&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">0&#46;7 &#40;1&#46;0&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T32</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1&#46;6 &#40;1&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1&#46;2 &#40;1&#46;4&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T48</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1&#46;5 &#40;1&#46;7&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">1&#46;0 &#40;1&#46;6&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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  " colspan="4" align="left" valign="top"></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="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Morning stiffness</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;413&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  " colspan="4" align="left" valign="top"></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="top"><span class="elsevierStyleBold">T0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">14&#46;2 &#40;14&#46;9&#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="top">32&#46;5 &#40;55&#46;2&#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="center" valign="top">&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="top"><span class="elsevierStyleBold">T1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">4&#46;8 &#40;12&#46;9&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">1&#46;9 &#40;5&#46;8&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">6&#46;2 &#40;13&#46;9&#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="top">4&#46;1 &#40;11&#46;5&#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="center" valign="top">&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="top"><span class="elsevierStyleBold">T12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">6&#46;6 &#40;22&#46;0&#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="top">2&#46;2 &#40;5&#46;0&#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="center" valign="top">&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="top"><span class="elsevierStyleBold">T32</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">12&#46;2 &#40;26&#46;2&#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="top">26&#46;9 &#40;76&#46;6&#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="center" valign="top">&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="top"><span class="elsevierStyleBold">T48</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">8&#46;8 &#40;15&#46;5&#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="top">11&#46;5 &#40;33&#46;3&#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="center" valign="top">&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  " colspan="4" align="left" valign="top"></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="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Knee flexion &#40;grade&#41;</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;661&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  " colspan="4" align="left" valign="top"></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="top"><span class="elsevierStyleBold">T0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">116&#46;1 &#40;14&#46;6&#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="top">115&#46;03 &#40;14&#46;5&#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="center" valign="top">&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="top"><span class="elsevierStyleBold">T1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">119&#46;4 &#40;16&#46;7&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">121&#46;97 &#40;16&#46;3&#41;</span><a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">120&#46;5 &#40;15&#46;3&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">123&#46;17 &#40;16&#46;4&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&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="top"><span class="elsevierStyleBold">T12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">120&#46;4 &#40;12&#46;5&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">121&#46;93 &#40;16&#46;9&#41;<a class="elsevierStyleCrossRef" href="#tfn5-cln64_12p1187">&#42;</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="center" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</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="top"><span class="elsevierStyleBold">T4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">5&#46;9 &#40;5&#46;5&#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="top">7&#46;5 &#40;5&#46;0&#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="top">&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="top" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">T12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top" style="border-bottom: 2px solid black">5&#46;5 &#40;5&#46;4&#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="top" style="border-bottom: 2px solid black">7&#46;6 &#40;5&#46;3&#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="top" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tfn10-cln64_12p1187"
              "etiqueta" => "&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara60">ANOVA for repeated measurements&#59;</p>"
            ]
            1 => array:3 [
              "identificador" => "tfn11-cln64_12p1187"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara70"><span class="elsevierStyleItalic">p&#60; 0&#46;05</span> &#40;p intra-group p in relation to T0&#41;&#58; Tukey multiple comparison test</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Use of number of sodium diclofenac tablets and oral prednisone &#40;doses&#41;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "t5-cln64_12p1187"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spara100" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">TH group</span>&#58; triamcinolone hexacetonide &#40;TH&#41;&#59; <span class="elsevierStyleBold">Sm&#47;TH group</span>&#58; <span class="elsevierStyleSup">153</span>SmPHYP &#43; TH&#59; <span class="elsevierStyleBold">SD</span>&#61; standard deviation</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col"><span class="elsevierStyleBold">ADVERSE EFFECTS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">Sm&#47;TH Group &#40;n&#61;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">TH Group &#40;n&#61;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">Post-injection flare</span> &#40;T1&#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="center" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&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="top"><span class="elsevierStyleBold">Urticaria</span> &#40;T1&#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="center" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Pruritus</span> &#40;T1&#44; T4&#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="center" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Chills</span> &#40;T1&#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="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Headache</span> &#40;T1&#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="center" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Rash on face</span> &#40;T1&#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="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Sweating</span> &#40;T1&#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="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Hot flashes</span> &#40;T1&#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="center" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">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="top"><span class="elsevierStyleBold">Hypertensive peak</span> &#40;T1&#44; T4&#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="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">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="top"><span class="elsevierStyleBold">Insomnia</span> &#40;T4&#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="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">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="top"><span class="elsevierStyleBold">Swelling of lower limbs</span> &#40;T12&#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="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Increased instability</span> &#40;T12&#44;T48&#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="center" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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  " colspan="3" align="left" valign="top"></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="top"><span class="elsevierStyleBold">EVENTS</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">Sm&#47;TH Group &#40;n&#61;30&#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="center" valign="top">TH Group &#40;n&#61;30&#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  " colspan="3" align="left" valign="top"></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="top"><span class="elsevierStyleBold">Polaciury</span> &#40;T1&#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="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">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="top"><span class="elsevierStyleBold">Urinary tract infection</span> &#40;T1&#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="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top"><span class="elsevierStyleBold">Acute sinus condition</span> &#40;T4&#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="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">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="top"><span class="elsevierStyleBold">Asthma episode</span> &#40;T4&#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="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">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="top"><span class="elsevierStyleBold">Vaginal Candidiasis</span> &#40;T32&#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="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">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="top"><span class="elsevierStyleBold">Femur fracture</span> &#40;T48&#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="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&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="top" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">Detached retina</span> &#40;T48&#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="center" valign="top" style="border-bottom: 2px solid black">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Distribution of the types of adverse effects and events between groups</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:35 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primer on rheumatic diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              RL Wilder \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:6 [
                        "editores" => "HRShumacher, JHKlippel, WJKoopman"
                        "titulo" => "Rheumatoid arthritis Epidemiology&#44; pathology and pathogenesis"
                        "paginaInicial" => "86"
                        "paginaFinal" => "89"
                        "edicion" => "10th ed"
                        "serieFecha" => "1993"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The occurrence and significance of hand deformities in early rheumatoid arthritis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => """
                              K Eberhardt \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              PM Johnson \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              L Rydgren \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/30.3.211"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Rheumatol"
                        "fecha" => "1991"
                        "volumen" => "30"
                        "paginaInicial" => "211"
                        "paginaFinal" => "213"
                        "link" => array:1 [
                          0 => array:2 [
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Article information
ISSN: 18075932
Original language: English
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es en pt

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