ML1CDCLCGIA DL LA INVLS1IGACICN UNIDAD II: DISLCS DL INVLS1IGACICN 1LCkIA 4 SLMANA C8IL1IVC DL LA CLASL Al nallzar la clase el alumno ser capaz de: 1.ConocerycomprenderlaesLrucLuradeunLsLudloCllnlco AleaLorlzado Sackeu DL., naynes k8., Guyau Gn., 1ugwe|| . Lp|dem|o|og|a c||n|ca. C|enc|a bs|ca para |a med|c|na c||n|ca. 2 ed. Madr|d: Ld|tor|a| Md|ca anamer|cana, 1994. I|etcher kn., I|etcher SW., Wagner Ln. Lp|dem|o|og|a c||n|ca. 2 ed. 8arce|ona: Masson-W||||ams & W||k|ns, 1998. Caracter|sncas de |os Lstud|os Lxper|menta|es LsLos esLudlosson uullzados para evaluar la !"#$#%$&'()*+%,$, de las lnLervenclones Lerapeuucas. Ll lnvesugador aslgna" la exposlcln. Ll conLrol que se uene sobre el dlseno, asegura la valldez de sus resulLados. jUL LS UN LS1UDIC CLINICC ALLA1CkI2ADC? Sackeu DL., naynes k8., Guyau Gn., 1ugwe|| . Lp|dem|o|og|a c||n|ca. C|enc|a bs|ca para |a med|c|na c||n|ca. 2 ed. Madr|d: Ld|tor|a| Md|ca anamer|cana, 1994. I|etcher kn., I|etcher SW., Wagner Ln. Lp|dem|o|og|a c||n|ca. 2 ed. 8arce|ona: Masson-W||||ams & W||k|ns, 1998. Friedman LM, Furberg CD, DeMets DL. Fundamentals of clinical trials. 3 rd. ed. New York: Springer Verlag; 1998.

Hulley SB, Cummings Sr. Designing clinical research. 2 nd. ed. Baltimore: Lippincott Williams and Wilkins; 2001.unLCAesunaevaluaclnexperlmenLaldeun producLo,susLancla,medlcamenLo,-.#/%#$ -(+$1.*2#$,queaLravesdesuapllcaclnenseres humanos preLende valorar su ecacla. Su Validez, radica en elproceso de Aleatorizacin MULS1kLC INILkLNCIA -So|ounbuenMuestreogaranuzaquelalnformacln quegeneraremosnospermlLaproyecLarvlldamenLelas concluslones al unlverso de lnLeres. or Conven|enc|a Consecunvo robab|||snco - AleaLorlo Slmple - AleaLorlo LsLraucado - AleaLorlo Agrupado ALLA1CkI2ACICN aralograrquelasnaLuralesd|ferenc|asex|stentesentre|os|nd|v|duospuedanquedar|gua|mented|str|bu|dasenlosdlferenLes grupos de esLudlo se recurre al azar. L|props|toesba|ancearentre|osgruposfactoresque puedan |nu|r sobre |a var|ab|e depend|ente. 34& 56'!78 !9 :;*(?@+$ ;Grupo 1 A+*1B C o oI I o o!D(#@B !D(#@B 1lLulo ldenucarelesLudlocomounLCAcondlsLrlbucln aleaLorla 8esumen resenLar un resumen esLrucLurado lnLroduccln lndlcarhlpLeslslnlclales,losob[euvoscllnlcosylos anllsls de cada grupo . MeLodosroLocolo uescrlblr: LapoblaclnplanlcadaysuscrlLerlosdelncluslny exclusln. LaslnLervenclonesplaneadasyelmomenLodesu apllcaclones. Las varlablesprlmarla y secundarla (s) y la(s) dlferenclas(s) mlnlma(s)relevanLe(s),elndlcarcomoseproyecLoel Lamano de muesLra deseado Aslgnacln uescrlblr: AleaLorlzacln (lndlvlduo,grupo) MeLodo uullzado para reallzar la aleaLorlzacln MeLodo de oculLacln de la aslgnacln y momenLo en que fue reallzada . (Sobres sellados, compuLaclonal) LnmascaramlenLo (obllgaLorlo) uesconoclmlenLo de la lnLervencln que reclben los su[eLos esLudlados, LraLanLes, evaluadores, qulenes recolecLan y anallzan los daLos. Clego slmple, uoble clego y 1rlple clego 8esulLadosllu[o y segulmlenLo de los paruclpanLes resenLar un dlagrama donde se resuma el u[o de paruclpanLes,elnumeroalmomenLodela as l gnacl nal eaL or l a,medl cl nl nl cl al , lnLervenclonesylasmedlclonesnalesalLermlnar el segulmlenLo.Anllsls CalcularlasmedldasdeefecLosobrelavarlable prlmarla y secundarlas, con un esumador y medlda de preclsln. ConslderaranllslsesLadlsucoporroLocolo, lnLencln de 1raLar y peor escenarlo resenLar daLos resumldos en Lablas y grcos con pruebas esLadlsucas adecuadas y deLalladas randomisedstudies comparingdisc prosthesis withfusion, the clinical outcome ofdisc prosthesis was atleast equivalent to that of fusion.8-11As surgical proce-dures should be evaluated against non-surgicalmethods,12 13we compared the efficacy of disc prosthe-sis and a multidisciplinary rehabilitation programme.METHODSStudydesignA multicentre study conducted at five university hos-pitals in Norway included patients with low back painand degenerative discs. Patients were included in theperiod between April2004 andMay 2007and weretreated within three months after randomisation.They were randomised in blocks with a website hostedby the medical faculty. Allocationwas concealedfor allpeople involved in the trial. A coordinating secretarynot involved in the treatment could access randomisa-tion details on the internet. The patient and the treatingunit were informed about the allocation shortly afterrandomisation. Randomisation was stratifiedby centre(the five university hospitals) and whether the patienthad had previous surgery (microsurgical decompres-sion) or not. Independent observers collectedandentered data. Storage of data was allowed by the Nor-wegian data inspectorate.ParticipantsPatients were referred from all health regions in Nor-way. They were recruited from local hospitals or pri-mary care to their nearest university hospital as usualwithout anysupplemental recruitment attempt. Anorthopaedic surgeon and a specialist in physical medi-cineandrehabilitationexaminedthepatientsbeforeenrolment. All patients were informed about the pro-cedures and told that neither of the treatment methodswas documentedas superior totheother. Eligiblepatientswereaged25-55andhadlowbackpainasthe main symptomfor at least a year, structuredphysiotherapyorchiropractictreatment for at leastsix months without sufficient effect, a score of at least30 on the Oswestry disability index, and degenerativeintervertebral disc changes inL4/L5 or L5/S1, or both.Degenerationhadtoberestrictedtothetwolowerlevels. We evaluated the following degenerativechanges: at least 40%reduction of disc height,14Modic changes type Ior II, or both,15high intensityzone in the disc,16and morphological changes classi-fied as changes in signal intensity in the disc of grade3 or 4.17The disc was classified as degenerative if thefirst criterion alone or at least two changes were foundon magnetic resonance imaging. The discs were inde-pendentlyclassifiedbytwoobservers (orthopaedicsurgeon/radiologist). Whentherewasdisagreement,a third observer classified the images and the outcomewas decided by simple majority.Degeneration of the facet joints was not an exclusioncriterion, but symptoms of nerveroot involvementwere. Detailsof furtherinclusionandexclusioncri-teria, compliance withrandomisation, and drop-outsare listed in the appendix 1 on bmj.com.StudyinterventionsRehabilitationTherehabilitationwas basedonthetreatment model describedby Broxet al4andconsistedof a cognitive approach and supervised physical exer-cise. A team of physiotherapists and specialists in phy-sical medicine and rehabilitation directed themultidisciplinary treatment. Other specialists, such aspsychologists, nurses, social workers, etc, could com-plete the team. The interventionwas standardisedthrough three seminars and videos and lecture sessionsfor the treatment providers before the study. The inter-ventionwasorganisedasanoutpatienttreatmentingroups at the involved university hospitals and lastedfor about 60 hours over three to five weeks. The treat-ment consisted of lectures and individual discussionsfocusing on relevant topics (such as anatomy and the3 patients excluded shortly after randomisationAllocated to rehabilitation (n=87)Started allocated intervention (n=80)Did not start allocated intervention (n=7)3 patients excluded shortly after randomisationAllocated to surgery (n=86)Received allocated intervention (n=77)Did not receive allocated intervention (n=9)AnalysedIntention to treat (n=86)Per protocol (n=60)AnalysedIntention to treat (n=86)Per protocol (n=71)Lost to follow-up at 6 weeks (n=8)Withdrew during treatment (n=6)Lost to follow-up at 6 weeks (n=0)Lost to follow-up at 3 months (n=0) Lost to follow-up at 3 months (n=9)Screened for eligibility (n=605)Randomised (n=179)Excluded (n=426)*:Did not meet inclusion criteria (n=378)Refused to participate (n=48)AllocationFollow-upAnalysisEnrolmentLost to follow-up at 6 months (n=2) Lost to follow-up at 6 months (n=13)Lost to follow-up at 1 year (n=4) Lost to follow-up at 1 year (n=14)Lost to follow-up at 2 years (n=4)** Lost to follow-up at 2 years (n=14)Fig 1 | Enrolment, randomisation, and follow-up of study patients, showing cumulative values attwo years. *Not enough degenerative change to satisfy inclusion criteria (n=29), degenerativechanges in more than two lower lumbar discs (n=80), Oswestry disability index score too low(n=88), did not want to undergo surgery (n=28), did not want to participate in rehabilitation(n=20), too much general pain (n=20), had previously been through similar training programme(n=26), and other reasons (n=135; deformity, psoriasis arthritis, language problems,coccygodynia, age, fracture, previous operation, tumour, spondylodiscitis, hip arthrosis).Coronary heart disease and heart attack some days after randomisation (n=1); obviousexclusion criterion discovered some days after randomisation (n=50; earlier large abdominaloperation (n=1), not enough degenerative change to satisfy inclusion criteria (n=2),degenerative changes in more than two lower lumbar discs (n=2). One patient received one oftwo disc prostheses because of bleeding. One patient with serious vascular complicationunderwent secondary leg amputation and was lost to follow-up. One patient crossed overbetween 6 months and 1 year and five patients between 1 year and 2 years. Five patientsunderwent surgery with disc prosthesis and one patient with fusion. **Two patients underwentsurgery with instrumented fusion before two year follow-up.One patient excluded becauseof missing baseline values and follow-up valuesRESEARCHpage2of11 BMJ | ONLINEFIRST| bmj.comjournal of orthopaedic & sports physical therapy|volume 37|number 3|march 2007|93Mann-Whitney U test. Because not all the questions in a domain were used from the LInsalataetal34questionnaire,thereli-ability and validity of the questions used in this study are unknown.ExternalrotationROMwasmea-suredinitiallyandattheendofeachof the6treatmentsessionsandcompared betweengroupsusinga2-by-7mixed-modelanalysisofvariance(ANOVA), withgroup(2levels)astheindepen-dentfactorandmeasurementsession astherepeatedfactor.Sincetherewas asignicantgroup-by-timeinteraction, independentt tests were performed be-tween groups for each time interval and pairedttestsperformedwithingroups toassessthediferenceintheexternal rotation ROM compared to baseline for eachgroupseparately.Becauseofthe number of tests performed, alpha was set at .003, to make correction for multiple comparisons.Thediferencesbetweenbaseline andthenaltreatmentsessionVAS painscoreswerecomparedwithinand betweengroupsusinga2-waymixed-modelANOVA.Functionalchanges withineachgroupovertimewereana-lyzedusingWilcoxonsigned-ranks tests.Questions1and2wereanalyzed betweengroupsatbaselineandafter6 treatmentsusingchi-squaretests,and thecombinedquestions3through5 wereanalyzedusingMann-WhitneyU tests. The Spearman rho was used to nd if there were any signicant correlations between changes in VAS pain scores and changes in the function scores, changes in VAS pain scores and changes in shoul-derexternalrotation,andchangesin function scores and changes in shoulder external rotation, independent of group. The alpha was set at .05.RESULTSSubjectsOftheinitial58patientsthat wereevaluated,38subjectswere excluded for the following reasons: abnormal radiographs (n = 13), presented with a proximal humerus fracture (n = 1), rotator cuf tears as diagnosed by arthro-grams (n = 2), neurological conditions of cerebral palsy and stroke (n = 2), a diag-nosis of tendonitis (n = 1), presented after havingamanipulationunderanesthetic (n = 3), planning on manipulation under anesthetic before 6 visits (n = 2), shoulder external rotation ROM decits primarily attributedtomuscleexibilitydecits, including1withexternalrotationROM that did not change with abduction (n = 14), and did not have English comprehen-sion sufcient to understand the consent forms (n = 2).Twenty subjects joined the study. Two subjects left the study before completion ofthe6treatmentsessions.Datafrom thesesubjectswereomittedfromthe analyses (FIGURE 4). Demographic data for the remaining 18 subjects who completed all treatment sessions are presented in TA-BLES 1 and 2. At baseline, the groups were determinedtobesimilarexceptforthe side of the afected arm. All subjects had markedpainfulrestrictionofactiveand passive shoulder ROM with external ro-tation being most limited. Thus the sub-jects in this study were presumed to be in Neviasers stage II to IV. 40,41TABLE 1Comparison of Subject Characteristics at Baseline by GroupSubject CharacteristicsAM Group (n = 10)PM Group (n = 8)P ValueAge (y)*54.78.050.46.9.24Height (cm)*166.910.2168.711.4.74Body mass (kg)*80.124.671.819.3.44Gender (females, males)8, 26, 2.80Dominant arm10 right8 right Afected arm9 right, 1 left3 right, 5 left.02Occupation6 sedentary, 4 manual6 sedentary, 2 manual.50Minor injury recalled3 yes, 7 no3 yes, 5 no.74Symptoms duration (mo)||8.4 (2,12)10.9 (4,60).36Abbreviations: AM, anterior mobilization; PM, posterior mobilization.* MeansSD. Independent t test. Chi-square test. Previous minor/trivial injury5,16,35,46 to afected shoulder.|| Median (minimum, maximum). Mann-Whitney U test.TABLE 2Comparison of Clinical Characteristics at Baseline by Group*Clinical CharacteristicsAM Group (n = 10)PM Group (n = 8)P ValuePassive abduction ()55.09.451.310.8.63Active external rotation ()11.115.51.316.8.21VAS pain scale (cm)8.32.97.42.3.48Function Q13.70.73.90.3.65Function Q22.30.72.70.9.70Function Q3-5||8.72.18.91.9.90Abbreviations: AM, anterior mobilization; PM, posterior mobilization; VAS, visual analogue scale.* Values expressed as meanSD. Independent t test. Q1 and Q2 (scores 0-4; 0 = best, 4 = worst). Chi-square test.|| Q3-5 (scores as above are summed, from 0-12). Mann-Whitney U testpain and disability subscales and total SPADI scores were sig-nicantinbothgroups(Table3).ComparisonofSPADItotalscorebetweenUSandshamUSgroupsareshowninFig.1.General healthstatusof thepatientswasevaluatedusingSF-36beforetreatment andat the3rdmonth. Therewasnostatisticallysignicant differenceinthe8domainsof SF-36andPCSandMCSsummaryscalesbetweenthetwogroups.Physical role, bodilypainandPCSscoresimprovedsigni-cantly in the US group, whereas bodily pain, vitality andPCSscores improved signicantly in the shamUSgroup.PCSandMCSscoresofthepatientsaregiveninTable3.The percentage of exercise compliance was calculated fromthechartsgiventothepatientsonthecontrolevaluation.Ex-ercise compliance of the shamUSgroupwas signicantlyhigher than the US group (76.6 15.2 vs. 67.1 14.9 respec-tively,p 0.04).4.DiscussionHeat agents (supercial and deep), analgesic modalities andexerciseareamongtheconventionallyusedphysical therapyregimensinadhesivecapsulitis[8].Althoughtheliteratureiscontroversial about its effectiveness, physical therapy isamongtherst-linetherapeuticchoicesinadhesivecapsulitis[3,5,7,20].Exercise and two different deep heat modalities (short wavediathermyandultrasound) wereappliedtothepatientswithadhesivecapsulitis byMaoet al. [6], whofoundthat deepheatmodalitiesimproveROMandjointspacecapacityespe-cially in early cases. The lack of a control group makes it dif-cult tostatethat physical therapyinterventionscausedthisclinical and radiographic improvement. In our study weTable2Shoulder range of motion (ROM) values and improvements in ROM values ofthepatientsbetweenpostepre-treatmentandcontrolepre-treatmentvaluesinultrasound(US)andShamUSgroupsUS ShamUS pAbductionPre-treatment 101.4 20.9 113.5 14.1 0.03Post-treatment 142.8 25.9 146.0 26.2 0.72Control(3rdmonth) 147.8 30.1* 148.0 26.5* 0.98Postepre-treatment 41.5 15.2 32.5 18.5 0.06Controlepre-treatment 45.4 26.9 34.4 21.3 0.15FlexionPre-treatment 133.2 16.0 143.7 16.3 0.01Post-treatment 162.6 12.4 165.4 15.0 0.31Control(3rdmonth) 163.7 16.5* 168.5 13.0* 0.34Postepre-treatment 29.4 15.2 21.7 11.4 0.04Controlepre-treatment 30.8 19.6 24.6 12.9 0.21InnerrotationPre-treatment 29.2 15.7 47.3 18.8 0.001Post-treatment 52.2 15.7 58.3 15.5 0.12Control(3rdmonth) 57.4 13.8* 60.9 15.3* 0.21Postepre-treatment 22.9 13.4 11.0 11.9 0.002Controlepre-treatment 27.6 17,5 12.8 13.4 0.001OuterrotationPre-treatment 34.8 14.7 55.8 17.2 0.000Post-treatment 58.0 16.6 71.3 14.9 0.004Control(3rdmonth) 65.7 19.4* 75.4 15.5* 0.05Postepre-treatment 23.2 12.4 15.4 12.4 0.02Controlepre-treatment 30.7 17.3 19.4 14.2 0.02*Signicant improvement inrepeatedmeasures of abduction, exion, innerandouterrotation( p < 0.0001).Table3Pain with motion (VAS), SPADI scores and SF-36 summary scores of the pa-tientsintheUSandshamUSgroupsUS(n 25) ShamUS(n 24) pPainwithmotion(VAS)Pre-treatment 80.8 18.2 78.0 18.4 0.59Post-treatment 39.6 25.3 40.7 20.3 0.56Control(3rdmonth) 24.8 29.9* 23.6 25.5* 0.83SPADIpainPre-treatment 66.9 13.8 57.7 18.0 0.04Post-treatment 40.1 18.6 35.6 13.7 0.37Control(3rdmonth) 31.0 20.0* 25.2 18.3* 0.39SPADIdisabilityPre-treatment 66.6 14.6 62.1 17.3 0.43Post-treatment 37.0 18.6 38.2 17.8 0.72Control(3rdmonth) 29.5 21.6* 26.4 19.6* 0.50SPADItotalPre-treatment 66.5 13.7 63.1 13.8 0.39Post-treatment 38.6 17.4 38.1 15.9 1.00Control(3rdmonth) 30.0 20.9* 25.5 17.8* 0.45SF-36PCSPre-treatment 38.9 7.9 36.6 9.8 0.36Control(3rdmonth) 44.2 8.4* 44.6 8.8* 0.83SF-36MCSPre-treatment 43.5 10.2 42.0 7.7 0.62Control(3rdmonth) 44.8 11.5 43.8 10.6 0.81*Signicant improvement inrepeatedmeasuresofpainwithmotion(VAS),SPADI pain, disability and total scores and PCS score of SF-36 ( p < 0.0001).Sham US USSPADI Total Score706050403020Pre-treatment Post-treatment ControlFig.1.ComparisonofShoulderPainandDisabilityIndex(SPADI)scorebe-tweenUSandshamUSgroups.448 H.Dogruetal./JointBoneSpine75(2008)445e450MLDIk = Aslgnar valor a una Var|ab|e CualqulercaracLerlsucaocualldadquepuedasermedlda,y que adems camble de un su[eLo a oLro, o en el mlsmo su[eLo en un deLermlnado uempo. Cuanntanvas: eso (kg) - 1alla (cm) -( ) de Pg (g/dl) E8FG(2H$?I Cua||tanvas: uolor, lunclonalldad E'*FG(2H$?I MAGNI1UD DLL LILC1C CuleslamagnlLuddelefecLodelalnLervencln?yCunpreclsaeslamagnlLud del resulLado observado? La magnlLud del efecLo se expresa en las MLDIDAS DL LILC1C, que en elcasodeCuLcomes8lnarlosoulcoLmlcos,sepuedecalcularunnumerodenomlnado LS1IMADCk UN1UAL (88, 8A, C8, nn1) Ln el caso de las varlables conunuas y ordlnales los resulLados se expresana Lraves de esLadlgrafos como romed|o y Desv|ac|n Lstndar noslnLeresacompararlaefecuvldaddeunnuevoLraLamlenLo A frenLe a la de oLro esLndar 8 en elLraLamlenLo de una paLologla x P0= no exlsLen dlferenclas enLre ambos LraLamlenLos P1= Ll LraLamlenLo A, es mas efecuvo que 8 para el uo de x nIC1LSISkUL8A DL CCN1kAS1L DL n Altman D.G. Practical Statistics for Medical Research. London: Chapman & Hall; 1991 Kelsey J.L., Whittemore A.S., Evans A., Thompson W.D. Methods in Observational Epidemiology. 2nd ed. New York: Oxford University Press; 1996. Argimon Palls J.M., Jimnez Villa J. Mtodos de investigacin clnica y epidemiolgica. 2 ed. Madrid: Ediciones Harcourt; 2000. LkkCk 1IC 1, o (A|fa)AlreallzarunanllslsesLadlsuco,podrlamoscorrerelrlesgodeequlvocarnos al rechazar la P0, cuando esLa es verdadera ! VALCkp LASIGNIIICACICNLS1ADIS1ICA!condlclnresulLanLedelrechazodeuna P0 (medlanLe pruebas esLadlsucas de slgnlcacln). Sl p0.03 !no rechaza P0 Prtega Daz S, Pita Fernndez S. Clculo del tamao muestral para la determinacin de factores pronsticos. Cad Aten Primaria 2002; 9: 30-33.En estadstica, un resultado se denomina estadsticamente significativo p