Interventions for treating tuberculous pericarditis (Review) MayosiBM This is a reprintof a Cochrane review, prepared and maintainedbyThe Cochrane

Col laboration andpublishedin TheCochraneLibrary2009, Issue 1 This is a reprintof a Cochrane review, prepared and maintainedbyThe Cochrane Col laboration andpublishedin TheCochraneLibrary2009, Issue 1 http://www.thecochranelibrary.com Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

TABLE OF CONTENTS HEADER ....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY .............................. 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 3 METHODS ...................................... 3 RESULTS ....................................... 4 DISCUSSION ..................................... 5 AUTHORS CONCLUSIONS ............................... 6 ACKNOWLEDGEMENTS ................................ 6 REFERENCES ..................................... 7 CHARACTERISTICSOFSTUDIES ............................. 8 DATAANDANALYSES.................................. 11 Analysis1.1.Comparison1Tuberculouspericarditis: steroidsvsplacebo,Outcome1Deathf romall causes. . . . 12 Analysis1.2.Comparison1Tuberculouspericarditis: steroidsvsplacebo,Outcome2Deathf rompericarditis. . . . 12 Analysis1.3.Comparison1Tuberculouspericarditis: steroidsvsplacebo,Outcome3Repeat pericardiocentesis. . . 13 Analysis1.4.Comparison1Tuberculouspericarditis: steroidsvsplacebo,Outcome4Perica rdiectomy. . . . . . 13 Analysis1.5.Comparison 1Tuberculouspericarditis: steroids vsplacebo,Outcome5Deat h orpersisting disease at2years followup. ................................... 14 Analysis2.1.Comparison2TuberculouspericarditisinHIVpositiveparticipants: steroid s vsplacebo,Outcome1Death fromall causes. ................................. 14 Analysis 2.2. Comparison 2 Tuberculous pericarditis in HIV positive participants : steroids vs placebo, Outcome 2 Constrictivepericarditis. .............................. 15 Analysis3.1.Comparison3Tuberculouspericardial effusion:opensurgicaldrainagevssta ndard care,Outcome1Death fromall causes. ................................. 15 Analysis3.2.Comparison3Tuberculouspericardial effusion:opensurgicaldrainagevssta ndard care,Outcome2Death frompericarditis.................................. 16 Analysis3.3.Comparison3Tuberculouspericardial effusion:opensurgicaldrainagevssta ndard care,Outcome3Repeat pericardiocentesis. ................................ 16

Analysis 3.4. Comparison 3 Tuberculous pericardial effusion: open surgical drain age vs standard care, Outcome 4 Pericardiectomy.................................. 17 Analysis3.5.Comparison3Tuberculouspericardial effusion: opensurgicaldrainagevsst andard care,Outcome5Death or persistingdiseaseat2yearsfollowup. ......................... 17 WHAT SNEW ..................................... 17 HISTORY....................................... 18 CONTRIBUTIONSOFAUTHORS ............................. 18 DECLARATIONSOFINTEREST .............................. 18 SOURCESOFSUPPORT ................................. 18 INDEXTERMS .................................... 18 Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

[Intervention Review] Interventionsfor treating tuberculouspericarditis Bongani MMayosi1 1TheCardiacClinic,E25GrooteSchuurHospital,CapeTown,SouthAfrica Contact address:BonganiMMayosi,TheCardiacClinic,E25GrooteSchuurHospital,Observat ory7925,CapeTown,SouthAfrica. bongani.mayosi@uct.ac.za. Editorial group: CochraneInfectious DiseasesGroup. Publication status and date: Edited(nochangeto conclusions),publishedinIssue1,2009. Review content assessed as up-to-date: 16June2002. Citation: MayosiBM.Interventionsfor treating tuberculouspericarditis. Cochrane Database of Systematic Reviews 2002,Issue4.Art. No.:CD000526. DOI:10.1002/14651858.CD000526. Copyright2009TheCochraneCollaboration. PublishedbyJohnWiley&Sons,Ltd. ABSTRACT Background Tuberculous pericarditis -tuberculosis infection of the pericardial membrane (pe ricardium) covering the heart -is becoming more common.Theinfection canresultinfluid around theheart orfibrosisof thepericardium ,which canbefatal. Objectives Inpeoplewith tuberculouspericarditis,toevaluatetheeffectsondeath,life-threatenin g conditions,andpersistentdisability of:1.6month antituberculousdrug regimens compared with regimensof9 monthsormore;2. corticost eroids;3.pericardialdrainage; and4. pericardiectomy.

Search strategy We searched theCochraneInfectious DiseasesGroup trials register(January 2005); t heCochraneControlledTrials Register (Issue4, 2004);MEDLINE(1966 toJanuary2005);EMBASE(1980 toJanuary2005);andcheckedtherefere ncelistsof existing reviews.We also contacted organizationsandindividualsworkinginthefield. Selection criteria Randomized andquasi-randomized controlled trialsof treatmentsfortuberculousperic arditis. Data collection and analysis Two reviewers independently assessed trial quality and extracted data. Meta-anal ysis using fixed effects models calculated summary statistics,provided therewasnostatistically significantheterogeneity,and express ed resultsasrisk ratio.Study authorswere contacted for additionalinformation. Main results Fourtrialsmettheinclusion criteria,with atotal of469participants.Treatmentsteste d wereadjuvant steroidsand surgicaldrainage. Twotrials with atotal of383participantstested adjuvant steroidsinparticipants wi th suspected tuberculouspericarditisinthepreHIV era.Fewerparticipantsdiedintheinterventiongroup,butnumbersweresmall(risk rat io[RR] 0.65; 95% confidenceinterval [CI] 0.36 to1.16,n =350).Onesmall trial tested steroidsinHIVpositiveparticipants with effusionshowed asimilarpattern(RR 0.50;95%CI0.19 to1.28,n =58). Onetrialexamined opensurgicaldrainage compared with conservativemanagement,and s howed surgery relieved cardiactamponade. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Authors conclusions Steroids couldhaveimportantclinicalbenefits,butthetrialspublishedtodatearetoosma lltodemonstrateaneffect.Thisrequireslarge placebo controlledtrials.Subgroupanalysis could explorewhethereffusionorfibrosis modifytheeffects.Therapeuticpericardiocentesis underlocal anaesthesia andpericardiectomy also requirefurther evaluation. PLAIN LANGUAGE SUMMARY Tuberculosis infection of the membrane around the heart is uncommon but life threatening. There is little reliable research on best practice in relation to what drugs to give and when and how to operate. Currentlydoctorsprescribe antituberculousdrugs and removethemembraneifitis makin g thepatientill.However,doctors varyin theway they managethis conditionintermsof whatantituberculousdrugstogiveand when tooperate.Wefound noclinical trials thattackled thelength of anti-TB treatment needed.Trials of steroidsgiven with a ntituberculousdrugs suggestpossiblebenefit,but thiswasnotdemonstrated conclusively.Opensurgicaldrainageof thefluid accumulating betweentheheart and themembraneusing general anaesthesia was associated with less life threatening re-accumulation of fluid (cardiac tamponade), but with more deaths,but conclusions arenotpossibleasthenumbersofpatientsstudied wastoosmall.

BACKGROUND Definition Tuberculous pericarditis is tuberculosis infection of the pericardial membrane(pericardium) covering theheart.Infectionof the pericardium canresultinabuild-upoffluid(effusion) aroundthe heart, which constrains its pumping action (tamponade), and is life threatening. Sometimes the infection causes a thickening of thepericardiumwithoutaneffusion,and this canalso constrain thepumping action (constrictivepericarditis).Tuberculouspericarditis manifests with fatigue, shortness of breath, and swelling of thebody,and can causedeath. Occurrence Healthcarepractitionersindeveloping countrieswheretuberculosisis commonarefamiliarwith the condition(Gelfand1957; Strang1984).Indeveloped countries,the conditionoccursinless than1%ofallpeople withtuberculosis(Lorell1997).Thehuman immunodeficiencyvirus(HIV) epidemicinsome countriesisresultinginmore casesof tuberculosis,and tuberculouspericarditis isbecoming more common(Cegielski1990). Management Beforeantituberculous chemotherapywasdiscovered,tuberculous pericarditiswasusuallyfatal,eitherintheacutestageowingto cardiactamponadeorlater asaresult of constrictionand theresultingdissemination oftuberculosisthroughoutthebody(Harvey 1937). With the advent of effective antituberculous chemotherapy in the 1940s, the mortality decreased to about 35% of cases by1970(Shapiro1953;Schepers1962;Hageman1964;Rooney 1970). However, even with modern drugs and surgery, the mortality rate remainshigh andis estimatedtobebetween8 and17% (Desai1979;Bhan1980). Debates 1. Length of treatment: various specialists recommend different treatment regimens ofdifferentlengths,from6 months (Strang1987;Strang1988)to9 months(Sagrista1988;Fowler 1991),and12 months(Koh1994).The first objectiveof this review was toidentify the most effective antituberculous drug combination and theoptimumduration of treatment. 2. Steroiddrugs: steroidsareanti-inflammatorydrugsthat maybeexpected toreducetheaccumulationof fluid or developmentof adhesionsin thepericardium that areinducedby the tuberculosisinfection.Some authors recommend the routine useof steroidsinall casesof tuberculouspericarditis(Alzeer Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

1993;Senderovitz1994;Strang1997).In contrast,otherexperts advisethat corticosteroidsshouldbereservedforpeoplewhoare criticallyill with recurrentlarge effusion and whodo not respond topericardialdrainage and antituberculousdrugsalone(Lorell 1997).This review aimed to assess steroidsin allpeople with tuberculouspericarditis, and to explore whether the type of disease(effusiveor constrictive)influenced outcomes. 3. Completedrainageof thepericardial fluid versusdrainage for complications:pericardialdrainageissometimesperformedas an open surgicalprocedure undergeneral anaesthesia(Strang 1988), orpercutaneously underlocal anaesthesia with ultrasound or fluoroscopicguidance.Therequirement and optimal method fordrainageis notknown(Strang1988). 4. Whentoremovethepericardiumsurgicallyinpeoplewith tuberculous constrictivepericarditis.Somespecialistsadvisean early conservativeapproachwith surgery applied to caseswhodo not respond afteraninitialperiod of antituberculous medication (Schrire1967).Othersadviseearly surgeryinall affected cases( Quayle1987). In reviewing these four areas, we sought any evidence of effect across the whole spectrum of the disease. We then intended to explore whether any effects identified were modified by: (1) the type of disease -early (effusive) disease compared to late forms (constrictive pericarditis); or (2) whether people were immunosuppressed (HIVpositive). OBJECTIVES Inpeople with tuberculouspericarditis, to evaluate the effects on death,life-threatening conditions,andpersistentdisability of: 1. 6-month antituberculous drug regimens compared with regimens of9 months or more; 2. corticosteroids; 3. pericardialdrainage; 4. pericardiectomy. METHODS Criteriafor considering studiesforthisreview Types of studies Randomized andquasi-randomized controlled trials. Types ofparticipants Peopleof all agesrequiring treatmentfor clinicallydiagnosed tuberculous pericarditis (effusive, constrictive, or effusive-constrictive) . Types ofinterventions Any intervention intended to treat tuberculous pericarditis, including antituberculous drugs, corticosteroids, or surgery. Types of outcome measures Primary

Allcausedeath. Secondary Death ordisabled at1 to2yearsfollowup. Disabled is defined asahistory of restrictedphysical activity, combined with signsof cardiac compromiseprespecifiedintheprotocol(suchas clinical, radiographic, and electrocardiogram evidence of persistingpericardialdisease). Death attributed topericarditis. Occurrence of tamponade requiringdrainage of the pericardium (pericardiocentesis). Needforexcision of thepericardium(pericardiectomy). Search methodsforidentificationof studies We have attempted to identify all relevant studies regardless of language orpublication status(published, unpublished,inpress, andinprogress). We searched theCochraneInfectious Diseases Group specialized trialsregisterforrelevanttrials(January2005) using thesearch terms pericarditis and tuberculosis .Themethodsused arepublishedinThe Cochrane Library inthe section onCollaborativeReviewGroups. We searched the Cochrane Controlled Trials Register published in The Cochrane Library (Issue 4, 2004) using the search terms pericarditis and tuberculosis . We searched the electronic databases, MEDLINE (1966 to January2005) andEMBASE(1980toJanuary2005), usingthetopic search terms in combination with the search strategy developed bytheCochraneCollaboration anddetailedin theCochraneReviewers Handbook( Clarke2000). We contacted organizations and individuals working in the field includingtheMRCHIVClinicalTrialsCentre,London,UK,and Faculty ofMedicine,University ofZimbabwe. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Externalrefereeswereaskedtocheckthecompletenessofthesearch strategy,andtoidentifyany additional unpublished, ongoing, and plannedtrials. We examined existing reviews of tuberculouspericarditisfor relevant citations(Schrire1967;Bhan1980;Fowler1991;Fowler 1992; Alzeer 1993; Senderovitz 1994; Fowler 1995; Cisneros 1996;Dooley1997;Strang1997). Data collection and analysis Selection of studies BMMayosi(BMM)andMNtskehe(MN)independentlyapplied theinclusion criteriatoallidentified trials. Data extraction and management Usingdatafromthepublishedarticles and unpublishedinformationsuppliedby thetrialists,weperformed ananalysis of allparticipants as they were randomized. We excluded only those who weretrulylost tofollow up andin whomithad notbeenpossible todetermine the relevant outcomes. Assessment of risk ofbiasinincluded studies We assessed the methodologicalquality of eachincluded trialfor theiradequacyof concealment of allocation,generationof allocation sequence,blinding, andfollow up ofparticipants, using the standard methods of theCochraneInfectious DiseasesGroup. Data synthesis We used meta-analysis with a fixed effects model to calculate the summary statistics,provided therewas no statistically significant heterogeneity,and expressed results as relative risk. We combined trialsthatincludedparticipantswith thedifferent clinical syndromes oftuberculouspericarditis(pericardial effusion and constrictivepericarditis) toestimatethesizeand significance of the effect of adjuvant corticosteroids on the outcomes. RESULTS Description of studies See:Characteristics ofincluded studies. Four trials met the inclusion criteria, three conducted in South AfricaandoneinZimbabwe,withatotalof469participants.Trial size varying from 28 to 240 participants (see Characteristics of included studies).ThethreeSouthAfricantrialswere conducted in the period before the human immunodeficiency virus (HIV) pandemic(Schrire 1959; Strang 1987; Strang 1988). One trial was conductedinHIVpositivepeople(Hakim2000). Participantswereeitherthosewithtuberculouspericardialeffusion (Schrire 1959; Strang 1988; Hakim 2000)or with tuberculous constrictivepericarditis(Strang1987). Interventions examinedwere:(1) adjuvant steroids(Schrire1959; Strang 1987; Strang 1988; Hakim 2000); and (2) open surgical drainage on admissioninparticipants withtuberculouspericardial

effusion(Strang1988). The length of follow up was unspecified in Schrire 1959, 18 monthsin Hakim2000, andtwoyearsin Strang1987and Strang 1988. The outcomes measured are listed in the Characteristics of included studies. All cause death was not reported in Strang 1987 and Strang1988;thisinformation was obtaineddirectlyfromthe authors.Strangdefined favourableclinical statusat24 months if thefollowing criteriawerefulfilled orif only onewasstill abnormal: unrestrictedphysical activity;pulse rate<100/minute;jugularvenouspulse< 5 cm; arterialpulsusparadoxus<10 mmHg; absenceof ascitesoroedema; cardiothoracicratio<55%; electrocardiogram voltage > 6 mm in V6 or > 4 mm along the frontal axis. Hakim2000 did notreport a category ofdeathsfrompericarditis, neitherwereoutcomes relatedto repeatpericardiocentesis andpericardiectomy reported. No information is given in Schrire 1959 about the basis for the diagnosis of tuberculous pericarditis. In Strang 1987, a definite diagnosis of tuberculosis was made in only 10% (14/143) of the participants with constrictive pericarditis, and in the pericardial effusion study Strang 1988, 144/240 (60%) of participants had evidence confirming or supporting a diagnosis of active tuberculosis. The tuberculosis diagnosis was confirmed in 22 (38%) of theparticipantsinthe Hakim2000 (12[41%] and10[35%]in thetreatment and controlgroups,respectively). Risk of biasinincluded studies Threetrialsappeared adequately concealed(Strang 1987;Strang 1988;Hakim2000).In onetrial, allocation was alternate and was thereforenot concealed(Schrire1959). Randomization in Strang 1987 and Strang 1988 was conducted using a register drawn up centrally in the UK. The investigators inSouthAfricaenteredparticipantsintothetrials consecutively according to the register, without prior knowledge of who was receiving active orplacebotreatment.IntheZimbabwe study( Hakim 2000), randomization was achieved using a computergenerated randomization list with an equal number assigned to receiveprednisolone andplacebo. Strang1987and Strang1988weredoubleblind. Schrire1959did not useblinding. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Strang 1987 and Strang 1988 reported onpatient characteristics whichdid not appear unbalanced. Schrire1959 did notprovide information aboutthe clinical characteristicsof theparticipants. Strang 1987 and Strang 1988 did not use an intention-to-treat analysis, resultingin the exclusion of17.5 to20% ofparticipants fromanalysisbecauseoffailureto complywiththestudyprotocol. Inthepublisheddata,29/143participants(20%) were excluded fromanalysisinthepericardial constrictionstudy(Strang1987), and42/240participants(17.5%) wereexcludedfrom analysisin thepericardial effusiontrial(Strang1988).Additional unpublisheddata obtainedfromthe authors regarding theparticipants whowerenotincludedintheanalysesindicatedthatlessthan10% ofparticipants werelost tofollow up. Effects ofinterventions Length of regimen Norandomized controlled trialswerefound that compared antituberculous drug regimens of different durations in tuberculous pericarditis, ortrialsthatexamined the effects ofpericardiectomy. Steroids(unknownHIV status) Acombined analysisofparticipantswith effusiveand constrictive pericarditis(Strang1987;Strang1988)suggests that steroids may be associated with fewer deaths, but this could have arisen by chance(relativerisk[RR]0.65;95% confidenceinterval[CI]0.36 to 1.16]. For other outcomes, the group receiving steroids were associatedwithfewermorbidoutcomes,butnonewerestatistically significant (needfor repeatpericardiocentesis [RR 0.45;95% CI 0.20 to1.05], needforpericardiectomy[RR0.85;95%CI0.51 to1.42]).In theSchrire trial of28participants, all4participants who required pericardiectomy were in the treatment group (RR 9.00;95%CI0.53 to152.93)(Schrire1959). The effect of steroids on death and persisting pericardial disease at2yearsfollow up was explored.There was significant statisticalheterogeneitybet weenthetrial ofparticipants with effusion( Strang1988)andthetrialofparticipantswithconstriction(Strang 1987)with regard to this outcome (chi-square 4.88, df = 1), so their results were considered separately. Participants on steroids forpericardialeffusionweremorelikelytobe cured at24 months (alive and symptomfree) thanparticipants onplacebo (RR0.48; 95%CI0.29to0.80)(Strang 1988).Ndifference wasdemonstratedinthetrial ofparticipantswith suspected constrictivepericarditis (RR1.08;95%CI0.65 to1.81)(Strang1987). We conducted asensitivity analysistoexplorepotential effectsof patientlosstofollow-upinthetrialof steroidsin effusion(Strang 1988).Inthe worstcasescenario ,assuming allparticipantslostto followupdied,statisticalsignificance waslost(12lostintreatment group,7inplacebogroup; sensitivity analysis assuming alldied: RR0.78;95%CI0.52 to1.18). Steroids(HIVpositive participants) Steroids were associatedwithfewerdeathsinHIVpositiveparticipants, but this was notstatistically significant (RR0.50;95%CI

0.19to1.28,Hakim2000).There was no effect of steroids onthe tendencytodeveloppericarditis (RR1.00;95%CI0.15 to6.63). The following outcomes were not reported as separate outcomes inthepublishedmanuscript:deathfrompericarditis, requirement for repeatpericardiocentesis, anddeath orpersisting disease at1 to2years. Open surgical drainagefor effusion In a comparison of routine open surgical drainage on admission versus no open surgical drainage comparison, 122/240 participants consented toparticipate(Strang 1988).Sevenparticipants inthedrainagegroupand3participantsinthe nodrainagegroup werelost tofollow up. Allcausedeathwassimilarinbothgroups(RR0.96;95%CI0.30 to 3.15). Cardiac tamponade was effectively prevented by open drainage(odds ratio0.04;95%CI0.00to0.64).Participants who underwentopen surgicaldrainage weremorelikelytohaveaworse clinical status ortohavedied at24 monthsfollow-up thanthose who did not, although this was not statistically significant (RR 1.74;95%CI0.88 to3.42). Open surgicaldrainage was associated withfewerpatients requiring pericardiectomy, but this was not statistical significant (RR 0.39;95%CI0.08 to1.91). There were no trials ofpercutaneousdrainage of thepericardium underlocal anaesthesia. DISCUSSION Antituberculousdrug regimens Weaimedtoidentifytheoptimaldrugcombinationandtreatment duration, but found no trials. As there are no biological reasons tobelievethat chemotherapyfortuberculouspericarditisshould belongerthantreatmentof othertuberculousdisease, recommendationsfor currentstandard regimensseemappropriate(Garner 2002),butthisisnotbased ontrialsspecifically treatingpatients with tuberculouspericarditis. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Adjuvant steroids Steroids show apotentially largebeneficial effect(approximately 50%)ondeath and requirementfor repeatpericardiocentesis,but wide confidenceintervalsaround thepoint estimatesthat overlap unity are consistent with a null effect. Only a subgroup analysis (participants with tuberculouspericardial effusion and unknown HIV status) showed a significant effect of adjuvant steroids on deathorpersistingdisease at24 monthsfollow up(Strang1988). Therefore, there is uncertainty regarding the beneficial effect of adjuvant steroidsinparticipants with suspected tuberculouspericarditis. Thereviewhashighlightedseveralproblemswiththeexistingtrials of adjuvant steroidsin tuberculouspericarditis: 1. Trialsweregenerallytoosmall todetectmortalitydifference in tuberculouspericarditis. 2. Mostdiagnoses weremade clinically,sothestudygroups potentiallyincludeparticipantswithpericardialdisease causedby other conditions. 3. Rifampicininducesthelivermetabolismof corticosteroids, soitispossible that thedosesgivenin the trials are toolow. Prednisone120 mg(rather than60 mg) maybe more appropriatefor adults(Commerford1991). 4. Trialshavedividedparticipantsintoeither effusive or constrictive tuberculouspericarditis.However,the combined pictureofeffusive-constrictivepericarditisisa commonclinical presentationinSouthAfrica(Commerford1991).The management of thisgroup ofparticipantsisproblematicbecause pericardiocentesisdoesnotrelievetheimpaired filling of the heartand surgical removal of the fibrinous exudate coating the visceralpericardiumis notpossible.In addition to antituberculous chemotherapy, serial echocardiographyisused to detect thedevelopment of apericardial skin thatis amenable to surgical stripping.Theplaceof corticosteroidsisunknownin suchpatients. Pericardialdrainage Strang1988foundopen surgicaldrainage undergeneralanaesthesiatobeeffectiveinpreve nting cardiactamponadeandpossibly subsequentprogressionto constrictionrequiringpericardiocentesis. Theseeffectswere counterbalancedby moredeathsattributed topericarditisand apoorer clinical statusat24 months.Thereare norandomized controlled trialsofclosedpercutaneousdrainage underlocal anaesthesia. Pericardectomy There are no randomized controlled trials studying the issue of timing of pericardiectomy in people with a diagnosis of tuber culous constrictive pericarditis. The current recommendation of pericardiectomyforpersistentsignsofconstrictionafteratleastsix weeks of antituberculous chemotherapy is based on expert opinion( Commerford1991). AUTHORS CONCLUSIONS

Implicationsfor practice 1. Notrialshaveassessed antituberculousdrug regimensin tuberculouspericarditis.Regimens are thereforebased on evidencefrom trials ofpulmonarydisease. 2. Theretended tobefewerdeathsinpatientsreceiving steroids,but trials and the meta-analysisdid not reach statistical significance; norwastheresufficientdatatoexplorewhetherany effectof steroidswasinallpatients,or confined totoparticular subgroups,suchaspatientswith effusiveor constrictivedisease. 3. Routine opensurgicaldrainageabolishestheoccurrenceof cardiac tamponade; this expensive andinvasiveprocedure confers no mortalitybenefit, and maybe associated with apoorer clinical status at24 months. 4. Thereisno clinical trialinformation onwhichtobase recommendations regarding theindications for and thetiming of pericardiectomyintuberculous constrictivepericarditis. Implicationsfor research Webelieveanadequatelypoweredrandomizedplacebo controlled trialofadjuvantsteroidsandpercutaneousdrainageintuberculous pericarditisis required.The trialshouldincludeparticipants with tuberculouspericardial effusion, effusive-constrictivepericarditis, and constriction. Outcomes should be stratified by human immunodeficiency virus status. ACKNOWLEDGEMENTS GeorgeStrangforprovidingunpublishedtrialdata;AndrewNunn (MRC HIV ClinicalTrials Centre,London) forproviding information on clinical trial data; Elizabeth Pienaar (SA Medical Research Council) for searching for trials; Paul Garner for help in writing up;SeokyungHahnforstatistical advice. Contributors to thefellowshipgrant forDr Mayosi: theMedical ResearchCouncil,SouthAfrica;MedtronicSouthernAfricaInstitute of Cardiovascular Medicine; Cardiac Clinic Research Fund; University of Cape Town, South Africa; and the Nuffield Trust, Oxford,UK. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

REFERENCES References to studies included in this review Fowler 1991 Hakim 2000 {published data only} Hakim J,Ternouth I,MushangiE,SiziyaS,RobertsonV,MalinA. Double blind randomisedplacebo controlled trial of adjuvant prednisoloneinthetreatment ofeffusivetuberculouspericarditisin HIVseropositivepatients. Heart 2000;84:183 8. Schrire 1959 {published data only} SchrireV.Experience withpericarditisatGrooteSchuurHospital, CapeTown: An analysis of onehundred and sixty cases over a sixyearperiod. South African Medical Journal 1959;33:810 7. Strang 1987 {published and unpublished data} Strang JIG, KakazaHHS,Gibson DG,Girling DJ,NunnAJ,Fox W.Controlled trial ofprednisolone asadjuvantintreatment of tuberculous constrictivepericarditisinTranskei. Lancet 1987;2 (8573):1418 22. Strang 1988 {published and unpublished data} Strang JIG, KakazaHHS,Gibson DG,AllenBW,Mitchison DA, Evans DJ, et al.Controlled clinical trial of complete open surgical

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tuberculosis: South African perspectives.CapeTown: OxfordUniversityPress,1991. Desai 1979 DesaiHN.Tuberculouspericarditis:A review of100 cases. South African Medical Journal 1979;55:877 80. Dooley 1997 Dooley DP,CarpenterJL,RademacherS.Adjunctivecorticosteroid therapyfortuberculosis: acritical reappraisal of theliterature. Clinical Infectious Diseases 1997;25:872 87. FowlerNO.Tuberculouspericarditis. JAMA 1991;266:99 103. Fowler 1992 FowlerNO.Pericardialdisease. Heart Disease & Stroke 1992;1: 85 94. Fowler 1995 FowlerNO.Constrictivepericarditis:itshistory andcurrentstatus. Clinical Cardiology 1995;18:341 50. Garner 2002 GarnerP,HolmesA.Treating tuberculosis. Clinical Evidence Concise 2002;7:146 7. Gelfand 1957 GelfandM. TheSickAfrican. The Sick African. 3rdEdition. Cape Town: Juta,1957:447. Hageman

1964 HagemanJH,D EsopoND,Glenn WWL.Tuberculosisof the pericardium:Along-term analysisofprovedcases. New England Journal of Medicine 1964;270:327 32. Harvey 1937 HarveyAM, WhitehillMR.Tuberculouspericarditis. Medicine 1937;16:45 94. Koh 1994 Koh KK,KimEJ,ChoCH,ChoiMJ,ChoSK,KimSS,et al.Adenosinedeaminase and carcinoembryonic antigenin pericardialeffusiondiagnosis, especiallyin suspected tuberculous pericarditis. Circulation 1994;89:2728 35. Lorell 1997 Lorell BH.Pericardialdiseases. In: BraunwaldE editor(s). Heart disease: a textbook of cardiovascular medicine. Philadelphia: W.B. Saunders,1997. Quayle 1987 Quayle JM,LipschikGY,HeurichAE.Managementof tuberculous pericarditis. Annals of Thoracic Surgery 1987;43:653 5. Rooney 1970 Rooney JJ,Crocco JA,LyonsHA.Tuberculouspericarditis. Annals of Internal Medicine 1970;72:73 8. Sagrista 1988 Sagrista-SauledaJ,Permanya-MiraldaG,Soler-Soler J.Tuberculous pericarditis:Tenyearexperience withaprospectiveprotocolfor diagnosis and treatment. Journal of the American College of

Cardiology 1988;11:724 8. Schepers 1962 SchepersGWH.Tuberculouspericarditis. American Journal of Cardiology 1962;9:248 76. Schrire 1967 SchrireV.Pericarditis(withparticular reference to tuberculous pericarditis). Australian Annals of Medicine 1967;16:41 51. Senderovitz 1994 SenderovitzT,Viskum K.Corticosteroidsandtuberculosis. Respiratory Medicine 1994;88:561 5. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Shapiro 1953 ShapiroJB.Tuberculouspericarditiswith effusion: Theimpact of antimicrobial therapy. American Journal of the Medical Sciences 1953;March:229 40. Strang 1984 Strang JIG.TuberculouspericarditisinTranskei. Clinical Cardiology 1984;5:667 70. Strang 1997 Strang JIG.Tuberculouspericarditis. The Journal of Infection 1997; 35:215 9. * Indicates the major publication for the study Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Hakim 2000 Methods Computer generated randomization list Double blind placebo controlledstudy Participants 58 participants who were on antituberculous chemotherapyfor suspect ed tuberculous pericarditis Interventions Intervention: Prednisolone for the first 6weeks of antituberculous chemotherapy Dose for adults: 60 mgfor the first week, and taperingby10 mg every week Control: Placebo Outcomes Primary outcomes: Death Resolution of pericardial effusion Secondary outcomes: Resolution ofpretreatment symptoms and signs, and ECG changes Corticosteroid related adverse effects Notes Studylocation: Harare, Zimbabwe Schrire 1959 Methods Alternate allocation of 28 patients to adjuvant steroids or no steroids Participants 28 participants who were on antituberculous chemotherapyfor suspect ed tuberculous pericarditis Interventions Steroids: While under antituberculous cover, cortisone with a loadingdose of300 mg and mai ntenance dose of100 mgdaily for severalweeks was prescribed for 14 participants Ata later date, prednisolone 60 mg/day with a maintenance dose of 20 mg was subs tituted Outcomes Constriction requiringpericardiectomy Notes Studylocation: Cape Town, South Africa The characteristics of the included participants were not provided Length of follow up not specified Strang 1987 Methods Central randomization Double blind placebo controlledstudy Participants 143 participants with suspected tuberculous constrictive pericardit is aged 5 years and older Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Strang 1987 (Continued) Interventions Intervention: Prednisolone for the first 11 weeks of antituberculous chemotherapy. Dose for ad ults: 60 mg for the first 4 weeks; 30 mgfor weeks 5 to 8;15 mgfor weeks 9 to 10; and 5 mgfor week 11 Control: Placebo Outcomes Death Death from pericarditis Favourable clinical status at 24 months Pericardiectomy Notes Studylocation: Umtata, South Africa Participants lost to follow up: we determined from published and unpublished dat a that 8 participants in the prednisolone group, and 6 placebo participants were lost to follow up Their outcome is unknown The participants in the treatment and control groups were well matched in terms of clinical characteristics and completion of antituberculous chemotherapy Strang 1988 Methods Central randomization Double blind placebo controlledstudy Factorial design Participants 240 participants aged 5 years or more diagnosed as having active tu berculous pericardial effusion Interventions Complete open surgical drainage on admission compared with no open drainage (122/240 participants consented) Prednisone versus placebo -similar regimen to Strang1987;(all240 participants) Outcomes Death Death from pericarditis Favourable clinical status at 24 months Tamponade requiringpericardiocentesis Constriction Pericardiectomy Notes Studylocation: Umtata, South Africa Complete open surgical drainage comparison: 8/64 participants in the interventio n group did not receive open surgical drainage Participants lost to follow up: we determined from published and unpublished dat a that 12 participants in the prednisolone group, and 7 participants in the placebo group were lost to follow up in the effusion study. In the drainage versus no drainage comparison, the losses to follow up were 7 and 3 par ticipants respectively Their outcome is unknown The participants in the treatmentand control groups were well matchedin terms of their clinicalcharacteristics and completion of antituberculous chemotherapy Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

DATA AND ANALYSES Comparison 1. Tuberculous pericarditis: steroids vs placebo No. of No. of Outcome or subgroup title Statistical method Effect size studies participants 1 Death from allcauses 2 350 Risk Ratio (M-H, Fixed, 95% CI) 0.65 [0.36, 1.16] 2 Death from pericarditis 2 350 Risk Ratio (M-H, Fixed, 95% CI) 0.43 [0.18, 0.99 ] 3 Repeat pericardiocentesis 1 221 Risk Ratio (M-H, Fixed, 95% CI) 0.45 [0.20, 1. 05] 4 Pericardiectomy 3 378 Risk Ratio (M-H, Fixed, 95% CI) 0.85 [0.51, 1.42] 5 Death or persisting disease at 2 2 350 Risk Ratio (M-H, Fixed, 95% CI) 0.69 [0 .48, 0.98] years follow up Comparison 2. Tuberculous pericarditis in HIV positive participants: steroids vs placebo No. of No. of Outcome or subgroup

title Statistical method Effect size studies participants 1Deathfromallcauses 1 58 RiskRatio(M-H,Fixed,95%CI) 0.5[0.19,1.28] 2Constrictivepericarditis 1 58 RiskRatio(M-H,Fixed,95%CI) 1.0[0.15,6.63] Comparison 3. Tuberculous pericardial effusion: open surgical drainage vs standard care No. of No. of Outcome or subgroup title Statistical method Effect size studies participants 1 Death from allcauses 1 112 Risk Ratio (M-H, Fixed, 95% CI) 0.96 [0.30, 3.15] 2 Death from pericarditis 1 112 Risk Ratio (M-H, Fixed, 95% CI) 1.29 [0.30, 5.49 ] 3 Repeat pericardiocentesis 1 112 Risk Ratio (M-H, Fixed, 95% CI) 0.04 [0.00, 0. 64] 4 Pericardiectomy 1 112 Risk Ratio (M-H, Fixed, 95% CI) 0.39 [0.08, 1.91] 5 Death or persisting disease at 2 1 112 Risk Ratio (M-H, Fixed, 95% CI) 1.74 [0 .88, 3.42] years follow up Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Analysis1.1. Comparison1Tuberculouspericarditis: steroidsvsplacebo,Outcome1Death fromall causes. Review: Interventions for treating tuberculous pericarditis Comparison: 1 Tuberculous pericarditis: steroids vs placebo Outcome: 1 Death from all causes Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1987 8/62 11/67 41.0 % 0.79 [ 0.34, 1.83 ] Strang 1988 8/105 16/116 59.0 %

0.55 [ 0.25, 1.24 ] Total (95% CI) 167 Total events: 16 (Treatment), 27 (Control) Heterogeneity: Chi2 = 0.35, df = 1 (P = 0.55); I2 =0.0% Test for overall effect: Z = 1.46 (P = 0.14) 183 100.0 % 0.65 [ 0.36, 1.16 ]

0.1 0.2 0.5 1 2 5 10 Favours Treatment Favours Control Analysis1.2. Comparison1Tuberculouspericarditis:steroidsvsplacebo,Outcome2Deathf

rom pericarditis. Review: Interventions for treating tuberculous pericarditis Comparison: 1 Tuberculous pericarditis: steroids vs placebo Outcome: 2 Death from pericarditis Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1987 2/62 7/67 39.2 % 0.31 [ 0.07, 1.43 ] Strang 1988 5/105 11/116 60.8 % 0.50 [

0.18, 1.40 ] Total (95% CI) 167 Total events: 7 (Treatment), 18 (Control) Heterogeneity: Chi2 = 0.27, df = 1 (P = 0.60); I2 =0.0% Test for overall effect: Z = 1.97 (P = 0.049) 183 100.0 % 0.43 [ 0.18, 0.99 ]

0.01 0.1 1 10 100 Favours Treatment Favours Control Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Analysis1.3. Comparison1Tuberculouspericarditis: steroidsvsplacebo,Outcome3Repea t pericardiocentesis. Review: Interventions for treating tuberculous pericarditis Comparison: 1 Tuberculous pericarditis: steroids vs placebo Outcome: 3 Repeat pericardiocentesis Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1988 7/105 17/116 100.0 % 0.45 [ 0.20, 1.05 ] Total (95% CI) 105 Total events: 7

(Treatment), 17 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.84 (P = 0.066) 116 100.0 % 0.45 [ 0.20, 1.05 ]

0.1 0.2 0.5 1 2 5 10 Favours Treatment Favours Control Analysis1.4. Comparison1Tuberculouspericarditis:steroidsvsplacebo,Outcome4Perica rdiectomy. Review: Interventions for treating tuberculous pericarditis Comparison: 1 Tuberculous pericarditis: steroids vs placebo Outcome: 4 Pericardiectomy

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Schrire 1959 4/14 0/14 1.8 % 9.00 [ 0.53, 152.93 ] Strang 1987 11/62 18/67 63.4 % 0.66 [ 0.34, 1.29 ] Strang 1988 7/105 10/116 34.8 % 0.77 [ 0.31, 1.96 ] Total (95% CI) 181 Total events: 22 (Treatment),

28 (Control) Heterogeneity: Chi2 = 3.27, df = 2 (P = 0.20); I2 =39% Test for overall effect: Z = 0.61 (P = 0.54) 197 100.0 % 0.85 [ 0.51, 1.42 ]

0.001 0.01 0.1 1 10 100 1000 Favours Treatment Favours Control Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Analysis1.5. Comparison1Tuberculouspericarditis: steroidsvsplacebo,Outcome5Death orpersisting disease at 2years follow up. Review: Interventions for treating tuberculous pericarditis Comparison: 1 Tuberculous pericarditis: steroids vs placebo Outcome: 5 Death or persisting disease at 2 years follow up Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1987 20/62 20/67 34.2 % 1.08 [ 0.65, 1.81 ]

Strang 1988 17/105 39/116 65.8 % 0.48 [ 0.29, 0.80 ] Total (95% CI) 167 Total events: 37 (Treatment), 59 (Control) Heterogeneity: Chi2 = 4.88, df = 1 (P = 0.03); I2 =80% Test for overall effect: Z = 2.08 (P = 0.038) 183 100.0 % 0.69 [ 0.48, 0.98 ]

0.1 0.2 0.5 1 2 5 10 Favours

Treatment Favours Control Analysis2.1. Comparison2TuberculouspericarditisinHIVpositiveparticipants:steroid svsplacebo, Outcome 1 Death from all causes. Review: Interventions for treating tuberculous pericarditis Comparison: 2 Tuberculous pericarditis in HIV positive participants: steroids vs placebo Outcome: 1 Death from all causes Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Hakim 2000 5/29 10/29 100.0 % 0.50 [

0.19, 1.28 ] Total (95% CI) 29 Total events: 5 (Treatment), 10 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.44 (P = 0.15) 29 100.0 % 0.50 [ 0.19, 1.28 ]

0.1 0.2 0.5 1 2 5 10 Favours treatment Favours control Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Analysis2.2. Comparison2TuberculouspericarditisinHIVpositiveparticipants:steroid svsplacebo, Outcome 2 Constrictive pericarditis. Review: Interventions for treating tuberculous pericarditis Comparison: 2 Tuberculous pericarditis in HIV positive participants: steroids vs placebo Outcome: 2 Constrictive pericarditis Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Hakim 2000 2/29 2/29 100.0 % 1.00 [ 0.15, 6.63 ] Total (95% CI)

29 Total events: 2 (Treatment), 2 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 29 100.0 % 1.00 [ 0.15, 6.63 ]

0.01 0.1 1 10 100 Favours treatment Favours control Analysis3.1. Comparison3Tuberculouspericardial effusion: opensurgicaldrainagevss tandard care, Outcome 1 Death from all causes. Review: Interventions for treating tuberculous pericarditis Comparison: 3 Tuberculous pericardial effusion: open surgical drainage

vs standard care Outcome: 1 Death from all causes Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1988 5/57 5/55 100.0 % 0.96 [ 0.30, 3.15 ] Total (95% CI) 57 Total events: 5 (Treatment), 5 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.06

(P = 0.95) 55 100.0 % 0.96 [ 0.30, 3.15 ]

0.1 0.2 0.5 1 2 5 10 Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Analysis3.2. Comparison3Tuberculouspericardial effusion: opensurgicaldrainagevss tandard care, Outcome 2 Death frompericarditis. Review: Interventions for treating tuberculous pericarditis Comparison: 3 Tuberculous pericardial effusion: open surgical drainage vs standard care Outcome: 2 Death from pericarditis Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1988 4/57 3/55 100.0 % 1.29 [ 0.30, 5.49 ] Total (95%

CI) 57 Total events: 4 (Treatment), 3 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.34 (P = 0.73) 55 100.0 % 1.29 [ 0.30, 5.49 ]

0.1 0.2 0.5 1 2 5 10 Analysis3.3. Comparison3Tuberculouspericardial effusion: opensurgicaldrainagevss tandard care, Outcome 3 Repeatpericardiocentesis. Review: Interventions for treating tuberculous pericarditis Comparison: 3 Tuberculous pericardial effusion: open surgical drainage vs standard care

Outcome: 3 Repeat pericardiocentesis Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1988 0/57 12/55 100.0 % 0.04 [ 0.00, 0.64 ] Total (95% CI) 57 Total events: 0 (Treatment), 12 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.28 (P = 0.023) 55 100.0

% 0.04 [ 0.00, 0.64 ]

0.001 0.01 0.1 1 10 100 1000 Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

Analysis3.4. Comparison3Tuberculouspericardial effusion: opensurgicaldrainagevss tandard care, Outcome 4 Pericardiectomy. Review: Interventions for treating tuberculous pericarditis Comparison: 3 Tuberculous pericardial effusion: open surgical drainage vs standard care Outcome: 4 Pericardiectomy Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1988 2/57 5/55 100.0 % 0.39 [ 0.08, 1.91 ] Total (95% CI) 57

Total events: 2 (Treatment), 5 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.17 (P = 0.24) 55 100.0 % 0.39 [ 0.08, 1.91 ]

0.01 0.1 1 10 100 Analysis3.5. Comparison3Tuberculouspericardial effusion: opensurgicaldrainagevss tandard care, Outcome5Death orpersistingdisease at2yearsfollowup. Review: Interventions for treating tuberculous pericarditis Comparison: 3 Tuberculous pericardial effusion: open surgical drainage vs standard care Outcome: 5 Death or

persisting disease at 2 years follow up Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI Strang 1988 18/57 10/55 100.0 % 1.74 [ 0.88, 3.42 ] Total (95% CI) 57 Total events: 18 (Treatment), 10 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.59 (P =

0.11) 55 100.0 % 1.74 [ 0.88, 3.42 ]

0.1 0.2 0.5 1 2 5 10 WHAT

S NEW

Last assessed as up-to-date:16June2002. 10 November 2008 Amended Converted to new review format with minor editing. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

12 January2005 Amended New studies found but not yet included or excluded. 17 June 2002 New citation required and conclusions have changed Substantive amen dment. Issue 4, 2002: Hakim 2000 added. New studies found and included or excluded 12 January2005 Amended New studies found but not yet included or excluded. 17 June 2002 New citation required and conclusions have changed Substantive amen dment. Issue 4, 2002: Hakim 2000 added. New studies found and included or excluded HISTORY Protocol firstpublished:Issue4,1997 Review firstpublished:Issue3,1998 18May2003 Amended Minor update CONTRIBUTIONS OF AUTHORS BMMayosi: conceived theideaforthereview,helpeddesignand writetheprotocol,extract and analysedata,writethereviewand review updates. M Ntsekhe: contributed to the first review update. JA Volmink: h elped design and write the protocol, extract and analysedata, and write the review.PJCommerford:helped write theprotocol and revi ew. DECLARATIONS OF INTEREST We certifythat wehavenoaffiliationswith orinvolvementinany organizationorentity with adirectfinancialinterestinthesubject matterof thereview(eg employment, consultancy,stockownership,honoraria,experttes timony). SOURCES OF SUPPORT Internal sources CardiacClinicResearchFund,University ofCapeTown, SouthAfrica. External sources DepartmentforInternational Development,UK. EuropeanCommission (DevelopmentDirectorateXII),Belgium. LiverpoolSchoolofTropicalMedicine,UK. Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.

INDEX TERMS MedicalSubjectHeadings(MeSH) AdrenalCortexHormones [therapeutic use];AntitubercularAgents [therapeutic use];D rainage;Pericardiectomy;Pericarditis,Tuberculous[* drug therapy; * surgery];Pericardium [surgery];RandomizedControlledTrials asTopic MeSH check words Humans Interventionsfor treating tuberculouspericarditis(Review) Copyright2009 The CochraneCollaboration.Published byJohnWiley&Sons,Ltd.