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PROTOCOLOpenAccessPhysicalactivityandtheprevention,reduction,andtreatmentofalcoholand/orsubstanceuseacrossthelifespan(ThePHASEreview):protocolforasystematicreviewTomP.
Thompson1*,AdrianH.
Taylor1,AmandaWanner1,KerrynHusk1,YinghuiWei2,SiobhanCreanor1,RebeccaKandiyali3,JoNeale4,JuliaSinclair5,MonaNasser1andGaryWallace6AbstractBackground:Alcoholandsubstanceuseresultsinsignificanthumanandeconomiccostgloballyandisassociatedwitheconomiccostsof21billionand15billionwithintheUK,respectively,andtrendsforusearenotimproving.
Pharmacologicalinterventionsarewellresearched,butrelapseratesacrossinterventionsforsubstanceandalcoholusedisordersareashighas60–90%.
Physicalactivitymayofferanalternativeoradjunctapproachtoreducingratesofalcoholandsubstanceusethatisassociatedwithfewadversesideeffects,iseasilyaccessible,andispotentiallycost-effective.
Throughpsychological,behavioural,andphysiologicalmechanisms,physicalactivitymayofferbenefitsintheprevention,reduction,andtreatmentofalcoholandsubstanceuseacrossthelifespan.
Whilstphysicalactivityiswidelyadvocatedasofferingbenefit,nosystematicreviewexistsofphysicalactivity(inallforms)anditseffectsonalllevelsofalcoholandsubstanceuseacrossallagestohelpinformpolicymakers,serviceproviders,andcommissioners.
Methods:Theobjectivesofthismixedmethodssystematicreviewaretodescribeandevaluatethequantitativeandqualitativeresearchobtainedbyadiversesearchstrategyontheimpactofphysicalactivityanditspotentialto:1.
Reducetheriskofprogressiontoalcoholand/orsubstanceuse(PREVENTION)2.
Supportindividualstoreducealcoholand/orsubstanceuseforharmreduction(REDUCTION),and3.
Promoteabstinenceandrelapsepreventionduringandaftertreatmentforanalcoholand/orsubstanceusedisorder(TREATMENT).
Withtheinputofkeystakeholders,weaimtoassesshowwhatweknowcanbetranslatedintopolicyandpractice.
Quantitative,qualitative,serviceevaluations,andeconomicanalyseswillbebroughttogetherinafinalnarrativesynthesisthatwilldescribethepotentialbenefitsofphysicalactivityforwhom,inwhatconditions,andinwhatform.
Discussion:Thisreviewwillprovidedetailsofwhatisknownaboutphysicalactivityandtheprevention,reduction,andtreatmentofalcoholand/orsubstanceuse.
Thesynthesisedfindingswillbedisseminatedtopolicymakers,serviceproviders,andcommissionersintheUK.
(Continuedonnextpage)*Correspondence:tom.
thompson@plymouth.
ac.
uk1PlymouthUniversityPeninsulaSchoolsofMedicineandDentistry,PlymouthSciencePark,Derriford,PlymouthPL68BX,UKFulllistofauthorinformationisavailableattheendofthearticleTheAuthor(s).
2018OpenAccessThisarticleisdistributedunderthetermsoftheCreativeCommonsAttribution4.
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0/),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedyougiveappropriatecredittotheoriginalauthor(s)andthesource,providealinktotheCreativeCommonslicense,andindicateifchangesweremade.
TheCreativeCommonsPublicDomainDedicationwaiver(http://creativecommons.
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0/)appliestothedatamadeavailableinthisarticle,unlessotherwisestated.
Thompsonetal.
SystematicReviews(2018)7:9DOI10.
1186/s13643-018-0674-0(Continuedfrompreviouspage)Systematicreviewregistration:PROSPEROnumber:CRD42017079322.
Keywords:Physicalactivity,Exercise,Alcoholuse,Substanceuse,Addiction,Prevention,Harmreduction,Treatment,MixedmethodBackgroundRationaleAlcoholandsubstanceuseiscommon:globally,5.
9%and1%ofdeathsareattributabletoalcoholandillicitdruguse,respectively[1].
IntheUK,alcoholuseisat-tributedtomorethanoneinfivedeathsofmenaged16–54yearsold[2],andalcoholharmsareassociatedwithaneconomicannualcostofaround21billion(3.
5billioninhealthcare[3]).
IllicitdruguseintheUKhasaneconomiccostofaround15billion[4](488millionthroughhealthcare[5]),withnearlyoneintenadultsaged16–59inEnglandandWaleshavingusedillicitdrugsinthepastyear[6].
Worldwide,alcohol-attributabledeathsincreasedfrom3.
8%in2004[1]to5.
9%in2012[7],andillicitdruguselevelshavefailedtodeclinebetween2005and2010[8],withaslightincreaseintheUKinrecentyears[6].
ScopeforidentifyingnewinterventionsPharmacologicalinterventionsforalcoholandsubstanceusedisordershavebeenwellresearchedandreportedonforthemanagementofwithdrawal,dependence,andre-lapseprevention.
TheCochraneDrugandAlcoholGrouphaspublished11and30reviewsofpharmaco-logicalinterventionsforalcoholandsubstanceuse,re-spectively,whilstpsychosocialinterventions(e.
g.
briefinterventionsandmotivationalinterviewing)arelesswellreported,withsixandeightpublishedreviews,re-spectively.
Preventiveinterventionsonlyhavefivere-viewsforalcoholuse,andthreereviewsforsubstanceuse[9].
Duetotheheterogeneityofthetypesofdrugsusedandstyleofintervention,itishardtosummarisemeaningfullytheavailabledataofexistinginterventions.
However,withrelapseratesashighas60%1yearaftertreatmentforsubstanceusedisorders(SUD)[10–12]and60–90%foralcoholusedisorders(AUD)[13–16]anddrugsubstitutiontherapiesbeingassociatedwithin-natecomplications[17–20],thereisaneedforevidencefornewtreatmentsandpreventiveinterventionstohelpaddressthegrowingburdenofalcoholand/orsubstanceuse.
Physicalactivity(PA;definedasanybodilymovementproducedbyskeletalmusclesthatrequiresenergyex-penditure,inclusiveoforganisedsport[21])andhealth-orientedexerciseinterventionscouldimpactonthepre-vention,reduction,andtreatmentofalcoholand/orsub-stanceuseandhavethepotentialtobecost-effective,flexible,accessible,acceptableacrosstherangeoflevelsofuseandhavealowerriskofadverseeventscomparedtopharmacologicaltreatment[22].
In2001(withup-datesin2005and2008),AT(withco-researchers)reviewedandreportedtheeffectsofexerciseonsmokingfromeightrandomisedcontrolledtrials(RCTs)aspartofaCochraneReview[23].
Thisevidencecontributedtoa2008reporttotheUSSurgeonGeneralonsmokingcessationwhichhighlightedthevalueofexerciseasanoptiontosupportsmokingcessation[24],andintheUK,manyNHSStopSmokingServicesnowadvocateexercise[25].
In2014,anupdatetotheCochraneReviewrevealedtherewere20RCTsofexerciseandsmokingcessation,suggestingarapidgrowthofinterestinthetopic[23].
Afirstsystematicreviewisnowneededofphysicalactivityinterventionsfortheprevention,reduc-tion,andtreatmentofalcoholand/orsubstanceusethatalsoincludesacomprehensivesearchofgreyliteratureandserviceevaluationstogeneratepracticalimplicationsforpracticeandpolicy.
EvidencefortheroleofPAforpreventingalcoholand/orsubstanceuseProspectivestudiesindicatethatsportsparticipationinadolescentsandyoungpeopleisassociatedwithanin-creaseinalcoholusebutdecreaseinillicitdruguse[26].
However,suchstudiesmayfailtoeliminateconfoundingfactors(e.
g.
,specificsportsmayattractthosemorepre-disposedtoengagingin'risky'behaviours).
Incontrast,arigorousstudyinFinlandtracked1870twinpairsfrom16to27yearsofageandconcludedthatlowlevelsofphysicalactivityincreasedtheriskofbothalcoholandillicitdruguse[27].
Thisfurtherdemon-stratestheneedforarobust,systematicreviewassessingtheroleofphysicalactivity(notjustparticipationinsports)onprogressiontoalcoholand/orsubstanceusedisorders.
EvidencefortheeffectsofPAinterventionsforharmreductionandtreatmentofalcoholand/orsubstanceuseThereisincreasinginterestintheroleofphysicalactiv-ityasatreatmentandreductionstrategyforalcoholand/orsubstanceuse.
In2011,theUSNationalInstituteonDrugAbuse(NIDA)invested$4.
3million[28]onaprogrammeofworkincludinghigh-qualityRCTssuchasSTRIDE[29]whichisinvestigatingstimulantusereduc-tionusingexercise.
ArecentsystematicreviewbyWangThompsonetal.
SystematicReviews(2018)7:9Page2of15etal.
[30]waslimitedbyanincompletesearchstrategy(e.
g.
,notCINAHL)andthusomittedkeypapers.
Theyidentifiedthreestudieswithafocusonalcohol,fivewithafocusonillicitdruguse,fouronmultipledruguse,and11onsmoking.
Thedatafromeachofthesestudieswerepooledusingmeta-analysis,despiteconsiderableapparentheterogeneityacrossinterventionsandout-comes.
Harm-reductionstudieswerenotconsidered.
Inanothersystematicreview,Zschuckeandcolleagues[31]foundninestudiesreportingtheeffectsofPAonAUDandeightonSUD,butagain,thatreviewdidnotincludekeysearchenginesanddidnotconsidergreyliteraturethatmaybemostinformativefortheUKcontext.
BoththesereviewsfocussedonAUDandSUDanddidnotconsiderthebroaderspectrumofusethatmaynotmeettheclassificationofadisorder,e.
g.
recreationalusethatisstillassociatedwithriskofharm.
Arigorousreviewoftheevidenceencompassingallaspectsofalcoholandsubstanceuseisstillneeded.
PlausiblemechanismsfortheeffectsofexerciseontheuseofanyaddictivesubstancePhysicalactivitymayaffectalcoholand/orsubstanceusethroughvariouspsychologicalmechanisms,suchasanacutereductionincravingsandurges,anincreaseinpositiveaffect,andachronicimprovementinco-morbiddepressionandanxietywhichmaymoderateoutcomesrelatedtoalcoholandsubstanceuse[32].
Fromthebe-haviouralperspective,exerciseinvolvementmayhelpavoidanceofcueswhichtriggercravingsandrelapse,andprovideexposuretonewenvironments,whichpro-vidediversionarysafeandimmediatelyrewardingexperi-ences[32].
ParticipationinmeaningfulstructuredactivitiesareakeypartofovercomingAUDandSUD,andsomephysicalactivitiesmayofferthechanceforidentitytransformationthroughexposuretomeaningfulroutineactivities,informalsocialcontrols,andpromotedpersonalagency[33].
Fromthephysiologicalperspective,thereisevidencefromanimalstudiestosuggestthatneurobiologicalchangesassociatedwithexercise[32,34,35]helptoexplaintheconsistentevidencethatexerciseacutelyreducesconsumptionofcocaine,morphine,nicotine,andalcohol[34,36–39].
Finally,recentstudiesindicatethatphysicalactivityin-terventionscanbeacceptableforthosewithAUDandSUD[40–42],butnoreviewexistsofthispublishedandgreyliteraturetohelpinformthedesignofthemostfeasibleandacceptableinterventionsacrossthespectrumoflevelsofuse.
PAmayinfluencealcoholand/orsubstanceuseinsimilarwaysandthroughcommonmechanismsandthereforeformthefocusofthisreview.
However,duetothedifferentwayinwhichalcoholandsubstanceuseareviewed,approached,andtreatedwithintheUK,theywillbeconsideredseparatelywithinthisreviewandnotcombinedinanyanalysesinordertoensurethemostpertinentfindingsforpolicyandpractice.
ImpactofstakeholderengagementStakeholderengagementhasmanybenefitsandcancon-tributetowardsthedevelopmentofsystematicreviews.
Stakeholderscanbefunders,serviceusers,healthcareprofessionals,orcharities,i.
e.
anyonewhowillimple-mentinterventionsbasedonthefindingsofthereviews.
Aresearchwhitepaperlookingatthebenefitsofstake-holderengagementinsystematicreviewswaspublishedbyCottrellandcolleaguesin2014[43].
Theyreviewedpapersandsuggestedthatthebenefitsofstakeholderen-gagementincludedidentifyingandprioritisingpotentialresearchtopics,helpingtorecruitparticipants,andpro-vidingusefulfeedbackonthesystematicreviewprotocol.
Otherbenefitsincludedhelpingtheresearcherstounderstandtheperspectiveoftheserviceusers/partici-pantsandensuringtheaccessibilityoftheresultswithwiderdissemination.
MoststudiesreviewedwereintheUK,andtheysuggestedthatthescopeforthereviewswasrefinedduetostakeholderengagementandthatgenerallytheoverallqualityofthereviewwasimproved.
Giventhebroadfocusofthisreviewacrossseveralsec-torsandserviceprovidersinwhatisanunder-researchedarea,involvingstakeholderswillmaximisetheapplicabilityandimpactofthefindings.
Aspartofthisprocess,ouroriginalquestionswerebasedonconcernshighlightedbythePlymouthCityCouncilPublicHealthteamandthePlymouthNHSHospitalTrustduetothehighnationalprevalenceofalcoholand/orsub-stanceuseandresultinghospitaladmissionsinthearea.
Weworkedwithalocalthirdsectororganisationwhichprovidesdaysupportforpersonsinthecommunityaf-fectedbytheuseofdrugsand/oralcohol,aswellasaneducationserviceasanalternativetopupilreferralunitsinPlymouth.
Stakeholdergroupswithinthisservice(threeserviceprovidersandeightserviceusers)supportedthefocusonourthreekeyresearchquestionsaboutpreven-tion,harmreduction,treatmentandrelapseprevention,andhighlightedtheimportanceofPAthroughtheirownnarratives,independentof,andinadditionto,standardtreatment.
Furtherengagementwithco-applicantsGaryWallace(SeniorSpecialistDrugsandAlcoholTeamMan-agerinthePlymouthPublicHealth),JuliaSinclair(Honor-aryConsultantinAlcoholLiaisonandWessexAlcohol(AHSN)Lead),JoanneNeale(leadforPPIaddictionre-searchgroupatKCL),andlocalthirdsectorleadersrefinedthescopeandmethodsforthereview.
Inaddition,co-applicantsAdrianTaylorandJoanneNealehavepreviouslyconductedandpublishedqualitativeresearchinvolvingpeoplewithSUDwhichhighlightedtheneedtofurtherde-velopappropriateinterventions[25,42].
ThescopeandThompsonetal.
SystematicReviews(2018)7:9Page3of15methodsforthisreviewhavebeenstronglyinfluencedbybothserviceprovideranduserperspectivesthroughoutthedevelopmentoftheapplicationandthisprotocol.
AimandobjectivesOuroverarchingaimistodescribeandevaluatethequan-titativeandqualitativeresearchontheimpactofphysicalactivityontheprevention,reduction,andtreatmentofal-coholand/orsubstanceuseacrossthelifespan.
Physicalactivityinterventions(includingthoseinvolv-ingsport,exercise,orgenerallifestylephysicalactivity)mayhavethepotentialtoimpactthreedomainsofalco-holand/orsubstanceuse:1.
Reducetheriskofprogressiontoalcoholand/orsubstanceuse(PREVENTION);2.
Supportindividualstoreducealcoholand/orsubstanceuseforharmreduction(REDUCTION),and3.
Promoteabstinenceandrelapsepreventionduringand/oraftertreatmentofAUDandSUD(TREATMENT).
Weaimtodescribeandevaluatetheavailablequantita-tiveandqualitativeresearchforeachofthesescenariosandseektoassesshowwhatweknowcanbestbetranslatedintopolicyandpracticewiththeinputofkeystakeholders,presentingwherepossibleanycost-effectivenessdata.
Thiswillbeachievedbythefollowingobjectives:a)Toquantifyanddescribequantitativedatarelatingtotheimpactofphysicalactivityonalcoholand/orsubstanceuseoutcomes(completingmeta-analyseswherepossible);b)Toanalyseanddescribequalitativedatarelatingtotheacceptability,feasibility,mechanisms,mediators,andmoderatorsofphysicalactivityinrelationtoalcoholand/orsubstanceuse(completingmeta-syntheseswherepossible);c)Todescribeandanalyseserviceevaluationswhichmaynotmeetpeer-reviewedquantitativeorqualita-tiveinclusioncriteriarelatingtotheimplementationandimpactofphysicalactivityinterventionsrelatingtoalcoholand/orsubstanceuse;d)Toquantifyanddescribepotentialcost-effectivenessdatarelatingtophysicalactivityanditsimpactonal-coholand/orsubstanceuse;e)Toproducepracticalrecommendationsaboutwhatisknownaboutwhatworksforwho,when,where,andhowthroughanarrativesynthesisinformedbystakeholderinput.
Eachoftheseobjectiveswilladdressthethreedomainsofprevention,reduction,andtreatment,separately,butsomecrossoverwillbeexpected.
Table1Outcomestabledbypopulation,intervention,control,andoutcomeagainstthethreedomainsofphysicalactivityanditspossibleimpactonalcoholandsubstanceuse(1)Prevention(2)ReductionTreatment(andrelapseprevention)PopulationAdolescents,atriskgroupsGeneralpopulationwhousealcoholorsubstancesbutnotreceivingacuteorlong-termcareforadiagnosedAUDand/orSUD,atriskgroupsThosereceiving/havereceivedacuteorlong-termcareforadiagnosedAUDand/orSUDInterventionSportandphysicalactivity-basedpro-grammes(schools,community,publichealthinterventions)Publichealthlevelinitiatives,targetedcommunity-andhealthcare-basedinterventionsAdjunctPAinterventions,prescribedandsupportedPAinterventions,motivationalinterventionsControlOthernon-PAcontrol,usualcare,ornointerventionOthernon-PAcontrol,usualcare,ornointerventionStandaloneusualcare,non-PAcontrolOutcome(a)QuantitativeaLevelsofsubsequentuseofalcoholand/orsubstances,prevalencerates%reductioninalcoholand/orsubstanceuse,prevalenceAbstinencerates,%daysabstinent,%reductioninalcoholand/orsubstanceuse,relapserates(b)QualitativeAcceptability,feasibility,barriersandfacilitatorsofPAAcceptability,feasibility,barriersandfacilitatorsofPA,perceivedutilityofPAAcceptability,feasibility,barriersandfacilitatorsofPA,perceivedutilityofPA(c)ServiceEvaluationsMixtureofabove(a)and(b)outcomes,implementationissuesMixtureofabove(a)and(b)outcomes,implementationissuesMixtureofabove(a)and(b)outcomes,implementationissues(d)EconomicCosts,cost-effectiveness,netbenefit,re-sourceuseandcost,economicmeasuresofbenefit(e.
g.
Quality-adjusted-life-years(QALYs),andwillingnesstopay(WTP)),summaryeconomicmeasures(e.
g.
incre-mentalcost-effectivenessratiosICERs)Costs,cost-effectiveness,netbenefit,re-sourceuseandcost,economicmeasuresofbenefit(e.
g.
Quality-adjusted-life-years(QALYs),andwillingnesstopay(WTP)),summaryeconomicmeasures(e.
g.
incre-mentalcost-effectivenessratiosICERs)Costs,cost-effectiveness,netbenefit,re-sourceuseandcost,economicmeasuresofbenefit(e.
g.
Quality-adjusted-life-years(QALYs),andwillingnesstopay(WTP)),summaryeconomicmeasures(e.
g.
incre-mentalcost-effectivenessratiosICERs)aOutcomeslistedareindicativeandnotexhaustiveThompsonetal.
SystematicReviews(2018)7:9Page4of15MethodsThisprotocolhasbeenpreparedusingthePreferredReportingItemsforSystematicReviewsandMeta-Analysesprotocols(PRISMA-P)guidelines[44](seeAdditionalfile1).
EligibilitycriteriaWewillnotlimitoursearchesbycountry;however,wewillonlyincludepaperspublishedinEnglish.
WhilstwerecognisethereisapotentialforbiastobeintroducedbecauseoflimitingthesearchestoEnglish,thedirectionanddegreeofsuchbiasareunknown.
AsoutlinedintheCochraneHandbookforSystematicReviewsofInterven-tions[45],thereisconflictingevidenceaboutthepoten-tialbiasintroducedbyanEnglishlanguagelimit:Juni[46]reportedthatnon-Englishtrialsweremorelikelytoreportsignificantresults,whilstMoher[47]reportednosignificantdifferenceinmeta-analyseswhichexcludedtrialsinlanguagesotherthanEnglish.
Studieswillbere-strictedfrom1978tothepresent:1978waschosenasacutoffpointbasedonafrequencyanalysisonasub-sampleofrelevantliterature.
TypesofstudiesWewillinclude(a)quantitativestudies(RCTs,quasi-RCTs,non-randomisedcontrolledtrials,controlledbe-foreandafterstudies,prospectiveorretrospectiveco-hortstudiesthatincludeacontrolgroup,historicallycontrolledtrials,nestedcase-controlstudies,case-controlstudies,andbefore-and-aftercomparisons);(b)qualitativeinvestigations(ofanyrecognisedqualitativemethodology);(c)localserviceevaluations;and(d)eco-nomicevaluations(fullandpartial).
TypeofsettingWewillnotlimitthesettingorcountryinwhichinter-ventionsaredelivered(althoughthiswillbeimpactedconsiderablybytheEnglishlanguagerestriction),andthisvariationwillbeconsideredinthenarrativesynthe-sis.
Studiesmayincludeinpatientandoutpatientpro-grammes,publichealthinterventions,andcommunity-basedinterventions.
Wewillnotplaceanylimitationsonwhodeliverstheinterventionandinwhatformat.
Participants/populationNolimitonparticipantswillbeapplied;alladultsandchildrenwillbeconsidered.
Weexpectmoststudiestoincludeadolescentsatriskofalcoholandsubstanceuse(prevention),adultsinacuterehabilitationforSUD/AUDandpost-acuterehabilitationforSUD/AUD(re-lapsepreventionandsupportingabstinence),andanyotheradultsreceivingsupportorinterventionforredu-cingalcoholandsubstanceuse(reduction).
Wewillrec-ordandconsiderthesediversitiesinthesynthesisofresults.
Weexpectcertainpopulationstobeofparticularsignificanceintheresearch(e.
g.
peoplewhoarehome-less,havementalhealthproblems,orbelongtogroupsexperiencingcomplexneedsordisadvantages),whereal-coholandsubstanceusemaynotbetheprimaryout-comeandphysicalactivitymaybepartofamorecomplexintervention.
Wherethistypeofstudyisidenti-fied,itwillbeassessedforrelevanceonacase-by-casebasis,discussedwithintheresearchteam,andincludedifitcontainsviabledatathatcanbeincludedwithinthereview'sdefinedprimaryoutcomes.
Intervention(s)andcomparator(s)Wewillincludeanystudiesevaluatingandcomparinginterventionsthatincludeaphysicalactivitypromotionelementeitherexplicitlytargetingareductioninalcoholandsubstanceuseorimplicitlyresultinginareductioninalcoholandsubstanceuse.
Thiscouldbewithinoneofthethreedomainsofprevention,reduction,ortreat-ment.
Thecomparatorcouldbenointervention,treat-mentasusual(e.
g.
pharmacotherapyandpsychologicaltherapies),oralternativephysicalactivityinterventions(e.
g.
runningvswalking).
Thescopeofthisreviewistoincluderesearchonal-coholandsubstanceuseinitsbroadestsense.
Weplantoincludedataonalcoholandsubstanceusewhichmaynotbeconsidereda'disorder'whichreflectslevelsandprevalenceofuse,aswellasincludingresearchonAUDandSUDasclassifiedinthediagnosticandstatisticalmanualofmentalhealthdisorders,fifthedition(DSM-V)[48].
OutcomesTheprimaryoutcomesaremappedagainstthefourplannedanalysesbythethreedomainsofPAanditspossibleimpactonalcoholand/orsubstanceuseinTable1.
SecondaryoutcomesSecondaryoutcomeswillbecollectedduringthedataextractionphaseinadditiontotheprimaryoutcomesabovewherepresent.
Theseinclude:Physicalactivitylevels/fitness;Biomedicaloutcomes(e.
g.
liverfunction,hepatitisCstatus);Mentalhealthandwellbeing;Adverseevents.
Wewillalsoextractdatareferringtotheidentificationoftheunderlyingpsychologicaltheoryinforminginter-ventions;interventionstructureandcontent;informa-tionrelatingtohowaninterventionmayworkincludingchallenges,barriers,andfacilitatorsofbehaviourchangeThompsonetal.
SystematicReviews(2018)7:9Page5of15(processevaluations);themechanismsofchange(media-torsandmoderators),acceptability,andfeasibilitydata;andanyevidenceofadose-responserelationship.
InformationsourcesWewilldevelopandtestahighlysensitivesearchstrat-egyofpublishedandgreyliteratureusingbackgroundscopingsearches,previouslyidentifiedrelevantresearch,andinconsultationwithsubjectexpertsandpublicandpatientinvolvement.
Thestrategywillincludesearchesofthefollowingsources:DatabasesearchingMEDLINE(Ovid)MEDLINE(PubMed)Embase(Ovid)PsycINFO(Ovid)CochraneLibrary(Wiley)(includingCochraneDatabaseofSystematicReviews,CochraneCentralRegisterofControlledTrials,DatabaseofAbstractsofReviewsofEffects,HealthTechnologyAssessmentDatabase,andNHSEconomicEvaluationDatabase)InternationalBibliographyoftheSocialSciences(ProQuest)WebofScienceCoreCollectionCINAHL(EBSCO)AMED(EBSCO)SocialPolicyandPractice(Ovid)AppliedSocialSciencesIndexandAbstracts(ProQuest)SocINDEX(Ebsco)SportDiscus(Ebsco)SupplementarydatabasesearchesGoogleandGoogleScholarOpenGreyProQuestDissertations&ThesesBritishLibraryEThOSScottishAddictionStudiesonlinelibraryHRBNationalDrugsLibraryNIDAInternationalDrugAbuseResearchAbstractDatabaseTuftsCEARegistryDatabaseofpromotinghealtheffectivenessreviews(DoPHER)NHSEvidence(NICE)BigLotteryFundDatabaseSearchstrategyAnInformationSpecialist(AW)willdesignandconductthesearchstrategywithexpertconsultation.
Thestrategywillbetranslatedforuseineachdatabasestatedabove,andamodifiedkeyword-onlystrategywillbeusedforgreyliteraturesearching.
Thesearchstrategywillbedesignedtoencompassthethreeaimsofthere-view(i.
e.
prevention,reduction,andtreatment).
SeeAppendix1forasamplesearchstrategy.
SearchingotherresourcesExtensivegreyliteraturesearchingwillbeconductedtoensuremaximumcoverageofthesubjectarea.
ThegreyliteraturestrategywillencompassfocusedsearchesinGoogle,severalspecialiseddatabases,andconsultationofsubjectexpertsforrecommendations.
Thisprocesswillgenerategreyliteraturepublicationsaswellasrele-vantwebsitesoflocalandnationalorganisationsintheUK,whichwillbehand-searchedforadditionalcitations.
Wewillalsoconductbackwardsandforwardscitationchainingofallincludedstudiestoidentifyfurtherrele-vantarticles,aswellasdirectlycontact-knownexpertsinthefieldandtheleadauthorsofkeypublicationsforknowledgeofanyotherrelevantwork.
WewillincludePhDtheses,butexcludeMSctheses.
Allgreyliteraturewebsitesandsearchengineswillbesearchedwithtargetedkeywordsandphrasesgeneratedfromouroriginalsearchstrategy.
Thefirst100hitsofeachsearchwillbescreenedbytitleandabstract.
Ifahighproportionofthefirst100hits(≥10%)canpoten-tiallybeincluded,thenafurther100hitswillbesearchedcontinuinguntilthenext100hitscontain≤10%ofpotentiallyincludablehits.
Iftheinitialsearchproducesfewerthan100hits,thenallhitswillbesearched.
SeeAppendix2forsamplegreyliteraturesearchstrategy.
StudyrecordsDatamanagementExportedcitationsfromtraditionaldatabaseswillbeen-teredandde-duplicatedintoEndNoteX8(ClarivateAn-alytics).
Greyliteratureresultswillbemanuallyenteredor,whereavailable,capturedthroughabrowser-basedcitationmanagementplug-in(suchasZotero[https://www.
zotero.
org/])thenimportedintoEndNote.
Usingastructuredandpiloteddataextractionform,wewillex-tractrelevantoutcomedata,studycharacteristics,andparticipantcharacteristicsfromeachincludedpaper.
Datawillbeextractedbyonereviewerandcheckedbyanother.
SelectionprocessIndexedandacademicdatabasesTwowavesofstudyselectionwillbeundertaken.
Titlesandabstractswillbescreenedbytworeviewersinde-pendentlyanddisagreementsresolvedbydiscussionor,Thompsonetal.
SystematicReviews(2018)7:9Page6of15wherenecessary,athirdreviewer(titleandabstractscreeningwillbeconductedusingRayyansoftware(QCRI;Doha,Qatar;https://rayyan.
qcri.
org/)).
Twoini-tialsubsetsof500resultswillbescreenedbytwore-viewersandinclusionandexclusiondiscrepanciesdiscussedfollowingeachinordertoensuregoodagree-mentbetweenreviewers.
Followingthis,asetof1000willbecompletedanddiscussedbeforetheremainingresultsbeingscreenedindependentlybytworeviewers.
Thiswillhelpensurereliableandconsistentscreening.
Fulltextswillbeobtainedforstudiesappearingtomeetthecriteriaaboveandscreenedbytworeviewers(eachpaperreviewedbyonememberoftheteamandcheckedbyanother).
Disagreementsareresolvedthroughdiscus-sionandathirdreviewer(AT).
RKwillbeconsultedinrelationtouncertaintyovereconomicevaluationsarisingfromthetwoindependentreviewers.
Thesameprocesswillapplyforgreyliteraturesearching.
Appraisalofstudies(qualityandbias)Wewillevaluateriskofbiasatthelevelofoutcomes.
RandomisedcontrolledtrialswillbeassessedforqualityandriskofbiasusingtheCochraneRiskofBiasTool[49],andnon-randomisedstudieswillbeassessedusingtheROBINS-I[50].
AnyeconomicevaluationswillbeassessedforstudyqualityusingtheConsolidatedHealthEconomicsEvaluationReportingStandards(CHEERS)[51]checklist.
Qualitativestudieswillbeassessedforqualityusingaten-itemchecklistforqualitativestudiesdevelopedandpublishedbytheCriticalSkillsAppraisalProgramme(CASP)[52]whichfocusesonrigour,cred-ibility,andrelevancewithoutbeingoverlyrestrictive.
CASPwillbeusedtoappraisestudiesbutnottoexcludeanystudies.
DatasynthesisDatasynthesiswillbeadaptedfromthemultilevelap-proachassuggestedintheCochraneHandbookofSys-tematicReviews:Quantitativeandqualitativeevidencewillbereviewedseparatelyandthencombinedintoanoverallnarrativesynthesis.
Anarrativesynthesisofser-viceevaluationsandeconomicdatawillbeintegratedintothemainsynthesistoaidincontextualisingthere-sultsintermsofimplementation.
Quantitativestudies(analysisA)Wheredataallow(e.
g.
dataonthesameoutcomefromatleasttwostudiesofsimilardesign,intervention,andpopulation),wewillconductameta-analysistoestimatetheoveralleffectandconsistencyoftheinterventionef-fectacrossstudies.
Asthepopulationandsettingofstudiesarelikelytobedifferent,wewillusearandom-effectsmodeltoobtainthesummaryresultasanestimateoftheaverageinterventioneffectratherthanthecommoneffectestimatedfromafixedeffectsmodel[53].
Wherepossible,wewillcreateandexaminefunnelplotsfortheassociationbetweenstudysizeandesti-matedeffectsize,whichcouldbeduetopublicationbias.
Wherepossible,wewillexploretheextenttowhichtheinterventioncharacteristics,studysetting(country,socioeconomicstatus,healthcaresystem),andpartici-pantcharacteristicsmoderatetheeffectofinterven-tions,throughconductingmeta-regressionsorsubgroupanalyses.
Wewillnotcombinedatafromnon-randomisedtrialswhichuseddifferentstudydesigns,ordatafromrando-misedtrialsandnon-randomisedtrials,inameta-analysis,astheestimatedinterventioneffectsfromdif-ferentstudydesignscanbeinfluencedbydifferentsourcesofbiasand/orincreasedheterogeneity[45].
Inthosecases,wheresuitablenumericaldataarenotavail-ableforpooling,orifpoolingisconsideredinappropri-ate,wewilluseotherapproachestoprovideasystematicsummaryofthestudies,includingtabulation,transform-ationofdataintocommonrubric(e.
g.
daysabstinent),groupingsandclusters(e.
g.
differentpopulationtoas-sessinfluenceofcountry,age,socioeconomicstatus,type/intensityofintervention,setting),andtextualde-scriptionsincludingadetailednarrativesynthesis[54].
Qualitativestudies(analysisB)Thequalitativesynthesisaimstodescribequalitativedatarelatingtotheacceptability,feasibility,mechanisms,mediators,andmoderatorsofphysicalactivityinrelationtoalcoholand/orsubstanceuse.
Dataonthedevelop-ment,design,methods,andthepopulationsinvolvedwillbeextractedfromqualitativestudiesusingabespokedataextractionform.
Thecomplete"findings"or"re-sults"sectionsofthequalitativestudyreportswillbeexportedintoNVivo10(QSRInternationalPtyLtd.
).
Eachsectionwillthenbereadandre-readbytwore-viewers,inconjunctionwiththedataextractionform,toenablethereviewerstofamiliarisethemselveswiththestudyfindingsinthecontextofthestudypopulation,setting,andmethods.
Adoptingathematicanalysisap-proach,reviewerswillcodeandidentifyemergentthemesandconceptsindependently(extractingassoci-atedquotes).
Thereviewerswillcometogethertocon-solidatethefindingsintoonesummaryofoverarchingthemes.
Associatedquoteswillbepresentedtosupporttheidentifiedthemes.
Thereviewteamwillthendrawoutimplicationsofthethemesforpolicyandpractice.
Serviceevaluations(analysisC)Serviceevaluationswillbeconsideredseparatelyfromtheacademicliterature,andthroughathematicsynthe-sisapproachwillbesummarisedtohelpunderstandThompsonetal.
SystematicReviews(2018)7:9Page7of15contextualandimplementationissuessurroundingthedeliveryofPAforalcoholand/orsubstanceuse.
Itwillalsobeused,wherepossible,tocontextualisedatafromtheacademicliteraturewithintheUKcontexttoaidwiththefinalnarrativesynthesis.
Economicevaluations(analysisD)Thereviewofresourceuse,costs,relativeeffectivenessandcost-effectivenesswillincludeadescriptivesummaryofthe(economic)studyquestions,methods,andresults,culminatinginanarrativesynthesis.
Sincethepurposeofourreviewistoprovideclearandconciseinformationontheexistingeconomicevidencebase,wewillalsoconsiderpartialeconomicevaluations.
Thesemayin-cludecostcomparisons,aswellasstudieswithanexclu-sivefocusonrelativebenefits,i.
e.
studiesthatdiscusswillingnesstopayorpreference-basedoutcomemea-sures.
Summarytableswillnotbelimitedtodescriptionofeconomicoutcomesaloneandwillincludeallrelevantinformationintegraltotheeconomicstudy.
Wewillex-tractdetailonanalyticmethods,studyperspective,priceyear,country,currency,andtimehorizonwithfurtherextractionfieldsinformedbysectionheadingswithintheCHEERS[51]checklist.
Sincewedonotanticipateasubstantialamountofeconomicliterature,ourmethodsmayfocusontranslatingfindingsfromthereviewforthepurposesofdisseminationandstakeholderinput.
Alltypesofcomparativeeconomicstudydesign,includingdecision-analyticmodellingapproaches,willbeincluded.
NarrativesynthesisTheanalysisofthequantitative(analysisA),qualitative(analysisB),serviceevaluation(analysisC),andeco-nomic(analysisD)datawillbeintegratedtodevelopanarrativesynthesis.
Thiswillbesummarisedfordissem-inationtoPPIgroupsandkeystakeholdersandusedasabasisforgeneratingcriticalinputtohelpunderstandtheimplicationsofthefindingsfordifferentgroups.
Measuresofinterventioneffects(quantitativedata)DichotomousdataWewillpresentdichotomousdataasriskratioswiththeirassociated95%confidenceintervals(CI).
ContinuousdataForcontinuousdata,wewillcalculatethemeandiffer-ences(MD)foroutcomesmeasuredbythesamescaleorthestandardisedmeandifferences(SMD)foroutcomesmeasuredbydifferentscalesandpresentbothwitha95%CI.
OutcomesatmultipletimepointsIfoutcomeswerecollectedatmultipletimepoints,wewillattempttopresentasummaryeffectoveralltimepoints.
Ifthisisnotpossible,wewillchooseonetimepointthatisthemostappropriateoneandreportthecorrespondingsummaryeffectatthattimepoint.
UnitofanalysisissuesClusterrandomisedtrialsaresusceptibletounit-of-analysiserrorsiftheanalysiswasperformedattheleveloftheindividualwithoutaccountingfortheclusteringinthedata.
Iftheclusteringeffecthasbeenaccountedforintheanalysis,theestimatedinterventioneffectwillbeobtainedfromthereportedsummarydata.
Ifthecluster-ingeffecthasnotbeenaccountedfor,wewillconductanapproximateanalysisusingtheintra-clustercorrel-ationcoefficient(ICC),assuggestedinthecurrentguidelines[45].
IftheICCisavailableinthestudyre-portsorcanbeobtainedfromsimilarstudies,wewillusetheavailableICCtocalculatetheinflatedstandarderrororeffectivesamplesizetoaccountforthecluster-ingeffect.
IfarelevantICCisnotavailable,wewillre-porttheestimatedinterventioneffectaspresentedbutreporttheissueofunitofanalysiserror.
DealingwithmissingdataIfastudydidnotprovidethesummarydataoftheinter-ventioneffects,wewillcontactthestudyauthorsononeoccasiontorequestthesedata.
Whereindividual-leveldataaremissingduetoparticipantdropout,wewillcon-ductavailablecaseanalysesandrecordanyissuesofmissingdatainthe'Riskofbias'table.
Ifstandarderrorisavailablebutstandarddeviationsarenotreportedinastudy,wewillestimatethestandarddeviationfromthereportedstandarderrorandthesamplesize.
Wewillcal-culatetheeffectestimateanditsstandarddeviationifthesearenotreported,butthe95%CIisreported.
AssessmentofstatisticalheterogeneityWewillassessstatisticalheterogeneitybyinspectionofforestplots,andbyformalstatisticaltestsofhomogen-eity(Chi-squared),measuresofinconsistency(I2)[55],andbetween-studyvariance(tau2).
Weinterpretthelevelofheterogeneityasfollows:theheterogeneityisnotimportantifI2islowerthan40%;thereismoderatehet-erogeneityifI2isbetween30and50%;andthereissub-stantialorconsiderableheterogeneityifI2isgreaterthan50%[45].
Ifsubstantialheterogeneityisidentifiedamongstudies,wewillexplorethepotentialcausesofhetero-geneitybyconductingsubgroupanalysesormeta-regressionwherepossible.
AssessmentofreportingbiasesWewillexaminethepossibilityofpublicationbiasandothersmallstudyeffectsusingfunnelplotsoftheinter-ventioneffectestimatesagainsttheinverseoftheirstandarderrorsandtestfunnelplotasymmetryusingThompsonetal.
SystematicReviews(2018)7:9Page8of15Egger'smethod[56]whenthereisasufficientnumberofstudies.
Thisisconsideredatleastten,asasmallernum-berwouldleavethepowerofthetesttoolowtodistin-guishchancefromrealsymmetry.
SensitivityanalysisWewillconductasensitivityanalysisbasedonqualityindicatorsthoughttobesignificantbythereviewteam.
Studiesthoughttobeathighriskofbiasduetospecificqualityindicators(e.
g.
lackofrandomisation)willbere-movedtoascertaintheireffectontheestimatedoveralleffect.
Wealsointendtoconductasensitivityanalysisusingfixed-effectmodels.
ConfidenceincumulativeevidenceThequalityofevidencewillbeassessedusingdomainsoftheGradingofRecommendations,Assessment,De-velopment,andEvaluation(GRADE)[57]guidelines.
Strengthofevidencewillbejudgedas'high'(furtherre-searchisveryunlikelytochangeconfidenceinourfind-ings),'moderate'(furtherresearchislikelytohaveanimportantimpactonourfindings),'low'(furtherresearchislikelytohaveanimportantimpactandchangeourfindings),'verylow'(furtherresearchisneededtodrawanyconclusions).
Externalvalidity/generalisabilityWewillexploregeneralisabilityatthestudylevelandontheleveloftheaggregatedevidence.
Wewillcollectthefollowingdatafromeachstudy:de-tailsoftheintervention,fidelityoftheinterventionandadherencetoit(thisincludeswhodeliverstheinterven-tion),rationalesupportingthechoiceofoutcomemea-sures,andsettinginwhichthestudywasconducted(country,socioeconomicstatusofthesetting,healthcaresystem).
Dependingonthetypeofavailabledata,wewillanalysethemusingsubgroupanalyses,meta-regression,orcontextualiseitthroughnarrativesynthesis.
AdvisorygroupsWewillestablishadvisorygroups:consistingofaca-demics,serviceproviders,andserviceusers.
Thesegroupswilloffervaryingperspectivesonpertinentissuesarisingandwillprovideinputintodifferentaspectsofthereview.
Theacademicgroupwillbeaskedtoprovideacriticalvoiceontheinterpretationoffindings,toensurenoas-pecthasbeenoverlooked,andtoaidinestablishingnet-worksforfindingdataanddisseminatingresults.
TheserviceprovidergroupwillofferinsightintotheUKcontextinwhichalcoholandsubstanceuseexists,whatthecommissioninglandscapelookslike,currentandfuturereachandstructureofservicesandinterven-tions,contextualisefindingstothecurrentUKclimate,andtoaidindisseminationandimplementationofresults.
Theserviceusergroupwillofferinputintowhatout-comesweshouldbesearchingfor,approachestopro-motephysicalactivity(i.
e.
sport,exercise,anddailyactivity)wouldbemostacceptabletopeople;andinwhatotherwayscouldsupportservices(who,where,when)besetuptomaximisethereachandeffectivenessforpromotingphysicalactivityfortheprevention,reduc-tion,andtreatmentofalcoholandsubstanceuse.
Tomaximisetheimpactofstakeholder,public,andpa-tientinvolvement,wewilldevelopauser-friendlysynthesisofthefindingsandnatureofinterventionsandtheirappar-entstrengthsandweaknessesworkingwiththeadvisorygroups.
Onceauser-friendlysynthesishasbeengenerated,itwillbedisseminatedtokeystakeholdergroupsandindi-vidualsandtheirfeedbackandinputwillbeusedtogainfurtherinsightsintowhattheevidencesuggestsandwhereanygapsmayexist.
Specifically,peoplewillrepresentdiffer-entstagesofaddiction,includingthosewhoareoccasionalusersatriskofprogressingtoregularusersofalcoholand/orsubstanceuse,non-treatmentseekerswhowishtomin-imiseharm,andthosecurrentlyreceivingtreatmentorwhoareinrecovery.
Thissynthesiswillthenbedisseminatedtokeystakeholdergroupsandindividualsandusedasthebasisforseveralgroupandindividualmeetingstogainfur-therinputintowhattheevidencesuggestsandwhereanygapsmayexist.
DisseminationandintendedpublicationsUponcompletionofthereview,wewilldevelopasum-maryofkeyfindingsofthereviewofliterature,asum-maryofthePPIassessmentofthefindings,andissuesassociatedwithservicedevelopmentanddeliveryhighlightedbypolicymakersandservicemanagers.
Wewillpresentthefindingsatrelevantacademicconfer-encesandawebsitethatwillbeestablishedtosummar-isethefindingsandimplications,withlinkstoaccessafinalreport.
Weintendalsotoorganiseaone-daycon-ferencetowhichkeystakeholders,advisoryboardmem-bers,andanyinterestedpartywillbeinvited.
Inadditiontoafinalreport,weanticipatesubmittingarticlesforpublicationinpeer-reviewedopenaccessjournals.
WewillalsodisseminatethefindingsbyphoneorSkypetoDirectorsofPublicHealth(orleadsforalcoholandsubstancemisuse)andmanagersoforganisationsacrosstheUKwhodoorcouldinvolvephysicallyactiveinterventionstogainafurtherinsightintotheissuesas-sociatedwithsecuringthenecessaryresources.
DiscussionThescopeandmethodsforthisreviewhavebeenstronglyinfluencedbybothserviceprovideranduserperspectivesthroughoutthedevelopmentoftheThompsonetal.
SystematicReviews(2018)7:9Page9of15applicationandthisprotocol.
Thereviewwillgenerateim-portantandtimelyinformationtoinformtheprovisionofservicesforalcoholandsubstanceuse.
Throughthecon-tinuedengagementwithstakeholders,theinformationproducedwillhaverelevanceacrossavarietyofsettingsinaddressingtheprevention,reduction,andtreatmentofal-coholand/orsubstanceusethroughouttheUK.
Awidevarietyofdisseminationplanswillensuretheinformationisaccessedbythemostrelevantservices,aswellasaidingtodirectfutureresearchefforts.
Thesizeandscopeofthereview,whilstchallenging,willensurethattheinformationbroughttogetherinthisreviewwillbeasencompassingaspossibleandwillprovideallthenecessaryinformationaboutwhatweknowaboutwhatworks,forwho,when,where,andhowinanaccessibleandappropriateway.
Informationgeneratedfromthisreviewwillhavethepotentialtodirectlyimpactonprovisioninsev-eraldomainsandaddress(wherepossible)issuesofaccept-ability,feasibility,implementation,andcost-effectiveness.
Appendix1SamplesearchstrategyDatabasestobesearchedTobeconductedbyAW.
MEDLINE(Ovid)MEDLINE(PubMed)Note:supplementarysearchonlyEmbase(Ovid)PsycINFO(Ovid)CochraneLibrary(Wiley)InternationalBibliographyoftheSocialSciences(ProQuest)WebofScienceCINAHL(Ebsco)AMED(EBSCO)SocialPolicyandPractice(Ovid)AppliedSocialSciencesIndexandAbstracts(ProQuest)ProQuestDissertations&Theses(ProQuest)SocIndex(Ebsco)SportDiscus(Ebsco)SampledatabasesearchtobetranslatedintothedatabasesaboveDatabase:MEDLINEHost:OvidDataparameters:OvidMEDLINE(R)EpubAheadofPrint,In-Process&OtherNon-IndexedCitations,OvidMEDLINE(R)DailyandOvidMEDLINE(R)1946toPresentDatesearches:2-jun-17Searcher:AWHits:12,860Strategy:#SearchesResults1expexercise/157,6032expexercisetherapy/41,2093expexercisemovementtechniques/67364sedentarylifestyle/58705exercis*.
ti,ab,kw.
255,6036Fitness.
ti,ab,kw.
57,6417sport*.
ti,ab,kw.
61,1278isometric.
ti,ab,kw.
29,6999yoga.
ti,ab,kw.
340410taichi.
ti,ab,kw.
130811qigong.
ti,ab,kw.
51912walk*.
ti,ab,kw.
96,51313Jog*.
ti,ab,kw.
210314(weightliftingorweightlifting).
ti,ab,kw.
119515sedentary.
ti,ab,kw.
24,68216pedometer*.
ti,ab,kw.
222317aerobic*.
ti,ab,kw.
74,00018(physicaladj1(train*orprogram*oractivit*orinactivityorfitnessorconditioning)).
ti,ab,kw.
100,13219((resistanceorstrengthorenduranceorweight)adj2train*).
ti,ab,kw.
17,36820or/1-19[physicalactivityterms]630,39521Substance-RelatedDisorders/88,74122Alcohol-RelatedDisorders/458823Alcohol-InducedDisorders/25124AlcoholicIntoxication/12,08225Alcoholism/72,14426BingeDrinking/106027Amphetamine-RelatedDisorders/267628Cocaine-RelatedDisorders/741329DrugOverdose/937530InhalantAbuse/17631MarijuanaAbuse/548732Opioid-RelatedDisorders/10,77333HeroinDependence/869534MorphineDependence/335635PhencyclidineAbuse/23836Psychoses,Substance-Induced/515937SubstanceAbuse,Intravenous/13,95038SubstanceWithdrawalSyndrome/20,48939AlcoholWithdrawalDelirium/190040AlcoholWithdrawalSeizures/24441alcoholics/78842drugusers/219443underagedrinking/293Thompsonetal.
SystematicReviews(2018)7:9Page10of15(Continued)#SearchesResults44AlcoholDrinkinginCollege/20045designerdrugs/129446expstreetdrugs/10,92447prescriptiondrugmisuse/107248AlcoholAbstinence/35049AlcoholDrinking/60,26450((alcoholorethanolordrug*orinhal*orinject*orsubstance)adj2(abstinenceorabstainorabuseorcraving*ordependenc*orillegalorillicitormisuseoroverdos*orprevent*orrecoveryorrecreationaloruse*orwithdrawal)).
ti,ab,kw.
243,66651(prescriptionadj2(abuseorcraving*ordependenc*orillegalorillicitormisuseornonmedicalornon-medicaloroverdos*orrecreationalorwithdrawal)).
ti,ab,kw.
196352(hard*adj1drug*).
ti,ab,kw.
55053(withdrawaladj2(symptom*orsyndrome*)).
ti,ab,kw.
868254hazardousdrinking.
ti,ab,kw.
83055harmfuldrinking.
ti,ab,kw.
35556bingedrinking.
ti,ab,kw.
383957alcohol-related.
ti,ab,kw.
10,71558alcoholics.
ti,ab,kw.
14,31359alcoholism.
ti,ab,kw.
27,72660alcoholintoxication.
ti,ab,kw.
263161addict*.
ti,ab,kw.
53,79262drugseeking.
ti,ab,kw.
229663polydrug.
ti,ab,kw.
134864bathsalt*.
ti,ab,kw.
30865cannabis.
ti,ab,kw.
12,22166cocaine.
ti,ab,kw.
34,89067coke.
ti,ab,kw.
165768crack.
ti,ab,kw.
703369designerdrug*.
ti,ab,kw.
123170dextroamphetamine.
ti,ab,kw.
64071ecstasy.
ti,ab,kw.
347172hallucinogen*.
ti,ab,kw.
318073hashish.
ti,ab,kw.
55974heroin.
ti,ab,kw.
12,72375hookah.
ti,ab,kw.
49576legalhigh*.
ti,ab,kw.
39577lsd.
ti,ab,kw.
463178lysergicacid.
ti,ab,kw.
188979marijuana.
ti,ab,kw.
10,94380mdma.
ti,ab,kw.
371581meth.
ti,ab,kw.
706182methamphetamine*.
ti,ab,kw.
998483methylenedioxyamphetamine.
ti,ab,kw.
569(Continued)#SearchesResults84opiate*.
ti,ab,kw.
23,80685opioid*.
ti,ab,kw.
71,71986opium.
ti,ab,kw.
220787phencyclidine*.
ti,ab,kw.
436988psychedelic*.
ti,ab,kw.
62889psychoactive.
ti,ab,kw.
801890psychostimulant*.
ti,ab,kw.
554491streetdrug*.
ti,ab,kw.
58292volatilesolvent*.
ti,ab,kw.
35693waterpipe*.
ti,ab,kw.
65694((alprazolamoramobarb*oramphetamine*oranalgesic*oranthramycinoranxiolytic*orbarbiturate*orbenzodiazepine*orbromazepamorbuprenorphineorchlordiazepoxideorclonazepamorclorazepateorcannabinoid*orcodeineordemerolordevazepideordiazepamordilaudidordronabinolorduloxetineorendocannabinoid*orephedrineorestazolamorestradiolorfentanylorflumazenilorflunitrazepamorflurazepamorgabapentinorhaloperidolorhydrocodoneorhydromorphoneorhypnoticsorketamine*orlorazepamormedazepamormeperidineormethadoneormethylphenidateormidazolamormorphineornarcotic*ornitrazepamoroxazepamoroxycodoneoroxycontin*orpentobarb*orpentobarbitalorpercocetorphenobarbitalorpiperazine*orpirenzepineorprazepamorpregabalinorpropranololorrelaxant*orritalinorsecobarb*orsedative*orsleepingpill*orstimulant*ortemazepamortetrahydrocannabinolortramadolortramadolortranquilizer*ortriazolamorvaliumorvicodinorzolpidem)adj2(abstinenceorabstainorabuseorcraving*ordependenc*orillegalorillicitormisuseornonmedicalornon-medicalornonprescriptionornon-prescriptionoroverdoseorprevent*orrecoveryorrecre-ationaloruse*orwithdrawal)).
ti,ab,kw.
38,25195or/21-94[substanceabuseterms]591,4869620and9515,7669796not(expanimals/not(expanimals/andhumans/))[removeanimalstudies]14,35798limit97to(englishlanguageandyr="1975-Current")12,860Appendix2GreyliteraturesearchstrategySearchenginesStrategy1GoogleGoogleScholar**Note:priortocommencingsearch,logoutofanygoogleservices(eggmail)ANDusebrowser's"incognito"modetoensuredepersonalisedresultsareshown.
Thompsonetal.
SystematicReviews(2018)7:9Page11of15**Note2:copyandpastetheentiresearchqueryintogoogleandgooglescholar*exactlyaswritten*.
Donotaddextraspaces,etc.
Twosearchqueries,bothtobeusedinbothgoogleANDgooglescholar:1substance|alcohol|drug|opioidabuse|misuse|withdrawal|abstinence|addict|craving|dependency|illegal|illicit|overdose|prevention|use|user|recreational|recoveryexercise|"physicalactivity"|fitness|sedentary2substance|alcohol|drug|opioidabuse|misuse|withdrawal|abstinence|addict|craving|dependency|illegal|illicit|overdose|prevention|use|user|recreational|recoveryexercise|"physicalactivity"|fitness|sedentaryUK|"UnitedKingdom"|England|Britain|NHSGreylitdatabasesStrategy1:ScottishAddictionStudiesonlinelibraryHRBNationalDrugsLibrary(use"allfields"search)NIDAInternationalDrugAbuseResearchAbstractDatabase(pressentertosearch;pressenterwithblanksearchtoseetotalcontentsofthedatabase)Searchesfortheabovedatabases:**Note:Eachofthesesearchesuse"physicalactivity"relatedterminologybecausethedatabasesabovearedrugandalcoholrelated.
FeelfreetosearchforotherrelevantterminologyasneededandrecordresultsinExcel.
1exercise2"physicalactivity"3fitness4sport5sedentaryStrategy2:BritishLibraryEThOSTuftsCEARegistry(Basicsearch–>Searchfor"articles")Searchesfortheabovedatabases:**Note:Eachofthesesearchesusea"physicalactivity"relatedtermcombinedwithadrug/alcoholmisuseterm.
FeelfreetosearchforotherrelevantcombinationsasneededandrecordresultsinExcel.
1drugsANDexercise2opioidsANDexercise(Continued)3substanceANDexercise4alcoholANDexercise5drugsAND"physicalactivity"6opioidsAND"physicalactivity"7substanceAND"physicalactivity"8alcoholAND"physicalactivity"Strategy3:NHSEvidenceSearchesfortheabovedatabase:Note:SearchesaresplitintotwobecauseofcharacterlimitsofNHSEvidencesearchbox1(substanceORalcoholORdrugORopioid)AND(abuseORmisuseORwithdrawalORabstinenceORaddictORcravingORdependencyORillegalORillicitORoverdoseORpreventionORuserORrecreationalORrecovery)AND(exerciseOR"physicalactivity")Select:"primaryresearch"insidebar2(substanceORalcoholORdrugORopioid)AND(abuseORmisuseORwithdrawalORabstinenceORaddictORcravingORdependencyORillegalORillicitORoverdoseORpreventionORuserORrecreationalORrecovery)AND(fitnessORsedentary)Select:"primaryresearch"insidebarStrategy4:OpenGreySearchfortheabovedatabase:1discipline:(05*OR06*)lang:"en"(substanceORalcoholORdrugORopioid)AND(abuseORmisuseORwithdrawalORabstinenceORaddictORcravingORdependencyORillegalORillicitORoverdoseORpreventionORuseORuserORrecreationalORrecovery)AND(exerciseOR"physicalactivity"ORfitnessORsedentary)Strategy5:Databaseofpromotinghealtheffectivenessreviews(DoPHER)(Select"freetext"radiobutton)Searchfortheabovedatabase:1(substanceORalcoholORdrugORopioid)AND(abuseORmisuseORwithdrawalORabstinenceORaddictORcravingORdependencyORillegalORillicitORoverdoseORpreventionORuseORuserORrecreationalORrecovery)AND(exerciseOR"physicalactivity"ORfitnessORsedentary)Thompsonetal.
SystematicReviews(2018)7:9Page12of15Strategy6:BigLotteryFundDatabasehttps://www.
biglotteryfund.
org.
uk/funding/search-past-grantspage=0Searchfortheabovedatabase:1DownloadallitemsfromthedatabaseandcreatesmartgroupinEndNote(n=216,850)Anyfieldwordbeginswithsubstance*;alcohol*;drug*;opioid*;addict*ANDAnyfieldwordbeginswithexercise*;fitness;"physicalactivity";fitness;sedentary;sport*=263hitsStrategy7:TobeconductedbyAW.
ProquestDissertationsandThesesUsingmodifiedsearchstrategiesfromthetraditionaldatabasesearches.
GreylitsearchingproceduresPart1:Database/searchengines1.
Conducteachsearchineachdatabase.
2.
Foreachsearch,record:a.
Dateb.
Databaseandsearchquery(infull)c.
Totalnumberofhits(ifavailable),orestimateifnot.
d.
Numberofpotentiallyrelevantcitationsfromsearch(notfullwebsites,justpapers/articles/etc.
)3.
Foreach,screenfirst100hits(bytitleandabstract).
Ifabove10%arerelevant,screennext100hits,andsoforth.
4.
Foreachpotentiallyrelevanthit:a.
Ifthehitisanarticleorpaper,addtoreferencemanagementsystem.
EnsureataminimumthattitleandURLarecaptured.
b.
Ifthehitisawebsite,addtoexcelspreadsheetforfollow-uplater(seebelow).
5.
Fromallpotentiallyrelevanthitsdownloadedtoreferencemanagementsoftware,full-textscreeningofgreyliteraturetobeconductedbytwopeople(halfofresultstobescreenedbyeach,withresultscheckedbysecondperson).
Part2:Websites1.
Foreachwebsiteidentifiedaspotentiallyrelevant(byexperts,googlesearches,oranyothersources),listwebsiteinExcelspreadsheetandconductasearchforrelevantarticles/papers.
2.
Foreachwebsite,searchstrategiesmightincludeanyofthebelow,asnecessary:a.
Handsearchingofmenusb.
Useofsearchbarswithrelevantterminologyfromsearchesabovec.
UseofGoogletosearchwithinthewebsite,suchas:i.
"substanceabuse"exercisesite:website.
comd.
UseofGoogletosearchwithinthewebsitetofindPDFs,suchas:i.
"substanceabuse"exercisesite:website.
comfiletype:pdf3.
Foreachsearch,recordinExcel:a.
Dateb.
Website,includingURLc.
Processused(e.
g.
searchbar,handsearching,whichmenusused,targetedgooglesitesearch,etc.
)d.
Numberofpotentiallyrelevanthitsfromeachwebsite.
4.
Foreachhit,addtoreferencemanagementsystem(itmaybeworthwhiletouseabrowserplug-in,suchasfromZoteroorMendeleytosemi-automatetheprocess).
5.
Fromallpotentiallyrelevanthitsdownloadedtoreferencemanagementsoftware,fulltextscreeningofgreyliteraturetobeconductedbytwopeople(halfofresultstobescreenedbyeach,withresultscheckedbysecondperson).
AdditionalfileAdditionalfile1:PRISMA-P2015Checklist.
(DOCX32kb)AbbreviationsAMED:Alliedandcomplementarymedicinedatabase;AUD:Alcoholusedisorder;CHEERS:ConsolidatedHealthEconomicsEvaluationReportingStandards;CI:Confidenceinterval;CINAHL:Thecumulativeindextonursingandalliedhealthliterature;DOH:DepartmentofHealth;DSM-V:Diagnosticandstatisticalmanualofmentalhealthdisorders,fifthedition;GRADE:Gradingofrecommendations,assessment,development,andevaluation;ICC:Intra-clustercorrelationcoefficient;MD:Meandifferences;NHS:NationalHealthService;NIHR:NationalInstituteofHealthResearch;PA:Physicalactivity;PPI:Patientandpublicinvolvement;PRISMA-P:PreferredReportingItemsforSystematicReviewsandMeta-analysisProtocols;RCT:Randomisedcontrolledtrial;ROBINS-I:Riskofbiasinnon-randomisedstudiesofinterventions;SMD:Standardisedmeandifference;SUD:Substanceusedisorder;UK:UnitedKingdomAcknowledgementsNotapplicable.
FundingThismanuscriptisindependentresearchfundedbytheNationalInstituteforHealthResearch(NIHR)(ResearchforPatientBenefitProgramme,Asystematicreviewofphysicalactivityforalcoholandsubstanceusedisorders:evidencesynthesiswithstakeholderengagementtoformulatepracticalrecommendations(PB-PG-0215-36117)).
TheviewsexpressedinthisThompsonetal.
SystematicReviews(2018)7:9Page13of15publicationarethoseoftheauthor(s)andnotnecessarilythoseoftheNationalHealthService(NHS),theNIHR,ortheDepartmentofHealth(DoH).
ThisresearchwassupportedbytheNIHRCollaborationforLeadershipinAppliedHealthResearchandCareSouthWestPeninsula.
Theviewsexpressedarethoseoftheauthor(s)andnotnecessarilythoseoftheNHS,theNIHRortheDoH.
SponsorPlymouthHospitalsNHSTrust.
AvailabilityofdataandmaterialsNotapplicable.
Authors'contributionsTTPrincipalInvestigator(PI)isresponsibleforoverseeingtheprojectatallstages,includingthedevelopmentofthesearchstrategy,screeningofidentifiedstudies,applyingthequalityassessmenttools,theanalysisplan,writingofreports,andmanagingPPIandstakeholderinput.
ATprovidesinputandguidanceonallaspectsoftheresearch,includingthesearchstrategy,qualityappraisalmethods,qualitativeandquantitativesyntheses,andtheproductionofthefinalreports.
YWoverseesthedevelopmentofthestatisticalanalysismethodsofthesynthesis,leadsthestatisticalanalysis,andinputtointerpretationsandsupportsreportproduction.
SCasatrialistandstatisticianprovidesinputintothedevelopmentofthestatisticalanalysismethods,datacapture,interpretation,analyses,andinputtoreports.
MNadvisesonallmethodologicalaspectsofthereview,thesearchstrategy,qualityappraisalandbiasassessment,thesynthesismethods,andreportproduction.
KHworksonguidingthesearchmethodsandstrategiesandsupportsreportproduction.
AWastheInformationSpecialistleadsandguidesonsearchstrategy.
JNadvisesonthesearchstrategy,qualitativeanalysis,identificationofPPIgroupsforinputanddissemination,withafocusonsubstanceusedisorders,synthesisoffindings,andreportproduction.
JSadvisesonthesearchstrategyandthedevelopmentofPPIinput,withafocusonalcoholusedisorders,thesynthesisoffindings,andreportproduction.
RKoverseesandguidestheeconomicreviewaspectsoftheresearchandsupportsreportproduction.
GWprovidesinputtomaximisestakeholderinput,impact,andrelevance,asalocalPublicHealthServicelead,andsupportsreportproduction.
Allauthorscontributedto,reviewed,andapprovedthefinalmanuscript.
EthicsapprovalandconsenttoparticipateNotapplicable.
ConsentforpublicationNotapplicable.
CompetinginterestsTheauthorsdeclarethattheyhavenocompetinginterests.
Publisher'sNoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.
Authordetails1PlymouthUniversityPeninsulaSchoolsofMedicineandDentistry,PlymouthSciencePark,Derriford,PlymouthPL68BX,UK.
2CentreforMathematicalSciences,SchoolofComputing,ElectronicsandMathematics,PlymouthUniversity,DrakeCircus,PlymouthPL48AA,UK.
3BristolMedicalSchool,BristolUniversity,Oakfieldgrove,Clifton,BristolBS82BN,UK.
4King'sCollegeLondon,InstituteofPsychiatry,PsychologyandNeuroscience,DenmarkHill,LondonSE58BB,UK.
5FacultyofMedicine,UniversityofSouthampton,4-12TerminusTerrace,SouthamptonSO143DT,UK.
6PlymouthCityCouncil,PublicDispensary,CatherineStreet,PlymouthPL12AA,UK.
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