Supplemental Table 1. QUALITY APPRAISAL SCORES, STRENGTHS, AND WEAKNESSES OF SELECTED STUDIES, CONTINUED

Supplemental Table 1. QUALITY APPRAISAL SCORES, STRENGTHS, AND WEAKNESSES OF SELECTED STUDIES

First Author, Year Design

CCAT or JBI scores

(average), % Strengths Weaknesses

Malignant Fungating Wounds Adderley et al,¹⁷

2014

Systematic review 95/95.4 (95.2)

Recommendations for practice based on appraisal of included studies’risk of bias and methodological limitations

Limitations of the study NR

Ousey et al,¹⁸2014 Integrative review 80/100 (90) Comprehensive search was conducted Eligibility assessment according to CASP criteria

Limitations of the study NR Lower Leg Ulcers

Weller et al,²⁰ 2018

Scoping review 70/80 (75) Comprehensive search was conducted No language restriction

Eligibility assessment conducted by at least two researchers according to specified criteria

Only one reviewer screened full-text articles and extracted data from guidelines in languages other than English

Several of the included guidelines did not report recommendation level of evidence

Andriessen et al,²¹ 2017

Review 100/90 (95) Comprehensive search was conducted Independent screening for inclusion Used AGREE II to review quality of guidelines

Limited to English and German publications The quality grade and methodological weaknesses of included studies NR Information on guideline implementation was lacking

Good clinical response to compression therapy not addressed

Neumann et al,¹⁹ 2016

Guideline 75/80 (77.5) Guidelines presented evidence-based approach for treatment supporting daily practice Recommendations are graded according to strength of evidence

Search terms not provided

Did not report number of researchers involved with eligibility assessment

Guideline specific to Europe, limited generalizability.

Working group did not use the scheme by the Wound Care Consultant Society (WCS)for the description of the treatment of wounds Ratliff et al,²²

2016

Algorithm development:

scoping review, consensus, content validation

70/90 (80) Comprehensive search was conducted Eligibility assessment conducted by three researchers with clinical expertise Consensus panel: a variety of clinicians from varied settings

Content validation done

Processes followed were comprehensive, feasible, and appropriate

The second search included only studies with products available in the USA. Limitation to generalizability

Limitations of the study NR

Carter,²⁶ 2014

Review 85/86.3

(85.6)

Eligibility determined according to clearly stated inclusion and exclusion criteria

Comprehensive search was conducted (1974 to 2013)

Evidence was graded

Limited to English publications

Number of researchers involved with eligibility assessment and quality appraisal was NR

Miller et al,²⁵ 2014

Prospective single-sample cohort

70/65 (67.5) The educational program and data collection tool were reviewed by clients, education and content experts prior to the study

Assessed several domains of behavior change Prompted future research

Limitations of the study were reported

Reported limitations:

Lack of standardized timeframes between intervention and data collection

Data from two related studies with different primary objectives

Limited generalization

Measurement tools not validated

Randomization and blinding techniques not clearly reported

Small sample sizes

(continues)

Supplemental Table 1. QUALITY APPRAISAL SCORES, STRENGTHS, AND WEAKNESSES OF SELECTED STUDIES, CONTINUED

First Author, Year Design

CCAT or JBI scores

(average), % Strengths Weaknesses

Canadian Agency for Drugs and Technologies in Health,²⁷2013

Review 80/75 (77.5) Transparency in reporting included guidelines’ and studies’characteristics, strengths and weaknesses

Limitations of the study were reported

Reported limitations of this review:

Limited high-grade evidence was found - several based on expert opinion.

Small sample sizes, primarily comprised of women.

Tang et al,²³2012 Review 60/60 (60) Wide range of studies included (principles of other chronic wounds and animal studies)

Limitations of the study NR Limited to English publications

Did not report number of researchers involved with eligibility assessment

Did not report on appraisal of methodological quality

Weller et al,²⁴ 2012

Cross-sectional survey

82.5/95 (88.7)

Survey tool developed from focus discussions and pilot tested.

Two independent coders analyzed qualitative data.

Low response rate: 36% (n = 54) Possibility of biased responses (only most knowledgeable nurses might have responded) Past experiences may be affected by recall bias Diabetic Foot Ulcers

Isei et al,³¹2016 Guideline 86/67.5 (76.7)

Recommendations are graded according to strength of evidence

Comprehensive search was conducted Comprehensive list of definitions of terminology provided

Search terms not provided

The method of assessing eligibility was NR No limitations reported

Guideline developed specifically for Japan thus limits generalizability

Lavery et al,³² 2016

Guideline 67.5/65

(66.2)

Recommendations are graded according to strength of evidence available

Rigorous Delphi technique used for separate guidelines

Update on previous guideline thus search terms not provided

Limited to English publications

Did not report number of researchers involved with eligibility assessment

Huang et al,³³ 2015

Guideline 75/77.5

(76.2)

Used the Institute of Medicine standards for reliable Clinical Practice Guidelines Reported on reviewers’characteristics and expertise

Systematic review conducted

Recommendations graded according to strength of evidence available

Search terms listed External review done

Most of the studies used only moderate or low-level evidence and conditional recommendations were made.

Canadian Agency for Drugs and Technologies in Health,²⁹2014

Review 100/85

(92.5)

Well-designed critical appraisal tools used to assess methodological quality

Mostly systematic reviews, meta-analyses, and randomized control trials

Only one reviewer assessed eligibility

Studies had small sample sizes and high potential for bias

Might have limited applicability Crawford et al,³⁴

2013

Guideline 90/85 (87.5) Recommendations graded according to strength of evidence available

Two reviewers involved with eligibility assessment

Restricted to English publications

This publication is a summary of the guideline Limitations of the study NR

Taylor et al,³⁰ 2011

Descriptive correlational

60/65 (62.5) Large sample size

Useful in daily practice as economic factors are mentioned

Convenient sampling (audit of current practice data)

Measures to ensure consistency of data capturing over an extended period were NR

Limitations of the study NR

(continues)

Supplemental Table 1. QUALITY APPRAISAL SCORES, STRENGTHS, AND WEAKNESSES OF SELECTED STUDIES, CONTINUED

First Author, Year Design

CCAT or JBI scores

(average), % Strengths Weaknesses

Pressure Ulcers Fujiwara et al,³⁸ 2018

Guideline 65/60 (62.5) Comprehensive search was conducted Comprehensive list of definitions of terminology provided

Levels A, B, C, D of recommendation for strength of evidence were not clearly defined Limited reporting of included studies’ weaknesses

Several dressings cited are not known in a global context (limited generalizability) The method of assessing eligibility and quality appraisal was NR

No limitations reported Canadian Agency

for Drugs and Technologies in Health,³⁶2013

Review 72.7/81.8

(77.2)

Appraisal of methodological quality of studies A clear description of each included study’s characteristics and limitations

Limited literature search 2008- 2013 narrowed to RCTs in English

Only one researcher screened for eligibility Reported limitation: could not restrict data analysis to intended population and included studies did not report publication bias Gelis et al,³⁷2012 Systematic review 81.8/95

(88.4)

Included the highest level of evidence (only clinical trials)

Transparent reporting of systematic review process and appraisal of methodological quality of the studies

Methodological shortcomings of included studies not clearly reported

Limitations of the study NR

Guihan et al,³⁵ 2012

Cross-sectional observation

60/75 (68) Large sample size (n = 131)

Comprehensive assessment of risk factors Limitations of the study reported

Convenience sampling

Validity of the scales/checklists used to assess risk factors was NR

Reported limitation: cognitive screening for inclusion based on primary care giver’s judgement

Atypical Wounds

Alavi et al,⁴⁰2018 Observational cross-sectional cohort

100/100 (100)

Comprehensive measurement with 4 validated tools.

Small sample sizes

Addison et al,³⁹ 2017

Descriptive prospective observational cohort

88/90 (89) Large prospective wound management study capturing real conditions in the health care system Detailed monitoring and documentation of the wound classification and sizing using the World Health Organization BU classification and Flanagan’s criteria to identify and monitor closure

Unequal sample sizes

Shanmugam et al,⁴² 2017

Review 60/70 (65) Comprehensive search of the literature Assessment for eligibility and appraisal of methodological quality were NR Pope et al,⁴¹2015 Consensus 80/70 (75) Involvement of a multidisciplinary expert group with

expertise in EB treatment, wound care biology, and clinical practice

Limitations of the study NR

The method to address scores <80% were NR Experts were mainly from colder countries which may influence dressing choices and management and therefore limits generalizability

(continues)

Supplemental Table 1. QUALITY APPRAISAL SCORES, STRENGTHS, AND WEAKNESSES OF SELECTED STUDIES, CONTINUED

First Author, Year Design

CCAT or JBI scores

(average), % Strengths Weaknesses

Local Wound Bed Factors Schultz et al,⁴⁴

2017

Modified Delphi method

77.5/80 (78.75)

Consensus reached through a rigorous Delphi technique involving a diverse group of experts selected for their expertise in the field

Full agreement was reached during final consensus round

Developed a new paradigm for biofilm management

Risk of bias: involvement of a wound care product company (however, the paper declared it as a conflict of interest)

Akhmetova et al,⁴³ 2016

Review 70/60 (75) Comprehensive search conducted Independent appraisal of quality Limitations reported

Although quality appraised, the quality of included papers was NR

The number of papers screened and included were NR

Sherman,⁴⁵2014 Review 95/95 (95) Comprehensive search conducted resulting 97 relevant papers

Eligibility assessment method (no. of researchers involved) NR

Quality appraisal NR Data extraction method NR Limitations of the study NR

Abbreviations: AGREE, Appraisal of Guidelines, Research and Evaluation; CASP, Critical Appraisal Skills Programme; CCAT, Crowe Critical Appraisal Tool; JBI, Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses; NR, not reported; WCS, Wound Care Consultancy Society.

Sup plemental T able 2 . CHARAC TERISTICS OF S E LEC TED RE VIE W S

FirstAuthor,YearStudyAimSearchStrategyNo.ofincludedstudies (no.relevant)MainFindings MalignantFungatingWounds Adderley etal,17 2014Toreviewtheevidence ontheeffectsof dressingsandtopical agentsonQOLand symptomsthatimpact QOLinpeoplewithMFW CochraneWoundGroup SpecializedRegisterand CentralRegisterof ControlledTrails;Ovid MEDLINEandEMBASE; EBSCOCINAHL. Searchtermsprovided. Nodateorlanguage restrictions.

4(4)NoevidenceavailableontheeffectofdressingsandtopicalagentsonQOLofpatientswithMFW. Weakevidencetosuggesttimetodiseaseprogressioncouldbeextendedwiththeuseoftopical6% miltefosinesolutionforsuperficialfungatingbreastcancerlesions. WeakevidencetosuggesteffectivenessofsilverfoamdressingstoreducemalodorofMFW. Evidenceinsupportofmanukahoney-coateddressingsversusnanocrystallinesilvercoateddressings formanagementofodor,cutaneouspain,exudateofMFWisnotsignificant. Evidencefortheuseoftopicalmetronidazolegeltocontrolmalodorisnotsignificant. Ouseyetal,18 2014Toilluminatethe constructofresiliencefor anypatientswho experienceda psychologicalimpact fromhavingawound.

CINAHL,Emabse, Medline,BNI,Psychinfo. Searchtermsprovided Upto2013 Languagerestriction: English

12(6)Noevidencefoundregardingresilienceasprimaryendpoint RelevancetoH2H: •Patient-centeredconcerns:personslivingwithachronicwoundexperienceloss(financial,capacity) andchangeinsocialroles.Isolatethemselves,developanxietyanddepressionandmentaldisorders thataffectsphysicalandpsychologicalfunctioning. •Livingwithpain,lossofmobility,alteredsleepingandeatinghabits,copingwithwoundtreatments. Adaptationandmaladaptationoccur. •Thepatient’sexperienceisnotalwaysapriorityofthehealthcarepractitioner •Personswithchronicwoundsindicatetheirneedfortreatmentbyskilledandupdatedhealthcare professionalswhoworkwithinmultidisciplinaryteamsaswellasindividualassessmenttoensure appropriatetreatment. •Aneedforsocialsupportandreducingstresstopromotewoundhealing RelevancetodiabeticfootulcersasH2Hwounds: •Personswithdiabetesandwoundsscoredlowerforhealth-relatedQOLwithadeclineinphysical andsocialfunctioning. •Psychologicalfactorsimpactedthedevelopmentofawound(n=333) •Depressionisapersistentriskfactorformortalityandan33%increasedriskofamputations. RelevancetoMFWs: •PainandfatigueareobstaclestomaintainingQOL. •Losingcontroloverbodilyfunctionscanimpederesilience •Lossofcontrolandresilienceiflackofinformationoradviceprovidedonhowtomanagethewound. •PatientswithanMFWcoulddevelopavoidanceanddestructivefeelings. (continues)

Supp lemental Ta ble 2 . CHARACTE RIST ICS O F S EL E C TE D R E V IE WS, C ONTI NUED

FirstAuthor,YearStudyAimSearchStrategyNo.ofincludedstudies (no.relevant)MainFindings LowerLegUlcers Welleretal,20 2018Todetermineifconsensusexistedin relationtorecommendationsfor compressionapplicationbasedonan ABPIreadingandclinicalassessmentCPGsorBPRswere sourcedfromAndriessen etalthroughsearchesof ScopusandPubMed. Searchtermsprovided Studiespublishedor updatedbetween 2000-2018 Nolanguagerestrictions

13(13)Recommendationsforclinicalpractice: •SafeapplicationforanABPIrange0.8-1.2mmHg. •CompressioniscontraindicatedifABPIis>1.2or<0.5mmHg •Referraltovascularspecialist:ABPIof<0.5mmHg.ReferralisrecommendedifAPBIis >1.2and<0.8mmHg. •ABPI>0.6to<0.8mmHg:graduatedcompressiontherapyifPADordiabetesmellitus wereexcluded.Re-assessevery12weeks •UncertaintyanddisagreementmostlyexistfortheABPIrangebetween0.6and0.8. •Comparisonbetweenguidelinesischallengedbytheinconsistentreportingoflevelof evidenceandgrading. Andriessen etal,21 2017Tooptimizetheprevention,treatment andmaintenanceapproachesthrough identificationofcomplications, adverseevents,riskfactorsand complicationsofcompressiontherapy.

PubMed,Medline, Embase,CINAHL, CochraneLibrarydata basis. Searchtermswere provided. January2009-April2016 Languagerestrictedto GermanandEnglish

20(20)Providesatablewithabsolute/relativecontraindicationsandcontraindicationswithout classificationinthearticles;arterialcirculationandABPI;andriskandadverseeffectsand complications Addresstheissueofnursecompetencyinachievingoutcomesandthemistakesof incompetencethatprolongshealing(addingtomaintenance) Addressmodifiedcompressionforcertainpatientgroups,againhighlightingthosepatients inwhomapooroutcomecanbepredicted. Noindicationofnonhealing.Maintenanceinthisarticlereferstocompressionhosiery afterthewoundhashealedtopreventrecurrence. Carter,26 2014Toassessthecosteffectivenessof newinterventionssystemdesignedto improvetheprevention/treatmentof chronicwoundsinadultpopulations againstcurrentcareandprovide decisionmakerswithinformationon whichtobasefuturechronicwound management

PubMed,Scopus,HTA, andNHSEEDSearch termsprovided. January1974-August 2013 Languagerestrictedto English

16(6)Goodevidencethattheuseofanevidence-basedpreventionprogramofPUswascost- effective. Moderateevidencethatintensiveglycemiccontrolandoptimalfootcarewas cost-effectiveoverthelifespanofapersonwithdiabetes Moderateevidencethatamultidisciplinaryapproachtowoundcarewascost-effective comparedwithusualcare. Someevidenceexiststhatitismorecost-effectivetotreatvenouslegulcersinspecialized (woundcare)clinics. (continues)

Sup plemental T able 2 . CHARAC TERISTICS OF S E LEC TED REVIEWS, CO NTIN UED

FirstAuthor,YearStudyAimSearchStrategy

No.ofincluded studies(no. relevant)MainFindings Canadian Agencyfor Drugsand Technologiesin Health,27 2013

Tosummarizetheclinical evidenceregardingthe needforspecialist-led advancedcare, indicationsforreferralto specialistcare,andthe guidelinesregarding multidisciplinary managementofchronic, nonhealing, non-pressure-related lowerextremitywounds LimitedsearchincludedOvidMEDLINE, PubMed,CochraneLibrary,UniversityofYork CRDdatabases,internationalhealthtechnology agencies,andfocusedInternetsearch Searchtermsnotprovided January2009-November2013 RestrictedtoEnglishpublications

5(3)Theneedformultidisciplinarymanagementisemphasizedandalsothatmoreevidenceis neededtocomparehealingwhenspecialist-ledwoundcareisprovidedversusnot. Themultidisciplinaryapproachshouldinvolvethecircleofcareandthepatient. Littleconsensusexistsonthemanagementofmixedarterialandvenousulcerations. RecommendationsregardingimmediateneedforspecialistreferralincludedPAD, nonadherence,doubtregardingetiology,suspectedmalignancy,evidenceofischemia,and woundswithatypicaldistribution. Referralforbiopsyisrecommendedforvenouswoundswithoutsignsofhealingfor3months, orthatdonotdemonstratetreatmentresponsefor6weeks,ifthewoundisatypical,orthere isdeteriorationorfailuretohealafter12weeksofactivetherapy Theaccesstospecialistcareshouldbeconsideredbecauseitisnotalwaysavailable Tangetal,23 2012Tohighlightnew findingstoassist practitionersandpatients inappropriatehealthcare decisionsanddrivefuture researchendeavors

MEDLINE,Embase,andCochrane reviewsformeta-analysis,systematicreview, randomizedcontroltrial,retrospectiveseries review,orclinical caseseries Validatedprinciplesforotherchronicwound typeswereincludedaswellasanimalstudies Excludedreviewarticlesandcase reports Searchtermsnotprovided January2006toJanuary2011 LimitedtoEnglishpublications

97(97)Diagnosis:confirmationoftheessenceofcorrectdiagnosisandexclusionofarterialdisease; APBIhashighspecificityandisthereforevalidtousefordetectingarterialocclusion. Addressproteindeficiency ImprovedhealingwithpolyhexanideascleansingsolutioncomparedwithLactatedRingeror saline. Referencetothemicrobialdensityasapredictorofnonhealing Compressionisessentialforwoundhealingandmultilayercompressionismoreeffective thansinglelayercompression Surgicaldebridementofnecroticanddevitalizedtissuewithmaintenancedebridementis beneficial Consistentongoingdocumentationofwoundhealing Topicaldressingsthatmaintainmoistenvironmentandprotectperiwoundarea. Costeffectiveandappropriatedressingtosettingandprovider Negative-pressurewoundtherapyandDakinsolutionpriortoskingraftdecreasesbacterial loadandresultedin100%takeandcompletehealingat1year. Lifelongcompressionstockingstopreventrecurrenceofulcers (continues)

Su pplementa l T ab le 2 . CHAR ACTE RIST ICS O F S ELECTE D R EVIEWS, C ONTINUED

FirstAuthor,YearStudyAimSearchStrategy

No.ofincluded studies (no.relevant)MainFindings DiabeticFootUlcers Canadian Agencyfor Drugsand Technologiesin Health,29 2014

NegativePressure WoundTherapyfor managingDiabeticFoot Ulcers:areviewof clinicaleffectiveness, cost-effectivenessand guidelines PubMed,Cochrane Library,UniversityofYork CRD,internationalhealth technologyagenciesand afocusedinternetsearch Searchtermsprovided January2009-July2014 Languagerestriction: English

16(16)EvidencesupportsgreaterclinicalefficacywiththeuseofNPWToverconventionaltreatmentsinDFU. AlthoughevidencesuggeststhatNPWTcouldbemorecosteffectivethanconventionaltreatment, furtherresearchisneededtosupportthis. PressureUlcers Canadian Agencyfor Drugsand Technologiesin Health,36 2013

Todeterminetheclinical effectivenessofand evidence-based guidelinesforthemost frequentlyusedwound dressing/productsfor managementofstageIII andIVpressureulcersfor bedriddenseniorsin long-termcarefacilities PubMed,Medline, CochraneLibrary, UniversityofYorkCRD, internationalhealth technologyagencies,and afocusedinternetsearch Searchtermsnot provided January2008-October 2013. Languagerestriction: English

3(3)Selectdressingsaccordingtotheneedsofthewoundtoensureaviablewoundbed,todecreasethebio-load andtoensureamoisturebalance;considerotherfactorssuchasincontinence. NoproofisavailabletosupporttheuseofaspecificdressinginstageIIIorIVpressureulcers Gelisetal,37 2012Todeterminetheroleof therapeuticpatient educationinpersonsat riskofand/orwitha pressureulcer.

PASCALBiomed, PubMed,Cochrane Library Searchtermsprovided 2000-2010 Restriction:clinicaltrials Languagerestriction: EnglishandFrench 6(6)Continuingtherapeuticeducationofolderadults,personswithspinalcordinjury,andothersatriskfor pressureulcersisrecommended Formulatepedagogicobjectivesaccordingtotheneedsofthespecificpopulation (continues)

Sup plemental T able 2 . CHARAC TERISTICS OF S E LEC TED REVIEWS, CO NTIN UED

FirstAuthor,YearStudyAimSearchStrategy

No.ofincluded studies (no.relevant)MainFindings AtypicalWounds Shanmugam etal,42 2017Toreviewtheliterature acrossmedicaland surgicalspecialtieson refractorychronic woundsassociatedwith vasculitisand autoimmunediseases anddelineate clinicaloutcomesof thesewoundsin responsetovascularand otherinterventions

Medline,PubMed,Cochrane Library,andScopus Searchtermsprovided Studiespublishedthrough March2016 Languagerestriction:English

NotclearlyreportedAlargewoundsurfaceareaandfailureofsplit-thicknessskingraftingmaybe signsofimmune-relatedpathologiesdemandingfurtherassessment Recalcitrantlegulcerwounds: •Considervasculitisandautoimmuneetiologiesinpatientsnotrespondingto vascularinterventionandstandardlocalwoundmanagement •Ensureaninterdisciplinaryapproachforinvestigationofunderlyingpathology •Includereticulardermisandsubcutaneoustissueinbiopsywhenvasculitisis inthedifferentialdiagnosis •Systematicandcomprehensiveapproachtohistorytaking,physical examination,andlaboratoryworkupimprovesoutcomes LocalWoundBedFactors Akhmetova etal,43 2016Tosummarizestudies focusingonodorcontrol inthemanagementof chronicwoundtherapies

PubMed,MEDLINE,Webof Science,GoogleScholar,LISTA (EBSCO),WileyOnlineLibrary, CochraneLibrary,Libraryof NazarbayevUniversity databases. Hardcopiesofpeer-reviewed publications Searchtermsprovided Nodateorlanguage restrictions.

Notclearlyreported (none)Studiesinthereviewtendedtohavesmallsamplesizes,shortdatacollection periods,andalackofmeasurementofmalodormagnitudewithvalidated instruments.Theauthorthereforesuggeststheneedforastandardized techniquefordetectingandmonitoringwoundodor. Severalofthestudieswerenonrandomizedcomparisoncohortstudies,case studies,ormultiplecaseseriesandonlytwowererandomizedcontrolledtrials; twowererandomized,placebo-controlled,double-blindtrialsevaluating metronidazole Sherman,45 2014Toexaminethebest clinicalandbasicscience evidenceof maggot-inducedwound healing

PubMed,Cochrane,andWiley OnlineLibrarydatabases Searchtermsprovided Studiesnotolderthan20years Languagerestrictionnot reported 93(93)Effectivedebridementmodality Fastereradicationofinfection Two-thirdsfeweramputations Significantlyfasterwoundhealinginthemaggot-treatedwounds Contributetoandsupportgrowthstimulation Safe,effectiveandlessdestructivetreatmentforwounds Abbreviations:ABPI:ankle-brachialpressureindex;BPR,bestpracticerecommendation;CPG,clinicalpracticeguideline;CRD:CentreforReviewsandDissemination;CINAHL:CumulativeIndexofNursingandHealthLiterature;H2H:hardtoheal;HTA:Health TechnologyAssessmentdatabase;MFW:malignantfungatingwounds;NHSEED:NationalHealthServiceEconomicEvaluationDatabase;QOL:qualityoflife.

Su pplemen tal T able 3 . CHARA C TERISTICS OF SELECTED ORIGIN AL STUDIES AND C O NSENSUS STUD IES

FirstAuthor, Year,CountryStudyAimDesignandSampleSizeSample CharacteristicsInterventionOutcomeMainFindingsofRelevance LowerLegUlcers Ratliffetal, 2016,22 USToaidcliniciansinthe selectionandapplication ofcompression,a consensus-and evidence-based algorithmwas constructedthatincluded theprimaryprevention, treatment,and preventionofrecurrent VLUsinpatients withCVI.

Scopingliterature reviewfollowedby consensusvotingand contentvalidation Consensuspanel:20 Contentvalidation panel:21 Consensuspanel: keyopinionleaders representing varietyofclinicians Contentvalidation panel:expertsin CVIandVLU management N/AValidatedalgorithmfor careofVLUsacrossthe continuum

Theneedforandcorrectapplicationofcompressionforpersons withCVIwithorwithoutVLUwasdesignedtoassistclinicians. Adjunctivetherapiesarenotendorsedbytheauthorsandremain controversial.However,theirpresenceinthedailypracticeof manycliniciansmanagingpatientswithCVIwithorwithoutVLU isreflectedbytheirpresenceinthealgorithmratherthanan endorsementofthesemedications,giventhepaucityofevidence. Whenchoosingcompression,thealgorithmprovidesevidence-or consensus-basedguidancetowardselectionofproduct categories;recommendationofanyspecificproductsis intentionallyavoided. Facilityconsiderationssuchascontractualarrangements, cliniciancomfortwithcertainproducts,andpatientindividual factorssuchasaccesstoproducts,tolerance,andaffordability haveaprofoundinfluenceonsuchchoices. Milleretal, 2014,25 Australia

Examinationofbehavior maintenanceassociated withacliente-learning VLUprogramacrossan average8-to9-month period Prospectivesingle samplecohort N=49 Initially,anactive legulcer. Communitybased patients.

E-learningVLUprogram followedbyanRCT comparingwound recurrenceassociated withtheuseofmoderate andhighcompression stockings. The49patientswhose ulcershadhealedwere transferredtotheRCT study.

Thesustainabilitythe behaviorchanges associatedwithan e-learningprogram.

Physicalactivitylevelsincreasedovertime. Legelevation,calfmuscleexercises,andsoapsubstituteuse fluctuated. Theuseofamoisturizergraduallydeclinedovertime. Hard-to-healwoundswereaddressedwithinterventionsand stepstoguidethisperiod. Facilitatethepreparationneededtogetapatienttoaccept havingamaintenancewound. Addressesrepetitivebreakdownwithinashorttimeframe,(a signofamaintenanceorheardtohealwounds). (continues)

Sup plemental T able 3 . CHARACTERISTICS OF SELECTED ORIGINAL ST UDIES AND C ONSENSU S S TUDIES, C ONTINUED

FirstAuthor, Year,CountryStudyAimDesignandSampleSizeSample CharacteristicsInterventionOutcomeMainFindingsofRelevance Welleretal, 2012,24 Australia

Toexplorecurrentpractice nursemanagementofvenous leg ulcerstodetermineif evidence-basedguidelines wereusedtoaid management Cross-sectionalsurvey N=151PNswere includedinthe distributionofthe survey;54replied.

PNsinamajor generalpractice networkin Melbourne(325 registeredgeneral practices). Thenetwork includes151PNs in142practices. Respondentswere predominantly womenolderthan 40yearsqualified asDivision1RNs (83%).

SurveysweredistributedMay- July2010.Thefinalsurveytool consistedof28questionsto determineVLUmanagementin generalpractice;knowledgeof andadherencetobestpractice guidelines;barriers,facilitators, andexperiencesregarding referraltospecialistwound clinics;andviewsonpotential improvementstoVLUcare.

N/AImprovedmanagementandreferralpathwaysfor peoplewithVLUareneeded Furtherinvestigationtodeterminethemost appropriatecoordinatedVLUmodelofcareis required Investigationofhealthprofessionaluptakeofthe AustraliaNewZealandguidelinesisrequired Furtherinvestigationandgreaterinvestmentin upskillingPNsinankle-brachialpressureindex measurementisrequired. CompressionapplicationmayimproveVLU managementinprimarycaresettings. DiabeticFootUlcers Taylor etal,30 2011,US

Toperformananalysisof functional outcomestoassesscurrent treatmentparadigm Descriptive correlationdesign N=917limbs

Meanage:64.2y Sex:men,61% Diabetestype2: 87%End-stage renalfailure:26% Approximately 50%ofulcers occurredonlimbs withconcomitant ischemia.

Endovascularrevascularization oropenbypassorno revascularization Ulcer healing,survival,limb salvage,amputation-free survival,maintenanceof ambulation,and independence.

Diabeticfootulcershaveaprotractedhealingtime withthemeanhealingtimeof33w Therewaslittledifferenceinulcerhealingratesfor patientswithorwithoutischemia,althoughitwasa significantmarkerofpooroutcomes Woundhealingwasanindependentpredictorof survivalandamputation-freesurvival (continues)

Sup plemental T able 3 . CHARACTERISTICS OF SELECTED ORIGINAL ST U D IES A ND CONS ENSUS S TUDIES, C ONTINUED

FirstAuthor, Year,CountryStudyAimDesignandSampleSizeSample CharacteristicsInterventionOutcomeMainFindingsofRelevance PressureUlcers Guihan etal,35 2012,US Todescribethepotentially modifiablemedicaland behavioralriskfactorsamong veteranswithSCIandsevere (stageIIIandIV)pelvicPIs.

Cross-sectional observational N=131

Meanage:55.9y Sex:97.7%men. Meanyearssince injury:22.2y(SD 12.8;range, 1-52y). Noparticipanthad aterminal diagnosis. Averageduration ofPIbefore admissionfor treatment:1y (range,1-13y)

NoneN/ANotmanysignificantdifferencesbetweengroup withmanycomorbiditiesversusthosewithfewer. PersonswithSCIandseverePIsingeneralhasto manageonaverage6.7comorbidconditionsin additiontotheSCIandPIs Overallknowledgetoeffectivelymanageand preventPIsoveralifetimewaslow Skincareandgoodnutritionaremodifiable behaviorsthatrequiremoreattention AtypicalWounds Alavietal,40 2018, Canada

Toinvestigatethecontribution ofsexualdysfunctiontotheQoL ofpatientswithHSandthe extenttowhichsexualhealth predictsQoLinpatientswithHS Observational cross-sectionalcohort intwolegs Intervention,50 Control,50

HSgroup: confirmedHS diagnosis regardlessof additional comorbidities. AverageBMI30.7 Controlgroup:age- andsex-matched healthyindividuals withno comorbiditiesor otherdermatologic condition.Average BMI25.45 Fourvalidatedsexualhealth questionnaireandDermatology LifeQualityIndex(DLQI)

MenwithHShad significantlylowersexual functionscoresthanthe healthycontrolgroup HSsignificantly correlatedtolower sexualfunctioningscores WomenwithHShad significantlyhigher distressrelatedtosexual functionthancontrol group

HShasasignificantimpactonsexualfunctionin bothsexes MenwithHSidentifysexualperformance impairment WomenwithHSidentifyincreasedsexualdistress PatientswithHShadsignificantlylessQoLthanthe controlonDLQI Sexualdysfunctionfromaskinconditionisan importantcontributortoimpairedQoL ImportanttoconnectpatientswithHSto psychologicalandcounsellingnetworkstominimize theimpactonself-image,self-esteem,depression andanxiety (continues)

Sup plemental T able 3 . CHARACTERISTICS OF SELECTED ORIGINAL ST UDIES AND C ONSENSU S S TUDIES, C ONTINUED

FirstAuthor, Year,CountryStudyAimDesignand SampleSizeSampleCharacteristicsInterventionOutcomeMainFindingsofRelevance Addison etal,39 2017,Ghana Toinvestigate theassessment andmanagement ofBUpatientsat PHCandSHC Quantitative descriptive prospective observational cohort N=133

PHC 111patientswith121 clinicallysuspected BU 53%youngerthan16 years=PCR 58.1%men Lesionlocation: Lowerextremity 93.3% Upperextremity 6.7% Rightside63.3% Underweight:6% SHC 22patientswith27 clinicallysuspected BU 77.3%olderthan15 years=PCRpositive BU 63.6%men= PCRpositiveBU 52.5%men= PCRnegativeBU Lesionlocation:Lower extremity87.5% Upperextremity 4.2% Rightside63.6% Face8.3% Underweight: 36% Comorbidities: PHClessthanSHC Courseofwound healingand predictorsof woundclosure, assessmentof infrastructure, supplyandstaff performancewere investigated prospectively for22consecutive months (2013-2015)ina PHCand3 consecutive months(2013)in SHC Casereportformof patientandwound histories,courseof healing,physical examination, wound assessment, photographs

Woundcategories:PHC52%CategoryI SHC82%CategoryIIIWoundhealingCompletehealing PCRpositiveBU:PHC 26(86.7%)nosurgeryoradjuncttreatment SHC8(40%)healed;12.5%noadjuncttreatment 75%aftersplit-skingrafting12.5%afterexcision PCRnegativeBU:PHC76(98.7%)wereeithercompletely oralmostclosedTimetohealingPHC Lessthan3mo65%3-6months26.9%After6mo7.7% DelayedhealingPHCPCRpositive:13.3%underlying pathologiesidentified:exposedbone(n=1) Woundinfection(n=1)Woundlocationatjoint(n=1) Pooradherencetotreatment(n=1)RecapturedPCRnegative: 5%missedpathologydiagnosisSHC60%underlying pathologiesidentified:woundinfection(n=1) venousandarterialinsufficiency(n=4) nutritiondeficiency(n=7)Woundinfection: PHC9%vs.SHC50%hadevidenceofinfectionatleastonce Pain:PHC54.8%experiencedpainatleastonce; Intermittentpain:52.9%Painduringwounddressing:55.6% Constantpain:47.1%Mildpain:23.5%Moderatepain:52.9% Severepain:23.5%SHClocalizedpain:59.1%surrounding tissuepainoronthelimb:53.8%Painduringwounddressing: 38%Analgesia:PHCNoanalgesiareceived.Analgesiausage unprescribed:52.9%SHC53.8%ofpatientswhocomplained aboutpainreceivedanalgesia.Infrastructureandwoundcare practicesPHCOnetreatmentroomforallwoundtypes–BU weretreatedafternon-BU.Availabilityandqualityofmaterials limited.Cleanwaterirrigationnotconsidered.Insufficient supplies.Bandageswashedinpatients’homesandre-used. Mechanicalcleansingofexudateinterferingwithgranulation. Paincontrolnotperceivedasimportant.SHC Separationofin-andoutpatientswithinfectionandwound managementstandardizedprotocolsinconsistent.

Largeorchroniculcersarea highriskforinvasiveandcostly treatmenttoachieveclosure. Nonhealingwoundscanbe predictedbywoundarea reductionbetween2to4w afterinitiationoftreatment PHClevelcanadequately managepatientswithBUwith basicinfrastructure,appropriate qualityofstandardsuppliesand equipment,welltrainedhealth staff,andadherenceto guidelines. PatientsmanagedatPHCcan maintainlivelihood,staycloser tofamilies,andarelessprone tofacility-acquiredinfection. PatientswithPCR-negative ulcersandclinicalBUsuspicion requirefollowuptocapture missedBUdiagnosisand therapeuticsignificant pathology. Hygiene,woundcare deficiencies,andlackof identifyingunderlying conditions,arrestedwound healing,andlackof advancementtoactivewound management Healthcareworkersneedtobe moresensitiveto patient-centeredconcerns (continues)

Sup plemental T able 3 . CHARACTERISTICS OF SELECTED ORIGINAL ST U D IES A ND CONS ENSUS S TUDIES, C ONTINUED

FirstAuthor, Year,CountryStudyAimDesignandSampleSizeSampleCharacteristicsInterventionOutcomeMainFindingsofRelevance Popeetal,41 2015, International

Togeneratea listof recommendations toenable practitionersto bettercarefor patientswith consensus approachtowound careinEB ModifiedDelphi Groupdrafting recommendations:11 Delphirounds:33 InternationalEB experts

Groupdrafting recommendations: (physiciansand nurses)withEB clinicalandresearch expertiseand backgroundinwound care,wound-healing biology,infectious diseases,and bone-marrow transplantation. Delphirounds:33 internationalEB experts

N/A17refined recommendationsNoRCTevidenceattimeofpublication. 17recommendationswereformulated,including: •EvaluateEBtype-specificinvolvement. •IdealmethodsofongoingassessmentofEBpatientsarelacking. •Increasedriskofsquamouscellcarcinomainthesecondandthirddecade oflifeinpatientswithsevereformsofEB. •Assessandmanagepoornutrition. •Optimizenutritionstatus. •Monitorandmaintainhemoglobinlevelsabove80g/L. •LowlevelsofhemoglobinmaydelayhealinginEBpatients. •NoidealmanagementapproachforanemiainEBpatients. •Addresspain,itch,odor,immobility,depressionandanxiety •Acentralizedinterprofessionalapproachwithcareco-ordinationismost effective. •Debridementinvolvesnonphysicalmethods.Puncturetheblisterto facilitatedrainageandleaveoverlyingskininsitu. •Longtermalternatinglowdoseantibacterialagentsmaybebeneficial •Woundsizereductionof20-40%in2-4weeksisareliablepredictorof healingat12weeks. •Cliffedgesareoftenseeninnonhealingwounds.Consideradvanced therapieswithnonadvancingedge. •Ifawoundisstalledorappearsatypical,consideraskinbiopsytoruleout cancer •Biopsywoundsthatrapidlyenlarge,haveachangeinappearance, increasedpainor“feeldifferent” •EBrequiresinvolvementofadedicatedteamwithexpertise. (continues)

Sup plemen tal Table 3 . CHARA C TERISTICS OF SELECTED ORIGINAL ST UDIES AND C O NSENSUS STUDIES, C ONTINUED

FirstAuthor, Year,CountryStudyAimDesignand SampleSizeSampleCharacteristicsInterventionOutcomeMainFindingsofRelevance LocalWoundBedFactors Schultzetal,44 2017, International Todevelop consensus statementsfor theidentification andmanagement ofbiofilms Modified Delphi 10experts

Selectedonbasisof peer-reviewed publications,scholarly activityandreputationas anexpertinchronic woundsandimpactof biofilm.Diversityin geographicalpractices, clinicalspecialists.

Delphiround1:scoring seriesofstatements Delphiround2:scoringor reformulatedstatements (forwhichconsensus wasnotachievedin round1) Extensivefollow-up discussionofstatements forwhichconsensuswas notreached.

Totalof61consensus statementsgroupin10generic topicareas

Consensusstatementswithstrongagreement: •Woundsthatcontainbiofilmmaynotbeidentified,resulting ineffectivetreatmentanddelayedhealing •Biofilmsarepresentinmostchronicwoundsandarelikelyto belocatedbothonthesurfaceandindeeperwoundlayers •Woundbiofilmsaredifficulttovisualizemacroscopically •Importantindicatorsthatawoundislikelytocontainabiofilm includerecalcitrancetotreatmentwithantibioticsorantiseptics •Themostimportantmeasureforfuturediagnosticsteststo considerisindicationofwherethebiofilmislocatedwithinthe wound •Debridementisoneofthemostimportanttreatment strategiesagainstbiofilms,butdoesnotremoveallbiofilmand thereforecannotbeusedalone •Biofilmscanreformrapidly;repeateddebridementaloneis unlikelytopreventbiofilmregrowth;effectivetopicalantiseptic applicationwithinthetime-dependentwindowcansuppress biofilmreformation •Effectivetopicalantisepticshouldhavestrongantibiofilm effectsinappropriateinvitrotestmodelsagainstmature biofilms •Invitrobiofilmmethodswithclinicallyrelevanttest conditionsareusefultoscreentreatmentsfortheirefficacy •RCTsandcomparativeclinicalevidenceofantibiofilm treatmentshouldbeusedtosupportclinicalguidelines, protocolsandtreatmentchoices. Abbreviations:BMI,bodymassindex;BU,Buruliulcer;CVI,chronicvenousinsufficiency;EB,epidermolysisbullosa;HS,hidradenitissuppurativa;N/A,notapplicable;PCR,polymerasechainreaction;PHC,primaryhealthcare;PI,pressureinjury;PN,practicenurse; QoL,qualityoflife;RCT,randomizedcontrolledtrial;SCI,spinalcordinjury;SHC,secondaryhealthcare;VLU,venouslegulcer.

S u pplementa l T ab le 4 . CHA R ACTE RIS T IC S O F S ELECTE D B EST-PRA CTICE GUIDELINES

Author/ Organization andYear TargetPopulation, Scope/Purpose,andCountry ofOrigin

EvidenceCollection, Quality,StrengthRating, andRecommendationsMainFindingsofRelevance LowerLegUlcer Neumann etal,192016Dermatologistsorother medicalspecialists Aguidelineforeveryday diagnosticsand treatmentofVLUby dermatologistsandother medicalspecialists Europe Systematicsearchof publicationsinMedline, CINAHLandCochrane from1995to2012. Alsobasedonanearlier VLUguidelineform2006 No.ofincludedstudies notreported. Evidencegradedusingan ABCDgradingscale

32recommendations;14areapplicabletotheresearchquestion. Generally,verygoodoverviewofVLUs.Singlementionofnonhealingulcersthatrespondwelltodeepdebridementofulcertobeyondthe levelofffibrosis Recommendation4:ABPIshouldalwaysbedeterminedbeforepressuretherapyisgiven Recommendation10:Itisrecommendedthatpatientswithalegulcershouldbesubjectedtoanadditionalinvestigationtoruleout concomitantarterialocclusivediseasebymeasuringsystolicABPI.Furtherarterialinvestigationmaybeundertakenonindication. Recommendation12:Takingmultiplebiopsiesshouldbeconsideredifanulcerdoesnotrespondorrespondsinadequatelyandhasan atypicalappearance. Recommendation14:Compressiontherapyisthetreatmentoffirstchoiceinanuncomplicatedvenouslegulcer. Recommendation15:Properlyappliedhigh-interfacepressureamplitudecompressionbandagesaretobeusedinuncomplicatedVLUs. Recommendation16:Reductionofedemamaybeachievedcheaplyandgenerallyquicklywhenshortstretchbandagesarecorrectly applied. Recommendation17:ThelevelofcleansingandexudatearethemostimportantparametersforfurtherVLUtreatment. Recommendation18:Thefollowingaspectsareimportantwhencleansinganulcer: Beginwithasurgicalnecrotomyifpossible. Collagenaseistheonlyagentforenzymatictreatment. Usenotopicalantiseptics. Cleansewoundswithtapwater. Recommendation19:Theworkinggroupadvisesmodernwounddressingsforachievingamoistwoundenvironmentalsobecausethe dressingsdonotneedfrequentchanging.Thechoiceofaparticularproductdependsmainlyonthelevelofexudate. Recommendation20:Silversulfadiazine/paraffinistheonlyeligibleantimicrobialagentfortopicaluse. Recommendation28:Painshouldbeadequatelytreated. Recommendation29:Compressiontherapywithmedicalelasticcompressionhosieryshouldbeprescribedtopreventrecurrenceaftera VLUhashealed. Recommendation31:AdequatepatientcareinthetreatmentofVLUsalsoincludesnutritionoptimization. Recommendation32:Providinginformationandadviceconcerninglifestyleisindispensablein: Avoidingimmobility Encouragingtheuseofthecalfmusclepump(walking,adequatefootwear) Avoiding(developing)overweight Encouragingadequatenutrition Discouragingsmoking LongbedrestisnotatreatmentoptionforVLUs (continues)

S u pplemental Table 4 . CHA R ACTE RIS T IC S O F S ELECTE D B EST -PR ACTICE GUIDELINE S, CON T INU E D

Author/ Organization andYear

TargetPopulation, Scope/Purpose,andCountry ofOriginEvidenceCollection,Quality,Strength Rating,andRecommendationsMainFindingsofRelevance DiabeticFootUlcer Iseietal,31 2016Medicalprofessionals Toprepareguidelinesfor themanagementof diabeticulcer/gangrene withtheemphasisonthe diagnosisandtreatment ofskinsymptoms. Japan

Medline,PubMed,JapanCentra RevouMedicinaWeb,Cochrane databasesystematicreviewsfrom January1980toDecember2008. PriorityplacedonRCTs,systematic reviews,cohortandcasecontrol studies EvidencelevelclassifiedonaIto VIscale.Recommendations classifiedaccordingtolevels1and 2andanABCDscaleusedto furthergradestrengthofevidence oftherecommendations

1.ComprehensiveassessmenttoexcludePAD,assessneuropathyandgradeulcer.Offloadingtotreatthecause 2.Surgicaldebridementisrecommendedtoremovenecrotictissue;usecautioninthepresenceofPAD.Maintenance debridementrecommended. 3.Earlydetectionofinfectiontopreventfurthercomplications.Useoftopicalantimicrobialsrecommended. Theuseofantibacterialagentscannotberecommendedbecauseofalackofsufficientevidence Forosteomyelitisantibioticsshouldbeadministeredforatleast2weeksafterremovalofinfectedbones.Ifinfectedbones cannotbesufficientlyremoved,theadministrationofantibacterialdrugsatleast6weeks. Bathingmayspreadinfectionorfungalpresencetootherareasonthefoot. 4.Assessefficacyoftreatmentmodalityweeklyandadjustaccordingly 6.Glycemiccontrolandattentiontonutritionisrecommended 7.HBOTisrecommendedasanoptionforthetreatmentofDFUs. 8.Regularfootexaminationsandtreatmentoftineapedisisrecommended. 9.Healthdialogueandpromotionofself-carecanreduceriskofamputation. Lavery etal,32 2016Clinicians Theobjectivesofthe WHSDFUguidelinesare tosystematically evaluatethemedical literaturetoassist cliniciansinmaking healthcaredecisions, identifyareasthatneed additionalresearch,and toclarifycontroversial diagnosisandtreatment strategies.UnitedStates

PubMed,Embase,andCochrane Librarydatabases. 205studiesincluded Evidencegradedusingadifferent approachtoevidencecitationsand pastapproachestoevidence-based guidelinesreliedonpublications regardingclinicalhumanstudies

1.Treatthecause.Clinicallysignificantarterialdiseaseshouldberuledout;patientswithischemiashouldbeconsideredfora revascularizationprocedure. 2.Assessneuropathy 3.Examinationofthewholepatientisimportanttoevaluateandcorrectcausesoftissuedamage. 4.Determinearterialbloodsupply 5.Optimizingglucosecontrolimproveswoundhealing. 6.Off-loadingtheareaofhighpressurehasbeenthemainstaytohealDFUsandpreventrecurrenceoffootulcerations. 7.Debridement:removeallnecroticordevitalizedtissue 8.Infection:reducethebacterialbioburdeninthewoundtoreducetheriskofclinicalinfectionandimprovewoundhealing. Osteomyelitisismosteffectivelytreatedbydebridementoftheinfectedbone.Withdailyassessmentoftemperaturechanges, patientscouldidentifyearlywarningsignsoftissueinflammationandreducetheiractivitytoavoidulceration.Woundsshould becleanedinitiallyandateachdressingchangeusinganeutral,nonirritating,nontoxicsolution. 9.Moisture:Applymoistwoundhealingprincipals. 10.Edgeadvancement:Patientswhofailtoshowareductioninulcersizeby50%ormoreafter4weeksoftherapyshouldbe re-evaluatedandothertreatmentsconsidered. 11.Patient-centeredconcerns:selectadressingthatiscosteffective;considerprovidertime,easeofuse,andhealingrate,as wellastheunitcostofthedressing. 12.Adjuvantagents:selectivelyuseadjuvants(negative-pressurewoundtherapy,HBOT)afterevaluatingapatientandtheir ulcercharacteristicsandwhenthereisalackofhealingprogressinresponsetomoretraditionaltherapies 13.Healthdialogue:self-caresuchasgoodfootcare,properbathing,andnailcareshouldbeincludedaspartofa comprehensiveeducationprogram. (continues)

S u pplementa l T ab le 4 . CHA R ACTE RIS T IC S O F S ELECTE D B EST-PRA CTICE GUIDELINES , CON T INU E D

Author/ Organization andYear

TargetPopulation, Scope/Purpose,andCountryof OriginEvidenceCollection,Quality,StrengthRating, andRecommendationsMainFindingsofRelevance Huang etal,33 2015Clinicians,patientsand policy-makers Aclinicalpracticeguideline fortheuseofHBOTinthe treatmentofDFUs UnitedStates Medline,Embase,CochranePublished systematicreviews,RCTs,and observationalstudiesuptoApril2015. Includedstudies: Evidencegradingusingthemethodology oftheGRADEWorkingGroup6

Aggressivelyaddressrevascularizationoftheischemicfoot,debrideddevitalizedtissue,manageddeformitiesby offloadingtheneuropathicfoot,andanti-infectivetherapiesbeforeorconcurrentlywithadjunctiveHBOT. InpatientswithWagnerGrade3orhigherDFUswhohavejusthadasurgicaldebridementofaninfectedfoot,add acutepostoperativeHBOTtothestandardofcaretoreducetheriskofmajoramputationandincompletehealing. Crawford etal,34 2013Physicians,nurses, therapists,andotherhealth careprofessionalswhowork withadultswhohaveorare atriskforlower-extremity neuropathicdisease Todevelopan evidence-basedclinical practiceguidelinefor managementofwoundsin patientswith lowerextremityneuropathic disease.UnitedStates

Medline,Cochranesystematicreviews Publishedworkbetween2003and2012 PriorityplacedonRCTs,systematic reviews,meta-analysesandretrospective studies No.ofstudiesincluded:notreported Evidencegradingusingastandard process

1.ComprehensiveassessmenttoexcludePAD,assessneuropathy,andgradeulcer.Offloadingtotreatthecause. Comprehensivefootassessment. 2.Surgicaldebridementisrecommendedastheinitialdebridementtoremovenecrotictissue;takecautioninthe presenceofPAD.Maintenancedebridementrecommended. 3.Earlydetectionofinfectiontopreventfurthercomplications.Useoftopicalantimicrobialsrecommended.For osteomyelitisantibioticsshouldbeadministeredforatleast2–weeksafterremovalofinfectedbones.Ifinfected bonescannotbesufficientlyremoved,theadministrationofantibacterialdrugsatleastover6weeks.Bathingmay spreadfungusandbacterialinfectiontootherpartsofthefoot. 4.Assessefficacyoftreatmentmodalityweeklyandadjustaccordingly 5.Glycemiccontrolandattentiontonutritionisrecommended 6.Adjunctivetherapy:HBOTisrecommendedasanoptionforthetreatmentofDFUs,especiallynonhealingwounds. 7.Regularfootexaminationsandtreatmentoftineapedisisrecommended. 8.Healthdialogueandpromotionofself-carecanreduceriskofamputation. 9.Assessfootwear. (continues)

Su pplemen tal T able 4 . CHARACTERISTICS OF SELECTED BEST- PRACTICE GUID E LINES, CONTINUED

Author/ Organization andYear TargetPopulation, Scope/Purpose,and CountryofOrigin

EvidenceCollection,Quality, StrengthRating,and RecommendationsMainFindingsofRelevance PressureUlcer Fujiwara etal,38 2018Medical professionals Toupdate evidence-based guidelinesfor multi-professional practitionerfor diagnosisand treatmentofPUs Japan

SearchedMedline,PubMed, JapaneseMedicalAbstracts SocietyandCochrane DatabaseofSystematic ReviewsfromJanuary1980 toDecember2013,aswell aspersonalreferencesof committeemembers. Includedsystematicreviews, RCTs,cohortstudiesand case-controlstudies Evidencelevelclassifiedon aItoVIscale. Recommendationsclassified accordingtolevels1and2 andanABCDscaleusedto furthergradestrengthof evidenceofthe recommendations Prevention Changethebodypositionregularlywithin2handuseapressurerelievingmattresstopreventpressuredamagefromhypoxia1A Checkbodypressureareasinwheelchair-boundindividualssuchasthosewithparaplegiaandpatientswithSCI2C Additionalnutritionsupportisrecommendedforthepreventionandmanagementofpressureulcers1A Pain Selectapressure-relievingmattressandspecificwounddressingstorelievepain2C Prescribenonsteroidalanti-inflammatorydrugsand/orpsychotropicdrugstomanagethepatient‘spain2C Manageinfectionifpresent Debridement Performacompleteorpartialsurgicalremovalofunderminedskinsupportedbycauterizationtocontrolbleeding1C Surgicaldebridementofnonviabletissueisproposedifpatient‘sconditioncantolerateit. Recommendedwoundcareproductsforremovalofdevitalizedtissueincludecadexomeriodine(1A),dextranomer(1B),andiodoform(1C). Recommendedproductsforremovalofdeadtissueinwoundwithlowexudatelevelsincludehydrogeldressings(1B)andsilversulfadiazine (1D).Note:theuseofwet-to-drydressingsisnotrecommended Infection Bathingofpatientswithpressureulcersisrecommended(1C) Doacomprehensiveassessmentofpatientandthewoundbedandperiwoundareatodiagnoseinfection Hematologicalandbloodchemistrytests1DRecommendedproductstodecreasebioloadofwoundbedincludecadexomeriodine(1A), silversulfadiazine(1A),povidone-iodinesugar(1A)andgel(1A),iodineointment(1D),andiodoform(1D).Note:theapplicationofointment containinganantibioticisnotrecommended(2A). (continues)

Su pplemen tal T able 4 . CHARA C TER IST ICS OF SELE CTED B E ST- PRACTICE GUID E LINES, CONTINUED

Author/ Organization andYear TargetPopulation, Scope/Purpose,and CountryofOrigin

EvidenceCollection,Quality, StrengthRating,and RecommendationsMainFindingsofRelevance Recommendeddressingsforalocalizedinfectionincludehydrofiberwithsilver(1A),polyurethanefoamcontainingsilver(1A),andalginate withsilver(1A) Administrationofsystemicantibioticsisrecommendedwithsignsofinflammationintheperiwoundareaorwithpyrexia,andincreased whitebloodcellcountorworseningoftheinflammatoryreaction,butalsowithpositivebacterialculturesfromwoundbed(1D) Moisturecontrol Recommendedproductsformanagementofhighexudatelevelsincludecadexomeriodine(1A),dextranomer(1A),povidoneiodinesugar (1A),andiodineointment(1D) Recommendeddressingstoabsorbexcessexudateincludealginate(1A),polyurethanefoam(1C),chitin(1C),hydrofiber(withsilver)(1C), hydropolymer(1C),andpolyurethanefoam/softsilicone(1D). Usehydrogelswhenexudateislowandwoundbedcontainseschar(1B) Usepovidoneiodinesugarforwoundswithhighexudatelevelsandunderminededges(1B) Woundswithveryhighexudatelevelsormassiveedemacouldbenefitfrombucladesinesodium,aluminumchlorohydroxyallantoinate,and povidoneiodinesugar. Woundswithnormaltolowexudatelevels(onlysuperficialwounds)couldbenefitfromtrafermin(1A),tretinoinortocopherol(1A), prostaglandin(1A),lysozymechloride(1B),whitepetrolatum(1D),zincoxide(1D),anddimethylisopropylazulene(1D) Manufacturedorhandmadenegative-pressurewoundtherapycanbeusedundercarefulobservation,afterdebridementtotreatstagesIII andIVpressureulcers.(1C) Infrared-visualtherapy(1A),low-powerlasertherapy(1B),Hydrotherapy(1A)andHBOTarerecommended(1C) Surgicalmanagement Surgicaland/orenzymaticdebridementandtreatmentofinfectionseveralweeksbeforesurgicalmanagementofStageIIIandIVpressure ulcersarestronglyrecommended.(1C) Doacomprehensiveassessmentofthewholepatientanddeterminethereasonsforreconstructiveinvasivesurgery.(1C) Evaluatenutritionstatus,cardiopulmonaryfunction,urinaryand/orfecalincontinence,homeenvironmentafterdischarge Dermatoplastyoraflapoperationissuccessfulforearlymanagementofpressureulcersthatpotentiallywillnothealortakealongtimeto heal.Fasciocutaneousflapsurgeryensureslongtermbetterresultscomparedtomusculocutaneousflapsurgery. Otherlocaltreatmentcouldincludehydrotherapy(1A),infraredtherapy(1A),lowerpowerlasertherapy(1B),HBOT(1C),ultraviolettherapy, andelectricstimulationtherapy(2A) Abbreviations:ABPI,ankle-brachialpressureindex;CINAHL,CumulativeIndexofNursingandHealthLiterature;DFU,diabeticfootulcer;HBOT,hyperbaricoxygentherapy;RCT,randomizedcontrolledtrial;VLU,venouslegulcer.