Signalering en behandeling cognitieve en emotionele gevolgen na glioom
Uitgangsvraag
Op welke wijze dienen de cognitieve en emotionele gevolgen van de tumor en/of behandeling te worden gesignaleerd en behandeld?
Aanbeveling
- Alle glioompatiënten en directe naasten dienen standaard en structureel gescreend te worden op lichamelijke, cognitieve, emotionele en gedragsmatige beperkingen.
- Alle glioompatiënten en directe naasten dienen standaard en structureel gescreend te worden op de behoefte aan psychosociale zorg en zo nodig worden doorverwezen.
- De werkgroep adviseert om bij het in kaart brengen van de gevolgen van de tumor en/of behandeling gebruik te maken van de Signaleringslijst Volwassenen met Niet-Aangeboren Hersenletsel en de Richtlijn Detecteren behoefte psychosociale zorg.
- De werkgroep adviseert om voor het maken van een eerste inschatting van de belasting van de mantelzorger de screeningsvragenlijst ‘Ervaren druk door informele zorg' (EDIZ) te gebruiken die is opgenomen in de richtlijn mantelzorg op http://www.oncoline.nl/. De werkgroep is van mening dat verwijzen naar een revalidatiearts, psycholoog of klinisch neuropsycholoog zinvol is voor glioompatiënten die hinder ervaren van fysieke en/of cognitieve en emotionele veranderingen waardoor zij beperkt worden in hun dagelijks leven of bij hun maatschappelijke participatie. Voor de behandeling wordt verwezen naar de volgende richtlijnen:
- Richtlijn Neuropsychiatrische gevolgen van niet-aangeboren hersenletsel
- Richtlijn Niet-aangeboren Hersenletsel en arbeidsparticipatie
- Er wordt geadviseerd bij de behandeling van vermoeidheidsklachten non-farmacologische interventies toe te passen, zoals deze onder meer beschreven staan in de Richtlijn Vermoeidheid bij kanker.
- Er wordt geadviseerd om bij de behandeling van angststoornissen en depressie gebruik te maken van de multidisciplinaire evidence-based GGZ-richtlijnen voor de diagnostiek en behandeling van patiënten met psychische stoornissen.
- Er wordt geadviseerd bij overbelasting van de informele zorgverleners van hooggradig glioompatiënten, psychologische interventies toe te passen die het mentaal functioneren en gevoelens van controle van informele zorgverleners stabiliseert of verbetert.
Onderbouwing
Conclusies
Cognitieve beperkingen
- Cognitieve revalidatieprogramma's ontwikkeld voor patiënten met niet-aangeboren hersenletsel, lijken ook bruikbaar voor glioompatiënten [Cicerone 2011].
- De werkgroep is van mening dat instrumenten ontwikkeld om veranderingen in emotie, cognitie en gedrag in kaart te brengen bij patiënten met niet aangeboren hersenletsel, mogelijk ook bruikbaar zijn bij glioompatiënten.
- De werkgroep is van mening dat de verschillende digitaal beschikbare evidence-based behandelprotocollen voor cognitieve stoornissen bij patiënten met niet-aangeboren hersenletsel, zinvol kunnen zijn voor glioompatiënten.
Cognitieve klachten
- Er is vaak een beperkte samenhang tussen cognitieve klachten en cognitieve beperkingen zoals deze gevonden worden in het neuropsychologisch onderzoek [Aaronson 2011, Boele 2014, Klein 2011].
- Klachten over vermoeidheid en klachten van depressieve aard kunnen cognitieve klachten versterken [Cull 1996].
- De werkgroep is van mening dat instrumenten ontwikkeld om bovengenoemde klachten in kaart te brengen bij patiënten met niet aangeboren hersenletsel bruikbaar zijn bij glioompatiënten.
Vermoeidheid
- Vermoeidheid is één van de meest voorkomende en meest ingrijpende symptomen bij glioompatiënten [Lovely 1999].
- Farmacologische behandeling van vermoeidheid met modafinil is niet effectiever dan een placebo [Boele 201323].
Stemmingsstoornissen
- Van alle oncologische patiënten hebben patiënten met een glioom de grootste kans op psychiatrische symptomen [Rooney 2011282].
- Er is vaak sprake van een multifactorieel beeld, waarbij bij één patiënt sprake is van zowel depressie als van vermoeidheid en cognitieve beperkingen [Taphoorn 2004341].
- De werkgroep is van mening dat verschillende digitaal beschikbare evidence-based behandelprotocollen voor patiënten met psychische stoornissen zinvol kunnen zijn voor glioompatiënten.
Partners
- De begeleiding van en zorg voor glioompatiënten heeft, in vergelijking met de begeleiding van en zorg voor andere kankerpatiënten, door de veranderingen van gedrag en cognitie een grotere invloed op het welbevinden van een informele zorgverlener [Boele 201323, Schubart 2008303].
- Er zijn aanwijzingen dat psychologische interventies het mentaal functioneren en de gevoelens van controle van informele zorgverleners van patiënten met hooggradig gliomen stabiliseren of verbeteren [Boele 201323].
Samenvatting literatuur
Cognitieve beperkingen
Glioompatiënten worden geconfronteerd met serieuze bedreigingen voor hun kwaliteit van leven [Liu 2009203]. De draaglast is hoog en het gevoel van onvermogen is aanzienlijk, vooral bij patiënten met hooggradige gliomen of bij een recidief van de tumor.
Ongeveer 80% van de glioompatiënten heeft cognitieve beperkingen [Giordana 2006111]. Deze beperkingen kunnen veroorzaakt worden door de tumor zelf of samenhangen met de medische behandeling, waaronder radiotherapie, chirurgie, en anti-epileptica [Taphoorn 2004341]. De cognitieve beperkingen kunnen veroorzaakt worden door corticale laesies, maar kunnen door de vele corticaal-subcorticale verbindingen ook de oorzaak zijn van subcorticale schade of schade aan cerebellaire structuren. Patiënten met een tumor in de dominante (linker) hemisfeer, hebben vaak meer in het oog springende cognitieve stoornissen dan patiënten met een tumor in de niet-dominante hemisfeer.
Beperkingen komen voor in verschillende cognitieve domeinen, maar voornamelijk in de aandachts- en concentratiefuncties, het geheugen en de executieve functies [Taphoorn 2004341]. Hoewel deze beperkingen relatief mild kunnen zijn, kunnen cognitieve beperkingen wel interfereren met het dagelijks leven, zoals werk, sociale- en gezinssituaties.
Relevant voor de screening van glioompatiënten is de Signaleringslijst Volwassenen met Niet-Aangeboren Hersenletsel. Aan de hand van deze vragenlijst, die is ontwikkeld voor patiënten met cerebrale schade die niet veroorzaakt is door hersentumoren, kunnen veranderingen in emotie, cognitie en gedrag in kaart worden gebracht. Deze signaleringslijst kan ook gebruikt worden ter signalering van dergelijke veranderingen bij glioompatiënten. Een geschikt moment voor afname ligt in de subacute fase binnen drie maanden na de diagnose en/of behandeling. Een aanvullend neuropsychologisch onderzoek is zinvol, indien sprake is van een onduidelijk beeld of om onderscheid te maken tussen een depressie en cognitieve problematiek.
Voor wat betreft cognitieve revalidatiemogelijkheden, lijken programma's, die overwegend zijn ontwikkeld voor patiënten met traumatisch hersenletsel en cerebrovasculaire schade, ook bruikbaar te zijn voor neuro-oncologische patiënten [Formica 2011102]. Ten aanzien van de mogelijkheden om cognitieve beperkingen te behandelen is het onderzoek van het door ZonMw gefinancierde consortium Cognitieve Revalidatie relevant. Dit consortium heeft in een aantal onderzoeksprojecten behandelingen van cognitieve stoornissen op effectiviteit geëvalueerd en dit heeft geresulteerd in de Richtlijn Cognitieve revalidatie bij Niet-Aangeboren Hersenletsel. De richtlijnen, ontwikkeld voor verschillende cognitieve stoornissen en gebaseerd zijn op de resultaten van onderzoek van dit consortium, zijn vooral toepasbaar in de settings die hebben deelgenomen aan de effectevaluaties (dit zijn revalidatieafdelingen, zowel binnen de revalidatiecentra als binnen het verpleeghuis en het ziekenhuis). Echter, ook andere settings waar patiënten met niet-aangeboren hersenletsel behandeld worden, kunnen baat hebben bij deze richtlijnen. Verschillende evidence-based behandelprotocollen zijn digitaal beschikbaar en kunnen worden gedownload. Hierbij is het nadrukkelijk van belang dat de deskundigheid van de zorgverlener van dien aard moet zijn, dat toepassing van de richtlijnen en gebruik van de protocollen verantwoord kan gebeuren.
Cognitieve klachten
De cognitieve klachten die patiënten rapporteren komen vaak niet overeen met de resultaten van het neuropsychologische onderzoek [Janda 2007153]. Patiënten met een depressieve stemming kunnen hun cognitieve mogelijkheden onderschatten en de cognitieve klachten die zij uiten zijn vaak een weergave van angstige of depressieve gevoelens of worden veroorzaakt door vermoeidheidsklachten in plaats van cognitieve beperkingen [Hermelink 2010134,Taphooorn 2004341]. Het hebben van vermoeidheidsklachten en/of een depressie kunnen cognitieve klachten dus versterken.
Om te kunnen beoordelen of verwijzing naar een revalidatiearts, psycholoog of klinisch neuropsycholoog zinvol is voor een individuele patiënt, is het van belang dat de gevolgen van het glioom en/of de behandeling goed in kaart worden gebracht.
In aanvulling op de Signaleringslijst Volwassenen met Niet-Aangeboren Hersenletsel dienen volgens de Kwaliteitscriteria neuro-oncologie, patiënten standaard gescreend te worden op de behoefte aan psychosociale zorg en zo nodig te worden doorverwezen. Screening vindt op meerdere ziekte- of behandelingsrelevante momenten in het zorgproces bij voorkeur plaats met de Lastmeter. De patiënt wordt geïnformeerd over de mogelijkheid voor psychosociale ondersteuning in het ziekenhuis of in de eigen omgeving van de patiënt en deze wordt op indicatie en in overleg doorverwezen naar gespecialiseerde aanbieders van psychosociale zorg. De follow-up frequentie wordt bepaald in overleg en op indicatie en is bekend bij patiënt en naasten. De werkwijze en frequentie van de follow-up staan beschreven in het dossier.
Bij het inschatten van de aard van de eventuele doorverwijzing kunnen onderstaande richtlijnen met betrekking tot neuropsychiatrische symptomen en gevolgen van hersenletsel voor de arbeidsparticipatie, die verschenen zijn voor patiënten met hersenletsel, ook voor glioompatiënten bruikbaar zijn.
Richtlijn Neuropsychiatrische gevolgen van niet-aangeboren hersenletsel, CBO en Nederlandse Vereniging voor Revalidatieartsen, 2007.
Richtlijn Niet-aangeboren Hersenletsel en arbeidsparticipatie, CBO 2012.
Vermoeidheid
Vermoeidheid is één van de meest voorkomende en meest ingrijpende symptomen bij glioompatiënten [Lovely 1999]. Het is het symptoom met de grootste invloed op de kwaliteit van leven en het dagelijks functioneren van patiënten en hun naasten [Wefel 2008]. Uit resultaten van een kleine studie bleek dat van alle geteste variabelen vermoeidheid de sterkste relatie had met kwaliteit van leven bij patiënten met een laaggradig glioom [Gustafsson 2006120].De meest gerapporteerde klachten zijn overmatige slaperigheid, lethargie, concentratieproblemen en onhandigheid [Pelletier 2002253]. Bij 80% van de glioompatiënten die behandeld worden met radiotherapie is er sprake van vermoeidheid. Vermoeidheid blijkt echter ook na behandeling, waarbij geen radiotherapie is gebruikt, te blijven bestaan, naar schatting bij 40% van de glioompatiënten [Struik 2008].
De behandeling van vermoeidheid bij gliomen is moeilijk, omdat er nog weinig bekend is over de pathofysiologie en er vaak meerdere factoren tegelijkertijd een rol spelen. De enige dubbelblinde RCT waarbinnen onderzocht werd of een farmacologische behandeling met modafinil beter was dan placebo in de behandeling van vermoeidheid, cognitief functioneren en kwaliteit van leven liet zien dat modafinil niet effectiever was dan placebo [Boele 201322]. Een wegens moeizame inclusie voortijdig beëindigde open-label RCT [Gehring 2012107] vond naast inconsistente effecten van methylfenidaat en modafinil op cognitie enige gunstige effecten op zelf-gerapporteerde vermoeidheid, stemming en kwaliteit van leven. Voor wat betreft de zelf-gerapporteerde uitkomsten waren er geen verschillen in de tijd tussen de condities.
Gezien het ontbreken van consistente effecten en de beperkte bereidheid van patiënten om medicatie te gebruiken voor vermoeidheidsklachten dienen non-farmacologische interventies overwogen te worden. Binnen de oncologische zorg is de Richtlijn Vermoeidheid bij kanker verschenen. Hierin wordt ook aandacht besteed aan non-farmacologische interventies gericht op onder meer het helpen vinden van een balans tussen inspanning en rust, het aanbieden van fysieke trainingsprogramma's, ontspanningstherapie en psychosociale ondersteuning.
Stemmingsstoornissen
Neuropsychiatrische problemen kunnen ontstaan door het ziekteproces zelf en door de behandeling van neurologische symptomen; zo kan het gebruik van hoge doses corticosteroïden resulteren in restverschijnselen zoals een labiel affect of gedragsveranderingen [Pelletier 2002253]. De primaire symptomen van een depressie zijn bij glioompatiënten moeilijk te onderscheiden van de gevolgen van de tumor of de medische behandeling [Rooney 2011282]. Daadwerkelijke klinische depressie komt echter regelmatig voor wanneer de gezondheidstoestand vermindert. Van alle kankerpatiënten hebben patiënten met een glioom de grootste kans op psychiatrische symptomen, waarbij de prevalentie van depressie bij glioompatiënten wordt geschat op 6-28% [Rooney 2011282]. De negatieve gemoedstoestand is geassocieerd met de neurologische uitval en wordt versterkt door comorbide psychosociale problemen zoals reactieve depressie, verlies van werk, financiële problemen en echtelijke conflicten [Pelletier 2002253].
Cognitieve beperkingen en vermoeidheidsklachten kunnen het beroepsmatig- en sociaal functioneren verder beperken en leiden tot gevoelens van frustratie en controleverlies, die een voedingsbodem zijn voor depressieve klachten [Sohlberg 2001]. Een groot deel van de patiënten spreekt hierover niet met zijn of haar behandelend arts, omdat ze deze te druk of onvoldoende toegerust achten om hierin begeleiding te bieden [Wefel 2011376].
Het cognitief functioneren is gecorreleerd met toenemende vermoeidheid en depressie [Liu 2009203]. Er is dan ook vaak sprake van een multifactorieel beeld, waarbij bij één patiënt sprake is van zowel depressie als van vermoeidheid en cognitieve beperkingen. Bij onderzoek naar specifieke symptoomclusters bij glioompatiënten vormen depressie, vermoeidheid, verstoring van de slaap en cognitieve beperkingen een cluster dat 29% van de variantie van kwaliteit van leven verklaart. Daarnaast vormen depressie, vermoeidheid, verstoring van slaap, cognitieve beperkingen en pijn een cluster dat 62% van de functionele status van de patiënt verklaart [Liu 2009203].
Bij de behandeling van angststoornissen en depressie kan gebruik worden gemaakt van de multidisciplinaire evidence-based richtlijnen voor de diagnostiek en behandeling van patiënten met psychische stoornissen. Deze richtlijnen zijn ontwikkeld onder auspiciën van de Landelijke Stuurgroep Multidisciplinaire Richtlijnontwikkeling in de GGZ en/of het Trimbos-instituut.
Partners
Net als bij andere ziektes heeft de diagnose van een glioom grote impact op het leven van de patiënt [Gupta 2011119]. Aangezien glioompatiënten naast fysieke symptomen ook worden geconfronteerd met veranderingen in cognitie, stemming en persoonlijkheid hebben zij meer ondersteuning nodig van hun omgeving dan patiënten met een tumor waarbij de hersenen niet zijn betrokken. Inherent aan de problematiek van glioompatiënten is de mogelijkheid dat door de ernst van de cognitieve stoornissen niet de patiënt degene is die de hulpvraag uit, maar zijn omgeving. In de meeste gevallen is de partner de primaire informele zorgverlener [Boele 201323]. Het verzorgen van een glioompatiënt heeft, in vergelijking met de verzorging van andere kankerpatiënten, door de veranderingen van gedrag en cognitie een grotere invloed op het welbevinden van een informele zorgverlener [Boele 201323, Schubart 2008303].
Patiënten en hun zorgverleners worden geconfronteerd met de taak de diagnose en behandeling te begrijpen en veranderingen bij de patiënt te identificeren en hiermee om te leren gaan [Gupta 2011119]. Sommige patiënten zullen na behandeling al snel compleet hersteld zijn; er is echter een groot deel van de patiënten dat steun en zorg nodig heeft in de jaren die daarop volgen [Janda 2007153. Deze zorg wordt over het algemeen gegeven door partners en naaste familie. De stress die met de verzorging gepaard gaat, is aanzienlijk en heeft een significant negatieve invloed op het welzijn van de informele zorgverlener zelf [Janda 2007153]. Bij 10% van de informele zorgverleners is sprake van een depressieve stemming [Janda 2006152] en met name informele zorgverleners van hooggradig glioompatiënten lijken in de acute fase van de ziekte het meeste risico te lopen [Boele 201323]. Daarnaast is er sowieso sprake van toenemende symptomen van angst, psychosomatische problemen, beperkingen van activiteiten, huwelijksproblemen en slechtere fysieke gezondheid bij informele zorgverleners van kankerpatiënten [Weitzner 1999377.Een recente RCT [Boele 201323] laat zien dat psychologische interventies het mentaal functioneren en gevoelens van controle van informele zorgverleners van patiënten met hooggradig gliomen kan stabiliseren of verbeteren. Voor het maken van een eerste inschatting van de belasting van de mantelzorger is de screeningsvragenlijst ‘Ervaren druk door informele zorg' (EDIZ) ontwikkeld die is opgenomen in de richtlijn mantelzorg op www.oncoline.nl/.
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Verantwoording
Autorisatiedatum en geldigheid
Laatst beoordeeld : 15-04-2015
Laatst geautoriseerd : 15-04-2015
Geplande herbeoordeling :
De geldigheid van richtlijnmodules zal bij herbeoordeling komen te vervallen wanneer nieuwe ontwikkelingen aanleiding geven om een herzieningstraject te starten. De Nederlandse Vereniging voor Neurologie is regiehouder van deze richtlijn en eindverantwoordelijke op het gebied van de actualiteitsbeoordeling van de richtlijnmodules. De andere aan deze richtlijn deelnemende wetenschappelijke verenigingen of gebruikers van de richtlijn delen de verantwoordelijkheid en informeren de regiehouder over relevante ontwikkelingen binnen hun vakgebied.
Algemene gegevens
De richtlijnontwikkeling werd ondersteund door het Integraal Kankercentrum Nederland IKNL).
Doel en doelgroep
De richtlijn gliomen geeft aanbevelingen over diagnostiek, behandeling, nazorg en organisatie van zorg bij patiënten met een glioom. De richtlijn beoogt hiermee de kwaliteit van de zorgverlening te verbeteren, het klinisch handelen meer te baseren op wetenschappelijk bewijs dan op ervaringen en meningen, de transparantie te vergroten en de diversiteit van handelen door professionals te verminderen.
De richtlijn is bestemd voor alle professionals die betrokken zijn bij de diagnostiek, behandeling en begeleiding van patiënten met een (verdenking op een) glioom. Deze zorg vereist een multidisciplinaire aanpak waarbij neuroloog, neurochirurg, radioloog, patholoog, radiotherapeut, internist-oncoloog, verpleegkundigen, verpleegkundig specialisten, klinisch neuropsychologen, huisartsen, IKNL-consulenten palliatieve zorg en het palliatief consult team betrokken kunnen zijn.
Samenstelling werkgroep
Voor de herziening van de richtlijn is in 2013 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen. De werkgroepleden zijn door hun beroepsverenigingen gemandateerd voor deelname. De werkgroep is verantwoordelijk voor de integrale tekst van deze richtlijn.
Werkgroep
- Mw. dr. T. Seute, neuroloog, Universitair Medisch Centrum Utrecht, gemandateerd namens de NVN (voorzitter)
- Mw. drs. M.A.B. Bakker-van der Jagt (namens NVRO - Radiotherapeutisch Instituut Friesland)
- Mw. S. Bossmann (namens V&VN - Radboudumc Nijmegen)
- Mw. dr. J.E.C. Bromberg (namens NVN, Erasmus MC - Daniel den Hoed Oncologisch Centrum)
- Mw. dr. A.M.E. Bruynzeel (namens NVRO - VU medisch centrum)
- Dhr. dr. W.F.A. Dunnen (namens NVVP - Universitair Medisch Centrum Groningen)
- Mw. drs. R.E.M. Fleischeuer (namens NVVP - Stg. Elisabeth Ziekenhuis)
- Mw. E. Gortmaker (namens V&VN - Medisch Centrum Haaglanden)
- Dhr. dr. Hendrikse (namens NVVR - Universitair Medisch Centrum Utrecht)
- Dhr. dr. M. Klein (namens NVN - VU medisch centrum)
- Mw. drs. J.H.F. Leemhuis (namens Leven met kanker-beweging (voorheen NFK)
- Dhr. J. Moonen (namens Leven met kanker-beweging (voorheen NFK)
- Mw. drs. S. Polman (namens NVN - Isala)
- Mw. dr. M. Smits (namens NVVR - Erasmus MC)
- Dhr. dr. A.J.P.E. Vincent (namens NVvN - Erasmus MC)
- Dhr. dr. F.Y.F.L. de Vos (namens NVMO - Universitair Medisch Centrum Utrecht)
- Mw. dr. A.M.E. Walenkamp (namens NVMO - Universitair Medisch Centrum Groningen)
- Mw. drs. H.L. Weide (namens NVRO - Universitair Medisch Centrum Groningen)
- Dhr. dr. P.C. de Witt Hamer (namens NVvN - VU Medisch Centrum)
Ondersteuning
- Mw. T.T.M. Bluemink-Holkenborg, secretaresse IKNL
- Mw. G.H. Schrier, MSc, adviseur richtlijnen IKNL, procesbegeleider
Inbreng patiëntenperspectief
Bij de ontwikkeling van deze richtlijn is tijdens alle fasen gebruik gemaakt van de input van patiënten. Twee patiëntvertegenwoordigers namen zitting in de richtlijnwerkgroep (één ervaringsdeskundige op het gebied van gliomen en één deskundige op het gebied van richtlijnontwikkeling). Deze input is nodig voor de ontwikkeling van kwalitatief goede richtlijnen. Goede zorg voldoet immers aan de wensen en eisen van zowel zorgverlener als patiënt. Door middel van onderstaande werkwijze is informatie verkregen en zijn de belangen van de patiënt meegenomen:
- Bij aanvang van het richtlijntraject hebben de patiëntvertegenwoordigers knelpunten aangeleverd. De gemandateerde patiëntvertegenwoordigers hebben in augustus 2013 ervaringen van patiënten met de zorgverlening geïnventariseerd door ervaringsdeskundigen te bevragen op een bijeenkomst van de patiëntenvereniging Cerebraal. De patiëntvertegenwoordigers waren aanwezig bij alle vergaderingen van de richtlijnwerkgroep.
- De patiëntvertegenwoordigers hebben de conceptteksten beoordeeld ten einde het patiëntenperspectief in de formulering van de definitieve tekst te optimaliseren.
- De Leven met kanker-beweging (voorheen NFK) is geconsulteerd in de landelijke commentaarronde.
Methode ontwikkeling
Evidence based
Implementatie
In de verschillende fasen van het ontwikkelproces is rekening gehouden met de implementatie van de richtlijnmodule en de praktische uitvoerbaarheid van de aanbevelingen. Daarbij is uitdrukkelijk gelet op factoren die de invoering van de module in de praktijk kunnen bevorderen of belemmeren. De implementatietabel is te vinden bij de aanverwante producten.
Werkwijze
De werkgroep is in juni 2013 voor de eerste maal bijeengekomen. Op basis van een eerste inventarisatie van de knelpunten door de werkgroepleden is door middel van een enquête onder professionals die betrokken zijn bij patiënten met gliomen een knelpunteninventarisatie gehouden. Na het versturen van de enquête hebben 101 professionals gerespondeerd en knelpunten geprioriteerd en/of ingebracht. De meest relevante knelpunten zijn uitgewerkt tot drie uitgangsvragen die evidence based zijn uitgewerkt. Voor iedere uitgangsvraag werd uit de richtlijnwerkgroep een subgroep geformeerd. Bij de evidence-based beantwoording van de drie uitgangsvragen verzorgde een externe methodoloog het literatuuronderzoek, de critical appraisal, de evidence tabellen en een concept literatuurbespreking. De werkgroepleden pasten vervolgens de conceptliteratuurbespreking en -conclusies aan en stelden overwegingen en aanbevelingen op volgens de checklist ‘overwegingen en formuleren van aanbevelingen’.
Voor de consensus-based beantwoording van de resterende uitgangsvragen raadpleegden de werkgroepleden de relevante bestaande literatuur. Op basis hiervan hebben de werkgroepleden de wetenschappelijke conclusies, overwegingen en aanbevelingen geformuleerd. Er is voor de consensus-based beantwoording geen verder systematisch literatuuronderzoek verricht.