FrancophonIA/ELRC3.0 huggingface dataset:
English: However if the missed dose is more than 12 hours late, skip that dose and take your next dose at the usual time.
Danish: Hvis det er mere end 12 timer siden, du skulle have taget dosen, skal du dog springe den glemte dosis over og tage den næste dosis på det sædvanlige tidspunkt.
English: Genital examinations (for women) and anal examinations are also recommended before and at the end of your treatment.
Danish: Der bør desuden gennemføres gynækologiske undersøgelser (hos kvinder) og undersøgelser af endetarmen før og efter behandlingen.
English: Tell your doctor immediately if you detect skin changes during and after treatment including: new wart, skin sore or reddish bump that bleeds or does not heal, or a change in size or colour of a mole.
Danish: Kontakt omgående lægen, hvis du opdager hudforandringer under eller efter behandlingen, herunder: nye vorter, sår i huden eller en rødlig bule, der bløder eller ikke heler, eller ændringer i et modermærkes størrelse eller farve.
English: If you are sick
Danish: Hvis du kaster op
English: Based on findings in animals, the use of encorafenib may impact fertility in males of reproductive potential (see section 5.3).
Danish: Baseret på fund hos dyr kan brug af encorafenib påvirke fertiliteten hos mænd (se pkt.
English: Transaminase increased* Blood creatinine increased* Lipase increased
Danish: Øgede transaminaser* Forhøjet kreatinin i blodet* Forhøjet lipase
English: Examples of strong CYP3A4 inhibitors include, but are not limited to, ritonavir, itraconazole, clarithromycin, telithromycin, posaconazole and grapefruit juice.
Danish: Eksempler på stærke CYP3A4-hæmmere omfatter, men er ikke begrænset til, ritonavir, itraconazol, clarithromycin, telithromycin, posaconazol og grapefrugtjuice.
English: Blood creatinine should be monitored as clinically indicated and creatinine elevation managed with dose modification or discontinuation (see Table 3 in section 4.2).
Danish: Blodkreatinin bør monitoreres som klinisk indiceret, og kreatininstigning håndteres med dosisjustering eller seponering (se tabel 3 i pkt.
English: Eye problems: Braftovi, when taken with binimetinib, can cause serious eye problems such as fluid to leak under the retina in the eye, leading to detachment of different layers in the eye (retinal epithelial pigmental detachment).
Danish: Øjenproblemer: Braftovi i kombination med binimetinib kan forårsage alvorlige øjenproblemer, såsom væske, der siver ud under nethinden i øjet med deraf følgende løsning af forskellige lag i øjet (løsning af retinalt pigmentepitel).
English: If you forget to take Braftovi
Danish: Hvis du har glemt at tage Braftovi
English: Model-based predictions for ketoconazole suggest an increase of approx. 5-fold for encorafenib AUC and 3 to 4-fold for encorafenib Cmax.
Danish: Modelbaserede beregninger vedrørende ketoconazol antyder, at der kan forventes en cirka 5-foldig stigning i AUC for encorafenib og en 3- til 4-foldig stigning i Cmax af encorafenib.
English: Braftovi 75 mg is available in packs of 42 capsules (7 blisters of 6 capsules each) or 168 capsules (28 blisters of 6 capsules each).
Danish: Braftovi 75 mg fås i pakninger med 42 kapsler (7 blisterkort med 6 kapsler hver) eller 168 kapsler (28 blisterkort med 6 kapsler i hver).
English: The embryo-foetal development study in rats indicated that encorafenib induced foetal toxicity with lower foetal weights and delays in skeletal development.
Danish: Et studie af den embryoføtale udvikling hos rotter viste, at encorafenib forårsagede føtal toksicitet med lavere fostervægt og forsinket skeletal udvikling.
English: If you stop taking Braftovi
Danish: Hvis du holder op med at tage Braftovi
English: The pharmacokinetics of encorafenib has not been evaluated clinically in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment.
Danish: Encorafenibs farmakokinetik er ikke blevet undersøgt klinisk hos patienter med moderat (Child-Pugh klasse B) eller svært (Child-Pugh klasse C) nedsat leverfunktion.
English: Additionally, the combination of encorafenib and binimetinib prevented the emergence of resistance in BRAFV600E mutant human melanoma xenografts in vivo.
Danish: Derudover forhindrede kombinationen af encorafenib og binimetinib fremkomst af resistens i xenografter af humane melanomer med BRAF V600-mutation in vivo.
English: As encorafenib is primarily metabolised and eliminated via the liver, based on PBPK modelling, patients with moderate to severe hepatic impairment may have greater increases in exposure than patients with mild hepatic impairment.
Danish: Eftersom encorafenib primært metaboliseres og elimineres via leveren, kan eksponeringen for encorafenib, baseret på PBPKmodellering være højere hos patienter med moderat til svært nedsat leverfunktion end hos patienter med let nedsat leverfunktion.
English: Braftovi 50 mg is available in packs of 28 capsules (7 blisters of 4 capsules each) or 112 capsules (28 blisters of 4 capsules each).
Danish: Braftovi 50 mg fås i pakninger med 28 kapsler (7 blisterkort med 4 kapsler hver) eller 112 kapsler (28 blisterkort med 4 kapsler i hver).
English: In Study CMEK162B2301-Part 2, in the Combo 300 arm, the incidence of liver laboratory abnormalities was:
Danish: I studiet CMEK162B2301-del 2, i Combo 300-armen, var forekomsten af abnorme levertal:
English: Simulations of 450 mg encorafenib co-administered with probe substrates for CYP2B6, CYP1A2, CYP2C9, CYP2C19 and CYP2D6 on Day 1 and Day 15 all indicated no clinically relevant interactions are expected.
Danish: Simuleringer med 450 mg encorafenib administreret sammen med probesubstrater for CYP2B6, CYP1A2, CYP2C9, CYP2C19 og CYP2D6 på dag 1 og dag 15 tydede alle på, at der ikke bør forventes klinisk relevante interaktioner.
English: Birth control medicines containing hormones (such as pills, injections, patches, implants and certain intrauterine devices (IUDs) that release hormones) may not work as well as expected while you are taking Braftovi.
Danish: Virkningen af hormonel prævention (såsom p-piller, p-injektioner, p-ringe, p-stave og visse spiraler, der frigiver hormoner) kan være nedsat, mens du tager Braftovi.
English: Combination with binimetinib
Danish: Kombination med binimetinib
English: Encorafenib is metabolised by CYP3A4, CYP2C19 and CYP2D6.
Danish: Encorafenib metaboliseres via CYP3A4, CYP2C19 og CYP2D6.
English: Fatigue * Pyrexia*
Danish: Træthed* Pyreksi*
English: Following a single oral dose of 100 mg [14C] encorafenib in healthy subjects, metabolism was found to be the major clearance pathway for encorafenib (approximately 88% of the recovered radioactive dose).
Danish: Efter en enkelt oral dosis af 100 mg [14C]-encorafenib hos raske forsøgsdeltagere var metabolisme den vigtigste clearancevej for encorafenib (cirka 88 % af den genfundne radioaktive dosis).
English: Following a single oral dose of 100 mg [14C] encorafenib in healthy subjects, at least 86% of the encorafenib dose was absorbed.
Danish: Efter en enkelt oral dosis af 100 mg [14C]-encorafenib hos raske forsøgsdeltagere blev mindst 86 % af encorafenib-dosen absorberet.
English: A thorough QT study to evaluate the QT prolongation potential of encorafenib has not been conducted.
Danish: Der er ikke gennemført nogen omfattende QT-studier med henblik på at evaluere risikoen for QT-forlængelse med encorafenib.
English: RPED occurred in 29.6% (81/274) of patients, most of them had Grade 1-2 and 1.8% (5/274) had Grade 3 events.
Danish: RPED forekom hos 29,6 % (81/274) af patienterne, hvoraf de fleste havde grad 1-2 og 1,8 % (5/274) havde grad 3-hændelser.
English: In the 4-week and 13-week monkey toxicity study, isolated/sporadic episodes of emesis and diarrhoea as well as ophthalmic lesions were observed at slightly above human therapeutic exposures.
Danish: I toksicitetsstudier hos aber af 4 og 13 ugers varighed blev der set enkeltstående/sporadiske episoder med emese og diarré samt oftalmiske læsioner ved behandlingseksponeringer, der var lidt højere end hos mennesker.
English: Preliminary Part 2 data, at a cut-off date of 9 November 2016, demonstrated the contribution of binimetinib with an improved median PFS estimate of 12.9 months (95% CI: 10.1, 14.0) for Combo 300 compared to 9.2 months (95% CI: 7.4, 11.0) for Enco 300 (Parts 1 and 2) per independent central review (BIRC).
Danish: Præliminære data for Del 2, ved skæringsdatoen 9. november 2016, viste binimetinibs bidrag med en forbedret estimat for median PFS på 12,9 måneder (95 % CI: 10,1, 14,0) for Combo 300 sammenlignet med 9,2 måneder (95 % CI: 7,4, 11,0) med Enco 300 (del 1 og 2) ifølge uafhængig central vurdering (BIRC).
English: QT Prolongation has been observed in patients treated with BRAF-inhibitors.
Danish: Der er set QT-forlængelse hos patienter i behandling med BRAF-hæmmere.
English: Renal failure events, including acute kidney injury and renal impairment, were reported in 3.3% (9/274) patients treated with encorafenib and binimetinib with Grade 3 or 4 events in 2.2% (6/274) of patients.
Danish: Hændelser med nyreinsufficiens, herunder akut nyreskade og nedsat nyrefunktion, blev indberettet hos 3,3 % (9/274) af de patienter, der blev behandlet med encorafenib og binimetinib, med hændelser af grad 3 eller 4 hos 2,2 % (6/274) af patienterne.
English: Amylase and lipase elevations were reported in 3.3% (9/274) and 5.1% (14/274) of patients, respectively.
Danish: Der blev rapporteret om forhøjet amylase og lipase hos henholdsvis 3,3 % (9/274) og 5,1 % (14/274) af patienterne.
English: Few patients required dose interruptions or dose reductions (0.7% or 2/274).
Danish: Hos nogle få patienter var det nødvendigt at pausere behandlingen eller reducere dosis (0,7 % eller 2/274).
English: Effect of transporters on encorafenib
Danish: Transportørers indvirkning på encorafenib
English: Other medicines and Braftovi
Danish: Brug af anden medicin sammen med Braftovi
English: Exceptions where dose modifications are necessary for binimetinib only (adverse reactions primarily related to binimetinib) are: retinal pigment epithelial detachment (RPED), retinal vein occlusion (RVO), interstitial lung disease/pneumonitis, cardiac dysfunction, creatine phosphokinase (CK) elevation and rhabdomyolysis, and venous thromboembolism (VTE).
Danish: Undtagelser, hvor det kun er nødvendigt at justere binimetinib-dosen (bivirkninger, der primært er relateret til binimetinib): løsning af retinalt pigmentepitel (RPED), retinal veneokklusion (RVO), interstitiel lungesygdom/pneumonitis, kardiel dysfunktion, stigning i kreatinfosfokinase (CK) og rabdomyolyse og venøs tromboemboli (VTE).
English: The confirmed ORR per BIRC was 65.9% (95% CI: 59.8, 71.7) for Combo 300 and 50.4% (95% CI: 44.3, 56.4) for Enco 300 (Parts 1 and 2).
Danish: Den bekræftede ORR ifølge BIRC var 65.9 % (95 % CI: 59,8, 71,7) for Combo 300 og 50,4 % (95 % CI: 44,3, 56,4) for Enco 300 (del 1 og 2).
English: Cutaneous malignancies such as cutaneous squamous cell carcinoma (cuSCC) including kerathoacanthoma has been observed in patients treated with BRAF-inhibitors including encorafenib.
Danish: Der er set kutane maligniteter, såsom kutant planocellulært karcinom (cuSCC), herunder keratoakantom, hos patienter i behandling med BRAF-hæmmere, herunder encorafenib.
English: Encorafenib is to be given in combination with binimetinib.
Danish: Encorafenib skal gives i kombination med binimetinib.
English: The management of adverse reactions may require dose reduction, temporary interruption or treatment discontinuation (see Tables 1 and 2).
Danish: Håndteringen af bivirkninger kan kræve dosisreduktion, pausering eller seponering af behandlingen (se tabel 1 og tabel 2).
English: Concurrent use of strong CYP3A inhibitors during treatment with encorafenib should be avoided.
Danish: Samtidig brug af stærke CYP3A-hæmmere bør undgås under behandlingen med encorafenib.
English: Package leaflet: Information for the patient Braftovi 50 mg hard capsules
Danish: Indlægsseddel: Information til patienten Braftovi 50 mg kapsler, hårde
English: Encorafenib and binimetinib should be continued without any dose modification.
Danish: Encorafenib og binimetinib bør fortættes uden dosisjustering.
English: If concomitant use with a strong CYP3A inhibitor is necessary, patients should be carefully monitored for safety (see section 4.5).
Danish: Hvis samtidig brug af en stærk CYP3A-hæmmer er nødvendig, bør patienten af sikkerhedshensyn monitoreres nøje (se pkt.
English: Based on a population pharmacokinetic analysis, age was found to be a significant covariate on encorafenib volume of distribution, but with high variability.
Danish: En populationsfarmakokinetisk analyse viste, at alder er et signifikant kovariat for encorafenibs distributionsvolumen, men med høj variabilitet.
English: Women of childbearing potential / Contraception in females Women of childbearing potential must use effective contraception during treatment with encorafenib and for at least 1 month following the last dose.
Danish: Kvinder i den fertile alder/kontraception hos kvinder Kvinder i den fertile alder skal anvende sikker kontraception under behandlingen og i mindst en måned efter behandlingen.
English: Effect of encorafenib on transporters
Danish: Encorafenibs indvirkning på transportører
English: Cerebral haemorrhage was reported in 1.5% (4/274) of patients, with fatal outcome in 3 patients.
Danish: Cerebral blødning blev rapporteret hos 1,5 % (4/274) af patienterne med dødelig udgang hos 3 patienter.
English: Based on in vitro studies, there is potential for encorafenib to inhibit renal transporters OCT2, OAT1, OAT3 and hepatic transporters OATP1B1 and OATP1B3 at clinical concentrations.
Danish: Baseret på in vitro-studier kan encorafenib potentielt hæmme nyretransportørerne OCT2, OAT1, OAT3 og levertransportørerne OATP1B1 og OATP1B3 ved kliniske koncentrationer.
English: Encorafenib should be resumed at a reduced dose when QTcF ≤500 ms.
Danish: Encorafenib skal genoptages i reduceret dosis, når QTcF ≥500 ms. Encorafenib bør seponeres, hvis der er mere end et tilbagefald.
English: • Grade 3
Danish: • Grad 3
English: Encorafenib should be maintained.
Danish: Encorafenib skal fortsættes.
English: In the pooled encorafenib 300 population, PPES was reported in 51.6% (112/217) of patients.
Danish: I den samlede encorafenib 300-population blev der rapporteret om PPES hos 51,6 % (112/217) af patienterne.
English: Diarrhoea led to dose discontinuation in 0.4% of patients and to dose interruption or dose modification in 4.4% of patients.
Danish: Diarré førte til seponering hos 0,4 % af patienterne og til pausering eller dosisjustering hos 4,4 % af patienterne.
English: Encorafenib should be withheld until improved to Grade 0 or 1 and resumed at the same dose if first occurrence, or resumed at a reduced dose if recurrent Grade 3.
Danish: Encorafenib skal pauseres indtil bedring til grad 0 eller 1, og genoptages i samme dosis, hvis det var første forekomst, eller i reduceret dosis, hvis det var tilbagevendende grad 3.
English: Examples of moderate CYP3A4 inhibitors include, but are not limited to, amiodarone, erythromycin, fluconazole, diltiazem, amprenavir and imatinib.
Danish: Eksempler på moderate CYP3A4-hæmmere omfatter, men er ikke begrænset til, amiodaron, erythromycin, fluconazol, diltiazem, amprenavir og imatinib.
English: When encorafenib was used at a dose of 300 mg once daily in combination with binimetinib 45 mg twice daily (Combo 300) in study CMEK162B2301-Part 2, the frequency category was lower compared to the pooled Combo 450 population for the following adverse reactions: anemia, peripheral neuropathy, haemorrhage, hypertension, pruritus (common); and colitis, increased amylase and increased lipase (uncommon).
Danish: Når encorafenib blev anvendt i en dosis på 300 mg én gang dagligt i kombination med binimetinib 45 mg to gange dagligt (Combo 300) i studiet CMEK162B2301-del 2, var frekvenskategorien lavere sammenlignet med den samlede Combo 450-population for følgende bivirkninger: anæmi, perifer neuropati, blødning, hypertension, pruritus (almindelig); og colitis, øget amylase og øget lipase (ikke almindelig).
English: Erythema*
Danish: Erytem*
English: The concomitant administration of encorafenib with grapefruit juice should be avoided (see sections 4.4 and 4.5)
Danish: Samtidig administration af encorafenib og grapefrugtjuice bør undgås (se pkt.
English: At the recommended dose (n = 274) in patients with unresectable or metastatic melanoma, the most common adverse reactions (>25%) occurring in patients treated with encorafenib administered with binimetinib were fatigue, nausea, diarrhoea, vomiting, retinal detachment, abdominal pain, arthralgia, blood CK increased and myalgia.
Danish: Ved brug af den anbefalede dosis (n=274) hos patienter med inoperabelt eller metastatisk melanom var de mest almindelige bivirkninger (> 25 %) hos patienter, der fik encorafenib i kombination med binimetinib, træthed, kvalme, diarré, opkastning, retinal løsning, mavesmerter, artralgi, øget CK i blodet og myalgi.
English: Based on a population pharmacokinetic analysis gender was not found to be a significant model covariate on clearance or volume of distribution.
Danish: En populationsfarmakokinetisk analyse viste, at køn ikke er et betydeligt modelkovariat for clearance eller distributionsvolumen.
English: Following a single oral dose of 100 mg [14C] encorafenib in healthy subjects, radioactivity was eliminated equally in both the faeces and urine (mean of 47.2%).
Danish: Efter en enkelt oral dosis af 100 mg [14C]-encorafenib hos raske forsøgsdeltagere blev radioaktiviteten elimineret ligeligt via fæces og urin (gennemsnitligt 47,2 %).
English: Patients receiving encorafenib should undergo a head and neck examination, chest/abdomen computerised tomography (CT) scan, anal and pelvic examinations (for women) and complete blood cell counts prior to initiation, during and at the end of treatment as clinically appropriate.
Danish: Hos patienter, der får encorafenib, bør der gennemføres en hoved- og halsundersøgelse, CT-scanning af brystet/abdomen, undersøgelse af endetarmen og underlivet (hos kvinder) og komplette blodtællinger inden opstart af behandlingen, under og efter behandlingen efter klinisk behov.
English: While binimetinib is a UGT1A1 substrate, it does not undergo gut extraction and therefore no DDI with encorafenib is expected.
Danish: Binimetinib er et UGT1A1-substrat, men det gennemgår ikke tarmekstraktion, og der forventes derfor ingen interaktioner med encorafenib.
English: Encorafenib induced CYP1A2, CYP2B6, CYP2C9 and CYP3A4 in human primary hepatocytes.
Danish: Encorafenib inducerede CYP1A2, CYP2B6, CYP2C9 og CYP3A4 i humane primære hepatocytter.
English: In vitro, encorafenib inhibited the hepatic transporter OCT1, but is unlikely to be an effective inhibitor clinically.
Danish: Encorafenib hæmmede levertransportøren OCT1 in vitro, men i klinisk praksis vil det sandsynligvis ikke være en effektiv hæmmer.
English: Additionally, no differences in exposure have been observed clinically when binimetinib is co-administered with encorafenib.
Danish: Derudover er der ikke set forskelle i eksponeringen ved klinisk samtidig administration af binimetinib og encorafenib.
English: The pharmacokinetics of encorafenib have not been studied in patients with severe renal impairment.
Danish: Encorafenibs farmakokinetik er ikke blevet undersøgt hos patienter med svært nedsat nyrefunktion.
English: Most events were mild, with Grade 3 or 4 events reported in 4.6% (10/217) of patients.
Danish: De fleste hændelser var milde; hændelser af grad 3 eller 4 blev indberettet hos 4,6 % (10/217) af patienterne.
English: Effect of encorafenib on CYP substrates
Danish: Encorafenibs indvirkning på CYP-substrater
English: In particular, tell your doctor if you are taking anything in this list or any other medicines: - some medicines to treat fungal infections (such as itraconazole, posaconazole, fluconazole) - some medicines to treat bacterial infections (such as rifampicin, clarithromycin, telithromycin,
Danish: Det er især vigtigt, at du fortæller det til lægen, hvis du tager noget fra denne liste eller anden medicin: - visse lægemidler til behandling af svampeinfektioner (såsom itraconazol, posaconazol,
English: Median DOR for confirmed responses per BIRC was 12.7 months [95% CI: 9.3, 15.1] for Combo 300 and 12.9 months [95% CI: 8.9, 15.5] for Enco 300.
Danish: Median DOR for bekræftet respons ifølge BIRC var 12,7 måneder [95 % CI: 9,3, 15,1] for Combo 300 og 12,9 måneder [95 % CI: 8,9, 15,5] for Enco 300.
English: If concomitant use of a strong CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety.
Danish: Hvis samtidig brug af en stærk CYP3A-hæmmer ikke kan undgås, bør patienten af sikkerhedshensyn monitoreres nøje.
English: • Capsule contents: copovidone (E1208), poloxamer 188, cellulose microcrystalline (E460i), succinic acid (E363), crospovidone (E1202), silica colloidal anhydrous (E551), magnesium stearate (E470b)
Danish: • Kapselindhold - copovidon (E1208), poloxamer 188, cellulose, mikrokrystallinsk (E460i), succinsyre (E363), crospovidon (E1202), silica, kolloid vandfri (E551), magnesiumstearat (E470b)
English: Based on a population pharmacokinetic analysis, body weight was found to be a significant model covariate on clearance and volume of distribution.
Danish: En populationsfarmakokinetisk analyse viste, at legemsvægt er et betydeligt modelkovariat for clearance og distributionsvolumen.
English: • First occurrence of Grade 3 (AST or ALT >5x ULN and blood bilirubin >2x ULN)
Danish: • Første forekomst af grad 3 (ASAT eller ALAT > 5x ULN og blodbilirubin > 2x ULN)
English: - Skin changes: Braftovi may cause other types of skin cancer such as cutaneous squamous cell carcinoma.
Danish: - Hudforandringer: Braftovi kan forårsage andre typer af hudkræft, såsom kutant planocellulært karcinom (cuSCC).
English: Basal cell carcinoma
Danish: Basalcellekarcinom
English: Liver laboratory values should be monitored before initiation of encorafenib and binimetinib and monitored at least monthly during the 6 first months of treatment, then as clinically indicated.
Danish: Levertallene bør kontrolleres inden opstart af encorafenib og binimetinib og mindst en gang om måneden i de første 6 måneder af behandlingen og herefter som klinisk indiceret.
English: Bleeding problems: Braftovi can cause serious bleeding problems.
Danish: Blødningsproblemer: Braftovi kan forårsage alvorlige blødningsproblemer.
English: Effect of CYP enzymes on encorafenib
Danish: CYP-enzymers indvirkning på encorafenib
English: Examples of moderate or strong CYP3A4 inducers include, but are not limited to carbamazepine, rifampicin, phenytoin and St. John's Wort.
Danish: Eksempler på moderate og stærke CYP3A4-induktorer omfatter, men er ikke begrænset til, carbamazepin, rifampicin, phenytoin og perikon.
English: The most common adverse drug reactions (ADRs) (>25%) reported with encorafenib 300 were hyperkeratosis, alopecia, PPES, fatigue, rash, arthralgia, dry skin, nausea, myalgia, headache, vomiting and pruritus.
Danish: De hyppigst indberettede bivirkninger (> 25 %) med encorafenib 300 var hyperkeratose, alopeci, PPES, træthed, udslæt, artralgi, tør hud, kvalme, myalgi, hovedpine, opkastning og pruritus.
English: LVD defined as symptomatic or asymptomatic decreases in ejection fraction has been reported when encorafenib is used in combination with binimetinib.
Danish: Der er rapporteret om LVD, defineret som symptomatisk eller asymptomatisk nedsat ejektionsfraktion, ved brug af encorafenib i kombination med binimetinib.
English: Talk to your doctor immediately if you get blurred vision, loss of vision, or other vision changes (e.g. coloured dots in your vision), halo (seeing blurred outline around objects).
Danish: Kontakt omgående lægen, hvis du får sløret syn, synstab eller andre ændringer af synet (f.eks. farvede pletter i dit synsfelt), korona (ser et sløret omrids rundt om genstande).