FrancophonIA/ELRC3.0 huggingface dataset:
English: LS mean percent change from baseline in fasting triglycerides based on the observed data are displayed.
Danish: Viser LS-middelværdien af den procentvise ændring i fastende triglycerider i forhold til baseline baseret på de observerede data.
English: Following a dose of 285 mg once weekly in patients with FCS, the estimated geometric mean (coefficient of variation % of geometric mean) steady-state Cmax is 8.92 µg/ml (35%), AUC0-168h is 136 µg*h/ml (38%), and Ctrough is 127 ng/ml (58%) in patients who remain negative for anti-drug antibody.
Danish: Efter en dosis på 285 mg én gang om ugen hos FCS-patienter er den estimerede geometriske middelværdi (variationskoefficient i % af geometrisk middelværdi) for Cmax ved steady state 8,92 µg/ml (35 %), AUC0168t er 136 µg*t/ml (38 %), og Ctrough er 127 ng/ml (58 %) hos patienter, der forbliver negative for antistoffer mod lægemidlet.
English: Your doctor will do a blood test before you start using this medicine to check the number of platelets, and then at regular intervals once you have started using Waylivra to check on platelet levels.
Danish: Lægen vil tage en blodprøve for at kontrollere antallet af blodplader, inden du begynder at bruge dette lægemiddel og regelmæssigt under behandlingen med Waylivra.
English: Before starting this medicine, you should be on a diet designed to help lower triglyceride levels in your blood.
Danish: Inden du begynder at tage dette lægemiddel, bør du følge en diæt, der hjælper med at sænke indholdet af triglycerider i blodet.
English: The other ingredients are water for injections, sodium hydroxide and hydrochloric acid (to adjust acidity level, see section 2 under ‘Sodium').
Danish: - Øvrige indholdsstoffer: vand til injektionsvæsker, natriumhydroxid og saltsyre (til justering af surhedsgraden, se 'Waylivra indeholder natrium' i punkt 2).
English: During this time this medicine may be kept at either room temperature or put back into the refrigerator, as needed.
Danish: I løbet af denne periode kan lægemidlet enten opbevares ved rumtemperaur eller sættes tilbage i køleskabet efter behov.
English: Waylivra can be kept at room temperature (up to 30 °C) in the original carton for up to 6 weeks after removing from the refrigerator.
Danish: Waylivra kan opbevares ved rumtemperatur (op til 30 °C) i den originale karton i op til 6 uger efter udtagning af køleskabet.
English: Percent of patientsb with fasting plasma triglyceride < 750 mg/dL (8.5 mmol/L)*
Danish: Procentdel af patienterb med fastende plasmatriglycerider < 750 mg/dl (8,5 mmol/l)*
English: The APPROACH study is a randomised, double-blind placebo-controlled 52-week multicentre clinical study in 66 patients with FCS, evaluating volanesorsen 285 mg administered as a subcutaneous injection (33 treated with volanesorsen, 33 with placebo).
Danish: APPROACH-studiet er et randomiseret, dobbeltblindet, placebokontrolleret klinisk multicenterstudie af 52 ugers varighed med 66 FCS-patienter til vurdering af subkutan injektion af 285 mg volanesorsen (33 behandlet med volanesorsen, 33 med placebo).
English: CS16-volanesorsen (Index Study Baselinea, N=3)
Danish: CS16-volanesorsen (Baseline i indeksstudiea, N=3)
English: If you get any of the following side effects, contact your doctor immediately: - Symptoms that could indicate low counts of platelets in your blood (platelets are cells important for blood clotting).
Danish: Kontakt straks lægen, hvis du får en eller flere af følgende bivirkninger: - Symptomer på lavt antal blodplader i blodet (blodplader er vigtige for blodstørkningen).
English: A history of documented acute pancreatitis was reported for 76% of patients and a history of diabetes was reported for 15% of patients; 21% of patients had a recorded history of lipaemia retinalis and 23% of patients had a recorded history of eruptive xanthomas.
Danish: Der blev rapporteret om dokumenteret akut pancreatitis i anamnesen hos 76 % af patienterne og om diabetes i anamnesen hos 15 % af patienterne; 21 % af patienterne havde registreret retinal lipæmi i anamnesen, og 23 % af patienterne havde registrerede eruptive xantomer i anamnesen.
English: In the APPROACH study, the numerical incidence of pancreatitis in patients treated with volanesorsen was lower compared with placebo (3 patients 4 events in 33 placebo patients vs 1 patient 1 event in 33 volanesorsen patients).
Danish: I APPROACH-studiet var der en numerisk lavere forekomst af pancreatitis hos de patienter, der blev behandlet med volanesorsen, end hos de patienter, der fik placebo (3 patienter 4 hændelser i 33 placebopatienter vs. 1 patient 1 hændelse i 33 volanesorsenpatienter).
English: The expiry date on the package refers to the life of the product when refrigerated.
Danish: Udløbsdatoen på pakningen gælder ved opbevaring i køleskabet.
English: An alternative dosing regimen of 285 mg volanesorsen every two weeks results in a Ctrough,ss of approximately 58.0 ng/ml with Cmax and AUC similar compared to the once weekly dosing regimen.
Danish: Et alternativt doseringsregime med 285 mg volanesorsen hver anden uge resulterer i et Ctrough,ss på cirka 58,0 ng/ml med Cmax og AUC af samme størrelsesorden som ved dosering én gang om ugen.
English: If you forget to use Waylivra
Danish: Hvis du har glemt at bruge Waylivra
English: In the volanesorsen group, of the 7 patients who had 24 adjudicated pancreatitis attacks in the prior 5 years, none of the patients experienced a pancreatitis attack during the 52 week treatment period.
Danish: Ud af de 7 patienter i volanesorsengruppen, der tilsammen havde 24 pancreatitisanfald i de sidste 5 år inden studiet, oplevede ingen af patienterne et pancreatitisanfald i løbet af behandlingsperioden på 52 uger.
English: Do not try to remove the air bubble before injecting.
Danish: Du må ikke forsøge at fjerne luftboblen inden indgivelsen.
English: This medicinal product contains less than 1 mmol sodium (23 mg) per dose of 285 mg, that is to say it is essentially ‘sodium-free'.
Danish: Dette lægemiddel indeholder mindre end 1 mmol (23 mg) natrium pr. dosis på 285 mg, dvs. det er i det væsentlige natrium-frit.
English: Dose and time-dependent reductions in platelet counts were observed in Cynomolgus monkey repeated dose studies.
Danish: Der blev set dosis- og tidsafhængige fald i trombocyttallet hos Cynomolgus-aber i studier med gentagen dosering.
English: APPROACH-volanesorsen (Index Study Baselinea, N=14)
Danish: APPROACH-volanesorsen (Baseline i indeksstudiea, N=14)
English: This medicinal product can be removed from refrigeration and stored, in the original carton, at room temperature (below 30 °C) for up to 6 weeks.
Danish: Dette lægemiddel kan tages ud af køleskabet og opbevares i den originale karton ved rumtemperatur (under 30 °C) i op til 6 uger.
English: Triglycerides Total Cholesterol
Danish: Triglycerider Totalkolesterol LDL-C
English: Water for injections, hydrocloric acid and sodium hydroxide.
Danish: Vand til injektionsvæsker, saltsyre og natriumhydroxid.
English: Remove the needle from the injection site by pulling out at the same angle it was inserted (Figure M).
Danish: Træk kanylen ud af injektionsstedet i samme vinkel, som du indførte den i (figur M).
English: Insomnia (1, 1%)
Danish: Insomni (1, 1 %)
English: In APPROACH and its open-label extension (CS7), patients discontinuing therapy due to platelet levels included 3 patients with platelet counts <25 x 109/L, 2 with platelet counts between 25 x 109/L and 50 x 109/L, and 5 with platelet counts between 50 x 109/L and 75 x 109/L.
Danish: I APPROACH og studieforlængelsen med åben behandling (CS7) omfattede de patienter, der fik seponeret behandlingen på grund af trombocytniveauet, 3 patienter med trombocyttal < 25 x 109/l, 2 med trombocyttal mellem 25 x 109/l og 50 x 109/l og 5 med trombocyttal mellem 50 x 109/l og 75 x 109/l.
English: Recommendations for adjustments to monitoring frequency and dosing are specified in Table 1 (see section 4.2).
Danish: De anbefalede monitoreringshyppigheder og dosisjusteringer er anført i tabel 1 (se pkt.
English: Accumulation in Ctrough was observed (7- to 14-fold) and little or no increase in Cmax or AUC was observed following weekly SC administration over a dose of 200 to 400 mg.
Danish: Der blev set akkumulation i Ctrough (7- til 14-foldig) og lille eller ingen stigning i Cmax eller AUC efter ugentlig subkutan administration af en dosis på 200 til 400 mg. Der blev set en vis akkumulation i AUC og Cmax for doser på 50 til 100 mg.
English: Treat the Injection Site
Danish: Behandl injektionsstedet
English: Background lipid-lowering therapies remained consistent throughout the study.
Danish: De lipidsænkende baggrundsbehandlinger forblev konstante i hele studiet.
English: Injection should be avoided at the waistline and other sites where pressure or rubbing may occur from clothing.
Danish: Det bør undgås at give injektionen i taljen eller andre steder, hvor patientens beklædning kan forårsage tryk eller gnidninger.
English: Within each frequency grouping, adverse reactions are presented in order of decreasing frequency.
Danish: Inden for hver hyppighedsgruppe er bivirkningerne opstillet efter, hvor alvorlige de er.
English: In nonclinical studies, levels of volanesorsen in milk were very low in lactating mice.
Danish: I prækliniske studier var niveauet af volanesorsen i mælken hos diegivende mus meget lavt.
English: It is important to rotate sites for injection.
Danish: Det er vigtigt, at der skiftes mellem forskellige injektionssteder.
English: There is limited clinical data for patients aged 65 and over (see sections 5.1 and 5.2).
Danish: Der er begrænsede kliniske data vedrørende patienter over 65 år (se pkt.
English: Monitoring for hepatotoxicity through serum liver enzymes and bilirubin should be assessed on a quarterly basis.
Danish: Det anbefales at monitorere for tegn på hepatotoksicitet gennem vurdering af leverenzymer og bilirubin i serum hvert kvartal.
English: Treatment should not be initiated in patients with thrombocytopenia (platelet count <140 x 109/L).
Danish: Der bør ikke startes behandling hos patienter med trombocytopeni (trombocyttal < 140 x 109/l).
English: % change from Baseline in CS16
Danish: %-vis ændring fra baseline i CS16
English: +92 (-301, +486) mg/dL +1 (-3, +5) mmol/L
Danish: +92 (-301; +486) mg/dl +1 (-3; +5) mmol/l mg/dl -19 (-24; -15) mmol/l mg/dl -20 (-26; -15) mmol/l
English: At the primary efficacy endpoint, the treatment difference between volanesorsen and placebo in mean fasting triglyceride percent change was -94% (95% CI: -122% -67%; p˂0.0001, with a decrease of77% from baseline (95% CI: -97, -56) in patients receiving volanesorsen and an increase of 18% from baseline (95% CI: -4, 39) in patients receiving placebo (Table 4).
Danish: Ved det primære effektendepunkt var behandlingsforskellen mellem volanesorsen og placebo, hvad angik den procentvise ændring i gennemsnitligt fastende triglyceridniveau, -94 % (95 % CI: -122 % -67 %; p ˂ 0,0001) med et fald på -77 % i forhold til baseline (95 % CI: -97, -56) hos de patienter, der fik volanesorsen, og en stigning på 18 % i forhold til baseline (95 % CI: -4, 39) hos de patienter, der fik placebo (tabel 4).
English: Open the carton and remove the syringe by grasping the syringe barrel and pulling it straight out (Figure C).
Danish: Åbn kartonen, og tag sprøjten ud ved at tage fat om sprøjtecylinderen og trække den ret op (figur C).
English: Non-interventional PASS: the applicant should conduct and submit the results of a study based on a Registry in order to evaluate the safety of Waylivra on thrombocytopenia and bleeding(including incidence rate, severity and outcomes) in FCS patients according to the dose recommendation and dose algorithm and investigate adherence with platelet monitoring and dose adjustment requirements.
Danish: (PASS): Ansøgeren skal gennemføre og fremlægge resultaterne af et studie baseret på et register med henblik på at vurdere Waylivras sikkerhed i forhold til trombocytopeni og blødning (herunder incidensrate, sværhedsgrad og resultater) hos patienter med FCS i henhold til dosisanbefalingen og dosisalgoritmen og undersøge overholdelse af kravet om monitorering af trombocyttallet og justering af dosis.
English: No data are available in patients with severe renal impairment.
Danish: Der foreligger ingen data fra patienter med svært nedsat nyrefunktion.
English: Common (may affect up to 1 in 10 people) - Blood tests showing unusually high or low levels of white blood cells in your blood - Easy or excessive bruising, or bruising without an obvious cause - Bleeding under the skin that appears as a rash, bleeding from the gums or mouth, blood in the urine or stools, nosebleed, or unusually heavy menstrual period - An allergic reaction, the symptoms of which include skin rash, joint stiffness or fever - Blood or protein in the urine - Changes to the results of some blood tests, including: o an increase in the level of some constituents in your blood: creatinine, urea, transaminases, liver enzymes o an increase in blood clotting time o a fall in levels of haemoglobin in your blood o a fall in the rate of blood passing through the kidneys - Diabetes, the symptoms of which include increased thirst, frequent need to pass urine (particularly ar night), extreme hunger, severe tiredness, and unexplained weight loss - Difficulty sleeping - Headaches, numbness, tingling or pins and needles, feeling faint or fainting, dizziness or shaking - Visual disturbances, such as flashing lights or brief, temporary blindness in one eye, bleeding under the surface of the eye, or blurred vision - High blood pressure - Hot flush, increased sweating, night sweats, chills, feeling hot, pain, flu-like illness or a general feeling of being unwell - Cough, difficulty breathing, a blocked nose, swelling of the throat, wheezing - Feeling or being sick, dry mouth, diarrhoea, swelling of the neck, face or gums, stomach pain or swelling, indigestion - Skin redness, rash, pimples, thickening or scarring, or itchiness of the skin known as ‘hives' (urticaria) - Muscle pain, pain in the hands or feet, joint pain or stiffness, back pain, neck pain, jaw pain, muscle spasms, or other body pains
Danish: - Hovedpine, følelsesløshed, snurren eller prikken og stikken i huden, besvimelsesfornemmelse eller besvimelse, svimmelhed eller rysten - Synsforstyrrelser såsom blinkende lys eller kortvarig og forbigående blindhed på ét øje, blødning under øjets overflade eller sløret syn - Højt blodtryk - Hedeture, øget svedtendens, nattesved, kulderystelser, varmefølelse, influenzalignende sygdom eller almen utilpashed - Hoste, vejrtrækningsbesvær, tilstoppet næse, hævelse i svælget, pibende vejrtrækning - Kvalme eller opkastning, mundtørhed, diarré, hævelse af nakken, ansigtet eller tandkødet, mavesmerter eller -udspiling, fordøjelsesbesvær - Hudrødme, udslæt, knopper, fortykkelse af huden eller ardannelse eller kløe i huden kaldet 'nældefeber' (urticaria) - Muskelsmerter, smerter i hænder eller fødder, ledsmerter eller -stivhed, rygsmerter, nakkesmerter, smerter i kæben, muskelsammentrækninger eller smerter i andre dele af kroppen.
English: At study entry, 55% of patients were on lipid lowering therapies (48% on fibrates, 29% on fish oils, 20% HMG-CoA reductase inhibitors), 27% were on pain medications, 20% were on platelet aggregation inhibitors, and 14% were on nutritional supplements.
Danish: Ved inklusionen i studiet var 55 % af patienterne i lipidsænkende behandling (48 % med fibrater, 29 % med fiskeolier, 20 % med HMG-CoA-reduktasehæmmere), 27 % fik smertelindrende midler, 20 % fik trombocytaggregationshæmmere, og 14 % fik kosttilskud.
English: If the syringe was in the refrigerator, allow the prefilled syringe to reach room temperature by removing it from the refrigerator at least 30 minutes before the injection.
Danish: Hvis den fyldte injektionssprøjte har ligget i køleskabet, skal du tage den ud af køleskabet mindst 30 minutter inden injektionen, så den opnår rumtemperatur.
English: (<1/10,000); and not known (cannot be estimated from available data).
Danish: 1/10), ikke almindelig (≥ 1/1.000 til < 1/100), sjælden (≥ 1/10.000 til < 1/1.000), meget sjælden (< 1/10.000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
English: Injecting the solution with the air bubble is harmless.
Danish: Det er ufarligt at indgive opløsningen med luftboblen.
English: Monitoring for evidence of nephrotoxicity by routine urine dipstick is recommended on a quarterly basis.
Danish: Det anbefales at monitorere for tegn på nefrotoksicitet ved rutinemæssigt at teste urinen med en urinstix hvert kvartal.
English: Waylivra is very commonly associated with reductions in platelet count in patients with FCS, which may result in thrombocytopenia (see section 4.8).
Danish: Waylivra er ofte forbundet med fald i trombocyttallet hos patienter med FCS, hvilket kan resultere i trombocytopeni (se pkt.
English: Together with a controlled low-fat diet, Waylivra helps to lower the levels of triglycerides in your blood.
Danish: Når Waylivra tages sammen med en kontrolleret diæt med lavt fedtindhold, hjælper det med at sænke indholdet af triglycerider i dit blod.
English: Weekly
Danish: Ugentligt
English: Following 3 months, dose frequency should be reduced to 285 mg every 2 weeks.
Danish: Doseringshyppigheden bør reduceres til 285 mg hver anden uge efter tre måneder.
English: If you see blood where you've injected, press the site lightly with the sterile cotton ball or gauze and bandage if needed (Figure O).
Danish: Hvis der er blod på injektionsstedet, kan du trykke let på stedet med en steril vatkugle eller gazetampon og om nødvendigt sætte et plaster på (figur O).
English: Do not use the pre-filled syringe if the liquid is cloudy or has floating particles.
Danish: Du må ikke bruge den fyldte injektionssprøjte, hvis væsken er uklar eller indeholder flydende partikler.
English: o Reporting of any adverse drug reaction to a health professional
Danish: o Indberetning af enhver bivirkning til sundhedspersonalet
English: Table 2 presents the adverse reactions from the Phase 3 studies in patients with FCS in receiving volanesorsen subcutaneously.
Danish: Bivirkningstabel Tabel 2 viser bivirkningerne i de fase 3-studier, hvor patienterne med FCS fik volanesorsen subkutant.
English: In the pivotal Phase 3 study in patients with FCS (the APPROACH study), confirmed reductions in platelet counts to below normal (140 x 109/L) were observed in 75% of FCS patients treated with volanesorsen and 24% of placebo patients; confirmed reductions to below 100 x 109/L were observed in 47% of patients treated with volanesorsen compared with no placebo patients.
Danish: I det pivotale fase 3-studie med FCS-patienter (APPROACH-studiet) blev der set bekræftede fald i trombocyttallet til under normalen (140 x 109/l) hos 75 % af de FCS-patienter, der blev behandlet med volanesorsen, og hos 24 % af placebopatienterne; bekræftede fald til under 100 x 109/l blev set hos 47 % af de patienter, der blev behandlet med volanesorsen, men ikke hos nogen af placebopatienterne.
English: Hepatic impairment The pharmacokinetics of volanesorsen in patients with hepatic impairment is unknown.
Danish: Nedsat leverfunktion Volanesorsens farmakokinetik hos patienter med nedsat leverfunktion er ikke klarlagt.
English: % change from Baseline in APPROACH n
Danish: %-vis ændring fra baseline i APPROACH n
English: Open-label extension study in patients with FCS
Danish: Studieforlængelse med åben behandling af FCS-patienter
English: This medicinal product should not be injected into tattoos, moles, birthmarks, bruises, rashes, or areas where the skin is tender, red, hard, bruised, damaged, burned, or inflamed.
Danish: Dette lægemiddel bør ikke injiceres i tatoveringer, skønhedspletter, modermærker, blå mærker, udslæt eller områder, hvor huden er øm, rød, hård, skrammet, skadet, forbrændt eller betændt.
English: Due to the poor oral bioavailability of volanesorsen, it is considered unlikely that these low milk concentrations would result in systemic exposure from nursing (see section 4.6).
Danish: På grund af den ringe orale biotilgængelighed af volanesorsen anses det for usandsynligt, at disse lave mælkekoncentrationer skulle resultere i systemisk eksponering ved amning (se pkt.
English: If a dose is missed and noticed within 48 hours, the patient should be directed to give the missed dose as soon as possible.
Danish: Hvis patienten glemmer en dosis og kommer i tanker om det inden for 48 timer, bør patienten rådgives til at tage den glemte dosis så hurtigt som muligt.
English: In the placebo group, of the 4 patients who had 17 adjudicated pancreatitis attacks in the prior 5 years, 3 patients experienced 4 pancreatitis attacks during the 52-week treatment period.
Danish: Ud af de 4 patienter i placebogruppen, der tilsammen havde 17 pancreatitisanfald i de sidste 5 år inden studiet, oplevede 3 patienter 4 pancreatitisanfald i løbet af behandlingsperioden på 52 uger.
English: Immunisation reaction (3, 3%) Hypersensitivity (1, 1%) Serum sickness-like reaction (1,
Danish: Immuniseringsreaktion (3, 3 %) Overfølsomhed (1, 1 %) Serumsygdomslignende reaktion (1,
English: Injection site reactions defined as any local cutaneous reaction at the injection site persisting more than 2 days occurred in 82% of volanesorsen-treated patients in the APPROACH study and its openlabel extension (CS7).
Danish: Reaktioner på injektionsstedet, der var defineret som enhver lokal kutan reaktion på injektionsstedet, der varede i mere end 2 dage, forekom hos 82 % af de volanesorsen-behandlede patienter i APPROACH
English: Injection site haematoma (7, 8%) Injection site reaction (6, 7%) Injection site urticaria (5, 6%) Injection site warmth (5, 6%) Chills (5, 6%)
Danish: Reaktion på injektionsstedet (6, 7 %) Urticaria på injektionsstedet (5, 6 %) Varme på injektionsstedet (5, 6 %) Kulderystelser (5, 6 %) Pyreksi (4, 5 %)
English: No evidence of altered safety profile or clinical response was associated with presence of anti-drug antibodies; however this is based on the limited long-term data (see section 4.4).
Danish: Der var ingen evidens for, at forekomst af antistoffer mod lægemidlet var forbundet med ændringer i sikkerhedsprofilen eller det kliniske; dette er imidlertid baseret på begrænsede langtidsdata (se pkt.
English: Discard this medicine immediately if not used within the 6 weeks after the first time it is removed from the refrigerator.
Danish: Bortskaf lægemidlet med det samme, hvis det ikke bliver brugt i løbet af 6 uger efter første udtagning af køleskabet.
English: Difference= LS Mean of [volanesorsen % Change - Placebo % Change] (ANCOVA model) p-value from ANCOVA model < 0.0001 at Month 3 (primary efficacy endpoint), Month 6 and Month 12 Additional efficacy results for changes in triglyceride are presented in Table 5.
Danish: Forskel = LS-middelværdi af [volanesorsen %-vis ændring - placebo %-vis ændring] (ANCOVA-model) P-værdi fra ANCOVA-model < 0,0001 ved måned 3 (primært effektendepunkt), måned 6 og måned 12.
English: Figure 1: LS Mean Percent Change in Fasting Triglycerides in Phase 3 Study in Patients with FCS (APPROACH)
Danish: LS-middelværdi af procentvis ændring i fastende triglycerider i fase 3-studiet med FCS-patienter (APPROACH)
English: Asthenia (8, 9%) Fatigue (8, 9%)
Danish: Fatigue (8, 9 %)
English: The date you first remove the pack from the refrigerator should be recorded on the outer carton in the space indicated.
Danish: Notér datoen for første udtagning af køleskabet på den ydre karton, hvor der er gjort plads til det.
English: Waylivra can be stored at room temperature (8 °C-30 °C), in the outer carton to protect from light, for up to 6 weeks.
Danish: Waylivra kan opbevares i op til 6 uger ved rumtemperatur (8 °C - 30 °C) i den ydre karton for at beskytte mod lys.
English: PARTICULARS TO APPEAR ON THE OUTER PACKAGING PACKAGING INNER CARTON - MULTIPACK WITHOUT BLUE BOX
Danish: MÆRKNING, DER SKAL ANFØRES PÅ DEN YDRE EMBALLAGE INDRE KARTON - MULTIPAKNING UDEN BLÅ BOKS
English: You may see a drop of liquid at the tip of the needle.
Danish: Der kan være en dråbe væske ved kanylens spids.
English: The pre-filled syringe should be allowed to reach room temperature prior to injection.
Danish: Den fyldte injektionssprøjte skal opnå rumtemperatur inden indgivelsen.