natgillin/translations-raw huggingface dataset:
Everolimus er en potent hæmmer af vækst og proliferation af tumorceller, endotelceller, fibroblaster og vaskulære glatte muskelceller og har vist at reducere glykolysen i solide tumorer in vitro og in vivo.
Everolimus is a potent inhibitor of the growth and proliferation of tumour cells, endothelial cells, fibroblasts and blood-vessel-associated smooth muscle cells and has been shown to reduce glycolysis in solid tumours in vitro and in vivo.
Patienten skal med det samme drikke hele suspensionen fra glasset.
The patient must immediately drink all of the oral suspension from the glass.
Sæt den fyldte sprøjte i et rent og tomt glas, så spidsen peger opad.
Put the filled oral syringe in the clean, empty glass with the tip pointing up.
Everolimus syntes spontant at forværre baggrundssygdomme (kronisk myokarditis hos rotter, Coxsackie virusinfektion i plasma og hjerte hos aber, coccidial infestation i mave-tarmkanalen hos minigrise, hudlæsioner hos mus og aber).
Everolimus appeared to spontaneously exacerbate background diseases (chronic myocarditis in rats, coxsackie virus infection of plasma and heart in monkeys, coccidian infestation of the gastrointestinal tract in minipigs, skin lesions in mice and monkeys).
Derfor bør omsorgspersoner undgå kontakt med suspensionen.
Therefore caregivers are advised to avoid contact with the suspension.
Seponer Votubia.
Discontinue Votubia.
I det andet studie med 34 personer med forskellige grader af nedsat leverfunktion, der blev sammenlignet med personer med normal leverfunktion var der 1,6 gange, 3,3 gange og 3,6 gange øget eksponering (dvs. AUC0-uendelig) for personer med henholdsvis let (Child-Pugh A), moderat (Child-Pugh B) og svært nedsat leverfunktion (Child-Pugh C).
In the second study of 34 subjects with different impaired hepatic function compared to normal subjects, there was a 1.6-fold, 3.3-fold and 3.6-fold increase in exposure (i.e. AUC0-inf) for subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, respectively.
Votubias sikkerhed og virkning hos børn i alderen 0 til 18 år med renal angiomyolipom i tilknytning til TSC under fravær af SEGA, er ikke klarlagt.
The safety and efficacy of Votubia in children aged 0 to 18 years with renal angiomyolipoma associated with TSC in the absence of SEGA have not been established.
Kvinder i den fertile alder skal anvende yderst sikker kontraception (fx orale, injicerede eller implanterede ikke-østrogen-indeholdende hormonale præventionsmetoder, progesteron-baserede kontraceptiva, hysterektomi, aflukning af æggeledere, fuldstændig afholdenhed, barriereprævention, intrauterint udstyr [IUD] og/eller kvindelig/mandlig sterilisation) under behandlingen med everolimus og i op til 8 uger efter endt behandling.
Women of childbearing potential must use a highly effective method of contraception (e.g. oral, injected, or implanted non-oestrogen-containing hormonal method of birth control, progesterone-based contraceptives, hysterectomy, tubal ligation, complete abstinence, barrier methods, intrauterine device [IUD], and/or female/male sterilisation) while receiving everolimus, and for up to 8 weeks after ending treatment.
Den primære analyses styrke og konsistens blev understøttet af: ændringen i primært SEGA-volumen ifølge den lokale investigators vurdering (p<0,001), hvor 75,0 % og 39,3 % af patienterne oplevede reduktioner på henholdsvis ≥30 % og ≥50 % ændringen i samlet SEGA-volumen ifølge uafhængig central gennemgang (p<0,001) eller den stedlige investigators vurdering (p<0,001).
The robustness and consistency of the primary analysis were supported by the: change in primary SEGA volume as per local investigator assessment (p<0.001), with 75.0% and 39.3% of patients experiencing reductions of ≥30% and ≥50%, respectively change in total SEGA volume as per independent central review (p<0.001) or local investigator assessment (p<0.001).
Kom ca. 25 ml vand i 30 ml doseringskoppen.
Add about 25 ml of water to the 30 ml dose cup.
Menstruationsforstyrrelser, såsom kraftig menstruation (menorragi) eller vaginal blødning Søvnløshed
Menstruation disorders such as heavy periods (menorrhagia) or vaginal bleeding Trouble sleeping (insomnia)
Medianalderen var 31 år (fra 18 til 61 år; 46,6 % var <30 år ved inklusion), 33,9 % var mænd, og 89,0 % var kaukasere.
Median age was 31 years (range: 18 to 61 years; 46.6% were <30 years at enrolment), 33.9% were male, and 89.0% were Caucasian.
På tidspunktet for den endelige analyse (4 år efter sidste patientrandomisering) var den mediane eksponeringsvarighed for everolimus 204,1 uger (interval 2 til 278).
At the time of the final analysis (4 years following the last patient randomisation), the median duration of exposure to everolimus was 204.1 weeks (range 2 to 278).
I en farmakokinetisk populationsanalyse af 170 patienter med fremskredne massive tumorer sås der ingen signifikant effekt af kreatininclearance (25-178 ml/min) på everolimus CL/F.
In a population pharmacokinetic analysis of 170 patients with advanced solid tumours, no significant influence of creatinine clearance (25-178 ml/min) was detected on CL/F of everolimus.
Fortæl det straks til din læge, hvis du oplever nogen af disse alvorlige bivirkninger, da det kan have livstruende konsekvenser.
If you experience any of these side effects, tell your doctor immediately as this might have lifethreatening consequences.
Respons var defineret som: ≥50 % reduktion i summen af angiomyolipom-volumen i forhold til baseline plus fravær af nyt angiomyolipom ≥1,0 cm for den længste diameter plus ingen stigning i renal volumen >20 % fra nadir plus fravær af grad ≥2 angiomyolipom-relateret blødning.
Response was defined as: ≥50% reduction in the sum of angiomyolipoma volume relative to baseline, plus absence of new angiomyolipoma ≥1.0 cm in longest diameter, plus no increase in renal volume >20% from nadir, plus absence of grade ≥2 angiomyolipoma-related bleeding.
Hvis du får Votubia til behandling af TSC med angiomyolipom i nyrerne, er den normale, daglige dosis 10 mg.
If you receive Votubia for the treatment of TSC with angiomyolipoma of the kidney, the usual dose is 10 mg, to be taken once daily.
I løbet af den dobbeltblindede periode var reduktionen af SEGA-volumen tydelig inden for de første 12 ugers behandling med Votubia: 29,7 % (22/74) af patienterne havde ≥50 % reduktion af volumen, og 73,0 % (54/74) havde ≥30 % reduktion af volumen.
During the double-blind period, reduction of SEGA volume was evident within the initial 12 weeks of Votubia treatment: 29.7% (22/74) of patients had ≥50% reductions in volume and 73.0% (54/74) had ≥30% reductions in volume.
Antimykotiske lægemidler må ikke anvendes, medmindre der er konstateret en svampeinfektion (se pkt.
Antifungal agents should not be used unless fungal infection has been diagnosed (see section 4.5).
I et fertilitetsstudie med hanrotter påvirkedes testikelmorfologien ved 0,5 mg/kg og derover, og sædcellemotilitet, antal sædceller og plasmatestosteronniveau faldt ved 5 mg/kg, hvilket er inden for det terapeutiske eksponeringsområde og medførte et fald i fertilitet hos hanrotterne.
In a male fertility study in rats, testicular morphology was affected at 0.5 mg/kg and above, and sperm motility, sperm head count, and plasma testosterone levels were diminished at 5 mg/kg, which is within the range of therapeutic exposure and which caused a reduction in male fertility.
Fase III-studie med SEGA-patienter
Phase III study in SEGA patients
Votubia må ikke bruges til børn og unge med TSC, som har angiomyolipom i nyrerne, men ikke SEGA, da det ikke er blevet undersøgt hos denne patientgruppe.
Votubia is not to be used in children or adolescents with TSC who have angiomyolipoma of the kidney in the absence of SEGA, as it has not been studied in such patients.
Vurdér everolimus-dal-niveauet 2 uger efter seponering af en af flere potente CYP3A4-induktorer.
Assess the everolimus trough level 2 weeks after discontinuation of one of multiple strong CYP3A4 inducers.
Baselineanfaldsfrekvensen var en væsentlig faktor for anfaldsresponset (oddsratio 0,978 [95 % CI: 0,959;
Baseline seizure frequency was a significant factor in the seizure response (with an odds ratio of 0.978 [95% CI: 0.959, 0.998]).
Votubia er også en medicin mod kræft, som kan forhindre visse celler i kroppen i at vokse.
Votubia is also an anti-tumour medicine which can block certain cells in the body from growing.
phenytoin, carbamazepin eller phenobarbital og andre lægemidler mod epilepsi, som bruges til at standse krampeanfald.
phenytoin, carbamazepine or phenobarbital and other anti-epileptics used to stop seizures or fits.
Dispergibel tablet.
Dispersible tablet.
De første symptomer kan omfatte feber, hududslæt, ledsmerter og betændelse.
The first symptoms may include fever, skin rash, joint pain and inflammation.
Dal-everolimus-koncentrationen bør måles 2 til 4 uger senere, eftersom der bør tages højde for den naturlige nedbrydningstid for de inducerede enzymer (se pkt.
The everolimus trough concentrations should be assessed 2 to 4 weeks later since the natural degradation time of the induced enzymes has to be taken into account (see sections 4.2 and 4.4).
• 2 rene glas • Ca. 30 ml vand
• 2 clean glasses • Approximately 30 ml of water
Respons var defineret som: ≥50 % reduktion i summen af SEGA-volumen i forhold til baseline, plus ingen utvetydig forværring af ikke-mål-SEGA-læsioner, plus fravær af ny SEGA ≥1 cm for den længste diameter, plus ingen ny eller forværret hydrocephalus Primær analyse for dobbeltblindet periode Endelig analyse inkluderer patienter, som skiftede over fra placebogruppen; median eksponeringsvarighed for everolimus på 204,9 uger
Response was defined as: ≥50% reduction in the sum of SEGA volume relative to baseline, plus no unequivocal worsening of non-target SEGA lesions, plus absence of new SEGA ≥1 cm in longest diameter, plus no new or worsening hydrocephalus Primary analysis for double blind period Final analysis includes patients who crossed over from the placebo group; median duration of exposure to everolimus of 204.9 weeks
Forhøjet blodfollikel-stimulerende hormon a
Uncommon Blood follicle stimulating hormone increased a
Genoptag behandlingen med Votubia ved samme dosis.
Re-initiate Votubia at same dose.
Vedvarende reduktion var tydelig ved uge 24; 41,9 % (31/74) af patienterne havde ≥50 % reduktion, og 78,4 % (58/74) af patienterne havde ≥30 % reduktion i SEGA-volumen.
Sustained reductions were evident at week 24, 41.9% (31/74) of patients had ≥50% reductions and 78.4% (58/74) of patients had ≥30% reductions in SEGA volume.
Grad 2 (≥1x10
Grade 2 (≥1x10
Hvis der kræves en højere dosis eller antal af tabletter, skal der klargøres en ekstra sprøjte.
If a higher dose or number of tablets is required, an additional syringe must be prepared.
Tag den orale 10 ml sprøjte og træk stemplet ud, så det adskilles helt fra sprøjtens cylinder.
Take the 10 ml oral syringe and pull out the plunger, removing it completely from the barrel of the syringe.
Votubia er indiceret som supplerende behandling hos patienter i alderen 2 år og ældre med refraktære partielle anfald, med eller uden sekundær generalisering, i forbindelse med tuberøst sklerosekompleks.
Votubia is indicated as adjunctive treatment of patients aged 2 years and older whose refractory partial-onset seizures, with or without secondary generalisation, are associated with tuberous sclerosis complex (TSC).
Det Europæiske Lægemiddelagentur har udsat forpligtelsen til at fremlægge resultaterne af studier med Votubia i en eller flere undergrupper af den pædiatriske population ved refraktær epilepsi i tilknytning til tuberøst sklerosekompleks (se pkt.
The European Medicines Agency has deferred the obligation to submit the results of studies with Votubia in one or more subsets of the paediatric population in refractory epilepsy associated with tuberous sclerosis complex (see section 4.2 for information on paediatric use).
De store målorganer var reproduktionsorganer hos begge køn (tubulær testikeldegeneration, reduceret mængde sædvæske i bitestikel og uterin atrofi) hos flere arter; og lunger (stigning i alveolære makrofager) hos rotter og mus; pankreas (degranulering og vakuolation af eksokrine celler i henholdsvis aber og minigrise samt degenerering af øceller i aber), og øjne (uklarheder ved lentikulare anteriore suturlinier) hos rotter alene.
The major target organs were male and female reproductive systems (testicular tubular degeneration, reduced sperm content in epididymides and uterine atrophy) in several species; lungs (increased alveolar macrophages) in rats and mice; pancreas (degranulation and vacuolation of exocrine cells in monkeys and minipigs, respectively, and degeneration of islet cells in monkeys), and eyes (lenticular anterior suture line opacities) in rats only.
Hvis Votubia tages med orale CYP3A4-substrater med et snævert terapeutisk vindue (fx pimozid, terfenadin, astemizol, cisaprid, kinidin, sekalealkaloider eller carbamazepin), bør patienten monitoreres for de bivirkninger, der er beskrevet i produktinformationen for det orale CYP3A4-substrat (se pkt.
If Votubia is taken with orally administered CYP3A4 substrates with a narrow therapeutic index (e.g. pimozide, terfenadine, astemizole, cisapride, quinidine, ergot alkaloid derivatives or carbamazepine), the patient should be monitored for undesirable effects described in the product information of the orally administered CYP3A4 substrate (see section 4.5).
De hyppigste grad 3-4 bivirkninger (incidens ≥1 %) var pneumoni, stomatitis, amenoré, neutropeni, pyreksi, uregelmæssige menstruationer, hypofosfatæmi, diarré og cellulitis.
The most frequent grade 3-4 adverse reactions (incidence ≥1%) were pneumonia, stomatitis, amenorrhoea, neutropenia, pyrexia, menstruation irregular, hypophosphataemia, diarrhoea, and cellulitis.
Lokaliserede og systemiske infektioner, herunder pneumoni, andre bakterielle infektioner, invasive svampeinfektioner, såsom aspergillose candidiasis eller pneumocystis jirovecii (carinii) pneumoni (PJP, PCP) og virale infektioner inklusive reaktivering af hepatitis B virus, er beskrevet hos patienter, der tager everolimus.
Localised and systemic infections, including pneumonia, other bacterial infections, invasive fungal infections such as aspergillosis, candidiasis or pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) and viral infections including reactivation of hepatitis B virus, have been described in patients taking everolimus.
Hvis du holder op med at tage Votubia Hold ikke op med at tage Votubia tabletter, medmindre lægen siger det.
If you stop taking Votubia Do not stop taking Votubia tablets unless your doctor tells you to.
Hos patienter med TSC og refraktære anfald indikerede en betinget logistisk regressionsanalyse, baseret på hovedfasen i studie CRAD001M2304, med formålet at estimere sandsynligheden for anfaldsrespons versus Time Normalized (TN)-Cmin, stratificeret efter aldersundergruppe, at en 2-fold stigning i TN-Cmin var forbundet med en 2,172-fold stigning (95 % CI: 1,339; 3,524) i odds for et anfaldsrespons over det observerede TN-Cmin-interval på 0,97 ng/ml til 16,40 ng/ml.
In patients with TSC and refractory seizures, a conditional logistic regression analysis based on the core phase of Study CRAD001M2304 to estimate the probability of seizure response versus Time Normalized(TN)-Cmin stratified by age sub-group, indicated that a 2-fold increase in TN-Cmin was associated with a 2.172-fold increase (95% CI: 1.339, 3.524) in the odds for a seizure response over the observed TN-Cmin ranges of 0.97 ng/ml to 16.40 ng/ml.
Du må ikke tage en dobbeltdosis som erstatning for de glemte dispergible tabletter.
Do not take a double dose to make up for the forgotten dispersible tablets.
• Samtidig administration af af PgP-hæmmeren cyclosporin forøger eksponeringen af everolimus i hjernebarken, hvilket er konsistent med hæmningen af PgP ved blod-hjernebarrieren.
• The co-administration of the PgP inhibitor, cyclosporine, enhances the exposure of everolimus in the brain cortex, which is consistent with the inhibition of PgP at the blood-brain barrier.
Hos patienter med SEGA var de geometriske middel-Cmin-værdier, normaliseret til mg/m dosis, hos patienter i alderen <10 år og 10-18 år henholdsvis 54 % og 40 % lavere end dem, der var observeret hos voksne (>18 år).
In patients with SEGA, the geometric mean Cmin values normalised to mg/m dose in patients aged <10 years and 10-18 years were lower by 54% and 40%, respectively, than those observed in adults (>18 years of age), suggesting that everolimus clearance was higher in younger patients.
Den bedste samlede SEGA-responsrate var steget til 57,7 % (95 % CI: 47,9; 67,0) ved den endelige analyse.
The best overall SEGA response rate had increased to 57.7% (95% CI: 47.9, 67.0) at the final analysis.
Åbn først blisterpakningen lige inden, du tager Votubia tabletter.
Open the blister just before taking the Votubia tablets.
INSTRUKTIONER FOR ANVENDELSE
INSTRUCTIONS FOR USE
Dyslipidæmi (inklusive hyperkolesterolæmi og hypertriglyceridæmi) er rapporteret hos patienter, der tager Votubia.
Dyslipidaemia (including hypercholesterolaemia and hypertriglyceridaemia) has been reported in patients taking Votubia.
Tilsvarende var andelen af patienter, som opnåede mindst 30 % reduktion af SEGA-volumen, 71,4 % (70/98) og 77,3 % (51/66) ved uge 96 og 192 efter start af everolimus.
Similarly, the proportion of patients achieving at least 30% reductions in SEGA volume was 71.4% (70/98) and 77.3% (51/66) at weeks 96 and 192 after start of everolimus treatment.
• En 30 ml doseringskop til at afmåle vand
• 30 ml dose cup for measuring water
Træk stemplet tilbage for at trække luft ind, indtil det står ud for 9 ml-mærket på sprøjten.
Pull the plunger slowly down to draw in air until it is at the 9 ml mark on the syringe.
Andelen af patienter, som opnåede mindst 50 % reduktion af SEGA-volumen, var 45,9 % (45/98) og 62,1 % (41/66) ved uge 96 og 192 efter start af everolimus.
The proportion of patients achieving at least 50% reductions in SEGA volume was 45.9% (45/98) and 62.1% (41/66) at weeks 96 and 192 after start of everolimus treatment.
Anvendelse af levende vacciner bør undgås under behandling med Votubia (se pkt.
The use of live vaccines should be avoided during treatment with Votubia (see section 4.5).
Der er blevet udført et prospektivt, open-label, enkelt-arm fase II-studie (studie CRAD001C2485) til evaluering af Votubias sikkerhed og effekt hos patienter med SEGA.
A prospective, open-label, single-arm phase II study (Study CRAD001C2485) was conducted to evaluate the safety and efficacy of Votubia in patients with SEGA.
Det skal du vide, før du begynder at tage Votubia
What you need to know before you take Votubia
Non-infektiøs pneumonitis (herunder interstitiel lungesygdom) er beskrevet som værende meget almindeligt hos patienter, der tager everolimus i forbindelse med renalcellecarcinom (RCC) (se pkt.
Non-infectious pneumonitis (including interstitial lung disease) was described very commonly in patients taking everolimus in the advanced renal cell carcinoma (RCC) setting (see section 4.8).
Votubia kan skade et barn, der ammes.
Votubia could harm a breast-fed baby.
Behandling med Votubia skal afbrydes i tilfælde, hvor der opstår svære symptomer på non-infektiøs pneumonitis, og brug af kortikosteroider kan være indiceret, indtil de kliniske symptomer forsvinder.
For cases where symptoms of non-infectious pneumonitis are severe, Votubia therapy should be discontinued and the use of corticosteroids may be indicated until clinical symptoms resolve.
Dosis kan øges, for at opnå en højere dal-koncentration inden for det målrettede interval, for at opnå optimal effekt under hensyntagen til tolerabiliteten.
The dose may be increased to attain a higher trough concentration within the target range to obtain optimal efficacy, subject to tolerability.
Stomatitis, herunder mundsår og oral mucositis, er den hyppigst rapporterede bivirkning hos patienter, der blev behandlet med Votubia (se pkt.
Stomatitis, including mouth ulcerations and oral mucositis, is the most commonly reported adverse reaction in patients treated with Votubia (see section 4.8).
Et enkeltarms-studie med postmenopausale brystkræftpatienter, der blev behandlet med Afinitor (everolimus) plus exemestan, tyder på, at en alkoholfri oral opløsning med kortikosteroid, administreret som mundskyllevæske i de første 8 ugers behandling, kan nedsætte forekomsten og alvorligheden af stomatitis (se pkt.
A single-arm study in postmenopausal breast cancer patients treated with Afinitor (everolimus) plus exemestane suggested that an alcohol-free corticosteroid oral solution, administered as a mouthwash during the initial 8 weeks of treatment, may decrease the incidence and severity of stomatitis (see section 5.1).
Tag kun Votubia dispergible tabletter som en suspension.
Take Votubia dispersible tablets as a suspension only.
• CRAD001C2485: Dette var et prospektivt, åbent, enkelt-arm fase II-studie med everolimus hos patienter med SEGA (n=28).
• CRAD001C2485: This was a prospective, open-label, single-arm phase II study of everolimus in patients with SEGA (n=28).
Der blev ikke rapporteret tilfælde af angiomyolipomrelateret nefrektomi blandt patienter behandlet med everolimus i løbet af studiet, og der blev kun rapporteret et tilfælde af renal embolisering.
Among patients treated with everolimus during the study, no cases of angiomyolipoma-related nephrectomy and only one case of renal embolisation were reported.
Formuleringer indeholdende perikon, må ikke anvendes under behandling med everolimus
Wort should not be used during treatment with everolimus
Medianalderen for den samlede population var 10,1 år (2,2-56,3 år; 28,4 % <6 år; 30,9 % 6 til <12 år; 22,4 % 12 til <18 år og 18,3 % >18 år).
The median age for the total population was 10.1 years (range: 2.2-56.3; 28.4% <6 years, 30.9% 6 to <12 years, 22.4% 12 to <18 years and 18.3% >18 years).
Det anbefales at monitorere nyrefunktionen, herunder måling af blodureanitrogen (BUN), urinprotein eller serumkreatinin, inden opstart af behandling med Votubia og med jævne mellemrum herefter.
Monitoring of renal function, including measurement of blood urea nitrogen (BUN), urinary protein or serum creatinine, is recommended prior to the start of Votubia therapy and periodically thereafter.
Dette kan resultere i behov for behandling med insulin og/eller orale midler til behandling af sukkersyge.
This may result in the need for insulin and/or oral antidiabetic agent therapy.
Votubia er en medicin mod kræft, som kan forhindre visse celler i kroppen i at vokse.
Votubia is an anti-tumour medicine which can block certain cells in the body from growing.
Det antages derfor, at steady state kan opnås tidligere hos patienter <3 år (se pkt.
Therefore it is assumed that steady-state could be reached earlier in patients <3 years of age (see section 4.2 for dosing recommendations).
SEGA i tilknytning til TSC
SEGA associated with TSC
Grad 3 & 4 (<50x10
Grade 3 & 4 (<50x10
Grad 2 (<75, ≥50x10
Grade 2 (<75, ≥50x10
Tabel 5 EXIST-3 -Responsrate for anfaldsfrekvens (primært endepunkt)
Table 5 EXIST-3 - Seizure frequency response rate (primary endpoint)
Tabel 6 EXIST-3 - Responsrate for anfaldsfrekvens efter alder
Table 6 EXIST-3 - Seizure frequency response rate by age
Medianvarigheden til progression af angiomyolipom var 11,4 måneder i placebo-armen og blev ikke nået i everolimus-armen (HR 0,08; 95 % CI: 0,02; 0,37; p<0,0001).
Median time to angiomyolipoma progression was 11.4 months in the placebo arm and was not reached in the everolimus arm (HR 0.08; 95% CI: 0.02, 0.37; p<0.0001).
Omsorgspersoner bør undgå hudkontakt med den orale suspension.
Caregivers should try to avoid skin contact with the oral suspension.
Yderligere relevante bivirkninger, observeret i kliniske, onkologiske studier og postmarketing spontane rapporter omfattede hjertesvigt, lungeemboli, dyb venetrombose, nedsat sårheling og hyperglykæmi.
Additional adverse reactions of relevance observed in oncology clinical studies and post-marketing spontaneous reports, were cardiac failure, pulmonary embolism, deep vein thrombosis, impaired wound healing and hyperglycaemia.