FrancophonIA/ELRC3.0 huggingface dataset:
English: The volume of distribution of romiplostim following intravenous administration of romiplostim decreased nonlinearly from 122, 78.8, to 48.2 mL/kg for intravenous doses of 0.3, 1.0 and 10 mcg/kg, respectively in healthy subjects.
Danish: Romiplostims fordelingsvolumen efter intravenøs indgift af romiplostim faldt non-lineært fra 122; 78,8; til 48,2 ml/kg for intravenøse doser på henholdsvis 0,3; 1,0 og 10 mikrog/kg hos raske forsøgspersoner.
English: • Do not touch vial stopper after cleaning it.
Danish: • Berør ikke hætteglasproppen, efter den er blevet renset.
English: If individual patient dose is < 23 mcg
Danish: Hvis individuel patientdosis er < 23 mikrog
English: Dose adjustment guidelines should be followed (see section 4.2).
Danish: Retningslinjerne for justering af dosis bør følges (se pkt.
English: The median (Q1, Q3) duration of treatment was 138.0 weeks (91.1 weeks, 186.0 weeks).
Danish: Den gennemsnitlige (Q1, Q3) behandlingsvarighed var 138,0 uger (91,1 uger, 186,0 uger).
English: In a prenatal and postnatal development study in rats an increase of the duration of gestation and a slight increase in the incidence of peri-natal pup mortality was found.
Danish: I en prænatal og postnatal udviklingsundersøgelse med rotter sås en forøgelse af drægtighedsperioden og en lille stigning i fosterdødeligheden.
English: Oropharyngeal pain***
Danish: Oropharyngeal smerte***
English: Uncommon: may affect up to 1 in 100 people (may show up in blood or urine tests)
Danish: Ikke almindelige: kan påvirke op til 1 ud af 100 personer (kan vise sig i blod- eller urinprøver)
English: If you experience a loss of response or failure to maintain a platelet response with romiplostim treatment, your doctor will investigate the reasons why including whether you are experiencing increased bone marrow fibres (reticulin) or have developed antibodies which neutralise romiplostim's activity.
Danish: Hvis virkningen ophører, eller hvis De ikke kan opretholde blodpladerrespons med romiplostimbehandling, vil Deres læge undersøge årsagerne til dette, herunder om De har et forøget antal knoglemarvsfibre (retikulin) eller har udviklet antistoffer, som neutraliserer romiplostims aktivitet.
English: Prior treatments included corticosteroids (98% of all patients), immunoglobulins (97%), rituximab (71%), danazol (37%), cytotoxic therapies (68%), and azathioprine (24%).
Danish: Tidligere behandlinger inkluderede kortikosteroider (98 % af alle patienter), immunglobuliner (97 %), rituximab (71 %), danazol (37 %), cytotoksiske behandlinger (68 %) og azathioprin (24 %).
English: Romiplostim must not be used for the treatment of thrombocytopenia due to MDS or any other cause of thrombocytopenia other than ITP outside of clinical trials.
Danish: Romiplostim må ikke anvendes til behandling af trombocytopeni, der skyldes MDS eller andre årsager til trombocytopeni end ITP, bortset fra kliniske forsøg.
English: Some of the adverse reactions seen in adults were reported more frequently in paediatric subjects such as cough, diarrhoea, rash, pyrexia and contusion reported very commonly (≥ 1/10) in paediatric subjects and purpura and urticaria were reported commonly (≥ 1/100 to < 1/10) in paediatric subjects.
Danish: Nogle af de bivirkninger, der sås hos voksne, blev rapporteret hyppigere hos pædiatriske patienter, såsom hoste, diarré, udslæt, pyreksi og kontusion, som var meget almindeligt rapporteret (≥ 1/10) hos pædiatriske patienter, og purpura og urticaria, som blev hyppigt rapporteret (≥ 1/100 til < 1/10) hos pædiatriske patienter.
English: If individual patient dose is ≥ 23 mcg
Danish: Hvis individuel patientdosis er ≥ 23 mikrog
English: Using: A new 1 mL syringe package and the vial of dissolved, clear Nplate.
Danish: Brug: En ny pakning med 1 ml sprøjte og hætteglasset med det opløste, klare Nplate.
English: If you are taking corticosteroids, danazol, and/or azathioprine, which you may be receiving to treat your ITP, these may be reduced or stopped when given together with Nplate.
Danish: Hvis De tager kortikosteroider, danazol og/eller azathioprin for ITP, kan dosis af disse lægemidler blive nedsat eller behandlingen med dem helt standse, når De tager Nplate.
English: Water should flow slowly onto powder.
Danish: Vandet skal strømme langsomt ned på pulveret.
English: The resulting concentration is 500 mcg/mL.
Danish: Den resulterende koncentration er 500 mikrog/ml.
English: The starting dose of romiplostim 1 mcg/kg and doses were adjusted to maintain (50 to 200 x 10
Danish: Startdosis af romiplostim var 1 mikrog/kg og doserne blev justeret for at opretholde (50 til 200 x 10
English: • fever (pyrexia);
Danish: • feber (pyrexi),
English: • Remove red (250 micrograms) or blue (500 micrograms) plastic cap from vial.
Danish: • Tag den røde (250 mikrogram) eller blå (500 mikrogram) plasthætte af hætteglasset.
English: Note: To prevent contamination of the product, do not touch the vial adapter spike or Luer lock.
Danish: Bemærk: For at undgå kontaminering af præparatet må spidsen af hætteglasadapteren eller Luer lock-sprøjten ikke berøres.
English: • swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing (angioedema);
Danish: • hævelse i ansigt, af læber, i mund, tunge eller hals, hvilket kan give synkebesvær og åndedrætsbesvær (angioødem),
English: All (100%) splenectomised patients who were receiving romiplostim were able to reduce the dose by more than 25% or discontinue the concurrent ITP medical therapies by the end of the treatment period compared to 17% of placebo treated patients.
Danish: For alle (100 %) splenektomerede patienter, som fik romiplostim, kunne dosis reduceres med mere end 25 %, eller samtidig medicinsk behandling af ITP kunne ophøre ved afslutningen af behandlingsperioden sammenlignet med 17 % af de patienter, som blev behandlet med placebo.
English: Doses were increased in increments of 2 mcg/kg every 2 weeks and the target platelet count was ≥ 50 x 10
Danish: Doserne blev trinvist øget med 2 mikrog/kg hver 2. uge, og måltrombocyttallet var ≥ 50 x 10
English: If you have been given less Nplate than you should, you may not experience any physical symptoms but your blood platelet counts may become low and this may increase the risk of bleeding.
Danish: Hvis De har fået mindre Nplate, end De skulle, vil De muligvis ikke føle nogen fysiske symptomer, men Deres blodpladetal kan blive lavt, hvilket kan øge risikoen for blødning.
English: Using: 2 alcohol swab packages, 1 vial, and 1 vial adapter package.
Danish: Brug: 2 pakninger med sprittamponer, 1 hætteglas og 1 pakning med hætteglasadapter.
English: Set up materials for an injection
Danish: Klargøring af materialerne til en injektion
English: • indigestion (dyspepsia);
Danish: • fordøjelsesbesvær (dyspepsi),
English: The risk of blood clotting may also be increased if you: have liver problems; are elderly (≥ 65 years); are bedridden; have cancer; are taking the contraceptive pill or hormone replacement therapy; have recently had surgery or suffered an injury; are obese (overweight); are a smoker.
Danish: Risikoen for blodpropper kan også øges, hvis De: har leverproblemer, er ældre (≥ 65 år), er sengeliggende, har kræft, tager p-piller eller får hormonbehandling, for nylig er blevet opereret eller har været ude for et uheld, er meget overvægtig, ryger.
English: Nplate should be injected once per week in order to keep your platelet counts up.
Danish: Nplate skal injiceres en gang om ugen for at holde Deres blodpladetal oppe.
English: The maximum deliverable volume for the 250 microgram vial is 0.5 mL and for the 500 microgram vial is 1 mL.
Danish: Den maksimale tilførte mængde for hætteglasset med 250 mikrogram er 0,5 ml, og for hætteglasset med 500 mikrogram er det 1 ml.
English: Sterile water for injections only should be used when reconstituting the medicinal product.
Danish: Der bør kun anvendes sterilt vand til injektioner ved rekonstitution af medicinen.
English: If you have been given more Nplate than you should, you may not experience any physical symptoms but your blood platelet counts may rise to very high levels and this may increase the risk of blood clotting.
Danish: Hvis De har fået mere Nplate, end De skulle, vil De muligvis ikke føle nogen fysiske symptomer, men Deres blodpladetal kan stige til et meget højt niveau, hvilket kan forøge risikoen for blodpropper.
English: 75 mcg x
Danish: 75 mikrog x
English: For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Danish: For instruktioner om rekonstitution af dette lægemiddel før administration, se pkt.
English: Summary of key efficacy results from placebo-controlled studies
Danish: En oversigt over de vigtigste effektresultater fra placebokontrollerede undersøgelser
English: Disposing of supplies
Danish: Bortskaffelse af materialer
English: • Wipe the site where Nplate is to be injected with an alcohol swab, using a circular motion.
Danish: • Aftør stedet, hvor Nplate skal injiceres, med en sprittampon og med en cirkulær bevægelse.
English: The median (Q1, Q3) of most frequent dose received by subjects during the treatment period was 5.0 mcg/kg (1.0 mcg/kg, 10.0 mcg/kg).
Danish: Medianen (Q1, Q3) for den mest hyppige dosis, der blev givet til forsøgspersonerne i behandlingsperioden, var 5,0 mikrog/kg (1,0 mikrog/kg, 10,0 mikrog/kg).
English: In addition the reactions listed below have been deemed to be related to romiplostim treatment.
Danish: Endvidere har man vurderet, at de bivirkninger, der angives nedenfor, er associeret til romiplostim-behandling.
English: Draw air into syringe to the 1 mL mark
Danish: Træk luft ind i sprøjte til 1 ml-mærket
English: In the event of overdose, platelet counts may increase excessively and result in thrombotic/thromboembolic complications.
Danish: I tilfælde af overdosering kan trombocyttallet stige voldsomt og medføre trombotiske/tromboemboliske komplikationer.
English: The median (Q1, Q3) duration of treatment was 135.0 weeks (95.0 weeks, 184.0 weeks).
Danish: Den gennemsnitlige (Q1, Q3) behandlingsvarighed var 135,0 uger (95,0 uger, 184,0 uger).
English: In both placebo-controlled, double-blind studies, patients already receiving ITP medical therapies at a constant dosing schedule were allowed to continue receiving these medical treatments throughout the study (corticosteroids, danazol and/or azathioprine).
Danish: I begge placebokontrollerede, dobbeltblindede undersøgelser fik patienter, som allerede fik medicinsk behandling for ITP i henhold til en konstant doseringsplan, lov til at fortsætte med disse medicinske behandlinger under hele undersøgelsen (kortikosteroider, danazol og/eller azathioprin).
English: 9/L, resume dosing with once weekly dose reduced by 1 mcg/kg
Danish: 9/l, genoptages indgivelsen med dosis én gang ugentligt, der er reduceret med 1 mikrog/kg
English: Mean no. weeks with platelet response c
Danish: Middelværdi for antal uger med trombocyt-respons c
English: Therefore, the risk of potential carcinogenicity of romiplostim in humans remains unknown.
Danish: Derfor er risikoen for mulig karcinogenicitet forbundet med brug af romiplostim hos mennesker uvis.
English: A total of 31 subjects (47.7%) used concurrent ITP therapy during the study including 23 subjects (35.4%) who used rescue medication and 5 subjects (7.7%) who used concurrent ITP medication at baseline.
Danish: I alt 31 forsøgspersoner (47,7 %) fik samtidig ITP-behandling i løbet af undersøgelsen, herunder 23 forsøgspersoner (35,4 %), der brugte "rescue"-lægemiddel, og 5 forsøgspersoner (7,7 %), der fik samtidig ITP-behandling ved baseline.
English: Action Increase once weekly dose by 1 mcg/kg
Danish: Handling Dosis én gang ugentligt forøges med 1 mikrog/kg
English: • itchy, runny or blocked nose (rhinitis);
Danish: • kløende, løbende eller blokeret næse (rhinitis),
English: • a rare type of anaemia in which the red blood cells, white blood cells and platelets are all reduced in number (aplastic anaemia);
Danish: • en sjælden form for anæmi, hvor antallet af røde blodlegemer, hvide blodlegemer og blodplader er nedsat (aplastisk anæmi),
English: In both adult placebo-controlled, double-blind studies, patients already receiving ITP medical therapies at a constant dosing schedule were allowed to continue receiving these medical treatments throughout the study (corticosteroids, danazol and/or azathioprine).
Danish: I begge placebokontrollerede, dobbeltblindede undersøgelser fik voksne patienter, som allerede fik medicinsk behandling for ITP i henhold til en konstant doseringsplan, lov til at fortsætte med disse medicinske behandlinger under hele undersøgelsen (kortikosteroider, danazol og/eller azathioprin).
English: Prior treatments included corticosteroids (90% of all patients), immunoglobulins (76%), rituximab (29%), cytotoxic therapies (21%), danazol (11%), and azathioprine (5%).
Danish: Tidligere behandlinger inkluderede kortikosteroider (90 % af alle patienter), immunglobuliner (76 %), rituximab (29 %), cytotoksiske behandlinger (21 %), danazol (11 %) og azathioprin (5 %).
English: Water must flow slowly onto powder.
Danish: Vandet skal flyde langsomt ind i pulveret.
English: Volume of sterile water for injection
Danish: Mængde sterilt vand til injektion
English: The vial contents may be swirled gently and inverted during dissolution.
Danish: Indholdet af hætteglasset kan hvirvles forsigtigt rundt og vendes op og ned under opløsning.
English: • Do not rub the injection site.
Danish: • Gnid ikke på injektionsstedet.
English: • bleeding under the skin (ecchymosis);
Danish: • blødning under huden (ekkymose),
English: In study S4, 62 subjects were randomised in a 2:1 ratio to receive romiplostim (n = 42) or placebo (n = 20) and stratified into 1 of 3 age cohorts.
Danish: I undersøgelse S4, blev 62 forsøgspersoner randomiseret i forholdet 2:1 til at få romiplostim (n = 42) eller placebo (n = 20) og stratificeret til 1 ud af 3 kohorter.
English: GENTLY swirl the vial until all of the powder has dissolved and the liquid in the vial is clear and colourless.
Danish: Drej FORSIGTIGT hætteglasset rundt, indtil alt pulveret er opløst, og væsken i glasset er klar og farveløs.
English: Holding the pre-filled syringe of water for injections with one hand, bend the tip of the white plastic cover downward with your other hand.
Danish: Hold den fyldte injektionssprøjte med vand til injektionsvæsker i den ene hånd og bøj spidsen af den hvide plastbeskyttelse nedad med den anden hånd.
English: Pull back on the pink safety cover toward the syringe and away from the needle.
Danish: Træk den lyserøde sikkerhedsbeskyttelse tilbage mod sprøjten og væk fra kanylen.
English: • Select your injection site.
Danish: • Vælg injektionssted.
English: • bone marrow disorder, including increased bone marrow fibres (reticulin);
Danish: • knoglemarvslidelse, herunder et forøget antal knoglemarvsfibre (retikulin),
English: The resulting concentration is 125 mcg/mL.
Danish: Den resulterende koncentration er 125 mikrog/ml.
English: Overdose may result in an excessive increase in platelet counts associated with thrombotic/thromboembolic complications.
Danish: Overdosering kan medføre en kraftig stigning i trombocyttal forbundet med trombotiske/tromboemboliske komplikationer.
English: The reconstituted solution should be clear and colourless and should not be administered if particulate matter and/or discolouration are observed.
Danish: Den rekonstituerede opløsning skal være klar og farveløs og bør ikke indgives, hvis der konstateres partikler og/eller misfarvning.
English: • Do not set filled syringe down after removing from vial.
Danish: • Sæt ikke den fyldte sprøjte ned, efter fjernelse fra hætteglasset.
English: Reoccurrence of thrombocytopenia and bleeding after cessation of treatment
Danish: Recidiv af trombocytopeni og blødning efter behandlingsophør
English: 4 vials.
Danish: 4 sprittamponer.
English: Special care should be taken to ensure that the appropriate volume of Nplate is withdrawn from the vial for subcutaneous administration - a syringe with graduations of 0.01 mL should be used.
Danish: Der skal udvises særlig forsigtighed for at sikre, at den rigtige volumen Nplate trækkes ud af hætteglasset til subkutan injektion; en sprøjte med inddelinger på 0,01 ml bør anvendes.
English: Clinical trials in adult ITP patients examined antibodies to romiplostim.
Danish: Kliniske forsøg med voksne ITP-patienter undersøgte antistoffer mod romiplostim.
English: • After injecting, use your thumb (or tip of your finger) to activate the pink safety cover by pushing the cover forward using the same hand until you hear and/or feel it click and lock into place over the needle.
Danish: • Brug tommelfingeren (eller en fingerspids) efter injektionen til at aktivere den lyserøde sikkerhedshætte ved at skubbe hætten fremad med samme hånd, indtil De hører og/eller mærker et klik, og lås hætten på plads på kanylen.
English: Serum concentrations of romiplostim in paediatrics with ITP were within the range observed in adult ITP subjects receiving the same dose range of romiplostim.
Danish: Serumkoncentrationer af romiplostim hos pædiatriske patienter med ITP lå inden for det samme interval, der blev observeret hos voksne ITP-patienter, som fik romiplostim inden for det samme dosisinterval.
English: Among the 75 subjects who received at least one dose of SOC, the total median exposure to SOC was 51 weeks and ranged from 0.4 to 52 weeks.
Danish: Blandt de 75 patienter, der fik mindst én dosis af standardbehandlingen, var den samlede mediane eksponering for standardbehandling 51 uger, interval 0,4 til 52 uger.
English: • trouble sleeping (insomnia);
Danish: • søvnløshed (insomni),
English: • Do not delay injecting Nplate.
Danish: • Udsæt ikke injektionen af Nplate.
English: In study S5, 22 subjects were randomised in a 3:1 ratio to receive romiplostim (n = 17) or placebo (n = 5).
Danish: I undersøgelse S5 blev 22 forsøgspersoner randomiseret i forholdet 3:1 til at få romiplostim (n = 17) eller placebo (n = 5).
English: In 1-month rat and monkey toxicology studies, a mild decrease in red blood cell count, haematocrit and haemoglobin was observed.
Danish: I toksikologiske undersøgelser af én måneds varighed hos rotter og aber blev der observeret et lille fald i røde blodlegemer, hæmatokrit og hæmoglobin.
English: Hydrochloric acid (for pH adjustment) Polysorbate 20
Danish: Saltsyre (til justering af pH) Polysorbat 20
English: Very slowly and gently expel all water into powder vial.
Danish: Pres meget langsomt og forsigtigt alt vandet ned i pulverhætteglasset.
English: Dissolving Nplate by injecting water into vial Step 5.
Danish: Opløsning af Nplate ved injektion af vand i hætteglasset Trin 5.
English: • Do make sure that all air bubbles are removed before injection.
Danish: • Kontrollér, at alle luftbobler er fjernet inden injektionen.
English: 13 mm vial adapter x1
Danish: 13 mm hætteglasadapter x1
English: • Step 3b: Holding the syringe with one hand, bend the tip of the white plastic cover downward with your other hand.
Danish: • Trin 3b: Bøj spidsen af den hvide plastbeskyttelse nedad med den ene hånd, mens sprøjten holdes med den anden hånd.
English: This medicine may be removed from the refrigerator for a period of 30 days at room temperature (up to 25ºC) when stored in the original carton.
Danish: Dette lægemiddel kan opbevares uden for køleskab i 30 dage ved stuetemperatur (op til 25 °C) i den originale karton.
English: Do visually inspect the reconstituted solution for particulate matter and/or discolouration.
Danish: Foretag en visuel kontrol af den rekonstituerede opløsning for partikler og/eller misfarvning.
English: Portal vein thrombosis Increase in transaminase
Danish: Portal venetrombose Forhøjet aminotransferase
English: Of those 62 subjects, 48 subjects had ITP > 12 months of duration (32 subjects received romiplostim and 16 subjects received placebo).
Danish: Af de 62 forsøgspersoner havde 48 forsøgspersoner haft ITP i > 12 måneder (32 forsøgspersoner fik romiplostim, og 16 forsøgspersoner fik placebo).
English: 1 sterile 1 mL Luer lock syringe.
Danish: 1 steril 1 ml Luer lock-sprøjte.
English: Turn clockwise to lock into Luer lock tip.
Danish: Drej med uret for at låse kanylen fast i Luer lock-spidsen.
English: Blood pressure increased Blood lactate dehydrogenase increased Body temperature increased Weight decreased Weight increased
Danish: Forhøjet blodtryk Forhøjet laktatdehydrogenase i blodet Forhøjet legemstemperatur Nedsat vægt
English: Prepare sterile water syringe Step 4.
Danish: Klargøring af sprøjte med sterilt vand Trin 4.
English: Keep the Nplate self injection kit refrigerated at 2ºC to 8ºC.
Danish: Selvinjektionssættet til Nplate skal opbevares i køleskab ved 2 °C til 8 °C.
English: Powder and solvent for solution for injection (powder for injection).
Danish: Pulver og solvens til injektionsvæske, opløsning (pulver til injektionsvæske).
English: Left over Nplate in vial must NEVER be re-used for another injection.
Danish: Resterende Nplate i hætteglasset må ALDRIG genbruges til en anden injektion.
English: Thrombocytopenia* Anaemia
Danish: Knoglemarvslidelse* Trombocytopeni* Anæmi
English: A clinically significant bleeding event was defined as a Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade ≥ 2 bleeding event.
Danish: Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
English: Injecting Nplate yourself
Danish: Hvis De selv skal injicere Nplate
English: Choose and prepare an injection site
Danish: Valg og klargøring af et injektionssted
English: • diarrhoea;
Danish: • diarré,
English: • Do not inject into areas with scars or stretch marks.
Danish: • Injicer ikke på steder, hvor der er ar eller mærker.
English: Sodium chloride solutions or bacteriostatic water should not be used when reconstituting the medicinal product.
Danish: Der bør ikke anvendes natriumchloridopløsninger eller bakteriostatisk vand til rekonstitution af lægemidlet.
English: Platelet counts should be monitored when combining romiplostim with other medicinal products for the treatment of ITP in order to avoid platelet counts outside of the recommended range (see section 4.2).
Danish: Trombocyttallet skal overvåges, når romiplostim kombineres med andre lægemidler til behandling af ITP, for at undgå trombocyttal uden for det anbefalede værdiområde (se pkt.
English: • When the syringe is empty, pull the needle out of the skin, being careful to keep it at the same angle as inserted.
Danish: • Træk kanylen ud af huden, når sprøjten er tom, og sørg for at holde kanylen i samme vinkel som ved indføringen.
English: No. (%) patients with overall platelet response b
Danish: Antal (%) patienter med generel trombocyt-respons b
English: • muscle tightness; muscular weakness; shoulder pain; muscle twitching;
Danish: • spændte muskler; muskelsvaghed; skuldersmerter; muskeltrækninger,
English: Ensure the correct amount of solution for the patient dose is in the administration syringe by injecting any excess solution back into the vial.
Danish: Sørg for, at injektionssprøjten indeholder den korrekte mængde opløsning i forhold til patientdosis ved at injicere eventuel overskydende opløsning tilbage i hætteglasset.
English: The mean duration of exposure to romiplostim in this study population was 50 weeks.
Danish: Den gennemsnitlige eksponeringsvarighed hos de patienter, der blev behandlet med romiplostim, var 50 uger.
English: b Overall platelet response is defined as achieving durable or transient platelet responses.
Danish: b Generel trombocytrespons defineres som opnåelse af varige eller forbigående trombocytresponser.
English: Based on an analysis of all adult ITP patients receiving romiplostim in 4 controlled and 5 uncontrolled clinical trials, the overall subject incidence of all adverse reactions for romiplostim-treated subjects was 91.5% (248/271).
Danish: En analyse af alle de voksne ITP-patienter, som fik romiplostim i fire kontrollerede og fem ikke-kontrollerede kliniske forsøg, viste, at den samlede bivirkningsforekomst hos patienter, der blev behandlet med romiplostim, var 91,5 % (248/271).
English: Volume to administer (mL) = 10 mcg / 125 mcg/mL = 0.08 mL
Danish: Indgivelsesvolumen (ml) = 10 mikrog/125 mikrog/ml = 0,08 ml.
English: • swelling in the limbs/hands/feet;
Danish: • hævelse i lemmer/hænder/fødder,