FrancophonIA/ELRC3.0 huggingface dataset:
English: Peripheral neuropathy is a very common, potentially severe, adverse reaction to treatment with thalidomide that may result in irreversible damage (see section 4.8).
Croatian: Periferna neuropatija je vrlo česta, potencijalno teška nuspojava liječenja talidomidom koja može rezultirati ireverzibilnim oštećenjem (vidjeti dio 4.8).
English: Prescribing and dispensing restrictions
Croatian: Ograničenja u propisivanju i izdavanju
English: The most commonly observed adverse reactions associated with the use of thalidomide in combination with melphalan and prednisone are: neutropenia, leukopenia, constipation, somnolence, paraesthesia, peripheral neuropathy, anaemia, lymphopenia, thrombocytopenia, dizziness, dysaesthesia, tremor and peripheral oedema.
Croatian: Najčešće opažene nuspojave povezane s uporabom talidomida u kombinaciji s melfalanom i prednizonom su: neutropenija, leukopenija, konstipacija, somnolencija, parestezije, periferna neuropatija, anemija, limfopenija, trombocitopenija, omaglica, dizestezija, tremor i periferni edem.
English: • Inflammation of the cells lining your stomach wall.
Croatian: • upala stanica koje oblažu želučanu stijenku
English: These symptoms may be signs of the rare and serious skin reactions Stevens-Johnson syndrome, toxic epidermal necrolysis or DRESS syndrome.
Croatian: Ovi simptomi mogu biti znakovi rijetkih i ozbiljnih kožnih reakcija: Stevens-Johnsonova sindroma, toksične epidermalne nekrolize ili reakcije na lijek s eozinofilijom i sistemskim simptomima.
English: If Stevens-Johnson syndrome, TEN or DRESS is suspected, use of thalidomide should not be resumed (see section 4.2 and 4.4).
Croatian: Ako se sumnja na Stevens-Johnsonov sindrom, toksičnu epidermalnu nekrolizu ili reakciju na lijek s eozinofilijom i sistemskim simptomima, talidomid se ne smije ponovno primijeniti (vidjeti dijelo ve 4.2 i 4.4).
English: • She understands the need for effective contraception, without interruption, at least 4 weeks before starting treatment, throughout the entire duration of treatment, and at least 4 weeks after the end of treatment
Croatian: • Shvaća potrebu za učinkovitom kontracepcijom, bez prekida, najmanje 4 tjedna prije početka liječenja, tijekom cjelokupnog trajanja liječenja, kao i najmanje 4 tjedna nakon završetka liječenja.
English: • Blurred vision.
Croatian: • zamućeni vid
English: • Need to avoid foetal exposure
Croatian: • potreba za izbjegavanjem fetalne izloženosti
English: Patients with renal or hepatic impairment
Croatian: Bolesnici s oštećenjem funkcije bubrega ili jetre
English: • Chest infection (pneumonia), lung disease.
Croatian: • infekcija u prsnom košu (upala pluća), bolest pluća
English: 28 hard capsules
Croatian: OBLIK I SADRŽAJ 28 tvrdih kapsula
English: For all patients Talk to your doctor before taking Thalidomide Celgene if
Croatian: Obratite se svom liječniku prije uzimanja lijeka Thalidomide Celgene:
English: Viral infections, including herpes zoster and hepatitis B virus reactivation
Croatian: Teške infekcije (npr. smrtonosna sepsa uključujući septički šok)†, virusne infekcije, uključujući herpes zoster i reaktivaciju virusa hepatitisa B†
English: Animal studies have shown excretion of thalidomide in breast milk.
Croatian: Ispitivanja na životinjama pokazala su da se talidomid izlučuje u majčino mlijeko.
English: • Need to tell treating doctor immediately upon suspicion of pregnancy o Safety advice for men
Croatian: • potreba da odmah obavijesti svog liječnika nakon sumnje na trudnoću o sigurnosni savjet za muškarce
English: Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/ml must be performed for women of childbearing potential as outlined below.
Croatian: Žene u reproduktivnoj dobi moraju se podvrgnuti testovima na trudnoću pod liječničkim nadzorom, osjetljivosti najmanje 25 mIU/ml, kako je to opisano u nastavku.
English: Therefore, these agents should be used with caution in multiple myeloma patients receiving thalidomide with prednisone and melphalan.
Croatian: Stoga je te lijekove nužno primjenjivati s oprezom u bolesnika s multiplim mijelomom koji primaju talidomid u kombinaciji s prednizonom i melfalanom.
English: Due to the sedative effect associated with thalidomide, administration at bedtime is known to generally improve tolerability.
Croatian: b Zbog sedacijskog učinka talidomida, primjena prije spavanja uglavnom poboljšava njegovu podnošljivost.
English: If pregnancy occurs in a partner of a male patient taking thalidomide, the female partner should be referred to a physician specialised or experienced in teratology for evaluation and advice.
Croatian: Ako partnerica bolesnika koji uzima talidomid zatrudni, treba je uputiti liječniku specijaliziranom ili iskusnom u teratologiji na pregled i savjetovanje.
English: The adverse reaction profile reported in patients > 75 years of age treated with thalidomide 100 mg once daily was similar to the adverse reaction profile observed in patients ≤ 75 years of age treated with thalidomide 200 mg once daily (see Table 3).
Croatian: Profil nuspojava prijavljenih u bolesnika starijih od 75 godina liječenih talidomidom u dozi od 100 mg jedanput na dan bio je sličan profilu nuspojava opaženih u bolesnika u dobi
English: Among invasive SPMs, cases of MDS/AML were observed in patients receiving lenalidomide in combination with melphalan or immediately following high dose melphalan and autologous stem cell transplantation.
Croatian: Među invazivnim drugim primarnim zloćudnim bolestima, slučajevi akutne mijeloične leukemije i mijelodisplastičnih sindroma opaženi su u bolesnika koji su primali lenalidomid u kombinaciji s melfalanom ili neposredno nakon visoke doze melfalana i transplantacije autolognih matičnih stanica.
English: Endocrine Disorders
Croatian: Endokrini poremećaji
English: • Adverse reaction reporting forms
Croatian: • obrasce za prijavljivanje nuspojava
English: Reproductive System and Breast Disorders
Croatian: Poremećaji reproduktivnog sustava i dojki
English: • The need for effective contraception, without interruption, at least 4 weeks before starting treatment, throughout the entire duration of treatment, and at least 4 weeks after the end of treatment
Croatian: • potrebu za učinkovitom kontracepcijom, bez prekida, najmanje 4 tjedna prije početka liječenja te kroz cjelokupno trajanje liječenja, kao i najmanje 4 tjedna nakon završetka liječenja
English: †, Atrial fibrillation Atrioventricular block
Croatian: Infarkt miokarda†, fibrilacija atrija†, atrioventrikularni blok†
English: If you are not sure if any of the above apply to you, talk to your doctor before taking Thalidomide Celgene.
Croatian: Ako niste sigurni odnosi li se navedeno na Vas, prije uzimanja lijeka Thalidomide Celgene obratite se svom liječniku.
English: Proportion thalidomide, the total mean recovery was 93.6 % of the administered dose by day 8.
Croatian: Nakon primjene pojedinačne oralne doze od 400 mg radioaktivno obilježenog talidomida, ukupna srednja vrijednost količine primijenjene doze do 8. dana iznosila je 93,6 %.
English: Adverse reactions from post-marketing experience such as febrile neutropenia and pancytopenia were reported with thalidomide.
Croatian: Nuspojave prijavljene nakon stavljanja lijeka u promet, kao što su febrilna neutropenija i pancitopenija, odnosile su se na talidomid.
English: • Male patients unable to follow or comply with the required contraceptive measures (see section 4.4).
Croatian: • Muški bolesnici koji ne mogu pratiti ili se ne mogu pridržavati potrebnih mjera kontracepcije
English: Teratogenicity
Croatian: Teratogenost
English: • Treatment initiation forms and/or equivalent tool for women with no childbearing potential should also include: o Confirmation that the physician has discussed the following:
Croatian: • obrasci za početak liječenja i/ili ekvivalentni materijal za žene bez reproduktivnog potencijala trebaju također uključivati: o potvrdu da je liječnik s bolesnicom raspravio sljedeće:
English: • Treatment initiation forms and/or equivalent tool for male patients should also include: o Confirmation that the physician has discussed the following:
Croatian: • obrasci za početak liječenja i/ili ekvivalentni materijal za muške bolesnike trebaju također uključivati: o potvrdu da je liječnik s bolesnikom raspravio sljedeće:
English: Toxic skin eruption, Rash, Dry skin
Croatian: Izbijanje kožnih promjena uzrokovano toksičnim učinkom lijeka, osip, suha koža
English: • Algorithm for Pregnancy Prevention Plan implementation o This shall assist with patient categorisation, and determination of required pregnancy prevention and testing measures.
Croatian: Plana prevencije trudnoće o pomoći će u kategorizaciji bolesnika i određivanju potrebnih mjera za sprječavanje trudnoće i mjera testiranja na trudnoću
English: Hepatic disorders, mainly abnormal liver test results, were reported.
Croatian: Zabilježeni su poremećaji funkcije jetre, najčešće poremećeni rezultati pretraga funkcije jetre.
English: • The need for pregnancy tests i.e. before treatment, at least every 4 weeks during treatment and after treatment
Croatian: • potrebu za testovima na trudnoću tj. prije liječenja, najmanje svaka 4 tjedna tijekom liječenja i nakon liječenja
English: Melphalan dosed once daily on Days 1 to 4 of each 42-day cycle.
Croatian: c Doza melfalana primijenjena jedanput na dan od 1. do 4. dana svakog 42-dnevnog ciklusa.
English: • That thalidomide is found in semen and the need to use condoms if sexual partner is pregnant or is a woman with childbearing potential not on effective contraception
Croatian: • da se talidomid može pronaći u spermi te da je potrebno upotrebljavati prezervative ako je partnerica trudna ili ako se radi o ženi u reproduktivnoj dobi koja ne upotrebljava učinkovitu kontracepciju
English: • Allergic reactions such as a localised or generalised pruritic rash and angioedema (types of allergic reaction that may be manifested as hives, rashes, swelling of eyes, mouth or face, difficulty of breathing, or itching).
Croatian: (tipovi alergijskih reakcija koji se mogu iskazati kao koprivnjača, osipi, oticanje očiju, usta ili lica, otežano disanje ili svrbež)
English: Acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) A statistically significant increase of AML and MDS was observed in one clinical study in patients with previously untreated MM receiving the combination of melphalan, prednisone, and thalidomide (MPT).
Croatian: Akutna mijeloična leukemija (AML) i mijelodisplastični sindromi (MDS) Statistički značajan porast broja slučajeva akutne mijeloične leukemije i mijelodisplastičnih sindroma bio je opažen u jednom kliničkom ispitivanju, u bolesnika s prethodno neliječenim multiplim mijelomom koji primaju kombinaciju melfalana, prednizona i talidomida (MPT).
English: Thalidomide causes birth defects and foetal death.
Croatian: Talidomid uzrokuje urođene mane i smrt ploda.
English: • The need for pregnancy tests i.e. before treatment, at least every 4 weeks during treatment and at least 4 weeks after treatment
Croatian: • potreba za testovima na trudnoću tj. prije liječenja, najmanje svaka 4 tjedna tijekom liječenja i najmanje 4 tjedna nakon liječenja
English: Pyrexia, Asthenia, Malaise
Croatian: Pireksija, astenija, opće loše osjećanje
English: Thalidomide Celgene with food, drink and alcohol Do not drink alcohol while you are taking Thalidomide Celgene.
Croatian: Thalidomide Celgene s hranom, pićem i alkoholom
English: Acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) AML and MDS were reported in one clinical study in patients with previously untreated multiple myeloma receiving the combination of melphalan, prednisone, and thalidomide (see section 4.4).
Croatian: Akutna mijeloična leukemija (AML) i mijelodisplastični sindromi (MDS) Slučajevi akutne mijeloične leukemije i mijelodisplastičnih sindroma opaženi su u jednom kliničkom ispitivanju koje je u tijeku, u bolesnika s prethodno neliječenim multiplim mijelomom koji primaju kombinaciju melfalana, prednizona i talidomida (vidjeti dio 4.4).
English: • The need to contact their doctor immediately upon suspicion of pregnancy
Croatian: • potrebu da se obrati svom liječniku čim posumnja na trudnoću
English: Thalidomide Celgene 50 mg hard capsules thalidomide
Croatian: Thalidomide Celgene 50 mg tvrde kapsule talidomid
English: Febrile neutropenia
Croatian: • osjećaj omaglice
English: • Underactive thyroid (hypothyroidism).
Croatian: • slabi rad štitne žlijezde (hipotireoidizam)
English: 200 mg daily 0.125 mg/kg daily 2 mg/kg daily
Croatian: 0,125 mg/kg na dan
English: • The need to stop thalidomide immediately upon suspicion of pregnancy
Croatian: • potreba za prekidom uzimanja talidomida odmah nakon sumnje na trudnoću
English: • The other excipients are: o The capsule content contains pregelatinised starch and magnesium stearate.
Croatian: o Kapsula sadrži prethodno geliran škrob i magnezijev stearat.
English: If powder from a broken Thalidomide Celgene capsule makes contact with the skin, wash the skin immediately and thoroughly with soap and water.
Croatian: Celgene dođe u dodir s kožom, odmah temeljito isperite kožu vodom i sapunom.
English: • The need to contact their doctor immediately upon suspicion of pregnancy o Male patients
Croatian: • potreba da se obrate svom liječniku čim se pojavi sumnja na trudnoću o za muške bolesnike
English: Absorption of thalidomide is slow after oral administration.
Croatian: Nakon peroralne primjene apsorpcija talidomida je spora.
English: Male patients should not donate semen or sperm during treatment (including during dose interruptions) and for at least 7 days following discontinuation of thalidomide.
Croatian: Muški bolesnici ne smiju darovati sjeme ili spermu tijekom liječenja (uključujući tijekom pauza u uzimanju lijeka) te još najmanje 7 dana nakon završetka liječenja talidomidom.
English: Thalidomide must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or drug reaction with eosinophilia and systemic symptoms (DRESS) is suspected and should not be resumed following discontinuation for these reactions.
Croatian: Primjena talidomida mora se trajno obustaviti u slučaju angioedema, osipa 4. stupnja, eksfolijativnog ili buloznog osipa ili sumnje na Stevens-Johnsonov sindrom (SJS), toksičnu epidermalnu nekrolizu (TEN) ili reakciju na lijek s eozinofilijom i sistemskim simptomima (engl. drug reaction with eosinophilia and systemic symptoms, DRESS).
English: Lymphopenia Thrombocytopenia
Croatian: Limfopenija Trombocitopenija
English: Hypothyroidism
Croatian: Hipotireoidizam†
English: Prednisone dosed once daily on Days 1 to 4 of each 42-day cycle.
Croatian: f Doza prednizona primijenjena jedanput na dan od 1. do 4. dana svakog 42-dnevnog ciklusa.
English: Unused medicinal product should be returned to your pharmacist.
Croatian: OD LIJEKA, AKO JE POTREBNO Neiskorišteni lijek morate vratiti ljekarniku.
English: • Sleepiness, feeling tired.
Croatian: • pospanost, osjećaj umora
English: What Thalidomide Celgene is
Croatian: Što je Thalidomide Celgene
English: Thalidomide Celgene 50 mg hard capsules
Croatian: NAZIV LIJEKA Thalidomide Celgene 50 mg tvrde kapsule
English: Immune System Disorders Not Known
Croatian: Poremećaji imunološkog sustava
English: • Treatment initiation forms and/or equivalent tool for women of childbearing potential should also include: o Confirmation that the physician has discussed the following:
Croatian: • obrasci za početak liječenja i/ili ekvivalentni materijal za žene u reproduktivnoj dobi trebaju također uključivati: o potvrdu da je liječnik s bolesnicom raspravio sljedeće:
English: Men
Croatian: Muškarci
English: • Do not crush or chew.
Croatian: • Nemojte lomiti ili žvakati kapsule.
English: Patients involved should be preferably naïve to the history of thalidomide.
Croatian: Uključeni bolesnici po mogućnosti ne bi trebali prethodno biti liječeni talidomidom.
English: Haematological disorders
Croatian: Hematološki poremećaji
English: How Thalidomide Celgene works
Croatian: Kako djeluje Thalidomide Celgene
English: Very Common Peripheral oedema Common
Croatian: Periferni edem
English: How to take Thalidomide Celgene
Croatian: Kako uzimati Thalidomide Celgene
English: Cases of pulmonary hypertension, some fatal, have been reported in patients treated with thalidomide.
Croatian: U bolesnika liječenih talidomidom zabilježeni su slučajevi plućne hipertenzije, neki od njih sa smrtnim ishodom.
English: What you need to know before you take Thalidomide Celgene
Croatian: Što je Thalidomide Celgene i za što se koristi Što morate znati prije nego počnete uzimati Thalidomide Celgene Kako uzimati Thalidomide Celgene Moguće nuspojave
English: The distribution of thalidomide is not influenced by age, gender, renal function and blood chemistry variables, to any significant level.
Croatian: Dob, spol, funkcija bubrega i biokemijski parametri krvi ne utječu značajno na raspodjelu talidomida.
English: Patients should be evaluated for signs and symptoms of underlying cardiopulmonary disease prior to initiating and during thalidomide therapy.
Croatian: Prije početka i tijekom terapije talidomidom treba procijeniti bolesnike s obzirom na moguće znakove i simptome podležeće kardiopulmonalne bolesti.
English: • That if she is pregnant or plans to be, she must not take thalidomide
Croatian: • da ne smije uzimati talidomid ako je trudna ili planira zatrudnjeti
English: , Worsening of Parkinson's disease symptoms
Croatian: Sindrom reverzibilne posteriorne encefalopatije (PRES)*,†, pogoršanje simptoma Parkinsonove bolesti†
English: Table 3: Adverse drug reactions (ADRs) reported in pivotal clinical study with thalidomide in combination with melphalan and prednisone and from post marketing use
Croatian: Tablica 3: Nuspojave na talidomid u kombinaciji s melfalanom i prednizonom prijavljene u pivotalnom kliničkom ispitivanju i nakon stavljanja lijeka u promet Klasifikacija organskih sustava
English: The benefit achieved with thalidomide and the risk of AML and MDS must be taken into account before initiating treatment with thalidomide in combination with melphalan and prednisone.
Croatian: Prije nego što se započne liječenje talidomidom u kombinaciji s melfalanom i prednizonom, valja uzeti u obzir korist postignutu talidomidom i rizik od akutne mijeloične leukemije i mijelodisplastičnih sindroma.
English: What Thalidomide Celgene is used for
Croatian: Za što se koristi Thalidomide Celgene
English: • Indigestion, feeling sick (nausea), being sick (vomiting), dry mouth.
Croatian: • probavne tegobe, mučnina, povraćanje, suha usta
English: Maximum daily melphalan dose: 24 mg (subjects ≤ 75 years old) or 20 mg (subjects > 75 years old).
Croatian: ≤ 75 godina) ili 20 mg (ispitanici stariji od 75 godina).
English: Thalidomide Celgene 50 mg thalidomide
Croatian: NAZIV LIJEKA Thalidomide Celgene 50 mg talidomid
English: All unused capsules should be returned to the pharmacist at the end of treatment.
Croatian: Po završetku liječenja sve neupotrijebljene kapsule potrebno je vratiti ljekarniku.
English: 100 mg daily 0.20 mg/kg daily 2 mg/kg daily
Croatian: 0,20 mg/kg na dan
English: • That he should not donate blood or semen during treatment (including during dose interruptions) and for at least 7 days following discontinuation of thalidomide
Croatian: • da ne smije darivati krv ili spermu tijekom liječenja (uključujući tijekom pauza u uzimanju lijeka) i najmanje 7 dana nakon završetka liječenja talidomidom
English: Patients should not donate blood during treatment (including during dose interruptions) and for at least 7 days following discontinuation of thalidomide.
Croatian: Bolesnici ne smiju darovati krv tijekom liječenja (uključujući tijekom pauza u uzimanju lijeka) te najmanje 7 dana nakon završetka liječenja talidomidom.
English: Cases of allergic reactions/angioedema and serious cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of Thalidomide.
Croatian: Uz primjenu lijeka Thalidomide Celgene prijavljeni su slučajevi alergijskih reakcija/angioedema i ozbiljnih kožnih reakcija, uključujući Stevens-Johnsonov sindrom, toksičnu epidermalnu nekrolizu i reakciju na lijek s eozinofilijom i sistemskim simptomima.
English: 100 mg daily 0.10 mg/kg daily 2 mg/kg daily
Croatian: 0,10 mg/kg na dan
English: Reporting of side effects
Croatian: Povećanje sedativnih učinaka drugih lijekova
English: How to store Thalidomide Celgene
Croatian: Kako čuvati Thalidomide Celgene
English: • you experience or have experienced in the past severe skin reactions called Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms(which is also known as DRESS or drug hypersensitivity syndrome).
Croatian: toksična epidermalna nekroliza ili reakcija na lijek s eozinofilijom i sistemskim simptomima (poznata i pod nazivom DRESS ili sindrom preosjetljivosti na lijek).
English: Frequency
Croatian: Omjer
English: 200 mg daily 0.25 mg/kg daily 2 mg/kg daily
Croatian: 0,25 mg/kg na dan
English: • That he should return the capsules to the pharmacist at the end of treatment
Croatian: • da na kraju liječenja sve neupotrijebljene kapsule treba vratiti ljekarniku
English: • That if his partner becomes pregnant he should inform his treating doctor immediately and always use a condom during intercourse
Croatian: • potreba da odmah izvijesti liječnika ako partnerica zatrudni te za upotrebom prezervativa pri svakom spolnom odnosu
English: Thalidomide Celgene 50 mg
Croatian: 16. PODACI NA BRAILLEOVOM PISMU Thalidomide Celgene 50 mg
English: Serious cutaneous reactions including Stevens-Johnson syndrome TEN and DRESS have been reported with the use of thalidomide therapy.
Croatian: Ozbiljne kožne reakcije, uključujući Stevens-Johnsonov sindrom, toksičnu epidermalnu nekrolizu i reakciju na lijek s eozinofilijom i sistemskim simptomima, prijavljene su uz liječenje talidomidom.
English: • Kidney disease (renal failure).
Croatian: • bolest bubrega (zatajenje bubrega).
English: • Periodic Safety Update Reports (PSUR)
Croatian: • Periodička izvješća o neškodljivosti
English: Convulsions
Croatian: Konstipacija
English: †, Menstrual disorders including amenorrhea
Croatian: Spolna disfunkcija†, poremećaj menstrualnog ciklusa uključujući amenoreju†
English: • That she should not donate blood during treatment (including during dose interruptions) and for at least 7 days following discontinuation of thalidomide
Croatian: • da ne smije darovati krv tijekom liječenja (uključujući tijekom pauza u uzimanju lijeka) i još najmanje 7 dana nakon završetka liječenja talidomidom.
English: †, Pancreatitis Gastrointestinal haemorrhage
Croatian: Perforacije u probavnom sustavu†, pankreatitis†, gastrointestinalno krvarenje†
English: • you have experienced or have existing neuropathy i.e. nerve damage causing tingling, abnormal co-ordination or pain in your hands or feet (see also section 4 “Possible side effects”).
Croatian: poremećenu koordinaciju ili bolove u šakama ili stopalima (vidjeti također dio 4 „Moguće nuspojave“).
English: • That thalidomide is found in semen and the need to use condoms if sexual partner is pregnant or is a woman with childbearing potential not using effective contraception
Croatian: • potreba za uporabom prezervativa ako je partnerica trudna ili je žena u reproduktivnoj dobi koja ne upotrebljava učinkovitu kontracepciju, zbog činjenice da se talidomid se može pronaći u spermi
English: • That he should not donate semen during treatment (including during dose interruptions) and for at least 7 days following discontinuation of thalidomide
Croatian: • zabrana darivanja sperme tijekom liječenja (uključujući tijekom pauza u uzimanju lijeka) i najmanje 7 dana nakon završetka liječenja talidomidom
English: NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER
Croatian: OZNAČIVANJE I UPUTA O LIJEKU