natgillin/translations-raw huggingface dataset:
Since the start of this review, two other direct-acting antivirals, Epclusa (sofosbuvir / velpatasvir) and Zepatier (elbasvir / grazoprevir), have been authorised in the EU.
Dovoljenje za promet v EU sta po začetku tega pregleda dobili dve drugi neposredno delujoči protivirusni zdravili, zdravilo Epclusa (sofosbuvir/velpatasvir) in zdravilo Zepatier (elbasvir/grazoprevir).
• Cases of hepatitis B re-activation (with severe consequences) have been reported in patients coinfected with hepatitis B and C viruses treated with direct-acting antivirals.
• Pri bolnikih, ki so bili okuženi z virusoma hepatitisa B in C ter zdravljeni z neposredno delujočimi protivirusnimi zdravili, so poročali o primerih reaktivacije hepatitisa B. Kaže, da tovrstna reaktivacija ni pogosta.
The hepatitis B re-activation is thought to be the consequence of the rapid treatment-induced reduction in hepatitis C virus (as co-infection is known to suppress the hepatitis B virus) and the lack of activity of direct-acting antivirals against hepatitis B virus.
Neposredno delujoča protivirusna zdravila za hepatitis C: agencija EMA potrjuje, da priporoča presejalno testiranje za hepatitis B
31 March 2016 EMA/174254/2016
31. marec 2016 EMA/174254/2016
More information on Exjade, including its indications in full, can be found on the Agency's website: ema.europa.eu/Findmedicine/Human medicines/European public assessment reports.
Več informacij o zdravilu Exjade, vključno z vsemi indikacijami, je na voljo na spletni strani agencije: ema.europa.eu/Findmedicine/Human medicines/European public assessment reports.
If you have any questions about your treatment, contact your doctor, pharmacist or nurse.
Če imate o svojem zdravljenju dodatna vprašanja, se posvetujte z zdravnikom, farmacevtom ali medicinsko sestro.
Dispersed in water, orange juice or apple juice.
Raztopljene v vodi, pomarančnem soku ali jabolčnem soku.
Measures to avoid medication errors with Exjade
Ukrepi za zmanjševanje napak pri dajanju zdravila Exjade
Description and strength
Opis in jakost
The doctor will tell you how much of the new tablet you need to take.
Zdravnik vam bo povedal, koliko nove tablete morate vzeti.
Not to be chewed or swallowed whole
Ne smete jih žvečiti ali pogoltniti celih
How to take tablets
Kako jemati tablete
This helps to correct iron overload and prevent the extra iron from damaging organs such as the heart and liver.
To pomaga pri zmanjševanju preobremenitve z železom in preprečuje dodatnemu železu, da bi poškodovalo organe, kot sta srce in jetra.
Once daily, must be taken on an empty stomach, at least 30 minutes before food
Enkrat dnevno na prazen želodec, vsaj 30 minut pred obrokom
• The summary of product characteristics and the educational materials on the use of Exjade should be followed because they give important information on its use.
• Upoštevati je treba povzetek glavnih značilnosti zdravila in izobraževalno gradivo o uporabi zdravila Exjade, saj vsebujeta pomembne podatke o njegovi uporabi.
When to take tablets
Kdaj jemati tablete
Educational material to raise awareness of dose variation between different types of tablets
Izobraževalno gradivo za povečanje ozaveščenosti o različnem odmerku pri različnih vrstah tablet
Healthcare professionals will be notified of the planned date for removing the dispersible tablets from the market.
Zdravstveni delavci bodo obveščeni o načrtovanem datumu umika disperzibilnih tablet s tržišča.
• To avoid errors, prescriptions for Exjade must specify the type of formulation (dispersible tablets or film-coated tablets), the prescribed dose in mg/kg/day, and the calculated dose per day with the strength of film-coated or dispersible tablets.
• Da bi se izognili napakam, morajo recepti za zdravilo Exjade določati vrsto formulacije (disperzibilne tablete ali filmsko obložene tablete), predpisani odmerek v mg/kg/dan in izračunani odmerek na dan z jakostjo filmsko obloženih ali disperzibilnih tablet.
Oval, blue tablets containing 90 mg (light blue), 180 mg (medium blue) and 360 mg (dark blue)
Ovalne modre tablete, ki vsebujejo 90 mg (svetlo modre), 180 mg (srednje modre) ali 360 mg (temno modre)
Does not contain lactose
Ne vsebuje laktoze
• Whereas the dispersible tablets have to be taken on an empty stomach 30 minutes before food, the film-coated tablets can be taken on an empty stomach or with a light meal.
• Medtem ko se disperzibilne tablete jemljejo na prazen želodec 30 minut pred obrokom, se filmsko obložene tablete lahko jemljejo na prazen želodec ali z lahkim obrokom.
Film-coated tablets containing 90, 180 and 360 mg are equivalent to dispersible tablets containing 125, 250 and 500 mg, respectively.
Filmsko obložene tablete, ki vsebujejo 90, 180 oz. 360 mg, so enakovredne disperzibilnim tabletam, ki vsebujejo 125, 250 oz. 500 mg.
• The dispersible tablets and the new film-coated tablets are to be taken once a day, preferably at the same time each day.
• Disperzibilne tablete in nove filmsko obložene tablete je treba jemati enkrat dnevno, najbolje vsak dan ob istem času.
This means that it attaches to iron in the body to form a ‘chelate' that can be excreted by the body, mainly in the stool.
To pomeni, da se veže na železo v telesu in tvori „kelat“, ki ga telo lahko izloči, in sicer pretežno z blatom.
Round, white tablets containing 125 mg, 250 mg and 500 mg (all white)
Okrogle bele tablete, ki vsebujejo 125 mg, 250 mg ali 500 mg (vse bele)
• You will be given a handbook with information on the two types of tablets and how to take them.
• Prejeli boste priročnik z informacijami o obeh vrstah tablet in o načinu jemanja.
Once daily, may be taken on an empty stomach or with a light meal
Enkrat dnevno na prazen želodec ali ob lahkem obroku
The dose depends on your weight, the amount of iron in your blood, how well your liver and kidneys work and the amount of blood transfusions you receive.
količine železa v vaši krvi, delovanja vaših jeter in ledvic ter količine transfuzij krvi, ki jih prejemate.
• Exjade film-coated tablets have been introduced.
• Uvedene so bile filmsko obložene tablete zdravila Exjade.
Exjade contains the active substance deferasirox which is an ‘iron chelator'.
Zdravilo Exjade vsebuje zdravilno učinkovino deferasiroks, ki je „kelator železa“.
If you are switching from dispersible tablets to the new film-coated tablets, you will need a smaller dose.
Če z disperzibilnih tablet prehajate na filmsko obložene tablete, boste potrebovali manjši odmerek.
Exjade is a medicine used to treat chronic iron overload (an excess of iron in the body) in patients with beta thalassemia or other blood disorders in which patients do not have enough normal haemoglobin in the blood.
Zdravilo Exjade je zdravilo, ki se uporablja za zdravljenje kronične preobremenitve z železom (prevelike količine železa v telesu) pri bolnikih z beta talasemijo ali drugo krvno boleznijo, pri kateri bolniki v krvi nimajo dovolj normalnega hemoglobina.
• Bioavailability of film-coated tablets is higher than of the dispersible tablets and the strength of film-coated tablets is correspondingly lower.
• Biološka razpoložljivost filmsko obloženih tablet je večja kot pri disperzibilnih tabletah, njihova jakost pa temu ustrezno manjša.
Exjade is a medicine used to remove excessive iron from the blood of patients with beta thalassemia or other blood disorders which result in excessive iron in the blood.
Zdravilo Exjade je zdravilo, ki se uporablja za odstranjevanje prevelike količine železa iz krvi bolnikov z beta talasemijo in drugimi krvnimi boleznimi, pri katerih pride do prevelike količine železa v krvi.
The two types of tablets can be easily distinguished by their shape, and the design of the outer cartons and blisters.
Obe vrsti tablet se zlahka razlikujeta po obliki ter po zasnovi zunanjih škatel in pretisnih omotov.
Swallowed whole with some water or crushed and sprinkled on soft food (e.g. yogurt or apple sauce)
Tablete je treba pogoltniti cele z vodo ali zdrobljene in primešane mehki hrani (npr. jogurtu ali jabolčni kaši)
• Exjade dispersible tablets will not be available in the future.
• Disperzibilne tablete zdravila Exjade v prihodnosti ne bodo več na voljo.
• Exjade (deferasirox) is now available as film-coated tablets in addition to the already authorised dispersible tablets.
• Zdravilo Exjade (deferasiroks) je zdaj na voljo v obliki filmsko obloženih tablet in v obliki že odobrenih disperzibilnih tablet.
Excipient: lactose
Pomožna snov: laktoza
Educational material will be given to patients and healthcare professionals using Exjade (deferasirox), following the introduction of a film-coated tablet to the already authorised dispersible tablet.
Izobraževalno gradivo bodo prejeli bolniki in zdravstveni delavci, ki uporabljajo zdravilo Exjade (deferasiroks), ko bodo poleg že odobrenih disperzibilnih tablet uvedene filmsko obložene tablete.
The education material will advise that the doses for the two types of Exjade tablets are different.
V izobraževalnem gradivu bo navedeno, da se odmerki med različnimi vrstami tablet zdravila Exjade razlikujejo.
Both types of tablets will be available for some time, which will allow doctors to switch patients from dispersible tablets to film-coated tablets.
Nekaj časa bosta na voljo obe vrsti tablet, kar bo zdravnikom omogočilo, da bodo pri bolnikih disperzibilne tablete zamenjali s filmsko obloženimi.
Contains lactose
Vsebuje laktozo
• Your doctor will have worked out the dose of Exjade you need.
• Odmerek zdravila Exjade, ki ga potrebujete, bo določil zdravnik.
The patient may receive too little or too much of the medicine if the dose is not correct when changing from one type of tablet to another.
Pri neustreznem odmerku zaradi prehoda z ene vrste tablet na drugo lahko bolnik prejme premalo ali preveč zdravila.
After this time Exjade dispersible tablets will no longer be marketed.
Po tem času disperzibilnih tablet zdravila Exjade ne bo več na tržišču.
A smaller dose is needed of the new film-coated tablets compared to that of the dispersible tablet.
Pri novih filmsko obloženih tabletah je v primerjavi z disperzibilnimi tabletami potreben manjši odmerek.
• Both types of tablets will be available for a limited period to allow doctors to switch patients from the dispersible tablets to the film-coated tablets.
• Določen čas bosta na voljo obe vrsti tablet, da bodo lahko zdravniki pri bolnikih disperzibilne tablete zamenjali s filmsko obloženimi.
• The following table describes the differences between the two formulations: Film-coated tablets
• Razlike med obema formulacijama so opisane v spodnji preglednici: Filmsko obložene tablete Disperzibilne tablete (v opuščanju)
• Read the package leaflet and other information you have been given with your tablets.
• Preberite navodilo za uporabo in druge informacije, ki ste jih prejeli skupaj s tabletami, saj vsebujejo pomembne podatke o vašem zdravljenju in jemanju zdravila.
Dispersible tablets (to be discontinued)
Razpon odmerkov (odrasli in otroci)
The European Commission granted a marketing authorisation valid throughout the EU for CoAprovel on 15 October 1998.
Evropska komisija je dovoljenje za promet z zdravilom CoAprovel, veljavno po vsej Evropski uniji, odobrila dne 15. oktobra 1998.
The full EPAR for CoAprovel can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
Celotno evropsko javno poročilo o oceni zdravila (EPAR) za zdravilo CoAprovel je na voljo na spletni strani agencije: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
Irbesartan on its own has been approved in the European Union (EU) since 1997 under the names Karvea and Aprovel.
Irbesartan je kot samostojno zdravilo v Evropski uniji (EU) odobren od leta 1997 pod imenoma Karvea in Aprovel.
Other information about CoAprovel
Druge informacije o zdravilu CoAprovel
This is a summary of the European public assessment report (EPAR) for CoAprovel.
To je povzetek evropskega javnega poročila o oceni zdravila (EPAR) za zdravilo CoAprovel.
What benefit has CoAprovel shown during the studies?
Kakšne koristi je zdravilo CoAprovel izkazalo med študijami?
The CHMP decided that CoAprovel's benefits are greater than its risks and recommended that it be given marketing authorisation.
CHMP je zaključil, da so koristi zdravila CoAprovel večje od z njim povezanih tveganj, in priporočil, da se zanj odobri dovoljenje za promet.
For more information about treatment with CoAprovel, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
Za več informacij o zdravljenju z zdravilom CoAprovel preberite navodilo za uporabo (ki je prav tako del EPAR) ali se posvetujte z zdravnikom ali farmacevtom.
It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for CoAprovel.
Pojasnjuje, kako je Odbor za zdravila za uporabo v humani medicini (CHMP) ocenil zdravilo CoAprovel, na podlagi česar je oblikoval mnenje za odobritev dovoljenja za promet z njim in priporočila glede pogojev njegove uporabe.
The most common side effects with CoAprovel (seen in between 1 and 10 patients in 100) are dizziness, nausea (feeling sick) or vomiting, abnormal urination, fatigue (tiredness), and increases in blood urea nitrogen (BUN, a breakdown product of protein), creatinine (a breakdown product of muscle) and creatine kinase (an enzyme found in muscle).
Najpogostejši neželeni učinki zdravila CoAprovel (opaženi pri 1 do 10 bolnikih od 100) so omotica, navzeja (slabost) ali bruhanje, nenormalno uriniranje, utrujenost in povečane vrednosti dušika sečnine v krvi (BUN, produkta razgradnje beljakovin), kreatinina (produkta metabolizma mišic) in kreatin kinaze (encima, ki ga najdemo v mišicah).
What is the risk associated with CoAprovel?
Kakšna tveganja so povezana z zdravilom CoAprovel?
It is available as tablets (150 mg or 300 mg irbesartan and 12.5 mg hydrochlorothiazide; 300 mg irbesartan and 25 mg hydrochlorothiazide).
Na voljo je v obliki tablet (150 mg ali 300 mg irbesartana in 12,5 mg hidroklorotiazida; 300 mg irbesartana in 25 mg hidroklorotiazida).
For the full list of all side effects reported with CoAprovel, see the package leaflet.
Za celoten seznam neželenih učinkov, o katerih so poročali pri uporabi zdravila CoAprovel, glejte navodilo za uporabo.
The dose of CoAprovel to be used depends on the dose of irbesartan or hydrochlorothiazide that the patient was taking before.
Odmerek zdravila CoAprovel, ki ga naj bolnik jemlje, je odvisen od odmerka irbesartana ali hidroklorotiazida, ki ga je bolnik jemal prej.
CoAprovel must not be used in people who are hypersensitive (allergic) to irbesartan, hydrochlorothiazide, sulfonamides, or any of the other ingredients.
Zdravila CoAprovel ne smejo uporabljati osebe, ki so preobčutljive za (alergične na) irbesartan, hidroklorotiazid, sulfonamide ali katero koli drugo sestavino zdravila.
CoAprovel is used in adults who have essential hypertension (high blood pressure) that is not adequately controlled by irbesartan or hydrochlorothiazide alone.
Zdravilo CoAprovel se uporablja pri odraslih z esencialno hipertenzijo (visokim krvnim tlakom), ki ni ustrezno uravnana z uporabo zgolj irbesartana ali zgolj hidroklorotiazida.
The combination of the two active substances has an additive effect, reducing the blood pressure more than either medicine alone.
Kombinacija obeh zdravilnih učinkovin daje pri zniževanju krvnega tlaka boljše rezultate kot katera koli od obeh učinkovin posamično.
Why has CoAprovel been approved?
Zakaj je bilo zdravilo CoAprovel odobreno?
It can be used with hydrochlorothiazide to treat hypertension.
Uporablja se lahko v kombinaciji s hidroklorotiazidom za zdravljenje visokega krvnega tlaka.
CoAprovel in combination with aliskiren-containing medicines (used to treat essential hypertension) must not be used in patients with diabetes, or moderate or severe kidney impairment.
Zdravilo CoAprovel se v kombinaciji z zdravili, ki vsebujejo aliskiren (ki se uporablja za zdravljenje esencialne hipertenzije), ne sme uporabljati pri bolnikih s sladkorno boleznijo ali zmerno do hudo ledvično okvaro.
How has CoAprovel been studied?
Kako je bilo zdravilo CoAprovel raziskano?
Care must be taken when using CoAprovel with other medicines that have an effect on blood potassium levels.
Posebna previdnost je potrebna, če se zdravilo CoAprovel jemlje sočasno z drugimi zdravili, ki vplivajo na koncentracijo kalija v krvi.
Increasing the dose to 300 mg irbesartan and 25 mg hydrochlorothiazide may give a further decrease in blood pressure.
S povečanjem odmerka na 300 mg irbesartana v kombinaciji s 25 mg hidroklorotiazida se lahko krvni tlak še dodatno zniža.
CoAprovel is a medicine that contains two active substances, irbesartan and hydrochlorothiazide.
CoAprovel je zdravilo, ki vsebuje dve zdravilni učinkovini, irbesartan in hidroklorotiazid.
CoAprovel must also not be used in patients who have severe liver, kidney or bile problems, blood potassium levels that are too low or blood calcium levels that are too high.
Zdravila CoAprovel prav tako ne smejo uporabljati bolniki s hudim obolenjem jeter, ledvic ali žolčnika ali bolniki s prenizko koncentracijo kalija v krvi ali s previsoko koncentracijo kalcija v krvi.
The full list of these medicines is given in the Package Leaflet.
Za celoten seznam teh zdravil glejte navodilo za uporabo.
The studies of Karvea/Aprovel used with hydrochlorothiazide as separate tablets were used to support the use of CoAprovel.
V podporo uporabi zdravila CoAprovel so bile uporabljene študije z zdraviloma Karvea in Aprovel, uporabljenima skupaj z hidroklorotiazidom v ločenih tabletah.
What is CoAprovel used for?
Za kaj se zdravilo CoAprovel uporablja?
CoAprovel may be added to some other treatments for hypertension.
Zdravilo CoAprovel se lahko uvede sočasno z nekaterimi drugimi zdravili za zdravljenje visokega krvnega tlaka.
CoAprovel was more effective than placebo (a dummy treatment) and than hydrochlorothiazide alone in reducing diastolic blood pressure.
Zdravilo CoAprovel je bilo pri zniževanju diastoličnega krvnega tlaka učinkovitejše od placeba (zdravila brez zdravilne učinkovine) in od hidroklorotiazida kot samostojnega zdravila.
How is CoAprovel used?
Kako se zdravilo CoAprovel uporablja?
CoAprovel contains two active substances, irbesartan and hydrochlorothiazide.
Zdravilo CoAprovel vsebuje dve zdravilni učinkovini, irbesartan in hidroklorotiazid.
How does CoAprovel work?
Kako zdravilo CoAprovel deluje?
What is CoAprovel?
Kaj je zdravilo CoAprovel?
Your doctor will confirm whether you should change to another treatment.
Zdravnik vam bo povedal, ali je treba pri vas spremeniti zdravljenje.
The review of ergot derivatives was initiated on 18 January 2012 at the request of France, under Article 31 of Directive 2001/83/EC.
Pregled derivatov ergot-alkaloidov je bil sprožen dne 18. januarja 2012 na zahtevo Francije v skladu s členom 31 Direktive 2001/83/ES.
• The available efficacy data for the described indications were considered to be very limited.
• razpoložljivi podatki o učinkovitosti pri navedenih indikacijah so bili zelo omejeni.
• If you are unsure whether you are affected, or if you have any questions, speak with your doctor or pharmacist.
• Če niste prepričani, ali omejitve veljajo tudi za vaše zdravilo, ali če imate kakršna koli vprašanja, se posvetujte z zdravnikom ali farmacevtom.
The severity of such adverse effects and their possible fatal outcome was underlined.
Odbor je izpostavil resnost teh neželenih učinkov in njihov morebitni smrtni izid.
25 October 2013 EMA/652753/2013
18. december 2013 EMA/27446/2014
More about the medicine
Več o zdravilih
In addition, scientific advisory groups held in December 2012 and October 2013 did not consider there was evidence of a therapeutic need for ergot derivatives in the indications covered by the review.
Poleg tega so znanstveno svetovalne skupine, ki so se sestale decembra 2012 in oktobra 2013, menile, da ni dokazov o terapevtski potrebi po uporabi derivatov ergot-alkaloidov pri indikacijah, obravnavanih v pregledu.
Restrictions on use of medicines containing ergot derivatives
Omejitev uporabe zdravil, ki vsebujejo derivate ergotalkaloidov
Patients were young (mean age 41 years-old), with a short time to onset after starting dihydroergotamine (less than 2 months, mean: 2 days).
Bolniki so bili mladi (v povprečju so bili stari 41 let), neželeni učinki pa so se pojavili zelo kmalu po začetku uporabe dihidroergotamina (v manj kot 2 mesecih, v povprečju pa v 2 dneh).
They will remain authorised for use by patients in those indications.
Pri teh indikacijah jih bodo bolniki lahko še naprej uporabljali.
These indications were not included in the CHMP review; therefore these products will remain authorised and may continue to be used in those indications.
Te indikacije so bile izvzete iz pregleda odbora CHMP, zato so ta zdravila še naprej odobrena in se lahko uporabljajo pri teh indikacijah.
Fibrosis can be a serious, sometimes fatal disease, which is often difficult to diagnose because of delayed symptoms and may be irreversible.
Fibroza je lahko resna in včasih tudi smrtna bolezen, ki jo je zaradi zapoznelih simptomov pogosto težko odkriti in je lahko tudi trajna.
The French medicines agency asked the CHMP to carry out an assessment of the benefit-risk balance and to issue an opinion on whether the marketing authorisations for these medicines should be maintained, varied, suspended or withdrawn across the European Union.
Francoska agencija za zdravila je odbor CHMP zaprosila, da oceni razmerje med tveganji in koristmi ter izda mnenje o tem, ali naj se dovoljenja za promet s temi zdravili v Evropski uniji ohranijo, spremenijo, začasno umaknejo ali ukinejo.
− Symptomatic treatment of veno-lymphatic insufficiency.
− simptomatsko zdravljenje veno-limfatične insuficience.
• Patients currently taking these medicines for any of the above indications should have their treatment reviewed at a routine (non-urgent) medical appointment.
• Pri bolnikih, ki jemljejo ta zdravila za katero koli od navedenih indikacij, je treba ob naslednjem rednem (neurgentnem) obisku pri zdravniku ponovno oceniti predpisano zdravljenje.
The review was initiated due to concerns identified by the French National Agency for the Safety of Medicine and Health Products (ANSM) in a national pharmacovigilance review in 2011.
Pregled je bil sprožen zaradi zadržkov, ki so se pojavili med nacionalnim farmakovigilančnim pregledom, ki ga je leta 2011 opravila Francoska nacionalna agencija za varnost zdravil in medicinskih pripomočkov (ANSM).
In the EU, medicines containing ergot derivatives have been authorised by national procedures and have been marketed under various trade names.
Zdravila, ki vsebujejo derivate ergot-alkaloidov, so bila v EU odobrena po nacionalnih postopkih in se tržijo pod različnimi trgovskimi imeni.
− Ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease (PAOD Stage II);
− dodatno zdravljenje intermitentne klavdikacije pri simptomatski periferni arterijski okluzivni bolezni (PAOD stadij II);
At the request of a manufacturer of medicines containing dihydroergotoxine, one of the ergot derivatives, the CHMP carried out a re-examination of its opinion on this medicine.
Na zahtevo izdelovalca zdravil, ki vsebujejo dihidroergotoksin, enega od derivatov ergot-alkaloidov, je nato opravil ponoven pregled mnenja o tem zdravilu.
On 27 June 2013, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended restricting the use of medicines containing ergot derivatives.
Odbor za zdravila za uporabo v humani medicini (CHMP) pri Evropski agenciji za zdravila je dne 27. junija 2013 priporočil omejitev uporabe zdravil, ki vsebujejo derivate ergot-alkaloidov.
benefits in these indications was very limited, the CHMP concluded that the benefits in the concerned indications did not outweigh the risk of fibrosis and ergotism.
Ob upoštevanju dejstva, da so dokazi o koristih teh zdravil pri navedenih indikacijah zelo omejeni, je odbor CHMP zaključil, da koristi pri zadevnih indikacijah ne odtehtajo tveganja za fibrozo in ergotizem.