natgillin/translations-raw huggingface dataset:
• High risk - having had within 3 days prior to dialysis an active bleed that stopped at the pre-dialysis phase; or having incurred surgical or traumatic wounds within 3 days prior to dialysis
• Veliko tveganje - aktivna krvavitev v 3 dneh pred dializo, ki se je ustavila v preddializni fazi, ali kirurške ali travmatske rane v 3 dneh pred dializo
Elevated serum glucose levels have been reported (see section 4.8).
Opisano je bilo zvišanje koncentracije glukoze v serumu (glejte poglavje 4.8).
Powder for solution for infusion: Mannitol
Prašek za raztopino za infundiranje: Manitol
The cold pouch must be regularly changed throughout the day, to maintain the temperature of the solution.
Hladno vrečko je treba čez dan redno menjavati, da se temperatura raztopine ohrani.
The recommended dose for renal dialysis should be exceeded only with careful monitoring of patient blood pressure.
Priporočeni odmerek za ledvično dializo je dovoljeno preseči le ob natančnem kontroliranju bolnikovega krvnega tlaka.
Abrupt withdrawal or interruption of infusion must be avoided, except in life-threatening situations.
Izogibati se moramo nenadnemu prenehanju ali prekinitvi infundiranja , razen v življenjsko nevarnih okoliščinah.
The main feature of overdose is likely to be hypotension.
Verjetno je, da je glavna značilnost prevelikega odmerjanja hipotenzija.
There are no data on the effects of epoprostenol on fertility in humans.
Podatkov o vplivu epoprostenola na plodnost pri človeku ni.
Due to the chemical instability, high potency and short half-life of epoprostenol, no precise and accurate assay has been identified as appropriate for quantifying epoprostenol in biological fluids.
Zaradi kemične nestabilnosti, velike učinkovitosti in kratkega razpolovnega časa epoprostenola, natančen preizkus za kvantificiranje epoprostenola v bioloških tekočinah ni znan.
Adverse events are listed below by system organ class and frequency.
Neželeni učinki so navedeni spodaj po organskih sistemih in pogostnosti.
If you have problems with the infusion pump or injection line that stops, or prevents treatment with Flolan, contact your doctor, nurse or hospital immediately.
Če imate z infuzijsko črpalko ali injekcijskim katetrom težave, ki prekinejo ali preprečijo zdravljenje z zdravilom Flolan, se nemudoma obrnite na svojega zdravnika, medicinsko sestro ali bolnišnico.
Any cold pouch used must be capable of maintaining the temperature of the reconstituted solution.
Vsaka uporabljena hladna vrečka mora biti zmožna vzdrževati temperaturo pripravljene raztopine.
At the end of the treatment period, 4 of 56 (7%) patients receiving epoprostenol died, whereas 5 of 55 (9%) patients receiving conventional therapy alone died.
Na koncu obdobja zdravljenja so umrli 4 od 56 (7 %) prejemnikov epoprostenola in 5 od 55 (9 %) prejemnikov konvencionalnega zdravljenja samega.
Patients who did not have clear evidence of bleeding just prior to their first study dialysis, but who bled within 3 days prior were classified as high risk of haemorrhage.
Bolniki, ki niso imeli jasnih znakov krvavitve tik pred prvo študijsko dializo, a so krvaveli v 3 dneh prej, so bili uvrščeni med bolnike z velikim tveganjem za krvavitev.
Powder and Solvent for solution for infusion: 3 years.
Prašek in vehikel za raztopino za infundiranje: 3 leta.
Other medicines and Flolan
Druga zdravila in zdravilo Flolan
It is not known whether the ingredients of Flolan can pass into breast-milk.
Ni znano, ali lahko sestavine zdravila Flolan prehajajo v materino mleko.
Particular care should be taken in the preparation of the infusion and in calculating the rate of infusion.
Posebno skrb je treba nameniti pripravi infuzije in izračunu hitrosti infundiranja.
Solvent for parenteral use:
Vehikel za parenteralno uporabo:
Increases in exercise capacity were accompanied by statistically significant improvements in dyspnoea, as measured by the Borg Dyspnea Index.
Povečanje obremenitvene zmogljivosti je spremljalo statistično značilno izboljšanje dispneje, merjene z Borgovim indeksom dispneje.
Hypotension may be profound in overdose and may result in loss of consciousness (see section 4.9).
Hipotenzija je lahko v primeru prevelikega odmerjanja huda in lahko povzroči izgubo zavesti (glejte poglavje 4.9)
The symptoms of this are:
Simptomi so:
In general, the need for increases in dose from the initial long-term dose should be expected over time.
Pričakovati bi morali, da je treba začetni dolgotrajni odmerek sčasoma povečati.
If you are not using a ‘cold pouch', the solution can be stored in the pump:
Če ne uporabljate "hladne vrečke", imate raztopino lahko shranjeno v črpalki:
Unlike many other prostaglandins, epoprostenol is not metabolised during passage through the pulmonary circulation.
V nasprotju s številnimi drugimi prostaglandini se epoprostenol ne presnovi med prehodom skozi pljučni obtok.
Flolan is indicated for:
Zdravilo Flolan je indicirano pri:
If the treatment is stopped too quickly you may get serious side effects, including dizziness, feeling weak and breathing difficulties.
Če se zdravljenje konča prehitro, se vam lahko pojavijo resni neželeni učinki, med drugim omotica, šibkost in težave z dihanjem.
At the end of the treatment period in the 12 weeks study, survival was improved in NYHA functional Class III and Class IV patients.
Na koncu obdobja zdravljenja v 12-tedenski študiji se je preživetje bolnikov v III. in IV. funkcijskem razredu po NYHA izboljšalo.
Flolan can also affect how some other medicines work if taken at the same time.
Tudi zdravilo Flolan lahko vpliva na delovanje nekaterih zdravil, če je uporabljeno hkrati z njimi.
Pulmonary Arterial Hypertension
Pljučna arterijska hipertenzija
Primary measurements of efficacy included intradialytic removal of BUN and creatinine, intradialytic removal of fluid (ultrafiltration), and clotting within the extracorporeal circuit.
Med primarnimi meritvami učinkovitosti so bile intradializno odstranjevanje sečnine in kreatinina, intradializno odstranjevanje tekočine (ultrafiltracija) ter strjevanje v zunajtelesnem obtoku.
• medicines to treat inflammation or pain (also called ‘NSAIDs')
• zdravila za zdravljenje vnetij ali bolečin (imenujemo jih tudi nesteroidna protivnetna zdravila ali
• with congestive heart failure arising from severe left ventricular dysfunction.
• s kongestivnim srčnim popuščanjem, ki je posledica hude disfunkcije levega prekata,
If overdose occurs reduce the dose or discontinue the infusion and initiate appropriate supportive measures as necessary; for example plasma volume expansion and/or adjustment to pump flow.
V primeru prevelikega odmerjanja je treba zmanjšati odmerek ali prekiniti infundiranje in uporabiti ustrezne podporne ukrepe, kot je potrebno, npr. nadomeščanje volumna plazme in/ali prilagoditev pretoka črpalke.
Only this concentrated solution is suitable for further dilution prior to use.
Le ta koncentrirana raztopina je primerna za nadaljnje razredčenje pred uporabo.
• feeling anxious, feeling nervous
• občutek tesnobe, občutek živčnosti,
Flolan is not a conventional anticoagulant.
Zdravilo Flolan ni običajno antikoagulantno zdravilo.
Eight of 40 (20%) patients receiving conventional therapy alone died, whereas none of the 41 patients receiving epoprostenol died (p=0.003).
Umrlo je 8 od 40 (20 %) bolnikov, ki so prejemali samo konvencionalno zdravljenje, med 41 bolniki, ki so prejemali epoprostenol, pa ni umrl nobeden (p = 0,003).
Reproductive studies in animals have shown no effects on fertility (see section 5.3).
Študije o sposobnosti razmnoževanja pri živalih niso pokazale vpliva na plodnost (glejte poglavje 5.3).
The dose will be increased, until your symptoms are relieved, and any side effects are manageable.
Odmerek vam bo povečeval, dokler vam zdravilo ne bo olajšalo simptomov in dokler bodo neželeni učinki obvladljivi.
Each patient was randomly assigned to a sequence of heparin or epoprostenol dialyses and received up to 6 dialyses per entry in one study and up to 3 dialyses per entry in another study.
Vsakega bolnika so naključno razvrstili na zaporedje dializ s heparinom ali epoprostenolom in so bili deležni do 6 dializ na vstop v eni študiji in do 3 dializ na vstop v drugi študiji.
Flolan can cause your heart to beat faster or slower.
Zdravilo Flolan lahko povzroči, da začne srce biti hitreje ali počasneje.
For a full list of excipents, see section 6.1
Za celoten seznam pomožnih snovi glejte poglavje 6.1.
• bleeding at various sites and bruising more easily than normal, for example from the nose or gums
• krvavitev na različnih mestih ali večja nagnjenost k podplutbam kot ponavadi, npr. krvavitev iz nosu ali dlesni,
If you stop taking Flolan
Če ste prenehali jemati zdravilo Flolan
As reported with other prostaglandin analogues, Flolan may reduce the thrombolytic efficacy of tissue plasminogen activator (t-PA) by increasing hepatic clearance of t-PA.
Tako, kot je opisano pri drugih prostaglandinskih analogih, lahko tudi zdravilo Flolan zmanjša trombolitično učinkovitost tkivnega aktivatorja plazminogena (t-PA), in sicer s povečanjem jetrnega očistka t-PA.
At normal physiological pH and temperature, epoprostenol breaks down spontaneously to 6-oxoprostaglandin F1 alpha, although there is some enzymatic degradation to other products.
Pri normalnem fiziološkem pH in pri normalni temperaturi se epoprostenol spontano razgradi v 6-oksoprostaglandin F1 alfa, nekaj pa je tudi encimske razgradnje v druge snovi.
No long-term animal studies have been conducted to determine the carcinogenic potential of epoprostenol.
Dolgoročne študije za oceno kancerogenosti epoprostenola na živalih niso bile izvedene.
If excessive hypotension occurs during administration of Flolan, the dose should be reduced or the infusion discontinued.
Če se med dajanjem zdravila Flolan pojavi čezmerna hipotenzija, je treba odmerek zmanjšati ali infundiranje prekiniti.
Minor clotting (sufficient to require intervention, but not permanently suspending dialysis or requiring changing of the artificial kidney) was reported more frequently during epoprostenol than during heparin dialyses.
Manj pomembno strjevanje (tolikšno, da je zahtevalo ukrepanje, ne pa trajne prekinitve dialize ali potrebe po menjavi umetne ledvice) je bilo med dializami z epoprostenolom pogostejše kot med dializami s heparinom.
Changes in the long-term infusion rate should be based on persistence, recurrence or worsening of the patient's symptoms of pulmonary arterial hypertension or the occurrence of adverse reaction due to excessive doses of Flolan.
Spremembe v dolgotrajni hitrosti infundiranja morajo temeljiti na trajanju, ponovitvi ali poslabšanju bolnikovih simptomov pljučne arterijske hipertenzije ali pojavu neželenih učinkov zaradi čezmernih odmerkov zdravila Flolan.
A short-term dose-ranging procedure administered via either a peripheral or central venous line is required to determine the long-term infusion rate.
Postopek kratkotrajnega ugotavljanja odmerka po periferni ali centralni venski liniji je potreben za določitev hitrosti dolgotrajnega infundiranja.
The effects of Flolan on heart rate may be masked by concomitant use of drugs which affect cardiovascular reflexes.
Vplive zdravila Flolan na srčno frekvenco lahko prikrije sočasna uporaba zdravil, ki vplivajo na kardiovaskularne reflekse.
During renal dialysis with Flolan it should be ensured that the cardiac output increases more than minimally so that delivery of oxygen to peripheral tissue is not diminished.
Med ledvično dializo z uporabo zdravila Flolan je treba poskrbeti, da se minutni volumen srca poveča več kot le minimalno, tako da se oskrba perifernih tkiv s kisikom ne zmanjša.
Before use, the powder needs to be dissolved in the liquid provided.
Pred uporabo je treba prašek raztopiti v priloženi tekočini.
Mean systemic arterial pressure was not significantly different between the two groups (-4.33 vs. -3.05 mm Hg).
Povprečni sistemski arterijski tlak se med skupinama ni značilno razlikoval (-4,33 v prim.
Six heparin-controlled studies and five emergency studies explored the place of epoprostenol in the general management of renal dialysis, using different techniques.
Šest s heparinom kontroliranih in pet urgentnih študij je raziskalo mesto epoprostenola v splošnem vodenju ledvične dialize z uporabo različnih tehnik.
• You feel that your heart is beating faster, or you have chest pain or shortness of breath.
• Čutite hitro bitje srca, imate bolečine v prsih ali kratko sapo.
Infusion of 4 nanograms/kg/min for 30 minutes have been shown to have no significant effect on heart rate or blood pressure, although facial flushing may occur at these levels.
Ugotovljeno je, da infundiranje 4 nanogramov/kg/min 30 minut ne vpliva pomembno na srčno frekvenco ali krvni tlak, lahko pa se pri tej hitrosti pojavi zardevanje obraza.
Mix well.
Dobro premešajte.
To establish that renal dialysis patients at increased risk of haemorrhage bleed less frequently with epoprostenol than heparin, 2 major prospectively controlled studies were conducted.
Za ugotavljanje, da imajo bolniki na ledvični dializi, ki imajo večje tveganje za krvavitve, z epoprostenolom krvavitve manj pogosto kot s heparinom, sta bili izvedeni 2 veliki prospektivni kontrolirani študiji.
In general, events seen after overdose of Flolan represent exaggerated pharmacological effects of the drug (e.g. hypotension and complications of hypotension).
Na splošno predstavljajo dogodki, opaženi po prevelikem odmerjanju zdravila Flolan, prekomerne farmakološke učinke zdravila (npr. hipotenzija in zapleti hipotenzije).
Increases in dose should be considered if symptoms of pulmonary arterial hypertension persist, or recur after improving.
Povečanje odmerka pride v poštev, če simptomi pljučne arterijske hipertenzije trajajo ali se po izboljšanju ponovijo.
Blood glucose increased * Associated with the delivery system for Flolan 1 Catheter-related infections caused by organisms not always considered pathogenic (including micrococcus) have been reported.
* Povezano z aplikacijskim sistemom za zdravilo Flolan 1 Opisane so bile s katetrom povezane okužbe z organizmi, ki ne veljajo vedno za patogene (vključno z mikrokoki).
Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension.
Zdravljenje sme vpeljati in nadzorovati le zdravnik, ki ima izkušnje z zdravljenjem pljučne arterijske hipertenzije.
Flolan is indicated for use in haemodialysis in emergency situations when use of heparin carries a high risk of causing or exacerbating bleeding or when heparin is otherwise contraindicated (see section 5.1).
Zdravilo Flolan je indicirano za uporabo pri hemodializi v nujnih okoliščinah, kadar uporabo heparina spremlja veliko tveganje za poslabšanje krvavitev, ali kadar je heparin kako drugače kontraindiciran (glejte poglavje 5.1).
They should be kept under 25°C and protected from light.
Shranjevati jo je treba pri temperaturi do 25 °C in zaščiteno pred svetlobo.
Once Flolan powder has been dissolved, and diluted, it should ideally be used immediately.
Ko je prašek zdravila Flolan raztopljen in razredčen, ga je najbolje uporabiti nemudoma.
Once the best dose has been found, a permanent tube (line) will be fitted into one of your veins.
Ko bo določen najprimernejši odmerek, vam bodo v eno od ven namestili stalno cevko (kateter).
Effect of Flolan on blood pressure and heart rate
Vpliv zdravila Flolan na krvni tlak in srčni utrip
Following establishment of a new infusion rate, the patient should be observed, and erect and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated.
Po določitvi nove hitrosti infundiranja je treba bolnika opazovati ter mu več ur kontrolirati krvni tlak in srčno frekvenco stoje in leže ter se tako prepričati, da prenese novi odmerek.
Elevated cAMP levels regulate intracellular calcium concentrations by stimulating calcium removal, and thus platelet aggregation is ultimately inhibited by the reduction of cytoplasmic calcium, upon which platelet shape change, aggregation and the release reaction depends.
Zvišana koncentracija cAMP uravnava znotrajcelično koncentracijo kalcija s stimulacijo odstranjevanja kalcija, tako da agregacijo trombocitov navsezadnje zavre znižanje kalcija v citoplazmi, od katerega so odvisne sprememba oblike trombocitov, njihova agregacija in reakcija sproščanja.
Your treatment may have an effect on the ability to drive or use machinery.
Vaše zdravilo lahko vpliva na sposobnost upravljanja vozil ali strojev.
Intravenously administered epoprostenol is rapidly distributed from blood to tissue.
Intravensko dani epoprostenol se iz krvi hitro porazdeli v tkiva.
Flolan is suitable for continuous infusion only, either intravascularly or into the blood supplying the dialyser.
Zdravilo Flolan je primerno le za stalno infundiranje, bodisi intravaskularno bodisi v kri, ki priteka v dializator.
Following the administration of radiolabelled epoprostenol to humans, the urinary and faecal recoveries of radioactivity were 82% and 4%, respectively.
Po uporabi radioaktivno označenega epoprostenola pri človeku se je v urinu pojavilo 82 % radioaktivnosti in v blatu 4 %.
Infusion rate (mL/h) = Infusion rate (mL/min) x 60
Hitrost infundiranja (ml/h) = hitrost infundiranja (ml/min) x 60
Once Flolan has been dissolved and diluted, any unused solution can be stored at 25oC and used within 12 hours.
Ko je zdravilo Flolan raztopljeno in razredčeno, je morebiti neporabljeno raztopino mogoče shraniti pri temperaturi 25 oC in jo uporabiti v 12 urah.
Many of the actions of epoprostenol are exerted via the stimulation of adenylate cyclase, which leads to increased intracellular levels of cyclic adenosine 3'5' monophosphate (cAMP).
Številna delovanja epoprostenola potekajo s stimulacijo adenilat-ciklaze, ki poveča znotrajcelično koncentracijo cikličnega adenozin-3'5'-monofosfata (cAMP).
Symptoms of overdose may include headache, nausea, vomiting, fast heart rate, warmth or tingling, or feeling like you might pass out (feeling faint/dizziness).
Med simptomi prevelikega odmerjanja so lahko glavobol, slabost, bruhanje, hitro bitje srca, občutek toplote ali mravljinčenja ali občutek, da boste omedleli (omedlevica/omotica).
Reconstitution and dilution should be carried out immediately prior to use.
Pripravo in razredčenje je treba opraviti tik pred uporabo.
Flolan is indicated for the treatment of pulmonary arterial hypertension (PAH) (idiopathic or heritable PAH and PAH associated with connective tissue diseases) in patients with WHO Functional Class III-IV symptoms to improve exercise capacity (see section 5.1).
Zdravilo Flolan je indicirano za zdravljenje pljučne arterijske hipertenzije (PAH) (idiopatske ali dedne PAH in PAH, povezane z vezivnotkivnimi boleznimi) pri bolnikih s simptomi funkcijskega razreda III-IV po Svetovni zdravstveni organizaciji (SZO) za izboljšanje obremenitvene sposobnosti (glejte poglavje 5.1).
The other ingredients are Mannitol, Glycine, Sodium Chloride, Sodium Hydroxide and Water.
Pomožne snovi so manitol, glicin, natrijev klorid, natrijev hidroksid in voda.
Epoprostenol is the most potent inhibitor of platelet aggregation known.
Epoprostenol je najmočnejši znani zaviralec agregacije trombocitov.
What Flolan is and what it is used for What you need to know before you take Flolan How to take Flolan
Kaj je zdravilo Flolan in za kaj ga uporabljamo Kaj morate vedeti, preden boste vzeli zdravilo Flolan Kako jemati zdravilo Flolan Možni neželeni učinki
• medicines used to treat high blood pressure
• zdravila za zdravljenje visokega krvnega tlaka,
The half-life for the spontaneous breakdown to 6-oxo-prostaglandin F1 alpha in man is expected to be no more than 6 minutes, and may be as short as 2 to 3 minutes, as estimated from in vitro rates of degradation of epoprostenol in human whole blood.
Pričakovani razpolovni čas spontane razgradnje v 6-okso-prostaglandin F1 alfa pri človeku ne presega 6 minut in je morda celo samo od 2 do 3 minute, če ocenjujemo glede na hitrost razgradnje epoprostenola v človeški polni krvi in vitro.
Thus, therapy with Flolan requires commitment by the patient to sterile drug reconstitution, drug administration, care of the permanent central venous catheter, and access to intense and ongoing patient education.
Zato zdravljenje z zdravilom Flolan zahteva, da bolnik skrbi za sterilno pripravo in dajanje zdravila, oskrbo stalnega centralnega venskega katetra ter možnost intenzivnega in stalnega izobraževanja.
At week 12, NYHA functional class improved in 21 of 51 (41%) patients treated with epoprostenol compared to none of the 48 patients treated with conventional therapy alone.
Po 12 tednih se je funkcijski razred po NYHA izboljšal pri 21 od 51 (41 %) bolnikov, zdravljenih z epoprostenolom, in pri nobenem od 48 bolnikov, ki so prejemali samo konvencionalno zdravljenje.
An abrupt interruption of therapy can induce a rebound of pulmonary arterial hypertension resulting in dizziness, asthenia, increase dyspnoea, and may lead to death (see section 4.2).
Nenadna prekinitev zdravljenja lahko povzroči preobratno pljučno arterijsko hipertenzijo s posledično omotico, astenijo, poslabšanjem dispneje ter lahko povzroči smrt (glejte poglavje 4.2).
If you take more Flolan than you should
Če ste vzeli večji odmerek zdravila Flolan, kot bi smeli
You will start with an infusion of Flolan.
Zdravljenje boste začeli z infuzijo zdravila Flolan.
Your dose may need to be reduced or your infusion stopped.
Morda vam bo moral zmanjšati odmerek ali prekiniti infundiranje zdravila.
However, the reverse was observed for postdialysis days with epoprostenol (N=1/5) compared to heparin (N=8/16).
Obratno pa je bilo ugotovljeno za dneve po dializi z epoprostenolom (n = 1/5) v primerjavi s heparinom (n = 8/16).
It is unknown if epoprostenol or its metabolites are excreted in human milk.
Ni znano, ali se epoprostenol ali njegovi presnovki pri človeku izločajo v materino mleko.
PHARMACEUTICAL FORM Powder for concentrate for solution for infusion: - White or off-white freeze dried powder Solvent for parenteral use: - Clear, colourless solution (pH 10.3 - 10.8)
FARMACEVTSKA OBLIKA Prašek za koncentrat za raztopino za infundiranje: - bel ali skoraj bel liofiliziran prašek Vehikel za parenteralno uporabo: - bistra, brezbarvna raztopina (pH 10,3-10,8)
Pain at the injection site*, chest pain
Pogosti bolečine na mestu injiciranja*, bolečina v prsih
Independent of technical difficulties which occurred rarely with either treatment, major dialysis-limiting clotting did not occur in 93% of all epoprostenol dialyses and 99% of all heparin dialyses.
Neupoštevaje tehnične težave (ki so bile pri obeh načinih zdravljenja redke) se pomembno strjevanje, ki bi omejilo dializo, ni pojavilo pri 93 % vseh dializ z epoprostenolom in pri 99 % vseh dializ s heparinom.
• feeling tired, weak
• utrujenost, šibkost.
For further instructions on reconstitution and dilution of the medicinal product before administration, (see section 6.6).
Za dodatna navodila o pripravi in razredčenju zdravila pred uporabo glejte poglavje 6.6.
Dry mouth
Občasni suha usta
During long-term infusion, the occurrence of dose-related pharmacological events similar to those observed during the dose-ranging period may necessitate a decrease in infusion rate, but the adverse reactions may occasionally resolve without dosage adjustment.
Med dolgotrajnim infundiranjem se lahko pojavijo z odmerkom povezani farmakološki učinki, podobni tistim med obdobjem ugotavljanja odmerka, in lahko zahtevajo zmanjšanje hitrosti infundiranja, neželeni učinki pa občasno lahko minejo brez prilagajanja odmerka.
However, more patients in both treatment groups (28/51 [55%] with epoprostenol and 35/48 [73%] with conventional therapy alone) showed no change in functional class, and 2/51 (4%) with epoprostenol and 13/48 (27%) with conventional therapy alone worsened.
Vendar pa se funkcijski razred pri večjem delu bolnikov v obeh terapevtskih skupinah ni spremenil (28/51 [55 %] z epoprostenolom in 35/48 [73 %] s konvencionalnim zdravljenjem samim), pri 2/51 (4 %) z epoprostenolom in 13/48 (27 %) s konvencionalnim zdravljenjem samim pa se je poslabšal.