FrancophonIA/ELRC3.0 huggingface dataset:
English: Photosensitivity Strong light may cause skin reactions and eye discomfort while TOOKAD is in the blood stream.
Croatian: Jaka svjetlost može uzrokovati reakcije na koži i nelagodu u oku dok se TOOKAD nalazi u krvotoku.
English: In certain cases, the bulbar location suggested that the stenosis was caused by urinary catheterisation.
Croatian: nekim slučajevima bulbarni položaj ukazuje na to da je stenoza izazvana postavljanjem urinarnog katetera.
English: Because the fibres that carry the light have to be inserted in such a way that the whole of the lobe of the prostate gland gets exposed, it is possible that some damage may occur outside of the prostate.
Croatian: Budući da se vlakna koja pronose svjetlost moraju umetnuti tako da se izloži čitav režanj žlijezde prostate, može doći do nekih oštećenja izvan prostate.
English: Activation within the illuminated tumour vasculature, generates oxygen radicals (•OH, O•
Croatian: Aktivacija unutar osvijetljenih krvnih žila tumora stvara radikale kisika (•OH, O•
English: TOOKAD is administered as part of focal VTP.
Croatian: TOOKAD se primjenjuje u sklopu fokalnog VTP-a.
English: All patients had Gleason score ≤ 3 + 3 at baseline.
Croatian: Svi bolesnici na početku ispitivanja imali su Gleason zbroj ≤ 3 + 3.
English: If the patient is sexually active with women who are capable of getting pregnant, he and/or his partner should use an effective form of birth control to prevent getting pregnant during a period of 90 days after the VTP procedure.
Croatian: Ako je bolesnik spolno aktivan sa ženom koja može zanijeti, on i/ili partnerica trebaju se koristiti učinkovitom zaštitom od trudnoće u razdoblju od 90 dana nakon VTP postupka.
English: TOOKAD is a medicine that contains padeliporfin (as potassium salt).
Croatian: TOOKAD je lijek koji sadrži padeliporfin (u obliku kalijeve soli).
English: In 18 patients the adverse event resolved with a median duration of 63.5 days (1-360), and the adverse event was still ongoing at the end of the study for 7 patients.
Croatian: U 18 bolesnika štetan događaj se povukao s medijanom trajanja od 63,5 dana (1 - 360), a štetan događaj bio je i dalje prisutan na završetku ispitivanja u 7 bolesnika.
English: For the 48 hours after the procedure you should avoid exposure to direct sunlight (including through windows) and all bright light sources, both indoors and outdoors.
Croatian: Tijekom 48 sati nakon postupka potrebno je izbjegavati izlaganje izravnoj sunčevoj svjetlosti (uključujući kroz prozore) i svim jakim svjetlosnim izvorima, vanjskim i unutarnjim.
English: The most common infections are orchitis, epididymitis and urinary tract infections including cystitis.
Croatian: Najčešće infekcije su orhitis, epididimitis i infekcije urinarnog sustava, uključujući cistitis.
English: In Phase II studies, treatment conditions corresponding to an LDI ≥ 1 were associated with a mean rate of necrosis of the targeted zone at day 7 of 89 % ± 20.75 for unilateral treatment.
Croatian: U ispitivanjima faze II, uvjeti liječenja koji su odgovarali LDI ≥ 1 bili su povezani sa srednjom stopom nekroze ciljane zone 7. dana od 89 % ± 20,75
English: For instructions to healthcare professionals on reconstitution of TOOKAD before injection, see “Reconstitution of the TOOKAD powder for solution for injection”.
Croatian: Za upute zdravstvenim radnicima o rekonstituciji lijeka TOOKAD prije injiciranja vidjeti dio „Rekonstitucija TOOKAD praška za otopinu za injekciju ”.
English: Perineal injury and perineal pain occurred in 46 (23.4 %) patients in the controlled Phase III European study.
Croatian: Perinealna ozljeda i perinealna bol pojavile su se u 46 (23,4 %) bolesnika u kontroliranom europskom ispitivanju faze III.
English: - You are not able to have general anaesthesia or invasive procedures.
Croatian: - ako ne možete podnijeti opću anesteziju ili invazivne postupke.
English: Perineal injury
Croatian: Perinealna ozljeda15
English: Normally this is just the fat around the prostate and is not important but nearby organs such as the bladder and rectum may potentially be affected.
Croatian: Obično se radi samo o masnom tkivu oko prostate, što nije važno, ali mogu se oštetiti organi u blizini poput mjehura i rektuma.
English: Severe long-term urinary incontinence was observed in a patient who underwent a previous transurethral prostatectomy (TURP).
Croatian: Teška dugoročna urinarna inkontinencija uočena je u bolesnika prethodno podvrgnutog transuretralnoj prostatektomiji (TURP).
English: Additional VTP procedures of the prostate are not recommended.
Croatian: Ne preporučuju se dodatne VTP terapije prostate.
English: The median time to onset of genito-urinary infections was 22.5 days (4-360).
Croatian: Medijan vremena do pojave genitalno-urinarnih infekcija iznosio je 22,5 dana (4 - 360).
English: This results in transient arterial vasodilatation that triggers the release of the vasoconstrictor, endothelin-1.
Croatian: To rezultira prolaznom arterijskom vazodilatacijom koja izaziva otpuštanje vazokonstriktora endotelina-1.
English: Age (years) Mean (SD) Range: min, max Patients aged > 75 year old, n (%) Unilateral disease, n (%) Bilateral disease, n (%)
Croatian: Dob (godine) Srednja vrijednost (SD) Raspon: min, maks Bolesnici starosti > 75 godina, n Unilateralna bolest, n (%) Bilateralna bolest, n (%)
English: In the Phase III European study, 25 (12.7 %) patients experienced urinary incontinence (including incontinence, stress urinary incontinence and urge incontinence).
Croatian: U europskom ispitivanju faze III, 25 (12,7 %) bolesnika iskusilo je urinarnu inkontinenciju (uključujući inkontinenciju, stres inkontinenciju i urgentnu inkontinenciju).
English: This event was not considered to be related to a faulty procedure but rather the pre-existing damage to the internal urethral sphincter from the TURP.
Croatian: Ovaj događaj ne povezuje se s nepravilnostima postupka, već više s od prije postojećim oštećenjem unutarnjeg uretralnog sfinktera zbog TURP-a.
English: Carcinogenicity and reproductive toxicity studies have not been conducted with padeliporfin.
Croatian: Ispitivanja kancerogenosti i reproduktivne toksičnosti nisu provedena s padeliporfinom.
English: In assessing overall tolerability by Month 24, post enrolment patients who underwent a radical therapy were also counted in the scoring of prostate symptoms and erectile function.
Croatian: U procjeni ukupne podnošljivosti do 24. mjeseca bolesnici koji su nakon uključivanja u ispitivanje podvrgnuti radikalnoj terapiji također su ubrojeni u rezultate simptoma prostate i erektilne funkcije.
English: In vitro genotoxicity testing identified padeliporfin as having weak potential to induce clastogenicity when illuminated by ultraviolet (UV); this correlates with the mechanism of action (formation of reactive oxygen species).
Croatian: In vitro ispitivanje genotoksičnosti pokazalo je da padeliporfin ima slab potencijal izazivanja klastogenosti pri osvjetljavanju ultraljubičastim svjetlom (UV); to je u korelaciji s mehanizmom djelovanja (stvaranje reaktivnih kisikovih spojeva).
English: The reconstituted solution for infusion is dark.
Croatian: Rekonstituirana otopina za infuziju je tamna.
English: No metabolites of padeliporfin were observed in these studies.
Croatian: U tim ispitivanjima nisu uočeni metaboliti padeliporfina.
English: In the Active Surveillance arm, the IPSS score slightly worsened over time until Month 24.
Croatian: U skupini s aktivnim praćenjem (AS), IPPS bodovi su se blago pogoršali s vremenom do 24. mjeseca.
English: Patients should avoid exposure to direct sunlight (including through windows) and all bright light sources, both indoors and outdoors.
Croatian: Bolesnici trebaju izbjegavati izlaganje izravnoj sunčevoj svjetlosti (uključujući kroz prozore) i svim jakim svjetlosnim izvorima, vanjskim i unutarnjim.
English: Longer follow-up will be required to determine whether TOOKAD-VTP will be curative in a proportion of patients.
Croatian: Potrebno je dulje praćenje da bi se odredilo ima li TOOKAD-VTP učinak izlječenja na udio bolesnika.
English: Read all of this leaflet carefully before you are given this medicine because it contains important information for you.
Croatian: Za postupak prijavljivanja nuspojava, pogledajte dio 4. Pažljivo pročitajte cijelu uputu prije nego primite ovaj lijek jer sadrži Vama važne podatke.
English: However, patients weighing more than 115 kg will receive more than 1 mmol potassium.
Croatian: Ipak, bolesnici tjelesne težine veće od 115 kg primit će više od 1 mmol kalija.
English: Of 58 patients that progressed in the TOOKAD-VTP arm, only 11 underwent radical therapy, 18 patients underwent a second VTP procedure and 29 had not received further treatment at the end of the study.
Croatian: Od 58 bolesnika s progresijom u skupini TOOKAD-VTP, samo njih 11 podvrgnuto je radikalnoj terapiji, 18 bolesnika podvrgnuto je drugoj VTP terapiji, a 29 ih nije primilo daljnje liječenje na kraju ispitivanja.
English: Prostatitis occurred in 7 (3.6 %) patients in the controlled Phase III European study.
Croatian: Prostatitis se pojavio u 7 (3,6 %) bolesnika u kontroliranom europskom ispitivanju faze III.
English: Padeliporfin is retained within the vascular system.
Croatian: Padeliporfin se zadržava u krvožilnom sustavu.
English: • Explain what side effects the Patient might expect and the likelihood of him getting them
Croatian: • Objašnjenje koje nuspojave bolesnik može očekivati i vjerojatnost dobivanja tih nuspojava.
English: Place a 0.22 μm injection filter on the syringe.
Croatian: Stavite injekcijski filtar od 0,22 μm na štrcaljku.
English: There was no significant correlation between the percentage of prostate necrosis on Day 7 MRI and the likelihood of a negative prostate biopsy at follow-up.
Croatian: Nije bilo značajne korelacije između postotka nekroze prostate na MR-u 7. dana i vjerojatnosti negativnog nalaza biopsije prostate u daljnjem praćenju.
English: LIST OF EXCIPIENTS Excipient: Mannitol
Croatian: POPIS POMOĆNIH TVARI Pomoćna tvar: manitol
English: 53 (26.9 %) patients experienced erectile dysfunction for more than 6 months, including 34 (17.3 %) patients in whom the erectile dysfunction had not resolved at the end of the study.
Croatian: 53 (26,9 %) bolesnika imala su erektilnu disfunkciju dulje od 6 mjeseci, uključujući 34 (17,3 %) bolesnika u kojih erektilna disfunkcija nije prestala do završetka ispitivanja.
English: Urinary retention immediately post procedure has been attributed to transient prostatic oedema and generally only short term recatheterisation was required.
Croatian: Urinarna retencija nastala odmah nakon postupka pridodaje se privremenom edemu prostate i općenito je potrebna samo kratkotrajna rekateterizacija.
English: The median duration was 10 days (1-344).
Croatian: Medijan trajanja iznosio je 10 dana (1 - 344).
English: The final solution concentration is 9.15 mg/mL.
Croatian: Konačna koncentracija otopine iznosi 9,15 mg/ml.
English: TOOKAD is contraindicated in patients who have been diagnosed with cholestasis (see section 4.3).
Croatian: TOOKAD je kontraindiciran u bolesnika s dijagnozom kolestaze (vidjeti dio 4.3).
English: - You experience difficulties in getting or maintaining an erection.
Croatian: - ako imate poteškoća u postizanju ili održavanju erekcije;
English: Rapid consumption of the •NO radicals, by oxygen radicals, leads to the formation of reactive nitrogen species (RNS) (e.g. peroxynitrite), in parallel to arterial constriction.
Croatian: Brza potrošnja radikala •NO putem radikala kisika dovodi do stvaranja reaktivnih dušikovih spojeva (npr. peroksinitrita), istodobno sa konstrikcijom arterija.
English: The median duration was 21 days (4-197).
Croatian: Medijan trajanja iznosio je 21 dan (4 - 197).
English: The equipment should be carefully calibrated and use the treatment guidance software to reduce the risk of clinically significant extraprostatic necrosis.
Croatian: Oprema mora biti pažljivo kalibrirana i potrebno se koristiti terapijskim vodičem u obliku programske podrške kako bi se smanjio rizik nastanka klinički značajne izvanprostatne nekroze.
English: Warnings and precautions TOOKAD should only be used by personnel trained in the VTP procedure.
Croatian: Upozorenja i mjere opreza TOOKAD smije upotrebljavati samo osoblje osposobljeno za primjenu VTP terapije.
English: In addition, impaired deformability is thought to enhance erythrocyte aggregability and formation of blood clots at the interface of the arterial supply (feeding arteries) and tumour microcirculation, results in occlusion of the tumour vasculature.
Croatian: Uz to, smatra se da promijenjena deformabilnost poboljšava agregaciju eritrocita i stvaranje krvnih ugrušaka na granici između opskrbnih arterija (hranidbene arterije) i tumorske mikrocirkulacije, što rezultira okluzijom krvnih žila tumora.
English: An LDI ≥ 1 appeared to be associated with a greater volume of necrosis on Day 7 MRI and greater share of patients with negative biopsy at 6 months compared with an LDI < 1 (see section 4.2).
Croatian: LDI ≥ 1 pokazao se povezan s većim volumenom nekroze na MR-u 7. dana i s većim udjelom bolesnika s negativnim nalazom biopsije nakon 6 mjeseci u usporedbi s LDI < 1 (vidjeti dio 4.2).
English: The body weight of patients (range 60-120 kg) presented a minor impact on the TOOKAD pharmacokinetic parameters for doses up to 5 mg/kg of padeliporfin di-potassium.
Croatian: Tjelesna težina bolesnika (raspon od 60 do 120 kg) predstavljala je manji utjecaj na farmakokinetičke parametre lijeka TOOKAD za doze padeliporfindikalija do 5 mg/kg.
English: Therefore, the possibility for some in vivo metabolism of padeliporfin cannot be fully excluded.
Croatian: Stoga se ne može potpuno isključiti mogućnost in vivo metabolizma padeliporfina.
English: • Information on adverse drug reactions and the likelihood of them getting them, including: erectile dysfunction, urinary incontinence, urinary retention/urethral stricture, and photosensitivity and the need to follow the rules to protect themselves against the light after the procedure for 48 hours.
Croatian: • informaciju o nuspojavama i vjerojatnosti njihovog pojavljivanja, uključujući: erektilnu disfunkciju, urinarnu inkontinenciju, urinarnu retenciju/uretralnu strikturu i fotoosjetljivost, te potrebu poštivanja pravila radi zaštite od svjetlosti idućih 48 sati nakon postupka.
English: Co-administration should be done with caution and close monitoring is recommended.
Croatian: Istodobna primjena se mora odvijati uz mjere opreza i preporučuje se pažljivo praćenje bolesnika.
English: • Patient information guide • Physician guideline
Croatian: • Vodič za bolesnike • Vodič za liječnike
English: 12-48 hours after VTP procedure
Croatian: 12 - 48 sati nakon VTP terapije
English: An overdose of the laser light may increase the risk of undesirable extraprostatic necrosis (see section 4.4).
Croatian: Prekomjerna doza laserskog svjetla može povećati rizik od neželjene izvanprostatne nekroze (vidjeti dio 4.4).
English: mpMRI may be used to improve the decision making but not, at present, to replace biopsy.
Croatian: Može se obaviti MR pregled u svrhu lakšeg donošenja odluke, ali još uvijek ne i kao zamjena za biopsiju.
English: Clinical stages
Croatian: Klinički stadij
English: This may also cause bruising, blood in the urine and/or local pain.
Croatian: To također može uzrokovati pojavu modrica, krvi u urinu i/ili lokalizirane boli.
English: Insufficient patients underwent retreatment of the ipsilateral lobe or sequential treatment of the contralateral lobe to determine the efficacy and safety of a second TOOKAD-VTP procedure.
Croatian: Kod nedovoljnog broja bolesnika je uslijedilo ponovno liječenje ipsilateralnog režnja ili uzastopno liječenje kontralateralnog režnja da bi se mogla utvrditi djelotvornosti i sigurnosti druge TOOKADVTP terapije.
English: You must remain under reduced light conditions, without exposing your skin and your eyes to daylight.
Croatian: Morate ostati pod prigušenim svjetlom i ne izlagati kožu i oči danjem svjetlu.
English: After the procedure, you should wear protective goggles and will be kept under medical surveillance for at least 6 hours in a room with reduced light.
Croatian: Nakon postupka treba nositi zaštitne naočale i ostati pod liječničkim nadzorom najmanje 6 sati u prostoriji s prigušenim svjetlom.
English: Padeliporfin was shown to be cytotoxic in the presence of UVA irradiation (in vitro) and considered phototoxic in the guinea pig (in vivo).
Croatian: Padeliporfin se pokazao citotoksičnim u prisutnosti UVA zračenja (in vitro) i smatra se fototoksičnim u zamoraca (in vivo).
English: The patient may watch television from a distance of 2 metres and, from 6 hours onwards, may use electronic devices such as smartphones, tablets and computers.
Croatian: Bolesnik smije gledati televiziju s udaljenosti od 2 metra i nakon 6 sati upotrebljavati elektroničke uređaje poput pametnog mobitela, tableta i računala.
English: These medicines should be stopped at least 10 days before the procedure with TOOKAD, and for at least 3 days after the procedure, or replaced by other treatments without photosensitising properties.
Croatian: Te lijekove treba prestati uzimati najmanje 10 dana prije postupka liječenja lijekom TOOKAD i najmanje 3 dana nakon postupka ili ih treba zamijeniti drugim lijekovima bez fotosenzibilizirajućih svojstava.
English: When activated with 753 nm wavelength laser light, padeliporfin triggers a cascade of pathophysiological events resulting in focal necrosis within a few days.
Croatian: Pri aktivaciji laserskim svjetlom valne duljine 753 nm padeliporfin pokreće kaskadu patofizioloških događaja koji dovode do fokalne nekroze unutar nekoliko dana.
English: TOOKAD-VTP should only be administered after careful clinical evaluation, to patients with a history of active rectal inflammatory bowel disease or any condition that may increase the risk of recto-urethral fistula formation (see section 4.3).
Croatian: TOOKAD-VTP smije se primijeniti samo nakon pažljive kliničke procjene bolesnika s anamnezom aktivne rektalne upalne bolesti crijeva ili bilo kojeg stanja koje može povećati rizik od stvaranja rektouretralne fistule (vidjeti dio 4.3).
English: Number of subjects who initiated a radical treatment, n (%)
Croatian: Broj ispitanika koji su započeli s radikalnim liječenjem, n (%)
English: In addition, inserting needles into the prostate gland and inserting a urinary catheter for the procedure may be associated with further side effects.
Croatian: Uz to, umetanje igala u prostatu i umetanje urinarnog katetera tijekom postupka mogu biti povezani s daljnjim nuspojavama.
English: Surgical procedure repeated Contusion
Croatian: Ponovljen kirurški postupak Kontuzija
English: To date information beyond two years after VTP procedure is limited and so, at this time, data are currently not available to know whether the benefit of TOOKAD-VTP is long-lasting.
Croatian: Za sada su informacije o razdoblju nakon dvije godine od VTP terapije ograničene i stoga, u ovom trenutku, podaci o dugotrajnoj koristi liječenja TOOKAD-VTP terapijom nisu dostupni.
English: This includes sunbeds, bright computer monitor screens and medical examination lights, such as ophthalmoscopes, otoscopes and endoscopy equipment, for 48 hours following the VTP procedure.
Croatian: To obuhvaća solarije, jarke računalne zaslone i medicinska osvjetljenja pri pregledu kao što su oftalmoskopska, otoskopska i endoskopska oprema tijekom 48 sati nakon primjene VTP terapije.
English: In the few days after the VTP procedure some patients may have difficulties (poor stream due to urethral narrowing) or inability to pass urine.
Croatian: Nekoliko dana nakon VTP terapije neki bolesnici mogu imati poteškoće pri mokrenju (slab mlaz zbog suženja mokraćne cijevi) ili nemogućnost mokrenja.
English: Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Croatian: Unutar svake skupine učestalosti nuspojave su prikazane redoslijedom prema sve manjoj ozbiljnosti.
English: It is used to treat adult men who have low-risk, localised prostate cancer in only one lobe, using a technique called Vascular-Targeted Photodynamic (VTP) therapy.
Croatian: Upotrebljava se za liječenje odraslih muškaraca s niskorizičnim lokaliziranim rakom prostate u samo jednom režnju uporabom tehnike pod nazivom vaskularno ciljana fotodinamička terapija (engl.
English: You may watch television at a distance of 2 metres and, from 6 hours after the procedure, you may use electronic devices such as smartphones, tablets and computers.
Croatian: Dopušteno je gledati televizor s udaljenosti od 2 metra i nakon 6 sati poslije postupka upotrebljavati elektroničke uređaje poput pametnog mobitela, tableta i računala.
English: Retreatment of the same lobe or sequential treatment of the contralateral lobe of the prostate are not recommended (see section 4.4).
Croatian: Ne preporučuje se ponovno liječenje istog režnja ili uzastopno liječenje kontralateralnog režnja prostate (vidjeti dio 4.4).
English: However, a prolongation of photosensitisation is possible and precautions against light exposure should be maintained for an additional 24 hours (see section 4.4).
Croatian: Ipak, moguće je produljenje fotoosjetljivosti i trebaju se poduzeti mjere zaštite od izlaganja svjetlosti dodatna 24 sata (vidjeti dio 4.4).
English: causing local hypoxia that induces the release of nitric oxide (•NO) radicals.
Croatian: 2 ) i uzrokuje lokalnu hipoksiju koja potiče otpuštanje radikala dušikovog oksida (•NO).
English: Healthy subjects have been exposed to doses up to 15 mg/kg of padeliporfin di-potassium (corresponding to 13.73 mg/kg of padeliporfin) without light activation and 23 patients have been treated with 6 mg/kg of padeliporfin di-potassium (corresponding to 5.49 mg/kg of padeliporfin) without significant safety issues.
Croatian: Zdravi ispitanici bili su izloženi dozama do 15 mg/kg padeliporfindikalija (što odgovara dozi od 13,73 mg/kg padeliporfina) bez svjetlosne aktivacije, a 23 bolesnika liječena su dozom od 6 mg/kg padeliporfindikalija (što odgovara dozi od 5,49 mg/kg padeliporfina) bez značajnih sigurnosnih problema.
English: The patient must stay in a dimmed light environment without any direct exposure of the skin and the eyes to daylight.
Croatian: Bolesnik mora ostati u prostoriji s prigušenim svjetlom bez izravnog izlaganja kože i očiju dnevnom svjetlu.
English: The patient should wear protective goggles and be kept under medical surveillance for at least 6 hours in a room with dimmed light.
Croatian: Bolesnik treba nositi zaštitne naočale i ostati pod liječničkim nadzorom barem 6 sati u prostoriji s prigušenim svjetlom.
English: The LDI corresponds to the ratio of the cumulative length of illuminated fibre tips (cm) to the volume (cc) of the targeted zone to be treated.
Croatian: LDI (indeks gustoće svjetlosti) odgovara omjeru kumulativne duljine osvijetljenih vrhova vlakana (cm) i volumenu (cm3) ciljane zone koja se liječi.
English: The recommended dose of TOOKAD is one single dose of 3.66 mg per kg of body weight, injected into a vein.
Croatian: Preporučena doza lijeka TOOKAD je jedna doza od 3,66 mg po kilogramu tjelesne težine, injicirano u venu.
English: The most frequently reported adverse reactions in the Phase II and III clinical studies were urinary and reproductive system disorders: dysuria (25.1 %), erectile dysfunction (21.1 %), haematuria (19.6 %), perineal pain/haematoma (15.3 %), urinary retention (13.3 %), micturition urgency (9.0 %), pollakiuria (7.3 %), urinary tract infection (5.5 %), incontinence (5.3 %) and ejaculation failure
Croatian: Najčešće prijavljene nuspojave u kliničkim ispitivanjima faze II i faze III bili su poremećaji urinarnog i reproduktivnog sustava: dizurija (25,1 %), erektilna disfunkcija (21,1 %), hematurija (19,6 %), perinealna bol / hematomi (15,3 %), urinarna retencija (13,3 %), urgencija (9,0 %), polakizurija (7,3 %), infekcija urinarnog trakta (5,5 %), inkontinencija (5,3 %) i nemogućnost ejakulacije (5,0 %).
English: Any medical condition that precludes the administration of a general anaesthetic or invasive procedures.
Croatian: Svako medicinsko stanje koje isključuje primjenu opće anestezije ili invazivnih postupaka.