natgillin/translations-raw huggingface dataset:
Your doctor will calculate the correct dose for you.
Zdravnik bo izračunal za vas ustrezen odmerek.
The data are from an open-label study and no firm conclusions can be drawn.
Podatki so iz odprte študije, trdnih zaključkov ni mogoče oblikovati.
These secondary endpoints were not adjusted for multiplicity
Ti sekundarni končni cilji niso prilagojeni na multipliciteto.
· The total number of infusions that you will be given depends on how you respond to the treatment and which indication is treated.
· Celotno število infuzij, ki jih boste dobili, bo odvisno od vašega odziva na zdravljenje in od tega, za katero indikacijo se zdravite.
In general, these symptoms were not severe (see section 4.8).
Na splošno ti simptomi niso bili hudi (glejte poglavje 4.8).
In most cases you will not have any symptoms.
Večinoma ne boste imeli zaradi tega nobenih simptomov.
Since the efficacy boundary was crossed at this analysis, this is considered the definitive analysis.
Ker je bila pri tej analizi prekoračena meja učinkovitosti, to velja za dokončno analizo.
· Heart problems can occur.
· Lahko se pojavijo težave s srcem.
See Table 6 and Figure 1.
Glejte preglednico 6 in sliko 1.
· Additional risk minimisation measures
· Dodatni ukrepi za zmanjševanje tveganj
Women who become pregnant must immediately contact their doctor.
Ženske, ki zanosijo, se morajo nemudoma posvetovati s svojim zdravnikom.
Transaminase elevations were generally transient.
Zvišanje transaminaz je bilo na splošno prehodno.
The schedule of administration should be adjusted to maintain a 3-week interval between doses.
Urnik uporabe je treba prilagoditi tako, da se ohrani 3-tedenski presledek med odmerki.
Patients may have received more than one HER2-targeted therapy.
Bolniki so lahko prejeli več kot eno proti HER2 usmerjeno zdravljenje.
Read all of this leaflet carefully before you start being given this medicine because it contains important information for you.
Pred začetkom prejemanja zdravila natančno preberite navodilo, ker vsebuje za vas pomembne podatke!
These symptoms may indicate nerve damage.
Ti simptomi lahko pomenijo okvaro živcev.
This is because there is no information on how well it works in this age group.
Podatkov o tem, kako deluje v tej starostni skupini, namreč ni.
Appropriate procedures for the preparation of chemotherapeutic medicinal products should be used.
Uporabiti je treba ustrezne postopke za pripravo kemoterapevtikov.
Kadcyla is not recommended for anyone under the age of 18 years.
Zdravilo Kadcyla ni priporočljivo za bolnike, mlajše od 18 let.
The next dose should be administered in accordance with the dosing recommendations above.
Naslednji odmerek je treba uporabiti v skladu z zgornjimi priporočili za odmerjanje.
Consideration for re-treatment should be based on clinical assessment of the severity of the reaction.
O ponovnem zdravljenju je treba presoditi glede na klinično oceno tega, kako huda je bila reakcija.
If a planned dose is missed, it should be administered as soon as possible; without waiting until the next planned cycle.
Če je bolnik načrtovani odmerek izpustil, mu ga je treba dati čim prej brez čakanja do naslednjega načrtovanega cikla.
All of the patients had received taxanes as part of neoadjuvant chemotherapy.
Vsi bolniki so prejemali taksane kot del neoadjuvantne kemoterapije.
It is not expected that Kadcyla will affect your ability to drive, cycle, use tools or machines.
Ni pričakovati, da bi zdravilo Kadcyla vplivalo na vašo sposobnost za upravljanje vozil, vožnjo s kolesom ali uporabo orodij ali strojev.
Delayed or missed dose
Zapoznel ali izpuščen odmerek
The requirements for submission of periodic safety update reports for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines webportal.
· Redno posodobljena poročila o varnosti zdravila (PSUR) Zahteve glede predložitve PSUR za to zdravilo so določene v seznamu referenčnih datumov EU (seznamu EURD), opredeljenem v členu 107c(7) Direktive 2001/83/ES, in vseh kasnejših posodobitvah, objavljenih na evropskem spletnem portalu o zdravilih.
The reconstituted product contains no preservative and is intended for single use only.
Pripravljeno zdravilo ne vsebuje konzervansov in je namenjeno samo za enkratno uporabo.
· You will be given one infusion every 3 weeks.
Prejemali boste po eno infuzijo na 3 tedne.
Male patients or their female partners should also use effective contraception.
Tudi moški bolniki ali njihove partnerke morajo uporabljati učinkovito kontracepcijo.
Cases of bleeding events with a fatal outcome have been observed in both MBC and EBC.
Primere krvavitev s smrtnim izidom so zabeležili pri MBC in EBC.
Women may begin breast-feeding 7 months after concluding treatment.
Dojiti lahko začnejo 7 mesecev po koncu zdravljenja.
Most patients will not have symptoms from the heart problems.
Večina bolnikov simptomov zaradi težav s srcem ne bo imela.
· Male patients or their female partners should also use effective contraception.
· Tudi moški bolniki ali njihove partnerke morajo uporabljati učinkovito kontracepcijo.
· Do not throw away any medicines via wastewater or household waste.
· Zdravila ne smete odvreči v odpadne vode ali med gospodinjske odpadke.
An updated RMP should be submitted: · At the request of the European Medicines Agency; · Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.
Posodobljen RMP je treba predložiti: · na zahtevo Evropske agencije za zdravila; · ob vsakršni spremembi sistema za obvladovanje tveganj, zlasti kadar je tovrstna sprememba posledica prejema novih informacij, ki lahko privedejo do znatne spremembe razmerja med koristmi in tveganji, ali kadar je ta sprememba posledica tega, da je bil dosežen pomemben mejnik (farmakovigilančni ali povezan z zmanjševanjem tveganja).
Kadcyla will be stored by the health professionals at the hospital or clinic.
Zdravilo Kadcyla bodo shranjevali zdravstveni delavci v bolnišnici ali ambulanti.
Lonzastrasse CH-3930 Visp Switzerland
Lonzastrasse CH-3930 Visp Švica
The key efficacy analyses were ORR based on independent radiologic review and duration of objective response.
Ključni analizi učinkovitosti sta bila delež objektivnega odgovora na zdravljenje na podlagi neodvisnega radiološkega pregleda in trajanje objektivnega odgovora.
· Swirl the vial gently until completely dissolved.
· Vialo rahlo vrtite, dokler se zdravilo povsem ne raztopi.
Appropriate aseptic technique should be used.
Uporabiti je treba ustrezen aseptični postopek.
· Kadcyla is available in packs containing 1 vial.
· Zdravilo Kadcyla je na voljo v pakiranjih z 1 vialo.
Patients received radiotherapy and/or hormonal therapy concurrent with study treatment as per local guidelines.
Bolniki so prejemali radioterapijo in/ali hormonsko zdravljenje sočasno z raziskovanim zdravljenjem, skladno z lokalnimi smernicami.
· Unexpected bruising and bleeding (such as nose bleeds).
· Nepričakovane modrice in krvavitve (na primer iz nosu).
The results of this descriptive follow-up analysis are consistent with the confirmatory OS analysis.
Rezultati te opisne analize spremljanja so v skladu s potrditveno analizo celokupnega preživetja.
If you develop lung disease your doctor may stop treatment with this medicine.
Če se pri vas pojavi pljučna bolezen, bo zdravnik morda končal zdravljenje s tem zdravilom.
Also you should not breast-feed for 7 months after your last infusion of Kadcyla.
Prav tako ne smete dojiti še 7 mesecev po zadnji infuziji zdravila Kadcyla.
Glucose (5%) solution should not be used for reconstitution or dilution since it causes aggregation of the protein.
Za pripravo ali razredčenje se ne sme uporabljati raztopine glukoze (5-%), ker povzroči agregacijo beljakovine.
These reactions have been observed more frequently within 24 hours of infusion.
Reakcije so pogosteje opažali v 24 urah po infundiranju.
Hierarchical testing applied for IDFS and OS 2.
Hierarhično testiranje se je nanašalo na IDFS in OS.
Kadcyla is not recommended if you are pregnant because this medicine may cause harm to the unborn baby.
Zdravilo Kadcyla ni priporočljivo, če ste noseči, ker lahko škoduje nerojenemu otroku.
The subgroup of patients 75 years or above did not demonstrate a benefit for PFS or OS, but was too small (n=25) to draw any definitive conclusions.
75 let ali več, ni bilo dokazane koristi za PFS ali celokupno preživetje, vendar je bila podskupina premajhna (n = 25), da bi omogočala dokončne sklepe.
Liver function should be monitored prior to initiation of treatment and each dose.
Delovanje jeter je treba kontrolirati pred uvedbo zdravljenja in pred vsakim odmerkom.
Date of latest renewal: 17 September 2018
Datum prve odobritve: 15. november 2013 Datum zadnjega podaljšanja: 17. september 2018
Emtansine refers to the MCC-DM1 complex.
Ime emtanzin se nanaša na kompleks MCC-DM1.
Diagnosis of NRH can be confirmed only by histopathology.
Diagnozo bolezni je mogoče potrditi le histopatološko.
At retreatment a dose reduction may be considered according to the dose reduction schedule (see Table 1).
Ob ponovnem zdravljenju pride v poštev zmanjšanje odmerka v skladu s shemo zmanjševanja odmerka (glejte preglednico 1).
As with all therapeutic proteins, there is the potential for an immune response to trastuzumab emtansine.
Tako kot pri vseh terapevtskih beljakovinah obstaja možnost imunskega odziva tudi na trastuzumab emtanzin.
Glucose (5%) solution should not be used (see section 6.2).
Raztopine glukoze (5-%) se ne sme uporabljati (glejte poglavje 6.2).
· If the first infusion is well tolerated, the infusion on your next visit may be given over 30 minutes.
· Če boste prvo infuzijo dobro prenesli, boste novi odmerek na naslednjem obisku lahko dobili v 30 minutah.
The median age was approximately 49 years (range 23-80 years), 72.8% were White, 8.7% were Asian and 2.7% were Black or African American.
Mediana starost je bila približno 49 let (razpon: od 23 do 80 let), 72,8 % je bilo belcev, 8,7 % azijskega porekla in 2,7 % črncev ali Afroameričanov.
Medicinal products to treat such reactions, as well as emergency equipment, should be available for immediate use.
Za takojšnjo uporabo morajo biti na voljo zdravila za zdravljenje takšnih reakcij in oprema za nujne primere.
3-year event-free rate and 5-year survival rate derived from Kaplan-Meier estimates 3.
Delež 3-letnega obdobja brez dogodka in delež 5-letnega preživetja sta pridobljena iz Kaplan-Meierjevih ocen.
3 weeks (n = 70).
intravensko na 3 tedne (n = 70).
· The first infusion will be given to you over 90 minutes.
· Prvo infuzijo boste dobivali 90 minut.
The initial dose should be administered as a 90 minute intravenous infusion.
Začetni odmerek je treba dati kot 90-minutno intravensko infuzijo.
Early Breast Cancer (EBC)
Zgodnji rak dojk (EBC)
Frequency categories are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).
(≥ 1/100 do < 1/10), občasni (≥ 1/1000 do < 1/100), redki (≥ 1/10.000 do < 1/1000), zelo redki (< 1/10.000) in ni znano (ni mogoče oceniti na podlagi podatkov, ki so na voljo).
Due to the low incidence of ADA, conclusions cannot be made on the impact of anti- trastuzumab emtansine antibodies on the pharmacokinetics, safety, and efficacy of trastuzumab emtansine.
Zaradi nizke incidence ADA ni mogoče sklepati o vplivu protiteles proti trastuzumabu emtanzinu na farmakokinetiko, varnost in učinkovitost trastuzumaba emtanzina.
A cumulative effect on transaminases has also been observed (the proportion of patients with Grade 1-2 ALT/AST abnormalities increases with successive cycles).
Opažali so tudi kumulativni učinek na transaminaze (delež bolnikov z nenormalnimi vrednostmi ALT/AST 1. do 2. stopnje se je v nadaljnjih ciklih povečeval).
· Your skin and whites of your eyes get yellow (jaundice) - these could be signs of severe liver damage.
· Porumenelost kože ali očesnih beločnic (zlatenica) - to so lahko znaki hude jetrne okvare.
Trastuzumab Emtansine N = 743
trastuzumab emtanzin n = 743
Kadcyla can make some existing conditions worse, or cause side effects.
Zdravilo Kadcyla lahko poslabša nekatera obstoječa stanja oz. bolezni ali povzroči neželene učinke.
· If you experience side effects, your doctor may decide to continue your treatment but lower your dose, delay the next dose or stop the treatment.
· Če se pri vas pojavijo neželeni učinki, se zdravnik lahko odloči za nadaljevanje zdravljenja z manjšim odmerkom, za odložitev naslednjega odmerka ali za prenehanje zdravljenja.
In general, the Grade ≥ 3 hepatic events were not associated with poor clinical outcome; subsequent follow-up values tended to show improvement to ranges allowing the patient to remain on study and continue to receive study treatment at the same or reduced dose.
Na splošno jetrni dogodki ≥ 3. stopnje niso bili povezani s slabim kliničnim izidom; nadaljnje vrednosti med spremljanjem so se praviloma izboljšale do mere, ki je bolnikom omogočala nadaljevanje študijskega zdravljenja in še naprej prejemati raziskovano zdravilo v enakem ali manjšem odmerku.
Your doctor will monitor you for signs and symptoms of neurological problems.
Zdravnik bo preverjal možnosti znakov in simptomov nevroloških težav.
Dose reductions or discontinuation for increased serum transaminases and total bilirubin are specified in section 4.2.
Zmanjšanja odmerkov ali prenehanje zdravljenja pri zvišanju serumskih transaminaz in celokupnega bilirubina je opredeljeno v poglavju 4.2.
Kadcyla (trastuzumab emtansine) is NOT a generic version of Herceptin (trastuzumab) and has different properties, indications and dose.
Kadcyla (trastuzumab emtanzin) NI generična različica zdravila Herceptin (trastuzumaba) in ima različne lastnosti, indikacije in odmerek.
Results from in vitro cytotoxicity assays show that DM1 is 20-200 times more potent than taxanes and vinca alkaloids.
Rezultati citotoksičnih preizkusov in vitro kažejo, da je DM1 od 20- do 200-krat močnejši od taksanov in alkaloidov vinke.
The study compared the safety and efficacy of trastuzumab emtansine with that of lapatinib plus capecitabine.
Študija je primerjala varnost in učinkovitost trastuzumaba emtanzina s kombinacijo lapatiniba in kapecitabina.
If you forget or miss your Kadcyla appointment, make another appointment as soon as possible.
Če pozabite priti na dajanje zdravila Kadcyla oziroma ga izpustite, se čim prej dogovorite za drug termin.
In vitro, DM1 was a substrate of P-glycoprotein (P-gp).
In vitro je bil DM1 substrat P-glikoproteina (P-gp).
The majority of events were asymptomatic Grade 1 or 2 decrease in LVEF.
V večini primerov so bila asimptomatska zmanjšanja LVEF 1. ali 2. stopnje.
ADRs were reported using NCI-CTCAE for assessment of toxicity.
Neželeni učinki so bili evidentirani po NCI-CTCAE za oceno toksičnosti.
Kadcyla is for intravenous use.
Zdravilo Kadcyla je namenjeno intravenski uporabi.
The European Medicines Agency has waived the obligation to submit the results of studies with trastuzumab emtansine in all subsets of the paediatric population in breast cancer (see section 4.2 for information on paediatric use).
Evropska agencija za zdravila je odstopila od zahteve za predložitev rezultatov študij s trastuzumabom emtanzinom za vse podskupine pediatrične populacije pri raku dojk (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
Requirement for further dose reduction
Potreba po nadaljnjem zmanjšanju odmerka
IDFS was defined as the time from the date of randomization to first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause.
IDFS je bilo opredeljeno kot čas od datuma randomizacije do prvega pojava istostranske ponovitve invazivnega tumorja dojk, istostranske lokalne ali regionalne ponovitve invazivnega raka dojk, oddaljene ponovitve, invazivnega raka dojk na nasprotni strani ali smrti zaradi kakršnega koli vzroka.
Kadcyla will be given to you by a doctor or nurse in a hospital or clinic: · It is given by a drip into a vein (intravenous infusion).
Zdravilo Kadcyla vam bo dal zdravnik ali medicinska sestra v bolnišnici ali ambulanti: Zdravilo boste dobili s kapalno (intravensko infuzijo) v veno.
It is not known whether the ingredients in Kadcyla pass into breast-milk.
Ni znano, ali sestavine zdravila Kadcyla prehajajo v materino mleko.
The median duration of response by IRC was not reached (95% CI, 4.6 months to not estimable).
Mediano trajanje odgovora na zdravljenje po IRC ni bilo doseženo (95-% interval zaupanja: 4,6 mesecev do neocenljivo).
Additional endpoints included IDFS including second primary non-breast cancer, disease-free survival (DFS), overall survival (OS), and distant recurrence-free interval (DRFI).
Dodatni končni cilji so obsegali IDFS (vključno z drugim primarnim rakom, ki ni bil rak dojk), preživetje brez bolezni (DFS - disease-free survival), celokupno preživetje (OS) in interval brez oddaljene ponovitve (DRFI - distant recurrence-free interval).
What Kadcyla is and what it is used for 2.
Kaj je zdravilo Kadcyla in za kaj ga uporabljamo 2.
Peripheral Neuropathy Grade 3-4
Periferna nevropatija 3.-4. stopnja
Patients should be observed closely for infusion-related reactions, especially during the first infusion.
Bolnike je treba natančno opazovati zaradi možnih reakcij, povezanih z infundiranjem, zlasti med prvim infundiranjem.
· DM1 - an anti-cancer substance that becomes active once Kadcyla enters the cancer cell.
· DM1 - to je učinkovina proti raku, ki postane aktivna, ko zdravilo Kadcyla vstopi v rakavo celico.
Table 3 shows pooled data from the overall treatment period in the MBC studies (N= 1871; median number of cycles of trastuzumab emtansine was 10) and in KATHERINE (N=740; median number of cycles was 14).
Preglednica 3 prikazuje združene podatke iz celotnega obdobja zdravljenja v študijah MBC (n = 1871; mediano število ciklov trastuzumaba emtanzina je bilo 10) in v študiji KATHERINE (n = 740; mediano število ciklov je bilo 14).
Overall, the majority of hypersensitivity reactions were mild or moderate in severity and resolved upon treatment.
V celoti je bila večina preobčutljivostnih reakcij blagih ali zmernih in so med zdravljenjem izginile.
A change of 5 points in the TOI-B is considered clinically significant.
TOI-B velja za klinično pomembno.
· The other ingredients are succinic acid, sodium hydroxide (see section 2 under ‘Important information about some of the ingredients of Kadcyla'), sucrose, and polysorbate 20.
· Druge sestavine zdravila so sukcinska kislina, natrijev hidroksid (glejte poglavje 2 Pomembne informacije o nekaterih sestavinah zdravila Kadcyla), saharoza in polisorbat 20.
Patients should be observed closely for hypersensitivity/allergic reactions, which may have the same clinical presentation as an IRR.
Bolnike je treba skrbno opazovati zaradi možnosti pojava preobčutljivostnih/alergijskih reakcij, ki imajo lahko enako klinično sliko kot reakcije, povezane z infundiranjem.
The significance of reported adverse reactions such as fatigue, headache, dizziness and blurred vision on the ability to drive or use machines is unknown.
Pomen opisanih neželenih učinkov, kot so utrujenost, glavobol, omotica in zamegljen vid, na sposobnost vožnje in upravljanja s stroji ni znan.
Discard any unused portion.
Ves neporabljeni del zavrzite.
When trastuzumab binds to HER2 it can stop the cancer cells growth and cause them to die.
Ko se trastuzumab veže na HER2, zaustavi rast teh celic in povzroči njihovo smrt.
These may be signs of inflammation of your lung, which may be serious, and even fatal.
To so lahko znaki vnetja pljuč, ki je lahko resno in se lahko konča celo s smrtjo.
Table 6 Summary of efficacy from study BO27938 (KATHERINE) Trastuzumab N = 743
Preglednica 6: Povzetek učinkovitosti iz študije BO27938 (KATHERINE) trastuzumab n = 743
Do not freeze or shake the infusion during storage.
Infuzije med shranjevanjem ne smete zamrzniti ali stresati.
Your doctor or nurse will check to see whether you are having any of these side effects.
Zdravnik ali medicinska sestra bosta preverjala, ali imate katerega od teh neželenih učinkov.
The decision to administer trastuzumab emtansine in MBC patients with low LVEF must be made only after careful benefit risk assessment and cardiac function should be closely monitored in these patients (see section 4.8).
Odločitev o uporabi trastuzumaba emtanzina pri bolnikih z MBC in nizkim LVEF se lahko sprejme šele po natančni oceni tveganja in koristi; pri teh bolnikih je treba skrbno spremljati delovanje srca (glejte poglavje 4.8).
If a patient requires 2 delays due to thrombocytopenia, consider reducing dose by one level.
Če bolnik zaradi trombocitopenije potrebuje 2 zapoznitvi odmerka, pride v poštev zmanjšanje odmerka za eno stopnjo.
What you need to know before you are given Kadcyla 3.
Kaj morate vedeti, preden boste dobili zdravilo Kadcyla 3.
Tumor prognostic characteristics including hormone receptor status (positive: 72.3%, negative: 27.7%), clinical stage at presentation (inoperable: 25.3%, operable: 74.8%) and pathological nodal status after preoperative therapy (node positive: 46.4%, node negative or not evaluated: 53.6%) were similar in the study arms.
Tumorske prognostične značilnosti so vključevale stanje hormonskih receptorjev (pozitivno: 72,3 %, negativno 27,7 %), klinični stadij ob postavitvi diagnoze (neoperabilen: 25,3 %, operabilen 74,8 %) in patološko stanje bezgavk po predoperativnem zdravljenju (pozitivne bezgavke: 46,4 %, negativne bezgavke ali neocenjeno: 53,6 %) in so bile v skupinah študije podobne.
If not used immediately, the reconstituted vials can be stored for up to 24 hours at 2°C to 8°C, provided it was reconstituted under controlled and validated aseptic conditions, and must be discarded thereafter.
Če ga ne uporabimo takoj, je mogoče pripravljene viale shranjevati do 24 ur pri temperaturi od 2 do 8 °C, če je bilo zdravilo pripravljeno v nadzorovanih in preverjenih aseptičnih pogojih, po tem pa ga je treba zavreči.
If a pregnant woman is treated with trastuzumab emtansine, close monitoring by a multidisciplinary team is recommended.
Če noseča ženska dobiva trastuzumab emtanzin, je priporočljivo, da jo natančno spremlja multidisciplinarna strokovna skupina.
In KATHERINE, consistent treatment benefit of trastuzumab emtansine for IDFS was seen in all the pre-specified subgroups evaluated, supporting the overall result.
V študiji KATHERINE so konsistentno korist zdravljenja s trastuzumabom emtanzinom za IDFS ugotovili v vseh vnaprej opredeljenih ocenjenih podskupinah, kar potrjuje celokupen rezultat.
It must be verified that the non-proprietary name is trastuzumab emtansine.
Preveriti je treba, da je nezaščiteno ime trastuzumab emtanzin.
If the prior infusion was well tolerated, subsequent doses of trastuzumab emtansine may be administered as 30 minute infusions.
Če je bolnik predhodno infuzijo dobro prenesel, je mogoče poznejše odmerke trastuzumaba emtanzina dati kot 30-minutno infuzijo.
In most patients, these reactions resolved over the course of several hours to a day after the infusion was terminated.
Pri večini bolnikov so reakcije minile v nekaj urah do enega dneva po koncu infundiranja.
In some of the observed cases the patients had thrombocytopenia, or were also receiving anti-coagulant therapy or antiplatelet therapy; in others there were no known additional risk factors.
V nekaterih od opaženih primerov so imeli bolniki trombocitopenijo ali pa so prejemali tudi antikoagulantno ali antitrombotično zdravljenje, pri drugih pa ni bilo znanih dodatnih dejavnikov tveganja.