natgillin/translations-raw huggingface dataset:
The preliminary results of the HPS2-THRIVE study showed that the study did not meet its primary endpoint (reduction of the risk of major vascular events such as heart attack and stroke) as well as a statistically significant increase in the incidence of non-fatal but serious adverse events in the nicotinic acid/laropiprant group compared to the placebo group. 
Predhodni rezultati študije HPS2-THRIVE so pokazali, da ni bil dosežen primarni cilj študije (zmanjšanje tveganja za večje vaskularne dogodke, kot sta srčna ter možganska kap) in da se je v skupini z nikotinsko kislino/laropiprantom v primerjavi s skupino s placebom statistično značilno povečala incidenca neželenih učinkov, ki so se sicer končali brez smrtnega izida, vendar so bili resni.
• The PRAC considered that acipimox is efficacious in reducing triglyceride levels in patients with hypertriglyceridaemia (Fredrickson type IV hyperlipoproteinaemia) and with hypercholesterolaemia and hypertriglyceridaemia (Fredrickson type IIb hyperlipoproteinaemia) but only, on the basis of available evidence including current medical knowledge on the use of acipimox, as a second or third line agent in patients who have not responded adequately to other treatments such as statin or fibrate treatment; 
• PRAC je menil, da je acipimoks učinkovit pri zniževanju ravni trigliceridov pri bolnikih s hipertrigliceridemijo (hiperlipoproteinemijo tipa IV po Fredricksonu) ter bolnikih s hiperholesterolemijo in hipertrigliceridemijo (hiperlipoproteinemijo tipa IIb po Fredricksonu), vendar, kot kažejo razpoložljivi dokazi, vključno s trenutnim medicinskim znanjem o uporabi acipimoksa, samo kot zdravilo druge ali tretje izbire pri bolnikih, ki se niso ustrezno odzvali na zdravljenje z drugimi zdravili, kot so statini ali fibrati;
The PRAC, as a consequence, concluded that the benefit-risk balance of the medicinal products containing acipimox identified in Annex I remains favourable, subject to the agreed changes to the product information. 
Posledično je PRAC zaključil, da je razmerje med tveganji in koristmi zdravil, ki vsebujejo acipimoks in so navedena v Prilogi I, še naprej ugodno pod pogojem, da se upoštevajo dogovorjene spremembe informacij o zdravilu.
The CMDh considered the below PRAC recommendation dated 7 November 2013 with regard to substances related to nicotinic acid (acipimox) indicated for the treatment of lipid disorders. 
Skupina CMDh je preučila spodnje priporočilo odbora PRAC z dne 7. novembra 2013 glede učinkovin, sorodnih nikotinski kislini (acipimoks), ki so indicirane za zdravljenje lipidnih motenj.
Based on the available data, acipimox was considered to be efficacious in reducing triglyceride levels in patients with hypertriglyceridaemia (Fredrickson type IV hyperlipoproteinaemia) and significantly superior to placebo in patients with hypercholesterolaemia and hypertriglyceridaemia (Fredrickson type IIb hyperlipoproteinaemia). 
Na podlagi razpoložljivih podatkov je zaključil, da je acipimoks učinkovit pri zniževanju ravni trigliceridov pri bolnikih s hipertrigliceridemijo (hiperlipoproteinemijo tipa IV po Fredricksonu) in veliko učinkovitejši od placeba pri bolnikih s hiperholesterolemijo in hipertrigliceridemijo (hiperlipoproteinemijo tipa IIb po Fredricksonu).
However, taking into account the available data as well as the current use of the product and on the basis of expert advice, the PRAC was of the opinion that acipimox should only be used to reduce triglyceride levels in patients who either do not tolerate statin or fibrates or who do not achieve triglyceride goals with statin or fibrate therapy alone and should therefore be used as an alternative or adjunct treatment to reduce triglyceride levels in these patients. 
Vendar pa je ob upoštevanju razpoložljivih podatkov, trenutne uporabe zdravila in izvedenskega svetovanja menil, da se lahko acipimoks uporablja samo za zniževanje ravni trigliceridov pri bolnikih, ki ne prenašajo statinov ali fibratov, in bolnikih, pri katerih samo s statini ali fibrati ni mogoče doseči želenih ravni trigliceridov, kar pomeni, da se lahko uporablja kot alternativno ali dodatno zdravilo za zniževanje ravni trigliceridov pri teh bolnikih.
It was noted that acipimox was of particular use in patients who either do not tolerate a statin or do not achieve triglyceride goals with statin therapy alone and could therefore be used as an alternative or adjunct treatment to reduce triglyceride levels in these patients. 
Upošteval je, da se acipimoks uporablja predvsem pri bolnikih, ki ne prenašajo statinov, in bolnikih, pri katerih samo s statini ni mogoče doseči želenih ravni trigliceridov, kar pomeni, da se lahko uporablja kot alternativno ali dodatno zdravilo za zniževanje ravni trigliceridov pri teh bolnikih.
No new significant information was identified regarding this risk. 
V zvezi s tem tveganjem niso bile odkrite nobene pomembne nove informacije.
The medicinal products will continue to be listed in the additional monitoring list. 
Zdravila bodo še naprej na seznamu za dodatno spremljanje.
Although several limitations exist, the study suggests that there was some transgenerational effect. 
Čeprav obstaja več omejitev, študija kaže, da je prisoten določen transgeneracijski učinek.
In the previous European review (2014)3, several educational measures for patients and healthcare professionals (HCPs) were recommended. 
V prejšnjem evropskem pregledu (2014)3 je bilo priporočenih več izobraževalnih ukrepov za bolnike in zdravstvene delavce.
The PRAC adopted a recommendation on 08 February 2018 which was then considered by the CMDh, in accordance with Article 107k of Directive 2001/83/EC. 
Odbor PRAC je 8. februarja 2018 sprejel priporočilo, ki ga je nato v skladu s členom 107k Direktive 2001/83/ES obravnavala skupina CMDh.
• The Pharmacovigilance Risk Assessment Committee (PRAC) considered the procedure under Article 31 of Directive 2001/83/EC for medicinal products containing substances related to valproate. 
• Odbor za oceno tveganja na področju farmakovigilance (PRAC) je obravnaval postopek v skladu s členom 31 Direktive 2001/83/ES za zdravila, ki vsebujejo valproatu sorodne snovi.
In addition all products should have in place a risk management plan. 
Poleg tega mora biti pri vseh zdravilih vzpostavljen načrt za obvladovanje tveganja.
From these consultations it was evident that the specialists are aware of the risks discussed, but the information is not adequately reaching the patients timely and effectively. 
Iz teh posvetovanj je bilo jasno, da se specialisti zavedajo omenjenih tveganj, vendar informacije do bolnikov ne pridejo pravočasno in učinkovito.
In addition to the boxed text this may include a symbol/pictogram, with the details to be adapted at national level. 
Poleg besedila v okvirčku lahko to vključuje simbol/piktogram s podrobnostmi, ki jih je treba prilagoditi na nacionalni ravni.
For the following risk minimisation measures, the CMDh clarified that: 
Pri ukrepih za zmanjševanje tveganj, navedenih v nadaljevanju, je skupina CMDh pojasnila naslednje:
This resulted in a value which was more than 25,000 times lower than the AUC in a woman treated orally with an equal dose (single oral dose 500 mg). 
Rezultat je bila vrednost, ki je bila 25 000-krat nižja od AUC pri ženski, peroralno zdravljeni z enakim odmerkom (enkratnim peroralnim odmerkom 500 mg).
The PRAC requested the conduct of a retrospective observational study to further characterise this theoretical risk. 
Odbor PRAC je zahteval izvedbo retrospektivne opazovalne študije za nadaljnje določanje tega teoretičnega tveganja.
They also provided experience from clinical practice on the management of women who wish to become pregnant or are pregnant. 
Podane so bile tudi izkušnje iz klinične prakse obravnavanja žensk, ki si želijo zanositi ali so noseče.
This included the responses submitted by the marketing authorisation holders in writing as well as the outcomes of the scientific advisory groups in neurology and psychiatry. 
To je vključevalo tudi odzive, ki so jih pisno predložili imetniki dovoljenja za promet z zdravilom ter zaključke znanstvenih svetovalnih skupin s področja nevrologije in psihiatrije.
Several tests for chromosome damage were positive. 
Več preskušanj okvar kromosomov je bilo pozitivnih.
Further investigation is recommended by PRAC. 
Odbor PRAC priporoča nadaljnje preiskave.
An early communication of complete information about the risks of valproate is considered essential. 
Velja, da je bistveno zgodnje sporočanje popolnih informacij o tveganjih valproata.
However, tests for gene mutations were negative. 
Vendar so bili preskusi mutacij genov negativni.
This was not shown for teratogenic effects as malformations in the first generation offspring was not observed in the second and third generation offspring (Choi et al, 2016)2. 
Za teratogene učinke to ni bilo dokazano, saj okvar iz prve generacije potomcev v drugi in tretji generaciji niso opazili (Choi et al., 2016)2.
The use of effective contraception without interruption during the all course of treatment should be included as well as a reminder for annual re-assessment. 
Vključiti je treba uporabo učinkovite kontracepcije brez prekinitve med celotnim potekom zdravljenja ter opomnik o letnem ponovnem ocenjevanju.
Having reviewed the PRAC recommendation, the CMDh agrees with the PRAC overall conclusions and grounds for recommendation. 
Po pregledu priporočila odbora PRAC se je skupina CMDh strinjala s končnimi zaključki odbora PRAC in s podlago za priporočilo.
There is no clear evidence that mitochondrial dysfunction caused by valproate is associated with the development of autism. 
Ni jasnega dokaza o tem, da je mitohondrijska disfunkcija, ki jo povzroča valproat, povezana z razvojem avtizma.
Nevertheless, as shown in the data reviewed in this procedure educational measures did not reach the targeted audience in a satisfactory rate in order to have any significant impact on prescriptions. 
Kot dokazujejo podatki, pregledani pri tem postopku, izobraževalni ukrepi kljub temu niso dosegli predvidene publike v zadostni meri, da bi kakor koli pomembno vplivali na predpisovanje.
Severe chromosome damage is expected to lead to death of sperm cells / reduced fertility and not to transmission of mutations to the offspring. 
Pričakovano je, da hude okvare kromosomov vodijo k odmrtju celic spermijev/zmanjšani plodnosti in ne k prenosu mutacij na potomce.
With regards to the patient card, the CMDh clarifies that the information is intended to act as a reminder for long-term use of valproate. 
V zvezi s kartico za bolnika skupina CMDh pojasnjuje, da so informacije predvidene kot opomnik za dolgotrajno uporabo valproata.
In addition, the PRAC considered the views of patient organisations, patients, families and carers, and the views of healthcare professionals in a public hearing and dedicated meeting. 
Poleg tega je odbor PRAC upošteval tudi stališča organizacij bolnikov, družin in skrbnikov ter stališča zdravstvenih delavcev, izražena v javni obravnavi in na temu namenjenem sestanku.
The PRAC re-iterate that a single version of educational materials is disseminated in each member state, where appropriate. 
PRAC znova izjavlja, da je treba v vseh državah članicah, v katerih je to smiselno, razdeljevati enotno različico izobraževalnega gradiva.
Every effort should be made to switch to appropriate alternative treatment prior to conception, and before contraception is discontinued. 
Treba je storiti vse potrebno za prehod na ustrezno drugo zdravilo pred spočetjem in pred prekinitvijo jemanja kontracepcije.
The potential impact of paternal use of valproate, the potential effect on the third generation offspring and the potential effects on mitochondria (mitochondrial toxicity) were discussed. 
Razpravljali so o morebitnem vplivu uporabe valproata pri očetu, morebitnem vplivu na tretjo generacijo potomcev in morebitnem vplivu na mitohondrije (mitohondrijski toksičnosti).
The MAHs are strongly encouraged to collaborate on the requested measures and to perform joint studies. 
Imetnikom dovoljenja za promet z zdravilom zelo priporočamo, da sodelujejo pri zahtevanih ukrepih in izvajajo skupne študije.
In addition to the measures to increase awareness about risks of valproate, the different expert consultations provided clear recommendations to restrict the use of valproate. 
Poleg ukrepov za krepitev zavedanja o tveganjih valproata so bila prek posvetovanj z različnimi strokovnjaki podana jasna priporočila za omejevanje uporabe valproata.
Genetic changes can be divided in gene mutations and chromosome aberrations. 
Genetske spremembe je mogoče razdeliti v mutacije genov in kromosomske aberacije.
This guide should be handed over to the patient. 
Ta vodnik je treba predati bolnici.
Core elements of a direct healthcare professional communication were agreed, together with the timelines for its distribution. 
Dogovorili so se o bistvenih elementih neposrednih sporočil za zdravstvene delavce in časovnih okvirih za njihovo razširjanje.
In view of the safety issues in discussion and the whole set of conditions for the risk minimisation aiming at minimising exposure in pregnancy, all MAHs need to have in place a risk management plan. 
Ob upoštevanju varnostnih vprašanj pri razpravi in celotnega nabora pogojev za zmanjševanje tveganja, ki so namenjeni zmanjševanju tveganja za nosečnost, morajo imeti vsi imetniki dovoljenja za promet z zdravilom vzpostavljen načrt za obvladovanje tveganja.
For their use in the treatment of bipolar disorders and prophylaxis of migraine these products are contraindicated in pregnancy. 
Za uporabo pri zdravljenju bipolarnih motenj in profilaksi migrene so ta zdravila v nosečnosti kontraindicirana.
The PRAC taking into account all the evidence as well the areas where information is limited requested several measures in order to further characterise the risks, increase the awareness of the risks, restrict the use and measure the effectiveness of the currently proposed measures. 
Ob upoštevanju vseh dokazov in področij, na katerih so informacije omejene, je odbor PRAC zahteval več ukrepov za nadaljnje prepoznavanje tveganj, povečanje zavedanja o tveganjih ter omejevanje uporabe in merjenje učinkovitosti trenutno predlaganih ukrepov.
Furthermore, in a literature overview regarding effects on mitochondria, known side effects were described such as liver toxicity, Reye-like syndrome, pancreatitis and immune deficiency (leukopenia). 
Poleg tega so bili v pregledu literature o učinkih na mitohondrije opisani znani neželeni učinki, kot so toksičnost za jetra, Reyevemu podoben sindrom, pankreatitis in imunska pomanjkljivosti (levkopenija).
The epigenetic mechanism refers to the possibility that changes in the gene expression in the gametes are transmitted to the gene expression in the embryo (for example by changes in DNA methylation). 
Epigenetski mehanizem se nanaša na možnost, da se spremembe izražanja genov v gametah prenašajo na izražanje genov v zarodku (na primer s spremembami metilacije DNA).
In one experiment it was shown that a change in gene expression (one gene) in male mice after exposure to a histone deacetylases (HDAC) inhibitor (not valproate) was observed also in the offspring of these mice (Jia et al, 2015)1, so possible in principle. 
V enem preskusu so dokazali, da je spremembo izražanja genov (enega gena) pri mišjih samcih po izpostavljenosti zaviralcu histonske deacetilaze (HDAC) (ne pri valproatu) mogoče opaziti tudi pri potomcih teh miši (Jia et al., 2015)1, zato je načeloma možna.
The PRAC is of the opinion that the currently available data do not warrant further investigation regarding the potential association between mitochondrial dysfunction and autism. 
Na podlagi podatkov, ki so trenutno na voljo, odbor PRAC meni, da nadaljnje raziskovanje morebitne povezave med mitohondrijsko disfunkcijo in avtizmom ni upravičeno.
In the course of the consultations that PRAC had in this procedure, some additional concerns have arisen, other than the well-known and documented harm to the foetus during in utero exposure. 
Med posvetovanji, ki jih je odbor PRAC opravil v tem postopku, se je poleg dobro znanih in dokumentiranih škodljivih učinkov na plod med izpostavljenostjo in utero pojavilo nekaj dodatnih pomislekov.
• For their use in pregnancy for the treatment of epilepsy, the PRAC concluded that these medicinal products are contraindicated unless there is no suitable alternative treatment option. 
• Pri uporabi teh zdravil za zdravljenje epilepsije med nosečnostjo je odbor PRAC zaključil, da so kontraindicirana, razen če ni druge primerne možnosti zdravljenja.
As the injectable formulations are indicated only for short use, the patient card is most likely to be of limited value. 
Ker so farmacevtske oblike za injiciranje indicirane le za kratkotrajno uporabo, ima kartica za bolnika najverjetneje le omejen pomen.
The PRAC therefore recommends that other tests could be performed (e.g. in vitro mouse lymphoma assay) to further explore this hypothesis. 
Odbor PRAC zato priporoča, da bi se za nadaljnjo raziskovanje te hipoteze lahko opravila druga preskušanja (npr. in vitro mišji limfomski preskus).
On 08 March 2017 France triggered a procedure under Article 31 of Directive 2001/83/EC, and requested the PRAC to assess the impact on the concerns regarding the effectiveness of the risk minimisation measures on the benefit-risk balance of medicinal products containing substances related to valproate and issue a recommendation on whether the marketing authorisation(s) of these products should be maintained, varied, suspended or revoked. 
Francija je 8. marca 2017 sprožila postopek v skladu s členom 31 Direktive 2001/83/ES in svetovalni odbor za oceno tveganja na področju farmakovigilance (PRAC) zaprosila, naj oceni utemeljenost pomislekov v zvezi z učinkovitostjo ukrepov za minimizacijo tveganja na razmerje med tveganji in koristmi zdravil, ki vsebujejo valproatu sorodne snovi, ter izda priporočilo, ali naj se dovoljenje(-a) za promet z zdravilom ohrani(-jo), spremeni(-jo), začasno umakne(-jo) ali prekliče(-jo).
The MAHs are encouraged to collaborate and liaise with the national competent authorities to facilitate the dissemination of the agreed educational material. 
Imetnike dovoljenja za promet z zdravilom se spodbuja, da za lažje razširjanje dogovorjenega izobraževalnega gradiva sodelujejo s pristojnimi nacionalnimi organi in se povežejo z njimi.
Regarding exposure via seminal fluid, estimation was made of the area under curve (AUC) for valproate in a woman following vaginal exposure to valproate via seminal fluid of a man treated with valproate. 
V zvezi z izpostavljenostjo prek semenske tekočine je bilo za valproat ocenjena površina pod krivuljo („area under curve“ - AUC) pri ženski po vaginalni izpostavljenosti valproatu prek semenske tekočine moškega, zdravljenega z valproatom.
The current ongoing drug utilisation study (DUS) should be adapted and continued to assess the effectiveness of the updated risk minimisation measures including the pregnancy prevention programme conditions and to further characterise the prescribing patterns for valproate. 
Študijo o uporabi zdravil (DUS), ki trenutno poteka, je treba prilagoditi in še naprej ocenjevati učinkovitost posodobljenih ukrepov za zmanjševanje tveganj, vključno s pogoji programa za preprečevanje nosečnosti, ter še naprej prepoznavati vzorce predpisovanja valproata.
PRAC also recommended postauthorisation studies to assess the effectiveness of the risk minimisation measures. 
Odbor PRAC je priporočil tudi študije po izdaji dovoljenja za promet z zdravilom za oceno učinkovitosti ukrepov za zmanjševanje tveganj.
It seems theoretically possible that gene mutations in sperm cells could be transmitted to the offspring. 
Teoretično se zdi mogoče, da bi se mutacije genov v celicah spermijev lahko prenesle na potomce.
It was shown in a transgenerational experiment in mice that administration of valproate during pregnancy (day 10) produced autism-like symptoms and increased expression of several proteins in the brains up to the third generation offspring. 
V transgeneracijskem preskusu pri miših so dokazali, da je dajanje valproata med brejostjo (10. dan) povzročilo avtizmu podobne simptome in povečano izražanje več proteinov v možganih vse do tretje generacije potomcev.
• The PRAC concluded that the minimisation measures for medicinal products containing valproate or related substances should be strengthened through contraindication in all indications (epilepsy, bipolar disorders and prophylaxis of migraine) in women/girls of childbearing potential unless the conditions of the pregnancy prevention programme are complied with. 
• Odbor PRAC je sklenil, da je treba ukrepe za zmanjševanje tveganj za zdravila, ki vsebujejo valproat ali sorodne snovi, poostriti s kontraindikacijami pri vseh indikacijah (epilepsiji, bipolarnih motnjah in profilaksi migrene) pri ženskah/dekletih v rodni dobi, razen če so upoštevani pogoji programa za preprečevanje nosečnosti.
• The PRAC concluded that the risk minimisation measures in place have not been sufficiently effective to prevent unintended in utero exposure to valproate and related substances in all indications. 
• Odbor PRAC je zaključil, da vzpostavljeni ukrepi za zmanjševanje tveganj niso bili dovolj učinkoviti, da bi pri vseh indikacijah preprečili izpostavljenost in utero valproatu in sorodnim snovem.
Among the requests from the patients and family members who were consulted was the implementation of a visual reminder on the outer package to warn the women on the harm to the unborn baby and to also promptly advise them to use effective contraception. 
Med zahtevami bolnic in družinskih članov, s katerimi so bili opravljeni posveti, je bila uvedba vizualnega opomnika na zunanji ovojnini, da so ženske opozorjene na škodo za nerojenega dojenčka in da jim je pravočasno svetovana uporaba učinkovite kontracepcije.
The PRAC recommended that a patient card to be made available in all MSs and for all patients who receive valproate. 
Odbor PRAC je priporočil, da je treba v vseh državah članicah in za vse bolnike, ki prejemajo valproat, priskrbeti kartice za bolnika.
With regards to the other pharmacovigilance activities and the studies are required to further investigate potential risks with products containing valproate and related substances and to measure the effectiveness of the RMMs, the CMDh clarified that these studies would not be relevant for the injectable products as the information that could be collected for these products would be limited and unlikely to be meaningful in view of the short duration of use, often in urgent situations and only when the oral formulations cannot be administered. 
V zvezi z drugimi dejavnostmi na področju farmakovigilance in potrebnimi študijami za dodatno raziskavo morebitnih tveganj pri zdravilih, ki vsebujejo valproat in sorodne snovi, in za merjenje učinkovitosti ukrepov za zmanjševanje tveganj je skupina CMDh pojasnila, da te študije ne bi bile relevantne za zdravila za injiciranje, saj bi bile informacije, ki bi jih bilo mogoče za ta zdravila zbrati, omejene in najverjetneje ne bi imele pomena glede na kratkotrajnost uporabe, do katere pogosto pride v nujnih situacijah in le, če peroralnih farmacevtskih oblik ni mogoče uporabiti.
• The PRAC also reviewed the available scientific evidence on the risk of malformations and neurodevelopmental disorders to offspring after paternal exposure, the risk of malformations and neurodevelopmental disorders to the third generation offspring and considered that further research is needed before conclusions can be drawn. 
• Odbor PRAC je pregledal tudi razpoložljive znanstvene dokaze o tveganju za okvare in motnje razvoja živčevja pri potomcih po izpostavljenosti pri očetu ter tveganju za okvare in motnje živčevja pri potomcih tretje generacije in menil, da so potrebne dodatne raziskave, preden bo mogoče priti do zaključkov.
Additionally, such patient card is to be attached to the packaging of valproate and related substances containing medicines, and serve as an additional reminder during the dispensing. 
Poleg tega je treba takšno kartico za bolnika pritrditi na ovojnino zdravil, ki vsebujejo valproat in sorodne snovi, služi pa kot dodatno opozorilo med izdajanjem.