natgillin/translations-raw huggingface dataset:
Almost all cases were serious (93% of the cases where seriousness was reported) and treatment with dihydroergotamine was discontinued in 91% of the cases (for which information is available) and in 57% of these cases, the outcome has been reported as improved or recovered. 
Gotovo svi slučajevi su bili ozbiljni (u 93% slučajeva prijavljena je ozbiljnost) te je prekinuto liječenje dihidroergotaminom u 91% slučajeva (za koje su dostupne informacije), a u 57% ovih slučajeva kao ishodi su prijavljeni poboljšanje ili oporavak.
• The Committee considered that a potential causal association between fibrotic reactions or ergotism and oral dihydroergotamine cannot be excluded. 
• Povjerenstvo smatra da se ne mogu isključiti potencijalne kauzalne poveznice između fibrotičkih reakcija ili ergotizma i oralnog dihidroergotamina.
A post-hoc analysis was performed in the sub-group of patients (n=288) with functional handicap and quality of life (QOL) decrease (defined by Migraine Specific Quality of Life, MSQ<80). 
Izvršena je post-hoc analiza u podgrupi bolesnika (n=288) s funkcionalnim hendikepom i smanjenom kvalitetom života (QOL) (definirano kvalitetom života specifičnom za migrenu, MSQ<80).
• The Committee considered the procedure under Article 31 of Directive 2001/83/EC for ergot derivatives containing medicinal products in the concerned indications. 
• Povjerenstvo je razmotrilo postupak sukladno članku 31. Direktive 2001/83/EC za lijekove koji sadrže derivate ergota u predmetnim indikacijama.
In order to lift the suspension, MAHs must identify a specific patient population for which the benefits of the product outweigh the risk. 
Da bi se ukinula suspenzija, nositelji odobrenja moraju identificirati određenu populaciju bolesnika, za koju koristi nadmašuju rizik.
It has long been used in the treatment of migraine on the grounds of its vasoconstrictor activity, which is milder than that of ergotamine. 
Dugo se već koristi u liječenju migrene zbog svog vazokonstrikcijskog djelovanja, koje je blaže od djelovanja ergotamina.
• Fibrosis is mentioned in several current European Summaries of Product Characteristics (SmPCs) and expected reactions are often under-reported 
• je fibroza spomenuta u nekoliko aktualnih europskih sažetaka opisa svojstava lijeka (SmPC) i očekivane reakcije su uvijek premalo prijavljivane
However, more than half of the cases of ergotism reported have been described out of a context of overdose or without the use of a contraindicated drug. 
No, više od polovice slučajeva prijavljenog ergotizma opisano je izvan konteksta predoziranja ili bez uporabe kontraindiciranog lijeka.
Efficacy was assessed by comparing absolute blood pressure measurements after treatment rather than comparing the differences between supine and standing position which was not considered acceptable. 
Djelotvornost je ocijenjena usporedbom mjerenja apsolutnog krvnog tlaka nakon liječenja, a ne usporedbom razlika između krvnog tlaka u ležećem i stajaćem položaju, što se ne smatra prihvatljivim.
The CHMP has considered the totality of the available data on the safety and efficacy of dihydroergotamine. 
CHMP je razmotrio ukupnost dostupnih podataka o sigurnosti i djelotvornosti dihidroergotamina.
The Committee therefore pointed out that the proposed measures are insufficient to avoid that some patients develop fibrosis and ergotism during treatment. 
Stoga je Povjerenstvo naglasilo da predložene mjere nisu dostatne kako bi se izbjeglo da pojedini bolesnici razviju fibrozu i ergotizam tijekom liječenja.
Therefore, the group was of the opinion that based on the available evidence there is no need for this substance as there is no clear subset of patients that would benefit from it. 
Stoga, grupa je bila mišljenja da na temelju dostupnih dokaza ne postoji potreba za ovom tvari s obzirom da nema jasnog podskupa bolesnika koji bi imali koristi od nje.
Ergotism is a serious reaction, which leads in rare cases reported to important sequelae following amputation or colon resection for example. 
Ergotizam je ozbiljna reakcija, koja u rijetkim prijavljenim slučajevima rezultira važnim sekvelama nakon kojih slijedi primjerice amputacija ili resekcija kolona.
Patient population was heterogeneous, or patients with hypotension induced by treatment with psychotropic drugs. 
Populacija bolesnika bila je heterogena ili bolesnici s hipotenzijom koja je inducirana liječenjem psihotropnim lijekovima.
On 18 January 2012, France triggered a referral under Article 31 of Directive 2001/83/EC for the following ergot derivatives containing medicinal products: dihydroergocryptine/caffeine, dihydroergocristine, dihydroergotamine, dihydroergotoxine and nicergoline. 
Dana 18. siječnja 2012. godine, Francuska je pokrenula postupak upućivanja sukladno članku 31. Direktive 2001/83/EZ za sljedeće lijekove koji sadrže derivate ergota: dihidroergokriptin/kafein, dihidroergokristin, dihidroergotamin, dihidroergotoksin i nicergolin.
• The Committee considered the overall submitted data provided by the MAHs and the outcome of the scientific advisory group. 
• Povjerenstvo je razmotrilo sve podnijete podatke koje su dostavili nositelji odobrenja i zaključak znanstvene savjetodavne grupe.
As expected, fibrosis occurred mostly in female patients (68%) after long time of treatment with dihydroergotamine (9.1 years on average) and the most frequent type of fibrosis reaction reported was retroperitoneal (36%), followed by cardiac (30%) and pleural (18%). 
Kako je očekivano, fibroza je nastupila većinom u ženskih bolesnika (68%) nakon dugotrajnog liječenja dihidroergotaminom (prosječno 9,1 godinu), a najčešće prijavljivani tip fibrotičke reakcije bio je retrorerotonealan (36 %), nakon čega slijedi srčani (30%) i pleuralni (18%).
• Fibrosis is also an insidious reaction that occurs after a long period of treatment and thus with often a delayed diagnosis. 
• je fibroza također spor i neprimjetan odgovor koji nastupa nakon dugog razdoblja liječenja i stoga često s kasnom dijagnozom.
The studies presented are old and of poor methodological quality: uncontrolled, open designed, with a low number of patients (n=12 in Wenzel, 1989, the most recent study). 
Dostavljena ispitivanja su stara i slabe metodičke kvalitete: nekontrolirana, otvorenog dizajna, s malim brojem bolesnika (n=12 u Wenzel, 189., najnovije ispitivanje).
The MAHs also submitted their own overviews and critical summaries of all spontaneous reports of fibrotic reactions (cardiac with or without pulmonary arterial hypertension, pulmonary, pleural, peritoneal, retroperitoneal, etc) and ergotism with their ergot derivatives-containing medicinal products. 
Nositelji odobrenja dostavili su, također, i svoje vlastite preglede i kritičke sažetke svih spontanih prijava fibrotičkih reakcija (srčanih s ili bez pulmonalne arterijske hipertenzije, pulmonalnih, pleuralnih, peritonealnih, retroperitonealnih, itd.) i ergotizma povezanih s njihovim lijekovima koji sadrže derivate ergota.
The number of patients included was small and the duration of treatment was too short. 
Uključen je mali broj bolesnika, a trajanje liječenja je prekratko.
This reaction occurred in young patients (mean age among cases reported: 41 years-old), with a short time to onset after dihydroergotamine initiation (less than 2 months, mean: 2 days). 
Ova reakcija nastupa u mladih bolesnika (prosječna dob prijavljenih slučajeva: 41 godina), s kratkim vremenom pojave nakon početka uzimanja dihidroergotamina (manje od 2 mjeseca, srednje: 2 dana).
Symptoms of ergotism are listed in the sections 4.8, 4.9 of all the SmPCs and ergotism is identified in section 4.4 as a consequence of a prolonged use of dihydroergotamine or high dosage. 
Simptomi ergotizma navedeni su u dijelovima 4.8, 4.9 svih sažetaka opisa svojstava lijeka, a ergotizam je definiran u dijelu 4.4 kao posljedica produžene uporabe dihidroergotamina ili velike doze.
Dihydroergotamine mesilate (dihydroergotamine - DHE) is a semi-synthetic derivative of ergotamine. 
Dihidroergotamin mesilat (dihidroergotamin - DHE) je polusintetički derivat ergotamina.
In addition, patients were included if they displayed a reduction of systolic blood pressure of more than 10 mmHg, which does not comply with the established definition of orthostatic hypotension (at least 20 mm Hg below baseline). 
Nadalje, bolesnici su uključeni ako su pokazali smanjenje sistoličkog krvnog tlaka veće od 10 mmHg, što ne udovoljava utvrđenoj definiciji ortostatske hipotenzije (najmanje 20 mm Hg ispod osnovne vrijednosti).
The seriousness of such adverse effects and their possible fatal outcome is underlined. 
Naglašena je ozbiljnost ovakvih nuspojava i njihov mogući smrtonosni ishod.
• The Committee is of the opinion that the evidence for clinically significant efficacy of oral dihydroergotamine in the currently assessed indications is very limited, and therefore the potential benefit for patients in these indications is outweighed by the above identified risk. 
• Povjerenstvo je mišljenja da su dokazi klinički značajne djelotvornosti oralnog dihidroergotamina za trenutno ocjenjene indikacije vrlo ograničeni, te stoga identificirani rizici nadmašuju potencijalne koristi za bolesnike u ovim indikacijama.
In the reported cases, dihydroergotamine is mostly indicated for migraine or headache (30 patients) and used with the recommended daily dosage. 
U prijavljenim slučajevima, dihidroergotamin je većinom indiciran za migrenu ili glavobolju (30 bolesnika), te se koristi s preporučenim dnevnim dozama.
Therefore, the group was of the opinion that there is not a clearly defined population, which unsatisfactorily responds to standard migraine prophylaxis treatment, where there is a therapeutic need for this substance as alternative/last line treatment. 
Stoga je mišljenje grupe da ne postoji jasno definirana populacija, koja nezadovoljavajuće odgovara na standardnu profilaksu migrene, kada postoji terapijska potreba za ovom tvari kao alternativno liječenje/posljednja opcija.
A total of 363 subjects were treated with dihydroergotamine or placebo during 4 months after 1 month of placebo “run-in”. 
Ukupno su liječene 363 osobe dihidroergotaminom ili placebom tijekom 4 mjeseca nakon 1 mjeseca „run-in“ razdoblja s placebom.
The design of this study was considered acceptable by the CHMP (i.e. controlled, randomised, double-blind) but the size of the study was considered small (n=58). 
CHMP smatra dizajn ovog ispitivanja prihvatljivim (odnosno kontrolirano, randomizirano, dvostruko slijepo), no smatra veličinu ispitivanja malom (n=58).
However, the CHMP noted that for most of these patients an improvement or recovering had been observed after corticosteroid treatment or surgery (valve replacement), and in most cases the improvement is stated based on clinical symptoms (no scan). 
No, CHMP je napomenuo da je u većini ovih bolesnika uočeno poboljšanje ili oporavak nakon liječenja kortikosteroidima ili kirurškog zahvata (zamjena zaliska), te je u većini slučajeva poboljšanje navedeno na temelju kliničkih simptoma (bez skeniranja).
In the acute treatment of migraine, it is administered parenterally or in the form of a nasal spray because of the low bioavailability of the unchanged drug by the oral route. 
U slučaju akutnog liječenja migrene, lijek se primjenjuje parenteralno ili u obliku spreja za nos zbog slabe bioraspoloživosti nepromijenjenog lijeka oralnoga puta.
The CHMP was therefore requested to give its opinion on whether the marketing authorisations for ergot derivatives containing medicinal products should be maintained, varied, suspended or withdrawn in relation to the below mentioned indications: 
Stoga je zatraženo od CHMP-a da iznese mišljenje trebaju li se odobrenja za stavljanje u promet lijekova koji sadrže derivate ergota zadržati, izmijeniti, suspendirati ili ukinuti s obzirom na niže navedene indikacije:
From the approved indications of the dihydroergotamine containing medicinal products the ones that are in the scope of this referral procedure and are approved in at least one Member State are the following (specific wording of the indication may vary from product to product): 
Od odobrenih indikacija za lijekove koji sadrže dihidroergotamin, sljedeće su indikacije predmetom ovog postupka upućivanja i odobrene su od barem jedne države članice (točna formulacija indikacije može varirati od proizvoda do proizvoda):
Moreover, the 8 new spontaneous notifications reported during the French survey conducted in 2011 show that the risk minimisation measures that are currently in place are not sufficient to prevent the risk of fibrotic reactions. 
Nadalje, 8 novih spontanih prijava zabilježeno je tijekom francuskog istraživanja provedenog 2011. godine, koji pokazuju da mjere za smanjivanje rizika, koje su trenutno na snazi nisu dostatne kako bi se spriječio razvoj fibrotičkih reakcija.
Only one study, Thulesius (1986), demonstrated a significant decrease of immediate drop in blood pressure after standing up with 10mg per day dihydroergotamine compared to placebo, in patients with hypotension induced by treatment with psychotropic drugs and it became available after the initial marketing authorisation was granted. 
Samo jedno ispitivanje, Thulesius (1986.), prikazalo je značajno smanjenje neposrednog pada u krvnom tlaku nakon ustajanja s 10 mg dihidroegotamina po danu u usporedbi s placebom u bolesnika s hipotenzijom koja je inducirana liječenjem psihotropnim lijekovima, te je postalo dostupno nakon prvotnog odobrenja za stavljanje lijeka u promet.
Twelve patients suffering from peripheral venous insufficiency were treated first with intravenous dihydroergotamine followed by oral dihydroergotamine administration for one week. 
Dvanaest bolesnika, koji su bolovali od periferne venske insuficijencije, liječeni su prvo intravenoznim dihidroergotaminom nakon čega je slijedila oralna primjena dihidroergotamina jednom tjedno.
One case was confounded by medical history and in 25 cases co-suspected drugs were reported: benfluorex (4 cases), dexflenfuramine (4 cases), pergolide (1 case), beta blockers (9 cases), fenofibrate (2 cases) and ergot derivative drug (8 cases). 
Jedan slučaj je zamijenjen anamnezom, a u 25 slučajeva prijavljeni su lijekovi koji mogu izazvati iste nuspojave: benfluoreks (4 slučaja), deksflenfuramin (4 slučaja), pergolid (1 slučaj), beta blokeri (9 slučajeva), fenofibrat (2 slučaja) i lijek koji sadrži derivat ergota (8 slučajeva).
For the indication “orthostatic hypotension” the submitted studies were considered by the CHMP of poor methodological quality: they were mainly uncontrolled trials with only 1 double-blind study but with low number of patients. 
Za indikaciju „ortostatska hipotenzija“, CHMP smatra da su dostavljena ispitivanja slabe metodičke kvalitete: to su bila uglavnom nekontrolirana istraživanja sa samo 1 dvostruko slijepim ispitivanjem, no mali brojem bolesnika.
• Acute retinopathies of vascular origin 
• akutne retinopatije vaskularnog porijekla
Following a national pharmacovigilance review held in 2011 new spontaneous notifications reported with some of those products identified serious cases of fibrosis and ergotism and France considered that this safety concern is not outweighed by the limited evidence of efficacy. 
Nakon nacionalnog farmakovigilancijskog pregleda provedenog 2011. godine, nove spontane prijave zabilježene za pojedine prethodno navedene lijekove identificirale su teške slučajeve fibroze i ergotizma, te je Francuska smatrala da ovo sigurnosno pitanje nije nadmašeno ograničenim dokazom djelotvornosti.
• Ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease 
• pomoćno liječenje intermitentne klaudikacije u slučaju simptomatske bolesti perifernih arterija
The double-blind, randomised, placebo-controlled studies were old and generally not carried out with the current up-to-date methodology. 
Dvostruko slijepa, randomizirana, placebom kontrolirana ispitivanja bila su zastarjela i načelno nisu provedena u skladu s aktualnom, suvremenom metodologijom.
For the indication “symptomatic treatment of veno-lymphatic insufficiency” very few studies have been conducted. 
Za indikaciju „simptomatsko liječenje vensko limfne insuficijencije“ proveden je vrlo mali broj ispitivanja.
Overall, the CHMP was of the opinion that no situation could justify exposing a patient to risk of fibrosis and ergotism considering the very limited data on efficacy. 
Načelno, mišljenje je CHMP-a da niti jedna situacija ne može opravdati izlaganje bolesnika riziku od fibroze i ergotizma uzimajući u obzir vrlo ograničene podatke o djelotvornosti.
The open label study (Wenzel-E et al, 1989) that became available after the granting of the initial marketing authorisation discusses the use of dihydroergotamine in venous insufficiency. 
Otvoreno ispitivanje (Wenzel-E et al, 1989.), koje je postalo dostupno nakon izdavanja prvotnog odobrenja za stavljanje lijeka u promet, razmatra uporabu dihidroergotamina za vensku insuficijenciju.
Ergot derivatives are recognised as being capable of inducing fibrosis, in particular heart valve fibrosis. 
Prepoznata je sposobnost derivata ergota za induciranje fibroze, a posebice fibroze srčanog zaliska.
• Ancillary treatment of visual acuity decrease and visual field disturbances presumably of vascular origin 
• pomoćno liječenje smanjenja oštrine vida i poremećaja vidnoga polja za koje se pretpostavlja da su vaskularnog porijekla
Based on the clinical experience the group considered that dihydroergotamine has only been used rarely for the treatment of orthostatic hypotension with no clear benefit to the patients. 
Na temelju kliničkog iskustva grupa je smatrala da se dihidroegotamin koristio samo rijetko za liječenje ortostatske hipotenzije bez jasne koristi za bolesnike.
To conclude, ergotism is an adverse reaction of ergot derivative drugs well-known to occur in a context of overdose or interaction. 
Zaključno, ergotizma je nuspojava lijekova koji sadrže derivate ergota, za koju je poznato da nastupa u kontekstu predoziranja ili interakcije.
Overall, 8 cases of fibrotic adverse reactions from a French survey conducted in 2011 and 50 cases among the 75 cases reported by the MAHs have been considered as potentially related to dihydroergotamine including 24 with no confounding factor. 
Načelno se za 8 slučaja fibrotičkih nuspojava iz francuskog ispitivanja provedenog 2011. godine i 50 slučajeva od 75 slučaja, koje su prijavili nositelji odobrenja, smatralo da su potencijalno povezani s dihidroergotaminom, uključujući 24 slučaja sa čimbenikom zabune.
After 4 months of treatment, the attack frequency decreased by 2.0 ± 1.6 (-60.0%) with dihydroergotamine versus 1.7 ± 1.5 (-48.8%) with placebo (p = 0.014 for the relative variations). 
Nakon 4 mjeseca liječenja učestalost napadaja smanjila se za 2,0 + 1,6 (-60,0 %) s dihidroergotaminom u odnosu na 1,7 + 1,5 (-48,8%) s placebom (p=0,014 za relativne varijacije).
Based on the clinical experience the group considered that no special population exists that could benefit from the treatment with this active substance in the prophylaxis of migraine headache. 
Na temelju kliničkog iskustva grupa smatra da ne postoji posebna populacija koja bi imala koristi od liječenja s ovom djelatnom tvari u profilaksi migrenske glavobolje.
Therefore, even if it is highly pharmacologically plausible that ergot derivatives acting as 5HT2B receptor agonists may induce "serotonergic" valve disease similar to that induced by carcinoid tumours or fibrotic lesions of other tissues, it must be remembered that some ergot derivatives are not 5-HT2B receptor agonists. 
Stoga, čak i ako je farmakološki vrlo plauzibilno da derivati ergota, koji djeluju kao agonisti 5-HT2B receptora, mogu inducirati „serotonergijsku“ bolest zaliska sličnu onoj koju induciraju karcinoidni tumori ili fibrotičke lezije drugih tkiva, treba upamtiti da pojedini derivati ergota nisu agonisti 5-HT2B receptora.
Overall, the varying affinity for serotoninergic receptors with the different ergot derivatives and the therapeutic doses used may explain the differences observed for notification rates for the fibrotic reactions. 
Ukupno gledano, varirajući afinitet serotoninskih receptora s različitim derivatima ergota i terapijskim dozama koje se koriste, može objasniti razlike uočene u prijavljenim stopama za fibrotičke reakcije.
Moreover, safety data provided by some MAHs are incomplete (gap between reviewing period and marketing period of the product) and it cannot be excluded that cases reported with their products are lacking. 
Nadalje, podaci o sigurnosti koje su dostavili nositelji odobrenja nisu bili potpuni (vremenski odmak između razdoblja pregleda i razdoblja stavljanja lijeka u promet) te se ne može isključiti da ne nedostaju slučajevi prijavljeni s njihovim lijekovima.
In conclusion, the studies provided by the MAHs were not carried out with up-to-date methodology. 
Zaključno, ispitivanja koja su proveli nositelji odobrenja nisu provedena u skladu sa suvremenom metodologijom.
The efficacy of dihydroergotamine in the acute treatment of migraine attack is not within the scope of this referral and will not be discussed. 
Djelotvornost dihidroergotamina u akutnom liječenju napadaja migrene nije predmetom ovog postupka upućivanja i neće se razmatrati.
The literature data indicate a possible efficacy of oral dihydroergotamine in migraine prophylaxis, but definite scientific proof remains weak. 
Bibliografski podaci ukazuju na moguću djelotvornost oralnog dihidroergotamina u profilaksi migrene, no konačan znanstveni dokaz i dalje je neuvjerljiv.
The authorised oral doses seem to have weak or null efficacy due to the low bioavailability of the drug. 
Čini se da su odobrene oralne doze imale slabo ili nikakvo djelovanje zbog male bioraspoloživosti lijeka.
A review of all other available data (i.e. literature data, pre-clinical data, and other clinical data including epidemiological studies) that were relevant to evaluate the risk of fibrosis was provided where possible. 
Ako je bilo moguće dostavljen je pregled svih drugih dostupnih podataka (odnosno bibliografskih podataka, predkliničkih podataka, i ostalih podataka uključujući epidemiološka ispitivanja), koji su relevantni za ocjenu rizika fibroze.
In these studies, dihydroergotamine seems to have some efficacy only by injection route or at doses higher than the authorised dose. 
Čini se da je u ovim ispitivanjima dihidroegotamin djelovao u određenoj mjeri samo na putu injekcije ili pri dozama većima od odobrene doze.
Some symptoms related to ergotism may be confounded with migraine symptoms and thus not reported as an adverse drug reaction. 
Određeni simptomi povezani s ergotizmom mogli su biti zamijenjeni s migrenskim simptomima te stoga nisu prijavljeni kao nuspojave na lijek.
− Is not favourable for orthostatic hypotension. 
nije povoljan za ortostatsku hipotenziju.
With regard to the risk of ergotism, the review of cases provided by the MAHs was not exhaustive and the methodology used to retrieve cases of ergotism was unclear for most of the MAHs. 
Vezano uz rizik od ergotizma, pregled slučajeva koje su dostavili nositelji odobrenja nisu bili iscrpni i metodologija koja se koristila za pronalazak slučajeva ergotizma bila je nejasna za većinu nositelja odobrenja.
However, a total of 134 cases of ergostim or symptoms potentially related to ergotism have been reported by the MAHs. 
No, nositelji odobrenja prijavili su ukupno 134 slučaja ergotizma ili simptoma potencijalno povezanih s ergotizmom.
The marketing authorisation holders (MAHs) submitted all available efficacy data from clinical trials and observational studies, including data that became available since the granting of the initial marketing authorisation. 
Nositelji odobrenja za stavljanje lijeka u promet (nositelji odobrenja) dostavili su sve dostupne podatke o djelotvornosti iz kliničkih ispitivanja i opservacijskih ispitivanja, uključujući i podatke koji su postali dostupni od trenutka izdavanja prvotnog odobrenja za stavljanje lijeka u promet.
With regard to the reported cases, the CHMP noted the problem of under-reporting for this product considering the period that it is on the market. 
Vezano uz prijavljene slučajeve, CHMP uočio je problem s nedostatnim prijavljivanjem za ovaj lijek, ako se uzme u obzir razdoblje tijekom kojeg je lijek u prometu.