natgillin/translations-raw huggingface dataset:
In the only study in this indication where superiority of tolperisone over placebo in the primary outcome was shown (Pratzel 1995), this was achieved using a new parameter in the formula for calculation which was not pre-determined but rather introduced in post-hoc efficacy analysis. 
Primarni rezultati edine študije (Pratzel 1995), opravljene v zvezi s to indikacijo, ki so pokazali večjo učinkovitost tolperizona v primerjavi s placebom, so bili pridobljeni z uporabo novega parametra v formuli za izračun, ki ni bil predhodno določen, temveč je bil vpeljan v post hoc analizi učinkovitosti.
• Peripheral level - stabilises the membrane of neurons, and consequently supresses the amplitude and frequency of the action potentials. 
• Periferno živčevje - stabilizira membrano živčnih celic ter s tem zmanjša obseg in pogostost akcijskih potencialov.
Parenteral formulation 
Parenteralna oblika
• The revocation of the marketing authorisation for the parenteral formulations of medicinal products referred to in annex I. 
• preklic dovoljenja za promet z zdravilom za parenteralne oblike zdravil iz Priloge I.
For the remaining indications (rehabilitation after orthopaedic and trauma surgery, treatment of obliterative vascular diseases as well as syndromes due to impaired vascular innervation, and Little's disease and other encephalopaties accompanied by dystonia) there is extremely limited evidence of efficacy, mainly based on small studies with inadequate design and including a heterogeneous population. 
O učinkovitosti zdravila v zvezi z ostalimi indikacijami (rehabilitacija po ortopedskih in travmatoloških operacijah, zdravljenje obliterativnih žilnih bolezni ter sindromov, ki so posledica motenj krvnega pretoka, cerebralna paraliza in druge encefalopatije, ki jih spremlja distonija) je na voljo zelo malo dokazov, ki pretežno temeljijo na majhnih študijah, ki so imele pomanjkljivo zasnovo in so zajele heterogeno populacijo bolnikov.
Hypotheses include tolperisone metabolites as hapten formations activating the patient's immune system through covalent modification of proteins, or structural similarity to the local anaesthetic lidocaine. 
Dve od hipotez sta, da se presnovki tolperizona obnašajo kot hapteni, ki prek kovalentne modifikacije beljakovin sprožijo bolnikov obrambni sistem, oziroma, da obstaja strukturna podobnost z lokalnim anestetikom lidokainom.
The Feher study (1985) used the Rivermead scale, which has shown high validity and reliability in assessment of motor function in stroke patients. 
V Feherjevi študiji (1985) je bila uporabljena Rivermeadska lestvica, ki se je izkazala za izredno zanesljiv in verodostojen instrument za ocenjevanje motoričnih funkcij pri bolnikih po možganski kapi.
The only study in this indication with a positive outcome contains significant methodological deficiencies which preclude any conclusion on the efficacy of the product. 
V edini študiji v zvezi s to indikacijo, ki je odkrila pozitivne rezultate, je bila uporabljena precej pomanjkljiva metodologija, zato je na podlagi te študije nemogoče podati kakršnekoli zaključke o učinkovitosti izdelka.
It is therefore not plausible how the reduction of a triggered PPT could have been translated into a clinically relevant effect in patients with painful reflex muscle spasm. 
Zato ni utemeljeno, kakšne klinično pomembne učinke bi lahko imelo znižanje števila sproženih PPT-jev na bolnike z bolečimi reflektornimi mišičnimi spazmi.
These are mostly observational and extremely limited documentation is available. 
Večinoma gre za opazovalne študije z zelo skopo dokumentacijo.
• Treatment of muscular hypertonicity and muscle spasms associated with locomotor diseases (e.g. spondylosis, spondylarthrosis, cervical and lumbar syndromes, arthrosis of large joints) 
• zdravljenje mišične hipertonije in mišičnih spazmov, povezanih z obolenji lokomotornega sistema (npr. spondiloza, spondilartroza, cervikalni in lumbalni sindrom ter artroza velikih sklepov);
Hypersensitivity can be a significant event and cases of anaphylactic reactions/anaphylactic shock have been reported. 
Preobčutljivost je lahko nezanemarljiv dogodek, zabeleženi pa so bili tudi primeri anafilaktičnih reakcij oziroma anafilaktičnega šoka.
In this respect, the CHMP took note of the fact that the marketing authorisation holder of the products for which these indications are approved concluded that the evidence of efficacy is insufficient to balance the risks associated to the product and proposed that the indications be deleted. 
Pri tem je CHMP upošteval dejstvo, da je imetnik dovoljenj za promet z zdravili, za katera so bile odobrene omenjene indikacije, sam ocenil, da je dokazov o učinkovitosti premalo, da bi lahko odtehtali tveganja, povezana s tem zdravilom, in predlagal, da se indikacije izbrišejo.
• Central-reticular level - An imbalance between supraspinal facilitatory and inhibitory control can also lead to an enhanced reflex activity and an increased muscle tone. 
• Osrednje živčevje - retikularna formacija: neravnovesje med spodbujevalnimi in zaviralnimi supraspinalnimi mehanizmi lahko prav tako povzroči povečano delovanje refleksov in povišan mišični tonus.
The CHMP endorsed a communication i.e. ‘Dear Healthcare Professional Communication (DHPC)' to communicate the outcome of the present review. 
CHMP je odobril t. i. „Neposredno obvestilo zdravstvenim delavcem”, v katerem so zapisani izsledki tega pregleda zdravila.
• Treatment of obliterative vascular diseases as well as syndromes due to impaired vascular innervation (e.g. acrocyanosis, dysbasia angioneurotica intermittens) 
• zdravljenje obliterativnih žilnih bolezni ter sindromov, ki so posledica motenj krvnega pretoka (npr. akrocianoza, intermitentna angionevrotična disbazija);
The MAHs also disagreed with the CHMP assessment of the safety profile of tolperisone. 
Imetnika dovoljenj za promet z zdravilom se prav tako nista strinjala z oceno varnostnega profila tolperizona, ki jo je opravil CHMP.
• The Committee is also of the opinion that there is evidence of clinically significant efficacy of tolperisone in the symptomatic treatment of post-stroke spasticity in adults. 
• da je odbor tudi mnenja, da obstajajo dokazi o klinično pomembni učinkovitosti tolperizona pri simptomatskem zdravljenju spastičnosti, ki je posledica možganske kapi pri odraslih;
In addition, the improvement in PPT was not accompanied by a corresponding improvement in the mobility of patients. 
Razen izboljšanja števila PPT študija ni zabeležila tudi ustreznega izboljšanja gibalnih sposobnosti bolnikov.
• Acute or chronic treatment of pathologically elevated skeletal muscle tone in organic neurological disorders 
• akutno ali kronično zdravljenje patološko povišanega tonusa skeletnih mišic pri organskih nevroloških motnjah;
Whereas 
Ob upoštevanju:
• The Committee also concluded that, in the absence of relevant data to support the efficacy in the dosing recommendations approved, the potential benefit of tolperisone-containing parenteral formulations is outweighed by the identified risk of hypersensitivity. 
• da je odbor sklenil tudi, da glede na pomanjkanje relevantnih podatkov, ki bi podprli učinkovitost odobrenih priporočil za odmerjanje, ugotovljena tveganja za preobčutljivostne reakcije odtehtajo morebitne koristi parenteralnih oblik zdravil, ki vsebujejo tolperizon.
As a result, the CHMP considered that none of the provided pooled analyses could be considered as supportive to demonstrate the efficacy of tolperisone in the “treatment of muscular hypertonicity and muscle spasms associated with locomotor diseases” indication, nor in the proposed restricted indication. 
Zato po njegovem mnenju za nobeno od predloženih združenih analiz ni mogoče šteti, da dokazuje učinkovitost tolperizona pri indikaciji „zdravljenje mišične hipertonije in mišičnih spazmov, povezanih z obolenji lokomotornega sistema,“ niti pri predlagani omejeni indikaciji.
Tolperisone reduces the sodium influx through the isolated nerve membrane in a dose dependent way, thus amplitude and frequency of action potentials are reduced. 
Tolperizon glede na velikost odmerka zmanjša prehajanje natrija skozi izolirano membrano živčnih celic, s čimer se zmanjšata obseg in pogostost akcijskih potencialov.
Grounds for the variation/revocation to the terms of the marketing authorisation 
Podlaga za spremembo pogojev/preklic dovoljenja za promet z zdravilom
In this randomised, double-blind, placebo controlled, multicentre study efficacy of tolperisone has been shown in the symptomatic treatment of patients with spasticity following cerebral stroke. 
Randomizirana, dvojno slepa, s placebom nadzorovana, multicentrična študija je pokazala, da je tolperizon učinkovit pri simptomatskem zdravljenju bolnikov s spastičnostjo, ki je posledica možganske kapi.
Furthermore, inhibitory effects on voltage dependent Ca2+ channels have been demonstrated, suggesting that tolperisone might also reduce the transmitter release in addition to its membrane stabilising effect. 
Poleg tega tudi dokazano zavira napetostno regulirane kalcijeve (Ca2+) kanale, kar pomeni, da bi lahko poleg tega, da pomaga pri stabilizaciji membrane, tudi zmanjšal sproščanje živčnih prenašalcev.
The Melka study can only be considered as providing supportive evidence of efficacy in the treatment of spasticity caused by neurological diseases. 
Študija Melke lahko tako zgolj ponudi dodatne dokaze o učinkovitosti pri zdravljenju spastičnosti, ki je posledica nevroloških motenj.
The SAG stated that it did not consider the results of the 4 pooled analyses to be supportive of the efficacy of tolperisone. 
Po mnenju te skupine rezultati štirih združenih analiz ne potrjujejo učinkovitosti tolperizona.
• Central-spinal level - tolperisone reduces the increased mono- and polysynaptic reflex activity in a dose-dependent manner to the physiological level. 
• Osrednje živčevje - hrbtenjača: tolperizon glede na količino odmerka zmanjša pojav monosinaptičnih in polisinaptičnih refleksov na fiziološko raven.
The CHMP also noted the MAH proposal to conduct a clinical study to collect additional evidence of the efficacy of tolperisone in the proposed restricted low back pain indication, as a post-referral commitment, as well as the related draft study synopsis. 
Upošteval je tudi predlog imetnika dovoljenja za promet z zdravilom za izvedbo klinične študije za pridobitev dodatnih dokazov o učinkovitosti tolperizona v zvezi s predlagano omejeno indikacijo za križ kot obveze po napotitvi ter s tem povezan povzetek osnutka študije.
The company that holds these marketing authorisations was asked to submit any existing data in support of its safety and dosing recommendations, but no relevant data was submitted for assessment as the marketing authorisation holder concluded itself that the data is insufficient to conclude that the benefits outweigh the risks and proposed that the marketing authorisations for the parenteral formulations be revoked. 
Na podjetje, ki ima dovoljenja za promet z zdravilom, je bila naslovljena prošnja za predložitev vseh obstoječih podatkov, ki bi podprli varnostna priporočila in priporočila za odmerjanje, vendar imetnik dovoljenj za promet z zdravilom ni predložil nobenih relevantnih podatkov, saj je sam ocenil, da nima dovolj podatkov, na podlagi katerih bi lahko ugotovili, da koristi zdravila odtehtajo tveganja, in je zato predlagal preklic dovoljenj za promet z zdravilom v parenteralnih oblikah.
With regard to the safety of tolperisone, the CHMP reviewed the available safety data and retained its previous conclusions that there is a risk of hypersensitivity reactions associated with tolperisone, with data showing that 10% of all reported cases of hypersensitivity were considered to be life-threatening. 
CHMP je v zvezi z varnostjo tolperizona pregledal razpoložljive podatke o varnosti in ostal pri svojih prejšnjih zaključkih, da obstaja tveganje za preobčutljivostne reakcije, povezane s tolperizonom, saj so podatki pokazali, da je 10 % vseh primerov, pri katerih so poročali o preobčutljivosti, veljalo za primere z življenjsko nevarnimi zapleti.
It is important to note that the evidence of efficacy is mainly based on the results of the Stamenova study, which only included patients with post-stroke spasticity. 
Ob tem je treba poudariti, da dokazi o učinkovitosti pretežno temeljijo na rezultatih študije Stamenove, ki pa je zajela zgolj bolnike s spastičnostjo, ki je posledica možganske kapi.
• The Committee is of the opinion that the evidence for clinically significant efficacy of tolperisone in the currently approved indications is extremely limited, and therefore the potential benefit for patients in these indications is outweighed by the identified risk. 
• da odbor meni, da so dokazi o klinično pomembni učinkovitosti tolperizona v zvezi s trenutno odobrenimi indikacijami izredno skopi, zato ugotovljena tveganja odtehtajo morebitne koristi za bolnike v zvezi s temi indikacijami;
While no fatal case of hypersensitivity was reported, around 10% of all cases reported with tolperisone were considered to be life-threatening. 
Čeprav ni poročil o smrtnih primerih zaradi preobčutljivosti, pa je bilo med poročili, povezanimi s tolperizonom, 10 % primerov z življenjsko nevarnimi zapleti.
Validation of new parameters needs to be done beforehand if proof of efficacy is to be derived from a study. 
Če želi študija zagotoviti verodostojne dokaze o učinkovitosti, mora biti postopek validacije novih parametrov opravljen pred začetkom analiz.
On the efficacy side, the existing dataset is indicative of a modest effect of tolperisone in the treatment of spasticity caused by neurological disorders, but it is important to note that the evidence is mainly based on the results of the Stamenova study - which only included patients with post-stroke spasticity. 
Obstoječi podatki v korist učinkovitosti tolperizona kažejo na zmerne učinke pri zdravljenju spastičnosti, ki je posledica nevroloških motenj, vendar je ob tem treba poudariti, da dokazi pretežno temeljijo na rezultatih študije Stamenove - ki je zajela izključno bolnike s spastičnostjo, ki je posledica možganske kapi.
Based on the totality of the data available on the safety and the efficacy of tolperisone and having noted the opinions of the BSWP and the SAG, the CHMP confirmed its initial conclusion that the risk of hypersensitivity is more significant than previously identified at the time of the initial marketing authorisation, and that as a consequence the benefits of tolperisone are outweighed by the risks in the indication “treatment of muscular hypertonicity and muscle spasms associated with locomotor diseases” as well as in the proposed restricted indication “short-term treatment of muscle spasms in adult patients with acute non-specific low back pain”. 
CHMP je na podlagi vseh razpoložljivih podatkov o varnosti in učinkovitosti tolperizona ter ob upoštevanju mnenj delovne skupine BSWP in znanstvene svetovalne skupine potrdil svoj prvotni zaključek, da je tveganje za preobčutljivostne reakcije večje, kot je bilo sprva ugotovljeno pri prvotnem dovoljenju za promet z zdravilom, ter da tveganja posledično prevladajo nad koristmi tolperizona v zvezi z indikacijo „zdravljenje mišične hipertonije in mišičnih spazmov, povezanih z obolenji lokomotornega sistema“ in predlagano omejeno indikacijo „kratkoročno zdravljenje mišičnih spazmov pri odraslih bolnikih z akutno nespecifično bolečino v križu“.
The only double-blind, placebo-controlled studies identified where parenteral tolperisone was used and that have acceptable methodological standards were conducted in indications where efficacy has not been demonstrated, that have never been approved for the product or included only a very small number of patients in the indication of interest.. No data was submitted in support of the dosing recommendations. 
Edine dvojno slepe, s placebom nadzorovane študije, v katerih je bil uporabljen tolperizon v parenteralni obliki in ki so zagotovile sprejemljive metodološke standarde, so bile izvedene v zvezi z indikacijami, pri katerih učinkovitost ni bila dokazana ali ki niso bile odobrene za ta izdelek, oziroma so vključile zelo majhno število bolnikov.
The mean improvement in the Ashworth score found in the Stamenova study was 32% in the overall ITT (intention-to-treat) population and 42% in the subgroup of patients receiving 300-450 mg/day). 
Študija Stamenove je pri splošni populaciji vključenih bolnikov v povprečju pokazala 32-odstotno izboljšanje na Ashworthovi lestvici, pri podskupini bolnikov, ki so prejemali dnevni odmerek 300-450 mg/dan, pa 42-odstotno.
While the results are difficult to interpret due to the lack of a placebo control group to verify assay integrity, this randomised, double-blind actively controlled study provides supporting evidence of efficacy of tolperisone in terms of improvement of mobility in patients with spasticity caused by neurological disorders. 
Ker analiza ni vključila kontrolne skupine s placebom, s katero bi lahko potrdili verodostojnost analize, je interpretacija rezultatov sicer otežena, vendar pa je randomizirana, dvojno slepa, aktivno nadzorovana študija zagotovila dodatne dokaze o učinkovitosti tolperizona pri izboljšanju gibalnih sposobnosti bolnikov s spastičnostjo, ki je posledica nevroloških motenj.
Treatment of pathologically elevated skeletal muscle tone in organic neurological disorders 
Zdravljenje patološko povišanega tonusa skeletnih mišic pri organskih nevroloških motnjah
Based on the totality of the data made available on the safety and the efficacy of tolperisone, the CHMP considered that the risk of hypersensitivity is more significant than previously identified, and that as a consequence the demonstrated clinical benefits only outweigh the risks in the restricted indication symptomatic treatment of post-stroke spasticity in adults. 
Na podlagi vseh razpoložljivih podatkov glede varnosti in učinkovitosti tolperizona je CHMP ocenil, da je tveganje za preobčutljivostne reakcije večje, kot je bilo sprva ugotovljeno, in da zato dokazane klinične koristi odtehtajo tveganja zgolj v zvezi z indikacijo simptomatsko zdravljenje spastičnosti, ki je posledica možganske kapi pri odraslih.
• Little's disease (infantile diplegia spastica) and other encephalopaties accompanied by dystonia 
• cerebralna paraliza (infantilna spastična diplegija) in druge encefalopatije, ki jih spremlja distonija.
Taken together, the existing dataset is indicative of a modest effect of tolperisone in the treatment of spasticity caused by neurological disorders. 
Vsi zbrani obstoječi podatki kažejo na skromne učinke tolperizona pri zdravljenju spastičnosti, ki je posledica nevroloških motenj.
The Committee also concluded that the benefit-risk balance of tolperisone-containing parenteral formulations is not positive, and recommends the revocation of the corresponding marketing authorisations. 
Odbor je zaključil tudi, da razmerje med tveganji in koristmi pri parenteralnih oblikah zdravil, ki vsebujejo tolperizon, ni pozitivno, ter zato predlaga preklic pripadajočih dovoljenj za promet z zdravilom.
Rehabilitation after orthopaedic and trauma surgery 
Rehabilitacija po ortopedskih in travmatoloških operacijah
Treatment of muscular hypertonicity and muscle spasms associated with locomotor diseases 
Zdravljenje mišične hipertonije in mišičnih spazmov, povezanih z obolenji lokomotornega sistema
In conclusion the Stamenova study can be regarded as a positive study, the results of which are indicative of a clinically relevant effect of tolperisone in the treatment of patients with post-stroke spasticity. 
Zaključimo lahko, da so rezultati študije Stamenove v korist zdravilu in kažejo na klinično pomembne učinke tolperizona pri zdravljenju bolnikov s spastičnostjo, ki je posledica možganske kapi.
Treatment of obliterative vascular diseases as well as syndromes due to impaired vascular innervation 
Zdravljenje obliterativnih žilnih bolezni ter sindromov, ki so posledica motenj krvnega pretoka
o Is not positive for treatment of muscular hypertonicity and muscle spasms associated with locomotor disease. 
o negativno pri zdravljenju mišične hipertonije in mišičnih spazmov, povezanih z obolenji lokomotornega sistema;
o Is not positive for rehabilitation after orthopaedic and trauma surgery. 
o negativno pri rehabilitaciji po ortopedskih in travmatoloških operacijah;
Relevant studies also exist in the locomotor indication, the majority of which failed to demonstrate the efficacy of the product. 
Pomembne študije so bile opravljene tudi v zvezi z učinkovitostjo tolperizona pri obolenjih lokomotornega sistema, vendar ta v večini študij ni bila dokazana.
Hypersensitivity reactions account for more than half of the spontaneous reports in the originators database, followed by adverse events (AEs) from the SOCs Gastrointestinal disorders, General disorders and administration site conditions and Nervous system disorders. 
Preobčutljivostne reakcije so bile podlaga za več kot polovico spontanih poročil, zabeleženih v podatkovnih bazah originatorjev, sledijo pa jim neželeni dogodki zaradi motenj prebavil, splošnih težav in sprememb na mestu aplikacije ter bolezni živčevja (glede na organski sistem).
• Rehabilitation after orthopaedic and trauma surgery 
• rehabilitacija po ortopedskih in travmatoloških operacijah;
o Is not positive for treatment of obliterative vascular diseases as well as syndromes due to impaired vascular innervation. 
o negativno pri zdravljenju obliterativnih žilnih bolezni ter sindromov, ki so posledica motenj krvnega pretoka;
Little's disease and other encephalopaties accompanied by dystonia 
Cerebralna paraliza in druge encefalopatije, ki jih spremlja distonija.
The Committee, as a consequence, concluded that the benefit-risk balance of tolperisone-containing oral formulations is positive under normal conditions of use only in the symptomatic treatment of post-stroke spasticity in adults, taking into account the changes to the product information agreed. 
Odbor je zato sklenil, da je razmerje med tveganji in koristmi pri peroralnih oblikah zdravil, ki vsebujejo tolperizon, v normalnih pogojih uporabe pozitivno zgolj pri simptomatskem zdravljenju spastičnosti, ki je posledica možganske kapi pri odraslih, pri čemer je treba upoštevati dogovorjene spremembe informacij o zdravilu.
The Committee concluded that the benefit-risk balance of tolperisone-containing oral formulations is positive under normal conditions of use only in the symptomatic treatment of post-stroke spasticity in adults, subject to the changes to the product information agreed. 
Odbor je sklenil, da je razmerje med tveganji in koristmi pri peroralnih oblikah zdravil, ki vsebujejo tolperizon, v normalnih pogojih uporabe pozitivno zgolj pri simptomatskem zdravljenju spastičnosti, ki je posledica možganske kapi pri odraslih, pri čemer je treba upoštevati dogovorjene spremembe informacij o zdravilu.
o Is not positive for Little's disease and other encephalopaties accompanied by dystonia. 
o negativno pri cerebralni paralizi in drugih encefalopatijah, ki jih spremlja distonija;
• The Committee therefore considered that the benefit-risk balance of tolperisone-containing oral formulations under normal conditions of use: o Is positive for symptomatic treatment of post-stroke spasticity in adults. 
• da je odbor zato ocenil, da je razmerje med tveganji in koristmi pri peroralnih oblikah zdravil, ki vsebujejo tolperizon, v normalnih pogojih uporabe:
The full EPAR for Clopidogrel ratiopharm can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. 
Celotno evropsko javno poročilo o oceni zdravila (EPAR) za zdravilo Clopidogrel ratiopharm je na voljo na spletni strani agencije: ema.europa.eu/Find medicine/Human medicines/European public assessment reports.
This means that Clopidogrel ratiopharm is similar to a ‘reference medicine' already authorised in the European Union (EU) called Plavix. 
To pomeni, da je podobno „referenčnemu zdravilu“, ki je že odobreno v Evropski uniji (EU), in sicer zdravilu Plavix.
This is a summary of the European public assessment report (EPAR) for Clopidogrel ratiopharm. 
To je povzetek evropskega javnega poročila o oceni zdravila (EPAR) za zdravilo Clopidogrel ratiopharm.