natgillin/translations-raw huggingface dataset:
Very common nausea, vomiting diarrhoea or stomach ache loss of appetite upper respiratory tract infection including: o infection of the upper chest or lungs, o infection of the sinuses with a feeling of pain and fullness behind your cheeks and eyes
Drugi neželeni učinki, ki se lahko pojavijo med jemanjem zdravila Qtrilmet so: Zelo pogosti - siljenje na bruhanje, bruhanje - driska ali bolečine v trebuhu - izguba teka - okužba zgornjih dihal, vključno z:
Experience in NYHA class I-II is limited in dapagliflozin.
Izkušenj z dapagliflozinom v razredih I in II po NYHA je malo.
The adjusted percent difference at week 52 between the treatment groups was
Prilagojena odstotna razlika med terapevtskima skupinama je bila po 52 tednih 16,2 %.
Immune related findings of minimal, nonprogressive, lymphoid hyperplasia in spleen, lymph nodes and bone marrow with no adverse sequelae have been reported in all species tested at exposures starting from 7 times the RHD.
Pri vseh testiranih živalskih vrstah so ob izpostavljenostih, ki so se začele s 7-krat tolikšno izpostavljenostjo, kot je ob priporočenem odmerku za človeka, opazili imunske spremembe: minimalno, neprogresivno limfoidno hiperplazijo v vranici, bezgavkah in kostnem mozgu, brez neželenih posledic.
• the increasing duration of treatment (treated > 24 months),
• naraščajoče trajanje zdravljenja (> 24 mesecev),
There is a need to consider whether regulatory action is necessary in light of the new elements.
Treba je proučiti, ali je glede na nove elemente potreben regulativni ukrep.
The PRAC adopted a revised version of the Risk Management Plan (RMP) reflecting the amendments agreed during the procedure.
Odbor PRAC je sprejel popravljeno različico načrta za obvladovanje tveganja (RMP), ki odraža spremembe, dogovorjene v postopku.
The balance between sensitivity and specificity in this range needs to be carefully considered.
Znotraj tega razpona je treba skrbno pretehtati ravnovesje med občutljivostjo in specifičnostjo.
In view of the above, on 29 April 2015 the European Commission triggered a procedure under Article 20 of Regulation (EC) No 726/2004, and asked the Agency to assess the above elements and their potential impact on the benefit-risk balance of Tysabri.
Na podlagi zgornjih podatkov je Evropska komisija 29. aprila 2015 sprožila postopek v skladu s členom 20 Uredbe (ES) št. 726/2004 in zahtevala od agencije, da oceni zgornje elemente in njihov morebitni vpliv na razmerje med tveganji in koristmi zdravila Tysabri.
In general, the positive serostatus results using the first and second generation assays were similar.
Na splošno so bili rezultati o pozitivnem serološkem statusu z uporabo testov prve in druge generacije podobni.
As of May 2015, 142,958 patients had received natalizumab worldwide with 432,814 patient-years of exposure.
Do maja 2015 je po celem svetu natalizumab prejelo 142 958 bolnikov z izpostavljenostjo 432 814 bolnik-let.
As the request results from the evaluation of data resulting from pharmacovigilance activities, the opinion should be adopted by the Committee for Medicinal Products for Human Use (CHMP) on the basis of a recommendation from the Pharmacovigilance Risk Assessment Committee (PRAC).
Ker je ta zahteva posledica vrednotenja podatkov, ki izhajajo iz dejavnosti farmakovigilance, mora Odbor za zdravila za uporabo v humani medicini (CHMP) mnenje podati na podlagi priporočila Odbora za oceno tveganja na področju farmakovigilance (PRAC).
The EC requested the Agency to give its opinion on whether a regulatory action with regard to the marketing authorisation for this product is necessary.
EK je od agencije zahtevala, naj poda svoje mnenje o tem, ali je za to zdravilo potreben regulativni ukrep v zvezi z dovoljenjem za promet.
Based on the data on antibody index stability from STRATIFY-2 the recommendation should be maintained.
Na podlagi podatkov o stabilnosti indeksa protiteles iz študije STRATIFY-2 je priporočilo treba ohraniti.
However, it is unclear whether a single index cut-point can be identified within the range of index thresholds assessed that will provide optimal clinical utility in terms of treatment decisions.
Vendar pa ni jasno, ali je mogoče določiti eno samo ločnico znotraj razpona ocenjenih pragov indeksa, ki bi zagotavljala klinično uporabnost v smislu odločitev o zdravljenju.
The wording of a Direct Healthcare Professional Communication has been adopted, together with a communication plan.
Sprejeto je bilo besedilo za neposredno komunikacijo z zdravstvenimi delavci in načrt komuniciranja.
• The PRAC considered Tysabri (natalizumab) in the procedure under Article 20 of Regulation (EC) No 726/2004, initiated by the European Commission
• odbor PRAC je za zdravilo Tysabri (natalizumab) obravnaval postopek v skladu s členom 20 Uredbe (ES) št. 726/2004, ki ga je uvedla Evropska komisija;
Tysabri (natalizumab) was approved in the EU on 27 June 2006 and is currently indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis (MS).
Zdravilo Tysabri (natalizumab) je bilo v EU odobreno 27. junija 2006 in je trenutno indicirano kot terapija, ki spreminja potek bolezni pri zelo aktivni recidivno-remitentni multipli sklerozi (MS).
In addition, the patient alert card and the treatment initiation and continuation forms are also updated, and a new treatment discontinuation form is introduced.
Poleg tega se posodobijo tudi bolnikova opozorilna kartica ter obrazca za uvedbo in nadaljevanje zdravljenja, uvede pa se nov obrazec za prekinitev zdravljenja.
While 10 cases have been reported in the US, most of the asymptomatic cases were reported from EU/ROW (83%, 52/62).
O desetih primerih so poročali iz ZDA, preostali asimptomatski primeri pa prihajajo iz EU in preostalega sveta (83 %, 52/62).
Early diagnosis of PML appears to be associated with improved outcomes.
Kaže, da je zgodnja diagnoza PML povezana z boljšimi izidi;
Increasing evidence indicates that T2-FLAIR is the most sensitive sequence for detecting PML.
Čedalje več dokazov kaže, da je T2/FLAIR najobčutljivejša sekvenca za odkrivanje PML.
All PML cases in patients who had received natalizumab occurred within 6 months of the last infusion.
Vsi primeri PML pri bolnikih, ki so prejemali natalizumab, so se pojavili v 6 mesecih po zadnji infuziji.
Patients who survive often have serious morbidity associated with serious and permanent disability.
Za preživele bolnike je pogosto značilna huda obolevnost, povezana s hudo in trajno prizadetostjo.
Thus, adequate guidance needs to be provided in the educational materials, and other tools may also be explored (e.g. web-based) for sharing MRIs and consultation of additional expertise.
Zato je treba v izobraževalno gradivo vključiti ustrezna navodila, preučiti pa je treba tudi druga orodja (npr. spletna) za deljenje MRS in dodatne strokovne posvete.
Current evidence suggests that risk increases with increasing antibody index but there is no clear cut off value.
Trenutni dokazi kažejo, da se tveganje z naraščanjem indeksa protiteles zvišuje, vendar jasne ločnice ni.
The PRAC agreed on the need to amend the physician information and management guideline and updated the key elements of the educational material accordingly.
Odbor PRAC se je strinjal glede potrebe po spremembi informacij za zdravnika in smernic za obravnavo ter je v skladu s tem posodobil ključne elemente izobraževalnega gradiva.
Natalizumab is a humanized monoclonal antibody targeting the α-chain of the α4β1 adhesion molecule.
Natalizumab je humanizirano monoklonsko protitelo, ciljno usmerjeno proti α-verigi adhezijske molekule α4β1.
• a history of immunosuppressive therapy.
• predhodno zdravljenje z imunosupresivi.
Scientific evidence on progressive multifocal leukoencephalopathy (PML) in patients treated with Tysabri is rapidly growing.
Število znanstvenih dokazov o progresivni multifokalni levkoencefalopatiji (PML) pri bolnikih, zdravljenih z zdravilom Tysabri, hitro narašča.
A total of 566 PML cases have been reported globally as of 04 June 2015, of which 133 patients died (23.5 % 0f PML patients).
Do 4. junija 2015 so skupaj poročali o 566 primerih PML, od katerih je 133 bolnikov umrlo (23,5 % bolnikov s PML).
Natalizumab is associated with the onset of progressive multifocal leukoencephalopathy (PML), which is caused by John Cunningham Virus (JCV).
Natalizumab je povezan s pojavom progresivne multifokalne levkoencefalopatije (PML), ki jo povzroča virus John Cunningham (JCV).
The onset of PML in MS has serious prognostic implications, as it leads to death in about 20% of patients or to serious disability in 40% of survivors.
Pojav PML pri MS močno vpliva na prognozo, saj pri približno 20 % bolnikih povzroča smrt, pri 40 % preživelih pa hudo prizadetost.
In sixty-two PML patients (10.9%) asymptomatic onset PML has been reported.
Pri 62 bolnikih s PML (10,9 %) so poročali o asimptomatskem pojavu PML.
Diagnosis of PML before development of clinical symptoms
Diagnoza PML pred pojavom kliničnih simptomov
Considering real world data from UNILABS from four EU countries showing that the upper annual serostatus change rate can be as high as 16%, the annual (negative to positive) serostatus change rate in the Physician Information and Management Guidelines needs to be updated.
Z upoštevanjem dejanskih podatkov, ki jih zagotavlja UNILABS za štiri države EU in kažejo, da je zgornja letna stopnja spremembe serološkega statusa celo do 16 %, je treba v informacijah za zdravnika in smernicah za obravnavo posodobiti letno stopnjo spremembe serološkega statusa (iz negativnega v pozitivnega).
Patients who have all three risk factors for PML have a significantly higher risk of PML.
Pri bolnikih z vsemi tremi dejavniki tveganja za PML je bistveno povečano tveganje za PML.
Sensitivity differs very little between the index of 0.9 and 1.5 but there is improved specificity with 1.5.
Občutljivost se med indeksoma 0,9 in 1,5 zelo malo razlikuje, pri indeksu 1,5 pa je specifičnost bistveno boljša.
Recent efforts to identify potential biomarkers are promising but have not resulted, to date, in the identification of new markers that can be used in clinical practice to enhance the existing PML risk stratification.
Nedavna prizadevanja za določitev potencialnih bioloških označevalcev so obetavna, vendar do zdaj novih označevalcev, ki bi jih lahko uporabili v klinični praksi za boljšo stratifikacijo tveganja za PML, še niso našli.
Since the auhtorisation of natalizumab, three main risk factors for PML have been identified:
Od izdaje dovoljenja za promet za natalizumab so prepoznali tri glavne dejavnike tveganja za PML:
Most importantly, in terms of outcomes, asymptomatic patients appeared to have less accrual of disability over time and higher survival rates compared with symptomatic patients (95% vs. 74%).
Kar zadeva izide, pa je najpomembnejše, da so imeli asimptomatski bolniki manjše naraščanje prizadetosti s časom in višje stopnje preživetja v primerjavi s simptomatskimi bolniki (95 % v primerjavi s 74 %).
• The PRAC also considered it necessary to update the existing educational material, particularly in relation to the risk estimates for development of PML in Tysabri-treated patients.
• odbor je menil tudi, da je treba posodobiti obstoječe izobraževalno gradivo, zlasti v povezavi z ocenami tveganja za pojav PML pri bolnikih, ki se zdravijo z zdravilom Tysabri.
For patients with prior immunosuppressant treatment, no significant difference was observed in median index between non-PML and PML patients.
Pri bolnikih, ki so se predhodno zdravili z imunosupresivi, niso opazili značilne razlike v srednji vrednosti indeksa med bolniki s PML in bolniki brez PML.
These data confirm previous observations that early PML diagnosis is critical in limiting the degree of permanent brain damage before immune reconstitution can be achieved, and reinforces the need to put in place strategies for the earliest possible identification of potential PML cases, if possible before the development of clinical symptoms of PML.
Ti podatki potrjujejo predhodna opažanja, da je zgodnja diagnostika PML bistvenega pomena pri omejevanju stopnje trajnih poškodb možganov, preden se doseže sprožitev imunske obnove, in krepijo potrebo po vzpostavitvi strategij za čim prejšnje prepoznavanje morebitnih primerov PML, po možnosti pred pojavom kliničnih simptomov PML.
• The PRAC reviewed all data presented by the MAH on the risk of PML in association with Tysabri, as well as other data made available during the procedure and the views expressed by the neurology scientific advisory group.
• odbor je preučil vse podatke, ki jih je predložil imetnik dovoljenja za promet z zdravilom o tveganju za PML v povezavi z zdravilom Tysabri, in druge podatke, na voljo med postopkom, ter stališča, ki jih je izrazila znanstvena svetovalna skupina za nevrologijo;
PML risk estimation
Ocena tveganja za PML
The shorter time to diagnosis of asymptomatic patients compared with symptomatic patients may have enabled earlier immune reconstitution following discontinuation of natalizumab.
Krajši čas do diagnoze pri asimptomatskih bolnikih v primerjavi s simptomatskimi je morda omogočil zgodnejšo sprožitev imunske obnove po prekinitvi zdravljenja z natalizumabom.
• the presence of JCV-specific antibodies,
• prisotnost protiteles, specifičnih za JCV,
Currently it is recommended that patients who are anti-JCV antibody negative should be tested for seroconversion twice yearly.
Trenutno se priporoča, da se bolniki, negativni za protitelesa proti JCV, dvakrat letno testirajo za serokonverzijo.
A mock-up of the updated physician information and management guideline can be found annexed to the RMP.
Osnutek posodobljenih informacij za zdravnika in smernic za obravnavo je na voljo v prilogi k RMP.
In particular, the inclusion of a KaplanMeier analysis of PML risk alongside the algorithm would allow to present cumulative risk of PML over time.
Uporaba Kaplan-Meierjeve analize tveganja za PML skupaj z algoritmom bi omogočila predstavitev časovnega kumulativnega tveganja za PML.
• The PRAC concluded that PML which is clinically asymptomatic at diagnosis represents more frequently localised disease in MRI, with a higher survival rate and better clinical outcome as compared to symptomatic PML.
• odbor je zaključil, da se PML, ki je ob diagnozi asimptomatska, na MRS pogosteje izkaže za lokalizirano bolezen, z višjo stopnjo preživetja in boljšim kliničnim izidom v primerjavi s simptomatsko PML.
The assumption of 55% positive serostatus for the overall natalizumab-treated population utilized in the PML risk algorithm calculations remains acceptable.
Predpostavka, da ima 55 % celotne populacije, ki se zdravi z natalizumabom, pozitiven serološki status, kar je številka, ki se uporablja pri izračunih algoritma za ugotavljanje tveganja za PML, ostaja sprejemljiva.
New information has become available on three key issues: risk estimates; the diagnosis of PML before the development of clinical symptoms; and anti-JC virus antibodies.
Na voljo so nove informacije o treh glavnih vprašanjih: ocenah tveganja, diagnozi PML pred pojavom kliničnih simptomov in protitelesih proti virusu JC.
In spite of limitations of the currently available evidence such as small numbers, lack of information about MRI frequency in PML patients, false positive and false negative rate of MRI screenings, patients with a high risk for PML development may in particular benefit from more frequent MRIs because periodic brain MRI are likely to provide earlier detection of PML, even before symptoms develop, and subsequently better outcomes.
Kljub omejitvam trenutno razpoložljivih dokazov, kot so majhno število, pomanjkanje informacij o pogostnosti opravljanja MRS pri bolnikih s PML, delež lažno pozitivnih in lažno negativnih rezultatov pri slikanju z MR, bolnikom z visokim tveganjem za pojav PML lahko zlasti koristi pogostejše MRS, saj z rednimi MRS možganov verjetno bolj zgodaj odkrijemo PML, še pred pojavom simptomov, kar pomeni boljše izide.
Currently available evidence suggests that the risk of PML is low at an index equal to or below 0.9 (and lower than previously estimated) and increases substantially above 1.5 for patients who have been on treatment with Tysabri for longer than 2 years.
Trenutno razpoložljivi dokazi kažejo, da je tveganje za PML pri indeksu do 0,9 nizko (in nižje, kot je bilo predhodno ocenjeno), a se bistveno zviša pri vrednosti nad 1,5 pri bolnikih, ki se zdravijo z zdravilom Tysabri več kot 2 leti.
In patients treated for longer than 2 years, the risk of PML is low at index values of 0.9 or less, and increases substantially at values above 1.5.
Pri bolnikih, ki se zdravijo dlje kot 2 leti, je tveganje za PML nizko pri vrednostih indeksa do 0,9, pri vrednostih nad 1,5 pa se bistveno zviša;
These findings support the current SmPC recommendation that physicians should remain vigilant for signs and symptoms of PML for approximately 6 months after natalizumab discontinuation, and that the same monitoring strategy should apply for up to 6 months after discontinuation.
Ti izsledki podpirajo trenutna priporočila v povzetku glavnih značilnosti zdravila, ki navajajo, da morajo biti zdravniki pozorni na znake in simptome PML še približno 6 mesecev po prenehanju zdravljenja z natalizumabom, in da enaka strategija spremljanja velja do 6 mesecev po prenehanju.
Diffusion -weighted imaging is highly sensitive for depicting acute demyelinisation and can also aid differentiation of acute PML lesions from chronic and subacute demyelinating PML lesions.
Difuzijsko obteženo slikanje je zelo občutljivo za prikaz akutne demielinizacije in lahko pripomore k razlikovanju med akutnimi lezijami PML ter kroničnimi in subakutnimi demielinizacijskimi lezijami PML.
In addition, it needs to be clarified that patients who test anti-JCV antibody positive at any time should be considered to beat an increased risk of PML, independent of any prior or subsequent antibody test result.
Poleg tega je treba pojasniti, da za bolnike, ki so kadar koli pozitivni za protitelesa proti JCV, velja, da imajo povišano tveganje za PML, ne glede na prejšnje ali naslednje rezultate testiranja za protitelesa.
The risk stratification algorithm in the educational material will be revised to include current estimates derived from a pooled study cohort (STRATIFY-2, TOP, TYGRIS and STRATA studies) of natalizumab-treated patients, and to incorporate anti-JCV antibody index.
Algoritem stratifikacije tveganja v izobraževalnem gradivu bo popravljen in bo vključeval trenutne ocene, izpeljane iz združene študijske kohorte (iz študij STRATIFY-2, TOP, TYGRIS in STRATA) bolnikov, zdravljenih z natalizumabom, ter indeks protiteles proti JCV.
The clinical presentation of natalizumab-associated PML is considered not distinct from classical PML, and consists in cognitive disorders in more than half of the patients together with motor symptoms, ataxia, neurovisual disturbances, and dysphasia or agnosia in more than 40% of cases.
Velja, da se klinična slika z natalizumabom povezane PML ne razlikuje od klasične PML in pri več kot polovici bolnikov vključuje kognitivne motnje z motoričnimi simptomi, ataksijo, motnjami živčevja in vida, pri več kot 40 % bolnikov pa disfazijo ali agnozijo.
Although asymptomatic PML patients had generally similar baseline clinical characteristics compared with symptomatic patients, a higher proportion of asymptomatic patients presented with more localized disease (64% unilobar PML) on Magnetic Resonance Image (MRI) at the time of diagnosis compared to symptomatic PML patients (36%).
Čeprav so imeli bolniki z asimptomatsko PML na splošno podobne izhodiščne klinične značilnosti v primerjavi s simptomatskimi bolniki, je imel večji delež asimptomatskih bolnikov ob diagnozi na magnetnoresonančnem slikanju (MRS) bolj lokalizirano bolezen (64 % unilobarne PML) kot simptomatski bolniki s PML (36 %).
Supplemental presentations of PML risk using different methodologies may be complementary to the information within the current algorithm and will provide additional information to physicians as they engage in benefit/risk discussions with their patients.
Informacije v trenutnem algoritmu se lahko dopolnijo z dodatnimi predstavitvami tveganja za PML z uporabo različnih metodologij, kar bo zdravnikom omogočilo več podatkov pri pogovorih z bolniki o razmerju med tveganji in koristmi.
Therefore a number of risk minimisation measures in relation to PML are in place for Tysabri.
Zato so za zdravilo Tysabri vzpostavljeni številni ukrepi za zmanjševanje tveganja v povezavi s PML.
Published data suggest that patients considered as having a high risk for PML development and who continue natalizumab treatment beyond 2 years of treatment may benefit from more frequent MRI screening e.g. every 3 to 6 months.
Objavljeni podatki kažejo, da bolnikom, za katere velja, da imajo večje tveganje za pojav PML, in ki se z natalizumabom zdravijo več kot 2 leti, lahko koristijo pogostejša slikanja z MR, npr. na 3 do 6 mesecev.
It is important to update the package leaflet concerning the risk of PML up to 6 months following Tysabri discontinuation.
Pomembno je, da se navodilo za uporabo posodobi z informacijami, da tveganje za PML traja 6 mesecev po prenehanju zdravljenja z zdravilom Tysabri.
• The PRAC also concluded that, in patients who have not received prior immunosuppressant therapy and are anti-JCV antibody positive, the level of anti-JCV antibody response (index) is associated with risk of developing PML.
• odbor je zaključil tudi, da je pri bolnikih, ki se predhodno niso zdravili z imunosupresivi in so pozitivni na protitelesa proti JCV, odziv (indeks) protiteles proti JCV povezan s tveganjem za pojav PML.
The Committee, as a consequence, recommended the variation to the terms of the marketing authorisation for Tysabri.
Odbor je posledično priporočil spremembo pogojev dovoljenja za promet z zdravilom Tysabri.
Available data to date suggest that anti-JCV antibody index is correlated with the risk of PML in anti-JCV antibody positive patients with no prior immunosuppressant use.
Podatki, ki so na voljo do zdaj, kažejo, da je indeks protiteles proti JCV povezan s tveganjem za PML pri bolnikih, pozitivnih na protitelesa proti JCV, ki se pred tem niso zdravili z imunosupresivi.
For patients without prior immunosuppressant use and with high anti-JCV antibody index, no further antibody testing is required, as more frequent MRI screening should be considered if natalizumab treatment is continued for more than 2 years.
Pri bolnikih, ki se predhodno niso zdravili z imunosupresivi in imajo visok indeks protiteles proti JCV, dodatno testiranje za protitelesa ni potrebno, ker je treba razmisliti o pogostejšem slikanju z magnetno resonanco, če zdravljenje z natalizumabom traja več kot 2 leti.
Biomarkers for PML development
Biološki označevalci za pojav PML
PML development after discontinuation of natalizumab
Pojav PML po prenehanju zdravljenja z natalizumabom
In patients with MRI lesions suggestive for PML, the MRI protocol should be extended to include contrast-enhanced T1-weighted imaging to detect inflammatory features and the possible coincidence of PML and PML-IRIS (Immune Reconstitution Inflammatory Syndrome), particularly during follow up.
Pri bolnikih z lezijami na MRS, ki kažejo na PML, je treba protokol MRS razširiti še na kontrastno, T1-obteženo slikanje, s katerim odkrivamo vnetne značilnosti in morebitno sopojavnost PML in PML-IRIS (vnetnega sindroma imunske obnove), zlasti v obdobju spremljanja.
Anti-JCV antibody index for guiding MRI monitoring frequency
Indeks protiteles proti JCV za določanje pogostnosti spremljanja z MRS
There is no significant impact of the second generation assay on the risk estimates within the algorithm.
Na ocene tveganja znotraj algoritma test druge generacije nima pomembnega vpliva.
• The PRAC recommended that patients with low anti-JCV antibody index who have not received prior immunosuppressant therapy should be retested every six months once they reach the 2-year treatment point.
• odbor je priporočil, da se bolniki z nizkim indeksom protiteles proti JCV, ki se predhodno niso zdravili z imunosupresivi, testirajo na šest mesecev, ko dolžina zdravljenja doseže 2 leti;