UPDATE ON GUIDELINES FOR PHARMACOLOGICAL TREATMENT OF MULTIPLE SCLEROSIS BY THE CROATIAN SOCIETY FOR NEUROVASCULAR DISORDERS OF THE CROATIAN MEDICAL ASSOCIATION AND CROATIAN SOCIETY OF NEUROIMMUNOLOGY AND NEUROGENETICS

Multipla skleroza (MS) je bolest središnjeg živčanog sustava koja se prezentira brojnim simptomima iz različitih funkcijskih cjelina toga sustava. Kako se posljednjih godina povećao broj dostupnih lijekova, ukazuje se potreba trajne provjere saznanja o dijagnostici i liječenju ove bolesti putem medicine temeljene na dokazima. Time se nameće i potreba kontinuiranog obnavljanja nacionalnih i međunarodnih smjernica, u našem slučaju, na razini regionalnih smjernica Europskog odbora za liječenje i istraživanje multiple skleroze (engl. ECTRIMS, European Committee of Treatment and Research in Multiple Sclerosis) i Europske neurološke akademije (engl. EAN, European Academy of Neurology) s ciljem omogućavanja najbolje medicinske terapije za svakog bolesnika, koja je temeljena na individualiziranom pristupu. Temelji novih smjernica su nedavno ažurirane EAN-ove preporuke za razvoj smjernica, koje su rezultat iscrpnog istraživanja literature do prosinca 2016. godine. S obzirom na rizik od sistemske pogreške, kvaliteta dokaza za svaki ishod bila je stupnjevana u četiri kategorije kako slijedi: vrlo visoka, visoka, niska i vrlo niska. S obzirom na kvalitetu dokaza te omjera rizika i dobrobiti preporukama je pridružena snažna i slaba jačina. Pozornost istraživanja bila je usmjerena na nekoliko najvažnijih pitanja, koja su obuhvaćala uspješnost liječenja, odgovor na primijenjenu terapiju, strategiju za prepoznavanje odgovarajućeg odgovora i sigurnost, te terapijsku strategiju liječenja multiple skleroze u trudnoći. Smjernicama su obuhvaćeni svi lijekovi koji modifi ciraju tijek bolesti, a koji su odobreni od strane Europske agencije za lijekove (engl. EMA, European Medicine Agency). U posebne skupine raspoređeni su bolesnici s klinički izoliranim sindromom koji ne ispunjavaju dijagnostičke kriterije za klinički defi nitivnu MS, dok su bolesnici s dokazanom MS podijeljeni s obzirom na različite kliničke podtipove MS-a sukladno važećim dijagnostičkim smjernicama.Multiple sclerosis (MS) affects the central nervous system (CNS) and presents by numerous symptoms from different CNS functional systems. As the number of available treatments has increased in recent years, the need has emerged for continuous evaluation on MS diagnosis and treatment based on evidence-based medicine. This implies the need for continuous renewal of national and international guidelines, in our case, based on the regional guidelines of the European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology (EAN) with the aim of providing the best medical therapy for each patient, based on an individualized approach. These new guidelines are based on the recently updated EAN recommendations that have been derived as the result of exhaustive literature research as of December 2016. Given the risk of system error, the quality of evidence for each outcome has been subdivided into four categories, as follows: very high, high, low and very low. Given the quality of evidence and the risk and benefit ratio, the recommendations are accompanied by strong and weak strength. The research was focused on several key issues, including treatment effectiveness, response to therapy applied, strategy for recognizing appropriate response and safety, and therapeutic strategy for MS treatment during pregnancy. The guidelines cover all medicines that modify the course of the disease and are approved by the European Medicines Agency. Patients with clinically isolated syndrome that do not meet diagnostic criteria for clinically definitive MS have been assigned to special groups while patients with proven MS are divided into different clinical subtypes of MS in accordance with valid diagnostic guidelines

UPDATE ON GUIDELINES FOR PHARMACOLOGICAL TREATMENT OF MULTIPLE SCLEROSIS BY THE CROATIAN SOCIETY FOR NEUROVASCULAR DISORDERS OF THE CROATIAN MEDICAL ASSOCIATION AND CROATIAN SOCIETY OF NEUROIMMUNOLOGY AND NEUROGENETICS

Multipla skleroza (MS) je bolest središnjeg živčanog sustava koja se prezentira brojnim simptomima iz različitih funkcijskih cjelina toga sustava. Kako se posljednjih godina povećao broj dostupnih lijekova, ukazuje se potreba trajne provjere saznanja o dijagnostici i liječenju ove bolesti putem medicine temeljene na dokazima. Time se nameće i potreba kontinuiranog obnavljanja nacionalnih i međunarodnih smjernica, u našem slučaju, na razini regionalnih smjernica Europskog odbora za liječenje i istraživanje multiple skleroze (engl. ECTRIMS, European Committee of Treatment and Research in Multiple Sclerosis) i Europske neurološke akademije (engl. EAN, European Academy of Neurology) s ciljem omogućavanja najbolje medicinske terapije za svakog bolesnika, koja je temeljena na individualiziranom pristupu. Temelji novih smjernica su nedavno ažurirane EAN-ove preporuke za razvoj smjernica, koje su rezultat iscrpnog istraživanja literature do prosinca 2016. godine. S obzirom na rizik od sistemske pogreške, kvaliteta dokaza za svaki ishod bila je stupnjevana u četiri kategorije kako slijedi: vrlo visoka, visoka, niska i vrlo niska. S obzirom na kvalitetu dokaza te omjera rizika i dobrobiti preporukama je pridružena snažna i slaba jačina. Pozornost istraživanja bila je usmjerena na nekoliko najvažnijih pitanja, koja su obuhvaćala uspješnost liječenja, odgovor na primijenjenu terapiju, strategiju za prepoznavanje odgovarajućeg odgovora i sigurnost, te terapijsku strategiju liječenja multiple skleroze u trudnoći. Smjernicama su obuhvaćeni svi lijekovi koji modifi ciraju tijek bolesti, a koji su odobreni od strane Europske agencije za lijekove (engl. EMA, European Medicine Agency). U posebne skupine raspoređeni su bolesnici s klinički izoliranim sindromom koji ne ispunjavaju dijagnostičke kriterije za klinički defi nitivnu MS, dok su bolesnici s dokazanom MS podijeljeni s obzirom na različite kliničke podtipove MS-a sukladno važećim dijagnostičkim smjernicama.Multiple sclerosis (MS) affects the central nervous system (CNS) and presents by numerous symptoms from different CNS functional systems. As the number of available treatments has increased in recent years, the need has emerged for continuous evaluation on MS diagnosis and treatment based on evidence-based medicine. This implies the need for continuous renewal of national and international guidelines, in our case, based on the regional guidelines of the European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology (EAN) with the aim of providing the best medical therapy for each patient, based on an individualized approach. These new guidelines are based on the recently updated EAN recommendations that have been derived as the result of exhaustive literature research as of December 2016. Given the risk of system error, the quality of evidence for each outcome has been subdivided into four categories, as follows: very high, high, low and very low. Given the quality of evidence and the risk and benefit ratio, the recommendations are accompanied by strong and weak strength. The research was focused on several key issues, including treatment effectiveness, response to therapy applied, strategy for recognizing appropriate response and safety, and therapeutic strategy for MS treatment during pregnancy. The guidelines cover all medicines that modify the course of the disease and are approved by the European Medicines Agency. Patients with clinically isolated syndrome that do not meet diagnostic criteria for clinically definitive MS have been assigned to special groups while patients with proven MS are divided into different clinical subtypes of MS in accordance with valid diagnostic guidelines

Smjernice za farmakološko liječenje epilepsije

SAŽETAK Međunarodne smjernice za farmakološko liječenje epilepsija općenite su, sveobuhvatne i ne prepoznaju lokalne specifičnosti poput ekonomskih i tehničkih mogućnosti u pojedinim državama, dostupnosti pojedinih antiepileptika ili drugih metoda liječenja i slično. Stoga se nameće potreba izrade nacionalnih smjernica, čiji su zapravo temelj međunarodne smjernice Internacionalne lige protiv epilepsije. Hrvatske smjernice za farmakološko liječenje epilepsija plod su suradnje svih relevantnih stručnih društava i referentnih centara u RH, na čelu s Hrvatskom ligom protiv epilepsije te Hrvatskim neurološkim društvom i Hrvatskim društvom za dječju neurologiju Hrvatskoga liječničkog zbora, a odražavaju aktualne socioekonomske i regulatorne specifičnosti u našoj zemlji, najnovije spoznaje farmakoloških profila i učinkovitosti pojedinih antiepileptika kao i ekspertna mišljenja. Antiepileptička terapija se uvodi nakon postavljanja dijagnoze epilepsije, stoga profilaktička primjena nije opravdana. Nakon postavljanja dijagnoze potrebno je bolesnika informirati o prognozi bolesti, mogućnostima liječenja i samopomoći, životnim ograničenjima te mogućim neželjenim događajima. Ciljevi farmakoterapije epilepsija su potpuna kontrola napada uz izbjegavanje nuspojava te održavanje ili poboljšanje kvalitete života. Zlatni standard liječenja je monoterapija odnosno primjena adekvatnog antiepileptika u adekvatnoj dozi. Izbor i titracija lijeka su individualni, a temelje se na smjernicama za liječenje pojedinih vrsta napada, karakteristikama bolesnika i regulatorno specifičnim čimbenicima. Nakon neuspjeha inicijalne monoterapije, potrebna je reevalucija anamnestičkih i dijagnostičkih podataka te potom postupna i spora zamjena antiepileptika. Racionalna politerapija podrazumijeva kombinaciju dvaju antiepileptika različitih mehanizama djelovanja, prvog ili eventualno drugog izbora za postavljenju dijagnozu, niskoga interakcijskog potencijala, različitog profila nuspojava i sinergističkog ili aditivnog djelovanja. Zamjena generičkih ili originalnog i generičkog oblika lijeka nije preporučljiva, a poglavito nakon postizanja remisije ili prilikom uzimanja visokih doza lijeka. Ukidanje antiepileptičke terapije treba biti postupno i sporo, u slučaju politerapije jedan po jedan lijek, a u donošenju odluke o ukidanju, kao i o uvođenju antiepileptika, mora biti uključen bolesnik i njegova obitelj

Detection of positive selection signatures in the genome of Croatian sheep

Ovčarstvo je jedan od najvažnijih stočarskih sektora u mediteranskom području Hrvatske odakle potječe većina hrvatskih autohtonih pasmina. Prisutni signali pozitivne selekcije posljedica su adaptacije na oskudne okolišne čimbenike, ali i odabira (selekcije) ljudi. U ovom istraživanju je uz autosome bio uključen i spolni kromosom X (kod ženskih jedinki), zbog utjecaja spolno vezanog nasljeđivanja na ekonomski i evolucijski važna svojstva. Cilj rada bio je identificirati signale pozitivne selekcije putem dvije metode, iHS i eROHi, koristeći uzorak veličine 102 jedinke iz 4 autohtone pasmine ovaca Hrvatske i 606 006 SNP-ova (Infinium® HD SNP BeadChip), na kojem je prije analize obavljena kontrola kvalitete. Obje metode temelje se na analizi genomskih varijacija unutar jedne velike metapopulacije, koja ovdje predstavlja hrvatske autohtone pasmine ovaca. Uočeni su mnogi ekonomski i evolucijski važni geni te je tako razjašnjena prisutnost pojedinih signala u populaciji. Za precizniju i pouzdaniju analizu potrebno je povećati uzorak te uključiti još metoda identifikacije.Sheep farming is one of the most important livestock sectors in the Mediterranean region of Croatia, where most of the Croatian autochthonous breeds originate from. The present positive selection signatures are a consequence of adaptation to scarce environmental factors, but also of artificial selection. In addition to autosomes, sex chromosome X (in females) was included in this study because of the known influence of sex-linked inheritance on many economically and evolutionarily important traits. The aim of this study was to identify positive selection signatures by two methods, iHS and eROHi, using a sample size of 102 individuals from 4 Croatian autochthonous breeds and 606 006 SNPs (Infinium® HD SNP BeadChip) on which quality control was performed before analysis. Both methods are based on the analysis of genomic variation within a large metapopulation, which here represents Croatian autochthonous sheep breeds. Many economically and evolutionarily relevant genes were identified, highlighting the presence of multiple signatures in the population. For a more accurate and reliable analysis, it is necessary to increase the sample size and include additional identification methods

Detection of positive selection signatures in the genome of Croatian sheep

Ovčarstvo je jedan od najvažnijih stočarskih sektora u mediteranskom području Hrvatske odakle potječe većina hrvatskih autohtonih pasmina. Prisutni signali pozitivne selekcije posljedica su adaptacije na oskudne okolišne čimbenike, ali i odabira (selekcije) ljudi. U ovom istraživanju je uz autosome bio uključen i spolni kromosom X (kod ženskih jedinki), zbog utjecaja spolno vezanog nasljeđivanja na ekonomski i evolucijski važna svojstva. Cilj rada bio je identificirati signale pozitivne selekcije putem dvije metode, iHS i eROHi, koristeći uzorak veličine 102 jedinke iz 4 autohtone pasmine ovaca Hrvatske i 606 006 SNP-ova (Infinium® HD SNP BeadChip), na kojem je prije analize obavljena kontrola kvalitete. Obje metode temelje se na analizi genomskih varijacija unutar jedne velike metapopulacije, koja ovdje predstavlja hrvatske autohtone pasmine ovaca. Uočeni su mnogi ekonomski i evolucijski važni geni te je tako razjašnjena prisutnost pojedinih signala u populaciji. Za precizniju i pouzdaniju analizu potrebno je povećati uzorak te uključiti još metoda identifikacije.Sheep farming is one of the most important livestock sectors in the Mediterranean region of Croatia, where most of the Croatian autochthonous breeds originate from. The present positive selection signatures are a consequence of adaptation to scarce environmental factors, but also of artificial selection. In addition to autosomes, sex chromosome X (in females) was included in this study because of the known influence of sex-linked inheritance on many economically and evolutionarily important traits. The aim of this study was to identify positive selection signatures by two methods, iHS and eROHi, using a sample size of 102 individuals from 4 Croatian autochthonous breeds and 606 006 SNPs (Infinium® HD SNP BeadChip) on which quality control was performed before analysis. Both methods are based on the analysis of genomic variation within a large metapopulation, which here represents Croatian autochthonous sheep breeds. Many economically and evolutionarily relevant genes were identified, highlighting the presence of multiple signatures in the population. For a more accurate and reliable analysis, it is necessary to increase the sample size and include additional identification methods

Genomic Diversity Analyses of Some Indigenous Montenegrin Sheep Populations

Montenegro has a great diversity of indigenous and locally developed sheep breeds, adapted to different regions and climates. However, the current trend of the steady decline in sheep populations means that some of them are threatened with extinction. The aim of this study was the investigation of the genetic diversity and population structure of five Montenegrin sheep populations, using the OvineSNP50K BeadChip. Data from the studied sheep were supplemented with publicly available genotypes of worldwide breeds to determine admixture contributions and genetic relationships. Higher genetic diversity and low inbreeding were observed in Pivska Pramenka and Sjenicka sheep, with Ho = 0.411, He = 0.423, and FROH>2Mb = 0.056 and Ho = 0.421, He = 0.421, and FROH>2Mb = 0.041, respectively. Zetska Zuja had much lower FIS (0.001) and high FROH inbreeding (0.090), indicating a small population size and genetic drift. An analysis of the genetic population structure showed that Montenegrin sheep populations are genetically distinct populations. This analysis revealed the presence of admixture in most sheep populations (high heterogeneity), while genetic purity was observed in Zetska Zuja. The obtained results will help in the conservation management of endangered Montenegrin sheep populations

High-Density Genomic Characterization of Native Croatian Sheep Breeds

A recent comprehensive genomic analysis based on 50K SNP profiles has shown that the regional Balkan sheep populations have considerable genetic overlap but are distinctly different from surrounding breeds. All eight Croatian sheep breeds were represented by a small number of individuals per breed. Here, we genotyped 220 individuals representing the native Croatian sheep breeds (Istrian Sheep, Krk Island Sheep, Cres Island Sheep, Rab Island Sheep, Lika Pramenka, Pag Island Sheep, Dalmatian Pramenka, Dubrovnik Sheep) and mouflon using the Ovine Infinium ® HD SNP BeadChip (606,006 SNPs). In addition, we included publicly available Balkan Pramenka and other Mediterranean sheep breeds. Our analyses revealed the complex population structure of Croatian sheep breeds and their origin and geographic barriers (island versus mainland). Migration patterns confirmed the historical establishment of breeds and the pathways of gene flow. Inbreeding coefficients (F ROH>2 Mb) between sheep populations ranged from 0.025 to 0.070, with lower inbreeding coefficients observed in Dalmatian Pramenka and Pag Island Sheep and higher inbreeding in Dubrovnik sheep. The estimated effective population size ranged from 61 to 1039 for Krk Island Sheep and Dalmatian Pramenka, respectively. Higher inbreeding levels and lower effective population size indicate the need for improved conservation management to maintain genetic diversity in some breeds. Our results will contribute to breeding and conservation strategies of native Croatian sheep breeds

High-Density Genomic Characterization of Native Croatian Sheep Breeds

A recent comprehensive genomic analysis based on 50K SNP profiles has shown that the regional Balkan sheep populations have considerable genetic overlap but are distinctly different from surrounding breeds. All eight Croatian sheep breeds were represented by a small number of individuals per breed. Here, we genotyped 220 individuals representing the native Croatian sheep breeds (Istrian Sheep, Krk Island Sheep, Cres Island Sheep, Rab Island Sheep, Lika Pramenka, Pag Island Sheep, Dalmatian Pramenka, Dubrovnik Sheep) and mouflon using the Ovine Infinium ® HD SNP BeadChip (606,006 SNPs). In addition, we included publicly available Balkan Pramenka and other Mediterranean sheep breeds. Our analyses revealed the complex population structure of Croatian sheep breeds and their origin and geographic barriers (island versus mainland). Migration patterns confirmed the historical establishment of breeds and the pathways of gene flow. Inbreeding coefficients (F ROH>2 Mb) between sheep populations ranged from 0.025 to 0.070, with lower inbreeding coefficients observed in Dalmatian Pramenka and Pag Island Sheep and higher inbreeding in Dubrovnik sheep. The estimated effective population size ranged from 61 to 1039 for Krk Island Sheep and Dalmatian Pramenka, respectively. Higher inbreeding levels and lower effective population size indicate the need for improved conservation management to maintain genetic diversity in some breeds. Our results will contribute to breeding and conservation strategies of native Croatian sheep breeds

High-Density Genomic Characterization of Native Croatian Sheep Breeds

A recent comprehensive genomic analysis based on 50K SNP profiles has shown that the regional Balkan sheep populations have considerable genetic overlap but are distinctly different from surrounding breeds. All eight Croatian sheep breeds were represented by a small number of individuals per breed. Here, we genotyped 220 individuals representing the native Croatian sheep breeds (Istrian Sheep, Krk Island Sheep, Cres Island Sheep, Rab Island Sheep, Lika Pramenka, Pag Island Sheep, Dalmatian Pramenka, Dubrovnik Sheep) and mouflon using the Ovine Infinium® HD SNP BeadChip (606,006 SNPs). In addition, we included publicly available Balkan Pramenka and other Mediterranean sheep breeds. Our analyses revealed the complex population structure of Croatian sheep breeds and their origin and geographic barriers (island versus mainland). Migration patterns confirmed the historical establishment of breeds and the pathways of gene flow. Inbreeding coefficients (FROH>2 Mb) between sheep populations ranged from 0.025 to 0.070, with lower inbreeding coefficients observed in Dalmatian Pramenka and Pag Island Sheep and higher inbreeding in Dubrovnik sheep. The estimated effective population size ranged from 61 to 1039 for Krk Island Sheep and Dalmatian Pramenka, respectively. Higher inbreeding levels and lower effective population size indicate the need for improved conservation management to maintain genetic diversity in some breeds. Our results will contribute to breeding and conservation strategies of native Croatian sheep breeds