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    Distribution of botulinum toxin in the central nervous system

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    Botulinum toksin tipa A je neurotoksični protein koji proizvodi anaerobna bakterija Clostridium botulinum, te predstavja jedan od najsmrtonosnijih otrova u prirodi. Mehanizam djelovanja BoNT/A uključuje cijepanje proteina SNAP-25 koji ima ključnu ulogu u egzocitozi acetilkolina na krajevima aksona, te posljedično svoje djelovanje manifestira nastankom mlohane paralize mišića. Tijekom godina bazičnih istraživanja, pokazano je da toksin osim na motoričke neurone, također djeluje i na senzorne neurone te tako interferira s prijenosom bolnih signala, što za posljedicu može imati izniman klinički značaj. Kontroliranom primjenom u pikomolarnim dozama toksin se koristi u terapiji stanja koja su uzrokovana hiperaktivnosti mišića, kao što su cervikalna distonija, strabizam, hiperhidroza, ali i u terapiji kroničnih migrena. Brojna istraživanja su rađena istražujući dodatne mogućnosti primjene BoNT/A u kliničke svrhe, između ostalog i u terapiji kronične boli, čije je liječenje do sad predstavljalo veliki izazov. Cilj ovog diplomksog rada bio je ispitati distribuciju botulinum toksina u različitim regijama mozga nakon njegove primjene u cisternu magnu. Eksperimenti su provedeni na mužjacima štakora Wistar na Zavodu za farmakologiju Medicinskog fakulteta Sveučilišta u Zagrebu u skladu s s aktualim propisima i Zakonom o zaštiti životinja. Nakon iniciranja 5 i.j./kg BoNT/A u cisternu magnu, prikupljeni su uzorci tkiva mozgova i pripremljeni za imunohistokemijsku analizu. Pratila se prisutnost pocijepanog SNAP-25 proteina kao pokazatelja prisutnost toksina, u različitim regijama mozga.Dobiveni rezultati ukazuju na prisutnost toksina u neposrednoj blizini mjesta iniciranja, u područjima trigeminalnog nucleus caudalisaihipokampusa, ali i u udaljenim regijama mozga. Ovi nalazi zahtjevaju daljnja istraživanja kako bi se objasnili načini distribucije toksina u udaljenija područja te njihovo značenje za djelovanje toksina, posebice u kliničkom okruženju.Botulinum toxin type A is a neurotoxic protein produced by the anaerobic bacterium Clostridium botulinum, and is one of the deadliest poisons in nature. The mechanism of action of BoNT/A involves the cleavage of the SNAP-25 protein, which plays a key role in the exocytosis of acetylcholine at the ends of axons, and consequently manifests its action in the occurrence of flaccid muscle paralysis. During the years of basic research, it was shown that the toxin not only acts on motor neurons, but also on sensory neurons and thus interferes with the transmission of pain signals, which as a result can have exceptional clinical significance. With controlled application in picomolar doses, the toxin is used in the treatment of conditions caused by muscle hyperactivity, such as cervical dystonia, strabismus, hyperhidrosis, but also in the treatment of chronic migraines. Numerous studies have been conducted investigating the additional possibilities of using BoNT/A for clinical purposes, among others in the therapy of chronic pain, the treatment of which has been a great challenge so far. The aim of this thesis was to examine the distribution of botulinum toxin in different regions of the brain after its application to the cisterna magna. The experiments were conducted on male Wistar rats at the Department of Pharmacology, Faculty of Medicine, University of Zagreb, in accordance with current regulations and the Animal Protection Act. After the initiation of 5 IU/kg BoNT/A into the cisterna magna, brain tissue samples were collected and prepared for immunohistochemical analysis. The presence of cleaved SNAP-25 protein was monitored as an indicator of the presence of toxins in different regions of the brain. The obtained results indicate the presence of toxins in the immediate vicinity of the initiation site, in the areas of the trigeminal nucleus of the caudalis and hippocampus, but also in distant regions of the brain. These findings require further research to explain the ways of toxin distribution to more distant areas and their significance for the action of the toxin, especially in the clinical setting

    Dietary supplements in women who have overcome hormone-dependent breast cancer

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    Dodaci prehrani definirani su kao pojedinačni ili kombinirani izvori hranjivih tvari namijenjeni za nadoknadu esencijalnih mikronutrijenata u svakodnevnoj prehrani u svrhu unaprjeđivanja ili održavanja zdravlja što je posebno važno za pacijente oboljele od malignih bolesti u čijoj je populaciji i zabilježena učestalija primjena dodataka prehrani. Iako dodaci prehrani imaju mnoge dobrobiti, postoji opravdana zabrinutost da njihova primjena može utjecati na učinkovitost kemoterapije i radioterapije. Tako primjerice antioksidansi mogu smanjiti učinak kemoterapije i radioterapije interferiranjem s reaktivnim kisikovim spojevima koji induciraju apoptozu tumorskih stanica, a primjena nezasićenih masnih kiselina može se povezati sa smanjenjem ukupne smrtnosti. U ovom istraživanju sudjelovalo je 310 pacijentica dobi od 27 do 91 godine, a cilj je bio ispitati navike primjene dodataka prehrani u populaciji pacijentica oboljelih od hormonski ovisnog raka dojke. Utvrđeno je da je primjena učestalija u pacijentica starije životne dobi i višeg stupnja obrazovanja. U primjeni su većinom dodaci prehrani jednostavnijeg sastava bez posebnog učinka na nuspojave terapije ili prevenciju samog raka dojke iz čega se može zaključiti da njihov potencijal nije iskorišten.Dietary supplements are defined as individual or combined sources of nutrients intended for the replacement of essential micronutrients in the daily diet for the purpose of improving or maintaining health, which is especially important for patients suffering from malignant diseases in whose population more frequent use of dietary supplements has been recorded. Although dietary supplements have many benefits, there is a legitimate concern that their use may affect the effectiveness of chemotherapy and radiotherapy. For example, antioxidants can reduce the effect of chemotherapy and radiotherapy by interfering with reactive oxygen compounds that induce apoptosis of tumor cells, and the use of unsaturated fatty acids can be associated with a reduction in overall mortality. 310 patients between the ages of 27 and 91 participated in this study, and the goal was to examine the habits of using dietary supplements in the population of patients with hormone-dependent breast cancer. It was found that the application is more frequent in patients of an older age and a higher level of education. Most of the food supplements in use are of simpler composition without any special effect on the side effects of therapy or the prevention of breast cancer itself, from which it can be concluded that their potential has not been used

    Attitudes, beliefs, and adherence of patients on direct oral anticoagulant therapy

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    Poremećaj u zgrušavanju krvi koji dovodi do tromboembolijske bolesti predstavlja veliki javnozdravstveni problem zbog visokog mortaliteta kojim rezultira, kako u razvijenim zemljama svijeta, tako i u Hrvatskoj. Liječenje kroničnog poremećaja koji „ne boli“ i koji je pacijentima neopipljiv, a izuzetno opasan, jako ovisi o samoj adherenciji ispitanika. Kao novija generacija lijekova, DOAK-i se sve češće propisuju zbog svojih boljih farmakokinetičkih karakteristika u odnosu na starije lijekove.Cilj ovog diplomskog rada bio je istražiti koji je najčešći DOAK u terapiji ispitanika, od kojih bolesti boluju ispitanici i provjeriti adherenciju ispitanika na DOAK-e. Istražiti stavove i uvjerenja o lijekovima i bolesti općenito kao bitnim čimbenicima o kojima ovisi adherencija te promotriti koji socio-demografski i klinički čimbenici utječu na adherenciju i na stavove i uvjerenja o lijekovima.Provedeno je presječno, opservacijsko istraživanje u koje su uključeni ispitanici na terapiji nekim od direktnih oralnih antikoagulansa. Adherencija je mjerena pomoću Upitnika o uzimanju lijekovima za procjenu adherencije (engl. Medication Adherence Report Scale, MARS-5), a stavovi i uvjerenja o lijekovima pomoću BMQ upitnika (engl. Beliefs about Medicines Questionnaire).U istraživanju je sudjelovalo 63 ispitanika, 30 žena (47.6%) i 33 muškaraca (52.4%).Medijan dobi bio je 73.5 godina (interkvartilni raspon 61.5-78). Najmlađi ispitanik imao je 25 godina, a najstariji 91 godinu. Rješavanjem MARS-5 upitnika pokazali su visoku adherenciju što nam pokazuje srednja vrijednost bodova koja iznosi 24.11± 1.493. Najčešći uzrok neadherencije bilo je propuštanje i zaboravljanje lijeka. Ostali socio-demografski i klinički podaci nisu pokazali značajan utjecaj na adherenciju.Stavovi i uvjerenja o lijekovima ispitanika su izuzetno pozitivni. Statistički značajna razlika pronađena je između visoko adherentnih bolesnika i onih s nešto nižom adherencijom utvrđena je za skalu ˝Zabrinutost zbog lijekova˝ iz Specifičnog dijela upitnika.(p= 0.008) , između mlađih od 65 godina i onih sa 65 godina i starijih za skalu „Nužnost“ iz Općeg dijela (p=0.036) te između osoba različitog stupnja obrazovanja za skale „Osjetljivost na lijekove“ – Opći dio i „Nužnost“ – Specifični dio. (p= 0.008;p=0.019) Ovim istraživanjem ustanovljeni su neki čimbenici koji utječu na adherenciju, stavove i uvjerenja o lijekovima te međusobni utjecaj stavova i uvjerenja o lijekovima na adherenciju. Bolje poznavanje čimbenika koji utječu na adherenciju, stavove i uvjerenja pomaže promjeni i poboljšanju istih.A blood clotting disorder leading to thromboembolic diseases represents a significant public health issue due to the elevated mortality it results in, both in developed countries worldwide and in Croatia. The treatment of a chronic disorder that is "silent" and imperceptible to patients yet exceedingly perilous heavily relies on the adherence of the subjects involved. As a more recent generation of medications, Direct Oral Anticoagulants (DOACs) are increasingly prescribed owing to their superior pharmacokinetic profiles compared to older drugs. The objective of this dissertation was to investigate the most common DOAC used in the therapy of subjects, identify the ailments afflicting the subjects, and assess the adherence of subjects to DOACs. The study aimed to explore attitudes and beliefs about medications and illnesses in general, as pivotal factors influencing adherence. Additionally, it aimed to examine the socio-demographic and clinical factors influencing both medication adherence and attitudes and beliefs about medications.A crosssectional observational study was conducted, involving subjects under treatment with some form of direct oral anticoagulant. Adherence was gauged using the Medication Adherence Report Scale (MARS-5), while attitudes and beliefs about medications were assessed using the Beliefs about Medicines Questionnaire (BMQ). The study enrolled 63 participants, with 30 females (47.6%) and 33 males (52.4%). The median age was 73.5 years (interquartile range 61.5-78). The youngest participant was 25 years old, and the oldest was 91 years old. By completing the MARS-5 questionnaire, participants demonstrated high adherence, as indicated by the mean score of 24.11±1.493. The most frequent cause of non-adherence was skipping doses and forgetting medication. Other sociodemographic and clinical data did not exhibit significant influence on adherence.Participant attitudes and beliefs about medications were notably positive. A statistically significant difference was identified between highly adherent patients and those with slightly lower adherence in the "Concerns about Medications" scale of the Specific section (p=0.008). Furthermore, differences were observed between individuals younger than 65 and those aged 65 and older in the "Necessity" scale of the General section (p=0.036), and between individuals with different educational levels for the "Perceived Sensitivity to Medications" scale of the General section and the "Necessity" scale of the Specific section (p=0.008; p=0.019).This research has elucidated certain factors influencing medication adherence, attitudes, and beliefs about medications, as well as the mutual impact of attitudes and beliefs on adherence. Enhanced comprehension of the factors affecting adherence, attitudes, and beliefs can facilitate their modification and improvement

    The impact of comprehensive medication management services on the lipid profile in elderly patients at the Zagreb-Center Health Center

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    Cilj ovog istraživanja bio je procijeniti utjecaj usluge upravljanja farmakoterapijom (CMM) na lipidogram kod starijih pacijenata koji koriste statine u terapiji u Domu zdravlja Zagreb Centar, opisati predložene intervencije za rješavanje terapijskih problema povezanih sa statinima te stupanj njihove prihvaćenosti, kao i procijeniti učinak CMM usluge na postizanje terapijskih ciljeva u liječenju hiperlipidemije, hipertenzije i šećerne bolesti tipa 2, najčešćih komorbiditeta povezanih s hiperlipidemijom. Provedeno je prospektivno intervencijsko istraživanje u trajanju od šest godina. U istraživanju je sudjelovalo 128 pacijenata prosječne starosti 74 godina i većinom ženskog spola. Najčešće intervencije koje su provedene radi rješavanja terapijskih problema vezanih uz statine uključivale su uvođenje nove terapije, povećanje doze lijeka, promjenu lijeka i kontrolu laboratorijskih nalaza. Istraživanje je pokazalo statistički značajan pad LDL kolesterola i ukupnog kolesterola kod starijih pacijenata. Rezultati su pokazali da CMM usluga doprinosi postizanju terapijskih ciljeva i optimizaciji liječenja hiperlipidemije te boljoj kontroli komorbiditeta kod starijih pacijenata, što ukazuje na potrebu širenja ove usluge u druge domove zdravlja radi unaprjeđenja zdravstvene skrbi za stariju populaciju.The objective of this study was to assess the impact of Comprehensive Medication Management (CMM) services on the lipid profile of elderly patients on statin therapy at the Zagreb-Center Health Center, to describe proposed interventions aimed at resolving drug therapy problems (DTP) with statins and their acceptance rates, and to evaluate the effectiveness of CMM in achieving therapeutic goals for managing hyperlipidemia, hypertension, and type 2 diabetes—the most common comorbidities associated with hyperlipidemia. This six-year prospective interventional study included 128 patients, with an average age of 74 years, the majority of whom were female. The most frequently proposed interventions to address DTP with statins included initiating new therapy, increasing drug doses, switching medications, and monitoring laboratory results. Most interventions involved atorvastatin and rosuvastatin, the statins most commonly used in therapy and those required the most adjustments. The results showed that CMM services contribute to achieving therapeutic goals, optimizing hyperlipidemia treatment, and improving control of comorbidities in elderly patients. These findings highlight the need to expand CMM services to other health centers to improve healthcare for the elderly population

    Evaluation of the method for the preparation of cerebrospinal fluid cytological preparations

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    Analiza cerebrospinalne tekućine (likvora) od ključne je važnosti za dijagnostiku neuroloških bolesti. Citološka analiza likvora često predstavlja izazov zbog malog broja stanica i potrebe za očuvanjem njihove morfologije tijekom obrade. U radu su evaluirane tri metode obogaćivanja likvora (albuminom, pool-om seruma i pool-om likvora) kako bi se smanjio raspad stanica i poboljšala kvaliteta citoloških preparata. Analizirano je 35 uzoraka likvora dobivenih lumbalnom punkcijom i postoperativnom drenažom. Stanice su brojane ručno u Fuchs-Rosenthalovoj komori i automatizirano na Sysmex XN1000 BF analizatoru. Statistička analiza pokazala je visoku sličnost između metoda brojanja za većinu staničnih populacija, osim za polimorfonuklearne leukocite. Sysmex analizator pokazao je tendenciju podcjenjivanja broja stanica, osobito kod uzoraka s manjim brojem stanica. Metoda obogaćivanja likvora albuminom kod pripreme preparata pokazala se kao najučinkovitija, s najmanjim udjelom stanica u raspadu i najvećom konzistentnošću rezultata. Usporedbom rezultata ručnog i automatiziranog diferenciranja dokazane su statistički značajne razlike samo u udjelu neutrofilnih granulocita između Sysmexa i preparata obogaćenih pool-om seruma. Ovim radom dokazano je da metoda obogaćivanja albuminom osigurava najbolju očuvanost stanica, omogućujući dobivanje kvalitetnih citoloških preparata, što doprinosi pouzdanijoj dijagnostici i boljoj obradi uzoraka likvora.The analysis of cerebrospinal fluid (CSF) is of key importance for the diagnosis of neurological diseases. Cytological analysis of cerebrospinal fluid is often a challenge due to the small number of cells and the need to preserve their morphology during processing. The paper evaluated three methods of CSF enrichment (albumin, serum pool, and CSF pool) in order to reduce cell decay and improve the quality of cytological preparations. 35 cerebrospinal fluid samples obtained by lumbar puncture and postoperative drainage were analyzed. Cells were counted manually in a Fuchs-Rosenthal chamber and automatically on a Sysmex XN1000 BF analyzer. Statistical analysis showed high similarity between counting methods for most cell populations, except for polymorphonuclear leukocytes. The Sysmex analyzer showed a tendency to underestimate the number of cells, especially in samples with a lower number of cells. The method of enriching the cerebrospinal fluid with albumin during the preparation of the preparation proved to be the most effective, with the lowest proportion of cells in disintegration and the highest consistency of results. By comparing the results of manual and automated differentiation, statistically significant differences were demonstrated only in the proportion of neutrophil granulocytes between Sysmex and preparations enriched with serum pool. This work proved that the albumin enrichment method ensures the best preservation of cells, enabling obtaining high-quality cytological preparations, which contributes to more reliable diagnostics and better processing of cerebrospinal fluid samples

    Therapeutic challenges in eating disorders

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    Poremećaji prehrane, uključujući anoreksiju nervozu, bulimiju nervozu i poremećaj prejedanja, predstavljaju ozbiljan javnozdravstveni problem s rastućom prevalencijom među adolescentima i mladim osobama. Osim što utječu na mentalno zdravlje, ovi poremećaji značajno narušavaju i fizičko zdravlje pojedinca te dovode do razvoja komorbiditeta kao što su depresija, anksioznost, kardiovaskularne i metaboličke bolesti. Etiologija ovih poremećaja iznimno je kompleksna, a uključuje interakciju bioloških, psiholoških i sociokulturnih čimbenika. Liječenje poremećaja prehrane zahtjeva multidisciplinaran pristup koji uključuje kognitivno-bihevioralnu terapiju, farmakoterapiju te alternativne i pomoćne terapije. Kognitivno-bihevioralna terapija pokazala se najučinkovitijom metodom liječenja navedenih poremećaja, ali svoj puni potencijal ostvaruje upravo u kombinaciji s farmakoterapijom. Dok kognitivno-bihevioralna terapija pomaže u liječenju same srži bolesti, farmakoterapija pomaže u smanjenju pratećih simptoma poput depresije i anksioznosti. Farmakoterapijske opcije još su uvijek uvelike ograničene u navedenom području. Za poremećaj prejedanja trenutno je odobren lisdeksamfetamin, za bulimiju nervozu fluoksetin, dok za anoreksiju nervozu ne postoji niti jedan odobreni lijek. Napretci u istraživanju svakako doprinose razvoju novih terapijskih opcija. Osim glavnih terapija, pomoćne metode poput joge i tjelovježbe, pokazale su pozitivne učinke kao nadopuna terapije u liječenju poremećaja prejedanja. Neuromodulacijske tehnike ostaju rezervirane samo za najteže slučajeve, ali pozitivni rezultati koje pokazuju otvaraju mogućnosti za potencijalnu širu primjenu u budućnosti. Sveobuhvatan pristup liječenju, koji uključuje rano prepoznavanje poremećaja, multidisciplinarni i individualizirani pristup, ključan je za poboljšanje zdravlja i kvalitete života oboljelih. Terapije koje kombiniraju psihološke i farmakološke pristupe pokazuju najveću učinkovitost, dok nova istraživanja daju nadu za poboljšanjem i napretkom liječenja poremećaja prehrane u budućnosti.Eating disorders, including anorexia nervosa, bulimia nervosa, and binge-eating disorder, represent a serious public health issue with increasing prevalence, particularly among adolescents and young adults. In addition to affecting mental health, these disorders significantly impair physical health and contribute to the development of comorbidities such as depression, anxiety, cardiovascular diseases, and metabolic disorders. The etiology of these disorders is highly complex, involving an interaction of biological, psychological, and sociocultural factors. Treatment of eating disorders requires a multidisciplinary approach, including cognitive-behavioral therapy, pharmacotherapy, and alternative and adjunct therapies. Cognitive-behavioral therapy has proven to be the most effective treatment method for these disorders, but it achieves its full potential when combined with pharmacotherapy. While cognitivebehavioral therapy addresses the core of the disorder, pharmacotherapy helps reduce accompanying symptoms such as depression and anxiety. Pharmacotherapeutic options are still largely limited in this area. Currently, lisdexamfetamine is approved for the treatment of binge-eating disorder, fluoxetine for bulimia nervosa, while there is no approved medication for anorexia nervosa. Advances in research are certainly contributing to the development of new therapeutic options. In addition to primary treatments, adjunctive methods such as yoga and exercise have shown positive effects as supplementary treatments for binge-eating disorder. Neuromodulation techniques remain reserved for the most severe cases, but the promising results they show open the door for potential broader applications in the future. A comprehensive approach to treatment, which includes early recognition of the disorder and a multidisciplinary and individualized approach, is crucial for improving the health and quality of life of those affected. Therapies that combine psychological and pharmacological approaches demonstrate the highest efficacy, while new research offers hope for further improvement and advancements in the treatment of eating disorders in the future

    Europski regulatorni okvir za ocjenu kakvoće biljnih lijekova

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    Cilj istraživanja Cilj ovog specijalističkog rada je opisati sadržaj i postupak ocjene dokumentacije o kakvoći biljnog lijeka i svih uvjeta koje je potrebno ispuniti kako bi se ustanovila odgovarajuća kakvoća, uzimajući u obzir primjenjive smjernice za kemijske lijekove i specifične smjernice za biljne lijekove te farmakopejske propise na razini Europske unije. Materijali i metode Istraživanje u okviru ovog rada je teorijskog karaktera i uključuje pregled dostupne znanstvene i stručne literature o predloženoj temi, zakonske akte koji reguliraju područje biljnih lijekova te smjernice dostupne na stranicama nadležnih regulatornih tijela koje se odnose na biljne lijekove. Dostupni podatci su kritički razmotreni i sistematično prikazani u obliku preglednog rada. Rezultati Sukladno Europskoj regulativi, u Republici Hrvatskoj biljni lijekovi mogu biti odobreni postupkom davanja odobrenja za stavljanje lijeka u promet kao biljni lijekovi, ili pojednostavljenim postupkom registracije kao tradicionalni biljni lijekovi. U dokumentaciji za davanje odobrenja za kakvoću se prilaže jednaka dokumentacija, bez obzira na zakonsku osnovu odobrenja. U HALMED-u se lijekovi ocjenjuju i odobravaju uzimajući u obzir sve relevantne zakone i pravilnike te smjernice i farmakopejske propise. Ispitivanjem kakvoće svake serije lijeka nakon davanja odobrenja, osiguravaju se sigurni i djelotvorni biljni lijekovi u prometu. Zaključak Postupak prikupljanja i prilaganja dokumentacije od strane podnositelja zahtjeva za davanje odobrenja odnosno registraciju biljnog lijeka, kao i njezina ocjena, kompleksni su procesi. Kako bi se osigurala sigurna i djelotvorna primjena biljnih lijekova temeljem odgovarajuće kakvoće, potrebno je poštivati zakonske akte i smjernice te ih pratiti i implementirati tijekom cijelog životnog ciklusa.Cilj istraživanja Cilj ovog specijalističkog rada je opisati sadržaj i postupak ocjene dokumentacije o kakvoći biljnog lijeka i svih uvjeta koje je potrebno ispuniti kako bi se ustanovila odgovarajuća kakvoća, uzimajući u obzir primjenjive smjernice za kemijske lijekove i specifične smjernice za biljne lijekove te farmakopejske propise na razini Europske unije. Materijali i metode Istraživanje u okviru ovog rada je teorijskog karaktera i uključuje pregled dostupne znanstvene i stručne literature o predloženoj temi, zakonske akte koji reguliraju područje biljnih lijekova te smjernice dostupne na stranicama nadležnih regulatornih tijela koje se odnose na biljne lijekove. Dostupni podatci su kritički razmotreni i sistematično prikazani u obliku preglednog rada. Rezultati Sukladno Europskoj regulativi, u Republici Hrvatskoj biljni lijekovi mogu biti odobreni postupkom davanja odobrenja za stavljanje lijeka u promet kao biljni lijekovi, ili pojednostavljenim postupkom registracije kao tradicionalni biljni lijekovi. U dokumentaciji za davanje odobrenja za kakvoću se prilaže jednaka dokumentacija, bez obzira na zakonsku osnovu odobrenja. U HALMED-u se lijekovi ocjenjuju i odobravaju uzimajući u obzir sve relevantne zakone i pravilnike te smjernice i farmakopejske propise. Ispitivanjem kakvoće svake serije lijeka nakon davanja odobrenja, osiguravaju se sigurni i djelotvorni biljni lijekovi u prometu. Zaključak Postupak prikupljanja i prilaganja dokumentacije od strane podnositelja zahtjeva za davanje odobrenja odnosno registraciju biljnog lijeka, kao i njezina ocjena, kompleksni su procesi. Kako bi se osigurala sigurna i djelotvorna primjena biljnih lijekova temeljem odgovarajuće kakvoće, potrebno je poštivati zakonske akte i smjernice te ih pratiti i implementirati tijekom cijelog životnog ciklusa

    Diagnostic value of human epididymal protein 4, ROMA index and antigen Ki-67 in stratification of patients with ovarian tumors

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    Rak jajnika vodeći je uzrok smrti žena s ginekološkim zloćudnim bolestima u Republici Hrvatskoj. Ovim istraživanjem ispitala se mogućnost predoperacijske diferencijacije ispitanica s tumorima jajnika ispitanica koristeći tumorske biljege ugljikohidratni antigen 125 (CA 125), humani epididimalni protein 4 (HE4) i multiparametarski model ROMA indeks. Na 159 ispitanica s tumorima jajnika, koje su liječene kirurškim putem, izmjerene su predoperacijske vrijednosti CA 125, HE4 i izračunan je ROMA indeks. Ispitivanjem dijagnostičke točnosti CA 125, HE4 i ROMA indeksa dobila se potvrda koji je serumski biljeg nadmoćniji, a ovisno o menopauzalnom statusu ispitanica. HE4 označava bolji izbor zbog dijagnostičkog kapaciteta nego biljeg CA 125 u svrhu diferencijalne dijagnoze tumora jajnika. Granične vrijednosti više su nego deklarirane te su se dokazale kao optimalne. HE4 ima najbolji dijagnostičku specifičnost kod dijagnoze tumora jajnika u pacijentica u predmenopauzi. ROMA indeks je onaj biljeg koji ima najbolju dijagnostičku sposobnost prepoznavanja malignog u bolesnica u postmenopauzi. HE4 i ROMA indeks nadmašuju CA 125 u diferencijalnoj dijagnozi tumora jajnika te su korisni alati u dijagnostici raka jajnika. Veće vrijednosti HE4 i CA 125 upozoravaju na uznapredovalu fazu bolesti kada dolazi do širenja izvan jajnika odnosno jajovoda. Provedena je korelacija s patohistološkim tipovima tumora: benignim tumorima, tumorima niskoga zloćudnog potencijala, zloćudnim tumorima, te tumorima sličnim lezijama koji su poslužili kao kontrolna grupa, dobivenih poslijeoperacijski. Naknadno iz 140 arhiviranih uzoraka deparafiniranih rezova odredila se ekspresija tkivnog biljega HE4 koji se rutinski ne određuje na tumorskom tkivu jajnika. Antigen Ki-67 kao pokazatelj stanične proliferacije može poslužiti kao dodatni biljeg tumorskog rasta. Podudarnost tkivne ekspresije HE4, antigena Ki-67 i serumskih vrijednosti HE4, CA 125 i ROMA indeksa sa stadijem proširenosti bolesti, a prema FIGO klasifikaciji, dokaz je prepoznavanja maligniteta te mogućeg što ranijeg prepoznavanja bolesti. Na taj način predoperacijske diferencijacije ispitanica s tumorima jajnika, koristeći biljege CA 125, HE4 i multiparametarski model ROMA indeks, omogućena je veća pouzdanost u diferencijalnoj dijagnostici karcinoma jajnika.Introduction Adnexal masses are formations originating from the ovaries, fallopian tubes, cervix and uterus or other pelvic organs, from which ovarian cancer stands out due to its high mortality rate. Ovarian cancer is diagnosed in an advanced stage, so the five-year survival rate is low. Ovarian cancer is a heterogeneous disease, it differs in histological type, grade, molecular features, and consequently the treatment differs. Despite the implementation of treatment that includes surgical treatment, systemic application of chemotherapy, immunotherapy, targeted therapy and hormonal therapy, the prognosis for patients is devastating. For this reason, the diagnostic value of the tumor markers HE4, CA 125 and ROMA index, as well as the expression of tissue HE4 and Ki-67 antigen in the preoperative differentiation of ovarian tumors, was investigated. This study examined the possibility of preoperative stratification in subjects with a tumor mass in the pelvis using markers CA 125, HE4 and the multiparameter model ROMA index. Regression analysis was used to compare the preoperative values of CA 125, HE4 and ROMA index, especially for identifying malignancy. Postoperatively, ovarian cancer was confirmed by pathohistological analysis, as well as other pathohistological subtypes of ovarian tumors: benign, borderline-malignant, tumors that have grafts and tumors resembling lesions that served as a control group. The expression of the tissue marker HE4, which is not routinely determined on ovarian tumor tissue, but according to pathohistological tumor types, was tested. Antigen Ki-67 is an indicator of cell proliferation, so determination of antigen Ki-67 on ovarian tumor tissues served as an indicator of tumor growth. The concordance of tissue expression of HE4, antigen Ki-67 and serum values of HE4, CA 125 and ROMA index with the stage of disease extension, and according to the FIGO classification, should be proof of whether the disease can be recognized as early as possible. Additionally, the association of the mentioned parameters with the size and blood supply of the ovarian tumor was investigated. Due to the influence of the habit of smoking cigarettes, it will be examined whether the habit of smoking has an influence on the measured results, especially for HE4. Materials and methods The research was carried out in the Department of Medical Biochemistry in Oncology at the University Hospital for Tumors, Sestre milosrdnice University Hospital Center, in cooperation with the Department of Gynecological-Oncological Surgery of the Institute for Surgical Oncology at the University Hospital for Tumors and the Clinical Institute of Pathology "Ljudevit Jurak", Sestre milosrdnice University Hospital Center. The criterion for inclusion in the study was evidence of an adnexal mass in the pelvis of unknown etiology in the subjects and an indication of surgical treatment. Preoperatively, the blood of 159 subjects was sampled for the purpose of measuring the serum values of the tumor markers HE4 and CA 125. For each subject, the ROMA index was calculated after classification according to menopausal status, and according to formulas for premenopause and postmenopause. The obtained results were used to examine the diagnostic potential of all three parameters: CA 125, HE4 and ROMA index. Postoperatively, the test subjects were divided according to pathohistological types of tumors by looking at the pathohistological findings in which the tumor tissue is described as benign, borderline-malignant or malignant, and the histological type and degree of tumor differentiation determined, microinvasion, assessment of the status of lymph nodes, the presence of ascites, involvement of the tubes, omentum, the presence of residual tumor and metastases. Subsequently, the expression of tissue marker HE4 and antigen Ki-67 was determined by immunohistochemistry from archived samples of deparaffinized sections of tumor tissue, which served as an additional marker for the assessment of cell proliferation. Monoclonal antibodies specific for tissue HE4 and Ki-67 antigen were used for samples, 140 in total, for which material was available. Tumor grade and disease stage according to the FIGO classification (stage I-IV): ovarian carcinomas limited to the ovaries (FIGO stage I), ovarian carcinomas extending to the pelvic organs (FIGO stage II), ovarian carcinomas with peritoneal metastases (FIGO stage III) and ovarian carcinomas with distant metastases (FIGO stage IV) were compared with all serum and tissue parameters. Results In the first part of the results, using the ROC (Receiver Operating Characteristics) statistical analysis, the curve visualized and classified the properties of three parameters: CA 125, HE4 and ROMA index. A regression analysis of the obtained results was made, separately for the premenopausal and postmenopausal groups. In the premenopausal group, the area under the ROC curves was 84.6 % for HE4, 86.7 % for CA 125, and 84.6 % for the ROMA index. The threshold values obtained in the ROC analysis are 86.1 pmol/L for HE4, 40.7 U/mL for CA 125, and 21.9 % for the ROMA index. Diagnostic sensitivity was 85.7 % for HE4, 75 % for CA 125, and 85 % for the ROMA index. Diagnostic specificity was 80 % for HE4, 69.3 % for CA 125, and 62 % for the ROMA index. The positive predictive value was 67 % for HE4, 35.3 % for CA 125, and 67 % for the ROMA index. The negative predictive value was 92.4 % for HE4, 91.9 % for CA 125 and 95.2 % for the ROMA index. In the postmenopausal group, the area under the ROC curves was 92.8 % for HE4, 89.9 % for CA 125, and 92.7 % for the ROMA index. The threshold values obtained in the ROC analysis are 99.8 pmol/L for HE4, 45.8 U/mL for CA 125, and 38.4 % for the ROMA index. Diagnostic sensitivity was 91.2 % for HE4, 88.9 % for CA 125, and 91.7 % for ROMA index. Diagnostic specificity was 80.3 % for HE4, 77.2 % for CA 125, and 80.3 % for the ROMA index. The positive predictive value was 75.6 % for HE4, 77.5 % for CA 125, and 91.2 % for the ROMA index. The negative predictive value was 92.4 % for HE4, 91.9 % for CA 125 and 95.2 % for the ROMA index. The tumor marker HE4, applied to the test subjects in our study, has a higher diagnostic capacity than CA 125 in the differential diagnosis of ovarian tumors, mainly in premenopausal patients. Analysis of the distribution of test subjects according to the pathohistological types of the disease and according to the menopausal status of the test subjects showed a significantly higher proportion of malignant cysts (84.2 %) in postmenopausal subjects, while a statistically significantly higher proportion of TLL was demonstrated in premenopausal subjects (65.22 %), p = 0.001. The youngest subjects were those who had TLL with a median age of 49.0 (43.5- 53.5) years and were significantly younger than benign cysts (P = 0.003), borderline changes (P = 0.010), malignant cysts (P < 0.001) and metastasis (P < 0.001). In the group of malignant cysts, the most represented status was IIIC with 23 (60.5 %) according to FIGO, and as for grades, the most represented was grade 3 (62.9 % of subjects with malignant cysts). The analysis of tumor flow and volume in the groups according to the pathohistological type of the disease was not statistically significant (P = 0.080). By tumor volume, benign cysts were significantly smaller than malignant (P < 0.001) and metastases (P = 0.021). The value of HE4 in the serum is 13.10 pmol/L, and the highest is 7700.00 pmol/L. The subgroup with malignant cysts had the highest values of serum HE4 with a median of 302.7 pmol/L, which were significantly higher than all other subgroups (P < 0.001) including metastases (P = 0.010). The metastasis subgroup had significantly higher values than all other subgroups except malignant cysts with a median of 117.65 pmol/L. A statistically significant difference between serum HE4 concentrations (P < 0.01) was demonstrated between individual subgroups: benign cyst subgroup versus malignant cyst subgroup, benign cyst subgroup versus metastasis subgroup, borderline subgroup versus malignant cyst subgroup, borderline subgroup versus metastasis subgroup, TLL subgroup vs. subgroups of malignant cysts, subgroups of TLL vs. subgroups of metastases. The malignant cyst subgroup had the highest tissue HE4 values which were significantly higher than the benign cyst subgroup (P = 0.049), the TLL subgroup (P < 0.001), and the metastases subgroup (P = 0.030). Subgroup TLL had the lowest value of tissue HE4: it had no expressed tissue HE4 at all, which was significantly lower compared to all other subgroups (P < 0.001). Differences in measured CA 125 values between subgroups of pathohistological types: the highest values were recorded in the group of metastases with a median of 241.8 U/mL, which were significantly higher than all other subgroups except for malignant cysts, median of 199.15 U/mL (P = 0.964). Ki-67 antigen in ovarian tissue was the most expressed in the group of malignant cysts with significantly higher values compared to all other pathohistological types (P < 0.001) except metastases (P = 0.183). Given that the ROMA index is calculated from HE4 and CA 125 values, the differences in values are similar to those values. The highest ROMA index values were in malignant cysts and were significantly higher than all other subgroups (P < 0.001). In the high-risk group, malignant cysts were the most common (45.3 %), while in the low-risk group those were benign cysts (63.1 %; P < 0.001). Also, in the group with high risk, the most represented was FIGO classification IIIC – 23 (67.6 %) respondents. The agreement of the clinical significance of the expression and serum concentration of HE4, Ki-67 and ROMA index with the FIGO classification, as well as the assessment of the clinical significance of the serum concentration of HE4 by comparison with the expression of HE4 in the tissue with the stage of the histological tumor grade, does not significantly correlate with any of the mentioned clinical values, while higher FIGO classification significantly positively correlates with serum HE4 (rho = 0.475, P = 0.004), CA 125 (rho = 0.530, P = 0.001) and ROMA index (rho = 0.546, P = 0.001). Considering the strength of the correlation coefficients, the strongest significant correlation is with the ROMA index itself, which points to clinical importance. Ki-67 did not significantly correlate with grade, FIGO classification, or ROMA index. Also, tissue HE4 did not significantly correlate with grade and FIGO classification. The research also examined the influence of smoking on the frequency and type of tumors. There is no proven connection between the pathohistological types of the disease in relation to the smoking status and the number of cigarettes smoked per day. Conclusion The HE4 marker improves the diagnostic specificity of CA 125 in distinguishing between benign and malignant pathology, allowing valuable surgical anticipation in case of a possible malignancy result. The regression analysis of the obtained measurement results showed differences for the premenopausal and postmenopausal groups. The limit values in our research are higher than declared by the manufacturer, and have proven to be optimal. Marker HE4 has the best diagnostic specificity in the diagnosis of ovarian tumors in premenopausal patients. Diagnostic sensitivity is equal for HE4 and ROMA index. The ROMA index is the marker that has the best diagnostic ability to recognize malignancy in postmenopausal patients, which proves the highest diagnostic sensitivity compared to CA 125 and HE4. This also affects the presence of malignant cysts in the high-risk group, so that HE4 and the ROMA index surpass CA 125 in the differential diagnosis of adnexal masses, and represent useful tools in the diagnosis of ovarian cancer. Malignant cysts had the highest values of serum HE4, which were significantly higher than all other examined subgroups, and the highest values of serum CA 125 were recorded in the group of metastases. Given that the ROMA index is calculated from HE4 and CA 125 values, the differences in values are similar to those values. Given the existence of statistically significant differences in the measured values of the HE4 marker in the serum, confirmation of its hypothetical value as a specific marker for ovarian cancer was obtained. This conclusion is in accordance with scientific evidence based on research on similar populations of patients. Tissue HE4 was expressed in all ovarian tumor subtypes, except in the control group, which was surprising. It can be concluded that the obtained results did not confirm the literature data stating that tissue HE4 as a marker is also expressed in healthy ovarian tissue, which represents the control group. Expression of the HE4 marker in all examined subtypes proves the growth of cells regardless of whether they are malignant or benign. Nevertheless, malignant cysts had the highest values of tissue HE4, so it can be concluded that determination of tissue HE4 for ovarian cancers is useful. The concordance of the clinical significance of the expression and serum concentration of HE4, Ki-67 and ROMA index with the FIGO classification, as well as the assessment of the clinical significance of the serum concentration of HE4 by comparison with the expression of HE4 in the tissue with the stage of the disease, differed by individual parameters. The strongest correlation was demonstrated for the ROMA index, which indicates its clinical importance. Ki-67 did not significantly correlate with grade, FIGO classification, or ROMA index. Also, tissue HE4 did not significantly correlate with grade and FIGO classification. The grade of the tumor does not significantly correlate with any of the mentioned clinical values. The conclusion is that the ROMA index is the most useful, given that it is a mathematical calculation based on the measured values of HE4 and CA 125

    Fitoterapijski potencijal biljnih anksiolitika i antidepresiva

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    Cilj istraživanja Cilj je ovoga specijalističkoga rada sveobuhvatan pregled znanstvenih spoznaja o biljnim anksioliticima i antidepresivima, a posebice usmjeren na kliničke studije. U radu se posebice ističe sigurnost primjene te precizne analize pravilnoga doziranja, moguće nuspojave te interakcije. Materijali i metode U ovom teorijskom specijalističkom radu napravljena je analiza znanstvene i stručne literature u području teme rada. U pretraživanju su korištene bibliografske baze podataka PubMed, Medline, Scopus, Science Direct i Cochrane Library, internetski su izvor stranice Europske agencije za lijekove EMA (engl., European Medicines Agency) te Europskoga znanstvenoga udruženja za fitoterapiju ESCOP (engl., Europe Scientific Cooperative on Phytotherapy). Rezultati Rezultati mnogobrojnih kliničkih ispitivanja podupiru primjenu gospine trave kod blage do umjerene depresije. Mnoge kliničke studije opravdavaju primjenu odoljena kao blagoga sedativa u liječenju nesanice i anksioznosti kada primjena sintetskih lijekova nije opravdana. Smatra se da djeluje smirujuće i ublažava znakove nervoze kao što su nemir, razdražljivost i napetost zbog psihičke preopterećenosti, a pri nesanici olakšava uspavljivanje. Pokazalo se da je pasiflora učinkovita kod generaliziranoga anksioznoga poremećaja, usporedivo s oksazepamom, te da može smanjiti preoperativnu anksioznost bez izazivanja sedacije ili utjecaja na psihomotorne funkcije. Zahvaljujući rezultatima kliničkih ispitivanja ukazuje se na potencijal ružičastoga žednjaka za ublažavanje tegoba blage tjeskobe i blage do umjerene depresije te za poboljšanje cjelokupnoga raspoloženja u odnosu na konvencionalnu terapiju. Osim navedenoga, postoje i klinički dokazi da šafran ublažava simptome blage do umjerene anksioznosti i depresije. Zaključak Iako klinička istraživanja podupiru primjenu gospine trave, pasiflore, odoljena, ružičastoga žednjaka i šafrana u suvremenoj fitoterapiji, potrebna su daljnja klinička ispitivanja koja će pružiti veću razinu dokaza o njihovu terapijskom potencijalu u liječenju anksioznih i depresivnih poremećaja.Objectives The aim of this research is a comprehensive review of scientific knowledge on herbal anxiolytics and antidepressants especially focused on clinical studies. Special attention will be paid to the safety of application and the correct dosage, possible side effects and interactions will be addressed. Materials and methods In this theoretical specialist work, analysis of scientific and professional literature was made in the field of the topic of the work. Relevant bibliographic database such as CurrentContents, ScienceDirect, Scopus, PubMed, Medline and Cochrane Library were searched. The websites of the European Medicines Agency (EMA) and the European Scientific Cooperative on Phytotherapy (ESCOP) were used as sources of information. Results The results of numerous clinical trials support the use of St. John's wort in mild to moderate depression. Many clinical studies justify the use of resist as a mild sedative in the treatment of insomnia and anxiety when the use of synthetic drugs is not justified. It is believed to have a calming effect and alleviate signs of nervousness such as restlessness, irritability and tension due to mental overload, and in insomnia it facilitates falling asleep. Passionflower has been shown to be effective in generalized anxiety disorder, comparable to oxazepam, and can reduce preoperative anxiety without inducing sedation or affecting psychomotor functions. Very promising results have been obtained indicating the potential of pink thirst to alleviate the symptoms of mild anxiety and mild to moderate depression and to improve overall mood with better tolerability than conventional therapy. There is clinical evidence that saffron relieves symptoms of mild to moderate anxiety and depression. Conclusion Although clinical research supports the use of St. John's wort, passionflower, valerian, rhodiola and saffron in modern phytotherapy, further clinical studies are required to provide a higher level of evidence of therapeutic potential in the treatment of anxiety disorders

    Značaj osobnog plana liječenja astme (OPLA) za bolesnika s astmom i zdravstveni sustav

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    Cilj istraživanja: Cilj ovog specijalističkog rada je prikazati način izrade osobnog plana liječenja astme (OPLA) i njegove segmente te istražiti koji je značaj uvođenja osobnog plana liječenja kao standarda zdravstvene skrbi za pacijente oboljele od astme. U ovom radu prikazat će se pregled dosadašnjih znanstvenih istraživanja na temu OPLA-e u pogledu učinkovitosti i benefita za bolesnike s astmom u kontekstu smanjenja simptoma, egzacerbacije astme i poboljšanja kvalitete života, te posljedične ekonomske koristi za zdravstveni sustav. Materijali i metode: U izradi ovog rada proveden je temeljit pregled odgovarajuće stručne literature iz područja pulmologije s naglaskom na pisani astma plan, zdravstvenu skrb za pacijente s astmom te kliničke i ekonomske ishode liječenja astme. Literatura je pretraživana u bazama podataka PubMed i Cochrane Library prema ključnim riječima: asthma action plan, asthma selfmanagement i cost-effectiveness of asthma self-management. Kao izvor podataka upotrijebljene su smjernice Globalne inicijative za astmu (GINA) i Smjernice Hrvatskog pulmološkog društva za dijagnosticiranje i liječenje astme u odraslih. Rezultati: Velika metaanaliza sustavnih pregleda i randomiziranih kliničkih istraživanja na temu zdravstvenih i ekonomskih benefita samoupravljanja astmom, provedena od strane Pinnock, Parke i suradnika 2017., pokazala je da samoupravljanje astmom može smanjiti hospitalizacije, posjete hitnoj pomoći i neplanirane posjete liječniku te poboljšati kontrolu bolesti i kvalitetu života pacijenata s astmom. Kada je riječ o korištenju zdravstvenih resursa, šest metaanaliza je pokazalo da su intervencije podrške samokontroli astme rezultirale manjim brojem prijema u bolnicu. Četiri od navedenih šest metaanaliza također su izvijestile o smanjenju broja dolazaka na hitnu medicinsku pomoć kod osoba koje su sudjelovale u programima podržanog samoupravljanja u usporedbi s kontrolnom skupinom. Osim toga, četiri narativne recenzije pokazale su smanjenje posjeta hitnoj medicinskoj pomoći u najmanje polovici uključenih istraživanja, dok su tri metaanalize izvijestile o manjem broju neplaniranih posjeta liječniku u intervencijskoj skupini u odnosu na kontrolnu skupinu. Kada je riječ o kontroli astme, tri metaanalize i tri narativne recenzije izvijestile su o smanjenju simptoma kod sudionika iz intervencijske skupine u usporedbi s kontrolnom skupinom te smanjenju izostanaka s posla ili iz škole. Zaključak: Astma je kronična bolest koja pogađa preko 300 milijuna ljudi diljem svijeta te predstavlja značajan javnozdravstveni problem. Samoupravljanje astmom, koje uključuje edukaciju pacijenata o samokontroli astme i izradu osobnog plana liječenja astme (OPLA), preporučeni je pristup prema svim međunarodnim i nacionalnim smjernicama. Osobni plan liječenja astme (OPLA) personalizirani je plan liječenja koji daje direktne upute pacijentu kako se ponašati u slučaju egzacerbacije astme. OPLA omogućava proaktivno sudjelovanje pacijenata u liječenju te olakšava brzu reakciju u hitnim situacijama. Brojna istraživanja pokazala su kako samoupravljanje astmom može smanjiti hospitalizacije, posjete hitnoj pomoći, te poboljšati kontrolu bolesti i kvalitetu života pacijenata. Unatoč preporukama, malo pacijenata ima osobne planove liječenja. Stoga je važno razmotriti nove modele skrbi za osobe s astmom, uključujući aktivno sudjelovanje ljekarnika.Objectives: The aim of this specialist paper is to present the method of creating a personal asthma action plan (AAP) and its segments, and to investigate the significance of introducing a personal treatment plan as a standard of health care for patients with asthma. This paper will present an overview of previous scientific research on the topic of AAP in terms of effectiveness and benefits for asthma patients in the context of reducing symptoms, asthma exacerbation and improving quality of life, as well as the consequent economic benefits for the health system. Materials and methods: In the preparation of this paper, a thorough review of relevant professional literature in the field of pulmonology was carried out, with an emphasis on the written asthma plan, health care for patients with asthma, and the clinical and economic outcomes of asthma treatment. The literature was searched in the PubMed and Cochrane Library databases according to the keywords: asthma action plan, asthma self-management and cost-effectiveness of asthma selfmanagement. The guidelines of the Global Initiative for Asthma (GINA) and the Guidelines of the Croatian Pulmonology Society for diagnosing and treating asthma in adults were used as a data source. Results: A large meta-analysis of systematic reviews and randomized clinical trials on the health and economic benefits of asthma self-management, conducted by Pinnock, Parke et al. in 2017, showed that asthma self-management can reduce hospitalizations, emergency room visits, and unscheduled physician visits and improve disease control. and the quality of life of patients with asthma. When it comes to the use of healthcare resources, six meta-analyses found that asthma self-management support interventions resulted in fewer hospital admissions. Four of the six meta-analyses also reported a reduction in emergency department visits in people who participated in assisted self-management programs compared to a control group. In addition, four narrative reviews showed a reduction in emergency department visits in at least half of the included studies, while three meta-analyses reported fewer unplanned doctor visits in the intervention group compared to the control group. When it comes to asthma control, three meta-analyses and three narrative reviews reported a reduction in symptoms in participants in the intervention group compared to the control group, and a reduction in absenteeism from work or school (2). Conclusion: Asthma is a chronic disease that affects over 300 million people worldwide, posing a significant public health issue. Asthma self-management, which involves patient education on asthma self-control and the creation of a personalized asthma action plan (AAP), is a recommended approach according to international and national guidelines. The Asthma Action Plan (AAP) is a personalized treatment plan that provides direct instructions to patients on how to respond in case of asthma exacerbation. AAP enables proactive patient involvement in treatment and facilitates rapid responses in emergency situations. Numerous studies have shown that asthma self-management can reduce hospitalizations, emergency room visits, and improve disease control and patients quality of life. Despite recommendations, few patients have personal action plans. Therefore, it is important to consider new care models for individuals with asthma, including the active participation of pharmacists

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