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Evaluation of lipid-lowering therapy in patients with cardiovascular diseases
No full textKardiovaskularne bolesti predstavljaju glavni uzrok morbiditeta i mortaliteta u RepubliciHrvatskoj, kao i širom svijeta. Ključnu ulogu u patogenezi kardiovaskularnih bolesti ima ateroskleroza koja nastaje kao posljedica visokih razina kolesterola u krvi. Dokazana je direktna povezanost redukcije LDL kolesterola sa smanjenjem kardiovaskularnih događaja. Pacijenti se prema desetogodišnjem riziku od smrtnih i ostalih kardiovaskularnog rizika svrstavaju u četiri skupine: nizak, umjereni, visoki i vrlo visoki kardiovaskularni rizik. Ovisno o razini kardiovaskularnog rizika određene su ciljne vrijednosti LDL kolesterola koje se postižu različitim hipolipemicima. U Republici Hrvatskoj dostupni su različiti lijekovi za sniženje lipida u serumu, uključujući statine, fibrate, PCSK-9 inhibitore i inklisiran. U ovo istraživanje uključeno je 88 ispitanika koji su zaprimljeni na Zavod za bolesti srca i krvnih žila Kliničke bolnice Dubrava u Zagrebu. Temeljni cilj istraživanja bio je analizirati farmakoterapiju hipolipemicima kod kardioloških pacijenata pri prijemu u bolnicu primjenom NMMP (Najbolja moguća medikacijska povijest). Isto tako, cilj je bio utvrditi učestalost interakcija hipolipemika s ostalim lijekovima koji pacijenti imaju u terapiji. Vrijednosti LDL kolesterola pri prijemu pacijenata bilježeni su putem BIS-a (Bolnički informacijski sustav), dok je za utvrđivanje stupnja klinički značajnih interakcija korišten program Lexicomp®. Od uključenih ispitanika, 93,18% je svrstano u kategoriju vrlo visokog rizika. U ovom istraživanju, 23,86% pacijenata zaprimljena u bolnicu imala su zadovoljavajuće LDL vrijednosti. Od toga, 21,95% pacijenata vrlo visokog rizika imalo je zadovoljavajući LDL pri prijemu, dok je 50% pacijenata umjerenog rizika imala ciljne vrijednosti LDL-a. Velik udio pacijenata imalo je propisanu politerapiju i prekomjernu politerapiju. Osim odabira odgovarajućeg hipolipemika, važno je razmotriti i potencijalne interakcije hipolipemika s drugim lijekovima. U potencijalnim klinički značajnim interakcijama lijekova najčešće su bili uključeni statini. Atorvastatin je bio najčešće utvrđeni hipolipemik u potencijalnim klinički značajnim interakcijama. Kako bi se poboljšala kontrola LDL- a, na prijemu u bolnicu osobito je važno utvrditi bolesnike s visokim/vrlo visokim kardiovaskularnim rizikom.Cardiovascular diseases are the leading cause of morbidity and mortality in the Republic of Croatia and worldwide. Atherosclerosis, caused by high levels of cholesterol in the blood, plays a crucial role in the pathogenesis of these diseases. There is a proven direct correlation between reducing LDL cholesterol and decreasing cardiovascular events. Patients are classified into four groups based on their ten-year risk of fatal and other cardiovascular events: low, medium, high and very high cardiovascular risk. Depending on the level of cardiovascular risk, target LDL cholesterol values are determined and achieved through the use of various hypolipemic agents. In the Republic of Croatia, various lipid-lowering drugs are accessible, such as statins, fibrates, PCSK-9 inhibitors, and others. This study involved 88 participants admitted to the Department of Cardiovascular Diseases at Dubrava Clinic Hospital in Zagreb. The primary aim of the study was to gain insight into the hypolipemic therapy of cardiology patients upon hospital admission using the Best Possible Medication History (BMPH). Another goal was to assess the frequency of interactions between hypolipemic drugs and other medications in the patient's therapy. LDL cholesterol levels at patient admission were documented using the Hospital Information System while the Lexicomp® program was utilized to assess the extent of clinically significant interactions. In total 93.18% patients were classified as patients with very high cardiovascular risk. In this study, 23.86% of patients admitted to the hospital had recommneded LDL values. Of these, 21.95% of very high-risk patients had recommended LDL at admission, while 50% of moderate-risk patients had LDL target values. A large proportion of patients had prescribed polytherapy and excessive polytherapy. In order to optimize pharmacitherapy, it is important to consider the potential interactions of the hypolipemic agents with other drugs. Statins were most often involved in potential clinically significant drug-drug interactions. Atorvastatin was the most frequently identified hypolipemic drug in potential clinically significant drug-drug interactions. In order to improve LDL control, it is particularly important to identify patients with high/very high cardiovascular risk at hospital admission
Electrochemical methods for simultaneous determination of amlodipine and other drugs for treating hypertension and hyperlipidemia
No full textHipertenzija je najučestalija kardiovaskularna bolest i broj oboljelih od nje raste iz dana u dan. Za liječenje
hipertenzije dostupan je velik broj lijekova različitih mehanizama djelovanja, koji se zbog prirode bolesti često
kombiniraju. Lijek često zastupljen u tim kombinacijama je amlodipin, blokator kalcijevih kanala s posebnim
značajkama koje ga razlikuju od njemu srodnih lijekova. U ovom preglednom diplomskom radu prikazane su
voltametrijske metode koje se mogu koristiti za analizu samog amlodipina kao i za istovremenu analizu njega i drugog
lijeka/lijekova (hidroklorotiazid, atorvastatin, rosuvastatin, valsartan, ramipril, amilorid, atenolol i drugi). Pritom su u
istraživanjima najčešče proučavane pravokutnovalna i diferencijalno pulsna voltametrija kao i stripping voltametrijske
metode. Elektrode koje su najšire primjenjivane su krute elektrode: grafitna, staklasta ugljikova elektroda, dijamantna
elektroda, čije su površine vrlo često bile modificirane različitim vrstama nanomaterijala kako bi se optimizirali
procesi oksidacije, a samim time i rezultati analize. Prikazana je međusobna usporedba dostupnih voltametrijskih
metoda kao i njihova usporedba s ostalim komparativnim metodama (npr. HPLC). Objašnjene su prednosti
voltametrijskih metoda u odnosu na one koje se također koriste za analizu antihipertenziva.Hypertension is the most common cardiovascular disease and the number of patients being diagnosed with it is getting
bigger and bigger every day. Many drugs with different mechanisms of action are available for treating hypertension
and because of the nature of the illness they are usually prescribed as a combination therapy. Medication often seen in
combination with other molecules is amlodipine, a calcium channel blocker with special features that differ him from
other calcium channel blockers.In this thesis, voltammetric methods that can be used for analysis of amlodipine alone
and for simultaneous analysis of amlodipine and other drug/drugs ( hydrochlorothiazide, atorvastatin, rosuvastatin,
valsartan, ramipril, amiloride, atenolol and others ) are shown. The most widely used methods for that purpose are
differential pulse and square - wave voltammetry, as well as adsorptive stripping voltammetric methods. Electrodes
described in this thesis are mainly solid electrodes: carbon paste electrode, boron – doped diamond electrode, glassy
carbon electrode etc, which surfaces were often modified using different nanomaterials. These modifications helped
optimising oxidation processes occuring on surface of electrodes and with that ensured getting better results of
analysis.Also, described voltammetric methods were compared to eachother as well as to other analytical methods also
used for determination of antihypertensive drugs ( for example HPLC). Advantages of voltammetric methods are also
listed in this thesis
Comparison of erythrocyte sedimentation rate measurement on automated SRS 100/II analyser and manually by modified Westergren method
No full textBrzina sedimentacije eritrocita rutinska je metoda koja se često koristi u medicinsko-biokemijskim
laboratorijima. Westergren metoda referentna je metoda, no danas se često u upotrebi nalaze
automatizirane i modificirane metode za određivanje brzine sedimentacije. Svrha ovog ispitivanja
usporedba je automatizirane modificirane metode na SRS 100/II analizatoru (Greiner Bio-One,
GmbH, Austrija) i ručne modificirane metode na graduiranom stalku. Budući da analiza na SRS
100/II analizatoru i na graduiranom stalku iziskuje nove spremnike, prije usporedbe metoda
provedena je tehnička i klinička validacija spremnika VACUETTE® Tube 4NC ESR volumena 1,5
i 2,75 mL s 3,2%-tnim natrijevim citratom. Također, ispitana je i ponovljivost pomoću uzoraka,
jednog unutar, jednog iznad referentnog intervala. Utvrđena je primjerenost uvođenja obaju
spremnika u rutinski rad, no, s obzirom na to da analizator koristi samo spremnike volumena 1,5
mL, usporedivost je ispitana samo na njima. SRS 100/II posjeduje mogućnost mjerenja u trajanju od
15 i 30 minuta, tako da su uspoređivani rezultati dobiveni i nakon 15 minuta i nakon 30 minuta s
rezultatima dobivenim na graduiranom stalku nakon 30 minuta. Statističkom analizom utvrđeno je
da za mjerenje u trajanju od 30 minuta ne postoji klinički značajno konstantno odstupanje, dok za
mjerenje u trajanju od 15 minuta da postoji klinički značajno konstantno odstupanje, stoga je
prihvaćena metoda na SRS 100/II s mjerenjem u trajanju od 30 minuta za uvođenje u rutinski rad.
Ispitivanjem ponovljivosti na toj metodi, dobiveni rezultati zadovoljavaju kriterije prihvatljivosti.Erythrocyte sedimentation rate is a routine method commonly used in medical-biochemical
laboratories. While the Westergren method is a reference method, today automated and modified
methods for measuring the sedimentation rate of erythrocytes are often in use. The purpose of this
examination is to compare the automated modified method on SRS 100/II analyzer (Greiner BioOne, GmbH, Austria) and the manual modified method on the graduated stand. Since the analysis
on the SRS 100/II analyser and on the graduated stand requires new test tubes, a technical and
clinical validation of THE VACUETTE ® tube 4NC ESR test tubes of 1.5 and 2.75 ml with 3.2%
sodium citrate was performed prior to the comparison of the methods. Also, repeatability using
samples was tested. The appropriateness of introducing both test tubes into routine was established,
however, since the analyser only uses 1,5 ml test tubes, comparability was only tested on them. The
SRS 100/II has the possibility of measuring for 15 and 30 minutes, so the results obtained after both
15 minutes and 30 minutes were compared with the results obtained on the graduated stand after 30
minutes. A statistical analysis showed that there is no clinically significant constant difference for a
30 minute measurement, while a clinically significant constant difference was found for a 15 minute
measurement. Therefore, a 30 minute measurement SRS 100/II method was adopted for routine
implementation. By testing repeatability on this method, the results were found to meet the
acceptability criteria
Suitability of donepezil-loaded chitosan-based in situ gelling system for nasal administration in the form of spray
No full textAlzheimerova bolest neurodegenerativna je bolest mozga s brojem oboljelih koji ubrzano raste. Donepezil
(inhibitor acetilkolinesteraze), najčešće korišteni lijek za liječenje Alzheimerove bolesti, dostupan je u oblicima za
oralnu primjenu (samostalno i u kombinaciji s memantinom) te u obliku transdermalnog flastera. Krvno-moždana
barijera je slabo propusna pa je potrebna visoka doza lijeka kod primjene per os, što dovodi do brojnih nuspojava
uzrokovanih perifernim djelovanjem acetilkolina. Nazalna primjena donepezila osigurava dostavu lijeka izravno u
mozak, pri čemu je potrebna značajno manja doza za postizanje terapijskog učinka u usporedbi s oralno primijenjenom
dozom te se posljedično očekuje značajno smanjenje incidencije nuspojava.
Cilj ovog rada bio je pripraviti kitozanske in situ gelirajuće sustave s donepezilom te ispitati utjecaj
koncentracije kitozana na viskoznost u mirovanju (η), temperaturu (T) faznog prijelaza otopina iz sol u gel stanje te
vrijeme (t) potrebno za fazni prijelaz otopina iz sol u gel stanje pri 34 °C. In situ gelirajući sustavi donepezila (0,30 mg
mL-1 ) pripravljeni su s kitozanom (6,15-9,23 mg mL-1) i β-glicerofosfatom (β-GP; 188,46 mg mL-1
) koji osiguravaju geliranje otopine ovisno o temperaturi. Temeljem rezultata reoloških ispitivanja (η = 206,37 ± 1,46 mPa s; T = 33,7 ± 0,1 °C; t = 0,0 ± 0,0 min) i kuta raspršenja (15,5 ± 0,4°), najboljim za nazalnu primjenu pokazao se in situ gelirajući
sustav pripravljen pri koncentraciji kitozana od 9,23 mg mL-1 , stoga je taj sustav izabran za ispitivanje profila nazalne
depozicije. Profil nazalne depozicije ispitan je in vitro, pomoću višedijelnog 3D printanog modela nosne šupljine, pod
kutovima 45°, 60° i 75° u odnosu na horizontalnu ravninu te pri simuliranju zadržavanja daha. Najveći udio
formulacije dostavljen je u ciljano olfaktorno područje (58,1 ± 8,9 %) pri primjeni spreja pod kutom od 75°. Ostvareni
rezultati upućuju na potencijal kitozanskog in situ gelirajućeg sustava za nazalnu primjenu donepezila.Alzheimer's disease is a neurodegenerative brain disease with an increasing prevalence. Donepezil
(acetylcholinesterase inhibitor), the most commonly used drug for the treatment of Alzheimer's disease, is available in
oral dosage forms (monotherapy and in combination with memantine) and as transdermal patch formulation. The
blood-brain barrier is poorly permeable, so a high dose of the drug is required when administered per os, which leads
to numerous side effects caused by the peripheral action of acetylcholine. Nasal administration of donepezil ensures
delivery of the drug directly to the brain, where a significantly lower dose is required to achieve a therapeutic effect
when compared to an orally administered dose, and consequently a significantly reduced incidence of side effects is
expected.
The aim of this study was to prepare chitosan in situ gelling systems for donepezil nasal delivery and to
examine the influence of chitosan concentration on the zero shear viscosity (η), the temperature (T) of the phase
transition of the sample from sol to gel state and the time (t) required for the phase transition from sol to gel state at 34
°C. Donepezil loaded in situ gelling systems (0.30 mg mL-1) were prepared with chitosan (6.15-9.23 mg mL-1) and βglycerophosphate (β-GP; 188.46 mg mL-1) which ensure gelation of the solution depending on the temperature. Based on the results of the rheological tests (η = 206.37 ± 1.46 mPa s; T = 33.7 ± 0.1 °C; t = 0.0 ± 0.0 min) and spray cone
angle (15.5 ± 0.4°), in situ gelling system prepared at chitosan concentration of 9.23 mg mL-1 proved to be the best for
nasal administration, therefore it was chosen for testing the nasal deposition profile. Nasal deposition profile was
tested in vitro, using a multi-sectional 3D printed nasal cavity model, at spray administration angle of 45°, 60° and 75°
from the horizontal plane, and simulating breath holding. The largest proportion of the formulation was delivered to
the targeted olfactory area (58.1 ± 8.9 %) when the spray was applied at an angle of 75°. The obtained results indicate
the potential of the chitosan in situ gelling system for the nasal donepezil delivery
The impact of comprehensive medication management service on the process of de-escalation of benzodiazepines and Z-drugs in patients at the primary level of health care
No full textCilj istraživanja: Prikazati učinak usluge upravljanja farmakoterapijom na uspješnost deeskalacije benzodiazepina i
Z-lijekova kod pacijenata na primarnoj razini zdravstvene skrbi.
Materijali i metode: Provedeno je prospektivno, intervencijsko istraživanje u FTS unutar DZZC gdje se provodila
usluga upravljanja farmakoterapijom u razdoblju od siječnja 2018. do travnja 2024. Kroz proces pružanja skrbi
prikupljeni su relevantni podatci o pacijentu, njegovim bolestima i lijekovima koje uzima. Na temelju prikupljenih
informacija identificirani su terapijski problemi te je izrađen plan skrbi s predloženim intervencijama. Kriterij za izbor
sudionika za ovo istraživanje je ustanovljen terapijski problem vezan uz primjenu benzodiazepina ili Z-lijeka na jednoj
od konzultacija. Kod tih ispitanika predložen je postupak deeskalacije i praćeni su ishodi. Prikupljene informacije
obrađene su metodom deskriptivne statistike pomoću Microsoft Excel programa.
Rezultati: U ispitivanju je sudjelovalo ukupno 118 pacijenata, od čega su 77,1% činile žene. Pacijenti su bili prosječne
dobi od 71,2±11,1 godina. Identificirano je ukupno 1201 komorbiditeta (prosječno po pacijentu 10,2±6,0) i 1192 lijekova
(prosječno po pacijentu 11,2±5,1). Ukupno je zabilježeno 115 lijekova iz skupine benzodiazepina i 24 iz skupine Zlijekova
, među kojima je najviše bio zastupljen diazepam (35,3%). Evidentirana su ukupno 1142 terapijska problema
od kojih je 151 povezan s primjenom benzodiazepina/Z-lijekova. Predložena je 151 intervencija za spomenute lijekove
od kojih je njih 140 predloženo s ciljem deeskalacije istih. Predloženo je 125 protokola deeskalacije te je kod 7 pacijenata
proveden protokol za više od 1 lijeka. Za 57 predloženih protokola (45,6%) nije dobivena povratna informacija. Kod
ostalih 68 protokola uspješan ishod postignut je za 51 ispitanika (75%), među kojima je 23 (33,8%) ispitanika u
potpunosti prestalo s primjenom lijeka. Najveća uspješnosti deeskalacije zabilježena je za diazepam (45,0%).
Zaključak: Farmaceut kroz uslugu upravljanja farmakoterapijom i suradnjom s liječnicima opće medicine može
značajno doprinijeti uspjehu u protokolu deeskalacije benzodiazepina i Z-lijekova te poboljšanju kliničkih ishoda
povezanih s neopravdanom primjenom ovih lijekova.Objective: To evaluate the efficacy of comprehensive medication management service in facilitating the de-escalation
of benzodiazepine and Z-drug use among primary care patients.
Materials and Methods: A prospective, interventional study was undertaken within the FTS of the DZZC to evaluate
the impact of comprehensive medication management service. The study period spanned from January 2018 to April
2024. Patient data, including comorbidities and medications, were collected during routine care. Therapeutic problems
were identified based on these data, and individualized care plans were developed. Inclusion criteria for the study were
the presence of established therapeutic problems related to benzodiazepine or Z-drug use, as identified during a
consultation. For these participants, de-escalation protocols were proposed, and outcomes were monitored. Descriptive
statistics were employed to analyze the collected data using Microsoft Excel.
Results: A prospective study involving 118 patients was conducted to evaluate the efficacy of a pharmaceutical care
management intervention. Participants were predominantly female (77.1%) with a mean age of 71.2 ± 11.1 years. A
comprehensive medication review identified a mean of 10.2 ± 6.0 comorbidities and 11.2 ± 5.1 medications per patient,
including 115 benzodiazepines and 24 Z-drugs. Of the 1142 therapeutic problems identified, 151 were directly related
to benzodiazepine/Z-drug use. De-escalation interventions were proposed for these problems, with 125 distinct deescalation
protocols implemented. While feedback was not available for all proposed protocols, a successful outcome
was achieved for 75% of the remaining protocols, with 33.8% of participants completely discontinuing the target
medications. Diazepam demonstrated the highest de-escalation success rate (45.0%).
Conclusion: Pharmacists, through comprehensive medication management service and collaborative efforts with
general practitioners, can substantially enhance the success of benzodiazepine and Z-drug de-escalation protocols and
improve clinical outcomes associated with the suboptimal use of these medications
Educating cardiovascular patients about prescribed therapy at hospital discharge
No full textOtpust iz bolnice kritična je točka u zdravstvenoj skrbi za bolesnika. Promjene u terapijskom režimu tijekom hospitalizacije su uobičajene i često praćene uvođenjem novih lijekova. Bolesnikovo nerazumijevanje promjena terapijskog režima može dovesti do slabe adherencije prema lijekovima, neučinkovitosti i nuspojava lijekova te rehospitalizacije. Ljekarničke usluge usklađivanja terapije, savjetovanja bolesnika o propisanoj terapiji te upravljanja farmakoterapijom mogu znatno unaprijediti ishode liječenja prilikom transfera skrbi. Cilj ovog rada bio je razviti protokol za savjetovanje kardiovaskularnih bolesnika o propisanoj terapiji prije otpusta iz bolnice te njegova pilot provedba i evaluacija u svrhu davanja preporuka za daljnja istraživanja. Studija je zamišljena kao prospektivno intervencijsko istraživanje s dvjema paralelnim skupinama te randomizacijom prilagođenom uvjetima istraživanja. Istraživanje je provedeno na Zavodu za bolesti srca i krvnih žila Kliničke bolnice „Sveti Duh“. Za razvoj protokola pretražena je relevantna literatura na temu savjetovanja pacijenata pri otpustu iz bolnice te su uzeti u obzir koncepti ljekarničke skrbi prema Cipolle i sur. Svi su ispitanici ispunili kratak upitnik o svom zdravstvenom stanju, medikacijskoj povijesti i poznavanju propisane terapije. Prilikom savjetovanja poseban se naglasak stavljao na prepoznate ispitanikove potrebe i nesigurnosti te se nastojao uspostaviti dobar terapijski odnos kao temelj kvalitetne ljekarničke skrbi, a u okviru savjetovanja ispitaniku je uručen pisani letak koji sadrži ključne informacije o svakom lijeku u terapiji. 30 dana nakon otpusta iz bolnice, svi su ispitanici telefonski kontaktirani radi telefonskog praćenja s ciljem procjenjivanja njihove adherencije, utilizacije zdravstvene skrbi i doživljaja vlastitog zdravlja. U istraživanje je uključeno 99 ispitanika medijalne dobi 70 godina i interkvartilnog raspona između 63 i 75 godina, s prosječno 10,91 ± 3,51 lijekova u terapiji pri otpustu iz bolnice. Nije pronađena statistički značajna razlika u adherenciji između intervencijske i kontrolne skupine niti u jednoj točki ispitivanja (p= 0,059 pri razgovoru u bolnici i p= 0,305 pri telefonskom praćenju). Za intervencijsku skupinu nije pronađena statistički značajna razlika između različitih točaka ispitivanja (p = 0,383), dok za kontrolnu skupinu jest (p =0,039). Statistički značajna razlika također nije pokazana za utilizaciju zdravstvene skrbi između intervencijske i kontrolne skupine (p = 0,568 za usluge hitne pomoći, p = 0,603 za broj dana provedenih u bolnici i p = 0,202 za posjete liječniku obiteljske medicine) te za ocjenu vlastitog zdravlja između intervencijske i kontrolne skupine (p = 0,266). Ispitanici u intervencijskoj skupini primjećuju veće poboljšanje vlastitog zdravlja sa statistički značajnom razlikom u odnosu na kontrolnu skupinu (p = 0,036) . Ispitanici u intervencijskoj skupini u najvećem broju smatraju da im je pružena usluga savjetovanja pomogla u razumijevanju njihove terapije, što pokazuje da razvijeni protokol može biti koristan u razvijanju kvalitetnog terapijskog odnosa i optimizaciji bolesnikovog terapijskog iskustva. Ovi rezultati, zajedno sa istraživačevim iskustvom prilikom pilot provedbe protokola, pokazuju da postoji potreba za edukacijom bolesnika o propisanoj terapiji, a posebice kod bolesnika s najvećim rizikom od neplanirane rehospitalizacije. Kako bi se ovaj protokol mogao implementirati u kliničku praksu, potrebna su daljnja istraživanja s većim brojem ispitanika, nasumičnom randomizacijom u intervencijsku i kontrolnu skupinu te dugoročnijim praćenjem ispitanika s više provedenih follow up savjetovanja.Hospital discharge is a critical point in patient health care. Changes in the therapeutic regimen during hospitalization are common and often accompanied by the introduction of new drugs. The patient's lack of understanding of changes in the therapeutic regimen can lead to poor adherence, ineffectiveness and side effects of medications, and rehospitalization. Pharmacy services for medication reconciliation, educating patients on prescribed therapy, and medication management can significantly improve treatment outcomes during the transition of care. The aim of this research was to develop a protocol for counseling cardiovascular patients about the prescribed at hospital discharge and to pilot and evaluate it in order to make recommendations for further research. The study was designed as a prospective intervention study with two parallel groups and randomization adapted to the research conditions. The research was conducted at the Institute for Cardiovascular Diseases of the "Sveti Duh" Clinical Hospital. During the development of the protocol, the relevant literature was searched on the topic of counseling patients at discharge from the hospital, and the concepts of pharmaceutical care practice, according to Cipolle et al., were taken into account. All subjects filled out a short questionnaire about their health state, medication history and their understanding of the prescribed therapy. During counseling, special emphasis was placed on the individual’s identified needs and insecurities, and an effort was made to establish a good therapeutic relationship, as it is the foundation of pharmaceutical care, and as part of the counseling, each subject was given a written leaflet containing the most important information about each medication in the therapeutic regimen. 30 days after discharge from the hospital, all subjects were contacted by telephone for a follow-up questionnaire with the aim of assessing their adherence, utilization of health care and their self-rated health. The study included 99 subjects with a median age of 70 years and an interquartile range between 63 and 75 years, with an average of 10,91 ± 3,51 drugs prescribed at hospital discharge. No statistically significant difference in adherence was found between the intervention and control groups at any point of the study (p= 0,059 at the interview in the hospital and p= 0,305 at the telephone follow-up). For the intervention group, no statistically significant difference was found between the different points of examination (p = 0,383), while for the control group there was a statistically significant difference (p = 0.039). A statistically significant difference was also not shown for the utilization of health care between the intervention and control groups (p = 0,568 for emergency room admissions, p = 0,603 for the number of days spent in the hospital and p = 0,202 for visits to the family medicine physician) and for the assessment of self-reported health between the intervention and control group (p = 0,266). Respondents in the intervention group notice a bigger improvement in their own health with a statistically significant difference compared to the control group (p = 0.036). Most subjects in the intervention group stated that the provided counseling service helped them a lot in understanding their therapy, which shows that the developed protocol succeeds in establishing a good therapeutic relationship and in optimizing the patient's therapeutic experience. These results, together with the researcher's experience during piloting of the protocol, show that there is a need for educating patients about their therapy at hospital discharge, especially for patients with the highest risk of unplanned rehospitalization. In order to integrate this protocol into clinical practice, further research need to be conducted with a larger number of subjects, computer generated randomization and longer monitoring of subjects with more follow-up counsellings
The prevalence of therapeutic problems in patients on statin therapy at the Pharmacotherapy Counseling Center of the Zagreb-Center Health Center.
No full textCilj ovog diplomskog rada bio je odrediti vrstu i učestalost terapijskih problema kod pacijenata
koji koriste statine, a kojima je pružena usluga upravljanja farmakoterapijom u
Farmakoterapijskom savjetovalištu Dom Zdravlja Zagreb Centar. Provedeno je prospektivno
intervencijsko 6-šestogodišnje istraživanje u koje su uključeni pacijenti stariji od 65 godina kojima
je na prvoj ili drugoj konzultaciji identificiran terapijski problem povezan sa statinom. U
istraživanje je uključeno 128, od kojih su većinu činile žene prosječne dobi od 74 godine. U ovom
istraživanju identificirano je ukupno 707 terapijskih problema na inicijalnoj konzultaciji vezanih
za uzimanje lijekova (prosječno 3,02 ± 2,60 terapijska problema po pacijentu). Dva najčešća
terapijska problema vezana uz korištene lijekove i dodatke prehrani identificirana na inicijalnoj
konzultaciji bili su potreba za uvođenjem dodatne terapije i preniska doza lijekova, dok su
atorvastatin, rosuvastatin i kolekalciferol bili najčešći lijekovi povezani s terapijskim problemima.
Najčešće identificirani terapijski problemi vezani uz statine na svim konzultacijama bili su
preniska doza, potreba za uvođenjem statina u terapiju i neadherencija pacijenata. Velika
učestalost terapijskih problema kod pacijenata koji koriste statine ukazuje na potrebu za
uključivanjem usluge upravljanja farmakoterapijom u zdravstvenu skrb pacijenata koji koriste
statine kako bi se smanjio rizik razvoja i pogoršanja kardiovaskularnih bolesti te osigurala
optimalna uporaba lijekova.This research aimed to determine the type and frequency of drug therapy problems (DTP) in
patients using statins who received Comprehensive Medication Management (CMM) services at
the Pharmacotherapy Counseling Centre of the Health Care Center Zagreb-Centar. A prospective
interventional was conducted during a 6-year study and involved older patients with DTPs related
to statin use identified during the first and second consultation (initial consultation). Overall, 128
patients were included in the study, mostly women with an average age of 74. This study identified
707 DTPs at the initial consultation (an average of 3.02 ±2.60 DTPs per patient). The two most
common DTPs identified at the initial consultation related to medication and dietary supplements
were “Needs additional drug therapy” and “Dosage too low”, with atorvastatin, rosuvastatin, and
cholecalciferol being the most frequent medications associated with DTPs. The most commonly
identified DTPs related to statins across all consultations were “Dosage too low”, “Needs
additional statin”, and "Nonadherence”. The high frequency of DTPs in patients using statins
highlights the need to integrate CMM services into the healthcare of patients using statins to
reduce the risk of developing and worsening cardiovascular diseases and ensure optimal
medication use
Razina dokaza koji podupiru smjernice za kliničku praksu Europskog društva za medicinsku onkologiju
No full textCilj istraživanja: Ovaj rad analizira kvalitetu i pouzdanost dokaza koji podržavaju kliničke
smjernice Europskog društva za medicinsku onkologiju (engl. The European Society for
Medical Oncology, ESMO). Cilj je procijeniti razinu dokaza i stupanj preporuka unutar ESMO
smjernica, uzimajući u obzir brzi razvoj novih znanja u onkologiji. Analiza sistematski
pregledava ESMO smjernice, istražujući promjene u preporukama i razinama dokaza tijekom
vremena.
Rad također naglašava važnost oslanjanja na visokokvalitetna istraživanja pri formiranju
smjernica, kako bi se osigurala najbolja skrb za pacijente. Poseban naglasak stavlja se na
transparentnost, rigoroznost i redovito ažuriranje kliničkih smjernica, kako bi se osiguralo da
one odražavaju najnovija znanstvena dostignuća u onkologiji.
Materijali i metode: U ovom istraživačkom radu koristile su se ESMO kliničke smjernice
objavljene od svibnja 2005. do listopada 2022. kako bi se ocijenila kvaliteta dokaza koji su
podupirali preporuke za liječenje onkoloških oboljenja. Smjernice su preuzete s mrežne stranice
ESMO, a svaka smjernica temeljito je pregledana s ciljem izvlačenja ključnih preporuka i
odgovarajućih razina dokaza.
Metodologija istraživanja obuhvatila je nekoliko koraka. Najprije su se izdvojile ESMO
smjernice koje su za ocjenu svojih preporuka koristile Američkoga društva za infektivne bolesti
(engl. Infectious Diseases Society of America, IDSA) sustav, kategorizirajući svaku preporuku
od I do IV, gdje I predstavlja najvišu razinu dokaza. Stupanj preporuke za svaku smjernicu bio
je ocijenjen na skali od A do D, pri čemu A predstavlja najviši stupanj preporuke. Također, iz
smjernica su izvučeni podaci o farmakoterapiji, terapiji zračenjem, potpornoj terapiji, kirurgiji,
patologiji tumora i genetskim promjenama, metodama probira, dijagnostičkim postupcima,
praćenju, stadiju bolesti, vrsti raka i transplantaciji. U radu su obrađene 82 smjernice za 41
sijelo maligne bolesti. Trenutne smjernice definirane su kao one objavljene na mrežnoj stranici
ESMO do 10. prosinca 2022. Prethodne verzije tih smjernica našle su se kao reference u
trenutnim smjernicama. Dodatno se pretraživala ESMO mrežna stranica i PubMed baza
podataka kako bi se pronašlo prvo izdanje analiziranih smjernica.
Plan istraživanja uključivao je niz koraka koji su započeli prikupljanjem svih relevantnih
ESMO smjernica i ekstrakcijom potrebnih podataka. Uslijedila je detaljna analiza svake
smjernice, njezinih razina dokaza i stupnjeva preporuke. Usporedba trenutnih smjernica s
prethodnim verzijama omogućila je identifikaciju promjena i trendova.
Pretraživala se svaka smjernica kako bi se identificirale preporuke navedene u sažetoj tablici
preporuka. Ako sažeta tablica nije bila dostupna, uključivale su se preporuke koje su bile jasno
istaknute u svakom dokumentu i odvojene od ostatka teksta. Ako nisu bile jasno odvojene,
pretraživao se cijeli tekst smjernica i izdvajale preporuke s pripadajućom razinom dokaza i
stupnjem preporuke. Ako su uz jednu preporuku bile dvije razine dokaza ili stupnja preporuka,
u analizu se uključivala ona s jačom razinom dokaza, odnosno višim stupnjem preporuke.
Prikupljeni podaci obrađeni su statističkim metodama. Interpretacija rezultata uključivala je
analizu i tumačenje prikupljenih podataka u kontekstu kvalitete i pouzdanosti ESMO smjernica.
Rezultati: Analizirano je ukupno 82 smjernice koje su pokazale značajan porast broja
preporuka tijekom vremena, od prvih, preko prethodnih do trenutnih verzija. Ukupan broj
preporuka povećao se za 106 % između prethodnih i trenutnih verzija.
Usporedba trenutnih i prethodnih smjernica pokazuje blagi pad preporuka s najvišom razinom
dokaza (engl. Level of Evidence, LOE) I i II od 10 %, ali rast preporuka temeljenih na najnižim
razinama dokaza (V) porastao je za 5%. Ovaj trend ukazuje na potrebu za boljim dizajniranim
i rigoroznijim istraživanjima kako bi se ojačali dokazi koji podupiru preporuke.
Farmakoterapija je imala najveći broj preporuka najviše razine dokaza, LOE I, 42%, dok su
dijagnostički postupci i kirurgija pokazali najniži udio preporuka s najvišom razinom dokaza
(16 %).
U analizi različitih izdanja smjernica, primjetne su bitne promjene u preporukama. Unatoč
smanjenju najviših razina dokaza (LOE I) u nekim područjima, zabilježen je rast stupnja
preporuka (engl. Grade of Recommendation, GOR), što ukazuje na veću sigurnost u preporuke.
Ovaj trend ukazuje na to da, iako se može dogoditi smanjenje kvalitete dokaza, povjerenje u
efikasnost preporuka nastavlja rasti.
Zaključak: Ova analiza ESMO kliničkih smjernica otkriva da je jedna trećina trenutnih
preporuka podržana najvišom razinom dokaza (LOE I), iako je opća razina LOE I blago
smanjena u odnosu na prethodne verzije. Postoje varijacije u razinama dokaza i stupnjevima
preporuka među različitim vrstama raka, s visokim stopama preporuka na temelju nižih razina
dokaza (LOE III-V), što izaziva zabrinutost zbog smanjene pouzdanosti smjernica. Potrebno je
provoditi više kvalitetno dizajniranih studija za povećanje visokokvalitetnih dokaza i
poboljšanje ishoda liječenja raka, uz redovito ažuriranje smjernica kako bi se odgovorilo na
brze promjene u terapijskim mogućnostima.Objective: This paper analyzes the quality and reliability of the evidence supporting the clinical
guidelines of the European Society for Medical Oncology (ESMO). The goal is to assess the
level of evidence and the grade of recommendations within ESMO guidelines, considering the
rapid development of new knowledge in oncology. The analysis systematically reviews ESMO
guidelines, exploring changes in recommendations and levels of evidence over time.
The paper also highlights the importance of relying on high-quality research when forming
guidelines to ensure the best care for patients. Particular emphasis is placed on transparency,
rigor, and regular updates of clinical guidelines to ensure they reflect the latest scientific
achievements in oncology.
The abstract underscores the significance of this research in the context of improving clinical
guidelines and healthcare, emphasizing the need for precise and up-to-date guidelines that
reflect the current state of scientific knowledge.
Materials and Methods: This research utilized ESMO clinical guidelines published from May
2005 to October 2022 to assess the quality of evidence supporting oncological treatment
recommendations. Guidelines were downloaded from the ESMO website, and each guideline
was thoroughly reviewed to extract key recommendations and corresponding levels of
evidence.
The research methodology involved several steps. Initially, ESMO guidelines that used the
IDSA system to assess their recommendations were selected, categorizing each
recommendation from I to IV, where I represents the highest level of evidence. The grade of
recommendation for each guideline was assessed on a scale from A to D, with A representing
the highest level of recommendation. Additionally, data about pharmacotherapy, radiation
therapy, supportive therapy, surgery, tumor pathology and genetic changes, screening methods,
diagnostic procedures, monitoring, disease stages, cancer types, and transplantation were
extracted from the guidelines. The study processed 82 guidelines for 41 malignant disease
topics. Current guidelines were defined as those published on the ESMO website
(www.esmo.org/guidelines) by December 10, 2022. Previous versions of these guidelines were
identified as references in the current guidelines. Further searches were conducted on the ESMO
website and the PubMed database to find the first edition of the analyzed guidelines.
The research plan included a series of steps starting with the collection of all relevant ESMO
guidelines and the extraction of necessary data. This was followed by a detailed analysis of each
guideline, its levels of evidence, and grades of recommendation. Comparing current guidelines
with previous versions enabled the identification of changes and trends.
Each guideline was searched to identify recommendations listed in the summary table of
recommendations. If no summary table was available, recommendations that were clearly
highlighted in each document and separated from the rest of the text were included. If they were
not clearly separated from the rest of the text, the entire text of the guidelines was searched, and
recommendations with their associated levels of evidence and grades of recommendation were
extracted. If a recommendation was associated with two levels of evidence or grades of
recommendation, the one with the stronger level of evidence or higher grade of
recommendation was included in the analysis.
Collected data were processed using statistical methods. The interpretation of the results
involved analyzing and interpreting the collected data in the context of the quality and reliability
of ESMO guidelines.
Results: A total of 82 guidelines were analyzed, showing a significant increase in the number
of recommendations over time, from the first through previous to current versions. The total
number of recommendations increased by 106% between the previous and current versions. A
comparison of the current and previous guidelines shows a slight decrease in recommendations
with the highest levels of evidence (LOE I and II) by 10%, but an increase in recommendations
based on the lowest levels of evidence (V) by 5%. This trend indicates a need for better designed
and more rigorous research to strengthen the evidence supporting the recommendations.
Pharmacotherapy had the highest number of recommendations at the highest level of evidence,
LOE I, at 42%, while diagnostic procedures and surgery showed the lowest proportion of
recommendations with the highest level of evidence (16%). In analyzing different versions of
the guidelines, significant changes in recommendations are noticeable. Despite a decrease in
the highest levels of evidence (LOE I) in some areas, there is an increase in the grade of
recommendations (GOR A), indicating enhanced confidence in the recommendations. This
trend suggests that, even though the quality of evidence may decrease, the confidence in the
effectiveness of the recommendations continues to grow.
Conclusion: This analysis of ESMO clinical guidelines reveals that one-third of current
recommendations are supported by the highest level of evidence (LOE I), although the overall
level of LOE I has slightly decreased compared to previous versions. Variations in levels of
evidence and grades of recommendations among different types of cancer, with high rates of
recommendations based on lower levels of evidence (LOE III-V), raise concerns about
decreased reliability of guidelines. An increase in GOR A recommendations has also been
noted, despite a decrease in LOE I in some areas, suggesting a trend towards increasing
unfounded security in recommendations. More high-quality studies are needed to increase highquality evidence and improve cancer treatment outcomes, along with regular updates to
guidelines to respond to rapid changes in therapeutic options
Modeling the reaction of quercetin with hydroxyl radical
No full textU brojnim biološkim pokusima utvrđeno povoljno djelovanje polifenola kvercetina na organizam tumači se između
ostalog i mogućim reakcijama kvercetina s vrlo reaktivnim kisikovim radikalskim spojevima (ROS). U tim
antioksidativnim reakcijama kvercetin može predati vodikov atom vrlo reaktivnom radikalu i tako ga prevesti u slabo
reaktivan i neopasan spoj. U takvim reakcijama nastaje i slabo reaktivni kvercetin radikal anion koji ne predstavlja
opasnost i može se ukloniti.
U ovom radu cilj je bio metodama računske kemije na modelnom sustavu ispitati mogući reakcijski mehanizam za
antioksidativno djelovanje polifenola kvercetina u fiziološkim uvjetima. U tu svrhu koristile su se DFT metode i analiza
„intrinzičnih veznih orbitala“ (IBO). Modelni sustav sastojao se od aniona kvercetina deprotoniranog na 4'-OH ili 7-OH
skupini, hidroksil radikala (OH• ) i 405 molekula vode. Provedeni su izračuni molekulske dinamike te se pokazalo da se
za niz trajektorija koje su dobivene može utvrditi da je došlo do reakcije prijenosa vodikovog atoma s molekule
kvercetina na hidroksil radikal. Također je utvrđeno da hidroksil radikal propagira kroz otapalo uglavnom
reorganizacijom vodikovih veza odnosno Grotthuss-ovim mehanizmom. Za niz trajektorija kod kojih je došlo do
prijenosa vodikovog atoma, provedena je IBO analiza. IBO analiza omogućuje identifikaciju molekulskih orbitala na
kemijski intuitivni način kao i praćenje preraspodjele molekulskih orbitala tijekom reakcije te je stoga uspješno korištena
za istraživanje reakcijskih mehanizama. Za sve provedene simulacije gdje je došlo do prijenosa vodikovog atoma,
provedena IBO analiza je pokazala da β spin elektron koji se uparuje s nesparenim α spin elektronom OH• dolazi iz π
IBO aromatskog sustava kvercetin aniona, dok oba elektrona vezne σ IBO OH skupine kvercetina nakon otpuštanja
protona ostaju na kvercetinu, a oba elektrona slobodnog elektronskog para OH• radikala stvore s prenesenim protonom σ veznu IBO nastale molekule vode.
U svim analiziranim slučajevima, IBO analiza trajektorija pokazala je da se prijelaz vodikovog atoma s neke od OH
skupine aniona kvercetina na OH•radikal odvija tako da su u proces prijelaza elektrona i protona uključene različite IBO
te se može pretpostaviti da se ova reakcija odvija reakcijskim mehanizmom spregnutog prijelaza elektrona i protona
(PCET).The beneficial effects of the polyphenol quercetin on the body, which have been determined in numerous biological
experiments, are explained, among other things, by the possible reactions of quercetin with highly reactive oxygen
species (ROS). In these antioxidative reactions, quercetin can quench the reactive radical by transferring a hydrogen
atom and turning it into a less reactive and harmless form. The less reactive quercetin radical anion formed in these
reactions does not pose any further danger and can be eliminated.
The goal of this thesis is to propose a possible reaction mechanism for the antioxidative effect of quercetin under
physiological conditions based on computational chemistry methods in a model system. DFT methods and 'intrinsic
bond orbital' (IBO) analysis were used for this purpose. The model system is composed of quercetin anion deprotonated
on either the 4'-OH or 7-OH group, hydroxyl radical (OH• ) and 405 molecules of water. Molecular dynamics simulations
are run on the system, and a number of trajectories, in which the reaction of hydrogen transfer from quercetin to hydroxyl
radical was successful, were identified. It has also been identified that the main method of hydroxyl radical propagation
through the medium is through reorganization of hydrogen bonds, also known as the Grotthuss reaction mechanism. On
the trajectories in which the hydrogen transfer reaction was confirmed, IBO analysis was performed. IBO analysis
enables the identification of molecular orbitals in a chemically intuitive way by means of which it is possible to monitor
the redistribution of molecular orbitals during the reaction and is therefore successfully used for the investigation of
reaction mechanisms. For all performed simulations where hydrogen atom transfer occured, the performed IBO analysis
showed that the β spin electron that pairs with the unpaired α spin electron of OH• comes from the IBO of the π aromatic
system of the quercetin anion, while both electrons of the σ bonding IBO of the OH group of quercetin after the release
of the proton remain on quercetin, and both electrons of the free electron pair of the OH• radical create the σ bonding
IBO of the resulting water molecule with the transferred proton.
In all analyzed cases, the IBO analysis of the trajectories has revealed that the hydrogen atom transfer from one of the
OH groups of the quercetin anion to the OH• radical utilizes different sets of IBOs for proton and for electron transfer,
and thus in this case, a proton coupled electron transfer (PCET) reaction mechanism can be proposed
Antimigrenski učinak običnog lopuha – Petasites hybridus (L.) P. Gaertn., B. Mey. et Schreb.
No full textCilj istraživanja
Cilj je ovog specijalističkog rada pružiti sveobuhvatan pregled znanstvenih spoznaja o
antimigrenskom učinku običnog lopuha – Petasites hybridus (L.) P. Gaertn., B. Mey. et Schreb
kako bi se prema znanstveno utemeljenim dokazima mogli donijeti relevantni zaključci o
njihovu biomedicinskom potencijalu.
Materijali
Istraživanje u ovom radu teorijskog je karaktera i uključuje detaljan pregled dostupnih stručnih
i znanstvenih podataka o toj temi. Pretražene su relevantne bibliografske baze podataka kao što
su PubMed, Scopus, ScienceDirect i Cochrane. Prikupljeni podaci uključivali su klinička
ispitivanja koja su zatim sustavno prezentirana.
Rezultati
Migrena je kronična bolest koja pogađa 12 % svjetske populacije, a svrstava se među najčešće
neurološke bolesti. Unatoč terapijskim mogućnostima i novim znanstvenim spoznajama o
patogenezi te bolesti, još uvijek nisu postignuti zadovoljavajući ishodi liječenja migrene. Velika
je potreba za preventivnim liječenjem migrene, kako bi se smanjila učestalost napadaja i
spriječilo napredovanje bolesti – što uključuje i tradicionalnu primjenu prirodnih ljekovitih
tvari. Učinkovitost običnog lopuha u sprječavanju glavobolja i migrena proizlazi iz njegova
protuupalnog i spazmolitičnog učinka. Klinički je ispitan jedino ekstrakt običnog lopuha
Petadolex® iz kojeg su uklonjene toksične alkaloidne sastavnice. Rezultati ukazuju na veliki
potencijal ekstrakta u profilaksi migrene u djece i odraslih, uz sigurnu primjenu u dnevnoj dozi
50 – 150 mg.
Zaključak
Iako je razina kliničkih dokaza o djelovanju običnog lopuha nedostatna, tradicionalna primjena
i dosadašnje znanstvene spoznaje ukazuju na njegov veliki potencijal i ohrabruju daljnja
klinička istraživanja.Objectives
The aim of this study is to provide a comprehensive overview of scientific knowledge on the
effects of the antimigrenic effect of butterbur - Petasites hybridus (L.) P. Gaertn., B. Mey. et
Schreb. in order to draw relevant conclusions about their potential for therapeutic application.
Materials and methods
The research in this work is theoretical and involves a detailed review of the available
professional and scientific data on the subject. Relevant bibliographic databases such as
PubMed, Scopus, ScienceDirect and Cochrane were searched. The collected data included
clinical trials, which were then systematically presented.
Results
Migraine is a chronic disease that affects 12 % of the world's population as one of the most
common neurological disorders. Despite the therapeutic possibilities and new scientific
knowledge about the pathogenesis of this disease, no satisfactory results have yet been achieved
in the treatment of migraine. There is a great need for preventive migraine treatment to reduce
the frequency of attacks and prevent the progression of the disease, including the traditional use
of natural products. Butterbur's effectiveness in preventing headaches and migraines is due to
its anti-inflammatory and antispasmodic effects. Petadolex® butterbur extract, from which the
toxic alkaloid components have been removed, is the only one that has been clinically tested.
The clinical studies carried out indicate great potential in the prophylaxis of migraine in children
and adults, with a daily dose of 50 – 150 mg being safe.
Conclusion
Although the clinical evidence for the effects of butterbur is insufficient, traditional use and
current scientific findings point to its great potential and encourage further clinical research