Trends in Statin Consumption and Cardiovascular Mortality in Croatia 2004–2012

Prescribing of statins showed an increasing trend in all developed countries, during the last two decades. The aim of this study was to research the trends in statin consumption in the period from 2004 to 2012 as well as trends of cardiovascular mortality during the 1990 to 2012 period, and to compare them between Croatia and several neighbouring countries. Data on statin expenditures and consumption expresed in defined daily doses per 1000 inhabitants per day (DDD/TID), were taken from annual reports of Croatian Agency for Medicinal Products and Medical Devices (HALMED). Data on crude mortality rates and standardized cardiovascular mortality rates, were taken from the Croatian Health Statistics Yearbooks. The utilization of statins increased by 196.7% during the observed period, with the highest consumption of atorvastatin and simvastatin. Financial expenditure of statins expanded at much faster rate in comparison with overall drug costs. Cardiovascular mortality rates decreased slightly, while maintaining higher level in comparison with some neighbouring countries

How effective is a brief educational intervention on prescribing first-line antibiotics in acute cystitis? A quasiexperimental study among general practitioners in Croatia

Aim To assess the effectiveness of a brief educational intervention on prescribing first-line antibiotics in acute cystitis. Methods This quasi-experimental before-after study was conducted over a period of eight months. We collected prescribing data related to urinary tract infections four months before the educational intervention and four months after it. Aggregate data on office visits, diagnoses, and issued prescriptions were collected from each practice’s electronic medical records based on monthly reports. Results Overall, 3581 prescriptions were issued: 1717 before and 1864 after the intervention. The total number of prescriptions increased by 8.5%. The use of first-line antibiotics increased by 21.2%, the use of fluoroquinolones decreased by 6.6%, while the use of beta-lactams remained unchanged. After the intervention, nitrofurantoin was the most prescribed first-line antibiotic. The proportion of women who were prescribed first-line antibiotic did not reach the acceptable range (80%-100%) according to the European Surveillance of Antimicrobial Consumption quality indicators. The proportion of fluoroquinolones (17.9%) use was well above the acceptable range (0%-5%). Conclusion A brief educational intervention proved to be a useful method in adopting better prescribing habits. Of particular importance is the considerable increase in the use of nitrofurantoin due to its reliable efficacy against multidrug-resistant urinary pathogens

Fifteen most utilized over-the-counter drugs in Croatia: longitudinal study based on routinely collected data

Uvod. Osim Izvještaja Hrvatske Agencije za lijekove i medicinske proizvode (HALMED) u kojima je potrošnja bezreceptnih (OTC) lijekova usputno spomenuta, u Hrvatskoj nema sustavne analize njihove potrošnje. Cilj je ovog rada istražiti desetogodišnju potrošnju 15 najčešćih OTC lijekova i upoznati liječnike obiteljske medicine s lijekovima koje bolesnici samostalno uzimaju, najčešće bez njihovog znanja. Metode. U radu su korišteni HALMEDovi izvještaji od 2005. do 2014. o lijekovima sukladno anatomsko-terapijskoj klasifikaciji i internacionalnom nezaštićenom imenu pojedinog lijeka. Budući da za neke od OTC lijekova ne postoje definirane dnevne doze, praćena je samo financijska potrošnja. Rezultati. Od 15 peroralnih OTC lijekova, najčešće se koristio paracetamol, sam i kombiniran s drugim lijekovima, te acetilsalicilna kiselina kao analgetik, antipiretik i kao antiagregacijsko sredstvo, pa antacidni pripravci s aluminijem, magnezijem i kalcijem i kontaktni laksativi, zatim vitamini (B i C), mukolitici i ekspektoransi. Znatan je porast lijekova za prostatu. Psihotropni lijekovi, ginko i valerijana, su također često uzimani. Od lokalnih lijekova više se koriste nesteroidni antireumatici, te oksimetazolin i nafazolin. Zaključak. Rezultati ukazuju na često korištenje i porast potrošnje OTC lijekova, koji nerijetko mogu imati znatne nuspojave i interakcije. Stoga bi pitanja o uzimanju OTC lijekova trebala biti sastavni dio razgovora sa svakim bolesnikom.Introduction. Lack of published data on the overthe-counter (OTC) drugs consumption in Croatia was the main reason for this investigation covering a ten-year period, 2005-2014. Methods. The Croatian Agency of Medicinal Products and Devices Annual reports on drug utilization (in which drugs are presented according to ATC and INN) were the main sources for data collection. Since some of OTC drugs have no defined daily doses, only financial utilisation (in kunas) and only for the 15 most utilised OTC drugs were collected. Results. Among the orally used OTC drugs, leading are analgesics and antipyretics, mostly acetaminophen (paracetamol) and acetylsalicylic acid (aspirin), followed by aspirin as an antiplatelet agent. An array of antacids was often used, as well as the laxative bisacodyl. Vitamins B and C shared the high places, and Sabal palm and silymarin for prostate and liver diseases. Mucolytics, bromhexine and acetylcysteine are also often used, as well as psychotropic Gingko biloba and valeriana. Among topical drugs, the most used are NSARs and nasal decongestants. Conclusions. OTC drugs are frequently and increasingly used in Croatia, with a growing probability of side-effects and drug-drug interactions. Therefore, the questioning about OTC drug utilization should be part of every consultation in family medicine, and the OTC drug consumption should be systematically investigated

WHICH MEDICINES WE PRESCRIBED MOSTLY IN 2012?

Uvod. Analiziranje lijekova s najvećim opsegom potrošnje, kao i onih s najvećim financijskim troškovima, daleko premašuje puki zdravstvenostatistički značaj, otvarajući brojna pitanja o njihovom pravom mjestu i ulozi u suvremenoj farmakološkoj terapiji. Cilj rada je istražiti ukupnu potrošnju lijekova u 2012. godini, terapijsku potrošnju izraženu u DDD i financijsku izraženu u kunama, te specifično, potrošnju najpropisivanijih lijekova u izvanbolničkoj zaštiti. Materijali i metode. Istraživanje je kritička analiza (audit), temeljena na rutinski prikupljenim podacima Hrvatske agencije za lijekove i medicinske proizvode. Iz javno dostupnih podataka o godišnjem potrošnji lijekova, prikupljeni su podaci o općoj potrošnji bolničkoj i izvanbolničkoj, te podaci o potrošnji dvadeset lijekova koji su najčešće propisani na recept na teret HZZO-a, dvadeset lijekova u režimu slobodne prodaje, te prvih dvadeset s obzirom na financijski trošak, kao i podaci o potrošnji lijekova po županijama. Rezultati. Najveća ukupna, bolnička i izvanbolnička potrošnja, terapijska (izražena stopom DDD/ 1000 stanovnika/ dan) i financijska, odnosila se na kardiovaskularne lijekove, iza kojih su slijedili lijekovi s djelovanjem na živčani sustav. Među 20 najpropisivanijih lijekova na recept u PZZ-u, na prvom mjestu su bili ramipril, amlodipin i diazepam, dok su prema financijskim pokazateljima na prva tri mjesta atorvastatin pantoprazol i lizinopril HCT. Također veliki udio u financijskoj potrošnji otpada na lijekove koji su propisani po preporuci kliničkih specijalista, kao što su atipični antipsihotici i biološki lijekovi. U potrošnji lijekova koje pacijenti sami kupuju (OTC lijekovi) najčešća je acetilsalicilna kiselina, te analgetici i antipiretici, uključujući i nesteroidne antireumatike. Također je uočena velika razlika u potrošnji među pojedinim županijama. Zaključak. U komparaciji s literaturnim spoznajama, visoka potrošnja kardiovaskularnih lijekova je razumljiva zbog javno-zdravstvenog značaja tih bolesti, ali bi se trebao preispitati, s terapijskog i financijskog gledišta, visok udio u potrošnji nekih lijekova, kao što su ramipril, atorvastatin, diazepam, pantoprazol kao i udio lijekova koji su izvan propisivačke ingerenciji liječnika obiteljske medicine.Introduction. Analysis of pharmaceuticals with the highest consumption rate, as well as those with the highest financial costs, significantly exceeds the mere health statistical importance, opening numerous questions on their true place and role in contemporary pharmacologic therapy. Aim. The aim was to investigate total drug consumption in 2012, therapeutic consumption expressed in defined daily doses (DDD/1000 inhabitants/day), financial consumption in kunas (HRK), and specifically, the use of most frequently prescribed drugs in community health care setting. Materials and methods. The research was a critical analysis (audit), based on routinely collected data from the Agency for Medicinal Products and Medical Devices of Croatia. Data on total drug consumption, in both community and hospital settings, of twenty most frequently prescribed refundable drugs, twenty most frequently prescribed non refundable drugs (OTC), twenty drugs withthe largest share in financial costs, and data on consumption at regional level (between counties) were extracted from the publicly available annual reports. Results. The highest total consumption (hospital and community), both therapeutic (in DDDs/1000 inhabitants/ day) and financial, was recorded for cardiovascular drugs, followed by nervous system drugs, were extracted from the publicly available annual reports. Among twenty most prescribed refundable pharmaceuticals in primary care were: ramipril, amlodipin and diazepam, while atorvastaton, pantoprazol and lisinopril HCT were three best-selling drugs which were responsible for high financial expenses. The great share in financial expenditure belonged to drugs prescribed upon recommendation of clinical specialists, such as atypical antiosychotics and biological agents. Acetylsalycilic acid and analgesics (including no steroid anti-inflammatory drugs) prevailed mostly among the OTC drugs. There were great differences in consumption among counties. Conclusion. When we compare our findings with those we found in literature, such a large use of cardiovascular drugs is understandable, because of cardiovascular diseases public health significance. High usage of several drugs, such as ramipril, atorvastatin, diazepam and pantoprazol should be revised from the therapeutic and financial point of view, as well as the proportion of drugs for which family practitioners are not competent to prescribe

Trends in Preventive Activities for the Adult Population in Family Medicine in Croatia: 1995–2012

A few preventive activities were recorded in Croatian family medicine (FM) from 1995 until 2003, and then in 2004, additional fee-for-service reimbursement for general check-ups for people aged 45 to 65 years was introduced. The aim of this study was to investigate the trends in preventive activities before and after the introduction of those measures by using the Croatian Health Service Yearbooks for 1995–2012 as the main database. Data on the number of preventive, general, and total number of check-ups were collected. The results showed that the total number of check-ups registered in FM was low, suggesting that the additional reimbursement did not bring any improvements. In fact, the trend in the number decreased after 2004. These results are not unexpected because of the ineffectiveness of general check-ups as indicated in the literature. General check-ups should be replaced by targeted preventive interventions with evidence-based effectiveness

Trends in Prescribing in Primary Care in Croatia, 2000–2012: Prescribing Volume, Costs and Regulatory Measures

The rise of pharmaceutical costs is a significant burden to overall health care expenditure. The Croatian Health Insurance Fund (CHIF) in attempts of its containment, use administrative measures directed toward the two greatest generators: pharmaceutical industry, through negotiating prices and periodic revisions of basic and suplemental drug lists, and primary care physicians, through limits in the volume of prescriptions, and annual financial expenditure. The aim of the study was to determine trends in quantity of issued prescriptions and pharmaceutical expanditure from 2000 to 2012. Data were obtained from the CHIF annual reports. Results clearly demonstrate two trends: the increase in quantity of issued prescriptions, together with accompanying rates: number of prescriptions per inhabitants, and per patients, and the increase in total cost of prescriptions until 2004, with their maintenance and slight variations since then. Despite controversies in app

High Interleukin 27 Production is Associated with Early Clinical Stage and Localized Disease in Patients with Melanoma

Background: The immune response in patients with melanoma is an important focus of research due to the tumor's resistance and immunotherapy possibilities. IL-27 is one of the cytokines with antitumor properties. The role of IL-27 in the pathogenesis of melanoma is still unclear. The aim of this study was to examine the association between serum IL-27 levels and the clinical parameters of melanoma patients. Methods: The IL-27 concentration was determined by commercial ELISA in serum samples from melanoma patients (n=72) and healthy control subjects (n=44). Patients were classified according to AJCC clinical stage, TNM stage, the length of progression-free interval (PFI) and the extent of the disease (localized or widespread). Results: Average IL-27 values were increased in patients with early stages of melanoma compared to patients with terminal stages and control values. The highest IL-27 concentration was found in stage Ila. Patients in stages III and IV had significantly lower values of IL-27 compared to control. Patients with localized melanoma and shorter PFI had insignificantly increased IL-27 levels compared to patients with widespread disease and longer PFI. Patients with metastatic disease and stage TNM4 had significantly lower average IL-27 values compared to control. Patients with high production of IL-27 (>1000 pg/mL) were most numerous in Ila AJCC stage, with initial tumor size TNM2 and in the group of patients with localized disease. Conclusions: High levels of IL-27 in patients with melanoma are associated with the initial stages and localized disease

Association between oxidative stress and melanoma progression

Background: Overproduction of free radicals accompanied with their insufficient removal/neutralization by antioxidative defense system impairs redox hemostasis in living organisms. Oxidative stress has been shown to be involved in all the stages of carcinogenesis and malignant melanocyte transformation. The aim of this study was to examine association between oxidative stress development and different stages of melanoma. Methods: The measured oxidative stress parameters included: superoxide anion radical, total and manganese superoxide dismutase, catalase and malondialdehyde. Oxidative stress parameters were measured spectrophotometrically in serum samples from melanoma patients (n=72) and healthy control subjects (n=30). Patients were classified according to AJCC clinical stage. Results: Average superoxide anion and malondialdehyde concentrations were significantly higher in melanoma patients than in control group, with the highest value of superoxide anion in stage III, while malondialdehyde highest value was in stage IV. The activity of total and manganese superoxide dismutase was insignificantly higher in melanoma patients than in control group, while catalase activity was significantly higher. The highest activity of total superoxide dismutase was in stage III, while the highest activity of manganese superoxide dismutase was in stage IV. Catalase activity was increasing with the disease progression achieving the maximum in stage III. Conclusions: Results of our study suggest that melanoma is oxidative stress associated disease, as well as deteriorated cell functioning at mitochondrial level

Treatment of urinary infections in primary health care: the effect of educational intervention on prescription quality indicators

Ciljevi istraživanja: Glavni je cilj istraživanja bio povećanje potrošnje antibiotika prve linije u liječenju nekompliciranih cistitisa. Edukacijska intervencija u obliku preglednog članka s prikazima slučajeva osmišljena je radi povećanja potrošnje antibiotika prve linije, kao i radi poboljšanja parametara potrošnje u skladu s ESAC indikatorima kvalitete propisivanja. Metode i ispitanici: Istraživanje je ustrojeno kao prospektivna intervencijska studija na uzorku od 42 liječnika obiteljske medicine. Podatci o broju posjeta s dijagnozama mokraćnih infekcija i izdanim receptima za antibiotike prikupljani su iz medicinskih računalnih programa na temelju mjesečnih izvješća. Svi su liječnici razmatrani kao jedinstven uzorak, a ispitivanje se učinkovitosti intervencije (potrošnje antibiotika prije i poslije intervencije) obavilo metodama analiziranja vezanog uzorka. Rezultati: U skrbi je liječnika bilo ukupno 67 547 osoba, od toga 31 214 muškaraca i 36 333 žena. Ukupno je propisan za nekomplicirani cistitis žena starijih od 18 godina 3581 recept, od čega 1717 prije i 1864 poslije edukacije. Potrošnja je porasla za 147 recepata (8,5 %). Broj se recepata antibiotika prve linije (nitrofurantoina, fosfomicina i trimetoprim-sulfametoksazola) povećao s 837 na 1015 (178 recepata ili 21,2 %), broj recepata za fluorokinolone smanjen je s 332 na 310 (6,6 %), dok je upotreba beta-laktama ostala nepromijenjena (30,3 %). Od antibiotika prve linije najviše je poslije edukacije propisivan nitrofurantoin (178 recepata ili 21,2 %). Opseg potrošnje poslije intervencije, s obzirom na indikatore kvalitete, iznosio je za indikator „a“ 100 %, za indikator „b“ 54,4 % te za indikator „c“ 16,6 %. Zaključak: Liječnici su nakon intervencije povećali propisivanje antibiotika prve linije, od toga najviše nitrofurantoina. Porast potrošnje nitrofurantoina i fosfomicina poslije edukacije postigao je statističku značajnost. Unatoč porastu potrošnje antibiotika prve linije (48,7 % prije i 54,4 % nakon intervencije), prihvatljivi rasponi nisu dosegnuli vrijednosti predviđene ESAC indikatorima kvalitete.Aims: The main goal of the study was to increase the consumption of first-line antibiotics in the treatment of uncomplicated cystitis. Educational intervention in the form of a review article with case reports was designed to increase the consumption of first-line antibiotics, as well as to improve the consumption parameters in accordance with the ESAC quality indicators for antibiotic prescribing. Methods and subjects: The study was organized as a prospective intervention study with the participation 42 family physicians. The data on the number of visits related to urinary tract infection diagnoses and issued antibiotic prescriptions were collected from medical computer programs, based on monthly reports. All physicians were considered as a single sample, and the examination of the effectiveness of the intervention (consumption of antibiotics before and after the intervention) was performed by methods of analyzing the paired sample. Results: A total of 67 547 people were in the care of doctors, of which 31 214 were men and 36 333 women. A total of 3581 prescriptions were prescribed for uncomplicated cystitis in women over the age of 18, of which 1717 before and 1864 after education. Consumption increased by 147 prescriptions (8.5 %). The number of prescriptions for first-line antibiotics (nitrofurantoin, fosfomycin and trimethoprim-sulfamethoxazole) increased from 837 to 1015 (178 prescriptions or 21.2 %), the number of prescriptions for fluoroquinolones decreased from 332 to 310 (6.6 %), while the use of beta-lactams remained unchanged (30.3 %). After the intervention, nitrofurantoin was the most prescribed of the first-line antibiotics (178 prescriptions, or 21.2 %). The total volume of consumption after the intervention, in terms of quality indicators, was 100 % for indicator “a”, 54 % for indicator “b”, and 16.6 % for indicator “c”. Conclusion: Following the intervention, family physicians increased their prescribing of first-line antibiotics, mostly nitrofurantoin. The difference in the change in the number of prescriptions before and after the educational intervention was statistically significant. Despite the increase in the consumption of first-line antibiotics (48.7 % before and 54.4 % after the intervention), the acceptable ranges did not reach the values predicted by the ESAC quality indicators