What does fixed-dose triple-combination treatment for arterial hypertension bring us?

Prevalencija arterijske hipertenzije (AH) i dalje je visoka. AH je najvažniji promjenjivi kardiovaskularni (KV) čimbenik rizika te je znatno povezana s visokim morbiditetom i mortalitetom od KV i cerebrovaskularnih (CV) bolesti. Stoga je AH velik javnozdravstveni problem. Ona je multifaktorijalna te je pristup njezinu liječenju zasnovan na kombiniranoj terapiji. Kombinirana se terapija sastoji od dvaju ili više antihipertenziva različitih skupina, različita mehanizma djelovanja, čime se brže postižu ciljne vrijednosti arterijskoga tlaka (AT). Prema smjernicama za liječenje arterijske hipertenzije koje su izdali Europsko društvo za hipertenziju (ESH) i Europsko kardiološko društvo (ESC), preporuka je da se kombinirana terapija može uvesti već u 1. stupnju bolesti, kao prva crta liječenja u slučaju visokog KV rizika i komorbiditeta, ili u slučaju neuspješnog liječenja jednim lijekom. Nažalost, uzimanjem više tableta tijekom dana smanjuje se adherentnost u liječenju. Svrha je suvremenog liječenja AH-a da se fiksnim kombinacijama antihipertenziva komplementarnog i sinergističkog djelovanja, postigne što učinkovitije liječenje AH-a. Arterijski tlak se mnogo bolje kontrolira već manjim dozama djelotvornih komponenti u kombinaciji, a time se smanjuje i incidencija nuspojava. Uzimanjem terapije jednom na dan, koja je djelotvorna i ne opterećuje bolesnika, znatno se povećava adherentnost u liječenju. Krajnji cilj ovakvoga uspješnog liječenja AH-a jest smanjenje morbiditeta i mortaliteta od KV i CV bolesti. Prema smjernicama ESH/ESC-a za liječenje hipertenzije, optimalna je kombinacija antihipertenziva triju skupina: inhibitori renin-angitenzin-aldosteronskog sustava, antagonisti kalcijevih kanala i diuretici.The prevalence of arterial hypertension (AH) is still high. Hypertension is the most important changeable cardiovascular (CV) risk factor and is significantly associated with high morbidity and mortality from cardiovascular and cerebrovascular (CBV) diseases. AH thus represents a significant healthcare problem. It is multifactorial, and the treatment approach is based on combination treatment. Combination treatment consist of two or more antihypertensives of different groups with different mechanisms, which results in faster achievement of target blood pressure (BP) values. According to the guidelines for the treatment of arterial hypertension published by the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC), it is recommended to introduce the combination therapy already in the first stage of the disease as the first line of treatment in case of high CV risk and comorbidity or in case of failed treatment with a single medication. Unfortunately, prescribing multiple tablets to be taken during the day reduces treatment adherence. The goal of modern AH treatment is to use fixed-dose combinations of antihypertensives with complementary and synergistic effects in order to achieve the most effective treatment. Management of BP is significantly improved even at smaller doses of the active components in the combination, which also reduces the incidence of side-effects. Receiving a treatment which is effective, does not burden the patient, and is taken once per day significantly increases patient adherence. The ultimate goal of such successful treatment of AH is the reduction of CV and CBV morbidity and mortality. According to the ESH/ESC guidelines for the treatment of hypertension, the optimal combination is that of three groups of antihypertensives: renin-angiotensin-aldosterone system inhibitors, calcium channel antagonists, and diuretics

Reducing Cardiovascular Mortality and Morbidity – What Else Can Be Done?

Budući da su kardiovaskularne bolesti (KVB) i dalje vodeći uzrok pobola i smrtnosti, pokušavamo unaprijediti naša nastojanja u svrhu njihova smanjenja. U svakodnevnom radu implementiramo smjernice kardiovaskularne (KV) prevencije te educiramo pacijente kako bi promijenili loše životne navike i stavili pod kontrolu KV čimbenike rizika. Međutim, sve to nije dovoljno bez potpore cjelokupnoga društva i politike države. Stoga se postavlja pitanje što trebamo još učiniti, kako djelovati. Na primjeru Nizozemske članak upućuje na to kojim su aktivnostima, akcijama i udrugama, ali i reformama uspješno smanjeni KV smrtnost i pobol.Since cardiovascular diseases (CVD) are still the leading cause of mortality and morbidity, we have been attempting to increase our efforts to reduce their incidence. In everyday practice we implement cardiovascular (CV) prevention guidelines and educate patients on changing bad lifestyle habits and controling CV risk factors. However, all of that is insufficient without the support of the whole society and public policies. So the question must be asked: what else can we do and how should we act? The example of the Netherlands is used to point out activities, initiatives, associations, and also reforms that have been successful in reducing CV mortality and morbidity

Management of measurable variable cardiovascular disease' risk factors

AIM: To summarize the main findings on variable cardiovascular risk factors and their management in everyday practice. ----- METHODS: A narrative review of the relevant literature known to the authors and incorporation of healthy changes tips in defined variable cardiovascular risk factors. ----- RESULTS: There are known variable cardiovascular risk factors to be claimed as those that should be changed in order to achieve a better prevention of cardiovascular disease development. But, most papers are informative and they didn't incorporate exact measures for each variable risk factor. Our paper shows exact measures for each variable cardiovascular risk factor that should be incorporate in everyday practice of family practitioners and cardiologists as well. ----- CONCLUSION: The best cardiovascular disease' prevention should include a multidisciplinary team of experts and the entire community with the support of governmental and non-governmental organizations that will contribute to improving the lifestyle of individuals and the entire community through their activities and legal provisions. The most important factors in cardiovascular disease management are: recognizing individual risk factors, monitoring them, and assisting in changes in life-style habits that directly affect the defined risk factors of a patient. The simplest and most practicable guidelines for CV prevention in accordance with the national, cultural and socioeconomic aspects of their country of work are needed

Usporedba dviju različitih metoda za testiranje osjetljivosti na tigeciklin u Acinetobacter baumannii

Tigecycline susceptibility testing (TST) presents a tremendous challenge for clinical microbiologists. Previous studies have shown that the Epsilometer test (E-test) and Vitek 2 automated system significantly overestimate the minimum inhibitory concentrations for tigecycline resistance compared to the broth microdilution method (BMM). This leads to very major errors or false susceptibility (i.e. the isolate is called susceptible when it is actually resistant). The aim of this study was to compare E-test against BMM for TST in carbapenem-resistant and carbapenem-susceptible Acinetobacter (A.) baumannii and to analyze changes in tigecycline susceptibility between two time periods (2009-2012 and 2013-2014), with BMM as the gold standard. Using the EUCAST criteria, the rate of resistance to tigecycline for the OXA-23 MBL-positive, OXA-23 MBL-negative and carbapenemase-negative strains for BMM was 54.5% (6/11), 29.4% (5/17) and 2.7% (1/37), respectively; the OXA-24/40 and OXA-58 producing organisms did not exhibit any resistance. With E-test, all OXA-23 MBL-positive organisms (11/11), 23.5% (4/17) of OXA-23 MBL-negative, and 4.1% of OXA-24/40 (3/74) strains displayed tigecycline resistance; there were no resistant strains among the OXA-58 and carbapenemase-negative isolates. Resistance emerged in the bacterial isolates from 2013 to 2014. Although tigecycline does not display cross-resistance, the highest rates of resistant A. baumannii isolates were observed among those producing VIM MBL, regardless of the testing method. These findings suggest that the commercial E-test does not provide reliable results for TST of A. baumannii. Further confirmation with the dilution method should be recommended, particularly in cases of serious infections.Testiranje osjetljivosti na tigeciklin (TST) je velik izazov za kliničke mikrobiologe. Prethodna istraživanja su pokazala da E-test i Vitek 2 daju veće vrijednosti minimalne inhibitorne koncentracije tigeciklina u odnosu na dilucijsku metodu, što uzrokuje vrlo veliku grešku (engl. very major error, što znači da je rezistentan izolat proglašen osjetljivim). Cilj istraživanja bio je usporediti dvije metode za testiranje osjetljivosti na tigeciklin (E-test i bujonska dilucijska metoda) u karbapenem osjetljvim i karbapenem rezistentnim izolatima Acinetobacter (A.) baumannii s različitim tipovima karbapenem-hidrolizirajućih oksacilinazama i analizirati promjenu u stopama osjetljivosti na tigeciklin u dva razdoblja istraživanja (2009.-2012. i 2013.-2014.). Dilucija u bujonu je bila referentna metoda. Testiranje osjetljivosti na tigeciklin je provedeno E-testom i bujonskom mikrodilucijskom metodom. Prema kriterijima EUCAST-a stopa rezistencije bila je 54,5% (6/11) za OXA-23 MBL-pozitivne sojeve, 29,4% (5/17) za OXA-23 MBL-negativne sojeve i 2,7% (1/37) za karbapenemaza-negativne sojeve uz bujonsku mikrodilucijsku metodu. OXA-24/40 i OXA-58 producirajući sojevi nisu iskazivali rezistenciju. E-testom su svi OXA-23 MBL pozitivni organizmi (11/11), 23,5% (4/17) OXA-23 MBL negativnih i 4,1% OXA-24/40 (3/74) pokazivali rezistenciju na tigeciklin. Svi OXA-58 pozitivni i karbapenemaza-negativni sojevi su bili osjetljivi na tigeciklin u E-testu. Rezistencija na tigeciklin se pojavila u razdoblju od 2013. do 2014. godine. Iako tigeciklin ne pokazuje križnu rezistenciju s drugim antibioticima najviše stope rezistencije su zapažene među VIM-pozitivnim izolatima bez obzira na metodu testiranja. Prema rezultatima našega istraživanja komercijalni E-test ne daje pouzdane rezultate TST u A. baumannii. Potrebna je potvrda dilucijskom metodom, osobito kod teških infekcija

EVOLUTION OF BETA-LACTAM ANTIBIOTIC RESISTANCE IN ENTEROBACTER SPP. IN CROATIA

Rezistencija na cefalosporine proširenog spektra u Enterobacter spp. nastaje zbog indukcije ili derepresije AmpC-β-laktamaze, produkcije β-laktamaza proširenog spektra (ESBL) ili karbapenemaza. Cilj istraživanja bio je utvrditi mehanizme rezistencije na β-laktamske antibiotike na kolekciji od 58 izolata prikupljenih metodom slučajnog odabira u tri klinička centra u Hrvatskoj i Kantonalnom zavodu za javno zdravstvo Zenica u Bosni i Hercegovini u razdoblju od 2008. do 2011. godine, kao i utvrditi evoluciju rezistencije na tu skupinu antibiotika tijekom perioda istraživanja. Pretpostavka je istraživanja da će izolati Enterobacter spp. rezistentni na ceftazidim pokazivati različite mehanizme rezistencije od inducibilne i dereprimirane AmpC-β-laktamaze do β-laktamaza proširenog spektra, a u kasnijim godinama i karbapenemaza. Očekivana je i razlika u fenotipu i mehanizmima rezistencije između različitih centara. Osjetljivost na antibiotike testirana je metodom dilucije u bujonu, a geni rezistencije testirani su PCR-om. Plazmidi su karakterizirani tipizacijom replikona PCR-om. Istraživanje je pokazalo dominaciju β-laktamaza proširenog spektra iz porodice CTX-M u kombinaciji s derepresijom AmpC-β-laktamaze kao dominantan mehanizam rezistencije na cefalosporine proširenog spektra. Plazmidi koji su kodirali ESBL pripadali su različitim inkompatibilnim grupama. U izolatima iz KBC-a Zagreb zapažena je u posljednjoj godini istraživanja (2010.) pojava prvih metalo-β-laktamaza iz VIM-serije, što pokazuje evoluciju rezistencije na cefalosporine proširenog spektra od dereprimiranih AmpC-β-laktamaza i ESBL-a na početku istraživanja do karbapenemaza na njegovu kraju.Enterobacter spp. develops resistance to expanded-spectrum cephalosporins by induction or derepression of chromosomal AmpC β-lactamase, or production of extended-spectrum β-lactamases (ESBLs) or carbapenemases. The aim of the study was to analyze the mechanisms of resistance to expanded-spectrum cephalosporins and the evolution of resistance mechanism during the study period (2008–2011) on a collection of 58 randomly collected Enterobacter spp. strains from three hospital centers in Croatia and Bosnia and Herzegovina during 2008-2010. The antibiotic susceptibility was determined by broth microdilution method according to CLSI. Resistance genes were determined by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). The hypothesis of the study was that there will be multiple mechanisms of ceftazidime resistance involved, from inducible and derepressed AmpC β-lactamases to extended-spectrum β-lactamases and carbapenemases at the end of the study. The isolates from different centers were expected to express different phenotypes and mechanisms of resistance. The study showed the predominance of derepressed AmpC β-lactamases combined with ESBLs belonging to CTX-M family as a mechanism of resistance to expanded-spectrum cephalosporins. The emergency of MBLs was reported in the last year of the study in University Hospital Center Zagreb. The plasmids encoding ESBLs belonged to different incompatibility groups. This points out to the evolution of β-lactam resistance in Enterobacter spp. from derepressed AmpC β-lactamases and ESBL to carbapenemases

Management of measurable changeable risk factors for the development of cardiovascular diseases

Kardiovaskularne bolesti (KVB) su glavni uzrok morbiditeta i mortaliteta. One su u glavnom uzrokovane aterosklerozom. KVB značajno povećavaju troškove zdravstvene zaštite. KVB uzrokuju više od polovice smrti u Europi. Gotovo 80% prijevremenih KV smrti se može prevenirati. Progresija i težina aterosklerotskog procesa ovisi o prisustvu i duljini trajanja niza rizičnih čimbenika. Nepromjenjivi KV rizični čimbenici uključuju obiteljsku anamnezu, obiteljsku dislipidemiju, dob i spol. Promjenjivi rizični čimbenici, koji su najodgovorniji za rastući KV morbiditet i mortalitet, uključuju: dislipidemiju, debljinu, pušenje, sjedilački način života-smanjenu tjelesnu aktivnost, arterijsku hipertenziju i šećernu bolest. Modifikacija rizičnih čimbenika je pokazala redukciju morbiditeta i mortaliteta. U svakodnevnom radu implementiramo smjernice KV prevencije u cilju promijena loših životnih navika i stavljanja pod kontrolu KV rizičnih čimbenika. Stoga je važno što bolje upravljanje mjerljivim promjenjivim rizičnim čimbenicima za razvoj KVB. Svi zdravstveni djelatnici trebaju sudjelovati u KV prevenciji. Kardiolozi trebaju biti konzultanti, voditi dijagnostičku obradu, evaluirati bolesnika i usmjeravati terapiju i daljnje praćenje u sekundarnoj prevenciji. Multidisciplinarno djelovanje zdravstvenih djelatnika, ali i uključivanja cjelokupne zajednice, dovest će do smanjenja KV morbiditeta i mortaliteta u društvu.Cardiovascular diseases (CVD) are the main cause of morbidity and mortality. They are mostly caused by atherosclerosis. CVD contribute in large part of the escalating costs of health care. CVD cause more than half of all deaths across the European region. Almost 80% of premature CV deaths are preventable. The progression and severity of the atherosclerotic process is related to the presence and duration of a series of risk factors. Unchangeable CV risk factors are: family history, familial dyslipidemia, age and gender. Changeable risk factors, which seem to be more responsible for increasing rates of CVD morbidity and mortality, are: dyslipidemia, obesity, smoking, sedentariness-physical inactivity, arterial hypertension and diabetes. Risk factors modification has been shown to reduce morbidity and mortality. In every day practice CV prevention guidelines are being implemented to change bad lifestyle habits and to control CV risk factors. Therefore it is important to better manage the measurable changeable CVD risk factors . All health care workers should participate in CV prevention. Cardiologist should consult and lead diagnostic processing, evaluate patients and guidance the therapy and secondary prevention. Multidisciplinary action of health care workers and involving all community will result in reduction of CV morbidity and mortality

Management of measurable changeable risk factors for the development of cardiovascular diseases

Kardiovaskularne bolesti (KVB) su glavni uzrok morbiditeta i mortaliteta. One su u glavnom uzrokovane aterosklerozom. KVB značajno povećavaju troškove zdravstvene zaštite. KVB uzrokuju više od polovice smrti u Europi. Gotovo 80% prijevremenih KV smrti se može prevenirati. Progresija i težina aterosklerotskog procesa ovisi o prisustvu i duljini trajanja niza rizičnih čimbenika. Nepromjenjivi KV rizični čimbenici uključuju obiteljsku anamnezu, obiteljsku dislipidemiju, dob i spol. Promjenjivi rizični čimbenici, koji su najodgovorniji za rastući KV morbiditet i mortalitet, uključuju: dislipidemiju, debljinu, pušenje, sjedilački način života-smanjenu tjelesnu aktivnost, arterijsku hipertenziju i šećernu bolest. Modifikacija rizičnih čimbenika je pokazala redukciju morbiditeta i mortaliteta. U svakodnevnom radu implementiramo smjernice KV prevencije u cilju promijena loših životnih navika i stavljanja pod kontrolu KV rizičnih čimbenika. Stoga je važno što bolje upravljanje mjerljivim promjenjivim rizičnim čimbenicima za razvoj KVB. Svi zdravstveni djelatnici trebaju sudjelovati u KV prevenciji. Kardiolozi trebaju biti konzultanti, voditi dijagnostičku obradu, evaluirati bolesnika i usmjeravati terapiju i daljnje praćenje u sekundarnoj prevenciji. Multidisciplinarno djelovanje zdravstvenih djelatnika, ali i uključivanja cjelokupne zajednice, dovest će do smanjenja KV morbiditeta i mortaliteta u društvu.Cardiovascular diseases (CVD) are the main cause of morbidity and mortality. They are mostly caused by atherosclerosis. CVD contribute in large part of the escalating costs of health care. CVD cause more than half of all deaths across the European region. Almost 80% of premature CV deaths are preventable. The progression and severity of the atherosclerotic process is related to the presence and duration of a series of risk factors. Unchangeable CV risk factors are: family history, familial dyslipidemia, age and gender. Changeable risk factors, which seem to be more responsible for increasing rates of CVD morbidity and mortality, are: dyslipidemia, obesity, smoking, sedentariness-physical inactivity, arterial hypertension and diabetes. Risk factors modification has been shown to reduce morbidity and mortality. In every day practice CV prevention guidelines are being implemented to change bad lifestyle habits and to control CV risk factors. Therefore it is important to better manage the measurable changeable CVD risk factors . All health care workers should participate in CV prevention. Cardiologist should consult and lead diagnostic processing, evaluate patients and guidance the therapy and secondary prevention. Multidisciplinary action of health care workers and involving all community will result in reduction of CV morbidity and mortality

Management of measurable changeable risk factors for the development of cardiovascular diseases

Kardiovaskularne bolesti (KVB) su glavni uzrok morbiditeta i mortaliteta. One su u glavnom uzrokovane aterosklerozom. KVB značajno povećavaju troškove zdravstvene zaštite. KVB uzrokuju više od polovice smrti u Europi. Gotovo 80% prijevremenih KV smrti se može prevenirati. Progresija i težina aterosklerotskog procesa ovisi o prisustvu i duljini trajanja niza rizičnih čimbenika. Nepromjenjivi KV rizični čimbenici uključuju obiteljsku anamnezu, obiteljsku dislipidemiju, dob i spol. Promjenjivi rizični čimbenici, koji su najodgovorniji za rastući KV morbiditet i mortalitet, uključuju: dislipidemiju, debljinu, pušenje, sjedilački način života-smanjenu tjelesnu aktivnost, arterijsku hipertenziju i šećernu bolest. Modifikacija rizičnih čimbenika je pokazala redukciju morbiditeta i mortaliteta. U svakodnevnom radu implementiramo smjernice KV prevencije u cilju promijena loših životnih navika i stavljanja pod kontrolu KV rizičnih čimbenika. Stoga je važno što bolje upravljanje mjerljivim promjenjivim rizičnim čimbenicima za razvoj KVB. Svi zdravstveni djelatnici trebaju sudjelovati u KV prevenciji. Kardiolozi trebaju biti konzultanti, voditi dijagnostičku obradu, evaluirati bolesnika i usmjeravati terapiju i daljnje praćenje u sekundarnoj prevenciji. Multidisciplinarno djelovanje zdravstvenih djelatnika, ali i uključivanja cjelokupne zajednice, dovest će do smanjenja KV morbiditeta i mortaliteta u društvu.Cardiovascular diseases (CVD) are the main cause of morbidity and mortality. They are mostly caused by atherosclerosis. CVD contribute in large part of the escalating costs of health care. CVD cause more than half of all deaths across the European region. Almost 80% of premature CV deaths are preventable. The progression and severity of the atherosclerotic process is related to the presence and duration of a series of risk factors. Unchangeable CV risk factors are: family history, familial dyslipidemia, age and gender. Changeable risk factors, which seem to be more responsible for increasing rates of CVD morbidity and mortality, are: dyslipidemia, obesity, smoking, sedentariness-physical inactivity, arterial hypertension and diabetes. Risk factors modification has been shown to reduce morbidity and mortality. In every day practice CV prevention guidelines are being implemented to change bad lifestyle habits and to control CV risk factors. Therefore it is important to better manage the measurable changeable CVD risk factors . All health care workers should participate in CV prevention. Cardiologist should consult and lead diagnostic processing, evaluate patients and guidance the therapy and secondary prevention. Multidisciplinary action of health care workers and involving all community will result in reduction of CV morbidity and mortality

Management of Measurable Variable Cardiovascular Disease' Risk Factors

AIM: To summarize the main findings on variable cardiovascular risk factors and their management in everyday practice. ----- METHODS: A narrative review of the relevant literature known to the authors and incorporation of healthy changes tips in defined variable cardiovascular risk factors. ----- RESULTS: There are known variable cardiovascular risk factors to be claimed as those that should be changed in order to achieve a better prevention of cardiovascular disease development. But, most papers are informative and they didn't incorporate exact measures for each variable risk factor. Our paper shows exact measures for each variable cardiovascular risk factor that should be incorporate in everyday practice of family practitioners and cardiologists as well. ----- CONCLUSION: The best cardiovascular disease' prevention should include a multidisciplinary team of experts and the entire community with the support of governmental and non-governmental organizations that will contribute to improving the lifestyle of individuals and the entire community through their activities and legal provisions. The most important factors in cardiovascular disease management are: recognizing individual risk factors, monitoring them, and assisting in changes in life-style habits that directly affect the defined risk factors of a patient. The simplest and most practicable guidelines for CV prevention in accordance with the national, cultural and socioeconomic aspects of their country of work are needed

Evolution of Beta-Lactamases in Urinary Klebsiella pneumoniae Isolates from Croatia; from Extended-Spectrum Beta-Lactamases to Carbapenemases and Colistin Resistance

K. pneumoniae isolates often harbor various antibiotic resistance determinants including extended-spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases (p-Amp-C) and carbapenemases. In this study we analyzed 65 K. pneumoniae isolates obtained from urinary tract infections in the outpatients setting, with regard to antibiotic susceptibility, β-lactamase production, virulence traits and plasmid content.Antibiotic susceptibility was determined by broth microdilution method. PCR was applied to detect genes encoding ESBLs, p-Amp-C and carbapenemases and plasmid incompatibility groups. Phenotypic methods were applied to characterize virulence determinants. Increasing resistance trend was observed for amoxicillin/clavulanate, imipenem, meropenem and ciprofloxacin. The study showed that ESBLs belonging to the CTX-M family, conferring high level of resistance to expanded-spectrum cephalosporins (ESC) were the dominant resistance trait among early isolates (2013 to 2016) whereas OXA-48 carbapenemase, belonging to class D, emerged in significant numbers after 2017. OXA-48 producing organisms coharbored ESBLs. KPC-2 was dominant among isolates from Dubrovnik in the recent years. Colistin resistance was reported in three isolates. Inc L/M was the dominant plasmid in the later period, encoding OXA-48. Hyperviscosity was linked to KPC positivity and emerged in the later period. This report describes evolution of antibiotic resistance in K. pneumoniae from ESBLs to carbapenemases and colistin resistance. The study demonstrated the ability of K. pneumoniae to acquire various resistance determinants, over time. The striking diversity of the UTI isolates could result from introduction of the isolates from the hospitals, transfer of plasmids and multidirectional evolution