Uvođenje nacionalnog elektroničkog sustava bilježenja zdravstvenih podataka u Srbiji: težak put s dobrim završetkom

Objectives: Many countries around the world have recognized the need for using an electronic health record (EHR) system. However, there is limited literature that could serve as a guide during a lengthy and challenging process of planning, development, and implementation of the e-Health system. Since the EHR system was recently introduced in Serbia, the purpose of this communication is to describe our experience and lessons learned along the way. Methods: The key personnel involved in the implementation of the EHR system in Serbia that began in 2015 conducted in 2019 a retrospective narrative review of the process and early outcomes. Results: An incremental approach in the planning, development, and implementation of the nationwide EHR system was taken. The process was split into phases with the gradual introduction of different regions of the country. The gradual shift from the existing to a new workflow for the prospective users was also implemented. The significant milestones were the achievement of quick legislative changes, the hiring of a professional team of experts in the field, the provision of timely and appropriate information and training to prospective users, the close collaboration between the implementation team and the Ministry of Health and mutual understanding of the aims and expectations, and the flexibility in accepting the evolving nature of the process, goals, and the system model. Conclusions: A successful implementation of the nationwide EHR system is feasible providing careful planning, the assembly of a multi-disciplinary team, the use of a stepwise approach, the early and continued involvement of the intended users, and the willingness to make adjustments along the way. The end-result sets the stage for the reform of the health care system itself.Ciljevi: Mnoge su zemlje diljem svijete prihvatile potrebu za uvođenjem elektroničkog sustava bilježenja zdravstvenih podataka. Cilj je ovog rada opisati nužne uvjete za početak razvitka i uvođenja sustava za e-Zdravlje u Srbiji te opis projekta koji je uveden u našoj zemlji. Metode: Opisali smo nužne uvjete za početak razvitka i uvođenja sustava e-Zdravlja i načina na koji je projekt uveden u našoj zemlji. Rezultati: Uvedena je metoda za postupni razvitak i uvođenje nacionalnog sustava elektroničkog bilježenja zdravstvenih podataka u Srbiji. Uvođenje je organizirano u fazama, postupnim uvođenjem regija pomoću funkcionalnih modula. Postepene promjene su također uvedene u rad medicinskih liječnika kao korisnika, od postojećih metoda prema planiranima. Najvažnije faze razvoja i uvođenja bile su: brze legislative promjene, pravovremeno i primjereno pružanje informacija korisnicima sustava, trening za primjereno korištenje sustava za sve korisnike, kolaboracija timova za implementaciju sustava i timova Ministarstva zdravstva, jasno razumijevanje ciljeva i očekivanja i od strane Ministarstva zdravstva i uvoditelja sustava, fleksibilnost u prihvaćanju promjena u ciljevima i primjerenim podešavanjem modela sustave te zapošljavanje primjerenog profesionalnog tima stručnjaka u tom polju. Zaključci: Elektronički sustav bilježenja zdravstvenih podataka smatrao se vrlo važnim alatom za uvođenje mnogih reformnih mjera u samom zdravstvenom sustavu

Simultaneous determination of amoxicillin and clavulanic acid in the human plasma by high performance liquid chromatography: Mass spectrometry (UPLC/MS)

Background/Aim. Quantitative analysis of amoxicillin and clavulanic acid in biological matrices requires sensitive and specific methods which allow determination of therapeutic concentration in μg/mL range. Analytical methods for determination of their concentrations in body fluids described in literature include high performance liquid chromatography coupled to UV detector (HPLC-UV) and liquid chromatography-mass spectrometry (LC-MS). The aim of this study was to develop sensitive and specific ultra performance liquid chromatography/ mass spectrometry (UPLC/MS) method which could be used for the spectral identification and quantification of the low concentrations of amoxicillin and clavulanic acid in the human plasma. Method. A sensitive and specific UPLC/MS method for amoxicillin and clavulanic acid determination was developed in this study. The samples were taken from the adult healthy volunteers receiving per os one tablet of amoxicillin (875 mg) in combination with clavulanic acid (125 mg). Results. Plasma samples were pretreated by direct deproteinization with perchloric acid. Quantification limit of 0.01 μg/ml for both amoxicillin and clavulanic acid was achieved. The method was reproducible day by day (RSD < 7 %). Analytical recoveries for amoxicillin ranged from 98.82% to 100.9% (for concentrations of 1, 5 and 20 μg/mL), and recoveries for clavulanic acid were 99,89% to 100.1% (for concentrations of 1, 2 and 5 μg/mL). This assay was successfully applied to a pilot pharmacokinetic study in healthy volunteers after a single-oral administration of amoxicillin/ clavulanic combination. The determined plasma concentrations of both amoxicillin and clavulanic acid were in the range of the expected values upon the literature data for HPLC-UV and LC-MS methods. Conclusion. The described method provided a few advantages comparing with LC/MS-MS method. The method is faster using running time of 5 minute, has lower limit of quantification (LOQ ) and it could be used in pharmacokinetic studies of both amoxicillin and clavulanic acid

Antibiotic consumption and healthcare-associated infections in a tertiary hospital in Belgrade, Serbia from 2011 to 2016

Introduction: Healthcare-associated infections (HAIs) and irrational use of antibiotics in healthcare settings are major global public health concerns. Surveillance of HAIs in intensive care units (ICU), surgical-site infections (SSIs), and Clostridium difficile infections (CDIs), together with implementation of antibiotic stewardship, are cornerstones of hospital infection prevention programs. The aim of this study was to evaluate antibiotic consumption, especially of broad spectrum antibiotics, in relation to HAI incidence density (ID). Methodology: The study was conducted from 2011 to 2016 in a tertiary hospital, the Military Medical Academy (MMA), in Belgrade, Serbia. Through regular hospital surveillance we identified all patients with a new HAI. Data on consumption of antibacterials for systemic use were expressed as defined daily dose per 100 bed days (DDD/100 BD). Results: The highest incidence density (ID) of HAI was observed among patients in surgical ICUs (47.2 per 1000 patient-days), while the highest incidence rate among SSI was 3.7%. Moreover, the highest ID of CDI in medical patients was 6.2 per 10,000 patient-days, while in surgical patients it was 4.3 per 10,000 patient-days. The most frequently used antibiotics were cephalosporins, aminoglycosides and carbapenems (16.0 +/- 2.3, 4.8 +/- 0.7, 4.3 f 0.7 DDD/100 BD, respectively). There was no significant correlation between consumption of any groups of antibiotics and ID of CDI in medical and surgical patients. Conclusion: The multidisciplinary healthcare team would have crucial importance in the implementation of the antibiotic stewardship program in order to decrease unnecessary exposures of patients treated in healthcare settings

Histohemijsko ispitivanje kardiotoksičnih efekta kod pacova tretiranih T-2 toksinom - semikvantitativna analiza

In this study female Wistar rats were treated with T-2 toxin (1 LD50 0.23 mg/kg sc) and sacrificed on days 1, 3, 5, 7, 14, 21, 28 and 60 after the treatment. Control groups of rats were treated by saline (1 ml/kg 0.9% NaCl). At each time-schedule, control groups of animals were sacrificed, too. Pathohistological alterations of the heart were evaluated in whole visual fields stained by haematoxylin and eosin (HE), periodic acid- -Schiff's (PAS), Masson-Trichrom's (MT) and Giemsa (GIM) methods. The changes observed were scored by using semiquantitative grading scale. The heart alterations detected in T-2 toxin-treated animals ranged from focal parenchymal or hyaline degeneration (HE = 2.5 - 4.0; p lt 0.05 vs. control) to diffuse necrosis of muscle cells (HE = 5.0; p lt 0.05 vs. control and 1st day after T-2 treatment). The myofibrils were slightly PAS-positive during the first week of the study (PAS = 2.0 - 3.2; p lt 0.05 vs. control and 1st day after T-2 treatment), while a diffuse distribution of glycogen granules in endo- and perimisium were observed from day 21 to 60 in the whole heart' tissue (PAS = 4.0; p lt 0.05 vs. control and 1st day after T-2 treatment). Massive hemorrhagic foci associated with diffuse accumulation and degranulation of MCs were the most intensive from day 28 to 60 of the study (MT = 5.0; p lt 0.05 vs. control and 1st day after T-2 treatment). During the whole study period, irregular distribution of glycogen granules, intensity and total number of haemorrhages were in correlation with the degree of heart structural lesions, which showed the highest coefficient of correlation (r = 0.8750; p lt 0.001). Our results indicate that basic histohemical methods can be a useful tool for evaluation of T-2 toxin-induced cardiac damage, which is probably a result of complex inflammatory mechanisms, eventually leading to vascular lesions and myocardial necrosis, as well as for some potential cardioprotectors in the future.U ovom radu su ispitani toksični efekti na srcu Wistar pacova akutno trovanih T-2 toksinom. Životinje, jednokratno tretirane T-2 toksinom u dozi od 0,23 mg/kg sc (1 LD50), žrtvovane su 1, 3, 5, 7, 14, 21, 28. i 60. dana posle aplikacije otrova. Kontrolne grupe životinja tretirane su fiziološkim rastvorom (1 ml/kg 0,9% NaCl) i žrtvovane u istim vremenskim intervalima. Procena patohistoloških promena izvršena je na uzorcima tkiva srca, bojenih standardnim histohemijskih metodama: hematoksilin i eozin (HE), Gimza (GIM), perjodna kiselina Schiff-ov reagens (PAS) i Masson trichrom (MT), primenom semikvantitativne analize. U srcu pacova tretiranih T-2 toksinom uočene su promene od fokalne parenhimatozne i hijaline degeneracije miofibrila (HE = 2,5-4,0; r lt 0,05 u poređenju sa kontrolom) do fokalne ili difuzne nekroze mišićnih ćelija (HE = 5,0; r lt 0,05 u poređenju sa kontrolom i 1. danom posle aplikacije T-2 toksina). Tokom prve nedelje ispitivanja miofibrile su bile blago PAS-pozitivne (PAS = 2,0-3,2; r lt 0,05 u poređenju sa kontrolom i 1. danom posle aplikacije T-2 toksina), dok je difuzna distribucija granula glikogena u endo- i perimizijumu zapažena od 21. do 60. dana (PAS = 4,0; p lt 0,05 u poređenju sa kontrolom i 1. danom posle aplikacije T-2 toksina). Masivna hemoragična polja, okružena mnogobrojnim inflamatornim ćelijama, naročito su izražena u periodu od 28. do 60. dana ispitivanja (MT = 5,0; p lt 0,05 u poređenju sa kontrolom i 1. danom posle aplikacije T-2 toksina). Tokom celog perioda ispitivanja, nepravilna distribucija granula glikogena, intenzitet krvarenja i ukupan broj mastocita su bili u korelaciji sa stepenom oštećenja tkiva srca (r = 0,8750; p lt 0,001). Dobijeni rezultati su potvrdili ranije iznetu tezu da su kardiotoksični efekti T-2 toksina verovatno rezultat kompleksnih inflamatornih mehanizama

Metamizole: Current status of the safety and efficacy

Metamizole is a nonsteroidal anti-inflammatory drug, with analgesic, antipyretic, spasmolytic, and weak anti-inflammatory properties. The analgesic effect of metamizole seems to be based on the inhibition of cyclooxygenase enzyme activity and stimulation of cannabinoid receptors. Its use is still controversial, mainly due to agranulocytosis, metamizole-induced serious adverse reaction. While in many countries it is withdrawn from the market, in some countries metamizole is available as a medication prescribed for strictly defined indications, while in the others like Mexico, Brazil and China it can be obtained as an Over-The-Counter drug. The most common adverse effects of metamizole are the skin and subcutaneous tissue disorders. Metamizole appears to be of similar efficacy to analgesics which are frequently used in the treatment of moderate to severe postoperative pain

Healthcare associated Clostridioides difficile infection in adult surgical and medical patients hospitalized in tertiary hospital in Belgrade, Serbia: a seven years prospective cohort study

Introduction: Clostridioides difficile (C. difficile) infection (CDI) is one of the most common healthcare-associated (HA) infections in contemporary medicine. The risk factors (RFs) for HA CDI in medical and surgical patients are poorly investigated in countries with a limited resource healthcare system. Therefore, the aim of the study was to investigate differences in patients’ characteristics, factors related to healthcare and outcomes associated with HA CDI in surgical and medical patients in tertiary healthcare centre in Serbia. Materials and Methods: A prospective cohort study was conducted including adult patients diagnosed with initial episode of HA CDI, first recurrence of disease, readmission to hospital, while deaths within 30 days of CDI diagnosis and in-hospital mortality were also recorded. Patients hospitalized for any non-surgical illness, who developed initial HA CDI were assigned to medical group, whereas those who developed initial HA CDI after surgical procedures were in surgical group. The data on patients’ characteristics and factors related to healthcare were collected, too. Results: During 7-year period, from 553 patients undergoing in-hospital treatment and diagnosed with CDI, 268 (48.5%) and 285 (51.5%) were surgical and medical patients, respectively. Age ≥ 65 years, use of proton pump inhibitors, chemotherapy and fluoroquinolones were positively associated with being in medical group, whereas admission to intensive care unit and use of second- and third-generation cephalosporins were positively associated with being in surgical group. Conclusions: Based on obtained results, including significant differences in 30-day mortality and in-hospital mortality, it can be concluded that medical patient were more endangered with HA CDI than surgical ones

Outcomes of Clostridioides difficile infection in adult cancer and non-cancer patients hospitalised in a tertiary hospital: a prospective cohort study

Background Clostridioides difficile infection (CDI) is one of the most common healthcare-associated (HA) infections. Cancer patients, particularly haemato-oncological patients, have an increased risk for CDI due to more risk factors compared with non-cancer patients. The aim of this study was to investigate differences in outcomes associated with HA CDI in patients with solid and haematological malignancies compared with patients with no underlying malignant disease in a tertiary healthcare centre in Serbia. Methods A prospective cohort study was conducted including adult patients diagnosed with an initial episode of HA CDI. Their demographic and clinical characteristics associated with risk factors for CDI were documented. Outcomes such as all-cause 30-day mortality, cure of infection, diarrhoea relaps and recurrence of disease were followed. Patients were assigned to cancer and non-cancer groups. Within the cancer group, patients were divided into the solid tumour subgroup and haematological malignancy subgroup. Results During a 7-year period, HA CDI was observed in 28 (5.1%) patients with haematological malignancy, 101 (18.3%) patients with solid tumours and 424 (76.7%) non-cancer patients. Older age (OR 1.04, 95% CI 1.02 to 1.07, p<0.001), admission to the intensive care unit (ICU) (OR 2.61, 95% CI 1.37 to 4.95, p=0.003), mechanical ventilation (OR 5.19, 95% CI 2.78 to 9.71, p<0.001) and use of antibiotics prior to CDI (OR 1.04, 95% CI 1.02 to 1.06, p=0.02) were associated with increased mortality. Compared with patients with solid tumours, patients with haematological malignancy were younger (65 vs 57 years, p=0.015), did not require ICU admission (25.0% vs 0%) or mechanical ventilation (8.9% vs 0%) and were treated longer with antibiotics prior to CDI (14 vs 24 days, p=0.002). Conclusions Patients with haematological malignancy were exposed to different risk factors for CDI associated with mortality compared with patients with solid tumours and non-cancer patients. Older age, ICU stay and mechanical ventilation, but not presence or type of cancer, predicted the all-cause 30-day mortality

Importance of pharmacogenetics for therapeutic use of clopidogrel

Cerebrovascular and cardiovascular diseases are the worldwide leading causes of mortality. Therefore, therapy of these diseases is of great importance. Antiplatelet therapy with clopidogrel alone and in combination with aspirin has a prominent place. The major problem in clopidogrel therapy is patients' poor response to standard protocols of treatment, followed by increased rate of repeated cardiovascular events. Main cause of the poor response to antiplatelet clopidogrel therapy is pharmacogenomic modification of cytochrome P450 as well as P-glycoprotein, responsible for absorption and bioavailability. Genetic testing is recommended for patients who respond poorly to standard antiplatelet therapy

Comparative pharmacokinetic characteristics of tacrolimus following application of its different pharmaceutical formulations in humans

Takrolimus is a cornerstone immunosuppressant in the prevention of solid organ rejection following transplantation. After long-term use of twice daily tacrolimus, a new era of application of extended release tacrolimus for once-daily dosing ensued. The aim of this short communication was to compare pharmacokinetic characteristics of tacrolimus following its application as twice daily drug capsules, each 12 hours, and once-daily capsules with extended release in healthy people and patients. However, only future clinical trials would show whether these two drug formulations are really comparable as far as pharmacokinetic parameters are concerned, and, what is more important, taking into account long-term safety of extended release tacrolimus, survival of grafts and patients themselves