Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study

OBJECTIVE: In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis. - - - - - METHOD: This observational, cross-sectional, drug utilization study included all adult patients receiving NSAIDs hospitalized in the Clinical Hospital Center Zagreb on the day of the study. Data on age, sex, comorbidities, indications for NSAID use, type/dose of NSAIDs and gastroprotectives, history of gastrointestinal events, active gastrointestinal symptoms and risk factors were evaluated. - - - - - MAIN OUTCOME MEASURE: Study outcomes were: (1) prevalence of prescription of gastroprotectives among NSAID-users at risk; (2) prevalence of prescription of gastroprotective in recommended dose; (3) association between risk factors and prescription of GPAs. - - - - - RESULTS: The rates of gastroprotectives prescription were significantly higher in NSAID-users with concomitant risk factors as compared to patients without risk factors [47/70 (67.1%) and 8/22 (36.4%), respectively; p = 0.01072]. However, gastroprotection in recommended ulcer-preventive dose was low in both groups [8/70 (11.4%) and 9/92 (9.8%), respectively]. The number of concomitant risk factors did not increase the odds of receiving anti-ulcer therapy (odds ratio 0.7279). Thirty-three percent of patients with concomitant risk factors were not prescribed gastroprotectives. Ibuprofen, NSAID with the lowest risk of inducing gastrointestinal complications, was prescribed in only two patients. - - - - - CONCLUSION: The results indicate high awareness among hospital physicians about possible NSAID-induced gastrointestinal complications, but insufficient knowledge about risk factors related to NSAID-induced gastrointestinal toxicity, recommended dose of gastroprotectives in NSAID-induced ulcer prophylaxis and gastrointestinal toxicity of different types of NSAIDs

Pain Relief in Medical Patients: Does Clinical Judgment and Prescribing Knowledge Suffice?

The aim of this study was to evaluate the quality of pain management in hospitalised patients. A cross-sectional study design that included all medical patients experiencing pain was used. Out of 167 patients hospitalized at the Department of Medicine at the University Hospital Zagreb, 41 patients were experiencing pain and 40 out of them received analgesics. Twenty-two out of 38 patients were treated for malignant pain, 16 for non-malignant pain, and 2 patients could not be classified. Adequate pain relief was reported in less than 25% of patients in both groups. Our study revealed under-prescribing of combination therapy, low utilization rates of strong opioids and prevailing »as needed« prescribing practice. In conclusion, unsatisfactory pain management in medical patients is often present if left solely to the clinical judgement and knowledge of the prescribing physician. Regular pain assessment, evidence-based guidelines, education and regular audits of implementation of these measures are a prerequisite for effective pain treatment, and should all be employed in patients experiencing pain

Distributed lags time series analysis versus linear correlation analysis (Pearson's r) in identifying the relationship between antipseudomonal antibiotic consumption and the susceptibility of Pseudomonas aeruginosa isolates in a single Intensive Care Unit of a tertiary hospital

The relationship between antibiotic consumption and selection of resistant strains has been studied mainly by employing conventional statistical methods. A time delay in effect must be anticipated and this has rarely been taken into account in previous studies. Therefore, distributed lags time series analysis and simple linear correlation were compared in their ability to evaluate this relationship. Data on monthly antibiotic consumption for ciprofloxacin, piperacillin/tazobactam, carbapenems and cefepime as well as Pseudomonas aeruginosa susceptibility were retrospectively collected for the period April 2006 to July 2007. Using distributed lags analysis, a significant temporal relationship was identified between ciprofloxacin, meropenem and cefepime consumption and the resistance rates of P. aeruginosa isolates to these antibiotics. This effect was lagged for ciprofloxacin and cefepime [1 month (R=0.827, P=0.039) and 2 months (R=0.962, P=0.001), respectively] and was simultaneous for meropenem (lag 0, R=0.876, P=0.002). Furthermore, a significant concomitant effect of meropenem consumption on the appearance of multidrug-resistant P. aeruginosa strains (resistant to three or more representatives of classes of antibiotics) was identified (lag 0, R=0.992, P<0.001). This effect was not delayed and it was therefore identified both by distributed lags analysis and the Pearson's correlation coefficient. Correlation coefficient analysis was not able to identify relationships between antibiotic consumption and bacterial resistance when the effect was delayed. These results indicate that the use of diverse statistical methods can yield significantly different results, thus leading to the introduction of possibly inappropriate infection control measures

Bullous Oral Eruptions Caused by Azithromycin

Makrolidi se smatraju najsigurnijom skupinom antibiotika i imaju vrlo nisku učestalost alergijskih reakcija (0,4 do 3 %). Opisali smo slučaj mladog pacijenta kod kojega se razvila bulozna erupcija na obraznoj sluznici i usnama nakon ingestije treće doze azitromicina. Nakon terapije kortikosteroidima lezije su se počele povlačiti, ali četvrti dan pojavila se na sluznici usne šupljine nova bulozna erupcija slabijeg intenziteta. To se može objasniti dugim vremenom poluraspada azitromicina u plazmi. Naime, taj se lijek može otkriti u lizatu neutrofila 28 dana nakon posljednje doze, što može biti povezano s većim rizikom od popratnih pojava. Prema našim spoznajama i dostupnim podacima iz literature, to je prvi opisani slučaj oralne erupcije u tijeku liječenja azitromicinom. Unatoč činjenici da azitromicin ostaje jedan od makrolida koji se najbolje toleriraju, ponekad može prouzročiti ozbiljne nuspojave.Macrolides are considered the safest group of antibiotics, with a very low prevalence of allergic reactions (0.4-3%). We present a case report of a young patient who developed bullous eruption on buccal mucosa and lips after ingestion of the third dose of azithromycin. After taking steroid therapy the lesions started to regress, but on the fourth day a new bullous eruption appeared on labial mucosa with lower intensity. This could be explained by the fact that azithromycin has a long plasma half-life and is detectable in neutrophil lysates 28 days after the last dose, which may be related to a higher risk of adverse effects. According to our knowledge and from the available literature. This is the first described case of oral eruption after azithromycin treatment. In spite of the fact that azithromycin remains one of the best tolerated macrolides, potentially severe adverse reactions may sometimes occur

Bullous Oral Eruptions Caused by Azithromycin

Makrolidi se smatraju najsigurnijom skupinom antibiotika i imaju vrlo nisku učestalost alergijskih reakcija (0,4 do 3 %). Opisali smo slučaj mladog pacijenta kod kojega se razvila bulozna erupcija na obraznoj sluznici i usnama nakon ingestije treće doze azitromicina. Nakon terapije kortikosteroidima lezije su se počele povlačiti, ali četvrti dan pojavila se na sluznici usne šupljine nova bulozna erupcija slabijeg intenziteta. To se može objasniti dugim vremenom poluraspada azitromicina u plazmi. Naime, taj se lijek može otkriti u lizatu neutrofila 28 dana nakon posljednje doze, što može biti povezano s većim rizikom od popratnih pojava. Prema našim spoznajama i dostupnim podacima iz literature, to je prvi opisani slučaj oralne erupcije u tijeku liječenja azitromicinom. Unatoč činjenici da azitromicin ostaje jedan od makrolida koji se najbolje toleriraju, ponekad može prouzročiti ozbiljne nuspojave.Macrolides are considered the safest group of antibiotics, with a very low prevalence of allergic reactions (0.4-3%). We present a case report of a young patient who developed bullous eruption on buccal mucosa and lips after ingestion of the third dose of azithromycin. After taking steroid therapy the lesions started to regress, but on the fourth day a new bullous eruption appeared on labial mucosa with lower intensity. This could be explained by the fact that azithromycin has a long plasma half-life and is detectable in neutrophil lysates 28 days after the last dose, which may be related to a higher risk of adverse effects. According to our knowledge and from the available literature. This is the first described case of oral eruption after azithromycin treatment. In spite of the fact that azithromycin remains one of the best tolerated macrolides, potentially severe adverse reactions may sometimes occur

Antibiotic Use Optimization Program in the Largest Croatian University Hospital – Benefits of Restrictions on Unlimited Antibiotic Use

The aim of this study was to obtain the relevant information on antibiotic use in a 750-bed Croatian university hospital. The study has been designed as a 2-point prevalence interventional analysis. For each patient on antibiotic therapy, diagnosis, indication for treatment, antibiotic therapy, dosage and route of administration together with the results of microbiological studies (if available) were obtained. After the first prevalence analysis in 2001, a restriction on unlimited antibiotic use was introduced. The second analysis, performed in 2002, after restrictions on antibiotic use, revealed reductions in the rates of restricted release antibiotics and overall antibiotic use with decreases from 38.6% to 36.9% and 23.4% to 23.2% respectively (p=0.87). The first survey showed that the 5 most often prescribed antibiotics in the therapy of bacterial infections were: gentamicin, other aminoglycosides, carbapenems, amoxycillin+clavulanate and vancomycin with proportions of 14.8%, 10.3%, 8.2%, 7% and 7% respectively. In the year 2002, the most prescribed antimicrobial drugs in the therapy of bacterial infections were: gentamicin, quinolones, vancomycin, carbapenems and cefuroxime with proportions of 18.6%, 11.4%, 9.7%, 9.3% and 8% respectively. A reduction in the proportions of doubtful antibiotic therapy, from 24.6% before the intervention, to 24.2% after the restrictions, accompanied by a 0.4% rise in the rates of indicated antibiotic therapy was also observed (p=0.93). Our study shows that restrictions on formerly unlimited use of antimicrobials, even when leading to an improvement in their prescribing, do not necessarily cause rapid and significant reduction in the overall use of antibiotics or explicit positive financial effects

Utjecaj kombinacije polimorfizma gena CYP2C9, VKORC1 i MDR1 na individualizaciju terapije varfarinom [Influence of combination of CYP2C9, VKORC1 and MDR1 gene polymorphisms on individualization of warfarine therapy]

Despite that warfarine has been used as an anticoagulant for many years it's dosing presents a challenging task owing to its narrow therapeutic range and large variability in dose-response relationship. Warfarine therapy usually started after assessment of clinical characteristics (age, body size, race), vitamin K intake and use of concomitant medications. Inappropriate dosing continues to contribute to significant morbidity and mortality due to thrombotic disease and bleeding complications. Genetic variations in the cytochrome P450 polypeptide 9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) have been identified as the most important enzymes in the warfarin pharmacological pathway. Observational studies have indicated CYP2C9, VKORC1 and MDR1 potential effect but randomized clinical trials resulted in contradictory findings. The aim of this study is to evaluate the influence of combination of CYP2C9, VKORC1 and MDR1 gene polymorphisms on individualization of warfarine therapy. We have not found statistically significant benefits from genotype guided dosing in deep-vein thrombosis and pulmonary embolism, but in atrial fibrillation percentage of time with INR therapeutic range was statistically significantly longer in this, than in clinically guided dosing group. Stable dose was achieved by statistically significantly larger number of patients whose dose had been determined by genotype and clinical characteristics than in clinically-only-guided dosing group

Influence of combination of CYP2C9, VKORC1 and MDR1 gene polymorphisms on individualization of warfarine therapy

Varfarin, iako lijek koji se jako dobro poznaje još uvijek zahtijeva vrlo pažljivu primjenu zbog svojih posebnosti - uskog terapijskog indeksa i velike varijabilnosti odnosa doze i učinka. Uvođenje varfarina do sada se temeljilo uglavnom na kliničkim parametrima svakog bolesnika: dobi, spolu, popratnim bolestima, tjelesnoj težini, a doza i učinak značajno ovise i o istodobnoj primjeni lijekova. Ipak u velikog dijela bolesnika stabilizacija parametara koagulacije i stabilizacija doze se ne postiže brzo. Opasnost od krvarenja kao i opasnost od ponovne tromboze je i dalje velika. Polimorfizam gena uključenih u farmakodinamiku (VKORC1) i farmakokinetiku (CYP2C9) varfarina mogu velikim dijelom objasniti individualne zahtjeve za dozom. Novija istraživanja ukazuju da bi i polimorfizam MDR1 gena mogao utjecati na indvidualizaciju doze jer P-glikoprotein kao transportni protein moguće ima važnu ulogu u raspoloživosti varfarina. Cilj ovog istraživanja bio je procijeniti učinak kombinacije polimorfizama sva tri gena na dozu primijenjenog varfarina. Nije utvrđena statistička značajnost genotipiziranog vođenja doziranja u bolesnika s dubinskovenskom trombozom i plućnom embolijom no ona je potvrđena u bolesnika s atrijskom fibrilacijom. Stabilna doza postignuta je u velikog broja bolesnika s genotipizacijom u odnosu na one s kliničkim vođenjem terapije.Despite that warfarine has been used as an anticoagulant for many years it's dosing presents a challenging task owing to its narrow therapeutic range and large variability in dose-response relationship. Warfarine therapy usually started after assessment of clinical characteristics (age, body size, race), vitamin K intake and use of concomitant medications. Inappropriate dosing continues to contribute to significant morbidity and mortality due to thrombotic disease and bleeding complications. Genetic variations in the cytochrome P450 polypeptide 9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) have been identified as the most important enzymes in the warfarin pharmacological pathway. Observational studies have indicated CYP2C9, VKORC1 and MDR1 potential effect but randomized clinical trials resulted in contradictory findings. The aim of this study is to evaluate the influence of combination of CYP2C9, VKORC1 and MDR1 gene polymorphisms on individualization of warfarine therapy. We have not found statistically significant benefits from genotype guided dosing in deep-vein thrombosis and pulmonary embolism, but in atrial fibrillation percentage of time with INR therapeutic range was statistically significantly longer in this, than in clinically guided dosing group. Stable dose was achieved by statistically significantly larger number of patients whose dose had been determined by genotype and clinical characteristics than in clinically-only-guided dosing group

Influence of combination of CYP2C9, VKORC1 and MDR1 gene polymorphisms on individualization of warfarine therapy

Varfarin, iako lijek koji se jako dobro poznaje još uvijek zahtijeva vrlo pažljivu primjenu zbog svojih posebnosti - uskog terapijskog indeksa i velike varijabilnosti odnosa doze i učinka. Uvođenje varfarina do sada se temeljilo uglavnom na kliničkim parametrima svakog bolesnika: dobi, spolu, popratnim bolestima, tjelesnoj težini, a doza i učinak značajno ovise i o istodobnoj primjeni lijekova. Ipak u velikog dijela bolesnika stabilizacija parametara koagulacije i stabilizacija doze se ne postiže brzo. Opasnost od krvarenja kao i opasnost od ponovne tromboze je i dalje velika. Polimorfizam gena uključenih u farmakodinamiku (VKORC1) i farmakokinetiku (CYP2C9) varfarina mogu velikim dijelom objasniti individualne zahtjeve za dozom. Novija istraživanja ukazuju da bi i polimorfizam MDR1 gena mogao utjecati na indvidualizaciju doze jer P-glikoprotein kao transportni protein moguće ima važnu ulogu u raspoloživosti varfarina. Cilj ovog istraživanja bio je procijeniti učinak kombinacije polimorfizama sva tri gena na dozu primijenjenog varfarina. Nije utvrđena statistička značajnost genotipiziranog vođenja doziranja u bolesnika s dubinskovenskom trombozom i plućnom embolijom no ona je potvrđena u bolesnika s atrijskom fibrilacijom. Stabilna doza postignuta je u velikog broja bolesnika s genotipizacijom u odnosu na one s kliničkim vođenjem terapije.Despite that warfarine has been used as an anticoagulant for many years it's dosing presents a challenging task owing to its narrow therapeutic range and large variability in dose-response relationship. Warfarine therapy usually started after assessment of clinical characteristics (age, body size, race), vitamin K intake and use of concomitant medications. Inappropriate dosing continues to contribute to significant morbidity and mortality due to thrombotic disease and bleeding complications. Genetic variations in the cytochrome P450 polypeptide 9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) have been identified as the most important enzymes in the warfarin pharmacological pathway. Observational studies have indicated CYP2C9, VKORC1 and MDR1 potential effect but randomized clinical trials resulted in contradictory findings. The aim of this study is to evaluate the influence of combination of CYP2C9, VKORC1 and MDR1 gene polymorphisms on individualization of warfarine therapy. We have not found statistically significant benefits from genotype guided dosing in deep-vein thrombosis and pulmonary embolism, but in atrial fibrillation percentage of time with INR therapeutic range was statistically significantly longer in this, than in clinically guided dosing group. Stable dose was achieved by statistically significantly larger number of patients whose dose had been determined by genotype and clinical characteristics than in clinically-only-guided dosing group