3Ps--Pharmacist, Physician and Patient: Proposal for Joint Cooperation to Increase Adherence to Medication.

OBJECTIVE: Older people receive medications for chronic diseases and therefore adherence is an important health and economic concern. The objective of the study is to determine relationships between pharmacist, patient and patient's family physician with special emphasis on the comparison of adherent and non-adherent patients. METHODS: The study was designed as a cross-sectional survey by use of a self-administered 33-item questionnaire. The study included 635 individuals collecting or buying drugs for the treatment of chronic diseases and 84 pharmacists dispensing drugs for chronic diseases to patients. RESULTS: The study included 265 (41.7%) adherent and 370 (58.3%) non-adherent patients. Comparison of particular answers between patients and pharmacists revealed a discrepancy, with a significant difference in five of eight answers. The highest difference was recorded in answers to the question whether a pharmacist offered thorough advice to the patient on how to take the drug; an affirmative answer to this question was given by 90.5% of pharmacists and only 57.2% of patients. The analysis of respondents' claims about their relation with one doctor shows that in the first place, with the highest number of positive responses, is the claim of the respondents that their doctor always explains the results of laboratory tests and other specialized findings (n = 489, 77.0%). CONCLUSION: Enhancing communication between the physician, the pharmacist and the patient is a key in boosting the patient's ability to follow a medication regimen. Pharmacist-physician-patient relationship can improve adherence to medication. It is very important to empower pharmacists to offer and allow time for patient counselling.

Beta-lactam antibiotics during pregnancy: a cross-sectional comparative study Zagreb-Novi Sad.

BACKGROUND AND OBJECTIVES: During pregnancy, a number of changes occur in women's body, and some medications are safe and some are not. The aim of our study was to establish the possible correlation between use of beta-lactam antibiotics in pregnancy and occurrence of congenital malformations. MATERIAL AND METHODS: The study included 893 pregnant women from Zagreb and 6099 pregnant women from Novi Sad. 527 pregnant women used beta-lactams. First part of the study (one month study) was performed at four maternity hospitals in Zagreb, Croatia. Second part were collected as a part of the study analysing the teratogenicity of drugs used in pregnancy, a longitudinal study performed in Novi Sad district. RESULTS: Pregnant women most frequently used antibacterial agents in the first trimester of pregnancy. They used 15 different antibacterial medications, most often beta-lactams. In Zagreb arm, out of the total number of pregnant women that used medications during pregnancy (859), 231 (26.9%) used beta-lactam antibiotics. Malformations were detected in 8 (3.5%) cases. The prevalence of malformations in newborns whose mothers did not take beta-lactam antibiotics in pregnancy (662) was 2.7% (18 newborns with malformations). In Novi Sad arm, out of the total number of pregnant women that used medications during pregnancy (2013), 296 (14.7%) used beta-lactam antibiotics. Malformations were detected in 14 (4.7%) cases. The prevalence of malformations in newborns whose mothers did not take beta-lactam antibiotics in pregnancy (5803) was 1.7% (99 newborns with malformations). DISCUSSION: The results show possible teratogenic potential even with those antibacterials which are considered safe (amoxicillin) but as those are usually minor malformations they often pass undetected. International pharmacoepidemiological studies of drug use in pregnancy could substantially contribute to the improvement of pharmacotherapy, and could be of great help in assessing the fetal risks.

Outpatient use of systemic antibiotics in croatia.

OBJECTIVE: The aim was to estimate the outpatient utilization of antibacterials for systemic use in Zagreb, Croatia, and to define the antibiotic utilization characteristics and consequences. METHOD: Using the WHO ATC/DDD methodology, the number of defined daily doses per 1000 inhabitants per day (DDDs/TID) was calculated for each individual antibiotic and ATC system levels were calculated from data collected on the number and size of packages prescribed and dispensed from pharmacies. The Drug Utilization 90% (DU90%) method was used to evaluate the quality of drug prescribing. RESULTS: The total utilization of antibiotics was found to be extremely high, 55.0 DDDs/TID. The leading antibiotic was amoxicillin + clavulanic acid with 14.7 DDDs/TID. Penicillins accounted for the highest utilization (46.3%) expressed in DDDs/TID (25.4), followed by cephalosporins and macrolides 25 and 12.5% of utilization, respectively expressed in DDDs/TID), tetracyclines, quinolones, aminoglycosides and other agents. Nine of 27 antibiotics fell within the DU90% segment. The cost/DDD foldrugs within DU90% segment was 1.2 EUR, for drugs beyond DU90% segment was 1.4 EUR, and the average was 1.2 EUR. CONCLUSION: Irrational prescribing and preference to more expensive drugs have been reported in Zagreb. Therefore, the risk of resistance of microorganisms to beta-lactamase antibiotics, macrolides and quinolones could be expected. Prescribing patterns should be changed by introducing national guidelines on rational antibiotic prescribing, monitoring and evaluation of their implementation. Additional continuing education of physicians and pharmacists from independent sources should be organized and proper education should be provided to patients.

General practitioners' patterns of antimicrobial drugs prescription in the therapy of acute pharyngitis.

OBJECTIVE: To analyse the patterns of antibiotic prescription in the treatment of acute pharyngitis among a group of general practitioners (GPs). DESIGN: From the records of their patients, 11 specialists in general practice have collected post hoc data on their patients and on acute pharyngitis in the period from October 1, 1994 to September 30, 1995. SETTING: 11 teaching practices in four health centres in Zagreb, Croatia. SUBJECTS: GPs grouped according to whether they had pre-school children in their care. MAIN OUTCOME MEASURES: The choice and cost of the prescribed antimicrobial drug, and the impact of the characteristics of the population in care to the prescription rate and structure. RESULTS: An antimicrobial drug was prescribed in 784 (72.1%) cases of pharyngitis. Two groups of GPs have shown significant differences in the prescription rate (p < 0.001), and in the choice of antimicrobial drugs (p < 0.001). CONCLUSION: GPs with a larger number of patients in their care suffering from chronic diseases tend to prescribe antimicrobial drugs more often in the treatment of acute pharyngitis.

[Presence of Chlamydia pneumoniae antibodies in patients with ischemic heart disease and acute myocardial infarct]. / Nazocnost protutijela protiv Chlamydia pneumoniae u bolesnika s ishemicnom bolesti srca i akutnim infarktom miokarda.

Numerous seroepidemiological studies that suggest an association of C. pneumoniae infection and atherosclerosis have been published in last decade. The aim of this study was to assess a prevalence of C. pneumoniae antibodies in population of Zagreb area, and to investigate possible differences in prevalence of antibodies in patients with atherosclerosis and healthy controls. Forty-seven patients with coronary artery disease or myocardial infarction and 54 controls without any previous history of atherosclerosis were enrolled in the study. Sera were examined by microimmunofluorescence test. Persons with IgA antibody titers > or = 1:32, and/or IgG antibody titers > or = 1:64 were considered as seropositive. We found 75% seropositive in a total number of subjects, although number of seropositive and higher titers of antibodies were found more often in patients with atherosclerosis compared to control group: 74.5% of IgA seropositive patients versus 33.3% seropositive in control group, and 89.4% of IgG seropositive patients compared to 63% seropositive controls. Chronic (persistent) infections with C. pneumoniae were noted in 74.5% of patients and 33.3% controls.

Azithromycin: single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome--a randomized study.

An open comparative study was undertaken in order to assess the efficacy and safety of a single dose of azithromycin in the treatment of community-acquired atypical pneumonia. A total of 100 adult patients with atypical pneumonia syndrome were randomized to receive 1.5 g of azithromycin as a single dose, or 500 mg once daily for 3 days. The presence of Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, and Legionella pneumophila infection was diagnosed by serological tests. Control clinical examinations were performed 72 h, 10-12 days and 4 weeks after treatment initiation. Among 96 patients (48 in each group) who were evaluable for clinical efficacy M. pneumoniae infection was confirmed in 24, C. pneumoniae in nine, C. psittaci in five, C. burnetii in six, and L. pneumophila in five. Forty-seven patients (97.9%) in each group were cured. Side effects were observed in two patients in the single-dose group, and one patient in the 3-day group. In conclusion, a single 1.5 g dose of azithromycin may be an alternative to the standard 3-day azithromycin regimen in the treatment of outpatients with atypical pneumonia syndrome.

Short-term treatment of pertussis with azithromycin in infants and young children.

A prospective, open, noncomparative study was conducted to assess the efficacy and safety of azithromycin given once daily for 3 or 5 days to eradicate Bordetella pertussis from the upper respiratory tract of infants and young children. Seventeen children received azithromycin in a dose of 10 mg/kg on day 1 followed by 5 mg/kg once daily for four consecutive days, and 20 were given 10 mg/kg once daily for 3 days. Seven days after the initiation of therapy, 33 of 35 (94.3%) patients had negative cultures for Bordetella pertussis. On day 14, cultures from all 34 evaluable patients were negative. These findings suggest that a controlled, comparative study of erythromycin versus short-term administration of azithromycin is justified.

Azithromycin versus amoxicillin/clavulanate in the treatment of acute sinusitis.

PURPOSE: To compare the efficacy and tolerability of a 3-day course of azithromycin with a 10-day course of amoxicillin/clavulanic acid in the treatment of acute sinusitis in adults. PATIENTS AND METHODS: One hundred adult patients with acute sinusitis were included in an open, randomized study. Clinical diagnosis of sinusitis was confirmed by nasal endoscopy, sinus radiography, and (when possible) by culture of sinus aspirate. Patients were randomized to receive azithromycin (500 mg once daily for 3 days) or amoxicillin/clavulanate (625 mg every 8 hours for 10 days). RESULTS: A significantly faster resolution of signs and symptoms of sinusitis was observed in the azithromycin-treated patients. By the end of therapy (days 10-12), 95% of the patients in the azithromycin group and 74% in the amoxicillin/clavulanate group were cured. The remaining patients' conditions were improved. By the follow-up visit, cure was achieved in 98% of the azithromycin-treated patients, and 91% of the amoxicillin/clavulanate-treated patients. Treatment failure was observed in three patients from the amoxicillin/clavulanate group, and relapse occurred in one patient from each group. Bacteriologic eradication was achieved in 23 of 23 and 21 of 24 patients treated with azithromycin and amoxicillin/clavulanate, respectively. Both drugs were well tolerated. Two patients (4%) from the azithromycin group and five patients (10%) from the amoxicillin/clavulanate group reported mild gastrointestinal disturbances. CONCLUSIONS: In adults with acute sinusitis, a 3-day course of azithromycin was as effective and well tolerated as a 10-day course of amoxicillin/clavulanic acid. A significantly simpler dosage regimen and faster clinical effect were the advantages of azithromycin.

[Acute respiratory infection in general clinical practice]. / Akutne respiratorne infekcije u praksi lijecnika opce medicine.

Due to high frequency, certain risk of related complications, absenteeism, direct and indirect costs related to them, acute respiratory infections represent a significant health problem. The aim of the paper is to examine the frequency and characteristics of acute respiratory infections, as well as the characteristics of patients with these infections among the population in care of general practitioners/family physicians. In 11 teaching general practices in Zagreb, data were collected from medical records on patients and acute respiratory infections which the patients developed over the period from October 1, 1994 to September 30, 1995. For statistical data processing description, distribution analysis and chi-square test were used. Out of 17,888 patients in care of general practitioners involved in the study, acute respiratory infections were noticed in 4,114 (22.9%) patients ranging in age from newborn to 97 years out of which 1,473 (35.8%) were males and 2,641 (64.2%) were females. A total of 5,892 acute respiratory infections were observed, in average 1.43 infections per patient, for which the patients visited their general practitioners 11,610 times (1.97 visits per infection). Most of the patients 2,958 (71.9%) attended their general practitioners because of one acute respiratory infection. The initial diagnosis of acute upper respiratory tract infection was registered in 4,601 (78.1%) infections, and final diagnosis in 4,475 (75.9%) infections. The most frequent diagnoses included: pharyngitis and tonsillitis (including streptococcal pharyngitis and tonsillitis), nasopharyngitis, sinusitis and bronchitis. In 4,874 (82.7%) cases, general practitioners based their diagnosis on patient history and clinical examination. Antibiotics were prescribed in 3,892 (66.1%) cases. Out of 42 (1.2%) patients treated in hospital, seven patients were admitted for tuberculosis and two for bronchi cancer detected during the acute respiratory infection. Follow-up was reported in 3,644 (60.3%) cases, and sick leave in 1,236 (31%) cases. The results of this study have shown significantly higher frequency of acute respiratory infections in the morbidity in outpatient health care, and also that management of patients with these diseases is mainly the responsibility of general practitioners. In order to improve professional competence of general practitioner/family physician and quality of work in the management of patients with acute respiratory infections in general practice/family medicine, it is necessary to continuously improve the knowledge on all characteristics of the management of patient with these diseases in general practice, as well as to make a critical assessment of the existing practice.

Azithromycin in the treatment of pneumonias caused by Chlamydia spp: a retrospective study.

A retrospective study was undertaken in order to compare the efficacy and safety of azithromycin and doxycycline in the treatment of pneumonias caused by Chlamydia spp. Patients with radiologically confirmed pneumonia and positive complement fixation test for chlamydial infection who were hospitalized in the University Hospital of Infectious Diseases, Zagreb during the years 1989-1992 were reviewed. Among them, 83 were treated with azithromycin, given in a total dose of 1.5 g over 5 days (500 mg once daily at day 1 followed by 250 mg at days 2-5, 60 patients) or 3 days (500 mg once daily, 23 patients). Twenty-two patients were treated with doxycycline (100 mg b.i.d. for 10 days). Treatment groups were comparable with respect to age, sex, and severity of signs and symptoms of illness. All the patients were cured. There were no differences in duration of fever after treatment initiation between patients treated with azithromycin (whether pretreated with beta-lactam antibiotics or not) and doxycycline (p > 0.05). In addition, 3- and 5-day azithromycin courses were equally effective (p > 0.05). Both drugs were well tolerated, and only two patients treated with azithromycin reported nausea. It may be concluded that in the treatment of pneumonias caused by Chlamydia spp. azithromycin is as effective and well tolerated as doxycycline.

Arachidonic acid metabolites and sinonasal polyposis. I. Possible prognostic value.

PURPOSE: The etiology of sinonasal polyps is sometimes obscure. This study was undertaken to evaluate the potential role of arachidonic acid metabolites (AAm) on recurrent polyposis. MATERIALS AND METHODS: Tissue production of prostaglandin E2 (PGE2), 6-keto-prostaglandin F1-alpha (PGI2), thromboxane A2 (TxA2), and leukotriene C4 (LTC4) by nasal mucosa was determined by radioimmunoassay in 27 patients with sinonasal polyposis (SNp) and in 10 volunteers. RESULTS: The group of patients with SNp with the evidence of recurrences in postoperative period (Group 1) showed significantly lower PGE2 concentrations than group of patients with SNp recurrences (Group 2). The differences in concentrations of PGI2 in mentioned groups were insignificant. In comparison with other groups, a group of patients who underwent surgery several times for SNp (Group 4) had a higher mean TxA2 concentration. The LTC4 concentrations were the highest in groups of patients where SNp recurrences were observed. When the incidence of polyposis recurrences (within 18 months after surgery) was correlated with the level of LTC4 production at the time of surgery, the rate of recurrence was significantly higher in patients with increased LTC4 level than in those with normal LTC4 levels. CONCLUSIONS: LTC4 might have a prognostic value. The possible role of AAm in occurrence of SNp is apparent and suggests possible role for medical intervention.

Azithromycin for treatment of community acquired pneumonia caused by Legionella pneumophila: a retrospective study.

A clinical, retrospective and non-comparative study was undertaken to assess the clinical efficacy and tolerability of azithromycin in the treatment of community-acquired pneumonia caused by Legionella pneumophila. A total of 16 patients with a serologically confirmed diagnosis of Legionnaires' diseases were included. Azithromycin was administered orally at a total dose of 1.5 g for either 3 or 5 days. All patients were no side-effects requiring discontinuation of the treatment. Further increase of abnormal baseline liver function was recorded in 2 patients and in 1 patient mild, transient eosinophilia. Equal clinical efficacy and tolerability were observed with the 3- and 5-day dosage regimen. These results indicate that azithromycin given at a standard dose of 1.5 g is effective and well tolerated in the treatment of Legionnaires' disease.

Gastric lesion development in normal and pylorus ligated rats after cervical vagotomy.

The main purpose of this study was to further investigate the effects of vagotomy on gastric lesion development. In contrast to the usual subdiaphragmal vagotomy, a different vagotomy at the level of the trigonum caroticum was used both alone and in combination with pylorus ligation (done immediately after vagal transection). The animals were killed 15 min, 30 min, 1 h and 6 h following vagotomy. No damaging effects of sham-vagotomy, or obvious negative effects of cervical vagotomy were noted. Prominent lesions appeared after 1 h in rats subjected to cervical vagotomy and significantly increased lesions in the early period of pylorus ligation were noted. No further aggravation in pylorus ligated rats (even an apparent amelioration at 1-h interval) and no lesions in rats with cervical vagotomy in the latter period could be explained in terms of a lack of reactivity due to exhaustion preceding fatal outcome. Consistent with this, the rats subjected to cervical vagotomy died shortly after the 6-h period.

Bioavailability of dihydroergosine in healthy volunteers.

Eight healthy volunteers received an oral dose of 10 mg and an intravenous dose of 0.75 mg of dihydroergosine. Plasma concentrations were measured by HPLC method, and some pharmacokinetic parameters were calculated. The biologic half-life in the elimination phase was 8.35 +/- 1.87 h after oral administration and 8.84 +/- 3.64 h after intravenous administration. In both cases of administration a secondary rise in plasma concentration of dihydroergosine was observed, which can be attributed to hepatic recycling. The calculated bioavailability of the drug was 9.80 +/- 2.8%.

HPLC method for determination of ergot alkaloids and some derivatives in human plasma.

Ergot alkaloids and their dihydrogenated methanesulphonate (ms) salts were determined and measured in human plasma. High-performance liquid chromatography (HPLC) with fluorometric detection was used for separation of ergot alkaloids in plasma. Several ergot alkaloids and their derivatives, including lysergide (LSD), can be identified in cases of poisoning.

Determination of serum diclofenac by high-performance liquid chromatography by electromechanical detection.

Diclofenac was isolated from plasma by double extraction with organic solvent. Chromatography was performed on Lichrosorb NH2 column with acetonitrile and perchloric acid (0.0025 mol/l; 35:65, v/v) as the mobile phase (flow rate 0.9 ml/min). The electrochemical detector was operated at +900 mV and sensitivity of 5-10 nA. The sensitivity of the method was 10 micrograms/l and the coefficients of variation below 10% in the entire range of the concentration in a dose interval.