Antibiotic use in an Italian university hospital.

The aim of this retrospective observational study was to investigate: a) expenditure for antibiotics with respect to the total pharmacy drug budget and to costs of other medical devices; b) the most frequently used antimicrobial classes and molecules; c) the clinical units that most frequently use antimicrobial therapy; d) the preferred route of administration; e) consumption patterns of antibiotics over two periods (January-September 1999 and January-September 2000). The consumption of a single antimicrobial agent was expressed as daily defined doses (DDD) per 100 bed days. In 1999 drugs accounted for 56% of the total costs but decreased to 46% in 2000. Antibiotics accounted for 15% of the pharmacy's overall acquisition costs in 1999 and dropped to 13% in 2000. In both 1999 and 2000, penicillins were used most, followed by cephalosporins and aminoglycosides. In 1999, the most frequently used antibiotic was amoxicillin (4.02 DDD per 100 bed days) followed by ceftazidime, ampicillin, ceftriaxone, and co-amoxiclav. In 2000 ceftriaxone was the most commonly used antibiotic (4.35 DDD per 100 bed days) followed by co-amoxiclav, amoxicillin, ceftazidime. The general surgery, medical therapy and infectious diseases units accounted for the majority of penicillin consumption, while cephalosporins were most widely used in general surgery, orthopedics and neurosurgery units. Parenteral administration was the most widely used route in both years.

Self-prescribed laxative use: a drug-utilization review.

This study was conducted to determine the reasons for the choice of self-prescribed laxatives and to acquire information on how they were used and tolerated. From November 1999 to February 2000, 70 pharmacies, uniformly located throughout the Campania region of southern Italy, distributed a questionnaire to purchasers of over-the-counter laxatives. The average age of the (mostly female) respondents was 45.9 years; 23.8% were elderly. Among the 7324 individuals who completed the survey, 77.6% selected an oral product; 22.4% preferred rectal administration. A physician influenced the choice of a laxative in 37.7% of the cases, a pharmacist in 20.5%; other suggestions came from relatives (14%), acquaintances (12.1%), advertisements (11.7%), and miscellaneous sources (4%). Only 59.8% of respondents used these drugs correctly, and 58.2% consulted a physician or pharmacist because of constipation. Adverse effects, mainly gastrointestinal symptoms, occurred in 6.1% of those surveyed. The long-term use or abuse of laxatives can cause serious medical consequences, as well as mask diseases, delaying diagnosis and appropriate treatment. Physicians, pharmacists, and other health-care personnel should counsel patients on the proper use of these easily available, ubiquitous drugs.

Management of hypertension by general practitioners: an Italian observational study.

Data on patients receiving antihypertensive therapy were collected from 20 general practitioners (GPs) in Campania, Italy, to determine the prescription of different antihypertensive classes and their use with other drugs for concomitant diseases, to investigate the main factors influencing antihypertensive choice, to document treatment outcome, and to assess adverse drug reactions (ADRs). Each GP completed a data card for each consultation that produced an antihypertensive prescription; 1900 cards were collected. The most frequently used antihypertensives were angiotensin-converting enzyme inhibitors (49.6%), calcium antagonists (24.8%), beta blockers (11.7%), angiotensin II-receptor blockers (5.5%), and alpha blockers (0.9%). In 82% of patients, blood pressure was reduced but did not reach normotensive levels. The choice of antihypertensive treatment was influenced by international guidelines (56%), clinical diagnosis (25%), concomitant diseases (8%), cost (4%), compliance (3%), and other factors (5%). ADRs--most often cough (35.7%), edema (22.7%), headache (13.3%), and tachycardia (7.8%)--occurred in 11.8% of patients.

Over-the-counter oral nonsteroidal anti-inflammatory drugs: a pharmacoepidemiologic study in southern Italy.

The Pharmacoepidemiologic Service of the Second University of Naples analyzed the use and tolerability of over-the-counter (OTC) oral nonsteroidal anti-inflammatory drugs (NSAIDs) purchased in Campania, a region of southern Italy. Forty private pharmacies uniformly distributed throughout the region were recruited. The study was conducted by means of a questionnaire completed by purchasers and lasted from December 1, 1999 to March 31, 2000; 2,053 questionnaires were collected. The age of respondents averaged 45.3 +/- 3.49 years (range, 17-85 years). The NSAIDs analyzed were acetylsalicylic acid, paracetamol, ibuprofen, ketoprofen, diclofenac, and piroxicam. Adverse effects, mainly gastrointestinal symptoms, were reported by 5.5% of the users and occurred primarily with diclofenac, piroxicam, ibuprofen, and ketoprofen. Because the use and availability of OTC NSAIDs are increasing, further studies of the tolerability of this important drug class are warranted.

Antibiotic drug prescription in respiratory tract infections: a pharmacoepidemiological survey among general practitioners in a region of Italy.

Data concerning patients undergoing antibiotic treatment for upper (URTI) or lower (LRTI) respiratory tract infections were collected from 23 General Practitioners (GPs) in the Campania Region of Italy from November 15, 1997 to March 15, 1998. The objectives of the study were: a) to assess the occurrence of URTIs and LRTIs; b) to document the factors that influence GPs' choice of therapy; c) to correlate antibiotic choice with duration and outcome of treatment; d) to assess the incidence of unwanted effects. 2198 questionnaires were collected. Patients were +/-43.9 of age. URTIs were diagnosed in 65.4% and 34.6% LRTIs. The mean duration of antibiotic treatment was 4.5 days in URTIs and 5.6 days in LRTIs. The choice of antibiotic treatment was influenced by clinical assessment of infections (67.1%). The most commonly used antibiotic categories in URTIs were macrolides (39.3%), penicillins (27.4%) and cephalosporins (23.8%) whereas for LRTIs mainly cephalosporins (63.8%), penicillins (9.2%) and fluoroquinolones (7.4%) were used. Adverse events were experienced by 3.9% of patients.

Anti-inflammatory and analgesic amides: new developments.

A series of substituted N-cycloalkyl benzamides, cinnamamides, and indole-3-carboxamides were synthesized and evaluated for their analgesic, antiinflammatory activities as well as for their gastrointestinal irritation liability. Indomethacin was used as reference drug in both tests. Compounds 1k, 1b, 1h, 1j, and 1g were the most active in the antiinflammatory paw edema inhibition test, with a sharply dose-dependent effect. In terms of the analgesic activity (acetic acid writhing test), the most active compound was 5a followed by 3a, but many other compounds were found to have a non-negligible potency. Even in this case, the effect was dose dependent.

Synthesis of N-[4-(propyl)cyclohexyl]-amides with anti-inflammatory and analgesic activities.

Seventeen (un)substituted N-[4-(propyl)cyclohexyl]-amides (6a-h, 7a-h and 8) were synthesized and tested as anti-inflammatory and analgesic agents. The substituents on the aromatic ring were chosen in order to study the influence of electron-withdrawing or electron-donating residues, that change the electronic density on the aromatic moiety. The pharmacological results allow drawing some preliminary considerations on structure-activity relationships.

Synthesis of N-[4-(alkyl)cyclohexyl]-substituted benzamides with anti-inflammatory and analgesic activities.

Two series of N-[4-(alkyl)cyclohexyl]-substituted benzamides, i.e. a series of N-[4-(tert-butyl)cyclohexyl]-substituted benzamides and a series of N-[4-(ethyl)cyclohexyl]-substituted benzamides, were synthesised and evaluated for their anti-inflammatory and analgesic potencies, and gastrointestinal irritation liability.

Antiinflammatory agents: new series of N-substituted amino acids with complex pyrimidine structures endowed with antiphlogistic activity.

A series of N-methyl-N-pyrimidin-2-yl glycines 2a-e, having the pyrimidine ring fused with a cyclohexane [N-methyl-N-(5,6,7,8-tetrahydroquinazolin-2-yl)glycine], cyclohexene [N-methyl-N-(5,6-dihydroquinazolin-2-yl)glycine], 1,2,3,4-tetrahydronaphthalene [N-methyl-N-(5,6-dihydrobenzo[e]quinazolin-2-yl)glycine], benzopyrane [N-methyl-N-(5-phenyl-5H-[1]benzopyrano[4,3-d]pyrimidin-2-yl)glyci ne] and benzothiopyrane [N-methyl-N-(5H-[1]benzothiopyrano[4,3-d]pyrimidin-2-yl)glycine] ring, was prepared and tested for antiinflammatory activity. With the same purpose a number of N-5H-[1]benzopyrano[4,3-d]pyrimidin-2-yl substituted amino acids 3a-e, having a different chain length and branching were also synthesized and tested. All the described products 2 and 3 showed an appreciable antiphlogistic activity, particularly 2b and 2c.

Bioequivalence assessment of two different tablet formulations of diltiazem after single and repeated doses in healthy subjects.

The study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally. The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design. The pharmacokinetic parameters AUC0-infinity (ng h/ml), Tmax(h) and Cmax (ng/ml) were calculated for the two formulations after a single dose, while AUCt1-t2 (= AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses. The bioequivalence assessment was the shortest 90% confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80-1.20). The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90% confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80-1.20 (80-120%).

A specialized apperception test for ambulatory-impaired adolescents.

A specialized apperception test for physically impaired adolescents was developed, and a pilot was conducted using ten nonimpaired and ten impaired adolescents. Ten cards depicting various scenes with physically impaired male and female models were designed to elicit themes that may be particularly relevant for this adolescent population. Two raters evaluated how well each card elicited issues identified in the literature as pertinent to physically challenged adolescents.

Antibiotic prophylaxis for surgical procedures: a survey from an Italian university hospital.

The aims of this study were: 1) to evaluate the surgical prophylaxis regimens adopted by surgeons of the University Hospital of the Faculty of Medicine and Surgery of the 2nd University of Naples during the period January-March 1996; 2) to compare uses of antibiotic prophylaxis carried out in surgical departments to standard international guidelines; 3) to assess the cost of surgical prophylaxis. Data from 1,085 surgical patients from January 1, 1996 to March 31, 1996, were collected, reporting surgical department, type of surgery, antibiotics used, dosage, and length of the prophylactic treatment. Collected data underwent computer-assisted evaluation and comparison to the international guidelines. Four-hundred and twenty-five patients with concomitant diseases, who did not meet inclusion criteria into standard guidelines, were excluded from the study. The remaining patients (N = 660) underwent clean or clean-contaminated surgical procedures. Two-hundred and twenty patients underwent clean surgical procedures, with prophylactic antibiotic treatment lasting from 1.1 +/- 0.3 to 4.6 +/- 2.8 days. Four-hundred and forty patients underwent a clean-contaminated surgical procedure, with antibiotic prophylaxis lasting from 3.6 +/- 2.4 to 5.2 +/- 3.7 days. Third generation cephalosporins were the most frequently used antibiotics both in patients undergoing clean (163 patients = 74.1%), and clean-contaminated surgical procedures (321 patients = 73%). The resulting costs were about ten-fold higher than costs of antibiotic prophylaxis carried out according to international guidelines. In conclusion, our research highlights the habit of non-compliance with standard guidelines for antibiotic prophylaxis both in terms of drug choice and treatment duration.

[Intensive hospital monitoring of adverse reactions to benzodiazepines and neuroleptic agents]. / Monitoraggio intensivo ospedaliero delle reazioni avverse da benzodiazepine e neurolettici.

BACKGROUND: The main aims of the programme were to highlight the incidence of adverse reactions to the drugs monitored and to define the risk/benefit ratio taking account of the main physiological and physiopathological variations of patients. This paper reports the results of the programme regarding to adverse effects correlated to the use of some psychiatric drugs (benzodiazepines and neuroleptics). METHODS: A total of 73 records were compiled for 64 patients treated with benzodiazepines and/or neuroleptics. RESULTS: A very high mean incidence of adverse events was documented (48%) without any severe undesirable effects. 92% of patients treated with neuroleptics reported adverse events. Haloperidol, which caused adverse effects in 80% of patients, revealed mild or moderate forms of parkinsonism (15%), spasm (15%), rigidity (10%), akathisia (5%), reversible postural hypotension (10%), temporary reduction of the visual field (10%), delayed menstrual flow (5%), xerostomia (10%), excessive sweating (10%) and sialorrhea (10%). All the patients treated with clozapine showed adverse effects including postural hypotension (29%), persistent tachycardia (14%), sialorrhea (29%), excessive sweating (14%) and akathisia (14%). Spasms (25%), rigidity (25%) and akathisia (25%) were correlated to the use of clothiapine, whereas postural hypotension was referred to clopenthixol. 44% of patients treated with benzodiazepines showed undesired effects. 20% of those taking chlordemethyldiazepam showed somnolence (33%), sedation (22%) and dysar-thria (44%). Prolonged sedation was observed in 30% of all patients treated with lorazepam. Prazepam was correlated with adverse effects in 75% of cases. No adverse event was documented with bromazepam. CONCLUSIONS: A higher incidence of adverse events was documented than literature data. Further periods of intensive monitoring will be required to obtain a greater quantity of data from the intensive monitoring of adverse events through the MIO '97 programme.

[Hospital intensive monitoring of adverse reactions of ACE inhibitors]. / Monitoraggio intensivo ospedaliero delle reazioni avverse da ACE-inibitori.

BACKGROUND AND AIMS: Angiotensin II converting enzyme (ACE) inhibitors represent one of the most important pharmacological instruments for the treatment of arterial hypertension and are currently also used for other cardiovascular indications. The actions of ACE-inhibitors mainly depends on blocking the ACE enzyme in the renin-angiotensin-aldosterone system. However, the ACE enzyme also has a kinase activity. The inhibition of this enzyme may also cause an accumulation of tissue mediators (bradykinin) responsible for a number of adverse reactions. METHODS: An intensive hospital monitoring programme of adverse reactions to drugs, known as MIO[symbol: see text]'96, was carried out by the Centre of Pharmacoepidemiology of the Faculty of Medicine and Surgery at the Second University of Naples during the period 25 March-18 April 1996. The main aims of the programme were to highlight the incidence of adverse reactions to the drugs monitored and the definition of the risk/benefit ratio taking account of the main physiological and pathophysiological variations of patients. This paper reports the results of the programme of adverse effects correlated to the use of ACE-inhibitors. A total of 175 records were compiled for 105 patients receiving antihypertensive treatment with a number of ACE-inhibitors (captopril, enalapril, lisinopril); a very high mean incidence of adverse events was documented (22%) without any severe undesirable effects. RESULTS: The following adverse events were documented (the cumulative incidence is given in brackets): dysgeusia (17%), flush (8%), headache (33%), exanthema (17%), diarrhoea (8%), vertigo (8%), xerostomia (8%). Coughing was not reported in any patient. CONCLUSIONS: Further periods of intensive monitoring will be required to obtain a greater quantity of data from the Intensive Monitoring of adverse events through the MIO[symbol: see text]'97 programme.

[Problems associated with the use and monitoring of cyclosporin. Experience at a Clinical Pharmacology Service]. / Problematiche connesse all'uso e al monitoraggio della ciclosporina. Esperienza di un Servizio di Farmacologia Clinica.

BACKGROUND: A study on cyclosporine A (CyA) monitoring in the January 1992-December 1995 period is reported. The aim of this work was to give epidemiological data on the use of CyA, to verify the progressive increase of CyA determinations and to evaluate the use in other diseases as well as to compare the different technics of CyA assay in blood samples, to stress the timing of blood samples and to underline the CyA monitoring importance. METHODS: The CyA dosage was evaluated by fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC). RESULTS: The study showed that 70% of CyA determinations come from patients undergone to renal, bone marrow and liver transplantations; the remaining 30% was associated to other diseases (psoriasis, uveitis, diabetes, rheumatoid arthritis). CONCLUSIONS: The results obtained showed a progressive and constant increase of CyA determinations. Moreover, the use of drug was increased in autoimmune diseases. It is stressed that CyA monitoring in blood samples is essential to optimize the therapeutic efficacy of drug and minimizing its toxicity.