Evaluation of the adherence to a new potassium chloride storage and handling hospital protocol: an observational study.

The study aim to deal with problem of manage potassium chloride concentrate solution after the introduction of a new protocol on correct use (storage and handling) of these drugs in a high specialization-teaching hospital. The study, conducted from January 2009 to March 2009, was divided in two part: observation of the compliance of concentrated electrolytes solutions storage in 14 wards and prospective observational study on the compliance to the new protocol in the steps of prescription, preparation and administration of these drugs. 49 preparations and administrations of electrolytes solutions were observed. Medical prescriptions were made in a dedicated schedule in 40.8% (20/49), in therapy sheet in 36.7% (18/49), in 14.3% (7/49) the prescription was verbal and after written. Patient identified data was present in 85.7% of cases, solvent type in 61.2%, prescription date in 69.4%, prescription hour in 10.2%, signature of prescriptor in 77.6%, administration speed in 57.1%, administration date in 71.4%, administration hour in 32.7%. Data show a scarce knowledge of the protocol by the physicians or a difficulty in using an additional schedule respect to the existent. Lack of the prescriptor's signature was an important problem such as the absence of speed, date and hour of administration.

Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions.

AIMS: Cutaneous manifestations are frequently reported in association with drug use. The aim of this study was to analyse the skin reactions reported to the spontaneous surveillance systems of four Italian regions (Friuli Venezia Giulia, Lombardy, Sicily and the Veneto), and correlate the reports with estimated drug consumption during the same period, paying particular attention to the reactions to antimicrobial agents and nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: All of the adverse drug reactions (ADRs) reported spontaneously between January 1996 and December 1997 to the surveillance systems of four Italian regions (a total population of about 20 million people) were analysed by a panel of experts including dermatologists. On the basis of the Critical Term List of the World Health Organization (WHO), the reactions were classified as either serious or nonserious events. Drug consumption was expressed as a daily defined dose (DDD)/1000 inhabitants/day. RESULTS: A total of 2224 adverse skin reaction reports (44.7% of all of the reported ADRs) were identified, making a reporting rate of about 5.5 per 100 000 inhabitants/year. The female/male ratio was 1.58, and the reporting rate progressively increased with age. The drug categories with the highest number of cutaneous reactions were antimicrobials, followed by NSAIDs, analgesics and radiology contrast media. There was a total of 372 (16.9%) serious reaction reports, the most frequent being angioedema (171 cases), erythema multiforme (68 cases) and photosensitivity (37 cases). Co-trimoxazole, followed by the cephalosporins and fluoroquinolones, were associated with the highest consumption-related reporting rate among the antimicrobials, and aspirin and dipyrone among the NSAIDs and analgesics. CONCLUSIONS: Spontaneous reports from four Italian regions revealed that the skin was the organ most frequently affected by ADRs. The paper shows the validity of a regional decentralized system in Italy.

Characteristics of users of inhaled long-acting beta 2-agonists in a southern European population.

We characterized the population of users of inhaled long-acting beta 2-agonists in the region of Friuli-Venezia Giulia, in Italy, and assessed changes in asthma treatment and control after initiating long-acting beta 2-agonists. All residents using formoterol or salmeterol between 1992 and 1996 were identified in the regional Health Databases. Utilization rates of asthma medications and hospitalization rates for asthma were computed for the year before and after the date of the first long-acting beta 2-agonist prescription. There were 3803 users of formoterol and 20,054 users of salmeterol. Overall, 65% of users were older than 54 years of age. All formoterol users and 86% of salmeterol users received their first prescription for the respective drug during the study period (new users). Among these new users, 50% had not received any asthma drug during the 4 months preceding the start of long-acting beta 2-agonist administration. Prior 1 yr utilization rates of asthma medications and hospitalization rates for asthma were greater among new users of long-acting beta 2-agonists than among new users of salbutamol and xanthines. In addition, formoterol new users had higher prior use of asthma drugs than new users of salmeterol. One year prior hospitalization rates for asthma were also higher among formoterol than salmeterol new users with rate ratios of 1.7 (95% CI 1.3-2.2) for patients younger than 45 and 1.5 (1.2-1.9) for older patients. Use of short-acting beta 2-agonists, oral steroids and xanthines significantly declined after starting formoterol, whereas the use of inhaled steroids increased after the start of either formoterol or salmeterol. Asthma hospitalizations decreased by 32% in patients under age 45, by 43% in older patients, during the year following the start of formoterol, and by 15% and 24%, respectively, after the start of salmeterol. We conclude that long-acting beta 2-agonists were mainly prescribed to middle-aged and elderly patients and that formoterol appeared to be preferentially prescribed to patients with more severe asthma than salmeterol. Changes in asthma treatment and reduction in hospitalization rates for asthma after starting formoterol and salmeterol are compatible with an improvement in the control of asthma.

Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes.

Evidence documenting the safety of acid-suppressing drugs in pregnancy is very limited. The authors assessed the prevalence of congenital malformations in first trimester-exposed pregnancies to cimetidine, omeprazole, and ranitidine and compared it with nonexposed pregnancies between 1991 and 1996. Two different sources were used, the United Kingdom General Practice Research Database and the Italian Friuli-Venezia Giulia Health Database. The final study cohort included 1,179 pregnancies from the United Kingdom and 1,057 from Italy. Abortions or ectopic pregnancies were not included. There were 20 stillbirths and 2,261 live-born babies in both cohorts combined, with 100 offspring identified with a malformation. The overall malformation rate was 4.4%. The relative risks for nongenetic congenital malformations associated with the use of cimetidine, omeprazole, and ranitidine were 1.2 (95% confidence interval (CI): 0.6, 2.3), 0.9 (95% CI: 0.3, 2.2), and 1.4 (95% CI: 0.8, 2.4), respectively, compared with the nonexposed. No specific grouping in the distribution of malformations was observed in any of the three exposed groups. Moreover, no relation was found between drug exposure and preterm delivery or growth retardation. These findings suggest that the use of acid-suppressing drugs during the first trimester of pregnancy is not associated with a major teratogenic risk.

Positive predictive value of ICD-9th codes for upper gastrointestinal bleeding and perforation in the Sistema Informativo Sanitario Regionale database.

We identified patients whose records in the Sistema Informativo Sanitario Regionale database in the Italian region of Friuli-Venezia Giulia showed a code of upper gastrointestinal bleeding (UGIB) and perforation according to codes of the International Classification of Diseases (ICD)-9th revision. The validity of site- and lesion-specific codes (531 to 534) and nonspecific codes (5780, 5781, and 5789) was ascertained through manual review of hospital clinical records. The initial group was made of 1779 potential cases of UGIB identified with one of these codes recorded. First, the positive predictive values (PPV) were calculated in a random sample. As a result of the observed high PPV of 531 and 532 codes, additional hospital charts were solely requested for all remaining potential cases with 533, 534, and 578 ICD-9 codes. The overall PPV reached a high of 97% for 531 and 532 site-specific codes, 84% for 534 site-specific codes, and 80% for 533 lesion-specific codes, and a low of 59% for nonspecific codes. These data suggest a considerable research potential for this new computerized health care database in Southern Europe.

Use of amoxicillin and amoxicillin-clavulanic acid and hospitalization for acute liver injury.

Increase of acute liver injury in patients taking amoxicillin-clavulanic acid (co-amoxiclav) as compared to those taking amoxicillin has been suggested. To further investigate the potential hepatotoxicity of the two drugs a historical cohort study was conducted in the Italian region of Friuli-Venezia Giulia. One hundred and eighteen potential cases of acute liver injury were identified through the regional hospital information system and medical records were reviewed for all of them. Overall, 12 cases of acute liver injury were identified: 3 cases occurred in the amoxicillin exposure category, 2 among co-amoxiclav group, and 7 in the non-use category. The adjusted estimate of the rate ratio was 5.7 (CI 95% 1.5-22.1) among users of amoxicillin alone and 6.2 (CI 95% 1.3-29.7) among users of co-amoxiclav.

Hormone replacement therapy and the risk of hospitalization for venous thromboembolism: a population-based study in southern Europe.

The authors evaluated the risk of venous thromboembolism associated with hormone replacement therapy in a cohort of 265,431 women aged 45-79 years who did not have major risk factors for venous thromboembolism. Through review of hospital charts, 171 cases were confirmed (pulmonary embolism = 77; deep venous thrombosis = 94). Ten thousand controls were randomly sampled. The risk of venous thromboembolism among nonusers of hormone replacement therapy was 1.3 per 10,000 women per year. Current users of hormone replacement therapy had 2.3 times higher risk of venous thromboembolism (95 percent confidence interval 1.0-5.3) compared with nonusers. The increased risk was restricted to the first year of treatment.

Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause substantial morbidity and mortality from upper gastrointestinal tract disease. Ketorolac tromethamine has been singled out as an NSAID with a distinct gastrotoxicity profile. Calcium channel blockers, a class of antihypertensive drugs, have also been found to increase the risk of gastrointestinal tract bleeding. METHODS: We identified 1505 patients hospitalized because of upper gastrointestinal tract bleeding and/or perforation, and we randomly sampled 20,000 controls in the source population. RESULTS: The adjusted relative risk (RR) for upper gastrointestinal tract bleeding and/or perforation in NSAID users compared with nonusers was 4.4 (95% confidence interval [CI], 3.7-5.3). The risk increased with higher daily doses. Ketorolac presented the highest risk (RR, 24.7; 95% CI, 9.6-63.5) and piroxicam ranked second (RR, 9.5; 95% CI, 6.5-13.8). Ketorolac was 5 times more gastrotoxic than all other NSAIDs (RR, 5.5; 95% CI, 2.1-14.4). The excess risk with ketorolac was observed with both oral and intramuscular administration and was already present during the first week of therapy. Among the various antihypertensive drug classes, beta-blockers were associated with the lowest relative risk (RR, 1.0; 95% CI, 0.7-1.4), and current use of calcium channel blockers with the highest (RR, 1.7; 95% CI, 1.3-2.1). The association with calcium channel blockers declined when adjusting for various markers of comorbidity (RR, 1.4; 95% CI, 1.1-1.8). Past use of calcium channel blockers was also associated with an increased risk (RR, 1.5; 95% CI, 1.3-1.8). CONCLUSIONS: The excess risk of major upper gastrointestinal tract complications associated with outpatient use of ketorolac suggests an unfavorable risk-benefit assessment compared with other NSAIDs. More data are required to reduce the uncertainty about the apparent small increased risk of upper gastrointestinal tract bleeding in patients using calcium channel blockers.

Ocular disorders in users of H2 antagonists and of omeprazole.

We have conducted a cohort study of users of omeprazole and H(2) antagonists in Italy to investigate whether the peroral use of these drugs may be associated with an increased incidence of ocular disorders leading to loss of vision. We have used the Sistema Informativo Sanitario Regionale (SISR database) in Friuli-Venezia-Giulia to identify all subjects who received at least one prescription for cimetidine, famotidine, niperotidine, nizatidine, omeprazole, ranitidine or roxatidine between 1 January 1991 and 31 December 1994. We have identified all hospital admissions for serious vascular or inflammatory ocular disorders following any such prescription, reviewed and validated all medical records. There were 71,108 users of any of the study drugs, contributing a total of 101,827 person years of observation. Seven cases of serious eye disorders were identified, giving an annual incidence rate of 7/100,000 persons. By comparison to non-users, the incidence rate ratio for current users of all of the study drugs together was 0, with a 95% confidence interval of 0 to 2.1. By comparison to non-users, the incidence rate ratio for past users was 0.47 (95% CI: 0.06-2.4). Our data are consistent with previous studies and add weight to the general impression of the ocular safety of these drugs.

Epidemiological impact of prolonged systematic use of topical SDD on bacterial colonization of the tracheobronchial tree and antibiotic resistance. A three year study.

OBJECTIVE: to evaluate the effect of the prolonged systematic use of topical SDD (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on ICU ecology as expressed by changes in tracheal colonization and bacterial resistances. DESIGN: Prospective microbiological survey. SETTING: Polyvalent ICU of a 2000 beds general hospital. PATIENTS: Data concerning bacterial strains isolated from the tracheo-bronchial aspirates of all the patients admitted to a polyvalent ICU over 3 consecutive periods of 12 months ('88, '89, '90) were prospectively entered in a database and subsequently analyzed. During a 3-year period 502 patients required artificial ventilation for more than 72 h and 332 of them ('89 and '90) were treated with SDD. All samples collected within 72 h from ICU admission were excluded as well as duplicate samples from the same patients. INTERVENTION: All the patients admitted to the ICU in '89 and '90 and submitted to artificial ventilation for at least 24 h were routinely treated with topical SDD without i.v. antibiotic prophylaxis; in '88 SDD was not employed. MEASUREMENTS AND RESULTS: Criteria for collecting sputum samples and microbiological procedures remained unchanged throughout the study-time. Positive sputum were significantly less in '89 (80.8% versus 92.3% p < 0.001) and this was due to a very sharp decrease in the isolation of Gram-negative strains from 43-28% (-64% p < 0.0001) involving both: Enterobacteriaceae (-45%) and Pseudomonaceae (-77%). In 1990; however, a new increase in Gram negative was observed, although the overall amount of Gram-negative was still 49% lower in '90 if compared to '88 (p < 0.0001). A dramatic increase in Pseudomonas isolation was the only factor responsible for the "rebound" observed. An increasing percentage of Pseudomonas developed a resistance towards tobramycin and only 45% of Pseudomonas strains turned out to be sensible to tobramycin in '90 against 79% in '88. A similar trend was registered for all aminoglycosides with the exception of amikacin. Gram-positive colonizations tended to increase (+63%) (p < 0.0001) and this was mainly due to Coagulase negative Staphylococci (+290% p < 0.0001) and S. pneumoniae, whereas S. aureus isolations decreased (-18%) but not significantly. CONCLUSIONS: Our data suggest that the prolonged use of SDD is associated with dramatic changes in ICU ecology: the incidence of Gram negative colonization is significantly diminished by SDD whereas Gram positive tend to increase. Pseudomonas developed an increasing resistance towards tobramycin one of the components of the SDD formula we used.

[Effectiveness of topical selective decontamination, without systemic antibiotic prophylaxis, in prevention of pulmonary infection in intensive care]. / Efficacia della sola decontaminazione selettiva, senza profilassi antibiotica sistemica, nella prevenzione delle infezioni polmonari in terapia intensiva.

Forty-seven patients admitted in our general ICU and treated with Selective Digestive Decontamination (SDD) without any systemic antibiotic prophylaxis, were prospectively studied and compared with an historical group of 50 non treated subjects. The 2 groups were no different as to underlying disease, age, sex and prognostic index (SAPS). In the treated group was recorded an important and statistically significant reduction in the incidence of pneumonia and in the frequency of pulmonary infections caused by enterobacteriaceae and pseudomonceae. Gram-positive identification in tracheal aspirates was not significantly different in the two groups as well as the incidence of "early pneumonia". In the treated group, a sharp decrease of the total amount of fever-days through ICU stay was observed. The antibiotic consumption resulted to be an overall 28.3% lower in the group treated with, SDD with particular regard to broad-spectrum ones.