Neonatal withdrawal syndrome following in utero exposure to antidepressants: a disproportionality analysis of VigiBase, the WHO spontaneous reporting database.

BACKGROUND: Evidence on neonatal withdrawal syndrome following antidepressant intrauterine exposure is limited, particularly for antidepressants other than selective serotonin reuptake inhibitor (SSRIs). METHODS: In our case/non-case pharmacovigilance study, based on VigiBase®, the WHO database of suspected adverse drug reactions, we estimated reporting odds ratio (ROR) and the Bayesian information component (IC) with 95% confidence/credibility intervals (CI) as measures of disproportionate reporting of antidepressant-related neonatal withdrawal syndrome. Antidepressants were first compared to all other medications, then to methadone, and finally within each class of antidepressants: SSRIs, tricyclics (TCA) and other antidepressants. Antidepressants were ranked in terms of clinical priority, based on semiquantitative score ratings. Serious v. non-serious reports were compared. RESULTS: A total of 406 reports of neonatal withdrawal syndrome in 379 neonates related to 15 antidepressants were included. Disproportionate reporting was detected for antidepressants as a group as compared to all other drugs (ROR: 6.18, 95% CI 5.45-7.01, IC: 2.07, 95% CI 1.92-2.21). Signals were found for TCAs (10.55, 95% CI 8.02-13.88), followed by other antidepressants (ROR: 5.90, 95% CI 4.74-7.36) and SSRIs (ROR: 4.68, 95% CI 4.04-5.42). Significant disproportionality emerged for all individual antidepressants except for bupropion, whereas no disproportionality for any antidepressant was detected v. methadone. Eleven antidepressants had a moderate clinical priority score and four had a weak one. Most frequent symptoms included respiratory symptoms (n = 106), irritability/agitation (n = 75), tremor (n = 52) and feeding problems (n = 40). CONCLUSIONS: Most antidepressants are associated with moderate signals of disproportionate reporting for neonatal withdrawal syndrome, which should be considered when prescribing an antidepressant during pregnancy, irrespective of class.

Pharmacovigilance of sodium-glucose co-transporter-2 inhibitors: What a clinician should know on disproportionality analysis of spontaneous reporting systems.

Sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) have consistently demonstrated a clinically significant reduction of cardiovascular mortality. However, their safety in clinical practice is still incompletely characterized, and post-marketing monitoring is required considering the expected increase in clinical use. Different analyses of international spontaneous reporting systems, known as disproportionality analyses (DAs), have highlighted the occurrence of ketoacidosis, amputations, acute renal failure and skin toxicity. In this viewpoint, we critically appraise these pharmacovigilance data on SGLT2-Is, with the aim of supporting clinicians in proper interpretation of these studies, and discussing their risk-benefit profile. To this aim, we offer a broad perspective on basic technical aspects subtending DAs of spontaneous reporting databases (describing peculiarities of the Food and Drug Administration Adverse Event Reporting System), their common and evolving uses, key pitfalls in presenting study results (in terms of "risk" or "association") and relevant strategies to account for major confounders. This will also facilitate reviewers and editors in proper evaluation of DAs, and prompt pharmacovigilance experts in converging towards a set of minimum requirements in standardization of design, performance and reporting of DAs. A consensus on quality assessment of DAs will finally establish their transferability to clinical practice. It is anticipated that DAs cannot be used per se as a standalone approach to assess a drug-related risk and cannot replace clinical judgment in the individual patient.

Ten years of vaccinovigilance in Italy: an overview of the pharmacovigilance data from 2008 to 2017.

Reporting and analysis of Adverse Events Following Immunization (AEFIs) are the cornerstones of vaccine safety surveillance prompting causality assessment and signal detection. This paper describes the impact of the Italian Pharmacovigilance System of vaccines over a 10-year period (2008-2017). The reporting rate (RR) per all distributed dose was calculated. Serious AEFIs and causality assessments for fatal cases were described. The main results from signal detection were reported. During the study period, 46,430 AEFIs were reported with an overall RR of 17.2 per 100,000 distributed doses. Italy showed the highest number of reports among European countries. Only 4.4% of the reports came from citizens. Of the total, 12.7% were classified as serious with a RR over the study period of 2.20 per 100,000 distributed doses. They were mainly related to hyperpyrexia and usually had a positive outcome. Fatal outcomes were reported in 0.3% of the cases and were primarily associated with the influenza vaccine in elderly patients. None of these outcomes had a consistent causal association with the vaccination. Febrile convulsions by the measles, mumps, rubella and varicella vaccines and intussusception by the rotavirus vaccine were among the highlighted signals. The reporting rate and the analysis of serious events from 10 years support the good risk/benefit profiles of vaccines.

Upper gastrointestinal bleeding associated with antiplatelet drugs.

BACKGROUND: The risk of major upper gastrointestinal bleeding associated with various antiplatelet drugs and the protection conferred by gastroprotective agents are not well defined. AIM: To estimate the risk of upper gastrointestinal bleeding associated with the use of antiplatelet drugs and its prevention by gastroprotective agents. METHODS: In a case-control study, we compared all cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients over 18 years of age (2813 cases), with 7193 matched controls. Odds ratios of upper gastrointestinal bleeding for individual antiplatelet drugs with adjustment for potential confounders were estimated. RESULTS: The individual risks of upper gastrointestinal bleeding were cardiovascular acetylsalicylic acid 4.0 (3.2-4.9), clopidogrel 2.3 (0.9-6.0), dipyridamole 0.9 (0.4-2.0), indobufen 3.8 (1.2-12.2), ticlopidine 3.1 (1.8-5.1) and triflusal 1.6 (0.9-2.7). Concomitant proton pump inhibitors decreased all risk estimates. For acetylsalicylic acid plus a proton pump inhibitor, the odds ratio was 1.1 (0.5-2.6). As a group, antiplatelet drugs accounted for 14.5% of all cases of upper gastrointestinal bleeding, i.e. 58 per million per year (334 per million per year among those older than 70 years). CONCLUSIONS: The risk of upper gastrointestinal bleeding is substantially decreased by the concomitant use of proton pump inhibitors. The risk of acetylsalicylic acid plus a proton pump inhibitor seems lower than that of ticlopidine or clopidogrel.

Adverse drug reactions associated with off-label use of ketorolac, with particular focus on elderly patients. An analysis of the Italian pharmacovigilance database and a population based study.

OBJECTIVE: This study aims to evaluate the frequency of off-label use of ketorolac in Italy and the related suspected adverse drug reactions (ADRs) reported. METHODS: All the suspected cases associated with ketorolac recorded in the Italian Pharmacovigilance database were retrieved. Case evaluations were carried out in order to identify the off-label use of ketorolac. Moreover, an analysis of the inappropriate use of ketorolac was conducted using the 'Arianna' database of Caserta local health unit. RESULTS: Up to December 2014, 822 reports of suspected ADRs related to ketorolac were retrieved in the database. The use of ketorolac was classified as off-label for 553 reports and on-label for 269. Among the off-label cases, 58.6% were serious compared to 39.0% of on-label cases. Gastrointestinal events were more frequently reported with off-label use. The analysis of Arianna database showed that 37,729 out of 61,910 patients, were treated off-label. CONCLUSIONS: The off-label use of ketorolac is widespread in Italy. This use increases the risk of serious ADR, especially in in case of prolonged duration of treatment and in elderly patients. The Italian Medicine Agency has decided to accurately monitor the appropriate use of the drug in Italy and, if necessary, take measures in order to minimize the risks.

Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study.

AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.

Adverse drug reactions related to the use of NSAIDs with a focus on nimesulide: results of spontaneous reporting from a Northern Italian area.

OBJECTIVE: To analyse and compare the adverse drug reactions (ADRs) associated with the use of nimesulide with those associated with diclofenac, ketoprofen, and piroxicam, reported spontaneously in a northern Italian area (Veneto and Trentino). METHODS: Data were obtained from the spontaneous reporting system database of Veneto-Trentino, the principal contributor to the Italian spontaneous surveillance system. All case reports that occurred in association with all formulations of the nonsteroidal anti-inflammatory drugs (NSAIDs) under investigation during the period from January 1988 to December 2000, were analysed in detail. Sales data from June 1996 to May 1999 and prescription data, from 1997 to 2000 from the Veneto region were utilised to select the most widely used NSAIDs to be included in the study. The prescription data were also used to look at the drug use in relation to age. RESULTS: During the study period, 10 608 reports describing 16 571 adverse reactions were entered into the surveillance system. We found 207 case reports for nimesulide, 187 for diclofenac, 174 for ketoprofen, and 137 for piroxicam. Analysis of sales and prescription data revealed that in the Veneto region nimesulide was the most widely prescribed drug followed at a long distance by diclofenac, piroxicam and ketoprofen. No age-related difference in the use of the four drugs was found. Analysis of the case reports revealed significantly different toxicity profiles for the four drugs. In particular, nimesulide was associated with fewer and less severe gastrointestinal (GI) ADRs compared with the other NSAIDs. Nimesulide was associated with about half the number of GI reactions (10.4%) than the other three NSAIDs (21.2% for diclofenac, 21.7% for ketoprofen, 18.6% for piroxicam). Two previously unreported reactions were also found for piroxicam and ketoprofen. CONCLUSIONS: Nimesulide is the most frequently used NSAID in Italy. Spontaneous reporting data suggest that nimesulide has the most favourable GI tolerability profile of the NSAIDs investigated, with few reports of severe GI reactions. A few reports of hepatic and renal impairment associated with nimesulide suggest caution in patients at risk. Age-related reporting analysis suggests a higher toxicity for diclofenac and piroxicam in the elderly compared with nimesulide and ketoprofen. This analysis of the Veneto-Trentino database on spontaneous reporting confirms that NSAIDs differ in their tolerability profile, and this fact should be taken into account in the choice of drugs in relation to patient characteristics.

Copper and zinc status in rheumatoid arthritis: studies of plasma, erythrocytes, and urine, and their relationship to disease activity markers and pharmacological treatment.

We studied the status of copper and zinc in rheumatoid arthritis (RA). The aims of the work were to ascertain whether or not RA is associated with copper and/or zinc deficiency, to establish the relationship between these trace metals and the main biohumoral and clinical indices of the disease, and to examine the effect on copper and zinc of the drugs normally used by RA patients. Metal levels were measured by atomic absorption spectroscopy in the plasma, whole blood cells and 24 hr urine of 120 RA patients; 70 patients suffering from primary osteoarthritis were used as the control group. In the plasma of RA patients copper and ceruloplasmin levels were found to be significantly increased whereas zinc levels were significantly decreased. No major variations were observed in the blood cell and 24 hr urine copper and zinc levels. Plasma copper was significantly correlated with some of the biohumoral markers of RA, but did not correlate with any of the clinical indices of the disease. Plasma zinc was significantly correlated with numerous of the biohumoral as well as clinical markers of RA. With the exception of an increased urinary excretion of copper in D-penicillamine treated RA patients, drug therapy did not influence the copper status in RA. Conversely, plasma zinc was found to be lower in RA patients taking NSAIDs and/or steroids. These results suggest the following conclusions: i) RA patients do not seem to be deficient in either copper or zinc; ii) plasma copper appears to be a poor index of RA severity; iii) plasma zinc could have some practical value in defining the overall severity of the disease.

Spontaneous reporting of drug-related hepatic reactions from two Italian regions (Lombardy and Veneto).

BACKGROUND AND AIMS: Many currently used drugs are implicated in liver disorders ranging from asymptomatic abnormal liver function tests to fatal liver failure, and drug-induced hepatic reactions are the most frequent cause of the withdrawal of drugs from the market in the United States, United Kingdom and Spain. The aim of this study was to review the drug-induced hepatic reactions notified to the spontaneous surveillance system of two Italian regions (Lombardy and the Veneto) up to 31 December 1998. PATIENTS AND METHODS: The reports of hepatic adverse drug reactions were extracted from an inter-regional database of spontaneous adverse drug reaction reports and analysed by reporter category, patient age and sex, the underlying disease, the adverse reaction and drug exposure. In the case of drugs involved in more than four reports, a search was made of the Medline, Hepatox, Micromedex and WHO databases. RESULTS: Between 1988 and 1998, there were 310 reports of hepatic lesions associated with single drugs or fixed combinations, the most frequently involved patient categories being females and the elderly. Sixty percent of the reactions were classified as serious, with three fatal cases. Thirteen drugs were associated with more than four reports and accounted for 35% of all of the hepatic reactions. Six drugs not known as hepatotoxic agents were associated with hepatic reactions. CONCLUSIONS: In this study, spontaneous reports have suggested previously unknown hepatotoxicty of six drugs, and have improved drug safety profiles as shown in an Italian inter-regional health service.

[Recurrences of epithelial tumors of the head and neck: review of the literature and a critical analysis of the problem]. / Le recidive dei tumori epiteliali della testa e del collo: revisione della letteratura ed analisi critica del problema.

Recurrence is a tumor renewal in a previously treated field or surgical wound after a disease-free period. The present work investigates loco-regional recurrences. In the first part of the work the most frequent recurrence sites, types and their characteristics (i.e. infiltrating, exophytic, ulcerating) are studied along with the problems in clinical and pathological diagnosis, new diagnostic imaging (CT and MR) and the UICC classification system. The second part of the work is dedicated to examining classical treatments (surgery, radiotherapy, chemotherapy and radiochemotherapy associations) as well new therapies (i.e. cryosurgery, hyperthermia, immunotherapy, photodynamic therapy). A review of the literature is made for indications, results and complications. An extensive study of the cases of the Head and Neck Group of the University of Turin during the 1983-1990 period is also reported. This experience is based on 312 cases: 68 (oropharynx and larynx) treated by surgery, 51 (neck nodes and stomal recurrences) treated by radiotherapy and hyperthermia, 35 (neck nodes) by hyperthermia alone, 168 (all sites) by chemotherapy and 20 by immunotherapy. In the third part of this work supportive therapies and practical problems are reported. In conclusion a therapeutic approach is proposed in relation to the site of the recurrence and previous treatments.

[Zinc sulfate in the treatment of psoriatic arthritis]. / Il solfato di zinco nella terapia dell'artrite psoriasica.

We evaluated oral zinc sulphate as a disease-modifying antirheumatic drug (DMARD) in psoriatic arthritis in a preliminary open uncontrolled trial. Twenty patients with psoriatic arthritis were given oral zinc sulphate three times a day at total dose of 600 mg/die, i.e. 120 mg/die of elemental zinc, for 6 months. The 18 patients who completed the trial showed a significant decrease in the number of swollen (p less than 0.01) and tender (p less than 0.05) joints, Ritchie articular index (p less than 0.01), need for nosteroidal anti-inflammatory drugs (p less than 0.001), erythrocyte sedimentation rate (p less than 0.01), and plasma copper level (p less than 0.001). We suggest that zinc sulphate may be an effective and well-tolerated DMARD in psoriatic arthritis. To more strictly verify these preliminary data, a double-blind placebo controlled study is in progress.

Identification of severe potential drug-drug interactions using an Italian general-practitioner database.

OBJECTIVE: To analyze prescriptions in a general-practitioner database over 1 year to determine the frequency, the characteristics, and the monitoring of the severe potential drug-drug interactions (DDIs). METHODS: We retrospectively analyzed the clinical records from 16 general practitioners in the Veneto region, an area in northern Italy. The study covered the period from January 1 to December 31, 2004. We selected all severe and well-documented interactions according to the book Drug Interaction Facts by David S. Tatro (Facts and Comparisons, St. Louis, MO, 2006). We grouped severe potential DDIs according to their specific potential risk, and for the most frequently interacting drug pairs, we investigated whether some specific tests had been prescribed by physicians for safety monitoring. RESULTS: During the study period, 16,037 patients (55% female) with at least one drug prescription were recorded, and a total of 185,704 prescriptions relating to 1,020 different drugs were analyzed. Ramipril was the most frequently prescribed drug followed by acetylsalicylic acid and atorvastatin. The final number of different types of severe potential DDIs was 119, which occurred 1,037 times in 758 patients (4.7% of the total number of patients). More than 80% of drugs involved in severe potential DDIs were cardiovascular drugs. Digoxin was the most frequently involved drug. Electrolyte disturbances, increase in serum digoxin levels, risk of hemorrhage, severe myopathy or rhabdomyolysis, and cardiac arrhythmias were the most commonly implicated potential risks. When considering patients using digoxin with loop or thiazide diuretics for more than 5 months, 72% had at least one test to monitor potential digoxin toxicity, whereas 28% had no tests. Sixty-four percent of patients using digoxin with amiodarone, verapamil, or propafenone had an ECG and/or digoxin monitoring, and 36% of them did not have any tests. CONCLUSIONS: The present study revealed that, in a group of Italian general practitioners, the risks of severe potential drug interactions are relatively low and the drugs concerned are few. Analyses of specific tests showed that physicians are generally aware of the potential risks caused by digoxin drug associations. However not all patients were closely monitored and this should be improved.

Use and safety profile of antiepileptic drugs in Italy.

OBJECTIVE: To analyse and discuss the use and the safety profile of individual antiepileptic drugs (AEDs) in Italy. METHODS: The AED safety data referred to the period January 1988-June 2005 and were obtained from the database of the Italian Interregional Group of Pharmacovigilance (GIF). This database collects all spontaneous reports of suspected adverse drug reactions (ADRs) from six Italian regions which are the main contributors to the Italian spontaneous reporting system. Individual AED consumption data (defined daily dose/1,000 inhabitants per day) in the GIF area and in the whole of Italy referred to the period January 2003-June 2005 and were derived from drug sales data (Institute for Medical Statistics Health). RESULTS: Phenobarbital was the most frequently used AED in the GIF area (4.26 DDD/1,000 inhabitants per day) followed by carbamazepine (1.97), valproic acid (1.33) and gabapentin (1.10). AED consumption in the whole of Italy showed a similar pattern. Gabapentin was the most frequently used AED among newer AEDs. In the GIF database 37,906 reports (up to June 2005) were present; 666 of them (1.76%) were associated with at least one AED (Anatomical Therapeutic Chemical code N03A). The AED with the highest number of reports was carbamazepine (208 reports) followed by phenobarbital (98), gabapentin (80), phenytoin (56), valproic acid (55), lamotrigine (51), oxcarbazepine (43) and vigabatrin (35). Use and toxicity profile were evaluated only for AEDs associated with at least 30 reports. Skin reactions were the most frequently reported ADRs, followed by haematological, general condition, hepatic, neurological and gastrointestinal adverse reactions. Phenobarbital, lamotrigine, carbamazepine and phenytoin had the highest percentage of skin reactions (69, 67, 60 and 54%, respectively). Many haematological reactions were reported for each AED; the highest percentage was related to valproic acid (25%). Vigabatrin was associated with the highest percentage of reactions related to hearing, vision and other senses (97%). Phenytoin and valproic acid had the highest percentage of hepatic reactions (30 and 20%), whereas gabapentin of nervous system, psychiatric, gastrointestinal and urinary reactions (26, 21, 21 and 14%, respectively) and phenobarbital of musculoskeletal reactions (13%). CONCLUSIONS: In Italy antiepileptic drug therapy appears to be still dominated by traditional drugs. Our analysis showed a different safety profile related to each AED. Some of the drug-adverse reaction associations discussed are not included in the Italian drug leaflets or have not been reported before in the literature.

Effect of omeprazole on gastric acid secretion by the rat isolated stomach.

The inhibitory effect of omeprazole has been investigated on the isolated gastric fundus from immature rats. Omeprazole (10(-7)-10(-5) M) inhibited basal acid secretion, conversely from H2-receptor antagonists, antimuscarinic compounds and calcium antagonists; the effect was mimicked only by KSCN (3 X 10(-4)-3 X 10(-2) M). Omeprazole (10(-6)-10(-5) M) caused an insurmountable antagonism of the hypersecretion induced by histamine and bethanechol, whereas it competitively antagonized the secretory response to isoprenaline and dibutyryl cAMP. Experiments carried out in low calcium media showed that calcium ions did not significantly affect the inhibitory potency of omeprazole when tested on basal acid secretion, whereas low calcium solutions enhanced the action of omeprazole against histamine-induced hypersecretion. The above data confirmed the potent antisecretory activity of omeprazole in different experimental conditions in which the common antisecretagogues are without effect and pointed out the novel site of action in the control of gastric acid secretion at intracellular level.

Copper and zinc status in rats with acute inflammation: focus on the inflamed area.

Status of copper and zinc in plasma, blood cells, liver and hind paws (sectioned at the tibio-tarsal joint) were evaluated in rats with carrageenan-induced paw-oedema; moreover, concentrations of copper and zinc in the supernatant and cell fractions obtained from exudates pooled from rats with carrageenan-induced pleurisy were also determined. The evaluation of copper and zinc status in the blood and in the liver of rats with carrageenan-induced paw oedema, showed that only minor variations differentiated this experimental pathology from the previously studied carrageenan-induced pleurisy in rat. In inflammatory exudates withdrawn from pleural cavity, copper concentrations were found to be higher than the basal values measured in the whole paw, whereas zinc concentrations were found to be dramatically lower. Thus, the induction of the carrageenan paw-oedema determined an increase in copper and a decrease in zinc concentrations in the inflamed paw; however, in the inflamed paw, the total amounts of both copper and zinc were found to be significantly increased.

Copper and zinc status in adjuvant-arthritic rat: studies on blood, liver, kidneys, spleen and inflamed paws.

The status of copper and zinc in plasma, blood cells, kidneys, spleen and hind paws was evaluated in tail-injected adjuvant-arthritic rats, during both the asymptomatic (3 and 7 days after the inoculum) and symptomatic (14, 21 and 30 days after the inoculum) phases of the experimental disease. During the symptomatic phase, inflamed rats were studied divided into two groups on the basis of their arthritic scores (low-score L.S. and high-score H.S. arthritic rats). Copper (both in concentration and total amount) was found significantly increased in plasma, blood cells, liver, spleen and arthritic paws, whereas, in the kidneys, it was found to be lower than normal. Zinc was found to be remarkably increased in the liver. In blood, zinc was found to be decreased in plasma, but almost unchanged in the cellular fraction. Zinc total amount (but not concentration) was increased in the spleen, most likely because of a significant increase in spleen weight. As previously described in the case of acute inflammation, zinc concentration was found to be significantly decreased in arthritic paws, whereas the total amount of the metal present in these inflamed tissues was higher than normal. The status of copper and zinc may well differentiate L.S. from H.S. arthritic rats, especially during the latest phase of the experimental disease, and particularly because of a normalization of the considered parameters in the low-score group. Many of the changes observed in the status of both metals were seen prior the appearance of arthritis. The overall accumulation of copper and zinc which is induced in rat by the development of adjuvant arthritis, is suggested to further sustain the hypothesis of increased body requirements for both metals during inflammation.

Antimicrobial drug utilisation in hospitals in Italy and other European countries.

Antibiotic prescribing patterns in hospitals are analysed in this review of three drug utilisation studies conducted in six European countries, with special emphasis to the third-generation cephalosporins. A great variability in the use of antimicrobial drugs is evident, both between countries and between hospitals in the same country. This variability is found also between patients with the same infectious disease. The possible reasons for these differences are discussed and a strategy to modify the hospital drugs prescribing is suggested.

Nimesulide and renal impairment.

OBJECTIVES: To analyse from spontaneous reporting data the renal adverse reactions associated with the use of nimesulide. METHODS: Case reports were obtained from a Northern Italian Regional database (Veneto Pharmacovigilance System), containing all the spontaneous reports filed between 1988 and 1997. The Veneto Region is the principal contributor to the Italian spontaneous reporting system, with an annual report rate of approximately 17 per 100,000 inhabitants. The clinical records of hospitalized patients were also analysed. RESULTS: Of the 120 reports associated with oral nimesulide, 11 referred to suspected renal adverse reactions. The drug was taken by ten patients for a short period. All the patients discontinued the therapy and hospitalization was required in six cases. Other risk factors were identified in six cases. DISCUSSION: Together with the new insights into the possible consequences of renal cyclooxygenase-2 (COX-2) inhibition, the reported cases should draw the attention of doctors and patients to the importance of recognizing any possible signs of renal impairment during nimesulide therapy, although only extensive epidemiological data can define the real impact of its renal toxicity.

Antibiotic prescribing patterns in Italian hospital inpatients with pneumonia, chronic obstructive pulmonary disease, and urinary tract infections.

OBJECTIVE: The primary objective of this study was to describe the antibiotic prescribing patterns in hospital inpatients with pneumonia (PN), exacerbations of chronic obstructive pulmonary disease (COPD), and urinary tract infections (UTIs). A second objective was to verify if some selected variables (i.e., risk factors, patient age, size of hospitals) were affecting the therapeutic choice. DESIGN: Survey was performed on 1609 patients. The data were collected by physicians using a special form, covering a six-month period. SETTING: Twenty-six medical wards and 8 geriatric wards in 24 acute-care hospitals in the Veneto Region in Northern Italy. PATIENTS: A consecutive sample of PN, COPD, and UTI patients treated with antibiotics. MAIN OUTCOME MEASURES: The following information was collected: patient and hospital demographics, risk factors, diagnoses, and antibiotic regimens. RESULTS: Sixty-three antimicrobial agents used, with 2115 administrations, 1227 of which were single-drug therapy. The most frequently used drugs were third-generation cephalosporins (24.6 percent), fluoroquinolones (15.4 percent), aminopenicillins (15.0 percent), and ureidopenicillins (9.7 percent). There is great variability of therapeutic regimens in the various hospitals for the same disease. However, this variability is not explained by the different types of hospitals or by the patients' characteristics (e.g., age, risk factors). CONCLUSIONS: Our results show that the use of broad-spectrum antibiotics probably is excessive. Moreover, the treatment seems to be based more on the opinion of the treating physician and the local habits rather than objective criteria. These factors may have negative repercussions not only in economic terms, but also in terms of alteration of the bacterial ecology.

Oral zinc sulphate as primary therapeutic intervention in a child with Wilson disease.

An 8-year-old boy with an hepatic form of Wilson disease was treated with oral zinc sulphate as the primary and sole therapy. After 4 months, liver function had dramatically improved, and the parameters characterizing copper metabolism had also normalized.