Antibiotic treatments for children ages 0-23 months in a northern Italy region: a cohort study.

BACKGROUND: This study aims to describe the pattern of antibiotic treatments in the community for children ages 0-23 months in Emilia-Romagna (a northern Italy region) pointing out possible changes of prescribed agents when first treatments in the life of each children are compared to successive ones. MATERIALS AND METHODS: The Regional Drug Prescription and the Resident Population databases were used as data sources to study the cohort of children born between January 1 and December 31, 2000 and resident in Emilia-Romagna. RESULTS: The cumulative incidences of children with at least one treatment were 22%, 55% and 82% at 6, 12 and 24 months of age, respectively. Broad spectrum penicillins were the most prescribed antibiotic class for children at their first treatment while cephalosporins were the most prescribed class for successive treatments and when pooling all treatments. CONCLUSION: Cephalosporins and other second line antibiotics are frequently prescribed to 0 to 23-month-old residents in Emilia-Romagna even when only first treatments are considered; further research is needed to quantify inappropriateness of antibiotic prescription.

Intra-arterial chemotherapy for liver metastases from colorectal cancer.

The aim was to investigate whether intra-arterial infusion of chemotherapy improves response to treatment in unresectable liver metastases from colorectal cancer. We treated 14 patients (pts) with intra-arterial chemotherapy. Arterial catheters were placed via percutaneous access. Treatment schedule was: 5-FU and mitomycin-C on day 1 every 21 days. Six pts also received from day 3 for 5 days, a continuous intra-arterial 24-hr infusion of interleukin-2 (IL-2). We had only one case of toxicity drug-related > grade 2 (neutropenia). We observed 2 partial response (PR) and 5 stable disease (SD). Median time to disease progression (TTP) and median survival (OS) were, respectively 4 and 15 months.

Antibiotic prescriptions in children.

OBJECTIVES: The aim of this study was to evaluate antibiotic prescription for children in Emilia Romagna, a Northern Italian region with 414 880 people aged 1-14 years. METHODS: The regional Prescription Database of drugs reimbursed by the Italian National Health Service was used in this study. Antibiotic use was estimated as the proportion of children who received at least one prescription during the year 2000 (number of children treated per 100 inhabitants per year). To evaluate the frequency of exposure for each child, all the prescriptions given within a period shorter than 12 days were considered as a single treatment. RESULTS: In the year surveyed, 511,270 antibiotic prescriptions in 219,257 children were identified. In all, 52.9% of children received at least one antibiotic; this percentage decreased with age, ranging from 70.4% in children 1-2 years old to 35.8% in children >11 years old. Fifty-two per cent of inhabitants under the age of 15 years were treated with systemic antibiotics at least once in the year. Cephalosporins were mostly prescribed in the youngest children, while macrolides were most frequently used in children over 6 years old. In all 3.9% of children were treated with topical antibiotics. CONCLUSIONS: This study has shown that paediatric antibiotic prescription rates can be derived from analysis of regional drug and resident databases. High antibiotic usage is shown in the paediatric population of Emilia Romagna, similar to that observed in other regions of Northern Italy. Broad-spectrum antibiotics are predominantly prescribed. Comparison with prescription rates from other countries' paediatric populations suggests there is extensive antibiotic overuse in Italy. This could be associated with selection for and dissemination of antibiotic resistance. Interventions are needed to reduce consumption.

Ticlopidine versus oral anticoagulation for coronary stenting.

BACKGROUND: A 2-4 week course of ticlopidine plus aspirin following coronary stenting is considered effective in preventing thrombotic occlusion of the stented vessel and safe in regards to bleeding and peripheral vascular complications. However, rare, although potentially life-threatening haematological complications have been reported with this drug regimen. OBJECTIVES: To evaluate the efficacy and safety of ticlopidine plus aspirin versus oral anticoagulants after coronary stenting SEARCH STRATEGY: Electronic search of the Cochrane Library, Medline, Embase from 1991 to June 1999; references from trials and experts. SELECTION CRITERIA: Randomised controlled trials comparing ticlopidine plus aspirin versus oral anticoagulants (either with or without aspirin) after elective or bail out coronary stenting. DATA COLLECTION AND ANALYSIS: Three reviewers assessed trial quality and compiled data on outcomes including: total mortality, non fatal myocardial infarction and revascularization occurring within the first 30 days after hospitalization, stent thrombosis on angiography, major and minor bleeding, neutropenia, thrombocytopenia, thrombotic thrombocytopenic purpura. MAIN RESULTS: Four trials (n=2436 patients) were included. Ticlopidine plus aspirin compared to oral anticoagulants significantly reduced the risk of non-fatal acute myocardial infarction and revascularization at 30 days, combined negative events (mortality, myocardial infarction, revascularization at 30 days) (RR: 0.41; 95% CI: 0.25-0.69; NNT for 30 days: 22; 95% CI: 14-45), and major bleeding (RR in high quality studies: 0.24; 95% CI: 0.07-0.79). Ticlopidine plus aspirin compared to oral anticoagulants significantly increased the risk of eutropenia, thrombocytopenia and neutropenia (RR 5; 95% CI: 1.08-13.07; NNT for 30 days: 142; 95% CI: 76-1000). Ticlopidine plus aspirin vs oral anticoagulation did not affect all cause mortality. Ticlopidine plus aspirin significantly reduced the risk of stent thrombosis (angiography) which was seen only on studies with blinded outcome assessment (RR: 0.14; 95% CI: 0.03-0.60; NNT for 30 days: 33; 95% CI:16-166). Minor bleeding was reported only in one study and no studies recorded thrombotic thrombocytopenic purpura (TTP). REVIEWER'S CONCLUSIONS: Ticlopidine plus aspirin after coronary stenting is effective in reducing the risk of the revascularization, non fatal myocardial infarction and bleeding complications when compared with oral anticoagulants. No effect is observed on total mortality. However, the haematological side effects of ticlopidine are still a matter of concern, and strict monitoring of blood-cell counts is recommended. Physicians should also be aware of the possibility of rare although potentially life-threatening complications such as TTP

European hospitals as a source for platinum in the environment in comparison with other sources.

The concentration of platinum in the sewage of five European hospitals originating from excreted antineoplastic drugs, cisplatin and carboplatin, was analyzed in a short term study to provide an order of magnitude of Pt emissions from hospitals into aquatic environments. These emissions were compared with a rough estimation of emissions by cars. The average daily concentrations in the hospital effluents were approximately < 10-601 ng l-1 Pt (20-3580 ng l-1 in 2-h mixed samples). As expected from consumption data, the daily average concentrations should range from < 10-710 ng l-1 Pt. Platinum emitted by hospitals is 3.3-12.3% (1.3-14.3 kg per year) the estimated amount emitted by cars equipped with catalytic converters in the different European countries. Compared to platinum emissions from other sources, the effluents of hospitals are a minor source of platinum in municipal sewage, but they should not to be disregarded. Other possible sources for the emission of platinum into the environment should be considered in further investigations.

Analysis of benzalkonium chloride in the effluent from European hospitals by solid-phase extraction and high-performance liquid chromatography with post-column ion-pairing and fluorescence detection.

A highly reproducible and specific method for the analysis of the quaternary ammonium compound, benzalkonium chloride, in effluents from European hospitals is presented. Benzalkonium chloride was extracted with end-capped RP-18 solid-phase cartridges and was selectively eluted. The resulting solution was analyzed by high-performance liquid chromatography (HPLC). After elution from the analytical column of the HPLC system, 9,10-dimethoxyanthracene-2-sulfonate was added continuously as a fluorescence marker, forming a hydrophobic ion-pair with benzalkonium chloride. The ion-pair was analyzed by fluorescence detection. The method was applied to highly complex effluent samples from different sized European hospitals. The measured concentrations were between 0.05 and 6.03 mg/l. The amounts emitted per bed and year were 4.5-362 g and did not correlate with the size of the hospital. The total amounts were 2.6-909 kg/year.

[Reuse of disposable equipment. Medicolegal viewpoint]. / Il riutilizzo dei dispositivi monouso. Il punto di vista medicolegale.

The ethical foundation supporting legislation on medical devices deals with safeguard of both individual and collective rights in health care and protection; there is no ethical reason in protecting individuals from reuse of medical devices, if reuse can be proved safe and efficacious, and if it is a way to ensure provision of services otherwise unextendable to all patients, due to lack of funds. This paper explores legal feasibility of reuse, and provides an interpretation of relevant legislation, with special concern on European Directives on Medical Devices. Whereas it is commonly accepted that controls can be imposed to test whether devices meet legal standards on safety and adherence to label indications, clinical investigations and research may as well illuminate different and wider features of the same items, not considered by the manufacturer and not included in the actual labelling. The present wording of the directives does not provide for an autonomous role of member states in asking for modifications in the provisions of the manufacturer, except when devices do not meet specific requirements stated by the directive. Nevertheless, there is no legal ground to emphasize labelling when contrasting with clinical research findings, thus leading to the conclusion that widening a possible manufacturer's understatement in therapeutic uses of medical devices is legally feasible. In the present situation in which responsibility for casualties from reused medical devices is unduly vested on physicians, Health Authorities in member States bear a moral responsibility in promoting adequate research trials to support safety and efficacy of reuse practices, thereby prompting manufacturers to apply for label modification.

[Transesophageal echocardiography in patients free of carotid disease with an ischemic stroke]. / L'ecocardiografia transesofagea in pazienti, esenti da patologia carotidea, colpiti da ictus ischemico.

BACKGROUND: Cardioembolism is the cause of cerebral infarct in 15 to 30% of cases. The aim of the present work is to detect, by transesophageal echocardiography (TEE), potential cardioembolic sources in patients with cerebral ischemia without atherosclerotic carotid disease at duplex carotid ultrasound examination. METHODS: From 1991 onwards, 420 consecutive patients who presented with cerebral ischemia, detected by computerized axial tomography, underwent an echotomography examination of the cerebral afferent vessels and a transthoracic echocardiogram (TTE). Three hundred and thirty out of these patients were excluded since they had carotid plaques; of the remaining 90, 80 (mean age 61.6 years range: 25-86, 50 males and 30 females) underwent a transesophageal examination. The patients were studied with an HP Sonos 1000 system with 2.5 and 3.5 MHz frequency probes for TTE; 7.5 and 5 MHz probes were used for echotomography and TEE respectively. RESULTS: The TEE identified cardioembolic sources in 81% of the cases, versus 46.2% using TTE (p < 0.0001) with a significant statistical difference for thrombus, spontaneous echo contrast and paradoxic shunt (p < 0.0001). When the patients with cerebral ischemic events (group A) were compared with the 156 cardiac patients (group B) (mean age: 59.7, range: 19-86, 92 males and 64 females), without ischemic events, group A showed a significant higher prevalence of thrombus, spontaneous echo contrast, calcification of the mitral anulus, interatrial aneurysm and paradoxic shunt. CONCLUSIONS: Our experience confirms that TEE is very useful and more sensitive than TTE for diagnosing cardioembolic sources; so, this new diagnostic tool should become a useful part of the diagnostic iter for patients with ischemic stroke and normal carotid vessels. The prevalence of some heart conditions in the stroke group poses the problem of whether to advise anticoagulant or antiplatelet therapy and, in selected cases, a surgical approach. The absence of heart and vascular conditions in the extracranial regions of patients who have had a cerebral stroke, suggests an intracranial condition and the problem of performing an angiographic examination arises.

[Reuse of single-use catheters: a dilemma to be clarified]. / Riutilizzo di cateteri mono-uso: un dilemma da riportare in luce.

This paper proposes a cost benefit approach in evaluating reuse of single-use catheters, introducing cost of disposal and the concept of financial risk. An estimation of relevant variable and fixed costs is discussed, according to conditions and prices presently existing in Northern Italy. A formal model is developed to compare alternative reuse and no-reuse strategies. Use of internal versus external (Service centers) sterilization is also briefly scrutinized. A short review of literature concerning reuse is aimed to place the issue in the proper framework, listing critical problems as far as safety, risks of rupture, identification and control procedures, legal responsibility, informed consent by the patient. The conclusion is proposed that reuse of Medium-to-High cost catheters is highly profitable from the economic standpoint, subject to the condition that stringent quality procedures and controls are implemented to assess reasonable safety on behalf of the patient. Further, size of potential savings and gain in number of procedures performed are likely to request at least some institutional attention. Last, pooling relevant risks among several institutions is a plausible way to lower costs and make reuse possible also to smaller centers. The model may be used for self-assessment purposes concerning reuse introduction; the actual estimate of risk is critical in evaluating results.

[Evaluation of atrial septum aneurysm with transesophageal echocardiography in cardioembolic cerebral ischemia]. / Valutazione ecocardiografica transesofagea dell'aneurisma del setto interatriale nell'ischemia cerebrale cardioembolica.

The prevalence and characteristics of atrial septal aneurysm were identified by transesophageal echocardiography (TEE) in a multicenter prospective study. One hundred and seventy-seven consecutive patients were evaluated in 2 years and 2 groups were compared: Group 1, 51 patients with documented cerebral ischemia event; Group 2, 126 patients affected by cardiac disease referred for other reasons. Group 1 included patients selected among 352 patients admitted to the Neurological and Geriatric Division of our Hospital in the period of this study. Patients with stroke-related carotid lesions and patients with a negative TC scan were excluded from this study. Atrial septal aneurysm was identified in 15 patients: 8 in Group 1 (16%), and 7 in Group 2 (5%), with a significant statistical difference between the groups (p = 0.02). All patients with atrial septal aneurysm underwent before TEE transthoracic echocardiography, leading to a correct diagnosis in 10 of 15 cases (66%); all patients underwent 24-hours ECG monitoring. A right to left shunt was detected by contrast echocardiography in 9 patients, 6 in Group 1 and 3 in Group 2, (NS). A more pronounced shunt was evident in Group 1. There was no difference between the 2 groups with regard to associated cardiac disease, arrhythmias and type of atrial septal aneurysm. The thickness of the septum was greater in Group 1, with significant statistical difference (p = 0.002). It is concluded that atrial septal aneurysm, diagnosed by TEE, is a potential source of embolic events.

The effect of continuous vasopressin infusion on splanchnic blood flow, liver function, and portal and central venous pressures in patients with cirrhosis.

Continuous vasopressin infusion has been shown to control bleeding from oesophageal varices in patients with cirrhosis of the liver. The mortality, however, has not been changed. To investigate whether reduction of portal blood flow over a period of hours deteriorates the liver function, we measured the splanchnic blood flow and galactose and oxygen consumption in five cirrhotic patients during liver vein catheterization. Vasopressin was given as a continuous infusion of 0.2 units per min for three h. The splanchnic blood flow was reduced to 70% of control values and remained so throughout the infusion. After three h no impairment of the liver function was found. The wedged hepatic pressure (portal pressure) rose slightly, probably due to the increase of the central venous pressure reflecting impaired cardiac function. The reported beneficial effect of vasopressin on varix bleeding probably depends on the reduced portal flow per se.

[Clinical significance of a prolonged sinus-node recovery time as the only pathological finding: follow-up]. / Significato clinico di un tempo di recupero del nodo del seno allungato come unico dato patologico: follow-up.

The Authors report their experience related to clinical follow-up (F.U.) study of a 12 patients group who showed a prolonged sinus node recovery time (SNRT) as the only pathologic datum. F.U. study appears extremely useful for clinical arrangement of these patients. In 6 patients a gastric ulcer was associated, which is considered a morbid equivalent of vagotonia. Therefore SNRT could be a false positive. In 3 patients following controls allow to document an initial ischemic cardiopathy. Tachicardic phase of S.S.S. was documented in 3 patients.

Evidence for liver cell proliferation during fatal acute liver failure.

Liver cell regeneration was assessed by determining the mitotic index and the frequency of liver cells with interploid DNA values in livers from patients dying from fulminant hepatitis. For comparison, the same parameters were determined in patients with uncomplicated hepatitis. We found comparable levels of regeneration in the two groups, indicating that the rate of liver cell destruction is a major determinant in the prognosis of acute liver failure. Accordingly, measures to prevent liver cell necrosis seem at least as important as stimulation of regeneration. Judged from available experimental evidence, substances with documented hepatotrophic effect in animals, such as insulin and glucagon, may therefore not be effective in acute liver failure unless the patient has impaired secretion of these substances.

[Malfunction of disc prostheses. Echocardiographic study of 5 cases (author's transl)]. / Malfunzionamento di protesi a disco. Studio ecocardiografico di cinque casi.

78 patients who underwent disc prostheses replacement, 36 in mitral area, 58 in aortic area were studied by echocardiography. The Authors found 5 cases of malfunction, 3 in mitral area and 2 in aortic area. Regarding mitral malfunctions in 1 case a valve thrombosis was found; in 2 cases there was a partial leak. Regarding aortic malfunctions there was paravalvular leak. In mitral area malfunctions the Authors found alterations of the disc morphology during diastolic opening time associated with alteration of opening time. An increased diastolic closure velocity in 2 cases of paraprosthetic leak was found. A diagnostic element in the case with thrombosis was variability of maximal disc escursion during the same recording, because opening time variability never got over 10 m. seconds. In aortic area malfunctions the Authors found a constant fluttering of anterior mitral leaflet, a sinergic septal motion with the posterior wall and in 1 case the presence of disc opening before the first component of the first sound. The Authors underline the importance of simultaneous eco-phonocardiographic examination and the check-ups for the time to be.

Effect of long-term disulfiram administration on rat liver.

No hepatotoxicity was demonstrated after 90 days in rats treated with two dose levels of disulfiram. A reversible inhibition of microsomal p-nitroanisole demethylase activity was found. In phenobarbital-treated rats disulfiram 100 mg/kg did not alter the induction response as indicated by the cytochrome P-450 content, but inhibited the p-nitroanisole activity to control levels. As no sign of histological liver damage was found, we conclude that the rare cases of disulfiram hepatotoxicity in man may be due to an allergic reaction.