R. Raschetti

Suspected adverse drug events requiring emergency department visits or hospital admissions.

AbstractObjective: To analyse the contribution of adverse drug events (ADEs) to the overall number of referrals or visits at an emergency department, to determine the proportion of more severe episodes requiring hospital admission and to characterize the different causes of drug-related visits or admissions. nn Methods: A 1-year prospective collection of data on visits performed at an emergency department. All visits, observed during 1 week every month, were analyzed in order to identify suspected ADEs. The effects of age and sex on the frequency of ADE-related visits and admissions were evaluated. All patients hospitalized because of an ADE were followed up in order to collect information about progress and outcome of the events, which were also assessed in terms of avoidability. nn Results: Among the 5497 patients who visited the Emergency Department over 1 year, 235 (4.3%) experienced an ADE, 45 of these (19.1%) were subsequently hospitalized, among whom there were five deaths. Dose-related therapeutic failures were the main causes of drug-related admissions (55.6%), whereas adverse drug reactions caused the most frequent drug-related visits to the Emergency Department (63.8%). Although the frequency of drug-drug interactions leading to a visit to the Emergency Department was small (3.8%), this type of event was more severe, because most of these patients were hospitalized. No age/sex effect was observed in the proportion of ADE-related hospital admissions. Twenty-five (1.4% of the total admissions) of the 45 ADE-related admissions were evaluated as preventable, contributing by more than 61% of the overall length of hospital stay.nn Conclusion: The high proportion of drug therapeutic failures leading to an admission highlights the need for public education, particularly to prevent non-compliance.

Use of unconventional medicine in Italy: a nation-wide survey

HeadingAbstractn Objective. To investigate the prevalence of use of unconventional therapies in Italy, the main health problems associated with and the motivations for use of these therapies.n Methods. Questions about the use of unconventional therapies were inserted in a nation-wide survey conducted by face-to-face interviews with all members of sampled families by the National Institute of Statistics during four quarters of the years 1999–2000. Data presented here are based on the results of the first two quarters of the survey (September and December 1999) during which a representative sample of 30,000 Italian families (70,898 individuals) was interviewed.n Results. Almost 9 million people (15.6% of the Italian population) used at least one unconventional therapy during the period 1997–1999. Homeopathy was the most frequently used (8.2% of the population), followed by manual treatments (7%), herbal medicine (4.8%) and acupuncture (2.9%). Homeopathy was also quite commonly used by children (7.7% of Italian children). The main reason for use was concern about potential toxicity of conventional medicine. The health problem most frequently treated with all kinds of unconventional therapies was pain.n Conclusions. Use of unconventional therapies has almost doubled since 1991. However, with 15.6% of the Italian population (9 million people) using at least one therapy, Italy ranks among the light users compared with other European countries. Homeopathy is the most frequently used therapy. The typical user is, as in other western countries, a highly educated woman aged 35–44xa0years and resident in the richest part of the country (north-eastern Italy).

Rat models of acute inflammation: a randomized controlled study on the effects of homeopathic remedies

BackgroundOne of the cardinal principles of homeopathy is the law of similarities, according to which patients can be treated by administering substances which, when tested in healthy subjects, cause symptoms that are similar to those presented by the patients themselves. Over the last few years, there has been an increase in the number of pre-clinical (in vitro and animal) studies aimed at evaluating the pharmacological activity or efficacy of some homeopathic remedies under potentially reproducible conditions. However, in addition to some contradictory results, these studies have also highlighted a series of methodological difficulties.The present study was designed to explore the possibility to test in a controlled way the effects of homeopathic remedies on two known experimental models of acute inflammation in the rat. To this aim, the study considered six different remedies indicated by homeopathic practice for this type of symptom in two experimental edema models (carrageenan- and autologous blood-induced edema), using two treatment administration routes (sub-plantar injection and oral administration).MethodsIn a first phase, the different remedies were tested in the four experimental conditions, following a single-blind (measurement) procedure. In a second phase, some of the remedies (in the same and in different dilutions) were tested by oral administration in the carrageenan-induced edema, under double-blind (treatment administration and measurement) and fully randomized conditions. Seven-hundred-twenty male Sprague Dawley rats weighing 170–180 g were used. Six homeopathic remedies (Arnica montana D4, Apis mellifica D4, D30, Atropa belladonna D4, Hamamelis virginiana D4, Lachesis D6, D30, Phosphorus D6, D30), saline and indomethacin were tested. Edema was measured using a water-based plethysmometer, before and at different times after edema induction. Data were analyzed by ANOVA and Student t test.ResultsIn the first phase of experiments, some statistically significant effects of homeopathic remedies (Apis, Lachesis and Phosporus) were observed (the reduction in paw volume increase ranging from 10% to 28% at different times since edema induction). In the second phase of experiments, the effects of homeopathic remedies were not confirmed. On the contrary, the unblinded standard allopathic drug indomethacin exhibited its anti-inflammatory effect in both experimental phases (the reduction in paw volume increase ranging from 14% to 40% in the first phase, and from 18% to 38% in the second phase of experiments).ConclusionThe discrepancies between single-blind and double-blind methods in animal pharmacological research are noteworthy and should be better investigated, also in non-homeopathic research.

Active monitoring of adverse drug reactions in children

An active monitoring system of adverse drug reactions (ADR) in children was developed through a network of family paediatricians. The reported Incidence of ADRs was 15.1 per 1000 children.

Gangliosides and Guillain-Barré syndrome

Cases of Guillain-Barré syndrome (GBS) associated with parenteral use of gangliosides have been reported in several European countries. To evaluate the hypothesis of association between ganglioside exposure and occurrence of GBS, a case-control study was conducted. GBS cases discharged during 1989 from public and private hospitals in three Italian provinces were identified: 42 GBS cases and 420 controls matched on age and gender were enrolled. Data of onset of symptoms of GBS was taken from clinical records. Exposure status of subjects was ascertained through the regional computerized drug prescription monitoring system. The odds ratio of association between ganglioside use, in the 30 days prior to onset of symptoms, and GBS was 9.1 (95% confidence interval 2.8-29.4). Although there are formidable difficulties in distinguishing prodromal therapy of GBS from drug causation, the association with ganglioside therapy is strong and supportive of the hypothesis of a role of ganglioside preparations in the occurrence of GBS.

Ketorolac use in outpatients and gastrointestinal hospitalization: a comparison with other non-steroidal anti-inflammatory drugs in Italy

AbstractObjective: To compare the risk of hospitalization for gastroduodenal ulcer associated with the use of ketorolac and other non-steroidal anti-inflammatory drugs (NSAIDs).nn Methods: A cohort and a nested case-control study were carried out. All residents in the region of Umbria (Italy), aged 35–84 years, who had been given at least one NSAID prescription in 1993 and 1994 were identified. Exposure to drugs was ascertained through a drug prescription database. We estimated rate ratios of hospitalization for gastroduodenal ulcer with or without complications in the current, recent or past period according to exposure to different NSAIDs.nn Results: Rate ratio estimates, adjusted for age and sex, were 2.8 for any current NSAID and 1.4 for any recent NSAID. The highest rate ratios of lesions of any severity for current NSAID use were observed for piroxicam (RR: 4.6) and ketorolac (RR: 3.4). For gastrointestinal haemorrhage or perforation the highest rate ratios were those for ketorolac (RR: 5.9) and piroxicam (RR: 4.8). Rate ratio estimates did not change after adjustment for concomitant use of gastrotoxic drugs, use of gastroprotective agents not associated with NSAIDs and prior use of NSAIDs. nn Conclusion: Our study demonstrates the need to adhere to the restrictions relating to the indications and duration of use of ketorolac. At present piroxicam represents a greater public health concern since it is confirmed to be among the most gastrotoxic NSAIDs and is one of the most commonly prescribed NSAIDs in Italy.

Reactogenicity in the elderly of nine commercial influenza vaccines : results from the Italian SVEVA study

A 10-fold increase of reported adverse events following influenza vaccination in the 1995-1996 campaign was reported. To evaluate the relative reactogenicity of different influenza vaccines a prospective observational study was conducted in 72 Italian local health units (LHU) in the period October-December 1996. Of the 16,637 enrolled individuals aged 65 or more, 27.4% reported the occurrence of at least one adverse event within 72 h of vaccination. The odds ratios, adjusted through a multivariate logistic model, were highest for whole vaccine recipients. Most of the observed events were of moderate clinical severity and were mainly represented by local symptoms. None of the products was found to show an unusual or concerning reactogenicity profile, and no severe events associated with immunization were reported.

Epidemiological use of drug prescriptions as markers of disease frequency: An Italian experience

All Italian citizens are covered by the National Health Service (NHS) and medical records of individual drug prescriptions are routinely collected and processed. A procedure entitled EPIFAR has been developed which, on the basis of a computer routine, makes it possible to trace back the prescription history of each individual included in the NHS. The validity of information gathered through the EPIFAR procedure to provide estimates of tuberculosis (TB) prevalence has been evaluated. A comparison with routine surveillance data has been made. The EPIFAR procedure identified a total figure of TB patients seven times higher than that from official notifications. A sample survey was conducted among the prescribing physicians in order to quantify the proportion of TB cases among subjects receiving prescriptions of anti-TB drugs. According to general practitioner recall 66.4% of the patients were treated because of TB diagnosis, TB prophylaxis and TB relapse.

Modulation of the Root effect in goldfish by ATP and GTP.

Both ATP and GTP are present in considerable amounts in red cells of the common goldfish Carassius auratus. They both influence the Root effect of the single major fish hemoglobin, but GTP is, depending on pH, 2-6 times more effective than ATP. The two triphosphates account for 3/4 of the effect of trichloroacetic acid supernatant obtained from hemolysate which contains still some compound(s) which can influence the shift of the Root effect toward higher pH.

Use of unconventional medicine in children in Italy.

Sir: In 1999, Professor Ernst published a systematic review on the use of complementary alternative medicine (CAM) among children [1]. Recently, in Italy, a large survey (60,000 families, approximately 180,000 individuals, of whom 20,219 were children) on ‘‘Health Conditions and Health Service Utilisation’’ was concluded. Face-to-face interview through a questionnaire was administered to all family members. A whole section on unconventional medicine was included in the questionnaire [2]. The results show that 9.1% of children aged 0–14 years were treated with an unconventional treatment in the period 1998–2000. The use was more frequent among children in the age group 2–10 years. Homeopathy was the most frequently used therapy (7.6% of children), followed by herbal medicine (2.4%), manual treatments (1.0%), another ‘‘unspecified’’ unconventional therapy (0.5%) and acupuncture (0.4%). Homeopathy was used in children mainly to treat acute diseases, herbal medicine to improve quality of life and manual treatments for painful conditions. Unconventional medicine was chosen for children because of its expected lower toxicity (58.2% of cases), greater efficacy (13.4%), only available therapy (11.3%), better patientphysician relationship with respect to conventional medicine (10.7%) and cultural belief of their parents (6.3%) (more than one answer could be given). Paediatricians were informed about the use of unconventional therapies for 65.1% of their patients. A high level of satisfaction was expressed by parents of young users of unconventional medicine: approximately 80% of cases declared to have had complete relief. Parents of young CAM users were mainly aged 35–44 years, highly educated, and with high income. No information about costs and safety could be collected through our survey. Although the proportion of users is not extremely high, it is, however, increasing. We certainly agree with Professor Ernst about the urgency of conducting rigorous research in this field in order to avoid the possibility that children could be treated, even for important health problems, with treatments of uncertain efficacy and which, in some cases, could do more harm than good.