The need for European harmonization of Nutrivigilance in a public health perspective: a comprehensive review.

According to the European Union regulation, some countries have established a pre-market notification system for food supplements while others have not. As this regulation is unfulfilled, a notified and marketed food supplement ingredient in one country may be forbidden in another. Even though food supplements shall not be placed on the market if unsafe, some products may still expose the consumers to risks. The risk is increased by easier access due to worldwide dissemination fostered by the internet and free movement of goods in the European Union. The Rapid Alert System for Food and Feed and the Emerging Risks Exchange Network are described. To date, the European Union legislation does not include a provision to establish a dedicated vigilance system for food supplements (Nutrivigilance). Six European Union countries have nevertheless set up national systems, which are presented. The present lack of European Union data collection harmonization, does not allow easy cooperation between countries. This article advocates for creating a coordinated European Nutrivigilance System to detect and scrutinize adverse effects of food supplements. This, to help in directing science-based risk assessments and reinforce the science-based decision of policy makers to improve public health safety.

The impact of prophylactic treatment on post-traumatic epilepsy after severe traumatic brain injury.

AIM: To assess the incidence of late post-traumatic epilepsy (PTE) in patients with very severe traumatic brain injury (TBI) who either received or did not receive anti-epileptic prophylactic treatment. METHODS: Two populations were studied: 55 patients retrospectively and 82 subjects prospectively. RESULTS: Ten patients (18%) in the first population showed late PTE. Although the incidence was lower in patients who did not receive prophylactic treatment, the difference between the treated and the non-treated group was not statistically significant. Sixty-nine patients in the second group (84%) had prophylactic treatment. Twenty-seven patients (39%) suffered from late PTE during the 2-year follow-up period and 17 of them (63%) showed EEG epileptic abnormalities. No patient who did not receive preventive therapy suffered from late PTE during the observation period. CONCLUSIONS: Due to the negative cognitive effects of anti-epileptic drugs, the preliminary results are of considerable interest for the rehabilitation of patients with very severe TBI.

Determinants of acquiring hepatitis A virus disease in a large Italian region in endemic and epidemic periods.

Viral hepatitis A is endemic in Puglia region (southeast Italy). Over the last 13 years, annual incidence rates have ranged from 4 to 138 per 100,000 inhabitants and periodical regional epidemics have been described. Between 1 January 1996 and 31 December 1997 over 11,000 cases of hepatitis A were reported accounting for an annual incidence rate over 130/100,000. To identify exposures during the epidemics, a case-control study was performed in two different rounds and since 1997, an enhanced surveillance system has permitted the monitoring of exposures of subsequent cases. Raw seafood consumption was identified as the major risk factor for hepatitis A. Adjusted odds ratio and 95% confidence intervals for this exposure from the first round of the case-control study was 38.6 (12.2-122.4) and for the second round for consumption of raw mussels it was 30.7 (16.0-52.0). Hepatitis A epidemiology in Puglia is consistent with an endemic situation sustained by locally contaminated seafood consumed raw and by the recurrence of large epidemics, where size is influenced by the accumulation of susceptible subjects in the population.

Hepatitis C virus infection in spouses: sexual transmission or common exposure to the same risk factors?

OBJECTIVES: The aim of this study was to evaluate whether the transmission of hepatitis C virus (HCV) between spouses occurs through sexual contact or through other types of exposure. METHODS: We consecutively enrolled 311 chronic HCV carriers and their spouses. The spouses underwent HCV blood testing. Exposure to parenteral risk factors was compared between couples of which both partners were HCV positive and couples with one positive partner. In couples with both partners positive, qualitative detection of serum HCV RNA and genotyping were performed. RESULTS: The prevalence among spouses was 10.3% (32/311). The mean age was higher for HCV-positive spouses (57.7 vs 49.6 yr for HCV-negative spouses; p < 0.01). The prevalence among spouses increased with the duration of marriage, whereas no difference was found in relation to the clinical status of the index case. The 32 HCV-positive spouses reported parenteral exposure (blood transfusion, drug use, and use of multiple-use glass syringes inside or outside the family) more often than the 279 HCV-negative spouses (84.4% vs 26.2%; odds ratio [OR], adjusted for age by multiple logistic regression analysis, 12.4; 95% CI = 4.5-34.0). The percentage of couples sharing glass syringes was significantly higher among those with both partners infected (65.6% vs 12.9%; OR = 12.9; 95% CI = 5.4-31.4). Qualitative serum HCV RNA was determined in 22 couples with both partners infected; in 13 of them, both partners were HCV RNA positive, whereas in the remaining nine, only one partner was positive. In eight of the 13 couples with both partners HCV RNA positive, the same genotype was found for both partners. CONCLUSIONS: The findings that the same genotype was detected for both partners in relatively few couples, and that a history of parenteral exposure was an independent predictor of HCV positivity, suggest that the risk of sexual transmission is low. The sharing of glass syringes may have played an important role in transmission between spouses.

Niflumic acid and cutaneous reactions in children.

In a case control study of adverse drug reactions in children, the odds ratio of developing a serious mucocutaneous event among users of niflumic acid, adjusted for concomitant use of all other drugs, was 4.9 (95% CI 1.9 to 12.8). Given the availability of safer analgesics and antipyretics, there is no indication, in our opinion, that requires the prescription of substances which bear an increased risk.

[Effects of socio-environmental factors on neurocognitive performance in premature or low-birth weight preschoolers]. / Effetti dei fattori socio-ambientali sugli esiti neurocognitivi in età prescolare dei bambini con prematurità o basso peso alla nascita.

Severely preterm neonates (gestational age < or = 32 weeks) and/or very low birth weight (VLBW, with weight at birth < or = 1500 g) are 2% of all newborns, with a rising incidence due to the increase of multiple gestations and of pregnancies at advanced age. These neonates may be affected by severe neurological pathologies (6-10% of cases), but they often have minor disabilities (such as distractibility, hyperactivity, learning and social competence disabilities, deficit of motor development) difficult to be early diagnosed, and frequently recognized only at pre-school or school age. A review of the current knowledge about the effects of potential risk factors responsible for deficits of neurocognitive development in pre-school age and for postnatal distress of mothers, and their inter-correlations, is reported.

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

OBJECTIVE: 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. 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. 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. CONCLUSION: The high proportion of drug therapeutic failures leading to an admission highlights the need for public education, particularly to prevent non-compliance.

[The characteristics of the use and the levels of diffusion of nonconventional medicine]. / Caratteristiche d'uso e livelli di diffusione della medicina non convenzionale.

The national trends of the utilisation of non conventional therapies suggest that an increasing number of patients employ remedies that are outside the mainstream of what has been defined as conventional western medicine. The extent to which these practices have clinical efficacy according to biomedical criteria is a matter of ongoing debate. It may be that independent of any such efficacy, the attraction of alternative medicine is related to the power of its underline shared beliefs and cultural assumptions. The fundamental premises are an advocacy of nature, vitalism, "science" and spirituality. For patients, who choose alternative medicine, the most important reason to abandon conventional therapies could be to move from the sterile "high-tech" realm of official medicine to a more intimate "high-touch" intervention offered by non-physicians.

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

OBJECTIVE: To compare the risk of hospitalization for gastroduodenal ulcer associated with the use of ketorolac and other non-steroidal anti-inflammatory drugs (NSAIDs). 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. 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. 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.

Hepatitis C virus infection in family setting.

To evaluate risk factors associated with intrafamiliar transmission of hepatitis C virus (HCV), 113 hepatitis C virus index subjects with chronic HCV infection and their 267 family contacts were studied from January 1994 to October 1995. Overall, 16 family contacts (6%) were positive for anti-HCV by ELISA II generation. The prevalence was 11.3% in spouses and 2.9% in other relatives (odds ratios: 4.2; 95% CI: 1.4-12.6). Spouses who had been married to the index cases longer than 20 years had a 7.5-fold risk (95% CI: 1.0-336.3) of HCV seropositivity as compared to those married less than 20 years. In univariate analysis HCV seropositivity was associated with surgical intervention, use of glass syringes and hospitalization. The results of multivariate logistic analysis showed that any parenteral exposure (odds ratios: 3.8; 95% CI: 1.2-12.8) and sexual contact with an anti-HCV index case (odds ratios: 3.0; 95% CI: 1.0-9.4) were both independent predictors of HCV seropositivity among household contacts of HCV positive index cases. These findings indicate that sexual contact and any parenteral exposure both play an independent role in the spread of HCV infection in the family setting.

Drug use and acute leukemia.

OBJECTIVE: To study the occurrence of acute leukemia in relation to preceding use of drugs a case-control study has been carried out in Rome, Italy. PATIENTS AND METHODS: Two hundred and two patients (age >15 years) with a diagnosis of acute leukemia during the period July 1992-June 1994 were enrolled. For each patient, 10 controls matched by age and gender were randomly drawn from the source population. Through the individual beneficiary code the information relevant to the drugs received within the National Health Service during the period January 1989-December 1992 was retrieved. The use of drugs was considered etiologically related to leukemia if the prescription occurred before the 12 months preceding the diagnosis. Exposure was categorized as 'any use' (at least one prescription during the etiologic period), 'high use' (duration of use greater than the median in the control group) and, for NSAIDs, 'very high use' (duration of use greater than 180 days). RESULTS: Among drugs suspected to cause leukemia, users of high doses of chloramphenicol presented an OR of 1.8 (95% CI: 0.6-5.3). Among other categories of drugs with an increase in the ORs, though not statistically significant, we found tricyclic antidepressants (OR=1.7; 0.8-3.4) and oral contraceptives (OR=1.8; 0.8-4.0). No excess risk was observed for users of calcium-channel blockers (OR=0.9; 0.5-1.7). Use of very high doses of NSAIDs appeared to decrease the occurrence of acute leukemia (OR=0.4; 0.1-1.5). CONCLUSION: Even with several limitations, this study provides an initial frame of reference for the potential causal role of drugs in acute leukemia.

Prevalence, risk factors, and genotype distribution of hepatitis C virus infection in the general population: a community-based survey in southern Italy.

In 1996 the prevalence, risk factors, and genotype distribution of hepatitis C virus (HCV) infection were assessed in the general population of a town in southern Italy. The sample was selected from the census by a systematic 1:4 sampling procedure. The participation rate was 96.6%. Among the 1,352 subjects enrolled, 195 (14.4%) tested reactive to antibody to HCV (anti-HCV) with enzyme immunoassay (EIA 3). When further tested with recombinant immunoblot assay (RIBA 3), 170 subjects (87.2%) tested positive, 23 subjects (11.8%) had indeterminate results, and 2 subjects (1%) tested negative. Thus, the overall anti-HCV EIA-positive RIBA-confirmed prevalence was 12.6% (170 of 1,352 subjects) and increased from 1.3% in subjects younger than 30 years to 33.1% in those > or =60 years of age. This latter age group accounted for 72.3% of all anti-HCV-positive subjects. Females tested positive more frequently than males (14.1% vs. 10.5%; P < .05). Alanine transaminase (ALT) concentrations were abnormal in only 4.1% (7/170) of anti-HCV EIA-positive RIBA-confirmed subjects. This suggests that ALT screening is not useful in the detection of anti-HCV-positive subjects in a general population. The results of multiple logistic regression analysis showed that an age of less than 45 years, the use of glass syringes, and dental therapy were all independent predictors of anti-HCV positivity. HCV RNA was detected by polymerase chain reaction in 75.9% of the 195 anti-HCV EIA-positive subjects: in 84.7% (144/170) of the RIBA-confirmed subjects; in 17.4% (4/23) tested as RIBA indeterminate; and in neither of the two subjects who tested RIBA negative. HCV type 1b was detected in 75 subjects (50.7%), type 2b in 1 subject (0.7%), type 2c in 66 subjects (44.6%), type 3a in 4 subjects (2.7%), and type 4 in two subjects (1.3%). These figures differ from those of Italian patients with chronic liver disease in whom genotype 2 is more rare. None of the individuals was infected with more than one genotype. The distribution of the two most common HCV viral types (1b and 2c) was not statistically different in terms of mean age, sex, or risk factors and suggests that they may have had a parallel spread in this community. These findings provide one of the highest overall anti-HCV prevalence rates in a general population with a likely cohort effect, i.e., decreased risk of infection along generations. These observations may indicate an epidemic or focus of hepatitis C that occurred several years earlier. The majority of anti-HCV-positive subjects in the oldest age group and with no clinical evidence suggests that HCV infection is a very prolonged and indolent disease.

Siesta, night sleep and blood pressure dropping.

BACKGROUND: The drop in blood pressure during the night sleeping hours is well documented. Less is known about the drop in blood pressure during daytime sleep. The objective of this survey is to describe the dropping during conventional and referred sleeping hours of night and afternoon sleep, and the relation of the dropping to individual characteristics.METHODS: One hundred and seven consecutive patients, who had undergone blood pressure monitoring between February 1993 and October 1994, were studied. Takeda automatic monitors programmed to provide readings at 0.5 h intervals during a period of 24 h were used. For each patient the following information was recorded: age, sex, height and weight, creatinine, and actual sleeping hours recorded on a diary. RESULTS: There was a clinically important decline both in diastolic (12 mmHg) and in systolic (15 mmHg) blood pressure during night sleep compared with awake time blood pressure. A greater decline was observed among untreated hypertensive individuals. No difference in the average blood pressure during the night sleep was observed between conventional sleeping hours and sleeping hours as recorded by the patient. Among patients with afternoon nap, a similar blood pressure was recorded during the sleeping hours (night and afternoon). No association was found between body mass index, estimated creatinine clearance and awake-asleep differences in blood pressure; only a weak correlation was found between age and blood pressure differences. CONCLUSION: Our findings confirm that a substantial decline of blood pressure occurs during night and afternoon sleep compared with that during awake time. We did not find a clinically relevant difference in blood pressure between conventional day-periods and awake and sleeping hours as reported by the patients.

Prevalence of hepatitis E in a central Italian town at high endemicity for hepatitis C virus.

In the spring of 1994, the occurrence of Hepatitis E virus antibodies was evaluated in 653 subjects representing all age-groups in the general population of a Central Italian town, where a high hepatitis C virus prevalence had been reported. The overall anti-HEV prevalence was 2.6% ranging from 1.4% in the 30-49 age-group to 5.7% (p < 0.01) in the 60-70 age-group; none of the subjects under 30 years of age were positive. Sociodemographic variables, such as family size and years of schooling were not associated with HEV exposure. Anti-HEV positivity was found in 1.8% (1/56) of the subjects who were positive for anti-HCV and in 2.7% (16/597) of those who were anti-HCV negative (O.R 1.5; C.I.: 95% = 0.2-11.7). Thus no association was found between HEV and HCV infections. These data suggest a past spread of HEV in this area and underline the occurrence of long-lasting antibodies in infected subjects.

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.

Estimate of parkinsonism prevalence through drug prescription histories in the Province of Rome, Italy.

INTRODUCTION: The objective of the study was to estimate the prevalence of parkinsonism in the Province of Rome using antiparkinsonian prescription histories from 1986 to 1991. METHODS: A subject was defined as a case of parkinsonism if he/she had received "specific" and "consistent" antiparkinsonian therapy in the study period. RESULTS: In November 1990, 6,572 patients were defined as prevalent cases of parkinsonism. The crude prevalence ratio, for the total population of the Province of Rome, is 173.5 per 100,000 inhabitants (165.9 per 100,000 in men and 180.5 per 100,000 in women). The method was validated by record-linkage with clinical records of all patients visited during 1990 at the Department of Neurological Sciences of the University of Rome "La Sapienza". The sensitivity of the prevalence study was 83.6%. CONCLUSIONS: The use of a computerized data base of all prescription data, routinely collected for administrative purposes, enabled us to obtain a prevalence estimate based on a very large population, with low costs and in a relatively short time.

Anticholinergic antiparkinsonian therapy in outpatients treated with neuroleptic drugs: a prescription survey.

Extrapyramidal adverse effects (EPAs) due to neuroleptic treatment are routinely treated with anti-cholinergic antiparkinsonian drugs (APDs). We studied the use of these drugs in the general population exposed to neuroleptic drugs to improve our knowledge of the epidemiology of EPAs. We selected all the neuroleptic and antiparkinsonian drug prescriptions delivered in the province of Rome (ca. 3,750,000 inhabitants) from 1986 to 1989. During the study period, 10.6% of neuroleptic-treated subjects were concurrently prescribed anticholinergic antiparkinsonian drugs. The influence of different factors on APD prescriptions was evaluated through a logistic regression model. The highest probability of receiving APDs was associated with trifluperidol treatment (odds ratio = 5.0, using chlorpromazine as baseline); among the commonly prescribed neuroleptics, sulpiride, levosulpiride and tiapride chlorydrate had the lowest probability of coprescription with APDs (odds ratios less than 0.1). The probability of being prescribed anticholinergic antiparkinsonian drugs decreased with age and increased with the amount of neuroleptics prescribed. This study surveys a very large sample using a population-based approach, whereas the same topics have previously only been studied in limited inpatient populations.