Analysing policy interventions to prohibit over-the-counter antibiotic sales in four Latin American countries.

OBJECTIVES: To describe and evaluate policies implemented in Chile, Colombia, Venezuela and Mexico (1995-2009) to prohibit antibiotic OTC sales and explore limitations in available data. METHODS: We searched and analysed legislation, grey literature and peer-reviewed publications on regulatory interventions and implementation strategies to enforce prohibition of OTC antibiotic sales. We also assessed the impact using private sector retail sales data of antibiotics studying changes in level and consumption trends before and after the policy change using segmented time series analysis. Finally, we assessed the completeness and data quality through an established checklist to test the suitability of the data for analysis of the interventions. RESULTS: Whereas Chile implemented a comprehensive package of interventions to accompany regulation changes, Colombia's reform was limited to the capital district and Venezuela's limited to only some antibiotics and without awareness campaigns. In Mexico, no enforcement was enacted. The data showed a differential effect of the intervention among the countries studied with a significant change in level of consumption in Chile (-5.56 DID) and in Colombia (-1.00DID). In Venezuela and Mexico, no significant change in level and slope was found. Changes in population coverage were identified as principal limitations of using sales data for evaluating the reform impact. CONCLUSION: Retail sales data can be useful when assessing policy impact but should be supplemented by other data sources such as public sector sales and prescription data. Implementing regulatory enforcement has shown some impact, but a sustainable, concerted approach will be needed to address OTC sales in the future.

The effects of abrupt antipsychotic discontinuation in cognitively impaired older persons: a pilot study.

BACKGROUND: Antipsychotic use for behavioural and psychological symptoms of dementia (BPSD) is controversial. Guidelines advise to reduce antipsychotics given the adverse effects and limited efficacy, to limit dose and treatment duration as well as to undertake discontinuation. METHODS: A pilot study with 40 hospitalised geriatric cognitively impaired patients, in which the effects of abrupt antipsychotic discontinuation were investigated, using neuropsychiatric inventory (NPI) scores before and one month after discontinuation. Withdrawal symptoms were monitored thrice a day with a checklist during five consecutive days. RESULTS: Participants (n = 40) had a mean age of 84 years (range 67-95) and 53% were male. The total mean baseline NPI score was 21 (SD 12) with predominantly behavioural rather than psychological disturbances. After abrupt discontinuation, mild withdrawal symptoms were observed in 72% of the patients, with frequencies of symptoms peaking on day 2 (53%) and day 3 (48%). After one month, 31 patients (85%) were still off antipsychotics and improved on the majority of NPI domains, with a total mean NPI score decreasing from 18 (SD 13) to 12 (SD 8, p = 0.003). In the relapse group, there was no deterioration associated with the abrupt discontinuation and subsequent resumption of therapy with a total mean NPI score decreasing from 31 (SD 12) at baseline to 27 (SD 8) at one-month follow-up (p = 0.345). CONCLUSION: Abrupt antipsychotic discontinuation appears to be feasible in older individuals with BPSD. Systematically performed discontinuation efforts in clinical practice are needed to differentiate between patients where antipsychotics have no added value and patients where the benefits outweigh the risks.

Implementing and optimising an Electronic Library of Health Care in Belgium: results of a pilot study.

Health care practitioners are expected to incorporate results from the best available, scientific information into their daily clinical decision-making process. Useful formats of evidence for practitioners include selected reviews, abstracts in which research results are discussed, "quick answer", evidence-based website including for example diagnostic and therapeutic algorithms, drugs prescription and non-drug therapy. An increasing amount of practitioners has access to the World Wide Web, either at home or at the office. However, easy and cheap access to objective and high quality research results is limited. Many practitioners lack the skills to efficiently navigate complicated medical databases. In 2003 an 'Electronic Library of Health Care' was introduced in Belgium. The main goal of the electronic library is to provide a gateway to scientific evidence to Belgian health care practitioners from different disciplines. This paper presents the results of a pilot project to implement the library in the field. It also describes recent developments and adjustments that increased the efficacy of this gateway to evidence.

Hospital consumption of antibiotics in 15 European countries: results of the ESAC Retrospective Data Collection (1997-2002).

OBJECTIVES: To collect reliable, comparable and publicly available data on hospital use of antibiotics in Europe aggregated at the national level (1997-2002). METHODS: Consumption data of systemic antibiotics in Anatomical Therapeutic Chemical (ATC) class J01 were collected and expressed in defined daily doses (DDD) per 1000 inhabitants per day. Valid data for 2002 were available for 15 countries, and 6 year trends for 10 countries. Comparison with ambulatory care (AC) consumption data was possible in 14 countries. RESULTS: In 2002, median national hospital antibiotic consumption in Europe was 2.1 DDD/1000 inhabitants/day in Europe, ranging from 3.9 in Finland and France to 1.3 in Norway and Sweden. Hospital care (HC) consumption as a proportion of total antibiotic consumption ranged from 17.8% to 6.4%. The consumption of hospital-specific antibiotics ranged from 0.43 DDD/1000 inhabitants/day in Greece and 0.08 in Sweden. Six-year trends in consumption were stable, except for rising co-amoxiclav exposure and more rapid market penetration of new antibiotics (e.g. levofloxacin) in some countries. There was a strong, positive correlation between the extent of antibiotic use in AC and in HC (Spearman coefficient 0.745; P = 0.002), both for overall use and for use of five main classes (not macrolides and 'others'). In contrast to AC consumption no substantial seasonal variation in consumption was observed. CONCLUSIONS: It was cumbersome but feasible to collect ecological data on hospital antibiotic consumption in a set of 15 European countries on a retrospective basis, illustrating substantial cross-national variations in the extent and distribution of exposure to antibiotics in hospital care.

Indicators of prescribing quality in drug utilisation research: report of a European meeting (DURQUIM, 13-15 May 2004).

An invitational expert meeting on indicators of prescribing quality was held on 13-15 May 2004, bringing together--from 19 European countries, the US, Canada, and Australia--40 researchers specialized in the development and application of indicators. The meeting was organized by the European Drug Utilization Research Group (EuroDURG), the Belgian National Health Insurance Institute (RIZIV-INAMI), and the World Health Organisation Regional Office for Europe (WHO-Euro). The field of prescribing quality was defined and delineated from the medical error field. A conceptual grid for classifying quality indicators was discussed, combining two axes (a drug/disease/patient axis and a structure/process/outcome axis). In addition, available databases were listed for continuous monitoring of drug utilization in Europe, with a description of the content and the richness of the collected data, as well as the impact on the potential and limitations to develop quality indicators. The importance of the origin of data for validity assessment was stressed, as data on drug utilization may originate from physician sources (prescribing data), from pharmacist or health insurer sources (distribution data), or directly from patient sources (compliance data). The different aspects of validity and their methods of assessment were listed. An overview of the (in)appropriate uses of indicators was given. The state of the art of the development and application of prescribing quality indicators in all represented countries was made, together with a first draft of a database of prescribing quality indicators, already subjected to validation procedures.

European surveillance of antimicrobial consumption (ESAC): data collection performance and methodological approach.

BACKGROUND: Europe is a continent with strong public healthcare systems, but diverging antibiotic policies and resistance patterns. AIMS: To describe the performance and methodological approach in a retrospective data collection effort (1997-2001), through an international network of surveillance systems, aiming to collect publicly available, comparable and reliable data on antibiotic use in Europe. METHODS: A central multidisciplinary management team co-ordinated a network of national representatives, liasing with national data providers and bodies responsible for antibiotic policy. The data collected were screened for bias, using a checklist. We focused on detection bias in sample and census data; errors in assigning medicinal product packages to the Anatomical Therapeutic Chemical Classification (ATC); errors in calculations of defined daily doses (DDD) per package; bias by over-the-counter sales and parallel trade; and bias in ambulatory care (AC)/hospital care (HC) mix. Datasets were corrected after national feedback, and classified as valid; valid but with minor bias; not valid. RESULTS: Of the 31 participating countries, 21 countries delivered AC data suitable for cross-national comparison (14 for all 5 years). Of these, 17 countries provided data on a quarterly basis for at least 1 year. For HC, 14 countries were able to deliver valid data (nine for all 5 years). A valid estimate of the total exposure of national populations to human antibiotic consumption could be made in 17 countries. CONCLUSION: In cross-national comparisons of antibiotic consumption in Europe, methodological rigour in correcting for various sources of bias and checking the validity of ATC/DDD assignment is needed.

Drugs used for euthanasia in Flanders, Belgium.

PURPOSE: Our aim was to describe and assess the medicinal products and doses used for euthanasia in a series of cases, identified within an epidemiological death certificate study in Belgium, where euthanasia was until recently legally forbidden and where guidelines for euthanasia are not available. METHODS: In a random sample of the deaths in 1998 in Belgium, the physicians who signed the death certificates were identified and sent an anonymous mail questionnaire. The questionnaires of the deaths classified as euthanasia cases were reviewed by a multi-disciplinary panel. RESULTS: A total of 22 among 1925 questionnaires pertained to voluntary euthanasia. In 17 cases, detailed information on the euthanatics (medicinal substances used for euthanasia) used was provided. Opioids were used in 13 cases (in 7 as a single drug). Time between last dose and expiry ranged from 4 to 900 min. The panel judged that only in 4 cases effective euthanatics were used. CONCLUSIONS: In the end-of-life decision cases perceived by Belgian physicians as euthanasia, pharmacological practices were disparate, although dominated by the use of morphine, in the very late phase of dying, in doses which were unlikely to be lethal. Most physicians clandestinely engaging in euthanasia in Belgium seemed unaware of procedures for guaranteeing a quick, mild and certain death. Information on the pharmacological aspects of euthanasia should be included in the medical curriculum and continuing medical education, at least in countries with a legal framework permitting euthanasia under specified conditions.

Attitudes, sociodemographic characteristics, and actual end-of-life decisions of physicians in Flanders, Belgium.

AIM: To study the effect of sociodemographic and attitudinal determinants of physicians making end-of-life decisions (ELDs). METHODS: The physicians having signed 489 consecutive death certificates in the city of Hasselt (Belgium) were sent an anonymous questionnaire regarding their ELDs and another on their attitudes toward voluntary euthanasia (EUTH) and physician-assisted suicide (PAS). RESULTS: 55% response rate. Nontreatment decisions occurred in 16.7% of all death cases; in 16%, there was potentially life-shortening use of drugs to alleviate pain and symptoms; in 4.8% of cases, death was deliberately induced by lethal drugs, including EUTH, PAS, and life termination without explicit request by the patient. In their attitudes toward EUTH and PAS, the 92 responding physicians clustered into 3 groups: positive and rule oriented, positive rule-adverse, and opposed. Cluster group membership, commitment to life stance, years of professional experience, and gender were each associated with specific ELD-making patterns.

A decade of growth in public and private pharmaceutical expenditures: the case of Belgium 1990-1999.

OBJECTIVE: To make a systematic, transparent, internationally comparable description of trends (1990-1999) in total, public and private (co-payment + out-of-pocket) spending on pharmaceuticals in Belgium. SETTING: Belgium, a western European country, with a Bismarck-type universal coverage healthcare system. NATURE OF THE STUDY: Descriptive analysis of time-series. METHODS: Collaborative data gathering effort between academic and private research institutes and IMS health. RESULTS: Mean annual growth rate was 3.9% for total, 5.3% for public, and 2.0% for private drug expenditures (expressed in constant 1999 EUR). The ratio of public to private spending shifted from 53.4% to 60.3%. Of the private spending, one third was co-payment for reimbursed medication and two thirds was out-of-pocket payment for non-reimbursed medication. CONCLUSION: Co-operation between several data gathering constituencies within one country was necessary to achieve completeness and detail in data collection on out-of-pocket payments for non-reimbursed medicines, and hence in total drug expenditures. Discrepancies were found between the estimate of the public/private mix and OECD health data 2000 for public drug spending.

Wet combing for head lice: feasibility in mass screening, treatment preference and outcome.

There is no scientific consensus on the best way to control head louse infestation in schoolchildren. A study was conducted to test the feasibility and acceptability of a screening campaign by wet combing and a community approach to head-louse control with home visits, and to explore parents' treatment preferences and treatment outcomes. A non-controlled intervention (advice on treatment options offered to all positive children) was nested within an epidemiological prevalence study. All children in three primary schools in Ghent, Belgium, were invited to take part in screening by wet combing (n=677, 3-11 years). Positive children were offered structural treatment advice, a home visit on day 7, and a check by wet combing on day 14. 83% of the children were screened. The prevalence of active infestation (living moving lice) was 13.0% in school 1 and 19.5% in school 3. In school 2, prevalence of signs of active and past infestation was 40.7%. A home visit was made to 58% of the positive children. 85% of the positive children were screened again on day 14. Wet combing was the most widely used treatment, followed by chemical treatment and a combination of the two. In school 1 and 3 51% were cured, and in school 2 24% became nit-free. A wet combing screening campaign and a community-oriented approach to head-louse control is feasible though resource-intensive. The prevalence of head lice was high and the cure rate was low, with either topical treatments or wet combing.

Buflomedil for intermittent claudication.

BACKGROUND: Intermittent claudication is pain, caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent claimed to have beneficial effects on the microcirculation. It is used chiefly to treat peripheral vascular disease and to a lesser extent for cerebrovascular arterial disease. However, its clinical efficacy for intermittent claudication has not yet been critically examined. OBJECTIVES: To evaluate the available evidence on the efficacy of buflomedil for intermittent claudication. SEARCH STRATEGY: We searched Medline, International Pharmaceutical Abstracts (IPA) and the Cochrane Controlled Trials Register. Abbott Laboratories, the distributor of buflomedil, was asked to provide reports of controlled clinical trials. Reference lists of retrieved articles were checked, and enquiries sent to authors of known trials, to identify additional trials. Finally, we conducted a Science Citation Index search. SELECTION CRITERIA: Trial reports had to be double-blinded, randomized, and conformed to our PIO-criteria (Patients, Intervention, Outcome) to be considered for inclusion. Patients were required to have proven intermittent claudication (Fontaine stage II); the intervention was to be oral administration of buflomedil compared to placebo; and outcomes had to include pain-free walking distance (PFWD) and maximum walking distance (MWD) analysed by standardized exercise test. DATA COLLECTION AND ANALYSIS: Searches of bibliographic databases yielded three eligible randomized controlled trials (RCTs) and a meta-analysis referring to nine eligible trials. Two of these nine trials had already been identified; two had been published in journals not referenced in traditional bibliographic indexes; and five were unpublished. Despite multiple requests, only one of the five unpublished trials was provided by the author of the meta-analysis, the other four could not be retrieved. Four of the six eligible trials retrieved were subsequently excluded after quality evaluation. Data on walking distances were extracted from the two remaining trials. Differences in incremental gain between active and placebo groups for PFWD and MWD with their confidence intervals were calculated. MAIN RESULTS: Both RCTs showed moderate improvements in PFWD for patients on buflomedil. In one trial this improvement (75 m, 95% CI 37-114) was statistically significant, but in the other, with a wholly diabetic population, it was non-significant (81m, 95% CI -9-170) compared to placebo. For both RCTs the gains in MWD were statistically significant, but with wide confidence intervals (81 m, 95% CI 30-131; and 171 m, 95% CI 27-316 respectively). Pooling of the data was not attempted. REVIEWER'S CONCLUSIONS: There is little evidence available to evaluate the efficacy of buflomedil for intermittent claudication. Most available trials are of poor quality and were excluded. The two trials included showed moderately positive results but these are undermined by publication bias since we know of another four unpublished, irretrievable, and inconclusive studies. There is a lack evidence for the efficacy of buflomedil in intermittent claudication.

Ethical issues in pharmacoepidemiological research in Belgium.

PURPOSE: To illustrate the ethical issues faced in pharmacoepidemiological research in Belgium. METHODS: The experience with three studies is described. The studies concern the use of drugs for euthanasia in medical practice, cytomegalovirus infection in single solid organ transplants and a comparison of benzodiazepine use in the general population and in acute self-poisoning. RESULTS: With some creativity, it was possible to meet the requirements of the ethics committees and the law on computer databases, e.g. by bringing data validation closer to the data entry process, by assuring anonymity in mailing procedures, or by deleting identification labels as soon as they are no longer necessary. CONCLUSIONS: The existing juridical vacuum has not really impeded pharmacoepidemiological research.

Oral vasoactive medication in intermittent claudication: utile or futile?

OBJECTIVE: To evaluate the role of orally administered vasoactive medication in the management of intermittent claudication. SETTING: We limited our study to the products on the market in Belgium: cinnarizine, cyclandelate, isoxsuprine, naftidrofuryl, pentoxifylline, xanthinol nicotinate and buflomedil. DATA SOURCES: We conducted a systematic literature search involving Medline, International Pharmaceutical Abstracts, the Cochrane Library, direct contact with marketing companies and key authors, snowballing and Science Citation Index search. We looked for randomised placebo-controlled trials (RCTs) in patients with Fontaine stage II, in which pain-free and/or maximal walking distance were measured using a standardised exercise test. For isoxsuprine and xanthinol nicotinate, no trials conforming to these criteria were found. Thirty-six trials on cinnarizine, cyclandelate, buflomedil, naftidrofuryl and pentoxifylline met our inclusion criteria. STUDY SELECTION: After quality assessment, 26 trials were excluded, mainly because of short trial duration (less than 12 weeks), small sample size (less than 30 patients) and/or failure to report details on variability (standard deviation or confidence limits). For cinnarizine and cyclandelate, none of the three selected RCTs was included. DATA EXTRACTION: For buflomedil, of six published RCTs, two were included after quality assessment, each showing a marginally positive effect of buflomedil versus placebo. For naftidrofuryl, nine RCTs were selected; six were included of which five showed a significant positive result. The likelihood of publication bias and the heterogeneity of the results within and between trials precluded a meta-analysis. For pentoxifylline, of the 18 selected RCTs, only two could be included, both with inconclusive results. CONCLUSION: A national consensus conference, based on this review, concluded that health resources should be allocated to prevention and rehabilitation of intermittent claudication rather than to reimbursement of these products with doubtful efficacy.

Systematic review of clinical efficacy of topical treatments for head lice.

OBJECTIVES: To collect and evaluate all trials on clinical efficacy of topical treatments for head lice. DESIGN: Systematic review of randomised trials identified from following data sources: Medline, International Pharmaceutical Abstracts, Science Citation Index, letters to key authors and companies, and hand search of journals. SETTING: Trials in schools or communities. SUBJECTS: Patients infested with lice. MAIN OUTCOME MEASURE: Cure rate (absence of live lice and viable nits) on day 14 after treatment. RESULTS: Total of 28 trials were identified and evaluated according to eight general and 18 lice specific criteria. Of the 14 trials rated as having low to moderate risk of bias, seven were selected as they used the main outcome measure. These seven trials described 21 evaluations of eight different compounds and placebo (all but two evaluations were of single applications). Only permethrin 1% creme rinse showed efficacy in more than two studies with the lower 95% confidence limit of cure rate above 90%. CONCLUSIONS: Only for permethrin has sufficient evidence been published to show efficacy. Less expensive treatments such as malathion and carbaryl need more evidence of efficacy. Lindane and the natural pyrethrines are not sufficiently effective to justify their use.

Medication utilization and patient information in homes for the aged.

A random cross-sectional sample of 198 residents was taken from a convenience sample of 20 Flemish, community-based nursing homes for the aged. Twenty trained interviewers reviewed the medication list of these residents and interviewed the nurses responsible for their daily care to assess their activities of daily living (ADL) and cognitive status. Direct interview was possible of 128 residents (65%); communication with the other 70 residents was impossible because of dementia (55 patients) or communication problems, such as aphasia and deafness (15 patients). An average of 4.5 different medicines was mentioned on the medication lists of the 198 residents. Drug use increases with age but stabilises after the age of 80 y. Medicines are ordered from local community pharmacies and are delivered to the ward rooms in original drug dispensing packs. The nursing staff is responsible for distribution inside the institution. Nursing personnel read the inserts of the medicines given to 98% of the residents and keep the inserts of 77% in the nursing office. Only 11% of the residents maintained some autonomy in ordering, keeping and taking their medication, although 42% were evaluated by the nurses as functionally and cognitively fit. Only 4% of the 128 residents able to respond to an interview had a notion of the potential adverse effects of their medication; the two most important sources of information about medicines mentioned by those residents were the general practitioner and the nursing personnel; 4% mentioned relatives and friends, or the pharmacist, as information sources.

Attitude of the public toward technical package inserts for medication information in Belgium.

We designed an 84-item questionnaire to determine the attitude of the Belgian public toward package inserts (PI) for medication information, written in technical language and intended for health professionals, within an original drug-dispensing distribution system. There were 398 respondents to this general public survey, based on a 0.05 percent selection from election registers of the districts of Gent and Liège. Eighty-nine percent of the respondents read the PI, focusing their attention principally on adverse effects (88 percent), dosage and dosing guidelines (85 percent), contraindications (82 percent), indications (79 percent), and medication shelf-life (76 percent). Compliance (83 percent), reassurance (57 percent), increased knowledge about the medication (50 percent), and decision to take the medicine (31 percent) were among the respondents' motives for reading the PI. Most respondents considered the PI information useful and complete, but difficult to remember and understand. Readers further criticized its legibility and poor graphic illustration. The PI was seen as a supplementary source of information, instrumental to the physician-pharmacist-patient relationship, without the power to overrule the physician's or pharmacist's instructions. Some respondents reported that the PI made them afraid to use the medication. Expectations for the ideal PI were contradictory and can only be met with a never-optimal compromise between comprehensiveness and conciseness.