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There are few studies on the personal view retrieved by patients in the spontaneous reports’ free-text section of suspected adverse drug reactions. We analysed the suspected adverse drug reactions (ADRs) spontaneous reports sent to the Catalan Centre of Pharmacovigilance between 2013 and 2017. The information provided in the free-text section was classified as (1) temporal sequence, (2) description of symptoms, (3) description of psychological impact, (4) withdrawal effects, (5) alternative causes, and (6) rechallenge. The concordance level between the perceived severity by the reporter and the pharmacovigilance team was assessed by the Kappa index (ƙ). Usual descriptive statistics were used to describe variables. Nationally, 190 spontaneous reports described 383 ADRs, which 28.6% were unknown or poorly known in the literature, and 52.1% were serious. The most frequent ADRs were gastrointestinal (19.3%) and neurological (19.1%), and among the most common 213 suspected medicines, there were those used for nervous system conditions (18.8%). The agreement on the perception of ADRs’ severity between citizens and centre’s technicians was ‘good’ (K = 0.62 (0.51–0.72)). An analysis of the free-text section of reports showed that one-quarter of the reports provided useful additional data, like the psychobiosocial impact, which could explain the discrepancy between patients and health professionals in the classification of the severity of some ADRs. Patients’ report free-text section provides relevant information, mainly about symptoms description, psychobiosocial impact and feelings. Therefore, it is a section to be enhanced and analysed. These findings should encourage the strengthening of citizens reporting.

The incidence of thyroid disfunction has not been analyzed in critically ill COVID-19 patients. Our objective was to analyze the relationship of the thyroid profile and in-hospital mortality in critically ill COVID-19 patients. This was a prospective single-center study involving critically ill COVID-19 patients admitted to the ICU of a tertiary University Hospital. Thyroid hormones were measured through drawing blood samples from a central venous catheter at ICU admission and on the fifth day. A multiple logistic regression analysis was performed to analyze the variables associated with mortality. The ability of the different thyroid hormones to predict in-hospital mortality was evaluated by calculating the receiver operating characteristics (ROCs) and the area under the curve (AUC). A total of 78 patients were included in the study at ICU admission, 72 had their thyroid profile measured at day 5. In-hospital mortality reached 29.5%. Multiple logistic regression analysis showed that variables associated with mortality were age and prior beta-blocker therapy at ICU admission and age fT4 at day 5. The AUC for in-hospital mortality predictions of fT4 at day 5 was 0.69. Thyroid responses are commonly observed in critically ill COVID-19 patients. fT4 at day 5 after ICU admission was associated with mortality.

(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and Pharmacovigilance (PV) has the potential to strengthen current antimicrobial stewardship (AMS) strategies. This study aimed to characterise AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre (Lareb); (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs).; (3) Results: Between 1998 and Jan 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n=89; 35%), colistin (n=30; 11,9%), ciprofloxacin (n=16; 6,35%), doxycycline (n=14; 5,5%) and aztreonam (n=12; 4,76%). The most frequently used PTs were drug ineffective (n=71; 28%), pathogen resistance (n=14; 5%) and drug resistance (n=13; 13%). A total of 119 reports (74%) suggested use-related issues. Watch antibiotics were in 54% of the reports and Reserve antibiotics were in 19%. In the Watch group, “Off label use” and “Product use in unapproved indication” were the most frequent PTs and majority of reports on Reserve antibiotics were coded as “Off label”. (4) Conclusions: Addressing AMR using the PV methods will provide an opportunity for PV expansion and could encourage further investment in both in AMS programs and PV systems.

To evaluate the clinical outcomes of daptomycin therapy and adherence to treatment recommendations, a retrospective cohort study was conducted with patients that received daptomycin during the period of the study. The adherence and nonadherence to clinical guidelines were assessed through organism identification, dose and time of treatment, management of bacteremia, and vancomycin treatment failure. A multiple logistic regression model analyzed the association between independent variables and clinical success (dependent variable), considering 5% of statistical significance. The study presented 52 patients who received daptomycin for the treatment of bacteremia (21.1%) or infections (osteomyelitis [63.5%], synovial fluid [15.4%]). Most patients (86.5%) received daptomycin as the second line of treatment, and 51.9% achieved clinical success. The patients had a better chance of clinical success when they followed the guideline indications (OR = 16.86; 95% CI = 1.45-195.88) and the medication was prescribed by a specialist in infectious diseases (OR = 4.84; 95% CI = 1.11- 21.09). The study demonstrated lower clinical success than that described in the literature because of patients who were not eligible according to the clinical guidelines. Adherence to recommendations and appropriate prescription of reserve antibiotics is important in limiting early resistance, and avoiding clinical failure and unnecessary expenditure.

Funding: The deprescribing tool was supported by Colciencias contract (110177758303 CT-792-2018) and Doctoral Fellowship Program 647-2015 The aim of this study was to develop and validate a stepwise tool to aid primary health care professionals in the process of deprescribing potentially inappropriate medication in older persons. We carried out a systematic review to identify previously published tools. A composite proposal of algorithm was made by following the steps from clinical experience to deprescribe medications. A 2-round electronic Delphi method was conducted to establish consensus. Eighteen experts from different countries (Colombia, Spain and Argentina) accepted to be part of the panel representing geriatricians, internists, endocrinologist, general practitioners, pharmacologists, clinical pharmacists, family physicians and nurses. Panel members were asked to mark a Likert Scale from 1 to 9 points (1= strongly disagree, 9= strongly agree). The content validity ratio, item-level content validity, and Fleiss' Kappa statistics was measured to establish reliability. The same voting method was used for round 2. A 7-question algorithm was proposed. Each question was part of a domain and conduct into a decision. In round 1, a consensus was not reached but statements were grouped and organized. In round 2, the tool met consensus. The inter-rater reliability was between substantial and almost perfect for questions with Kappa=0.77 (95% CI 0.60-0.93), for domains with Kappa= 0.73 (95%CI 0.60-0.86) and for decisions with Kappa= 0.97 (95%CI 0.90-1.00). This is a novel tool that captures and supports healthcare professionals in clinical decision-making for deprescribing potentially inappropriate medication. This includes patient's and caregiver's preferences about medication. This tool will help to standardize care and provide guidance on the prescribing/deprescribing process of older persons' medications. Also, it provides a holistic way to reduce polypharmacy and inappropriate medications in clinical practice.

Background: In Uganda, national tuberculosis (TB) treatment guidelines were revised to include the newer generation fluoroquinolones among the second-line treatment options for multidrug-resistant TB. This study was designed to analyze if the prescription of these quinolones is compliant with country recommendations. Methods: This was an observational retrospective study of consumption data for 2017 and 2018 across four selected regional referral hospitals. The sources of consumption data were hospital pharmacy stock cards and the dispensing register. The medical files of patients who had been prescribed fluoroquinolones were also assessed to study compliance with the Uganda Clinical Guidelines and the British National Formulary (BNF). Results: None of the 371 levofloxacin prescriptions analyzed complied with the Uganda Clinical Guidelines, although 250 (67.3%) were prescribed for indications included in the BNF. According to WHO prescription indicators, only 220 (59.3%) prescriptions were appropriate. Conclusion: The prescription of levofloxacin and moxifloxacin increased in the hospitals studied, but in a high proportion of cases, they were not compliant with country recommendations. The findings call for the strengthening of national antimicrobial stewardship programs.

The study aimed to identify and describe adverse drug reactions and adherence to clinical guidelines in patients receiving treatment for type 2 diabetes mellitus (T2DM) in Cameroon. The method used was a cross-sectional study at a tertiary diabetes care service in Yaounde, Cameroon. Adult T2DM patients attending the diabetes clinic were interviewed using a pre-structured data collection form. Adverse drug reactions (ADRs) were self-reported by the patients. Naranjo’s algorithm and Hartwig and Siegel’s scale were used for assessment of causality and severity of ADRs, respectively. A blinded senior endocrinologist assessed whether treatment pattern of patients was “adherent” or not to local clinical guidelines for the management of diabetes. Of a total of 350 patients enrolled into the study 61.1% were on oral hypoglycaemic agents only, 24.9% were on both oral hypoglycaemic agents and insulin, while 13.4% were on insulin alone. Metformin was used by 96.3% of the patients. Ninety patients reported 101 suspected ADRs. The proportion of ADRs among patients with poor adherence to clinical guidelines was higher than ADRs reported among adherent patients (Chi-square test = 7.3273; p = 0.007). Hypoglycaemia was more frequent ADR among non-adherent (25.7% of the suspected ADR) than adherent participants (11.6%). In the participants whose treatment pattern did not adhere to local clinical guidelines, ADRs were definite in 63.9%, probable in 16.6%, doubtful in 13.9% and possible in 5.6% of the cases. ADRs were moderate in 61.1% and severe in 19.4% of cases whose treatment pattern was non-adherent to clinical guidelines. Adverse drug reactions may be frequent in type 2 diabetes patients whose treatment pattern does not adhere to local clinical guidelines in Cameroon. Therefore, the promotion of active pharmacovigilance and the design of training activities to promote the appropriate use of medicines at hospital level in Cameroon could help to improve the management of diabetes and reduce the incidence of avoidable ADRs in the future.

Background Previous studies in Europe and the USA have reported a high prevalence of adverse drug reactions (ADRs), but data on local ADRs in Myanmar are sparse. Objective Our objective was to study ADRs in patients admitted to selected wards of Yangon General Hospital (YGH) and Yangon Specialty Hospital (YSH), Myanmar. Methods This was a prospective observational study in three hospital wards during the first quarter of 2019. Suspected ADRs were carefully investigated in a face-to-face interview with each patient and via review of clinical records. Patients transferred to other wards or discharged were followed-up by the researchers until day 28 after admission. ADRs were divided into those that (1) led to the admission and (2) occurred during the hospital stay or after discharge (up to day 28 after admission). Results A total of 65 ADRs were identified, with 47 (29.4%) of 160 patients experiencing at least one ADR. Among these, 16 (24.6%) had led to hospital admission and 49 (75.4%) occurred in 31 patients during their hospital stay. Of 160 patients, 21 had taken at least one herbal remedy and six of these developed an ADR. Five ADR–drug associations (hypokalaemia with methylprednisolone, increased transaminase levels with standard antituberculosis drugs, upper gastrointestinal bleeding with nonsteroidal anti-inflammatory drugs, constipation with tramadol, and increased transaminase levels with herbal remedies) represented 18 (27.7%) of the 65 ADRs in this study. According to the Schumock and Thornton preventability scale, more than half of these ADRs (35 [53.9%]) were preventable. Conclusion The present study highlights the existence of ADRs among patients attending these hospitals. The implementation of active pharmacovigilance in hospitals could be a helpful first step to improving the awareness of unwanted effects of medicines and patient safety, as well as a way to strengthen the national pharmacovigilance system in countries such as Myanmar. Electronic supplementary material The online version of this article (10.1007/s40801-020-00180-0) contains supplementary material, which is available to authorized users.

The completeness and accuracy of the reports of suspected adverse drug reactions is important in pharmacovigilance. The aim of the present study was to analyze the quality of the information included in the reports sent to the Pharmacovigilance Centre of São Paulo (Brazil).A sample of 999 reports received from January 2013 to December 2014 was selected. The quality of the filled information was evaluated according to a 'sufficiency' criterion to apply the Karch-Lasagna causality algorithm.There were 820 reports from manufacturers and 179 from health centres. Only 4.4% (44) were fully filled, thus allowing the adequate analysis of the causal relationship between the suspected medication and the adverse event. In 30% of the reports from manufacturers, the information about the critical variables was lacking or incomplete, preventing the adequate evaluation of the report. It was also noted that the reports' poor filling quality was not related with less severity or with old and well-known medicines.The poor quality of the information included in the reports received by this centre, especially those sent by pharmaceutical manufacturers, hampers the identification of potential safety signals. Measures to improve the quality of the reports must be urgently adopted.

The widespread use of dopaminergic agents for the treatment of Parkinson's disease has revealed the presence of gambling disorder (GD) as an uncommon, but serious, adverse reaction to these agents. We describe the main characteristics of drug-induced GD reports received by the Spanish Pharmacovigilance System during the period from 1983 to 2016. Fifteen reports of GD have been identified. Dopaminergic agonists, especially pramipexole, are the main drugs involved in inducing GD. Physicians prescribing these drugs should warn patients and families about this disorder. Knowledge of this disorder will encourage early diagnosis, treatment, and reporting of this clinically and socially relevant disorder.

Introduction Selling antibiotics without prescription is common in many countries; beyond the administrative restrictions, this practice is a risk for patients and society. The aim of the study was to evaluate the information provided by the staff of the pharmacy to a simulated patient requesting an antibiotic. Material and methods A prospective study was carried out in January 2013 – February 2014 in the Health Region of Tarragona, in which a mystery shopper visited 220 pharmacies requesting an antibiotic to be sold. Results The actress was not asked about allergies in 73.9% of cases and never was asked about possible pregnancy. Recommendation to see a doctor was observed in 36.1% of cases. When antibiotics were not sold, the explanation provided by the staff was reasoned only in 9.9% of the cases. Conclusion It is necessary and urgent to improve the training of pharmacists in dispensing antibiotics but also strengthen basic health knowledge among the population.

Historically, somatropin has been used for conditions related with ageing, but since the marketing of recombinant human growth hormone (rhGH), increasing promotional pressure has prompted aesthetic uses, despite lack of evidences about its efficacy and safety for those purposes. A routine analysis of the Pharmacovigilance Center of Sao Paulo (Brazil) showed reports of suspected adverse reactions in young adults and mature patients receiving rhGH. After presuming an off-label use of this expensive product, a drug utilisation study within the pharmacovigilance database has been carried out. The analysis showed a bimodal age distribution of the rhGH reports. Up to 17.1% of the 1289 reports (n = 220) involved patients aged ≥ 20 years taking rhGH for off-label uses. This information was the basis to design interventions in order to reduce inappropriate utilisation of this expensive product. Analyses of how medicines are being used through pharmacovigilance databases are a way to identify its irrational utilisation, thus facilitating preventive actions to improve how medicines are used and reducing avoidable adverse effects.

Aims The aims were to analyze the dynamics of the medicines formulary in a middle-income country and to analyze the concordance of the included medicines with the national Clinical Practices Guidelines (CPG). Methods Medicines and their indications of use included in the Mexican Reference Drug List (Mex-RDL) from 1996 to 2013 were analyzed. The top 10 indications with the highest number of medicines in 2013 were analyzed retrospectively until 1996 in order to identify the increase in the number of medicines to treat each one, as well as the progressive specificity of the indication according to the International statistical Classification of Diseases (ICD-10). The concordance between the CPG and medicines approved for the top 10 indications was studied. Results The number of medicines included in the Mex-RDL kept constantly growing from 454 drugs in 1996 to 811 in 2013. Up to 26.3% of these medicines were approved to treat only 10 indications (1.5% of all possible indications of use). Many of these new medicines had been approved for more and more specific indications, while the oldest ones had been approved for general indications. Up to 27.6% of the medicines approved for these top 10 indications do not appear in the updated recommendations of the specific CPG for those indications. Conclusions During the last 18 years, the new medicines and indications included in the Mex-RDL were redundant and concentrated into few similar clinical conditions. This is a factor that promotes an irrational use of these medicines and, thus, unnecessarily raises the price of health care, undermines the quality of the health system and probably increases the uncertainty of treatments.

Purpose Gliptins are new oral antidiabetic drugs that increase insulin levels through dipeptidyl peptidase-4 inhibition. Recently, the association of serious musculoskeletal (MSk) adverse effects with the gliptin use has been suggested. The aim is to describe and analyze the characteristics of spontaneous reports related to these adverse effects and gliptin use. Methods All spontaneous reports with MSk disorders associated with gliptins gathered in the Spanish pharmacovigilance database until May 2012 were described and analyzed using a case/non-case method. Results Gliptins were reported as the suspected drug in 332 cases: 208 involved sitagliptin, 115 vildagliptin, and nine saxagliptin. In 34 patients (10.2% of total reports with gliptins), MSk reactions were described (22 women [64.7%] and 12 men [35.3%]). Their mean age was 65.1 years; 41.2% were younger than 65 years. Only seven cases were serious, but the gliptin had to be withdrawn in 22 patients because of intolerance and/or persistence of MSk discomfort, and patients recovered after its discontinuation. A positive re-challenge was observed in two cases. In seven cases, the patients were on previous chronic treatment with statins, and began to present MSk complaints shortly after starting a gliptin. The reporting odds ratio (ROR) for myalgia and arthralgia were strongly associated with gliptin use (ROR 1.96 [95% CI 1.12–3.43], p

Objective To assess the prevalence of potential drug–drug interactions (DDIs) in bone marrow transplantation (BMT) patients at the time of pre-infusion (day −1), to describe the potential DDIs and assess their frequency and severity. Setting The study was developed in a tertiary care hospital in Sao Paulo, Brazil. Method Cross-sectional study based on examining the medical prescriptions from the pre-infusion day (day −1) of 70 BMT patients. Potential DDIs were analyzed using Drug-Reax® and categorized according to levels of severity, evidence, and onset (rapid and delayed). Only interactions of major or moderate severity were included in the potential DDI analysis. Main outcome measure: Prevalence of potential DDIs in patients during the preinfusion phase of BMT. Results Data were analysed for 70 BMT patients. The median age was 36.5 years; 52.9% (37) of the patients were male, and 65.7% (46) were undergoing autologous BMT. The patients received a median of 8 drugs each. Up to 128 potential DDIs were detected, 60.0% (42) of patients had at least 1 potential DDI and 21.4% (15) were exposed to at least 1 major potential DDI. The most commonly involved drugs were cyclosporine (9, 28.1%), phenytoin (8, 25%) and fluconazole (5, 15.6%). Most potential DDIs had moderate severity (110, 85.9%), a pharmacokinetic mechanism (67, 52.3%), and were classified as delayed onset (106, 82.8%). For major interactions, fluconazole + sulfamethoxazole/trimethoprim, diazepam + fentanyl, fluconazole + levofloxacin and fentanyl + fluconazole were the most frequent. Conclusions The prevalence of potential DDIs during the conditioning period of BMT was high as a consequence of the therapeutic complexity of the procedure. Most potential DDIs identified in the study may result in clinically relevant consequences as they could lead to nephrotoxicity, cardiotoxicity, and other undesirable adverse effects. Careful monitoring of clinical and laboratory parameters is essential to ensure a successful BMT and to avoid adverse drug events related to DDI.

Background Underreporting suspected adverse drug reactions (ADRs) is one of the main problems that face the pharmacovigilance (PhV) systems based on yellow card schemes. Objectives To measure the knowledge level on the suspected ADR voluntary reporting system among physicians and pharmacists in Venezuela and to study its relationship with different variables. Methods A population-based, anonymous, and self-administered questionnaire was addressed to health professionals along the national territory of Venezuela. An algorithm was developed to classify the knowledge level on the voluntary reporting system. Results Taken as a whole, the level of knowledge on the voluntary reporting system was “poor.” Among the 515 participant physicians, 62.3% (95%CI = 58.0–66.5%) had a “poor” level of knowledge; PhV was associated with “control” of medicines use, and only 24.7% had ever reported a suspected ADR. “Medical specialty” was the only variable that showed a relationship with the knowledge level (p = 0.0041). Among the 78 participant pharmacists, 66.7% had a “poor” knowledge level (95%CI = 55.1–76.9%). Conclusions The knowledge level on the voluntary reporting system among physicians and pharmacists in Venezuela is poor. These results strengthen the hypothesis that being unaware of the adverse effects of medicines and not knowing the existence of a PhV system is a major cause of underreporting. A careful study of the actual knowledge of PhV could be the basis to set up interventions specifically designed to overcome misleading concepts and to improve the reporting rate at a national level. Copyright © 2011 John Wiley & Sons, Ltd.

Background: Hemorrhage and hypertensive disorders are major contributors to death after delivery in developing countries. The GIRMMAHP Initiative was designed to describe the actual delivery care in five Latin American countries and to educate and motivate clinical staff at 17 hospitals with the purpose of implementing their own clinical practice guidelines to prevent postpartum hemorrhage. Methods: A multicountry education intervention was developed in four consecutive stages, using two analyses: (a) an observational study of the clinical records in eight teaching and nine nonteaching hospitals and (b) a study of the long-term changes measured 12 months after completion of an education intervention and writing a local clinical guideline. Results: Data from 2,247 pregnant women showed that only 23.3 percent had an active management of the third stage of labor and that 22.7 percent received no prenatal care visit. These data were used to prepare local clinical practice guidelines in each participant hospital. The proportion of active management increased to 72.6 percent of deliveries at 3 months and 58.7 percent 1 year later. Use of oxytocin during the third stage of labor increased to 85.9 percent of included deliveries. The proportion of women who had postpartum hemorrhage decreased from 12.7 percent at baseline to 5 percent at 1 year after the intervention. Conclusions: An education intervention and discussion of actual clinical practice problems with health professionals and their involvement in drafting clinical guidelines helped improve health care quality and practitioners’ adherence to these guidelines. (BIRTH 35:4 December 2008)

*Self-medication is extensively practised in both developed and less-developed countries, sometimes inappropriately. *Educational intervention in secondary schools has been proven to be useful. *Most educational interventions in adolescent populations have focused on the reduction of addictive substance abuse.*Educational intervention can improve knowledge about self-medication and reduce misconceptions about diarrhoea, common cold and vitamins in an adolescent population. *A specific lecture followed by small working-group seminars produces better results than a general lecture alone in terms of 'knowledge' and 'attitude'. *The positive effects of the intervention are detectable even 1 year later. Yearly reinforcing interventions while in secondary school would allow long-lasting effects.Improving knowledge about rational drug use at an early age may be a good way to increase the population's awareness of health, medicines and self-medication. We set out to evaluate the short- and long-term effects of an educational intervention to promote rational drug use and self-medication in secondary school students.A non-randomized, controlled clinical trial. The participants were 367 female students (10-13 years old) from two secondary public schools of the metropolitan district of Quito (Ecuador). The educational campaign had two components [a specific lecture (intervention and control schools) and subsequent small working group seminars (intervention school)] providing short and clear messages of five topics related to rational drug use. The main outcome measures were an increase in 'knowledge' short term (1 month) and long term (up to 1 year) after intervention and the relative risk (RR) reduction in misconceptions or wrong ideas about medicine use.The intervention group showed a significant increase in knowledge both short and long term and in comparison with the control group, mainly regarding oral rehydration salts preparation (+59.4%; P0.001), lack of multivitamin energizer action (+57.4%; P0.001), healthy growth effects (+53.3%; P0.001) and the perception that medicines' promotional activities do not teach how to take care of health (+54.0%; P0.001). A RR reduction in misconceptions about drugs was found short term and long term. The intervention group was less predisposed to consume antidiarrhoeals [RR = 0.75, 95% confidence interval (CI) 0.62, 0.92], cough suppressants (0.44, 95% CI 0.35, 0.55) and other medicines for the common cold (0.56, 95% CI 0.45, 0.70). Misconceptions concerning the benefits of multivitamin preparations were reduced in 73%; additionally, the intervention group showed a decrease in their consumption (43.9% basal; 25.3% short term and 25.6% long term; P0.001).It is possible to achieve a favourable modification of attitudes to appropriate use of medicines in a teenage population and this modification lasts at least 1 year. Continuous reinforcing interventions would allow better and long-lasting effects and could help to fill the gap in health education of the general population.

Moyano J, Figueras A. J Pain Res. 2012;5:237–242.Jairo Moyano is also affiliated with Deparment de Farmacologia, Terapeutica i Toxicologia, Universitat Autonoma de Barcelona, Barcelona, Spain, which was not included in the original publication.Read the original article

Renal impairment associated with dronedarone use is hardly known. Our aim is to describe the characteristics of spontaneous reports involving renal adverse reactions with use of dronedarone.In the Spanish Pharmacovigilance database, reports with renal reactions and dronedarone until May 2014 were retrieved and analyzed. Also, a review of case reports of renal failure and dronedarone was conducted in MEDLINE.Dronedarone was found as a suspected drug in 192 reports, 10 (5.2%) of these reports described renal reactions. Renal reactions appeared until 3 months after the onset of dronedarone treatment. In 5 out of 10 cases, dronedarone was withdrawn and the patient recovered. The Reporting Odds Ratio was 2.88 [95% CI 1.52 - 5.46; p0.05]. Additionally, eight cases were found in the medical literature. In five of them, the patient outcome was described as recovered. One patient had to undergo hemodialysis for the treatment of their renal impairment.The effect of dronedarone on the renal function is supported by limited information; therefore, the cases from spontaneous reporting system and those from the medical literature could give relevant additional information. Our analysis shows a potential relationship between dronedarone use and renal impairment. Further studies are needed to confirm these findings.

Background During the 20th century, silver nitrate (SN) eye drops instillation to newborns had been the best prophylaxis against ophthalmia neonatorum (ON) caused by Neisseria gonorrheae, the most frequent cause of ocular infections leading to blindness. At present, this treatment has been questioned because there is a growing prevalence of other pathogens such as Chlamydia trachomatis, and SN is associated with chemical conjunctivitis (ChC). In addition, SN could present some conservation problems in tropical climates. Among other alternative drugs, 2.5% povidone-iodine has a proven efficacy, not only against Neisseria, but also against Chlamydia, has no conservation problems, has not been associated with ChC and is cheap. Methods The recently created Setor de Farmacovigilancia (SF) of the Sao Paulo State in Brazil has created a pharmacovigilance network of 11 big public hospitals. During a periodical signal searching process, the SF found a cluster of 33 ChC reports from one of the network hospitals. Results The problem was discussed with the remaining participant hospitals and this signal was used as a way to strengthen the network. Thirteen months later, 622 ChC reports were received from six hospitals. Discussion Thus, this well-known side-effect in the literature was highlighted as a ‘real’ problem in Brazil, and some participant hospitals began a discussion period together with the delivery and newborn care professionals in order to switch SN by povidone-iodine. This is an example of both, how a simple pharmacovigilance exercice could improve the implication of health professionals with their own therapeutic problems and how a pharmacovigilance network could be strengthened. Copyright © 2004 John Wiley & Sons, Ltd.

Adverse drug reactions (ADRs) represent a major public health problem in the aged. In order to better evaluate this problem in Brazil, this study was designed to assess the prevalence of ADRs in an elderly hospitalised population, identify the most common ADRs and the principal medications involved, evaluate the appropriateness of use of these drugs in elderly people and determine the risk factors implicated in the appearance of such ADRs.The study population was comprised of 186 elderly patients (or =60 years of age) admitted to the internal medicine service of a teaching hospital. The patients were assessed by a single observer using an intensive drug surveillance method to identify and report ADRs. The degree of probability for each adverse reaction was determined using the Naranjo algorithm.The mean (+/- SD) age of the patients studied was 73.6 +/- 9.1 years. Up to 115 patients (61.8%) of the study population presented at least one ADR. A total of 199 ADRs were found, at an average of 1.7 per patient. The ADRs appeared during hospitalisation in 46.2% of the study population, were present at the time of the admission but did not cause hospitalisation in 17.2% of patients, and were the cause of admission in 11.3% of patients. The most frequent ADR that caused hospitalisation was digitalis toxicity (22.7% of such ADRs). Hypokalaemia as a result of diuretics was the most prevalent ADR both during hospitalisation (11.8%) and at the time of admission without being the cause (12.1%). Captopril was the most frequently prescribed drug (138 prescriptions), and led to an ADR in 18.1% of patients who received the drug. Almost a quarter of the patients presenting an ADR were prescribed drugs considered inappropriate for the elderly. By means of a multiple logistic regression model, the following were considered to be significant risk factors for the appearance of ADRs: number of diagnoses (odds ratio [OR] 1.40; 95% CI 1.06, 1.86), number of drugs (OR 1.07; 95% CI 1.01, 1.13) and use of drug that is inappropriate for the elderly (OR 2.32; 95% CI 1.17, 4.59).The main contribution of the present study was identification of use of drugs that are considered inappropriate for elderly populations as a major risk factor for presenting an ADR. This finding is useful for continuous education programmes, therapeutic committees and policy makers, because adverse effects complicate the course of diseases in aged patients, cause hospitalisation and/or require the prescription of additional drugs. In addition to contributing to a reduction in healthcare costs, continuous efforts to promote rational drug use could also benefit elderly patients by preventing some avoidable drug toxicity.A significant prevalence of ADRs was found among hospitalised elderly people. The risk factors associated with ADRs in this population included use of drugs considered to be inappropriate for that population, number of previous diagnoses and number of administered drugs. More appropriate drug prescription could avoid part of this burden of disease by minimising preventable ADRs.

Prescribing is a complex decision-making process influencednot only by patients’ needs, but also by other factors, such asavailable resources, priorities of national healthcare policies,and market pressures [1]. The information on medicines andtherapeutics that reaches prescribers is also one of thesefactors. The need for continuous updating of this informationis vital for both healthcare professionals and healthcaresystems, although keeping up with therapeutic advances inhealth care is challenging [2].In the last two decades, access to scientific publicationsand other sources of medical information has changeddramatically, from the need to gain access to information tothe need to select it. More than ever, genuine data and newsare diluted in an ocean of banalities. For example, it took20 years, hundreds of studies, and millions of treatedpatients to realize that the so-called second-generationantipsychotics are actually no better than the older drugsin terms of efficacy and side-effect profiles [3].New information and communication technologies giveusers the opportunity to retrieve a wealth of information[4, 5]. Nevertheless, the reliability, quality, and relevanceof the information retrieved to clinical and public healthvary, and the information overload carries an inevitablerisk of “infoxication”.Too often commercial interests—rather than clinical ortherapeutic needs—drive the conception, design, analysis,interpretation, and dissemination of clinical research [6, 7].In addition, recent cases of fraud, suppression of negativeresults, and selectivity in terms of publication, such asthose on selective COX-2 inhibitors [8], selective serotoninre-uptake inhibitors, antidepressants [9], and rosiglitazone[10], have shown that peer-reviewed medical literaturecannot always be regarded as a valid and reliable source ofinformation [11, 12]. The design of pre-marketing trials, theconduct of post-marketing surveillance, and communicationtoprescribersaredrivenbytheneedtosell.Table 1 summarizesthe main problems associated with the dissemination ofinformation on medicines.The real meaning of words: is it possible to define“essential information” in therapeutics?More than 30 years ago, a World Health Organization(WHO) expert committee noted that despite the fact thatthousands of medicines had been marketed in previousyears, their public health impact was uncertain. WHOdefined essential medicines as those that satisfy thehealthcare needs of the majority of the population [13].The WHO concept of essential medicines, launched in1977, helped to establish that some medicines are morehelpful than others and that essential medicines shouldtherefore be available at all times in adequate amounts andin the appropriate dosage forms—and at a price thatindividuals and the community can afford [14].Similarly, in order to promote a healthy and cost-effectiveuse of medicines, prescribers, other healthcare professionals

Sir, We have readwith special interest the paper by Zapata-Cachafeiro et al. about the practice, still continuing, of dispensing antibiotics without medical prescription in Spain. Zapata-Cachafeiro et al. found in their questionnaire-based study that 64.7% of the pharmacists acknowledged having undertaken dispensing of antibiotics without a medical prescription. In 2008, with the use of a mystery shopper, our group found that 45.2% of pharmacies sold an antibiotic without a medical prescription. Between January 2013 and February 2014 we used the same design and methodology with the aim of determining whether the practice of selling antibiotics without a medical prescription has changed in Spanish pharmacies. A mystery shopper presented requesting an antibiotic to 220 pharmacies in the Tarragona Health District, an area covering 596508 inhabitants in a region of Catalonia (Spain), while feigning the symptoms of three different scenarios, the same cases used in the previous study: an uncomplicated urinary tract infection, an episode of sore throat and a case of acute bronchitis. The mystery shopper was previously trained in how she should perform as well as her answers to possible questions. At each pharmacy studied, one of these three different request scenarios was randomly chosen to be enacted. She was very polite and explained that she was not from the neighbourhood and that she was passing through. Antibiotics were sold in 54.1% of the pharmacies, with important differences depending on the simulated disease (81.1% for urinary tract infection, 47.9% for sore throat and 32.9% for acute bronchitis; P,0.001). The results obtained in 2014 are even worse than those observed in 2008. An increase in the sale of antibiotics without prescription was observed for the three simulated cases, but the tendency doubled in the case of acute bronchitis Q1 (Table 1). Although the sale of antibiotics without prescription in Spain is still illegal now, as in 2008, if pharmacists did not sell the antibiotic we asked about the reason. The pharmacist claimed purely administrative reasons for not selling the drug in 70.3% of cases, referring to the prohibition of selling an antibiotic without an official prescription. In the other pharmacies, a response related to health or resistance was given (29.7%). The results of this study demonstrate that antibiotics continue to be sold without a prescription in Spain and are in line with the results of Zapata-Cachafeiro et al. In a short period of time, antibioticswill not be effective because bacteria are becoming resistant even to modern antibiotics, and we are therefore losing the battle against infectious diseases. Eliminating the dispensing of antibiotics without a prescription must constitute one of the most valuable strategies to accomplish this objective. The present study shows that, at least in some regions, buying antibioticswithout prescription is still possible in Europe, and in our country is easier than 6 years ago. With the objective of improving the outcomes obtained in this study, there will be educational sessions with pharmacists of the Tarragona Health District, where we will discuss our findings, and wewill inform them about the importance of rational utilization of antibiotics today. The European Community countries should have a common health policy, including educative actions and ways to control over-the-counter antibiotic sales. Educative measures and enforcement of the prohibition of selling antibiotics over-the-counter is needed to preserve the effectiveness of these drugs.

In 1996, a National Pharmacoepidemiology Network was set up in Cuba in order to disseminate problem-oriented information and develop continuing education activities on drug therapy, to perform research on drug utilisation and to promote interventions to improve drug use. It is coordinated by the Centre for the Development of Pharmacoepidemiology, which is also in charge of regulatory and administrative duties and collaborates with the National Pharmaceutical Industry. By 2001, a number of educational and information initiatives had been undertaken, particularly in primary health care, which resulted in improvement of indicators of drug use. Cuba keeps good health standards in spite of a short health budget.

To assess the rationality of the Mexican Formulary List (MEX-LIST). MEX-LIST was compared with the World Health Organization Essential Medicines List (WHO-LIST) to identify drugs classified as unmet needs. For the MEX-LIST rationality evaluation, the assessment of a non-sponsored, systematic and unbiased source (Prescrire Journal) was used for medicines not listed in WHO-LIST. The rating scale of Prescrire classifies medicines as Bravo, Real Advance, Offers an Advance, Possibly Helpful, Nothing New (NN), Judgment Reserved (JR), or Not Acceptable (NA) depending on their comparative therapeutic value. The NN, JR, and NA categories of medicines are further classified as non-added value. The MEX-LIST contains 771 medicines, which is 2.4-fold more than the WHO-LIST (n = 321). Up to 236 medicines in the MEX-LIST perfectly match the WHO-LIST medicines, 40 could be considered as reasonable substitutes, but 45 (14.0 %) present in the WHO-LIST are not present in the MEX-LIST, including an oversupply of 495 medicines. Rationality level could be analyzed for 353 of these: 43.1 % (n = 152) were classified as NN, 12.2 % (n = 43) as NA, and 6.2 % (n = 22) as JR due to limited available information. In summary, 61.5 % of the evaluated medicines present in the MEX-LIST but not included in the WHO-LIST (n = 217) can be considered drugs that do not add substantial therapeutic benefits, this accounts for 28.1 % of the medicines in the MEX-LIST. MEX-LIST is characterized by a twofold irrationality in that essential medicines to treat prevalent diseases are missing and medicines without any rational added value are in oversupply. This type of study can be easily applied to other countries with the aim of providing a forum for further discussion and improvement of the medicines offered by their national formularies.

Jairo Moyano,1 Albert Figueras21Anesthesia Department, Pain Service, Hospital Universitario Fundación Santafé de Bogotá, Avenida 9 No 117-20, Bogotá, Republic of Colombia; 2Fundació Institut Català de Farmacología, Departamento de Farmacología Universitat Autónoma de Barcelona, Barcelona, SpainIntroduction: Review of opioid prescriptions in a hospital provides valuable information to health care professionals which may contribute to proper pain management; opioid utilization studies may help uncover factors that can be improved for better prescribing. To evaluate the use of opioid analgesics in a university hospital, a review of opioids prescribed in hospitalized patients was developed.Methods: Information was obtained from the pharmacy database and medical records. The study period was 1 month.Results: Medical records of 1156 patients admitted in July 2009 were analyzed. The most widely prescribed opioid was tramadol; the preferred administration route was intravenous; the main indication was severe pain; and major prescribers were from surgical departments.Discussion: Underutilization of potent opioids for acute and chronic pain seems to occur.Conclusion: Most prescribers prefer weak opioids, given intravenously to treat acute and chronic pain, while some patients may benefit from the prescription of more potent opioids.Keywords: drug utilization, pain, tramadol, morphine, hydromorphone, pethidineCorrigendum for this paper has been published

a Pharmacology, Therapeutics and Toxicology Department, UniversitatAutonoma de Barcelona, 08193 Bellaterra (Cerdanyola del Valles), Spain b Clinical Pharmacology Department, Hospital Universitari Germans TriasiPujol, Carretera de Canyet s/n, 08916 Badalona, Spain c FundacioInstitutCatala de Farmacologia, PasseigValld'Hebron 119-129, 08035 Barcelona, Spain d Catalan Centre of Pharmacovigilance, Barcelona, Spain

Prescribing is an essential part of physicians' daily work, a professional and ethical responsibility. It implies a complex decision-making process that is conditioned not only by physicians' academic and cultural background but also by other factors such as pharmaceutical market width, medicines promotion by the pharmaceutical industry, access to independent information, medical care context in which the physician works and continuous education programmes or incentives from healthcare provider organisations. Left to pharmaceutical market whims, prescribing is known to be shifted towards newer and usually more expensive medicines.1 The most appropriate drugs for patients should be selected according to principles well described in the WHO ‘Guide to good prescribing’, such as comparative effectiveness, safety, convenience and cost.2 The rational use of medicines is defined as ‘the prescription of the most appropriate medicine to the patient in need of them, at an adequate dose and time duration, and giving to the patient the needed information to use them’; it was agreed at a WHO conference in 1985.3 Although rational drug prescription does not guarantee that medicines expenditure is limited, this concept may represent a crucial step towards a more efficient use of drugs.4 Intensive marketing of new and more expensive drugs, demographic changes, rising patient expectations or stricter clinical targets have pushed pharmaceutical expenditure to increase more rapidly than any other component of health care.5 Concomitantly, the excessive …

Background Drug-drug interactions (DDIs) are one of the main causes of adverse reactions related to medications, being responsible for up to 23% of hospital admissions. However, only a few studies have evaluated this problem in elderly Brazilians. Objectives To determine the prevalence of potential DDIs (PDDIs) in community-dwelling elderly people in Brazil, analyse these interactions with regard to severity and clinical implications, and identify associated factors. Methods A population-based cross-sectional study was carried out involving 2143 elderly (aged ≥60 years) residents of the metropolitan area of Sao Paulo, Brazil. Data were obtained from the SABE (Saude, Bem estar e Envelhecimento [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out in seven countries of Latin America and the Caribbean, coordinated by the Pan-American Health Organization. PDDIs were analysed using a computerized program and categorized according to level of severity, onset, mechanism and documentation in the literature. The STATA software statistical package was used for data analysis, and logistic regression was conducted to determine whether variables were associated with PDDIs. Results Analysis revealed that 568 (26.5%) of the elderly population included in the study were taking medications that could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed to PDDIs were women, 50.7% were aged ≥75 years, 71.7% reported having fair or poor health and 65.8% took 2–5 medications. A total of 125 different PDDIs were identified; the treatment combination of an ACE inhibitor with a thiazide or loop diuretic (associated with hypotension) was the most frequent cause of PDDIs (n=322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed that 70.4% were of moderate severity, 64.8% were supported by good quality evidence and 56.8% were considered of delayed onset. The multivariate analysis showed that the risk of a PDDI was significantly increased among elderly individuals using six or more medications (odds ratio [OR] 3.37) and in patients with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR 3.36). Conclusions Approximately one-quarter of the elderly population living in Sao Paulo could be taking two or more potentially interacting medicines. Polypharmacy predisposes elderly individuals to PDDIs. More than half of these drug combinations (57.6%, n=72) were part of commonly employed treatment regimens and may be responsible for adverse reactions that compromise the safety of elderly individuals, especially at home. Educational initiatives are needed to avoid unnecessary risks.

The objective of this study was to analyze the level of evidence regarding the efficacy, effectiveness and safety of over-the-counter (OTC) cough medications registered in Brazil. The National Health Surveillance Agency database was used to identify the drugs. Clinical trials, systematic reviews, meta-analyses, and studies on safety were searched on the Medline baseline, the Cochrane Library and SIETES (System of Essential Information in Therapeutics and Health; database in Spanish). Most drugs (62.5%) were sold as a fixed-dose combination of two or more drugs. Randomized clinical trials were found for only three drugs: bromhexine, dextromethorphan and guaifenesin. No clinical trials were found for fixed-dose combinations. Systematic reviews on Cochrane did not report any evidence in favor of or against the effectiveness of cough drugs. Efficacy is also unclear, especially regarding fixed-dose combinations. The evidence for the efficacy of OTC cough medications available in Brazil is poor due to the lack of quality studies. Pharmacovigilance of OTC cough medications should be encouraged.O objetivo deste trabalho foi analisar o nível de evidências sobre a eficácia, a efetividade e a segurança dos medicamentos para tosse registrados no Brasil. A base de dados da Agência Nacional de Vigilância Sanitária foi empregada para identificar os medicamentos. Os ensaios clínicos, as revisões sistemáticas, as metanálises e os estudos de segurança foram pesquisados no Medline, the Cochrane Library e SIETES (Sistema de Informações Essenciais em Terapêutica e Saúde, base de dados em espanhol). A maioria dos medicamentos (62,5%) eram comercializados como associação em dose fixa com dois ou mais fármacos. Ensaios clínicos randomizados foram encontrados apenas para três fármacos: bromexina, dextrometorfano e guaifenesina; para associações a dose fixa não foram encontrados ensaios clínicos. Revisões sistemáticas publicadas pela Cochrane não encontraram evidências favoráveis ou contrárias à efetividade dos medicamentos para tosse. Essa eficácia não é clara, especialmente a das associações a dose fixa. As evidências sobre a eficácia dos medicamentos para tosse isentos de prescrição disponíveis no mercado brasileiro são fracas, devido à falta de pesquisas de boa qualidade. A farmacovigilância de medicamentos para tosse isentos de prescrição deve ser incentivada.

Self-medication in older adults can be problematic, especially if remedies taken without prescription interact with prescribed medications or if they produce adverse effects. Before designing interventions to improve self-medication, it is important to characterize patterns of self-medicating in local populations. This can be easily achieved through the conduct of simple surveys.To quantify and describe the demographic, socioeconomic and pharmacological characteristics of self-medication among a geriatric urban population in Chiapas, Mexico.An observational, descriptive, cross-sectional study was conducted, using a conglomerate sampling technique. A total of 245 older (agedor =65 years) residents in the downtown area of Tuxtla Gutierrez (Chiapas, Mexico) participated in the study. Information on self-medication and demographic and socioeconomic variables was obtained from a specific structured interview that was conducted by a single specially trained physician.More than half of the 245 interviewed older adults (131 [53.5%; 95% CI 47.2, 59.7]) reported taking a medicine without prescription during the last 30 days. Self-medication was significantly more frequent among older adults who lived alone compared with married people (p = 0.0274) and among the illiterate or those with a low level of education compared with people with secondary and high-school degrees (p = 0.0036). NSAIDs (36.2% of medications) and antihistamines (12.6%) were the most frequent drugs taken as self-medication. The most frequently cited reasons for self-medicating were muscle and joint pain (19.9% of medications), upper respiratory tract problems (15.9%) and cough (7.3%). However, 13% of people who self-medicated took a remedy for hypertension (11% of all medications) without medical supervision. Previous prescriptions could have served as the basis for future self-medication in 33 (25.2%) patients. Finally, 35 (26.7%) patients who self-medicated reported that they had experienced adverse effects from the drug they were taking.Self-medication in older adults is a problem that should be carefully addressed in public health policies. Surveys such as the present one are easy to carry out (and could conveniently be conducted in primary care settings), rapidly yield information about the true nature of self-medication in local populations, and provide a basis on which to design future interventions. Factors associated with self-medication in this study, including both socioeconomic characteristics (e.g. most self-medicators were poorly educated or lived alone) and therapeutic considerations (e.g. substantial proportions of patients self-medicated for hypertension, used previous prescriptions as the basis for self-medication, or reported adverse effects of self-medication), are vital clues to the design of effective and appropriately targeted interventions in the future.

Six years ago the Nicaraguan government asked us to implement treatment guidelines for the most prevalent health problems of the country in six months. After some discussion, a stepwise development of a treatment guideline for postpartum haemorrhage was selected as a training example. Several Nicaraguan institutions had already published treatment guidelines for postpartum haemorrhage, but the real management of delivery differs from their recommendations. The causes seemed simple: treatment guidelines are written far from the clinical reality and are usually …

BACKGROUND: Metabolic control in type 2 diabetes depends on patient adherence to therapy. Quantitative consumption data do not supply information regarding the appropriate use of medicine. Drug utilization studies are useful to identify treatment adherence problems and, thus, design interventions to improve drug use. OBJECTIVE: To describe the treatment and outcome in terms of degree of metabolic control in these patients, assess the agreement between the doses of antidiabetic drugs reported by the patient and those written in the medical record, and describe the drug utilization characteristics in relation to the standards of care. METHODS: This drug utilization study was conducted in primary care centers in Barcelona, Spain. Consecutive patients with type 2 diabetes attending a follow-up visit were interviewed regarding lifestyle, diet, glycosylated hemoglobin level, and treatment. Concordance between the information obtained through medical records and patient interviews was analyzed. RESULTS: Metabolic control was deficient in 73 (40%), acceptable in 50 (28%), and good in 58 (32%) of the 181 patients with available information. For 38 (19%) patients, there was disagreement between the dose of the antidiabetic drug reported by the patient and that written in the medical record. For 83 (41%) patients, the treatment in the medical history was in agreement with published standards. CONCLUSIONS: Identification of disagreement between standards of care and clinical practice in type 2 diabetes management is the basis to improve drug utilization and achieve better metabolic control in these patients.

We aimed to analyse the quality of newspaper articles (NAs) concerning the therapeutic use of cannabis published in Spanish newspapers. A preliminary questionnaire of the Index of Scientific Quality was used [scores ranged from 0 (no misleading) to 14 (misinformation in each item)]. Of the 29 NAs analysed, 16 (55.2%) were scored as 4 or lower, and 6 (20.7%) scored 7 or higher. Up to 23 NAs (79.3%) did not manage the knowledge related to cannabinoids; 20 (69%) gave a sensationalist message; 11 (37.9%) were able to wrongly influence clinical decision taking; and 8 (27.6%) misled medical concepts. The leading medical journals could play an especially relevant role while preparing their press releases if they specify study limitations and context.

Background: The effectiveness of voluntary reporting systems in pharmacovigilance highly depends on the number of assembled reports. Aim: The aim of this study was to measure the effect of the periodical distribution of a bulletin on drug safety issues and of including yellow cards in prescription pads on the rate of adverse drug reaction (ADR) reporting. Study Design and Methods: The Catalan Centre of Pharmacovigilance began its activities at the end of 1982. Since 1985, an ADR bulletin (ADRB) has been mailed approximately quarterly to all physicians in its catchment area, with one yellow card enclosed. Additionally, from 1991–1994, a yellow card was included in the prescription pads of the Catalan Health Service. Time series methodology, with adjustment of the monthly number of reports to an Auto-Regressive Integrated Moving Average (ARIMA) model, was used to evaluate the effect of these two measures. Results: From January 1983—October 1995, 6240 spontaneous ADR reports were received, and 41 issues of the ADRB were sent out. Initially, the mean monthly spontaneous ADR reporting rate was 34.4 (SD = 14.1; n = 106 months). After the inclusion of yellow cards in prescription pads, the mean monthly spontaneous ADR reporting rate increased to 53.9 (SD = 14.4; n = 48 months). According to an ARIMA model, when a bulletin was send out (MONTH1), a mean increase of 9.4 reports was produced in that month, plus 12.3 additional reports in the following month (MONTH2), and 6.3 in the second month after sending the ADRB (MONTH3). A yellow card in the prescription pads elicits a monthly mean increase of 19.8 in the number of reports. Conclusions: The present study suggests that ADRBs elicit a temporal increase of the ADR reporting rate. Including a yellow card in prescription pads was followed by an even greater increase in the reporting rate, possibly because it guarantees that yellow cards are available at the workplace.

This study was set up to document the variability of prescribing information from different sources concerning indications, side effects and cautions of selected drugs. An original method to measure the degree of information agreement among different written materials, such as summaries of product characteristics, package inserts and data sheets, and a widely accepted reference text was developed. The results show that there is substantial disagreement in the materials available to prescribers and patients in different countries. Disagreement was even found within a single country when written materials from different brands of the same drug were compared. The discordance can be explained by the fact that the evidence available for each drug is considered/assessed differently by separate countries. It is argued that the discrepancies found may mislead prescribers, patients and those comparing drug-use patterns across countries. National regulatory authorities have a key role to play in remedying this situation, and a two-pronged approach is proposed. At the international level, national authorities should strengthen collaboration and information interchange and, at the national level, should implement appropriate measures aimed at removing contradictory statements on drug-information materials that have no reason to be different. Finally, further training and continued education aimed at drug regulatory officials could provide the necessary knowledge and enable national authorities to meet the need for drug information that is independent of commercial interests.

Rapid drug regulatory decisions regarding phenylpropanolamine (PPA)-containing common cold remedies and diet pills were taken in some Latin American countries following a US Food and Drug Administration (FDA) decision in the US. This situation is described as one that illustrates the important changes that regulatory decisions are experiencing as a consequence of globalisation. The evidence for the efficacy of PPA as a nasal decongestant and as an appetite-suppressant is very limited, at least by modern standards. Its potential to increase blood pressure and induce haemorrhagic stroke was described soon after its marketing. Although this poor benefit/risk ratio had been known for more than 20 years, regulatory action was taken in Latin America only after the US FDA withdrew the drug in the US on the basis of the results of a case-control study which added limited new evidence to the already known risk of stroke, but which, on the other hand, had attracted much attention from the media.

Reporting of therapeutic ineffectiveness through adverse drug reaction spontaneous reporting systems has been proposed by some authors. In the WHO Adverse Reactions Terminology (WHO-ART) and Medical Dictionary for Regulatory Activities (MedDRA) terminology, the term therapeutic ineffectiveness includes drug interactions, resistance, tolerance and tachyphylaxis, as well as pharmaceutical defects such as substandard, adulterated, and counterfeit drugs. Under certain circumstances, reporting therapeutic ineffectiveness may contribute to identifying pharmaceutical defects. However, the best approach to avoid their occurrence would be implementing good manufacturing practices and strengthening quality control activities. This would prevent the misuse of spontaneous reporting of adverse drug reactions (e.g. when reporting of therapeutic ineffectiveness is 'suggested' by interested parties, especially when a generic product has been substituted for a branded original product).

EDITOR—The increasing global gap between rich and poor countries leads to inequalities in access to drugs and to the knowledge and skills needed for their rational use. It also leads to qualitatively different information needs. Therapeutic information on the management of HIV infection and AIDS flows at two separate levels: although some doctors debate about the potential benefits of new viral transmembrane protein blockers, others are wondering how to manage a patient with pneumocystis pneumonia because of insufficient financial resources to purchase co-trimoxazole. These people …

Prescribing is an essential part of physicians' daily work, a professional and ethical responsibility. It implies a complex decision-making process that is conditioned not only by physicians' academic and cultural background but also by other factors such as pharmaceutical market width, medicines promotion by the pharmaceutical industry, access to independent information, medical care context in which the physician works and continuous education programmes or incentives from healthcare provider organisations. Left to pharmaceutical market whims, prescribing is known to be shifted towards newer and usually more expensive medicines.1 The most appropriate drugs for patients should be selected according to principles well described in the WHO ‘Guide to good prescribing’, such as comparative effectiveness, safety, convenience and cost.2 The rational use of medicines is defined as ‘the prescription of the most appropriate medicine to the patient in need of them, at an adequate dose and time duration, and giving to the patient the needed information to use them’; it was agreed at a WHO conference in 1985.3 Although rational drug prescription does not guarantee that medicines expenditure is limited, this concept may represent a crucial step towards a more efficient use of drugs.4 Intensive marketing of new and more expensive drugs, demographic changes, rising patient expectations or stricter clinical targets have pushed pharmaceutical expenditure to increase more rapidly than any other component of health care.5 Concomitantly, the excessive volume of marketing and …

Failure of drug treatment may be due to wrong diagnosis, selection of an inappropriate drug or dosage, use of an adulterated or fake drug, the patient's non-adherence, a drug's poor bioavailability or lack of efficacy, medication error, or occurrence of an adverse reaction. The potential causes of therapeutic failure depend on a complex interplay of social and medical factors. Failures can occur at every step of the therapeutic chain, which is the process describing the life of medicines in a community. This process includes development, regulation (including registration), marketing, distribution, prescription, dispensing, and use of the drug.1 The following are only some examples of failures in drug treatment. In 2001 the top five best selling medicines globally were atorvastatin, omeprazole, simvastatin, lansoprazole, and amlodipine, although available evidence indicates that only two of these drugs are first choice in their class. In recent years, various non-essential non-innovative drugs had to be withdrawn from the market because of serious adverse effects after a few years of growth in sales. One of these drugs, troglitazone, was associated with a risk of liver failure, which had been played down by the manufacturing company.2 More recently, serious flaws in the published pivotal trial that served as the basis for the global promotion of celecoxib were made public,3 and alosetron was reapproved by FDA amid accusations that the FDA had become a servant of the …

Spontaneous reporting of suspected adverse drug reactions (ADRs) is the most extended drug safety monitoring method. Currently, 65 countries participate in the WHO Programme for International Drug Monitoring. Spontaneous reporting partly depends upon prescribers’ knowledge, skills and willingness to report [1]. This can be favoured by means of close collaboration, regular contact, and provision of feedback information. The Cuban National Network of Pharmacoepidemiology (NNP) was set up in 1996. It consists in 175 centres, each one located at the chief pharmacy in every municipality of the country (with more than one centre in large cities). Each centre is run by an experienced family practitioner with additional training in pharmacoepidemiology. This was provided through a specific Diploma in Pharmacoepidemiology, with a 360 teaching hours programme in clinical pharmacology, methods in epidemiology, clinical trials, drug utilization studies, observational analytical studies, and other relevant methods for benefit/risk assessment. The whole NNP is coordinated by the Centre for the Development of Pharmacoepidemiology (CDP). The main objectives of the NNP are (a) disseminating accurate problem-orientated therapeutic information among health professionals, (b) implementing continuing education activities on drug therapy, with particular emphasis on common health problems and other therapeutic priorities identified through drug utilization studies, (c) carrying out research on drug utilization, and (d) promoting educational and administrative interventions aimed at improving drug prescription and use [2]. In 1994 Cuba became a member of the WHO Programme for International Drug Monitoring. In 1998, the Cuban System of Pharmacovigilance gathered around 900 reports (equivalent to a reporting rate of 75 per million inhabitants). In 1999 the responsibility for drug safety monitoring was transferred to the CDP, and a National Coordinating Unit of Pharmacovigilance was set up. Since then, promotion of ADR reporting became a part of the continuous education activities of the NNP. A plausible effect has been a dramatic increase in the yearly number of reports: in 1999, 21125 reports were received (1920 per million inhabitants), and in 2000 the figure was 28450 (2543 per million inhabitants). These rates are an order of magnitude higher than those achieved in those more developed countries with the highest reporting rates [3]. Table 1 shows additional information on the reports gathered in 2000. Table 1 Voluntary reporting of adverse drug reactions to the Cuban Pharmacovigilance System, 2000. The main limitations of spontaneous reporting are underreporting, selective reporting, and incomplete drug histories [4]. Different approaches have been tried in order to limit underreporting, such as adding a yellow card in the prescription pads of the national health system, inviting other health professionals apart from physicians (e.g. pharmacists, nurses) and even patients to report, introducing fees for reporting, coupling electronic reporting with electronic information systems and in software for electronic medical records, etc. Our approach consisted in integrating ADR reporting with training and continuous education of physicians. We feel that it is of special interest that this experience was developed in a less developed country, during a deep economic crisis, but with a universal and equitable health care system. The efficiency of spontaneous reporting for detecting new, previously undescribed, ADRs depends both on the number and the quality of reports. Now that a high reporting rate has been achieved, the next step will be improving the relevance and quality of reporting, by specifically promoting reporting of suspicions of ADRs related with recently marketed drugs, and by encouraging reporting of severe and poorly known adverse events.

A number of factors influence how medicines are used in each community but drug registration is the initial and usually necessary step. In the course of an external advisory consultation the list of approved medicines in Peru in 1998 was examined. Of 1672 newly approved forms 119 were of 49 new chemical entities. Sildenafil meloxicam nimesulide candesartan irebesartan naratriptan trovafloxacin and grepafloxacin were among them. Several aspects about the new global drug situation and "real" health needs versus "induced" health needs are discussed from this example. (authors)

Several studies have reported an association between upper gastrointestinal bleeding (UGIB) and the previous use of acetylsalicylic acid (ASA) [1–11] or non-steroidal anti-inflammatory drugs (NSAIDs) as a whole [12–14]. However, specific estimates for individual drugs are not available because the lower prevalence of use of each individual NSAID — compared with that of ASA — limits the statistical power of any analytical study designed to quantify individual risks.