Challenges facing drug utilization research in the Latin American region.

PURPOSE: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region. METHODS: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region. RESULTS: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions. CONCLUSIONS: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system.

The importance of correct estimation of renal function for drug treatment in hospitalized elderly patients, especially women: A prospective observational study
.

AIM: To compare renal function by several GFR formulas (particularly cystatin C eGFR-"CAPA") in relation to renal risk drugs (RRDs) in patients admitted to two geriatric wards in a university geriatric department. MATERIALS AND METHODS: This was a prospective quality improvement study including 108 patients, 2/3 women, age ≥ 75 years, admitted with multimorbidity. Renal function tests were performed with Cockcroft & Gault with uncalibrated (C&Guc) and calibrated creatinine (C&Gcc), and 3 - 4 points' iohexol clearance (mGFR) in mL/min, and eGFR with MDRD4, CKD-EPI, CAPA, and BIS2 clearance in mL/min/1.73m2. Agreement was tested by Bland & Altman analysis. The number and type of RRDs were analyzed. RESULTS: Measured GFR, C&Gcc, and C&Guc were mean 37, 39, and 32 mL/min, respectively. Estimated GFR by MDRD4, CKD-EPI, CAPA, and BIS2 were mean 56, 52, 45, and 40 mL/min/1.73m2, respectively. Compared to mGFR, women had significantly higher clearance for all estimates except for C&Gcc and C&Guc. C&Gcc, C&Guc, and BIS2 showed the lowest bias. 38 RRDs were identified. 96 patients used a mean of 2.3 RRDs per patient, and 1.7 RRDs needed dose adjustments. Cardiovascular drugs and analgesics were the most frequent RRDs. DISCUSSION: The C&Gcc, C&Guc, and BIS2 equations gave the best estimate of kidney function in relation to mGFR for drug dosing in the elderly. The eGFR methods showed significantly higher clearance than mGFR, C&Gcc, C&Guc, and BIS2. RRDs that needed dose adjustment were common in this geriatric population. If the eGFR formulas (MDRD4, CKD-EPI, and CAPA) are used instead of C&Gcc, C&Guc, and BIS2, higher and potentially more risky doses of RRDs may be administered to geriatric patients over 75 years, women in particular.

A European community pharmacy-based survey to investigate patterns of prescription fraud through identification of falsified prescriptions.

AIM: To identify prescription drugs involved in falsified prescriptions in community pharmacies in 6 European countries. METHODS: A cross-sectional survey among 2,105 community pharmacies in Belgium, France, Italy, the Netherlands, Spain and Sweden was carried out to collect all suspect prescription forms. For each reported drug, the number of reported falsified prescriptions per thousand inhabitants was estimated. A falsification ratio was calculated by dividing the number of reports by the number of defined daily doses per 1,000 inhabitants per day for this drug, computed from national sale or reimbursement data. RESULTS: On 862 prescription forms, benzodiazepines (zolpidem, bromazepam, alprazolam), buprenorphine (as an opioid maintenance drug) and tramadol were the most frequently reported. Depending on their level of use in each country, methylphenidate, morphine and flunitrazepam presented the highest falsification ratios, particularly in Spain, Belgium and France. CONCLUSIONS: Stimulants, opioids and some benzodiazepines were the most frequently reported drugs in this survey on falsified prescriptions, but differences between countries were observed.

Multi-country rapid adverse drug event assessment: the Asian Pharmacoepidemiology Network (AsPEN) antipsychotic and acute hyperglycaemia study.

PURPOSE: To undertake a multi-country study to investigate the risk of acute hyperglycaemia with antipsychotic use. METHODS: Using a distributed network model with a common minimal data set, we performed a prescription sequence symmetry analysis (PSSA) to investigate the risk of acute hyperglycaemia associated with antipsychotic initiation. Incident insulin prescriptions were used as a proxy indicator of acute hyperglycaemia. Participating countries and population datasets included Australia (300,000 persons), Japan I (300,000 persons), Japan II (200,000 persons), Korea (53 million persons) Taiwan (1 million persons), Sweden (9 million persons), USA-Public (87 million persons) and USA-Private (47 million persons). RESULTS: Olanzapine showed a trend towards increased risk in most databases, with a significant association observed in the USA-Public database (Adjusted sequence ratio (ASR) = 1.14; 95% Confidence Interval (CI) 1.10-1.17) and Sweden (ASR = 1.53; 95% CI 1.13-2.06). Null or negative associations were observed for haloperidol, quetiapine and risperidone. CONCLUSION: Acute hyperglycaemia appears to be associated with olanzapine use, however, this effect was only observed in two large databases. Despite different patterns of utilization of both antipsychotics and insulin, PSSA analysis results for individual antipsychotic medicines were qualitatively similar across most countries. PSSA, used in conjunction with existing methods, may provide a simple and timely method further supporting multi-national drug safety monitoring.

Efficacy of Single-Dose Albendazole for the Treatment of Soil-Transmitted Helminthic Infections among School Children in Rwanda-A Prospective Cohort Study.

Mass drug administration (MDA) of single-dose albendazole to all at-risk populations as preventive chemotherapy (deworming) is recommended by WHO to halt transmission of soil-transmitted helminth (STH) in endemic countries. We assessed the effectiveness of single-dose albendazole against STH infection in the western province of Rwanda, where STH prevalence remains high despite the implementation of preventive chemotherapy for over a decade. Two weeks before the scheduled MDA, 4998 school children (5-15 years old) were screened for STH infections (Ascaris lumbricoides, Trichuris trichiura, and hookworm), and 1526 children who tested positive for at least one type of STH parasite were enrolled and received single-dose albendazole (400 mg) through MDA. A follow-up stool exam was performed at three weeks post-treatment using Kato-Katz. Efficacy was assessed by cure rate (CR), defined as the proportion of children who became egg-free, and egg reduction rates (ERRs) at three weeks post-treatment. The CR and ERR for hookworms (CR = 96.7%, ERR = 97.4%) was above, and for Ascaris lumbricoides (CR = 95.1%, ERR = 94.6%) was borderline compared with the WHO efficacy threshold (CR and ERR ≥ 95%). However, the CR and ERR for T. trichiura (CR = 17.6% ERR = 40.3%) were below the WHO threshold for efficacy (CR and ERR ≥ 50%). Having moderate-to-heavy infection intensity and coinfection with another type of STH parasites were independent risk factors for lower CR and ERR against Trichirus trichiura (p < 0.001). Single-dose albendazole used in the MDA program is efficacious for the treatment and control for hookworms and Ascaris lumbricoides infections but not effective for Trichirus trichiura. An alternative treatment regimen is urgently needed to prevent, control, and eliminate STH as a public health problem.

Efficacy of Single-Dose Praziquantel for the Treatment of Schistosoma mansoni Infections among School Children in Rwanda.

Preventive chemotherapy with single-dose praziquantel is the WHO-recommended intervention strategy to eliminate schistosomiasis as a public health problem in endemic countries. Surveillance of drugs used in mass drug administration (MDA) programs is recommended to evaluate its effectiveness in reducing transmissions. After a decade-long implementation of a school-based MDA program in Rwanda, we conducted efficacy surveillance of single-dose praziquantel MDA against S. mansoni infection. Two weeks before MDA, stool examinations were performed to screen MDA-eligible school children (n = 4998) for S. mansoni infection using the Kato-Katz technique, and 265 (6.5%) children tested positive for the infection. All children received praziquantel and albendazole as preventive chemotherapy through the MDA campaign. Infected children were enrolled and followed for efficacy monitoring, and stool examination was repeated after three weeks post-MDA (n = 188). Before treatment, 173 (92%) had a light infection, and 15 (8%) had a moderate infection intensity. The primary and secondary outcomes were parasitological cure and egg reduction rates at three weeks post-treatment. The overall cure and egg reduction rates for S. mansoni infection were 97.9% (95% CI = 94.6-99.4) and 97.02%, respectively. Among the 173 children with light infection intensity, 170 (98.3%, 95% CI = 95.0-99.6) were cured, and among the 15 children who had moderate infection intensity, 14 (93.3%) were cured. No significant association between cure rate and pre-treatment infection intensity was observed. We conclude that single-dose praziquantel is efficacious against light-to-moderate S. mansoni infection. Preventive chemotherapy with praziquantel effectively reduces schistosome reservoirs and transmission among school-age children.

Safety of Praziquantel and Albendazole Coadministration for the Control and Elimination of Schistosomiasis and Soil-Transmitted Helminths Among Children in Rwanda: An Active Surveillance Study.

INTRODUCTION: School-based preventive chemotherapy (Deworming) with praziquantel and albendazole to control and eliminate schistosomiasis and soil-transmitted helminths as public health problems is recommended by the World Health Organization (WHO). Safety monitoring during mass drug administration (MDA) is imperative but data from sub-Saharan Africa are scarce. OBJECTIVE: The aim of this active safety surveillance study was to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass administration of praziquantel and albendazole. METHODS: Overall, 8037 school children aged 5-15 years in Rwanda were enrolled. Baseline sociodemographic, medical history and any pre-existing clinical symptoms were recorded. Participants received a single dose of praziquantel and albendazole during MDA. AEs were actively monitored on days 1, 2, and 7 post MDA. RESULTS: Overall, 3196 AEs were reported by 1658 children; 91.3%, 8.4%, and 0.3% of the AEs were mild, moderate, and severe, respectively, and most resolved within 3 days. Headache (21%), dizziness or fainting (15.2 %), nausea (12.8%) and stomach pain (12.2%) were the most common AEs. The overall cumulative incidence of experiencing at least one type of AE was 20.6% (95% confidence interval [CI] 19.7-21.5%), being significantly higher (p < 0.001) in children with pre-MDA clinical events (27.5%, 95% CI 25.4-29.6%) than those without (18.7%, 95% CI 17.7-19.7%). Females, older age, having pre-MDA events, types of food taken before MDA and taking two or more praziquantel tablets were significant predictors of AEs. CONCLUSIONS: Praziquantel and albendazole MDA is safe and well-tolerated; however, one in five children experience transient mild to moderate, and in few cases severe, AEs. The incidence of AEs varies significantly between sex and age groups. Pharmacovigilance in the MDA program is recommended for timely detection and management of AEs.

Comparative Assessment of the Pharmacovigilance Systems within the Neglected Tropical Diseases Programs in East Africa-Ethiopia, Kenya, Rwanda, and Tanzania.

Monitoring the safety of medicines used in public health programs (PHPs), including the neglected tropical diseases (NTD) program, is a WHO recommendation, and requires a well-established and robust pharmacovigilance system. The objective of this study was to assess the pharmacovigilance systems within the NTD programs in Ethiopia, Kenya, Rwanda, and Tanzania. The East African Community Harmonized Pharmacovigilance Indicators tool for PHPs was used to interview the staff of the national NTD programs. Data on four components, (i) systems, structures, and stakeholder coordination; (ii) data management and signal generation; (iii) risk assessment and evaluation; and (iv) risk management and communication, were collected and analyzed. The NTD programs in the four countries had a strategic master plan, with pharmacovigilance components and mechanisms to disseminate pharmacovigilance information. However, zero individual case safety reports were received in the last 12 months (2017/2018). There was either limited or no collaboration between the NTD programs and their respective national pharmacovigilance centers. None of the NTD programs had a specific budget for pharmacovigilance. The NTD program in all four countries had some safety monitoring elements. However, key elements, such as the reporting of adverse events, collaboration with national pharmacovigilance centers, and budget for pharmacovigilance activity, were limited/missing.

Fluconazole-induced intoxication with phenytoin in a patient with ultra-high activity of CYP2C9.

PURPOSE: The cytochrome P450 enzyme CYP2C9 metabolizes several important drugs, such as warfarin and oral antidiabetic drugs. The enzyme is polymorphic, and all known alleles, for example, CYP2C9*2 and*3, give decreased activity. Ultra-high activity of the enzyme has not yet been reported. METHODS: We present a patient with Behçet's disease who required treatment with high doses of phenytoin. When fluconazole, a potent inhibitor of CYP2C9, was added to the treatment regimen, the patient developed ataxia, tremor, fatigue, slurred speech and somnolence, indicating phenytoin intoxication. On suspicion of ultra-high activity of CYP2C9, a phenotyping test for CYP2C9 with losartan was performed. RESULTS: The patient was shown to have a higher activity of CYP2C9 than any of the 190 healthy Swedish Caucasians used as controls. CONCLUSIONS: Our finding of an ultrarapid metabolism of losartan and phenytoin may apply to other CYP2C9 substrates, where inhibition of CYP2C9 may cause severe adverse drug reactions.

Prevalence, Intensity, and Correlates of Soil-Transmitted Helminth Infections among School Children after a Decade of Preventive Chemotherapy in Western Rwanda.

Preventive chemotherapy (PC) is a WHO-recommended core intervention measures to eliminate Soil-Transmitted Helminths (STH) as a public health problem by 2020, defined as a reduction in prevalence to <1% of moderate or high-intensity infection. We conducted a cross-sectional study to investigate the prevalence, intensity, and correlates of STH after a decade of PC in Rwanda. A total of 4998 school children (5-15 years old) from four districts along Lake Kivu in the western province were screened for STH using Kato-Katz. The overall prevalence of Soil-transmitted helminths among school children was 77.7% (range between districts = 54% to 92%). Trichirus trichiura was the most common STH (66.8%, range between districts = 23% to 88.2%), followed by Ascaris lumbricoides (49.9%, range between district = 28.5% to 63.3%) and hookworms (1.9%, range between districts = 0.6% to 2.9%). The prevalence of single, double and of triple parasite coinfection were 48.6%, 50.3%, and 1.1%, respectively. The overall prevalence of moderate or high-intensity infection for Trichirus trichiura and Ascaris lumbricoides was 7.1% and 13.9, respectively. Multivariate logistic regression model revealed that male sex, district, stunting, and schistosomiasis coinfection as significant predictors of STH infection. Despite a decade of PC implementation, STH remain a significant public health problem in Rwanda.

Comparative Assessment of the National Pharmacovigilance Systems in East Africa: Ethiopia, Kenya, Rwanda and Tanzania.

INTRODUCTION: The increased access to medicinal products in Africa is not well-matched with the pharmacovigilance capacity to monitor drug safety. The objective of this study was to assess the functionality and identify the strengths and limitations of the national pharmacovigilance systems in Ethiopia, Kenya, Rwanda, and Tanzania, and compare these systems. METHODS: Legal and statutory documents governing the pharmacovigilance systems of each participating country were examined by assessors prior to on-site review. The staff of the pharmacovigilance unit of the National Medicines Regulatory Authorities (NMRAs) were interviewed using the East African Community Harmonized Pharmacovigilance Indicators tool, supplemented with indicators from the World Health Organization (WHO) Global Benchmarking Tool. Responses were recorded, and data were analyzed. RESULTS: The pharmacovigilance systems were supported by law and regulations in line with international standards. Standard operating procedures for receiving, processing, and communicating suspected adverse event reports were in place, but reporting of suspected medicine-related harm from stakeholders was inadequate in all countries. The number of Individual Case Safety Reports (ICSRs) received by NMRAs in Kenya, Ethiopia, and Tanzania (mainland) were 35.0, 6.7, and 4.1 per million inhabitants, respectively, in the last calendar year. At the time of assessment, Rwanda did not have an operational system. Overall, ≤ 1% of the total number of health facilities per country submitted ICSRs. Only Kenya and Tanzania had a designated budget for pharmacovigilance activities and an electronic ICSR reporting system. The national pharmacovigilance systems in all four countries did not have access to data on drug utilization. CONCLUSIONS: The national pharmacovigilance systems in the four East African countries have policy and legal frameworks defined by law and regulation to conduct pharmacovigilance activities. However, the four national pharmacovigilance systems are at different levels of capacity and performance with respect to conducting pharmacovigilance activities. Targeted interventions are needed to strengthen the pharmacovigilance systems to enable evidence-based decision making for patient safety.

Guidelines for submitting adverse event reports for publication.

Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' web sites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation and reporting of suspected drug or other medical product adverse events.

Financial incentives linked to self-assessment of prescribing patterns: a new approach for quality improvement of drug prescribing in primary care.

BACKGROUND: Financial incentives have been suggested to be effective in increasing the quality and efficiency of drug prescribing. Concern has been raised in relation to potential negative consequences on the quality of care. AIMS: To describe and analyse the impact of an incentives model linking payment with adherence to drug and therapeutics committee (DTC) guidelines and self-reflection of prescribing pattern in a 'prescribing quality report'. METHODS: The study was performed in the county of Stockholm, Sweden, with 139 (out of 154) primary healthcare centres (PHCs) participating in the project and 15 PHCs not participating. The study consisted of two parts: a quantitative observational study of prescribing patterns and a qualitative analysis of the submitted prescribing quality reports. All prescriptions issued from PHCs and dispensed at pharmacies during October to December 2005 and October to December 2006 were analysed, using adherence to the regional DTC guidelines as the main outcome measure. Adherence was assessed using the drug utilisation 90% methodology, i.e. focusing on drugs constituting 90% of the prescribed volume and the proportion of drugs included in the guidelines. The qualitative analysis focused on reports on the quality of drug prescribing submitted by each PHC in early 2007. RESULTS: The 139 PHCs participating in the programme accounted for 85% of all prescriptions issued in primary care during October to December 2006. Mean adherence to guidelines increased among participating practices by 3.3 percentage units (95% confidence interval (CI) 2.9-3.7%) to 83% (82.6-83.7%) during the year. The adherence among practices not participating increased by 3.1 percentage units (95% CI 1.7-4.4%) to 78.8% (95% CI 76.7-80.9%). The higher adherence achieved during the year corresponded to savings estimated at five times greater than the cost of running the programme including the financial incentives. In addition, many areas for improving prescribing were identified, such as limiting the prescribing of drugs with uncertain safety profiles and documentation as well as reporting adverse drug reactions. CONCLUSION: Although no causal effect can be attributed without a control group, we have shown the feasibility of a model linking payment to DTC adherence. This approach with its own quality assessment and goal setting offers an example to other regions and countries of how to increase the quality and efficiency of drug prescribing within limited resources.

Drug utilisation 90% (DU90%) profiles of antibiotics in five Chinese children's hospitals (2002-2006).

This study surveyed the pattern of inpatient antibiotic use in five Chinese children's hospitals between 2002 and 2006, focusing on the antibiotics accounting for 90% of the volume utilised as well as the level of adherence to guidelines. The Anatomical Therapeutical Chemical Classification/Defined Daily Doses (ATC/DDD) and the drug utilisation 90% (DU90%) methodologies were used. In October 2004, national antibiotic guidelines were issued that divided antibiotics into non-restricted, restricted and special use grades. In five children's hospitals, a total of 56 different systemic antibiotics were used during the study period. Antibiotics that could be injected accounted for 59.0-99.8%. beta-Lactam antibacterials (ATC codes J01C and J01D) were the most used subgroups. The numbers of antimicrobial agents and non-restricted antibiotics within the DU90% segment were 11-20 and 5-9, respectively. The proportion of non-restricted antibiotic consumption was ca. 40% in 2006 in four hospitals, which varied among hospitals during the period 2002-2005. There was considerable variation both in the pattern and amount of antibiotics used in the five hospitals, with amoxicillin/clavulanic acid, cefuroxime and cefazolin being the most commonly used substances. We also observed a decrease in the ranks of some restricted and special use antibiotics after the guidelines were issued in one hospital. The DU90% profiles were proven to be useful in studying the pattern of antibiotic use in hospitals. Finally, the study observed the effectiveness of guidelines for antibiotic use in some hospitals, although injectable antibiotics were widely used in children's hospitals in China.

CYP2D6 is a major determinant of metoprolol disposition and effects in hospitalized Russian patients treated for acute myocardial infarction.

PURPOSE: To investigate individual metabolism-related determinants of metoprolol disposition and effects in patients receiving the drug as standard treatment for acute myocardial infarction (AMI). METHODS: We recruited 187 AMI patients receiving metoprolol on clinical grounds and genotyped them for CYP2D6 *3, *4, *10, and gene duplication. Heart rates (HR) at admission and discharge were registered. Clinical details were derived from the case histories. Metoprolol and alpha-hydroxy-metoprolol were analyzed by HPLC in plasma before and after 2, 6 and 12 h post dose in the first 115 patients. HR at rest was registered after each sampling. Ventricular rhythm disturbance (VRD) association with CYP2D6 activity, found accidentally, was studied in a newly formed subgroup (n = 23). RESULTS: Metoprolol represented 85% of all beta-blocker prescriptions. CYP2D6 genotype distribution was comparable with other Caucasian populations. Genotypically poor metabolizers (PM, n = 2) exhibited the most pronounced bradycardia at discharge, while in the ultrarapid metabolizers (UM, n = 7) therapeutic effect was not achieved. Metoprolol and alpha-hydroxy-metoprolol plasma concentration AUCs differed significantly between the genotypes corresponding to predicted metabolic activity (P < 0.005). Correspondingly, the mean HRs were lower in PMs and increased with increasing number of active CYP2D6 genes (P < 0.05). Trough metoprolol concentrations were only quantifiable in patients with at least one mutated allele. Neither decreased cardiac ejection fraction nor age and gender influenced metoprolol disposition. Higher mean number of active CYP2D6 genes was found in patients with VRDs (2.2 vs. 1.7), which could not be clearly explained by metoprolol concentrations. CYP2D6 gene duplication was overrepresented in this group (22 vs. 2%, P = 0.0002). CONCLUSION: Metoprolol disposition and effects are mainly controlled by CYP2D6 genotype. Patients with gene duplication are at high risk of not benefiting from treatment due to lower metoprolol concentrations. Higher CYP2D6 activity seems to be associated with VRDs complicating AMI, being a negative prognostic factor for patients' survival.

Quality use of medicines: a new method of combining antibiotic consumption and sensitivity data--application in a Russian hospital.

PURPOSE: Antibiotic use and resistance is subject of great concern. There is a need for internationally comparable and locally useful data collection and reporting. We developed a new method to combine and present data on antibiotic use and resistance in a figure in a Russian 1300 bed-hospital. METHODS: We applied World Health Organization (WHO) Anatomic Therapeutic Chemical (ATC) classification/defined daily doses (DDD) analysis on antibacterials for systemic use (ATC: J01) delivered by the pharmacy for the years 2003-2005. Microbial resistance data were presented within the range of drugs accounting for 90% of the volume in DDD, i.e. drug utilisation 90% (DU90%). RESULTS: From the DU90% profile the following was seen: in 2003, 12 of 25 drugs accounted for 90% of the volume. For six of the most commonly used antibiotics, including the two cheapest (gentamicin, ampicillin), a significant number of the strains tested were resistant. For the remaining antibiotics no resistance data were available. These data were discussed in early 2004. A general decrease of antibiotic use and resistance was seen in 2005 (by 57% from 15.5 to 8.8 DDD/100 bed days) with a concomitant decrease in expenditures (by 64%) and a shift to more potent antibiotics. CONCLUSIONS: The created profile highlighted potential problems in a clear and easy form. Besides being an indicator of the quality of antibiotic use it was a powerful alert and driving force for change. It can be used for external comparisons and for local monitoring of antibiotic use and resistance and can be applied with routinely available data in any hospital.

Guidelines for submitting adverse event reports for publication.

Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' websites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation, and reporting of suspected drug or other medical product adverse events.