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Ibuprofen was the first member of Propionic acid derivatives introduced in 1969. It is a popular domestic and over the counter analgesic and antipyretic for adults and children. Ibuprofen has been rated as the safest conventional NSAID by spontaneous adverse drug reaction reporting systems in the UK. This article summarizes the main pharmacological effects, therapeutical applications and adverse drug reactions, drug-drug interactions and food drug interactions of ibuprofen that have been reported especially during the last 10 years. [ABSTRACT FROM AUTHOR]

The study aimed to compare performance between the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) methods in identifying serious adverse drug reactions (ADRs) using the Thai FDA spontaneous database. The two methods were retrospectively applied to identify new, Serious ADRs reported with antiretroviral therapy (ART) drugs using the data set between 1990 and 2006. We plotted the ROR and the information component against time to compare the differential timing of signal detection and the pattern of signaling over time between these methods. The ROR and the BCPNN methods identified the associations between ART drugs and serious ADRs at the same time. Both methods were similar in detecting the first signal of a potential ADR. However, the pattern of signaling seems relatively different with each method. Additional analyses of different drugs, ADRs, and databases will contribute to increase understanding of methods for post- marketing surveillance using spontaneous reporting system. [ABSTRACT FROM AUTHOR]

The optimum timing of drug safety data mining for a new drug is uncertain. The objective of this study was to compare cumulative data mining versus mining with sliding time windows. Adverse Event Reporting System data (2001-2005) were studied for 27 drugs. A literature database was used to evaluate signals of disproportionate reporting (SDRs) from an urn model data-mining algorithm. Data mining was applied cumulatively and with sliding time windows from 1 to 4 years in width. Time from SDR generation to the appearance of a publication describing the corresponding adverse event was calculated. Cumulative data mining and 1- to 2-year sliding windows produced the most SDRs for recently approved drugs. In the first postmarketing year, data mining produced SDRs an average of 800 days in advance of publications regarding the corresponding drug-event combination. However, this timing advantage reduced to zero by year 4. The optimum window width for sliding windows should increase with time on the market. Data mining may be most useful for early signal detection during the first 3 years of a drug's postmarketing life. Beyond that, it may be most useful for supporting or weakening hypotheses. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the incidence of adverse drug reactions (ADRs) in children in Camagüey Province, Cuba. METHODS: A national pharmacovigilance programme has been established in Cuba and involves suspected ADRs being reported to provinces. All suspected ADRs reported to Camagüey Province during 2008 were analysed and classified in relation to causality and severity. RESULTS: Over a 12-month period, there were 124 reports of 152 suspected ADRs in children. Most ADRs were mild (98, 79%), but two were fatal and five others were severe. Antibiotics were the group of medicines most likely to be associated with ADRs. The overall report rate of suspected ADRs was 634 per million children per year, which is considerably higher than previously reported rates. CONCLUSIONS: ADRs in children are more frequent than previously reported. A successful pharmacovigilance programme can be established in lower middle income countries. [ABSTRACT FROM AUTHOR]

Background: Theoretically, angiotensin II receptor blockers (ARBs) have certain advantages over angiotensin-converting enzyme inhibitors, but the contribution of these advantages to the clinical effect of ARBs is not known. Objective: To compare the efficacy and tolerability of telmisartan with enalapril in patients of essential hypertension. Materials and Methods: Patients of mild to moderate hypertension were randomized to receive either 40 mg of telmisartan or enalapril 10 mg once a day orally for 12 weeks. At each visit, the systolic blood pressure (BP), diastolic BP and heart rate of each patient were recorded. Investigations such as hemogram hemoglobin, total leucocytes count (Hb, TLC), serum creatinine, serum glutamic oxaloacetic transaminase, serum glutamic pyruric transaminase (SGOT, SGPT) random blood sugar and urine examination were performed at baseline and after 12 weeks of the treatment period. Results: The mean reduction in systolic BP in the telmisartan/enalapril group was 26.38 ± 10.98/26.74 ± 8.24 mmHg while the mean reduction in diastolic BP in the telmisartan/enalapril group was 14 ± 2.98/9.71 ± 4.23 mmHg, respectively, at 12 weeks. When the reduction in systolic BP in the two groups was compared, there was no significant difference between the groups (P > 0.05). However, the mean reduction in diastolic BP achieved with telmisartan at 12 weeks was significantly higher (P < 0.001) than that achieved with enalapril after the corresponding period. The overall frequency of adverse-effects was similar. However, in the enalapril group, the incidence of dry cough was higher as compared to that in the telmisartan group (11.43% vs. 0%, respectively; P < 0.05). Conclusion: Telmisartan produces a greater reduction in diastolic BP than enalapril and is free from the adverse-effect of dry cough that is commonly encountered with enalapril. [ABSTRACT FROM AUTHOR]

Objective Qin Kai Ling (QKL) injection, which is based upon the traditional Chinese medicine formulation 'An Gong Niu Huang Wan', is widely used in treatment of many diseases. This review aims to assess the safety of QKL. Methods We searched Chinese databases CNKI and VIP for articles published between January 1987 and April 2009. Results A total of 1486 cases were included in this review. We were unable to determine the frequency of ADR/AE induced by QKL due to the lack of complete production and market information. We estimate, based on the limited data, that the risk of ADR/AE from QKL use should be low. We found some ADR/AE may have been induced by incorrect use of QKL, such as use in infants, or use with incompatible drugs, and some places may not suite for use of QKL, for example, four of seven patients died in private clinics or patient's home. We unable to distinguish whether incidents were ADRs or AEs because the poor reports. Conclusion Current evidence, while weak, indicates that QKL carries a low risk of ADR/AE, and some adverse events that do occur may be ascribed to improper use of the drug. Reporting of ADR/AEs needs to be greatly improved, and should follow the 'Recommendations for reporting traditional Chinese medicine adverse drug reaction'. [ABSTRACT FROM AUTHOR]

Abstract: Comparative effectiveness reviews (CERs) are systematic reviews that evaluate evidence on alternative interventions to help clinicians, policy makers, and patients make informed treatment choices. Reviews should assess harms and benefits to provide balanced assessments of alternative interventions. Identifying important harms of treatment and quantifying the magnitude of any risks require CER authors to consider a broad range of data sources, including randomized controlled trials (RCTs) and observational studies. This may require evaluation of unpublished data in addition to published reports. Appropriate synthesis of harms data must also consider issues related to evaluation of rare or uncommon events, assessments of equivalence or noninferiority, and use of indirect comparisons. This article presents guidance for evaluating harms when conducting and reporting CERs. We include suggestions for prioritizing harms to be evaluated, use of terminology related to reporting of harms, selection of sources of evidence on harms, assessment of risk of bias (quality) of harms reporting, synthesis of evidence on harms, and reporting of evidence on harms. [Copyright &y& Elsevier]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Gabapentin enacarbil is a transported prodrug of gabapentin that provides sustained, dose-proportional exposure to gabapentin by taking advantage of high-capacity transport pathways expressed throughout the intestinal tract. This prodrug has shown efficacy in multiple clinical trials for the treatment of moderate-to-severe primary restless legs syndrome and could potentially represent the first non-dopaminergic treatment for this important disease. WHAT THIS STUDY ADDS • Unlike gabapentin, gabapentin enacarbil is actively absorbed from the intestine by multiple pathways, including the monocarboxylate transporter type-1 transporter (MCT-1). Although drug interactions of gabapentin have been reported in the literature, the distinctly different absorption pathway of gabapentin enacarbil requires a separate evaluation of the potential for interaction with other substrates of MCT-1. To achieve this, the pharmacokinetics of gabapentin enacarbil were examined in healthy adults when administered alone or in combination with naproxen, a known MCT-1 substrate. • After absorption, gabapentin enacarbil is completely hydrolyzed to gabapentin, and the released gabapentin is excreted by renal elimination. Gabapentin is a substrate for the organic cation transporter type-2 (OCT2) present in the kidney. To examine the potential for an elimination-site drug interaction resulting from administration of the prodrug, the pharmacokinetics of gabapentin enacarbil were examined in healthy adults when administered alone or in combination with cimetidine, a known substrate of OCT2. AIM Gabapentin enacarbil, a transported prodrug of gabapentin, provides sustained, dose-proportional exposure to gabapentin. Unlike gabapentin, the prodrug is absorbed throughout the intestinal tract by high-capacity nutrient transporters, including mono-carboxylate transporter-1 (MCT-1). Once absorbed, gabapentin enacarbil is rapidly hydrolyzed to gabapentin, which is subsequently excreted by renal elimination via organic cation transporters (OCT2). To examine the potential for drug-drug interactions at these two transporters, the pharmacokinetics of gabapentin enacarbil were evaluated in healthy adults after administration alone or in combination with either naproxen (an MCT-1 substrate) or cimetidine (an OCT2 substrate). METHODS Subjects ( n= 12 in each study) received doses of study drug until steady state was achieved; 1200 mg gabapentin enacarbil each day, followed by either naproxen (500 mg twice daily) or cimetidine (400 mg four times daily) followed by the combination. RESULTS When gabapentin enacarbil was co-administered with naproxen, gabapentin Css,max increased by, on average, 8% and AUC by, on average, 13%. When gabapentin enacarbil was co-administered with cimetidine, gabapentin AUCss increased by 24% and renal clearance of gabapentin decreased. Co-administration with gabapentin enacarbil did not affect naproxen or cimetidine exposure. Gabapentin enacarbil was generally well tolerated. CONCLUSIONS No gabapentin enacarbil dose adjustment is needed with co-administration of naproxen or cimetidine. [ABSTRACT FROM AUTHOR]

A number of drug interactions that may potentially occur with local anaesthetic preparations are listed in the British National Formulary (BNF) and Summaries of Product Characteristics (SmPC). Many are theoretical or are associated with higher doses of local anaesthetic preparations than those used for dental procedures in primary care. Reports of serious interactions between medicines and local anaesthetic preparations occurring in dental practice are exceedingly rare. Practitioners can minimize the risk of interactions by using an aspirating syringe, which reducesthe likelihood of the local anaesthetic being administered directly into a blood vessel. Adhering to the dosage recommendations in the product literature will also minimize the risk. This paper will explore the clinical significance of potential interactions between dental local anaesthetic preparations used in primary care and other medicines as listed in the BNF and SmPCs. These are summarized in Tables 1 and 2. Clinical Relevance: A knowledge of potential drug interactions with local anaesthetic preparations is essential for clinicians. [ABSTRACT FROM AUTHOR]

It was predicted from the mechanism of action that, compared to older non-steroidal anti-inflammatory drugs, rofecoxib (Vioxx) would reduce gastrointestinal bleeding, but also that it would increase the occurrence of cardiovascular thrombosis. From the patient’s point of view, both effects are important and should be investigated and reported similarly. We studied how they have been reported over time. We searched PubMed for abstracts on rofecoxib that commented on gastrointestinal bleeding or cardiovascular thrombosis or both. Two researchers, blinded to date of publication and authors, assessed the abstracts independently. We judged the authors' view on rofecoxib and comments on gastrointestinal bleeding and thrombosis as being favourable, neutral or unfavourable towards rofecoxib. We included 393 abstracts commenting on gastrointestinal bleeding (72%) and cardiovascular thrombosis (54%) or both. Before October 2000, all abstracts ( n = 27) mentioned only gastrointestinal bleeding and 89% were positive towards rofecoxib. The year before the withdrawal of rofecoxib (October 2003 to September 2004) ( n = 46), 59% of abstracts commented on gastrointestinal bleeding only, 17% on thrombosis only, 24% on both and 67% were still positive. From October 2006 to September 2007 ( n = 54), 13% mentioned gastrointestinal bleeding, 54% thrombosis, 33% mentioned both and only 11% were positive. The reporting of benefits and harms was not balanced and changed markedly over time. Knowledge of increased risk of thrombosis existed early on, but the harms came into focus too late, when the drug was already withdrawn, and when tens of thousands of patients had been harmed unnecessarily. [ABSTRACT FROM AUTHOR]

Objective To investigate: (1) the feasibility of establishing active paediatric surveillance for adverse drug reactions (ADRs), (2) whether electronic reporting is effective and (3) whether such a system could complement the Medicines and Healthcare products Regulatory Agency (MHRA) yellow card system. Design Between January 2006 and February 2007 ADRs in children under 16 were reported each month by consultant paediatricians and paediatric pharmacists in Scotland. For 8 months respondents received a postal card, after which half were selected to report electronically via an email card for a further 6 months and half continued with the postal card. Reports of paediatric ADRs severe enough to warrant hospital admission or to delay discharge of hospitalised patients or resulting from an outpatient prescription were followed up. A postal questionnaire evaluated the system at the end of the study. Results Following a 2-month lead-in period, 83% of the cards were returned over the year, 84% by paediatricians and 82% by pharmacists. With electronic reporting the response rate was 80%. Eighty-seven confirmed reports of a drug being associated with one or more adverse reactions were reported in 67 children. Only eight children were also identified through the MHRA yellow card system. Respondents indicated continuing willingness to contribute to an active (preferably electronic) reporting system. Conclusions Active paediatric ADR surveillance is feasible; electronic reporting is effective and data collected are different to, but could complement, those collected by the MHRA yellow card. [ABSTRACT FROM AUTHOR]

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MEDWATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MEDWATCH, please consider sharing the account with our readers. Write to Dr. Shuster at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-947-7797; fax: 215-914-1492; e-mail: joel.shuster@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MEDWATCH program and Temple University School of Pharmacy. ISMP is an FDA MEDWATCH partner. [ABSTRACT FROM AUTHOR]

Background The possible role of leukotriene receptor antagonist (LTRA) therapy in the pathogenesis of Churg- Strauss syndrome (CSS) is uncertain. The aim was to examine the association between LTRA therapy and CSS in cases registered in the FDA Adverse Event Reporting System (AERS) database. Methods All cases of suspected drug-induced CSS reported to the AERS database between November 1997 and April 2003 were reviewed. Subjects in whom LTRAs were the suspected medication and sufficient documentation existed to confirm the diagnosis of CSS were sequentially categorised into one of the following groups: (A) CSS before treatment initiation; (B) oral or inhaled corticosteroids reduced or stopped within 6 months of CSS onset; (C) possible prodromal phase of CSS at treatment initiation; (D) unstable asthma at treatment initiation; (E) stable asthma at treatment initiation. Results There were 181 case reports of suspected druginduced CSS with sufficient documentation to confirm a diagnosis of CSS; in 163 (90%) an LTRA was a suspect medication. In 140 of these 163 cases there was sufficient documentation to sequentially categorise the case into groups, with 13 (9%) in A, 27 (19%) in B, 11 (8%) in C, 28 (20%) in D and 61 (44%) in E. Conclusion LTRA therapy was a suspect medication in most confirmed cases of CSS reported in the AERS database. In the majority of cases treated with an LTRA, CSS could not be explained by either corticosteroid withdrawal or pre-existing CSS. These findings are informative in considering the potential associations between LTRA therapy and CSS. [ABSTRACT FROM AUTHOR]

Clearly report adverse effect or adverse event occurred in the clinical practice is very important for understanding the potential risk of using a drug for treatment of diseases, and with other advantages. This document aims to help healthcare providers to organize, report, and publish information on ADR/AE occurrences and to identify the nature of the ADR/AE in TCM and integrative medicine practice. This document provides recommendations on constructing a title, basic factors of writing an abstract and the text of ADR/AE reporting. In each part, there are some samples could be references for the development of a report and ADR/AE. We welcome any comments for improving this recommendation. [ABSTRACT FROM AUTHOR]

Background While reporting of adverse drug events (AE) and adverse drug reactions (ADR) following Chinese materia medica (CM) injection is becoming more common, the reporting quality is of concern. Methods A checklist about the reporting quality of AE/ADR was set up, and the ADR/AE reporting of Herba Houttuyniae injection was chosen as an example. Electronic databases Chinese Journal Net (1994-2009) and Chinese Science and Technological Journal Net (VIP) (1989-2009) were searched for target literature. Results Based on our search strategy, 210 articles were included, with 175 articles reporting single or several cases of ADR/AE following Herba Houttuyniae injection (type I report). There were seven reports from regional or national ADR monitoring centers (type II report), and 28 summary reports from a single hospital or medical center (type III report). All 210 papers mentioned 'adverse effect,''safety' or related meaning words in their titles, but 199 articles did not have abstract. Patient demographic characteristics were not fully reported in these articles. In type I articles, only 97 cases (43.11%) mentioned whether patients had or did not have a history of allergies, whereas 128 cases (56.89%) in type II papers and 14 (50%) type III papers, did not mention allergic history of patients. Only three articles (3/210, 1.43%), all of them type I, mentioned the syndrome type in Chinese medicine. None of the papers gave clear indications of the type and grade of ADR/AE of patients. Most papers did not report details of the CM injection procedure, such as the drug company, product serial number, or the drug's validity period. Data about the occurrence time and management of ADR/AE was also inadequately reported. Conclusion and recommendations The current reporting format of ADR/AE in clinical CM injections is not standardized. Much fundamental information of ADR/AE following CM injection is therefore missing. A standard reporting format for ADR should be developed, and should include the following: (1) a title mentioning adverse effects and safety; (2) a structured abstract including adequate information about the patient and the disease treated, the drug used, the specific ADR/AE, physician response to the ADR/AE, and result of management; (3) demographic characteristic of the patients (gender, age, etc.); (4) clinical characteristics of patients (disease, syndrome, etc); (5) allergic history of patients; (6) diagnosis and syndrome based on Chinese medicine theory; (7) detailed information about the CM intervention (the manufacturer of the drug, series number, valid dates, dosage, route of administration, menstruum, dripping speed, etc.); (8) concomitant drug use; (9) time and symptoms of ADR/AE; (10) type and grading of ADR/AE; (11) physiological systems affected by ADR/AE; (12) specific treatment and prognosis for ADR/AE; (13) evidence of the cause and effect of ADR/AE; and (14) any other possibility of ADR/AE. Also, a ADR/AE registration system should be established. [ABSTRACT FROM AUTHOR]

Data mining is used in pharmacovigilance as an adjunct to traditional pharmacovigilance practices. There remains ongoing debate as to the impact automated signal detection would have on pharmacovigilance resources. An important component of this debate is the value of each statistical alert or signal of disproportional reporting (SDR) and the resources needed to evaluate SDRs that are clinically unimportant. Using the terminology of diagnostic testing, such SDRs are called false positives as they are statistically positive but are clinically negative. Based on the clinical testing paradigm, a more stringent threshold increases the sensitivity of the test by lowering the number of false positives; however, the trade off of increased sensitivity is a reduced specificity, i.e. potentially missing clinically relevant problems. In developing the protocol to assess the clinical validity of an SDR, a literature search was conducted to determine what threshold(s) were commonly used for data mining adverse event databases. Of the more than 100 manuscripts identified, 41 published the results of data mining excursions with a clearly identified threshold for significance. The commonly used data mining algorithms were proportional reporting ratio (PRR), reporting odds ratio (ROR), multi-item gamma Poisson shrinker (MGPS) and Bayesian confidence propagation neural network (BPCNN). There was some variation in the threshold used for each algorithm. For the PRR, thresholds of 1.0, 1.5 and 2.0 were reported. Some authors required a Chi-squared test statistic of >4.0. Minimum drug-event pair counts were most often required for the frequentist measures of disproportionality, PRR and ROR. Among the Bayesian algorithms, MGPS and BPCNN, there was variation in the metric used and, within a metric, variation in thresholds and the use of minimum case counts. Metrics based on the MGPS algorithm that have been used to determine statistical significance include the empirical Bayes geometric mean (EBGM), the lower 95% confidence interval of the EBGM, the lower 95% confidence interval of the empirical Bayes arithmetic mean, EBlog2 and interaction signal score. Based on the published literature, there is considerable variation in defining a significant alert or SDR among practitioners of pharmacovigilance data mining. Research into the impact of such variations in practice on SDR volume and value is urgently needed. [ABSTRACT FROM AUTHOR]

Alzheimer-disease-associated β-amyloid (Aβ) is produced by sequential endoproteolysis of β-amyloid protein precursor (βAPP): the extracellular portion is shed by cleavage in the juxtamembrane region by β-amyloid-cleaving enzyme (BACE)/β-secretase, after which it is cleaved by presenilin (PS)/γ-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces Aβ generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce Aβ production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces Aβ generation without affecting BACE or PS/γ-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and βAPP, which reduces β-cleavage of βAPP. Therefore, the data demonstrate that Dx-E represents a novel Aβ-reducing process which could have fewer side effects than secretase inhibitors. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The ultimate goal of pharmacovigilance is to protect patients from drug-induced harm and allow them to derive maximum benefits from medicines. All pharmacovigilance centres have an interest in showing the extent to which they achieve this aim. A core activity is spontaneous reporting. We have considered here whether it is possible to construct appropriate performance indicators for this method. Methods: We set out the stages in the process of pharmacovigilance and sought to decide what specific objectives of the centres could be helpful as practical indicators related to desired outcomes of pharmacovigilance and considered criteria to assess the practicality of an indicator. Results: We constructed a model of the pharmacovigilance process, listed the core functions and deduced a series of potential performance indicators that would be used in practice. Examples included number of reports per million population; proportion of valid reports; number of signals identified; regulatory or clinical action taken. For example data from USA compared to African country show how huge resources in USA give myriad reports, signals and regulatory decisions compared to Africa. Discussion: Pharmacovigilance centres have limited influence over the many complex interactions between patient, prescriber, manufacturer, government and media. However the proposed indicators can be measured in different countries, regions and at different times and allow comparisons. Conclusion: The pharmacovigilance system is a subsystem of a larger healthcare system and is affected by many factors. It is not easy to demonstrate the benefits of pharmacovigilance towards patient safety. However pharmacovigilance centres need to show the extent to which they achieve their objective such as number of reports, number of signals identified, regulatory or clinical action taken. These allow comparison between countries and overtime. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To examine the influence of the proposed symptom cluster of fatigue, nausea and vomiting, and sleep disturbances on clinical outcomes defined as behavior changes, depression, and performance status in children and adolescents before and after receiving cisplatin, doxorubicin, or ifosfamide chemotherapy.Design: A prospective, descriptive, within-group, before-and-after-chemotherapy design was used.Setting: Two major childhood cancer treatment hospitals in the United States.Sample: 67 patients aged 7-18 years who were receiving chemotherapy courses of cisplatin, doxorubicin, or ifosfamide.Methods: Fatigue, depression, behavior, and performance assessments were completed on the first day of cisplatin, doxorubicin, or ifosfamide therapy and one week later. Patients wore a wrist actigraph on the nondominant hand during the course of therapy and for 48 hours after discharge from the hospital. Nausea and vomiting were measured every 24 hours during the course of therapy and for 48 hours after discharge. A linear mixed model was used to evaluate the influence of the symptom cluster. Regression analysis was used to examine the associations between performance status and the symptom cluster. Principal component analysis with varimax rotation was used to produce the correlation of sleep symptoms.Main Research Variables: Fatigue, nausea and vomiting, sleep disturbances, behavior, depression, and performance.Findings: Adolescents with the cluster of increased fatigue and sleep disturbances experienced more depressive symptoms and behavior changes. Children with higher levels of fatigue had increased depressive symptoms. The more fatigue parents perceived in their children or adolescents, the more behavior and emotional difficulties were reported.Conclusions: Fatigue, sleep disturbance, and nausea and vomiting, when clustered, impacted depressive symptoms and behavior changes in adolescents after chemotherapy. In children, fatigue alone impacted depressive symptoms and behavior changes.Implications for Nursing: Symptom clusters can have a significant impact on children's and adolescents' quality of life during cancer treatment. Early recognition and intervention for these symptoms are an important nursing role. [ABSTRACT FROM AUTHOR]

Introduction: Adverse drug reactions (ADRs) are an important cause of morbidity and mortality among hospitalized patients. Objectives: This study was designed to describe the frequency, severity, and causality of ADRs in internal medicine units at a third-level university hospital. Materials and methods: A descriptive study was performed at internal medicine units, by means of a structured format, review of clinical records, and interview of hospitalized patients. The Naranjo algorithm was applied to patient adverse events to define causality. Additionally, ADRs were classified according to the Rawlins and Thompson criteria. Results: One hundred patients (50 men and 50 women) were included in the study. Ninety nine (99) adverse events were found among the patients. The Naranjo algorithm was applied to adverse events, resulting in twenty nine (29) probable ADRs, twenty (20) possible ADRs and fifty (50) doubtful ADRs. Cardiovascular drugs and antibiotics were the most frequent therapeutic groups associated with ADRs. In addition, two preventable medication errors were identified. Conclusions: Frequency of ADRs was similar to the number reported in other studies in internal medicine units. It is necessary to systematize efforts of pharmacological surveillance in hospital wards, toward an opportune detection and prevention of ADRs. [ABSTRACT FROM AUTHOR]

Objective: the purpose of the present study was to identify the number of adverse drug reactions in hospitalized patients, through active search for prescription of antihistamines, biperiden and vitamin K. Methods: we conducted an observational, descriptive study from July 2008-June 2009, by the search in medical records in the Clinica Universitaria Bolivariana, n=143. We estimated the frequency of probable or possible adverse drug reactions and spontaneous medical report. Results: we assessed 892 inpatient cases with antihistamines, biperiden or vitamin K prescription; 143 cases were included in the study for their relationship with treatment of possible or probable adverse drug reactions. We found a frequency of cases with no spontaneous medical report in 72.7% (n=104), the time for presentation of the latter was with a mean of 8.1 days, a median of 4 days, IQR (1-11) and a range in days of 0-37. Conclusion: we observed a low frequency of adverse drug reactions with spontaneous medical report and an average of eight days for notification when it was reported. Therefore, it is necessary to promote spontaneous and timely reporting that can help improve the safety in administered drugs. [ABSTRACT FROM AUTHOR]

The detection and reporting of serious adverse drug reactions (SADRs) have become important components of monitoring and evaluation activities performed in hospitals. We present the implementation of a prospective pharmacovigilance program based on automatic laboratory signals (ALSs) at a hospital. We also report the general findings after the first year of operation of the program, which involved ALSs that indicate various SADRs: agranulocytosis, aplastic anemia, liver injury, thrombocytopenia, hyponatremia, and rhabdomyolysis. The number of hospitalizations during the year was 54,525, and 1,732 patients experienced at least one ALS. The review of electronic medical records (EMRs) showed that no alternative cause (i.e., no non-SADR explanation) for the ALS was identified in 520 (30%) of the patients. After the individual ALS–patient evaluation, a total of 110 SADRs (6.35% of those identified after reviewing EMRs and 21.15% of those requiring individual patient evaluations) were identified. In other words, in order to identify a single SADR, we had to review the electronic records of approximately 16 patients and personally visit 5 patients. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the agreement among the US Department of Veterans Affairs (VA) listing of “critical” drug–drug interactions (DDIs) and two standard drug-interaction compendia. A list of critical DDIs, as defined by the VA, was compared with two standard commercially available compendia (Micromedex DRUG-REAX and Drug Interactions: Analysis and Management (DIAM)) in order to determine the level of agreement among the systems. Of 982 DDIs classified as critical by the VA, only 136 DDIs (13.7%) were considered critical in all three systems. Our conclusion was that, overall, there is poor agreement among the compendia and the VA system. [ABSTRACT FROM AUTHOR]

Letrozole which acts as an aromatase inhibitor is used in the treatment strategy for oestrogen receptor-positive breast cancer. Cutaneous adverse effects including vasculitis and erythema nodosum of letrozole have been rarely described in literature. Recently reported eczematous skin eruption due to letrozole is one of the side effects that known to be developed by this drug. To our knowledge letrozole induced linear drug eruption has not been described in previous reports. We report 52-year-old woman who had unilateral pruritic lichenoid eruption over left tight following Blaschko lines after using letrozole. Cutaneous side effects of aromatase inhibitors can be serious as progressive cutaneous vasculitis or can be presented with mild cutaneous side effects as in our case. The physicians should be aware of this benign clinical condition. The decision to discontinue medication is dependent to the knowledge of severity of the side effects. [ABSTRACT FROM AUTHOR]

The article presents a study aimed at establishing incident reporting feedback experience and attitudes among medical personnel to understand the reasons behind findings of the British National Health Service (NHS) staff in a secondary care setting in Great Britain.

The author argues on the plural of a "Yellow Card" anecdote about spontaneous reports (SRs) of suspected adverse drug reactions (ADRs) in Great Britain. Topics include the number of countries that have contributed to the World Health Organization (WHO) database of SRs, an argument that the plural of the anecdote is not data in the context of SRs, and the origin of the phrase about anecdotes.

As part of a patient safety curriculum, we developed a Web-based hazard and near-miss reporting system for postbaccalaureate nursing students to use during their clinical experiences in the first year of their combined BS-MS advanced practice nurse program. The 25-week clinical rotations included 2 days per week for 5 weeks each in community, medical-surgical, obstetrics, pediatrics, and psychiatric settings. During a 3-year period, 453 students made 21,276 reports. Of the 10,206 positive (yes) responses to a hazard or near miss, 6,005 hazards (59%) and 4,200 near misses (41%) were reported. The most common reports were related to infection, medication, environmental, fall, and equipment issues. Of the near misses, 1,996 (48%) had planned interceptions and 2,240 (52%) had unplanned interceptions. Types of hazards and near misses varied by rotation. Incorporating hazard and near-miss reporting into the patient safety curriculum was an innovative strategy to promote mindfulness among nursing students. [ABSTRACT FROM AUTHOR]

Background and purpose: Complaints about side-effects of antiepileptic drugs (AEDs) may be overlooked in clinical practice. We assessed the value and risks of an active intervention policy for reported complaints in a randomized controlled pragmatic trial. Methods: This randomized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals. They were considered well-managed by their treating physician, but reported moderate to severe complaints on a questionnaire (SIDAED, assessing SIDe effects in AED treatment). The intervention was adjustment of AED treatment (53 patients), either reduction of dose or switch of AED, versus continuation of treatment unchanged (58 control patients) during 7 months. Primary outcomes were quality of life (Qolie-10) and complaints score. Secondary outcome measures were the occurrence of seizures or adverse events. Results: After 7 months, the relative risk (RR) for improvement in quality of life was 1.80 (1.04–3.12) for the intervention group compared to control and the RR of decrease in complaints was 1.34 (0.88–2.05). In 58% of patients randomized to adjustment, the medication had indeed been changed. Discussion: In conclusion, despite a possible risk of seizure recurrence, adjustment of drug treatment in well-managed patients with epilepsy, who report considerable complaints, improves the quality of life. [ABSTRACT FROM AUTHOR]

Adverse drug reaction reporting is an important means of establishing new knowledge and generating early signals of possible drug complications. Several reporting systems exist for adverse events however these reporting systems are associated with relatively low levels of reporting. The quality of the reporting is also important which ultimately depends upon the information furnished by the clinician in the available form. In order to improve the quality of information provided in the form, healthcare professional should know the importance of any information that he/she is providing. In this study hundred filled ADR reporting forms were selected and analyzed with respect to the quality of information provided. It was observed that the columns which were required to be filled completely, but were not filled correctly were diagnosis, description of the event, outcome attributed to adverse event, relevant test/lab data, concomitant medications. These are important details that must be reported, for evaluation of cause–effect relationship. Thus health care professionals should be aware of the importance of the information they are providing in the form and they should get proper instructions for filling the form, so as to improve the quality of information provided in the form. More CMEs and workshops should be conducted to improve awareness. In this article an attempt is made to provide information on how to fill the form completely. [ABSTRACT FROM AUTHOR]

The article offers information on various issues to be considered on the care of transition patients with pediatric illnesses including cerebral palsy (CP), congenital heart disease (CHD) and cystic fibrosis. It mentions that patients desire parental presence when intravenous or inhaled anesthesia is inducted; however, the presence of parents in postanesthesia care unit must not be tolerated to avoid hard situations. It notes that the after effects of the treatment must always be considered.

The article presents abstracts on topics related to drug administration and utilization including the evaluation of the community pharmacist's perception on adverse drug reactions (ADR) reporting in Northern Malaysia, pharmacovigilance in Argentina's tertiary care hospital, and the improper use of drug in the hospitalized elderly population.

Objective: To examine: (1) the reliability of the severity rating scale used by the National Reporting and Learning System (NRLS) in England and Wales for medication errors; and (2) the likelihood of reporting medication errors among healthcare professionals. [ABSTRACT FROM PUBLISHER]

Objective. Consistent and reliable standards for reporting of regional anesthetic adverse events are lacking. The quality of reporting of regional anesthetic morbidity has not been assessed critically. Aim. To evaluate quality of regional anesthesia outcomes reporting. Methods. Published retrospective or prospective observational cohort or randomized controlled trials in peer-reviewed journals were reviewed, and judged according to seven criteria related to quality of reporting of regional anesthesia complications: method of accrual, duration of data collection, definition of complication, morbidity and mortality rates, grade of complication severity, exclusion criteria, and study follow up. Differences in reporting outcomes according to study design, sample size and time period were compared. Results. Ninety-one articles published from 1996–2006 involving 8,833 patients were analyzed. The majority of studies (75%) met ≤4 reporting criteria. Recently published, prospective studies with >200 patients were associated with significantly higher-quality reporting ( P < 0.05). Fewer than 50% of studies reported at least one recognized, accepted complication with defined criteria or indicated duration of follow up. Reporting compliance was worse (29%) for reporting of actual morbidity rates, and complications leading to death. Complication severity grading related to regional anesthesia was reported in 2% of studies. Conclusion. Consistent and comparative regional anesthesia outcome data are lacking in peer-reviewed journals. A graded regional anesthetic morbidity and mortality system according to the intensity of therapy required for the treatment of the defined complication is proposed, along with a structured format for the reporting of regional anesthesia complications according to defined reporting standards. [ABSTRACT FROM AUTHOR]

Purpose: In 2006 the Institute of Medicine reported that at least 400,000 preventable adverse drug events (ADEs) occur annually among patients being hospitalized, with costs of $3.5 billion (or $8,750 per preventable ADE). Recommended medication error prevention technologies include computerized prescriber order entry, bar-code medication administration, and computerized intravenous (IV) safety systems with dose-error reduction software. When St. Joseph's/Candler Health System replaced its existing IV pumps, the decision to incur the incremental cost for "smart" IV safety systems rather than traditional IV pumps resulted in financial benefits, improved safety, improved quality of care, and increased nursing satisfaction. Methods: Electronic data recorded at the bedside as caregivers administered medications provided information from which actual cost avoidance could be more readily calculated and presented objective evidence of the fiscal value of investments in innovative technologies. Results: Over a 5-year period, implementation of these smart systems reduced high-risk medication errors and patient-controlled analgesia-related undesired outcomes, helped avert at least 471 preventable ADEs, and provided a 5-year return on investment (ROI) of $1.87 million, with an internal rate of return of 81%. Conclusion: Financial analysis of the incremental costs of IV safety systems can help calculate anticipated ROI accurately and better prioritize implementation of these systems. [ABSTRACT FROM AUTHOR]

Databases of spontaneously reported cases of adverse drug reactions play a significant role in the safety monitoring of marketed medicinal products. However, the inherent limitations of such data render the interpretation of results fairly difficult. One major issue is the bias introduced by under-reporting or differential reporting of events. Despite considerable progress in the development of analytical tools for spontaneously reported data, the issue of reporting bias has not been effectively addressed in the literature. This article discusses the problem of handling reporting bias, considers the plausibility of adapting techniques from other areas of application and suggests directions for future research. While the problems associated with spontaneous reporting data are complex and multifaceted, it is concluded that judicious and careful use of rigorous statistical techniques to assess bias can help enhance the reliability of research on the relative toxicity of marketed products. [ABSTRACT FROM AUTHOR]

Abstract: Recently, the steroidal CYP17 inhibitor Abiraterone entered phase II clinical trial for the treatment of androgen-dependent prostate cancer. As 17α-hydroxylase-17,20-lyase (CYP17) catalyzes the last step in androgen biosynthesis, inhibition of this target should affect not only testicular but also adrenal androgen formation. Therefore CYP17 inhibitors should be advantageous over existing therapies, for example with GnRH analogues. However, steroidal drugs are known for side effects which are due to affinities for steroid receptors. Therefore we decided to synthesize non-steroidal compounds mimicking the natural CYP17 substrates pregnenolone and progesterone. The synthesis and biological evaluation of a series of 15 novel and highly active non-steroidal CYP17 inhibitors are reported. The compounds were prepared via Suzuki-cross-coupling, Grignard reaction and CDI-assisted SNt-reaction with imidazole and their inhibitory activity was examined with recombinant human CYP17 expressed in Escherichia coli. Promising compounds were further tested for their selectivity against the hepatic enzyme CYP3A4 and the glucocorticoid-forming enzyme CYP11B1. All compounds turned out to be potent CYP17 inhibitors. The most active compounds 7 and 8 were much more active than Ketoconazole showing activity comparable to Abiraterone (IC50 values of 90 and 52nM vs. 72nM). Most compounds also showed higher selectivities than Ketoconazole, but turned out to be less selective than Abiraterone. Docking studies using our CYP17 protein model were performed with selected compounds to study the interactions between the inhibitors and the amino acid residues of the active site. [Copyright &y& Elsevier]

Objectives: The objectives of this study were to initiate a pharmacist-coordinated program to improve the adverse drug reaction (ADR) reporting on complementary and alternative medicines (CAM) in a tertiary care hospital and to evaluate the pattern of the reported ADRs. Design: A targeted approach was taken in increasing the ADR reporting to CAM in a tertiary care hospital in South India. Suspected ADRs to CAM spontaneously reported over a period of 24 months were selected for evaluation. Reported ADRs were evaluated for patient demographics, reaction and drug characteristics, causality, severity, and outcome. Results: A total of 12 ADRs to CAM were reported, which included 9 to Ayurvedic and 3 to homeopathic medicines, which accounted for 1.5% of the ADRs reported to the ADR reporting unit. ADR resulted in hospitalization in 5 patients. The system organ class most commonly involved included skin and appendage disorders (58.3%). Only four of the reactions were previously reported in the literature. The mean time for onset of the ADR after the administration of the drug was 27.8 ± 36.1 days. The suspected drug was withdrawn in all the reports that resulted in recovery, with mean time for recovery 5.9 ± 3.6 days. The majority (66.6%) were moderate in severity and 2 were severe in nature. On causality assessment, 6 were probable in nature and the remaining were possible. Conclusions: Even though there were fewer ADRs reported by this spontaneous reporting system, it gave valuable information regarding the potential for adverse effects with these agents. The study has reinstated the potential role of spontaneous reporting in identifying lesser reported ADRs, including those to CAM. Such hospital-based programs can contribute much in increasing the safety-related data of these agents. [ABSTRACT FROM AUTHOR]

BACKGROUND/AIMS: To compare the intraocular pressure (IOP) lowering efficacy and side effects of latanoprost 0.005% and bimatoprost 0.03% in subjects with chronic primary angle closure glaucoma (PACG). METHODS: This was an observer-masked randomised crossover study of 60 PACG subjects who received either latanoprost or bimatoprost for 6 weeks, after which they were crossed over to the other medication for another 6 weeks. The IOP-reducing effect of the medications was assessed by the reduction in IOP after 6 weeks of treatment compared with baseline. RESULTS: Fifty-four subjects (80 eyes) completed the study. Latanoprost reduced IOP (mean (SD)) by 8.4 (3.8) mm Hg and bimatoprost by 8.9 (3.9) mm Hg from a baseline of 25.2 (3.6) mm Hg and 25.2 (3.6) mm Hg respectively (p = 0.23). Adverse events were mild in both groups; however there were twice as many reports of an adverse event in the bimatoprost group (81%) compared with the latanoprost group (40%, p<0.01). Ocular irritation was the most frequently reported adverse event in both groups; 22 subjects (37.9%) treated with bimatoprost experienced ocular hyperaemia as compared with 13 subjects (22.4%) treated with latanoprost (p = 0.11). CONCLUSIONS: Bimatoprost once daily was similarly effective in reducing IOP compared with latanoprost once daily in subjects with chronic PACG. Both drugs were well tolerated with mild ocular adverse events. [ABSTRACT FROM AUTHOR]

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MEDWATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MEDWATCH, please consider sharing the account with our readers. Write to Dr. Shuster at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-947-7797; fax" 215-914-1492; e-mail: joel.shuster@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MEDWATCH program and Temple University School of Pharmacy. ISMP is an FDA MEDWATCH partner. [ABSTRACT FROM AUTHOR]

Since its introduction into clinical practice in 1921, millions of epidurals are performed daily around the world. Anesthesiologists were quick to grasp its use for prolonged or continuous analgesia and routinely use it alone or in combination with general anesthesia. It has been found to be associated with less complications as compared to spinal analgesia and has taken a major chunk out of spinal practice. The success of epidural depends upon successful location and deposition of drugs into the epidural space. Blind identification of epidural space by loss of resistance or negative epidural space pressure has resulted in mixed results. The figures vary among the researchers but in about 25-30% cases, drugs are deposited at wrong place (outside epidural space). Epidurography offers the best method of confirming the needle or catheter tip location in the space, and has evolved itself a standard practice now. Although very rarely adverse reactions to the technic1ue or the contrast media have been reported, the method is highly recommendable and the pain practitioners and anesthesiologists are encouraged to use it more judiciously. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADRs) pose a significant burden on patients and the health system. ADR reporting contributes to data that guide patient safety strategies. Despite numerous strategies aimed to improve ADR reporting rates, ADRs continue to be under-reported. Aim: To compare the effectiveness and efficiency of identifying institutional ADRs using the International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) clinical coding surveillance and spontaneous reporting. Method: Medical records of multi-day (staying overnight or longer) inpatient separations (single patient encounter resulting in discharge) assigned an ADR-related ICD-10-AM code were retrospectively reviewed to verify if an ADR had occurred and whether the codes assigned were appropriate. ADR reports received via the spontaneous reporting system were also reviewed. ADRs were assessed for causality, seriousness and type of reaction. The drugs, type of adverse reactions involved and the resource implications of this reporting method were also investigated. Results: ICD-10-AM coding surveillance and spontaneous reporting resulted in an ADR reporting rate of 3.3% and 0.4% of inpatient separations, respectively. ICD-10-AM coding surveillance was more likely to identify type A ADRs than spontaneous reports although there were no significant differences in seriousness or causality. The ICD-10-AM codes assigned were appropriate in 94% of cases, with the omission of drugs being the most common discrepancy. Conclusion: The ICD-10-AM coding surveillance is an effective and efficient method of improving ADR reporting by utilising data collected for administrative purposes. [ABSTRACT FROM AUTHOR]

Abstract: Hemicrania continua (HC) is a daily continuous unilateral headache of moderate intensity with super imposed exacerbations of more severe pain accompanied by migrainous and cranial autonomic features. Response to indomethacin is an essential feature in the IHS diagnostic criteria. However, indomethacin is associated with a number of side effects. HC is a life long condition, and skipping of a single dose of indomethacin usually leads to reappearance of headache. Various drugs have been tried as alternatives to indomethacin in the patients intolerant to indomethacin. We report two cases of HC responsive to topiramate and review the available alternatives for the patients of HC. We also discuss the side effects of indomethacin in the various headache disorders and other painful conditions, and suggest the need for trial of other drugs for the patients of HC. [Copyright &y& Elsevier]

This article discusses the challenges associated with limiting the adverse cognitive effects of antiepileptic drugs. The long-term side effects of these medications are considered because of the risks of sedation, somnolence, insomnia, and dizziness in epileptic patients. The difficulties associated with identifying individual side-effects when the drug regimens taken by epileptic patients involves multiple medications are noted. Because of these difficulties and the challenges associated with uncertainties in the aetiology of epilepsy, accurate assessments of drug side-effects are difficult to obtain.

Lumiracoxib (Prexige; 2-[(2-fluoro-6-chlorophenyl)amino]-5-methyl-benzeneacetic acid) is a cyclooxygenase-2 selective inhibitor for the symptomatic treatment of osteoarthritis. Recently, the drug has been withdrawn in several countries due to serious liver side effects. Li et al. recently have shown that lumiracoxib is bioactivated to a proposed quinone imine that is trapped by N-acetylcysteine (NAC) to form two NAC adducts in human and rat liver microsomal incubations. The current study demonstrated that the lumiracoxib metabolite 4′-hydroxylumiracoxib (M5) can also be bioactivated by peroxidases such as horseradish peroxidase, myeloperoxidase, and prostaglandin H synthases. Efforts were also made to identify GSH adducts formed by P450s in human liver microsomal incubations of lumiracoxib. We herein report the detection and characterization of mono-, di-, tri-, and tetra-GSH adducts in these oxidizing systems. Most of the conjugates were generated as a result of bioactivation of M5 by both peroxidases and P450s. Quinone imine (M15) and two GSH-conjugated quinone imines (M17 and M18) were identified as intermediates in the formation of these conjugates. The latter two were formed through sequential elimination of the fluorine and chlorine groups of GSH-conjugated M15. An additional GSH adduct, which appeared to be formed directly from parent, was only observed in human liver microsomal incubations. A mechanism was proposed for the bioactivation of lumiracoxib and the formation of the observed GSH adducts. These results suggest that bioactivation of lumiracoxib and M5 may result in GSH depletion, covalent binding to proteins, and oxidative stress and may potentially lead to hepatotoxicity. [ABSTRACT FROM AUTHOR]

This study was designed to investigate attitudes to and incentive for reporting adverse drug reactions (ADRs) in general and towards nurses as reporters of ADRs in particular in a sample of hospital physicians. A questionnaire was sent to 1,201 randomly selected hospital physicians. The main factors for the decision to report an ADR were the severity of the reaction, a reaction to a new drug, and an unusual reaction. The most important factor for refraining from reporting was that the reaction was well known. There were no significant differences between males and females or between age groups in these aspects. A majority were positive or neutral to nurses as reporters. Only 6% stated that their willingness to report ADRs would be affected in a negative way if nurses were involved in the program for reporting. The results of this survey showed that inclusion of hospital nurses as reporters will not decrease the reporting rate from the physicians. [ABSTRACT FROM AUTHOR]

A record number of deaths and serious injuries associated with drug therapy were reported to the US Food and Drug Administration (FDA) in the first quarter of 2008. Serious injuries associated with drug therapy reached a total of 20,745 new cases; there were a total of 4,824 reported deaths, a 2.6-fold increase from the previous quarter. In addition, varenicline (Chantix, Champix), an aid to smoking cessation, accounted for more reported serious injuries than any other prescription drug for a second quarter, with a total of 1,001 new cases and including 50 additional deaths. Varenicline was the subject of a previous Quarter Watch Special Report' and a separate FDA Public Health Alert about psychiatric adverse events. Ranked second in reported serious injuries was heparin, a drug that helps prevent injury from blood clots. Heparin was the subject of a major product recall after a potentially lethal contaminant was identified and traced to suppliers in China. In the first quarter of 2008, the FDA received reports of 779 cases of serious injury in which heparin was the principal suspect drug. These findings come from a program being developed by the Institute for Safe Medication Practices (ISMP) for improvement of patient safety through increasing understanding of how and why drug-related injuries and medication errors occur. The results are from analyses of new adverse drug event reports submitted to the FDA. The agency releases computer excerpts of these reports for research use after personal-identifying information has been removed. However, the results of this monitoring program should be interpreted with caution because of the known limitations of these data and the nature of the overall system through which adverse events are monitored in the United States. Because reporting is voluntary, only a small fraction of adverse drug events that occur are ever reported to the FDA or to drug manufacturers who then investigate and forward reports to the agency. Although the sum totals of reported adverse event reports usually provide an accurate overall adverse event profile for a drug, the individual reports themselves do not prove that the drug caused the event described. [ABSTRACT FROM PUBLISHER]

Background: Recent studies have shown that adverse drug reactions (ADRs) are underreported. This may be particularly true of ADRs associated with complementary and alternative medicine (CAM). Data on CAM-related ADRs, however, are sparse. Objective was to evaluate the impact of an educational intervention and monitoring programme designed to improve physician reporting of ADRs in a primary care setting. Methods: A prospective multicentre study with 38 primary care practitioners specialized in CAM was conducted from January 2004 through June 2007. After 21 month all physicians received an educational intervention in terms of face-to-face training to assist them in classifying and reporting ADRs. The study centre monitored the quantity and quality of ADR reports and analysed the results. To measure changes in the ADR reporting rate, the median number of ADR reports and interquartile range (IQR) were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Interrater reliability between the physicians and the study centre was calculated using Cohen's kappa with a 95% confidence interval (CI). We used Mann Whitney U-test for testing continuous data and chi-square test was used for categorical data. The level of statistical significance was set at P < 0.05. Results: A total of 404 ADRs were reported during the complete study period. An initial 148% increase (P = 0.001) in the number of ADR reports was observed after the educational intervention. Compared to baseline the postinterventional number of ADR reportings was statistically significant higher (P < 0.005) through the first 16 months after the intervention but not significant in the last 4-month period (median: 8.00 (IQR [2.75; 8.75]; P = 0.605). The completeness of the ADR reports increased from 80.3% before to 90.7% after the intervention. The completeness of the item for classifying ADRs as serious or non-serious increased significantly (P < 0.001) after the educational intervention. The quality of ADR reports increased from kappa 0.15 (95% CI: 0.08; 0.29) before to 0.43 (95% CI: 0.23; 0.63) after the intervention. Conclusion: The results of the present study demonstrate that an educational intervention can increase physician awareness of ADRs. Participating physicians were able to incorporate the knowledge they had gained from face-to-face training into their daily clinical practice. However, the effects of the intervention were temporary. [ABSTRACT FROM AUTHOR]

Background: Despite surveillance efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur after marketing. The aim of this article is to analyse ADRs reported by available ADR signal detection approaches and to explore which information about new and unexpected ADRs these approaches have detected. Methods: We selected three therapeutic cases for the review: antibiotics for systemic use, non-steroidal anti-inflammatory medicines (NSAID) and selective serotonin re-uptake inhibitors (SSRI). These groups are widely used and represent different therapeutic classes of medicines. The ADR studies were identified through literature search in Medline and Embase. The search was conducted in July 2007. For each therapeutic case, we analysed the time of publication, the strengths of the evidence of safety in the different approaches, reported ADRs and whether the studies have produced new information about ADRs compared to the information available at the time of marketing. Results: 79 studies were eligible for inclusion in the analysis: 23 antibiotics studies, 35 NSAID studies, 20 SSRI studies. Studies were mainly published from the end of the 1990s and onwards. Although the drugs were launched in different decades, both analytical and observational approaches to ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. The studies primarily dealt with analyses of ADRs of the type A and B and to a lesser extent C and D, cf. Rawlins' classification system. The therapeutic cases provided similar results with regard to detecting information about new ADRs despite different time periods and organs attacked. Approaches ranging higher in the evidence hierarchy provided information about risks of already known or expected ADRs, while information about new and previously unknown ADRs was only detected by case reports, the lowest ranking approach in the evidence hierarchy. Conclusion: Although the medicines were launched in different decades, approaches to the ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. Both descriptive and analytical designs were applied. Despite the fact that analytical studies rank higher in the evidence hierarchy, only the lower ranking descriptive case reports/spontaneous reports provided information about new and previously undetected ADRs. This review underscores the importance of systems for spontaneous reporting of ADRs. Therefore, spontaneous reporting should be encouraged further and the information in ADR databases should continuously be subjected to systematic analysis. [ABSTRACT FROM AUTHOR]

The article compares the adverse events (AE) percentage identified among in-hospital patients through Global Trigger Tool (GTT) Methodology developed by the USA Institute for Healthcare Improvement-IHI with the event reports by voluntary reporting and interviews to patients in Barranquilla-Colombia. It mentions methodologies for measuring AE incidence are based on voluntary reporting and clinical-administrative information. It mentions A table to Adverse Events detected by GTT Methodology.

A significant proportion of patients on proton pump inhibitors (PPI) reports insufficient control of symptoms, most probably resulting from ongoing reflux of non-acid and acid material. As reflux mainly occurs during transient lower esophageal sphincter relaxations (TLESRs), drugs targeting this motor pattern may be of great interest to further reduce symptoms. Baclofen, a GABAB receptor agonist, is the prototype of reflux inhibitors, reducing the number of TLESRs, reflux, and symptoms, but the central side effects are significant. Peripheral acting GABAB agonists hopefully devoid of these side effects are currently under study. Alternatively, antagonists to the metabotropic glutamate receptor 5 (mGluR5) reported to reduce TLESRs and reflux may be of interest. Upcoming clinical trials with these reflux inhibitors will hopefully answer the question whether reflux inhibitors are indeed a new approach to treat GERD. [Copyright &y& Elsevier]