Search

Background: Spontaneous reporting of adverse drug reactions (ADRs) is essential for the post-marketing safety evaluation of drugs. Therefore, good monitoring of ADRs is vital for strengthening drug supervision, management, and guiding rational drug use. Chinese medical institutions are the primary source of ADR case reports, but the proportion of the reports in grade IIIA hospitals is still low due to serious under-reporting. The 3rd Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People's Hospital, also has such a problem. Objective: To improve the quantity and quality of ADR reports and enhance the level of pharmacovigilance in hospitals, the Third Affiliated Hospital of Chengdu Medical College, People's Hospital of Chengdu Pidu District experienced 10 years to gradually establish a management model to improve the medical staff's reporting rate of spontaneous reporting of ADRs. The management model is led by clinical pharmacists and combines the PDCA with Teach-back methods. The purpose of this paper is to introduce the management model and discuss its advantages and shortcomings of this model. Methods: This study was conducted at the Third Affiliated Hospital of Chengdu Medical College—Chengdu Pidu District People's Hospital. From 2016, the daily management of reporting, auditing, and data improvement of adverse drug reactions in the hospital was carried out by clinical pharmacists, who used the PDCA method combined with the Teach-back method to continuously improve the reporting program of ADRs in the hospital during 2016–2021. Then, the proportion of spontaneous reports of total, new, and serious ADRs was compared before and after the intervention. Also, we performed a time series analysis using an autoregressive moving average model to assess changes in the total number of spontaneous ADR reports before the intervention (2013–2015), the first intervention (2016–2018), and the second intervention (2019–2021). Results: After the combined PDCA and Teach-back method intervention, the median number of reported ADRs per year increased from 50 (range 37–55) in the pre-intervention period to 88 (range 83–162) in the first intervention period and to 374 in the second (range 312–566). Breakpoint regression analysis of the spontaneous reporting rate of ADRs showed that the instantaneous increase after the first intervention was not statistically significant (P = 0.526). However, the reporting rate of ADRs increased at a month-by-month growth rate during the second intervention compared to the first intervention. Its spontaneous reporting rate improved 1.034 times (P = 0.002). After the second intervention, the spontaneous reporting rate of ADRs transiently increased 6.111-fold (P < 0.001), and the month-to-month growth rate increased 1.024-fold (P < 0.001) again. Conclusion: The management model that combines the PDCA and the Teach-back method significantly improves the reporting rate of adverse drug reactions. [ABSTRACT FROM AUTHOR]

Background: The growing list of non-antiarrhythmic drugs associated with QT prolongation and the relevant regulatory interventions have generated concern for two reasons. First, QT prolongation is sometimes viewed as an intrinsic effect of a whole therapeutic class (for example, antihistamines), whereas, in many cases, it is displayed only by some compounds within a given class of non-antiarrhythmic drugs because of an effect on cardiac repolarisation. Second, drug-induced Torsades de Pointes are still considered idiosyncratic, totally unpredictable adverse drug reactions, whereas a number of risk factors for their occurrence is now recognised. Objectives: In order to increase awareness among prescribing physicians that many non-antiarrhythmic drugs can affect cardiac repolarisation, we would like to propose a comprehensive and updated list of QT-prolonging drugs that should be a starting point to maintain a "consensus list" to be periodically updated. Methods: The drug list was generated by performing a Medline search, by using published lists as starting points to retrieve the relevant references quoted in each article and by considering the International Registry for Drug-induced Arrhythmias maintained by the Georgetown University and mainly based on the FDA approved labelling. Results: The drug list presented in this paper: (1) includes virtually all non-antiarrhythmic drugs with QT-prolonging potential, (2) organises the available information on each drug at different levels of clinical relevance and (3) is as up-to-date as possible in order to provide a fast track for the clinical pharmacologist to retrieve the original publications. Conclusions: This list should be considered as a starting point to call for consensus on: (1) the criteria used to generate the list, (2) possible ways to implement the use of this list as a quick reference for clinicians, for instance by providing a "proarrhythmic score" for each drug, and (3) inclusion/exclusion of a given agent into the list on the basis of evidence that may not be available to us. [ABSTRACT FROM AUTHOR]

Background: Spontaneous reporting of adverse drug reactions (ADRs) is an important source of information for post-marketing drug safety evaluation. Most countries have public access to reporting systems, but patients report only 3% of all ADRs. Little is known about factors affecting patient reporting. Our aim was to explore patients' experiences reporting ADRs and their views on the usability of the Canadian Vigilance reporting forms on MedEffect. Methods: An interpretive description qualitative study was used. Adults in Canada, who experienced an ADR, were invited to participate through social media (Kijiji, Facebook, Twitter) and by associations (e.g., Patients Canada or Canadian Arthritis Society). Participants were interviewed in English and French using structured interview guides. Inductive content analysis was used. Results: Fifteen interviews were conducted from October 2014 to May 2015. Two participants reported ADRs to MedEffect, and others to physicians and/or pharmacists. Motives for reporting were intolerable side effect impacting daily activities and encouragement from others to report (e.g., family, colleagues). Factors that interfered with reporting were physicians normalized or minimized the side effect, confusion on what to report, no feedback after report submission to MedEffect, and previous experience with side effects. MedEffect forms were described as comprehensive and important, but its usability was affected by the number of questions and complexity of some questions. Conclusions: Most participants were unaware of MedEffect and reported ADRs to physicians and pharmacists. Several barriers and motives affected patients' reporting of ADRs. MedEffect form could be simplified for use by patients. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the cumulative incidence of adverse drug reactions (ADRs) in women with high-risk pregnancy hospitalized in an obstetric intensive care unit, then to describe the medicines involved and to identify major risk factors. Methods: From June 2016 to December 2017, patients admitted to the ICU with high-risk pregnancy were considered eligible in this observational, longitudinal, prospective study. Patients were investigated daily for the occurrence of ADRs through pharmaceutical anamnesis, active search in medical records and questioning of the health team. Suspected ADRs were classified according to Naranjo's algorithm. Written informed consent was obtained from all patients. Univariate and multivariate logistic regression were used to identify risk factors of ADR. Results: The study population consisted of 607 high-risk pregnancies from 851 women admitted to the ICU, of whom 244 admitted for non-obstetric conditions, with an ICU stay less than 24 h or readmitted to the ICU were excluded. The mean age was 27.0 ± 7.5 years-old, mean gestational age was 33.8 ± 6.3 weeks. ADR were observed in 165 women (27.2%). No severe ADR was observed and 29.7% were of moderate severity. The most often implicated medicine was magnesium sulphate (25.2%) with 44.5% of patients administered that substance experiencing ADRs consisting of somnolence (68.6%), absent patellar reflex (21.6%) and hypotension (9.8%). Risk factors of ADR were blood pressure (adjusted odds-ratio (aOR) 1.02), haemoglobin level (aOR 1.21) and body temperature (aOR 0.71). Conclusions: ADRs affect about one third of high-risk pregnancies, mainly due to magnesium sulphate administrations. High blood pressure, lower body temperature, and high haemoglobin concentration on admission were associated with an increased risk of ADR. [ABSTRACT FROM AUTHOR]

Introduction: Osteomalacia and osteoporosis are two metabolic bone disorders that increase the risk of fracture due to several causes. In terms of drugs, apart from corticosteroids, which are known to induce bone disorders, several other drugs used in chronic disease management have also been linked with an increased risk of osteoporosis and osteomalacia. Purpose: The aim of this study was to describe spontaneous reports of drug-induced osteoporosis and osteomalacia in the French (FPVDB) and Spanish (SPVDB) pharmacovigilance databases. Methods: Data were provided by the FPVDB and SPVDB. All reports of osteoporosis and osteomalacia recorded from 1985 up to 31 December 2015 inclusive were selected. Taking the time to onset of bone loss into account, all cases occurring in less than 1 month were excluded. Results: A total of 369 reports (44 cases of osteomalacia, 325 cases of osteoporosis) were registered in the FPVDB and 64 (22 cases of osteomalacia, 42 cases of osteoporosis) in the SPVDB. In France, the top 5 drugs involved in the onset of osteoporosis were corticosteroids accounting for approximately half of the reports (n = 170) followed by systemic antiviral (n = 87), antacid (n = 29), antiepileptic (n = 27) and antithrombotic (n = 24) drugs. The 2 main classes of drugs implicated in osteomalacia were systemic antiretroviral drugs for half of the reports (n = 21) and antiepileptic drugs (n = 15). In Spain, corticosteroids were involved in 35.7% of reported cases of osteoporosis (n = 15) followed by systemic antiviral drugs (n = 12). There was no spontaneous report for antacid drugs. For osteomalacia, the 2 main drug classes were systemic antiretroviral drugs (n = 18, 81.8%) followed by antiepileptics (n = 2, 9.0%). In both countries, concomitant administration of systemic corticosteroids with other suspected drugs did not significantly modify the time to onset of drug-induced osteoporosis. Conclusion: Despite some differences between the French and Spanish PVDBs, our data consistently show that bone loss is not only restricted to glucocorticoids but also involves antivirals, antiepileptic drugs, antacid drugs or antidepressants. Further analysis might prove useful in exploring the characteristics of drug-induced bone loss on a larger scale. [ABSTRACT FROM AUTHOR]

The article focuses on Pitolisant which is new drug with a new mechanism of action, inverse agonist at the H3 histamine receptor, marketed in narcolepsy and excessive daytime sleepiness in obstructive sleep apnea syndrome. Topics include examines the clinical trials found that its main adverse events are neuropsychiatric, including headache, insomnia, anxiety, and depression, but also vomiting and weight gain.

Purpose: Spontaneous reporting of adverse drug reactions (ADRs) is a cornerstone in pharmacovigilance. However, information about the underlying consumption of drugs is rarely used when analysing spontaneous reports. The purpose of this study was to combine ADR reports with drug consumption data to demonstrate the additional information this gives in various scenarios, comparing different drugs, gender-stratified sub-populations and changes in reporting over time.Methods: We combined all Norwegian ADR reports in 2004-2013 from the EudraVigilance database (n = 14.028) with dispensing data from the Norwegian Prescription Database (more than 800 million dispensed prescriptions during 2004-2013). This was done in order to calculate drug-specific consumption-adjusted adverse drug reaction reporting rates (CADRRs) by dividing the number of reports for each drug with the number of users of the drug during the same time period.Results: Among the ten drugs with the highest number of ADR reports and the ten drugs with the highest CADRR, only four drugs were in both categories. This indicates that drugs with a high number of reports often also have a high number of users and that CADRR captures drugs with potentially relevant safety issues but a smaller number of users. Comparing reported ADRs in females and males using methylphenidate, we found that the two groups report different ADRs. Finally, we showed that changes in ADR reporting for simvastatin and atorvastatin during 2004-2013 were due to changes in consumption and that atorvastatin had a higher CADRR but fewer reports than simvastatin.Conclusions: CADRR provides additional information compared with number of reports alone in studies using spontaneous reports. It is important for researchers to adjust for consumption whenever possible in pharmacovigilance studies. [ABSTRACT FROM AUTHOR]

Purpose: Ceftriaxone has been recognized as a well-tolerated drug; however, in some instances, liver dysfunction occurs after using high-dose ceftriaxone. We aimed to assess the incidence of liver injury due to high-dose ceftriaxone and to determine whether there is a dose-dependent risk of liver injury with this drug. Methods: We conducted a retrospective cohort study of hospitalized adult patients treated with ceftriaxone at a tertiary care hospital from January 2012 to October 2013. We collected demographic and clinical data by reviewing their medical records. The incidence of liver injury based on biochemical criteria, defined as a primary outcome, was compared between patients treated with high-dose ceftriaxone (4 g/day) and those treated with a normal dose of ceftriaxone (2 g/day) for ≥5 consecutive days. A propensity score for the use of high-dose ceftriaxone was calculated from five factors. Results: We identified 37 patients treated with high-dose ceftriaxone and 434 patients treated with a normal dose of ceftriaxone. Among these 471 patients, 15 patients (3.2 %) experienced liver injury, of whom six patients (6/37, 16.2 %) had received high-dose ceftriaxone and nine patients (9/434, 2.1 %) had received normal doses of ceftriaxone. In the multivariate analysis adjusted for the propensity score, high-dose ceftriaxone was independently associated with liver injury (odds ratio, 7.23; 95 % confidence interval, 2.01-26.0). Conclusions: The present study revealed that high-dose ceftriaxone was associated with a significantly higher incidence of liver injury compared with the normal-dose regimen. Therefore, clinicians should carefully observe for signs of liver injury after high-dose ceftriaxone use. [ABSTRACT FROM AUTHOR]

Purpose: Hospital mortality related to adverse drug reactions (ADRs) is a relevant clinical problem with major health and economic consequences. We conducted a study to assess hospital mortality related to ADRs, the drugs most frequently involved, and the possible risk factors associated with fatal ADRs. Methods: A retrospective observational study was conducted, reviewing the clinical records of 1388 consecutive adult patients (18-101 years) who died during a 22-month period in a tertiary hospital in Southern Europe (Granada, Spain). The main outcome was the prevalence of hospital death suspected to be related to administered drugs. Results: Out of the 1388 adult deaths studied, 256 (18.4 %) were suspected of being related to drugs. Drugs were suspected of causing death in 146 inpatients (10.5 %) and contributing to death in 110 (7.9 %). Drugs related to death were administered during the hospital stay in 161 cases (11.5 %) and before hospital admission in 95 (6.84 %). The most frequent fatal ADRs were cardiac arrhythmia, gastrointestinal bleeding, and respiratory failure. The drugs most frequently involved in fatal ADRs were antithrombotics (anticoagulants or antiplatelets) (23 %), psychotropic drugs (21.2 %), and digoxin (11.3 %). Independent risk factors for ADR-related death were the presence of ≥4 diseases (OR = 1.43) and the receipt of ≥10 drugs (OR = 3.24), but no significant association with gender or age was found. Conclusions: A high percentage of hospital deaths were suspected of being associated with ADRs, especially in patients with comorbidity and/or polypharmacy. Antithrombotics, psychotropics, and digoxin were the drugs most frequently associated with in-hospital drug-related deaths. [ABSTRACT FROM AUTHOR]

The safe and effective use of medicines is an integral part of the medicine safety agenda. We present a phenomenological topic review of the literature relating to the use of unlicensed medicines (ULM). There is evidence to demonstrate that the use of ULM is associated with increased incidence of adverse drug reactions, and that despite advances in medicine regulation and guidance from professional organisations, the use of ULM in at risk populations has not reduced. There is also evidence to suggest that patients and their carers are not being provided with adequate information about their medicines and that ULM are being used where safer licensed alternatives are available. This is contrary to the philosophy of 'patient-focussed care'. We conclude that organisational governance processes and professional guidelines have not kept pace with regulatory developments or changes in legal and ethical understanding. We recommend that governance procedures for ULM be updated across healthcare settings to ensure that patients are involved in the decisions made about their medicines including the regulatory status of the medicine. This includes ensuring adequate consent is obtained from the patient (or their advocate). We also recommend that professional bodies clarify their position on when ULM can be used instead of licensed medicines to ensure that licensed medicines are used wherever possible. In the current economic environment, commissioners and clinicians must resist the temptation to use lower-quality ULM in place of licensed ones to cut costs. We go on to recommend areas of further research including the extent of ULM prescribing where licensed alternatives exist and the geographical and social factors that influence clinician prescribing of ULM. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to determine the patterns of analgesic adverse drug reactions (ADRs) and to assess their preventability and contributing factors. Methods: This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported to the Bordeaux pharmacovigilance center from January 2011 to June 2012. Results: The 141 cases selected for the analysis included 16 cases of medication errors (11.3 %) and 15 addiction cases (10.6 %). In total, 214 ADRs were registered, for which 173 analgesic medicines were suspected. The most frequent ADRs reported were nervous system disorders (26.6 %), psychiatric disorders (15.0 %), and skin and subcutaneous tissue disorders (12.1 %). Tramadol alone or in combination (17.3 %), followed by morphine (15 %), fentanyl (9.8 %), and paracetamol (8.7 %) were the most frequently involved analgesics. More than half of the cases (54.6 %) were serious and led to hospitalization or prolonged hospitalization. Preventability was determined for 134 cases (95 %): 51.5 % were considered as preventable, 26.1 % not preventable, and 22.4 % not assessable. The main contributing factors for the preventable cases included negligence of recommendations for analgesic use and failure to consider patients' risk factors when prescribing. Conclusions: A significant number of analgesic ADRs could be prevented, and being aware of their contributing factors promotes efficient analgesia with minimum risks to the patients. [ABSTRACT FROM AUTHOR]

Purpose: Disproportionality screening analysis is acknowledged as a tool for performing signal detection in databases of adverse drug reactions (ADRs), e.g., in the European Union (EU) Drug Authority setting. The purpose of this study was to explore the possibility of decreasing false-positive signals of disproportionate reporting (SDR) by calculating the proportional reporting ratio (PRR)-by-therapeutic area (TA), while still maintaining the ability to detect relevant SDRs. Methods: In the EudraVigilance (EV) Database, output from PRR calculated with a restricted TA comparator background was compared in detail to output from conventional authority-setting PRR calculations for four drugs: bicalutamide, abiraterone, metformin, and vildagliptin, within the TAs of prostate gland disease and type 2 diabetes mellitus. Results: ADR reports per investigated drug ranged from 2,400 to 50,000. The PRR-TA's ability to detect true-positive SDRs (as acknowledged in approved labeling) was increased compared to the conventional PRR, and performed 8-31 % better than a recently proposed stricter EU-SDR definition. The PRR-TA removed false SDRs confounded by disease or disease spill-over by up to 63 %, while retaining/increasing the number of unclassified SDRs relevant for manual validation, and thereby improving the ratio between confounded SDRs (i.e., noise) and unclassified SDRs for all investigated drugs (possible signals). Conclusions: The performance of the PRR was improved by background restriction with the PRR-TA method; the number of false-positive SDRs decreased, and the ability to detect true-positive SDRs increased, improving the signal-to-noise ratio. Further development and validation of the method is needed within other TAs and databases, and for disproportionality analysis methods. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to analyse non-warfarin-associated bleeding adverse drug events reported to the Norwegian spontaneous reporting system, with characterisation of the bleeding locations, outcome and drug interactions. In addition, concordance in assessments between reporters and evaluators, trend shifts in reporting, and detection of potentially new adverse drug interaction signals were studied. Methods: Data on bleeding events reported between 1 January 2003 and 31 December 2005 were retrieved from the Norwegian spontaneous reporting system database. Results: Of 327 case reports of non-warfarin-associated bleeding events, 270 reports (82.6 %) were characterised as serious and 69 (21.1 %) had a fatal outcome. One hundred and eighty-seven bleeds (57.5 %) were gastrointestinal, 57 (17.4 %) were cerebral, and 81 (24.8 %) were from other bleeding sites. The bleeding sites differed with respect to the patient's age, drug use, diagnoses and outcomes. Of drugs associated with bleeding, nonsteroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors (145 reports) and acetylsalicylic acid (128 reports) were most frequently used. Only fibrinolytics were associated with increased mortality. There was a 67.4 % correlation between reporters and evaluators in assessment of drugs associated with bleeding ( P < 0.001), with considerable variation in concordance between drug groups. Conclusion: Non-warfarin-associated bleeding events are associated with substantial mortality. Old age, cerebral bleeds, number of drugs used, and use of fibrinolytics are all independently associated with increased mortality. The recognition of the bleeding risk of commonly used drugs such as acetylsalicylic acid and heparins may be insufficient among prescribers. [ABSTRACT FROM AUTHOR]

Over the years since 1961 and the identification of thalidomide as the common link in thousands of birth defects, daily pharmacovigilance activities and signal generation have evolved from the analysis of individual case reports and imputology, to case series and underreporting, to spontaneous report databases and disproportionality analyses, to data mining in population databases. Regulatory requirements have also changed from purely passive monitoring and reacting to alerts to a proactive approach that includes risk management plans and risk minimization, and from reporting only by healthcare professionals to patient reporting and exploration of social media. The emphasis only on risk assessment is changing towards assessment of the risk/benefit ratio and the exploration of real-life efficacy studies to complement the measure of real-life risk. The interactions between industry and regulators have been amplified and strengthened. However, most adverse reactions, including severe ones, are related to well-known and often pharmacological effects of the older drugs, possibly with genetic predispositions. Prevention is the next frontier for pharmacovigilance, beyond simply generating alerts, and it involves not only the removal of drugs from the market, but also promotion of proper drug prescribing by better trained physicians and the proper use of drugs by better informed patients. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to characterize Adverse Drug Reactions (ADRs) related to drug-drug interactions (DDIs) related to involvement of cytochrome P450 (CYP450) isoenzymes in a pharmacovigilance database. Methods: ADRs recorded by Midi-Pyrénées PharmacoVigilance center (France) between 1 January and 31 August 2008 were extracted from the French PharmacoVigilance Database (FPVD). Results: Among the 1,205 reported ADRs, 16 (1.3 %), can be explained by involvement of CYP450 isoenzymes (including 4 'serious'). All interactions involved CYP inhibitors, mainly for CYP3A4/5. Conclusion: The percentage of ADRs reported in the pharmacovigilance database and related to CYP450-induced DDIs appears to be relatively low (~ 1-2 %). [ABSTRACT FROM AUTHOR]

Aim: To test the ability a new Spanish primary care research database (BIFAP) to capture the association between upper gastrointestinal bleeding (UGIB) and NSAIDs and other drugs and compare the results with previous studies. Methods: We performed a nested case-control study in persons aged 40-90 years old included in the period 2001-2005. Potential cases were selected through a computer search followed by an individual blinded review. Controls matched for age, sex and calendar year were randomly selected. The exposure window was defined as 0-30 days before the index date. Adjusted odds ratios were obtained through unconditional logistic regression models. Results: In a study cohort of 669,115 subjects (1,576,442 person-years) we retrieved 1,193 valid incident cases. Increased risks were found with current use of NSAIDs (RR = 1.72; 95 %CI: 1.41-2.09), metamizole (1.52; 1.09-2.13), low-dose aspirin (1.74; 1.37-2.21), other antiplatelet drugs (1.73; 1.27-2.36), and oral anticoagulants (2.00; 1.44-2.77). We did not find an increased risk with current use of oral corticosteroids (1.11; 0.66-1.86), SSRIs (1.05; 0.77-1.42), or paracetamol (1.00; 0.82-1.23). Acid-suppressing drugs reduced the risk among users of NSAIDs (0.58; 0.39-0.85), particularly in users with antecedents of peptic ulcer (0.16; 0.05-0.58). We detected a decreasing time-trend in the relative risk and the population attributable proportion associated with NSAIDs over the study period. Conclusions: The increased risk of UGIB associated with NSAIDs was lower than previously reported, which could partly be explained by methodological differences, but a decreasing burden over time of this drug safety problem is suggested. BIFAP has shown to be a valuable tool for pharmacoepidemiological research. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the importance of drug-drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database. Methods: All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that contained mention of one of the serotoninergic reuptake inhibitor (SRI) antidepressants marketed in France were reviewed. DDIs were identified according to the French National Drug Formulary (Vidal) and the interaction supplement of the French independent drug bulletin La Revue Prescrire. ADRs explained by DDIs were characterised. Results: Among the 2,101 spontaneous reports recorded, 177 involved at least one SRI antidepressant. Among the 156 ADRs with at least one theoretical DDI, 41% (95% confidence interval 34-49%) could be explained by a DDI. The most frequent antidepressant involved in DDIs was escitalopram, followed by fluoxetine and citalopram. Among the 65 ADRs related to DDIs, 37 (52.9%) were 'serious', mainly bleedings, confusion and falls, hyponatremia and serotoninergic syndromes. The most frequent drug interactions occurred with psychotropics (antipsychotics, benzodiazepines, among others), followed by antithrombotic agents (antagonists of vitamin K, antiplatelets), diuretics and angiotensin II antagonists. The group with ADRs related to DDIs was older than the group with ADRs not related to DDIs. ADRs were threefold more 'serious' in the case of DDIs. Conclusion: Around 40% of ADRs reported with SRIs were related to DDIs. Most of these occurred after association with psychotropics, antithrombotics, or diuretics, especially in the elderly. [ABSTRACT FROM AUTHOR]

To establish a web-based quantitative signal detection system for adverse drug reactions (ADRs) based on spontaneous reporting to the Guangdong province drug-monitoring database in China. Using Microsoft Visual Basic and Active Server Pages programming languages and SQL Server 2000, a web-based system with three software modules was programmed to perform data preparation and association detection, and to generate reports. Information component (IC), the internationally recognized measure of disproportionality for quantitative signal detection, was integrated into the system, and its capacity for signal detection was tested with ADR reports collected from 1 January 2002 to 30 June 2007 in Guangdong. A total of 2,496 associations including known signals were mined from the test database. Signals (e.g., cefradine-induced hematuria) were found early by using the IC analysis. In addition, 291 drug-ADR associations were alerted for the first time in the second quarter of 2007. The system can be used for the detection of significant associations from the Guangdong drug-monitoring database and could be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs for the first time in China. [ABSTRACT FROM AUTHOR]

Background: Evidence has accrued that several non-cardiac drugs may prolong cardiac repolarisation (hence, the QT interval of the surface electrocardiogram) to such a degree that potentially life-threatening ventricular arrhythmias (e.g. torsades de pointes) may occur, especially in case of overdosage or pharmacokinetic interactions. Discussion: This has fostered discussion on the molecular mechanisms underlying the class-III anti-arrhythmic effect shared by apparently disparate classes of drugs, on the clinical relevance of this side effect and on possible guidelines to be followed by drug companies, ethics committees and regulatory agencies in the risk–benefit assessment of new and licensed drugs. This review provides an update on the different classes of non-cardiac drugs reported to prolong the QT interval (e.g. histamine H1-receptor antagonists, antipsychotics, antidepressants and macrolides), on the possible underlying molecular mechanisms and on the clinical relevance of the QT prolonging effect. Identification and widespread knowledge of risk factors that may precipitate prolongation of the QT interval into life-threatening arrhythmias becomes an important issue. Risk factors include congenital long QT syndrome, clinically significant bradycardia or heart disease, electrolyte imbalance (especially hypokalaemia, hypomagnesaemia), impaired hepatic/renal function and concomitant treatment with other drugs with known potential for pharmacokinetic/pharmacodynamic interactions (e.g. azole antifungals, macrolide antibacterials and class-I or -III anti-arrhythmic agents). Future perspectives for drug research and development are also briefly outlined. [ABSTRACT FROM AUTHOR]

Within an ongoing drug surveillance project (AMÜP) in psychiatric hospitals, a comparative study was carried out to evaluate two methods commonly used in the field of adverse drug reaction assessment. Two raters, who have cooperated with the project since its inception, evaluated 80 randomly selected ADRs twice; first, by an empirical (implicit) approach, and second, 4 weeks later, by using an algorithm as proposed by Kramer et al. 1979. Agreement on medication and related probability ratings was obtained in 81% of all 80 cases for the empirical method (weighted Kappa=0.41), and in 69% for the algorithmic method (weighted Kappa=0.62), indicating that agreement exceeded chance for both methods. By comparison with assessments made in previous case conferences of the project, empirical ratings were found to be reliable over time due to homogeneous use of criteria by project raters. In contrast to the reports on the subject, agreement between raters appeared to be superior in the empirical method as compared to the algorithmic assessment. Analysis of disagreements suggested that probability ratings based on the empirical method were nonspecific, due to conventional criteria applied in the project. Inter-rater agreement was reduced by polypharmacy, especially in the case of algorithmic assessments. The consistency of assessment was also lowered by the fact that the 2 methods assigned different weights to particular assessment criteria. [ABSTRACT FROM AUTHOR]

A system for monitoring adverse drug reactions (ADR) in psychiatric inpatients was introduced in psychiatric hospitals in the FRG in May 1979. It consists of intensive drug monitoring (IDM) and a so-called 'organized spontaneous reporting system' (OSR). ADR are rated separately according to impact on therapy and probability of causal relationship. With IDM all ADR (Grades I-III) are assessed in a randomly selected sample of inpatients. With OSR only ADR leading to discontinuation of the drugs in question (=ADR Grade III) are assessed. In 406 drug-treated inpatients monitored by IDM in the psychiatric hospitals of Berlin and Munich from May 1979 to Dec. 1981, ADR were observed in 60,4%. In 15% of IDM-patients ADR led to discontinuation of the drugs in question; with OSR the relative frequency of these Grade III ADR was 9,0% in 5096 patients monitored throughout the entire period. Life-threatening events were observed in 1,2% of patients undergoing IDM as well as 1.2% of those undergoing OSR. The most frequently observed ADR by IDM were sedation, extrapyramidal signs, disturbances of the autonomic nervous system and increase in transaminases, and by OSR Parkinsonism, akathisia, sedation, toxic delirium and increased transaminases. The relative frequency of Grade III ADR was similar for neuroleptics and antidepressants (5,4% and 5,3% in OSR); a very low relative frequency of ADR Grade III was found for tranquilizers and hypnotics (0,7% and 0,2%). Methodological aspects of this drug monitoring system are discussed in the light of current literature. [ABSTRACT FROM AUTHOR]

A comparative study of adverse drug reactions (ADR) leading to hospital admission showed that 103 (4.1%) out of 2499 medical admissions in Jerusalem and 167 (5.7%) out of 2933 admissions in Berlin were due to such reactions. Sex distribution in the two patient - populations was almost equal but the Jerusalem patients were younger. The most frequent ADRs were digitalis intoxication (in Berlin) and reactions to antibiotics (in Jerusalem). Other important differences were noted in the relative frequencies of ADRs associated anticoagulants, hypoglycemic agents and oral contraceptives. They were probably related to differences in drug usage in the two countries. The most common major side effects were arrhythmias, allergic reactions, bleeding, congestive heart failure, bronchospasm and hypoglycemia. The following risk factors were identified in both cities: old age, female sex, impaired renal function, previous history of ADR and polypragmasia. [ABSTRACT FROM AUTHOR]

Objectives: Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. Material and methods: Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. Results: Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. Discussion and conclusion: The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS – compared with dramatic improvements of pre-approval trials – implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on anatomical localizations of bleedings between vitamin K antagonists and direct oral anticoagulants.

The information and case quality of 500 spontaneous and 500 published adverse drug reaction (ADR) reports were compared, including a study of the most common criteria used in different causality assessment methods. The criteria were more often of positive value in the published reports. Nevertheless, spontaneous reports play an important role in the detection of new ADRs. [ABSTRACT FROM AUTHOR]