World Health Organization-Uppsala Monitoring Centre Research Articles

Acute Generalized Exanthematous Pustulosis in Association with Hydroxyzine and Cetirizine

Purpose: Describe our review of the occurrence of acute generalized exanthematous pustulosis (AGEP) with hydroxyzine, and its active metabolites, cetirizine, and levocetirizine.Methods: The Division of Pharmacovigilance of the Food and Drug Administration (FDA) searched the FDA Adverse Event Reporting System (FAERS) and the medical literature for cases of AGEP reported in association with use of hydroxyzine, cetirizine, and levocetirizine. Causality was assessed using a modified World Health Organization Uppsala Monitoring Centre (WHO-UMC) causality assessment tool.Results: The FDA identified 26 cases of AGEP reported in association with the use of hydroxyzine (n = 21), cetirizine (n = 5), and levocetirizine (n = 3) (three cases included more than one drug product). Hydroxyzine causality was probable in five of the cases, and cetirizine causality was probable in two of the cases. All levocetirizine cases were assessed as unlikely. Conclusions: Our findings supported an association between hydroxyzine and cetirizine and AGEP. As a result, FDA has required labeling changes for hydroxyzine products to inform clinicians to avoid using hydroxyzine, cetirizine, and levocetirizine in patients who have experienced AGEP or other hypersensitivity reactions to any one of the above agents due to the risk of cross-reactivity.

Hospitalizaciones evitables por reacciones adversas a medicamentos en una unidad geriátrica de agudos. Análisis de 3.292 pacientes

ObjectiveTo determine prevalence of admissions due to an adverse drug reaction (ADR) and determine whether or not admission was avoidable, and what drugs and risk factors were implicated. DesignCross-sectional observational study. Study sampleAll patients hospitalized in an acute geriatric unit during the period January 2001 to December 2010 were studied. MeasurementTo determine whether admissions were due toADR, we used the World Health Organization-Uppsala Monitoring Centre criteria and the Naranjo scale. Beers criteria were used to detect potentially inappropriate medication. ResultsA total of 3,292 patients (mean age 84.7 years, 60.1% women) were studied. Of these, 197 (6%) were admissions for ADR and nearly three quarters (76.4%, 152 cases) were considered avoidable admissions. The 5 most frequent drugs associated with admissions for ADR were digoxin, nonsteroidal anti-inflammatory drugs, benzodiazepines, diuretics and antibiotics. Independent risk factors for admissions for ADR were being female (OR 1.84; 95% CI 1.30-2.61), inappropriate medication according to Beers criteria (OR 4.20; 95% CI 2.90-6.03), polypharmacy (>5 drugs) (OR 1.50; 95% CI 1.04-2.13), glomerular filtration rate<30mL/min (OR 3; 95% CI 2.12-4.23) and sedative use (OR 1.40; 95% CI 1-1.91). ConclusionADR were responsible for 6% of admissions to an acute geriatric unit, and over 75% of these admissions were considered avoidable. Associated risk factors were being female, inappropriate medication, polypharmacy, renal insufficiency and sedative use.

Evaluation of Facebook and Twitter Monitoring to Detect Safety Signals for Medical Products: An Analysis of Recent FDA Safety Alerts.

IntroductionThe rapid expansion of the Internet and computing power in recent years has opened up the possibility of using social media for pharmacovigilance. While this general concept has been proposed by many, central questions remain as to whether social media can provide earlier warnings for rare and serious events than traditional signal detection from spontaneous report data.ObjectiveOur objective was to examine whether specific product–adverse event pairs were reported via social media before being reported to the US FDA Adverse Event Reporting System (FAERS).MethodsA retrospective analysis of public Facebook and Twitter data was conducted for 10 recent FDA postmarketing safety signals at the drug–event pair level with six negative controls. Social media data corresponding to two years prior to signal detection of each product–event pair were compiled. Automated classifiers were used to identify each ‘post with resemblance to an adverse event’ (Proto-AE), among English language posts. A custom dictionary was used to translate Internet vernacular into Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms. Drug safety physicians conducted a manual review to determine causality using World Health Organization-Uppsala Monitoring Centre (WHO-UMC) assessment criteria. Cases were also compared with those reported in FAERS.FindingsA total of 935,246 posts were harvested from Facebook and Twitter, from March 2009 through October 2014. The automated classifier identified 98,252 Proto-AEs. Of these, 13 posts were selected for causality assessment of product–event pairs. Clinical assessment revealed that posts had sufficient information to warrant further investigation for two possible product–event associations: dronedarone–vasculitis and Banana Boat Sunscreen--skin burns. No product–event associations were found among the negative controls. In one of the positive cases, the first report occurred in social media prior to signal detection from FAERS, whereas the other case occurred first in FAERS.ConclusionsAn efficient semi-automated approach to social media monitoring may provide earlier insights into certain adverse events. More work is needed to elaborate additional uses for social media data in pharmacovigilance and to determine how they can be applied by regulatory agencies.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-016-0491-0) contains supplementary material, which is available to authorized users.

Antibiotic-Related Adverse Drug Reactions at a Tertiary Care Hospital in South Korea.

Background Adverse drug reactions (ADRs) are any unwanted/uncomfortable effects from medication resulting in physical, mental, and functional injuries. Antibiotics account for up to 40.9% of ADRs and are associated with several serious outcomes. However, few reports on ADRs have evaluated only antimicrobial agents. In this study, we investigated antibiotic-related ADRs at a tertiary care hospital in South Korea. Methods This is a retrospective cohort study that evaluated ADRs to antibiotics that were reported at a 2400-bed tertiary care hospital in 2015. ADRs reported by physicians, pharmacists, and nurses were reviewed. Clinical information reported ADRs, type of antibiotic, causality assessment, and complications were evaluated. Results 1,277 (62.8%) patients were considered antibiotic-related ADRs based on the World Health Organization-Uppsala Monitoring Center criteria (certain, 2.2%; probable, 35.7%; and possible, 62.1%). Totally, 44 (3.4%) patients experienced serious ADRs. Penicillin and quinolones were the most common drugs reported to induce ADRs (both 16.0%), followed by third-generation cephalosporins (14.9%). The most frequently experienced side effects were skin manifestations (45.1%) followed by gastrointestinal disorders (32.6%). Conclusion Penicillin and quinolones are the most common causative antibiotics for ADRs and skin manifestations were the most frequently experienced symptom.

Adverse drug reactions in Type 2 diabetes mellitus patients on oral antidiabetic drugs in a diabetes outpatient department of a tertiary care teaching hospital in the Eastern India

Background: Diabetes mellitus is a major healthcare problem in India. Pharmacovigilance of antidiabetic drugs is crucial in detecting adverse drug reactions (ADRs)and providing feedback to physicians on their possibility. In India, few reports are available on the ADR profile of antidiabetic agents. Objectives: This study aims to detect frequency and total burden of different ADRs due to oral antidiabetic drug (OAD)use in a diabetes outpatient in a medical college in Eastern India. Materials and Methods: An observational study was conducted on Type 2 diabetes mellitus patients on oral antidiabetic agents, attending Diabetes Clinic of a Tertiary Care Teaching Hospital in West Bengal between April and September 2013. Details of adverse event history, history of medication suspected of having caused the ADR were recorded in the format followed in the Pharmacovigilance Programme of India. The causality relationship was assessed by the World Health Organization-Uppsala Monitoring Centre criteria. Results: A total of 1000 patients were screened, of which 276 were suspected of having at least one ADR. On causality assessment, 43 of these 276 cases had insufficient evidence about causality and were excluded from the analysis. Out of the remaining 233 patients, 275 suspected ADRs were detected. Among them, metformin contributed 51% of total ADR reported, in the form of dyspepsia and diarrhea, followed by glimepiride-induced hypoglycemia. Voglibose-induced dyspepsia, pioglitazone-induced pedal edema were also common. Conclusions: ADRs due to OADs is a frequent problem. Few multicentric studies are needed for a strong antidiabetic drug ADR database in India.

An assessment of reported adverse drug reactions in a Tertiary Care Hospital in South India: A retrospective cross-sectional study.

Objective:The primary objective of this study was to assess the causality of ADRs using World Health Organization-Uppsala Monitoring Centre (WHO–UMC), Naranjo and Liverpool ADR Causality Assessment Tool (LCAT). Other primary objective was to assess the agreement between the WHO-UMC criterion, Naranjo algorithm and LCAT. The secondary objective was to assess the reported adverse drug reactions in a tertiary care hospital in South India.Materials and Methods:This was a cross-sectional retrospective study. All the ADRs which were reported by the Pharmacovigilance Unit between July 2016 and March 2017 were assessed. Causality assessment was performed by two well-trained independent pharmacologists by applying the three methods–WHO, Naranjo and LCAT. Concurrence between the two algorithms was compared using the Cohen's weighted kappa statistic.Results:Causality assessment of adverse reactions according to Naranjo criteria shows that 81% cases were of probable type, 9.5% cases were possible and 9.5% cases were unlikely. Causality assessment of adverse reactions according to WHO-UMC criteria shows that 85.7% cases were of probable type, 4.8% cases were possible, 4.8% cases were unlikely and 4.8% cases were definite. Causality assessment of adverse reactions according to Liverpool criteria shows that 61.9% cases were of probable type, 4.8% cases were possible and 33.3% cases were definite. Cohen's kappa test shows that negative and poor concurrence was seen between WHO and Naranjo causality comparison (κ = −0.161). Positive but poor concurrence based on kappa values was seen between Liverpool and Naranjo's causality comparison (κ = 0.133). Negative and poor concurrence based on kappa values was seen between WHO and Liverpool causality comparison (κ = −0.161).Conclusion:The most frequent causality category observed by the WHO-UMC criteria, Naranjo as well as the Liverpool algorithm was “Probable.” Full concurrence was not found between any of two scales of causality assessment.

An analysis of serious adverse drug reactions at a tertiary care teaching hospital.

Objective:The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs) such as clinical presentation, causality, severity, and preventability occurring in a hospital setting.Materials and Methods:All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization –Uppsala Monitoring Center (WHO-UMC) criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo's algorithm), severity (Hartwig and Siegel scale), and preventability (Schumock and Thornton criteria).Results:Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%). The common causal drug group was antitubercular (129, 34.4%) followed by antiretroviral (76, 20.3%) agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7%) followed by hospitalization (158, 42.1%). Majority of the serious ADRs were continuing (191, 50.9%) at the time of reporting, few recovered (101, 26.9%), and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8%) followed by probable (173, 46.1%) in nature.Conclusion:Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.

Monitoring of Cutaneous Adverse Drug Reactions in a Tertiary Care Hospital

Introduction: Cutaneous adverse drug reactions (ADRs) are the most frequently occurring ADRs to drugs. These reactions have a varied morphology and are responsible for significant mortality and morbidity. The aim of this study is to characterize the morphological patterns of cutaneous ADRs and to determine the incriminating agents. Method: The study was carried out in the Dermatology, Venereology and Leprosy department, Guru Nanak Dev Hospital, Government Medical College, Amritsar from 1st March 2014 to 31st May 2015. World Health Organization– Uppsala monitoring centre (WHO-UMC) causality scale was used to determine the causality of cutaneous ADRs and severity was assessed using Hartwigs severity scale. Results: In the present study, the highest incidence of cutaneous ADRs was in the age group of 31-40 years (25.0%), and more frequently in female patients (54.2%). Antimicrobials were the most commonly implicated drugs (37.5%) followed by Non-Steroidal Anti-inflammatory drugs (NSAIDs) (25.0%), various combination drugs (10.0%), corticosteroids and antiepileptics (6.6%). The most commonly observed morphological pattern was of Fixed drug eruptions (33.3%) followed by maculopapular rash (30.8%) and Steven Johnson Syndrome (5.8%). Causality assessment was certain, probable and possible for 1.6%, 93.3% and 41.5% of the reactions, respectively. 109 cases were of level 3 severities, 10 cases to level 4 severities and one case of level 7 where ADR was responsible for death in one patient. Discussion: Most of the adverse drug reactions are preventable, provided the drugs are used rationally. Antimicrobials were the most common causative group and fixed drug eruption was the most frequently encountered morphological pattern. Therefore it is imperative that in each patient the risk of drug administration should be weighed against the expected therapeutic benefit.

Adverse Drug Reactions Reported to a National HIV & Tuberculosis Health Care Worker Hotline in South Africa: Description and Prospective Follow-Up of Reports.

The National HIV & Tuberculosis Health Care Worker (HCW) Hotline provides advice on the management of suspected adverse drug reactions (ADRs). We describe suspected ADRs reported to the hotline by HCWs, concordance with advice, and patient outcomes. We reviewed suspected ADRs in HIV-infected patients, patients taking antiretrovirals and patients taking anti-tuberculosis therapy reported from May 2013 to October 2014. We performed causality assessment using the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria. We included suspected ADRs categorized as certain, probable or possible in further analysis. We received 772 ADR reports, of which 87/772 (11.3%) were classified as certain, 176/772 (22.8%) as probable, 361/772 (46.8%) as possible, and 148/772 (19.2%) as unlikely or unassessable. The most frequent ADRs were rash, drug-induced liver injury (DILI) and kidney injury, comprising 110/624 (17.6%), 87/624 (13.9%), and 77/624 (12.3%), respectively. The ADR was severe in 27.3% of rashes, 36.4% of kidney injury reports and 88.5% of DILI reports. Most frequently implicated drugs, either alone or in combination with other potentially causative drugs, were efavirenz (rashes), efavirenz and anti-tuberculosis drugs (DILI) and tenofovir (kidney injury). In 383 cases with HCW follow-up, 254 (66.3%) improved, 9 (2.3%) had complete resolution, 32 (8.4%) remained unchanged, 6 (1.6%) deteriorated, 10 (2.6%) died and 72 (18.8%) had unknown outcome. Advice provided was followed in 93.2% of these cases. Of 223 ADRs with preventability data, 40 (17.9%) were preventable. Queries about rashes, DILIs and kidney injuries were common. Detection and management of these ADRs should be included in HCW training. In cases with follow-up, concordance with advice was high, and HCWs reported improvement in the majority.

Initial development and testing of an instrument for patient self-assessment of adverse drug reactions

To develop and conduct preliminary testing of a causality assessment tool for patients, for potential use in encouraging both discussions with clinicians about suspected adverse drug reactions (ADRs) and reporting to authorities. Ten causality statements, developed from qualitative studies involving patients, with a scoring system allowing categorization, were embedded in a questionnaire which also included a symptom checklist and additional details about one suspected ADR and medicine, selected for causality assessment. Patients with experiences of suspected ADRs were involved in cognitive interviews (15), piloting (20) and psychometric testing (120). Test-retest reliability, construct validity and criterion-related validity were evaluated, through repeated causality assessment, comparison with a visual analogue scale assessing certainty of causality and comparison with causality assessment using World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria, respectively. The study involved outpatients at a university hospital in northeast Thailand. Ninety-eight patients completed causality assessment twice: both causality scores (Spearman rs = 0.715; p < 0.001) and causality classification [percentage of positive agreement (PPA) = 68.4; κ = 0.419; p < 0.001] showed satisfactory reliability. Causality scores were positively correlated with certainty of causality (Spearman rs = 0.556; p < 0.01). There was moderate agreement against WHO-UMC criteria [PPA = 70.4; κ = 0.440; p < 0.001]. Of the 91 completing an evaluation, 88% agreed that the tool should be used routinely, 78% agreed that it gave them useful results and 80% agreed that it was easy to use. This novel instrument has satisfactory psychometric properties and was acceptable to Thai patients, but it requires further testing. It has potential for use in supporting patients with suspected ADRs to discuss these with health professionals, and perhaps to report directly.

Drug utilization pattern of NSAIDs assessed with the anatomical therapeutic chemical classification/defined daily dose system in an orthopedic department

To study the drug utilization pattern of NSAIDs using the Anatomical Therapeutic Chemical classification/Defined Daily Dose (ATC/DDD) system in patients admitted to the orthopedic department of a tertiary-care teaching hospital. A cross-sectional prospective observational study was carried out in 200 patients from March to August 2014. Demographic information, disease related details, drug history and adverse drug reactions (ADRs) were recorded by personal interview and from case files daily for drug utilization analysis. The majority of patients were aged 18–30 years (30 %), most were male (80 %) and the most common orthopaedic condition causing hospitalization was fracture/dislocation (77 %). The most commonly prescribed drug group was analgesics, with NSAIDs being the most commonly prescribed type of analgesic (97 %). The majority of prescribed drugs were from the World Health Organization (WHO) Essential Medicine List (92 %) and Indian national essential drug list (100 %). Polypharmacy and high polypharmacy was reported in 71 and 14.5 % of patients respectively. No fixed-dose combinations of analgesics were used. Oral tablet diclofenac (M01AB05) 50 mg was the most frequently prescribed analgesic (97 % of patients; 840.5 DDD), followed by intravenous injection tramadol (N02AX02) in 56 % (189.3 DDD), intramuscular injection diclofenac (M01AB05) 75 mg in 55 % (87 DDD) and oral tablet paracetamol (N02BE01) 500 mg in 38.5 % (58.3 DDD) of patients. ADRs (mainly gastritis despite concomitant use of histamine H2 blockers) were reported in 4 % of patients; all ADRs were of ‘possible’ category according to the WHO–Uppsala Monitoring Centre causality assessment method. Fracture-dislocation and arthritis were the most common causes for hospitalization in the orthopedic department. Selection of analgesics and their dosage regimen complied with the WHO guidelines of pain management.

Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines.

Objective:Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: “Combinations of oral blood-glucose lowering medicines” (A10BD), “dipeptidyl peptidase-4 (DDP-4) inhibitors” (A10BH), and “other blood glucose lowering medicines” (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment.Methods:For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status.Findings:A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with “other blood glucose lowering medications,” the remaining 2 (13%) with “DDP-4 inhibitors.”Conclusion:Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs.

Nevirapine: Most Common Cause of Cutaneous Adverse Drug Reactions in an Outpatient Department of a Tertiary Care Hospital.

Skin is the most commonly involved organ in adverse drug reactions. Most of the cutaneous adverse drug reactions (CADRs) being of mild to moderate severity are likely to be diagnosed and treated in an outpatient setting. Consequently, knowledge regarding morphological pattern, severity and drugs implicated in causation of these CADRs has important implications for healthcare personnel. To determine the current clinical pattern of CADRs and to assess their causality and severity with the help of standard scales. A prospective, observational study was conducted in the outpatient department of skin and venereal disease in a tertiary care hospital. Patients with suspected CADR after consumption of systemic drug(s) were enrolled in the study. Data regarding demographics, clinical manifestations of CADR, drug history preceding the reaction, concomitant illness, relevant laboratory investigations etc was obtained. This data was then analysed for morphological pattern, causality and severity. CADRs with causality assessment possible and above on the basis of World Health Organization-Uppsala Monitoring Centre causality assessment system were considered for analysis. Descriptive statistics were used to express results of pattern, severity and causality of CADRs. Ninety patients were enrolled in the study. Male to female ratio for CADRs was 1:2.33. Maculopapular rash was most commonly encountered CADR in 76.67% cases followed by urticaria (8.89%), Stevens-Johnson syndrome (4.4%) and fixed dose eruptions (3.33%). Antiretrovirals were implicated in 75.56% (68/90) of CADRs. Nevirapine was suspected in 52 out of 90 (57.77%) cases of CADRs which included 39 cases of maculopapular rash, five cases of urticaria, four cases of Stevens-Johnson syndrome, and two cases each of pustular rash and angioedema respectively. Antimicrobials, antiepileptics and Non-steroidal Anti-inflammatory Drugs (NSAIDs) were other suspected drugs. Antiretrovirals especially nevirapine was implicated in variety of CADRs ranging from maculopapular rash to life-threatening reactions like Stevens-Johnson syndrome in an outpatient setting. Women were twice as susceptible as men for CADRs.

Adverse Drug Reaction in the Neonatal Intensive Care Unit: A Single Center Study

Purpose: Little research has been conducted on adverse drug reactions in neonates, particularly in Korea, where no studies have been reported. Methods: We conducted a retrospectively study using medical records in a neonatal intensive care unit from August 1, 2013 to July 31, 2014. The adverse drug reactions were evaluated according to the Naranjo algorithm, World Health OrganizationUppsala Monitoring Centre, and the Korean adverse drug reaction algorithm. Results: Of the 410 infants hospitalized during the study period, 57 cases of adverse drug reactions were reported in 40 infants (9.8%). The average gestational age was 28.4±4.3 weeks, the average birth weight was 1,184.1±622.0 g, and the adverse drug reactions were reported at an average of 21.0±29.7 days after birth. Causative agents were identified as electrolytes (36.8%), respiratory medication (14.0%), total parenteral nutrition (12.3%), lipid emulsion (10.5%), antibiotics (7.0%), non-steroidal antiinflammatory drugs (NSAIDs, 7.0%), sedatives (7.0%), vaccine (3.5%), and an antiviral medication (1.8%). Of the 57 cases, 55 (96.5%) cases demonstrated meaningful adverse drug reactions, defined as those given a score of “possible or above” in all 3 adverse drug reaction algorithms. Conclusion: More emphasis is warranted in the field of neonatal adverse drug reactions.

Visual Impairment Owing to Adverse Drug Reaction: Incidence and Routine Monitoring in the United Kingdom

Visual Impairment Owing to Adverse Drug Reaction: Incidence and Routine Monitoring in the United Kingdom

Arterial Hypertension and Posterior Reversible Cerebral Edema Syndrome Induced by Risperidone

Posterior reversible cerebral edema syndrome is a generally reversible neurologic condition that is diagnosed based on distinctive clinical and radiologic findings. The condition, which is mostly associated with severe arterial hypertension, has also been reported to be induced by several medications. We made the diagnosis of hypertension with posterior reversible cerebral edema syndrome in a lean 12-year-old girl treated with the second-generation antipsychotic risperidone. We applied the Naranjo Adverse Drug Reaction Probability Scale and the World Health Organization-Uppsala Monitoring Centre system for causality assessment to the present case. Both scales indicated that a relationship to risperidone was likely. Second-generation antipsychotic agents may occasionally induce an increase in blood pressure even in the absence of overweight. Given this possibility, we recommend routine monitoring of blood pressure during therapy with these agents.

A study of agreement between the Naranjo algorithm and WHO-UMC criteria for causality assessment of adverse drug reactions

Objectives:Reliability and usefulness of various adverse drug reaction (ADR) causality assessment scales have not been fully explored. There is no universally accepted method for causality grading of ADRs. In the present study we assessed agreement between the two widely used causality assessment scales, that is, the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria and the Naranjo algorithm.Materials and Methods:The same observer assessed all ADRs (n = 913) collected between January 2010 and December 2012 using the WHO-UMC criteria and Naranjo algorithm at a tertiary care hospital in India. We found that the most frequently assigned causality category was “possible” with both the scales.Results:A disagreement in the causality assessment was found in 45 (4.9%) cases reflecting “poor” agreement between the two scales (Kappa statistic with 95% confidence interval = 0.143 [0.018, 0.268]). The mean time taken to assess causality of the ADR using the WHO-UMC criteria was shorter than that by the Naranjo algorithm.Conclusion:This study showed that there is a poor agreement between the WHO-UMC criteria and Naranjo algorithm with the former being less time-consuming.

Polypharmacy and Adverse Drug Events Leading to Acute Care Hospitalization in Japanese Elderly

Background: Elderly patients are considered to be at risk of developing adverse drug events (ADEs) because they tend to receive a greater number of medications. The purpose of our study is to determine the prevalence of ADEs related to polypharmacy and causative admissions of patients in Japanese acute care hospitalization. Methods: In retrospective cohort study, we analyzed 700 consecutive elderly patients admitted to the department of medicine of a Japanese community hospital in 2011. ADEs were defined by World Health Organization–Uppsala Monitoring Centre criteria. Polypharmacy was defined as five or more medications. Results: The mean age was 79.5 years (men, 54%). The mean number of medications was 6.36 +/− 4.15 (maximum, 26). Polypharmacy was observed in 63% of cases. ADEs were identified in 4.9% (95% CI, 3.5–6.7%). The mean numbers of medications among patients with ADEs and those without ADEs were 9.3 +/− 3.4 and 6.2 +/− 4.1, respectively. A greater number of medications was significantly associated with ADEs (p < 0.001). Polypharmacy was identified in 91% of patients with ADEs, while it was noted in 62% of patients without ADEs (p = 0.001). Using logistic regression analysis, polypharmacy was significantly associated with ADEs (Odds ratio 5.89, 95% CI 1.74–19.9). The highest number of ADEs were identified among patients on antiplatelets or anticoagulants (n = 8), followed by benzodiazepines and NSAIDs (n = 4 for both). The most common ADEs were gastrointestinal bleeding, nausea and congestive heart failure. Conclusion: ADEs complicated to about 5% of acute care elderly hospitalizations in Japan. Polypharmacy was significantly associated with these ADEs.

Evaluation of adverse reactions to contrast media in the hospital

To determine and analyse the characteristics of contrast media adverse reactions (CM-ARs) reported in a hospital. A retrospective review of CM-ARs from the electronic spontaneous adverse drug reaction (ADR) report system between January 2011 and August 2012 was conducted. CM-ARs were evaluated in terms of causality, severity, preventability and affected organs. Also, agreement and correlation among the tools used to evaluate CM-ARs were analysed. The overall reaction rate was 1.5% (n = 286). In total, 269 CM-ARs were identified. For ADR causality, 96.7% (n = 260) and 98.5% (n = 265) were evaluated as "probable" ADR using the Naranjo probability scale and the World Health Organization-Uppsala Monitoring Centre causality categories, whereas 98.1% (n = 264) were evaluated as "certain" with Korean algorithm v. II. Of these, 91.4% (n = 246) were mild in severity and 96.7% (n = 260) were unpreventable. Most patients (n = 233, 86.7%) could be managed with observation and/or simple treatment. The most frequent reaction (n = 383, 79.5%) was dermatological. Spearman's correlation coefficient was 0.667 (p < 0.01), and the agreement was 98.1% between the Naranjo scale and the World Health Organization-Uppsala Monitoring Centre categories. No relationship was seen between CM-AR severity and gender or between in- and outpatients. In our study, most CM-ARs were mild and managed with simple treatment. However, as the number of patients undergoing CT procedures continues to increase, it is essential to identify and observe patients at risk for CM-ARs to prevent severe ADRs. Continuous careful review of reporting and treatment protocols of CM-ARs is needed to prevent morbidity and mortality.

Adverse Effects of Antiepileptic Drugs in North Indian Pediatric Outpatients

The present study investigates the pattern and predictors of treatment-emergent adverse drug reactions (ADRs) in children diagnosed with epilepsy. We conducted prospective observational study in a tertiary care teaching hospital on 277 epileptic children. Antiepileptic drug (AED)-associated ADRs, demographic and clinical characteristics, AED regimen, and so on were recorded. Causality, severity, and preventability were performed by World Health Organization-Uppsala Monitoring Center scale, Hartwig's severity scale, and Schumock and Thornton questionnaire, respectively. Of the enrolled population, 53% children had symptomatic epilepsy, and 51% were in 5- to 10-year age group. More than two-thirds of children were on monotherapy, with phenytoin (n = 176, 63.5%) being the most common AED. Three hundred fifty-three AED-related ADRs were recorded in 175 children (63.2%). Poor scholastic performance (19%) was the most common ADR, followed by gum hypertrophy (13.3%), headache (10.2%), behavioral problems (5.7%), drowsiness (5.7%), and others. Two hundred sixteen ADRs were probable, and 126 ADRs were possible. Severe ADRs were noted in 6 children. Girls (odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.07-3.45; P = 0.03), children with secondary epilepsy (OR, 3.31; 95% CI, 1.76-6.23; P ≤ 0.001), children older than 5 years (5-10 years; OR, 6.28; 95% CI, 2.79-14.12; P ≤ 0.001), and those older than 10 years (OR, 9.04; 95% CI, 3.69-22.17; P ≤ 0.001) were found to be at higher risk of experiencing ADRs. Monotherapy was the preferred treatment. Phenytoin was the most common ADR causative agent. Female sex, symptomatic epilepsy, and older age (> 5 years) were found to be associated with higher probability of ADR development.