History Of Adverse Drug Reactions Research Articles

Factors related with adverse drug reaction reporting: a cross-sectional study among pharmacists in the West of Iran

Adverse drug reaction includes all negative, random and unexpected effects a drug may have on human which could be observed in doses used to prevent diagnosis and treatment; which report it could be helpful to prevent and decrease the side effects. The aim of this study was to determine the prevalence and factors related with adverse drug reaction reporting among pharmacists. In this cross-sectional study, conducted in the west of Iran, a total of 117 pharmacists, were randomly selected to participate voluntarily in the study during 2014. Participants filled out a self-administered questionnaire. Data were analyzed by SPSS version 21 using bivariate correlations, logistic and linear regression statistical tests. Almost 21.4% of the participants had history of adverse drug reaction reporting. The best predictors for adverse drug reaction reporting was perceived behavioral control (OR: 1.227) and attitude (OR: 1.164). In addition, attitude was the best predictor for intention to adverse drug reaction reporting among pharmacists (B: 0.490 & P: 0.001). Based on our result, it seems that designing and implementation of retraining programs to improve positive attitude towards adverse drug reaction reporting and incensing pharmacist’s behavioral control to adverse drug reaction reporting may be usefulness of the results in order to promotion of adverse drug reaction reporting.

Emergency department visits caused by adverse drug reactions: results of aTurkish university hospital.

We aimed to evaluate adverse drug reaction (ADR)-related emergency department (ED) visits in the ED of the Dokuz Eylül University Hospital prospectively. Patients who were admitted to the ED during 1-week periods of four different seasons between July 2010 and April 2011 were enrolled. Demographics of patients, previous ADR history, clinical progress, and outcomes were recorded. Causality assessment was done according to World Health Organization Uppsala Monitoring Centre categories. ADRs were categorized as certain, probable, or possible. Patients who were on medications (26.5%, n = 1838) were evaluated for ADR-related ED admissions. ADRs accounted for 5.9% of cases (n = 108). The most frequently affected systems were the gastrointestinal (35.2%, n = 38), dermatological (23.1%, n = 25), and hematological (10.2%, n = 11) systems (7.4%, n = 8). The most common causes of ADRs were antiinfectives (31.6%, n = 33). Amoxicillin, Coumadin, and paracetamol were the most common medications that caused ADRs. Nearly 6% of the admissions were ADR-related. ADRs should always be considered when patients who are on medication are admitted to the ED. Multicenter epidemiologic studies are required to know the real rates of ADR cases in EDs in Turkey.

Provocation proven drug allergy in Thai children with adverse drug reactions.

Adverse drug reactions (ADRs) are a common healthcare problem. The drug provocation test (DPT) is a gold standard for ADR diagnosis. To evaluate a correlation between history of ADRs, skin prick test (SPT), intradermal test (ID) and DPT in Thai children. This was a retrospective review of 211 children under 16 years of age who had a history of ADRs and underwent DPT from January 2006 to December 2012. Two hundred and thirty six (236) DPTs were performed in 211 children with a history of ADRs. The median age at which DPTs were performed was 4 years. Thirty-four children (14.4%) had positive DPT. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, likelihood ratio (LR) + and LR- of SPT were 50, 85.7, 6.9, 98.8%, 5.8 and 0.9, respectively. The PPV, NPV, sensitivity, specificity, LR+ and LR- of ID were 33.3, 84.6, 20, 91.7%, 2.4 and 0.9, respectively. Different presentation of symptoms (maculopapular rashes, urticaria, angioedema and anaphylaxis) did not predict SPT, ID and DPT results. Positive human immunodeficiency virus (HIV), but not atopy, was a risk in the present scope of evaluation for drug allergy (odds ratio 11.44, 95% confidence interval 2.60-50.41). Drug allergy, denoted by positive DPT, was present in 14.4% of Thai children with a history of ADRs. Antibiotics were the most common cause of ADRs. Both SPT and ID had high NPV and specificity but did not predict DPT results. HIV positivity is a risk factor of drug allergy in Thai children.

Nocebo effect in Dermatology.

Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specific neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of 'permanent cure' and frequent relapses of skin disorders. While finasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the conflict between patients' right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.

Prevalence, Determinants, and Reasons for the Non-Reporting of Adverse Drug Reactions by Pharmacists in the Miyagi and Hokkaido Regions of Japan

Little is known about the potential of adverse drug reaction (ADR) non-reporting by Japanese pharmacists. The aim of the present study was to clarify the prevalence, determinants, and reasons for ADR non-reporting by pharmacists in the Miyagi and Hokkaido regions of Japan. In this cross-sectional, self-administered questionnaire-based study, we contacted 3,164 pharmacists who belonged to the Miyagi Prefecture Hospital Pharmacists Association or the Hokkaido Society of Hospital Pharmacists during the 3-month period between January to March 2013. Of the 1,795 respondents 22.4% were <30 years of age, 25.6% were ≥ 50 years of age, and 42.1% were female. A total of 77.6% of the respondents did not have a personal history of ADR reporting. The multivariate logistic regression analysis showed that female sex (odds ratio, 1.52; 95% confidence interval, 1.17-1.97), having <10 years of practical experience (2.59, 1.39-4.82 for 5-9 years; 7.03, 2.94-16.83 for <5 years), working at a community pharmacy or drugstore (1.90, 1.16-3.12), having <5 pharmacists in the workplace (2.01, 1.48-2.75), and not understanding the ADR reporting system (5.93, 4.23-8.33) were significantly and independently associated with not having a personal history of ADR reporting. The most common reason for ADR non-reporting was “It was a well-known adverse drug reaction” (43.0%) followed by “Association between the drug and adverse reaction was not clear” (38.0%), “It was a minor adverse drug reaction” (29.0%), “Did not know how to make a report” (17.4%), and “Never been consulted about ADRs” (17.2%). As an understanding the ADR reporting system was strongly associated with ADR reporting, a more aggressive promotion of the ADR reporting system among pharmacists is warranted.

Challenge test to bisphosphonates in patients with hypersensitivity reactions to drugs

BackgroundBisphosphonates are a commonly used class of drugs with known efficacy in the prevention and treatment of postmenopausal and steroid-induced osteoporosis, Paget's disease of bone, hypercaelcemia of malignancy, osteolytic lesions of multiple myeloma, and bone metastases. Nitrogen-containing bisphosphonates have a favourable tolerability and safety profile, cutaneous reactions have been reported. MethodsThis is a retrospective case series study, based on the analysis of data from 1429 patients admitted to the Allergy and Clinical Immunology Division of the University of Messina between January 2011 and December 2012. Most patients had previous adverse drug reactions (ADRs) and referred to us for a challenge test with an alternative drug. ResultsWe observed six patients with a past history of adverse drug reaction who needed to be tested for bisphosphonates: three patients for risedronate, two for clodronate and one for alendronate. In two years only two patients were referred to us for an adverse reaction to bisphosphonates: one to alendronate and one to risedronate. Another patient presented a previous reaction to strontium ranelate. The other three patients reported previous hypersensitivity reactions to at least two different classes of drugs. All the patients experienced no reaction using the tested drugs. ConclusionsIn our experience drug challenge tests for bisphosphonates are safe and reliable.

ATTITUDES ON WARFARIN PHARMACOGENETIC TESTING IN CHINESE PATIENTS AND PUBLIC

Genetic factors affecting warfarin maintenance dose have been well established, but patient acceptance is a necessary consideration for the successful clinical implementation of warfarin pharmacogenetic testing (WPGT). In this study, we aimed to determine the attitudes toward WPGT among Singaporean Chinese. A total of 194 warfarin patients and 187 members of the public completed a structured survey on paper and the Internet, respectively. Attitudes were expressed as willingness to undergo WPGT (single item with 5-point response) and expectations and concerns about WPGT (two multi-item scales). Relationships between attitudes and socio-demographic and clinical variables were explored using Fisher's exact test, Student's t-test, one-way analysis of variance or Pearson's correlation. Majority of respondents were willing to or neutral about undergoing WPGT. Both patients and public had relatively high expectations (mean [SD]: 3.77 [0.63], and 3.97 [0.55], respectively) and moderately high concerns (mean [SD]: 3.30 [0.69] and 3.33 [0.68], respectively) about WPGT. Willingness to undergo WPGT was associated with gender, educational status, length of warfarin treatment, and number of chronic diseases among warfarin patients, and with history of adverse drug reactions and number of chronic diseases among the public. Higher expectation of WPGT was associated with higher willingness (p < .001 in both populations), while higher concern was associated with lower willingness to undergo WPGT among the public (p = .004) but not among patients (p = .072). Patient acceptance is not a major barrier to clinical implementation of WPGT but patient education is necessary and the ethical, social, and legal issues should be addressed.

Anaphylaxis due to fentanyl during radiofrequency ablation

This case report describes a life-threatening anaphylaxis to fentanyl during radiofrequency ablation (RFA). A 50-year-old woman with hepatocellular carcinoma was admitted for RFA. She denied any history of adverse drug reactions or past adverse anesthetic reaction. Physical examination, vital signs, any laboratory findings were all within normal limits. Ten minutes after intravenous administration of 50 mcg of fentanyl before starting RFA, she developed generalized erythema and sudden onset of bronchospasm followed by respiratory arrest. Cardiopulmonary resuscitation (CPR) commenced with 100% oxygen and intravenous administration of epinephrine 1 mg. After 5 minutes of CPR, she had the return of spontaneous circulation. Chest X-ray revealed pulmonary edema which resolved over two days. She recovered completely and was discharged home. After six weeks, intradermal tests performed with fentanyl, remifentanyl, midazolam, and profopol. Among those, only fentanyl induced positive skin response. Fentanyl induced anaphylaxis was diagnosed for this case, and fentanyl was avoided in the subsequent general anesthesia for liver transplantation. This case suggested that fentanyl could induce anaphylaxis combined with uncommon comorbidities like pulmonary edema. (Allergy Asthma Respir Dis 2013;1:284-287)

Is Severity Of Drug Induced Anaphylaxis Dependent Of Its Etiology?

RationaleAdverse drug reactions (ADR) are common in clinical practice. Drug induced anaphylaxis is severe and responsible for most of deaths due to ADRs, although its prevalence is unknown. We describe a sample of drug induced anaphylaxis and analyze their etiology, severity and the use of epinephrine.MethodsRetrospective cohort of patients with history of ADRs who had answered a standardized questionnaire. We included patients with a diagnosis of anaphylaxis through international diagnostic criteria. We evaluated gender and age variables, the causative agent, clinical features, frequency of anaphylactic shock and the use of epinephrine in the treatment.ResultsWe evaluated 806 patients, of whom 122 (15.1%) met the criteria of anaphylaxis. The average age was 38.9 years and 81.9% were female. The probable etiology was defined in 88 patients (72.1%), and nonsteroidal anti-inflammatory drugs (NSAIDs) were involved in 67%, followed by latex, local anaesthetics and antibiotics. Epinephrine was used in 33.6% of reactions. There has been hypotension and/or shock in 31.1%. Anaphylactic shock accounted for 60% of latex anaphylaxis, 50% of those due to antibiotics and 22.4% of NSAIDs induced anaphylaxis.ConclusionsThe number of drug induced anaphylaxis is high, although the diagnosis of anaphylaxis is neglected and epinephrine is underutilized. NSAIDs were the drugs most commonly implicated, but antibiotics were not as involved as previously described. Latex was an important agent in perioperative anaphylaxis. Cases of anaphylactic shock were associated to IgE-mediated hypersensitivity mechanism, as we observed in latex and antibiotics allergies. RationaleAdverse drug reactions (ADR) are common in clinical practice. Drug induced anaphylaxis is severe and responsible for most of deaths due to ADRs, although its prevalence is unknown. We describe a sample of drug induced anaphylaxis and analyze their etiology, severity and the use of epinephrine. Adverse drug reactions (ADR) are common in clinical practice. Drug induced anaphylaxis is severe and responsible for most of deaths due to ADRs, although its prevalence is unknown. We describe a sample of drug induced anaphylaxis and analyze their etiology, severity and the use of epinephrine. MethodsRetrospective cohort of patients with history of ADRs who had answered a standardized questionnaire. We included patients with a diagnosis of anaphylaxis through international diagnostic criteria. We evaluated gender and age variables, the causative agent, clinical features, frequency of anaphylactic shock and the use of epinephrine in the treatment. Retrospective cohort of patients with history of ADRs who had answered a standardized questionnaire. We included patients with a diagnosis of anaphylaxis through international diagnostic criteria. We evaluated gender and age variables, the causative agent, clinical features, frequency of anaphylactic shock and the use of epinephrine in the treatment. ResultsWe evaluated 806 patients, of whom 122 (15.1%) met the criteria of anaphylaxis. The average age was 38.9 years and 81.9% were female. The probable etiology was defined in 88 patients (72.1%), and nonsteroidal anti-inflammatory drugs (NSAIDs) were involved in 67%, followed by latex, local anaesthetics and antibiotics. Epinephrine was used in 33.6% of reactions. There has been hypotension and/or shock in 31.1%. Anaphylactic shock accounted for 60% of latex anaphylaxis, 50% of those due to antibiotics and 22.4% of NSAIDs induced anaphylaxis. We evaluated 806 patients, of whom 122 (15.1%) met the criteria of anaphylaxis. The average age was 38.9 years and 81.9% were female. The probable etiology was defined in 88 patients (72.1%), and nonsteroidal anti-inflammatory drugs (NSAIDs) were involved in 67%, followed by latex, local anaesthetics and antibiotics. Epinephrine was used in 33.6% of reactions. There has been hypotension and/or shock in 31.1%. Anaphylactic shock accounted for 60% of latex anaphylaxis, 50% of those due to antibiotics and 22.4% of NSAIDs induced anaphylaxis. ConclusionsThe number of drug induced anaphylaxis is high, although the diagnosis of anaphylaxis is neglected and epinephrine is underutilized. NSAIDs were the drugs most commonly implicated, but antibiotics were not as involved as previously described. Latex was an important agent in perioperative anaphylaxis. Cases of anaphylactic shock were associated to IgE-mediated hypersensitivity mechanism, as we observed in latex and antibiotics allergies. The number of drug induced anaphylaxis is high, although the diagnosis of anaphylaxis is neglected and epinephrine is underutilized. NSAIDs were the drugs most commonly implicated, but antibiotics were not as involved as previously described. Latex was an important agent in perioperative anaphylaxis. Cases of anaphylactic shock were associated to IgE-mediated hypersensitivity mechanism, as we observed in latex and antibiotics allergies.

P02-452 - Dystonia and acute psychotic episode complicated by neuroleptic malignant syndrome in an adolescent with CYP2D6 deficiency

IntroductionCYP2D6 gene encodes an isozyme of the P450 cytochrome mono-oxygenase family, responsible for hepatic metabolism of the majority of neuroleptics. Phenotypes of CYP2D6 activity are ultrarapid, extensive, intermediate, and poor metabolizers. Prevalence of poor metabolizers is relatively high in European Caucasian population and ranges between 5–10%. The subjects with such phenotype are more likely to manifest adverse reactions and toxicity following administration of drugs in standard doses.ObjectiveWe describe a case report of a 16 year old male patient with dystonia and acute psychotic episode who developed neuroleptic malignant syndrome (NMS) associated with antipsychotic medication and a non-functional CYP2D6*4 allele.MethodsThe patient's clinical course is a case report.ResultsThe patient developed NMS after treatment with standard doses of antipsychotics. Genotyping revealed that this patient was homozygous for non-functional CYP2D6*4 allele. Ziprasidone was used for a follow-up treatment after recovery from the NMS. Persistent neuropsychiatric impairment was noted after 9-months.ConclusionsInitial symptoms developed by this patient may be explained by overuse OTC cough medication. This case suggest that as in adult population, non-functional CYP2D6 allele could be associated with NMS in pediatric population. This means that screening for CYP2D6*4 allele in pediatric patients with NMS and history of adverse drug reactions could be helpful in the treatment of residual state after NMS.

Usefulness of drug provocation tests in children with a history of adverse drug reaction

PurposeThere are very few reports of adverse drug reactions (ADR) and almost no study of drug provocation test (DPT) in Korean children. We aimed to assess the role of DPT in children with unpredictable ADRs, and compare the causative drugs and clinical characteristics between detailed history of ADRs and result of DPTs.MethodsWe included 16 children who were experienced ADRs referred to pediatric allergy clinic at Ajou University Hospital (January 2006 to December 2009). With various suspected drugs, 71 DPTs were done in 16 patients using our own protocol, and skin tests to antibiotics were combined in ADRs to antibiotics in medical history.ResultsThere were 17 (23.9%) positive DPTs results out of 71 individual DPTs, and 11 patients (68.8%) from 16 patients were positive to at least one drug. Drugs causing positive reactions were acetaminophen in 5 (31%), Non-steroidal anti-inflammatory drugs in 4 (25%), penicillin in 3 (19%), cephalosporin in 2 (13%), and cotrimoxazole, macrolide and lactose in 1 each.ConclusionDPT seems a safe and useful procedure to confirm causative drug and identify safely administering alternative drugs in children with ADR.

Rapid endoscopic improvement is important for 1-year avoidance of colectomy but not for the long-term prognosis in cyclosporine A treatment for ulcerative colitis

Intravenous (IV) cyclosporine A (CSA) is one of the treatments of choice for patients with steroid-refractory severe ulcerative colitis (UC). In this study, we evaluated the overall experience with CSA treatment in UC patients, from their initial response to long-term prognosis. The medical records of 72 patients admitted to our hospital with a severe UC flare-up and treated with IV CSA between November 1996 and October 2008 were reviewed retrospectively. The initial response to CSA was assessed using a clinical activity index, and colectomy was assigned as the endpoint for the long-term prognosis. Overall, 53 of 72 (73.6%) patients responded initially to CSA. We could not determine any specific parameters that predicted an initial response. A life-table analysis for all patients revealed that 54.4% of patients required a colectomy within 11years. The long-term risk of surgery was associated with a shorter disease duration, history of adverse reactions against medications and lack of immunomodulator use. In addition, endoscopic improvement at day 14 was associated with colectomy at 1year, but not with the long-term prognosis. Although CSA can exert high initial efficacy for severe attacks of UC, >50% of patients who relapse require a colectomy. Specifically, mucosal healing evaluated by endoscopy was associated with the 1-year colectomy rate. In contrast, a history of adverse drug reactions was correlated with the long-term colectomy rate. Therefore, we propose that treatment of severe UC with CSA requires consideration of both initial remission and long-term maintenance as management goals.

Allergic and Non-Allergic Drug Hypersensitivity Reactions in Children

Adverse drug reactions (ADR) are an important medical problem. The aim of this study is to investigate the clinical characteristics of children with ADR and to assess the tolerability of alternative drugs in children (under 16 yrs of age) with a history of ADR. We studied 278 children (132 males and 146 females). Patients were studied by recording personal history and performing in vivo skin testing, in vitro laboratory tests and challenge tests. Patients who had experienced mild adverse reactions underwent challenge tests without any premedication; patients with a clinical history of moderate reactions, received a premedication with sodium chromolyn 30 min before the oral challenge; patients with a clinical history of severe reactions or undergoing parenteral challenges, were given an antihistamine 30 minutes before. A total of 660 adverse events were reported with 126 different drugs involved. Antimicrobial agents were the most involved drugs (51.7%). Non-steroidal anti-inflammatory drugs were involved in 22.7% of episodes. The most reported symptoms were cutaneous. Allergy testing was negative in 272 patients. A diagnosis of drug allergy was reported for 6 patients. A total of 669 challenge tests were performed. 639 were negative at first attempt while 22 were positive. Eight were repeated using a different premedication and resulted negative. Hypersensitivity drug reactions in children are mainly non-allergic. A premedication with sodium cromolyn or with oral H1-antihistamines may be useful in preventing ADR.

Reacciones adversas a medicamentos en pacientes que acudieron a un hospital general: un meta-análisis de resultados

The aim of this study was to present the results of a meta-analysis on adverse drug reactions (ADR) in spanish patients admitted to hospital and presenting to emergency department over the past 20 years. An exhaustive review was undertaken of relevant articles in the IME (Spanish Medical Index) and MEDLINE databases and published between 1985 and 2006, rigorously selecting 12 out of 30 publications after applying inclusion and exclusion criteria. Information was required on: symptomatology, prognosis, type, drugs involved, imputability and admissions for ADR; and factors associated with ADR onset, e.g., age, sex, number of drugs, previous history of ADR, method used for ADR detection, and length of study period. A random-effects model (DerSimonian and Laird) and the STATA 9.1 programme were used for the meta-analysis. The combined estimation of the percentage of Spanish patients with ADR was 13% (95% CI); with severe ADR, 12 % (95% CI) and with fatal ADR, 0.1% (95% CI). ADR diagnosis was definite in 36% (95% CI), probable in 49.6% (95% CI), and type A in 71% (95% CI) of cases. Among patients in the Emergency Department for ADR, 5.1% (95% IC) were hospitalized. No association was found with number of prescriptions or previous history. Association was established with advanced age and female sex. Digestive, skin, nervous and cardiovascular systems were those most affected by ADR. The drugs most frequently implicated included NSAIDs, digoxin, IACE, calcium antagonists, furosemide, i.v. metamizol, antidiabetics, benzodiazepines, adrenergic bronchodilators and classic antipsychotics. ADRs constitute a major medical and economic problem with aspects that have yet to be defined. Greater efforts are warranted to unify criteria for the publication of results in observational studies on ARD and to determine the role played by some factors associated with their onset, e.g., sex, previous history and comorbidities.

Adverse reactions of anti‐tuberculosis drugs in hospitalized patients: incidence, severity and risk factors

Tuberculosis (TB) has been a common chronic infectious disease in human communities. Besides disease-related complications, there could be serious adverse reactions due to anti-tuberculosis (anti-TB) drug therapy. To assess the incidence and severity of adverse drug reactions (ADRs) induced by anti-TB drugs. To determine possible covariates associated with detected ADRs. All patients with respiratory TB admitted to a teaching hospital who received anti-TB drugs during the research period entered the study and were monitored for ADRs. Socio-demographic and medical history of patients were used as independent covariates. The relationship between independent covariates with frequency and severity of ADRs was analysed using multivariate logistic regression. Preliminary analyses of the Mann-Whitney, Chi-square, Kruskal-Wallis and the Fisher's exact tests were applied to determine factors unlikely associated with the independent variables. Among 204 patients admitted, there were 92 patients (45.1%) with ADRs induced by anti-TB drugs. Patients with a previous history of anti-TB drugs usage (OR = 5.81, 95% confidence interval [95%CI]: 1.31-25.2), patients with a history of drug allergy (OR = 6.68, CI: 1.28-36.2), those from Afghani ethnic (OR = 4.91, 95%CI: 1.28-18.30) as well as smoker patients with concurrent diseases (OR = 19.67, CI: 1.24-341.51) had a higher rate of ADR incidence. Being female (OR = 1.63, 95%CI: 1.96-36.40) and having previous history of ADR (OR = 17.46, 95%CI: 1.96-20.42) were identified as risk factors. Anti-TB drugs could cause severe and frequent adverse effects. Females, those with a previous history of ADRs to anti-TB drugs and Afghani patients, should be considered as high-risk groups.

Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia

This study investigated the relevance of the cytochrome P450 (CYP) 2D6 genotype to the adverse drug reactions (ADRs) of H1-antihistamines and the level of sedation. Japanese participants in a health screening program were asked to describe any past history of ADRs. Any subjects reporting ADRs induced by H1-antihistamines were then individually interviewed and defined as cases. Excessive daytime sleepiness, which had occurred in the cases as an H1-antihistamine-induced ADR, was assessed by the Epworth sleepiness scale (ESS), and an ESS score >or=12 was considered hypersomnia. CYP2D6*4, *5, *14, and *10 were genotyped by a panel of polymerase chain reaction techniques. Out of 2,074 participants, 100 cases (M:F = 37:63, mean age 51.9 +/- 9.2 years) were eligible for analysis. The most common etiological drug was chlorpheniramine, which is the most frequently used H1-antihistamine in Japan. CYP2D6*10 allele and genotypes were more frequently found in the cases than in the healthy Japanese population in a large study (P < 0.005 and P = 0.039, respectively), but no difference was observed in the null alleles and genotypes. The ESS scores in 75 cases (M:F=25:50) who had experienced excessive daytime sleepiness were 9.5 +/- 5.5 in men and 12.9 +/- 6.1 in women (P < 0.001, cases vs. 34 subjects without symptoms; P = 0.001 men vs. women). The occurrence of hypersomnia increased as the number of CYP2D6 mutant alleles increased (P = 0.045). The results suggest that the presence of the CYP2D6*10 allele is a risk factor for development of H1-antihistamine-induced ADRs in Japanese.

Reacciones adversas medicamentosas en pacientes que consultaron a instituciones prestadoras de servicios en Pereira, Colombia

Describing adverse drug reactions (ADR) and analyzing the factors associated with their appearance in patients attending two hospitals' emergency services. Descriptive, medicine-surveillance study of people consulting the emergency service at the Rosales hospital and the basic total health attention unit in Pereira, Colombia, between July and September 2005 for any symptom related to taking medicine. Naranjo's Adverse Drug Reaction probability scale was used. A total of 91 patients were found; 62,6 % were women having an average age of 36,3+/-22,4 (range 0-85). Antibiotics (24,2 %) NSAIDs (17,6 %), analgesics (9,9 %) and antidiabetic agents (8,8 %) were the most used drugs. 39,6 % of the patients only used one medicine; the average of drugs per patient was 2,4+/-1,5. Self-medication was present in 25,3 %. The most common ADRs arose from urticaria (31,9 %), hypoglycaemia (8,8 %), gastritis (6,6 %), angioedema (5,5 %) and anaphylaxis (4,4 %). 13,2 % of ADRs were serious and 54,9 % were avoidable. 14,3 % of ADRs were classified as being definite and 75,8 % probable. Only 14,3 % of patients had a past history of ADR. The average cost of being attended was US$ 78,1 dollars. Analgesic use was associated with anaphylaxis, antibiotics with urticaria whilst NSAIDs was associated with gastritis and gastrointestinal bleeding, antidiabetic agents with hypoglycaemia, antipsychotic and antidepressants agents with neurological symptoms and warfarin with bleeding. The most important ADR-associated risk factors in patients attending emergency services were determined. Special care must be paid to patients using NSAIDs, warfarin, metoclopramide, metamizole, antipsychotic and antidepressants agents, antidiabetic agents and antibiotics, having a past history of ADR, being more than 55 years old and presenting urticaria, digestive and/or neurological symptoms

Reacciones adversas a medicamentos: una revisión actualizada del problema en España

Adverse drug reactions (ADR) are an important clinical problem and their impact on the Spanish population is unknown. The aim of this study was to provide an overview of ADR based on a review of observational studies published in Spain since 1974. Twenty-seven studies of Spanish patients were selected from a total of 90 articles published in national and international journals between 1974 and 2004. Studies eligible for inclusion were identified with an especially designed checklist. The incidence of ADR among 139,799 patients was 3%; 0.6% of the events led to death, and 17% led to severe illness. Two-thirds (67%) of the ADR were classified as type A. The rate of hospitalization for ADR was 6.5%, and mean length stay was 4 +/- 1.3 days. Thirteen percent of the ADR were considered confirmed, and 57% were considered probable. Half (50%) of the ADR were considered preventable. The groups of medications involved most frequently were antibacterial, NSAID, psychoactive medications, bronchodilators, digoxin, non-opiate analgesics, vasodilators, antidiabetics and loop diuretics. The organs and systems involved most frequently were the digestive tract, skin, central nervous system, cardiovascular, endocrine and respiratory systems. The factors associated most strongly with ADR were advanced age and use of multiple medications. The relationships of gender, previous history of ADR and comorbidity with the incidence of ADR have yet to be established. This review of ADR provides useful information on the incidence of ADR in the Spanish population and serves as a baseline for future studies.

Use of the Beers Criteria to Predict Adverse Drug Reactions Among First-Visit Elderly Outpatients

To determine whether the Beers criteria can predict adverse drug reactions (ADRs) in first-visit elderly outpatients. Prospective cohort study. Outpatient clinics of a tertiary care and academic medical center in southern Taiwan. Eight hundred eighty-two patients aged 65 years or older who were prescribed drugs at their first visit to either the medical center's outpatient internal medicine clinic or family medicine clinic between March 1, 2001, and July 31, 2001. Telephone survey conducted 1 week after clinic visit. Potentially inappropriate drugs were assessed by the updated Beers criteria. Adverse drug reactions were detected by telephone survey and evaluated by the Naranjo criteria 1 week after drug administration. Of the 550 respondents, 64 (11.6%) had potentially inappropriate drugs prescribed and 126 (22.9%) had ADRs. Multiple logistic regression analysis revealed associations between ADRs and potentially inappropriate drug prescribing (relative risk [RR] 15.3, 95% confidence interval [CI] 4.0-58.8), number of prescribed drugs (RR 1.3, 95% CI 1.1-1.5), history of ADRs (RR 2.1, 95% CI 1.3-3.4), and noncompliance with prescribed drugs (RR 2.0, 95% CI 1.1-3.7). In patients who had potentially inappropriate drugs prescribed, the number of prescribed drugs was not significantly associated with ADRs (RR 0.8, 95% CI 0.6-1.1). In patients who did not have potentially inappropriate drugs prescribed, more prescribed drugs increased the risk of ADRs (RR 1.3, 95% CI 1.1-1.5). A positive association exists between potentially inappropriate drug prescribing, as defined by the Beers criteria, and ADRs in first-visit elderly outpatients. Clinicians should be alert to the possibility of ADRs if a patient takes more than five drugs, has a history of ADRs, or exhibits poor compliance with prescribed drugs.

Adverse effect of drug-induced emotional problems on work and daily activities. A principal component as an independent predictor of ADRs in Shanghai patients with osteo-arthropathy taking nabumetone.

To discover principal components among assessed items from the WHO-SF36 survey by principal component analysis (PCA) and then to establish the relationship between the candidate principal component and the incidence of ADRs induced by nabumetone in Shanghai osteoarthropathy patients. A total of 145 patients were interviewed using the WHO-SF36 questionnaire for quality of life (QOL) assessment before the administration of nabumetone. The sub-items of the questionnaire were analyzed using PCA and several comprehensive variables were established. Relationships between these newly formed variables and the overall incidence of adverse drug reactions (ADRs) caused by nabumetone were evaluated using univariate and multivariate analyses. Several principal components were identified and their linear parameters were estimated using PCA. Through univariate analysis, only 1 principal component--"adverse effect on work and daily activities as a result of emotional problems"--was found related to the incidence of ADRs. The odds ratio (OR) was 1.28 with 95% confidence intervals (CI) of 1.11 and 1.48, p = 0.0384. This result was validated using a multivariate logistic analysis performed on all the alternative candidate covariates, including family income, a history of ADRs on NSAIDs, the course of the disease, level of education, control of stress, coffee consumption and consumption of salty food. The covariate information was taken from other parts of the clinical report form (CRF) used in this research. The analysis proved that the principal component, adverse effect on work and daily activities as a result of emotional problems, was an independent factor related to the overall incidence of ADRs. The odds ratio (OR) from the logistic analysis was 1.34, with 95% confidence intervals (CI) of 1.16 and 1.55, p = 0.0309. The principal component identified can be applied to overcome some limitations in the WHO-SF36 questionnaire such as high correlation between variables, information overlaps and weak representation of variables and the statistical data analysis of QOL can therefore be made more effective. The study shows that the principal component "adverse effect on work and daily activities as a result of emotional problems" is an independent predictor of the overall incidence of ADRs induced by nabumetone.