Choosing Appropriate Theories for Understanding Hospital Reporting of Adverse Drug Events, a Theoretical Domains Framework Approach.

Adverse drug events (ADEs) may cause serious injuries including death. Spontaneous reporting of ADEs plays a great role in detection and prevention of them; however, underreporting always exists. Although several interventions have been utilized to solve this problem, they are mainly based on experience and the rationale for choosing them has no theoretical base. The vast variety of behavioural theories makes it difficult to choose appropriate theory. Theoretical domains framework (TDF) is suggested as a solution. The objective of this study was to select the best theory for evaluating ADE reporting in hospitals based on TDF. We carried out three focus group discussions with hospital pharmacists and nurses, based on TDF questions. The analysis was performed through five steps including coding discussions transcript, extracting beliefs, selecting relevant domains, matching related constructs to the extracted beliefs, and determining the appropriate theories in each domain. The theory with the highest number of matched domains and constructs was selected as the theory of choice. A total of six domains were identified relevant to ADE reporting, including "Knowledge", "Skills", "Beliefs about consequences", "Motivation and goals", "Environmental context and resources" and "Social influences". We found theory of planned behavior as the comprehensive theory to study factors influencing ADE reporting in hospitals, since it was relevant theory in five out of six relevant domains and the common theory in 55 out of 75 identified beliefs. In conclusion, we suggest theory of planned behavior for further studies on designing appropriate interventions to increase ADE reporting in hospitals.

Pediatric hospital admission due to adverse drug reactions: Report from a tertiary center.

OBJECTIVE: Adverse drug reactions (ADRs) are known as a cause of hospital admission. We have carried out a prospective study to characterize and assess the frequency, probability, preventability, and severity of ADRs, which lead to hospital admission in children. METHODS: In a prospective observational study, a cohort of children admitted to a tertiary pediatric hospital was randomly screened to assess ADR as the cause of admission from June 2014 to January 2015. ADRs causing admissions were detected based on patients' records, interviewing their parents, and confirmation by medical team. The probability of the ADRs was assessed based on WHO criteria and Naranjo tool. The preventability assessment was performed using Schumock and Thornton questionnaire. FINDINGS: Of the 658 evaluated emergency admissions, 27 were caused by an ADR giving an incidence of 4.1%. Among ADRs, 37.1% were estimated to be preventable. Antibiotics were the most common medication class which caused hospital admission. CONCLUSION: Pediatric pharmacotherapy still needs evidence-based strategies to improve child care including education, monitoring, planning for medications after ADR occurrence, and implementing preventive measures when applicable.

Perceived barriers to reporting adverse drug events in hospitals: a qualitative study using theoretical domains framework approach.

BACKGROUND: Adverse drug events (ADEs) are a major source of morbidity and mortality, estimated as the forth to sixth cause of annual deaths in the USA. Spontaneous reporting of suspected ADEs by health care professionals to a national pharmacovigilance system is recognized as a useful method to detect and reduce harm from medicines; however, underreporting is a major drawback. Understanding the barriers to ADE reporting and thereafter design of interventions to increase ADE reporting requires a systematic approach and use of theory. Since multiple theories in behavior change exist that may have conceptually overlapping constructs, a group of experts suggested an integrative framework called theoretical domains framework (TDF). This approach considers a set of 12 domains, came from 33 theories and 128 constructs, covering the main factors influencing practitioner behavior and barriers to behavior change. The aim of this study is to apply TDF approach to establish an evidence-based understanding of barriers associated with ADE reporting among nurses and pharmacists. METHODS: A total of three focus group discussions were conducted; among them two consisted of nurses and one involved pharmacists. Discussions were guided by questions designed based on TDF. Transcriptions of discussions were then thematically analyzed, and detected barriers to reporting ADEs were categorized based on extracted themes. RESULTS: A total of 34 nurses and pharmacists attended the group discussions. Six domains were identified to be relevant to barriers of ADE reporting in hospitals. These domains included "Knowledge," "Skills," "Beliefs about consequences," "Motivation and goals (intention)," "Social influences (norms)," and "Environmental constraints." We detected several barriers to ADE reporting, such as lack of knowledge of what should be reported, fear of punishment and criticism, lack of time, lack of teamwork, and lack of active support by hospital managements and other colleagues. Based on detected barriers, "Cognitive and behavioral factors," "Motivational factors and teamwork," in addition to "Organizational processes and resources" could be targeted in designing appropriate interventions. CONCLUSIONS: Detection of barriers to reporting ADEs is necessary to design appropriate interventions. The TDF is a comprehensive approach that enables us to better understand barriers to behavior change in reporting ADEs.

Cytotoxic glucose degradation products in fluids for peritoneal dialysis.

During the standard heat sterilization process of the lactate-buffered peritoneal dialysis solutions, glucose (an osmotic active substance) degrades to form compounds called glucose degradation products which are cytotoxic and affect the survival of the peritoneal membrane. This case presentation is based on an observation of 224 aseptic peritonitis cases of unknown etiology. For the purpose of clarification, we analyzed the peritoneal dialysis solutions for the presence of acetaldehyde by using a developed and validated high-performance liquid chromatography (HPLC) pre-column derivitazation. The method was validated with respect to validation factors such as linearity, precision, recovery and (LOD). The acetaldehyde level of solutions before heat sterilization was 1.78 ± 2.7 ppm whereas in samples after heat sterilization was about 20 ± 2.07 ppm. Based on the forementioned findings, we hypothesized that the higher levels of acetaldehyde and possibly the other glucose degradation products may have been an etiological factor in these 224 cases of chemical peritonitis. So it is important for the manufacturers to carefully review the heat of sterilization process in the production line.

Adverse drug reactions induced by cardiovascular drugs in cardiovascular care unit patients.

PURPOSE: To detect the type, rate, seriousness, and preventability of adverse drug reactions (ADRs) attributable to cardiovascular drugs in cardiovascular care unit; and to determine the relationship between patient factors and detected ADRs. METHODS: Patients admitted to cardiovascular care units in Tehran Heart Center over an eight month period who received at least one cardiovascular drug were eligible to enter the study. ADRs were recorded based on information collected by interviewing patients, reviewing patients' charts, laboratory test monitoring, and confirmation by physicians. The World Health Organization definition for ADR, its seriousness and casualty criteria, was used to evaluate the reactions. The preventability was estimated based on Schumock and Thornton questioning. The relationship between possible risk factors and ADRs occurrence were assessed by statistical analysis. RESULTS: During the study period, 677 patients entered the study. A total number of 189 ADRs were registered of which 22.2% were serious. The highest ADR rates were observed with Streptokinase (59.3%). The rate of preventable ADRs was 6.9%. Multivariate logistic regression analysis showed that patients with lower weight (OR = 0.95, 95%CI: 0.9-0.99) and patients with smoking history who had concurrent diseases (OR = 8.72, 95%CI: 1.53-49.52) had a higher risk of experiencing ADRs. CONCLUSION: The rate of ADRs induced by cardiovascular drugs in this study was 24.2%. This study has shown that anti-arrhythmic and thrombolytic agents need more attention.

Developing an adverse drug reaction reporting system at a teaching hospital.

Adverse drug reactions (ADRs) are a frequent cause for hospitalization and occur often in hospitalized patients. The objective of this study was to establish an ADR reporting and monitoring system at a teaching hospital. The pharmacovigilance unit of Masih Daneshvari hospital was established by a clinical pharmacist and a clinical pharmacologist. Healthcare professionals were encouraged to report any suspected ADRs encountered in in-patients. The incidence, pattern, seriousness, severity and preventability of the reported ADRs were analysed. During the period of 12 months, for 6840 patients, 112 spontaneous reports were received. The most frequently reported reactions were due to anti-infective agents (58.2%). Ceftriaxone accounted for the highest number of the reported ADRs among anti-infective agents. The skin and appendages system was the most frequently affected system (32.5% of all reactions). Seventeen per cent of the ADRs were reported as serious reactions. Although the incidence of ADRs reported by physicians and nurses was found to be low, this programme was useful as a preliminary programme in initiating a culture of ADR reporting among healthcare professionals. Improved communication between the physicians and nurses with the pharmacovigilance centre in the hospital is suggested.

Adverse drug reactions induced by cardiovascular drugs in outpatients

Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. Objectives: To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. Methods: This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. Results: The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05). ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05). With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05). Conclusion: Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases (AU)

Teniendo en cuenta el aumento del uso de medicamentos cardiovasculares y las limitaciones en los estudios pre-comercialización, parece necesaria la evaluación de reacciones adversas (RAM) producidas por este grupo de medicamentos. Objetivos: Determinar la tasa y la gravedad de las RAM producidas por medicamentos cardiovasculares en pacientes ambulatorios. Comparar las diferencias de sexo y edad en la aparición de reacciones adversas con medicamentos cardiovasculares. Evaluar la relación entre las frecuencias de RAM y la cantidad de medicamento usado. Métodos: Este estudio transversal se realizó en la clínica cardiovascular del hospital universitario. Se evaluó a todos los pacientes durante un periodo de 8 meses en busca de RAM inducidas por medicamentos cardiovasculares. Se analizaron las variables de pacientes y las reacciones. Se comparó el sexo y la edad de los pacientes con y sin RAM utilizando el test chi cuadrado. Mediante un análisis de Pearson se evaluó la relación entre la frecuencia de RAM y los medicamentos usados. Resultados: El número de pacientes visitados en la clínica fue de 518. Se detectaron RAM en 105 pacientes (20,3%). Las RAM más frecuentes aparecieron en el grupo de 51-60 años. La tasa más alta de RAM registrada estaba inducida por dialtiazem (23,5%) y la más baja con atenolol (3%). La RAM más frecuente fue el dolor de cabeza. Al evaluar la gravedad y preventabilidad de las RAM se reveló que el 1,1% de las RAM detectadas eran graves, y el 1,9% eran prevenibles. Las mujeres desarrollaron significativamente más RAM en este estudio (chi cuadrado=3,978, p<0,05). Las RAM aparecieron más frecuentemente con la edad (chi cuadrado=18,871, p<0,05). Al aumentar el número de medicamentos, la frecuencia de RAM aumentaba (Pearson=0.259, P<0.05). Conclusión: Es de gran importancia seguir las RAM en pacientes que usan medicamentos cardiovasculares ya que este grupo de medicamentos es utilizado generalmente por ancianos en condiciones críticas y con enfermedades subyacentes (AU)

Adverse drug reactions induced by cardiovascular drugs in outpatients.

UNLABELLED: Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. OBJECTIVES: To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. METHODS: This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. RESULTS: The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05). ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05). With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05). CONCLUSION: Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

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

BACKGROUND: 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. OBJECTIVES: To assess the incidence and severity of adverse drug reactions (ADRs) induced by anti-TB drugs. To determine possible covariates associated with detected ADRs. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Fatalities following skin exposure to arsenic.

Arsenic is a toxic metal that can cause death following exposure. In an unusual event, seven patients unintentionally applied a 30% arsenic solution to their entire body instead of a benzyl benzoate solution to treat their scabies. Hours later they developed severe skin reactions, including bullae, and were admitted to the hospital with gastrointestinal and cardiovascular disorders. Despite therapeutic interventions, three patients died and the rest were discharged from hospital with neurological sequelae. Toxicological analysis confirmed the presence of arsenic in the solution used by patients.

Applying quantitative methods for detecting new drug safety signals in pharmacovigilance national database.

OBJECTIVES: To applies three different methods of signal detection to the registered adverse events in Iranian Pharmacovigilance database over the period of 1998-2005. METHODS: All adverse drug reactions (ADRs) reported to Iranian Pharmacovigilance Center (IPC) from March 1998 through January 2005, were used for the analysis. The data were analysed based on three different signal detection methods including reporting odds ratios (RORs), information component (IC) and proportional reporting ratios (PRRs). The signals detected were categorised based on the number of reports per drug-adverse event combination, severity of the event and labelled or unlabelled ADRs. RESULTS: During the study period, 6353 cases of ADR reports describing 11 130 reactions were received by IPC. The dataset involved 4975 drug-adverse event combinations. The count of drug-event combinations was 1, 2 and 3 or more for 3470, 726 and 779 combinations, respectively. According to PRRs, there were 2838, 872 and 488 drug-event combinations known as a signal for the pairs with the reporting frequency of 1, 2 and 3 reports, respectively. The results of estimating RORs showed that 2722, 862 and 481 drug-adverse event combinations were detected to be signal for the pairs with the reporting frequency of 1, 2 and 3 reports, respectively, while measuring IC and IC-2SD detected 1120, 378 and 235 for the same reporting frequencies. Diclofenac-induced paralysis and tramadol-induced severe reactions were the most important signals. CONCLUSION: Applying quantitative signal detection methods to the database of national pharmacovigilance centres is necessary to early detection of drug safety alerts.

Evaluación de las reacciones adversas de los antituberculosos en pacientes hospitalizados / Evaluation of anti-tuberculosis induced adverse reactions in hospitalized patients

Antecedentes: La tuberculosis ha sido una de las enfermedades comunes de la humanidad. Además de las complicaciones relacionadas con la enfermedad, existen efectos adversos graves debidos al tratamiento antituberculoso (Anti-TB). Objetivos: Evaluar la tasa de reacciones adversas a medicamentos (RAM) inducidas por medicamentos Anti-TB en el departamento de enfermedades infecciosas durante el periodo de un año. Detectar las RAM reconocidas como graves y prevenibles. Métodos: Entraron en el estudio todos los pacientes admitidos que recibían medicamentos Anti-TB en el departamento de infecciosos del Hospital Universitario terciario Iman en Irán entre julio 2001 y julio 2002. Se monitorizaron las RAM de estos pacientes durante su estancia hospitalaria. Se clasificaron las RAM en función de los factores de los pacientes y de las reacciones. Se determinaron la causalidad y la gravedad de las reacciones adversas utilizando el algoritmo de Naranjo y el cuestionario de Hartwig, respectivamente. Resultados: Durante el periodo de estudio, 83 pacientes recibieron medicamentos Anti-TB; de ellos, 44 desarrollaron al menos una RAM. El número total de RAM detectadas en este estudio fue de 81. Las RAM se reconocieron como la causa principal de ingreso hospitalario en 11 (13,3%) pacientes. El órgano-sistema más frecuentemente afectado fue el hígado y el sistema biliar (37%). Se observó hepatitis en 21 (25,3%) de los pacientes, y condujo a la muerte en dos casos. Conclusión: Los medicamentos Anti-TB podrían causar significativos efectos adversos tanto en cantidad como en gravedad, conduciendo a hospitalización, prolongación de la estancia e incluso la muerte. Se necesita prestar más atención para prevenir estas reacciones (AU)

Background: Tuberculosis has been one of the common diseases of human communities. Besides of disease-related complications, there are serious adverse reactions due to Anti-tuberculosis (Anti-TB) drug therapy. Objectives: To assess the rate of Adverse Drug Reactions (ADRs) induced by Anti-TB drugs in the infectious disease department for a period of one year. To detect serious and preventable recognized ADRs. Methods: All patients admitted to the infectious disease department at Imam tertiary teaching hospital in Iran who received Anti-TB drugs from July 2001 to July 2002 entered the study. These patients were monitored for ADRs during hospital stay. The ADRs were then classified based on patients and reactions factors. The causality and severity of the reactions were determined using Naranjo algorithm and Hartwig questionnaire, respectively. Results: During the study period, 83 patients received Anti-TB drugs; of them 44 developed at least one ADR. Total number of 81 ADRs was detected in this study. ADRs were recognized as the major cause of hospital admission in 11 (13.3%) patients. The most frequent system-organ class affected by ADRs was Liver and biliary system (37%). Hepatitis was observed in 21 (25.3%) patients leading to death in two patients. Conclusion: Anti-TB drugs could cause significant adverse effects both in quantity and severity leading to hospitalization, prolonged hospital stay and even death. More attention is needed to prevent these reactions (AU)

Evaluation of anti-tuberculosis induced adverse reactions in hospitalized patients.

BACKGROUND: Tuberculosis has been one of the common diseases of human communities. Besides of disease-related complications, there are serious adverse reactions due to Anti-tuberculosis (Anti-TB) drug therapy. OBJECTIVES: To assess the rate of Adverse Drug Reactions (ADRs) induced by Anti-TB drugs in the infectious disease department for a period of one year. To detect serious and preventable recognized ADRs. METHODS: All patients admitted to the infectious disease department at Imam tertiary teaching hospital in Iran who received Anti-TB drugs from July 2001 to July 2002 entered the study. These patients were monitored for ADRs during hospital stay. The ADRs were then classified based on patients and reactions factors. The causality and severity of the reactions were determined using Naranjo algorithm and Hartwig questionnaire, respectively. RESULTS: During the study period, 83 patients received Anti-TB drugs; of them 44 developed at least one ADR. Total number of 81 ADRs was detected in this study. ADRs were recognized as the major cause of hospital admission in 11 (13.3%) patients. The most frequent system-organ class affected by ADRs was Liver and biliary system (37%). Hepatitis was observed in 21 (25.3%) patients leading to death in two patients. CONCLUSION: Anti-TB drugs could cause significant adverse effects both in quantity and severity leading to hospitalization, prolonged hospital stay and even death. More attention is needed to prevent these reactions.