A novel way to overcome the challenge of under-reporting of adverse drug reactions in a tertiary care hospital: A pharmacovigilance study

Background: Adverse drug reactions (ADRs) constitute a major clinical problem in terms of human suffering and increased health-care costs all over the world. Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects, or any other drug related problems. Thus, the information generated is useful in educating doctors about ADRS as well in the official regulation of drug use. However, the pharmacovigilance program faces the challenge of under reporting of ADRs and one needs to find the ways to overcome it. Aim and Objectives: The aim of the study was to improve the reporting of ADRs from the hospital and overcome the problem of under-reporting of ADRs. Materials and Methods: A prospective observational study was conducted as part of pharmacovigilance program over 6 months between June 2021 and December 2021. Undergraduate students were trained to collect cases of ADR from hospital during their clinical postings. The details of cases obtained by such active surveillance were filled into suspected ADR–CDSCO forms and submitted to pharmacovigilance unit. Causal relationship was assessed and categorized by Naranjo algorithm and WHO-UMC causality scale. All values were expressed in percentages. Results: A total of 120 cases were reported over 6 months compared to just 20 cases during the past year. Among them, 66% were in males and 55% were in females. The majority of ADRs were due to antimicrobial agents (40.78%) followed by hematinics (12%) and anti-epileptics (10%). The maximum number of patients (30.25%) reported with dermatological manifestations. The highest number of ADRs was reported from the Department of Medicine (45%). As per Naranjos scale, 54% reports were assessed as probable and 46% as possible. Conclusion: This new way of training and involving undergraduates significantly improved the number of ADR cases being reported to the pharmacovigilance center. This helped overcome the problem of under reporting of cases and has strengthened the pharmacovigilance activity in our institute.

Eventos adversos a medicamentos entre idosos no Brasil antes e após o início da pandemia da COVID-19 / Adverse drug events among older adults in Brazil before and after the onset of the COVID-19 pandemic

Introdução: Danos decorrentes de eventos adversos relacionados a medicamentos (EAM) estão entre os mais frequentes no mundo. Logo, seu monitoramento é essencial, especialmente entre os idosos que apresentam maior risco de sofrer tais danos. Adicionalmente, a pandemia da COVID-19, a sua elevada incidência entre idosos e o uso frequente de medicamentos off-label reforçaram a importância do monitoramento de EAM nessa população. Objetivo: Descrever as suspeitas de EAM entre idosos no Brasil antes e após o início da pandemia por COVID-19. Método: Foi realizada a descrição das suspeitas de EAM notificadas no sistema VigiMed da Agência Nacional de Vigilância Sanitária envolvendo idosos (idade ≥ 65 anos) no período pré-pandemia (01/2019 a 03/2020) e pós-início da pandemia (04/2020 a 06/2021). A diferença entre a proporção de EAM graves entre os períodos foi avaliada mediante teste qui-quadrado de Pearson. Resultados: Foram notificadas 57.167 suspeitas de EAM no período global avaliado; 22,2% envolviam idosos. No período pré-pandemia, 2.924 suspeitas de EAM foram notificadas (44,2% eram EAM graves), destacando-se aquelas envolvendo antineoplásicos, antimicrobianos e anticoagulantes. No período pós-início da pandemia, 9.771 suspeitas de EAM foram notificadas (57,5% graves), destacando-se a hidroxicloroquina e as vacinas contra a COVID-19. A diferença na proporção de suspeitas de EAM graves notificadas para idosos entre os períodos avaliados foi estatisticamente significativa (p < 0,001). Conclusões: Notificações de EAM e estudos que avaliem EAM entre idosos são essenciais para gerar informações que possam subsidiar a otimização da farmacoterapia e a priorização de redução de danos entre eles, sobretudo no contexto pandêmico que afeta consideravelmente essa população.

Introduction: Harm resulting from adverse drug events (ADE) is among the most frequent in the world. Therefore, its monitoring is essential, especially among older adults, who are at greater risk of suffering such type of harm. Additionally, the COVID-19 pandemic, its high incidence among older adults and frequent use of off-label medications have reinforced the importance of monitoring ADE in this population. Objective: To describe the suspected ADE among older adults in Brazil before and after the beginning of the COVID-19 pandemic. Method: A description of suspected ADEs reported in the VigiMed system of the National Health Surveillance Agency was carried out, involving older adults (age ≥ 65 years) in the pre- (01/2019 to 03/2020) and post-onset of the pandemic period (04/2020 to 06/2021). The difference between the proportion of severe ADE between the periods was evaluated using Pearson's chi-square test. Results: 57,167 suspected ADE were reported in the global period evaluated; 22.2% involved older adults. In the pre-pandemic period, 2,924 suspected ADEs were reported (44.2% were severe ADEs), especially those involving antineoplastic, antimicrobial, and anticoagulant drugs. In the post-pandemic period, 9,771 suspected ADEs were reported (57.5% severe), especially related to hydroxychloroquine and vaccines against COVID-19. The difference in the proportion of severe suspected ADE reported for the older adults between the periods evaluated was statistically significant (p < 0.001). Conclusions: ADE notifications and studies that evaluate ADE among older adults are essential to generate information that can support drug therapy optimization and prioritization of harm reduction among them, especially in the pandemic context that considerably affects this population.

Impact of an educational intervention on knowledge and attitude regarding pharmacovigilance and adverse drug reaction reporting among postgraduate students of a tertiary care teaching hospital

Background: Doctors doing postgraduation (PG) are backbone of any teaching-hospital and are in close contact with patients. It is important they have adequate knowledge and attitude towards adverse drug reaction (ADR)-reporting and Pharmacovigilance Programme of India (PvPI). Aim and Objectives: To study the impact of an educational intervention on knowledge and attitude of 1st year PG residents toward ADR reporting and Pharmacovigilance. Materials and Methods: An educational intervention was conducted among 1st-year postgraduate students, including a lecture on importance and need of pharmacovigilance, hands-on-training on how to fill Suspected ADR Reporting Form and group based interactive discussion. Knowledge and attitude of participants were recorded in pre-post intervention questionnaire and analyzed. Results: Sixty-three postgraduate students from clinical (82.5%), paraclinical (12.7%), and preclinical (4.7%) departments participated. Mean test-score improved from 7.27 to 11.65 (P < 0.005). Need for pharmacovigilance, ADR-reporting related terminologies, PvPI, who can report and where to report ADR, signal generation, types of ADR-forms, and legal implications of reporting were the major areas with significant improvement. About 87% agreed post-intervention that ADRs are a major cause of morbidity, 96% agreed there should be an ADR-Reporting Centre in every institute and 92% agreed they will try to find whether some drug might be responsible for any unusual symptom in patient. Conclusion: Educational intervention could improve knowledge as well as attitude toward ADR reporting among postgraduate doctors, long-term impact needs further assessment.

Formulários de notificação de reações adversas a medicamento nos sistemas de farmacovigilância do Brasil e outros doze países latino-americanos: análise comparativa / Adverse drug reaction notification forms of the pharmacovigilance systems in Brazil and twelve other Latin-American countries: a comparative analysis

Resumo Avaliou-se os formulários de notificação de suspeitas de reações adversas a medicamentos (RAM) do sistema de farmacovigilância do Brasil e outros doze países latino-americanos. O estudo foi composto por três etapas. Na primeira, os formulários foram pontuados em relação à presença de itens essenciais para compor uma notificação de RAM. Na segunda, as variáveis dos formulários foram quantificadas e classificadas, quanto à razoabilidade em contribuírem para a avaliação de causalidade. Na última etapa, recorreu-se à análise de agrupamento hierárquico para identificar os formulários similares. O formulário da Venezuela obteve a maior pontuação (18 pontos). A mediana das variáveis nos formulários dos países foi de 41 [26 (Guatemala) a 95 (Brasil)]. A maioria das variáveis dos formulários foram classificadas como vitais e a maior parte contribui como fator de explicação alternativo para a avaliação de causalidade. Quatro agrupamentos foram identificados (1, 2, 3 e 4). Os formulários do Brasil e da Bolívia formaram dois grupos distintos, 1 e 3 respectivamente. Há necessidade de modificação dos formulários dos países ou até mesmo exclusão de variáveis, tornando-os mais adequados ao processo de avaliação da causalidade das RAM.

Abstract The scope of this study was to assess the forms used to report suspected adverse drug reactions (ADR) to the pharmacovigilance system in Brazil and twelve other Latin-American countries. The study comprised three stages. In the first stage, the forms were attributed a score relating to the presence of critical items to generate ADR notification. In the second stage, the variables of the forms were quantified and classified regarding feasibility to contribute to an appropriate assessment of causality. In the last stage, hierarchical clustering was used to identify similar forms. The Venezuelan form achieved the highest score (18 points). The median number of variables in the forms of each country was 41 [26 (Guatemala) to 95 (Brazil)]. Most of the variables of the form were classified as life-critical and the majority contribute as an alternative explanation to causality assessment. Four clusters were identified (1, 2, 3 and 4). The forms of Brazil and Bolivia formed two distinct groups, 1 and 3 respectively. The results of this study indicate the need to change the forms of the different countries studied or even delete some variables, making them more appropriate for the process of assessment of ADR causality.

Detección de errores de medicación mediante un programa de seguimiento y minimización en pacientes ambulatorios de Colombia, 2018-2019 / Identification of medication errors through a monitoring and minimization program in outpatients in Colombia, 2018-2019

Resumen | Introducción. El uso de medicamentos puede conllevar errores de medicación que desemboquen en la hospitalización del paciente, el aumento de los costos relacionados con la atención e, incluso, la muerte. Objetivos. Determinar la prevalencia de errores de medicación notificados en un sistema de información de farmacovigilancia en Colombia entre el 2018 y el 2019. Materiales y métodos. Se hizo un estudio observacional a partir del registro de errores de medicación de un sistema de farmacovigilancia que cubre a 8,5 millones de pacientes ambulatorios afiliados al sistema de salud de Colombia. Los errores se categorizaron en ocho grupos de la A (situaciones potenciales de error) hasta la I (error que pudo llevar a la muerte). Se hizo el análisis descriptivo y se estableció la prevalencia de los errores de medicación. Resultados. Durante los años 2018 y 2019, se reportaron 29.538 errores de medicación en pacientes ambulatorios, con una prevalencia general de 1,93 por cada 10.000 medicamentos dispensados. En el 0,02 % (n=6) de los casos, se presentaron errores que llegaron a afectar a los pacientes y causaron daño (tipos E, F e I). La mayoría de los errores se asoció con la dispensación (n=20.636; 69,9 %) y la posible causa más común fue la falta de concentración en el momento de dispensar los medicamentos (n=9.185; 31,1 %). Los grupos farmacológicos más implicados en errores de medicación fueron los antidiabéticos (8,0 %), los inhibidores del sistema renina-angiotensina (7,6 %) y los analgésicos (6,0 %). Conclusiones. Los errores de medicación son relativamente poco frecuentes y con mayor frecuencia se catalogan como circunstancias o eventos capaces de generar un error de tipo A. Muy pocas veces, pueden causarle daño al paciente, incluso, hasta la muerte.

Abstract | Introduction: The use of drugs may involve medication errors leading to hospitalization, increased costs related to care, and even death. Objective: To determine the prevalence of medication errors reported in a pharmacovigilance information system in Colombia between 2018 and 2019. Materials and methods: We conducted an observational study based on the records of medication errors from a pharmacovigilance system covering 8.5 million outpatients affiliated with the Colombian health system. The errors were categorized from A (potential situations to error) to I (an error that could lead to death). We performed a descriptive analysis and established the prevalence of medication errors. Results: During 2018 and 2019, 29,538 medication errors in outpatients were reported with a general prevalence of 1.93 per 10,000 drugs dispensed. The errors that reached the patient and caused damage (types E, F, and I) occurred in 0.02% (n=6) of the patients. Most of them were related to the dispensation (n=20,636; 69.9%) and the possible most common cause was the lack of concentration at the time of dispensing (n=9185; 31.1%). The pharmacological groups most involved in medication errors were antidiabetics (8.0%), renin-angiotensin system inhibitors (7.6%), and analgesics (6.0%). Conclusions: Medication errors are relatively rare situations, generally classified as circumstances or events capable of generating the error (type A error). In low proportion, they can reach the patient and cause damage or even death.

Retrospectiva de 20 anos de atividade da Unidade de Farmacovigilância do Porto, Portugal / Looking back on 20 years of work at the Porto Pharmacovigilance Centre, Portugal / Retrospectiva de 20 años de actividad de la Unidad de Farmacovigilancia de Oporto, Portugal

Resumo: Desde 1963 que a farmacovigilância foi reconhecida como uma área prioritária na saúde pública a nível global pela Organização Mundial da Saúde, garantindo a monitorização permanente da segurança dos medicamentos. O objetivo deste trabalho foi caracterizar as reações adversas a medicamentos recebidas pela Unidade de Farmacovigilância do Porto (UFPorto), Portugal, ao longo de duas décadas de atividade. Foram consideradas todas as notificações de suspeitas de reações adversas a medicamentos recebidas entre janeiro de 2001 e dezembro de 2019. Foram calculadas as taxas de notificação anuais, assim como a sua distribuição por origem, tipo de notificador e local de exercício da atividade, gravidade, conhecimento prévio e causalidade das reações adversas a medicamentos notificadas. No período em estudo, a UFPorto recebeu 9.711 notificações de suspeitas de reações adversas a medicamentos. As instituições hospitalares são aquelas que mais notificam (n = 6.003; 64%), assim como o médico entre os profissionais de saúde (n = 5.284; 54,4%). Os eventos adversos mais frequentemente reportados são graves (n = 6.275; 72%) e encontram-se descritos no respectivo Resumo das Características do Medicamento (n = 6.978; 72%). À maioria das notificações avaliadas pela UFPorto foi atribuído o grau de causalidade "provável" (n = 7.473; 77%), independentemente do tipo de notificador. Os resultados obtidos são concordantes com outros dados previamente reportados na literatura médica internacional e em relatórios oficiais nacionais. Contudo, continua-se a verificar taxas de subnotificação acentuadas, face ao esperado. Ao longo de aproximadamente 20 anos de atividade da UFPorto, tem-se verificado um aumento da sua atividade nas diversas vertentes da segurança do medicamento.

Abstract: Since 1963, the World Health Organization has acknowledged pharmacovigilance as a priority area in global public health, guaranteeing permanent monitoring of drug safety. This study aimed to characterize the reports of adverse drug reactions received by the Porto Pharmacovigilance Centre (UFPorto), Portugal, in the unit's two decades of work. The analysis included all reports of suspected adverse drug reactions received from January 2001 to December 2019. We calculated the annual reporting rates and distribution by origin, type of notifier and place of work, severity, prior knowledge, and causality of the reported adverse drug reactions. During the study period, UFPorto received 9,711 notifications of suspected adverse drug reactions. Hospital institutions reported the most suspected adverse drug reactions (n = 6,003; 64%), as did physicians among healthcare workers (n = 5,284; 54.4%). The most frequently reported adverse events were severe (n = 6,275; 72%) and are described in the respective Summary of Product Characteristics (n = 6,978; 72%). Most of the reports received by UFPorto were evaluated as having "probable" causality (n = 7,473; 77%), independently of the type of notifier. The results are consistent with other data previously reported in the international medical literature and official national reports. However, the underreporting rates are still higher than expected. In approximately 20 years, UFPorto has experienced an increase in its activity in various areas of drug safety.

Resumen: Desde 1963 la farmacovigilancia fue reconocida por la Organización Mundial de la Salud, como un área prioritaria en la salud pública a nivel global, garantizando la monitorización permanente de la seguridad de los medicamentos. El objetivo de este trabajo fue caracterizar las reacciones adversas a medicamentos recibidas por la Unidad de Farmacovigilancia de Oporto (UFPorto), Portugal, a lo largo de dos décadas de actividad. Se consideraron todas las notificaciones de sospechas de reacciones adversas a medicamentos, recibidas entre enero de 2001 y diciembre de 2019. Se calcularon las tasas de notificación anuales, así como su distribución por origen, tipo de notificador y lugar de ejercicio de la actividad, gravedad, conocimiento previo y causalidad de las reacciones adversas a medicamentos notificadas. En el período de estudio, la UFPorto recibió 9.711 notificaciones de sospechas reacciones adversas a medicamentos. Las instituciones hospitalarias son quienes más notifican (n = 6.003; 64%), así como el médico entre los profesionales de salud (n = 5.284; 54,4%). Los eventos adversos más frecuentemente reportados son graves (n = 6.275; 72%) y se encuentran descritos en lo respectivo Resumen de las Características del Medicamento (n = 6 978; 72%). A la mayoría de las notificaciones evaluadas por la UFPorto se le atribuyó el grado de causalidad "probable" (n = 7.473; 77%), independientemente del tipo de notificador. Los resultados obtenidos son concordantes con otros datos previamente reportados en la literatura médica internacional y en informes oficiales nacionales. No obstante, se continúa verificando tasas de subregistro acentuadas, frente a lo esperado. A lo largo de aproximadamente 20 años de actividad de la UFPorto, se ha verificado un aumento de su actividad en las diversas vertientes de la seguridad del medicamento.

Potential kidney damage associated with the use of remdesivir for COVID-19: analysis of a pharmacovigilance database / Potencial nefropatia associada ao uso do remdesivir para COVID-19: análise de uma base de dados de farmacovigilância / Potenciales lesiones renales asociadas con el uso de remdesivir para la COVID-19: análisis de una base de datos de farmacovigilancia

Abstract: The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

Resumo: De acordo com a Agência de Controle de Alimentos e Medicamentos dos Estados Unidos (FDA), a prescrição do remdesivir deve ser feita com cautela em pacientes com taxa de filtração glomerular estimada (TFGe) < 30, sendo que diversos estudos relatam risco de eventos adversos renais. São limitados os dados disponíveis sobre o perfil de segurança renal do remdesivir. Assim, analisamos as reações adversas renais e urinárias atribuídas ao remdesivir e notificadas em um grande base de dados abertos de farmacovigilância. Obtivemos notificações sobre remdesivir e outros medicamentos usados para tratar a COVID-19 (tocilizumabe, hidroxicloroquina, lopinavir/ritonavir) registradas até 30 de setembro de 2020 do Sistema de Notificação de Eventos Adversos da FDA (FAERS). Analisamos as razões de chances de notificação (RORs) para notificações de eventos adversos renais e urinários referentes ao remdesivir e outros medicamentos. Encontramos 2.922 notificações sobre remdesivir registradas no FAERS para COVID-19. Entre esses casos, foram notificados 493 efeitos adversos renais e urinários (16,9%). Os eventos mais frequentes foram lesão renal aguda (338; 11,6%), comprometimento renal (86; 2,9%) e insuficiência renal (53; 1,8%). Comparado com a hidroxicloroquina, lopinavir/ritonavir ou tocilizumabe, o uso do remdesivir esteve associado com um aumento das chances de notificação de transtornos renais e urinários, independentemente do sexo e idade dos pacientes (2,53; IC95%: 2,10-3,06). A ROR permaneceu significativo quando limitamos a análise à hidroxicloroquina (4,31; IC95%: 3,25-5,71) ou ao tocilizumabe (3,92; IC95%: 2,51-6,12). Nossos resultados corroboram outros estudos e destacam a utilidade para profissionais da saúde que usam esse novo antiviral para tratar a COVID-19, sobretudo em função de sua baixa eficácia.

Resumen: La Agencia Americana de Control de Alimentos y Medicamentos (FDA) ha destacado que la prescripción de remdesivir debe ser prudente con pacientes con tasa de filtración glomerular estimada (TGFe) < 30; además, algunos estudios informaron del riesgo de reacciones adversas renales. La información disponible sobre el perfil de seguridad renal, en el caso del remdesivir, es limitada. Por ello, analizamos las reacciones adversas renales y urinarias atribuidas al remdesivir e notificadas en una extensa base de datos abierta de farmacovigilancia. Obtuvimos las notificaciones de remdesivir y otros medicamentos usados para tratar la COVID-19 (tocilizumab, hidroxicloroquina, lopinavir/ritonavir) registrados el 30 de septiembre de 2020 por el Sistema de Notificación de Eventos Adversos de la FDA (FAERS). Analizamos las odds ratios informadas (RORs) en el caso de informes de eventos adversos renales y urinarios adversos relacionados con el remdesivir y otros medicamentos. En el FAERS, encontramos 2.922 notificaciones de remdesivir registradas como medicament sospechoso usado en COVID-19. De estos, habían 493 con efectos renales y urinarios adversos (16,9%). Los efectos adversos más frecuentes fueron lesiones renales agudas (338; 11,6%), insuficiencia renal (86; 2,9%), y fallo renal (53; 1,8%). Frente a hidroxicloroquina, lopinavir/ritonavir, o tocilizumab, el uso de remdesivir se asoció con un riesgo mayor de notificar alteraciones renales y urinarios, independientemente del género y edad de los pacientes (2,53; IC95%: 2,10-3,06). La ROR permaneció significativo al restringir el análisis a la hidroxicloroquina (4,31; IC95%: 3,25-5,71) o tocilizumab (3,92; IC95%: 2,51-6,12). Nuestros resultados corroboran datos previos, algo que podría ser extremadamente útil para los profesionales de la salud que decidan usar este nuevo antiviral para tratar la COVID-19, sobre todo conociendo su baja eficacia.

Efficacy of Nicorandil in the treatment of unstable angina pectoris in 30 patients / 中国基层医药

Objective:To investigate the efficacy of Nicorandil in the treatment of unstable angina pectoris.Methods:Sixty patients with unstable angina pectoris who received treatment in Department of Cardiovascular Disease, Suixi Hospital of Traditional Chinese Medicine, China during January-July 2020 were included in this study. They were randomly assigned to receive either conventional treatment including antiplatelet, increasing coronal blood flow velocity, lipid-lowering treatment and stabilization of atherosclerotic plaque (control group, n = 30) or Nicorandil treatment and conventional treatment (observation group, n = 30). Clinical efficacy was compared between the two groups. Angina attack, electrocardiogram changes and adverse reactions in each group were analyzed before and after treatment. Results:Total effective rate in the observation group was significantly higher than that in the control group [88.67% (26/30) vs. 53.33% (16/30), χ2 = 7.937, P = 0.005]. The frequency and duration of angina pectoris in the observation group were (1.53 ± 0.62) times/week, (1.93 ± 0.78) minutes, which were significantly lower or shorter than those in the control group [(1.97 ± 0.71) times /week, (2.60 ± 1.00) minutes, t = -2.359, -3.162, P = 0.025, 0.004). The total effective rate of electrocardiogram in the observation group was significantly higher than that in the control group [70.00% (22/30) vs. 43.34% (13/30), χ2 = 5.554, P = 0.018]. There was no significant difference in the incidence of adverse drug reactions such as nausea, dizziness and palpitation between the two groups (all P > 0.05). Conclusion:Based on conventional treatment, Nicorandil treatment for unstable angina pectoris can improve the clinical symptoms and electrocardiogram changes, exhibit remarkable efficacy, and therefore deserve clinical promotion.

Medication evaluation and adverse reaction monitoring in patient on peritoneal dialysis with pancytopenia induced by vancomycin / 药学实践杂志

Objective To provide reference for anti-infection treatment and individual pharmaceutical care in patient on peritoneal dialysis. Methods The plasma concentration of vancomycin in patient on peritoneal dialysis was monitored by clinical pharmacists. The anti-infection treatment plan was evaluated and adjusted according to the bacterial culture and drug sensitivity results of the abdominal dialysis fluid. The adverse reactions of pancytopenia induced by vancomycin were documented. Results Infection in the patient on peritoneal dialysis was effectively controlled. The related indicators of pancytopenia were improved. Conclusion A case of pancytopenia induced by vancomycin in the patient on peritoneal dialysis was analyzed to get clinical staff's attention to this adverse reaction and improve the safety of vancomycin administration.

Avaliação do desempenho do Sistema Nacional de Notificações para a Vigilância Sanitária: uma ferramenta do sistema de farmacovigilância no Brasil / Evaluation of the Performance of the Brazilian Notification System for Health Surveillance: A Tool in Brazil's Pharmacovigilance System

Resumo Avaliar o desempenho do Sistema Nacional de Notificações para a Vigilância Sanitária no que diz respeito ao registro de informações sobre danos à saúde relacionados com medicamentos (Notivisa-medicamento) a partir de atributos previamente selecionados. Realizou-se um estudo de avaliação em saúde de corte transversal, entre 2008 e 2013, que empregou oito atributos previstos em diretrizes para avaliação de sistemas de vigilância da saúde pública (simplicidade, aceitabilidade, representatividade, completude, validade, consistência, erro preditivo positivo e oportunidade). No período estudado, 63.512 registros foram identificados no Notivisa-medicamento, sendo a maioria classificados como graves (60,5%). O desempenho do Notivisa-medicamento foi considerado satisfatório para dois dos oito atributos (validade e erro preditivo positivo) e deficitário para os demais (simplicidade, aceitabilidade, representatividade, completude, consistência e oportunidade). É necessário discutir e implementar maneiras de como aprimorar o sistema com vistas a fornecer informações completas, oportunas e confiáveis para diferentes segmentos da sociedade brasileira, sobretudo os gestores de vigilância sanitária.

Abstract The scope of this paper is to assess the performance of the Brazilian Notification System for Health Surveillance, with respect to the registration of information on adverse drug-related effects on health (Notivisa/medication) based on previously selected attributes. A cross-sectional health evaluation study was conducted between 2008 and 2013 using eight attributes established by international guidelines to assess public health surveillance systems: simplicity, acceptability, representativeness, completeness, validity, consistency, positive predictive error and timeliness. In the study period, 63,512 registrations were identified in Notivisa/medication, the majority being considered severe (60.5%). The performance of Notivisa/medication was considered satisfactory with respect to two of the eight attributes (validity and positive predictive error) and deficient in six of the remaining attributes (simplicity, acceptability, representativeness, completeness, consistency and timeliness). Quality improvement strategies to remedy the system need to be discussed and implemented in order to provide complete, timely and reliable surveillance information for different segments of Brazilian society, especially health surveillance managers.

1．Spontaneous Report Database and Case-control Studies / 薬剤疫学

In the current review, the relationship between the reporting odds ratio (ROR) and the case-control study is addressed.The proportional mortality ratio (PMR) obtained in the proportional mortality studies in the death registry cannot be regarded as the risk ratio (RR) in the cohort study, but, the mortality odds ratio (MOR) estimated by using deaths unrelated to the exposure as ‘controls’ can be regarded as the RR.In 2004, Rothman et al proposed to estimate the ROR which can be regarded as the RR by using proper ‘control events’ in the spontaneous reports database. However, in the study conducted in Japan where the RORs estimated from 20 ‘control events’ were compared with the RRs obtained from many ‘drug use investigations’, the ROR vs RR plots were so diverse.The author of the current review concludes that the study estimating the ROR in the spontaneous reports cannot be regarded as the case-control study as the case-control study should estimate the RR of the cohort study in the source population as the odds ratio (OR).The ‘disproportionality measures’ like the ROR in the spontaneous reports database should be used primarily to detect the signals of the association between a drug and an adverse outcome. However, spontaneous reports can contribute to the characterization of the adverse drug reactions and to determining the causal relationship as well. The methods of signal detection are evolving and it is hoped that Japanese researchers contribute to their further developments.

A prospective observational study on incidence of adverse drug reactions in a tertiary care teaching hospital: a pharmacovigilance study

Background: An adverse drug reaction (ADRs) is determined as response to a drug that is noxious unintended excludes therapeutic failures, overdose, drug abuse, noncompliance, and medication errors. The main aim of the study is to detect, understand and report ADR扴.Methods: This study is prospective observational study conducted for 6 months in in-patient setting in a tertiary care hospital. Naranjo抯, WHO causality scale, Siegel scale, Schumock and Thornton scale are used to assess ADR. Graph Pad Prism and SAS software抯 are used.Results: Data was collected from a total of 1000 patients of which 121 (12.1%) patients were effected with 150 ADRs. Among 121 patients AdrAd was 60.66% and AdrIn was 39.33%. Of 121 patients 97 patients with single ADR, 28 patients with 2 ADRs, 10 patients were with three ADRs. ADR onset divides acute (10%), Latent (39%) and sub-acute (51%). ADR occurred are recovered (54%), Recovering (13%). Naranjos scale interprets definite (0.9%), probable (50.9%), possible (42.97%). According to WHO scale certain (2.7%), unlikely (2.7%), possible (38.84%). Hartwig and Siegel scale results are mild (12.4%), moderate (66.12%) and severe (12.4%). Schumock and Thornton preventability results are definitely (25.45%), probably (68.18%) and not preventable (6.36%).Conclusions: Every health care professional should be aware of the Pharmacovigilance principles and also should be aware of suspected ADR reporting form of PVPI. By applying the above scales it is easy for health care professionals to assess an ADR.

A study on the knowledge, attitude and practice on adverse drug reactions and pharmacovigilance among post graduate residents in Gandhi Medical College, Bhopal

Background: Resident doctors should consider adverse drug reaction (ADR) reporting as their professional obligation and should be aware of the existing pharmacovigilance mechanisms in their countries. In India, pharmacovigilance implementation is essential due to the absence of a vibrant ADR monitoring system. The present study primary objective was to evaluate the knowledge, attitude and practices (KAP) of the postgraduate students towards pharmacovigilance and ADR reporting in GMC, Bhopal as they observe and attend to the patients round the clock while the patient is admitted in the hospital.Methods: A cross-sectional-observational study was carried out using a pretested questionnaire having 17 questions in all. Data was compiled, entered in Microsoft Excel sheet and analysed by descriptive statistics.Results: A total of 127 duly filled responses were analysed. Study shows ADR is necessary and Pharmacovigilance should be taught in detail to postgraduate students is an important finding from our study. In this study there was also a wide gap between the ADR experienced in professional practice (71%) and ADR reported (23%).Conclusions: In our present study, the average knowledge score was 64% in contrast to 32% residents who didn’t answered correctly. Though majority (87%) of the residents had a positive attitude towards awareness about Pharmacovigilance and ADR reporting, however in clinical scenario even as ADR reporting was considered to be important by a large majority of the participants, the actual practices of ADR reporting was very low.

Knowledge, attitude and practice among consumers about adverse drug reaction reporting

Background: Background: Adverse Drug Reaction (ADR) reporting by consumers is quite low in India. Assessing knowledge and attitude of consumers regarding ADR reporting and observing practice of ADR reporting among them can help explore probable causes for underreporting of ADRs by consumers.Methods: This was a cross-sectional study conducted in a tertiary care teaching hospital using investigator-administered questionnaire and interviewing indoor patients of Surgery, Medicine, Obstetrics & Gynaecology and Dermatology departments. The questionnaire was prepared to assess knowledge, attitude and practice of consumers about ADR reporting. Data was analysed using mean, standard deviation and percentages.Result: A total of 820 consumers of medicines were included. It was found that 32.2% consumers were not aware that a drug can produce adverse effects. After being explained about adverse drug reactions, 94.6% consumers felt that adverse drug reactions should be reported. However, 98.8% consumers were not aware of Pharmacovigilance Programme of India. After consulting about consumer reporting programme, majority of respondents (96.1%) felt that the direct consumer reporting programme helps reporting of ADRs. Moreover, 93.7% of consumers were willing to use it to report ADRs in future. Consumers preferred the Telephonic method with a Toll free number for ADR reporting followed by informing a health care professional.Conclusion: Poor knowledge and awareness about ADR reporting is the major factor for low to nearly absent ADR reporting by consumers in India.

Evaluation of trigger tool method for adverse drug reaction reporting by nursing staff at a tertiary care teaching hospital

Background: To sensitize nurses about Trigger Tool Method (TTM) and to evaluate the impact of TTM on adverse drug event (ADE) reporting by nurses at a tertiary care teaching hospital in India.Methods: This was prospective, interventional, single center study conducted among nursing health professionals of Civil Hospital Ahmedabad (CHA) posted in Medicine Department. They were sensitized about ADE reporting, pharmacovigilance, methods of ADRs reporting and details about TTM. Also, a list of 17 triggers was prepared by the investigator and given to nurses. They were educated to report ADEs using TTM. At the initiation and end of study, questionnaires were given to evaluate knowledge, attitude and practice of ADR reporting among participant nurses. All triggers and ADEs reported were analyzed in terms of association between them, effectiveness of trigger in detecting an ADR and in terms of Positive Predictive Value (PPV). Reported ADRs were also assessed for causality, severity and preventability.Results: A total 758 patients were admitted during the study period in the respective medicine department. List of 17 triggers consists of 9 drug triggers (DT), 1 laboratory trigger (LT) and 7 patient triggers (PT). Of these 17 triggers, 14 triggers were identified by nurses. These 14 triggers were noticed 130 times. These included DT (100 times), LT (0 times) and PT (30 times). Of the various triggers observed, 7 DT and 4 PT were related to ADRs. Hence, 11 triggers (64.70%) were positive (related to ADRs), out of 17 total triggers under evaluation. 21 ADRs were observed using TTM by nurses.Conclusions: The TTM helps to detect and report ADRs by nurses. Educational interventions about TTM help in better detection and reporting of ADRs.

Comparison of the efficacy of rituximab injection and splenectomy for the treatment of chronic primary immune thrombocytopenia / 中国基层医药

Objective@#To compare the efficacy and adverse reaction of rituximab injection(Rituximab) and splenectomy in the treatment of adult chronic idiopathic thrombocytopenic purpura(ITP).@*Methods@#From March 2013 to June 2015, 105 chronic ITP patients who were treated in the Fifth People's Hospital of Datong were divided into rituximab group(n=43) and splenectomy group(n=62). The clinical efficacy, adverse reaction and survival time of the two groups were compared.@*Results@#There was no statistically significant difference in baseline characteristics between the two groups.After treatment for 3 months, the response rates of the splenectomy group and the rituximab group were 91.9%(57/62), 69.8%(30/43), respectively, the difference was statistically significant between the two groups(χ2=5.04, P=0.005). After treatment for 12 months, the response rates of the splenectomy group and the rituximab group were 88.7%(55/62), 58.1%(25/43), respectively, the difference was statistically significant between the two groups (χ2=6.83, P=0.001), respectively.After treatment for 3, 12 months, the complete response rates of the splenectomy group were 82.2%(51/62), 80.6%(50/62), respectively, which were higher than those of the rituximab group [39.5%(17/43), 34.9%(15/43)] (χ2=7.25, P<0.001). There was no statistically significant difference in adverse reactions after treatment for 1 year between the two groups(P>0.05). The survival time of the splenectomy group was longer, but there was no statistically significant difference(t=4.85, P=0.18).@*Conclusion@#The curative effect of splenectomy in the treatment of adult ITP is better than rituximab, and the adverse reaction is not obvious between two methods.

Comparison of the efficacy of rituximab injection and splenectomy for the treatment of chronic primary immune thrombocytopenia / 中国基层医药

Objective To compare the efficacy and adverse reaction of rituximab injection( Rituximab) and splenectomy in the treatment of adult chronic idiopathic thrombocytopenic purpura ( ITP). Methods From March 2013 to June 2015,105 chronic ITP patients who were treated in the Fifth People＇s Hospital of Datong were divided into rituximab group(n=43) and splenectomy group( n =62).The clinical efficacy,adverse reaction and survival time of the two groups were compared.Results There was no statistically significant difference in baseline character-istics between the two groups. After treatment for 3 months, the response rates of the splenectomy group and the rituximab group were 91. 9%( 57/62 ), 69. 8%( 30/43 ), respectively, the difference was statistically significant between the two groups(χ2 =5.04,P=0.005).After treatment for 12 months,the response rates of the splenectomy group and the rituximab group were 88.7%(55/62),58.1%(25/43),respectively,the difference was statistically significant between the two groups ( χ2 =6. 83, P =0. 001 ), respectively. After treatment for 3,12 months, the complete response rates of the splenectomy group were 82.2%(51/62),80.6%(50/62),respectively,which were higher than those of the rituximab group [39.5%(17/43),34.9%(15/43)] (χ2 =7.25,P＜0.001).There was no statistically significant difference in adverse reactions after treatment for 1 year between the two groups(P>0.05). The survival time of the splenectomy group was longer,but there was no statistically significant difference( t=4.85, P=0.18).Conclusion The curative effect of splenectomy in the treatment of adult ITP is better than rituximab,and the adverse reaction is not obvious between two methods.

Clinical analysis of levetiracetam in the treatment of children and adolescents with epilepsy / 中国基层医药

Objective To explore and compare the clinical efficacy of levetiracetam tablets and compound sodium valproate sustained release tablets in the treatment of children and adolescents with epilepsy.Methods From April 2017 to April 2018,80 children and adolescents with epilepsy treated in Chaonan Minsheng Hospital of Shantou were selected as study objects,and they were randomly divided into two groups by drawing lots,with 40 cases in each group.The observation group was given levetiracetam tablets,and the control group was treated with valproate.The improvement of EEG after therapy,the total effective rate,and the incidence of adverse reactions were observed and evaluated.Results The EEG improvement rates after treatment for 6 months in the observation group and control group were 41.17％,45.71％,respectively,the difference was not statistically significant(x2 =0.508,P ＞0.05).The EEG improvement rates after treatment for 9 months in the observation group and control group were 70.58％,74.28％,respectively,the difference was not statistically significant (x2 =0.225,P ＞ 0.05).The total effective rate in the observation group was 92.50％,which was 95.00％ in the control group,the difference was not statistically significant between the two groups (x2 =0.354,P ＞ 0.05).However,the incidence rate of adverse reactions of the observation group(22.50％) was significantly lower than that of the control group(45.00％)(x2 =6.864,P ＜ 0.05).Conclusion Both levetiracetam tablets and compound sodium valproate sustained release tablets have appreciable efficacy and safety in the treatment of epilepsy in children and adolescents,but levetiracetam therapy has less adverse reactions,which deserves further promotion in monotherapy of epilepsy in children and adolescents.

Adverse drug reactions

There are no drugs without the risk of potential adverse reactions. All pharmacologically active substances can cause adverse drug reactions (ADRs). This paper aims at introducing recent trends in pharmacosurveillance systems for ADRs, which can be broadly classified into type A and B reactions. Since type A reactions are associated with drug pharmacology, they are usually dose-dependent and predictable. Whereas, type B reactions occur in some susceptible individuals, regardless of the pharmacological action of drug. Drug hypersensitivity reactions are typical examples of type B reactions and are subclassified according to the underlying pathomechanism. Recent advancements in pharmacogenomics have enlightened the understanding of individual differences in drug efficacy and susceptibility to ADRs. Therefore, expectations for safe personalized medicines are higher than ever before. However, premarketing clinical trials are too small and too short to uncover rare but serious ADRs and detect long-standing ADRs. In the past, post-marketing surveillance systems mainly focused on passive ADR monitoring systems, based on spontaneous reports. Recently, the importance of active pharmacovigilance systems, which use big data, is growing with recent advancements in medical informatics. Thus, regarding ADRs, suspecting and detecting the causative drug using causality assessment based on data science may contribute to decrease suffering induced by ADRs.

Investigation on Perceptions, Attitudes, and Contributing Factors to Spontaneous Adverse Drug Reaction Reporting among Community Pharmacists: Results from a Web-based Survey

OBJECTIVE: To examine the perceptions and attitudes toward spontaneous adverse drug reaction (ADR) reporting system among community pharmacists and identify factors that influence reporting, by implementing a survey. METHODS: A structured questionnaire was developed and distributed online. Request for the survey was posted on the website of pharmacy's billing program, and the survey was conducted for 8 days. We collected the participants' response on their work environment, experience of ADR reporting, and their perception and attitude on the reporting system. Multivariate logistic regression was used to evaluate factors influencing ADR reporting. RESULTS: A total of 382 pharmacists participated in the survey. Significant contributing factors for reporting level were age (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.84–0.96), knowledge of reporting method (OR, 53.56; 95% CI, 9.10–315.41), installation of reporting program (OR, 31.92; 95% CI, 4.16–244.75), and encouragement from the Korean pharmaceutical association (OR, 4.13; 95% CI, 1.11–15.35). Regarding the attitude toward spontaneous ADR reporting system, ‘lack of time for reporting’ (OR, 0.29; 95% CI, 0.15–0.53) and ‘complexity of reporting procedure’ (OR, 0.51; 95% CI, 0.31–0.84), were associated with a low likelihood of reporting. CONCLUSION: Our results indicated that the knowledge of ADR reporting method, installation of the reporting program, and encouragement from the Korean Pharmaceutical Association contribute to active reporting. It is necessary to simplify the reporting method, make the ADR reporting program user-friendly, and provide educational interventions to increase participation in spontaneous reporting by the community pharmacists.