Use of Antidepressants and the Risk of Upper Gastrointestinal Tract Bleeding: A Case-control Study.

PURPOSE: To investigate the association between the use of antidepressants and the risk of upper gastrointestinal tract bleeding (UGIB). METHODS: A Case-control study was conducted in a Brazilian hospital complex. Cases were defined as patients with a diagnosis of UGIB and controls as patients admitted for reasons unrelated to gastrointestinal bleeding, gastric concerns, or complications associated with low-dose aspirin (LDA) or nonsteroidal anti-inflammatory drugs (NSAIDs) use. Sociodemographic and clinical data, comorbidities, drug therapy in use (long-term use and self-medication), and lifestyle habits were recorded through face-to-face interviews. Two groups were defined: use of antidepressants in general and use of antidepressants according to their affinity for serotonin transporters. The presence of synergism between the concomitant use of antidepressants and LDA or NSAIDs on the risk of UGIB was also explored. FINDINGS: A total of 906 participants were recruited (200 in the case group and 706 in the control group). The use of antidepressants was not associated with the risk of UGIB (odds ratio [OR] = 1.503; 95% CI, 0.78-2.88) or the use of antidepressants with high affinity for serotonin receptors (OR = 1.983; 95% CI, 0.81-4.85). An increased risk of UGIB was observed in concomitant users of antidepressants and LDA (OR = 5.489; 95% CI, 1.60-18.81) or NSAIDs (OR = 18.286; 95% CI, 3.18-105.29). Despite the lack of significance, the use of antidepressants appears to be a positive modifier of UGIB risk in LDA and NSAID users. IMPLICATIONS: These findings indicate an increased risk of UGIB in concomitant users of antidepressants and LDA or NSAIDs, suggesting the need to monitor antidepressant users, especially those most likely to develop UGIB. In addition, further studies with larger sample sizes are needed to confirm these findings.

Development and validation of the clinical report form for nodular thyroid pathologies

Abstract Objectives: The aim of this study is to develop and validate a novel clinical report form in the format of a structured interview to enable the characterization of the Portuguese population of the Baixo Vouga region with different subtypes of nodular thyroid pathologies (NTyPs). Materials and methods: A structured interview was developed and to the best of our knowledge, this is the first structured interview built and validated for that purpose in Portugal. Results: This structured interview enables the identification of possible correlations between each subtype of nodular lesions and sociodemographic data, consumption habits and lifestyle, endocrine history, and family predisposition. Conclusion: The novel structured interview will simultaneously, enable a detailed characterization of the group of patients with nodular thyroid lesions and will support future metabolomic studies.

Development and validation of the clinical report form for nodular thyroid pathologies.

Objective: The aim of this study is to develop and validate a novel clinical report form in the format of a structured interview to enable the characterization of the Portuguese population of the Baixo Vouga region with different subtypes of nodular thyroid pathologies (NTyPs). Materials and methods: A structured interview was developed and to the best of our knowledge, this is the first structured interview built and validated for that purpose in Portugal. Results: This structured interview enables the identification of possible correlations between each subtype of nodular lesions and sociodemographic data, consumption habits and lifestyle, endocrine history, and family predisposition. Conclusion: The novel structured interview will simultaneously, enable a detailed characterization of the group of patients with nodular thyroid lesions and will support future metabolomic studies.

Early Real-World Data to Assess Benefits and Risks of COVID-19 Vaccines: A Systematic Review of Methods.

Since the authorization of the first COVID-19 vaccines in December 2020, multiple studies using real-world data (RWD) have been published to assess their effectiveness/safety profile. This systematic review aimed to characterize the methods and outcomes of studies using RWD for assessment of COVID-19 vaccines, four months after vaccine approval. MEDLINE and EMBASE were searched to identify published studies until 6 May 2021. Two independent researchers selected relevant publications and extracted data from included studies. The risk of bias was assessed using New-Castle Ottawa tools. After screening 1086 studies, 15 were included. Out of the 15 studies, 12 (80%) followed a cohort design, 8 (53%) were based on USA data, 7 (47%) assessed health care professionals, and 14 articles (93%) assessed the BNT162b2 vaccine. Data sources included institutional databases, electronic health records, and patient-generated data. The primary endpoint mainly described was SARS-CoV-2-infection. Hospitalization and mortality were assessed in 2 studies. For the comparability domain, six studies (40%) had a high risk of bias. A few months after the beginning of COVID-19 vaccination, Real-world Evidence (RWE) provided timely safety surveillance and comparative effectiveness with findings that showed similar findings to Randomized control trial (RCT). Most of the initiatives assessed BNT162b2 and were conducted in the USA and used healthcare workers' data.

Hospitalizations of older people in an emergency department related to potential medication-induced hyperactive delirium: a cross-sectional study.

Background Although delirium is one of the most common adverse drug reactions observed in hospitalized older people, it remains underdiagnosed. Aim To estimate the prevalence of hospitalization of older people with potential medication-induced hyperactive delirium in the emergency department (ED); to identify the risk factors and the medicines frequently associated with the occurrence of the syndrome. Method A cross-sectional, retrospective study was performed with older people (age ≥ 60) admitted in 2018 to a Brazilian ED. The hospitalizations with suspected hyperactive delirium were screened with the aid of trigger-tools: International Code of Diseases-10th Revision, intra-hospital prescriptions of antipsychotics, and trigger-words related to the syndrome. A chart-review and medication review were developed to establish the causality assessment between adverse event and medicine. Logistic regression was used to determine risk factors for occurrence. Results Among the hospitalizations included, 67.5% (193/286) were screened by at least one trigger-tool. Of these, potential medication-induced hyperactive delirium was observed in 26.0% (50/193). The prevalence estimated in the ward was 17.5% (50/286). Opioids (31.9%), benzodiazepines (18.8%) and corticosteroids (10.6%) were the commonest medicines associated with delirium. Long-lived patients (p = 0.005), potentially inappropriate medicines (PIMs) (p = 0.025), and high weighted deliriogenic load (p = 0.014) were associated with potential medication-induced hyperactive delirium. Conclusion Approximately one in six hospitalizations of older people in the ED showed potential medication-induced hyperactive delirium. Data suggest PIMs and high weighted deliriogenic load, rather than polypharmacy or anticholinergic burden, are considered the most important characteristics of pharmacotherapy associated with avoidable hyperactive delirium among long-lived patients.

Impact of pharmacist intervention in patients with Alzheimer's disease

Abstract To assess the therapy relative to indication, effectiveness, safety and adherence in patients with Alzheimer's disease (AD). An interventional, prospective, non-randomized study was conducted in a single secondary care center in Brazil. The pharmacist-led medication therapy management (MTM) was conducted to detect drug-related problems (DRPs) at baseline and after six months of intervention. The health status outcomes (i.e. cognitive screening tests; levels of glucose; total cholesterol; triglycerides; thyroid stimulating hormone; serum free thyroxine and blood pressure) were measured. 66 patients with AD were included, of whom 55 patients completed the follow-up of six months. 36 patients (36/55) were non-adherent to AD drug therapy. Out of detected 166 DRPs, 116 were solved. Four patients were withdrawn from the AD protocol due to resolution of prodromal symptoms. On the conclusion of the study, the MTM improved and controlled blood pressure, glucose, total cholesterol, triglycerides levels (p<0.05). The pharmacist-led MTM was effective in solving 69.8% of DRPs, improving and controlling the clinical parameters evaluated

Risk factors associated with drug therapy among elderly people with Alzheimer's disease: a cross-sectional study.

BACKGROUND: Improving knowledge and establishing strategies and policies for better patient safety are worldwide priorities. OBJECTIVE: To evaluate drug safety among elderly people with Alzheimer's disease (AD). DESIGN AND SETTING: Cross-sectional study among elderly people within the National AD Assistance Protocol (PCDTDA/MS) who were living in the municipality of Araraquara, Brazil, in 2017. METHODS: Through interviews conducted with relatives/caregivers of elderly people with diagnoses of AD, the following variables were evaluated: comorbidities, drug therapy used, use of potentially inappropriate medications for the elderly (PIMs), presence of potentially inappropriate interactions (PIIs) and medication regimen complexity index. Factors associated with AD severity were also evaluated. Multivariate and simple logistic regressions were applied. RESULTS: 143 elderly people enrolled in PCDTDA/MS were analyzed. The majority were women (67.1%); assisted only through the public healthcare system (75.5%); polymedicated (57.4%); using at least one PIM (63.6%); presenting at least one PII (63.6%); and under drug therapy of low to medium complexity (92.2%). No semi-annual monitoring of the effectiveness of PCDTDA/MS drugs was identified. The proportion using AD drug therapy at daily doses differing from those recommended by the World Health Organization was 75.6%. However, these doses were not associated with drug risk. CONCLUSION: The data from this study raise the hypothesis that use of polypharmacy might show a correlation with severity of AD. The drug safety risk may be associated with comorbidities of the metabolic syndrome, anxiety and off-label use of PIMs, such as risperidone and quetiapine, and benzodiazepines (i.e. clonazepam and flunitrazepam).

Risk factors associated with drug therapy among elderly people with Alzheimers disease: a cross-sectional study

ABSTRACT BACKGROUND: Improving knowledge and establishing strategies and policies for better patient safety are worldwide priorities. OBJECTIVE: To evaluate drug safety among elderly people with Alzheimer's disease (AD). DESIGN AND SETTING: Cross-sectional study among elderly people within the National AD Assistance Protocol (PCDTDA/MS) who were living in the municipality of Araraquara, Brazil, in 2017. METHODS: Through interviews conducted with relatives/caregivers of elderly people with diagnoses of AD, the following variables were evaluated: comorbidities, drug therapy used, use of potentially inappropriate medications for the elderly (PIMs), presence of potentially inappropriate interactions (PIIs) and medication regimen complexity index. Factors associated with AD severity were also evaluated. Multivariate and simple logistic regressions were applied. RESULTS: 143 elderly people enrolled in PCDTDA/MS were analyzed. The majority were women (67.1%); assisted only through the public healthcare system (75.5%); polymedicated (57.4%); using at least one PIM (63.6%); presenting at least one PII (63.6%); and under drug therapy of low to medium complexity (92.2%). No semi-annual monitoring of the effectiveness of PCDTDA/MS drugs was identified. The proportion using AD drug therapy at daily doses differing from those recommended by the World Health Organization was 75.6%. However, these doses were not associated with drug risk. CONCLUSION: The data from this study raise the hypothesis that use of polypharmacy might show a correlation with severity of AD. The drug safety risk may be associated with comorbidities of the metabolic syndrome, anxiety and off-label use of PIMs, such as risperidone and quetiapine, and benzodiazepines (i.e. clonazepam and flunitrazepam).

Harmonization of Pharmacovigilance Regulation in Brazil: Opportunities to Improve Risk Communication.

Brazilian pharmacovigilance regulations involve 3 spheres: health services, Marketing Authorization Holders (MAHs), and sanitary agency. Drug tolerability began to be effectively assessed in Brazil after the founding of the National Agency of Sanitary Surveillance, which developed the Sentinel Network Project. The objective of the Sentinel Network Project is to increase the adverse drug reaction (ADR) reporting rate by health care professionals in the hospital setting. Pharmacovigilance practices became mandatory for MAHs, and patient tolerability issues were considered in drug policy in Brazil only as recently as 2000. However, despite recent events, the regulatory advancements in pharmacovigilance in Brazil are only equivalent to international practices (ie, those of the European Union). The pharmacovigilance system in the European Union integrates the national authorities, the European Commission, and the European Medicines Agency, which is responsible for the scientific evaluation, supervision, and safety monitoring of medicines for human and veterinary use in the European Union. Furthermore, ADR patient reporting is included in the new EU pharmacovigilance regulations. Numerous possible ways are available to improve the Brazilian pharmacovigilance system, mainly through regulations of biosimilar, nanotechnology, and veterinary medicines or by training health care professionals and patients to report nonserious cases and quality deviations. It is necessary to encourage and develop strategies for decentralizing pharmacovigilance actions in the whole country, as is common practice in several EU countries. Motivating and considering ADR reports by patients and improving feedback and audit practices in health care services and MAHs are also necessary measures. With the inclusion of Brazil as a member of the International Conference of Harmonization, significant changes in pharmacovigilance regulation are expected; these updates, which will consider international standards, will improve signal detection and risk communication.

Imputation of adverse drug reactions: Causality assessment in hospitals.

BACKGROUND & OBJECTIVES: Different algorithms have been developed to standardize the causality assessment of adverse drug reactions (ADR). Although most share common characteristics, the results of the causality assessment are variable depending on the algorithm used. Therefore, using 10 different algorithms, the study aimed to compare inter-rater and multi-rater agreement for ADR causality assessment and identify the most consistent to hospitals. METHODS: Using ten causality algorithms, four judges independently assessed the first 44 cases of ADRs reported during the first year of implementation of a risk management service in a medium complexity hospital in the state of Sao Paulo (Brazil). Owing to variations in the terminology used for causality, the equivalent imputation terms were grouped into four categories: definite, probable, possible and unlikely. Inter-rater and multi-rater agreement analysis was performed by calculating the Cohen´s and Light´s kappa coefficients, respectively. RESULTS: None of the algorithms showed 100% reproducibility in the causal imputation. Fair inter-rater and multi-rater agreement was found. Emanuele (1984) and WHO-UMC (2010) algorithms showed a fair rate of agreement between the judges (k = 0.36). INTERPRETATION & CONCLUSIONS: Although the ADR causality assessment algorithms were poorly reproducible, our data suggest that WHO-UMC algorithm is the most consistent for imputation in hospitals, since it allows evaluating the quality of the report. However, to improve the ability of assessing the causality using algorithms, it is necessary to include criteria for the evaluation of drug-related problems, which may be related to confounding variables that underestimate the causal association.

Confounding Variables and the Performance of Triggers in Detecting Unreported Adverse Drug Reactions.

PURPOSE: This study explored the performance of trigger in detecting adverse drug reactions (ADRs), the confounding variables impairing the causal association of the ADRs, and the underreporting rate by hospital health professionals. METHODS: A 6-month cross-sectional study was conducted in a public general hospital. Data collection was conducted in 2 stages: (1) screening of patient hospitalizations to identify suspected ADRs with 9 triggers developed by the Institute of Healthcare Improvement; and (2) chart review to perform the causality assessment of the suspected ADRs identified, to describe the confounding variables associated with detection of suspected ADRs that were not drug induced, and to analyze the positive predictive value of triggers in recognizing ADRs. To estimate the underreporting rate, ADRs detected by using the tool were compared with ADRs reported by health professionals during the same period. FINDINGS: During the study period, 3318 hospitalizations were analyzed. A total of 837 suspected ADRs were identified. However, after causality assessment, 356 were definite ADRs. Confounding variables associated with the detection-suspected ADRs were related to the clinical conditions of inpatients. The use of triggers contributed to increased ADR detection by 10.5%. The performance ranged from 0.00 to 0.75, with an overall positive predictive value of 0.43. Six ADRs were spontaneously reported, of which just 1 was also detected by using the trigger tool. Only 1 of 356 potential ADRs was reported by health professionals. IMPLICATIONS: Findings show that the use of triggers contributes to detecting ADRs underreported by health professionals. However, confounding variables impaired the performance of the tool because they underestimated the causal association. Furthermore, both methods are complementary to early recognition of drug-induced harm and should be applied together in health institutions to contribute to policies of risk management, drug safety, and optimization of pharmacotherapy.

[The Portuguese Pharmacovigilance System]. / O Sistema Português de Farmacovigilância.

In Portugal, the National Pharmacovigilance System (NPS) was created in 1992, completing during this year 20 years of existence. Having been established in a centralized manner, it soon became aware that its geographic decentralization would bring advantages in terms of proximity of the System to health professionals as well as the involvement of the universities. The NPS currently has four regional pharmacovigilance centres, which cover the entire mainland, which became centers of scientific vocation, carrying out pharmacoepidemiological studies in the area of drug safety. Also, they are the guarantee of proper collection, processing and evaluation of spontaneous reports of adverse drug reactions (ADRs), as well as the continuing disclosure of the System among health professionals and promotion of spontaneous reporting. Over these 20 years, the NPS has been adapting to the EU requirements in the area of pharmacovigilance, and is currently a mature and well implemented system, with the objectives of the evaluation of the safety profile of marketed drugs and triggering of actions to reduce the risk of these drugs. From the second half of 2012, new adaptation will be run with the implementation of recent European legislation on Pharmacovigilance, published in December 2010. Among other changes, there is the possibility for consumers to report their suspicious of ADR directly to the NPS (exclusive, so far, to health professionals). This work aims to be a reflection about the evolution of the National Pharmacovigilance System and its growing importance in the protection of public health.

Estratégias para aumentar a sensibilidade da farmacovigilância em Portugal / Estrategias para aumentar la sensibilidad de la farmacovigilancia en Portugal / Strategies to increase the sensitivity of pharmacovigilance in Portugal

OBJETIVO: Avaliar os resultados de intervenção para melhoria da quantidade e relevância das notificações de reacções adversas a medicamentos. MÉTODOS: Foi implementado um estudo controlado aleatorizado, por agrupamentos em farmacêuticos a exercer actividade profissional na região norte de Portugal, em 2007. Após aleatorização, 364 indivíduos foram alocados ao grupo de intervenção (261 na intervenção telefónica e 103 nos workshops); o grupo de controlo foi constituído por 1.103 farmacêuticos. Na intervenção educativa foram abordados a problemática das reacções adversas a medicamentos, o impacto na saúde pública e a notificação espontânea. Quanto à relevância, as reações adversas foram classificadas em graves e inesperadas. A análise estatística foi efectuada com base no princípio intention-to-treat; aplicaram-se modelos lineares generalizados mistos, utilizando o método penalized quasi-likelihood. Os farmacêuticos estudados foram seguidos durante um período de 20 meses. RESULTADOS: A intervenção aumentou três vezes a taxa de notificação espontânea das reações adversas (RR = 3,22; IC 95 por cento: 1,33; 7,80) relativamente ao grupo de controlo. Houve incremento da relevância das notificações com aumento das reações adversas graves em cerca de quatro vezes (RR = 3,87; IC 95 por cento: 1,29;11,61) e inesperadas em cinco vezes (RR = 5,02; IC 95 por cento: 1,33;18,93), relativamente ao grupo de controlo. CONCLUSÕES: As intervenções educativas aumentam significativamente, por até quatro meses, a quantidade e a relevância das notificações espontâneas de reacções adversas a medicamentos por parte dos farmacêuticos da região norte de Portugal.

OBJETIVO: Evaluar los resultados de intervención para mejoría de la cantidad y relevancia de las notificaciones de reacciones adversas a medicamentos.MÉTODOS: Fue implementado un estudio controlado aleatorio, por agrupaciones de farmacéuticos que ejercen actividad profesional en la región norte de Portugal, en 2007. Posterior a la aleatoriedad, 364 individuos fueron distribuidos en el grupo de intervención (261 en la intervención telefónica y 103 en los workshops); el grupo control fue constituido por 1.103 farmacéuticos. En la intervención educativa fueron abordados la problemática de las reacciones adversas a medicamentos, el impacto en la salud pública y la notificación espontánea. Con relación a la relevancia, las reacciones adversas fueron clasificadas en graves e inesperadas. El análisis estadístico fue efectuado con base en el principio intention-to-treat; se aplicaron modelos lineares generalizados mixtos, utilizando el método penalized quasi-likelihood. Los farmacéuticos estudiados fueron seguidos durante un período de 20 meses. RESULTADOS: La intervención aumentó tres veces la tasa de notificación espontánea de las reacciones adversas (RR=3,22; IC95%:1,33;7,80) con relación al grupo control. Hubo un incremento en la relevancia de las notificaciones con aumento de las reacciones adversas graves en cerca de cuatro veces (RR=3,87; IC95%:1,29;11,61) e inesperadas en cinco veces (RR=5,02; IC 95%: 1,33;18,93), con relación al grupo control. CONCLUSIONES: Las intervenciones educativas aumentan significativamente, en hasta cuatro meses, la cantidad y la relevancia de las notificaciones espontáneas de reacciones adversas a medicamentos por parte de los farmacéuticos de la región Norte de Portugal.

Strategies to increase the sensitivity of pharmacovigilance in Portugal.

OBJECTIVE: To evaluate the results of an intervention to improve the number and relevance of reports of adverse drug reactions. METHODS: A cluster-randomized controlled trial was conducted with pharmacists working in Northern Portugal, in 2007. After randomization, 364 individuals were placed into the intervention group (261 in telephone interviews and 103 in workshops), while the control group was comprised of 1,103 pharmacists. The following were approached in the educational intervention: the problem of adverse drug reaction, the impact on public health and spontaneous reporting. With regard to relevance, adverse reactions were classified into severe and unexpected. Statistical analysis was performed, based on the intention-to-treat principle; generalized linear mixed models were applied, using the penalized quasi-likelihood method. The pharmacists studied were followed during a period of 20 months. RESULTS: The intervention increased the rate of spontaneous reporting of adverse reactions three times (RR = 3.22; 95% CI 1.33;7.80), when compared to the control group. The relevance of reporting rose, with an increase in severe adverse reactions by approximately four times (RR = 3.87; 95% CI 1.29;11.61) and in unexpected adverse reactions by five times (RR = 5.02; 95% CI 1.33;18.93), compared to the control group. CONCLUSIONS: During a period of up to four months, educational interventions significantly increased the number and relevance of spontaneous reporting of adverse drug reactions by pharmacists in Northern Portugal.