The role of CYP2C9*2, CYP2C9*3 and VKORC1-1639 variants on the susceptibility of upper gastrointestinal bleeding: A full case-control study.

Purpose: To investigate whether interindividual variability in the CYP2C9 (*2 and *3 alleles) and VKORC1 (rs9923231) genes is associated with increased risk of upper gastrointestinal bleeding (UGIB) in users of non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: A full case-control study including 200 cases of patients diagnosed with UGIB and 706 controls was conducted in a Brazilian hospital complex. To perform an analysis of NSAIDs dose-effect, the defined daily dose (DDD) for NSAIDs was calculated in the 7-day etiologic window preceding the data index. Three categories of DDD, considering the genotypes of the genetic variants, were established: non-users of NSAIDs (DDD = 0), DDD ≤0.5, and DDD >0.5. Genetic variants and LDA or NSAIDs use synergism was estimated through Synergism Index (SI) and Relative Excess Risk Due To Interaction (RERI). Results: For DDDs of NSAIDs upward of 0.50, a risk of UGIB was identified in carriers of the *3 allele (OR: 15,650, 95% CI: 1.41-174.10) and in carriers of the variant homozygous genotype (TT) of rs9923231 (OR: 38,850, 95% CI: 2.70-556.00). In LDA users, the risk of UGIB was observed to be similar between carriers of the wild type homozygous genotype and carriers of the variant alleles for the CYP2C9 and VKORC1 genes. No synergism was identified. Conclusion: Our findings suggest an increased risk of UGIB in carriers of the variant allele of rs9923231 and in carriers of the *3 allele associated with doses of NSAIDs greater than 0.5. Hence, the assessment of these variants might reduce the incidence of NSAIDs-related UGIB and contribute to the safety of the NSAIDs user.

Genetic polymorphisms associated with upper gastrointestinal bleeding: a systematic review.

Non-variceal upper gastrointestinal bleeding (non-variceal UGIB) is a frequent and severe adverse drug reaction. Idiosyncratic responses due to genetic susceptibility to non-variceal UGIB has been suggested. A systematic review was conducted to assess the association between genetic polymorphisms and non-variceal UGIB. Twenty-one publications and 7134 participants were included. Thirteen studies evaluated genetic polymorphism in patients exposed to non-steroidal anti-inflammatory drugs, low-dose aspirin, and warfarin. Eight studies present at least one methodological problem. Only six studies clearly defined that the outcome evaluated was non-variceal UGIB. Genetic polymorphisms involved in platelet activation and aggregation, angiogenesis, inflammatory process, and drug metabolism were associated with risk of non-variceal UGIB (NOS3, COX-1; COX-2; PLA2G7; GP1BA; GRS; IL1RN; F13A1; CDKN2B-AS1; DPP6; TBXA2R; TNF-alpha; VKORC1; CYP2C9; and AGT). Further well-designed studies are needed (e.g., clear restriction to non-variceal UGIB; proper selection of participants; and adjustment of confounding factors) to provide strong evidence for pharmacogenetic and personalized medicine.

Traditional Lectures Actually Improve the Body of Knowledge, Skills, and Attitudes of Health Care Professional for Health Incident Reporting System.

Introduction: A solid patient safety culture lies at the core of an effective event reporting system in a health care setting requiring a professional commitment for event reporting identification. Therefore, health care settings should provide strategies in which continuous health care education comes up as a good alternative. Traditional lectures are usually more convenient in terms of costs, and they allow us to disseminate data, information, and knowledge through a large number of people in the same room. Taking in consideration the tight money budgets in Brazil and other countries, it is relevant to investigate the impact of traditional lectures on the knowledge, skills, and attitudes to incident reporting system and patient safety culture. Objective: The study aim was to assess the traditional lecture impact on the improvement of health care professional competency dimensions (knowledge, skills, and attitudes) and on the number of health care incident reports for better patient safety culture. Participants and Methods: An open-label, nonrandomized trial was conducted in ninety-nine health care professionals who were assessed in terms of their competencies (knowledge, skills, and attitudes) related to the health incident reporting system, before and after education intervention (traditional lectures given over 3 months). Results: All dimensions of professional competencies were improved after traditional lectures (P < .05, 95% confidence interval). Conclusions: traditional lectures are helpful strategy for the improvement of the competencies for health care incident reporting system and patient safety.

Extemporaneous Compounding: A Possible Trigger Tool to Detect Potential Health Incidents.

BACKGROUND: Extemporaneous compounding (EC) involves the preparation of a therapeutic product for specific patient need. However, there is a potential relationship between this procedure and the occurrence of health incidents (HI). The use of trigger tools increases HI identification. OBJECTIVE: This study assessed the performance of EC as a trigger to detect potential health incidents arising from this procedure. METHODS: A one-month observational and cross-sectional study was performed in internal medicine ward and intensive care unit of medium-sized hospital. Data collection was carried out in 5 stages: all triggered patients with dysphagia or enteral feeding tube with prescription of EC were included; EC executed in prescribed standardized drugs was observed; the procedure was compared with the hospital guide and scientific literature; HI monitoring and their evaluation using WHO and NCC MERP algorithms; a search for pharmaceutical alternatives (PA) that would avoid the observed EC. RESULTS: 197 patients were recruited. Almost half of them were triggered by EC from 84 standardized drugs. 48 patients met the inclusion criteria. 28 adverse drug reactions, 01 therapeutic ineffectiveness, and 29 medication errors were identified. EC as a trigger tool showed a PPV value of 0.38. Only 24 drugs have PA available in the market, which could avoid one third of all observed EC. CONCLUSION: It was possible to detect potentially HI in one of two patients with enteral feeding tubes using EC as a trigger tool. The use of EC as a trigger tool contributes to identifying potential HI arising from drugs, which have not gotten pharmaceutical alternatives to be administered via enteral feeding tube.

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.

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.

Iodine deficiency in women of childbearing age in Brazil: systematic review and meta-analysis / Deficiencia de yodo en mujeres en edad fabricante en Brasil: revisión sistemática y metanálisis

Background: Despite current policies of salt iodination, iodine deficiency is still a global public health problem, especially in women. So far, conflicting evidence has been suggested for the prevalence of iodine deficiency in Brazil. Objective: To estimate the prevalence of iodine deficiency and associated factors in women of childbearing age in Brazil. Methods: A systematic review was conducted using databases (PubMed, LILACS, WHO, Scopus, and Capes' dissertation and thesis), from inception to May 2020. Meta-analyses of proportions were performed using the variance inverse for the fixed model. Reporting and methodological quality were assessed using the Joanna Briggs Institute tool to prevalence studies. Results: Our review identified seven studies published between 2002 e 2017, including 1354 participants, especially pregnant women. All studies presented at least one quality limitation, mainly regarding the sampling method (i.e., convenience) and small sample size. The prevalence of iodine deficiency ranged among studies from 16% to 62%. In contrast, the meta-analysis identified a mean prevalence of 40% (95% confidence interval, CI 37%-43%) for pregnant women and 13% (95% CI 4%-24%) for non-pregnant women. Cumulative meta-analysis suggests a tendency of higher iodine deficiency prevalence from 2018 in pregnant women. Conclusions: Although this systematic review identified studies with poor methodological and reporting quality, a high prevalence of iodine deficiency was identified in pregnant women, reinforcing the importance of national nutritional policies for monitoring iodine status in this population. Future studies should consider random probabilistic sampling, appropriate sample size, and pre-defined subgroup analysis to adequately inform the prevalence of iodine deficiency and associated factors in women of childbearing age and support health policies

Antecedentes: A pesar de las políticas actuales de yodación de la sal, la deficiencia de yodo sigue siendo un problema de salud pública mundial, especialmente en las mujeres. Hasta ahora, se han sugerido pruebas contradictorias sobre la prevalencia de la deficiencia de yodo en Brasil. Objetivo: Estimar la prevalencia de deficiencia de yodo y factores asociados en mujeres en edad fértil, en Brasil. Métodos: Se realizó una revisión sistemática, buscando en PubMed, LILACS, OMS, Scopus y la base de datos de disertaciones y tesis de Capes desde el inicio hasta mayo de 2020. Se realizaron metanálisis de proporciones utilizando la variancia inversa para el modelo fijo. La calidad de información y metodológica se evaluó utilizando la herramienta del Institute Joanna Briggs para estudios de prevalencia. Resultados: Nuestra revisión identificó siete estudios publicados entre 2002 y 2017, incluyendo 1354 participantes, especialmente mujeres embarazadas. Todos los estudios presentaron al menos una limitación de calidad, principalmente con respecto al método de muestreo (es decir, la conveniencia) y el pequeño tamaño de la muestra. La prevalencia de la deficiencia de yodo varió entre los estudios del 16% y el 62%, mientras que el metanálisis identificó una prevalencia media del 40% (intervalo de confianza del 95%, IC 37%-43%) para las mujeres embarazadas y del 13% (IC del 95% 4%-24%) para mujeres no embarazadas. El metanálisis acumulativo sugiere una tendencia a una mayor prevalencia de deficiencia de yodo a partir de 2018 en mujeres embarazadas. Conclusiones: Si bien esta revisión sistemática identificó estudios con mala calidad metodológica y de reporte, se identificó una alta prevalencia de deficiencia de yodo en mujeres embarazadas, lo que refuerza la importancia de las políticas nutricionales nacionales para monitorear el estado de yodo en esta población. Los estudios futuros deben considerar el muestreo probabilístico aleatorio, el tamaño de muestra apropiado y el análisis de subgrupos predefinidos para informar adecuadamente la prevalencia de la deficiencia de yodo y los factores asociados en mujeres en edad fértil y para respaldar las políticas de salud

Development of instrument to report and assess causality of adverse events related to herbal medicines / Desarrollo de un instrumento para reportar y evaluar la causalidad de los eventos adversos asociados a plantas medicinales

Background: The use of herbal medicines is justified empirically using ethnopharmacological knowledge, which has limitations. Reports of adverse events (AE) may contribute for safety, quality, and effectiveness assessment. Objectives: This study aimed to develop an instrument to allow detection and evaluation of the causal likelihood of AE related to herbal medicines. Methods: A quantitative methodological development research intervention was performed with primary care health professionals. Two cases were distributed in an interval of one week in order to allow for completion of the proposal form. The within-rater reliability was calculated and classified into satisfactory, regular, and unsatisfactory, according to essential, necessary, and recommended items reported. Results: Fifty-seven professionals were enrolled. A high degree of the within-rater reliability was observed for the most essential, necessary, and recommended fields. The instrument contributed to assessment of definite causal association, once the duration of reactions including evolution, withdrawal, and reposition items showed high reliability. Most fields poor and weak filled were related to quality defects, such as popular name and appearance. Conclusions: Data suggest the instrument is adequate to report AE arising from herbal medicines. Owing to information regarding to organoleptic characteristics, the instrument is different from drug instruments. Therefore, it is intended to improve AE reports related to herbal medicines and contribute for appropriate use.

Antecedentes: Hierbas medicinales son utilizadas empíricamente con la base en el conocimiento etnofarmacobotánico, los cuales tienen limitaciones. Los informes de los eventos adversos (EA) pueden contribuir a la seguridad, la calidad y la evaluación de la eficacia de estos productos. Objetivos: El objetivo del estudio fue desarrollar un formulario para permitir la detección y evaluación de la probabilidad causal de EA relacionado al uso de plantas medicinales e fitoterápicos. Métodos: Investigación cuantitativa, de desenvolvimiento se llevó a cabo con los profesionales sanitarios de atención primaria. Dos casos fueran distribuidos, en un intervalo de una semana, con el fin de ser llenado en el formulario propuesto. La fiabilidad inter-observadores del instrumento fue evaluada y los resultados fueran clasificados en satisfactorio, regular e insatisfactorio, según los datos esenciales, necesarios y recomendados que fueran rellenados en el formulario de notificación. Resultados: Cincuenta y siete profesionales fueran elegibles. Se observó alto grado de fiabilidad entre observadores para la mayoría de los campos esenciales, necesarios y recomendados. El formulario contribuyó para la evaluación de la asociación causal definitiva, una vez que los campos de duración de las reacciones; evolución, retirada y re- exposición tuvieran alta fiabilidad. La mayoría de los campos flacamente llenados estaban relacionados con defectos de calidad, tales como: nombre popular y apariencia. Conclusiones: Los datos sugieren que el formulario propuesto es adecuado para reportar EA derivados de hierbas medicinales. Por la información relativa a las características organolépticas, el instrumento es diferente de lo instrumento para notificación de medicamentos. Por lo tanto, se pretende mejorar los informes de EA relacionados con los productos naturales y contribuir para el uso apropiado.

Pharmacist-led patient education on antiretroviral therapy: is it enough to improve adherence? / ¿Es la educación terapéutica la mejor estrategia para aumentar la adherencia de la terapia antirretroviral?

Case presentation: A 58-year-old man with AIDS, under ART treatment for 12 years, presenting non-compliance due pharmacotherapy complexity and lack of knowledge regarding disease and treatment. A care plan including pharmaceutical and educational interventions was established during a 7-month follow up. The plan mainly contemplated individual educational interventions with a few adjustments in the pharmacotherapy. Improvement of adherence and increase in quality of life where achieved in the end of the interventions, but no clinical impact was observed. Conclusion: Although increase in self-care and compliance to ART were enhanced, less complex regimens decided in cooperation between pharmacists and physicians could achieve better outcomes and solve some adverse-effects.

Risk factors for early prediction of adverse drug events related to hospitalizations / Factores de riesgo para la predicción de eventos adversos de medicamentos relacionados con la hospitalización

The prevalence of hospital admissions because of possible adverse drug events (ADEs) vary from 0.56% to 54.5% in Brazil. In addition, nearly 43% of inpatients may develop adverse drug reactions (ADRs) during their hospital stays. Clinical outcomes arising from drug-related problems are almost never identified by health professionals because the signs and symptoms are nonspecific and may mimic pathologies.

Jaw stiffness and dental extractions due to pharmacodynamic interaction between mirtazapine and chlorpromazine / Bruxismo y extracciones dentales debido a la interacción farmacodinámica entre mirtazapina y la clorpromazina

A comprehensive assessment of the patient's drug related needs allows identifying health problems drug-induced. It has been demonstrated that each dollar spent on clinical pharmacy services reduces the pooled median cost of health by 4.81 dollars. Jaw stiffness (bruxism) can be a serotonergic manifestation related to drugs with serotonin reuptake inhibition activity. Clinical manifestations also include: agitation, tachycardia, high blood pressure, tremor, fever, dyspnea, diarrhea, mental confusion and insomnia

Possible adverse drug events leading to hospital admission in a Brazilian teaching hospital

OBJECTIVES: Drug safety problems can lead to hospital admission. In Brazil, the prevalence of hospitalization due to adverse drug events is unknown. This study aims to estimate the prevalence of hospitalization due to adverse drug events and to identify the drugs, the adverse drug events, and the risk factors associated with hospital admissions. METHOD: A cross-sectional study was performed in the internal medicine ward of a teaching hospital in São Paulo State, Brazil, from August to December 2008. All patients aged ≥18 years with a length of stay ≥24 hours were interviewed about the drugs used prior to hospital admission and their symptoms/complaints/causes of hospitalization. RESULTS: In total, 248 patients were considered eligible. The prevalence of hospitalization due to potential adverse drug events in the ward was 46.4%. Overprescribed drugs and those indicated for prophylactic treatments were frequently associated with possible adverse drug events. Frequently reported symptoms were breathlessness (15.2%), fatigue (12.3%), and chest pain (9.0%). Polypharmacy was a risk factor for the occurrence of possible adverse drug events. CONCLUSION: Possible adverse drug events led to hospitalization in a high-complexity hospital, mainly in polymedicated patients. The clinical outcomes of adverse drug events are nonspecific, which delays treatment, hinders causality analysis, and contributes to the underreporting of cases. .