Frailty and health-related quality of life among older people living with HIV pre- and post-COVID-19 pandemic onset: A cross-sectional study.

INTRODUCTION: Antiretroviral therapy increased the survival and life expectancy of People living With HIV (PWH). Frailty-related syndromes among older PWH (aged 50+ years) may affect their Health-related Quality of Life (HQoL). Additionally, the COVID-19 pandemic has impacted health-related outcomes. This study aimed to estimate the prevalence of frailty and pre-frailty among older PWH, and to explore associations of HQoL with the study assessment period and frailty status. METHODS: Cross-sectional study conducted pre- (23-Mar-2019 to 5-Mar-2020) and post-COVID-19 pandemic onset (23-Jun-2021 to 5-May-2022), among older PWH at INI-Fiocruz, the largest cohort of PWH in Rio de Janeiro, Brazil. We measured frailty using Fried assessment, consisting of five domains: unintentional weight loss; self-reported exhaustion, weakness, slow walking speed, low physical activity. HQoL was assessed using the ACTG SF-21, which contains 21 questions divided into 8 domains. We used Chi-Square test, Fisher's exact test, Kruskal-Wallis and ranksum test for comparisons. RESULTS: We included 250 older PWH: 109 (43.6 %) pre- and 141 (56.4 %) post-COVID-19 pandemic onset. Median age was 60-years (IQR: 55‒64). Most self-identified as cisgender men 152 (60.8 %), Pardo/Black 146 (58.4 %), with completed secondary education or less 181 (72.7 %) and low income 132 (52.8 %). Overall, prevalence of frailty and pre-frailty were 9.2 % (95 % CI: 8.1‒10.3) and 61.6 % (95 % CI: 54.0‒69.2). Prevalence of frailty in the pre- and pos-COVID-19 pandemic periods were 7.3 % and 10.6 % (p = 0.66). HQoL scores were lower among participants with frailty compared to those with non-frailty and pre-frailty in all eight domains, and among those included in the post-COVID-19 compared to pre-COVID-19 period for four domains. CONCLUSIONS: We observed low prevalence of frailty, but high prevalence of pre-frailty among older PWH. Frailty status did not differ according to the COVID-19 assessment period. Assessment of frailty and HQoL should be incorporated in clinical practice for older PWH. Programs to reverse or prevent frailty should be implemented within the public health system.

Frailty and health-related quality of life among older people living with HIV pre- and post-COVID-19 pandemic onset: A cross-sectional study

ABSTRACT Introduction: Antiretroviral therapy increased the survival and life expectancy of People living With HIV (PWH). Frailty-related syndromes among older PWH (aged 50+ years) may affect their Health-related Quality of Life (HQoL). Additionally, the COVID-19 pandemic has impacted health-related outcomes. This study aimed to estimate the prevalence of frailty and pre-frailty among older PWH, and to explore associations of HQoL with the study assessment period and frailty status. Methods: Cross-sectional study conducted pre- (23-Mar-2019 to 5-Mar-2020) and post-COVID-19 pandemic onset (23-Jun-2021 to 5-May-2022), among older PWH at INI-Fiocruz, the largest cohort of PWH in Rio de Janeiro, Brazil. We measured frailty using Fried assessment, consisting of five domains: unintentional weight loss; self-reported exhaustion, weakness, slow walking speed, low physical activity. HQoL was assessed using the ACTG SF-21, which contains 21 questions divided into 8 domains. We used Chi-Square test, Fisher's exact test, Kruskal-Wallis and ranksum test for comparisons. Results: We included 250 older PWH: 109 (43.6 %) pre- and 141 (56.4 %) post-COVID-19 pandemic onset. Median age was 60-years (IQR: 55‒64). Most self-identified as cisgender men 152 (60.8 %), Pardo/Black 146 (58.4 %), with completed secondary education or less 181 (72.7 %) and low income 132 (52.8 %). Overall, prevalence of frailty and pre-frailty were 9.2 % (95 % CI: 8.1‒10.3) and 61.6 % (95 % CI: 54.0‒69.2). Prevalence of frailty in the pre- and pos-COVID-19 pandemic periods were 7.3 % and 10.6 % (p = 0.66). HQoL scores were lower among participants with frailty compared to those with non-frailty and pre-frailty in all eight domains, and among those included in the post-COVID-19 compared to pre-COVID-19 period for four domains. Conclusions: We observed low prevalence of frailty, but high prevalence of pre-frailty among older PWH. Frailty status did not differ according to the COVID-19 assessment period. Assessment of frailty and HQoL should be incorporated in clinical practice for older PWH. Programs to reverse or prevent frailty should be implemented within the public health system.

Long COVID-19 syndrome associated with Omicron XBB.1.5 infection: a case report.

BACKGROUND: There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES: The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS: We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS: The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS: This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.

SARS-CoV-2 Reinfection Cases in a Household-Based Prospective Cohort in Rio de Janeiro.

This was a household-based prospective cohort study conducted in Rio de Janeiro, in which people with laboratory-confirmed coronavirus disease 2019 (COVID-19) and their household contacts were followed from April 2020 through June 2022. Ninety-eight reinfections were identified, with 71 (72.5%) confirmed by genomic analyses and lineage definition in both infections. During the pre-Omicron period, 1 dose of any COVID-19 vaccine was associated with a reduced risk of reinfection, but during the Omicron period not even booster vaccines had this effect. Most reinfections were asymptomatic or milder in comparison with primary infections, a justification for continuing active surveillance to detect infections in vaccinated individuals. Our findings demonstrated that vaccination may not prevent infection or reinfection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Therefore we highlight the need to continuously update the antigenic target of SARS CoV-2 vaccines and administer booster doses to the population regularly, a strategy well established in the development of vaccines for influenza immunization programs.

Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil.

BACKGROUND: The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil. METHODS: Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy. RESULTS: A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4-54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2-17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2-52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy. CONCLUSIONS: We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients' therapeutic regimens should be implemented.

The Role of Children in Household Transmission of SARS-CoV-2 Across Four Waves of the Pandemic.

BACKGROUND: It is important to understand the dynamics of SARS-CoV-2 transmission in close-contact settings such as households. We hypothesized that children would most often acquire SARS-CoV-2 from a symptomatic adult caregiver. METHODS: This prospective cohort study was conducted from April 2020 to July 2022 in a low-resource, urban settlement in Brazil. We recruited families who brought their children to a public clinic. We collected nasopharyngeal and oral swabs from household members and tracked symptoms and vaccination. RESULTS: In total, 1256 participants in 298 households were tested for SARS-CoV-2. A total of 4073 RT-PCR tests were run with 893 SARS-CoV-2 positive results (21.9%). SARS-CoV-2 cases were defined as isolated cases (N = 158) or well-defined transmission events (N = 175). The risk of household transmission was lower if the index case was a child (OR: 0.3 [95% CI: 0.16-0.55], P < .001) or was vaccinated (OR: 0.29 [95% CI: 0.1-0.85], P = .024), and higher if the index was symptomatic (OR: 2.53 [95% CI: 1.51-4.26], P < .001). The secondary attack rate for child index cases to child contacts was 0.29, whereas the secondary attack rate for adult index cases to child contacts was 0.47 (P = .08). CONCLUSIONS: In this community, children were significantly less infectious to their household contacts than adolescents or adults. Most children were infected by a symptomatic adult, usually their mother. There was a double benefit of vaccination as it protected the vaccine from severe illness and prevented onward transmission to household contacts. Our findings may also be valid for similar populations throughout Latin America.

Reduced ability to neutralize the Omicron variant among adults after infection and complete vaccination with BNT162b2, ChAdOx1, or CoronaVac and heterologous boosting.

COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted.

Accuracy of saliva for SARS-CoV-2 detection in outpatients and their household contacts during the circulation of the Omicron variant of concern.

BACKGROUND: While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening. METHODS: To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance. RESULTS: Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91). CONCLUSIONS: Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.

Severe maternal morbidity and mortality during the COVID-19 pandemic: a cohort study in Rio de Janeiro.

Objectives: To identify factors associated with adverse maternal outcomes during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a single-centre prospective cohort study at a maternity department in a public general hospital in Rio de Janeiro. All pregnant women evaluated for emergency care, labour and delivery, respiratory symptoms, obstetric reasons or medical reasons between May 2020 and March 2022 at the study institution were invited to enrol in this study. The endpoint was maternal mortality or intensive care unit (ICU) admission. Results: In total, 1609 pregnant women were enrolled in this study. Of these, 25.5% (n=410) were infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) based on reverse transcription polymerase chain reaction or an antigen test. There were 21 deaths and 67 ICU admissions in 4% of the cohort. The incidence of severe maternal morbidity and mortality was higher during the Gamma wave than during the Delta wave (P=0.003). Vaccination conferred protection against the endpoint [relative risk (RR) 0.4, 95% confidence interval (CI) 0.1-0.9; P=0.0169]. Factors associated with severe morbidity and mortality included caesarean section (RR 3.7, 95% CI 1.7-7.9; P=0.0008), SARS-CoV-2 infection in the third trimester (RR 2.4, 95% CI 1.1-5.6; P=0.0006) and comorbidities (RR 3, 95% CI 1.8-5.2; P<0.0001). Conclusions: COVID-19 was significantly associated with the risk of severe maternal morbidity and mortality. Immunization of pregnant women against COVID-19 was highly protective against adverse outcomes, and should be encouraged during pregnancy.

Long COVID-19 syndrome associated with Omicron XBB.1.5 infection: a case report

BACKGROUND There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.

[Deaths from adverse drug events in Brazil: Mortality Information System as a source of information]. / Óbitos por eventos adversos a medicamentos no Brasil: Sistema de Informação sobre Mortalidade como fonte de informação.

Adverse drug events (ADEs) are harmful events caused by medication, and some of which can lead to death. Death records are an important source of information when using codes from the 10th revision of the International Classification of Diseases (ICD-10) suggestive of ADE. This study aimed to identify the ADEs registered in Brazililian Mortality Information System (SIM), analyzing data distribution by year, age group, and type of event. This is an ecological study with retrospective data collection, identifying ADEs in the SIM, using the ICD-10 codes. The study included deaths that occurred in Brazil from 2008 to 2016. An increase in the number of deaths associated with ADE was observed from 2008 to 2016, with a mortality rate per 1 million inhabitants ranging from 8.70 to 14.40 in the period. Most events corresponded to mental and behavioral disorders due to the use of psychotropic drugs. Most deaths (12,311) related to ADE codes were identified in several chapters of the ICD-10. Chapter XX, about adverse events, allowed the identification of a smaller number of deaths (4,893). Higher event rates were observed among individuals aged 60 years and over (39.8/1 million) and children younger than one year (22.0/1 million). The identification of ADE-related deaths on the SIM is an important strategy for addressing undesirable drug-related events. Deaths related to the use of psychotropic drugs were the most frequent ADE-related deaths and the elderly were the age group most affected by ADEs.

Os eventos adversos a medicamentos (EAM) são danos aos pacientes relacionados ao uso de medicamentos, parte dos quais pode levar à morte. Os registros de óbitos são fonte importante de informação, quando se empregam os códigos da 10ª revisão da Classificação Internacional de Doenças (CID-10) sugestivos de EAM. O estudo identificou os EAM registrados no Sistema de Informação sobre Mortalidade (SIM), analisando sua distribuição por ano, faixa etária e tipo de evento. Trata-se de um estudo ecológico com coleta de dados retrospectiva de identificação de EAM no SIM, por meio dos códigos da CID-10. O estudo compreendeu óbitos ocorridos no Brasil, de 2008 a 2016. Houve aumento nas proporções de óbitos associados aos EAM de 2008 a 2016, com taxa de mortalidade por 1 milhão de habitantes indo de 8,70 para 14,40 no período. A maioria dos eventos correspondeu aos transtornos mentais e comportamentais em razão do uso de psicofármacos. A maioria dos óbitos (12.311) relacionados a códigos de EAM foram identificados em diversos capítulos da CID-10. Já o capítulo XX, específico para eventos adversos, permitiu identificar parcela menor de óbitos (4.893). As maiores taxas de eventos ocorreram entre indivíduos com 60 anos ou mais (39,8/1 milhão) e crianças menores de um ano (22,0/1 milhão). A identificação de óbitos associados aos EAM, por meio do SIM, constitui uma estratégia importante para a abordagem dos eventos indesejáveis relacionados aos medicamentos. Os óbitos relacionados ao uso de psicofármacos foram os de maior frequência e os idosos foram a faixa etária mais acometida por EAM.

Los eventos adversos a los medicamentos (EAM) son daños a los pacientes relacionados con el uso de medicamentos, algunos de los cuales pueden provocar la muerte. Los registros de defunciones son fuente importante de información, cuando se emplean los códigos de la 10ª revisión de la Clasificación Internacional de Enfermedades (CIE-10) sugestivos de EAM. Identificar los EAM registrados en el Sistema de Información sobre Mortalidad (SIM), analizando su distribución, por año, grupo de edad y tipo de evento. Estudio ecológico con recolección de datos retrospectiva, de identificación de EAM en el SIM, por medio de los códigos de la CIE-10. El estudio comprendió muertes ocurridas en Brasil, de 2008 a 2016. Hubo aumento en las proporciones de muertes asociadas a la EAM de 2008 a 2016, con la tasa de mortalidad por 1 millón de habitantes pasando de 8,70 para 14,40, en el período. La mayoría de los eventos correspondieron a los trastornos mentales y del comportamiento debidos al consumo de psicofármaco. La mayoría de las muertes (12.311) relacionadas con los códigos EAM se identificaron en varios capítulos de la CIE-10. El capítulo XX, sobre eventos adversos, identificó un número menor de muertes (4.893). Las tasas más altas de eventos ocurrieron entre personas de 60 años o más (39.8/1 millón) y niños menores de un año (22.0/1 millón). La identificación de muertes asociadas a los EAM, por medio del SIM, constituye una estrategia importante para el enfoque de los eventos indeseables relacionados con los medicamentos. Las muertes relacionadas con el uso de psicofármacos fueron las más frecuentes y los ancianos fueron el grupo de edad más afectado por EAM.

Correction: Vertical transmission of chikungunya virus: A systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0249166.].

Diretrizes para organização, funcionamento e avaliação de farmácias de ensaios clínicos no Brasil: revisão de escopo / Guidelines for organization, operation and evaluation of clinical trials pharmacies in Brazil: a scope review

Resumo O desenvolvimento de novos medicamentos depende de etapas científicas que culminam nos ensaios clínicos em seres humanos. A farmácia de ensaios clínicos (FEC) é o local destinado ao recebimento, preparação, armazenamento e dispensação do produto investigacional (PI). Para tanto, deve possuir infraestrutura e procedimentos que garantam a segurança do participante e a qualidade da pesquisa. Este trabalho teve por objetivo sistematizar diretrizes para FEC no Brasil. Foi realizada uma revisão de escopo e as diretrizes foram organizadas utilizando o método de Ishikawa ("método 6Ms"). No total foram selecionadas 51 publicações, sendo 39 diretrizes e normas e 12 artigos científicos para cada "M"; 25 descreveram o ciclo de assistência farmacêutica (procedimentos para assegurar a segurança dos participantes, desde a requisição do produto até a destinação final), 14 indicadores de qualidade, 12 de recursos humanos, 11 de infraestrutura e recursos materiais e 5 descreveram PIs. para organização, funcionamento e avaliação de FEC no Brasil e corroboram a necessidade da presença do profissional farmacêutico no ciclo da assistência farmacêutica no contexto dos ensaios clínicos, contribuindo ainda na preparação para monitorias, auditorias e inspeções de agências regulatórias.

Abstract The development of new drugs depends on several scientific steps, which culminate in clinical trials. The clinical trials pharmacy (CTP) is the place for receiving, preparing, storing and dispensing the investigational product or study drug. Therefore, it must have infrastructure and procedures that guarantee participant safety and quality of research data. This study aimed to systematize guidelines for CTP in Brazil. We conducted a scope review and organized the results using the Ishikawa Method (6Ms). In total, 51 publications were selected for each "M", 39 laws, regulations or guidelines and 12 scientific articles: 25 publications for pharmaceutical services (pharmacy procedures to ensure participant safety from investigational product ordering to final disposition), 14 for Quality Indicators, 12 for Human Resources, 11 for Infrastructure, 11 for Material Resources and 5 for Investigational Product. Our results synthesize information for the organization, operation and evaluation of CTP in Brazil, emphasizes the inclusion of the pharmacist within the clinical trials context, and contributes to preparation for monitoring, auditing, and inspections conducted by regulatory agencies.

Guidelines for organization, operation and evaluation of clinical trials pharmacies in Brazil: a scope review. / Diretrizes para organização, funcionamento e avaliação de farmácias de ensaios clínicos no Brasil: revisão de escopo.

The development of new drugs depends on several scientific steps, which culminate in clinical trials. The clinical trials pharmacy (CTP) is the place for receiving, preparing, storing and dispensing the investigational product or study drug. Therefore, it must have infrastructure and procedures that guarantee participant safety and quality of research data. This study aimed to systematize guidelines for CTP in Brazil. We conducted a scope review and organized the results using the Ishikawa Method (6Ms). In total, 51 publications were selected for each "M", 39 laws, regulations or guidelines and 12 scientific articles: 25 publications for pharmaceutical services (pharmacy procedures to ensure participant safety from investigational product ordering to final disposition), 14 for Quality Indicators, 12 for Human Resources, 11 for Infrastructure, 11 for Material Resources and 5 for Investigational Product. Our results synthesize information for the organization, operation and evaluation of CTP in Brazil, emphasizes the inclusion of the pharmacist within the clinical trials context, and contributes to preparation for monitoring, auditing, and inspections conducted by regulatory agencies.

O desenvolvimento de novos medicamentos depende de etapas científicas que culminam nos ensaios clínicos em seres humanos. A farmácia de ensaios clínicos (FEC) é o local destinado ao recebimento, preparação, armazenamento e dispensação do produto investigacional (PI). Para tanto, deve possuir infraestrutura e procedimentos que garantam a segurança do participante e a qualidade da pesquisa. Este trabalho teve por objetivo sistematizar diretrizes para FEC no Brasil. Foi realizada uma revisão de escopo e as diretrizes foram organizadas utilizando o método de Ishikawa ("método 6Ms"). No total foram selecionadas 51 publicações, sendo 39 diretrizes e normas e 12 artigos científicos para cada "M"; 25 descreveram o ciclo de assistência farmacêutica (procedimentos para assegurar a segurança dos participantes, desde a requisição do produto até a destinação final), 14 indicadores de qualidade, 12 de recursos humanos, 11 de infraestrutura e recursos materiais e 5 descreveram PIs. para organização, funcionamento e avaliação de FEC no Brasil e corroboram a necessidade da presença do profissional farmacêutico no ciclo da assistência farmacêutica no contexto dos ensaios clínicos, contribuindo ainda na preparação para monitorias, auditorias e inspeções de agências regulatórias.

Methods to Assess Adult and Adolescent Patients' Adherence to Antimalarial Treatment: A Systematic Review.

Malaria is a curable disease for which early diagnosis and treatment, together with the elimination of vectors, are the principal control tools. Non-adherence to antimalarial treatment may contribute to therapeutic failure, development of antimalarial resistance, introduction or resurgence of malaria in non-endemic areas, and increased healthcare costs. The literature describes several methods to directly or indirectly assess adherence to treatment, but no gold standard exists. The main purpose of this review is to systematize the methods used to assess patient adherence to antimalarial treatment. A systematic review was performed, in accordance with the PRISMA statement, of the following databases: LILACS, EMBASE, PUBMED, COCHRANE, GOOGLE SCHOLAR, WEB OF SCIENCE, SCOPUS, and OPENGREY, through 14 December 2021. A snowball search was also performed by screening the references of the included studies as well as those cited in relevant reviews. Inclusion criteria were reporting assessment of the patient's adherence to antimalarials in individuals with laboratory diagnosis of malaria, the description of antimalarials prescribed, and adherence estimates. Exclusion criteria were studies exclusively about directly observed therapy, studies of populations ≤12 yo and guidelines, commentaries, reviews, letters, or editorials. Study quality was assessed using MINORS and the Cochrane Risk of Bias Tool. Proportions were calculated to measure frequencies considering the number of articles as the denominator. Twenty-one studies were included in this review. Most of them (76.5%) assessed adherence to falciparum malaria treatment. Seventeen studies (80.9%) used a combination of methods. The methods described were pill counts, self-reports, biological assays, use of electronic pillboxes, and clinical cure. It was possible to identify different adherence classifications for all the methods used. Our review found that indirect methods like pill counts and self-reports are the most commonly used. Combining an method that gives solid proof of the ingestion of medication and a method that completes the research with information regarding factors, beliefs or barrier of adherence seems to be the best approach. Future studies of antimalarial treatment should standardize adherence classifications, and collect data on the types and causes of nonadherence, which can contribute to the development of tools to promote medication adherence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020148054, identifier CRD42020148054.

Post-acute COVID-19 syndrome after reinfection and vaccine breakthrough by the SARS-CoV-2 Gamma variant in Brazil.

We describe a case of prolonged COVID-19 caused by the SARS-CoV-2 Gamma variant in a fully vaccinated healthcare worker, 387 days after an infection caused by lineage B.1.1.33. Infections were confirmed by whole-genome sequencing and corroborated by the detection of neutralizing antibodies in convalescent serum samples. Considering the permanent exposure of this healthcare worker to SARS-CoV-2, the waning immunity after the first infection, the low efficacy of the inactivated vaccine at preventing COVID-19, the immune escape of the Gamma variant (VOC), and the burden of post-COVID syndrome, this individual would have benefited from an additional dose of a heterologous vaccine.

Identifying adverse drug events in patients at a pediatric ward in a Brazilian hospital: application and performance of the triggers / Identificação de eventos adversos a medicamentos em pacientes de enfermaria pediátrica em um hospital brasileiro: aplicação e desempenho de rastreadores

Abstract Objectives: to evaluate the performance of a trigger tool in identifying adverse drug events (ADE) in hospitalized children. Methods: a retrospective cohort study review on 133 medical records at a federal maternal and child reference hospital in Rio de Janeiro in 2016. A list of 14 triggers was developed to detect ADE in the pediatric population. Three steps were performed: (1) search for triggers; (2) selection of suspected cases of ADE and (3) final determination of ADE by experts' consensus. Results: 360 triggers were identified in 100 hospitalizations (75.2%), with an average of 2.7 triggers/ hospitalization. The most frequent triggers were "abrupt medication stop" (79.7%); "antiemetics use" (8.9%) and "laxatives use" (7.2%); while the "diphenhydramine use", "phytomenadione use" and "excessive sedation/lethargy/fall/hypotension" obtained the highest performance indicating ADE every time they occurred. Thirty-one ADE were identified in 12.8% of the hospitalizations; 11 (35.5%) ADE were detected without the aid of the triggers thus, pruritus and diarrhea were the most frequent. Conclusion: the trigger tool proved to be useful in identifying ADE in hospitalized children, especially if high performance and high frequency triggers are used in identifying the events. The inclusion of the triggers "diarrhea" and "pruritus", may favor the identification of ADE in patients at pediatric wards.

Resumo Objetivos: avaliar o desempenho de uma ferramenta de rastreamento de eventos adversos a medicamentos (EAM) em crianças hospitalizadas. Métodos: estudo de coorte retrospectivo com revisão de 133 prontuários de hospital federal de referência materno infantil no Rio de Janeiro, em 2016. Uma lista de 14 rastreadores foi usada para detecção de EAM na população pediátrica. Foram realizadas 3 etapas: (1) busca de rastreadores; (2) seleção dos casos suspeitos de EAM e (3) determinação final do EAM por consenso entre especialistas. Resultados: foram identificados 360 rastreadores em 100 internações (75,2%), com média de 2,7 rastreadores/internação. Os rastreadores mais frequentes foram "interrupção abrupta da medicação" (79,7%); "uso de antieméticos" (8,9%) e "uso de laxantes" (7,2%) enquanto que "uso de difenidramina", "uso de fitomenadiona" e "excesso de sedação/letargia/queda/hipotensão" obtiveram o maior rendimento indicando EAM em todas as vezes que ocorreram. Trinta e um EAM foram identificados em 12,8% das internações; 11(35,5%) EAM foram detectados sem auxílio dos rastreadores, sendo prurido e diarreia os mais frequentes. Conclusão: a ferramenta de rastreadores mostrou-se útil para a identificação de EAM em crianças hospitalizadas, principalmente se forem utilizados rastreadores com alto rendimento e alta frequência na identificação de eventos. A inclusão dos rastreadores diarreia e prurido pode favorecer a identificação de EAM em pacientes de enfermaria pediátrica.

SARS-CoV-2 Infection Dynamics in Children and Household Contacts in a Slum in Rio de Janeiro.

OBJECTIVES: To investigate the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a vulnerable population of children and their household contacts. METHODS: SARS-CoV-2 reverse transcription polymerase chain reaction assays and coronavirus disease 2019 (COVID-19) immunoglobulin G serology tests were performed in children and their household contacts after enrollment during primary health care clinic visits. Participants were followed prospectively with subsequent specimens collected through household visits in Manguinhos, an impoverished urban slum (a favela) in Rio de Janeiro at 1, 2, and 4 weeks and quarterly post study enrollment. RESULTS: Six hundred sixty-seven participants from 259 households were enrolled from May to September 2020. This included 323 children (0-13 years), 54 adolescents (14-19 years), and 290 adults. Forty-five (13.9%) children had positive test results for SARS-CoV-2 polymerase chain reaction. SARS-CoV-2 infection was most frequent in children aged <1 year (25%) and children aged 11 to 13 years (21%). No child had severe COVID-19 symptoms. Asymptomatic infection was more prevalent in children aged <14 years than in those aged ≥14 years (74.3% and 51.1%, respectively). All children (n = 45) diagnosed with SARS-CoV-2 infection had an adult contact with evidence of recent infection. CONCLUSIONS: In our setting, children do not seem to be the source of SARS-CoV-2 infection and most frequently acquire the virus from adults. Our findings suggest that, in settings such as ours, schools and child care potentially may be reopened safely if adequate COVID-19 mitigation measures are in place and staff are appropriately immunized.

Investigation of SARS-CoV-2 infection in dogs and cats of humans diagnosed with COVID-19 in Rio de Janeiro, Brazil.

BACKGROUND: Infection by SARS-CoV-2 in domestic animals has been related to close contact with humans diagnosed with COVID-19. Objectives: To assess the exposure, infection, and persistence by SARS-CoV-2 of dogs and cats living in the same households of humans that tested positive for SARS-CoV-2, and to investigate clinical and laboratory alterations associated with animal infection. METHODS: Animals living with COVID-19 patients were longitudinally followed and had nasopharyngeal/oropharyngeal and rectal swabs collected and tested for SARS-CoV-2. Additionally, blood samples were collected for laboratory analysis, and plaque reduction neutralization test (PRNT90) to investigate specific SARS-CoV-2 antibodies. RESULTS: Between May and October 2020, 39 pets (29 dogs and 10 cats) of 21 patients were investigated. Nine dogs (31%) and four cats (40%) from 10 (47.6%) households were infected with or seropositive for SARS-CoV-2. Animals tested positive from 11 to 51 days after the human index COVID-19 case onset of symptoms. Three dogs tested positive twice within 14, 30, and 31 days apart. SARS-CoV-2 neutralizing antibodies were detected in one dog (3.4%) and two cats (20%). In this study, six out of thirteen animals either infected with or seropositive for SARS-CoV-2 have developed mild but reversible signs of the disease. Using logistic regression analysis, neutering, and sharing bed with the ill owner were associated with pet infection. CONCLUSIONS: The presence and persistence of SARS-CoV-2 infection have been identified in dogs and cats from households with human COVID-19 cases in Rio de Janeiro, Brazil. People with COVID-19 should avoid close contact with their pets during the time of their illness.

Vertical transmission of chikungunya virus: A systematic review.

OBJECTIVES: To describe and estimate the frequency of pregnancy outcomes, clinical and laboratory characteristics of vertical transmission of CHIKV in the neonate. STUDY DESIGN: We performed a systematic review evaluating the clinical presentation of perinatally-acquired CHIKV infection in neonates. The search was performed using Medline (via PubMed), LILACS, Web of Science, Scielo, Google Scholar and Open grey to identify studies assessing vertical transmission of CHIKV up to November 3, 2020. There were no search restrictions regarding the study type, the publication date or language. Studies with no documented evidence of CHIKV infection in neonates (negative RT-PCR or absence of IgM) were excluded. RESULTS: From the 227 studies initially identified, 42 were selected as follows: 28 case reports, 7 case series, 2 cross-sectional studies and 5 cohort studies, for a total of 266 CHIKV infected neonates confirmed by serological and/or molecular tests. The vertical transmission rate was 50% in the Reunion Island outbreak, which was the subject of the majority of the studies; the premature delivery were reported in 19 (45.2%) studies; the rate of fetal distress was 19.6% of infected babies and fetal loss occurred in 2% of the cases. Approximately 68.7% of newborns were diagnosed with encephalopathy or encephalitis after perinatally acquired CHIKV. Most of the infected neonates were born healthy, developing CHIKV sepsis clinical syndrome within the first week of life. CONCLUSIONS: We alert neonatologists to the late manifestations of neonatal CHIKV infection, relevant to the management and reduction of morbidity. A limitation of our review was that it was not possible to carry out meta-analysis due to differences in study design and the small number of participants.