Hidroxicloroquina para Pacientes com COVID-19 não Hospitalizados: Uma Revisão Sistemática e Metanálise de Ensaios Clínicos Randomizados / Hydroxychloroquine for Non-Hospitalized COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Resumo Fundamento: Revisões sistemáticas anteriores não identificaram benefício do uso da hidroxicloroquina ou da cloroquina em pacientes com COVID-19 não hospitalizados. Após a publicação dessas revisões, os resultados do COPE, o maior ensaio clínico randomizado até hoje, tornaram-se disponíveis. Objetivos: Conduzir uma revisão sistemática e metanálise de ensaios clínicos randomizados (ECRs) para sintetizar as evidências sobre a eficácia e a segurança da hidroxicloroquina e da cloroquina em pacientes com COVID-19 não hospitalizados em comparação a controle ou tratamento padrão. Métodos: As buscas foram conduzidas nos bancos de dados PubMed, Embase, The Cochrane Library e ClinicalTrials.gov, e complementadas por busca manual. Foram realizadas metanálises diretas e avaliações de risco de viés e certeza da evidência, incluindo análise do tamanho ótimo da informação (OIS, optimal information size). Um nível de significância de 0,05 foi adotado na metanálise. PROSPERO: CRD42021265427. Resultados: Oito ECRs com 3219 participantes foram incluídos. As taxas de internação por COVID-19 e de eventos adversos não foram significativamente diferentes entre hidroxicloroquina (5,6% e 5,1%) e controle (7,4% e 20,4%) [risco relativo (RR) 0,77, intervalo de confiança 95% (IC95%), 0,57-1,04, I2: 0%; RR 1,78, IC95% 0,90; 3,52, I2: 93%, respectivamente)]. O OIS (7880) não foi alcançado para hospitalização por COVID-19, independentemente da simulação para a taxa de evento e redução do RR estimados. Conclusão: A evidência de muito baixa qualidade indicou falta de benefício com hidroxicloroquina em prevenir internações por COVID-19. Apesar de ser a revisão sistemática com o maior número de participantes incluídos, o OIS, considerando a resposta à infecção anterior à vacinação, não foi atingido.

Abstract Background: Previous systematic reviews have identified no benefit of hydroxychloroquine and chloroquine in non-hospitalized COVID-19 patients. After publication of these reviews, the results of COPE, the largest randomized trial conducted to date, became available. Objectives: To conduct a systematic review and meta-analyses of randomized clinical trials (RCTs) to synthesize the evidence on the efficacy and safety of hydroxychloroquine and chloroquine for non-hospitalized COVID-19 patients compared to placebo or standard of care. Methods: Searches were conducted in PubMed, Embase, The Cochrane Library, and ClinicalTrials.gov complemented by manual search. Pairwise meta-analyses, risk of bias, and evidence certainty assessments were conducted, including optimal information size analysis (OIS). A level of significance of 0.05 was adopted in the meta-analysis. PROSPERO: CRD42021265427. Results: Eight RCTs with 3,219 participants were included. COVID-19 hospitalization and any adverse events rates were not significantly different between hydroxychloroquine (5.6% and 35.1%) and control (7.4% and 20.4%) (risk ratio, RR, 0.77, 95% confidence interval, CI, 0.57-1.04, I2: 0%; RR 1.78, 95%-CI 0.90; 3.52, I2: 93%, respectively). The OIS (7,880) was not reached for COVID-19 hospitalization, independently of the simulation for anticipated event rate and RR reduction estimate. Conclusion: Evidence of very low certainty showed lack of benefit with hydroxychloroquine in preventing COVID-19 hospitalizations. Despite being the systematic review with the largest number of participants included, the OIS, considering pre-vaccination response to infection, has not yet been reached.

Economic burden of respiratory syncytial and parainfluenza viruses in children of upper-middle-income countries: a systematic review

Abstract Objective: To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries. Methods: The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757. Results: No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed. Conclusion: The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.

Análise dos custos diretos e indiretos da COVID-19 em um hospital brasileiro / Analysis of the direct and indirect costs of COVID-19 in a Brazilian hospital

Objetivo: Avaliar os custos diretos na perspectiva hospitalar e do Sistema Único de Saúde (SUS), bem como os custos indiretos de pacientes hospitalizados por COVID-19. Métodos: Estudo observacional com coleta de dados por micro e macrocusteio, realizado com pacientes admitidos por COVID-19 em um hospital paulista (março a setembro de 2020). Custos indiretos foram obtidos pelos métodos de capital humano e de anos de vida ajustados pela incapacidade (DALY). Análises de Mann-Whitney e regressão linear foram realizadas. Resultados: Foram incluídos 158 indivíduos com mediana de idade de 57 anos (IIQ 42-68 anos). A mediana de custo da internação na perspectiva do SUS e hospitalar foi de, respectivamente, R$ 2.009,46 (IIQ: R$ 1.649,11; R$ 4.847,36), principalmente devido à unidade de terapia intensiva (UTI), e R$ 19.055,91 (IIQ: R$ 8.399,47; R$ 38.438,00), principalmente devido a recursos humanos. Tempo total de internação (p < 0,001), óbito (p < 0,001) e ventilação invasiva (p < 0,001) foram preditores de aumento de custo. Foi identificada perda de 381,5 DALY e perda de produtividade de 128 anos, equivalente a US$ 855.307. Conclusão: Os principais direcionadores de custo foram recursos humanos e UTI. Entretanto, na perspectiva da sociedade, foi identificado o maior impacto devido à perda de produtividade e DALY. Tempo de hospitalização foi um dos grandes contribuidores do custo, e esse fator pode estar atrelado a gravidade da doença e protocolos de cuidado ao paciente.

Objective: To evaluate the direct costs from the hospital and Unified Health System (SUS) perspective, as well as the indirect costs of patients hospitalized by COVID-19. Methods: Observational study with data collection by micro- and macro-costing, carried out with patients hospitalized in a hospital in São Paulo (March-September 2020). Indirect costs were obtained using human capital and disability-adjusted life years (DALY) methods. Mann-Whitney and linear regression analyzes were performed. Results: 158 individuals were included, with a median age of 57 years (IQR 42-68 years). The median cost of admission in the SUS and hospital perspective was, respectively, R$ 2,009.46 (IQR: R$ 1,649.11; R$ 4,847.36), mainly due to the intensive care unit (ICU) and R$ 19,055.91 (IQR: R$ 8,399.47; R$ 38,438.00), mainly due to human resources. The total length of stay in hospital (p < 0.001), death (p < 0.001) and invasive ventilation (p < 0.001) were predictors of cost increase.

Deficiency and Insufficiency of Vitamin D in Women of Childbearing Age: A Systematic Review and Meta-analysis / Deficiência e insuficiência de vitamina D em mulheres na idade reprodutiva: Uma revisão sistemática e meta-análise

Abstract Objective To estimate the prevalence of inadequate vitamin D level and its associated factors for women of childbearing age in Brazil. Methods A systematic reviewwas conducted (last updatedMay 2020).Meta-analyses were performed using the inverse-variance for fixed models with summary proportion calculation by Freeman-Tukey double arcsine. Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. Results Our review identified 31 studies, comprising 4,006 participants. All the studies had at least one weakness, mainly due to the use of convenience sampling and small sample size. The overall prevalence of vitamin D deficiency, insufficiency, and both deficiency and insufficiency were 35% (confidence interval, 95%CI: 34-37%), 42% (95%CI: 41-44%), and 72% (95%CI: 71-74%), respectively. Conclusion Although the magnitude of the prevalence of inadequate levels of vitamin D is uncertain, the evidence suggests that presence of vitamin D deficiency or insufficiency in women of reproductive age can cause moderate to severe problems.

Resumo Objetivo Estimar a prevalência de níveis inadequados de vitamina D e seus fatores associados para mulheres em idade fértil no Brasil. Métodos Uma revisão sistemática foi realizada (última atualização em maio de 2020). As meta-análises foram realizadas usando o inverso da variância para o modelo fixo com cálculo de proporção sumarizada por transformação arco-seno duplo de Freeman-Tukey. A qualidade metodológica e de reporte foi avaliada usando a ferramenta do Joanna Briggs Institute para estudos de prevalência. Resultados Nossa revisão identificou 31 estudos, compreendendo 4.006 participantes. Todos os estudos apresentaram pelo menos uma limitação, principalmente devido ao uso de amostra de conveniência e tamanho amostral pequeno. As prevalências gerais de deficiência, insuficiência e deficiência de vitamina D foram 35% (intervalo de confiança, IC 95%: 34-37%), 42% (IC 95%: 41-44%) e 72% (IC 95%: 71-74%), respectivamente. Conclusão Embora a magnitude da prevalência de níveis inadequados de vitamina D seja incerta, a evidência sugere que presença de deficiência ou insuficiência de vitamina D em mulheres em idade reprodutiva pode causar problemas moderados a graves.

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

Deficiency of vitamins C and E in women of childbearing age in Brazil: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Despite the several options available for supplements containing vitamins C and E, evidence regarding the prevalence of deficiency or insufficiency of these vitamins is weak. OBJECTIVES: To estimate the prevalence of deficiency or insufficiency of vitamins C and E and associated factors among women of childbearing age, in Brazil. DESIGN AND SETTING: Systematic review and meta-analysis conducted at a Brazilian public university. METHODS: A search from index inception until May 2020 was conducted. Meta-analyses were performed using inverse variance for fixed models, with summary proportions calculation using Freeman-Tukey double arcsine (base case). Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. RESULTS: Our review identified 12 studies, comprising 1,316 participants, especially breastfeeding women. There was at least one quality weakness in all studies, mainly regarding sampling method (i.e. convenience sampling) and small sample size. The prevalence of vitamin C deficiency ranged from 0% to 40%. Only vitamin E deficiency was synthetized in meta-analyses, with mean prevalences of 6% regardless of the alpha-tocopherol cutoff in plasma, and 5% and 16% for cutoffs of < 1.6-12.0 mmol/l and < 16.2 mmol/l, respectively. The cumulative meta-analysis suggested that a trend to lower prevalence of vitamin E deficiency occurred in recent studies. CONCLUSIONS: Although the studies identified in this systematic review had poor methodological and reporting quality, mild-moderate vitamin C and E deficiencies were identified, especially in breastfeeding women. Thus, designing and implementing policies does not seem to be a priority, because the need has not been properly dimensioned among women of childbearing age in Brazil. REGISTRATION NUMBER IN PROSPERO: CRD42020221605.

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

Possíveis desfechos de longo prazo da Covid-19: uma revisão sistemática de escopo / Possible long-term outcomes of Covid-19: a systematic scoping review

Objetivo: mapear os possíveis desfechos de longo prazo da COVID-19 no mundo. Métodos: em acordo com as recomendações do Joanna Briggs Institute, foi realizada uma revisão sistemática de escopo de estudos experimentais e observacionais com busca nas bases de dados PubMed e Scopus, complementada por busca manual. Resultados: de 5.325 registros, 121 atenderam aos critérios de elegibilidade, os quais incluíram 1.638 recuperados da COVID-19. Foram identificados 52 potenciais desfechos de longo prazo da COVID-19, principalmente disfunção olfatória (n=605), disfunção gustativa (n=372), dispneia (n=233) e lesões pulmonares (n=225). Entre os cuidados de longo prazo, destacam-se início de terapia medicamentosa, terapia de substituição renal e amputação. Conclusão: foram mapeados 52 possíveis desfechos de longo prazo da COVID-19 e recomendações de continuação de cuidados, que variaram de manifestações leves a graves com duração menor ou igual a um mês e maior que um mês.

Objective: to map these possible long-term outcomes of COVID-19 worldwide. Methods: In accordance with the recommendations of the Joanna Briggs Institute, a systematic scoping review of experimental and observational studies was carried out with a search in PubMed and Scopus databases, complemented by manual search. Results: Of 5,325 records, 121 met eligibility criteria, which included 1,638 recovered from COVID-19. Fifty-two (52) potential long-term outcomes of COVID-19 were identified, mainly olfactory dysfunction (n=605), taste dysfunction (n=372), dyspnea (n=233) and lung injuries (n=225). Long-term care included initiation of drug therapy, renal replacement therapy and amputation. Conclusion: Fifty-two (52) possible long-term outcomes of COVID-19 and recommendations for continued care were mapped, ranging from mild to severe manifestations lasting less than or equal to one month and greater than one month.

Drug interactions for elderly with respiratory disorders and times of covid-19: a systematic scoping review / Interacciones farmacológicas para ancianos con enfermedades respiratorias y tiempos de covid-19: una revisión sistemática del alcance

Background: The elderly people have high morbimortality associated with respiratory disorders, in addition to the presence of other safety risk factors, such as the use of potentially inappropriate medication and the occurrence of drug interactions. Objective: Considering the current pandemic scenario, it was intended to identify explicit criteria-based tools that reported drug interactions between potentially inappropriate medication and respiratory system disorders and possibly worse prognosis of COVID-19 infection. Methods: A systematic scoping review was conducted until February 2020. Study characteristics of explicit criteria-based tools, and potentially inappropriate medication, drug interactions, and therapeutic management, were extracted. Results: Nineteen explicit criteria-based tools were included. Nineteen drug interactions and 17 potentially inappropriate medications with concerns for three respiratory disorders (asthma, chronic pulmonary obstructive disease, and respiratory failure) were identified. The most frequent pharmacological classes reported were benzodiazepines and beta-blockers. For clinical management, the tools recommend using cardioselective beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II type I receptor blockers and benzodiazepines with a short or intermediate half-life. Conclusion: Considering the increased risk of COVID-19 infection in the elderly, drug interactions and the use of potentially inappropriate medication associated with the occurrence of adverse drug events in the respiratory system may also worsening COVID-19 infection in patients with uncontrolled respiratory disorders. Thus, it is essential to assess drug therapy in use, to identify safety risks and monitor the elderly in general and those with a worse prognosis concerning COVID-19, promoting patient safety.

Antecedentes: Los ancianos tienen alta morbimortalidad asociada a trastornos respiratorios, además de la presencia de otros factores de riesgo de seguridad, como el uso de medicación potencialmente inapropiada y la ocurrencia de interacciones medicamentosas. Objetivo: Teniendo en cuenta el escenario pandémico actual, se pretendía identificar herramientas explícitas basadas en criterios que informaran interacciones farmacológicas entre medicamentos potencialmente inapropiados y trastornos del sistema respiratorio y posiblemente un peor pronóstico de la infección por COVID-19. Métodos:Se realizó una revisión sistemática del alcance hasta febrero de 2020. Se extrajeron las características del estudio de las herramientas explícitas basadas en criterios y la medicación potencialmente inapropiada, las interacciones entre medicamentos y el manejo terapéutico. Resultados: Se incluyeron diecinueve herramientas explícitas basadas en criterios. Se identificaron diecinueve interacciones farmacológicas y 17 medicamentos potencialmente inapropiados con preocupaciones por tres trastornos respiratorios (asma, enfermedad pulmonar obstructiva crónica e insuficiencia respiratoria). Las clases farmacológicas más frecuentes comunicadas fueron las benzodiacepinas y los betabloqueantes. Para el manejo clínico, las herramientas recomiendan el uso de betabloqueantes cardioselectivos, bloqueadores de los canales de calcio, inhibidores de la enzima convertidora de angiotensina y bloqueadores del receptor de angiotensina II tipo I y benzodiacepinas con una vida media corta o intermedia. Conclusión: Teniendo en cuenta el mayor riesgo de infección por COVID-19 en los ancianos, las interacciones farmacológicas y el uso de medicamentos potencialmente inapropiados asociados con la aparición de eventos farmacológicos adversos en el sistema respiratorio también pueden empeorar la infección por COVID-19 en pacientes con trastornos respiratorios no controlados. Por tanto, es fundamental evaluar la farmacoterapia en uso, identificar los riesgos de seguridad y monitorizar a los ancianos en general y a aquellos con peor pronóstico en relación con el COVID-19, promoviendo la seguridad del paciente.

Rational use of chloroquine and hydroxychloroquine in times of COVID-19

Considering the COVID-19 pandemic declared, part of the researchers' efforts has been in studies of repurposing chloroquine (CQ) and hydroxychloroquine (HCQ), cheap medicines that have been used for decades with indication for malaria, rheumatoid arthritis and systemic lupus erythematosus. Chinese and South Korean health officials recommended the use of QC and HCQ for prophylaxis and treatment of COVID-19, encouraging researchers around the world to assess the potential of these medicines as antivirals. To date, results of three clinical trials have been released. Two studies show divergent results for virological clearance, while the third suggests a benefit in terms of radiological and clinical improvement. The three studies have methodological limitations and low overall quality of evidence, in view of the absence of randomization, allocation concealment, blinding patients, health care providers, and outcome assessors, missing data and/or selective reporting of results, as well as probable heterogeneity of patients and treatments, imprecision due to the reduced statistical power of the studies, indirect evidence for patients with severe form of the disease or patients with high severity comorbidities. The irresponsible self-medication of these medicines is of concern both for the potential risk of shortages, as well as for the adverse events and potentially fatal intoxications. Thus, in the USA, Europe and Brazil, regulatory agencies have positioned themselves in an emergency, authorizing the use of CQ and HCQ under medical criteria and/or in the context of clinical trials. In Brazil, to restrict irresponsible self-medication and possible shortages, Anvisa included the drugs in a special control list. Evidence on the efficacy and safety of QC and HCQ remains uncertain, so the results of ongoing studies are needed to adequately guide public policy and clinical practice. Evidence-based health assumptions must be maintained even in times of international emergency due to the risk of having to deal with future complications from the irrational use of these medicines.(AU)

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

Gastrointestinal bleedings (GIB) are one of the most frequent adverse drug reactions. Among the GIB upper gastrointestinal bleeding (UGIB) stands out due to their high mortality. The different idiosyncratic responses related to UGIB ​​in medication users may be due to the presence of genetic variants in the genes that encode enzymes that are targets of pharmacokinetic and pharmacodynamic activity of the metabolism of the drugs, such as cyclooxygenase 1, endothelial nitric oxide synthase, cytochrome P450, among others. Although a review has focused on assessment whether the presence of CYP2C9*2 and CYP2C9*3 could increase UGIB diagnosis, the search is outdated, and more evidence can be identified regarding both CYP polymorphisms and other genes potentially involved with UGIB. The objective of the systematic review is to explore case-control or case-case studies to assess the epidemiological association between genetic polymorphisms and UGIB. This review will consider genetic polymorphisms of case-control and case-case studies and their association with the UGIB, in the presence or absence of drugs exposure. Electronic searches will be performed in PubMed, Scopus and the Cochrane Library with no time limit. Two researchers will select registries and extract data on study and population characteristics, exposure, covariates, and outcomes. Critical appraisal will consider Joanna Briggs tool for case-control studies. Studies will, where possible, be pooled with statistical meta-analysis. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation, where appropriate.(AU)

Análise de impacto orçamentário: uma revisão prática de conceitos e aplicações para o gestor / Budget impact analysis: a practical review of concepts and applications for the manager

Avaliações econômicas em saúde são essenciais para a tomada de decisão de gestores, visto que as inovações no setor nem sempre podem ser incorporadas conforme as expectativas dos usuários e da indústria. Logo, a análise de impacto orçamentário (AIO), uma das principais ferramentas da avaliação de tecnologias em saúde (ATS), permite aos gestores estimar o potencial número de indivíduos elegíveis para determinada tecnologia ao longo dos anos, prever quanto será necessário gastar para incorporar a tecnologia ou, eventualmente, se haverá economia nos cofres do pagador com a inclusão dela. Com a crescente publicação de artigos científicos sobre AIO no Brasil, surge a preocupação a respeito da qualidade metodológica desses estudos. O objetivo desta revisão é apresentar recomendações-chave para a elaboração de uma AIO adequada e expor a utilidade prática da AIO para a tomada de decisão de gestores de saúde por meio da análise de quatro estudos publicados. O formato de apresentação de uma AIO possibilita rápido entendimento e possui atributos que permitem evidenciar o maior valor de produtos e serviços de saúde junto aos tomadores de decisão em saúde, contribuindo para as melhores escolhas do ponto de vista clínico e econômico, nos sistemas público e privado. Porém, cabe ressaltar que alguns estudos ainda carecem de evidências de mundo real ou dados epidemiológicos para as estimativas e trabalham de maneira insuficiente as ferramentas para a redução de incertezas paramétricas.

Health economics evaluations are essential for decision makers, since innovations can not always be incorporated according to expectations of users and industry. Therefore, the Budget Impact Analysis (BIA), one of the main tools in Health Technology Assessment (HTA), allows managers to estimate the potential number of individuals eligible for a given technology over the years, to predict how much it will be necessary to spend for incorporate the technology or, eventually, whether there will be savings in the payer's coffers with the inclusion of the same. With the growing publication of scientific articles on BIA in Brazil, there is concern about the methodological quality of these studies. The objective of this review is to present key recommendations to elaborate an adequate BIA, commenting on four published studies, aiming to expose the practical utility of BIA for health managers. The presentation format of the BIA provides a quick understanding and has attributes that allows evidence of the highest value of health products and services among health decision makers, contributing to the best clinical and economic choices in public and private health systems. However, it should be noted in some studies there is still a lack of real-world evidence or epidemiological data for the estimates and insufficient using of tools to reduce parametric uncertainties.

Assessment tool for potentially inappropriate medication use in the elderly: a scoping review protocol

Potentially Inappropriate Medication for the elderly (PIM) are drugs in which the safety risks may exceed the benefits, especially when there are safer alternatives. The use of PIM is associated with increased hospitalizations and it is estimated that one every five prescriptions presents at least one PIM. In this context, there are several assessment tools for identification of PIM. The first assessment tool developed was Beers criteria and since its publication, new tools have been developed. The objective of this scoping review is to explore studies presenting assessment tools of PIM to map characteristics, justifications, and therapeutic equivalents. This review will consider studies that developed or validated an assessment tool of PIM. Electronic searches will be performed in PubMed and Scopus with no time limit. Two researchers, independently, will select registries and extract data of studies and tool characteristics, PIM and potentially inappropriate interaction, condition, justification, and therapeutic equivalents. The findings will be presented in narrative form including tables and figures to aid in data presentation, where appropriate.(AU)

Pharmacist-led interventions in Brazil: a scoping review protocol

Drug-related problems consist an important avoidable risk factor to the hospitalization in the general population. The increase of technologies to promote and recovery health and their use makes the design of services aimed at preventing health and drug problems, as well as their adequate management, a priority for public health. Pharmacist-led interventions are capable to optimize the use of medicines. However, it is important to know the characteristics and assessed outcomes of interventions, since, as a complex intervention, the variability between services can explain different performances. The objective of the scoping review is to explore randomized and non-randomized clinical trial, quasi-experimental and cohort studies to explore characteristics and assessed outcome of pharmacist-led interventions conducted in Brazil. This review will consider studies about pharmacist-led interventions, regardless of patient profile or health setting. Electronic searches will be performed in PubMed, Scopus, and LILACS databases with no time limit of publication. Two researchers, independently, will select registries and extract data of study and service characteristics, and outcomes measures. The findings will be presented in a narrative form including tables and figures to aid in data presentation, where appropriate.(AU)

Quality of evidence of anti-obesity pharmacotherapy: an overview of systematic reviews

The safety and effectiveness of main anti-obesity drugs are controversial, and there is no consensus among regulatory agencies regarding anti-obesity drugs. We undertook an overview of systematic reviews (SR) of randomized controlled trials (RCT) to summarize the quality of evidence related to anti-obesity drugs. Data sources included Medline, Scopus, The Cochrane Library and PROSPERO. Twenty-one SR (564 RCT; average of 2,356 participants per review) satisfied the inclusion criteria. Ten SR presented a high level of heterogeneity, and only five SR included sensitivity analyses. The most important limitations reported by the SR were a high level of attrition, a small sample size, and a short follow-up. Eight different outcomes for efficacy were used, 15 different outcomes for biomarkers were used, and nine different outcomes for safety were used. Conclusions: In conclusion, the quality of SR pertaining to anti-obesity drugs is low, and these reviews have a high level of heterogeneity. Future SR should present more detailed population inclusion criteria, larger sample sizes, and focus variables reported in a predefined anti-obesity core outcome set.(AU)

Prescription errors and associated factors in patients with oncologic and hematologic diseases in a tertiary hospital

Medication errors extend inpatient stay, increase costs and double the risk of death. Identify patients more likely to present prescription errors would be one manner that could be used to decrease the impact of such events. Thus, the present study identified the prevalence of prescription errors with patients with oncohematologic diseases and the factors associated with these events. Methods: A cross-sectional study was performed in a Brazilian tertiary hospital. Data regarding service, patients and their clinical condition, drug therapy and prescription errors were retrieved and analyzed. Results: Of 344 drug prescriptions identified, 26.2% showed at least one prescription error, mainly involving a wrong drug (48.3%). According to the logistic regression, the factors associated with errors include: presence of neutropenia OR 1.92 (95% CI 1.10­3.35), physicians on holiday or weekend shifts OR 0.40 (95% CI 0.18­0.86) and prescriptions with higher proportion of parenteral administration route OR 1.05 (95% CI 1.03­1.08). Conclusion: In conclusion, identify the factors associated with errors can be useful in developing clinical tools for predicting patients at higher risk for the occurrence of prescribing errors, as well as to contribute to the optimization of health professionals' clinical performance.(AU)

Systematic review and meta-analysis of the efficacy and safety of amfepramone and mazindol as a monotherapy for the treatment of obese or overweight patients

The aim of this study was to evaluate efficacy and safety of amfepramone, fenproporex and mazindol as a monotherapy for the treatment of obese or overweight patients. A systematic review of primary studies was conducted, followed by a direct meta-analysis (random effect) and mixed treatment comparison. Medline and other databases were searched. Heterogeneity was explored through I2 associated with a p-value. Of 739 identified publications, 25 were included in the meta-analysis. The global evaluation of Cochrane resulted in 19 studies with a high level of bias and six with unclear risk. Due to the lack of information in primary studies, direct meta-analyses were conducted only for amfepramone and mazindol. Compared to placebo, amfepramone resulted in higher weight loss in the short-term (<180 days; mean difference (MD) -1.281 kg; p<0.05; I2: 0.0%; p=0.379) and long-term (≥180 days; MD -6.518 kg; p<0.05; I2: 0.0%; p=0.719). Only studies with long-term follow up reported efficacy in terms of abdominal circumference and 5-10% weight reduction. These results corroborated the finding that the efficacy of amfepramone is greater than that of placebo. Treatment with mazindol showed greater short-term weight loss than that with placebo (MD -1.721 kg; p<0.05; I2: 0.9%; p=0.388). However, metabolic outcomes were poorly described, preventing a meta-analysis. A mixed treatment comparison corroborated the direct meta-analysis. Considering the high level of risk of bias and the absence of important published outcomes for anti-obesity therapy assessments, this study found that the evaluated drugs showed poor evidence of efficacy in the treatment of overweight and obese patients. Robust safety data were not identified to suggest changes in their regulatory status.