Methodological Quality of Pulmonary Arterial Hypertension Treatment Evidence-Based Guidelines: A Systematic Review Using the AGREE II and AGREE REX Tools.

PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis, and its management should be grounded in well-developed clinical practice guidelines (CPG). Thus, we critically assess the methodological quality of the available CPG for pharmacological treatments for PAH. METHODS: A systematic review (CRD42023387168) was performed in PubMed, Cochrane, Embase, and Tripdatabase (Jan-2023). Eligible records were appraised by four reviewers using the Appraisal of Guidelines, Research, and Evaluation Collaboration tool (AGREE II) and the complementary tool for assessing recommendations' quality and certainty, AGREE REX. Descriptive statistics were used to summarize the data. RESULTS: Overall, 31 guidelines, mainly authored by professional societies (90%), targeting only physicians as primary users (84%), were identified. Guidelines presented a moderate overall quality (scores of 63% and 51% in AGREE II and AGREE REX, respectively), with a few domains showing slight improvements over the years. AGREE II "Scope and Purpose" (94%) and "Presentation Clarity" (99%) domains obtained the highest scores. The items related to "Stakeholder involvement," "Editorial independence," and "Clinical applicability" (AGREE REX) were fairly reported. Conversely, CPG lacks rigor in development (32% score, AGREE II), scarcely discusses the role of stakeholders, and provides deficient data on the implementation of recommendations (scores of 35% and 46% in AGREE II and AGREE REX, respectively). No differences in the quality of guidelines published by different developers or countries were observed (p > 0.05). CONCLUSION: Methodological weaknesses are common among guidelines addressing PAH treatment, especially regarding scientific rigor, stakeholders' values and preferences, and facilitators and barriers to implementability. Particular attention should be given to developing future guidelines.

Application of trigger tools for detecting adverse drug events in older people: A systematic review and meta-analysis.

OBJECTIVE: To identify trigger tools applied to detect adverse drug events (ADEs) in older people and describe their utility and performance. METHODS: A systematic review was conducted in the PubMed, Lilacs, and Scopus databases (January 2024). Studies that developed, applied, or validated trigger tools and evaluated their utility and/or performance for detecting ADEs in older people were considered. Direct proportion meta-analyses using the inverse-variance method were performed for prevalence of ADEs and positive predictive value (PPV). RESULTS: Twenty-four studies (25 publications) were included. Twelve trigger tools were identified, of which six were developed for detecting ADEs in older population, four developed for general population and modified for older people, and two developed for general population. No tools for detecting ADEs in older people receiving palliative care or hospitalized in intensive or surgical care units were found. The performance of triggers was presented through PPV (11.5-71%), negative predictive values (83.3%), and sensitivity (30-94.8%). The overall PPV was 33.3% (95%CI: 32.5-34.2%). Triggers with good performance were changes in plasma levels of digoxin, glucose, and potassium; changes in international normalized ratio; abrupt medication stop; hypotension; and constipation. The prevalence of ADEs ranged from 2.8 to 66%, with overall prevalence of ADEs of 20% (95%CI: 19.3-20.8%). Preventability ranged from 8.4 to 94.4%. Metabolic or electrolyte disturbances induced by diuretics, constipation induced by opioids, and falls and delirium induced by benzodiazepines were the most prevalent ADEs. CONCLUSION: The trigger tools are flexible and easy to apply, and they can contribute to the detection of ADEs, their associated risk factors, the level of harm, and preventability in different health settings. However, there is no consensus on good or poor values of PPV, which indicate the performance of triggers. Furthermore, there is limited evidence regarding the evaluation of performance through negative predictive value, sensitivity, and specificity. PROSPERO: CRD42022379893.

Mapping the characteristics, concepts and methodologies of matching-adjusted indirect comparison studies assessing pharmacological therapies in oncology: a scoping review protocol.

INTRODUCTION: Matching-adjusted indirect comparison (MAIC) studies are a subtype of indirect comparison, which uses propensity score weighting to enhance comparability. This method adjusts aggregated data based on covariables from individual patient data from studies to produce population-adjusted indirect comparisons. Some national Health Technology Assessment agencies have recently received submissions containing MAIC models. However, there can be a lack of confidence in its estimates when they are poorly reported and inconsistent with other techniques. The objective of this study is to map the characteristics, concepts and methodology of MAIC studies used for pharmacological therapies in the field of oncology. METHODS AND ANALYSIS: A scoping review methodology will be applied following the Joanna Briggs Institute framework and the results will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews. Studies that used MAIC to compare treatments in oncology conditions will be considered eligible. A systematic search will be conducted in PubMed, Embase and the Cochrane Library. No restriction of location or language will be applied. Study screening will be documented and presented in a Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram. Data will be extracted and recorded on a predefined data form and will be presented in a tabular form accompanied by a descriptive summary. ETHICS AND DISSEMINATION: No ethical approval is required for this study. The results of this scoping review will be disseminated through peer-reviewed publications.

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

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.

Cost of Illness in Patients With COVID-19 Admitted in Three Brazilian Public Hospitals.

OBJECTIVES: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives. METHODS: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission. RESULTS: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively. CONCLUSIONS: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.

Eficácia e segurança de romosozumabe para o tratamento de osteoporose grave em mulheres na pós-menopausa: revisão sistemática e meta-análise em rede / Efficacy and safety of romosozumab for the treatment of severe osteoporosis in postmenopausal women: systematic and network meta-analysis

Introdução: A osteoporose é uma das principais causas de morbimortalidade, principalmente em idosos e mulheres na pós-menopausa, devido ao aumento da fragilidade óssea e maior suscetibilidade a fraturas. Objetivo: Avaliar a eficácia e segurança do romosozumabe, comparado aos tratamentos farmacológicos atualmente disponíveis no Sistema Único de Saúde para o manejo de mulheres na pós-menopausa com osteoporose grave e alto risco de fraturas. Métodos: Foi realizada uma busca seguida por meta-análises indiretas, por ensaios clínicos randomizados (ECR) nas bases PubMed Central e Medline, Embase e Cochrane Library e por busca manual. O risco de viés (RoB 2.0) e a qualidade da evidência (GRADE) foram analisados. Meta-análises indiretas foram realizadas para desfechos de fraturas, densidade mineral óssea e eventos adversos. Resultados: Sete ECR (n= 19.951 mulheres) foram incluídos nesta revisão. Romosozumabe seguido de alendronato reduziu risco de fraturas não vertebrais em 12 meses (RR: 0,64, IC 95%: 0,49-0,84; alta certeza de evidência) e em 24 meses (RR: 0,52, IC 95%: 0,43-0,64; (alta certeza de evidência) na comparação ao alendronato. Achados semelhantes foram identificados para outros desfechos. Ácido zoledrônico foi associada a maior risco de descontinuação por evento adverso que placebo (RR: 1,02, IC 95%: 1,01-1,03). Conclusão: Foi identificado que romosozumabe ou romosozumabe seguido por alendronato são eficazes e seguros na comparação com alendronato.

Background: Osteoporosis is a major cause of morbidity and mortality, especially in the elderly and postmenopausal women, due to increased bone fragility and greater susceptibility to fractures. Objective: To evaluate the efficacy and safety of romosozumab, compared to pharmacological treatments currently available in the Unified Health System of Brazil for the management of postmenopausal women with severe osteoporosis and high risk of fractures. Methods: A search was carried out followed by indirect meta-analyses, randomized controlled trials (RCTs) in PubMed Central and Medline, EMBASE, and Cochrane Library databases and manual search. Risk of bias (RoB 2.0) and quality of evidence (GRADE) were assessed. Indirect frequentist meta-analyses were carried out for outcomes related to fractures, bone mineral density, and adverse events. Results: Seven RCTs (n= 19,951 woman) were included in this review. Romosozumab followed by alendronate reduced the risk of non-vertebral fractures at 12 months (RR: 0.64, 95% CI: 0.49-0.84; high certainty of evidence) and at 24 months (RR: 0.52, CI 95 %: 0.43-0.64; (high certainty of evidence) in comparison to alendronate. Similar findings were identified for other outcomes. Zoledronic acid was associated with a higher risk of discontinuation due to adverse events than placebo (RR: 1.02, 95% CI: 1.01-1.03). Conclusion: This review identified that romosozumab or romosozumab followed by alendronate are effective and safe compared to alendronate.

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.

Hospitalization costs of coronaviruses diseases in upper-middle-income countries: A systematic review.

BACKGROUND: COVID-19, SARS and MERS are diseases that present an important health burden worldwide. This situation demands resource allocation to the healthcare system, affecting especially middle- and low-income countries. Thus, identifying the main cost drivers is relevant to optimize patient care and resource allocation. OBJECTIVE: To systematically identify and summarize the current status of knowledge on direct medical hospitalization costs of SARS, MERS, or COVID-19 in Upper-Middle-Income Countries. METHODS: We conducted a systematic review across seven key databases (PubMed, EMBASE, BVS Portal, CINAHL, CRD library, MedRxiv and Research Square) from database inception to February 2021. Costs extracted were converted into 2021 International Dollars using the Purchasing Power Parity-adjusted. The assessment of quality was based on the protocol by the BMJ and CHEERS. PROSPERO 2020: CRD42020225757. RESULTS: No eligible study about SARS or MERS was recovered. For COVID-19, five studies presented cost analysis performed in Brazil, China, Iran, and Turkey. Regarding total direct medical costs, the lowest cost per patient at ward was observed in Turkey ($900.08), while the highest in Brazil ($5,093.38). At ICU, the lowest was in Turkey ($2,984.78), while the highest was in China ($52,432.87). Service care was the most expressive (58% to 88%) cost driver of COVID-19 patients at ward. At ICU, there was no consensus between service care (54% to 87%) and treatment (72% to 81%) as key burdens of total cost. CONCLUSION: Our findings elucidate the importance of COVID-19 on health-economic outcomes. The marked heterogeneity among studies leaded to substantially different results and made challenging the comparison of data to estimate pooled results for single countries or regions. Further studies concerning cost estimates from standardized analysis may provide clearer data for a more substantial analysis. This may help care providers and policy makers to organize care for patients in the most efficient way.

A comprehensive look at explicit screening tools for potentially inappropriate medication: A systematic scoping review.

OBJECTIVE: To map explicit screening tools to identify potentially inappropriate medication (PIMs), and the characteristics and limitations of these tools. Including PIMs-interactions, therapeutic alternatives and the clinical management of PIMs. METHODS: A systematic scoping review was conducted in PubMed and Scopus (until May 2021). The number of PIMs listed as essential drugs was identified in Model List of Essential Medicines by the World Health Organization (WHO) and National List of Essential Medicines (Brazil). In addition to reporting the therapeutic alternatives and clinical management proposed by explicit screening tools to identify PIMs, we suggested our own alternatives for the PIMs most frequently reported. RESULTS: Fifty-eight tools reported 614 PIMs and 747 PIMs-interactions. Limited overlap between the tools was observed: 123 (69.1%) of 178 therapeutic alternatives proposed by the tools were considered inappropriate by other tools, and 222 (36.1%) of the 614 PIMs identified were named as being inappropriate only once. Only 21 tools were developed by a Delphi panel technique associated with systematic review. The PIMs listed as essential medication in Brazil and by the WHO were 30.6% and 23.3% of the total reported, respectively. For the most-cited PIMs, such as non-steroidal anti-inflammatory drugs, tricyclic antidepressants and benzodiazepines, we suggested the use of non-opioid and opioid analgesics; agomelatine, bupropion or moclobemide; and melatonin, respectively. CONCLUSIONS: The next stages in the development of explicit screening tools to identify PIMs include achieving more consensus between them and improving their applicability across countries. Further, it is recommended that tools include PIMs risks and advice on therapeutic alternatives.

Deficiency and Insufficiency of Vitamin D in Women of Childbearing Age: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the prevalence of inadequate vitamin D level and its associated factors for women of childbearing age in Brazil. METHODS: A systematic review was conducted (last updated May 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.

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%: 34­37%), 42% (IC 95%: 41­44%) e 72% (IC 95%: 71­74%), 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.

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

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

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.

Drug interactions for elderly people with mental and behavioral disorders: a systematic scoping review.

OBJECTIVES: To identify drug interactions of potentially inappropriate medications and mental and behavioral disorders, according to explicit potentially inappropriate medications criteria-based tools. METHODOLOGY: A systematic scoping review was conducted in February 2020. Study characteristics, potentially inappropriate medications, drug interactions, rationale, and therapeutic management proposed were extracted. The commercialization and potentially inappropriate medications standard as essential in Brazil and in the world were identified. Therapeutic management was proposed for the most cited potentially inappropriate medications. RESULTS: 36 tools including 151 drug interactions, in addition to 132 potentially inappropriate medications with concerns related to six mental and behavioral disorders were identified. Cognitive impairment and dementia were the most frequently disorders reported and antipsychotics, anticholinergics, and benzodiazepines were the pharmacological classes more involved in the drug interactions. Despite the tools recommended risperidone and quetiapine when the use of antipsychotics were inevitable; levodopa + carbidopa for Parkinson's disease; and short and intermediate half-life benzodiazepines; the quality of the evidence needs to be assessed. In this review, sleep hygiene; deprescription; medication review; and clinical monitoring of adverse drug reactions are strongly recommended. In addition, to consider agomelatine, bupropion, moclobemide and melatonin as potential safer options for benzodiazepines. CONCLUSION: Knowing the clinical conditions or risk morbidities associated with the use of potentially inappropriate medications and management of these medications for safer therapeutic equivalents or non-pharmacotherapeutic alternatives are relevant for patient safety.

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.

Clinical pharmacy services in Brazil, particularly cardiometabolic diseases: a systematic scoping review and meta-analyses

OBJECTIVE: To map the clinical pharmacy services conducted in Brazil, their characteristics, outcomes, and process measures in general population, as well as the assessment of the clinical impact on people with cardiometabolic diseases (cardiovascular diseases and metabolic diseases). METHODS: A systematic scoping review and meta-analysis were conducted. The electronic searches were re-run in March 2020. To the clinical impact assessment, meta-analyses of cardiometabolic outcomes (i.e., change of systolic (SBP) and diastolic blood pressure (DBP), triglycerides, total cholesterol, glycated hemoglobin (HbA1c), fasting glycemia, LDL-, and HDL-cholesterol) were led. The risk of bias was assessed with the Cochrane Collaboration tools. RESULTS: 71 studies were identified (7,402 patients), being the majority quasi-experimental studies (n=41) and published by research groups of Southeast Brazil (n=33). Medication therapy management (n=62) was the most frequent clinical pharmacy service, performed on outpatient setting (n=45), with adults or elderly people (n=58) with hypertension (n=18) or diabetes (n=10). Process measures (n=58) (e.g. resolution of drug related-problem) were widely used as indicator, followed by clinical (n=44) (e.g. change in SBP), humanistic (n=12) (e.g. change in quality-of-life score assessed by Short-Form 36 Health Survey Questionnaire), and economic outcomes (n=3) (incremental cost-effectiveness ratio for reduction in HbA1c). Regarding the assessment of clinical impact of the services, 20 studies were included in meta-analyses, showing improvement in most cardiometabolic outcomes when considered individual studies. However, the evidence presents high risk of bias, high heterogeneity (median 67-90%) and imprecision, contributing to wide prediction intervals and low reliability. CONCLUSIONS: A predominance of studies on cardiometabolic diseases, process measures, and clinical outcomes were identified. Considering the assessment of the clinical impact of clinical pharmacy services in cardiometabolic diseases, an improvement in most cardiometabolic outcomes was showed, however, with low confidence and wide prediction interval. Therefore, development of larger studies with low risk of bias and major homogeneity is necessary for a better comprehension of clinical pharmacy service characteristics, benefits, and the population groups most benefited

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