Efficacy and safety of immunotherapies for the treatment of high-grade gliomas: a systematic review and meta-analysis

Background/Aim: High-grade gliomas are aggressive brain neoplasms usually refractory to treatment. Recently new treatment approaches have emerged, including immunotherapies. Hence, the aim of the present study was to evaluate the efficacy and safety of immunotherapies in adult patients with high-grade gliomas. Methods: Searches were performed in three databases for relevant studies published until December 2020. Title and abstract screening, full-text review, data extraction, and risk of bias assessment were performed independently by two reviewers. Risk of bias assessment was performed according to the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Meta-analyses were performed with Review Manager software (version 5.4.1), using risk ratio and 95% confidence intervals as measure of effect, the Mantel-Haenszel method, and random effects models. The quality of evidence assessment was conducted according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nineteen studies were included in the systematic review, of which 15 reported comparable data for meta-analyses. The outcomes assessed in the meta-analyses were overall survival (OS) and progression-free survival (PFS), with subgroups at 6, 12, and more than 12 months. No statistical differences were observed between immunotherapy and conventional treatment, except for the OS subgroup over 12 months. The certainty on the evidence was moderate. Conclusion: There was no evidence of an additional benefit of immunotherapy compared to standard treatment in the synthesis of results from clinical trials. Further high-quality clinical trials are needed to improve the quality of evidence concerning immunotherapies for the treatment of high-grade gliomas.

Pharmacovigilance: an evaluation on the practice of pharmacists acting in pharmacies and drugstores

Abstract Pharmacists acting in pharmacies and drugstores stores are some of the most accessible healthcare providers and the last to intervene before the patient takes their medicine. This puts the pharmacist in a position of authority that should be harnessed for the benefit of health. Thus, this professional is strategic for performing pharmacovigilance. Our objective of this study was to interrogate the practice of pharmacists in relation to pharmacovigilance activities, and to identify difficulties and possible stimuli for the improvement these activities in pharmacies and drugstores. The information was collected through an online questionnaire via Survey Monkey®. The data were analyzed statistically using SPSS software. Responses were received from 5174 pharmacists: mostly young women within five years of graduation and experience in pharmaceutical retail. 81% of them reported having identified suspected substandard medicines, but only 16% used the Brazilian notification system Notivisa. More than 85% of pharmacists agreed with the importance of pharmacovigilance and the recognition of reporting services as part of pharmacist duties and pharmaceutical care. The main barriers to making notifications were the lack of access and knowledge about Notivisa. Pharmacists agreed that simplifying the system would be a stimulus for notifications, and requested more feedback from notifications, as well as material and courses to understand the notification process. Pharmacists have important data to feed into pharmacovigilance systems, recognize their responsibilities and are willing to contribute, but still demonstrate low compliance. Simplification of the system and training on it are likely to increase notifications.

Análise do acesso a medicamentos por usuários da atenção primária / Analysis of access to medicines by users of primary health care

O acesso aos medicamentos se dá por quatro variáveis: a disponibilidade destes, sua acessibilidade geográfica, a capacidade aquisitiva das pessoas e a aceitabilidade. O presente estudo teve como objetivo analisar o acesso a medicamentos pelos usuários da Atenção Primária do município de Piraquara - PR, para assim compreender as dificuldades e facilidades de acesso aos medicamentos fornecidos pelo Sistema Único de Saúde (SUS) no município. Foi realizado um estudo transversal por meio de entrevistas com usuários da Atenção Primária do município de maio a agosto de 2020. Os resultados obtidos demonstraram que 46,7% retiram medicação tanto na Atenção Primária quanto na secundária, e 29,6% dos entrevistados retiram medicação somente na Atenção Primária, sendo que 68,2% destes acessam o serviço a pé. As dificuldades mais levantadas pela população entrevistada para adquirir medicação e acessar os medicamentos foram a distância, a falta de medicação disponível no SUS, a infraestrutura até o local e a compra das medicações no sistema privado. Foi possível perceber com o estudo que o acesso aos medicamentos não é sinônimo somente da disponibilidade destes e que a melhora do serviço deve ser contínua.

Access to medicines occurs through four variables: their availability, their geographical accessibility, people's purchasing capacity and acceptability. The present study aimed to analyze access to medicine by users of primary health care in the city of Piraquara - PR in order to understand the difficulties and facilities of the access to medicines provided by the Unified Health System (SUS) in this city. A cross-sectional study was carried out using interviews with users of the primary health care in the city from May 2020 to August 2020. The results obtained showed that 46.7% withdraw medication in both primary and secondary care services, and 29.6% withdraw medication only in primary care service, with 68.2% of these users accessing this service on foot. The main difficulties raised by the population interviewed was he purchase of medication and the distance to access medications, the lack of medication available in the system, the infrastructure to get to the place and the purchase of medications in the private system. The study showed that having access to medicines does not mean the availability of these medicines and that the improvement of the service must be continuous.

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.

Effectiveness and tolerability of direct-acting antivirals for chronic hepatitis C patients in a Southern state of Brazil

ABSTRACT Background This study aimed to evaluate the clinical effectiveness in terms of sustained virological response and tolerability of available second generation direct-acting antivirals in Brazilian patients. Methods This was a retrospective observational study conducted in six centers in Southern Brazil. The sample comprised adult patients who were chronically infected with hepatitis C virus, regardless of virus genotype, fibrosis stage, or prior treatment. Statistical analysis was performed to compare the effectiveness among the treatments, and also to uncover the factors influencing the achievement of sustained virological response. Results A total of 296 patients were included in the study, with the majority receiving sofosbuvir with daclatasvir (59%) or sofosbuvir with simeprevir (26%). Overall sustained virological response rates were approximately 91.6%. For genotype 1, sofosbuvir with daclatasvir had an sustained virological response rate of approximately 95%, while the sustained virological response rate of sofosbuvir with simeprevir was 92%; this difference was statistically significant only for subtype 1b. The only treatment used for genotype 3 patients was sofosbuvir with daclatasvir, and lower rates of sustained virological response were observed for this group, compared to genotype 1 (84% versus 95%, p < 0.05). Apart from this difference between genotypes, and a difference between patients who achieved rapid virologic response compared with those who did not, there were no other statistically significant factors associated with sustained virological response. Conclusions The results point to the effectiveness of second-generation direct-acting antivirals in hepatitis C virus Brazilian patients, especially those with genotype 1. Furthermore, that patients with genotype 3 need more attention and adjustments in available treatment options.

Treatment interruption of biological drugs and tofacitinib in rheumatoid arthritis: A systematic review of case reports

The aim of this study was to evaluate interruption of treatment with biological drugs and tofacitinib due to adverse events in patients with rheumatoid arthritis. A systematic review was performed in the electronic databases MEDLINE, Cochrane, Scopus, CRD, IPA, Lilacs and Scielo. Case reports addressing interruption of treatment due to any adverse event related to abatacept (ABA), adalimumab (ADA), anakinra (ANA), certolizumab pegol (CER), etanercept (ETA), golimumab (GOL), infliximab (IFX), rituximab (RTX), secukinumab (SEC), tocilizumab (TCZ), tofacitinib (TOF) or ustekinumab (UST) in rheumatoid arthritis patients were evaluated. Baseline data, patient profile, previous and current treatments, cause of discontinuation and information on reintroduction of treatment were extracted from the case reports. One hundred and fifty-four studies (154 patients) reported 162 discontinuations of rheumatoid arthritis treatment due to adverse events (ETA = 57; IFX = 46; ADA = 32; TCZ = 13; RTX = 5; ANA = 3; GOL = 2; ABA = 2; TOF = 1; CER = 1; SEC = 0 and UST = 0). The mean age of patients was 56 (± 12.1) years and 82% were female. Seventy-four adverse events were confirmed (related to used drug), and 138 were observed in patients using anti-TNF. The most common adverse events were infections (21%), skin disease (15%), autoimmune disease (13%) and hematological disorders (9%). Case reports are important in the detection of rare adverse events and should be considered in the choice of appropriate therapy for patients.