Valor terapéutico añadido de los nuevos medicamentos aprobados en Brasil desde 2004 a 2016

O objetivo foi avaliar o nível de inovação terapêutica de novos medicamentos aprovados no Brasil ao longo de 13 anos e se eles atendem a necessidades de saúde pública. Foi feita uma análise comparativa descritiva da avaliação de valor terapêutico realizada pela Câmara de Regulação do Mercado de Medicamentos (CMED) e pelo boletim de medicamentos francês Prescrire para novos medicamentos licenciados no Brasil entre 1º de janeiro de 2004 e 31 de dezembro de 2016. Examinamos em que medida os novos medicamentos atendem a necessidade de saúde pública por meio de: checagem da inclusão em listas de medicamentos financiados pelo governo e/ou diretrizes clínicas; comparação de códigos da Classificação Anatômica Terapêutica Química (ATC, em inglês) e indicações de medicamentos com a lista de condições que mais contribuem para a carga de doença nacional; e avaliação de se os novos medicamentos tinham por objetivo tratar doenças negligenciadas. Foram aprovados 253 novos medicamentos. Antineoplásicos, imunossupressores, antidiabéticos e antivirais foram os mais frequentes. Trinta e três (14%) dos 236 medicamentos avaliados pela Câmara brasileira e 16 (8,2%) dos 195 avaliados pelo boletim francês Prescrire foram considerados inovadores. Trinta e seis medicamentos (14,2%) foram selecionados para cobertura no Sistema Único de Saúde (SUS), sete dos quais eram inovadores do ponto de vista terapêutico e nenhum dos quais tinha por objetivo tratar uma doença negligenciada. Em torno de 1/3 dos medicamentos aprovados tinha por objetivo o tratamento de doenças que figuram entre as principais contribuidoras da carga de doença no Brasil. Poucos medicamentos inovadores do ponto de vista terapêutico entraram no mercado brasileiro, dos quais apenas uma pequena proporção foi aprovada para ser coberta pelo SUS. Nossos resultados sugerem uma divergência entre necessidades de saúde pública, pesquisa e desenvolvimento (P&D) e procedimentos de licenciamento de medicamentos.This study aimed to assess the level of therapeutic innovation of new drugs approved in Brazil over 13 years and whether they met public health needs. Comparative descriptive analysis of therapeutic value assessments performed by the Brazilian Chamber of Drug Market Regulation (CMED) and the French drug bulletin Prescrire for new drugs licensed in Brazil, from January 1st 2004 to December 31st 2016. The extent to which new drugs met public health needs was examined by: checking inclusions into government-funded drug lists and/or clinical guidelines; comparing Anatomical Therapeutic Chemical Classification (ATC) codes and drug indications with the list of conditions contributing the most to the national disease burden; and assessing new medicines aimed to treat neglected diseases. 253 new drugs were approved. Antineoplastics, immunossupressants, antidiabetics and antivirals were the most frequent. Thirty-three (14%) out of 236 drugs assessed by the Brazilian chamber and sixteen (8.2%) out of 195 assessed by the French bulletin Prescrire were considered innovative. Thirty-six drugs (14.2%) were selected for coverage by the Brazilian Unified National Health System (SUS), seven of which were therapeutically innovative, and none were aimed to treat neglected disease. About 1/3 of the drugs approved aimed to treat conditions among the top contributors to Brazil’s disease burden. Few therapeutically innovative drugs entered the Brazilian market, from which only a small proportion was approved to be covered by the SUS. Our findings suggest a divergence between public health needs, research & development (R&D) and drug licensing procedures.El objetivo fue evaluar el nivel de innovación terapéutica de los nuevos medicamentos aprobados en Brasil durante 13 años y si cumplen con las necesidades sanitarias. Llevamos a cabo un análisis comparativo descriptivo acerca del valor terapéutico presente en las evaluaciones realizadas por la Cámara de Regulación del Mercado de Medicamentos (CMED) y la revista francesa Prescrire sobre los nuevos medicamentos autorizados en Brasil, desde el 1º de enero 2004 hasta el 31de diciembre de 2016. Su alcance, es decir, hasta qué punto los nuevos medicamentos cumplían con las necesidades de salud pública se comprobaron revisando las inclusiones en listas de medicamentos subvencionados por el gobierno y/o directrices clínicas; comparando los códigos de la Classificación Anatómicos Terapéuticos Químicos (ATC por sus siglas en inglés) y las indicaciones de los medicamentos respecto a la lista de enfermedades que contribuían a la mayor carga de morbilidad nacional; y asesorando si los nuevos medicamentos tenían como objetivo tratar enfermedades desatendidas. Se aprobaron 253 nuevos medicamentos. Los antineoplásicos, inmunosupresores, antidiabéticos y antivirales fueron los más frecuentes. Treinta y tres (14%), aparte de los 236 medicamentos evaluados por la Cámara Brasileña, y 16 (8,2%), aparte de los 195 evaluados por la revista francesa Prescrire, se consideraron innovadores. Treinta y seis medicamentos (14,2%) se seleccionaron para que tuvieran cobertura por el Sistema Único de Salud (SUS), siete de ellos eran terapéuticamente innovadores, y ninguno tenía como meta tratar enfermedades desatendidas. Alrededor de 1/3 de las medicinas aprobadas tenían como meta tratar problemas de salud entre las enfermedades con mayor carga de morbilidad en Brasil. Pocos medicamentos terapéuticamente innovadores accedieron al mercado brasileño y de éstos sólo una pequeña parte fueron aprobados para que fueran cubiertos por el SUS. Nuestros resultados sugieren una divergencia entre las necesidades públicas de salud, investigación & desarrollo (I&D) y los procedimientos para la autorización de medicamentos

Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF- beta(1) as compared with healthy nasal mucosa

Objective: To evaluate TGF-beta(1) expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).Methods: Cross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-beta 1 visualization. Then, the percentage of TGF-beta 1 expression in stroma and epithelium was objectively quantified using UT Morph software.Results: A lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05).Conclusion: the lower percentage of TGF-beta(1) expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.Universidade Federal de São Paulo, Dept Otolaryngol Head & Neck Surg, São Paulo, BrazilUniv Ghent, Ghent Univ Hosp, Dept Otorhinolaryngol, Upper Airway Res Lab, B-9000 Ghent, BelgiumUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otolaryngol Head & Neck Surg, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilWeb of Scienc

Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears

Rotator cuff tear is a common orthopedic condition. Metalloproteinases (MMP) and their inhibitors (TIMP) seem to play a role in the development of joint injuries and in the failure of tissue healing. However, the mechanisms of regulation of gene expression in tendons are still unknown. Epigenetic mechanisms, such as DNA methylation and microRNAs regulation, are involved in the dynamic control of gene expression. Here, the mRNA expression and DNA methylation status of MMPs (MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14) and TIMPs (TIMP1-3) and the expression of miR-29 family members in ruptured supraspinatus tendons were compared with non-injured tendons of individuals without this lesion. Additionally, the gene expression and methylation status at the edge of the ruptured tendon were compared with macroscopically non-injured rotator cuff tendon samples from the anterior and posterior regions of patients with tendon tears. Moreover, the possible associations between the molecular alterations and the clinical and histologic characteristics were investigated. Dysregulated expression and DNA methylation of MMP and TIMP genes were found across the rotator cuff tendon samples of patients with supraspinatus tears. These alterations were influenced at least in part by age at surgery, sex, smoking habit, tear size, and duration of symptoms. Alterations in the studied MMP and TIMP genes may contribute to the presence of microcysts, fissures, necrosis, and neovascularization in tendons and may thus be involved in the tendon healing process. In conclusion, MMPs and their inhibitors are regulated by epigenetic modifications and may play a role in rotator cuff tears.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Patol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Patol, Sao Paulo, SP, BrazilFAPESP: 2011/22548-2FAPESP: 2012/14768-5FAPESP: 2016/01392-8FAPESP: 2016/15785-1FAPESP: 2013/10691-0FAPESP: 2013/10791-5Web of Scienc

Disease awareness campaigns in printed and online media in Latvia : Cross-sectional study on consistency with WHO ethical criteria for medicinal drug promotion and European standards

Funding Information: Teresa Leonardo Alves declares no conflicts of interest. She has worked in the past for not-for-profit organizations which have advocated against the relaxation of the direct-to-consumer advertising ban in the European Union, namely Prescrire (2012–2016) and Health Action International (2006–2011). Elita Poplavska is a board member of not-for-profit organizations - Health Projects for Latvia and Health Action International (which aim to promote rational use of medicines and reduce influence of pharmaceutical advertisement). Signe Mezinska is a board member of not-for-profit organizations - Health Projects for Latvia and Health Action International (which aim to promote rational use of medicines and reduce influence of pharmaceutical advertisement). Ieva Salmane-Kulikovska declares no conflicts of interest. Liga Andersone declares no conflicts of interest. Aukje Mantel-Teeuwisse is the Managing Director of the WHO Collaborating Centre for Pharmaceutical Policy & Regulation, which receives no direct funding or donations from private parties, including the pharmaceutical industry. Research funding from public-private partnerships, e.g. IMI, Lygature (https://www.lygature.org), is accepted under the condition that no company-specific product or company-related study is conducted. The Centre has received unrestricted research funding from public sources, e.g. Netherlands Organisation for Health Research and Development (ZonMW), Zorg Instituut Nederland (ZIN), the Dutch Medicines Evaluation Board (MEB), and the Dutch Ministry of Health. Barbara Mintzes has acted as an expert witness on behalf of plaintiffs in a Canadian class action suit on cardiovascular risks of testosterone therapy. Publisher Copyright: © 2018 The Author(s).Background: European legislation prohibits direct-to-consumer advertising of prescription medicines, but allows drug manufacturers to provide information to the public on health and diseases. Our aim was to measure the frequency of disease awareness campaigns in Latvian media and assess their compliance with international and European standards. Methods: Materials on health/disease and treatments were collected between April and September 2015 from 12 newspapers and magazines and six online portals. Disease awareness campaigns were assessed using a previously developed instrument based on the WHO Ethical Criteria for Medicinal Drug promotion and European standards (EU law and pharmaceutical industry self-regulatory guidelines). Collected materials were used to examine the information provided on medical conditions and their diagnosis and treatment. The inter-rater reliability was calculated. Results: We collected 263 materials from print (n = 149) and online media (n = 114); 94 were news items and 169 were disease-awareness advertisements. Cancer, cardiovascular problems, allergies and respiratory diseases were common topics. Of the 157 campaigns assessed, non-compliance was identified in 149 cases (inter-rater reliability 90%), mainly due to misleading or incomplete information, lack of balance and the absence of a listed author/sponsor. Six disease awareness campaigns directly mentioned a pharmaceutical product by brand name and other four included the logo or name of a manufacturer, referred to a condition and indirectly mentioned a treatment, all in contravention with European law. Conclusions: The compliance of disease awareness campaigns in Latvian media with international and European standards is low. This raises concerns about the nature of information being conveyed. Through lack of balance, missing sponsorship information, and misleading or incomplete information, these campaigns could contribute to inaccurate self-diagnosis and generate demand among those who might not need medical treatment.publishersversionPeer reviewe

Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions: A cross-sectional study in six EU member states

Objective: In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector vaccines Vaxzevria® and Jcovden®. This study aimed to describe the public's knowledge of TTS and how it affected the willingness to be vaccinated with COVID-19 vaccines and other vaccines in six European countries. Methods: From June to October of 2022, a multi-country cross-sectional online survey was conducted in Denmark, Greece, Latvia, Netherlands, Portugal, and Slovenia. The minimum target of participants to be recruited was based on the size of the country's population. The results were analysed descriptively. Results: In total, 3794 respondents were included in the analysis; across the six countries, 33.3 %–68.3 % reported being familiar with signs and symptoms of TTS, although 3.1–61.4 % of those were able to identify the symptoms correctly. The reported changes in willingness to be vaccinated against COVID-19 and with other vaccines varied per country. The largest reported change in the willingness to be vaccinated with Vaxzevria® and Jcovden® was observed in Denmark (61.2 %), while the willingness to be vaccinated with other COVID-19 vaccines changed most in Slovenia (30.4 %). The smallest decrease in willingness towards future vaccination against COVID-19 was reported in the Netherlands (20.9 %) contrasting with the largest decrease observed in Latvia (69.1 %). Conclusion: Knowledge about TTS seemed to have influenced the public's opinion in Europe resulting in less willingness to be vaccinated with Vaxzevria® and Jcovden®. Willingness for vaccination against COVID-19 with other vaccines and widespread use of vaccines to prevent other diseases also differed and seemed to be determined by the approaches taken by national health authorities when reacting to and communicating about COVID-19 vaccination risks. Further investigation of optimal risk communication strategies is warranted

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio