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Rotational crossbreeding has not been widely studied in relation to the enteric methane emissions of dairy cows, nor has the variation in emissions during lactation been modeled. Milk infrared spectra could be used to predict proxies of methane emissions in dairy cows. Therefore, the objective of this work was to study the effects of crossbreeding on the predicted infrared proxies of methane emissions and the variation in the latter during lactation. Milk samples were taken once from 1,059 cows reared in 2 herds, and infrared spectra of the milk were used to predict milk fat (mean ± SD; 3.79 ± 0.81%) and protein (3.68 ± 0.36%) concentrations, yield (21.4 ± 1.5 g/kg dry matter intake), methane intensity (14.2 ± 2.0 g/kg corrected milk), and daily methane production (358 ± 108 g/d). Of these cows, 620 were obtained from a 3-breed (Holstein, Montbéliarde, and Viking Red) rotational mating system, and the rest were purebred Holsteins. Milk production data and methane traits were analyzed using a nonlinear model that included the fixed effects of herd, genetic group, and parity, and the 4 parameters (a, b, c, and k) of a lactation curve modeled using the Wilmink function. Milk infrared spectra were found to be useful for direct prediction of qualitative proxies, such as methane yield and intensity, but not quantitative traits, such as daily methane production, which appears to be better estimated (450 ± 125 g/d) by multiplying a measured daily milk yield by infrared-predicted methane intensity. Lactation modeling of methane traits showed daily methane production to have a zenith curve, similar to that of milk yield but with a delayed peak (53 vs. 37 d in milk), whereas methane intensity is characterized by an upward curve that increases rapidly during the first third of lactation and then slowly till the end of lactation (10.5 g/kg at 1 d in milk to 15.2 g/kg at 300 d in milk). However, lactation modeling was not useful in explaining methane yield, which is almost constant during lactation. Lastly, the methane yield and intensity of cows from 3-breed rotational crossbreeding are not greater, and their methane production is lower than that of purebred Holsteins (452 vs. 477 g/d). Given the greater longevity of crossbred cows, and their lower replacement rate, rotational crossbreeding could be a way of mitigating the environmental impact of milk production.
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Lactação , Leite , Feminino , Gravidez , Animais , Bovinos , Hibridização Genética , Reprodução , MetanoRESUMO
Medicines are special goods that cover the health needs of the population. In recent decades, the pharmaceutical industry has changed its research and development strategy, shifting its focus from the exploration of medicines for chronic diseases affecting a large part of the population to the search for drugs for rare diseases that affect a small number of people.This lack of a mass consumer base is reflected in a selective offer of a few very high-cost products aimed at certain diseases, which hinders both patient access and financial coverage.This article reviews the issue of high-cost medicines, including its cultural, legal, political, economic, and health aspects. It emphasizes the differences between various medicines in terms of their efficacy in changing the natural course of diseases, their market price, the consequences of their cost for healthcare funders, and the cost-opportunity ratio of having to pay for them at the expense of other essential resources.Finally, the article reflects on the legitimate rights of each individual to claim access to high-cost medicines when they are considered essential to recover a person's health, and on how guaranteeing such coverage can affect the collective rights of the population. Concrete examples that illustrate this situation are provided.
Medicamentos são bens especiais que atendem às necessidades de saúde da população. Nas últimas décadas, a indústria farmacêutica mudou sua estratégia de pesquisa e desenvolvimento, deixando de explorar medicamentos para doenças crônicas que afetam grande parte da população e passando a buscar medicamentos para poucas pessoas com doenças raras.Esse número limitado de consumidores se reflete em uma oferta seletiva de poucos produtos de preço elevado para determinadas doenças, dificultando o acesso dos pacientes e a obtenção de cobertura dos agentes financiadores da saúde.Neste artigo, analisa-se a questão dos medicamentos de alto custo e incorpora-se ao debate o contexto sanitário, cultural, jurídico, político e econômico. São enfatizados os seguintes aspectos: diferenças entre os diferentes medicamentos em termos da eficácia em mudar o curso natural das doenças para as quais são indicados; determinação do preço pelo qual esses medicamentos são vendidos no mercado; consequências desse preço para os agentes financiadores da saúde; e a relação custo-oportunidade de ter de pagar por esses medicamentos em detrimento de outros recursos considerados essenciais.Por fim, reflete-se sobre os direitos legítimos de cada indivíduo de reivindicar acesso a medicamentos de alto custo, por considerá-los essenciais para recuperar a própria saúde, e como a garantia dessa cobertura pode afetar os direitos coletivos da população; também são fornecidos exemplos concretos que ilustram essa situação.
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Objective: Conduct an analysis to determine the existence and updating of national essential medicines lists (EMLs) and clinical practice guidelines (CPGs) for the treatment of diabetes in Latin America and the Caribbean (LAC); and compare the medicines included in each country's list and guidelines both with each other and with those of the World Health Organization (WHO). Methods: Cross-sectional study. EMLs and CPGs for diabetes were found on the websites of the Pan American Health Organization and national health authorities. Medicines were noted and analyzed according to pharmacological group, based on the fourth level of nomenclature of the Anatomical Therapeutic Chemical (ATC) classification system. F1 scoring was used to assess the proximity of EMLs to the WHO Model List of Essential Medicines (MLEM). Results: Of the total number of countries, 87.2% have EMLs, and 91% have CPGs (78% and 45% updated in the last five years, respectively). Compared to the six hypoglycemic groups of the MLEM, the EMLs had a median (range) of 6 (4-13) and an F1 score of 0.80; This indicates proper alignment. CPGs had a median (range) of 12 (1-12) hypoglycemic drugs compared to eight in the WHO guidelines. CPGs had a median of 15 more drugs than their respective EMLs. Conclusions: While most LAC countries have EMLs and CPGs for diabetes, the lack of concordance among them limits their effectiveness. It is necessary to align the processes and criteria for the development of these two tools for policymaking on medicines.
Objetivos: Analisar a existência e a atualização das listas nacionais de medicamentos (LNMs) e guias de prática clínica (GPCs) para o tratamento do diabetes na América Latina e no Caribe (ALC). Comparar os medicamentos incluídos nas listas e nas diretrizes de cada país entre si e com as da Organização Mundial da Saúde (OMS). Métodos: Estudo transversal. Foram identificadas LMNs e GPCs para o diabetes nos sites da Organização Pan-Americana da Saúde e das autoridades sanitárias nacionais. Os medicamentos foram pesquisados e analisados por grupo farmacológico de acordo com o quarto nível da classificação ATC. A pontuação F1 foi utilizada para avaliar o grau de proximidade das LMNs com a lista-modelo de medicamentos essenciais (LMME) da OMS. Resultados: Do total de países, 87,2% dispõem de uma LNM e 91%, de GPCs (78% e 45%, respectivamente, atualizadas nos últimos 5 anos). Em comparação com os seis grupos de agentes hipoglicemiantes da LMME, as LMNs tinham uma mediana (intervalo) de 6 (4 a 13) e uma pontuação F1 de 0,80, o que indica uma conformidade adequada. As GPCs tinham uma mediana (intervalo) de 12 (1 a 12) agentes hipoglicemiantes, em comparação com 8 nos guias da OMS. As GPCs tinham uma mediana de 15 medicamentos a mais do que as respectivas LNMs. Conclusões: Embora a maioria dos países da América Latina e do Caribe disponha de LNMs e GPCs para o diabetes, a falta de concordância entre elas limita sua eficácia. É necessário alinhar os processos e os critérios de desenvolvimento dessas duas ferramentas da política de medicamentos.
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Biosimilars are biological medicines highly similar to a previously licensed reference product and their licensing is expected to improve access to biological therapies. This study aims to present an overview of biosimilars approval by thirteen regulatory authorities (RA). The study is a cross-national comparison of regulatory decisions involving biosimilars in Argentina, Australia, Brazil, Chile, Canada, Colombia, Europe, Hungary, Guatemala, Italy, Mexico, Peru and United States. We examined publicly available documents containing information regarding the approval of biosimilars and investigated the publication of public assessment reports for registration applications, guidelines for biosimilars licensing, and products approved. Data extraction was conducted by a network of researchers and regulatory experts. All the RA had issued guidance documents establishing the requirements for the licensing of biosimilars. However, only three RA had published public assessment reports for registration applications. In total, the investigated jurisdictions had from 19 to 78 biosimilars approved, most of them licensed from 2018 to 2020. In spite of the advance in the number of products in recent years, some challenges still persist. Limited access to information regarding the assessment of biosimilars by RA can affect confidence, which may ultimately impact adoption of these products in practice.
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Objective: Compare the health outcomes and financial outcomes of two systems for the procurement of prostheses: the traditional system, in which procurement is initiated when a product is requested; and the "Prosthesis Bank" model, based on a current inventory of supplies. Methods: Descriptive-analytical study of users of Ministry of Health services in the province of Buenos Aires, Argentina. The patients belonged to two study groups: 1) prostheses were provided through the traditional computerized system for hospital procurement and contracting, known as SIPACH; and 2) prostheses were provided by the Prosthesis Bank. The study was limited to endovascular prostheses (coronary stents) and hip prostheses. Official government databases were used. The study period was from 01/01/2018 to 31/10/2022. The variables analyzed were: age, sex, diagnosis, hospital, type of implant or prosthesis, date of request, date received, unit price, direct and indirect costs, average cost of daily hospitalization, cost-effectiveness, and budgetary impact. Results: A total of 4 106 applications were analyzed. In the traditional system: 13.5% of patients did not get their prostheses; it took 50 days longer than with the Prosthesis Bank; and total costs were higher in SIPACH (coronary stent, +463%; hip prosthesis, +133%). The Prosthesis Bank saved USD 3.2 million annually and prevented 22 deaths through early provision of endovascular prostheses. Conclusions: The Prosthesis Bank proved to be superior to the traditional model for providing prostheses, both in terms of health-by achieving better access, shortening waiting times, and avoiding deaths-and financially-by significantly reducing unit and overall prices, achieving significant savings in allocated budgets.
Objetivo: Comparar os resultados econômicos e sanitários de dois sistemas de aquisição de próteses: um sistema tradicional, no qual a compra é iniciada mediante solicitação, e um modelo em estoque chamado Banco de Próteses (BDP). Métodos: Estudo descritivo-analítico com usuários do Ministério da Saúde da província de Buenos Aires, Argentina. Os pacientes pertenciam a dois grupos de estudo: 1) próteses fornecidas pelo método tradicional do Sistema Informatizado de Aquisição e Contratações Hospitalares (SIPACH); e 2) próteses fornecidas pelo BDP. A análise se restringiu a próteses endovasculares do tipo stent coronariano e próteses de quadril. Foram utilizados bases de dados oficiais do governo. O período do estudo foi de 01/01/2018 a 31/10/2022. As variáveis analisadas foram: idade, sexo, diagnóstico, hospital, tipo de implante ou prótese; data de solicitação; data de aquisição; preço unitário, custos diretos e indiretos; custo médio diário de internação, relação custo-efetividade e impacto orçamentário. Resultados: Foram analisadas 4 106 solicitações. No sistema tradicional, 13,5% dos pacientes não receberam as próteses e houve 50 dias a mais de espera do que pelo BDP. Além disso, os custos totais foram maiores no SIPACH (+463% no caso dos stents coronários e +133% para as próteses de quadril). O BDP economizou US$ 3,2 milhões ao ano e evitou 22 mortes com o fornecimento precoce de próteses endovasculares. Conclusões: O BDP demonstrou superioridade em relação ao modelo tradicional de fornecimento de próteses, tanto em termos sanitários, ao oferecer maior acesso, diminuir o tempo de espera e evitar mortes, quanto em termos econômicos, ao reduzir significativamente os preços unitários e totais, gerando economias significativas nos orçamentos alocados.
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PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.
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Uso de Medicamentos , Armazenamento e Recuperação da Informação , Humanos , América Latina , Inquéritos e QuestionáriosRESUMO
The Covid-19 pandemic with its associated quarantine and isolation has had a dramatic impact on the elderly. In order to mitigate this, the National University of La Plata and the Agence Universitaire de la Francophonie set up a health surveillance and early warning project for the elderly in Buenos Aires, Argentina. This interventional study, has included 1,964 people. A general health and quality of life questionnaire was completed by all participants at the beginning of the isolation, and another time a year later.
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COVID-19 , Idoso , Argentina/epidemiologia , Humanos , Pandemias , Qualidade de Vida , QuarentenaRESUMO
This work describes select narratives pertaining to undergraduate teaching and mentorship at UCLA Chemistry and Biochemistry by Alex Spokoyny and his junior colleagues. Specifically, we discuss how individual undergraduate researchers contributed and jump-started multiple research themes since the conception of our research laboratory. This work also describes several recent innovations in the inorganic and general chemistry courses taught by Spokoyny at UCLA with a focus of nurturing appreciation for research and creative process in sciences including the use of social media platforms.
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OBJECTIVE: To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. METHODS: Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating "R" for each region of Argentina, and this data was compared with other countries. RESULTS: The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. CONCLUSIONS: The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.
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OBJECTIVE: Evaluate the feasibility of monitoring the quality of use of medicines in health institutions in countries of the Region of the Americas by means of rational prescription indicators. METHODOLOGY: A quantitative study of the use of medicines was conducted during the period 2016-2018. Rational prescription indicators were developed and selected in accordance with international reference values and the best available evidence for: 1) anti-inflammatory drugs: prescription of ibuprofen and/or naproxen as a percentage of all prescribed non-steroidal anti-inflammatory drugs; 2) oral antidiabetics: metformin as a percentage of all prescribed antidiabetics, and metformin and/or sulfonylureas as a percentage of all prescribed antidiabetics; 3) insulins: crystalline insulin and NPH as a percentage of total prescribed insulins; and 4) antihypertensive drugs: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs-II), and thiazide diuretics as a percentage of all prescribed antihypertensives. The defined daily dose (DDD) per 1 000 inhabitants was used as a measure of consumption per institution. RESULTS: Prescription of metformin as a percentage of all antidiabetics was lower than the value of the reference indicator (27.9%-67.6% vs. 88%), while the prescription of metformin and/or a sulfonylurea was comparable with that value (80.9%-97.5% vs. 88%). The values of NPH, crystalline, and NPH/crystalline insulin in relation to all prescribed insulins were variable with respect to the reference indicator (37.1%-100% vs. 75%). Prescription of ibuprofen and naproxen was below the value of the indicator (20%-50% vs. 80%). The percentage of ACE inhibitors, ARBs, and thiazides with respect to all antihypertensives ranged from 65.2%-77.2% to 65%, consistent with the value of the proposed indicator. CONCLUSIONS: The feasibility of applying the selected and constructed indicators of rational prescription was demonstrated. These indicators provide useful information for analyzing the quality of prescription in health institutions in countries in the Region and are a useful tool for periodically monitoring it.
OBJETIVO: Avaliar a viabilidade de monitorar a qualidade do uso de medicamentos em instituições de saúde em países da Região das Américas por meio de indicadores de prescrição racional. MÉTODOS: Foi realizado um estudo quantitativo do uso de medicamentos durante o período 2016-2018. Indicadores de prescrição racional foram desenvolvidos e selecionados de acordo com referências internacionais e as melhores evidências disponíveis para: 1) anti-inflamatórios: prescrições de ibuprofeno e/ou naproxeno como porcentagem da prescrição total de anti-inflamatórios não esteroidais; 2) antidiabéticos orais: prescrições de metformina como porcentagem de todos os antidiabéticos prescritos, metformina e/ou sulfonilureias como porcentagem de todos os antidiabéticos prescritos; 3) insulinas: insulina cristalina e NPH como porcentagem do total de insulinas prescritas; e 4) anti-hipertensivos: porcentagem de inibidores da enzima de conversão da angiotensina (IECA), antagonistas do receptor da angiotensina II (BRA) e diuréticos tiazídicos sobre o total de anti-hipertensivos prescritos. A dose diária definida (DDD) por 1 000 habitantes por dia (DHD) foi usada como medida de consumo por instituição. RESULTADOS: A prescrição de metformina em relação a todos os antidiabéticos foi inferior ao valor do indicador de referência (27,9%-67,6% x 88%), enquanto a prescrição de metformina e/ou uma sulfonilureia foi comparável ao valor de referência (80,9%-97,5% x 88%). As porcentagens de prescrição de insulina NPH, cristalina e NPH/cristalina em relação a todas as insulinas prescritas foram variáveis em relação ao valor de referência (37,1%-100% x 75%). A prescrição de ibuprofeno e naproxeno foi inferior ao valor de referência (20%-50% x 80%). A porcentagem de IECA, BRA e tiazídicos em relação a todos os anti-hipertensivos variou entre 65,2% e 77,2%, compatível com o valor do indicador proposto (65%). CONCLUSÕES: Demonstrou-se a viabilidade de aplicação dos indicadores de prescrição racional aqui selecionados e construídos, os quais fornecem informações úteis para analisar a qualidade da prescrição nas instituições de saúde dos países da Região e representam uma ferramenta útil para seu monitoramento periódico.
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OBJECTIVE: The objective of this study was to propose a model of health care for sexual workers (SWs) and transvestites (Ts) groups who were historically excluded from health services. MATERIALS AND METHODS: A prospective descriptive/analytical study with an intervention stage was performed, focusing on the health status of SWs and Ts. Access to health system, inclusion into social programs, beneficiaries' participation, and rate of risk behaviors were variables measured before and after intervention that consist in a program based on promotion/prevention activities and complete health care service suitable to SW-T needs. RESULTS: Nine hundred and fifty SW-Ts were included. At baseline, 99.7% lacked health insurance and 90.1% had no access to the health care. These data were compared with those obtained after attention quadruplicated among SW because of the implementation of the program. Risky sexual behaviors were reduced by 25 times. SWs have their own leader of health institutions and coordinate themselves with the program's activities. CONCLUSION: Responsibility of the state's authorities on vulnerable groups must focus on their inclusion. To this end, health services must adapt themselves in order to attend those community groups with special needs. Active participation of the target population contributes to viability of this type of proposals, and it is essential for the project's success.
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Atenção à Saúde/organização & administração , Profissionais do Sexo , Adulto , Argentina , Atenção à Saúde/métodos , Acessibilidade aos Serviços de Saúde/organização & administração , Humanos , Masculino , Modelos Organizacionais , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , Travestilidade , Sexo sem Proteção/prevenção & controleRESUMO
INTRODUCTION: The economic consequences of mandatory coverage, through judicial means, of high-priced medications constitutes a growing problem, which merits knowing its local characteristics to provide possible solutions. OBJECTIVE: To identify medications, diseases involved, economic impact and contextual factors of the judicialization of high-priced medications in the Argentine Health System(MEP). METHODS: Quali-quantitative descriptive study that retrospectively analyzed legal protection resources by MEP from three national and provincial databases from January 2017 to December 2020, evaluating the existing relationship between lawsuits with regulatory approval, inclusion in benefit packages and relationship with journalistic articles for the three most frequently prosecuted drugs. RESULTS: 405 lawsuits were included, mainly from the Ministry of National Health. The three most prosecuted medications were nusinersen (21.7%), palbociclib (5.9%) and agalsidase-alfa (4.7%). Only 69.4% of medications were approved for marketing in Argentina at the time of the protection; 45.7% were incorporated into the Single Reimbursement System, and 16.8% had a report from the National Commission for the Evaluation of Health Technologies and Clinical Excellence (CONETEC), which was negative in 87.1% of cases. The average time from request to provision of the medication was 150 days. A temporal correlation was observed between the appearance of the MEP in the national graphic press and the appeals occurrence. CONCLUSIONS: Judicialization focused on very highpriced medications for rare or oncological diseases. The rulings were mostly in favor of the plaintiff, and access times to the medication took a long time. The mass media anticipated the judicial processes.
Introducción: Las consecuencias económicas de la cobertura obligatoria, vía judicial, de medicamentos de alto precio constituye un problema creciente, que amerita conocer sus características locales para aportar posibles soluciones. OBJETIVO: Identificar medicamentos, enfermedades, impacto económico y factores contextuales de la judicialización de medicamentos de alto precio (MEP) Argentina. Métodos: Estudio descriptivo cuali-cuantitativo que analizó retrospectivamente recursos de amparos legales por MEP de tres bases de datos nacionales y provinciales durante 4 años, evaluando relación existente entre amparos con aprobación regulatoria, inclusión de los MEP al paquete de beneficios y relación con notas periodísticas. RESULTADOS: Se incluyeron 405 amparos provenientes principalmente del Ministerio de Salud Nacional. Los tres medicamentos más judicializados fueron nusinersen (21.7%), palbociclib (5.9%) y agalsidasa-alfa (4.7%). Solo el 69.4% de los medicamentos se encontraban aprobados para la comercialización en Argentina al momento del amparo; el 45.7% se encontraban incorporados al Sistema Único de Reintegros y el 16.8% contaban con informe de la Comisión Nacional de Evaluación de Tecnologías Sanitarias y Excelencia Clínica (CONETEC), negativa en el 87.1% de casos. El tiempo promedio desde la solicitud hasta la provisión del medicamento fue de 150 días. Se observó una correlación temporal entre la aparición del MEP en la prensa nacional gráfica y la presentación de amparos de dicho MEP. CONCLUSIONES: La judicialización se concentró en medicamentos de altísimo precio para enfermedades poco frecuentes u oncológicas. Los fallos fueron mayoritariamente a favor del demandante, siendo los tiempos de acceso al medicamento prolongados. Los medios de comunicación anticiparon los procesos judiciales.
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Custos de Medicamentos , Argentina , Humanos , Estudos Retrospectivos , Custos de Medicamentos/legislação & jurisprudência , Custos de Medicamentos/estatística & dados numéricosRESUMO
The tyrosine kinase Inhibitor (TKI) imatinib is approved for the treatment of the chronic phase of chronic myeloid leukemia (CP-CML). Pharmacokinetic studies have highlighted the importance of inter-patient variability on imatinib plasma trough concentrations (ima[C]min). In the OPTIM-imatinib trial, we demonstrated that therapeutic drug monitoring (TDM) is able to improve the molecular response of CP-CML patients treated with imatinib. Here, we analyzed the constitutional exomes and RNAseq data of these patients. We performed an association analysis between the constitutional genetic variants of the patients and their ima[C]min, measured after 12 weeks of treatment with 400 mg once daily. Using linear regression, we identified 50 SNPs that showed excess heterozygosity depending on the ima[C]min. Ten SNPs were from non-coding sequences, and among the 40 remaining, 30 (from 25 genes) could be split into two categories. The first group of 16 SNPs concerns genes encoding extracellular matrix, cell junction, and membrane proteins. Coincidentally, cell adhesion proteins were also identified by RNA-seq as being overexpressed in patients with high ima[C]min. The other group of 14 SNPs were from genes encoding proteins involved in transcription/translation. Although most of the SNPs are intronic variants (28), we also identified missense (3), synonymous (4), 5'/3' (2), splicing (1), and upstream (4) variants. A haplotype analysis of four genes showed a significant association with high ima[C]min. None of the SNPs were significantly associated with the response. In conclusion, we identified a number of ima[C]min-associated SNPs, most of which correspond to genes encoding proteins that could play a role in the diffusion and transit of imatinib through membranes or epithelial barriers.
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BACKGROUND: Biosimilar medicines are defined as biological products highly similar to an already licensed biological product (RP). The market entry of biosimilars is expected to reduce the costs of biological treatments. OBJECTIVE: This study aims to evaluate the range of differences between the prices of biosimilars and the corresponding RP for biologicals approved in four countries. METHOD: This is a cross-national comparison of pricing of biosimilars in Argentina, Australia, Brazil, and Italy. The study examined online price databases provided by the national authorities of the investigated countries. Biosimilar price difference was calculated by subtracting the unit price of the biosimilar by the unit price of the RP, and then dividing it by the unit price of the RP. The results were presented as percentage. RESULTS: Brazil had the highest median price reduction (- 36.3%) in biosimilars price, followed by Italy (- 20.0%) and Argentina (- 18.6%). All the biosimilars in Italy were priced below the RP presenting a minimum reduction of 6.3%, while in Australia, most of the prices of biosimilars were equal to the RP. In Argentina, one infliximab-biosimilar displayed price above the RP (40.7%) while the lower priced brand had a reduction of 14.4%. Brazil had four biosimilars with prices above the respective RP, including isophane insulin (1), insulin glargine (1) and somatropin (2). CONCLUSION: The study revealed a marked dispersion in the price's differences between biosimilars and RP across the studied countries. Governments should evaluate whether their policies have been successful in improving affordability of biological therapies.
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Medicamentos Biossimilares , Medicamentos Biossimilares/economia , Itália , Argentina , Brasil , Austrália , Humanos , Custos de Medicamentos , Custos e Análise de CustoRESUMO
An 11-year-old girl with a history of imperforate anus, urinary tract infection, and intermittent episodes of constipation presented with abdominal pain and nausea for 1 week. The x-rays revealed hydrometrocolpos and fused pelvic kidney with a single hydronephrotic ureter. The vaginal examination revealed a nonpermeable transverse vaginal septum. The collection was temporarily drained and symptoms resolved. The patient was scheduled for definitive vaginal reconstructive surgery. In this case, it is worth noting the association of infrequent malformations and also the signs and symptoms very common in pediatric practice due to a pathology rarely considered in the differential diagnosis, and the importance of an early and complete assessment of this type of malformations for a timely treatment.
Una niña de 11 años de edad con antecedentes de ano imperforado, infección urinaria y episodios de constipación intermitentes se presentó a la consulta con cólicos abdominales y náuseas de una semana de evolución. Estudios radiológicos revelaron hidrometrocolpos y fusión renal pélvica con uréter único hidronefrótico. El examen vaginal evidenció un tabique transverso no permeable. Se evacuó temporalmente la colección con resolución de los síntomas. La paciente fue programada para cirugía vaginal reconstructiva definitiva. Se destaca en este caso no solo la asociación de malformaciones infrecuentes, sino una sintomatología muy común en la práctica pediátrica a causa de una patología rara vez considerada en el diagnóstico diferencial, y la importancia de una evaluación precoz y completa de este tipo de malformaciones para un tratamiento oportuno.
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Anus Imperfurado , Rim , Vagina , Humanos , Feminino , Adolescente , Dor Abdominal/etiologia , Náusea/etiologia , Anus Imperfurado/diagnóstico , Anus Imperfurado/cirurgia , Infecções Urinárias , Ureter/diagnóstico por imagem , Constipação Intestinal , Vagina/anormalidades , Vagina/diagnóstico por imagem , Cintilografia , Imageamento por Ressonância Magnética , Rim/diagnóstico por imagemRESUMO
INTRODUCTION: Knowing the characteristics of the pharmaceutical market allows obtaining sensitive information to understand the supply, demand and access of the population to medicines. In order to provide primary data regarding the marketing of drugs in Argentina, the following research was performed. METHOD: This is a cross-sectional quantitative-qualitative descriptive study of the Argentine pharmaceutical market, taking into account 30 years of official information provided by the National Regulatory Agency (ANMAT). RESULTS: Two hundred and sixteen laboratories (182 national) drug producers / importers, 53 distributors and 479 drugstores (wholesale drug distribution establishments) were identified. A high concentration of marketing was detected, grouping 90% in only 5 intermediaries. There are currently 6670 products/certificates in the country, an amount that fluctuated over the last 30 years. Six laboratories are owners of between 116 and 208 certificates; 84% of these products come from national laboratories, 5002 are mono-drugs, while 83% are marketed under a fancy name. The three main indications for which the registration of drugs in Argentina is intended are diseases of digestive system, nervous system and infectious diseases; 58% of the marketed products consist of oral formulations. DISCUSSION: Based on data provided by this study, it is possible to assert that the Argentinian pharmaceutical market has a majority share of national capital, with a great concentration in a few pharmaceutical companies and distributors. The products are mostly available as non-combined drugs, in their oral form, and available by their brand names.
Introducción: Conocer las características del mercado farmacéutico permite obtener información sensible para entender la oferta, la demanda y el acceso de la población a los medicamentos. Con el objetivo de aportar datos primarios respecto a la comercialización de fármacos en Argentina, se desarrolló la siguiente investigación. Métodos: Se trata de un estudio descriptivo cuantitativo-cualitativo transversal del mercado farmacéutico argentino, tomando en cuenta 30 años de información oficial aportada por la Agencia Reguladora Nacional (ANMAT). Resultados: Se identificaron 216 laboratorios (182 nacionales) productores/importadores de medicamentos, 53 distribuidores y 479 droguerías (establecimientos de distribución de medicamentos al por mayor). Se detectó una alta concentración de la comercialización, agrupándose el 90% de la misma, en solo 5 intermediarios. En el país existen actualmente 6670 productos/certificados, cantidad que fluctuó a lo largo de los últimos 30 años. Seis laboratorios son dueños de entre 116 y 208 certificados. El 84% de estos productos provienen de laboratorios nacionales, 5002 son monofármacos, mientras que el 83% se comercializa bajo un nombre de fantasía. Las tres principales indicaciones a las que se destina el registro de medicamentos en la Argentina son enfermedades del aparato digestivo, sistema nervioso, e infecciosas; el 58% es comercializado como formulaciones orales. Discusión: el presente trabajo muestra que el mercado farmacéutico argentino tiene una participación mayoritaria de capitales nacionales, existiendo gran concentración en pocas empresas productoras y distribuidoras. Los productos son mayormente monodrogas comercializadas en forma oral y ofrecidas por su nombre de fantasía.
Assuntos
Estudos Transversais , Humanos , Argentina , Preparações FarmacêuticasRESUMO
INTRODUCTION: In Argentina, high-cost drugs (HCD) induce a high economic burden for all the health system sectors. However, it does not exist in Argentina any data that indicates the real problem of HCD for Social Security. That is why, the present study explores the economic impact of the HCD for one of the main Institutions of the country. METHODS: A descriptive study with an analytical stage was carried out based on data obtained from management, pharmacy and accounting area. Each drug was classified according to WHO recommendation (Anatomical-Therapeutic-Chemical-ATC classification). The prices were expressed in three ways: nominal value at the time of acquisition in local currency, updated using the CER (reference stabilization coefficient), and in US dollars. A total of 105 324 HCD dispensed were evaluated, which corresponded to 258 011 units destined to 10 450 patients. RESULTS: Total annualized spend was US$57 million (US$6220 per patient). Only 1.9% of affiliates required HCD, although those expenses represented 21.9% of the institutions' total income. The first 5 drugs associated to the highest expenditure were enzalutamide, bevacizumab, nivolumab, palbociclib, pembrolizumab. Oncological and rheumatological diseases represented 62.8% of the HCD costs. CONCLUSION: Considering the results obtained, it can be deduced that if the HCD problem is approached in a scattered way by each subsector, it will become a potential risk for health system defund. The HCD topic requires of global policies at national or even regional level.
Introducción: En Argentina, los medicamentos de alto costo (MAC) generan una carga económica elevada que deben afrontar las instituciones sanitarias. Sin embargo, no existe a la fecha un estudio en Argentina que indique la magnitud del real problema de los MAC para la Seguridad Social. El presente trabajo, explora cuál es su impacto económico para una de las principales Obras Sociales del país. Métodos: Se realizó un estudio descriptivo con etapa analítica a partir de datos obtenidos en gerencia de prestaciones, área farmacia y área contable de la institución. Cada medicamento fue clasificado según recomendación de OMS (clasificación Anatómica-Terapéutica- Química-ATC). Los precios fueron consignados en tres valores: nominal al momento de adquisición, actualizado a pesos fin de 2021 utilizando el CER (coeficiente de estabilización de referencia), y en dólares (USD). Se evaluaron 105 324 dispensas de MAC, correspondientes a 258 011 unidades para 10 450 afiliados. Resultados: El gasto total anualizado fue 57 millones de dólares (USD), y por usuario 6220 USD. Solo 1.9% de los afiliados requirieron MAC, aunque el gasto fue del 21.9% de los ingresos (aportes + contribuciones). Los primeros 5 medicamentos que generaron el mayor gasto fueron enzalutamida, bevacizumab, nivolumab, palbociclib, pembrolizumab. Las enfermedades oncológicas y reumatológicas representaron el 62.8% del gasto. Conclusión: A la luz de los resultados, se deduce que los MAC constituyen un riesgo potencial de desfinanciación del sistema de salud si son abordados de manera atomizada por cada subsector. Los MAC requieren de políticas globales de carácter nacional y/o regional.
Assuntos
Gastos em Saúde , Previdência Social , Humanos , ArgentinaRESUMO
The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere with a given protein-protein interaction (IP) is a promising strategy with potential clinical application. Little is known about the impact of fusing a TPP with an IP, both in terms of internalization and functional effect. Here, we analyze these aspects in the context of breast cancer, targeting PP2A/SET interaction, using both in silico and in vivo approaches. Our results support the fact that state-of-the-art deep learning approaches developed for protein-peptide interaction modeling can reliably identify good candidate poses for the IP-TPP in interaction with the Neuropilin-1 receptor. The association of the IP with the TPP does not seem to affect the ability of the TPP to bind to Neuropilin-1. Molecular simulation results suggest that peptide IP-GG-LinTT1 in a cleaved form interacts with Neuropilin-1 in a more stable manner and has a more helical secondary structure than the cleaved IP-GG-iRGD. Surprisingly, in silico investigations also suggest that the non-cleaved TPPs can bind the Neuropilin-1 in a stable manner. The in vivo results using xenografts models show that both bifunctional peptides resulting from the combination of the IP and either LinTT1 or iRGD are effective against tumoral growth. The peptide iRGD-IP shows the highest stability to serum proteases degradation while having the same antitumoral effect as Lin TT1-IP, which is more sensitive to proteases degradation. Our results support the development of the TPP-IP strategy as therapeutic peptides against cancer.
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An antimicrobial consumption (AMC) study was performed in Trinidad and Tobago at the Eastern Regional Health Authority (ERHA). A retrospective, cross-sectional survey was conducted from 1 November 2021 to 30 March 2022. Dosage and package types of amoxicillin, azithromycin, co-amoxiclav, cefuroxime, ciprofloxacin, levofloxacin, moxifloxacin, nitrofurantoin and co-trimoxazole were investigated. Consumption was measured using the World Health Organization's Antimicrobial Resistance and Consumption Surveillance System methodology version 1.0, as defined daily doses (DDD) per 1000 population per day (DID). They were also analyzed using the 'Access', 'Watch' and 'Reserve' classifications. In the ERHA, AMC ranged from 6.9 DID to 4.6 DID. With regards to intravenous formulations, the 'Watch' group displayed increased consumption, from 0.160 DID in 2017 to 0.238 DID in 2019, followed by a subsequent drop in consumption with the onset of the COVID-19 pandemic. Oral co-amoxiclav, oral cefuroxime, oral azithromycin and oral co-trimoxazole were the most highly consumed antibiotics. The hospital started off as the higher consumer of antibiotics, but this changed to the community. The consumption of 'Watch' group antibiotics increased from 2017 to 2021, with a drop in consumption of 'Access' antibiotics and at the onset of COVID-19. Consumption of oral azithromycin was higher in 2021 than 2020.
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INTRODUCTION AND IMPORTANCE: Nodular melanoma is the second most frequent cutaneous melanoma worldwide and due to its rapid growth rate and non-malignant appearance, is the most aggressive one. In its polypoid form, it is usually found in mucosal areas, but can also be seen on the trunk. This case is presented because it is an unusual manifestation and surgical treatment required wide excision, however, the patient's evolution is favorable. CASE PRESENTATION: 70-year-old female patient shows a progressively growing lesion with irregular border, abnormal color and a heterogeneous appearance. The biopsy yields the histological diagnosis of nodular polypoid melanoma. The surgical technique results in the resection of a 10 × 9 × 67 cm piece with favorable evolution of the patient. CLINICAL DISCUSSION AND CONCLUSIONS: The surgical technique of margin widening is considered a recommended option for polypoid nodular back melanomas. Although the excision is considered vast, the patient's evolution may turn out to be favorable.