[Concordance between essential medicines lists and diabetes guidelines in Latin America and the CaribbeanConcordância entre as listas de medicamentos essenciais e diretrizes para diabetes na América Latina e no Caribe]. / Concordancia entre las listas de medicamentos esenciales y las guías para diabetes en América Latina y el Caribe.

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.

Biosimilars approvals by thirteen regulatory authorities: A cross-national comparison.

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.

[Financial and health impact of two models of providing prostheses in a public health systemImpacto econômico e sanitário de dois modelos de fornecimento de próteses em um sistema público de saúde]. / Impacto sanitario económico de dos modelos de provisión de prótesis desde un sistema público de salud.

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.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

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.

[Implementation of a support system for isolated elderly people to limit the consequences of the Covid-19 epidemic in Buenos Aires]. / Un système de soutien aux personnes âgées isolées pour limiter les conséquences de la Covid-19 à Buenos Aires.

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.

Disparities in antimicrobial consumption and resistance within a country: the case of beta-lactams in Argentina.

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.

[Indicators of rational prescription of medicines: feasibility of application in institutions in the AmericasIndicadores de prescrição racional de medicamentos: viabilidade de aplicação em instituições das Américas]. / Indicadores de prescripción racional de medicamentos: factibilidad de aplicación en instituciones de las Américas.

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.

[Judicialization of high priced medications in Argentina: quali-quantitative study]. / Judicialización de medicamentos de alto precio en Argentina: estudio cuali-cuantitativo.

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.

Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients.

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.

A Cross-National Comparison of Biosimilars Pricing in Argentina, Australia, Brazil, and Italy.

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.

[Characterization of the drug supply in Argentina]. / Caracterización de la oferta de medicamentos en la República Argentina.

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.

[Economic impact of high-price/cost medicines on social security in Argentina. The case of the Institute for the Armed and Security Forces]. / Impacto económico de medicamentos de alto precio/costo en la Seguridad Social de Argentina. El caso del Instituto de Obra Social para las Fuerzas Armadas y de Seguridad.

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.

In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer.

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.

Antimicrobial Consumption from 2017 to 2021 in East Trinidad and Tobago: A Study in the English-Speaking Caribbean.

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.

Association between Consumption of Fluoroquinolones and Carbapenems and Their Resistance Rates in Pseudomonas aeruginosa in Argentina.

BACKGROUND: Irrational use of antimicrobials (ATMs) triggers microbial resistance (AMR) which has severe consequences for human health. ATM consumption varies among countries and within each territory. These data should be known, in order to perform local policies towards AMR reduction. This work aimed to expose the association of the level of consumption of carbapenems and fluoroquinolones with their resistance rates in Pseudomonas aeruginosa in Argentina. METHOD: Consumption of antimicrobials was expressed by defined daily dose (DDD)/1000 inhabitants for each ATM during one year period, discriminating by each country region. Resistance of P. aeruginosa to carbapenems/fluoroquinolones groups was recorded. Consumption/resistance ratio "R" was calculated for each region of the country, comparing results with other countries. RESULTS: P. aeruginosa resistance rate to fluoroquinolone (F) was 26.4% in blood samples and 29.7% in urine samples, whereas resistance rates to carbapenems (C) were 19.9 and 17.7% in blood and urine, respectively. Correlation between consumption and resistance was demonstrated for both antimicrobials (C : R = 0.58; p=0.003 and F : R = 0.77; p=0.0001). Great fluctuations of resistance levels were seen among regions within the country, always correlating resistance with areas in which a higher level of ATM consumption was detected. CONCLUSION: P. aeruginosa resistance to fluoroquinolone/carbapenems in Argentina directly correlated with antimicrobial consumption levels. A great heterogeneity in resistance profile was observed among areas where ATMs were widely used. Global data at the national level might mask local realities that require specific health policies in order to control the irrational use of ATMs.

"CUIDARAS " : A Nominal and Personalized Health Care Model. Effectiveness of a Massive Screening for Colorectal Cancer Detection at Community level.

Health systems provides care only to those people who spontaneous demand for attention; excluding those who dont perceive illness or are not aware enough to consult. Alternative healthcare models based on the nominal-personalized care like "University Center for Integrated Care of Referred Health Care" (CUIDARAS) may have better results. In order to demonstrate benefits of this model, it was performed an experience based in colorectal cancer (CRC) detection and care that focused the entire population of the town. METHODS: It is an intervention study for early detection of CRC. A survey and a physical examination were performed in each adult from "CH" town. Two visits were made. Blood in stool test (BIST) was self-collected, analyzed and results delivered with appointment for a programmed video-colonoscopy (VCC) when test was positive. RESULTS: people enrolled (n546) had 59.9+/-6.4 yrs. Adherence was 93.8% of the target population; 99.2% performed BIST; while 95.3% a positive BIST had access to VCC and treatment. Overall cost of the experience (stool test, VCC, biopsy, local treatment) was 7685 USD, while costs associated to an advanced CRC classic treatment was USD 9577/patient (USD 26098 if treatment included bevacizumab). CONCLUSION: The present study based on preventive actions like blood in stool test, applied as a screening to all inhabitants in town, had 93.8% of adherence and high level of CRC early detection. A health model based on personalized care (CUIDARAS), achieved more effective results in terms health care and disease prevention, with a favorable benefit/cost ratio compared with classical health care provide by current system. Key words: Model of care; colorectal cancer; CUIDARAS; personalized care.

Medicines withdrawn in other countries due to safety concerns: should they continue to be available in the Argentine pharmaceutical market? / [Medicamentos retirados en otros países por problemas de seguridad: ¿Deben seguir presentes en el mercado farmacéutico argentino?]

Introduction: Numerous medicines have been withdrawn from the market because of the risks of serious adverse effects. The objective of this study was to identify in the Argentine pharmaceutical market (APM) the presence of medicines withdrawn in other countries due to safety problems, to analyze the information on their risks and to propose recommendations. Method: observational, descriptive study that explored the presence in the APM, until May 2021, of 462 medicines withdrawn in other countries. Those medicines on this list that are present in the APM and that are not currently authorized in countries with high sanitary surveillance were studied. Results: 17 medicines are still present in the APM, one over-the-counter. The package insert for 11 of the 17 medicines does not mention the adverse effects that led to their withdrawal. It was considered that the permanence in the APM of 16 of them should be reassessed. Conclusions: recommendations are made on actions to be taken by the regulatory authorities with the 17 medicines already present in the APM.

Introducción: Numerosos fármacos han sido retirados del mercado por sus riesgos de efectos adversos graves. El objetivo de este trabajo fue identificar en el mercado farmacéutico argentino (MFA) la presencia de medicamentos retirados en otros países por problemas de seguridad, analizar información sobre sus riesgos y proponer recomendaciones. Método: estudio observacional, descriptivo que exploró la presencia en el MFA, hasta mayo de 2021, de 462 medicamentos retirados en otros países. Se estudiaron aquellos medicamentos de esta lista presentes en el MFA y que no estuvieran autorizados actualmente en países de alta vigilancia sanitaria. Resultados: 17 medicamentos siguen presentes en el MFA, uno de venta libre.  El prospecto de 11 de los 17 fármacos no menciona los efectos adversos que motivaron su retiro. Se consideró que la permanencia en el MFA de 16 de ellos debería ser reevaluada. Conclusiones: se realizan recomendaciones sobre acciones a tomar por las autoridades reguladoras con los 17 medicamentos aún presentes en el MFA.

Antimicrobial Consumption in Latin American Countries: First Steps of a Long Road Ahead.

BACKGROUND: Irrational antimicrobial consumption (AMC) became one of the main global health problems in recent decades. OBJECTIVE: In order to understand AMC in Latin-American Region, we performed the present research in 6 countries. METHODS: Antimicrobial consumption (J01, A07A, P01AB groups) was registered in Argentina, Chile, Colombia, Costa Rica, Paraguay, and Peru. Source of information, AMC type, DDD (Defined Daily Doses), DID (DDD/1000 inhabitants/day), population were variables explored. Data was analyzed using the Global Antimicrobial Resistance and Use Surveillance System (GLASS) tool. RESULTS: Source of information included data from global, public, and private sectors. Total AMC was highly variable (range 1.91-36.26 DID). Penicillin was the most consumed group in all countries except in Paraguay, while macrolides and lincosamides were ranked second. In terms of type of AMC according to the WHO-AWaRe classification, it was found that for certain groups like "Reserve," there are similarities among all countries. CONCLUSION AND RELEVANCE: This paper shows the progress that 6 Latin-American countries made toward AMC surveillance. The study provides a standardized approach for building a national surveillance system for AMC data analysis. These steps will contribute to the inclusion of Latin-America among the regions of the world that have periodic, regular, and quality data of AMC.

[Costly drugs: analysis and proposals for the Mercosur countries]. / Medicamentos de alto costo: análisis y propuestas para los países del Mercosur.

OBJECTIVE: Determine how the Mercosur countries access, regulate, and finance costly drugs and propose joint selection and financing strategies at the subregional level. METHODS: Qualitative design, using content analyses of primary and secondary sources, document reviews, interviews, focus groups, and case studies. The variables selected included: selection criteria, access, financing, and regulations in the various countries. Costly drugs were divided into those that do not alter the natural course of the disease and those with demonstrated efficacy, using the defined daily dose to compare the costs of classical treatments and those involving costly drugs. RESULTS: The Mercosur countries generally lack formal strategies for dealing with the demand for costly drugs, and governments and insurers wind up financing them by court order. The case studies show that there are costly drugs whose efficacy has not been established but that nonetheless generate demand. The fragmentation of procurement, international commitments with regard to intellectual property, and low negotiating power exponentially increase the price of costly drugs, putting health system finances in jeopardy. CONCLUSIONS: Costly drugs must be regulated and rationally selected so that only those that substantively benefit people are accepted. To finance the drugs so selected, common country strategies are needed that include such options as flexible in trade agreements, the creation of national resource funds, or joint procurement by countries to enhance their negotiating power.

Healthcare model based on personalised attention: impact on maternal mortality and health system quality.

BACKGROUND: Latin America's public healthcare model has traditionally offered health services on demand including provision for the most deprived inhabitants. However, this care model has not provided the expected improvement in health conditions or equity for the indigent population. AIM: To compare maternal health indicators between previous services and a new healthcare model based on personalised care and a named healthcare worker. METHODS: Pregnant women in La Plata, Argentina were observed during two periods: a control period using a historical model and an intervention period where a new healthcare model was provided, each period lasting 12 months. Indicators of the quality of antenatal care services were measured, including mortality rate, number of pregnancy related consultations, vaccination coverage, gestational age at delivery, newborn weight, laboratory and scan monitoring, early pregnancy detection and type of delivery. RESULTS: The number of patients undergoing antenatal surveillance increased almost five-fold during the period of the new healthcare model. Also the rate of early detection of pregnancy, average number of health consultations and vaccination coverage were significantly higher with the new model compared with previous care. Maternal gestation at delivery increased from 37.4±3.8% to 39.3±2.5% weeks (P<0.001) and neonatal weight increased from 3048 AE 612 g to 3301 AE 580 g (P=0.003). There were no maternal deaths in the intervention group compared with seven deaths in the control group. Child mortality rate was 13.7 and 11.8 per 1000 for control and intervention groups respectively (P=0.039). CONCLUSIONS: A named responsible health worker and personalised care helped contribute to improvements in quality of antenatal care in the health system.