[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.

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.

Regulatory reliance to approve new medicinal products in Latin American and Caribbean countries.

OBJECTIVE: To describe the current status of regulatory reliance in Latin America and the Caribbean (LAC) by assessing the countries' regulatory frameworks to approve new medicines, and to ascertain, for each country, which foreign regulators are considered as trusted regulatory authorities to rely on. METHODS: Websites from LAC regulators were searched to identify the official regulations to approve new drugs. Data collection was carried out in December 2019 and completed in June 2020 for the Caribbean countries. Two independent teams collected information regarding direct recognition or abbreviated processes to approve new drugs and the reference (trusted) regulators defined as such by the corresponding national legislation. RESULTS: Regulatory documents regarding marketing authorization were found in 20 LAC regulators' websites, covering 34 countries. Seven countries do not accept reliance on foreign regulators. Thirteen regulatory authorities (Argentina, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Mexico, Panama, Paraguay, Peru, Uruguay, and the unique Caribbean Regulatory System for 15 Caribbean States) explicitly accept relying on marketing authorizations issued by the European Medicines Agency, United States Food and Drug Administration, and Health Canada. Ten countries rely also on marketing authorizations from Australia, Japan, and Switzerland. Argentina, Brazil, Chile, and Mexico are reference authorities for eight LAC regulators. CONCLUSIONS: Regulatory reliance has become a common practice in the LAC region. Thirteen out of 20 regulators directly recognize or abbreviate the marketing authorization process in case of earlier approval by a regulator from another jurisdiction. The regulators most relied upon are the European Medicines Agency, United States Food and Drug Administration, and Health Canada.

What is happening with not recommended drugs for dementia in Argentina? Prescription patterns and direct costs analysis.

OBJECTIVES: The only recommended pharmacological treatments for specific dementias are donepezil, galantamine, rivastigmine, and memantine (recommended drugs, RD). However, other drugs without recommendations (not recommended drugs, NRD) are often used to treat patients with cognitive impairment (CI) in Argentina. The INSSJyP is the largest health insurance in Argentina. The objective of this study is to analyze the prescription pattern, cost, and implications of NRD used for the treatment of CI in the INSSJyP. MATERIALS: This is a retrospective, population-based study of the INSSJyP outpatients' prescriptions database for drugs usually prescribed for CI during 2015. These data were compared with the same database in 2009. The number of "prescriptions" always refers to dispensed packages. RESULTS: A total of 3 255 438 packages of drugs usually indicated for CI were prescribed during 2015: 1 912 476 packages of RD (59%) and 1 342 962 packages of NRD (41%).Comparing the results with those obtained in 2009, there is a 148% gross increase in the prescription of both RD and NRD for CI, although the rates/1000 affiliates/year show a lesser rise for NRD (70.1%) compared to RD (103.9 %).The expenditure on CI drugs prescribed during 2015 was 77 million USD. NRD cost represented approximately 20 million USD. CONCLUSION: Inappropriate drug use increases health costs in developing countries. We found a high number of patients with a probable diagnosis of CI treated with NRD. It is extremely relevant that all the healthcare professionals can update their knowledge and modify behavioral insights about appropriate prescription for specific dementias.

[Psychotropic drugs prescription to elderly people in the national institute of social services for retirees and pensioners of argentina (PAMI)]. / Prescripción de psicofármacos a personas mayores en el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados de Argentina (PAMI).

OBJECTIVE: To analyze the prescribing pattern of psychotropic drugs to affiliates over 60 years of age at the National Institute of Social Services for Retirees and Pensioners of Argentina (PAMI). MATERIALS AND METHODS: We conducted a retrospective study of the at the National Institute of Social Services for Retirees and Pensioners of Argentina (PAMI) database on the population over 60 years of age who received at least one psychotropic drug during 2016. RESULTS: During the year 2016, 30% of the population over 60 years of age received the prescription of at least one psychotropic drug. There was a greater prescription of psychotropic drugs to women than to men (75.3% vs. 24.7%). Of the drugs prescribed, 67% were benzodiazepines, 20% were antidepressants, 9% were antipsychotics and 4% were non-benzodiazepine hypnotics. 54% of the drugs prescribed were clonazepam and alprazolam. 21% of the population received three or more prescriptions during the period studied. There was a relatively greater prescription of psychotropic drugs in the population of 75 years old or older. CONCLUSIONS: Taking into account the risks of adverse effects, interactions and the inclusion of some of these drugs among those that should not be prescribed among older adults, the high prescription rate of some of these drugs is alarming. It is necessary to develop strategies among general practitioners, specialists and also among the general population in order to reduce the prescription of psychotropic drugs.

[Cardiovascular risk of non-steroidal anti-inflammatory drugs]. / Riesgo cardiovascular de los antiinflamatorios no esteroideos.

Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs. Both the analgesic and antiinflammatory effects, as well as the cardiovascular adverse effects, depend on the COX-2 inhibition. This paper reviews the available evidence of the increased risk of thrombotic events for both coxibs and traditional NSAID. The prothrombotic effect could be due to the inhibition of endothelial COX-2, with a decrease in production of prostacyclin and a relative increase in platelet thromboxane levels. Coxibs and diclofenac 150 mg/day seem to increase the risk of major vascular events by more than a third. Ibuprofen 2400 mg/day could slightly increase the risk of coronary events. Naproxen 1000 mg/day apparently does not increase the risk of vascular events. Besides ibuprofen and naproxen have the potential to decrease the cardioprotective effect of low doses of aspirin. Naproxen (= 1000 mg/day) and low doses of ibuprofen (= 1200 mg/day) are considered to have the most favorable thrombotic cardiovascular safety profiles of all NSAIDs. Therapeutic decisions should be based on an assessment of a person's individual risk factors, using the safest NSAIDs, at the lowest effective doses, for the shortest duration necessary to control symptoms, restricting their use in patients with increased cardiovascular risk.

[Prevalence of cognitive impairment in a high social risk population older then 60 years from Neuquén capital, Argentina]. / Prevalencia de deterioro cognitivo en población mayor de 60 años con alto riesgo social de Neuquén capital.

INTRODUCTION: The information that exists on dementia and cognitive impairment is scarce in Argentina, particularly in Patagonia. OBJECTIVE AND METHODS: The aim of the study was to determine the prevalence of cognitive impairment. A door to door survey was performed to all people over 60 who lived in a high social risk neighborhood in Neuquen city, where geriatric and cognitive variables were evaluated, including Folstein Mini-Mental State Examination, clock test and test set according to the level of instruction. RESULTS: Of the 78 surveys assessed, the mean age was 70.75 years, 37 female, with an average of 4.37 years of schooling, with 33% of functional illiterates. Cognitive impairment was evidenced in 29.49%, being high er at older and less educated respondents. CONCLUSIONS: The prevalence of cognitive impairment in the study population was higher than in other Argentine studies associated with an illiteracy rate higher than in other jurisdictions.

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.

Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination.

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves. Our data indicate that neddylation exerts a global influence on the complex transcriptional and posttranscriptional program by simultaneously regulating the expression and function of multiple essential myelination signals, including the master transcription factor EGR2 and the negative regulators c-Jun and Sox2, and inducing global secondary changes in downstream pathways, including the mTOR and YAP/TAZ signaling pathways. This places neddylation as a critical regulator of myelination and delineates the potential pathogenic mechanisms involved in CMT mutations related to neddylation.

[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.

CHLOROQUINE INDUCED MACULAR TOXICITY IN A PATIENT LATER DEVELOPING SECTOR RETINITIS PIGMENTOSA: A CASE REPORT.

PURPOSE: To describe how underlying retinal diseases, such as retinitis pigmentosa, increase the risk of chloroquine-induced macular toxicity. METHODS: Observational case report. RESULTS: We present the case of a 57-year-old woman being annually followed-up in the Ophthalmology service due to a systemic treatment with chloroquine (CQ). The explorations were successive normal, until a 10:2 visual field (VF) shows central defects in both eyes. Despite CQ treatment is discontinued, 10:2 VF reveal slowly progressive macular defects. During follow-up, fundus examination disclosed bone spicules in the inferonasal middle periphery: the electroretinogram (ERG) shows slow amplitude responses under scotopic conditions and the electrooculogram (EOG) also shows pathological responses. Therefore, the diagnosis of sector retinitis pigmentosa plus chloroquine maculopathy is made. Currently, the slow but constant progression of both peripheral and central defects is evident, despite having discontinued CQ treatment more than 15 years ago. CONCLUSION: Underlying retinal diseases seem to increase the risk of photoreceptor damage when undergoing a toxic insult. Thus, we hypothesize a potential interplay between retinal dystrophies and toxic maculopathy induced by CQ, and the influence of each of them in the evolution and prognosis of the other.

Selective Focal Laser Therapy as the Primary Treatment for Exudative Perifoveal Vascular Anomalous Complex (ePVAC): Case Series and Literature Review.

Perifoveal anomalous exudative vascular complex (PEVAC) was first described in 2011. Since then, individual clinical cases and a couple of case series have been published, and their characteristics have been studied in multi-modal images. To date, there is no consensus on its treatment. Initially, it was thought that PEVACs could be left to spontaneous evolution because they presented a slow progression. But it has been shown that the growth of the lesion covers a spectrum from non-exudative lesions to PEVAC with vision impairment over time. We present an updated bibliographic review of this pathology. We explain the changes in the diagnostic criteria that have been undergone. And we focus the discussion on selective treatment with focal laser, which has shown an excellent anatomical response and visual improvement or stabilization in the cases described and in our series of three patients systematically treated with focal laser. [Ophthalmic Surg Lasers Imaging Retina 2023;54:43-49.].

Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting.

There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, ß-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive ß-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.

[Use of benzodiazepines and related drugs in social security for older adults in Argentina]. / Uso de benzodiazepinas y fármacos relacionados en el Seguro Social para adultos mayores de Argentina.

The clinical use of benzodiazepines (BZD) and related drugs is a controversial issue, especially prolonged prescription in older adults, which is contrary to general recommendations. Our objective was to describe the use of BZD and the hypnotics called Z drugs (zolpidem, zopiclone and eszopiclone) in elderly beneficiaries of the National Institute of Social Services for Retirees and Pensioners (INSSJP-PAMI) of Argentina. An observational, descriptive, cross-sectional drug use study was conducted based on the Institute's drug dispensing database. Beneficiaries of both sexes aged 65 years and over were included. The prevalence of use in 2018 and the defined daily doses (DDD) per 1000 inhabitants / day (DHD) were calculated for each drug. A total of 3 864 949 beneficiaries were included (77.6% of the Argentine population of that age, 61.2% women), with 184 000 nonagenarians and more than 5000 centenarians; 30.3% of whom received at least one dispensation of BZD or "Z drugs" during 2018, with a higher prevalence of use in women (35.6%) than in men (22.0%) and with a progressive increase until 85-89 years, with a subsequent decrease. The most prescribed BZDs were alprazolam (41.6%) and clonazepam (41.1%), followed by lorazepam (9.9%). The dispense drugs reached 252.7 DHD, representing an average of 0.8 DDD per user and per day, a value that decreased with age. The prevalence of use found is among the highest at international level, justifying the implementation of clinical and public health interventions to improve this situation.

El uso clínico de las benzodiazepinas (BZD) y fármacos relacionados es un tema controversial, especialmente la prescripción prolongada en adultos mayores, que es contraria a las recomendaciones generales. Nuestro objetivo fue describir el uso de BZD y de los hipnóticos denominados fármacos Z (zolpidem, zopiclona y eszopiclona) en los adultos mayores beneficiarios del Instituto Nacional de Servicios Sociales para Jubilados y Pensionados (INSSJP-PAMI) de Argentina. Se realizó un estudio de utilización de medicamentos observacional, descriptivo, de corte transversal, a partir de la base de datos de dispensa de medicamentos del Instituto. Se incluyeron los beneficiarios de ambos sexos de 65 años y más. Se calculó para cada fármaco la prevalencia de uso en 2018 y las dosis diarias definidas (DDD) por cada 1000 habitantes/día (DHD). Se incluyeron 3 864 949 beneficiarios (77.6 % de la población argentina de esa edad, 61.2 % mujeres), con 184 000 nonagenarios y más de 5000 centenarios. El 30.3 % recibió al me nos una dispensa de BZD o fármacos Z durante 2018, con mayor prevalencia de uso en mujeres (35.6%) que en varones (22.0%) y con aumento progresivo hasta los 85-89 años, y descenso posterior. Las BZD más recetadas fueron alprazolam (41.6%) y clonazepam (41.1%), seguidas por lorazepam (9.9%). La dispensa alcanzó 252.7 DHD, representado un promedio de 0.8 DDD por usuario y por día, valor que disminuyó con la edad. La prevalencia de uso encontrada está entre las más elevadas a nivel internacional, justificando la implementación de intervenciones clínicas y de salud pública para mejorar esta situación.

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.

[Drug advertising and promotion: regulations and extent of compliance in five Latin American countries]. / Publicidad y promoción de medicamentos: regulaciones y grado de acatamiento en cinco países de América Latina.

OBJECTIVE: To analyze differing regulations regarding drug promotion, and the extent of compliance as seen in samples of advertising directed to the public in Argentina, Colombia, Ecuador, Nicaragua, and Peru. METHODS: A total of 683 pieces of promotional material on display in health facilities, pharmacies, and on the street were collected, 132 of which were randomly selected for analysis. The regulations governing pharmaceutical advertising, taken from official websites and interviews with regulatory officials and Ministry of Health staff in the five countries covered, were reviewed, along with their adherence to the ethical criteria of the World Health Organization (WHO). The contents of the materials in the sample were evaluated to determine their degree of compliance with national regulations and WHO recommendations on drug promotion. RESULTS: The countries have regulations incorporating WHO ethical criteria. Over 80% of the material analyzed included the indications for the drug, while over 70% omitted information on adverse effects. Fifty percent of the advertisements for over-the-counter (OTC) drugs on display in pharmacies listed indications not approved by the relevant health authority. In advertising in pharmacies, the risks from inadequate information were not found to differ significantly for OTC or prescription medications. Compared with materials provided in health facilities, the relative risk of the absence of information on dosage in the material distributed in pharmacies was 2.08 (confidence interval 95% 1.32-3.39). CONCLUSIONS: Although regulations on drug promotion and advertising in the five countries studied generally incorporate the WHO recommendations, promotional materials often fail to reflect the fact.

Potential negative impact of reputed regulators' decisions on the approval status of new cancer drugs in Latin American countries: A descriptive analysis.

BACKGROUND: Many new cancer drugs are being approved by reputed regulatory authorities without evidence of overall survival benefit, quality of life improvement, and often based on clinical trials at high risk of bias. In recent years, most Latin American (LA) countries have reformed their marketing authorization (MA) rules to directly accept or abbreviate the approval process in case of earlier authorization by the European Medicines Agency (EMA) and the US Food and Drug Administration, mainly. This study assessed the potential impact of decisions taken by EMA regarding the approval of new cancer drugs based on no evidence of overall survival or in potentially biased clinical trials in LA countries. DESIGN: Descriptive analysis. SETTING: Publicly accessible marketing authorization databases from LA regulators, European Public Assessment Report by EMA, and previous studies accessing EMA approvals of new cancer drugs 2009-2016. MAIN OUTCOME AND MEASURES: Number of new cancer drugs approved by LA countries without evidence of overall survival (2009-2013), and without at least one clinical trial scored at low risk of bias, or with no trial supporting the marketing authorization at all (2014-2016). RESULTS: Argentina, Brazil, Chile, Colombia, Ecuador, Panama and Peru have publicly accessible and trustful MA databases and were included. Of the 17 cancer drugs approved by EMA (2009-2013) without evidence of OS benefit after a postmarketing median time of 5.4 years, 6 LA regulators approved more than 70% of them. Of the 13 drugs approved by EMA (2014-2016), either without supporting trial or with no trial at low risk of bias, Brazil approved 11, Chile 10, Peru 10, Argentina 10, Colombia 9, Ecuador 9, and Panama 8. CONCLUSIONS: LA countries keep approving new cancer drugs often based on poorly performed clinical trials measuring surrogate endpoints. EMA and other reputed regulators must be aware that their regulatory decisions might directly influence decisions regarding MA, health budgets and patient's care elsewhere.

[Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017]. / Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017.

In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.

En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

[Benzodiazepine and Z-drug consumption in a national social security organization in Argentina: rational or excessive use?] / Consumo de benzodiazepinas y fármacos Z en una organización de la seguridad social nacional argentina: ¿uso racional o excesivo?

Benzodiazepines and "Z-drugs" (BZD/Z) are overprescribed in many countries. This study evaluates their consumption in a social security sector health insurance provider with national coverage in Argentina. With a descriptive and observational approach, outpatient dispensations of BZD/Zs were analyzed for people over 18 years old from April 2020 to March 2021, disaggregated by sex, age, active ingredient, and half-life. An annual prevalence of use of 11.6% was found among the 431,445 adult affiliates, with higher rates in women and in those over age 60. Overall consumption of BZD/Zs was 77.6 defined daily doses (DDD) per 1000 enrollee-days. The average user received 5.1 annual dispensations and the equivalent of 1.4 DDD for each day of the year. BZD/Zs with long half-life were the most used. We found high levels of BZD/Z consumption and for longer periods than recommended. It is necessary to improve the quality of consumption and reduce the negative impact of inappropriate use of these drugs among treated individuals.

Las benzodiazepinas y los "fármacos Z" (BZD-Z) se prescriben en exceso en muchos países. Este estudio evaluó su consumo en una organización de la seguridad social (obra social) de Argentina de alcance nacional. A partir de un diseño observacional descriptivo se analizó la dispensa ambulatoria de BZD-Z, entre abril 2020 y marzo 2021, a mayores de 18 años; desagregada por sexo, edad, principio activo y vida media. Se encontró una prevalencia anual de uso del 11,6% entre los 431.445 afiliados adultos, con valores más elevados en las mujeres y mayores de 60 años. El consumo global de BZD-Z fue de 77,6 dosis diarias definidas (DDD) cada 1.000 afiliados-día. El usuario promedio recibió 5,1 dispensas anuales y el equivalente a 1,4 DDD por cada día del año. Las BZD-Z más usadas fueron las de vida media larga. El consumo de BZD-Z resultó elevado y más prolongado que lo recomendado. Es necesario mejorar la calidad en el consumo y reducir el impacto negativo del uso inapropiado de estos fármacos entre los individuos tratados.