BACKGROUND. Various mechanisms may contribute to and direct the progression of antibiotic resistance. A prominent driver associated with antibiotic resistance is inappropriate use or consumption. The sudden emergence of coronavirus disease 2019 (COVID-19 ) changed the conventional practices related to antibiotic utilisation through repurposing the use of antibiotics. Apart from the implementation of antibiotic stewardship programmes, the pressure COVID-19 placed on healthcare systems resulted in poor prescribing and medication review practices, potentially exacerbating antibiotic resistance. Furthermore, the public health system has issues that make it difficult to routinely monitor, quantify antibiotic consumption, and offer evaluation, feedback and intervention, particularly in low- and middle-income countries such as South Africa (SA). Therefore, this study aimed to determine antibiotic utilisation before and during the COVID-19 pandemic in a Gauteng provincial tertiary hospital (GPTH) in SA. OBJECTIVE. To determine, examine, and compare antibiotic consumption among intensive care unit (ICU) patients admitted to a GPTH during the pre-COVID-19 period and during the COVID-19 pandemic, in addition to determining the prevalence of the World Health Organisation (WHO) 'watch' category antibiotics before and following the emergence of COVID-19. METHODS. A retrospective cross-sectional data analysis was undertaken of 335 medical files of ICU patients hospitalised in a GPTH between January 2017 and December 2021. Descriptive statistics were used to examine patient characteristics and antibiotic prescribing variables (antibiotic selection, dosage, route of administration, frequency, duration of course and indication for which antibiotic was prescribed). RESULTS. The study found that the most frequently prescribed antibiotics were amoxicillin in combination with clavulanate (pre-pandemic 31.99%; amid-COVID-19 38.43%), followed by ceftriaxone (pre-pandemic 15.44%; amid-COVID-19 14.55%), piperacillin in combination with tazobactam (pre-pandemic 11.40%; amid-COVID-19 8.58%) and azithromycin (pre-pandemic 7.725%; amid-COVID-19 19.78%). CONCLUSION. The macrolide and penicillin (in combination with a beta-lactamase inhibitor) classes demonstrated an increase in consumption from the pre-pandemic period moving into the COVID-19 pandemic. This highlights the need for improved antibiotic stewardship programmes and policies to combat inappropriate and unnecessary antibiotic usage.

Abstract Background The COVID-19 pandemic has triggered crises in the public health sector that have complex and multifaceted interrelationships with antimicrobial resistance. It is important to evaluate the impact of COVID-19 on microbiological profile, antibiotic and alcohol gel consumption in Intensive Care Units (ICU). Methods This is a retrospective study undertaken in an infectious disease hospital located in Bahia/Brazil during three periods: from March 2019 to February 2020; from March 2020 to February 2021; and from March 2021 to February 2022. It was evaluated the incidence density of Candida spp and of multidrug-resistant Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE group) in blood, urine and tracheal secretion isolated 48 h after the patient's admission to the ICU, as well as the use of alcohol gel (in milliliters) and consumption of antibiotics in Defined Daily Dose (DDD) per 1,000 ICU patient-days in the previous year and in the first two years of COVID-19 pandemic. Results There was an increase in Candida spp. (5.81, p < 0.001, IRR = 10.47, 95 % CI 2.57‒42.62) and in carbapenem-resistant A. baumannii in clinical cultures (4.71, p < 0.001, IRR = 8.46, 95 % CI 2.07‒34.60), the latter mainly in tracheal secretions (3.18, p =0.02, IRR = 11.47, 95 % CI 1.58‒83.39). A rise in the consumption of ceftriaxone and piperacillin-tazobactam, along with an increase in the utilization of alcohol gel were observed. Conclusion The shifting microbiological profile can be attributed to both the unique characteristics of patients with COVID-19 and the adjustments made to healthcare facilities' structural and work routines. Understanding these changes is essential in addressing the accelerated impact of antimicrobial resistance during the pandemic. Therefore, conducting thorough reviews of institutional practices and routines becomes critical in mitigating the consequences of antimicrobial resistance and its implications for patient care. COVID19 COVID 19 COVID-1 ICU. . (ICU) BahiaBrazil Bahia Brazil periods 201 202 2022 multidrugresistant multidrug resistant faecium aureus pneumoniae aeruginosa ESKAPE group blood 4 s milliliters DDD (DDD 1000 1 000 1,00 patientdays days 5.81, 581 5 81 (5.81 0001 0 001 0.001 1047 10 47 10.47 9 2.57‒42.62 2574262 2 57 42 62 carbapenemresistant carbapenem 4.71, 471 71 (4.71 846 8 46 8.46 2.07‒34.60, 2073460 2.07‒34.60 , 07 34 60 2.07‒34.60) 3.18, 318 3 18 (3.18 002 02 =0.02 1147 11 11.47 1.58‒83.39. 1588339 1.58‒83.39 58 83 39 1.58‒83.39) piperacillintazobactam, piperacillintazobactam piperacillin tazobactam, tazobactam piperacillin-tazobactam observed facilities Therefore care COVID1 COVID- (ICU 20 100 00 1,0 5.81 (5.8 0.00 104 10.4 2.57‒42.6 257426 6 4.71 7 (4.7 84 8.4 207346 2.07‒34.6 3.18 31 (3.1 =0.0 114 11.4 158833 1.58‒83.3 1, 5.8 (5. 0.0 10. 2.57‒42. 25742 4.7 (4. 8. 20734 2.07‒34. 3.1 (3. =0. 11. 15883 1.58‒83. 5. (5 0. 2.57‒42 2574 4. (4 2073 2.07‒34 3. (3 =0 1588 1.58‒83 ( 2.57‒4 257 207 2.07‒3 158 1.58‒8 2.57‒ 25 2.07‒ 15 1.58‒ 2.57 2.07 1.58 2.5 2.0 1.5 2. 1.

SUMMARY OBJECTIVE: The objective of this study was to evaluate the impact of the implementation of a bundle of interventions through a "Program for Antibiotic Management and Nosocomial Infection Prevention" in the intensive care unit on antibiotic and devices use and healthcare-associated infections. METHODS: This was a quasi-experimental study of consecutive series of cases in periods before and after the establishment of protocols and checklists for the use of antibiotics as well as other measures to prevent healthcare-associated infection as part of a quality improvement program. Antimicrobial consumption was assessed by the defined daily dose. RESULTS: A total of 1,056 and 1,323 admissions in the pre-intervention and post-intervention phases, respectively, were evaluated. The defined daily dose per 100 patient-day decreased from 89±8 to 77±11 (p=0.100), with a decrease in carbapenems, glycopeptides, polymyxins, penicillins, and cephalosporins. The rates of ventilator and central venous catheter use decreased from 52.8 to 44.1% and from 76 to 70%, respectively. The rates of healthcare-associated infection decreased from 19.2 to 15.5%. CONCLUSION: Quality improvement actions focused primarily on antimicrobial management and prevention of healthcare-associated infection are feasible and have the potential to decrease antibiotic use and healthcare-associated infection rates. OBJECTIVE Program Prevention healthcareassociated healthcare associated infections METHODS quasiexperimental quasi experimental program RESULTS 1056 1 056 1,05 1323 323 1,32 preintervention pre intervention postintervention post phases respectively evaluated 10 patientday patient day 898 89 8 89± 7711 77 11 77±1 p=0.100, p0100 p p=0.100 , 0 (p=0.100) carbapenems glycopeptides polymyxins penicillins cephalosporins 528 52 52. 441 44 44.1 7 70 70% 192 19 2 19. 155 15 5 15.5% CONCLUSION 105 05 1,0 132 32 1,3 771 77± p010 p=0.10 (p=0.100 4 44. 15.5 1, 13 3 p01 p=0.1 (p=0.10 15. p0 p=0. (p=0.1 p=0 (p=0. p= (p=0 (p= (p

Abstract This study aimed to describe the pattern of antimicrobial agent usage in a general tertiary care hospital in Rio de Janeiro. Some prescriptions were evaluated for its therapeutic indication, dose, route of administration, and duration of treatment based on Antimicrobial Application Sheets and daily medical prescriptions. Consumption was expressed by using Defined Daily Dose per 100 bed-days. Within the 20,182 validated prescriptions, 9,356 were eligible for the study. The first-choice therapy was prescribed 6,175 (66.01%) times. It was verified that 5,455 (58.31%) of the prescribed antimicrobial agents were associated with bacteriologic culture tests, and among 2,484 (45.54%) of such cultures, at least one microorganism was identified. Negative results were obtained in 2,971 (54.46%) processed cultures, in which 1,289 patients (43.49%) had already initiated antimicrobial therapy. From patients with negative cultures, 518 (33.99%) prescriptions had alternative treatments, and from these, 495 (95.96%) could have been changed. Therefore, de-escalation of antimicrobial therapy has not been a practice in the institution. Among prescriptions that needed renal function dose adjustments, this was performed in 81.11%. In general, prescriptions were adjusted for dose (70.03%), route of administration (99.63%) and duration of treatment (74.70%). Piperacillin/tazobactam was the mostly used antimicrobial (3,923 DDD/100 bed-days). Janeiro indication 10 beddays. beddays bed days. days bed-days 20182 20 182 20,18 9356 9 356 9,35 firstchoice first choice 6175 6 175 6,17 66.01% 6601 66 01 (66.01% times 5455 5 455 5,45 58.31% 5831 58 31 (58.31% tests 2484 2 484 2,48 45.54% 4554 45 54 (45.54% cultures identified 2971 971 2,97 54.46% 5446 46 (54.46% 1289 1 289 1,28 43.49% 4349 43 49 (43.49% 51 33.99% 3399 33 99 (33.99% treatments these 95.96% 9596 95 96 (95.96% changed Therefore deescalation escalation institution adjustments 8111 81 11 81.11% 70.03%, 7003 70.03% , 70 03 (70.03%) 99.63% 9963 63 (99.63% 74.70%. 7470 74.70% . 74 (74.70%) Piperacillintazobactam Piperacillin tazobactam 3,923 3923 3 923 (3,92 DDD100 DDD DDD/10 bed-days) 2018 18 20,1 935 35 9,3 617 17 6,1 66.01 660 0 (66.01 545 5,4 58.31 583 (58.31 248 48 2,4 45.54 4 (45.54 297 97 2,9 54.46 544 (54.46 128 28 1,2 43.49 434 (43.49 33.99 339 (33.99 95.96 959 (95.96 811 8 81.11 700 70.03 7 (70.03% 99.63 996 (99.63 747 74.70 (74.70% 3,92 392 92 (3,9 DDD10 DDD/1 201 20, 93 9, 61 6, 66.0 (66.0 5, 58.3 (58.3 24 2, 45.5 (45.5 29 54.4 (54.4 12 1, 43.4 (43.4 33.9 (33.9 95.9 (95.9 81.1 70.0 (70.03 99.6 (99.6 74.7 (74.70 3,9 39 (3, DDD1 DDD/ 66. (66. 58. (58. 45. (45. 54. (54. 43. (43. 33. (33. 95. (95. 81. 70. (70.0 99. (99. 74. (74.7 3, (3 (66 (58 (45 (54 (43 (33 (95 (70. (99 (74. ( (6 (5 (4 (9 (70 (74 (7

BACKGROUND: South African legislation advocates for equitable access to mental healthcare services integrated into general healthcare settings. Mental, neurological, and substance use (MNS) disorders are often comorbid. Pharmacoepidemiology provides indirect evidence of service provision for conditions amenable to medicine treatment. AIM: The study aims to evaluate medicine procurement for MNS disorders at different service levels in the health system. SETTING: The Public health sector, Gauteng province formed the setting for the study. METHOD: A secondary analysis of the Gauteng pharmaceutical database was conducted using Anatomic Therapeutic Chemical (ATC) and defined daily dose (DDD) methodology. Anatomic Therapeutic Chemical classes of medicines for MNS disorders were included. Defined daily doses and costs were calculated per 1000 population served by each facility and service level. Statistical comparisons were made using chi-square testing. RESULTS: General healthcare settings accounted for 90% (R118 638 248) and specialised hospitals for 10% (R13 685 032) of expenditure on medicines for MNS disorders, procuring 94% (n = 49 442 474) and 6% (n = 3 311 528) of DDDs, respectively. Although district clinics procured 60% of DDDs, they procured the least per 1000 population served, whereas district hospitals procured the most. For almost all ATC classes, procurement differed significantly between municipalities at every service level and between specialised hospitals. CONCLUSION: In Gauteng province, most medicines for MNS disorders are procured by general healthcare services, but access to care may not be equitable. While population coverage at district clinics appears low, district hospitals may experience the greatest care burden. Research regarding quality of care at each service level is recommended. CONTRIBUTION: This study provides insight into service provision for MNS disorders.

Resumen Objetivo: Describir el tipo de pacientes que superan la dosis diaria definida (DDD) de fentanilo de liberación inmediata en un área sanitaria. Material y métodos: Estudio observacional, descriptivo, realizado en un área sanitaria de 256.807 habitantes en el que se incluyeron todos los pacientes que superaban la DDD de fentanilo de liberación inmediata en diciembre de 2019. Resultados: Se detectaron 29 pacientes, 58,6% mujeres, con una mediana de edad de 59 (31-87) años, que superaban una media de 3 (1,1-10) veces la DDD de fentanilo de liberación inmediata, en sus distintas presentaciones, siendo la indicación en el 69% de los casos dolor crónico no oncológico (DCNO). La mayoría de los pacientes tomaba benzodiacepinas (79,3%) y el mayor porcentaje de primeras prescripciones de fentanilo de liberación rápida procedía de atención primaria (38%). Conclusiones: En nuestro estudio el uso inadecuado o posible abuso de fentanilo de liberación inmediata se da en mayor proporción en pacientes con DCNO, y en la mayoría de los casos la primera prescripción se realizó en atención primaria. No observamos relación clara con patología psiquiátrica ni otras adicciones.

Abstract Objective: To describe the type of patients that exceed the defined daily dose (DDD) of immediate-release fentanyl in a health area. Material and methods: Observational, descriptive study, carried out in a health area of 256,807 inhabitants, which included all patients who passed the immediate-release fentanyl DDD in December 2019. Results: 29 patients were detected, 58.6% female, with a median age of 59 (31-87) years, who exceeded an average of 3 (1.1-10) times the immediate-release fentanyl DDD, in its different presentations, being the indication in 69% of cases chronic non-cancer pain (CNCP). The majority of patients took benzodiazepines (79.3%) and the highest percentage of first-prescriptions for inmediate-release fentanyl came from primary care (38%). Conclusions: In our study, the inappropriate use or possible abuse of immediate-release fentanyl occurs in a greater proportion in patients with CNCP, and in most cases the first prescription was made in primary care. We did not observe a clear relationship with psychiatric pathology or other addictions.

Resumen Introducción: El método recomendado para la medición de consumo de antimicrobianos (AMB) en pediatría es el cálculo del indicador Días de Terapia estandarizado por ocupación (DOT-std). Sin embargo, en hospitales que no cuentan con fichas electrónicas, obtener el numerador de los días de terapia (DOT) requiere revisión directa de las indicaciones del paciente, dificultando su aplicabilidad. Objetivos: Validar el sistema de registros electrónicos de dispensación de medicamentos desde farmacia como fuente para el cálculo de DOT y DOT-std en la Unidad de Cuidados Intensivos Pediátrica (UCIP). Materiales y Métodos: Se revisaron las prescripciones de AMB desde la ficha clínica (método manual) y se compararon con los registros de dispensación de AMB a la UCIP (método informático) obtenidos del sistema de medicamentos de farmacia. Se evaluó la concordancia entre los DOT obtenidos mediante el Coeficiente de Correlación Intraclase. Resultados: Los AMB más utilizados fueron vancomicina, meropenem y piperacilina/tazobactam. En 9 de 12 AMB se encontró concordancia significativa entre ambos métodos. Conclusiones: Tras un proceso de validación local, los registros del sistema informático de dispensación de medicamentos desde farmacia podrían utilizarse para el cálculo de DOT en pediatría en hospitales que no cuenten con una ficha electrónica que permita su cálculo directo.

Abstract Background: The recommended indicator for measuring antimicrobial (AMB) consumption in pediatric patients is the Days of Therapy indicator (DOT), which is then standardized by hospital occupancy rates (DOT-std). However, in hospitals that do not have electronic health records, obtaining the DOT requires a direct review of each pharmacological indication, which is not feasible in the long term. Aims: To validate electronic records from the pharmacy dispensation system as a source for calculating DOT and estimating DOT-std in a Pediatric Intensive Care Unit (PICU). Methods: AMB prescriptions at the PICU of a university hospital were directly reviewed (manual method) and compared with AMB dispensation records (computer method) obtained from the hospital pharmacy system. The Intraclass Correlation Coefficient was used to evaluate the agreement between the DOT obtained by both methods. Results: The most used AMB were vancomycin, meropenem, and piperacillin/tazobactam. A significant agreement between the DOT obtained by using manual and computer methods was found in 9 of 12 evaluated AMB. Conclusions: After a local validation process, the electronic records of the pharmacy drug dispensation system could be considered a valid source for calculating DOT in PICUs in hospitals where electronic health records with prescription data are not yet available.

RESUMEN Objetivo. Evaluar el cumplimiento de los hospitales de segundo y tercer nivel en la presentación mensual de información sobre el consumo de antibióticos en el Sistema Nacional de Vigilancia en Salud Pública de Colombia (SIVIGILA-INS) y describir el consumo de antibióticos reportado en el período 2018-2020. Métodos. Este estudio incluyó un análisis secundario de los datos del consumo de antibióticos reportado en SIVIGILA-INS. Se evaluó la frecuencia de los informes hospitalarios y se comparó con los informes esperados, desglosados por unidad de cuidados intensivos (UCI) y otros servicios distintos a la UCI, y por región geográfica. El consumo se expresó en dosis diaria definida (DDD) por 100 camas ocupadas para siete antibióticos. Resultados. Más del 70% de los hospitales notificaron el consumo de antibióticos al menos una vez en cada uno de los tres años (79% en la UCI y 71% en los servicios distintos a la UCI). De estos, el 59% de las UCI completaron los informes mensuales (12 informes en un año) entre el 2018 y el 2019, pero solo el 4% en el 2020. El 52% de los servicios distintos a la UCI completó los informes en el 2019 y el 2% en el 2020. En la mayoría de las regiones hubo una disminución general de la notificación en el 2020. El análisis del consumo de antibióticos mostró un aumento de piperacilina/tazobactam, ertapenem y cefepima del 2019 al 2020. Conclusiones. Se encontraron disparidades en la coherencia y en la frecuencia de la presentación de informes. Es necesario destinar esfuerzos para mejorar el cumplimiento de la notificación mensual, que disminuyó en el 2020 posiblemente debido a la pandemia de COVID-19. La falta de cumplimiento en la presentación de los reportes y los problemas de calidad de los datos deben abordarse con los hospitales para facilitar la interpretación válida de las tendencias de consumo de antibióticos.

RESUMO Objetivo. Avaliar o cumprimento da exigência de notificar mensalmente o consumo de antibióticos em hospitais secundários e terciários ao Sistema Nacional de Vigilância em Saúde Pública da Colômbia (SIVIGILA-INS) e descrever o consumo informado de antibióticos de 2018 a 2020. Métodos. Este estudo envolveu uma análise secundária dos dados de consumo de antibióticos enviados para o SIVIGILA-INS. A frequência de notificação pelos hospitais foi avaliada e comparada com a frequência esperada. Os dados foram desagregados entre unidades de terapia intensiva (UTIs) e enfermarias gerais e por regiões geográficas. O consumo foi expresso como dose diária definida (DDD) por 100 leitos ocupados para sete antibióticos. Resultados. Mais de 70% dos hospitais notificaram consumo de antibióticos pelo menos uma vez em cada um dos três anos (79% na UTI e 71% nas enfermarias gerais). Entre eles, 59% dos hospitais enviaram todas as notificações relativas a UTIs (12 notificações mensais) no período de 2018 a 2019, mas apenas 4% o fizeram em 2020. No caso das enfermarias gerais, 52% dos hospitais enviaram todas as notificações em 2019 e 2% o fizeram em 2020. A maioria das regiões teve uma diminuição geral no número de notificações enviadas em 2020. A análise do consumo de antibióticos revelou um aumento no uso de piperacilina/tazobactam, ertapeném e cefepima de 2019 para 2020. Conclusões. Houve lacunas na uniformidade e frequência das notificações. São necessários esforços para melhorar o cumprimento da exigência de notificações mensais, que, possivelmente devido à pandemia de COVID‑19, diminuiu em 2020. Problemas relacionados ao não cumprimento da exigência de notificação e à qualidade dos dados devem ser resolvidos junto aos hospitais para permitir uma interpretação válida das tendências de consumo de antibióticos.

ABSTRACT Objective. To assess the compliance in secondary and tertiary level hospitals with monthly reporting of antibiotic consumption to the Colombian National Public Health Surveillance System (SIVIGILA-INS), and to describe reported antibiotic consumption during 2018–2020. Methods. This study involved a secondary analysis of antibiotic consumption data reported to SIVIGILA-INS. Frequency of hospital reporting was assessed and compared against expected reports, disaggregated by intensive care units (ICU)/non-ICU wards and geographical regions. Consumption was expressed as defined daily dose (DDD) per 100 occupied beds for seven antibiotics. Results. More than 70% of hospitals reported antibiotic consumption at least once in each of the three years (79% in ICU and 71% in non-ICU wards). Of these, ICU monthly reporting was complete (12 monthly reports per year) for 59% in the period 2018–2019 but only 4% in 2020. Non-ICU reporting was complete for 52% in 2019 and for 2% in 2020. Most regions had an overall decrease in reporting in 2020. Analysis of antibiotic consumption showed an increase for piperacillin/tazobactam, ertapenem, and cefepime from 2019 to 2020. Conclusions. There were gaps in the consistency and frequency of reporting. Efforts are needed to improve compliance with monthly reporting, which declined in 2020, possibly due to the COVID-19 pandemic. Non-compliance on reporting and data quality issues should be addressed with the hospitals to enable valid interpretation of antibiotic consumption trends.

ABSTRACT OBJECTIVE To analyze the consumption of drugs for Alzheimer’s disease on the Brazilian private market and its geographical distribution from 2014 to 2020. METHODS National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels. RESULTS Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020. CONCLUSION The consumption of medicines indicated to treat Alzheimer’s disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases. Alzheimers Alzheimer s 201 2020 donepezil galantamine rivastigmine dose1000 dose 1 000 dose/1,00 inhabitantsyear inhabitants year national regional levels 5000 5 5,00 doses1000 doses doses/1,00 160001000 16 16,000/1,00 variation country services use chronicdegenerative chronic degenerative diseases 20 202 dose100 00 dose/1,0 500 5,0 doses100 doses/1,0 16000100 16,000/1,0 2 dose10 0 dose/1, 50 5, doses10 doses/1, 1600010 16,000/1, dose1 dose/1 doses1 doses/1 160001 16,000/1 dose/ doses/ 16000 16,000/ 1600 16,000 160 16,00 16,0 16,

RESUMO OBJETIVO Analisar o consumo de medicamentos para a doença de Alzheimer no mercado privado brasileiro e sua distribuição geográfica entre os anos de 2014 e 2020. MÉTODOS Foram utilizados dados do Sistema Nacional de Gerenciamento de Produtos Controlados relativos às vendas de donepezila, galantamina, rivastigmina e memantina, entre janeiro de 2014 a dezembro de 2020, em todo o território nacional. Os dados de venda foram utilizados como proxy para o consumo dos medicamentos, avaliado em dose diária definida (DDD)/1.000 habitantes/ano em nível nacional, regional, por unidade federativa e microrregião. RESULTADOS O consumo dos medicamentos passou de 5.000 DDD/1.000 habitantes em 2014 para mais de 16.000 DDD/1.000 habitantes em 2020, e todas as unidades de federação apresentaram variação positiva. A região Nordeste apresentou o maior consumo acumulado no período, porém exibiu disparidades microrregionais. A região Norte apresentou o menor consumo. Os medicamentos mais consumidos foram donepezila e memantina, os quais também apresentaram maior crescimento do consumo no intervalo de tempo entre os anos de 2014 e 2020. CONCLUSÃO O consumo de medicamentos para o tratamento da doença de Alzheimer triplicou no Brasil entre os anos de 2014 e 2020, o que pode estar relacionado ao aumento da prevalência da doença no país e/ou maior acesso a serviços de saúde, assim como estar ligado, também, à utilização inapropriada destes medicamentos. Este é um desafio para gestores e profissionais de saúde num cenário de envelhecimento populacional e aumento da prevalência de doenças crônico-degenerativas. 201 2020 galantamina memantina nacional DDD1000 DDD /1.000 1 000 (DDD)/1.00 habitantesano ano regional microrregião 5000 5 5.00 DDD/1.00 16000 16 16.00 positiva período microrregionais eou ou ligado crônicodegenerativas. crônicodegenerativas crônico degenerativas. degenerativas crônico-degenerativas 20 202 DDD100 1000 /1.00 00 (DDD)/1.0 500 5.0 DDD/1.0 1600 16.0 2 DDD10 100 /1.0 0 (DDD)/1. 50 5. DDD/1. 160 16. DDD1 10 /1. (DDD)/1 DDD/1 /1 (DDD)/ DDD/ / (DDD) (DDD

ABSTRACT OBJECTIVE To analyze the consumption of drugs for Alzheimer’s disease on the Brazilian private market and its geographical distribution from 2014 to 2020. METHODS National data from the Brazilian National System of Controlled Product Management were used, regarding sales of donepezil, galantamine, rivastigmine, and memantine from January 2014 to December 2020. Sales data were used as a proxy for drug consumption and expressed as defined daily dose/1,000 inhabitants/year at national, regional, federative unit and microregion levels. RESULTS Drug consumption went from 5,000 defined daily doses/1,000 inhabitants, in 2014, to more than 16,000/1,000 inhabitants, in 2020, and all federative units showed positive variation. The Brazilian Northeast had the highest cumulative consumption in the period but displayed microregional disparities while the North region had the lowest consumption. Donepezil and memantine were the most consumed drugs, with the highest growth in consumption from 2014 to 2020. CONCLUSION The consumption of medicines indicated to treat Alzheimer’s disease tripled in Brazil between 2014 and 2020, which may relate to the increase in the prevalence of the disease in the country, greater access to health services, and inappropriate use. This challenges managers and healthcare providers due to population aging and the increased prevalence of chronic-degenerative diseases.

RESUMO OBJETIVO Analisar o consumo de medicamentos para a doença de Alzheimer no mercado privado brasileiro e sua distribuição geográfica entre os anos de 2014 e 2020. MÉTODOS Foram utilizados dados do Sistema Nacional de Gerenciamento de Produtos Controlados relativos às vendas de donepezila, galantamina, rivastigmina e memantina, entre janeiro de 2014 a dezembro de 2020, em todo o território nacional. Os dados de venda foram utilizados como proxy para o consumo dos medicamentos, avaliado em dose diária definida (DDD)/1.000 habitantes/ano em nível nacional, regional, por unidade federativa e microrregião. RESULTADOS O consumo dos medicamentos passou de 5.000 DDD/1.000 habitantes em 2014 para mais de 16.000 DDD/1.000 habitantes em 2020, e todas as unidades de federação apresentaram variação positiva. A região Nordeste apresentou o maior consumo acumulado no período, porém exibiu disparidades microrregionais. A região Norte apresentou o menor consumo. Os medicamentos mais consumidos foram donepezila e memantina, os quais também apresentaram maior crescimento do consumo no intervalo de tempo entre os anos de 2014 e 2020. CONCLUSÃO O consumo de medicamentos para o tratamento da doença de Alzheimer triplicou no Brasil entre os anos de 2014 e 2020, o que pode estar relacionado ao aumento da prevalência da doença no país e/ou maior acesso a serviços de saúde, assim como estar ligado, também, à utilização inapropriada destes medicamentos. Este é um desafio para gestores e profissionais de saúde num cenário de envelhecimento populacional e aumento da prevalência de doenças crônico-degenerativas.

RESUMO Objetivo: Descrever o perfil de dispensação de medicamentos da saúde mental analisando o uso antes e durante a pandemia de COVID-19 no âmbito do Sistema Único de Saúde (SUS). Métodos: Estudo farmacoepidemiológico a partir da análise retrospectiva dos registros de dispensação de psicofármacos na base de dados do SUS no estado de Minas Gerais (MG) nos períodos antes (2018–2019) e durante a pandemia de COVID-19 (2020–2021). Um banco de dados com os registros de dispensação dos municípios foi elaborado, sendo verificada a consistência de lançamento pelo teste de Análise de Variância (ANOVA). O consumo dos medicamentos foi mensurado em dose diária definida (DDD) por 1.000 habitantes/dia para o SUS, sendo a diferença entre os períodos avaliada pelo teste estatístico t de Student. Resultados: Durante a pandemia de COVID-19 houve aumento no consumo de psicofármacos no SUS-MG. Os medicamentos mais consumidos foram cloridrato fluoxetina, diazepam e fenobarbital sódico (DDD=5,89; 3,42; 2,49) no componente básico (CBAF), e olanzapina, risperidona e hemifumarato de quetiapina (DDD=0,80; 0,47; 0,38) no componente especializado da Assistência Farmacêutica (CEAF). Os maiores aumentos percentuais no consumo foram atribuídos ao clonazepam (75,37%) e carbonato de lítio (35,35%) no CBAF e levetiracetam (3.000,00%) e cloridrato de memantina (340,00%) no CEAF. Conclusão: A alteração do perfil de dispensação de psicotrópicos durante a pandemia de COVID-19 alerta quanto à necessidade de produção de mais estudos a fim de completar, confirmar ou afastar este perfil e monitorar o uso de psicofármacos pela população no contexto pós-pandêmico.

ABSTRACT Objective: To describe the profile of dispensation of mental health drugs by analyzing trends in use before and during the COVID-19 pandemic within the Unified Health System (Sistema Único de Saúde [SUS]). Methods: Pharmacoepidemiological study based on the retrospective analysis of records regarding the dispensation of psychotropic medicines in the SUS database in the state of Minas Gerais between 2018 and 2021, considering the periods before (2018–2019) and during the COVID-19 pandemic (2020–2021). A database with the records of dispensation of municipalities was created, and the consistency of releases was verified using the Analysis of Variance (ANOVA) test. Medicine consumption was measured in a defined daily dose (DDD) per 1,000 inhabitants/day for SUS, and the difference between periods was evaluated using Student's t-test. Results: During the COVID-19 pandemic, there was an increase in the consumption of psychotropic drugs in SUS-MG. The most consumed medicines were fluoxetine hydrochloride, diazepam and phenobarbital sodium (DDD=5.89; 3.42; 2.49) in the Basic Pharmaceutical Services Component(CBAF), and olanzapine, risperidone and quetiapine hemifumarate (DDD=0.80; 0.47; 0.38) in the Specialized Pharmaceutical Services Component (CEAF). The highest percentage increase in consumption was attributed to clonazepam (75.37%) and lithium carbonate (35.35%), in CBAF, and levetiracetam (3,000.00%) and memantine hydrochloride (340.0%) in CEAF. Conclusion: The change in the psychotropic drug dispensation profile during the COVID-19 pandemic highlights the need to produce more studies to complete, confirm or rule out this profile and monitor the use of psychotropic drugs by the population in the post-pandemic context.

ABSTRACT Objective: To describe the profile of dispensation of mental health drugs by analyzing trends in use before and during the COVID-19 pandemic within the Unified Health System (Sistema Único de Saúde [SUS]). Methods: Pharmacoepidemiological study based on the retrospective analysis of records regarding the dispensation of psychotropic medicines in the SUS database in the state of Minas Gerais between 2018 and 2021, considering the periods before (2018–2019) and during the COVID-19 pandemic (2020–2021). A database with the records of dispensation of municipalities was created, and the consistency of releases was verified using the Analysis of Variance (ANOVA) test. Medicine consumption was measured in a defined daily dose (DDD) per 1,000 inhabitants/day for SUS, and the difference between periods was evaluated using Student's t-test. Results: During the COVID-19 pandemic, there was an increase in the consumption of psychotropic drugs in SUS-MG. The most consumed medicines were fluoxetine hydrochloride, diazepam and phenobarbital sodium (DDD=5.89; 3.42; 2.49) in the Basic Pharmaceutical Services Component(CBAF), and olanzapine, risperidone and quetiapine hemifumarate (DDD=0.80; 0.47; 0.38) in the Specialized Pharmaceutical Services Component (CEAF). The highest percentage increase in consumption was attributed to clonazepam (75.37%) and lithium carbonate (35.35%), in CBAF, and levetiracetam (3,000.00%) and memantine hydrochloride (340.0%) in CEAF. Conclusion: The change in the psychotropic drug dispensation profile during the COVID-19 pandemic highlights the need to produce more studies to complete, confirm or rule out this profile and monitor the use of psychotropic drugs by the population in the post-pandemic context. Objective COVID19 COVID 19 COVID-1 Sistema SUS. . [SUS]) Methods 201 2021 2018–2019 20182019 2019 (2018–2019 2020–2021. 20202021 2020–2021 2020 (2020–2021) created ANOVA (ANOVA test DDD (DDD 1000 1 000 1,00 inhabitantsday inhabitants day Students Student s ttest. ttest t t-test Results SUSMG. SUSMG MG. MG SUS-MG DDD=5.89 DDD589 5 89 (DDD=5.89 3.42 342 3 42 2.49 249 2 49 ComponentCBAF, ComponentCBAF CBAF , Component(CBAF) olanzapine DDD=0.80 DDD080 0 80 (DDD=0.80 0.47 047 47 0.38 038 38 CEAF (CEAF) 75.37% 7537 75 37 (75.37% 35.35%, 3535 35.35% 35 (35.35%) 3,000.00% 300000 00 (3,000.00% 340.0% 3400 340 (340.0% Conclusion complete postpandemic post context COVID1 COVID- [SUS] 20 202 2018–201 2018201 (2018–201 2020202 2020–202 (2020–2021 100 1,0 DDD=5.8 DDD58 8 (DDD=5.8 3.4 34 4 2.4 24 Component(CBAF DDD=0.8 DDD08 (DDD=0.8 0.4 04 0.3 03 (CEAF 75.37 753 7 (75.37 353 35.35 (35.35% 3,000.00 30000 (3,000.00 340.0 (340.0 [SUS 2018–20 201820 (2018–20 202020 2020–20 (2020–202 10 1, DDD=5. DDD5 (DDD=5. 3. 2. DDD=0. DDD0 (DDD=0. 0. 75.3 (75.3 35.3 (35.35 3,000.0 3000 (3,000.0 340. (340. 2018–2 20182 (2018–2 20202 2020–2 (2020–20 DDD=5 (DDD=5 DDD=0 (DDD=0 75. (75. 35. (35.3 3,000. 300 (3,000. (340 2018– (2018– 2020– (2020–2 DDD= (DDD= (75 (35. 3,000 30 (3,000 (34 (2018 (2020– (7 (35 3,00 (3,00 (3 (201 (2020 ( 3,0 (3,0 (20 (202 3, (3, (2

RESUMO Objetivo: Descrever o perfil de dispensação de medicamentos da saúde mental analisando o uso antes e durante a pandemia de COVID-19 no âmbito do Sistema Único de Saúde (SUS). Métodos: Estudo farmacoepidemiológico a partir da análise retrospectiva dos registros de dispensação de psicofármacos na base de dados do SUS no estado de Minas Gerais (MG) nos períodos antes (2018–2019) e durante a pandemia de COVID-19 (2020–2021). Um banco de dados com os registros de dispensação dos municípios foi elaborado, sendo verificada a consistência de lançamento pelo teste de Análise de Variância (ANOVA). O consumo dos medicamentos foi mensurado em dose diária definida (DDD) por 1.000 habitantes/dia para o SUS, sendo a diferença entre os períodos avaliada pelo teste estatístico t de Student. Resultados: Durante a pandemia de COVID-19 houve aumento no consumo de psicofármacos no SUS-MG. Os medicamentos mais consumidos foram cloridrato fluoxetina, diazepam e fenobarbital sódico (DDD=5,89; 3,42; 2,49) no componente básico (CBAF), e olanzapina, risperidona e hemifumarato de quetiapina (DDD=0,80; 0,47; 0,38) no componente especializado da Assistência Farmacêutica (CEAF). Os maiores aumentos percentuais no consumo foram atribuídos ao clonazepam (75,37%) e carbonato de lítio (35,35%) no CBAF e levetiracetam (3.000,00%) e cloridrato de memantina (340,00%) no CEAF. Conclusão: A alteração do perfil de dispensação de psicotrópicos durante a pandemia de COVID-19 alerta quanto à necessidade de produção de mais estudos a fim de completar, confirmar ou afastar este perfil e monitorar o uso de psicofármacos pela população no contexto pós-pandêmico. Objetivo COVID19 COVID 19 COVID-1 SUS. . (SUS) Métodos MG (MG 2018–2019 20182019 2018 2019 (2018–2019 2020–2021. 20202021 2020–2021 2020 2021 (2020–2021) elaborado ANOVA. ANOVA (ANOVA) DDD (DDD 1000 1 000 1.00 habitantesdia habitantes dia Student Resultados SUSMG. SUSMG MG. SUS-MG fluoxetina DDD=5,89 DDD589 5 89 (DDD=5,89 3,42 342 3 42 2,49 249 2 49 CBAF, , (CBAF) olanzapina DDD=0,80 DDD080 0 80 (DDD=0,80 0,47 047 47 0,38 038 38 CEAF (CEAF) 75,37% 7537 75 37 (75,37% 35,35% 3535 35 (35,35% 3.000,00% 300000 00 (3.000,00% 340,00% 34000 340 (340,00% Conclusão completar póspandêmico. póspandêmico pós pandêmico. pandêmico pós-pandêmico COVID1 COVID- (SUS 2018–201 2018201 201 (2018–201 2020202 2020–202 202 (2020–2021 (ANOVA 100 1.0 DDD=5,8 DDD58 8 (DDD=5,8 3,4 34 4 2,4 24 (CBAF DDD=0,8 DDD08 (DDD=0,8 0,4 04 0,3 03 (CEAF 75,37 753 7 (75,37 35,35 353 (35,35 3.000,00 30000 (3.000,00 340,00 3400 (340,00 2018–20 201820 20 (2018–20 202020 2020–20 (2020–202 10 1. DDD=5, DDD5 (DDD=5, 3, 2, DDD=0, DDD0 (DDD=0, 0, 75,3 (75,3 35,3 (35,3 3.000,0 3000 (3.000,0 340,0 (340,0 2018–2 20182 (2018–2 20202 2020–2 (2020–20 DDD=5 (DDD=5 DDD=0 (DDD=0 75, (75, 35, (35, 3.000, 300 (3.000, 340, (340, 2018– (2018– 2020– (2020–2 DDD= (DDD= (75 (35 3.000 30 (3.000 (340 (2018 (2020– (7 (3 3.00 (3.00 (34 (201 (2020 ( 3.0 (3.0 (20 (202 3. (3. (2

Abstract Objectives: High economic impact medicines (HIM) are challenging health services of the European countries. Nevertheless, there is no consensus on what constitutes a HIM. The aim of the study is to compile a list of HIM dispensed by Spanish hospital pharmacy services and to analyze the situation regarding those medicines in Spain. Methods: Drugs with a cost higher than €10,000 per year (HCM) or high volume of consumption (HVM) were considered HIM. The ex-factory price (PVL) per defined daily dosage or prescribed daily dose was calculated. Results: A total of 147 active ingredients were HCM, corresponding to ATC code: L (69.4%), J (10.9%) and A (10.2%). Mean daily PVL of HCM was € 218.6 (28.6-2,892.5). 38.8% were innovative drugs, 26.5% were orphan products and 34.0% were biological drugs. A total of 16 medicines (5.8%) were priced more than € 10,000/pack. The HVM belonged mainly to group L (45.0%) and J (35.0%). Average daily PVL of HVM was € 154.4 (1.1-1,629.3). 35% were first-in-class drugs, 5% orphan medicines and 60% biological drugs. Conclusions: This study shows that a large number of HIM are dispensed by the hospital pharmacy services, mainly antineoplastic and antiinfective drugs. Although the minimum daily PVL to consider a medicine as HCM was € 27.4. The average daily price of HCM was >€ 200. However, given the high consumption of some drugs, medicines with a daily cost as low as € 1.1 can be considered HIM. A new category of HCM, ultra-premium-priced medicines, could be established for drugs with a cost higher than € 10,000 per pack.

Resumen Objetivos: Los medicamentos de alto impacto económico (MAIE) constituyen un reto para los servicios de salud públicos de los países europeos. Sin embargo, no existe consenso sobre qué constituye un MAIE. El objetivo del estudio fue configurar una lista de MAIE dispensados por los servicios de farmacia hospitalarios y analizar la situación respecto a estos fármacos en España. Métodos: Se consideraron MAIE aquellos fármacos con un coste >10.000 €/año (MAC) o con un elevado volumen de consumo (MEC). Se estimaron los precios (PVL) por dosis diaria definida o dosis diaria prescrita. Resultados: Un total de 147 principios activos fueron considerados MAC, correspondiendo mayoritariamente con los grupos: L (69,4%), J (10,9%) y A (10,2%). El PVL medio diario de los MAC fue 218,6 € (28,6-2.892,5). El 38,8% de los MAC fueron innovadores, 26,5% huérfanos y 34,0% biológicos. Dieciséis medicamentos tuvieron un coste >10.000 €/envase. Los MEC pertenecieron principalmente al grupo L (45,0%) y J (35,0%). El PVL medio diario de los MEC fue 154,4 € (1,1-1.629,3). El 35,5% fueron innovadores, 5,0% huérfanos y 60,0% biológicos. Conclusiones: Un elevado número de MAIE son dispensados por los servicios de farmacia hospitalarios, principalmente antineoplásicos y antiinfecciosos. Aunque el PVL mínimo diario para considerar un medicamento de alto impacto es 27,4 €, el PVL medio diario de los MAC fue >200 €. Sin embargo, el elevado consumo de algunos fármacos, hace que medicamentos con un coste tan bajo como 1,1 € puedan ser considerados MAIE. Se puede establecer una nueva categoría de MAC para aquellos con un coste >10.000 €/envase.

ABSTRACT Objective: There is little data about the remission phase in adolescents and young adults with newly diagnosed type 1 diabetes mellitus (T1D). The aims of this study were to determine the prevalence of remission and its predicting factors among adolescents and young adults with newly diagnosed T1D and to assess the association between remission and long-term glycemic control in this population. Subjects and methods: This is a longitudinal and retrospective study including 128 type 1 diabetic patients aged between 12 and 30 years at diabetes onset. Clinical, biological and therapeutic features were collected at diagnosis and for 5 years after diagnosis. Remission was defined by an HbA1c < 6.5% with a daily insulin dose < 0.5 IU/kg/day. Results: Twenty-three patients (18%) experienced a remission. The peak of remission prevalence was at 6 months after diabetes diagnosis. An insulin dose at discharge <0.8 IU/kg/day was independently associated with remission (p=0.03, adjusted OR [CI 95%] = 0.2 [0.1-0.9]). A low socioeconomic level was independently associated with non remission (p=0.02, adjusted OR [CI 95%] = 4.3 [1.3-14.3]). HbA1c was significantly lower during the first five years of follow-up in remitters. The daily insulin dose was significantly lower during the first four years of follow-up in remitters. Conclusions: Occurrence of remission in adolescents and young adults with newly diagnosed T1D is associated with better glycemic control and lower insulin requirements during the first 5 years of follow-up. A lower initial dose of insulin was associated with a higher percentage of remission.

RESUMO Objetivo: Avaliar a probabilidade de atingir o alvo pela razão entre a área sob a curva e a concentração inibitória mínima de vancomicina em pacientes pediátricos após o esquema de dose empírica e demonstrar a aplicabilidade desse método para o monitoramento da vancomicina. Metódos: Foi realizado um estudo de coorte retrospectivo que incluiu pacientes pediátricos com função renal normal internados entre janeiro e dezembro de 2020. O modelo de um compartimento com cinética de primeira ordem foi utilizado para estimar os parâmetros farmacocinéticos, e a área sob a curva foi calculada pela regra do trapézio. O alvo terapêutico foi definido como a razão entre a área sob a curva e a concentração inibitória mínima ≥ 400 e < 600. O teste do qui-quadrado foi aplicado para comparar a probabilidade de atingir o alvo nos grupos etários, enquanto os parâmetros farmacocinéticos foram comparados pelo teste de Kruskal-Wallis com o teste de Dunn para análises post hoc. Consideraram-se significativos os valores de p < 0,05. Resultados: Foram analisados, no total, 42 pares de níveis de vancomicina de 17 pacientes inscritos neste estudo. Após a dose diária empírica de vancomicina, o alvo terapêutico foi atingido em cinco (29%) pacientes; quatro pacientes (24%) apresentavam razão entre a área sob a curva inicial supraterapêutica e o valor de concentração inibitória mínima (> 600mg.h/L) e oito (47%) tinham valores subterapêuticos (< 400mg.h/L). Os patógenos mais identificados foram Staphylococcus spp. (n = 7). Os níveis de vale e as áreas sob a curva mostraram valores moderados de correlação (R2 = 0,73). Um (6%) paciente apresentou lesão renal aguda. Conclusão: A maioria dos pacientes não atingiu o alvo terapêutico com esquema de dose empírica de vancomicina, e a implementação de dosagem baseada na área sob a curva usando duas medições de amostra permitiu ajustes de dose em tempo real com base nos parâmetros farmacocinéticos dos indivíduos.

ABSTRACT Objective: To assess the percentage of vancomycin area under the curve/minimum inhibitory concentration target attainment in pediatric patients after the empirical dose regimen and to demonstrate the applicability of this method for vancomycin monitoring. Methods: A retrospective cohort study was performed including pediatric patients with normal renal function admitted between January 2020 and December 2020. The one-compartment model with first-order kinetics was used to estimate the pharmacokinetic parameters, and the area under the curve was calculated by the trapezoidal rule. The therapeutic target was defined as area under the curve/minimum inhibitory concentration ≥ 400 and < 600. The Chi-squared test was applied to compare the percentage of target attainment over age groups, while the pharmacokinetic parameters were compared by the Kruskal-Wallis test with Dunn’s test for post hoc analyses. We considered significant p-values < 0.05. Results: In total, 42 pairs of vancomycin levels were analyzed from 17 patients enrolled in this study. After empirical vancomycin daily dosing, the therapeutic target was achieved in five (29%) patients; four patients (24%) had a supratherapeutic initial area under the curve/minimum inhibitory concentration value (> 600mg.h/L), and eight (47%) patients had subtherapeutic values (< 400mg.h/L). The most identified pathogens were Staphylococcus spp. (n = 7). Trough levels and areas under the curve showed moderate correlation values (R2 = 0.73). Acute kidney injury occurred in one (6%) patient. Conclusion: Most patients did not reach the therapeutic target with a vancomycin empirical dose regimen, and the implementation of area under the curve-based dosing using two sample measurements allowed for real-time dose adjustments based on individuals’ pharmacokinetic parameters.