Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Report 46: Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Socioeconomic Determinants of Antibiotic Consumption in the State of São Paulo, Brazil: The Effect of Restricting Over-The-Counter Sales.

BACKGROUND: Improper antibiotic use is one of the main drivers of bacterial resistance to antibiotics, increasing infectious diseases morbidity and mortality and raising costs of healthcare. The level of antibiotic consumption has been shown to vary according to socioeconomic determinants (SED) such as income and access to education. In many Latin American countries, antibiotics could be easily purchased without a medical prescription in private pharmacies before enforcement of restrictions on over-the-counter (OTC) sales in recent years. Brazil issued a law abolishing OTC sales in October 2010. This study seeks to find SED of antibiotic consumption in the Brazilian state of São Paulo (SSP) and to estimate the impact of the 2010 law. METHODS: Data on all oral antibiotic sales having occurred in the private sector in SSP from 2008 to 2012 were pooled into the 645 municipalities of SSP. Linear regression was performed to estimate consumption levels that would have occurred in 2011 and 2012 if no law regulating OTC sales had been issued in 2010. These values were compared to actual observed levels, estimating the effect of this law. Linear regression was performed to find association of antibiotic consumption levels and of a greater effect of the law with municipality level data on SED obtained from a nationwide census. RESULTS: Oral antibiotic consumption in SSP rose from 8.44 defined daily doses per 1,000 inhabitants per day (DID) in 2008 to 9.95 in 2010, and fell to 8.06 DID in 2012. Determinants of a higher consumption were higher human development index, percentage of urban population, density of private health establishments, life expectancy and percentage of females; lower illiteracy levels and lower percentage of population between 5 and 15 years old. A higher percentage of females was associated with a stronger effect of the law. CONCLUSIONS: SSP had similar antibiotic consumption levels as the whole country of Brazil, and they were effectively reduced by the policy.

The Impact of Restricting Over-the-Counter Sales of Antimicrobial Drugs: Preliminary Analysis of National Data.

To describe the nationwide impact of a restrictive law on over-the-counter sales of antimicrobial drugs, implemented in Brazil in November 2010. Approximately 75% of the population receives healthcare from the public health system and receives free-of-charge medication if prescribed. Total sales in private pharmacies as compared with other channels of sales of oral antibiotics were evaluated in this observational study before and after the law (2008-2012). Defined daily dose per 1000 inhabitants per day (DDD/TID) was used as standard unit. In private pharmacies the effect of the restrictive law was statistically significant (P < 0.001) with an estimated decrease in DDD/TID of 1.87 (s.e. =  0.18). In addition, the trend of DDD/TID before the restrictive law was greater than after the intervention (P < 0.001). Before November 2010, the slope for the trend line was estimated as 0.08 (s.e. = 0.01) whereas after the law, the estimated slope was 0.03 (s.e. = 0.01). As for the nonprivate channels, no difference in sales was observed (P = 0.643). The impact in the South and Southeast (more developed) regions was higher than in the North, Northeast, and Mid-West. The state capitals had a 19% decrease, compared with 0.8% increase in the rest of the states. Before the law, the sales of antimicrobial drugs were steadily increasing. From November 2010, with the restrictive law, there was an abrupt drop in sales followed by an increase albeit at a significantly lower rate. The impact was higher in regions with better socio-economic status.

National prevalence survey in Brazil to evaluate the quality of microbiology laboratories: the importance of defining priorities to allocate limited resources.

This report describes a survey of microbiology laboratories (n = 467) serving Brazilian hospitals with ≥10 intensive care beds and/or involved in the government health care adverse event reporting system. Coordinators were interviewed and laboratories classified as follows: Level 0 (no minimal functioning conditions-85.4% of laboratories); Level 1 (minimal functioning conditions but inadequate execution of basic routine-6.7%); Level 2 (minimal functioning conditions and adequate execution of basic routine but no adequate procedures for quality control-5.8%); Level 3 (minimal functioning conditions, adequate execution of basic routine, and adequate procedures for quality control, but no direct communication with the infection control department-0.9%); Level 4 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, and direct communication with infection control, but no available advanced resources-none); and Level 5 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, direct communication with infection control, and available advanced resources-0.9%). Twelve laboratories did not perform Ziehl-Neelsen staining; 271 did not have safety cabinets; and >30% without safety cabinets had automated systems. Low quality was associated with serving hospitals not participating in government adverse-event program; private hospitals; nonteaching hospitals; and those outside state capitals. Results may reflect what occurs in many other countries where defining priorities is important due to limited resources.

National prevalence survey in Brazil to evaluate the quality of microbiology laboratories: the importance of defining priorities to allocate limited resources / Encuesta de prevalencia nacional para evaluar la calidad de los laboratorios de microbiología en el Brasil: importancia de la definición de prioridades para asignar recursos limitados

This report describes a survey of microbiology laboratories (n = 467) serving Brazilian hospitals with >10 intensive care beds and/or involved in the government health care adverse event reporting system. Coordinators were interviewed and laboratories classified as follows: Level 0 (no minimal functioning conditions-85.4% of laboratories); Level 1 (minimal functioning conditions but inadequate execution of basic routine-6.7%); Level 2 (minimal functioning conditions and adequate execution of basic routine but no adequate procedures for quality control-5.8%); Level 3 (minimal functioning conditions, adequate execution of basic routine, and adequate procedures for quality control, but no direct communication with the infection control department-0.9%); Level 4 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, and direct communication with infection control, but no available advanced resources-none); and Level 5 (minimal functioning conditions, adequate execution of basic routine, adequate procedures for quality control, direct communication with infection control, and available advanced resources-0.9%). Twelve laboratories did not perform Ziehl-Neelsen staining; 271 did not have safety cabinets; and >30% without safety cabinets had automated systems. Low quality was associated with serving hospitals not participating in government adverse-event program; private hospitals; nonteaching hospitals; and those outside state capitals. Results may reflect what occurs in many other countries where defining priorities is important due to limited resources.

Este artículo describe una encuesta realizada en Brasil en laboratorios de microbiología (n = 467) que prestaban servicio a hospitales que contaban al menos con 10 camas de cuidados intensivos. Se entrevistó a los coordinadores y los laboratorios se clasificaron de la siguiente manera: nivel 0 (sin condiciones de funcionamiento mínimas: 85,4% de los laboratorios), nivel 1 (condiciones de funcionamiento mínimas pero ejecución inadecuada del trabajo habitual básico: 6,7%), nivel 2 (condiciones de funcionamiento mínimas y ejecución adecuada del trabajo habitual básico, pero sin procedimientos de control de calidad apropiados: 5,8%), nivel 3 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico y procedimientos de control de calidad apropiados, pero sin comunicación directa con el departamento de control de infecciones: 0,9%), nivel 4 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico, procedimientos de control de calidad apropiados y comunicación directa con el departamento de control de infecciones, pero sin recursos avanzados disponibles: ningún laboratorio) y nivel 5 (condiciones de funcionamiento mínimas, ejecución adecuada del trabajo habitual básico, procedimientos de control de calidad apropiados, comunicación directa con el departamento de control de infecciones y recursos avanzados disponibles: 0,9%). Doce laboratorios no realizaban la tinción de Ziehl-Neelsen, 271 no contaban con cámaras de seguridad biológica, y más de 30% de los laboratorios que carecían de cámaras de seguridad biológica tenían sistemas automatizados. La escasa calidad se asoció a la falta de participación en el programa gubernamental de notificación de acontecimientos adversos, a los hospitales privados, a los hospitales no docentes y a la ubicación de los hospitales fuera de las capitales de los estados. Los resultados pueden reflejar lo que ocurre en muchos otros países con recursos limitados, donde es importante definir las prioridades.

Cost-effectiveness of sick leave policies for health care workers with influenza-like illness, Brazil, 2009.

We describe the effect of influenza-like illness (ILI) during the outbreak of pandemic (H1N1) 2009 on health care worker (HCW) absenteeism and compare the effectiveness and cost of 2 sick leave policies for HCWs with suspected influenza. We assessed initial 2-day sick leaves plus reassessment until the HCW was asymptomatic (2-day + reassessment policy), and initial 7-day sick leaves (7-day policy). Sick leaves peaked in August 2009: 3% of the workforce received leave for ILI. Costs during May-October reached R$798,051.87 (≈US $443,362). The 7-day policy led to a higher monthly rate of sick leave days per 100 HCWs than did the 2-day + reassessment policy (8.72 vs. 3.47 days/100 HCWs; p<0.0001) and resulted in higher costs (US $609 vs. US $1,128 per HCW on leave). ILI affected HCW absenteeism. The 7-day policy was more costly and not more effective in preventing transmission to patients than the 2-day + reassessment policy.

Successful control program to implement the appropriate antibiotic prophylaxis for Cesarean section.

OBJECTIVE: Describe implementation of a successful program to reduce doses (cefazolin 2 to 1 g) used for antimicrobial prophylaxis. METHODS: Evaluation of an intervention program to reduce prophylactic antimicrobial doses. The intervention included weekly staff discussions, automatic dispensation of 1g-vial of cefazolin by the pharmacy unless expressly requested by surgeon and increase in post-discharge surveillance as a strategy to reassure surgeons of the safety of the reduction. In the pre and post intervention periods, a prospective study of antimicrobial consumption and surgical site infections were measured. RESULTS: There were 5,164 and 5,204 deliveries in 2001-2002 and 2003-2004, respectively; 1,524 (29.5%) and 1,363 (26%) were cesarean sections. There was a 45% decrease in cefazolin vials used on average per cesarean section (2.29 to 1.25). Patients evaluated increased from 16% to 67% and the SSI rates in both periods were 3.34% to 2.42%, respectively. CONCLUSION: An ample intervention, including administrative and educational measures, led to high compliance with dose reduction and saved more than US$4,000 in cefazolin, considered important because government reimbursement in Brazil for cesarean section is $80.

Successful control program to implement the appropriate antibiotic prophylaxis for cesarean section

OBJECTIVE: Describe implementation of a successful program to reduce doses (cefazolin 2 to 1 g) used for antimicrobial prophylaxis. METHODS: Evaluation of an intervention program to reduce prophylactic antimicrobial doses. The intervention included weekly staff discussions, automatic dispensation of 1g-vial of cefazolin by the pharmacy unless expressly requested by surgeon and increase in post-discharge surveillance as a strategy to reassure surgeons of the safety of the reduction. In the pre and post intervention periods, a prospective study of antimicrobial consumption and surgical site infections were measured. RESULTS: There were 5,164 and 5,204 deliveries in 2001-2002 and 2003-2004, respectively; 1,524 (29.5 percent) and 1,363 (26 percent) were cesarean sections. There was a 45 percent decrease in cefazolin vials used on average per cesarean section (2.29 to 1.25). Patients evaluated increased from 16 percent to 67 percent and the SSI rates in both periods were 3.34 percent to 2.42 percent, respectively. CONCLUSION: An ample intervention, including administrative and educational measures, led to high compliance with dose reduction and saved more than US$4,000 in cefazolin, considered important because government reimbursement in Brazil for cesarean section is $80.

OBJETIVO: descrever a implantação de um programa de redução de doses usadas para profilaxia antimicrobiana em cesárea. MÉTODOS: Descrição a implantação de um programa de redução de profilaxia com cefazolina de 2 g para 1 g através de discussões semanais com profissionais, dispensação automática de frascos de 1 g de cefazolina pela farmácia exceto quando feito pedido expresso pelo cirurgião. Houve um trabalho para aumentar a vigilância pós alta, com o objetivo de tranquilizar os cirurgiões quanto à segurança da nova dose. Foi realizada uma avaliação prospectiva, antes e depois da implantação do programa, do consumo de cefazolina e das taxas de infecção obtidas por vigilância durante a hospitalização e após a alta. RESULTADOS: Houve 5.164 e 5.204 partos em 2001-2 e 2003-4, respectivamente, sendo que 1.524 (29,5 por cento) e 1.363 (26 por cento) foram cesáreas. Houve uma queda de consumo de frascos de cefazolina de 45 por cento (2,29 para 1,25 por cesárea). O número de pacientes avaliados para infecção hospitalar aumentou de 16 por cento para 67 por cento, e as taxas de infecção foram 3,34 por cento e 2,42 por cento, respectivamente. CONCLUSÃO: Uma intervenção ampla, que incluiu medidas administrativas e educacionais, levou a uma alta adesão ao programa de redução de dose profilática em cesárea e permitiu uma economia acima de US$ 4.000 apenas considerando custos com cefazolina. Esta pode ser considerada importante especialmente porque o reembolso do SUS para parto cesárea é aproximadamente US$ 80.