Primary healthcare protects vulnerable populations from inequity in COVID-19 vaccination: An ecological analysis of nationwide data from Brazil.

Background: There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage. Methods: We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels. Findings: From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations. Interpretation: In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations. Funding: This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.

Characterisation of the first 250,000 hospital admissions for COVID-19 in Brazil: a retrospective analysis of nationwide data.

BACKGROUND: Most low-income and middle-income countries (LMICs) have little or no data integrated into a national surveillance system to identify characteristics or outcomes of COVID-19 hospital admissions and the impact of the COVID-19 pandemic on their national health systems. We aimed to analyse characteristics of patients admitted to hospital with COVID-19 in Brazil, and to examine the impact of COVID-19 on health-care resources and in-hospital mortality. METHODS: We did a retrospective analysis of all patients aged 20 years or older with quantitative RT-PCR (RT-qPCR)-confirmed COVID-19 who were admitted to hospital and registered in SIVEP-Gripe, a nationwide surveillance database in Brazil, between Feb 16 and Aug 15, 2020 (epidemiological weeks 8-33). We also examined the progression of the COVID-19 pandemic across three 4-week periods within this timeframe (epidemiological weeks 8-12, 19-22, and 27-30). The primary outcome was in-hospital mortality. We compared the regional burden of hospital admissions stratified by age, intensive care unit (ICU) admission, and respiratory support. We analysed data from the whole country and its five regions: North, Northeast, Central-West, Southeast, and South. FINDINGS: Between Feb 16 and Aug 15, 2020, 254 288 patients with RT-qPCR-confirmed COVID-19 were admitted to hospital and registered in SIVEP-Gripe. The mean age of patients was 60 (SD 17) years, 119 657 (47%) of 254 288 were aged younger than 60 years, 143 521 (56%) of 254 243 were male, and 14 979 (16%) of 90 829 had no comorbidities. Case numbers increased across the three 4-week periods studied: by epidemiological weeks 19-22, cases were concentrated in the North, Northeast, and Southeast; by weeks 27-30, cases had spread to the Central-West and South regions. 232 036 (91%) of 254 288 patients had a defined hospital outcome when the data were exported; in-hospital mortality was 38% (87 515 of 232 036 patients) overall, 59% (47 002 of 79 687) among patients admitted to the ICU, and 80% (36 046 of 45 205) among those who were mechanically ventilated. The overall burden of ICU admissions per ICU beds was more pronounced in the North, Southeast, and Northeast, than in the Central-West and South. In the Northeast, 1545 (16%) of 9960 patients received invasive mechanical ventilation outside the ICU compared with 431 (8%) of 5388 in the South. In-hospital mortality among patients younger than 60 years was 31% (4204 of 13 468) in the Northeast versus 15% (1694 of 11 196) in the South. INTERPRETATION: We observed a widespread distribution of COVID-19 across all regions in Brazil, resulting in a high overall disease burden. In-hospital mortality was high, even in patients younger than 60 years, and worsened by existing regional disparities within the health system. The COVID-19 pandemic highlights the need to improve access to high-quality care for critically ill patients admitted to hospital with COVID-19, particularly in LMICs. FUNDING: National Council for Scientific and Technological Development (CNPq), Coordinating Agency for Advanced Training of Graduate Personnel (CAPES), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ), and Instituto de Salud Carlos III.

An international comparison of the cost of fluid resuscitation therapies.

OBJECTIVE: Fluid resuscitation is a ubiquitous intervention in the management of patients treated in the intensive care unit, which has implications for intensive care unit resourcing and budgets. Our objective was to calculate the relative cost of resuscitation fluids in several countries to inform future economic evaluations. METHODS: We collected site-level data regarding the availability and cost of fluids as part of an international survey. We normalised costs to net present values using purchasing power parities and published inflation figures. Costs were also adjusted for equi-effective dosing based on intravascular volume expansion effectiveness and expressed as US dollars (USD) per 100 mL crystalloid equivalent. RESULTS: A total of 187 sites had access to cost data. Between countries, there was an approximate six fold variation in the cost of crystalloids and colloids overall. The average cost for crystalloids overall was less than 1 USD per 100 mL. In contrast, colloid fluids had higher average costs (59 USD per 100 mL). After adjusting for equi-effective dosing, saline was ∼27 times less costly than albumin (saline: 0.6 USD per 100 mL crystalloid equivalent; albumin 4-5%: 16.4 USD; albumin 20-25%: 15.8 USD) and ∼4 times less costly than hydroxyethyl starch solution (saline: 0.6 USD; hydroxyethyl starch solution: 2.5 USD). Buffered salt solutions, such as compound sodium acetate solutions (e.g., Plasmalyte®), had the highest average cost of crystalloid fluids, costing between 3 and 4 USD per 100 mL. CONCLUSION: The cost of fluid varies substantially between fluid types and between countries, although normal (0.9%) saline is consistently less costly than colloid preparations and some buffered salt solutions. These data can be used to inform future economic evaluations of fluid preparations.

Intensive care inequity in Rio de Janeiro: the effect of spatial distribution of health services on severe acute respiratory infection. / Desigualdades na terapia intensiva no Rio de Janeiro: efeitos da distribuição espacial dos serviços de saúde na infecção respiratória aguda grave.

OBJECTIVE: To analyze the distribution of adult intensive care units according to geographic region and health sector in Rio de Janeiro and to investigate severe acute respiratory infection mortality in the public sector and its association with critical care capacity in the public sector. METHODS: We evaluated the variation in intensive care availability and severe acute respiratory infection mortality in the public sector across different areas of the city in 2014. We utilized databases from the National Registry of Health Establishments, the Brazilian Institute of Geography and Statistics, the National Mortality Information System and the Hospital Admission Information System. RESULTS: There is a wide range of intensive care unit beds per capita (from 4.0 intensive care unit beds per 100,000 people in public hospitals in the West Zone to 133.6 intensive care unit beds per 100,000 people in private hospitals in the Center Zone) in the city of Rio de Janeiro. The private sector accounts for almost 75% of the intensive care unit bed supply. The more developed areas of the city concentrate most of the intensive care unit services. Map-based spatial analysis shows a lack of intensive care unit beds in vast territorial extensions in the less developed regions of the city. There is an inverse correlation (r = -0.829; 95%CI -0.946 to -0.675) between public intensive care unit beds per capita in different health planning areas of the city and severe acute respiratory infection mortality in public hospitals. CONCLUSION: Our results show a disproportionate intensive care unit bed provision across the city of Rio de Janeiro and the need for a rational distribution of intensive care.

Desigualdades na terapia intensiva no Rio de Janeiro: efeitos da distribuição espacial dos serviços de saúde na infecção respiratória aguda grave / Intensive care inequity in Rio de Janeiro: the effect of spatial distribution of health services on severe acute respiratory infection

RESUMO Objetivo: Analisar a distribuição das unidades de terapia intensiva para adultos, segundo a região geográfica e o setor sanitário no Rio de Janeiro, e investigar a mortalidade por infecção respiratória aguda grave no setor público e sua associação com a capacidade de terapia intensiva no setor público. Métodos: Avaliamos a variação da disponibilidade de terapia intensiva e a mortalidade por infecção respiratória aguda grave no setor público em diferentes áreas da cidade em 2014. Utilizamos as bases de dados do Cadastro Nacional de Estabelecimentos de Saúde, do Instituto Brasileiro de Geografia e Estatística, do Sistema de Informações sobre Mortalidade e do Sistema de Informações Hospitalares do SUS. Resultados: Foi ampla a variação na disponibilidade de leitos em unidades de terapia intensiva per capita (desde 4,0 leitos de terapia intensiva por 100 mil habitantes em hospitais públicos na zona oeste até 133,6 leitos em unidades de terapia intensiva por 100 mil habitantes nos hospitais privados na zona central) na cidade do Rio de Janeiro. O setor privado respondeu pelo suprimento de quase 75% dos leitos em unidades de terapia intensiva. Uma análise espacial com base em mapas mostrou falta de leitos em unidades de terapia intensiva em vastas extensões territoriais nas regiões menos desenvolvidas da cidade. Houve correlação inversa (r = -0,829; IC95% -0,946 - -0,675) entre a quantidade de leitos públicos em unidade de terapia intensiva per capita em diferentes áreas de planejamento em saúde na cidade e a mortalidade por infecção respiratória aguda grave em hospitais públicos. Conclusão: Nossos resultados mostram disponibilidade desproporcional de leitos em unidades de terapia intensiva na cidade do Rio de Janeiro e a necessidade de uma distribuição racional da terapia intensiva.

ABSTRACT Objective: To analyze the distribution of adult intensive care units according to geographic region and health sector in Rio de Janeiro and to investigate severe acute respiratory infection mortality in the public sector and its association with critical care capacity in the public sector. Methods: We evaluated the variation in intensive care availability and severe acute respiratory infection mortality in the public sector across different areas of the city in 2014. We utilized databases from the National Registry of Health Establishments, the Brazilian Institute of Geography and Statistics, the National Mortality Information System and the Hospital Admission Information System. Results: There is a wide range of intensive care unit beds per capita (from 4.0 intensive care unit beds per 100,000 people in public hospitals in the West Zone to 133.6 intensive care unit beds per 100,000 people in private hospitals in the Center Zone) in the city of Rio de Janeiro. The private sector accounts for almost 75% of the intensive care unit bed supply. The more developed areas of the city concentrate most of the intensive care unit services. Map-based spatial analysis shows a lack of intensive care unit beds in vast territorial extensions in the less developed regions of the city. There is an inverse correlation (r = -0.829; 95%CI -0.946 to -0.675) between public intensive care unit beds per capita in different health planning areas of the city and severe acute respiratory infection mortality in public hospitals. Conclusion: Our results show a disproportionate intensive care unit bed provision across the city of Rio de Janeiro and the need for a rational distribution of intensive care.

A saúde na Agenda 2030 de Desenvolvimento Sustentável na América Latina: quem está publicando? / Health in the Sustainable Development Agenda 2030 in Latin America: who is publishing? / La salud en la Agenda 2030 de Desarrollo Sostenible en América Latina: ¿Quién está publicando?

Este artigo apresenta um trabalho que consistiu no levantamento quantitativo das publicações sobre a Agenda 2030 de Desenvolvimento Sustentável na América Latina, ou que foram escritas por autores afiliados às instituições da região, focando no tema saúde. Foram realizadas buscas em bancos de dados, para o período entre janeiro de 2009 e maio de 2017, e encontradas 127 publicações voltadas para o Objetivo de Desenvolvimento Sustentável 3 ­ Boa Saúde e Bem-Estar. A maior parcela dos resultados (92%) é constituída de artigos científicos que foram descritos segundo o ano e veículo de publicação, instituições de filiação dos autores e sua localização. Quase a metade das publicações (47%) foi feita sem a participação de organizações latino-americanas e em apenas 30% dos casos o primeiro autor pertence a uma organização latino-americana. Esse quadro se torna mais nítido quando se observa a concentração da produção latinoamericana em torno de organizações brasileiras: a produção científica sobre as resoluções da Agenda 2030 em relação à saúde ainda está ausente em grande parte do território latino-americano.

This article presents a work that consisted of a quantitative research about publications on Agenda 2030 on Sustainable Development in Latin America, or written by authors affiliated with institutions in the region, focusing on health. A search using databases on the subject for the period between January 2009 and May 2017 was made, and 127 publications focusing on Sustainable Development Goal 3 ­ Good Health and Well-Being. The majority (92%) of the publications were scientific articles and were described in relation to the year and vehicle of publication, authors' affiliation institutions and their location. Almost half of the publications (47%) were made without the participation of Latin American organizations and only 30% of cases have the first author who belongs to a Latin American organization. This picture becomes clearer when we see the concentration of Latin American production at Brazilian organizations: scientific production onAgenda 2030 regarding health is still absent in much of the Latin American territory.

Este artículo presenta un trabajo que ha consistido en el levantamiento cuantitativo de las publicaciones sobre la Agenda 2030 en América Latina o que fueron escritas por autores afiliados a instituciones de la región con el foco en salud. Se realizaron búsquedas en bancos de datos para el período entre 2009 y mayo de 2017. Se encontraron 127 publicaciones sobre el Objetivos de desarrollo sostenible 3 ­ Salud y Bienestar. Constituyen la mayoría (92%) artículos científicos que fueron descritos según el año y el vehículo de publicación, las instituciones de filiación de los autores y su ubicación. En casi la mitad de las publicaciones (47%) no hubo participación de organizaciones latinoamericanas y solamente en 30% de los casos el primer autor pertenece a una organización latinoamericana. Este cuadro es más nítido cuando observada la concentración de la producción latinoamericana en organizaciones brasileñas: La producción científica sobrela Agenda 2030 en el área de la salud todavía está ausente en gran parte de la América Latina.

Availability of resources to treat sepsis in Brazil: a random sample of Brazilian institutions. / Disponibilidade de recursos para tratamento da sepse no Brasil: uma amostra aleatória de instituições brasileiras.

OBJECTIVE: To characterize resource availability from a nationally representative random sample of intensive care units in Brazil. METHODS: A structured online survey of participating units in the Sepsis PREvalence Assessment Database (SPREAD) study, a nationwide 1-day point prevalence survey to assess the burden of sepsis in Brazil, was sent to the medical director of each unit. RESULTS: A representative sample of 277 of the 317 invited units responded to the resources survey. Most of the hospitals had fewer than 500 beds (94.6%) with a median of 14 beds in the intensive care unit. Providing care for public-insured patients was the main source of income in two-thirds of the surveyed units. Own microbiology laboratory was not available for 26.8% of the surveyed intensive care units, and 10.5% did not always have access to blood cultures. Broad spectrum antibiotics were not always available in 10.5% of surveyed units, and 21.3% could not always measure lactate within three hours. Those institutions with a high resource availability (158 units, 57%) were usually larger and preferentially served patients from the private health system compared to institutions without high resource availability. Otherwise, those without high resource availability did not always have broad-spectrum antibiotics (24.4%), vasopressors (4.2%) or crystalloids (7.6%). CONCLUSION: Our study indicates that a relevant number of units cannot perform basic monitoring and therapeutic interventions in septic patients. Our results highlight major opportunities for improvement to adhere to simple but effective interventions in Brazil.

OBJETIVO: Caracterizar a disponibilidade de recursos a partir de amostra aleatória representativa das unidades de terapia intensiva do Brasil. MÉTODOS: Realizou-se um questionário estruturado on-line para ser respondido pelo diretor médico de cada unidade participante do estudo SPREAD (Sepsis PREvalence Assessment Database), um estudo de prevalência de um único dia para avaliar o ônus da sepse no Brasil. RESULTADOS: Uma amostra representativa de 277 das 317 unidades convidadas participou por meio de resposta ao questionário estruturado. Em sua maior parte, os hospitais participantes tinham menos que 500 leitos (94,6%), com mediana de 14 leitos na unidade de terapia intensiva. A principal fonte de recursos financeiros para dois terços das unidades pesquisadas era o atendimento de pacientes do sistema público de saúde. Não havia disponibilidade de laboratório de microbiologia próprio em 26,8% das unidades de terapia intensiva pesquisadas, e 10,5% geralmente não tinham acesso à realização de hemoculturas. Em 10,5% das unidades pesquisadas geralmente não estavam disponíveis antibióticos de amplo espectro, e 21,3% das unidades geralmente não podiam obter mensurações de lactato dentro de 3 horas. As instituições com alta disponibilidade de recursos (158 unidades; 57%) eram, em geral, maiores e atendiam principalmente pacientes do sistema de saúde privado. As unidades sem alta disponibilidade de recursos geralmente não dispunham de antibióticos de amplo espectro (24,4%), vasopressores (4,2%) e cristaloides (7,6%). CONCLUSÃO: Um número importante de unidades não tem condições para realizar intervenções básicas de monitoramento e terapêutica em pacientes sépticos. Nossos resultados salientam importantes oportunidades que o Brasil tem para melhorar, em termos de adesão a intervenções simples, porém eficazes.

Disponibilidade de recursos para tratamento da sepse no Brasil: uma amostra aleatória de instituições brasileiras / Availability of resources to treat sepsis in Brazil: a random sample of Brazilian institutions

RESUMO Objetivo: Caracterizar a disponibilidade de recursos a partir de amostra aleatória representativa das unidades de terapia intensiva do Brasil. Métodos: Realizou-se um questionário estruturado on-line para ser respondido pelo diretor médico de cada unidade participante do estudo SPREAD (Sepsis PREvalence Assessment Database), um estudo de prevalência de um único dia para avaliar o ônus da sepse no Brasil. Resultados: Uma amostra representativa de 277 das 317 unidades convidadas participou por meio de resposta ao questionário estruturado. Em sua maior parte, os hospitais participantes tinham menos que 500 leitos (94,6%), com mediana de 14 leitos na unidade de terapia intensiva. A principal fonte de recursos financeiros para dois terços das unidades pesquisadas era o atendimento de pacientes do sistema público de saúde. Não havia disponibilidade de laboratório de microbiologia próprio em 26,8% das unidades de terapia intensiva pesquisadas, e 10,5% geralmente não tinham acesso à realização de hemoculturas. Em 10,5% das unidades pesquisadas geralmente não estavam disponíveis antibióticos de amplo espectro, e 21,3% das unidades geralmente não podiam obter mensurações de lactato dentro de 3 horas. As instituições com alta disponibilidade de recursos (158 unidades; 57%) eram, em geral, maiores e atendiam principalmente pacientes do sistema de saúde privado. As unidades sem alta disponibilidade de recursos geralmente não dispunham de antibióticos de amplo espectro (24,4%), vasopressores (4,2%) e cristaloides (7,6%). Conclusão: Um número importante de unidades não tem condições para realizar intervenções básicas de monitoramento e terapêutica em pacientes sépticos. Nossos resultados salientam importantes oportunidades que o Brasil tem para melhorar, em termos de adesão a intervenções simples, porém eficazes.

ABSTRACT Objective: To characterize resource availability from a nationally representative random sample of intensive care units in Brazil. Methods: A structured online survey of participating units in the Sepsis PREvalence Assessment Database (SPREAD) study, a nationwide 1-day point prevalence survey to assess the burden of sepsis in Brazil, was sent to the medical director of each unit. Results: A representative sample of 277 of the 317 invited units responded to the resources survey. Most of the hospitals had fewer than 500 beds (94.6%) with a median of 14 beds in the intensive care unit. Providing care for public-insured patients was the main source of income in two-thirds of the surveyed units. Own microbiology laboratory was not available for 26.8% of the surveyed intensive care units, and 10.5% did not always have access to blood cultures. Broad spectrum antibiotics were not always available in 10.5% of surveyed units, and 21.3% could not always measure lactate within three hours. Those institutions with a high resource availability (158 units, 57%) were usually larger and preferentially served patients from the private health system compared to institutions without high resource availability. Otherwise, those without high resource availability did not always have broad-spectrum antibiotics (24.4%), vasopressors (4.2%) or crystalloids (7.6%). Conclusion: Our study indicates that a relevant number of units cannot perform basic monitoring and therapeutic interventions in septic patients. Our results highlight major opportunities for improvement to adhere to simple but effective interventions in Brazil.

Qualidade de vida pós-unidades de terapia intensiva: protocolo de estudo de coorte multicêntrico para avaliação de desfechos em longo prazo em sobreviventes de internação em unidades de terapia intensiva brasileiras / Quality of life after intensive care unit: a multicenter cohort study protocol for assessment of long-term outcomes among intensive care survivors in Brazil

RESUMO Objetivo: Avaliar a prevalência de incapacidades físicas, cognitivas e psiquiátricas, fatores associados e sua relação com qualidade de vida em pacientes sobreviventes de internação em unidades de terapia intensiva brasileiras. Métodos: Um estudo de coorte prospectivo multicêntrico está sendo conduzido em dez unidades de terapia intensiva adulto clínico-cirúrgicas representativas das cinco regiões geopolíticas do Brasil. Pacientes com idade ≥ 18 anos que receberam alta das unidades de terapia intensiva participantes e permaneceram internados na unidade de terapia intensiva por 72 horas ou mais, nos casos de internação clínica ou cirúrgica de urgência, e por 120 horas ou mais, nos casos de internação cirúrgica eletiva, serão incluídos de forma consecutiva. Estes pacientes serão seguidos por 1 ano, por meio de entrevistas telefônicas estruturadas 3, 6 e 12 meses pós-alta da unidade de terapia intensiva. Dependência funcional, disfunção cognitiva, sintomas de ansiedade e depressão, sintomas de estresse pós-traumático, qualidade de vida relacionada à saúde, re-hospitalizações e mortalidade em longo prazo serão avaliados como desfechos. Discussão: O presente estudo tem o potencial de contribuir para o conhecimento a respeito da prevalência e dos fatores associados à síndrome pós-cuidados intensivos na população de pacientes adultos sobreviventes de internação em unidades de terapia intensiva brasileiras. Ademais, a associação entre síndrome pós-cuidados intensivos e qualidade de vida relacionada à saúde poderá ser estabelecida.

ABSTRACT Objective: To establish the prevalence of physical, cognitive and psychiatric disabilities, associated factors and their relationship with the qualities of life of intensive care survivors in Brazil. Methods: A prospective multicenter cohort study is currently being conducted at 10 adult medical-surgical intensive care units representative of the 5 Brazilian geopolitical regions. Patients aged ≥ 18 years who are discharged from the participating intensive care units and stay 72 hours or more in the intensive care unit for medical or emergency surgery admissions or 120 hours or more for elective surgery admissions are consecutively included. Patients are followed up for a period of one year by means of structured telephone interviews conducted at 3, 6 and 12 months after discharge from the intensive care unit. The outcomes are functional dependence, cognitive dysfunction, anxiety and depression symptoms, posttraumatic stress symptoms, health-related quality of life, rehospitalization and long-term mortality. Discussion: The present study has the potential to contribute to current knowledge of the prevalence and factors associated with postintensive care syndrome among adult intensive care survivors in Brazil. In addition, an association might be established between postintensive care syndrome and health-related quality of life.

Preventable adverse drug events in critically ill HIV patients: Is the detection of potential drug-drug interactions a useful tool?

OBJECTIVES: The aim of this study was to develop a strategy to identify adverse drug events associated with drug-drug interactions by analyzing the prescriptions of critically ill patients. METHODS: This retrospective study included HIV/AIDS patients who were admitted to an intensive care unit between November 2006 and September 2008. Data were collected in two stages. In the first stage, three prescriptions administered throughout the entire duration of these patients' hospitalization were reviewed, with the Micromedex database used to search for potential drug-drug interactions. In the second stage, a search for adverse drug events in all available medical, nursing and laboratory records was performed. The probability that a drug-drug interaction caused each adverse drug events was assessed using the Naranjo algorithm. RESULTS: A total of 186 drug prescriptions of 62 HIV/AIDS patients were analyzed. There were 331 potential drug-drug interactions, and 9% of these potential interactions resulted in adverse drug events in 16 patients; these adverse drug events included treatment failure (16.7%) and adverse reactions (83.3%). Most of the adverse drug reactions were classified as possible based on the Naranjo algorithm. CONCLUSIONS: The approach used in this study allowed for the detection of adverse drug events related to 9% of the potential drug-drug interactions that were identified; these adverse drug events affected 26% of the study population. With the monitoring of adverse drug events based on prescriptions, a combination of the evaluation of potential drug-drug interactions by clinical pharmacy services and the monitoring of critically ill patients is an effective strategy that can be used as a complementary tool for safety assessments and the prevention of adverse drug events.

Quality of life after intensive care unit: a multicenter cohort study protocol for assessment of long-term outcomes among intensive care survivors in Brazil. / Qualidade de vida pós-unidades de terapia intensiva: protocolo de estudo de coorte multicêntrico para avaliação de desfechos em longo prazo em sobreviventes de internação em unidades de terapia intensiva brasileiras.

OBJECTIVE: To establish the prevalence of physical, cognitive and psychiatric disabilities, associated factors and their relationship with the qualities of life of intensive care survivors in Brazil. METHODS: A prospective multicenter cohort study is currently being conducted at 10 adult medical-surgical intensive care units representative of the 5 Brazilian geopolitical regions. Patients aged ≥ 18 years who are discharged from the participating intensive care units and stay 72 hours or more in the intensive care unit for medical or emergency surgery admissions or 120 hours or more for elective surgery admissions are consecutively included. Patients are followed up for a period of one year by means of structured telephone interviews conducted at 3, 6 and 12 months after discharge from the intensive care unit. The outcomes are functional dependence, cognitive dysfunction, anxiety and depression symptoms, posttraumatic stress symptoms, health-related quality of life, rehospitalization and long-term mortality. DISCUSSION: The present study has the potential to contribute to current knowledge of the prevalence and factors associated with postintensive care syndrome among adult intensive care survivors in Brazil. In addition, an association might be established between postintensive care syndrome and health-related quality of life.

OBJETIVO: Avaliar a prevalência de incapacidades físicas, cognitivas e psiquiátricas, fatores associados e sua relação com qualidade de vida em pacientes sobreviventes de internação em unidades de terapia intensiva brasileiras. MÉTODOS: Um estudo de coorte prospectivo multicêntrico está sendo conduzido em dez unidades de terapia intensiva adulto clínico-cirúrgicas representativas das cinco regiões geopolíticas do Brasil. Pacientes com idade ≥ 18 anos que receberam alta das unidades de terapia intensiva participantes e permaneceram internados na unidade de terapia intensiva por 72 horas ou mais, nos casos de internação clínica ou cirúrgica de urgência, e por 120 horas ou mais, nos casos de internação cirúrgica eletiva, serão incluídos de forma consecutiva. Estes pacientes serão seguidos por 1 ano, por meio de entrevistas telefônicas estruturadas 3, 6 e 12 meses pós-alta da unidade de terapia intensiva. Dependência funcional, disfunção cognitiva, sintomas de ansiedade e depressão, sintomas de estresse pós-traumático, qualidade de vida relacionada à saúde, re-hospitalizações e mortalidade em longo prazo serão avaliados como desfechos. DISCUSSÃO: O presente estudo tem o potencial de contribuir para o conhecimento a respeito da prevalência e dos fatores associados à síndrome pós-cuidados intensivos na população de pacientes adultos sobreviventes de internação em unidades de terapia intensiva brasileiras. Ademais, a associação entre síndrome pós-cuidados intensivos e qualidade de vida relacionada à saúde poderá ser estabelecida.

Preventable adverse drug events in critically ill HIV patients: Is the detection of potential drug-drug interactions a useful tool?

OBJECTIVES: The aim of this study was to develop a strategy to identify adverse drug events associated with drug-drug interactions by analyzing the prescriptions of critically ill patients. METHODS: This retrospective study included HIV/AIDS patients who were admitted to an intensive care unit between November 2006 and September 2008. Data were collected in two stages. In the first stage, three prescriptions administered throughout the entire duration of these patients' hospitalization were reviewed, with the Micromedex database used to search for potential drug-drug interactions. In the second stage, a search for adverse drug events in all available medical, nursing and laboratory records was performed. The probability that a drug-drug interaction caused each adverse drug events was assessed using the Naranjo algorithm. RESULTS: A total of 186 drug prescriptions of 62 HIV/AIDS patients were analyzed. There were 331 potential drug-drug interactions, and 9% of these potential interactions resulted in adverse drug events in 16 patients; these adverse drug events included treatment failure (16.7%) and adverse reactions (83.3%). Most of the adverse drug reactions were classified as possible based on the Naranjo algorithm. CONCLUSIONS: The approach used in this study allowed for the detection of adverse drug events related to 9% of the potential drug-drug interactions that were identified; these adverse drug events affected 26% of the study population. With the monitoring of adverse drug events based on prescriptions, a combination of the evaluation of potential drug-drug interactions by clinical pharmacy services and the monitoring of critically ill patients is an effective strategy that can be used as a complementary tool for safety assessments and the prevention of adverse drug events.

The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study.

BACKGROUND: The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. METHODS: We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. FINDINGS: On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. INTERPRETATION: The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the burden of sepsis in resource-limited settings, highlighting the need to establish programmes aiming for sepsis prevention, early diagnosis, and adequate treatment. FUNDING: Fundação de Apoio a Pesquisa do Estado de São Paulo (FAPESP).

The effects of performance status one week before hospital admission on the outcomes of critically ill patients.

PURPOSE: To assess the impact of performance status (PS) impairment 1 week before hospital admission on the outcomes in patients admitted to intensive care units (ICU). METHODS: Retrospective cohort study in 59,693 patients (medical admissions, 67 %) admitted to 78 ICUs during 2013. We classified PS impairment according to the Eastern Cooperative Oncology Group (ECOG) scale in absent/minor (PS = 0-1), moderate (PS = 2) or severe (PS = 3-4). We used univariate and multivariate logistic regression analyses to investigate the association between PS impairment and hospital mortality. RESULTS: PS impairment was moderate in 17.3 % and severe in 6.9 % of patients. The hospital mortality was 14.4 %. Overall, the worse the PS, the higher the ICU and hospital mortality and length of stay. In addition, patients with worse PS were less frequently discharged home. PS impairment was associated with worse outcomes in all SAPS 3, Charlson Comorbidity Index and age quartiles as well as according to the admission type. Adjusting for other relevant clinical characteristics, PS impairment was associated with higher hospital mortality (odds-ratio (OR) = 1.96 (95 % CI 1.63-2.35), for moderate and OR = 4.22 (3.32-5.35), for severe impairment). The effects of PS on the outcome were particularly relevant in the medium range of severity-of-illness. These results were consistent in the subgroup analyses. However, adding PS impairment to the SAPS 3 score improved only slightly its discriminative capability. CONCLUSION: PS impairment was associated with worse outcomes independently of other markers of chronic health status, particularly for patients in the medium range of severity of illness.

Cost of surviving sepsis: a novel model of recovery from sepsis in Drosophila melanogaster.

BACKGROUND: Multiple organ failure, wasting, increased morbidity, and mortality following acute illness complicates the health span of patients surviving sepsis. Persistent inflammation has been implicated, and it is proposed that insulin signaling contributes to persistent inflammatory signaling during the recovery phase after sepsis. However, mechanisms are unknown and suitable pre-clinical models are lacking. We therefore developed a novel Drosophila melanogaster model of sepsis to recapitulate the clinical course of sepsis, explored inflammation over time, and its relation to impaired mobility, metabolic disturbance, and changes in lifespan. METHODS: We used wild-type (WT), Drosomycin-green fluorescent protein (GFP), and NF-κB-luc reporter male Drosophila melanogaster 4-5 days of age (unmanipulated). We infected Drosophila with Staphylococcus aureus (infected without treatment) or pricked with aseptic needles (sham). Subsets of insects were treated with oral linezolid after the infection (infected with antibiotics). We assessed rapid iterative negative geotaxis (RING) in all the groups as a surrogate for neuromuscular functional outcome up to 96 h following infection. We harvested the flies over the 7-day course to evaluate bacterial burden, inflammatory and metabolic pathway gene expression patterns, NF-κB translation, and metabolic reserve. We also followed the lifespan of the flies. RESULTS: Our results showed that when treated with antibiotics, flies had improved survival compared to infected without treatment flies in the early phase of sepsis up to 1 week (81 %, p = 0.001). However, the lifespan of infected with antibiotics flies was significantly shorter than that of sham controls (p = 0.001). Among infected with antibiotic sepsis survivors, we observed persistent elevation of NF-κB in the absence of any obvious infection as shown by culturing flies surviving sepsis. In the same group, geotaxis had an early (18 h) and sustained decline compared to its baseline. Geotaxis in infected with antibiotics sepsis survivors was significantly lower than that in sham and age-matched unmanipulated flies at 18 and 48 h. Expression of antimicrobial peptides (AMP) remained significantly elevated over the course of 7 days after sepsis, especially drosomycin (5.7-fold, p = 0.0145) on day 7 compared to that of sham flies. Infected with antibiotics flies had a trend towards decreased Akt activation, yet their glucose stores were significantly lower than those of sham flies (p = 0.001). Sepsis survivors had increased lactate levels and LDH activity by 1 week, whereas ATP and pyruvate content was similar to that of the sham group. CONCLUSIONS: In summary, our model mimics human survivors of sepsis with persistent inflammation, impaired motility, dysregulated glucose metabolism, and shortened lifespan.