Clinical features, etiologies, and outcomes of central nervous system infections in intensive care: A multicentric retrospective study in a large Brazilian metropolitan area.

PURPOSE: The goal of this study was to investigate severe central nervous system infections (CNSI) in adults admitted to the intensive care unit (ICU). We analyzed the clinical presentation, causes, and outcomes of these infections, while also identifying factors linked to higher in-hospital mortality rates. MATERIALS AND METHODS: We conducted a retrospective multicenter study in Rio de Janeiro, Brazil, from 2012 to 2019. Using a prediction tool, we selected ICU patients suspected of having CNSI and reviewed their medical records. Multivariate analyses identified variables associated with in-hospital mortality. RESULTS: In a cohort of 451 CNSI patients, 69 (15.3%) died after a median 11-day hospitalization (5-25 IQR). The distribution of cases was as follows: 29 (6.4%) had brain abscess, 161 (35.7%) had encephalitis, and 261 (57.8%) had meningitis. Characteristics: median age 41 years (27-53 IQR), 260 (58%) male, and 77 (17%) HIV positive. The independent mortality predictors for encephalitis were AIDS (OR = 4.3, p = 0.01), ECOG functional capacity limitation (OR = 4.0, p < 0.01), ICU admission from ward (OR = 4.0, p < 0.01), mechanical ventilation ≥10 days (OR = 6.1, p = 0.04), SAPS 3 ≥ 55 points (OR = 3.2, p = 0.02). Meningitis: Age > 60 years (OR = 234.2, p = 0.04), delay >3 days for treatment (OR = 2.9, p = 0.04), mechanical ventilation ≥10 days (OR = 254.3, p = 0.04), SOFA >3 points (OR = 2.7, p = 0.03). Brain abscess: No associated factors found in multivariate regression. CONCLUSIONS: Patients' overall health, prompt treatment, infection severity, and prolonged respiratory support in the ICU all significantly affect in-hospital mortality rates. Additionally, the implementation of CNSI surveillance with the used prediction tool could enhance public health policies.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Central nervous system infection in the intensive care unit: Development and validation of a multi-parameter diagnostic prediction tool to identify suspected patients.

BACKGROUND: Central nervous system infections (CNSI) are diseases with high morbidity and mortality, and their diagnosis in the intensive care environment can be challenging. Objective: To develop and validate a diagnostic model to quickly screen intensive care patients with suspected CNSI using readily available clinical data. METHODS: Derivation cohort: 783 patients admitted to an infectious diseases intensive care unit (ICU) in Oswaldo Cruz Foundation, Rio de Janeiro RJ, Brazil, for any reason, between 01/01/2012 and 06/30/2019, with a prevalence of 97 (12.4%) CNSI cases. Validation cohort 1: 163 patients prospectively collected, between 07/01/2019 and 07/01/2020, from the same ICU, with 15 (9.2%) CNSI cases. Validation cohort 2: 7,270 patients with 88 CNSI (1.21%) admitted to a neuro ICU in Chicago, IL, USA between 01/01/2014 and 06/30/2019. Prediction model: Multivariate logistic regression analysis was performed to construct the model, and Receiver Operating Characteristic (ROC) curve analysis was used for model validation. Eight predictors-age <56 years old, cerebrospinal fluid white blood cell count >2 cells/mm3, fever (≥38°C/100.4°F), focal neurologic deficit, Glasgow Coma Scale <14 points, AIDS/HIV, and seizure-were included in the development diagnostic model (P<0.05). RESULTS: The pool data's model had an Area Under the Receiver Operating Characteristics (AUC) curve of 0.892 (95% confidence interval 0.864-0.921, P<0.0001). CONCLUSIONS: A promising and straightforward screening tool for central nervous system infections, with few and readily available clinical variables, was developed and had good accuracy, with internal and external validity.

An international perspective on the frequency, perception of utility, and quality of interprofessional rounds practices in intensive care units.

PURPOSE: To describe international variation in interprofessional rounds in intensive care units (ICUs). MATERIALS AND METHODS: Survey of ICU clinicians on their practices and perceptions of rounds using societal mailing lists and social media. RESULTS: Out of 2402 respondents, 1752 (72.8%) use rounds. Teams are mostly composed of intensivists, nurses and medical trainees. The majority of rounds (57.5%) last >2 h, and North Americans report the highest rates of rounds allowing family attendance (92.4%). Shorter rounds (1-2 h, OR 0.67, 0.52-0.86, p < 0.01; <1 h, OR 0.72, 0.53-0.97, p = 0.03), and strategies such as designating a person for writing (OR 0.73, 0.57-0.95, p = 0.01), and designating a person to assist other patients (OR 0.75, 0.57-0.98, p = 0.04) are associated with a lower perception of negative outcomes. Using daily goals during rounds is associated with a higher perception of positive outcomes (OR 1.85, 1.17-2.90, p < 0.01). CONCLUSIONS: Three-quarters of respondents perform rounds, and models of rounds are heterogeneous, creating challenges for future studies on improving rounds. Respondents reporting better outcomes also experience shorter rounds, and adopt strategies such as discussion of daily goals, and designation individuals for writing or assisting other patients during rounds.

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.

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.

External validation of SAPS 3 and MPM0-III scores in 48,816 patients from 72 Brazilian ICUs.

BACKGROUND: The performance of severity-of-illness scores varies in different scenarios and must be validated prior of being used in a specific settings and geographic regions. Moreover, models' calibration may deteriorate overtime and performance of such instruments should be reassessed regularly. Therefore, we aimed at to validate the SAPS 3 in a large contemporary cohort of patients admitted to Brazilian ICUs. In addition, we also compared the performance of the SAPS 3 with the MPM0-III. METHODS: This is a retrospective cohort study in which 48,816 (medical admissions = 67.9%) adult patients are admitted to 72 Brazilian ICUs during 2013. We evaluated models' discrimination using the area under the receiver operating characteristic curve (AUROC). We applied the calibration belt to evaluate the agreement between observed and expected mortality rates (calibration). RESULTS: Mean SAPS 3 score was 44.3 ± 15.4 points. ICU and hospital mortality rates were 11.0 and 16.5%. We estimated predicted mortality using both standard (SE) and Central and South American (CSA) customized equations. Predicted mortality rates were 16.4 ± 19.3% (SAPS 3-SE), 21.7 ± 23.2% (SAPS 3-CSA) and 14.3 ± 14.0% (MPM0-III). Standardized mortality ratios (SMR) obtained for each model were: 1.00 (95% CI, 0.98-0.102) for the SAPS 3-SE, 0.75 (0.74-0.77) for the SAPS 3-CSA and 1.15 (1.13-1.18) for the MPM0-III. Discrimination was better for SAPS 3 models (AUROC = 0.85) than for MPM0-III (AUROC = 0.80) (p < 0.001). We applied the calibration belt to evaluate the agreement between observed and expected mortality rates (calibration): the SAPS 3-CSA overestimated mortality throughout all risk classes while the MPM0-III underestimated it uniformly. The SAPS 3-SE did not show relevant deviations from ideal calibration. CONCLUSIONS: In a large contemporary database, the SAPS 3-SE was accurate in predicting outcomes, supporting its use for performance evaluation and benchmarking in Brazilian ICUs.

Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients: A Randomized Clinical Trial.

IMPORTANCE: The effectiveness of checklists, daily goal assessments, and clinician prompts as quality improvement interventions in intensive care units (ICUs) is uncertain. OBJECTIVE: To determine whether a multifaceted quality improvement intervention reduces the mortality of critically ill adults. DESIGN, SETTING, AND PARTICIPANTS: This study had 2 phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes, conducted between August 2013 and March 2014 in 118 Brazilian ICUs. Phase 2 was a cluster randomized trial conducted between April and November 2014 with the same ICUs. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase. INTERVENTIONS: Intensive care units were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care. MAIN OUTCOMES AND MEASURES: In-hospital mortality truncated at 60 days (primary outcome) was analyzed using a random-effects logistic regression model, adjusted for patients' severity and the ICU's baseline standardized mortality ratio. Exploratory secondary outcomes included adherence to care processes, safety climate, and clinical events. RESULTS: A total of 6877 patients (mean age, 59.7 years; 3218 [46.8%] women) were enrolled in the baseline (observational) phase and 6761 (mean age, 59.6 years; 3098 [45.8%] women) in the randomized phase, with 3327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3434 patients in ICUs (n = 59) assigned to routine care. There was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1096 deaths (32.9%) and 1196 deaths (34.8%), respectively (odds ratio, 1.02; 95% CI, 0.82-1.26; P = .88). Among 20 prespecified secondary outcomes not adjusted for multiple comparisons, 6 were significantly improved in the intervention group (use of low tidal volumes, avoidance of heavy sedation, use of central venous catheters, use of urinary catheters, perception of team work, and perception of patient safety climate), whereas there were no significant differences between the intervention group and the control group for 14 outcomes (ICU mortality, central line-associated bloodstream infection, ventilator-associated pneumonia, urinary tract infection, mean ventilator-free days, mean ICU length of stay, mean hospital length of stay, bed elevation to ≥30°, venous thromboembolism prophylaxis, diet administration, job satisfaction, stress reduction, perception of management, and perception of working conditions). CONCLUSIONS AND RELEVANCE: Among critically ill patients treated in ICUs in Brazil, implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01785966.

Lung in dengue: computed tomography findings.

BACKGROUND: Dengue is the most important mosquito-borne viral disease in the world. Dengue virus infection may be asymptomatic or lead to undifferentiated fever, dengue fever with or without warning signs, or severe dengue. Lower respiratory symptoms are unusual and lung-imaging data in patients with dengue are scarce. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate lung changes associated with dengue infection, we retrospectively analyzed 2,020 confirmed cases of dengue. Twenty-nine of these patients (11 females and 18 males aged 16-90 years) underwent chest computed tomography (CT), which yielded abnormal findings in 17 patients: 16 patients had pleural effusion (the sole finding in six patients) and 11 patients had pulmonary abnormalities. Lung parenchyma involvement ranged from subtle to moderate unilateral and bilateral abnormalities. The most common finding was ground-glass opacity in eight patients, followed by consolidation in six patients. Less common findings were airspace nodules (two patients), interlobular septal thickening (two patients), and peribronchovascular interstitial thickening (one patient). Lung histopathological findings in four fatal cases showed thickening of the alveolar septa, hemorrhage, and interstitial edema. CONCLUSIONS/SIGNIFICANCE: In this largest series involving the use of chest CT to evaluate lung involvement in patients with dengue, CT findings of lower respiratory tract involvement were uncommon. When abnormalities were present, pleural effusion was the most frequent finding and lung involvement was often mild or moderate and bilateral. Extensive lung abnormalities are infrequent even in severe disease and when present should lead physicians to consider other diagnostic possibilities.

Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil.

A vaccination campaign against pandemic influenza A (H1N1)pdm09 was held in Brazil in March 2010, using two types of monovalent split virus vaccines: an AS03-adjuvanted vaccine and a non-adjuvanted vaccine. We compared the reactogenicity of the vaccines in health professionals from a Clinical Research Institute in Rio de Janeiro, Brazil and there were no serious adverse events following immunization (AEFI) among the 494 subjects evaluated. The prevalence of any AEFI was higher in the AS03-adjuvanted vaccine at 2 h and 24 h post-vaccination [preva-lence ratio (PR): 2.05, confidence interval (CI) 95%: 1.55-2.71, PR: 3.42, CI 95%: 2.62-4.48, respectively]; however, there was no difference between the vaccines in the assessments conducted at seven and 21 days post-vaccination. The group receiving the AS03 post-adjuvanted vaccine had a higher frequency of local reactions at 2 h (PR: 3.01, CI 95%: 2.12-4.29), 24 h (PR: 4.57, CI 95%: 3.29-6.37) and seven days (PR: 6.05, CI 95%: 2.98-12.28) post-vaccination. We concluded that the two types of vaccines caused no serious AEFI in the studied population and the adjuvanted vaccine was more reactogenic, particularly in the 24 h following vaccination. This behaviour must be confirmed and better characterised by longitudinal studies in the general population.

Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil

A vaccination campaign against pandemic influenza A (H1N1)pdm09 was held in Brazil in March 2010, using two types of monovalent split virus vaccines: an AS03-adjuvanted vaccine and a non-adjuvanted vaccine. We compared the reactogenicity of the vaccines in health professionals from a Clinical Research Institute in Rio de Janeiro, Brazil and there were no serious adverse events following immunization (AEFI) among the 494 subjects evaluated. The prevalence of any AEFI was higher in the AS03-adjuvanted vaccine at 2 h and 24 h post-vaccination [preva-lence ratio (PR): 2.05, confidence interval (CI) 95%: 1.55-2.71, PR: 3.42, CI 95%: 2.62-4.48, respectively]; however, there was no difference between the vaccines in the assessments conducted at seven and 21 days post-vaccination. The group receiving the AS03 post-adjuvanted vaccine had a higher frequency of local reactions at 2 h (PR: 3.01, CI 95%: 2.12-4.29), 24 h (PR: 4.57, CI 95%: 3.29-6.37) and seven days (PR: 6.05, CI 95%: 2.98-12.28) post-vaccination. We concluded that the two types of vaccines caused no serious AEFI in the studied population and the adjuvanted vaccine was more reactogenic, particularly in the 24 h following vaccination. This behaviour must be confirmed and better characterised by longitudinal studies in the general population.

Eventos adversos relacionados a interações medicamentosas em pacientes com SIDA em terapia intensiva / Adverse events related to drug interactions in AIDS patients in intensive care

Introdução: Eventos adversos a medicamentos (EAM) são frequentes em meio hospitalar, principalmente em pacientes em terapia intensiva, com consequências diretas no tempo de internação, mortalidade e custos hospitalares. Pacientes com infecções graves tais como HIV/SIDA e criticamente doentes, possuem risco elevado de EAM devido à necessidade de terapias com múltiplos fármacos o que predispõe a interações medicamentosas. A investigação de potenciais interações medicamentosas (PIMs) e de EAMs a elas relacionados podem ser ferramentas úteis para a avaliação do risco a que estes pacientes estão expostos. Objetivo: Analisar e classificar as PIMs e os EAMs em pacientes com HIV/SIDA criticamente enfermos. Métodos: Estudo descritivo retrospectivo, com revisão dos prontuários de pacientes com HIV/SIDA internados no Centro de Terapia Intensiva do Instituto de Pesquisa Clínica Evandro Chagas- Fiocruz, no período de 10/2006 a 10/2008, avaliando as PIMs e EAMs associadas às mesmas. O estudo foi realizado em duas fases. Na primeira, as PIMs foram identificadas e classificadas segundo as bases de dados Drugs.com e Micromedex, comparando-se o grau de concordância através do índice kappa. Na segunda fase, foi realizada a busca em prontuário dos EAMs associados às PIMs identificadas pela base Micromedex. Os EAMs observados foram classificados segundo a causalidade. Resultados: Foi observada maior frequência de PIMs moderadas, de mecanismo farmacocinético, tempo de aparecimento do evento tardio e com bom nível de evidência. A concordância entre as bases de dados segundo a gravidade e mecanismo de ação foi considerada moderada (kappa=0,43) e substancial (kappa=0,61) respectivamente. Dentre as PIMs identificadas, 9 porcento resultaram em eventos adversos, incluindo falhas terapêuticas e reações adversas. Houve predomínio das reações adversas de causalidade possível e que afetam o sistema gastrointestinal. Dos pares de fármacos envolvidos, destaca-se o Omeprazol x Fluconazol, representando 16 porcento (5/29) das interações relacionadas aos EAM identificados e cujo uso recomenda vi monitorização do paciente. Conclusão: Os resultados deste estudo demonstram que há alta frequência de PIMs nas prescrições de pacientes criticamente enfermos com HIV/SIDA. A difusão do conhecimento para a equipe multiprofissional sobre os fatores de risco associados às interações medicamentosas e eventos adversos assim como o monitoramento destes, pode constituir um importante instrumento na prevenção de problemas relacionados a medicamentos, garantindo a segurança do paciente.

Introduction: Adverse drug events (ADE) are common in hospitals, especially in patients in intensive care, with direct consequences on the length of stay, mortality and hospital costs. Patients with severe infections such as HIV / AIDS and critically ill, have high risk of ADE due to the need for multiple drug therapy which predisposes to drug interactions. The investigation of potential drug-drug interactions (DDIs) and ADEs related to them can be useful tools for assessing the risk that these patients are exposed. Objective: To analyze and classify the DDIs and the ADEs in patients with HIV / AIDS critically ill. Methods: Retrospective descriptive study with retrospective chart review of patients with HIV / AIDS admitted to the Intensive Care Unit of the Clinical Research Institute Evandro Chagas-Fiocruz, in the period 10/2006 10/2008, evaluating the DDIs and ADEs associated with the same. The study was conducted in two stages. At first, the PIMs were identified and classified according to the database Micromedex and Drugs.com, comparing the degree of agreement using the Kappa index. In the second phase, the search was conducted in the medical records of ADEs associated with DDIs identified by Micromedex. Results: It was observed a higher frequency of moderate DDIs, pharmacokinetic mechanism, delayed onset time and good scientific documentation. The agreement between the databases according to the severity and mechanism of action was considered moderate (kappa = 0.43) and substantial (kappa = 0.61) respectively. Among the identified DDIs, 9 percent resulted in adverse events, including adverse reactions and therapeutic failures. There was a predominance of adverse reactions of causality possible that affect the gastrointestinal system. Between pairs of drugs involved, stands out Omeprazole/Fluconazole, representing 16 percent (5/29) of interactions related to EAM identified and whose use is recommended patient monitoring. Conclusion: The results of this study demonstrate that there is a high frequency of DDIs in the viii prescriptions of critically ill patients with AIDS. The diffusion of knowledge to the multidisciplinary team about the risk factors associated with DDIs and ADEs as well as monitoring of these may constitute an important tool in preventing drug-related problems, ensuring patient safety.