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.

Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients.

BACKGROUND: The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients. METHODS: Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT). RESULTS: 184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation. CONCLUSIONS: A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.

Fatal Brazilian spotted fever in a healthy military man during field training in Rio de Janeiro city, southeastern Brazil.

Brazilian spotted fever, a zoonotic disease transmitted by ticks, is caused by Rickettsia rickettsii. We report a fulminant case of this zoonosis in a healthy 46-year-old military man in the urban region of Rio de Janeiro city, in October, 2021. Ticks and capybaras (Amblyomma sculptum, Hydrochoerus hydrochaeris, respectively) were identified in the military fields, pointing to the participation of this large synanthropic rodent, recognized as an efficient amplifier host of Rickettsia rickettsii in Brazil. As the military population is considered a risk group for spotted fever, it is necessary to alert health professionals to the importance of the early detection of the disease and its adequate management, mainly in populations that are particularly at risk of exposure to ticks, in order to avoid fatal outcomes.

In-hospital mortality and severe outcomes after hospital discharge due to COVID-19: A prospective multicenter study from Brazil.

Background: We evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort. Methods: This prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed. Findings: 1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge. Interpretation: High in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge. Funding: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ.

Fatal Brazilian spotted fever in a healthy military man during field training in Rio de Janeiro city, southeastern Brazil

ABSTRACT Brazilian spotted fever, a zoonotic disease transmitted by ticks, is caused by Rickettsia rickettsii. We report a fulminant case of this zoonosis in a healthy 46-year-old military man in the urban region of Rio de Janeiro city, in October, 2021. Ticks and capybaras (Amblyomma sculptum, Hydrochoerus hydrochaeris, respectively) were identified in the military fields, pointing to the participation of this large synanthropic rodent, recognized as an efficient amplifier host of Rickettsia rickettsii in Brazil. As the military population is considered a risk group for spotted fever, it is necessary to alert health professionals to the importance of the early detection of the disease and its adequate management, mainly in populations that are particularly at risk of exposure to ticks, in order to avoid fatal outcomes.

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.

Resuscitation fluid practices in Brazilian intensive care units: a secondary analysis of Fluid-TRIPS. / Práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras: uma análise secundária do estudo Fluid-TRIPS.

OBJECTIVE: To describe fluid resuscitation practices in Brazilian intensive care units and to compare them with those of other countries participating in the Fluid-TRIPS. METHODS: This was a prospective, international, cross-sectional, observational study in a convenience sample of intensive care units in 27 countries (including Brazil) using the Fluid-TRIPS database compiled in 2014. We described the patterns of fluid resuscitation use in Brazil compared with those in other countries and identified the factors associated with fluid choice. RESULTS: On the study day, 3,214 patients in Brazil and 3,493 patients in other countries were included, of whom 16.1% and 26.8% (p < 0.001) received fluids, respectively. The main indication for fluid resuscitation was impaired perfusion and/or low cardiac output (Brazil: 71.7% versus other countries: 56.4%, p < 0.001). In Brazil, the percentage of patients receiving crystalloid solutions was higher (97.7% versus 76.8%, p < 0.001), and 0.9% sodium chloride was the most commonly used crystalloid (62.5% versus 27.1%, p < 0.001). The multivariable analysis suggested that the albumin levels were associated with the use of both crystalloids and colloids, whereas the type of fluid prescriber was associated with crystalloid use only. CONCLUSION: Our results suggest that crystalloids are more frequently used than colloids for fluid resuscitation in Brazil, and this discrepancy in frequencies is higher than that in other countries. Sodium chloride (0.9%) was the crystalloid most commonly prescribed. Serum albumin levels and the type of fluid prescriber were the factors associated with the choice of crystalloids or colloids for fluid resuscitation.

OBJETIVO: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. MÉTODOS: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. RESULTADOS: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. CONCLUSÃO: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.

Predictive Accuracy of the Quick Sepsis-related Organ Failure Assessment Score in Brazil. A Prospective Multicenter Study.

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

Quality Indicators of End-of-Life Care Among Privately Insured People With Cancer in Brazil.

PURPOSE: To examine quality indicators of end-of-life (EOL) care among privately insured people with cancer in Brazil. METHODS: We evaluated medical records linked to health insurance databank to study consecutive patients who died of cancer. We collected information about demographics, cancer type, and quality indicators of EOL care including emergency department (ED) visits, intensive care unit (ICU) admissions, chemotherapy use, medical imaging utilization, blood transfusions, home care support, days of inpatient care, and hospital deaths. RESULTS: We included 865 patients in the study. In the last 30 days of life, 62% visited the ED, 33% were admitted to the ICU, 24% received blood transfusions, and 51% underwent medical imaging. Only 1% had home care support in the last 60 days of life, and 29% used chemotherapy in the last 14 days of life. Patients had an average of 8 days of inpatient care and 52% died in the hospital. Patients with advanced cancer who used chemotherapy were more likely to visit the ED (78% vs 59%; P < .001), undergo medical imaging (67% vs 51%; P < .001), and die in the hospital (73% vs 50%; P = .03) than patients who did not use chemotherapy. In the multivariate analysis, chemotherapy use near death and advanced cancer were associated with ED visits and ICU admissions, respectively (odds ratio >1). CONCLUSION: Our study suggests that privately insured people with cancer receive poor quality EOL care in Brazil. Further research is needed to assess the impact of improvements in palliative care provision in this population.

Trends in Health-Care Utilization at the End of Life Among Patients With Hematologic Malignancies in a Middle-Income Country: Challenges and Opportunities in Brazil.

Patients with hematologic malignancies (HMs) often receive poor-quality end-of-life care. This study aimed to identify trends in end-of-life care among patients with HM in Brazil. We conducted a retrospective cohort study (2015-2018) of patients who died with HM, using electronic medical records linked to health insurance databank, to evaluate outcomes consistent with health-care resource utilization at the end of life. Among 111 patients with HM, in the last 30 days of life, we found high rates of emergency department visits (67%, n = 75), intensive care unit admissions (56%, n = 62), acute renal replacement therapy (10%, n = 11), blood transfusions (45%, n = 50), and medical imaging utilization (59%, n = 66). Patients received an average of 13 days of inpatient care and the majority of them died in the hospital (53%, n = 58). We also found that almost 40% of patients (38%, n = 42) used chemotherapy in the last 14 days of life. These patients were more likely to be male (64% vs 22%; P < .001), to receive blood transfusions (57% vs 38%; P = .05), and to die in the hospital (76% vs 39%; P = .009) than patients who did not use chemotherapy in the last 14 days of life. This study suggests that patients with HM have high rates of health-care utilization at the end of life in Brazil. Patients who used chemotherapy in the last 14 days of life were more likely to receive blood transfusions and to die in the hospital.

Prevalence and intensity of dyspnea, pain, and agitation among people dying with late stage dementia compared with people dying with advanced cancer: a single-center preliminary study in Brazil.

BACKGROUND: As death approaches, there may be similarities in terms of physical symptoms among dementia and cancer. This study aimed to estimate the prevalence and intensity of dyspnea, pain, and agitation among people dying with late stage dementia versus those dying with advanced cancer. Methods: A retrospective analysis, conducted in a post-acute care facility (PACF) in Rio de Janeiro, Brazil. We reviewed the electronic charts for the Edmonton Symptom Assessment System (ESAS) scores, from death backwards in time (3 days). METHODS: A retrospective analysis, conducted in a post-acute care facility (PACF) in Rio de Janeiro, Brazil. We reviewed the electronic charts for the Edmonton Symptom Assessment System (ESAS) scores, from death backwards in time (3 days). RESULTS: We included 57 patients who died with dementia and 54 patients who died with cancer. The prevalence of dyspnea (dementia: n=34, 60% vs. cancer: n=39, 72%; P=0.23), and agitation (dementia: n=7, 13% vs. cancer: n=14, 25%; P=0.17) were statically similar between the two groups. Pain was less common in dementia (dementia: n=19, 34% vs. cancer: n=31, 57%; P=0.02). There were no significant differences in the percentage of patients with moderate to severe dyspnea (dementia: n=28, 49% vs. cancer: n=33, 61%; P=0.28), and moderate to severe agitation (dementia: n=4, 7% vs. cancer: n=12, 23%; P=0.09). Dementia patients were less likely to experience moderate to severe pain than cancer patients (dementia: n=14, 25% vs. cancer: n=25, 46%; P=0.03). The diagnosis of cancer was independently associated with pain, severe symptoms, and the co-occurrence of dyspnea, pain, and agitation (odds ratio >1). CONCLUSIONS: People dying with dementia and those dying with cancer experienced similar rates of dyspnea, and agitation. However, pain was significantly more prevalent and intense among people dying with cancer.

Hemoglobin metabolism by-products are associated with an inflammatory response in patients with hemorrhagic stroke. / Subprodutos do metabolismo da hemoglobina se associam com resposta inflamatória em pacientes com acidente vascular cerebral hemorrágico.

OBJECTIVE: To evaluate the relationships of brain iron and heme with the inflammatory response of the systemic and central nervous systems and to investigate the role of defensive systems against the toxicity of iron and heme in the central nervous system. METHODS: We assessed a prospective cohort of patients presenting with intracerebral and subarachnoid hemorrhage. We assayed plasma and cerebrospinal fluid samples for the presence of iron, heme, hemopexin, haptoglobin, enolase, S100-ß and cytokines for the first three days following hemorrhagic stroke. We also analyzed the dynamic changes in these components within both fluids and their relationship with early mortality rates. RESULTS: Hemopexin and haptoglobin concentrations were nearly negligible in the brain after intracerebral and subarachnoid hemorrhage. Cerebrospinal fluid iron and heme concentrations correlated with a pro-inflammatory response in the central nervous system, and plasmatic and cerebrospinal fluid inflammatory profiles on the third day after hemorrhagic stroke were related to early mortality rates. Interleukin 4 levels within the cerebrospinal fluid during the first 24 hours after hemorrhagic stroke were found to be higher in survivors than in non-survivors. CONCLUSION: Iron and heme are associated with a pro-inflammatory response in the central nervous system following hemorrhagic stroke, and protections against hemoglobin and heme are lacking within the human brain. Patient inflammatory profiles were associated with a poorer prognosis, and local anti-inflammatory responses appeared to have a protective role.

Epidemiology of sepsis in Brazil: Incidence, lethality, costs, and other indicators for Brazilian Unified Health System hospitalizations from 2006 to 2015.

BACKGROUND: Sepsis is considered a major worldwide health burden, with high mortality and associated costs. Health indicators are essential to define strategies to improve the treatment of diseases, and the epidemiology information of sepsis in developing countries is scarce. Thus, the aim of this work is to assess trends in the incidence, lethality, costs, and other indicators of sepsis for Brazilian Unified Health System (SUS-Sistema Único de Saúde) hospitalizations for the period from January 2006 to December 2015. MATERIALS AND METHODS: We conducted this study using data from the SUS hospital information system. We selected registries of SUS hospitalizations of patients diagnosed with sepsis (total of 724,458 cases from 4,271 public and private Brazilian hospitals). RESULTS: From 2006 to 2015, the annual sepsis incidence increased 50.5% from 31.5/100,000 to 47.4/100,000 persons. The mean hospital length of stay (LOS) was 9.0 days. A total of 29.1% of the hospitalizations had admission to the intensive care unit (ICU) with a mean ICU LOS of 8.0 days. The mean cost per hospitalization was US$624.0 and for hospitalizations requiring intensive care was U$1,708.1. The overall sepsis lethality rate was 46.3%, and for hospitalizations with admission to the ICU, it was 64.5%. During the study period, the lethality rate for children/teenagers decreased 40.1%, but for all other age groups it increased 11.4%. The sepsis lethality rate in public hospitals (55.5%) was higher than private hospitals (37.0%) (p < 0.001). The mean hospitalization LOS for public hospitals (10.3 days) was higher than private hospitals (7.6 days) (p < 0.001). CONCLUSIONS: The incidence and lethality rate of sepsis increased in SUS hospitalizations during the study period. The SUS's low reimbursement to hospitals for treating sepsis may be one of the reasons for the high lethality rate.

Subprodutos do metabolismo da hemoglobina se associam com resposta inflamatória em pacientes com acidente vascular cerebral hemorrágico / Hemoglobin metabolism by-products are associated with an inflammatory response in patients with hemorrhagic stroke

RESUMO Objetivo: Avaliar o relacionamento entre os níveis cerebrais de ferro e heme e a resposta inflamatória sistêmica e no sistema nervoso central, assim como o papel dos sistemas de defesa contra a toxicidade do ferro e do heme, no sistema nervoso central. Métodos: Avaliamos uma coorte prospectiva de pacientes com quadro de hemorragia intracraniana e subaracnóidea. Realizamos ensaios em amostras de plasma e líquido cefalorraquidiano quanto à presença de ferro, heme, hemopexina, haptoglobina, enolase, S100-β e citocinas nos primeiros 3 dias após um acidente vascular cerebral hemorrágico. Analisamos também as alterações dinâmicas em todos os componentes de ambos os líquidos e seu relacionamento com as taxas de mortalidade precoce. Resultados: As concentrações de hemopexina e haptoglobina foram quase desprezíveis no cérebro após hemorragia intracraniana e subaracnóidea. As concentrações de ferro e heme no líquido cefalorraquidiano se correlacionaram com resposta pró-inflamatória no sistema nervoso central, e os perfis inflamatórios no líquido cefalorraquidiano no terceiro dia após acidente vascular cerebral hemorrágico se correlacionaram com as taxas de mortalidade precoce. Identificamos que os níveis de interleucina 4 no líquido cefalorraquidiano durante as primeiras 24 horas após acidente vascular cerebral hemorrágico foram mais altos nos sobreviventes do que nos que não sobreviveram. Conclusão: Os níveis de ferro e heme se associaram com resposta pró-inflamatória no sistema nervoso central após acidente vascular cerebral hemorrágico, e o cérebro humano não tem proteção contra hemoglobina e heme. Os perfis inflamatórios dos pacientes se associaram com prognósticos piores, e as respostas inflamatórias locais pareceram ter um papel protetor.

ABSTRACT Objective: To evaluate the relationships of brain iron and heme with the inflammatory response of the systemic and central nervous systems and to investigate the role of defensive systems against the toxicity of iron and heme in the central nervous system. Methods: We assessed a prospective cohort of patients presenting with intracerebral and subarachnoid hemorrhage. We assayed plasma and cerebrospinal fluid samples for the presence of iron, heme, hemopexin, haptoglobin, enolase, S100-β and cytokines for the first three days following hemorrhagic stroke. We also analyzed the dynamic changes in these components within both fluids and their relationship with early mortality rates. Results: Hemopexin and haptoglobin concentrations were nearly negligible in the brain after intracerebral and subarachnoid hemorrhage. Cerebrospinal fluid iron and heme concentrations correlated with a pro-inflammatory response in the central nervous system, and plasmatic and cerebrospinal fluid inflammatory profiles on the third day after hemorrhagic stroke were related to early mortality rates. Interleukin 4 levels within the cerebrospinal fluid during the first 24 hours after hemorrhagic stroke were found to be higher in survivors than in non-survivors. Conclusion: Iron and heme are associated with a pro-inflammatory response in the central nervous system following hemorrhagic stroke, and protections against hemoglobin and heme are lacking within the human brain. Patient inflammatory profiles were associated with a poorer prognosis, and local anti-inflammatory responses appeared to have a protective role.

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.

Role of organisational factors on the 'weekend effect' in critically ill patients in Brazil: a retrospective cohort analysis.

INTRODUCTION: Higher mortality for patients admitted to intensive care units (ICUs) during the weekends has been occasionally reported with conflicting results that could be related to organisational factors. We investigated the effects of ICU organisational and staffing patterns on the potential association between weekend admission and outcomes in critically ill patients. METHODS: We included 59 614 patients admitted to 78 ICUs participating during 2013. We defined 'weekend admission' as any ICU admission from Friday 19:00 until Monday 07:00. We assessed the association between weekend admission with hospital mortality using a mixed logistic regression model controlling for both patient-level (illness severity, age, comorbidities, performance status and admission type) and ICU-level (decrease in nurse/bed ratio on weekend, full-time intensivist coverage, use of checklists on weekends and number of institutional protocols) confounders. We performed secondary analyses in the subgroup of scheduled surgical admissions. RESULTS: A total of 41 894 patients (70.3%) were admitted on weekdays and 17 720 patients (29.7%) on weekends. In univariable analysis, weekend admitted patients had higher ICU (10.9% vs 9.0%, P<0.001) and hospital (16.5% vs 13.5%, P<0.001) mortality. After adjusting for confounders, weekend admission was not associated with higher hospital mortality (OR 1.05, 95% CI 0.99 to 1.12, P=0.095). However, a 'weekend effect' was still observed in scheduled surgical admissions, as well as in ICUs not using checklists during the weekends. For unscheduled admissions, no 'weekend effect' was observed regardless of ICU's characteristics. For scheduled surgical admissions, a 'weekend effect' was present only in ICUs with a low number of implemented protocols and those with a reduction in the nurse/bed ratio and not applying checklists during weekends. CONCLUSIONS: ICU organisational factors, such as decreased nurse-to-patient ratio, absence of checklists and fewer standardised protocols, may explain, in part, increases in mortality in patients admitted to the ICU mortality on weekends.

Post-Acute Care Facility as a Discharge Destination for Patients in Need of Palliative Care in Brazil.

Patients with complex palliative care needs can experience delayed discharge, which causes an inappropriate occupancy of hospital beds. Post-acute care facilities (PACFs) have emerged as an alternative discharge destination for some of these patients. The aim of this study was to investigate the frequency of admissions and characteristics of palliative care patients discharged from hospitals to a PACF. We conducted a retrospective analysis of PACF admissions between 2014 and 2016 that were linked to hospital discharge reports and electronic health records, to gather information about hospital-to-PACF transitions. In total, 205 consecutive patients were discharged from 6 different hospitals to our PACF. Palliative care patients were involved in 32% (n = 67) of these discharges. The most common conditions were terminal cancer (n = 42, 63%), advanced dementia (n = 17, 25%), and stroke (n = 5, 8%). During acute hospital stays, patients with cancer had significant shorter lengths of stay (13 vs 99 days, P = .004), a lower use of intensive care services (2% vs 64%, P < .001) and mechanical ventilation (2% vs 40%, P < .001), when compared to noncancer patients. Approximately one-third of discharges from hospitals to a PACF involved a heterogeneous group of patients in need of palliative care. Further studies are necessary to understand the trajectory of posthospitalized patients with life-limiting illnesses and what factors influence their decision to choose a PACF as a discharge destination and place of death. We advocate that palliative care should be integrated into the portfolio of post-acute services.

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.

Highly active antiretroviral therapy for critically ill HIV patients: A systematic review and meta-analysis.

INTRODUCTION: It is unclear whether the treatment of an HIV infection with highly active antiretroviral therapy (HAART) affects intensive care unit (ICU) outcomes. In this paper, we report the results of a systematic review and meta-analysis performed to summarize the effects of HAART on the prognosis of critically ill HIV positive patients. MATERIALS AND METHODS: A bibliographic search was performed in 3 databases (PubMed, Web of Science and Scopus) to identify articles that investigated the use of HAART during ICU admissions for short- and long-term mortality or survival. Eligible articles were selected in a staged process and were independently assessed by two investigators. The methodological quality of the selected articles was evaluated using the Methodological Index for Non-Randomized Studies (MINORS) tool. RESULTS: Twelve articles met the systematic review inclusion criteria and examined short-term mortality. Six of them also examined long-term mortality (≥90 days) after ICU discharge. The short-term mortality meta-analysis showed a significant beneficial effect of initiating or maintaining HAART during the ICU stay (random effects odds ratio 0.53, p = 0.02). The data analysis of long-term outcomes also suggested a reduced mortality when HAART was used, but the effect of HAART on long-term mortality of HIV positive critically ill patients remains uncertain. CONCLUSIONS: This meta-analysis suggests improved survival rates for HIV positive patients who were treated with HAART during their ICU admission.

Revisão sistemática de fatores prognósticos a curto prazo de pacientes HIV internados em uma unidade de cuidados intensivos / Systematic review of short-term prognostic factors of HIV patients admitted to an intensive care unit

Conhecer os fatores prognósticos de curto prazo de pacientes HIV, criticamente doentes, na era de terapia antirretroviral combinada, é importante para adoção de medidas preventivas e mais efetivas de tratamento. Para identificar os fatores mais significativos e comuns que determinam a mortalidade a curto prazo, uma revisão sistemática da literatura mais relevante foi conduzida. Método: Uma busca na internet foi conduzida em 3 bases de dados de artigos científicos indexados (PubMed, Scopus e Web of Science) para estudos que investigaram fatores prognósticos de mortalidade ou sobrevivência a curto prazo (em UTIs, ou em outros setores do hospital, seguindo a internação na UTI) de pacientes HIV criticamente enfermos. Os artigos foram selecionados de acordo com critérios pré-estabelecidos e avaliados independentemente por 2 pesquisadores. As variáveis coletadas foram autor, ano, local e tipo do estudo, número de pacientes com HIV, mortalidade, fatores significativos em regressão logística simples e múltipla, principais causas de admissão e critérios de inclusão. Resultados: Vinte e seis artigos foram selecionados para revisão sistemática. Quinze lidaram com fatores que determinavam mortalidade na UTI, 9 com mortalidade hospitalar após internação em UTI, e 2 com ambos. Conclusões: Fatores associados à gravidade de doença aguda, como escores prognósticos, albumina e disfunção orgânica (choque e insuficiência respiratória) parecem ser mais importantes como determinantes da mortalidade a curto prazo que aqueles associados ao HIV.

Knowing the short-term prognostic factors of critically ill HIV patients admitted to intensive care units (ICUs) in the era of combination antiretroviral therapy (cART) is important for the adoption of preventive measures and more effective treatment. To identify the most significant and common factors that determine short-term mortality, a systematic review of the relevant literature was carried out. Method: An internet search was conducted in three databases indexing scientific articles (PubMed, Scopus, and Web of Science) for studies investigating the prognostic factors of mortality or short-term survival (in ICUs and elsewhere in hospitals following ICU admission) of critically ill HIV-infected patients. The articles were selected according to pre-established criteria and evaluated independently by two researchers. The variables collected were author, year, study location, study type, number of patients with HIV, mortality, significant factors in simple logistic regression and multiple regression, main causes of admission, and inclusion criteria. Results: Twenty-six articles were selected for systematic review. Fifteen dealt with factors that determine mortality in the ICU, nine with hospital mortality following ICU admission, and two with both. Conclusions: Factors associated with the severity of acute disease, such as prognostic scores, albumin, and organ failure (shock and respiratory failure), seem to be more important as determinants of short-term mortality than those associated with HIV