Sociodemographic factors associated with COVID-19 in-hospital mortality in Brazil.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has highlighted inequalities in access to healthcare systems, increasing racial disparities and worsening health outcomes in these populations. This study analysed the association between sociodemographic characteristics and COVID-19 in-hospital mortality in Brazil. STUDY DESIGN: A retrospective analysis was conducted on quantitative reverse transcription polymerase chain reaction-confirmed hospitalised adult patients with COVID-19 with a defined outcome (i.e. hospital discharge or death) in Brazil. Data were retrieved from the national surveillance system database (SIVEP-Gripe) between February 16 and August 8, 2020. METHODS: Clinical characteristics, sociodemographic variables, use of hospital resources and outcomes of hospitalised adult patients with COVID-19, stratified by self-reported race, were investigated. The primary outcome was in-hospital mortality. The association between self-reported race and in-hospital mortality, after adjusting for clinical characteristics and comorbidities, was evaluated using a logistic regression model. RESULTS: During the study period, Brazil had 3,018,397 confirmed COVID-19 cases and 100,648 deaths. The study population included 228,196 COVID-19-positive adult in-hospital patients with a defined outcome; the median age was 61 years, 57% were men, 35% (79,914) self-reported as Black/Brown and 35.4% (80,853) self-reported as White. The total in-hospital mortality was 37% (85,171/228,196). Black/Brown patients showed higher in-hospital mortality than White patients (42% vs 37%, respectively), were admitted less frequently to the intensive care unit (ICU) (32% vs 36%, respectively) and used more invasive mechanical ventilation (21% vs 19%, respectively), especially outside the ICU (17% vs 11%, respectively). Black/Brown race was independently associated with high in-hospital mortality after adjusting for sex, age, level of education, region of residence and comorbidities (odds ratio = 1.15; 95% confidence interval = 1.09-1.22). CONCLUSIONS: Among hospitalised Brazilian adults with COVID-19, Black/Brown patients showed higher in-hospital mortality, less frequently used hospital resources and had potentially more severe conditions than White patients. Racial disparities in health outcomes and access to health care highlight the need to actively implement strategies to reduce inequities caused by the wider health determinants, ultimately leading to a sustainable change in the health system.

Short- and medium-term prognosis of HIV-infected patients receiving intensive care: a Brazilian multicentre prospective cohort study.

OBJECTIVES: The characteristics of critically ill HIV-positive patients and the causes of their admission to intensive care units (ICUs) are only known through retrospective and unicentric studies. This study aims to fill this knowledge gap. METHODS: This is a prospective, multicentre cohort study of short- and medium-term prognostic factors. The setting consisted of ICUs of three tertiary referral hospitals from the three largest metropolitan areas in Brazil in the period January 2014 to November 2015. In all, 161 HIV patients over 18 years old were included. RESULTS: The clinical data of the outcomes (ICU mortality, hospital mortality and 90-day survival) were extracted from medical records using the REDCap®ï¸ web-based form and analysed with the MedCalc®ï¸ application. Median age was 41.7 [interquartile range (IQR): 34-50] years, the Simplified Acute Physiologic Score 3 (SAPS 3) was 64 (IQR: 56-74), and the Sequential Organ Failure Assessment Score (SOFA) was 6 (IQR: 4-9) points. The main causes of admission were sepsis (54.5%) and acute respiratory failure (13.7%). ICU and hospital mortality rates were 32.3% and 40.4%, respectively. In a multivariate analysis, time until ICU admission ≥ 3 days (P = 0.0013), performance status (Eastern Cooperative Oncology Group score, P = 0.0344), coma (Glasgow Coma Scale ≤ 8 points, P = 0.0213) and sepsis (P = 0.0003) were associated with increased hospital mortality. Coma (P = 0.0002) and sepsis (P = 0.0008) were independently associated with 90-day survival. CONCLUSIONS: Delayed ICU admission and the severity of critical illness determine the short- and medium-term mortality rates of HIV-infected patients admitted to the ICU, rather than factors associated with HIV infection. These results suggest that prognostic factors of HIV-infected patients in the ICU are similar to those of non-HIV-infected populations.

Predicting acquisition of carbapenem-resistant Gram-negative pathogens in intensive care units.

BACKGROUND: Infections by multidrug-resistant Gram-negative (MDRGN) bacteria are among the greatest contemporary health concerns, especially in intensive care units (ICUs), and may be associated with increased hospitalization time, morbidity, costs, and mortality. AIM: The study aimed to predict carbapenem-resistant MDRGN acquisition in ICUs, to determine its risk factors, and to assess the impact of this acquisition on mortality rate. METHODS: A matched case-control study was performed in patients admitted to the ICU at a large Brazilian hospital over a five-year period. Cases were defined as patients who acquired carbapenem-resistant MDRGN bacteria during hospitalization. Controls were defined as patients who had no detection of carbapenem-resistant MDRGN bacteria. Cases were matched to controls according to the admission period. Risk factors were identified by multiple logistic regression using a stepwise selection method. FINDINGS: In total, 343 cases and 1029 controls were analysed. The 30-day mortality rate for subjects with ICU-associated carbapenem-resistant MDRGN was 37.6%. Five variables were identified as statistically significant and more relevant for the acquisition of multidrug-resistant strains: increased Simplified Acute Physiology Score 3, patients with severe chronic obstructive pulmonary disease and exposure to haemodialysis catheter, central venous catheter, or mechanical ventilation. Models developed displayed good results with an accuracy of ∼90%. Patients who acquired MDRGN were 2.72 times more likely to die than non-MDRGN acquisition patients. CONCLUSION: Finding risk factors and developing predictive models may benefit patients through early detection and by controlling the spread of MDR. The presence of mechanical ventilation and central venous catheter were the main risk factors demonstrated, and their use requires special attention.

Adverse birth outcomes associated with Zika virus exposure during pregnancy in São José do Rio Preto, Brazil.

OBJECTIVES: We aimed to report the first 54 cases of pregnant women infected by Zika virus (ZIKV) and their virologic and clinical outcomes, as well as their newborns' outcomes, in 2016, after the emergence of ZIKV in dengue-endemic areas of São Paulo, Brazil. METHODS: This descriptive study was performed from February to October 2016 on 54 quantitative real-time PCR ZIKV-positive pregnant women identified by the public health authority of São José do Rio Preto, São Paulo, Brazil. The women were followed and had clinical and epidemiologic data collected before and after birth. Adverse outcomes in newborns were analysed and reported. Urine or blood samples from newborns were collected to identify ZIKV infection by reverse transcription PCR (RT-PCR). RESULTS: A total of 216 acute Zika-suspected pregnant women were identified, and 54 had the diagnosis confirmed by RT-PCR. None of the 54 women miscarried. Among the 54 newborns, 15 exhibited adverse outcomes at birth. The highest number of ZIKV infections occurred during the second and third trimesters. No cases of microcephaly were reported, though a broad clinical spectrum of outcomes, including lenticulostriate vasculopathy, subependymal cysts, and auditory and ophthalmologic disorders, were identified. ZIKV RNA was detected in 18 of 51 newborns tested and in eight of 15 newborns with adverse outcomes. CONCLUSIONS: Although other studies have associated many newborn outcomes to ZIKV infection during pregnancy, these same adverse outcomes were rare or nonexistent in this study. The clinical presentation the newborns we studied was mild compared to other reports, suggesting that there is significant heterogeneity in congenital Zika infection.

Comparison of two databases to detect potential drug-drug interactions between prescriptions of HIV/AIDS patients in critical care.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug events (ADE), common and underestimated in ICU patients, have direct consequences on length of stay, mortality and hospital costs. Critically ill patients with HIV/AIDS are at a high risk of ADE because of their need for multiple drug therapies. ADE can be prevented, especially by the identification of potentially harmful drug-drug interactions (DDIs). Electronic databases are useful tools for the investigation of DDIs to avoid potential ADEs, thereby increasing patient safety. The purpose of this study was to compare the classification and severity rating of potential adverse drug interactions seen in the prescriptions for patients with HIV/AIDS in two databases, one with free access (Drugs.com(™)) and another requiring payment for access (Micromedex(®)). METHODS: A cross-sectional retrospective study of the prescriptions issued for 40 ICU HIV/AIDS patients on mechanical ventilation, admitted for more than 48 h, in a referral hospital for infectious diseases in Rio de Janeiro, Brazil, was undertaken. One prescription was reviewed each week for each patient from the second day after admission. A list of all drug-drug interactions was generated for each patient using the two drug-drug interactions databases. The weighted kappa index was estimated to assess the agreement between the classifications of DDIs identified by both databases and qualitative assessment made of any discordant classification of recorded drug-drug interactions. RESULTS AND DISCUSSION: Of the 106 prescriptions analysed, Micromedex(®) and Drugs.com identified 347 and 615 potential DDIs, respectively. A predominance of moderate interactions and pharmacokinetic interactions was observed. The agreement between the databases regarding the severity rating was only 68.3%. The weighted kappa of 0.44 is considered moderate. Better agreement (82.4%) was observed in the classification of mechanism of interaction, with a weighted kappa of 0.61. WHAT IS NEW AND CONCLUSION: DDIs are common between the prescriptions of patients with HIV/AIDS admitted to the ICU. Although both databases were able to identify the clinically relevant DDIs, we observed a significant discrepancy in the classification of the severity of DDIs in the two bases. The free access database could serve as an alternative to the identification of DDIs in resource-limited settings; however, there is a need for better evidence-based assessments for your use on clinical management of more serious DDIs.

Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases.

BACKGROUND: Worldwide, dengue is the most prevalent human arbovirus disease. Dengue infection may cause a range of clinical manifestations from self-limiting febrile illness through to a life-threatening syndrome accompanied by both bleeding and shock. Thrombocytopenia is frequently observed in mild and severe disease; however, the mechanisms involved in DENV-induced platelet activation and thrombocytopenia are incompletely understood. PATIENTS AND METHODS: Freshly isolated platelets from patients with dengue were evaluated for markers of activation, mitochondrial alteration and activation of cell death pathways. In parallel, we examined direct DENV-induced activation and apoptosis of platelets obtained from healthy subjects. RESULTS: We found that platelets from DENV-infected patients exhibited increased activation by comparison to control subjects. Moreover, platelets from DENV-infected patients exhibited classic signs of the intrinsic pathway of apoptosis that include increased surface phosphatidylserine exposure, mitochondrial depolarization and activation of caspase-9 and -3. Indeed, thrombocytopenia was shown to strongly associate with enhanced platelet activation and cell death in DENV-infected patients. Platelet activation, mitochondrial dysfunction and caspase-dependent phosphatidylserine exposure on platelets were also observed when platelets from healthy subjects were directly exposed to DENV in vitro. DENV-induced platelet activation was shown to occur through mechanisms largely dependent on DC-SIGN. CONCLUSIONS: Together our results demonstrate that platelets from patients with dengue present signs of activation, mitochondrial dysfunction and activation of the apoptosis caspase cascade, which may contribute to the development of thrombocytopenia in patients with dengue. Our results also suggest the involvement of DC-SIGN as a critical receptor in DENV-dependent platelet activation.

Beneficial effects of high positive end-expiratory pressure in lung respiratory mechanics during laparoscopic surgery.

BACKGROUND: The effect of neuromuscular blockade (NMB) and positive end-expiratory pressure (PEEP) on the elastic properties of the respiratory system during pneumoperitoneum (PnP) remains a controversial subject. The main objective of the present study was to evaluate the effects of NMB and PEEP on respiratory mechanics. METHODS: We performed a dynamic analysis of respiratory mechanics in patients subjected to PnP. Twenty-one patients underwent cholecystectomy videolaparoscopy and total intravenous anesthesia. The respiratory system resistance (R(RS)), pulmonary elastance (E(P)), chest wall elastance (E(CW)), and respiratory system elastance (E(RS)) were computed via the least squares fit technique using an equation describing the motion of the respiratory system, which uses primary signs such as airway pressure, tidal volume, air flow, and esophageal pressures. Measurements were taken after tracheal intubation, PnP, NMB, establishment of PEEP (10 cmH2O), and PEEP withdrawal [zero end-expiratory pressure (ZEEP)]. RESULTS: PnP significantly increased E(RS) by 27%; both E(P) and E(CW) increased 21.3 and 64.1%, respectively (P < 0.001). NMB did not alter the respiratory mechanic properties. Setting PEEP reduced E(RS) by 8.6% (P < 0.05), with a reduction of 10.9% in E(P) (P < 0.01) and a significant decline of 15.7% in R(RS) (P < 0.05). These transitory changes in elastance disappeared after ZEEP. CONCLUSIONS: We concluded that the 10 cmH2O of PEEP attenuates the effects of PnP in respiratory mechanics, lowering R(RS), E(P), and E(RS). These effects may be useful in the ventilatory approach for patients experiencing a non-physiological increase in IAP owing to PnP in laparoscopic procedures.

FDG-PET in patients at risk for acute respiratory distress syndrome: a preliminary report.

OBJECTIVE: To compare the pattern of lung uptake of 18F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) imaging in patients with lung contusion that developed or did not progress to acute respiratory distress syndrome (ARDS). DESIGN: Prospective, observational study. SETTING: Trauma Center (academic urban hospital). PATIENTS AND INTERVENTIONS: Eight patients with blunt thoracic trauma and pulmonary contusion, confirmed by computed tomography (CT) on admission, underwent repeat CT and FDG-PET (on the same day) 24-72 h after admission. RESULTS: No subjects met the criteria for ARDS at the time of the PET and second CT. Four subjects subsequently developed ARDS 1-3 days after the PET scan; the other four did not develop the syndrome. Three of the four subjects who subsequently developed ARDS showed diffuse FDG uptake throughout the entire lungs, while those who did not develop ARDS showed significant FDG uptake only in areas of focal lung opacity (non or poorly aerated lung units) on CT. FDG uptake in normally aerated lung regions was higher for those who subsequently developed ARDS than those who did not, approaching statistical significance. The normally aerated tissue:liver ratio was significantly higher in subjects who developed ARDS than in those who did not (P = 0.029). CONCLUSION: In this small series of patients with thoracic trauma, diffuse lung uptake of FDG was detected by PET imaging 1-3 days prior to clinically determined ARDS.

Limited-sampling strategy models for itraconazole and hydroxy-itraconazole based on data from a bioequivalence study.

The extensive interindividual variability in oral bioavailability of itraconazole prompted an assessment of the bioequivalence of two formulations marketed in Brazil, namely, Sporanox (reference) and Traconal (test). Eighteen healthy volunteers received single 200-mg oral doses of each formulation at 2-week intervals in a randomized, crossover protocol. The concentrations of itraconazole and hydroxy-itraconazole in plasma were measured by high-performance liquid chromatography, and the datum points (n = 396) were subsequently used to develop limited-sampling strategy models for estimation of the areas under the curve (AUCs) for both compounds. The 90% confidence intervals for individual percent ratios (test/reference formulations) of the maximum concentration of drug in serum, the AUC from 0 to 48 h and the AUC from time zero to infinity (AUC0-infinity) for itraconazole and hydoxy-itraconazole were below the range of 80 to 125%, suggesting that these formulations are not bioequivalent. Linear regression analysis of the AUC0-infinity against time and a "jackknife" validation procedure revealed that models based on three sampling times accurately predict (R2, >0.98; bias, <3%; precision, 3 to 7%) the AUC0-infinity for each of the four formulation-compound pairs tested. Increasing the number of sampling points to more than three adds little to the accuracy of the estimates of AUC0-infinity. The three-point models developed for the reference formulation were validated retrospectively and were found to predict within 2% the AUC0-infinity reported in previous studies performed under similar protocols. In conclusion, the data in this study indicate (i) that the tested formulations are not bioequivalent when single doses are compared and (ii) that limited-sampling strategy models based on three points predict accurately the AUC0-infinitys for itraconazole and hydroxy-itraconazole and could be a valuable tool in pharmacokinetic and bioequivalence studies of single oral doses of itraconazole.