Effectiveness of the fourth dose of COVID-19 vaccines against severe COVID-19 among adults 40 years or older in Brazil: a population-based cohort study.

Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3-46.0), with some waning during follow-up (rVE 7-60 days 46.8% [95% CI 44.4-49.1], rVE after 120 days 33.8% [95% CI 18.0-46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75-0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93-1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Global representativeness and impact of funding sources in cost-effectiveness research on systemic therapies for advanced breast cancer: A systematic review.

BACKGROUND: Breast cancer (BC) is the most incident tumor and, consequently, any new intervention can potentially promote a considerable budget impact if incorporated. Cost-effectiveness (CE) studies assist in the decision-making process but may be influenced by the country's perspective of analysis and pharmaceutical industry funding. METHODS: A systematic review of Medline, Scopus, and Web of Science from January 1st, 2012 to July 8th, 2022 was conducted to identify CE studies of tumor-targeted systemic-therapies for advanced BC. Articles without incremental cost-effectiveness ratio calculations were excluded. We extracted information on the country and class of drug studied, comparator type, authors' conflicts of interest (COI), pharmaceutical industry funding, and authors' conclusions. RESULTS: 71 studies comprising 204 CE assessments were included. The majority of studies were from the United States and Canada (44%), Asia (32%) and Europe (20%). Only 8% were from Latin America and none from Africa. 31% had pharmaceutical industry funding. The most studied drug classes were cyclin-dependent-kinase inhibitors (29%), anti-HER2 therapy (23%), anti-PD(L)1 (11%) and hormone therapy (11%). Overall, 34% of CE assessments had favorable conclusions. Pharmaceutical industry-funded articles had a higher proportion of at least one favorable conclusion (82% vs. 24%, p-value<0.001), European countries analyzed (45% vs. 9%, p-value = 0.003), and CE assessments with same class drug comparators (56% vs. 33%, p-value = 0.004). CONCLUSIONS: Breast cancer CE literature scarcely represents low-and-middle-income countries' perspectives and is influenced by pharmaceutical industry funding which targets European countries', frequently utilizes comparisons within same-drug class, and is more likely to have favorable conclusions.

Spatial Immunoprofiling of Adenoid Cystic Carcinoma Reveals B7-H4 Is a Therapeutic Target for Aggressive Tumors.

PURPOSE: Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets. EXPERIMENTAL DESIGN: Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm software. The B7-H4 antibody-drug conjugate AZD8205 was tested in ACC patient-derived xenografts (PDX). RESULTS: RNA deconvolution revealed that most ACCs are immunologically "cold," with approximately 30% being "hot." ACC-I tumors with a poor prognosis harbored a higher density of immune cells; however, spatial analysis by IMC revealed that ACC-I immune cells were significantly restricted to the stroma, characterizing an immune-excluded TME. ACC-I tumors overexpressed the immune checkpoint B7-H4, and the degree of immune exclusion was directly correlated with B7-H4 expression levels, an independent predictor of poor survival. Two ACC-I/B7-H4-high PDXs obtained 90% complete responses to a single dose of AZD8205, but none were observed with isotype-conjugated payload or in an ACC-II/B7-H4 low PDX. CONCLUSIONS: Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.

Human papillomavirus status and prognosis of oropharyngeal high-grade neuroendocrine carcinoma.

BACKGROUND: The prognostic impact of human papillomavirus (HPV) infection or smoking on oropharyngeal high-grade neuroendocrine carcinoma (HG-NEC) is not established. METHODS: Retrospective study with patients with oropharyngeal HG-NEC seen at MD Anderson Cancer Center from 1997 to 2020, and previously reported patients with oropharyngeal HG-NEC and known p16 and HPV status from the literature review. Survival was estimated with the Kaplan-Meier method, and survival differences assessed with the log-rank test and Cox proportional hazards models. RESULTS: Thirty patients were included; most had a heavy (≥10 pack-years) smoking history (52%), locoregional disease (stage III-IVB; 77%), and p16-positive tumor (92%). HPV was positive in 65% of tested samples (15/23). Of 24 patients treated with curative intent, the objective response rates was 90% (9/10) and 81% (17/21), respectively, for induction chemotherapy and definitive radiotherapy. During follow-up, 54% (13/24) recurred, mostly (11/13) at distant sites. Median overall survival (OS) was 46 months (95% CI, 14.3 - NA). OS was not associated with HPV status (HR 0.73, P = 0.6) or smoking (HR 1.16, P = 0.8). Among 63 patients with known HPV status after the literature review (19 HPV- and 44 HPV + ), HPV status remained unassociated with OS (P = 0.92). CONCLUSIONS: This is the largest retrospective cohort of oropharyngeal HG-NEC. Distant recurrence rate after curative treatment was high, suggesting that multimodality treatment including systemic therapy may benefit patients with locally advanced disease. HPV infection did not affect survival outcomes, therefore should not lead to therapy de-intensification for this histology.

Mortality over time among COVID-19 patients hospitalized during the first surge of the pandemic: A large cohort study.

BACKGROUND: Capacity strain negatively impacts patient outcome, and the effects of patient surge are a continuous threat during the COVID-19 pandemic. Evaluating changes in mortality over time enables evidence-based resource planning, thus improving patient outcome. Our aim was to describe baseline risk factors associated with mortality among COVID-19 hospitalized patients and to compare mortality rates over time. METHODS: We conducted a retrospective cohort study in the largest referral hospital for COVID-19 patients in Sao Paulo, Brazil. We investigated risk factors associated with mortality during hospitalization. Independent variables included age group, sex, the Charlson Comorbidity Index, admission period according to the stage of the first wave of the epidemic (early, peak, and late), and intubation. RESULTS: We included 2949 consecutive COVID-19 patients. 1895 of them were admitted to the ICU, and 1473 required mechanical ventilation. Median length of stay in the ICU was 10 (IQR 5-17) days. Overall mortality rate was 35%, and the adjusted odds ratios for mortality increased with age, male sex, higher Charlson Comorbidity index, need for mechanical ventilation, and being admitted to the hospital during the wave peak of the epidemic. Being admitted to the hospital during the wave peak was associated with a 33% higher risk of mortality. CONCLUSIONS: In-hospital mortality was independently affected by the epidemic period. The recognition of modifiable operational variables associated with patient outcome highlights the importance of a preparedness plan and institutional protocols that include evidence-based practices and allocation of resources.

Outcomes of Critically Ill Lung Cancer Patients Initiating Targeted Therapy or Immunotherapy in the Intensive Care Unit: A Single-Center Report.

Introduction: Targeted therapy and immune checkpoint inhibitors (ICI) have drastically improved outcomes of metastatic non-small cell lung cancer (NSCLC) patients in outpatient settings. Because trials on critically ill patients are improbable, little is known about their efficacy among patients admitted to intensive care units (ICU). Methods: We retrospectively analyzed the clinical outcomes of critically-ill NSCLC patients receiving either ICI or targeted therapy during ICU admission at the MD Anderson Cancer Center from April 2016 to August 2020. We collected data on ICU admission diagnoses, sequential organ failure assessment (SOFA), previous cancer therapies, tumor gene mutations or translocations, and PD-L1 expression. Overall survival (OS) was calculated from the date of drug initiation using the Kaplan-Meier method. Results: Of 9898 ICU admissions, 9 patients with metastatic NSCLC who received either targeted therapy (5) or PD-1 ICI (4) during ICU admission were included. The most common reasons for ICU admissions were tumor visceral crisis (3/9) and sepsis (3/9). The median (range) admission SOFA was 4 (2-11). Six patients were naïve to systemic therapy. Five patients required mechanical ventilation. The median OS was 77 days (95%CI, 36-NA), and 5 patients were discharged alive (all received targeted therapy). The median OS of patients who received ICI was 25.5 days (95%CI, 8-NA) and for those who received targeted therapy was 218 days (95%CI, 77-NA). At 6 and 12 months follow-up, 3 and 2 patients who received targeted therapy were still alive, respectively. Conclusions: Our exploratory findings indicate a possible benefit of targeted therapy but suggest a lack of clinical utility of PD-1 ICI for critically ill metastatic NSCLC patients. Because of the small sample size, further studies are needed to expand on this topic.

Usefulness of ECG criteria to rule out left ventricular hypertrophy in older individuals with true left bundle branch block: an observational study.

BACKGROUND: Advanced age is associated with both left bundle branch block (LBBB) and hypertension and the usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with LBBB is still unclear. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined by stricter ECG criteria is unknown. The aim of this study was to compare diagnostic accuracy and clinical utility of ECG criteria in patients with advanced age and strict LBBB criteria. METHODS: Retrospective single-center study conducted from Jan/2017 to Mar/2018. Patients undergoing both ECG and echocardiogram examinations were included. Ten criteria for ECG-based LVH were compared using LVH defined by the echocardiogram as the gold standard. Sensitivity, specificity, predictive values, likelihood ratios, AUC, and the Brier score were used to compare diagnostic performance and a decision curve analysis was performed. RESULTS: From 4621 screened patients, 68 were included, median age was 78.4 years, (IQR 73.3-83.4), 73.5% with hypertension. All ECG criteria failed to provide accurate discrimination of LVH with AUC range between 0.54 and 0.67, and no ECG criteria had a balanced tradeoff between sensitivity and specificity. No ECG criteria consistently improved the net benefit compared to the strategy of performing routine echocardiogram in all patients in the decision curve analysis within the 10-60% probability threshold range. CONCLUSION: ECG-based criteria for LVH in patients with advanced age and true LBBB lack diagnostic accuracy or clinical usefulness and should not be routinely assessed.

Therapeutic approaches and outcomes in patients with larynx or hypopharynx high-grade neuroendocrine carcinoma: A single-center retrospective analysis.

BACKGROUND: High-grade neuroendocrine carcinoma of the larynx (HG-NECL) is rare and aggressive with limited data regarding response to systemic therapy. We evaluated clinicopathological features, therapeutic approaches, and outcomes in patients with laryngeal or hypopharyngeal HG-NECL. METHODS: Data were retrospectively collected through 1997-2020. Median disease-free (mDFS), progression-free (mPFS), and overall survival (mOS) were estimated using the Kaplan-Meier method. RESULTS: Fifteen patients were identified; most had locoregional (N = 7) or metastatic disease (N = 5). The main curative-intent treatment was chemoradiation concurrent with platinum-based chemotherapy; the rate of complete response was 78%. Most patients (80%) developed recurrence; the mDFS was 13.1 months. For the first-line palliative therapy, the ORR and mPFS were 50% and 3.1 months, respectively. For all patients, the mOS was 17.8 months, and 8.6 months for metastatic disease. CONCLUSION: Laryngeal HG-NEC is associated with high relapse rates and dismal prognosis for those with recurrent/metastatic disease. Novel therapeutic strategies are needed.

Clinical applicability and diagnostic performance of electrocardiographic criteria for left ventricular hypertrophy diagnosis in older adults.

Recently, a new ECG criterion, the Peguero-Lo Presti (PLP), improved overall accuracy in the diagnosis of left ventricular hypertrophy (LVH)-compared to traditional ECG criteria, but with few patients with advanced age. We analyzed patients with older age and examined which ECG criteria would have better overall performance. A total of 592 patients were included (83.1% with hypertension, mean age of 77.5 years) and the PLP criterion was compared against Cornell voltage (CV), Sokolow-Lyon voltage (SL) and Romhilt-Estes criteria (cutoffs of 4 and 5 points, RE4 and RE5, respectively) using LVH defined by the echocardiogram as the gold standard. The PLP had higher AUC than the CV, RE and SL (respectively, 0.70 vs 0.66 vs 0.64 vs 0.67), increased sensitivity compared with the SL, CV and RE5 (respectively, 51.9% [95% CI 45.4-58.3%] vs 28.2% [95% CI 22.6-34.4%], p < 0.0001; vs 35.3% [95% CI 29.2-41.7%], p < 0.0001; vs 44.4% [95% CI 38.0-50.9%], p = 0.042), highest F1 score (58.3%) and net benefit for most of the 20-60% threshold range in the decision curve analysis. Overall, despite the best diagnostic performance in older patients, the PLP criterion cannot rule out LVH consistently but can potentially be used to guide clinical decision for echocardiogram ordering in low-resource settings.

Community-acquired pneumonia severity assessment tools in patients hospitalized with COVID-19: a validation and clinical applicability study.

OBJECTIVE: To externally validate community-acquired pneumonia (CAP) tools on patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia from two distinct countries, and compare their performance with recently developed COVID-19 mortality risk stratification tools. METHODS: We evaluated 11 risk stratification scores in a binational retrospective cohort of patients hospitalized with COVID-19 pneumonia in São Paulo and Barcelona: Pneumonia Severity Index (PSI), CURB, CURB-65, qSOFA, Infectious Disease Society of America and American Thoracic Society Minor Criteria, REA-ICU, SCAP, SMART-COP, CALL, COVID GRAM and 4C. The primary and secondary outcomes were 30-day in-hospital mortality and 7-day intensive care unit (ICU) admission, respectively. We compared their predictive performance using the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, likelihood ratios, calibration plots and decision curve analysis. RESULTS: Of 1363 patients, the mean (SD) age was 61 (16) years. The 30-day in-hospital mortality rate was 24.6% (228/925) in São Paulo and 21.0% (92/438) in Barcelona. For in-hospital mortality, we found higher AUCs for PSI (0.79, 95% CI 0.77-0.82), 4C (0.78, 95% CI 0.75-0.81), COVID GRAM (0.77, 95% CI 0.75-0.80) and CURB-65 (0.74, 95% CI 0.72-0.77). Results were similar for both countries. For the 1%-20% threshold range in decision curve analysis, PSI would avoid a higher number of unnecessary interventions, followed by the 4C score. All scores had poor performance (AUC <0.65) for 7-day ICU admission. CONCLUSIONS: Recent clinical COVID-19 assessment scores had comparable performance to standard pneumonia prognostic tools. Because it is expected that new scores outperform older ones during development, external validation studies are needed before recommending their use.

Comparative assessment of mortality risk factors between admission and follow-up models among patients hospitalized with COVID-19.

OBJECTIVES: This study aimed to compare differences in mortality risk factors between admission and follow-up incorporated models. METHODS: A retrospective cohort study of 524 patients with confirmed COVID-19 infection admitted to a tertiary medical center in São Paulo, Brazil from 13 March to 30 April 2020. Data were collected on admission, and the third, eighth and fourteenth days of hospitalization. The hazard ratio (HR) was calculated and 28-day in-hospital mortality risk factors were compared between admission and follow-up models using a time-dependent Cox regression model. RESULTS: Of 524 patients, 50.4% needed mechanical ventilation. The 28-day mortality rate was 32.8%. Compared with follow-up, admission models under-estimated the mortality HR for peripheral oxygen saturation <92% (1.21 versus 2.09), heart rate >100 bpm (1.19 versus 2.04), respiratory rate >24/min (1.01 versus 1.82) and mechanical ventilation (1.92 versus 12.93). Low oxygen saturation, higher oxygen support and more biomarkers-including lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea remained associated with mortality after adjustment for clinical factors at follow-up compared with only urea and oxygen support at admission. CONCLUSIONS: The inclusion of follow-up measurements changed mortality hazards of clinical signs and biomarkers. Low oxygen saturation, higher oxygen support, lactate dehydrogenase, C-reactive protein, neutrophil-lymphocyte ratio, and urea could help with prognosis of patients during follow-up.

Correction: Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: A prospective observational Brazilian study.

[This corrects the article DOI: 10.1371/journal.pone.0244532.].

Lung ultrasound score predicts outcomes in COVID-19 patients admitted to the emergency department.

BACKGROUND: During the COVID-19 pandemic, creating tools to assess disease severity is one of the most important aspects of reducing the burden on emergency departments. Lung ultrasound has a high accuracy for the diagnosis of pulmonary diseases; however, there are few prospective studies demonstrating that lung ultrasound can predict outcomes in COVID-19 patients. We hypothesized that lung ultrasound score (LUS) at hospital admission could predict outcomes of COVID-19 patients. This is a prospective cohort study conducted from 14 March through 6 May 2020 in the emergency department (ED) of an urban, academic, level I trauma center. Patients aged 18 years and older and admitted to the ED with confirmed COVID-19 were considered eligible. Emergency physicians performed lung ultrasounds and calculated LUS, which was tested for correlation with outcomes. This protocol was approved by the local Ethics Committee number 3.990.817 (CAAE: 30417520.0.0000.0068). RESULTS: The primary endpoint was death from any cause. The secondary endpoints were ICU admission and endotracheal intubation for respiratory failure. Among 180 patients with confirmed COVID-19 who were enrolled (mean age, 60 years; 105 male), the average LUS was 18.7 ± 6.8. LUS correlated with findings from chest CT and could predict the estimated extent of parenchymal involvement (mean LUS with < 50% involvement on chest CT, 15 ± 6.7 vs. 21 ± 6.0 with > 50% involvement, p < 0.001), death (AUC 0.72, OR 1.13, 95% CI 1.07 to 1.21; p < 0.001), endotracheal intubation (AUC 0.76, OR 1.17, 95% CI 1.09 to 1.26; p < 0.001), and ICU admission (AUC: 0.71, OR 1.14, 95% CI 1.07 to 1.21; p < 0.001). CONCLUSIONS: In COVID-19 patients admitted in ED, LUS was a good predictor of death, ICU admission, and endotracheal intubation.

Mortality and other outcomes of patients with coronavirus disease pneumonia admitted to the emergency department: A prospective observational Brazilian study.

BACKGROUND: The first cases of coronavirus disease (COVID-19) in Brazil were diagnosed in February 2020. Our Emergency Department (ED) was designated as a COVID-19 exclusive service. We report our first 500 confirmed COVID-19 pneumonia patients. METHODS: From 14 March to 16 May 2020, we enrolled all patients admitted to our ED that had a diagnosis of COVID-19 pneumonia. Infection was confirmed via nasopharyngeal swabs or tracheal aspirate PCR. The outcomes included hospital discharge, invasive mechanical ventilation, and in-hospital death, among others. RESULTS: From 2219 patients received in the ED, we included 506 with confirmed COVID-19 pneumonia. We found that 333 patients were discharged home (65.9%), 153 died (30.2%), and 20 (3.9%) remained in the hospital. A total of 300 patients (59.3%) required ICU admission, and 227 (44.9%) needed invasive ventilation. The multivariate analysis found age, number of comorbidities, extension of ground glass opacities on chest CT and troponin with a direct relationship with all-cause mortality, whereas dysgeusia, use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker and number of lymphocytes with an inverse relationship with all-cause mortality. CONCLUSIONS: This was a sample of severe patients with COVID-19, with 59.2% admitted to the ICU and 41.5% requiring mechanical ventilator support. We were able to ascertain the outcome in majority (96%) of patients. While the overall mortality was 30.2%, mortality for intubated patients was 55.9%. Multivariate analysis agreed with data found in other studies although the use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker as a protective factor could be promising but would need further studies. TRIAL REGISTRATION: The study was registered in the Brazilian registry of clinical trials: RBR-5d4dj5.

Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19).

BACKGROUND: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19). METHODS: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. RESULTS: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. CONCLUSIONS: Administration of NAC in high doses did not affect the evolution of severe COVID-19. CLINICAL TRIALS REGISTRATION: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).

Methemoglobinemia and hemolytic anemia after COVID-19 infection without identifiable eliciting drug: A case-report.

We report a second case of methemoglobinemia and non-autoimmune hemolytic anemia after contracting the SARS-CoV-2 infection in the absence of an identifiable eliciting drug. A 35-year old male without previous known comorbidities was admitted after he was diagnosed with the COVID-19 infection and had large pulmonary involvement. Seven days later, he desaturated but was without any signs of respiratory distress. A check of arterial blood gas revealed normal partial pressure of oxygen and follow-up tests confirmed a methemoglobinemia diagnosis. Over the next few days, hemolysis was established after decreased levels of hemoglobin and increased levels of indirect bilirubin and lactate dehydrogenase. A hemolytic anemia investigation panel came back normal, including G6PD. A second G6PD test was ordered at the 5-month follow-up appointment and revealed decreased levels. Clinicians should thus be aware of possible false negative tests when testing for G6PD during hemolytic crisis. In addition, whether the COVID-19 infection alone would be responsible for this chain of events remains a challenging question.

External validity of type 2 diabetes clinical trials on cardiovascular outcomes for a multimorbid population.

AIM: To investigate the external validity of recent antihyperglycaemic trials evaluating cardiovascular outcomes in a multimorbid population. MATERIALS AND METHODS: Selection criteria of 15 randomized controlled trials from the 2020 American Diabetes Association Standard of Care statement were applied in a stepwise manner to tertiary care patients with type 2 diabetes. Primary outcomes were the number of patients eligible per individual trial and for the aggregate of trials. Secondary outcomes included patient predictors of trial eligibility. RESULTS: Of 1059 patients, the mean (SD) age was 66 (10.74) years, the median (IQR) Charlson index was 2 (2, 3) and 458 (43%) had documented cardiovascular disease. The median (IQR) number of patients included in individual trials was 263 (174.25-308.75) and 795 (75.1%) of them were eligible for at least one trial. Among those 264 ineligible, 127 (48.1%) had an HbA1c level of 7% or less and no cardiovascular disease; 53.5% and 34.4% of the patients were eligible for two and three different classes of drugs, respectively. The strongest predictor of trial eligibility was cardiovascular disease (risk ratio 2.17, 95% CI 2.01-2.35). CONCLUSIONS: A considerable proportion of multimorbid patients would be eligible for recent antihyperglycaemic trials. This positive finding can be attributed to development guidance in diabetes trials and the different approach we took, in which we evaluated inclusion by trials as an aggregate.

First-attempt intubation success and complications in patients with COVID-19 undergoing emergency intubation.

Objectives: To evaluate the first-attempt success rates and complications of endotracheal intubation of coronavirus disease 2019 (COVID-19) patients by emergency physicians. Methods: This prospective observational study was conducted from March 24, 2020 through May 28, 2020 at the emergency department (ED) of an urban, academic trauma center. We enrolled patients consecutively admitted to the ED with suspected or confirmed COVID-19 submitted to endotracheal intubation. No patients were excluded. The primary outcome was first-attempt intubation success, defined as successful endotracheal tube placement with the first device passed (endotracheal tube) during the first laryngoscope insertion confirmed with capnography. Secondary outcomes included the following complications: hypotension, hypoxemia, aspiration, and esophageal intubation. Results: A total of 112 patients with confirmed or suspected COVID-19 were enrolled. Median age was 61 years and 61 patients (54%) were men. The primary outcome, first-attempt intubation success, was achieved in 82% of patients. Among the 20 patients who were not intubated on the first attempt, 75% were intubated on the second attempt and 20% on the third attempt; cricothyrotomy was performed in 1 patient. Forty-eight (42%) patients were hypotensive and required norepinephrine immediately post-intubation. Fifty-eight (52%) experienced peri-intubation hypoxemia, and 2 patients (2%) had cardiac arrest. There were no cases of failed intubation resulting in death up to 24 hours after the procedure. Conclusion: Emergency physicians achieve high success rates when intubating COVID19 patients, although complications are frequent. However, these findings should be considered provisional until their generalizability is assessed in their institutions and setting.

Prevalence and predictors of overweight and obesity in Brazilian immigrants in Massachusetts.

BACKGROUND: Overweight and obesity are important risk factors for chronic non-communicable diseases, and their prevalence is on the rise worldwide. This study seeks to describe the prevalence and predictors of overweight and obesity in Brazilian immigrants living in Massachusetts, United States of America (USA). METHODS: Modeled after a survey on behavioral risk factors for chronic disease conducted annually in Brazil (Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico: Vigitel), Brazilian immigrants aged 18+ (n = 361) were surveyed between December 2013 and March 2014. Information was obtained from consenting participants regarding their demographic characteristics, physical activity, dietary and lifestyle habits, and other behavioral risk factors. Weight status was estimated from body mass index (BMI), calculated from self-reported height and weight data. Participants were categorized as overweight/obese if their BMI was ≥25; overweight and obese categories were combined to ensure appropriate sample size. Prevalence of overweight/obesity was estimated using STATA, and significant predictors were identified via multi-variable logistic regression. Odds ratio (OR), 95% confidence intervals (95% CI) and p-values were determined. RESULTS: The overall prevalence of overweight/obesity in the sample was 47.6%. Significant predictors of overweight and obesity were gender (men OR 2.30, 95% CI: 1.10, 3.78; women are comparison group), working in the 3 months prior to the survey (OR 2.90, 95% CI: 1.01, 8.30), and longer duration living in the USA (OR per additional year 1.06, 95% CI: 1.02, 1.11). Significant dietary predictors of overweight/obesity included 5 or more days per week of consumption of red meat (OR red meat 3.70, 95% CI: 1.47, 9.26) or of sweetened beverages, like soft drinks also known as soda (OR soda 2.40, 95% CI: 1.00, 5.78) compared with less frequent consumption of these foods. CONCLUSIONS: This study suggests that long duration of time lived in the USA increases odds of overweight and obesity for Brazilian immigrants living in Massachusetts. Efforts to curb increases in overweight and obesity in this population should focus not only on the men and those who work but also the women. Possible intervention measures should target soda (soft drink) and red meat consumption in Brazilian immigrants.