Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Activity of cefiderocol and innovative ß-lactam/ß-lactamase inhibitor combinations against isogenic strains of Escherichia coli expressing single and double ß-lactamases under high and low permeability conditions.

OBJECTIVES: To analyse the impact of the most clinically relevant ß-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/xeruborbactam and meropenem/nacubactam against recombinant Escherichia coli strains. METHODS: We constructed 82 E. coli laboratory transformants expressing the main ß-lactamases circulating in Enterobacterales (70 expressing single ß-lactamase and 12 producing double carbapenemase) under high (E. coli TG1) and low (E. coli HB4) permeability conditions. Antimicrobial susceptibility testing was determined by reference broth microdilution. RESULTS: Aztreonam/avibactam, cefepime/zidebactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam were active against all E. coli TG1 transformants. Imipenem/relebactam, meropenem/vaborbactam, cefepime/taniborbactam and cefepime/enmetazobactam were also highly active, but unstable against most of MBL-producing transformants. Combination of ß-lactamases with porin deficiency (E. coli HB4) did not significantly affect the activity of aztreonam/avibactam, cefepime/zidebactam, cefiderocol or meropenem/nacubactam, but limited the effectiveness of the rest of carbapenem- and cefepime-based combinations. Double-carbapenemase production resulted in the loss of activity of most of the compounds tested, an effect particularly evident for those E. coli HB4 transformants in which MBLs were present. CONCLUSIONS: Our findings highlight the promising activity that cefiderocol and new ß-lactam/ß-lactamase inhibitors have against recombinant E. coli strains expressing widespread ß-lactamases, including when these are combined with low permeability or other enzymes. Aztreonam/avibactam, cefiderocol, cefepime/zidebactam and meropenem/nacubactam will help to mitigate to some extent the urgency of new compounds able to resist MBL action, although NDM enzymes represent a growing challenge against which drug development efforts are still needed.

Role of Incretins in Muscle Functionality, Metabolism, and Body Composition in Breast Cancer: A Metabolic Approach to Understanding This Pathology.

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

Therapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery.

Epigenetic dysregulation has been reported in multiple cancers including leukemias. Nonetheless, the roles of the epigenetic reader Tudor domains in leukemia progression and therapy remain unexplored. Here, we conducted a Tudor domain-focused CRISPR screen and identified SGF29, a component of SAGA/ATAC acetyltransferase complexes, as a crucial factor for H3K9 acetylation, ribosomal gene expression, and leukemogenesis. To facilitate drug development, we integrated the CRISPR tiling scan with compound docking and molecular dynamics simulation, presenting a generally applicable strategy called CRISPR-Scan Assisted Drug Discovery (CRISPR-SADD). Using this approach, we identified a lead inhibitor that selectively targets SGF29's Tudor domain and demonstrates efficacy against leukemia. Furthermore, we propose that the structural genetics approach used in our study can be widely applied to diverse fields for de novo drug discovery.

Preconception dietary glycemic index and risk for large-for-gestational age births.

OBJECTIVES: Diets with a high glycemic index (GI) leading to elevated postprandial glucose levels and hyperinsulinemia during pregnancy have been inconsistently linked to an increased risk for large-for-gestational-age (LGA) births. The effects of prepregnancy dietary GI on LGA risk are, to our knowledge, unknown. We examined the association of prepregnancy dietary GI with LGA births and joint associations of GI and maternal overweight/obesity and infant sex with LGA births among 10 188 infants born without congenital anomalies from 1997 to 2011, using data from the National Birth Defects Prevention Study (NBDPS). The aim of this study was to investigate this association among infants without major congenital anomalies (controls) who participated in the NBDPS and to evaluate how prepregnancy BMI and infant sex may modify this association on the additive scale. METHODS: Dietary intake was ascertained using a 58-item food frequency questionnaire. We dichotomized dietary GI into high and low categories using spline regression models. Infants with a birth weight at or above the 90th percentile for gestational age and sex, according to a U.S. population reference, were considered LGA. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the infants, 859 (9%) had a high dietary GI (cut-point: 59), and 1244 infants (12%) were born LGA. Unadjusted analysis suggested an inverse association between high dietary GI and LGA (OR, 0.79; 95% CI, 0.62-0.99). No association was observed in multivariable models when comparing high dietary GI intake between LGA births and all other births (OR, 0.94; 95% CI, 0.74-1.20) or when excluding small-for-gestational-age (SGA) births (OR, 0.94; 95% CI, 0.73-1.19). No joint associations with maternal overweight/obesity or infant sex were observed. CONCLUSION: High prepregnancy maternal GI was not associated with LGA births independently of or jointly with other factors.

Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2.

The ACTN2 gene encodes α-actinin 2, located in the Z-disc of the sarcomeres in striated muscle. In this study, we sought to investigate the effects of an ACTN2 missense variant of unknown significance (p.A868T) on cardiac muscle structure and function. Left ventricular free wall samples were obtained at the time of cardiac transplantation from a heart failure patient with the ACTN2 A868T heterozygous variant. This variant is in the EF 3-4 domain known to interact with titin and α-actinin. At the ultrastructural level, ACTN2 A868T cardiac samples presented small structural changes in cardiomyocytes when compared to healthy donor samples. However, contractile mechanics of permeabilized ACTN2 A868T variant cardiac tissue displayed higher myofilament Ca2+ sensitivity of isometric force, reduced sinusoidal stiffness, and faster rates of tension redevelopment at all Ca2+ levels. Small-angle X-ray diffraction indicated increased separation between thick and thin filaments, possibly contributing to changes in muscle kinetics. Molecular dynamics simulations indicated that while the mutation does not significantly impact the structure of α-actinin on its own, it likely alters the conformation associated with titin binding. Our results can be explained by two Z-disc mediated communication pathways: one pathway that involves α-actinin's interaction with actin, affecting thin filament regulation, and the other pathway that involves α-actinin's interaction with titin, affecting thick filament activation. This work establishes the role of α-actinin 2 in modulating cross-bridge kinetics and force development in the human myocardium as well as how it can be involved in the development of cardiac disease.

Adipose Tissue Denervation Blunted the Decrease in Bone Formation Promoted by Obesity in Rats.

The impact of obesity upon bone metabolism is controversial since both beneficial or harmful effects have been reported. Bone remodeling is modulated by the central nervous system through cytokines, hormones and neuromodulators. The present study aimed to evaluate the effects evoked by bilateral retroperitoneal white adipose tissue (rWAT) denervation (Dnx) upon bone mineral metabolism and remodeling in an experimental model of obesity in rats. Male Wistar rats were fed during 18 weeks with high-fat diet (HFD) or standard diet (SD) as controls, and rWAT Dnx or Sham surgery was performed at the 14th week. Biochemical and hormonal parameters, bone histomorphometry, rWAT and hypothalamus protein and gene expression were analyzed. The HFD group presented decreased bone formation parameters, increased serum and bone leptin and FGF23, increased serum and hypothalamic neuropeptide Y (NPY) and decreased serum 1,25-dihydroxyvitamin D3 and PTH. After rWAT Dnx, bone markers and histomorphometry showed restoration of bone formation, and serum and hypothalamic NPY decreased, without alteration in leptin levels. The present study shows that the denervation of rWAT improved bone formation in obese rats mediated by a preferential reduction in neurohormonal actions of NPY, emphasizing the relevance of the adipose tissue-brain-bone axis in the control of bone metabolism in obesity.

Telemedicine in Brazil: Teleconsultations at the Largest University Hospital in the Country.

The coronavirus disease (COVID-19) pandemic leveraged telemedicine worldwide mainly due to the need for social distancing, patient safety, and infection prevention. The Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) was a key reference site in the treatment of COVID-19 severe cases in the country. To continue patient's health care, it became necessary to increase the number of teleconsultations and standardize it institutionally. Herein, we briefly described how the HCFMUSP improved the teleconsultation health care service during the COVID-19 pandemic, highlighting the implementation of important innovations and the throughout standardization process, including patients and professional workflow. We also detailed the methodology used to implement or improve teleconsultation in a medical/multidisciplinary specialty at HCFMUSP. All these efforts made the HCFMUSP reach the goal of converting 15% of all face-to-face consultations into teleconsultations only in 2021. In addition, there were more than 370,000 teleconsultations until the end of 2022. Our experience has shown that having a supporting team, a digital certification process, and the data integration were key factors toward the successful implementation of the teleconsultation services. We believe that progressing toward teleconsultation will improve the population covered by health care services in Brazil, as well as contribute to a reduction of waiting time, and solving costs to health care institutions and patients. We expect this report of our experience in teleconsultation implementation could inspire and guide other health care institutions in the development of telemedicine.

Tele-Intensive Care Unit Program in Brazil: Implementation and Expansion.

In this scientific report, we aimed to describe the implementation and expansion of a Tele-Intensive Care Unit (Tele-ICU) program in Brazil, highlighting the pillars of success, improvements, and perspectives. Tele-ICU program emerged during the COVID-19 pandemic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), focusing on clinical case discussions and training of health practitioners in public hospitals of the state of São Paulo in Brazil, to support health care professionals for treating COVID-19 patients. The success of implementing this initiative endorsed the project expansion to other five hospitals from different macroregions of the country, leading to the Tele-ICU-Brazil. These projects assisted 40 hospitals, allowing more than 11,500 teleinterconsultations (exchange of medical information between health care professionals using a licensed online platform) and training more than 14,800 health care professionals, reducing mortality and length of hospitalized patients. A segment in telehealth for the obstetrics health care was implemented after detecting these were a susceptible group of patients to COVID-19 severity. As a perspective, this segment will be expanded to 27 hospitals in the country. The Tele-ICU projects reported here were the largest digital health ICU programs ever established in Brazilian National Health System until know. Their results were unprecedented and proved to be crucial for supporting health care professionals nationwide during the COVID-19 pandemic and guide future initiatives in digital health in Brazil's National Health System.

Negative Charges Introduced Near the IT Helix of Cardiac Troponin T Stabilize the Active State of Actin Filaments.

The disordered and basic C-terminal 14 residues of human troponin T (TnT) are essential for full inhibition of actomyosin ATPase activity at low Ca2+ levels and for limiting activation at saturating Ca2+. In previous studies, stepwise truncation of the C-terminal region of TnT increased activity in proportion to the number of positive charges eliminated. To define key basic residues more closely, we generated phosphomimetic-like mutants of TnT. Phosphomimetic mutants were chosen because of reports that phosphorylation of TnT, including sites within the C terminal region, depressed activity, contrary to our expectations. Four constructs were made where one or more Ser and Thr residues were replaced with Asp residues. The S275D and T277D mutants, near the IT helix and adjacent to basic residues, produced the greatest activation of ATPase rates in solution; the effects of the S275D mutant were recapitulated in muscle fiber preparations with enhanced myofilament Ca2+ sensitivity. Actin filaments containing S275D TnT were also shown to be incapable of populating the inactive state at low Ca2+ levels. Actin filaments containing both S275D/T284D were not statistically different from those containing only S275D in both solution and cardiac muscle preparation studies. Finally, actin filaments containing T284D TnT, closer to the C-terminus and not adjacent to a basic residue, had the smallest effect on activity. Thus, the effects of negative charge placement in the C-terminal region of TnT were greatest near the IT helix and adjacent to a basic residue.

Interplay between OXA-10 ß-Lactamase Production and Low Outer-Membrane Permeability in Carbapenem Resistance in Enterobacterales.

The OXA-10 class D ß-lactamase has been reported to contribute to carbapenem resistance in non-fermenting Gram-negative bacilli; however, its contribution to carbapenem resistance in Enterobacterales is unknown. In this work, minimum inhibitory concentrations (MICs), whole genome sequencing (WGS), cloning experiments, kinetic assays, molecular modelling studies, and biochemical assays for carbapenemase detection were performed to determine the impact of OXA-10 production on carbapenem resistance in two XDR clinical isolates of Escherichia coli with the carbapenem resistance phenotype (ertapenem resistance). WGS identified the two clinical isolates as belonging to ST57 in close genomic proximity to each other. Additionally, the presence of the blaOXA-10 gene was identified in both isolates, as well as relevant mutations in the genes coding for the OmpC and OmpF porins. Cloning of blaOXA-10 in an E. coli HB4 (OmpC and OmpF-deficient) demonstrated the important contribution of OXA-10 to increased carbapenem MICs when associated with porin deficiency. Kinetic analysis showed that OXA-10 has low carbapenem-hydrolysing activity, but molecular models revealed interactions of this ß-lactamase with the carbapenems. OXA-10 was not detected with biochemical tests used in clinical laboratories. In conclusion, the ß-lactamase OXA-10 limits the activity of carbapenems in Enterobacterales when combined with low permeability and should be monitored in the future.

Phase Angle in Head and Neck Cancer: A Sex-Differential Analysis from Biological and Clinical Behavior to Health-Related Quality of Life.

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women's group.

Patterns of Prescription Medication Use during the First Trimester of Pregnancy in the United States, 1997-2018.

The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and distributions of use within demographic subgroups. We conducted a descriptive secondary analysis using data from 9,755 women whose infants served as controls in two large United States case-control studies from 1997-2011 and 2014-2018. After excluding vitamin, herbal, mineral, vaccine, i.v. fluid, and topical products and over-the-counter medications, the proportion of women that reported taking at least one prescription medication in the first trimester increased over the study years, from 37% to 50% of women. The corresponding proportions increased with increasing maternal age and years of education, were highest for non-Hispanic White women (47%) and lowest for Hispanic women (24%). The most common indication for first trimester use of a medication was infection (12-15%). Increases were observed across the years for medications used for indications related to nausea/vomiting, depression/anxiety, infertility, thyroid disease, diabetes, and epilepsy. The largest relative increase in use among women was observed for medications to treat nausea/vomiting, which increased from 3.8% in the earliest years of the study (1997-2001) to 14.8% in 2014-2018, driven in large part by ondansetron use. Prescription medication use in the first trimester of pregnancy is common and increasing. Many medical conditions require treatments among pregnant women, often involving pharmacotherapy, which necessitates consideration of the risk and safety profiles for both mother and fetus.

Respiratory arousal threshold among patients with isolated sleep apnea and with comorbid insomnia (COMISA).

Insomnia and obstructive sleep apnea (OSA) are common sleep disorders and frequently coexist (COMISA). Arousals from sleep may be a common link explaining the frequent comorbidity of both disorders. Respiratory arousal threshold (AT) is a physiologic measurement of the level of respiratory effort to trigger an arousal from sleep. The impact of COMISA on AT is not known. We hypothesized that a low AT is more common among COMISA than among patients with OSA without insomnia. Participants referred for OSA diagnosis underwent a type 3 sleep study and answered the insomnia severity index (ISI) questionnaire and the Epworth sleepiness scale. Participants with an ISI score ≥ 15 were defined as having insomnia. Sleep apnea was defined as an apnea hypopnea index (AHI) ≥ 15 events/h. Low AT was determined using a previously validated score based on 3 polysomnography variables (AHI, nadir SpO2 and the frequency of hypopneas). OSA-only (n = 51) and COMISA (n = 52) participants had similar age (61[52-68] vs 60[53-65] years), body-mass index (31.3[27.7-36.2] vs 32.2[29.5-38.3] kg/m2) and OSA severity (40.2[27.5-60] vs 37.55[27.9-65.2] events/h): all p = NS. OSA-only group had significantly more males than the COMISA group (58% vs 33%, p = 0.013. The proportion of participants with a low AT among OSA-only and COMISA groups was similar (29 vs 33%, p = NS). The similar proportion of low AT among COMISA and patients with OSA suggests that the respiratory arousal threshold may not be related to the increased arousability of insomnia.

Safety Profile of Homologous and Heterologous Booster COVID-19 Vaccines in Physicians in Quito-Ecuador: A Cross-Sectional Study.

More than 600 healthcare workers died due to COVID-19 infection until January 2022 in Ecuador. Even though the COVID-19 vaccines are safe, local and systemic reactions were reported among physicians. This study aims to analyze the adverse events of COVID-19 with an emphasis on comparing the homologous and heterologous booster doses in physicians that received three approved vaccines in Ecuador. An electronic survey was performed in Quito, Ecuador, directed at physicians who were vaccinated with the three doses of COVID-19 vaccines. A total of 210 participants were analyzed after administering any dose of the vaccines. At least one AE was identified in 60.0% (126/210) of the sample after the first dose, 52.40% (110/210) after the second dose, and 75.2% (158/210) after the booster dose. The most frequent AEs were localized pain, myalgia, headache, and fever. At least one drug was used in 44.3% of the population after the first dose, 37.1% after the second dose, and 63.8% in the booster dose. Heterologous booster produces more AEs compared with homologous booster (80.1% vs. 53.8%), and 77.3% of participants reported that interfered with daily activities. Similar studies agree that reactogenicity occurs mainly with heterologous vaccination compared to homologous vaccination. This situation affected physicians' performance in daily activities and led them to use medication for the symptoms. In the future, it is recommended to perform cohort studies, where adverse events that are associated with vaccine boosters in the general population can be analyzed longitudinally, thus improving the level of evidence of the results.

Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: Prospective cohort study.

BACKGROUND: Coronavirus disease (COVID-19) survivors exhibit multisystemic alterations after hospitalization. Little is known about long-term imaging and pulmonary function of hospitalized patients intensive care unit (ICU) who survive COVID-19. We aimed to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and identify risk factors associated with chest computed tomography (CT) lesion severity. METHODS: A prospective cohort study of COVID-19 patients admitted to a tertiary hospital ICU in Brazil (March-August/2020), and followed-up six-twelve months after hospital admission. Initial assessment included: modified Medical Research Council dyspnea scale, SpO2 evaluation, forced vital capacity, and chest X-Ray. Patients with alterations in at least one of these examinations were eligible for CT and pulmonary function tests (PFTs) approximately 16 months after hospital admission. Primary outcome: CT lesion severity (fibrotic-like or non-fibrotic-like). Baseline clinical variables were used to build a machine learning model (ML) to predict the severity of CT lesion. RESULTS: In total, 326 patients (72%) were eligible for CT and PFTs. COVID-19 CT lesions were identified in 81.8% of patients, and half of them showed mild restrictive lung impairment and impaired lung diffusion capacity. Patients with COVID-19 CT findings were stratified into two categories of lesion severity: non-fibrotic-like (50.8%-ground-glass opacities/reticulations) and fibrotic-like (49.2%-traction bronchiectasis/architectural distortion). No association between CT feature severity and altered lung diffusion or functional restrictive/obstructive patterns was found. The ML detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity(sensitivity,0.78±0.02;specificity,0.79±0.01;F1-score,0.78±0.02;positive predictive rate,0.78±0.02; accuracy,0.78±0.02; and area under the curve,0.83±0.01). CONCLUSION: ICU hospitalization due to COVID-19 led to respiratory system alterations six-twelve months after hospital admission. Male sex and critical disease acute phase, characterized by a longer ICU and IMV period, and need for tracheostomy and vasoactive drugs, were risk factors for severe CT lesions six-twelve months after hospital admission.

Comparative Effects of Low-Dose Rosuvastatin, Placebo, and Dietary Supplements on Lipids and Inflammatory Biomarkers.

BACKGROUND: Supplements are commonly used by individuals with indications for lipid-lowering therapy, but evidence of their effectiveness to lower low-density lipoprotein cholesterol (LDL-C) is lacking, particularly when compared with statins. OBJECTIVES: The trial objective was to compare the efficacy of a low-dose statin with placebo and 6 common supplements in impacting lipid and inflammatory biomarkers. METHODS: This was a single-center, prospective, randomized, single-blind clinical trial among adults with no history of atherosclerotic cardiovascular disease (ASCVD), an LDL-C of 70 to 189 mg/dL, and an increased 10-year risk of ASCVD. Participants were randomized to rosuvastatin 5 mg daily, placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice. The primary endpoint was the percent change in LDL-C from baseline for rosuvastatin 5 mg daily compared with placebo and each supplement after 28 days. The primary endpoint was evaluated in a hierarchical fashion with rosuvastatin first compared with placebo, then each supplement in a prespecified order using analysis of covariance. RESULTS: A total of 190 participants completed the study. The percent LDL-C reduction with rosuvastatin was greater than all supplements and placebo (P < 0.001). The difference in LDL-C reduction with rosuvastatin compared with placebo was -35.2% (95% CI: -41.3% to -29.1%; P < 0.001). None of the dietary supplements demonstrated a significant decrease in LDL-C compared with placebo. Adverse event rates were similar across study groups. CONCLUSIONS: Among individuals with increased 10-year risk for ASCVD, rosuvastatin 5 mg daily lowered LDL-C significantly more than placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice. (Supplements, Placebo, or Rosuvastatin Study [SPORT]; NCT04846231).

Validation of an overnight wireless high-resolution oximeter for the diagnosis of obstructive sleep apnea at home.

Obstructive sleep apnea (OSA) is extremely common and has several consequences. However, most cases remain undiagnosed. One limitation is the lack of simple and validated methods for OSA diagnosis at home. The aim of this study was to validate a wireless high-resolution oximeter with a built-in accelerometer linked to a smartphone with automated cloud analysis (Biologix) that was compared with a home sleep test (HST, Apnea Link Air) performed on the same night. We recruited 670 patients out of a task force of 1013 patients with suspected OSA who were referred to our center for diagnosis. The final sample consisted of 478 patients (mean age: 56.7 ± 13.1 years, mean body mass index: 31.9 ± 6.3 kg/m2). To estimate the night-to-night OSA severity variability, 62 patients underwent HST for two consecutive nights. The HST-apnea-hypopnea index (AHI) and the Biologix-oxygen desaturation index (ODI) was 25.0 ± 25.0 events/h and 24.9 ± 26.5 events/h, respectively. The area under the curve-sensibility/specificity to detect at least mild (HST-AHI > 5), moderate-to-severe (HST-AHI > 15), and severe OSA (HST-AHI > 30) were (0.983)-94.7/92.8, (0.986)-94.8/93.9, and (0.990)-95.8/94.3, respectively. The limits of agreement originating from the Bland-Altman plot and the correlation between HST-AHI and Biologix-ODI were lower than the night-to-night HST-AHI variability (25.5 and 34.5 events/h, respectively, p = 0.001). We conclude that Biologix is a simple and reliable technique for OSA diagnosis at home.

Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome.

Background: Sociodemographic and environmental factors are associated with incidence, severity, and mortality of COVID-19. However, little is known about the role of such factors in persisting symptoms among recovering patients. We designed a cohort study of hospitalized COVID-19 survivors to describe persistent symptoms and identify factors associated with post-COVID-19 syndrome. Methods: We included patients hospitalized between March to August 2020 who were alive six months after hospitalization. We collected individual and clinical characteristics during hospitalization and at follow-up assessed ten symptoms with standardized scales, 19 yes/no symptoms, a functional status and a quality-of-life scale and performed four clinical tests. We examined individual exposure to greenspace and air pollution and considered neighbourhood´s population density and socioeconomic conditions as contextual factors in multilevel regression analysis. Results: We included 749 patients with a median follow-up of 200 (IQR = 185-235) days, and 618 (83%) had at least one of the ten symptoms measured with scales. Pain (41%), fatigue (38%) and posttraumatic stress disorder (35%) were the most frequent. COVID-19 severity, comorbidities, BMI, female sex, younger age, and low socioeconomic position were associated with different symptoms. Exposure to ambient air pollution was associated with higher dyspnoea and fatigue scores and lower functional status. Conclusions: We identified a high frequency of persistent symptoms among COVID-19 survivors that were associated with clinical, sociodemographic, and environmental variables. These findings indicate that most patients recovering from COVID-19 will need post-discharge care, and an additional burden to health care systems, especially in LMICs, should be expected.

Chronic lung lesions in COVID-19 survivors: predictive clinical model.

OBJECTIVE: This study aimed to propose a simple, accessible and low-cost predictive clinical model to detect lung lesions due to COVID-19 infection. DESIGN: This prospective cohort study included COVID-19 survivors hospitalised between 30 March 2020 and 31 August 2020 followed-up 6 months after hospital discharge. The pulmonary function was assessed using the modified Medical Research Council (mMRC) dyspnoea scale, oximetry (SpO2), spirometry (forced vital capacity (FVC)) and chest X-ray (CXR) during an in-person consultation. Patients with abnormalities in at least one of these parameters underwent chest CT. mMRC scale, SpO2, FVC and CXR findings were used to build a machine learning model for lung lesion detection on CT. SETTING: A tertiary hospital in Sao Paulo, Brazil. PARTICIPANTS: 749 eligible RT-PCR-confirmed SARS-CoV-2-infected patients aged ≥18 years. PRIMARY OUTCOME MEASURE: A predictive clinical model for lung lesion detection on chest CT. RESULTS: There were 470 patients (63%) that had at least one sign of pulmonary involvement and were eligible for CT. Almost half of them (48%) had significant pulmonary abnormalities, including ground-glass opacities, parenchymal bands, reticulation, traction bronchiectasis and architectural distortion. The machine learning model, including the results of 257 patients with complete data on mMRC, SpO2, FVC, CXR and CT, accurately detected pulmonary lesions by the joint data of CXR, mMRC scale, SpO2 and FVC (sensitivity, 0.85±0.08; specificity, 0.70±0.06; F1-score, 0.79±0.06 and area under the curve, 0.80±0.07). CONCLUSION: A predictive clinical model based on CXR, mMRC, oximetry and spirometry data can accurately screen patients with lung lesions after SARS-CoV-2 infection. Given that these examinations are highly accessible and low cost, this protocol can be automated and implemented in different countries for early detection of COVID-19 sequelae.