Operando studies reveal active Cu nanograins for CO2 electroreduction.

Carbon dioxide electroreduction facilitates the sustainable synthesis of fuels and chemicals1. Although Cu enables CO2-to-multicarbon product (C2+) conversion, the nature of the active sites under operating conditions remains elusive2. Importantly, identifying active sites of high-performance Cu nanocatalysts necessitates nanoscale, time-resolved operando techniques3-5. Here, we present a comprehensive investigation of the structural dynamics during the life cycle of Cu nanocatalysts. A 7 nm Cu nanoparticle ensemble evolves into metallic Cu nanograins during electrolysis before complete oxidation to single-crystal Cu2O nanocubes following post-electrolysis air exposure. Operando analytical and four-dimensional electrochemical liquid-cell scanning transmission electron microscopy shows the presence of metallic Cu nanograins under CO2 reduction conditions. Correlated high-energy-resolution time-resolved X-ray spectroscopy suggests that metallic Cu, rich in nanograin boundaries, supports undercoordinated active sites for C-C coupling. Quantitative structure-activity correlation shows that a higher fraction of metallic Cu nanograins leads to higher C2+ selectivity. A 7 nm Cu nanoparticle ensemble, with a unity fraction of active Cu nanograins, exhibits sixfold higher C2+ selectivity than the 18 nm counterpart with one-third of active Cu nanograins. The correlation of multimodal operando techniques serves as a powerful platform to advance our fundamental understanding of the complex structural evolution of nanocatalysts under electrochemical conditions.

Gold Nanoparticle-Decorated Catalytic Micromotor-Based Aptassay for Rapid Electrochemical Label-Free Amyloid-ß42 Oligomer Determination in Clinical Samples from Alzheimer's Patients.

Micromotor (MM) technology offers a valuable and smart on-the-move biosensing microscale approach in clinical settings where sample availability is scarce in the case of Alzheimer's disease (AD). Soluble amyloid-ß protein oligomers (AßO) (mainly AßO42) that circulate in biological fluids have been recognized as a molecular biomarker and therapeutic target of AD due to their high toxicity, and they are correlated much more strongly with AD compared to the insoluble Aß monomers. A graphene oxide (GO)-gold nanoparticles (AuNPs)/nickel (Ni)/platinum nanoparticles (PtNPs) micromotors (MMGO-AuNPs)-based electrochemical label-free aptassay is proposed for sensitive, accurate, and rapid determination of AßO42 in complex clinical samples such as brain tissue, cerebrospinal fluid (CSF), and plasma from AD patients. An approach that implies the in situ formation of AuNPs on the GO external layer of tubular MM in only one step during MM electrosynthesis was performed (MMGO-AuNPs). The AßO42 specific thiolated-aptamer (AptAßO42) was immobilized in the MMGO-AuNPs via Au-S interaction, allowing for the selective recognition of the AßO42 (MMGO-AuNPs-AptAßO42-AßO42). AuNPs were smartly used not only to covalently bind a specific thiolated-aptamer for the design of a label-free electrochemical aptassay but also to improve the final MM propulsion performance due to their catalytic activity (approximately 2.0× speed). This on-the-move bioplatform provided a fast (5 min), selective, precise (RSD < 8%), and accurate quantification of AßO42 (recoveries 94-102%) with excellent sensitivity (LOD = 0.10 pg mL-1) and wide linear range (0.5-500 pg mL-1) in ultralow volumes of the clinical sample of AD patients (5 µL), without any dilution. Remarkably, our MM-based bioplatform demonstrated the competitiveness for the determination of AßO42 in the target samples against the dot blot analysis, which requires more than 14 h to provide qualitative results only. It is also important to highlight its applicability to the potential analysis of liquid biopsies as plasma and CSF samples, improving the reliability of the diagnosis given the heterogeneity and temporal complexity of neurodegenerative diseases. The excellent results obtained demonstrate the analytical potency of our approach as a future tool for clinical/POCT (Point-of-care testing) routine scenarios.

In situ and in vitro evaluation of two antiseptics for blood bank based on chlorhexidine gluconate/isopropyl alcohol and povidone-iodine.

BACKGROUND: Poor disinfection is the main cause of blood contamination, so its elimination is key to limiting the entry of bacteria into the collection system. With the advancement of antiseptic technology, antiseptics with sterile, disposable applicators are now available. AIM: To evaluate in situ two antiseptics (with and without applicators) for blood banks and to demonstrate in vitro antiseptic activity on bacterial biofilms of importance in transfusion medicine. METHODS: Antiseptic A (2% sterile solution of chlorhexidine gluconate/70% isopropyl alcohol provided with applicator) and bulk antiseptic B (10% povidone-iodine) were evaluated. The deferred blood donor arms were subjected to disinfection with antiseptics A and B and the contralateral arms were cultured to determine the baseline bacterial load (control). Antiseptic activity was assessed by ANOVA and logaritmic reduction values (LRV) and percentage reduction values (PRV) were calculated. Finally, the in vitro activity of antiseptic A was analyzed by confocal laser scanning microscopy (CLSM) on biofilm models. RESULTS: Prior to disinfection tests, commensal and clinically important bacteria were identified; antiseptic A showed post-disinfection bacterial growth rates of zero compared to controls (p < 0.0001). The frequency of bacterial growth with antiseptic B was 74%. A significant difference was identified between both antiseptics, where antiseptic A showed higher activity (p < 0.5468). LRV and PRV were 0.6-2.5/100% and 0.3-1.7/66.7-99.7% for antiseptics A and B, respectively. Through CLSM, disinfectant A (without applicator) showed lower in vitro antiseptic activity on the tested biofilms at the exposure times recommended by the manufacturer. CONCLUSIONS: Sterile solution of chlorhexidine gluconate/isopropyl alcohol with applicator showed advantages disinfection in deferred blood donors over povidone-iodine.

Time Course of Mechanical Ventilation Driving Pressure Levels in Pediatric Acute Respiratory Distress Syndrome: Outcomes in a Prospective, Multicenter Cohort Study From Colombia, 2018-2022.

OBJECTIVES: High driving pressure (DP, ratio of tidal volume (Vt) over respiratory system compliance) is a risk for poor outcomes in patients with pediatric acute respiratory distress syndrome (PARDS). We therefore assessed the time course in level of DP (i.e., 24, 48, and 72 hr) after starting mechanical ventilation (MV), and its association with 28-day mortality. DESIGN: Multicenter, prospective study conducted between February 2018 and December 2022. SETTING: Twelve tertiary care PICUs in Colombia. PATIENTS: One hundred eighty-four intubated children with moderate to severe PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range [IQR]) age of the PARDS cohort was 11 (IQR 3-24) months. A total of 129 of 184 patients (70.2%) had a pulmonary etiology leading to PARDS, and 31 of 184 patients (16.8%) died. In the first 24 hours after admission, the plateau pressure in the nonsurvivor group, compared with the survivor group, differed (28.24 [IQR 24.14-32.11] vs. 23.18 [IQR 20.72-27.13] cm H2O, p < 0.01). Of note, children with a Vt less than 8 mL/kg of ideal body weight had lower adjusted odds ratio (aOR [95% CI]) of 28-day mortality (aOR 0.69, [95% CI, 0.55-0.87]; p = 0.02). However, we failed to identify an association between DP level and the oxygenation index (aOR 0.58; 95% CI, 0.21-1.58) at each of time point. In a diagnostic exploratory analysis, we found that DP greater than 15 cm H2O at 72 hours was an explanatory variable for mortality, with area under the receiver operating characteristic curve of 0.83 (95% CI, 0.74-0.89); there was also increased hazard for death with hazard ratio 2.5 (95% CI, 1.07-5.92). DP greater than 15 cm H2O at 72 hours was also associated with longer duration of MV (10 [IQR 7-14] vs. 7 [IQR 5-10] d; p = 0.02). CONCLUSIONS: In children with moderate to severe PARDS, a DP greater than 15 cm H2O at 72 hours after the initiation of MV is associated with greater odds of 28-day mortality and a longer duration of MV. DP should be considered a variable worth monitoring during protective ventilation for PARDS.

Micromotor-based dual aptassay for early cost-effective diagnosis of neonatal sepsis.

Given the long-life expectancy of the newborn, research aimed at improving sepsis diagnosis and management in this population has been recognized as cost-effective, which at early stages continues to be a tremendous challenge. Despite there is not an ideal-specific biomarker, the simultaneous detection of biomarkers with different behavior during an infection such as procalcitonin (PCT) as high specificity biomarker with one of the earliest biomarkers in sepsis as interleukin-6 (IL-6) increases diagnostic performance. This is not only due to their high positive predictive value but also, since it can also help the clinician to rule out infection and thus avoid the use of antibiotics, due to their high negative predictive value. To this end, we explore a cutting-edge micromotor (MM)-based OFF-ON dual aptassay for simultaneous determination of both biomarkers in 15 min using just 2 µL of sample from low-birth-weight neonates with gestational age less than 32 weeks and birthweight below 1000 g with clinical suspicion of late-onset sepsis. The approach reached the high sensitivities demanded in the clinical scenario (LODPCT = 0.003 ng/mL, LODIL6 = 0.15 pg/mL) with excellent correlation performance (r > 0.9990, p < 0.05) of the MM-based approach with the Hospital method for both biomarkers during the analysis of diagnosed samples and reliability (Er < 6% for PCT, and Er < 4% for IL-6). The proposed approach also encompasses distinctive technical attributes in a clinical scenario since its minimal sample volume requirements and expeditious results compatible with few easy-to-obtain drops of heel stick blood samples from newborns admitted to the neonatal intensive care unit. This would enable the monitoring of both sepsis biomarkers within the initial hours after the manifestation of symptoms in high-risk neonates as a valuable tool in facilitating prompt and well-informed decisions about the initiation of antibiotic therapy.These results revealed the asset behind micromotor technology for multiplexing analysis in diagnosing neonatal sepsis, opening new avenues in low sample volume-based diagnostics.

Implementation of a Bleeding Management Algorithm in Liver Transplantation: A Pilot Study.

Objectives: The aims of the study were to compare the consumption of blood products before and after the implementation of a bleeding management algorithm in patients undergoing liver transplantation and to determine the feasibility of a multicentre, randomized study. Background: Liver transplantation remains the only curative therapy for patients with end-stage liver disease, but it carries a high risk of surgical bleeding. Materials and Methods: Retrospective study of patients treated before (group 1) and after (group 2) implementation of a haemostatic algorithm guided by viscoelastic testing, including use of lyophilized coagulation factor concentrates (prothrombin complex and fibrinogen concentrates). Primary outcome was the number of units of blood products transfused in 24 h after surgery. Secondary outcomes included hospital stay, mortality, and cost. Results: Data from 30 consecutive patients was analysed; 14 in group 1 and 16 in group 2. Baseline data were similar between groups. Median total blood product consumption 24 h after surgery was 33 U (IQR: 11-57) in group 1 and 1.5 (0-23.5) in group 2 (p = 0.028). Significantly fewer units of red blood cells, fresh frozen plasma, and cryoprecipitate were transfused in group 2 versus group 1. There was no significant difference in complications, hospital stay, or in-hospital mortality between groups. The cost of haemostatic therapy was non-significantly lower in group 2 versus group 1 (7,400 vs. 15,500 USD; p = 0.454). Conclusion: The haemostatic management algorithm was associated with a significant reduction in blood product use during 24 h after liver transplantation. This study demonstrated the feasibility and provided a sample size calculation for a larger, randomized study.

Rapid Environmental Contamination with Candida auris and Multidrug-Resistant Bacterial Pathogens Near Colonized Patients.

BACKGROUND: Environmental contamination is suspected to play an important role in Candida auris transmission. Understanding speed and risks of contamination after room disinfection could inform environmental cleaning recommendations. METHODS: We conducted a prospective multicenter study of environmental contamination associated with C. auris colonization at six ventilator-capable skilled nursing facilities and one acute-care hospital in Illinois and California. Known C. auris carriers were sampled at five body-sites followed by sampling of nearby room surfaces before disinfection and at 0, 4, 8, and 12-hours post-disinfection. Samples were cultured for C. auris and bacterial multidrug-resistant organisms (MDROs). Odds of surface contamination after disinfection were analyzed using multilevel generalized estimating equations. RESULTS: Among 41 known C. auris carriers, colonization was detected most frequently on palms/fingertips (76%) and nares (71%). C. auris contamination was detected on 32.2% (66/205) of room surfaces pre-disinfection and 20.5% (39/190) of room surfaces by 4-hours post-disinfection. A higher number of C. auris-colonized body sites was associated with higher odds of environmental contamination at every time point following disinfection, adjusting for facility of residence. In the rooms of 38 (93%) C. auris carriers co-colonized with a bacterial MDRO, 2%-24% of surfaces were additionally contaminated with the same MDRO by 4-hours post-disinfection. CONCLUSIONS: C. auris can contaminate the healthcare environment rapidly after disinfection, highlighting the challenges associated with environmental disinfection. Future research should investigate long-acting disinfectants, antimicrobial surfaces, and more effective patient skin antisepsis to reduce the environmental reservoir of C. auris and bacterial MDROs in healthcare settings.

Operando High-Energy-Resolution X-ray Spectroscopy of Evolving Cu Nanoparticle Electrocatalysts for CO2 Reduction.

Advances in electrocatalysis research rely heavily on building a thorough mechanistic understanding of catalyst active sites under realistic operating conditions. Only recently have techniques emerged that enable sensitive spectroscopic data collection to distinguish catalytically relevant surface sites from the underlying bulk material under applied potential in the presence of an electrolyte layer. Here, we demonstrate that operando high-energy-resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) is a powerful spectroscopic method which offers critical surface chemistry insights in CO2 electroreduction with sub-electronvolt energy resolution using hard X-rays. Combined with the high surface area-to-volume ratio of 5 nm copper nanoparticles, operando HERFD-XAS allows us to observe with clear evidence the breaking of chemical bonds between the ligands and the Cu surface as part of the ligand desorption process occurring under electrochemical potentials relevant for the CO2 reduction reaction (CO2RR). In addition, the dynamic evolution of oxidation state and coordination number throughout the operation of the nanocatalyst was continuously tracked. With these results in hand, undercoordinated metallic copper nanograins are proposed to be the real active sites in the CO2RR. This work emphasizes the importance of HERFD-XAS compared to routine XAS in catalyst characterization and mechanism exploration, especially in the complicated electrochemical CO2RR.

Analysis of microsamples by miniaturized magnetic-based pipette tip microextraction: determination of free cortisol in serum and urine from very low birth weight preterm newborns.

Miniaturized magnetic-based pipette tip microextraction is presented as a sample preparation approach for microsamples. It involves quick dispersion of a diminutive amount of a magnetic sorbent material in a low-volume sample (10 µL) to entrap the target analytes. Next, the dispersion is aspirated using a (semi)automatic pipette through a pipette tip with a small cubic neodymium magnet inside, which retrieves the magnetic sorbent containing the analytes. After discarding the rest of the sample, the sorbent is properly rinsed by aspirating/dispensing deionized water, and then, the analytes are eluted by aspirating/dispensing an appropriate solvent. This approach was employed for the determination of free cortisol in serum and urine from very low birth weight preterm newborns, a vulnerable patient group who present low availability for sampling biological fluids. A magnetic immunosorbent made of a cortisol antibody was employed for the selective extraction, followed by liquid chromatography-tandem mass spectrometry. Good analytical features were obtained, such as limits of detection and quantification of 0.08 and 0.27 ng mL-1, respectively, linearity up to 50 ng mL-1 (R2 > 0.999), RSD values under 15% and relative recoveries between 91 and 111%. The cross-reactivity with other glucocorticoids (i.e., cortisone and prednisolone) was evaluated to show the selectivity of the extraction. Finally, the method applicability was demonstrated towards the determination of free cortisol in the serum and urine samples from low birth weight preterm newborns.

Continuous Glucose Monitoring for Patients with COVID-19 Pneumonia: Initial Experience at a Tertiary Care Center.

OBJECTIVE: Patients hospitalized with COVID-19 and hyperglycemia require frequent glucose monitoring, usually performed with glucometers. Continuous glucose monitors (CGMs) are common in the outpatient setting but not yet approved for hospital use. We evaluated CGM accuracy, safety for insulin dosing, and CGM clinical reliability in 20 adult patients hospitalized with COVID-19 and hyperglycemia. METHODS: Study patients were fitted with a remotely monitored CGM. CGM values were evaluated against glucometer readings. The CGM sensor calibration was performed if necessary. CGM values were used to dose insulin, without glucometer confirmation. RESULTS: CGM accuracy against glucometer, expressed as mean absolute relative difference (MARD), was calculated using 812 paired glucometer-CGM values. The aggregate MARD was 10.4%. For time in range and grades 1 and 2 hyperglycemia, MARD was 11.4%, 9.4%, and 9.1%, respectively, with a small variation between medical floors and intensive care units. There was no MARD correlation with mean arterial blood pressure levels, oxygen saturation, daily hemoglobin levels, and glomerular filtration rates. CGM clinical reliability was high, with 99.7% of the CGM values falling within the "safe" zones of Clarke error grid. After CGM placement, the frequency of glucometer measurements decreased from 5 to 3 and then 2 per day, reducing nurse presence in patient rooms and limiting viral exposure. CONCLUSION: With twice daily, on-demand calibration, the inpatient CGM use was safe for insulin dosing, decreasing the frequency of glucometer fingersticks. For glucose levels >70 mg/dL, CGMs showed adequate accuracy, without interference from vital and laboratory values.

Efficacy of a lay community health worker (promotoras de salud) program to improve adherence to emollients in Spanish-speaking Latin American pediatric patients in the United States with atopic dermatitis: A randomized, controlled, evaluator-blinded study.

BACKGROUND: Latin American patients in the United States experience significant health disparities. Community health workers (promotoras de salud) reduce disparities by providing culturally appropriate education. While educational interventions have been studied in atopic dermatitis (AD), a chronic dermatologic condition affecting children, none have evaluated the use of promotoras in Spanish-speaking pediatric patients in the United States. OBJECTIVE: To create and evaluate a promotora-led education program for Spanish-speaking caregivers of Latin American, pediatric patients with AD through a randomized, controlled, evaluator-blinded study. METHODS: Children with moderate/severe AD (n = 48) were recruited from the pediatric dermatology clinic at Children's Health℠ in Dallas, TX and randomized to receive clinic education (n = 26) or clinic education plus promotora home visits (n = 22). The primary outcome was overall adherence to topical emollients over the 12-week study, quantified by MEMSCap™ devices; several secondary endpoints were evaluated. RESULTS: Intention-to-treat analysis revealed a trend toward increased overall adherence to emollients over the 12-week study period in promotora (median [interquartile range, IQR]: 43% [26%-61%]) versus non-promotora (median [IQR]: 20% [11%-49%]) (p = .09) groups. SCORAD, AD knowledge, and Spanish-language Parental Quality of Life Questionnaire for AD (Sp-PIQoL-AD) improved in both groups, although there was no statistically significant difference between groups. There was a trend toward increased AD knowledge at Week 4 (p = .06) in the promotora group. CONCLUSIONS: A promotora-led educational intervention is a promising approach in increasing caregiver medication adherence in pediatric, Latin American patients with AD in the United States. Further research using creative and culturally appropriate strategies to increase medication adherence is necessary to reduce health disparities in other racial and ethnic minority populations in the United States.

Extracellular Vesicles from Immune Cells: A Biomedical Perspective.

Research on the role of extracellular vesicles (sEV) in physiology has demonstrated their undoubted importance in processes such as the transportation of molecules with significance for cell metabolism, cell communication, and the regulation of mechanisms such as cell differentiation, inflammation, and immunity. Although the role of EVs in the immune response is actively investigated, there is little literature revising, in a comprehensive manner, the role of small EVs produced by immune cells. Here, we present a review of studies reporting the release of sEV by different types of leukocytes and the implications of such observations on cellular homeostasis. We also discuss the function of immune cell-derived sEV and their relationship with pathological states, highlighting their potential application in the biomedical field.

Scalable Strategies to Increase Efficiency and Augment Public Health Activities During Epidemic Peaks.

OBJECTIVE: Scalable strategies to reduce the time burden and increase contact tracing efficiency are crucial during early waves and peaks of infectious transmission. DESIGN: We enrolled a cohort of SARS-CoV-2-positive seed cases into a peer recruitment study testing social network methodology and a novel electronic platform to increase contact tracing efficiency. SETTING: Index cases were recruited from an academic medical center and requested to recruit their local social contacts for enrollment and SARS-CoV-2 testing. PARTICIPANTS: A total of 509 adult participants enrolled over 19 months (384 seed cases and 125 social peers). INTERVENTION: Participants completed a survey and were then eligible to recruit their social contacts with unique "coupons" for enrollment. Peer participants were eligible for SARS-CoV-2 and respiratory pathogen screening. MAIN OUTCOME MEASURES: The main outcome measures were the percentage of tests administered through the study that identified new SARS-CoV-2 cases, the feasibility of deploying the platform and the peer recruitment strategy, the perceived acceptability of the platform and the peer recruitment strategy, and the scalability of both during pandemic peaks. RESULTS: After development and deployment, few human resources were needed to maintain the platform and enroll participants, regardless of peaks. Platform acceptability was high. Percent positivity tracked with other testing programs in the area. CONCLUSIONS: An electronic platform may be a suitable tool to augment public health contact tracing activities by allowing participants to select an online platform for contact tracing rather than sitting for an interview.

Phylogeography and evolutionary history of the Panamic Clingfish Gobiesox adustus in the Tropical Eastern Pacific.

The Panamic Clingfish Gobiesox adustus is widely distributed in the Tropical Eastern Pacific (TEP), from the central Gulf of California, Mexico to Ecuador, including the oceanic Revillagigedo Archipelago, and Isla del Coco. This cryptobenthic species is restricted to very shallow rocky-reef habitats. Here, we used one mitochondrial and three nuclear DNA markers from 155 individuals collected across the distribution range of the species in order to evaluate if geographically structured populations exist and to elucidate its evolutionary history. Phylogenetic analyses recovered a monophyletic group, with four well-supported, allopatric subgroups. Each subgroup corresponded to one of the following well-known biogeographic regions/provinces: 1) the Revillagigedo Archipelago, 2) the Cortez + Mexican provinces (Mexico), 3) the Panamic province (from El Salvador to Ecuador), and 4) Isla del Coco. A molecular-clock analysis showed a mean date for the divergence between clade I (the Revillagigedos and Cortez + Mexican provinces) and clade II (Panamic province and Isla del Coco) in the Pliocene, at ca. 5.33 Mya. Within clade I, the segregation between the Revillagigedos and Cortez + Mexican province populations was dated at ca. 1.18 Mya, during the Pleistocene. Within clade II, the segregation between samples of Isla del Coco and the Panamic province samples was dated at ca. 0.77 Mya, during the Pleistocene. The species tree, Bayesian species delimitation tests (BPP and STACEY), the ΦST, AMOVA, and the substantial genetic distances that exist between those four subgroups, indicate that they are independent evolutionary units. These cladogenetic events seem to be related to habitat discontinuities, and oceanographic and geological processes that produce barriers to gene flow for G. adustus, effects of which are enhanced by the intrinsic ecological characteristics of this species.

Efficiency of an up-flow Anaerobic Sludge Blanket reactor coupled with an electrochemical system to remove chloramphenicol in swine wastewater.

The application and design of treatment systems in wastewater are necessary due to antibiotics' potential toxicity and resistant genes on residual effluent. This work evaluated a coupled bio-electrochemical system to reduce chloramphenicol (CAP) and chemical oxygen demand (COD) on swine wastewater (SWW). SWW characterization found CAP of <10 µg/L and 17,434 mg/L of COD. The coupled system consisted of preliminary use of an Up-flow Anaerobic Sludge Blanket Reactor (UASB) followed by electrooxidation (EO). The UASB reactor (primary stage) was operated for three months at an organic load of 8.76 kg of COD/m3d and 50 mg CAP/L as initial concentration. In EO, we carried out a 22 (time operation and intensity) factorial design with a central composite design; we tried two Ti cathodes and one anode of Ti/PbO2. Optimal conditions obtained in the EO process were 240 min of operation time and 1.51 A of current intensity. It was possible to eliminate 44% of COD and 64.2% of CAP in the preliminary stage. On bio-electrochemicals, total COD and CAP removal were 82.35 and >99.99%, respectively. This coupled system can be applied to eliminate antibiotics and other organic pollutants in agricultural, industrial, municipal, and other wastewaters.

Chronic-pharma: New Platform for Chronic Patients Pharmacotherapy Optimization.

We describe the technological development of a web platform named CHRONIC-PHARMA that integrates three prescription support tools for patients with chronic diseases: Anticholinergic Burden Calculator (ABC), LESS-CHRON criteria and TRIGGER-CHRON. They focus on the optimization and evaluation of pharmacotherapy in patients with chronic diseases, resulting in a useful, single platform that can facilitate the review of pharmacotherapy and improve the safety of chronically ill patients. This is achieved by estimating and reducing the anticholinergic risk (ABC), detecting opportunities for deprescribing drugs and monitoring its success (LESS-CHRON criteria), as well as calculating the risk of adverse drug events (TRIGGER-CHRON). The platform is freely accessible online ( https://chronic-pharma.com/ ) as well as through a mobile application, and therefore easily accessible among the healthcare community.

Estimating the impact of the COVID-19 pandemic on diagnosis and survival of five cancers in Chile from 2020 to 2030: a simulation-based analysis.

BACKGROUND: The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies and planning to mitigate the forthcoming cancer-related health impacts of the pandemic in Chile. METHODS: We developed a microsimulation model of five cancers in Chile (breast, cervix, colorectal, prostate, and stomach) for which reliable data were available, which simulates cancer incidence and progression in a nationally representative virtual population, as well as stage-specific cancer detection and survival probabilities. We calibrated the model to empirical data on monthly detected cases, as well as stage at diagnosis and 5-year net survival. We accounted for the impact of COVID-19 on excess mortality and cancer detection by month during the pandemic, and projected diagnosed cancer cases and outcomes of stage at diagnosis and survival up to 2030. For comparison, we simulated a no COVID-19 scenario in which the impacts of COVID-19 on excess mortality and cancer detection were removed. FINDINGS: Our modelling showed a sharp decrease in the number of diagnosed cancer cases during the COVID-19 pandemic, with a large projected short-term increase in future diagnosed cases. Due to the projected backlog in diagnosis, we estimated that in 2021 there will be an extra 3198 cases (95% uncertainty interval [UI] 1356-5017) diagnosed among the five modelled cancers, an increase of nearly 14% compared with the no COVID-19 scenario, falling to a projected 10% increase in 2022 with 2674 extra cases (1318-4032) diagnosed. As a result of delayed diagnosis, we found a worse stage distribution for detected cancers in 2020-22, which is estimated to lead to 3542 excess cancer deaths (95% UI 2236-4816) in 2022-30, compared with the no COVID-19 scenario, among the five modelled cancers, most of which (3299 deaths, 2151-4431) are projected to occur before 2025. INTERPRETATION: In addition to a large projected surge in diagnosed cancer cases, we found that delays in diagnosis will result in worse cancer stage at presentation, leading to worse survival outcomes. These findings can help to inform surge capacity planning and highlight the importance of ensuring appropriate health system capacity levels to detect and care for the increased cancer cases in the coming years, while maintaining the timeliness and quality of cancer care. Potential delays in treatment and adverse impacts on quality of care, which were not considered in this model, are likely to contribute to even more excess deaths from cancer than projected. FUNDING: Harvard TH Chan School of Public Health. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

SARS-CoV-2: preliminary study of infected human nasopharyngeal tissue by high resolution microscopy.

BACKGROUND: The novel coronavirus SARS-CoV-2 is the etiological agent of COVID-19. This virus has become one of the most dangerous in recent times with a very high rate of transmission. At present, several publications show the typical crown-shape of the novel coronavirus grown in cell cultures. However, an integral ultramicroscopy study done directly from clinical specimens has not been published. METHODS: Nasopharyngeal swabs were collected from 12 Cuban individuals, six asymptomatic and RT-PCR negative (negative control) and six others from a COVID-19 symptomatic and RT-PCR positive for SARS CoV-2. Samples were treated with an aldehyde solution and processed by scanning electron microscopy (SEM), confocal microscopy (CM) and, atomic force microscopy. Improvement and segmentation of coronavirus images were performed by a novel mathematical image enhancement algorithm. RESULTS: The images of the negative control sample showed the characteristic healthy microvilli morphology at the apical region of the nasal epithelial cells. As expected, they do not display virus-like structures. The images of the positive sample showed characteristic coronavirus-like particles and evident destruction of microvilli. In some regions, virions budding through the cell membrane were observed. Microvilli destruction could explain the anosmia reported by some patients. Virus-particles emerging from the cell-surface with a variable size ranging from 80 to 400 nm were observed by SEM. Viral antigen was identified in the apical cells zone by CM. CONCLUSIONS: The integral microscopy study showed that SARS-CoV-2 has a similar image to SARS-CoV. The application of several high-resolution microscopy techniques to nasopharyngeal samples awaits future use.

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.