Rapid and Comprehensive Screening for Urogenital and Gastrointestinal Schistosomiasis with Handheld Digital Microscopy Combined with Circulating Cathodic Antigen Testing.

Novel methods are required to aid the monitoring of schistosomiasis control and elimination initiatives through mass drug administration. Portable digital and mobile phone microscopy is a promising tool for this purpose. This cross-sectional study evaluated the diagnostic operating characteristics of a converted mobile phone microscope (the SchistoScope) for the detection of Schistosoma haematobium eggs, as determined by community-based field workers and expert microscopists, compared with a field gold standard of light microscopy. Three hundred sixty-five urine samples were evaluated by conventional light microscopy, with 49 (13.4%) positive for S. haematobium. Compared with light microscopy, the sensitivity and specificity of S. haematobium detection by field microscopists trained to use the SchistoScope were 26.5% (95% CI: 14.9-41.1%) and 98.4% (95% CI: 96.3-99.5%), respectively. The sensitivity and specificity of S. haematobium detection by expert microscopists using the SchistoScope was 74% (95% CI: 59.7-85.4%) and 98.1% (95% CI: 95.9-99.3%), respectively, compared with light microscopy. The sensitivity rose to 96.1% and 100% when evaluating for egg counts greater than five and 10 eggs per 10 mL, respectively. A point-of-care circulating cathodic anion (POC CCA) test was used to evaluate Schistosoma mansoni; however, there were too few positive samples to reliably comment on diagnostic characteristics. This study demonstrated that a "urine-only" approach to rapidly screen for schistosomiasis at the point of sample collection can be conducted with mobile phone microscopy (S. haematobium) coupled with POC CCA (S. mansoni). Such an approach may aid in streamlined schistosomiasis control and elimination initiatives.

Health-related quality of life for pediatric patients with end-stage kidney disease: A systematic review and meta-analysis of the Pediatric Quality of Life Inventory (PedsQL).

INTRODUCTION: Health-related quality of life (HRQoL) studies demonstrate the impact of end-stage renal disease (ESRD) on the physical and psychosocial development of children. While several instruments are used to measure HRQoL, few have standardized domains specific to pediatric ESRD. This review examines current evidence on self and proxy-reported HRQoL among pediatric patients with ESRD, based on the Pediatric Quality of Life Inventory (PedsQL) questionnaires. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis on HRQoL using the PedsQL 4.0 Generic Core Scale (GCS) and the PedsQL 3.0 ESRD Module among 5- to 18-year-old patients. We queried PubMed, Embase, Web of Science, CINAHL, and Cochrane databases. Retrospective, case-controlled, and cross-sectional studies using PedsQL were included. FINDINGS: Of 435 identified studies, 14 met inclusion criteria administered in several countries. Meta-analysis demonstrated a significantly higher total HRQoL for healthy patients over those with ESRD (SMD:1.44 [95% CI: 0.78-2.09]) across all dimensional scores. In addition, kidney transplant patients reported a significantly higher HRQoL than those on dialysis (PedsQL GCS, SMD: 0.33 [95% CI: 0.14-0.53]) and (PedsQL ESRD, SMD: 0.65 [95% CI: 0.39-0.90]) concordant with parent-proxy reports. DISCUSSION: Patients with ESRD reported lower HRQoL in physical and psychosocial domains compared with healthy controls, while transplant and peritoneal dialysis patients reported better HRQoL than those on hemodialysis. This analysis demonstrates the need to identify dimensions of impaired functioning and produce congruent clinical interventions. Further research on the impact of individual comorbidities in HRQoL is necessary for developing comprehensive, integrated, and holistic treatment programs.

Oxygen debt as a predictor of high-flow nasal cannula therapy failure in SARS-CoV-2 patients with acute respiratory failure: A retrospective cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is known for its rapid progression to acute hypoxemic respiratory failure (AHRF). The increased use of oxygen therapy during the pandemic and the progression of AHRF have highlighted the need to promptly determine the need for orotracheal intubation (OTI). OBJETIVE: To determine the validity of quantitative measurement of oxygen debt (DEOx) according to arterial gases compared to the use of iROX in patients with high-flow nasal cannula (HFNC) therapy requirement, presenting with acute respiratory failure as a consequence of SARS-CoV-2 infection. In addition, we aimed to identify the factors associated with the need for orotracheal intubation (OTI). METHODS: A retrospective observational cohort study of a database collected from patients with SARS-CoV-2 infection admitted to intensive care units with AHRF and had received HFNC upon admission during the Covid-19 pandemic (March 23, 2020 through August 02, 2021). The variables of interest were factors determining the predictive ability of DEOx and iROX. We used a multiple logarithmic regression model to correct for confounding and mixed-effects variables, and validated for OTI in patients treated with HFNC. RESULTS: From a total of 373 patients treated with HFNC, 317 patients (84.9%) required invasive mechanical ventilation. APACHE II (AOR 1.44; 95% CI: 1.14-1.83, p 0,032), vasopressor use (AOR 27.7; 95% CI: 1.83 - 420,63, p 0,017), and DEOx (AOR 1.26; 95% CI: 1.10 - 1.44, p 0,001) were associated with the need for intubation. The predictive model between iROX and DEOx evidenced an AUC of 0.535 vs. 0.606, respectively, with a DEOx cut off point of 7.14 (±10.16, p < 0.01). DEOx as an independent factor of OTI presents an OR 2,48 with cut point 4.5 mlO2/kg (AUC 0.780, CI 95%, 0.753 - 0.808, p < 0.01). CONCLUSIONS: DEOx is a valuable measurment to identify the need for OTI in patients with SARS-CoV-2 who were under management with HFNC with a predictive value superior to iROX, being a reproducible and valid quantitative method for the need OTI that can be implemented in other critically illconditions. Further studies are required to characterize the usefulness of DEOx more precisely.

Euro-Burn I: Assessment of burnout syndrome in health workers in a mediterranean country during the SARS-CoV-2 pandemic.

BACKGROUND: Burnout syndrome (BS) has a negative impact among health professionals. AIMS: Our research objective is to quantify the level of burnout in health workers of the Spanish National Health System during the COVID-19 pandemic using and comparing two independent measurement instruments. METHODS: Cross-sectional, descriptive and multicenter study conducted through an anonymous online survey among health workers of the National Health System, measuring the level of burnout using the Maslach Burnout Inventory (MBI) and the Copenhagen Burnout Inventory (CBI). RESULTS: A total of 448 questionnaires were analyzed, the mean age of the participants was 43.53 years (range: 20-64), 365 (81.5%) women. 161 (35.9%) participants presented BS measured with the MBI and 304 (67.9%) measured with the CBI. Regarding work contract, those who had greater job stability presented a higher degree of cynicism with respect to the eventual ones (p = .010), the eventual ones presenting higher mean scores in professional efficacy (p = .034). Urban workers had higher scores of exhaustion (p < .001) and cynicism (p < .001) than those living in rural areas. When comparing both tests, a high predictive value for exhaustion and cynicism was found to measure BS through the CBI (AUC = 0.92 and 0.84, respectively) and a low AUC with respect to the predictive value for efficacy (AUC = 0, 59). CONCLUSIONS: The results obtained show a high level of BS among the health workers who participated in our study. Both tests have an excellent correlation in the degree of exhaustion and cynicism, but not in efficacy. The BS measurement must be performed with at least two validated instruments to increase its reliability.

Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Health Care Transition in Adolescents and Young Adults With Chronic Kidney Disease: Focus on the Individual and Family Support Systems.

Health care transition (HCT) from pediatric to adult-focused services is a longitudinal process driven by the collaboration and interactions of adolescent/young adult patients, their families, providers, health care agencies, and environment. Health care providers in both pediatric and adult-focused settings must collaborate, as patients' health self-management skills are acquired in the mid-20s, after they have transferred to adult-focused care. Our manuscript discusses the individual and family support systems as they relate to adolescents and young adults with chronic or end-stage kidney disease. In the individual domain, we discuss demographic/socioeconomic characteristics, disease complexity/course, cognitive capabilities, and self-management/self-advocacy. In the family domain, we discuss family composition/culture factors, family function, parenting style, and family unit factors. We provide a section dedicated to patients with cognitive and developmental disability. Furthermore, we discuss barriers for HCT preparation and offer solutions as well as activities for HCT preparation.

Efectividad de la Terapia Física en Mujeres con Disfunción Sexual: Scoping Review / Effectiveness of Physical Therapy in Women with Sexual Dysfunction: Scoping Review

Introducción. Las disfunciones sexuales femeninas son altamente prevalentes a lo largo de la vida, sin embargo, no son de fácil abordaje para los profesionales de salud. Los aspectos físicos de las disfunciones sexuales y su tratamiento, frecuentemente son subvalorados, porque la evidencia sobre la terapia física en estas disfunciones es limitada. Lo que genera que sean parcialmente tratadas y su sintomatología se pueda mantener y/o aumentar en el tiempo, impactando en la función sexual y en la calidad de vida. Objetivo. Revisar la literatura disponible sobre la terapia física en disfunciones sexuales femeninas y establecer su efectividad. Metodología. Se realizaron búsquedas bibliográficas, entre los años 2012 y 2022 en inglés y portugués, disponibles en diferentes bases de datos como; Pubmed, Scielo, Cochrane, Pedro y en Google Scholar. Se incluyeron los registros que hicieran referencia a la terapia física en las disfunciones sexuales femeninas y que cumplieran con nuestros criterios de inclusión y exclusión. Resultados. Se incluyeron 8 registros en la síntesis cualitativa. Se identificaron 3 modalidades: herramientas de terapia física, valoración de la función sexual y del dolor. Conclusión. La terapia física demuestra ser efectiva para el tratamiento de las disfunciones sexuales femeninas. La evidencia disponible que demuestre su uso y efectividad aún es escasa, lo que limita su difusión para ser considerada en el abordaje multidisciplinario habitual. Se requiere aumentar la investigación en esta área, enfocada en el rol de la terapia física y sus modalidades terapéuticas, en el tratamiento de las disfunciones sexuales femeninas.

Background. Female sexual dysfunction is highly prevail throughout our life, nevertheless, they are not easily addressed by health professionals. The physical aspects of sexual dysfunctions and their treatment are frequently undervalued because the evidence about physical therapy in these dysfunctions is limited. What causes them to be partly treated and their symptoms can be maintained and/or increased over time and having an impact on sexual function and quality of life. Objetive. To review through literature about physical therapy in female sexual dysfunction and to establish its effectiveness. Methods. Through 2012 and 2012 it was carried out bibliographic searches in English and Portuguese, available in different databases, such as Pubmed, Scielo, Cochrane, Pedro and Google Scholar. Records referring to physical therapy in female sexual dysfunction and that fulfill our requirements of inclusion and exclusion criteria were included. Results. Eight records were included in the qualitative synthesis. Three modalities were identified: physical therapy tools, assessment of sexual function and pain. Conclusion. Physical therapy proves to be effective for the treatment of female sexual dysfunctions. The available evidence that demonstrates its use and effectiveness is still scarce, which limits its diffusion to be considered in the regular multidisciplinary approach. More researches are demand in this area, focused on the role of physical therapy and its therapeutic modalities, in the treatment of female sexual dysfunctions.

Rapid detection of SARS-CoV-2 RNA in saliva via Cas13.

Rapid nucleic acid testing is central to infectious disease surveillance. Here, we report an assay for rapid COVID-19 testing and its implementation in a prototype microfluidic device. The assay, which we named DISCoVER (for diagnostics with coronavirus enzymatic reporting), involves extraction-free sample lysis via shelf-stable and low-cost reagents, multiplexed isothermal RNA amplification followed by T7 transcription, and Cas13-mediated cleavage of a quenched fluorophore. The device consists of a single-use gravity-driven microfluidic cartridge inserted into a compact instrument for automated running of the assay and readout of fluorescence within 60 min. DISCoVER can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva with a sensitivity of 40 copies µl-1, and was 94% sensitive and 100% specific when validated (against quantitative PCR) using total RNA extracted from 63 nasal-swab samples (33 SARS-CoV-2-positive, with cycle-threshold values of 13-35). The device correctly identified all tested clinical saliva samples (10 SARS-CoV-2-positive out of 13, with cycle-threshold values of 23-31). Rapid point-of-care nucleic acid testing may broaden the use of molecular diagnostics.

Efficacy of Parainfluenza Virus 5 (PIV5)-vectored Intranasal COVID-19 Vaccine as a Single Dose Vaccine and as a Booster against SARS-CoV-2 Variants

Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has greatly reduced coronavirus disease 2019 (COVID-19)-related deaths and hospitalizations, but waning immunity and the emergence of variants capable of immune escape indicate the need for novel SARS-CoV-2 vaccines. An intranasal parainfluenza virus 5 (PIV5)-vectored COVID-19 vaccine CVXGA1 has been proven efficacious in animal models and blocks contact transmission of SARS-CoV-2 in ferrets. CVXGA1 vaccine is currently in human clinical trials in the United States. This work investigates the immunogenicity and efficacy of CVXGA1 and other PIV5-vectored vaccines expressing additional antigen SARS-CoV-2 nucleoprotein (N) or SARS-CoV-2 variant spike (S) proteins of beta, delta, gamma, and omicron variants against homologous and heterologous challenges in hamsters. A single intranasal dose of CVXGA1 induces neutralizing antibodies against SARS-CoV-2 WA1 (ancestral), delta variant, and omicron variant and protects against both homologous and heterologous virus challenges. Compared to mRNA COVID-19 vaccine, neutralizing antibody titers induced by CVXGA1 were well-maintained over time. When administered as a boost following two doses of a mRNA COVID-19 vaccine, PIV5-vectored vaccines expressing the S protein from WA1 (CVXGA1), delta, or omicron variants generate higher levels of cross-reactive neutralizing antibodies compared to three doses of a mRNA vaccine. In addition to the S protein, the N protein provides added protection as assessed by the highest body weight gain post-challenge infection. Our data indicates that PIV5-vectored COVID-19 vaccines, such as CVXGA1, can serve as booster vaccines against emerging variants. ImportanceWith emerging new variants of concern (VOC), SARS-CoV 2 continues to be a major threat to human health. Approved COVID-19 vaccines have been less effective against these emerging VOCs. This work demonstrates the protective efficacy, and strong boosting effect, of a new intranasal viral-vectored vaccine against SARS-CoV-2 variants in hamsters.

Principles of melting in hybrid organic-inorganic perovskite and polymorphic ABX3 structures.

Four novel dicyanamide-containing hybrid organic-inorganic ABX3 structures are reported, and the thermal behaviour of a series of nine perovskite and non-perovskite [AB(N(CN)2)3] (A = (C3H7)4N, (C4H9)4N, (C5H11)4N; B = Co, Fe, Mn) is analyzed. Structure-property relationships are investigated by varying both A-site organic and B-site transition metal cations. In particular, increasing the size of the A-site cation from (C3H7)4N → (C4H9)4N → (C5H11)4N was observed to result in a decrease in T m through an increase in ΔS f. Consistent trends in T m with metal replacement are observed with each A-site cation, with Co < Fe < Mn. The majority of the melts formed were found to recrystallise partially upon cooling, though glasses could be formed through a small degree of organic linker decomposition. Total scattering methods are used to provide a greater understanding of the melting mechanism.

The presence of a large patent foramen ovale reduces acute and chronic success in atrial fibrillation ablation.

PURPOSE: In this study, we analyzed PFO implications in atrial fibrillation (AF) ablation. METHODS: Six hundred and twenty-five consecutive patients with AF undergoing PV isolation were included. We considered that a large and/or compliant PFO was present if the catheters advanced gently into the LA without puncturing the septum. Atrial tachyarrhythmias after the 3-month blanking period were classified as a recurrence. RESULTS: Out of the 625 patients included, 36 (5.8%) were found to have PFO. No significant differences were observed in the clinical characteristics of patients with PFO compared with patients without PFO. Nevertheless, patients with PFO had lower acute success in PV isolation compared with patients without PFO (98.2% vs. 88.5%; p = 0.006) even after adjusting for age, sex, type of AF, LA area, cardiomyopathy, time from AF diagnosis to the ablation, and ablation technique (odds ratio: 0.1; 95% confidence interval (CI): 0.02-0.9; p = 0.039). In 546 patients followed more than 6 months, the recurrence rate of any atrial tachyarrhythmia after 18.6 ± 11.9 months was significantly higher in patients with PFO compared with patients without PFO (41.9 vs. 70%; p = 0.012). This difference remained significant after adjusting for age, sex, type of AF, LA area, cardiomyopathy, time from AF diagnosis to the ablation, and ablation technique (hazard ratio: 1.9; 95% CI: 1.1-3.3; p = 0.015). CONCLUSIONS: The presence of a large and/or compliant PFO is an independent factor for PV isolation failure and arrhythmia recurrence rate after the ablation.

Contribución de los estudios por imágenes en el diagnóstico de cáncer de mama

RESUMEN El cáncer de mama es el más frecuente en las mujeres y representa la segunda causa de muerte entre las féminas. Resulta fundamental la prevención mediante los programas de pesquizaje. El diagnóstico por imagen de este tumor ha evolucionado en los últimos años. En mamografía, se han incorporado las técnicas digitales, los aparatos de ultrasonidos son de mejor calidad y la resonancia magnética ha adquirido mayor protagonismo entre todos los algoritmos diagnósticos, no obstante, la mamografía sigue representando el examen de elección para la detección de este tipo de neoplasia en la población general. El objetivo del presente artículo es describir los aspectos imagenológicos de importancia que contribuyen al diagnóstico del cáncer de mama, para ello se realizó una revisión de la bibliografia, en diferentes bases de datos con el descriptor de estudios por imágenes en el cáncer de mama.

ABSTRACT Breast cancer is the most common in women and represents the second leading cause of death. Prevention through screening programs is essential. Imaging of this tumor has evolved in recent years. In mammography, digital techniques have been incorporated, ultrasound machines are of better quality and magnetic resonance imaging has acquired greater prominence among all diagnostic algorithms, however, mammography continues to represent the test of choice for the detection of this type of neoplasia in the general population. The aim of this article is to describe the important imaging aspects that contribute to the diagnosis of breast cancer, for this, a review of the literature was carried out in different databases with the descriptor of imaging studies in breast cancer.

Accelerated RNA detection using tandem CRISPR nucleases.

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided recognition of RNA that triggers cleavage and release of a fluorescent reporter molecule1,2, but long reaction times hamper sensitivity and speed when applied to point-of-care testing. Here we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 RNA copies/microliter in 20 minutes. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that detected SARS-CoV-2 RNA from nasopharyngeal samples with PCR-derived Ct values up to 29 in microfluidic chips, using a compact imaging system. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables direct RNA detection in a format amenable to point-of-care infection diagnosis, as well as to a wide range of other diagnostic or research applications.

Knowledge and Impact of COVID-19 on Middle-Aged and Older People living with HIV in Lima, Peru

COVID-19 has had an unprecedented worldwide impact, and Peru has had one of the highest COVID-19 case rates despite implementation of an early strict nationwide quarantine. Repercussions on Perus healthcare system may impact vulnerable populations, particularly people with HIV (PWH). We explored the knowledge of COVID-19 and the socioeconomic and health impact of the pandemic among middle-aged and older PWH. A cross-sectional telephone survey was administered to 156 PWH age [≥]40 years receiving care in one of two large HIV clinics in Lima, Peru. The majority of PWH (age 52{+/-}7.7 years, 41% female, 65% completed secondary school or less) were knowledgeable regarding COVID-19 symptoms and prevention methods. Nearly half of those employed prior to the pandemic reported job loss. Female sex (unadjusted prevalence ratio [PR] 1.85 [95%CI 1.27-2.69]), low educational level (PR 1.62 [1.06-2.48]) and informal work (PR 1.58 [1.06-2.36]) were risk factors for unemployment but not in adjusted models. Increased anxiety was reported in 64% and stress in 77%. COVID-19 has had a substantial socioeconomic and mental health impact on PWH living in Lima, Peru, particularly those with lower educational levels and informal workers. Efforts are needed to ensure continued medical care and socioeconomic support of PWH in Peru.

Accelerated RNA detection using tandem CRISPR nucleases

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided recognition of RNA that triggers cleavage and release of a fluorescent reporter molecule1,2, but long reaction times hamper sensitivity and speed when applied to point-of-care testing. Here we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of [~]30 RNA copies/microliter in 20 minutes. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that detected SARS-CoV-2 RNA from nasopharyngeal samples with PCR-derived Ct values up to 29 in microfluidic chips, using a compact imaging system. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables direct RNA detection in a format amenable to point-of-care infection diagnosis, as well as to a wide range of other diagnostic or research applications.

Rapid, point-of-care molecular diagnostics with Cas13.

Rapid nucleic acid testing is a critical component of a robust infrastructure for increased disease surveillance. Here, we report a microfluidic platform for point-of-care, CRISPR-based molecular diagnostics. We first developed a nucleic acid test which pairs distinct mechanisms of DNA and RNA amplification optimized for high sensitivity and rapid kinetics, linked to Cas13 detection for specificity. We combined this workflow with an extraction-free sample lysis protocol using shelf-stable reagents that are widely available at low cost, and a multiplexed human gene control for calling negative test results. As a proof-of-concept, we demonstrate sensitivity down to 40 copies/µL of SARS-CoV-2 in unextracted saliva within 35 minutes, and validated the test on total RNA extracted from patient nasal swabs with a range of qPCR Ct values from 13-35. To enable sample-to-answer testing, we integrated this diagnostic reaction with a single-use, gravity-driven microfluidic cartridge followed by real-time fluorescent detection in a compact companion instrument. We envision this approach for Diagnostics with Coronavirus Enzymatic Reporting (DISCoVER) will incentivize frequent, fast, and easy testing.

Effectiveness of Prone Positioning in Nonintubated Intensive Care Unit Patients With Moderate to Severe Acute Respiratory Distress Syndrome by Coronavirus Disease 2019.

BACKGROUND: In the treatment for severe acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19), the World Health Organization (WHO) recommends prone positioning (PP) during mechanical ventilation for periods of 12-16 h/d to potentially improve oxygenation and survival. In this prospective observational study, we evaluated the ability of long PP sessions to improve oxygenation in awake intensive care unit (ICU) patients with moderate or severe ARDS due to COVID-19. METHODS: The study was approved by the ethics committee of Galicia (code No. 2020-188), and all patients provided informed consent. In this case series, awake patients with moderate or severe ARDS by COVID-19 admitted to the ICU at University Hospital of Santiago from March 21 to April 5, 2020 were prospectively analyzed. Patients were instructed to remain in PP as long as possible until the patient felt too tired to maintain that position. Light sedation was administered with dexmedetomidine. The following information was collected: number and duration of PP sessions; tissue O2 saturation (StO2) and blood gases before, during, and following a PP session; need of mechanical ventilation; duration of ICU admission; and ICU outcome. Linear mixed-effects models (LMM) were fit to estimate changes from baseline with a random effect for patient. RESULTS: Seven patients with moderate or severe ARDS by COVID-19 were included. All patients received at least 1 PP session. A total of 16 PP sessions were performed in the 7 patients during the period study. The median duration of PP sessions was 10 hours. Dexmedetomidine was used in all PP sessions. Oxygenation increased in all 16 sessions performed in the 7 patients. The ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FIO2) significantly increased during PP (change from baseline 110 with 97.5% confidence interval [CI], 19-202) and, after PP, albeit not significantly (change from baseline 38 with 97.5% CI, -9.2 to 85) compared with previous supine position. Similarly, tissue oxygenation underwent a small improvement during PP (change from baseline 2.6% with 97.5% CI, 0.69-4.6) without significant changes after PP. Two patients required intubation. All patients were discharged from the ICU. CONCLUSIONS: We found that PP improved oxygenation in ICU patients with COVID-19 and moderate or severe ARDS. PP was relatively well tolerated in our patients and may be a simple strategy to improve oxygenation trying to reduce the number of patients in mechanical ventilation and the length of stay in the ICU, especially in COVID-19 pandemic.

Rapid detection of SARS-CoV-2 with Cas13

Rapid nucleic acid testing is a critical component of a robust infrastructure for increased disease surveillance. Here, we report a microfluidic platform for point-of-care, CRISPR-based molecular diagnostics. We first developed a nucleic acid test which pairs distinct mechanisms of DNA and RNA amplification optimized for high sensitivity and rapid kinetics, linked to Cas13 detection for specificity. We combined this workflow with an extraction-free sample lysis protocol using shelf-stable reagents that are widely available at low cost, and a multiplexed human gene control for calling negative test results. As a proof-of-concept, we demonstrate sensitivity down to 40 copies/L of SARS-CoV-2 in unextracted saliva within 35 minutes, and validated the test on total RNA extracted from patient nasal swabs with a range of qPCR Ct values from 13-35. To enable sample-to-answer testing, we integrated this diagnostic reaction with a single-use, gravity-driven microfluidic cartridge followed by real-time fluorescent detection in a compact companion instrument. We envision this approach for Diagnostics with Coronavirus Enzymatic Reporting (DISCoVER) will incentivize frequent, fast, and easy testing.