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Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Objective Measurement‐based care tools in psychiatry are useful for symptom monitoring and detecting response to treatment, but methods for quick and objective measurement are lacking especially for acute psychosis. The aim of this study was to explore potential language markers, detected by natural language processing (NLP) methods, as a means to objectively measure the severity of psychotic symptoms of schizophrenia in an acute clinical setting. Methods Twenty‐two speech samples were collected from seven participants who were hospitalized for schizophrenia, and their symptoms were evaluated over time with SAPS/SANS and TLC scales. Linguistic features were extracted from the speech data using machine learning techniques. Spearman's correlation was performed to examine the relationship between linguistic features and symptoms. Various machine learning models were evaluated by cross‐validation methods for their ability to predict symptom severity using the linguistic markers. Results Reduced lexical richness and syntactic complexity were characteristic of negative symptoms, while lower content density and more repetitions in speech were predictors of positive symptoms. Machine learning models predicted severity of alogia, illogicality, poverty of speech, social inattentiveness, and TLC scores with up to 82% accuracy. Additionally, speech incoherence was quantifiable through language markers derived from NLP methods. Conclusions These preliminary findings suggest that NLP may be useful in identifying clinically relevant language markers of schizophrenia, which can enhance objectivity in symptom monitoring during hospitalization. Further work is needed to replicate these findings in a larger data set and explore methods for feasible implementation in practice.

Urine output is an important indicator of renal function. In hospitals, urine is collected using a catheter connected to a urine collection bag that has volume gradation markings. This type of visual measurement has low levels of accuracy and is labor-intensive. This paper developed an Internet-of-Things enabled system that continuously monitors the urine volume collected via the urine collection system. The device is built utilizing a strain gauge load cell, an integrated circuit that contains an amplifier, analog-to-digital converter, and a WiFi-enabled microcontroller. The data is sent via wireless networking to a data collection and analysis server, which provides accurate analyses of urine output. A mobile application utilizing the Blynk.io system is used to display the data. This device and mobile application were built at a minimal cost of 26 USD. The device has been tested multiple times and reported urine output accurately, with minimal difference between actual versus measured volumes. In the future, further development of this device can provide hospitals and physicians worldwide with easy access to affordable, accurate, and real-time urine measurement, which would translate into better, life-saving medical care.

Abstract Background Hearing loss is the third leading global cause of disability and is associated with poorer quality of life. Hearing aids are often recommended for hearing loss; however, hearing aid uptake and use rates are perpetually low. Motivational interviewing (MI) is a patient-centered counseling aimed at addressing the desire in the patient to change their behavior. The aim of this study is to investigate the impact of one-on-one MI sessions on hearing aid use among new adult users. Methods A multi-center, prospective, randomized patient-blind controlled trial with a pre- and post-tests design. New hearing aid users ≥ 18 years of age will be recruited from Vancouver, Canada. They will be randomly assigned to a treatment or control group. The treatment group will attend a one-on-one MI session hosted by a practicing MI therapist in addition to standard in-person audiological care. The control group will receive standard in-person audiological care. Data is collected at baseline and at 1, 3, 6, and 12 months’ follow-ups. The primary outcomes are data-logged hearing aid use hours and patient-reported outcomes as measured by the International Outcome Inventory for Hearing Aids questionnaire. Associations between intervention and hearing aid use hours and self-reported outcome measures will be assessed. Discussion This trial is designed to evaluate the efficacy of one-on-one MI in improving hearing aid use in new adult users in the short and long terms. Results will contribute to the evidence on whether MI counseling has an effect on hearing aid use and may guide future clinical practices. Trial registration ClinicalTrials.gov NCT04673565 . Registered on 17 December 2020.

Abstract Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. Methods A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1–9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures—kappa coefficient ( $$\kappa$$ κ ) value > 0.61. Results After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. Conclusion This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years. Graphical abstract

Rotavirus (RV) replicates within viroplasms, membraneless electron-dense globular cytosolic inclusions with liquid–liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single- and double-stranded virus RNAs, and host components such as microtubules, perilipin-1, and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

AZD7442 (tixagevimab-cilgavimab) is a combination of two human monoclonal antibodies for pre-exposure prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients who do not mount a reliable vaccine response. Foremost among these are hematologic malignancy patients with limited clinical trial or realworld experience to assess the effectiveness of this combination treatment since the emergence of Omicron and its subvariants. We performed a retrospective study of 892 high-risk hematologic malignancy patients who received AZD7442 at Memorial Sloan Kettering Cancer Center in New York City from January 1, 2022 to July 31, 2022. We evaluated demographic, clinical, and laboratory characteristics and performed regression analyses to evaluate risk factors for breakthrough infection. We also evaluated the impact of updated AZD7442 dosing regimens on the risk of breakthrough infection. Among 892 patients, 98 (10.9%) had a breakthrough infection during the study period. A majority received early outpatient treatment (82%) and eventually eight (8.2%) required hospitalization for management of Coronavirus Disease 2019 (COVID-19), with a single instance of severe COVID-19 and death. Patients who received a repeat dose or a higher firsttime dose of AZD7442 had a lower incidence of breakthrough infection. Univariate analyses did not reveal any significant predictors of breakthrough infection. While AZD7442 is effective at reducing SARS-CoV-2 breakthrough infection in patients with hematologic malignancies, no risk factors reliably predicted risk of infection. Patients who received updated dosing regimens as per Food and Drug Administration guidelines had better protection against breakthrough infection.

Cardiovascular (CV) disease prevention with low-dose aspirin can be less effective in patients with a faster recovery of platelet (PLT) cyclooxygenase (COX)-1 activity during the 24-hour dosing interval. We previously showed that incomplete suppression of TXA2 over 24 hours can be rescued by a twice daily aspirin regimen. Here we show that reduced PLT glycoprotein (GP)Ibα shedding characterizes patients with accelerated COX-1 recovery and may contribute to higher thrombopoietin (TPO) production and higher rates of newly formed PLT, escaping aspirin inhibition over 24 hours. Two hundred aspirin-treated patients with high CV risk (100 with type 2 diabetes mellitus) were stratified according to the kinetics of PLT COX-1 activity recovery during the 10- to 24-hour dosing interval. Whole proteome analysis showed that PLT from patients with accelerated COX-1 recovery were enriched in proteins involved in cell survival, inhibition of apoptosis and cellular protrusion formation. In agreement, we documented increased plasma TPO, megakaryocyte maturation and proplatelet formation, and conversely increased PLT galactose and reduced caspase 3, phosphatidylserine exposure and ADAM17 activation, translating into diminished GPIbα cleavage and glycocalicin (GC) release. Treatment of HepG2 cells with recombinant GC led to a dose-dependent reduction of TPO mRNA in the liver, suggesting that reduced GPIbα ectodomain shedding may unleash thrombopoiesis. A cluster of clinical markers, including younger age, non-alcoholic fatty liver disease, visceral obesity and higher TPO/GC ratio, predicted with significant accuracy the likelihood of faster COX-1 recovery and suboptimal aspirin response. Circulating TPO/GC ratio, reflecting a dysregulation of PLT lifespan and production, may provide a simple tool to identify patients amenable to more frequent aspirin daily dosing.

Abstract Background Achieving maternal health outcomes in the SDGs requires the implementation of more targeted policies and strategies. While the MDGs may have deepened our understanding in this regard, we know little about the trends in maternal health services utilisation among primigravidas, and how age and geographical regions could have influenced these trends. In this study, we examined utilisation of antenatal and skilled delivery services among primigravidas in Uganda, a country with one of the highest maternal mortality ratios, and where early childbearing and its attendant challenges are common. Methods Guided by Andersen’s Behavioural Model, we fitted multivariate regression models to a pooled dataset of the 2006, 2011 and 2016 Ugandan Demographic and Health Survey (n = 3477) to understand the dynamics in Antenatal Care (ANC) and Skilled Birth Attendance (SBAs) utilisation among primigravidas. Post-estimation margins were employed to further highlight the effect of age and geographical regions. Results The analyses show an improvement in access to maternal health services among primigravidas from 2006 to 2016. Compared to 2006, primigravidas in 2016 were 48%, 24% and 2.98 times more likely to have early ANC, four or more ANC visits, and SBAs, respectively. Altogether, a primigravida in 2016 relative to 2006 was 42% more likely to meet all three maternal health service indicators. Post-estimation margins analyses on age and geographical disparities revealed that younger primigravidas have lower probability, while primigravidas in Eastern Region, one of the most deprived in the country, have the lowest probability of accessing maternal health services. Also, the study found education, wealth, women’s household decision-making power, place of residence as important determinants of ANC visits and SBAs. Conclusions Based on our findings, it is important to address the vulnerabilities of primigravidas, particularly younger individuals, in accessing early ANC. Uganda should scale-up decentralisation and integration of maternal health delivery in local communities as a strategy of addressing lingering geographical disparities, and ultimately improve maternal health outcomes in the SDGs period.

IntroductionSafe spaces are an alternative to emergency departments, which are often unable to provide optimum care for people experiencing emotional distress and/or suicidal crisis. At present, there are several different safe space models being trialled in Australia. However, research examining the effectiveness of safe space models, especially in community settings, is rare. In this paper, we present a protocol for a study in which we will investigate the implementation, effectiveness, and sustainability of safe space models as genuine alternatives for people who might usually present to the emergency department or choose not to access help due to past negative experiences.Material and methodsWe will use a mixed methods, co-designed study design, conducted according to the principles of community-based participatory research to obtain deep insights into the benefits of different safe space models, potential challenges, and facilitators of effective practice. We developed the study plan and evaluation framework using the RE-AIM framework, and this will be used to assess key outcomes related to reach, effectiveness, adoption, implementation, and maintenance. Data collection will comprise quantitative measures on access, use, satisfaction, (cost) effectiveness, distress, and suicidal ideation; and qualitative assessments of service implementation, experience, feasibility, acceptability, community awareness, and the fidelity of the models to service co-design. Data will be collected and analysed concurrently throughout the trial period of the initiatives.DiscussionThis study will enable an extensive investigation of safe spaces that will inform local delivery and provide a broader understanding of the key features of safe spaces as acceptable and effective alternatives to hospital-based care for people experiencing emotional distress and/or suicidal crisis. This study will also contribute to a growing body of research on the role and benefits of peer support and provide critical new knowledge on the successes and challenges of service co-design to inform future practice.

OBJECTIVE:Cash transfers are a common intervention to incentivize salutary behavior in resource-constrained settings. Many cash transfer studies do not, however, account for the effect of the size of the cash transfer in design or analysis. A randomized, controlled trial of a cash-transfer intervention is planned to incentivize appropriate surgical utilization in Guinea. The aim of the current study is to determine the size of that cash transfer so as to maximize compliance while minimizing cost. METHODS:Data were collected from nine coastal Guinean hospitals on their surgical capabilities and the cost of receiving surgery. These data were combined with publicly available data about the general Guinean population to create an agent-based model predicting surgical utilization. The model was validated to the available literature on surgical utilization. Cash transfer sizes from 0 to 1,000,000 Guinean francs were evaluated, with surgical compliance as the primary outcome. RESULTS:Compliance with scheduled surgery increases as the size of a cash transfer increases. This increase is asymptotic, with a leveling in utilization occurring when the cash transfer pays for all the costs associated with surgical care. Below that cash transfer size, no other optima are found. Once a cash transfer completely covers the costs of surgery, other barriers to care such as distance and hospital quality dominate. CONCLUSION:Cash transfers to incentivize health-promoting behavior appear to be dose-dependent. Maximal impact is likely only to occur when full patient costs are eliminated. These findings should be incorporated in the design of future cash transfer studies.

Abstract Background Delirium is a frequent and detrimental complication of inpatient hospitalization. Multicomponent intervention in selected groups has been shown to prevent and treat delirium, though little data exists on the effect of intervention in neurological patients. We studied the efficacy of a multicomponent delirium care pathway implemented on a largely neurology and neurosurgery hospital ward among unselected patients. Methods We incorporated a multicomponent delirium care pathway into the workflow of a university hospital for patients older than 50 years. The pathway involved risk-stratification for development of delirium, delirium screening, and non-pharmacologic behavioral prevention and intervention. We then retrospectively reviewed admissions before and after implementation of the care pathway. Our primary endpoint was incidence of delirium; secondary endpoints included delirium days, length of stay, restraint use, readmission rates, and discharge disposition. Results Seven hundred ninety eight admissions from before the delirium care pathway went into effect and 797 admissions from afterwards were reviewed. Baseline characteristics between groups were similar. Delirium incidence between the two groups did not change (7.0% before vs 7.2% after, p = 0.89). Length of stay among delirious patients significantly decreased after implementation of the delirium care pathway (9.60 before vs 7.06 after, β = − 0.16, adjusted p-value = 0.001). Conclusion Implementation of a delirium care pathway on a neurosciences ward was not associated with changes in the rate of delirium development, though length of stay among delirious patients decreased. In a largely neurologic population, multicomponent intervention to prevent and treat delirium may not change delirium incidence, but may be effective in mitigating delirium complications.

Despite the demonstrated need for sustainable and effective carceral health care, justice-involved medical education curricula are limited, and it’s unclear if informal clinical education is sufficient. Investigators aimed to quantify medical student involvement with carceral populations and explore how students’ knowledge of and attitudes towards justice-involved patients changed over the course of their training. A survey was designed by the investigators and sent to all current medical students at a single United States medical school. Stata 14.0 was used to compare results between the years of medical school. Differences between groups were tested using linear regression. Most 4th year students reported working in a carceral health setting. An increase in overall knowledge of justice-involved patients was observed as carceral medicine education (ptrend = 0.02), hours worked in a jail (ptrend < 0.01), and substance abuse training (ptrend < 0.01) increased. Overall attitude score increased with the students’ reported number of hours working in a jail (ptrend < 0.01) and the amount of substance abuse training (ptrend < 0.01). Finally, we found a trend of increasing knowledge and attitude scores as the year of standing increased (ptrend < 0.01). Our data suggest that most USC medical students work in a carceral setting during medical school. Didactic and experiential learning opportunities correlated with improved knowledge of and attitude toward justice-involved patients, with increases in both metrics increasing as the year in medical school increased. However, senior medical students still scored poorly. These findings underscore the need for a formal curriculum to train our healthcare workforce in health equity for carceral populations.

School-based mental health programs (SBMHP) are vital to providing youth access to mental health services. This study aims to characterize changes in therapy encounters and psychotropic medication prescriptions in an urban SBMHP during the COVID-19 pandemic. We used electronic medical records to extract demographic, clinical, and utilization data from encounters through a SBMHP associated with an urban mid-Atlantic academic medical institution from September 2019 to September 2021. We compared encounter trends in the 3 months preceding the onset of the COVID-19 pandemic (December 2019-February 2020) and the first 3 months of the pandemic (March-May 2020). Using all data from the study period, we plotted encounter statistics and conducted an interrupted time series analysis to examine longitudinal trends in encounter type and attendance, psychotropic medication prescriptions by therapeutic indication, and medication dosage increase before and after schools closed due to COVID-19 pandemic-related restrictions. A total of 625 students with 25,641 encounters were included. Students had a median age of 11 years (range 5-18 years) and the majority identified as Black (57.9%), and non-Hispanic (74.4%). Average monthly encounter volume increased by 557% from March to May 2020 compared to the prior 3 months, 88.6% of which were video encounters, compared to 0% previously. In contrast, psychotropic medication prescriptions decreased by 7.4%. Medication dosage adjustments declined in the period after March 2020, when a state mandate to close schools was ordered due to COVID-19, with the most prominent decline being in ADHD medication prescriptions, which averaged 6 increases per month pre-pandemic versus 1 per month during the pandemic period. In this SBMHP, encounters increased during the pandemic period, primarily in video encounters, while psychotropic medication prescriptions, mostly ADHD medications, declined during the pandemic. Reasons for this decline warrant further study.

DNA barcoding is both an important research and science education tool. The technique allows for quick and accurate species identification using only minimal amounts of tissue samples taken from any organism at any developmental phase. DNA barcoding has many practical applications including furthering the study of taxonomy and monitoring biodiversity. In addition to these uses, DNA barcoding is a powerful tool to empower, engage, and educate students in the scientific method while conducting productive and creative research. The study presented here provides the first assessment of Marine Park (Brooklyn, New York, USA) biodiversity using DNA barcoding. New York City citizen scientists (high school students and their teachers) were trained to identify species using DNA barcoding during a two-week long institute. By performing NCBI GenBank BLAST searches, students taxonomically identified 187 samples (1 fungus, 70 animals and 116 plants) and also published 12 novel DNA barcodes on GenBank. Students also identified 7 ant species and demonstrated the potential of DNA barcoding for identification of this especially diverse group when coupled with traditional taxonomy using morphology. Here we outline how DNA barcoding allows citizen scientists to make preliminary taxonomic identifications and contribute to modern biodiversity research.

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

A growing interest in living labs as a mechanism for innovation has drawn significant attention to both the different flavours of this methodology and to the organizations that put it into practice. However, little has been done to assess its impact and to compare its contribution to other innovation methodologies. This article aims to cover that gap by summarizing the most common European living labs approaches and positioning them in the landscape of user-contributed innovation methodology. The merits and appropriateness of living labs in these settings are also assessed.

Simon G Royce, Melissa Lee, Mimi L K TangDepartment of Allergy and Immunology, Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, Victoria 3052, AustraliaAbstract: L-selectin is a cell adhesion molecule, which mediates leukocyte rolling on bronchopulmonary endothelium. Previous studies in a murine model of allergic airways disease have shown that L-selectin plays a role in the regulation of airway hyperresponsiveness in asthma via mechanisms independent of inflammation. Airway remodeling has been shown to modulate airway hyperresponsiveness independently of inflammation.Purpose: Our aim was to determine if L-selectin influenced airway hyperresponsiveness via modulation of structural changes as a result of airway remodeling.Method: A chronic ovalbumin-induced allergic airways disease model was applied to L-selectindeficient mice and wild-type control mice. The development of airway inflammation was assessed by examining leukocyte influx into bronchoalveolar lavage fluid. Airway remodeling changes were determined via histology and morphometric analysis of lung tissue sections, and the development of airway hyperresponsiveness was assessed by invasive plethysmography.Results: Total cell counts, but not individual differential cell counts, were reduced in the ovalbumin-treated L-selectin-deficient mice compared to wildtype ovalbumin-treated mice. L-selectin-deficient mice had significantly reduced epithelial thickness and smooth muscle thickness. Airway hyperresponsiveness was abrogated in ovalbumin treated L-selectin-deficient mice compared to wild-type controls.Conclusion: L-selectin plays an important role in regulating airway remodeling in an animal model of chronic allergic airways disease. Abrogated airway hyperresponsiveness may be related to reduced remodeling changes in L-selectin-deficient mice. L-selectin represents a potential target for novel asthma treatment for airway remodeling and airway hyperresponsiveness.Keywords: asthma, L-selectin, airway hyperresponsiveness, airway remodeling

Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment. Methods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration. Findings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB. Conclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.

Puerperal group A streptococcal infections, a major postpartum killer during the late 19th and early 20th centuries, have become (fortunately) rare. We describe a cluster of 4 serious peripartum group A streptococcal infections occurring within the past five years at a single medical center. These cases were not epidemiologically linked and serve to illustrate the continuing risk of these potentially fulminant infections.

Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of "Castration-Resistant" prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6-8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa.