Acute myeloid leukemia complicated by post COVID-19 multi-system inflammatory syndrome-children

Corona Virus disease 2019 (COVID-19) pandemic has presented a huge challenge to the health care system in terms of magnitude of cases and to pediatric oncology units with varied clinical presentations. Acute myeloid leukemia(AML) is a rare heterogenous cancer of childhood with an induction mortality around 15% in our country due to neutropenic sepsis. Multisystem inflammatory syndrome in children(MIS-C) is an hyperinflammatory syndrome seen 4–6 weeks after COVID-19 infection. COVID infection in some of these children would have gone unnoticed. Here we report a two year eight months old boy diagnosed with AML on induction chemotherapy developed post COVID MIS-C. © 2022

Twins early development study (teds): A genetically sensitive investigation of mental health outcomes in the mid-twenties

The Twins Early Development Study (TEDS) is a longitudinal study following a cohort of twins born 1994-1996 in England and Wales. Of the 13,759 families who originally consented to take part, over 10,000 families remain enrolled in the study. The current focus of TEDS is on mental health in the mid-twenties. Making use of over 25 years of genetically sensitive data, TEDS is uniquely placed to explore the longitudinal genetic and environmental influences on common mental health disorders in early adulthood. This paper outlines recent data collection efforts supporting this work, including a cohort-wide mental health assessment at age 26 and a multi-phase Covid-19 study. It will also provide an update on data linkage efforts and the Children of TEDS (CoTEDS) project. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics

Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy;reliable estimates of waiting times and ‘patient flow' would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees' movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36–3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males;p<0.001) and attending with a baby (18.8 minutes longer than those without;p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700;p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46–100]) than outdoors (2.5% [IQR 0–35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1–75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-touch estimation of occupancy density may help guide interventions to improve patient flow.

Student satisfaction with use of an online peer feedback system

We contribute to the growing evidence of the positive effect of use of online peer feedback tools on students' teamwork skills development. We do so by exploring individual and contextual factors underlying satisfaction with using a peer feedback system alongside team projects. Employing path analytical framework and bootstrap methods, we analysed data from an international sample of 100 project teams in management studies. Drawing on procedural justice theory, we theorised and found support that students' uncertainty avoidance orientation and virtuality in collaboration were positively related to their satisfaction with use of a peer feedback system. Such satisfaction in turn allowed them to be more effective team members. Our findings provide evidence for higher education institutions and instructors considering the adoption of online peer feedback systems alongside teamwork in their curricula. Specifically, peer feedback appears to be effective in the development of teamwork skills and students appreciate the opportunity to provide feedback to their peers in a structured and dedicated environment. Our findings are timely and of important practical significance as educational institutions increasingly rely on the use of computer-mediated technology during the COVID-19 pandemic. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Psychotic Disorders in the Elderly: Diagnosis, Epidemiology, and Treatment.

This review covers the latest advances in our understanding of psychosis in the elderly population with respect to diagnosis, epidemiology, and treatment. Major topics of discussion include late life psychiatric disorders such as schizophrenia, schizoaffective disorder, and delusional disorder as well as dementia-related psychosis. Clinical differences between early-onset and late-onset disorders are reviewed in terms of prevalence, symptomatology, and approach to treatment. Newly revised research and clinical criteria for dementia-related psychosis are referenced. The evidence base for emerging therapies including citalopram and pimavanserin in relation to conventional therapies such as atypical antipsychotics are discussed..

Predictive accuracy of neutrophil-to-lymphocyte ratio on severity and outcomes in COVID-19 patients: A retrospective study

Background/Aims: Neutrophil-to-lymphocyte ratio (NLR) is a proven marker in coronavirus disease 2019 (COVID-19) severity and mortality. However, the utility of a sequential NLR 2 (on day 5) in comparison to baseline NLR in predicting clinical outcomes and severity remains largely unexplored. Methods: This was a hospital-based retrospective observational study. Results: Higher mortality (19.9% vs. 48%) and a more severe disease (14.8% vs. 21%) were observed with elevated NLR 1 and NLR 2, respectively. NLR 2 at a cutoff of 9.88 was a better predictor of mortality, when compared to NLR 1 at 5.67, and NLR 2 has a strong correlation with mortality rates in COVID-19. Conclusion: Our study demonstrated that NLR 1 and NLR 2 were more reliable predictors of mortality than disease severity;in comparison, NLR 2 is a more accurate predictor of mortality than NLR 1. The study unravels the potential role of a sequential NLR 2, to have a better correlation in predicting the clinical severity and outcomes. The potential role of NLR 2 in assessing the interim progression of the disease and thereby initiating specific interventions at critical junctures to influence the outcome is unveiled and merits exploration in detail by larger studies. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics.

Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and 'patient flow' would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees' movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36-3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p<0.001) and attending with a baby (18.8 minutes longer than those without; p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46-100]) than outdoors (2.5% [IQR 0-35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1-75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-touch estimation of occupancy density may help guide interventions to improve patient flow.

Using Remotely Supervised At-Home TES for Enhancing Mental Resilience.

We are in the midst of a mental health crisis with major depressive disorder being the most prevalent among mental health disorders and up to 30% of patients not responding to first-line treatments. Noninvasive Brain Stimulation (NIBS) techniques have proven to be effective in treating depression. However, there is a fundamental problem of scale. Currently, any type of NIBS treatment requires patients to repeatedly visit a clinic to receive brain stimulation by trained personnel. This is an often-insurmountable barrier to both patients and healthcare providers in terms of time and cost. In this perspective, we assess to what extent Transcranial Electrical Stimulation (TES) might be administered with remote supervision in order to address this scaling problem and enable neuroenhancement of mental resilience at home. Social, ethical, and technical challenges relating to hardware- and software-based solutions are discussed alongside the risks of stimulation under- or over-use. Solutions to provide users with a safe and transparent ongoing assessment of aptitude, tolerability, compliance, and/or misuse are proposed, including standardized training, eligibility screening, as well as compliance and side effects monitoring. Looking into the future, such neuroenhancement could be linked to prevention systems which combine home-use TES with digital sensor and mental monitoring technology to index decline in mental wellbeing and avoid relapse. Despite the described social, ethical legal, and technical challenges, the combination of remotely supervised, at-home TES setups with dedicated artificial intelligence systems could be a powerful weapon to combat the mental health crisis by bringing personalized medicine into people's homes.

Outcomes of multiple sclerosis patients admitted with COVID-19 in a large veteran cohort.

BACKGROUND: Given concerns over immune function, the decision whether to continue disease modifying therapy (DMT) in multiple sclerosis (MS) patients during the COVID-19 pandemic has been challenging, complicated by the risk of MS disease progression in the absence of treatment. METHODS: This retrospective analysis of patients treated for COVID-19 infection at veteran affairs healthcare systems across the United States, investigated 30-day all-cause mortality after first positive COVID-19 in patients with and without MS. We examined mortality risk impact of disease modifying therapy for MS, accounting for other relevant factors known to be associated with COVID-19 mortality. Patients were propensity score matched in a 1:20 fashion based on MS diagnosis. RESULTS: 49,737 COVID-19 inpatient cases were identified, of which 258 were diagnosed with MS. In the propensity score matched cohort, MS patients taking DMT (excluding those receiving anti-CD20 antibodies) had a lower odds of 30 day mortality (OR: 0.18 [95%CI: 0.00988-0.94] p=0.041). Similarly, in the unmatched cohort, patients on DMT had a lower risk of death (OR: 0.16 [95%CI: 0.01-0.82] p=0.023). There was no statistically significant difference in mortality between those with and without MS. In the propensity matched cohort, age over 65, heart failure, chronic kidney disease (CKD), and diabetes increased the risk of mortality while vaccination reduced the risk of mortality. CONCLUSION: Veteran patients with MS hospitalized for COVID-19 were less likely to die when taking DMTs (excluding those receiving anti-CD20 antibodies), accounting for other relevant factors. Results suggest that, in relation to the COVID-19 pandemic, not only is it safe to continue most DMTs in people with MS, but it may be beneficial given the decreased risk of COVID-19 mortality and decreased risk of MS disease progression.

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants.

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titres of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titres in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

Regional Impact of COVID-19-Associated Pulmonary Aspergillosis (CAPA) during the First Wave.

BACKGROUND: Critically ill COVID-19 patients have proven to be at risk for developing invasive fungal infections. However, the incidence and impact of possible/probable COVID-19-associated pulmonary aspergillosis (CAPA) in severe COVID-19 patients varies between cohorts. We aimed to assess the incidence, risk factors, and clinical outcome of invasive pulmonary aspergillosis in a regional cohort of COVID-19 intensive care patients. METHODS: We performed a regional, multicentre, retrospective cohort study in the intensive care units (ICUs) in North Brabant, The Netherlands. We included adult patients with rt-PCR-confirmed SARS-CoV-2 infection (COVID-19), requiring mechanical ventilation for acute respiratory distress syndrome. Demographics, clinical course, biomarker value, and treatment outcomes were compared between the groups with possible/probable CAPA from the main study centre and the regional centres, and without signs of CAPA from the main study centre as controls. The primary aim was to assess the regional impact of possible/probable CAPA in COVID-19 ICU patients, measured as all-cause mortality at 30 days after ICU admission. Secondary outcomes were risk factors for developing CAPA, based on underlying host factors and to identify the value of the mycological arguments for the diagnosing of CAPA. RESULTS: Between 1 March and 30 April 2020, we included 123 patients with severe COVID-19: 29 patients (30.9%) in the main ICU with possible/probable CAPA, and 65 (69.1%) with no signs of CAPA; 29 patients in the regional ICUs with signs of CAPA. Patients' characteristics and risk factors did not differ for CAPA and non-CAPA patients. Patients with COPD and/or chronic steroid medication developed CAPA more frequently, although this was not statistically significant. CAPA patients were admitted to the ICU earlier, had lower PF-ratios, and more often required renal replacement therapy. All-cause 30-day mortality was significantly higher in mechanically ventilated COVID-19 patients with possible/probable CAPA 39.7% (23/58) compared to patients without evidence for CAPA 16.9% (11/65) (OR 3.2 [95% CI 1.4-7.4] p = 0.005). CONCLUSION: The high incidence of possible and probable CAPA in critically ill COVID-19 patients is alarming. The increase in 30-day mortality in CAPA highlights the need for active surveillance and management strategies in critically ill COVID-19 patients.

Feasibility of infection control measures in hemodialysis units to prevent outbreaks of COVID-19: A descriptive study from quebec

Background: In-center hemodialysis (HD) units pose the perfect conditions for COVID-19 transmission yet limited space and resources are obstacles to infection prevention and control (IPAC) measures. We aimed to describe IPAC measures implemented and document the infection rates within HD units during the first year of the pandemic. Methods: We invited leaders of Quebec's HD units to collect information on IPAC measures from March 1st to June 30th 2020 and HD unit characteristics. Participating units were contacted again in March 2021 to collect information about the total number of cases. The cumulative infection rate of each unit was compared to the regional cumulative infection rate using a standardized infection ratio (SIR). Results: Data was obtained from 38 units, representing 90% of Quebec's HD patients. 30% of units were perceived as crowded, and this was associated with objective distance measures between stations, which was much more likely to be <2m in units considered crowded (83.3% vs 19.2% p<0.001). IPAC measures regarding general prevention, screening procedures, physical distancing, and PPE use were implemented in 50% of units by 3 weeks and the remainder by 6 weeks. Data on cumulative infection rate was obtained in 26 units providing care to 3942 patients. The cumulative infection rate was disproportionally elevated in HD units compared to regional rates (Median SIR:2.68 IQR:1.58;4.45)(Figure 1). No difference was noted in the SIR related to specific IPAC measures or to the physical characteristics of the units. Conclusions: Hemodialysis units throughout Quebec were able to rapidly implement modified IPAC measures. Despite this, infection rates were disproportionally elevated.

Cryo-EM structure determination of small proteins by nanobody-binding scaffolds (Legobodies).

We describe a general method that allows structure determination of small proteins by single-particle cryo-electron microscopy (cryo-EM). The method is based on the availability of a target-binding nanobody, which is then rigidly attached to two scaffolds: 1) a Fab fragment of an antibody directed against the nanobody and 2) a nanobody-binding protein A fragment fused to maltose binding protein and Fab-binding domains. The overall ensemble of ∼120 kDa, called Legobody, does not perturb the nanobody-target interaction, is easily recognizable in EM images due to its unique shape, and facilitates particle alignment in cryo-EM image processing. The utility of the method is demonstrated for the KDEL receptor, a 23-kDa membrane protein, resulting in a map at 3.2-Šoverall resolution with density sufficient for de novo model building, and for the 22-kDa receptor-binding domain (RBD) of SARS-CoV-2 spike protein, resulting in a map at 3.6-Šresolution that allows analysis of the binding interface to the nanobody. The Legobody approach thus overcomes the current size limitations of cryo-EM analysis.

Rapid mortality surveillance using a national population register to monitor excess deaths during SARS-CoV-2 pandemic in South Africa.

This paper describes how an up-to-date national population register recording deaths by age and sex, whether deaths were due to natural or unnatural causes, and the offices at which the deaths were recorded can be used to monitor excess death during the SARS-CoV-2 pandemic, both nationally, and sub-nationally, in a country with a vital registration system that is neither up to date nor complete. Apart from suggesting an approach for estimating completeness of reporting at a sub-national level, the application produces estimates of the number of deaths in excess of those expected in the absence of the SARS-CoV-2 epidemic that are highly correlated with the confirmed number of COVID-19 deaths over time, but at a level 2.5 to 3 times higher than the official numbers of COVID-19 deaths. Apportioning the observed excess deaths more precisely to COVID, COVID-related and collateral deaths, and non-COVID deaths averted by interventions with reduced mobility and gatherings, etc., requires access to real-time cause-of-death information. It is suggested that the transition from ICD-10 to ICD-11 should be used as an opportunity to change from a paper-based system to electronic capture of the medical cause-of-death information.

Estimating ventilation rates in rooms with varying occupancy levels: Relevance for reducing transmission risk of airborne pathogens.

BACKGROUND: In light of the role that airborne transmission plays in the spread of SARS-CoV-2, as well as the ongoing high global mortality from well-known airborne diseases such as tuberculosis and measles, there is an urgent need for practical ways of identifying congregate spaces where low ventilation levels contribute to high transmission risk. Poorly ventilated clinic spaces in particular may be high risk, due to the presence of both infectious and susceptible people. While relatively simple approaches to estimating ventilation rates exist, the approaches most frequently used in epidemiology cannot be used where occupancy varies, and so cannot be reliably applied in many of the types of spaces where they are most needed. METHODS: The aim of this study was to demonstrate the use of a non-steady state method to estimate the absolute ventilation rate, which can be applied in rooms where occupancy levels vary. We used data from a room in a primary healthcare clinic in a high TB and HIV prevalence setting, comprising indoor and outdoor carbon dioxide measurements and head counts (by age), taken over time. Two approaches were compared: approach 1 using a simple linear regression model and approach 2 using an ordinary differential equation model. RESULTS: The absolute ventilation rate, Q, using approach 1 was 2407 l/s [95% CI: 1632-3181] and Q from approach 2 was 2743 l/s [95% CI: 2139-4429]. CONCLUSIONS: We demonstrate two methods that can be used to estimate ventilation rate in busy congregate settings, such as clinic waiting rooms. Both approaches produced comparable results, however the simple linear regression method has the advantage of not requiring room volume measurements. These methods can be used to identify poorly-ventilated spaces, allowing measures to be taken to reduce the airborne transmission of pathogens such as Mycobacterium tuberculosis, measles, and SARS-CoV-2.

A Simple Ventilator Designed To Be Used in Shortage Crises: Construction and Verification Testing.

BACKGROUND: The COVID-19 pandemic has demonstrated the possibility of severe ventilator shortages in the near future. OBJECTIVE: We aimed to develop an acute shortage ventilator. METHODS: The ventilator was designed to mechanically compress a self-inflating bag resuscitator, using a modified ventilator patient circuit, which is controlled by a microcontroller and an optional laptop. It was designed to operate in both volume-controlled mode and pressure-controlled assist modes. We tested the ventilator in 4 modes using an artificial lung while measuring the volume, flow, and pressure delivered over time by the ventilator. RESULTS: The ventilator was successful in reaching the desired tidal volume and respiratory rates specified in national emergency use resuscitator system guidelines. The ventilator responded to simulated spontaneous breathing. CONCLUSIONS: The key design goals were achieved. We developed a simple device with high performance for short-term use, made primarily from common hospital parts and generally available nonmedical components to avoid any compatibility or safety issues with the patient, and at low cost, with a unit cost per ventilator is less than $400 US excluding the patient circuit parts, that can be easily manufactured.