Supplemental Oxygen Requirement Research Articles

Steroid prescribing practices for mildly symptomatic and asymptomatic COVID-19 patients, among doctors of selected Sri Lankan hospitals

Introduction: Effects of infection by SARS-COV-2 virus (COVID-19) range from asymptomatic infection to respiratory failure with multi-organ dysfunction. Steroids are indicated in patients with severe pneumonia, who require oxygen supplementation. There is evidence of harm if steroids are given for asymptomatic or mildly symptomatic patients.Objectives: This study assesses the steroid prescribing practices among Sri Lankan doctors for mildly symptomatic and asymptomatic COVID-19 patients.Methodology: This clinical survey was conducted during 20/11/2021 to 15/03/2022 using an electronic questionnaire, sent to doctors in 16 hospitals, representing all provinces of Sri Lanka. Doctors who have not treated nor advised patients with COVID-19 were excluded.Results: Hundred and thirty-five participants were incorporated into the study. The mean age was 33.7 years (SD=7.82). The majority did not prescribe steroids routinely for asymptomatic (n=132, 97.8%) and mildly symptomatic (n=124, 91.9%) COVID-19. Dexamethasone was the most prescribed steroid. Doctors who treated COVID-19 patients in the private sector were more likely to prescribe steroids for mild symptoms (p=0.016). The majority (n=101, 81.5%) identified a decrease of oxygen saturation to below 94% on room air as an indication to start steroids.Conclusions: Most of the study participants adhered to the recommended guidelines and refrained from prescribing steroids in mildly symptomatic and asymptomatic COVID-19 patients.

Large-bore aspiration thrombectomy versus catheter-directed thrombolysis for the treatment of pulmonary embolism: A retrospective case review from a community hospital

Objectives: This study aimed to assess acute outcomes following pulmonary embolism (PE) treatment with large-bore aspiration thrombectomy (LBAT) versus catheter-directed thrombolysis (CDT). Material and Methods: This single-center retrospective analysis included patients who received interventional therapy for acute PE from 2018 to 2022. The primary outcomes were changes in pre-procedural mean pulmonary artery pressure (PAP), heart rate (HR), oxygen saturation, and supplemental requirements following the procedure. Mean PAP was measured immediately post-procedure for LBAT patients and on postoperative day 1 (POD#1) for CDT patients. Results: A total of 48 patient cases were reviewed, 31 underwent LBAT and 17 underwent CDT. The majority of patients were female and most had intermediate-high-risk PE. No major bleeding events or device-related complications occurred. LBAT resulted in a significant decrease in average mean PAP immediately post-procedure (31.3 ± 9.0–21.4 ± 8.1 mmHg; P < 0.001). On POD#1, CDT resulted in a significant decrease in mean PAP (31.7 ± 11.2–25.6 ± 7.9 mmHg; P = 0.005). The decrease in mean PAP was greater in the LBAT versus CDT group (P < 0.05). Through POD#1, a similar reduction in average HR was observed between groups; however, a statistically significant reduction in HR was noted immediately post-procedure with LBAT and not with CDT. LBAT patients had a significant reduction in average supplemental oxygen requirements post-procedure. Conclusion: LBAT was associated with a greater reduction in mean PAP than CDT at an earlier post-procedural time point. LBAT may be advantageous over CDT due to rapid thrombus extraction; however, further studies with increased sample sizes are needed. Evidence-based medicine: Level of Evidence: Level 3, Local non-random sample.

Evaluating fluvoxamine for the outpatient treatment of COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to evaluate the efficacy, safety, and tolerability of fluvoxamine for the outpatient management of COVID-19. We conducted this review in accordance with the PRISMA 2020 guidelines. Literature searches were conducted in MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, Web of Science, and CENTRAL up to 14 September 2023. Outcomes included incidence of hospitalisation, healthcare utilization (emergency room visits and/or hospitalisation), mortality, supplemental oxygen and mechanical ventilation requirements, serious adverse events (SAEs) and non-adherence. Fluvoxamine 100mgtwice a day was associated with reductions in the risk of hospitalisation (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58-0.97; I 2 =0%) and reductions in the risk of healthcare utilization (RR 0.68, 95% CI 0.53-0.86; I 2 =0%). While no increased SAEs were observed, fluvoxamine 100mgtwice a day was associated with higher treatment non-adherence compared to placebo (RR 1.61, 95% CI 1.22-2.14; I 2 =53%). In subgroup analyses, fluvoxamine reduced healthcare utilization in outpatients with BMI ≥30kg/m2 , but not in those with lower BMIs. While fluvoxamine offers potential benefits in reducing healthcare utilization, its efficacy may be most pronounced in high-risk patient populations. The observed non-adherence rates highlight the need for better patient education and counselling. Future investigations should reassess trial endpoints to include outcomes relating to post-COVID sequelaes. Registration: This review was prospectively registered on PROSPERO (CRD42023463829).

88. Fostamatinib for the Treatment of Hospitalized Patients With COVID-19 Who Required Oxygen Supplementation: Results of a Phase 3 Trial

Abstract Background Severe COVID-19 is linked to hyperactivation of the host immune response involving signaling through multiple spleen tyrosine kinase (SYK) pathways. Fostamatinib is an orally administered potent and selective inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune thrombocytopenia (ITP). Methods We conducted a double-blind, randomized, placebo-controlled phase 3 trial of fostamatinib in adults hospitalized for COVID-19 who required oxygen supplementation (NCT04629703). Patients (pts) were randomly assigned 1:1 to receive fostamatinib (150 mg BID administered orally) or placebo for 14 days. All pts additionally received standard of care at their hospital. The primary endpoint was days on oxygen (days 1-29). Results A total of 280 pts underwent randomization (with 141 assigned to fostamatinib and 139 to placebo). The primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs. 7.6 days, P=0.0136; Table 1). Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in pts who received fostamatinib vs. placebo (P=0.0092,Table 1). Furthermore, 6 pts were enrolled with a baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30. A significantly higher proportion of pts who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (P=0.0029,Table 1). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (P=0.0213 and P=0.0271, respectively, Table 1). Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups. Conclusion The addition of fostamatinib to standard of care treatment resulted in significantly fewer days on oxygen, an improved 8-point ordinal scale score, and significantly more patients alive and oxygen-free by Day 60 compared to placebo in pts with COVID-19 requiring hospitalization and supplemental oxygen. Disclosures Deepa B. Gotur, MD, FCCP, FCCM, GSK: Advisor/Consultant|GSK: Speaker at ATS|Moderna: Advisor/Consultant Vadim Markovtsov, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Lucy Yan, MD, PhD, Rigel Pharmaceuticals, Inc.: Employee|Rigel Pharmaceuticals, Inc.: Stocks/Bonds Wolfgang Dummer, MD, PhD, Rigel Pharmaceuticals, Inc.: Stocks/Bonds.

1213. Application of Short Course Criteria for Community-Acquired Pneumonia (CAP) Among Patients Admitted Within a 17-community Hospital Telehealth Antimicrobial Stewardship Program (Tele-ASP)

Abstract Background A recent randomized controlled trial by Dinh et al. found three days of antibiotics was appropriate for certain community-acquired pneumonia (CAP) patients, but the real-world applicability of this study remains to be evaluated. In February 2022, a telehealth antimicrobial stewardship program (Tele-ASP) intervention was implemented across 17 small community hospitals to identify patients meeting clinical stability criteria used by Dinh et al. for short course therapy (3 days). An alert was implemented to notify the infectious diseases telehealth (Tele-ID) pharmacist of patients on room air for whom an antibiotic was ordered for pneumonia. Methods This IRB-approved study aimed to evaluate feasibility and impact of the intervention. Patients with severe or complicated CAP, known immunosuppression, or who were transferred were excluded. The primary outcome was total antibiotic duration. Secondary outcomes included whether the total duration was greater than 5 and 7 days and total IV antibiotic duration. Continuous antibiotic duration endpoints were assessed using Mann Whitney U and Fisher's Exact tests were used for categorical endpoints. Results Of 480 patients screened, only 148 (31%) patients met early clinical stability criteria. The primary reason for not meeting criteria was requirement of supplemental oxygen on Day 3 or greater on antibiotics (n=145). This proportion is far lower than previous studies, including that by Dinh et al., which found 60-70% patients met stability criteria. Of the 90 patients included, 27 patients had a Tele-ID review. Patients with an intervention were less likely to receive > 5 days of antibiotics (59% vs 73%) and > 7 days of antibiotics (19% vs. 32%), although these differences were not statistically significant. Conclusion This study relied on accuracy of oxygen charting, which may partly explain relatively lower proportion of patients meeting strict clinical stability criteria and likely limits feasibility of a scalable intervention. A pragmatically modified approach for this Tele-ASP intervention (i.e. allowance for no more than 1 unmet criterion) is an important area for further exploration and could improve the feasibility of a scalable telehealth intervention. Disclosures All Authors: No reported disclosures

A Clinicoradiological Profile of H3N2 Outbreak in Western India

Abstract Introduction: Although H3N2 outbreaks were once rare, they have become more common in recent years. With a significant toll on health-care resources and the ability to cripple any society, the epidemiological significance of this disease is paramount. While most of the previous studies on influenza outbreaks have reported H1N1 disease, there is a scarcity of literature regarding the H3N2 clinicoradiological profile. Hereby, we present the clinicoradiological profile of a series of H3N2 cases from western India. Materials and Methods: This is a retrospective chart-based review of clinicoradiological profile of a series of cases that were reported to a tertiary care center in western India between February 2023 and March 2023. Results: A total of 10 patients had tested positive for H3N2. All patients had a history of fever lasting an average of 4.7 days, and six had varying degrees of dyspnea. One patient had gastrointestinal symptoms, and six developed tachypnea with hypoxemia requiring oxygen supplementation. One patient with multiple comorbidities required invasive mechanical ventilation and had a complicated course with a superadded bacterial infection. Out of the four patients with radiographic findings, two had atypical pneumonia/acute infective etiology. Conclusion: This study provides valuable insights into the clinical presentation and management of H3N2 infections. The findings highlight the importance of influenza vaccination and early detection of H3N2 infections to prevent severe complications. The successful outcomes of the patients in this study demonstrate the effectiveness of prompt intervention and appropriate treatment in managing H3N2 infections.

Oxygen Requirement and Associated Risk Factors in Post-COVID-19 Patients Admitted to a Tertiary Care Center: A Cross-Sectional Study.

COVID-19 commonly affects the lungs and may lead to mild to severe hypoxemia. The supplemental oxygen requirement gradually reduces with the improvement in lung pathology. However, a few patients may have exertional desaturation, and ongoing oxygen needs at the time of hospital discharge. The objective of this research was to study the requirement of oxygen therapy in the immediate post-COVID-19 period and its associated risk factors. An analytical cross-sectional study was conducted on the admitted post-COVID-19 patients who had recently tested real-time polymerase chain reaction (RT-PCR) negative in a tertiary care center from August 2021 to mid of October 2021. Nonprobability consecutive sampling was used, and the sample size was 108. The data were analyzed using the Statistical Package for the Social Sciences (IBM-SPSS), version 23. The mode of oxygen therapy (nasal cannula, face mask, reservoir mask, or mechanical ventilation) in the first two weeks of the study was presented appropriately in a table. The nonparametric statistical tests were applied to determine the association between the duration of post-COVID-19 oxygen therapy and several other risk factors such as age, gender, comorbidities, smoking status, exposure to firewood, COVID-19 vaccination, and severity of COVID-19. 95 (87.96%) cases required oxygen therapy in their immediate post-COVID-19 period. The overall median duration of oxygen therapy was 6.00 (4.00-10.00) days. The nasal cannula was the most commonly used mode of oxygen supplement. The duration of oxygen therapy was significantly higher in patients aged more than 60 years (6.00 [5.00-11.00], p = 0.013), chronic obstructive pulmonary disease (10.00 [6.00-12.75], p = 0.006), history of chronic smoking (9.00 [5.50-13.00], p = 0.044), and severe COVID-19 infection (7.00 [5.00-10.50], p = 0.042). The proportion of patients requiring oxygen therapy in the immediate post-COVID-19 period was higher than that reported in other studies. In addition, old age (>60 years), chronic obstructive pulmonary disease, chronic smoking, and severe COVID-19 infection significantly increased the duration of oxygen therapy. So, these factors should be assessed while discharging patients from COVID-19 facilities, and oxygen supplementation should be planned for needy patients.

Prevalence of Sleep Disordered Breathing in Adult Sickle Cell Clinic Patients and Cardiovascular Correlates

Sleep disordered breathing (SDB) is strongly correlated with hypertension and cardiovascular disease in the general population, and especially in African Americans. In Sickle Cell Disease (SCD), the adverse effect of nocturnal hypoxemia is anticipated to have additional adverse effects with the sickling of red blood cells and microvascular thrombosis unique to the disease. Prospective data regarding the prevalence and consequences of SDB in this population are lacking. In an ongoing study, 27 adult subjects (age > 18 years), with homozygous HbSS genotype, presenting to the Howard University Sickle Cell Center for routine follow up have been recruited irrespective of the presence of sleep symptoms. Exclusion criteria include previous diagnosis or treatment of a sleep disorder or requirement for supplemental oxygen. Testing occurs when subjects are in a stable phase of disease, with no hospitalizations or medication changes for 4 weeks. In addition to clinical history and questionnaires, participants are assessed with blood work, 6 minute walk testing, pain and sleep diaries during 1 week actigraphy, transthoracic echocardiography and overnight in lab polysomnography with capnography. At the time of this interim analysis, the mean age is 42 (range 29-71, +/- std dev 11) and male:female distribution is 17:10. The mean BMI is 20.4 (+/- 4.5). Mean Hgb is 9.1 g/dl (+/- 1.8) and mean LDH is 325 iu/L (+/- 163). Polysomnography scoring utilized a 3% desaturation criterion for hyponeas as per American Academy of Sleep Medicine Scoring Manual Chapter VIII, 1A. Mean sleep efficiency is 77% ( std dev +/- 4.2%). 48% of subjects demonstrate some degree of sleep disordered breathing as defined by an AHI > 5 events/hour (33% mild, 4% moderate, 11% severe). 70% of subjects demonstrate an RDI > 5 events/hour (40% mild, 19% moderate, 11% severe). Twelve participants (44%) exhibit more than 5 minutes sleep duration at saturations <89% (mean = 187 minutes). Hypercapnia is not suggested as an important component of SDB with the mean ET CO2 = 40.7 mm Hg (range 30-46 mm Hg). Echocardiographic values (LVPWd, Lad, MV E/A, PVV, and RVSP) do not correlate with any indices of sleep disordered breathing other than minutes <89% saturation correlating with RVSP. In summary, this interim analysis of sleep in a population of unselected Sickle Cell Clinic patients demonstrates a striking frequency of sleep disordered breathing. This is despite a generally low BMI for these patients which is typically considered one of the most important risk factor for sleep apnea. Ongoing recruitment is planned to confirm these findings. Correlation with clinical outcomes and potential response to therapeutic interventions will be important future research questions.

Rare Sighting of an Unstable Hemoglobin Variant [ Β11 (A8) Val → Asp]: Hemoglobin Windsor

Hemoglobin (Hb) is the major blood oxygen carrier where Hb subunits bind oxygen via the heme iron buried within a hydrophobic pocket that faces the outside of HbA tetramers. Iron must be in its reduced (ferrous, Fe2+) state for Hb to bind oxygen. Oxidized or metHb (ferric, Fe3+) cannot bind oxygen and is relatively unstable. Globin mutations that alter amino acids within the ligand pocket lead to changes in affinity for oxygen, and increased rates of metHb formation and heme loss. We present the case of a patient with a rare variant “Hb Windsor” which has only been described once in the literature. The patient is a 20-year-old Mexican male with a history of hepatitis B presenting with three days of fevers, chills, nausea and vomiting. The patient reported a diagnosis of hepatitis at the age of eight in Mexico and with jaundice all his life. He had no prior hospitalizations or blood transfusions. He denied any unusual food ingestions or recent foreign travel. In the emergency room, the patient was hypoxic with a SpO2 73% and tachypneic which improved with supplemental oxygen. On physical examination, the patient was jaundiced with scleral icterus and the spleen was easily palpable to the midline. CT scan confirmed splenomegaly measuring 20 cm. Labs showed a white blood count 21.6 nl, hemoglobin 4.2 g/dl, platelet count 33 nl, lactate dehydrogenase 13 unit/L and reticulocyte count 24%, total bilirubin 16 mg/dl, direct bilirubin 4 mg/dl and methemoglobin 20.9%. The patient was administered methylene blue and transfused two units of packed red blood cells with hemoglobin increasing to 7.1 g/dl. HIV, hepatitis B and C, direct antiglobulin test, and G6PD testing were negative. The peripheral smear showed numerous nucleated red cells, increased polychromasia with red cells showing numerous microspherocytes, microanthocytes, and bubbled cells with significant basophilic stippling. No fragmented cells were present. The clinical history and lab findings suggested a chronic hemolytic anemia, and the peripheral smear suggested a possible hemoglobinopathy. Hemoglobin electrophoresis by high performance liquid chromatography showed an unknown hemoglobin of 22.5%. Isoelectric focusing showed Hb A 71.9%, F, Hb A2 4.6%, Hb F 0.3%, and an abnormal band of 23% in the hemoglobin M range. Specimens were sent for DNA sequencing and a point mutation in the beta chain was found leading to a valine to aspartate substitution in the A8 position. Protein analysis showed a valine is substituted with aspartic acid in the ligand pocket which is the unstable varian Hb Windsor. This substitution in the base of the heme pocket results in instability of the hemoglobin molecule and an increase in oxygen affinity. The residues lining the heme pocket function as a hydrophobic basket from the heme iron, preventing its oxidation to the ferric state. Valine, which occupies position A8 is a hydrophobic amino acid. However, in Hb Windsor, the valine is substituted by aspartic acid, a polar molecule. The hydrophilic nature of aspartic acid, a polar molecule, may disrupt the hydrophobic nature of the heme pocket. The valine at position A8 also acts as a contact with the H helix which is lost in Hb Windsor leading to decreased Hb stability. These substitutions cause heme iron to auto-oxidize which results in methemoglobinemia. Hb M has iron in the ferric state (Fe3+) and is unable to carry oxygen which produces cyanosis. Our patient was found to be hypoxic requiring oxygen supplementation and found to have methemoglobinemia. We present a rare case of a hemoglobin variant Hb Windsor in a Mexican adult which has only been previously documented in a nine-month-old Anglo-Saxon infant. This variant seems to be a spontaneous de novo mutation as both patients had no family history of anemia. It is hypothesized that the hemolysis was precipitated by oxidative stress of an acute infection in the setting of an unstable hemoglobin. The patient was found to have stable hemoglobin of 12 g/dl and methemoglobin of 4.9% in follow up several years later.

The impact of impaired insulin regulation on severity of SARS-CoV-2 infection: a 2-year retrospective single-center analysis

Background: The COVID-19 pandemic has caused an international healthcare crisis and produced a large healthcare burden. Diabetes mellitus (DM) is a common disease that can be controlled via pharmacologic agents; however, many patients have poor glycemic control, leading to disease-related complications. DM has been reported in the literature to be associated with increasing morbidity and mortality in COVID-19 patients. The authors aim to assess the associations between glucose homoeostasis and COVID-19 disease severity and mortality. Methods: A retrospective chart review of patients ages 18–100 years of age admitted with COVID-19 between January 2020 and December 2021 was performed. The primary outcome was COVID-19 mortality with respect to haemoglobin A1C levels of less than 5.7%, 5.7–6.4%, and 6.5% and greater. Disease severity was determined by degree of supplemental oxygen requirements (ambient air, low-flow nasal cannula, high-flow nasal cannula, non-invasive mechanical ventilation, and invasive mechanical ventilation). COVID-19 mortality and severity were also compared to blood glucose levels on admission as grouped by less than 200 mg/dl and greater than or equal to 200 mg/dl. Results: A total of 1156 patients were included in the final analysis. There was a statistically significant association between diabetic status and mortality (P=0.0002). Statistical significance was also noted between admission blood glucose ≥200 mg/dl and mortality (P=0.0058) and respiratory disease severity (P=0.0381). A multivariate logistic regression for predicting mortality showed increasing haemoglobin A1C was associated with increased mortality (odds ratio 1.72 with 95% CI of 1.122–2.635). Conclusions: In our 2-year retrospective analysis, there was an association between a diagnosis of DM and COVID-19-related mortality. Hyperglycaemia on admission was found to be statistically significant with mortality in patients diagnosed with COVID-19. Glucose homoeostasis and insulin dysregulation likely play a contributing factor to COVID-19 disease severity and mortality.

Duration and aetiology of extended hospitalization among COVID-19 patients in United Arab Emirates.

A retrospective review of the early stages of the COVID-19 pandemic in 2020 and the challenges faced by hospitals is essential in the post-pandemic era of 2022. To identify the reasons for prolonged hospitalization after recovery for COVID-19 patients in the United Arab Emirates. This was a retrospective observational study of 150 (18.75%) patients with prolonged hospitalization in a tertiary hospital in Dubai from 1 April to 1 July 2020. Data was obtained from the electronic medical records of the hospital. Continuous variables are reported as mean and standard deviation, and categorical variables are reported as numbers and percentages. The mean duration of hospitalization was 48.5 (9-272) days, with an interquartile range (IQR) of 22 days. The mean duration of extended stay was 27.5 (2-231) days, with an IQR of 17 days. The common reasons for prolonged hospitalization were mandatory isolation 28% (n = 62), hospital-acquired infections 17% (n = 37), acute respiratory distress syndrome 15% (n = 32), myopathy/neuropathy 14% (n = 31), pulmonary fibrosis requiring oxygen supplementation 14% (n = 31), and completion of COVID-19 treatment 12% (n = 25). To make optimal use of available hospital resources, reasons that directly or indirectly contributed to the prolonged hospitalization of patients should be considered and addressed during future pandemics or disease outbreaks.

Gabapentin May Not Decrease Opioid Use in Pediatric Enhanced Recovery After Surgery Protocols

IntroductionIn adults, the use of gabapentin in Enhanced Recovery After Surgery (ERAS) protocols is associated with increased morbidity and clinically insignificant improvement in postoperative pain control. Furthermore, there are limited data supporting its use in pediatric ERAS protocols. MethodsA single-institution retrospective study was performed to examine the correlation of gabapentin use and postoperative outcomes among children who underwent elective general, urologic, and orthopedic surgeries. Because gabapentin was removed from our institutional ERAS protocols in August 2020, we compared eligible patients from January 2018 to September 2021 using univariate and multivariable analysis. Due to heterogeneity between the treatment groups, a propensity score–matched analysis was also performed. Significance was defined as P < 0.05. ResultsIn this study, 196 patients were included, with 91 (46.4%) who received gabapentin and 105 (53.6%) who did not. When used in combination with opioids, gabapentin was not associated with a reduction in the amount of opioids consumed (β = −0.4, 95% confidence interval = −1.9, 1.1). Instead, children who received gabapentin had increased odds of requiring oxygen supplementation (odds ratio = 3.1, 95% confidence interval = 1.2, 9.0), but this finding did not persist after propensity score–matched analysis. ConclusionsThe use of gabapentin in multimodal pain regimens in children following elective surgery was not associated with a decrease in postoperative narcotic use. Inclusion of gabapentin in perioperative pain medication protocols should be further evaluated with prospective studies.

Neurological disorders associated with COVID-19 in Sri Lanka

BackgroundNeurological manifestations of SARS-CoV-2 infection have been reported from many countries around the world, including the South Asian region. This surveillance study aimed to describe the spectrum of neurological disorders associated with COVID-19 in Sri Lanka.MethodsCOVID-19 patients manifesting neurological disorders one week prior and up to six weeks after infection were recruited from all the neurology centres of the government hospitals in Sri Lanka from May 2021 – May 2022. Data was collected using a structured data form that was electronically transmitted to a central repository. All patients were evaluated and managed by a neurologist. Data were analysed using simple descriptive analysis to characterise demographic and disease related variables, and simple comparisons and logistic regression were performed to analyse outcomes and their associations.ResultsOne hundred and eighty-four patients with neurological manifestations associated with COVID-19 were recruited from all nine provinces in Sri Lanka. Ischaemic stroke (31%) was the commonest neurological manifestation followed by encephalopathy (13.6%), Guillain–Barre syndrome (GBS) (9.2%) and encephalitis (7.6%). Ischaemic stroke, encephalitis and encephalopathy presented within 6 days of onset of COVID-19 symptoms, whereas GBS and myelitis presented up to 10 days post onset while epilepsy and Bell palsy presented up to 20 – 40 days post onset. Haemorrhagic stroke presented either just prior to or at onset, or 10 – 25 days post onset of COVID-19 symptomatic infection. An increased frequency of children presenting with encephalitis and encephalopathy was observed during the Omicron variant predominant period.A poor outcome (no recovery or death) was associated with supplemental oxygen requirement during admission (Odds Ratio: 12.94; p = 0.046).ConclusionsThe spectrum and frequencies of COVID-19 associated neurological disorders in Sri Lanka were similar to that reported from other countries, with strokes and encephalopathy being the commonest. Requiring supplemental oxygen during hospitalisation was associated with a poor outcome.

Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19.

Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens and often promote inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and nonhuman primates. Using a mouse model of MC deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed through detection of MC-specific proteases, including chymase, the levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention.

Anemia and a New Supplemental Oxygen Requirement in a 2-year-old Boy.

Anemia and a New Supplemental Oxygen Requirement in a 2-year-old Boy.

Remdesivir Is Associated With Reduced Mortality in COVID-19 Patients Requiring Supplemental Oxygen Including Invasive Mechanical Ventilation Across SARS-CoV-2 Variants.

This comparative effectiveness study investigated the effect of remdesivir on in-hospital mortality among patients hospitalized for coronavirus disease 2019 (COVID-19) requiring supplemental oxygen including low-flow oxygen (LFO), high-flow oxygen/noninvasive ventilation (HFO/NIV), or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) across variant of concern (VOC) periods. Patients hospitalized for COVID-19 between December 2020 and April 2022 and administered remdesivir upon admission were 1:1 propensity score matched to patients not administered remdesivir during their COVID-19 hospitalization. Analyses were stratified by supplemental oxygen requirement upon admission and VOC period. Cox proportional hazards models were used to derive adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for 14- and 28-day mortality. Patients treated with remdesivir (67 582 LFO, 34 857 HFO/NIV, and 4164 IMV/ECMO) were matched to non-remdesivir patients. Unadjusted mortality rates were significantly lower for remdesivir-treated patients at 14 days (LFO: 6.4% vs. 8.8%; HFO/NIV: 16.8% vs. 19.4%; IMV/ECMO: 27.8% vs. 35.3%) and 28 days (LFO: 9.8% vs. 12.3%; HFO/NIV: 25.8% vs. 28.3%; IMV/ECMO: 41.4% vs. 50.6%). After adjustment, remdesivir treatment was associated with a statistically significant reduction in in-hospital mortality at 14 days (LFO: aHR, 0.72; 95% CI, 0.66-0.79; HFO/NIV: aHR, 0.83; 95% CI, 0.77-0.89; IMV/ECMO: aHR, 0.73; 95% CI, 0.65-0.82) and 28 days (LFO: aHR, 0.79; 95% CI, 0.73-0.85; HFO/NIV: aHR, 0.88; 95% CI, 0.82-0.93; IMV/ECMO: aHR, 0.74; 95% CI, 0.67-0.82) compared with non-remdesivir treatment. Lower risk of mortality among remdesivir-treated patients was observed across VOC periods. Remdesivir treatment is associated with significantly reduced mortality among patients hospitalized for COVID-19 requiring supplemental oxygen upon admission, including those requiring HFO/NIV or IMV/ECMO with severe or critical disease, across VOC periods.

Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.

COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.

Liver Involvement during SARS-CoV-2 Infection Is Associated with a Worse Respiratory Outcome in COVID-19 Patients.

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be complicated by life-threatening interstitial pneumonia. SARS-CoV-2 infection may also damage several tissues and/or organs beyond the lungs, including the liver. However, controversy still exists as to whether SARS-CoV-2-induced liver alterations can have an impact on the outcome of COVID-19. The aim of this study was therefore to assess whether SARS-CoV-2-infected patients with liver abnormalities at the time of hospital referral had a worse outcome with respect to patients with no liver biochemistry alterations. To this end, the medical records of 123 patients admitted to our COVID center between the end of 2020 and spring 2021 were retrospectively reviewed. Patients were divided into two groups: those with normal liver biochemistries (group 1, 77 patients) and those with altered liver function tests (group 2, 46 patients). Serum levels of aminotransferases (AST and ALT) and bile duct cell injury markers (γ-GT and ALP) were used to dichotomize patients. A higher percentage of patients with liver enzyme alterations were found to develop COVID-19 pneumonia with respect to group 1 patients (74% vs. 65%); moreover, they needed more days of respiratory support and, more importantly, more intensive administration of supplemental oxygen. A statistically significant correlation was also found between aminotransferase levels and duration of respiratory support. The mortality rate was not superior in group 2 vs. group 1 patients. In conclusion, liver abnormalities on admission predisposed COVID-19 patients to development of more severe interstitial pneumonia, because of a longer requirement for supplemental oxygen and a more intensive respiratory support, indicative of a worse disease evolution in these patients.

The Impact of COVID-19 Vaccination on Bulgarian Patients with Uncomplicated Type 2 Diabetes Mellitus as the Only Chronic Condition

Abstract Objective: This retrospective study aimed to investigate the impact of COVID-19 vaccination on Bulgarian patient cohorts with uncomplicated diabetes mellitus type 2 as the only documented chronic comorbidity. We conducted a comparison of fully vaccinated and non-vaccinated populations, considering gender, age groups and vaccine type, across ambulatory, hospital, and ICU settings. Design: Between March 2020 and June 2022, a comprehensive retrospective analysis was conducted on a national level, utilizing data from the Ministry of Health of the Republic of Bulgaria database obtained after a formal written request. The study included a total of 1,126,946 confirmed COVID-19 patients. Results: Among the 1,126,946 confirmed COVID-19 patients, 3,792 individuals (0.33% of the total confirmed cases) had diabetes mellitus as a single chronic condition. Among the 247,441 hospitalized COVID-19 cases, 1,382 patients (0.56% of the total) had type 2 diabetes mellitus. Notably, the majority of patients requiring hospitalization due to supplemental oxygen requirement were unvaccinated women aged between 60 and 69, accounting for 240 patients. The highest mortality rates were observed in both unvaccinated men and women aged between 70 and 79, with 88 patients in each group. Statistical analysis revealed significant findings in favor of reduced rates of ambulatory care [OR = 0.76 (95% CI 0.6471 to 0.8891); p = 0.0006], intensive care admission [OR = 0.38 (95% CI 0.2698 to 0.5282); p &lt; 0.0001], in-hospital mortality [OR = 0.18 (95% CI 0.0864 to 0.3604); p &lt; 0.0001], and ICU-related mortality [OR = 0.17 (95% CI 0.0893 to 0.3436); p &lt; 0.0001]. The vaccinated cohorts who received BNT162b2 demonstrated the lowest observed death rates, with 9 deaths out of 485 individuals (1.8%) across all age groups. Conclusion: In conclusion, this retrospective analysis indicates reduced mortality in patients with uncomplicated type II diabetes mellitus who received vaccination against SARS-CoV-2. Vaccinated individuals also showed significant reduction in ICU admissions.

Toxic Tetrahydrocannabinol (THC) Dose in Pediatric Cannabis Edible Ingestions.

The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions. This is a retrospective review of children aged <6 years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015-October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses. Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8-4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6-6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%). The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.