Supplemental Oxygen Requirement Research Articles

Clinico-Epidemiological Profile of COVID-19 of Patients Presenting to Emergency Department of a Tertiary Medical College of Central Nepal

Background Clinico-epidemiological profile of COVID-19 includes varied clinical symptoms like fever, cough, and fatigue, with a potential for rapid community spread through respiratory droplets. Understanding the clinical characteristics of patients is crucial for planning human resources and logistics support. This study aims to identify the clinical characteristics observed in patients suspected of having COVID-19 presenting to emergency department of College of Medical Sciences and Teaching Hospital. MethodsThis is a retrospective cross-sectional study conducted at Department of General Practice and Emergency Medicine of College of Medical Sciences, Bharatpur, Nepal from April 2020 to February 2021. Ethical approval was taken from institutional review committee of College of Medical Sciences. Data was collected from record file of emergency department. Data was entered and analyzed by using descriptive statistical tools in SPSS-20.ResultsMajority (25.2%) of them were in the age group 50-60 years. Mean±SD of age was 55.2±16.5 years. Majority (54.3%) respondents were male. In presenting complaints 71.42% had cough, 69.5% had fever, 62.9% had shortness of breath. Also, 34.28% had severe symptoms, and 33.34% had moderate symptoms, 20% were asymptomatic and 12.38% had mild symptoms. Finding showed that 69.52% of patients required oxygen supplementation. The motility of COVID-19 patients during emergency stay was 6.67% while 36.19% were admitted in ward and 31.43% were admitted in ICU, 20% patients were sent for home isolation.Conclusions Young adults were the most commonly affected age group and males showed a higher incidence of COVID-19. Since many patients were symptomatic with fever and cough as the typical presentations in the emergency department. Majority of patients during presentation had moderate and severe symptoms and needed oxygen supplementation.

Itaconic acid regulation of TFEB-mediated autophagy flux alleviates hyperoxia-induced bronchopulmonary dysplasia

BackgroundPremature infants often require oxygen supplementation, which can elicit bronchopulmonary dysplasia (BPD) and lead to mitochondrial dysfunction. Mitochondria play important roles in lung development, in both normal metabolism and apoptosis. Enhancing our comprehension of the underlying mechanisms in BPD development can facilitate the effective treatments. MethodsPlasma samples from BPD and non-BPD infants were collected at 36 weeks post-menstrual age and used for metabolomic analysis. Based on hyperoxia-induced animal and cell models, changes in mitophagy and apoptosis were evaluated following treatment with itaconic acid (ITA). Finally, the mechanism of action of ITA in lung development was comprehensively demonstrated through rescue strategies and administration of corresponding inhibitors. ResultsAn imbalance in the tricarboxylic acid (TCA) cycle significantly affected lung development, with ITA serving as a significant metabolic marker for the outcomes of lung development. ITA improved the morphological changes in BPD rats, promoted SP-C expression, and inhibited the degree of alveolar type II epithelial cells (AEC II) apoptosis. Mechanistically, ITA mainly promotes the nuclear translocation of transcription factor EB (TFEB) to facilitate dysfunctional mitochondrial clearance and reduces apoptosis in AEC II cells by regulating autophagic flux. ConclusionThe metabolic imbalance in the TCA cycle is closely related to lung development. ITA can improve lung development by regulating autophagic flux and promote the nuclear translocation of TFEB, implying its potential therapeutic utility in the treatment of BPD.

Comparing Healthcare Needs in Extremely Low Birth Weight Infants With NEC and Spontaneous Intestinal Perforation

BackgroundNecrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) affect 6–8% of extremely low birth weight (ELBW) infants. SIP has lower mortality than NEC, but with similar short-term morbidity in length of stay, growth failure, and supplemental oxygen requirements. Comparative long-term neurodevelopmental outcomes have not been clarified. MethodsData were prospectively collected from 59 North American neonatal units, regarding ELBW infants (401–1000 g or 22–27 weeks gestational age) born between 2011 and 2018 and evaluated again at 16–26 months corrected age. Outcomes were collected from infants with laparotomy-confirmed NEC, laparotomy-confirmed SIP, and those without NEC or SIP. The primary outcome was severe neurodevelopmental disability. Secondary outcomes were weight <10th percentile, medical readmission, post-discharge surgery and medical support at home. Adjusted risk ratios (ARR) were calculated. ResultsOf 13,673 ELBW infants, 6391 (47%) were followed including 93 of 232 (40%) with NEC and 100 of 235 (42%) with SIP. There were no statistically significant differences in adjusted risk of any outcomes when directly comparing NEC to SIP (ARR 2.35; 95% CI 0.89, 6.26). However, infants with NEC had greater risk of severe neurodevelopmental disability (ARR 1.43; 1.09–1.86), rehospitalization (ARR 1.46; 1.17–1.82), and post-discharge surgery (ARR 1.82; 1.48–2.23) compared to infants without NEC or SIP. Infants with SIP only had greater risk of post-discharge surgery (ARR 1.64; 1.34–2.00) compared to infants without NEC or SIP. ConclusionsELBW infants with NEC had significantly increased risk of severe neurodevelopmental disability and post-discharge healthcare needs, consistent with prior literature. We now know infants with SIP also have increased healthcare needs. Levels of EvidenceLevel II.

Prediction of bronchopulmonary dysplasia by the chest radiographic thoracic area on day one in infants with exomphalos.

To determine if infants with exomphalos had abnormal antenatal lung growth as indicated by lower chest radiographic thoracic areas (CRTA) on day one compared to controls and whether the CRTA could predict the development of bronchopulmonary dysplasia (BPD). Infants with exomphalos cared for between January 2004 and January 2023 were included. The controls were term, newborn infants ventilated for absent respiratory drive at birth, without lung disease and had no supplemental oxygen requirement by 6 h of age. The radiographs were imported as digital image files by Sectra PACS software (Sectra AB, Linköping, Sweden). Free-hand tracing of the perimeter of the thoracic area was undertaken and the CRTA calculated by the software. Sixty-four infants with exomphalos and 130 controls were included. Infants with exomphalos had a lower median (IQR) CRTA (1,983 [1,657-2,471] mm2) compared to controls (2,547 [2,153-2,932] mm2, p<0.001). Following multivariable regression analysis, infants with exomphalos had lower CRTAs compared to controls (p=0.001) after adjusting for differences in gestational age and male sex. In the exomphalos group, the CRTAs were lower in those who developed BPD (n=14, 1,530 [1,307-1,941] mm2) compared to those who did not (2,168 [1,865-2,672], p<0.001). Following multivariable regression analysis, the CRTA was associated with BPD development (p=0.021) after adjusting for male sex and gestational age. Lower CRTAs on day one in the exomphalos infants compared to the controls predicted BPD development.

Racial and Ethnic Disparities in COVID-19 Treatments in the United States.

Racial and ethnic disparities in patient outcomes following COVID-19 exist, in part, due to factors involving healthcare delivery. The aim of the study was to characterize disparities in the administration of evidence-based COVID-19 treatments among patients hospitalized for COVID-19. Using a large, US hospital database, initiation of COVID-19 treatments was compared among patients hospitalized for COVID-19 between May 2020 and April 2022 according to patient race and ethnicity. Multivariate logistic regression models were used to examine the effect of race and ethnicity on the likelihood of receiving COVID-19 treatments, stratified by baseline supplemental oxygen requirement. The identified population comprised 317,918 White, 76,715 Black, 9297 Asian, and 50,821 patients of other or unknown race. There were 329,940 non-Hispanic, 74,199 Hispanic, and 50,622 patients of unknown ethnicity. White patients were more likely to receive COVID-19 treatments, and specifically corticosteroids, compared to Black, Asian, and other patients (COVID-19 treatment: 87% vs. 81% vs. 85% vs. 84%, corticosteroids: 85% vs. 79% vs. 82% vs. 82%). After covariate adjustment, White patients were significantly more likely to receive COVID-19 treatments than Black patients across all levels of supplemental oxygen requirement. No clear trend in COVID-19 treatments according to ethnicity (Hispanic vs. non-Hispanic) was observed. There were important racial disparities in inpatient COVID-19 treatment initiation, including the undertreatment of Black patients and overtreatment of White patients. Our new findings reveal the actual magnitude of this issue in routine clinical practice to clinicians, policymakers, and guideline developers. This is crucial to ensuring equitable and appropriate access to evidence-based therapies.

Flow-resistive loading and diaphragmatic muscle function in term and preterm infants.

We aimed to assess diaphragmatic function in term and preterm infants with and without history of bronchopulmonary dysplasia (BPD), before and after the application of inspiratory flow resistive loading. Forty infants of a median (range) gestational age of 34 (25-40) weeks were studied. BPD was defined as supplemental oxygen requirement for >28 days of life. Seventeen infants were term, 17 preterm without history of BPD, and six preterm with a history of BPD. The diaphragmatic pressure-time index (PTIdi) was calculated as the mean to maximum trans-diaphragmatic pressure ratio times the inspiratory duty cycle. The PTIdi was calculated before and after the application of an inspiratory-flow resistance for 120 s. Airflow was measured by a pneumotachograph and the transdiaphragmatic pressure by a dual pressure catheter. The median (interquartile range [IQR]) pre-resistance PTIdi was higher in preterm infants without BPD (0.064 [0.050-0.077]) compared with term infants (0.052 [0.044-0.062], p = .029) and was higher in preterm infants with BPD (0.119 [0.086-0.132]) compared with a subgroup of preterm infants without BPD (0.062 [0.056-0.072], p = .004). The median (IQR) postresistance PTIdi was higher in preterm infants without BPD (0.101 [0.084-0.132]) compared with term infants (0.067 [0.055-0.083], p < .001) and was higher in preterm infants with BPD [0.201(0.172-0.272)] compared with the preterm subgroup without BPD (0.091 [0.081-0.108],p = .004). The median (IQR) percentage change of the PTIdi after the application of the resistance was higher in preterm infants without BPD (65 [51-92] %) compared with term infants (34 [20-39] %, p < .001). Preterm infants, especially those recovering from BPD, are at increased risk of diaphragmatic muscle fatigue under conditions of increased inspiratory loading.

Supplemental oxygen requirement after tonsillectomy in children >3 years of age

IntroductionThe indications for postoperative admission after tonsillectomy in children >3 years of age are less well defined than for children <3 years old, and typically include severe obstructive sleep apnea (OSA), obesity, comorbidities, or behavioral factors. Inpatient care after tonsillectomy typically consists of respiratory monitoring and support, as respiratory compromise is the most common complication after pediatric tonsillectomy. We aim to evaluate risk factors associated with postoperative oxygen supplementation and to identify high risk populations within the admitted population who use additional resources or require additional interventions. MethodsRetrospective chart review of patients between the ages of 3 and 18 years old who underwent tonsillectomy by four surgeons at a tertiary care children's hospital was performed. Data including demographics, comorbidities, surgical intervention, pre- and postoperative AHI, admission, postoperative oxygen requirement, and postoperative complications was collected and analyzed. ResultsThere were 401 patients included in the analysis. Of the patients in this study, 65.59% were male, 43.39% were Latino, and 53.87% were ages 3 to 7. Of the 397 patients with a record for supplemental oxygen, 36 (9.07%) received supplemental oxygen. The LASSO regression odds ratios (OR) found to be important for modeling supplemental oxygen use (in decreasing order of magnitude) are BMI ≥35 (OR = 2.30), pre-op AHI >30 (OR = 2.28), gastrointestinal comorbidities (OR = 2.20), musculoskeletal comorbidities (OR = 1.91), cardiac comorbidities (OR = 1.20), pulmonary comorbidities (OR = 1.14), and BMI 30 to <35 (OR = 1.07). Female gender was found to be negatively associated with risk of supplemental oxygen use (OR = 0.84). Age, race, AHI ≥15–30, neurologic comorbidities, syndromic patients, admission reason, and undergoing other procedures concomitantly were not found to be associated with increased postoperative oxygen requirement. ConclusionBMI ≥30, pre-op AHI >30, male gender, and gastrointestinal, musculoskeletal, cardiac, and pulmonary comorbidities are all associated with postoperative supplemental oxygen use. Age, race, AHI ≥15–30, neurologic comorbidities, syndromic patients, admission reason, and undergoing other procedures concomitantly were not found to be associated with increased postoperative oxygen requirement.

Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin–angiotensin–aldosterone system on COVID-19 disease

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin–angiotensin–aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19.MethodsOur preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19.ResultsOur study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels.ConclusionsAlthough there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response.Clinical trial registration: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.

Remdesivir for the Treatment of COVID-19: A Narrative Review.

Despite the wide availability of effective vaccines, COVID-19 continues to be an infectious disease of global importance. Remdesivir is a broad-spectrum antiviral and was the first US Food and Drug Administration-approved treatment for COVID-19. In clinical guidelines, remdesivir is currently the only recommended antiviral for use in hospitalized patients with COVID-19, with or without a supplemental oxygen requirement. It is also recommended for nonhospitalized patients with COVID-19 and hospitalized patients with severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) infection who are at high risk of progression to severe disease. This narrative review explores the evidence for remdesivir across various clinical outcomes and evolution of clinical guidelines through a survey over time of randomized controlled trials, observational studies, and meta-analyses. Remdesivir, compared to standard of care, appears to improve survival and disease progression in a variety of patient populations with COVID-19 across a spectrum of disease severity and SARS-CoV-2 variant periods. Remdesivir also appears to improve time to clinical recovery, increase rate of recovery, and reduce time on supplemental oxygen and readmission rates. More recent large, real-world studies further support the early use of remdesivir in a range of patient populations, including those with immunocompromising conditions.

Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study.

Systemic thrombolysis improves outcomes in patients with pulmonary embolism (PE) but is associated with the risk of hemorrhage. The data on efficacy and safety of reduced-dose alteplase are limited. The study objective was to compare the characteristics, outcomes, and complications of patients with PE treated with full- or reduced-dose alteplase regimens. Multicenter retrospective observational study. Tertiary care hospital and 15 community and academic centers of a large healthcare system. Hospitalized patients with PE treated with systemic alteplase. None. Pre- and post-alteplase hemodynamic and respiratory variables, patient outcomes, and complications were compared. Propensity score (PS) weighting was used to adjust for imbalances of baseline characteristics between reduced- and full-dose patients. Separate analyses were performed using the unweighted and weighted cohorts. Ninety-eight patients were treated with full-dose (100 mg) and 186 with reduced-dose (50 mg) regimens. Following alteplase, significant improvements in shock index, blood pressure, heart rate, respiratory rate, and supplemental oxygen requirements were observed in both groups. Hemorrhagic complications were lower with the reduced-dose compared with the full-dose regimen (13% vs. 24.5%, p = 0.014), and most were minor. Major extracranial hemorrhage occurred in 1.1% versus 6.1%, respectively (p = 0.022). Complications were associated with supratherapeutic levels of heparin anticoagulation in 37.5% of cases and invasive procedures in 31.3% of cases. The differences in complications persisted after PS weighting (15.4% vs. 24.7%, p = 0.12 and 1.3% vs. 7.1%, p = 0.067), but did not reach statistical significance. There were no significant differences in mortality, discharge destination, ICU or hospital length of stay, or readmission after PS weighting. In a retrospective, PS-weighted observational study, when compared with the full-dose, reduced-dose alteplase results in similar outcomes but fewer hemorrhagic complications. Avoidance of excessive levels of anticoagulation or invasive procedures should be considered to further reduce complications.

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 &lt; 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 &lt; 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).

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 &amp;gt; 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 &amp;gt; 5 events/hour (33% mild, 4% moderate, 11% severe). 70% of subjects demonstrate an RDI &amp;gt; 5 events/hour (40% mild, 19% moderate, 11% severe). Twelve participants (44%) exhibit more than 5 minutes sleep duration at saturations &amp;lt;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 &amp;lt;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.

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 &amp;gt; 5 days of antibiotics (59% vs 73%) and &amp;gt; 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.

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.