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Background/Aims Rheumatology is a complex specialty covering many conditions of varying severity, from muscle pain through inflammatory arthritis such as Rheumatoid arthritis (RA) and connective tissue diseases. Most of the conditions can be managed in an outpatient/day case setting. However, acutely ill patients require safe and prompt inpatient management including specific intravenous infusions. This need to be done urgently and cannot wait to be accommodated through the Infusion unit at our hospital. Historically Medicine Acute Admission Unit has been the route to bring in these patients. However, operational bed pressures faced challenges leading to instances of delayed treatment with complications including fatality. This led to creating a direct inpatient admission pathway to the specialist ward. Methods Ward Matron designed the following robust pathway for direct patient admission to our specialist Rheumatology ward, Jevington ward. This was implemented in February 2022 after discussion and agreement with Clinical Lead consultant, pharmacist, clinical site managers and other colleagues. Rheumatology team and nurses covered the ward during working hours and by the on-call team out of hours. The overall responsibility remained with the rheumatology team. The referrals accepted only after completing appropriate paperwork. Patients carried out Lateral Flow Test (LFT) at home prior to admission. We ensured negative results and followed the Trust COVID 19 screening protocols. Subsequent screenings were done according to the updated guidelines. The planned assessment and treatments were carried out by the ward team complying with BSR/ EULAR Guidelines, infusion protocols such as standard and continuous Iloprost Infusion Protocols of the Trust. Results We assessed the delay in patient's admission, length of stay, patient outcome and experience after implementing the pathway. The significant change has been in the time to admit;from two weeks in 2018 & 19 to two days this year. This is reflected in the patient feedback. All our acutely ill patients were assessed, treated and discharged promptly on this specialist ward. Conclusion This pathway allowed safe and prompt treatment, prognosis and excellent experience for acutely ill patients with rheumatological disorders. This additionally enabled reduced length of stay supporting financial sustainability of the Trust. (Table Presented).
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Background: The pathogenetic mechanisms behind the development of long- COVID (LC) are largely unknown. Because both plasma SARS-CoV-2 RNAemia and dysregulated immunity have been correlated with COVID-19 severity, we evaluated whether they are associated with LC. Method(s): We consecutively enrolled unvaccinated hospitalized COVID-19 patients during acute-COVID-19 (T0) in March-October 2020 who either developed LC at a follow-up visit 2-3 months from virologic clearance (T1) or did not. LC was defined as persistence >=2 months after recovery of >=1 symptom: anosmia, dysgeusia, fever, gastrointestinal symptoms, dyspnoea, fatigue, musculoskeletal pain, muscle weakness, brain fog. We measured: SARS-CoV-2 RNAemia (RT-qPCR, log10(copies/mL)), magnitude (ELISA, AUC) and functionality (pseudovirus neutralization, ID50;Fc-mediated functions, %ADCC) of SARS-CoV-2-specific antibodies, SARS-CoV-2-specific B and CD4-T-cells (Immunophenotype, AIM and ICS assays). Result(s): We enrolled 48 COVID-19 individuals, 38/48 (79.2%) developed LC (LC+) and 10 did not (LC-). LC+ and LC- had similar co-morbidities and symptoms in the acute phase (Fig.1A), and the majority showed a radiologically documented SARS-CoV-2 pneumonia. The SARS-CoV-2 RNAemia did not differ between groups at both time points. The levels of RBD-specific Abs, as well as their functionality, appeared to increase over time in the LC- group but not in the LC+ (Fig.1B-D). Similarly, a trend towards increased RBD-specific B-cells was observed over time in the LC- group but not in LC+ (Fig.1E). B-cell immunophenotyping showed a significant increase over time of classical memory B cells (MBCs) at the expenses of activated MBCs (Fig.1F-G) as well as an IgA class-switching in the LC- group compared to LC+ (Fig.1H-I). Furthermore, LC+ showed a faster decline of SARS-CoV-2-specific (CD69+CD137+) CD4- TEMRA and CD4-TEM (Fig.1L-M). Finally, IFN-gamma-producing TREG of LC- individuals increased over time (Fig.1N). Conclusion(s): Acutely ill, hospitalized COVID-19 patients developing LC feature a dysregulated SARS-CoV-2-specific humoral as well as B- and T-cell response, in both magnitude and functionality, suggesting a link between dysregulated SARS-CoV-2-specific adaptive immunity and LC development. The fine understanding of the factors contributing to such dysregulation in LC patients is strongly needed, that might further inform targeted therapeutic interventions. (Figure Presented).
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Introduction: COVID-19 is a widespread disease having more impact on elderly as compared to younger age group. [2] Although many parameters have emerged as predictors of prognosis of COVID-19, a simple clinical score at baseline can be used for early risk stratification. NEWS2 (National Early Warning Score) is one such scoring system which was originally developed to improve detection of deterioration in acutely ill patients.[8] Therefore, the present study has been conducted to assess the effectiveness of NEWS2 in predicting critical outcomes and mortality in geriatric patients with COVID-19. Material(s) and Method(s): A cross sectional Observational study was done on 200 Geriatric patients hospitalised with confirmed COVID-19 between December 2020 to November 2022. Baseline NEWS2 score was calculated. The sensitivity, specificity, Positive Predictive Value and Negative Predictive Value were established for NEWS2 score of 5 or above. Result(s): In critical group, all 109 (100%) patients' deterioration was predicted, and in non-critical group, in 14 (15.4%) patients non deterioration was predicted while 77 (84.6%) patients' deterioration was predicted. Statistically significant association has been observed between the critical, non-critical groups and NEWS2 scale (P=0.001). Deterioration was predicted by NEWS2 scale in all the critical patients. Conclusion(s): NEWS2 score of 5 or more on admission predicts poor prognosis in geriatric patients with COVID-19 with good sensitivity and it can easily be applied for risk stratification at baseline. We recommend further studies in the Indian setting to validate this simple score and use it further in Geriatric patients with COVID-19.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.
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Introduction: Due to the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the humoral immune system, gastrointestinal, and metabolic activities, malnutrition in COVID-19 is inevitable. This study aimed to assess the prevalence, identify COVID-19 patients at risk of malnutrition, and determine the nutritional risk profile of COVID-19 patients and the need for ongoing nutritional support after ICU stay. Method(s): A monocentric observational study based on data collected from 200 COVID-19 patients at hospital discharge in Dubai, UAE. Male and female residents and citizens (>= 18 years) who tested positive for COVID-19 upon ICU admission and who were ready for discharge were included. The 'MUST' malnutrition screening was performed to identify patients at high risk of malnutrition who required ONS and other treatments. Result(s): The present study included two hundred patients where male participants constituted 68% compared to females (32%). The included population was neither acutely ill nor had nutritional intake for more than 5 days. 45% of COVID-19 patients experienced a reduced dietary intake at hospital, and 58% lost weight during ICU/hospital stays. About 25% received enteral nutrition in the ICU, whereas (2%) required ongoing homecare nutritional support after hospital discharge. Almost 80% were advised to follow up with a dietitian and 96% were provided additional dietary counseling. Regarding the COVID-19 patients' post-ICU stay nutritional support, the adjusted odds ratio of follow-up consultation with dietitian significantly decreased by 66% among patients aged from 18 to 49 years, compared to older patients (ORa = 0.34, 95% CI 0.12-0.86, p = 0.032). Conclusion(s): Close assessment, evaluation, and monitoring of malnutrition are critical in severely ill COVID-19 patients post-ICU. ONS is highly recommended for high-risk patients to provide support against muscle loss during ICU stay and improve the recovery of the patients at discharge.
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Malnutrition estimates range between 5 and 69% in acute Coronavirus disease 2019 (COVID-19) patients. With respect to body composition (BC) and muscle function, low values of phase angle (PhA) and handgrip strength (HGS) have been related to poor disease outcomes. Little evidence is available in post-acute patients. We aimed to combine the evaluation of nutritional status, BC, and muscle strength in a real-life cross-sectional cohort of post-acute COVID-19 patients referred to a rehabilitation center after hospital discharge. The study population included 144 patients (M=95;mean age 64.8yrs), of which 37% bedridden (M=60%). Nutritional status was evaluated with the Mini-Nutritional Assessment (MNA) and Controlling Nutritional status (CONUT) scores. Fat-free mass (FFM), skeletal muscle (SM), and raw variables, i.e. PhA, were estimated with bioelectrical impedance analysis. HGS was measured with a digital handle dynamometer for both dominant and non-dominant body sides. Dynapenia was identified according to the 2019 EWGSOP criteria. According to MNA, 18% of patients were malnourished and 62% at risk of malnutrition. As for CONUT, 21% of patients had moderate-severe malnutrition, while 58%light malnutrition. Overall, malnutrition was highly prevalent in older patients with more comorbidities. Marked abnormalities of PhAand HGSwere more frequent in bedridden or malnourished patients, and when FFM or SM were low. Dynapenic patients were 65% males and 47% females. Malnutrition, BC alterations, and low HGS occur in post-acute COVID-19 patients. Future studies will help to tailor screening algorithms for full nutritional status assessment to appropriate care processes and rehabilitation strategies.
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Aim and Objectives: To characterize the functional recovery of hospitalized patients diagnosed with COVID-19 at 3-, 6-, 9- and 12-months post-discharge. Method(s): We are conducting a multi-regional prospective cohort study in hospitalized COVID-19 patients 18 years and older in Canada. Patients are assessed upon admission and at 3-, 6-, 9-, and 12-months follow-up. Data collection is completed via telephone interviews in addition to home visits. Outcomes include the Activity Measure for Post-Acute Care Mobility and Cognition scales and lung function. Result(s): Preliminary data from 242 hospitalized COVID-19 patients (60.1 +/- 13.0 yrs) indicate that the most common self-reported symptoms are fatigue (47%) and shortness of breath (35%) at 12-months follow-up. Our lung function data suggests that 39-46% of post-acute patients with COVID-19 have impaired FEV1 (<80% predicted), and 38- 49% have impaired FVC (<80% predicted) at 3-,6-, 9- and 12-month follow-up. At 12-months, 38-45% of patients continue to have clinically important deficits in cognition and mobility below premorbid levels, respectively, and 55.4% of patients report that COVID-19 continues to impact their daily life activities (Figure 1). Conclusion(s): There is a high prevalence of functional limitations in COVID-19 survivors over 12 months of followup. Our data support the need for multi-disciplinary rehabilitation for patients post-hospitalisation for COVID-19.
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Background: T-cell response against SARS-CoV-2 is essential for disease control and to understand correlates of protection against various disease outcomes in COVID-19. This makes T-cell measurement an important tool for clinical management. Aim(s): To evaluate the IFN-gamma-releasing T-cell response against spike (S), nucleocapsid (N) and membrane (M) SARS-CoV-2 antigens using an ELISPOT-based assay in acute, convalescent, and vaccinated individuals. Method(s): Blood samples were collected from acute (n=71) and convalescent (n=59) individuals classified according to severity;and from vaccinated (n=48) and non-vaccinated (n=80) controls. After stimulating with S, N and M antigens overnight, T-cell response was measured (T-SPOT Discovery SARS-CoV-2. Oxford Immunotec, UK). IgG against S and N were also measured. Result(s): S antigen triggered the highest number of T-cell responses (46%), although responses against N and M were in a large percentage of individuals. The majority of convalescent individuals (93%) had a reactive T-cell response more than 200 days after diagnosis. Such response increased with severity. Acute patients had fewer positive responses (68%). S antigen triggered most responses in vaccinated controls, but only in half of them T-cell response was observed after the second dose. A higher percentage of individuals showed IgG response compared to IFN-gamma-releasing T-cell responses, and moderate correlations between both quantitative responses were seen. Conclusion(s): T-cell response against SARS-CoV-2 is low during acute phase but may increase over time, as seen in convalescent individuals. Regarding vaccinated individuals, half had a positive test result after the second dose.
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Background: Treatments are being developed against severe Covid-19 symptoms, among them the use of convalescent plasma. Two drawbacks are, the large volumes of plasma needed for treatment can lead to circulatory overload, and the plasma contains unnecessary components that can lead to unwanted side-effects. We investigated the use of immunoadsorption followed by tangential flow filtration as a method to obtain highly concentrated Covid-19 antibody concentrates free of additional plasma components. Method(s): Five convalescent plasma donors (3 men and 2 women) have participated in this study. Two donors donated twice with 1 year gap between the donations. Immunoadsorption was performed with an affinity column adsorber pair (Miltenyi Biotec, Bergisch-Gladbach, Germany). The resulting eluate contained antibodies dissolved in a glycine buffer with a total volume of 1100- 1500mL. Tangential Flow Filtration System was used to concentrate all eluates 15- 21.3-fold using an Omega 30 kD membrane (Pall Corp, Dreieich, Germany) and to exchange the glycine buffer with 0.9% NaCl. Eluates were then filtered through a sterile filter, before storage at 4degreeC and -80degreeC. Result(s): All donors have tolerated the immunoadsorption very well with no side effects. The final product contained between 5mg and 194mg of CoV-2 antibodies per donation at a median end-volume of 61+/-20ml leading to probably eight times more COVID-19 antibodies than in one plasma unit while preserving or even increasing their neutralization capacity up to ten-fold. Glycine levels were reduced to non-hazardous 12.6+/-20 mumol (see table 1). The product was sterile and remained stable for 0.5 to 1 year in storage. In two cases the concentration of SARS-COV2 antibodies even increased during storage. Conclusion(s): Immunoadsorption followed by tangential flow filtration produces CoV2 antibody concentrates of high concentrations without simultaneous removal of unnecessary plasma components. The procedure can be done within one day, including the donation, without compromising the donor's immune system. Whether these donated antibodies can be used as passive immunization in acutely infected patients remains to be elucidated. (Table Presented).
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INTRODUCTION: Since the start of the COVID-19 pandemic there has been an evolution of variant strains that have spread throughout the world. As time has passed, clinicians have appreciated that these variants have different symptomology and clinical course. As our understanding of the disease process has progressed, medical management has evolved. Throughout, cancer patients have represented a uniquely at-risk population. We sought to compare the characteristics of critically ill cancer patients with Omicron variant to those infected with the ancestral strain. METHOD(S): Single-center retrospective cohort study analyzed all cancer patients >=18 years of age with current or past (< 2 years) diagnosis of cancer, who were admitted to ICU with COVID-19. The ancestral strain period was defined as March 1 to June 30, 2020, and the Omicron variant period was December 15, 2021 to April 1, 2022. Demographics, clinical and laboratory data of critically ill cancer patients were extracted from electronic health record and an ICU database. RESULT(S): A total of 127 patients were analyzed (38 Omicron and 89 ancestral strain). Median age was similar (67 years Omicron, 65 ancestral) and slightly higher male (47% Omicron, 58% ancestral). There was a higher number of hematologic malignancy (53% Omicron, 43% ancestral). Mechanical ventilation and vasopressors were less commonly used (58% and 53% Omicron, 67% and 71% ancestral), respectively. Prone positioning was utilized less frequently (47% Omicron, 56% ancestral) as was tracheostomy (11% omicron, 34% ancestral). ICU mortality was similar in both groups, (39% vs 37% however, hospital mortality was higher (55% Omicron group, 45% ancestral). CONCLUSION(S): Critically ill cancer patients infected with the Omicron variant may be less likely to undergo tracheostomy however, they are more likely to die during their hospitalization. Even with higher hospital mortality Omicron patients also seemed to be less acutely ill as their requirement for mechanical ventilation, vasopressors and prone positioning was lower. This should be considered as we counsel patients and set expectations about what might happen during a COVID admission to the ICU.
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SESSION TITLE: Late Breaking Posters in Critical Care SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Multiple mechanisms may cause acute kidney injury (AKI) after mechanical ventilation. Cross-talk between the lung and kidney precipitates other complications such as fluid overload, electrolyte derangements and pro-inflammatory cytokine production. In this study, we compared hospital mortality rates in unvaccinated COVID-19 patients with respiratory failure (requiring mechanical ventilation) who developed oliguric AKI. METHODS: Using an observational database, we analyzed 3183 unvaccinated hospitalized COVID-19 PCR-positive patients at Methodist Health System (Dallas, TX) from March 2020 to December 2020. The primary endpoint was all-cause in-hospital mortality in patients with respiratory failure requiring mechanical ventilation who developed AKI (as defined by the kidney disease improving global outcomes (KDIGO) guidelines). We also counted the rate of kidney replacement therapy and degree of kidney recovery among the survivors who developed AKI. Chi-square (X2), Fischer’s exact test, and odds ratio tests were used to analyze observed variables. RESULTS: Of the 3183 COVID-19 patients, 351 (11%) developed respiratory failure requiring invasive mechanical ventilation. Of those, 313 (89%) had previously normal kidney function (no documented CKD). Of the 313 intubated patients, 186 (59.4%) developed AKI and 127 (40.5%) patients did not. Thirty-five (18.9%) of the patients who developed AKI survived hospital admission, while 54 (42.5%) patients without AKI survived (OR = 3.306, 95% CI = 1.98-5.51, P<0.001). Ischemic acute tubular necrosis from septic shock was the most common cause of AKI. Hyperkalemia and metabolic acidosis were the most common indication for kidney replacement therapy, and continuous kidney replacement therapy was the most common modality used. The mean age for the AKI vs no AKI groups were 63.5 (SD 14.5) vs 62 (SD 14.49) years old. Mean BMI was comparable between both groups 32 (SD 9.7) vs 32 (SD 9.64), while the BUN level 26 (SD 26.75) vs 19 (SD 9.9) mg/dl and Cr 1.15 (SD 1.59) vs 0.08 (SD 0.27) mg/dl were higher in the AKI group. In the AKI group, kidney replacement therapy was prescribed in 73(39.2%) patients, of which only 33 (17.7%) recovered meaningful kidney function. CONCLUSIONS: As the world emerged from the COVID-19 pandemic, there are innumerable lessons still to be learned. In our study, we demonstrated that AKI in COVID-19 patients with respiratory failure is associated with a higher incidence of mortality compared to patients without AKI. CLINICAL IMPLICATIONS: The risk of new SARS-CoV-2 variants and the possibility of future pandemics makes the recognition of high-risk medical complications of COVID-19 crucial to improve outcomes in acutely ill patients. A true multi-disciplinary team and an incredible amount of resources is required to identify and treat such patients. This study reminds us that kidney replacement therapy is only a means of supportive treatment rather than a cure to COVID-19-related kidney pathology. DISCLOSURES: No relevant relationships by Victor Canela No relevant relationships by Manavjot Sidhu No relevant relationships by Lucas Wang
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SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune activation in response to a variety of insults including malignant, autoimmune and infectious processes. The most common infectious trigger is a viral infection, but other pathogens have also been implicated including Mycobacterium tuberculosis (MTB) CASE PRESENTATION: 62-year-old male from Bangladesh presented due to lethargy, weakness, and anorexia for several weeks. He also reported fevers, diarrhea, and unintentional weight loss. On examination, he appeared acutely ill with diffuse bibasilar crackles on lung exam. Labs showed platelets of 132, ESR 45 mm/hr, CRP 9.6mg/dL, ferritin 1,765ng/mL and transaminitis. A viral panel was positive for Rhinovirus. Computed tomography (CT) of the chest showed diffuse bilateral ground-glass opacities and he was started on antibiotics for pneumonia. On day 3, his respiratory status worsened and he was emergently intubated. He underwent bronchoscopy and bronchoalveolar lavage (BAL) and started on high-dose steroids for possible hypersensitivity pneumonitis. On day 5, he was extubated to nasal cannula, however, his condition worsened despite treatment. Extensive infectious workup, including HIV, Covid and P jirovecii PCR, sputum, and blood cultures, and preliminary AFB smear were negative. Subsequent labs noted rising ferritin levels (4,164 ng/mL), high triglycerides, pancytopenia and transaminitis. Calculated H score was 211 which gave a 93-96% probability of HLH. Initiation of Etoposide was discussed but family deferred. He was later transferred to another facility. On follow-up, IL-2 receptor antibodies were elevated, bone marrow biopsy showed hemophagocytosis and necrotizing granulomas. He was intubated for worsening hypoxemia. Repeat bronchoscopy and BAL analysis showed many acid-fast bacilli. Anti TB treatment (ATT) was deferred due to his critical state. He further declined and eventually expired. DISCUSSION: The exact mechanism for which MTB triggers HLH is unclear, however, it is thought that MTB serves as an obligate intracellular pathogen after phagocytosis by phagocytic cells to induce TH1-mediated cytotoxicity, activating macrophages and NK cells, further releasing a large quantity of cytokines and chemokines. The lack of specific clinical signs, low sensitivity for acid-fast staining, and time-consuming culture make the diagnosis of TB-HLH difficult. However, the use of NAATs has improved the yield of sputum testing. Exceedingly high ferritin levels should serve as a red flag in cases of undetermined diagnosis. Moreso, Cytopenias, elevated LFTs, and coagulation dysfunction are other clues that a diagnosis of HLH should be on the differential. It is believed that early and effective ATT is the key to preventing HLH in TB patients. CONCLUSIONS: It is paramount to both recognize the features of TB as well as HLH as early diagnosis and treatment favor better outcomes. Reference #1: Padhi S, Ravichandran K, Sahoo J, Varghese RG, Basheer A. Hemophagocytic Lymphohistiocytosis: An Unusual Complication in Disseminated Mycobacterium Tuberculosis. Lung India (2015) 32(6):593–601. doi: 10.4103/0970-2113.168100 Reference #2: Dalugama, C., Gawarammana, I.B. Fever with pancytopenia: unusual presentation of extrapulmonary tuberculosis: a case report. J Med Case Reports 12, 58 (2018). https://doi.org/10.1186/s13256-018-1596-0 Reference #3: O M P Jolobe, Timely recognition of hematophagocytosis attributable to coexistence of lymphoma and tuberculosis, QJM: An International Journal of Medicine, Volume 112, Issue 4, April 2019, Page 315, https://doi.org/10.1093/qjmed/hcy198 DISCLOSURES: No relevant relationships by Katherine Acosta No relevant relationships by Chika Winifred Akabusi No relevant relationships by Uma Medapati No relevant relationships by Hector Ojeda-Martinez No relevant relationships by Busala Oke No relevant relationships by Mar o Torres
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Introduction: COVID-19 outbreak has generated an unprecedented surge of deteriorating and critically ill patients with severe and sustained pressures on intensive care units (ICUs) and staff. This has resulted in major staff redeployment from other areas, including some critical care outreach into ICU leaving the wards uncovered. Critical care outreach has the potential to optimise acutely ill and deteriorating patients on the wards and avert critical care admission;but its benefit during a pandemic is unclear. Objectives: To determine the clinical need for critical care outreach during the Coronavirus disease 2019 pandemic. To evaluate patients' outcomes to guide decision-making and resource prioritisation. Methods: We evaluated all consecutive patients referred to critical care outreach during a twelve-month period from 1 March 2020 to 28 February 2021. We reported the cumulative number of activities and interventions, and baseline characteristics, acuity level and clinical outcomes. Results: Amongst 4849 patients referred, 3913 had a clinical review and of those 895 were COVID-19 positive. Non-invasive ventilation was mostly delivered to COVID-19 patients (COVID-19 +VE: 853/895, 95% vs COVID-19 -VE: 119/3018, 4%) alongside awake positioning (COVID-19 +VE: 232/895, 26% vs COVID-19 -VE: 0/3018, 0%). Compared to prepandemic, patients were sicker meeting Level 2 acuity (observed: 51% vs historical: 21%;P= 0.003), however ICU admissions did not increase significantly (observed: 12% vs historical: 9%;P= 0.065), but greater mortality (observed: 14% vs historical: 8%;P= 0.046) was observed. Conclusion: Critical care outreach support the delivery of non-invasive respiratory support bridging the gap between intensive care units and general wards. Critical care outreach act as a valuable resource in optimising and triaging acutely unwell patients and potentially averting critical care admissions.
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Introduction: Focused Ultrasound in Intensive Care (FUSIC) refers to the use of ultrasound by a trained bedside clinician to guide patient management in real-time. Ultrasound is widely applied in practice and there is growing consensus that it is an essential tool for managing acutely ill patients in the intensive care unit (ICU). The Critical Care Outreach Team uses FUSIC as an additional assessment tool to guide management and decision-making plan for deteriorating patients on the wards. Objectives: To investigate whether how often information gained fromFUSICimaging had an impact on patient care and management decisions in a critical care outreach setting. Methods: A single-centre observational study at an academic tertiary referral institution. We included all patients reviewed by critical care outreach who were assessed by ultrasound during a 12-month period. Routine procedures for teaching purposes were not included. Results: Forty-six patients were assessed and supported by a combined focused lung and heart ultrasound performed at the patient bedside on the wards. In 46 patients FUSIC was instrumental in the differential diagnostic workup and in guiding the clinical management. In 32 (70%) patients FUSIC aided fluid therapy or diuresis (in case of pulmonary oedema) and helped targeting fluid balance. In three patients though to have consolidation on chest x-ray we were able to identify significant pleural effusions without needing an additional CT scan. In four patients with hypotension, an additional CT-PA was warranted due to dilated right ventricle (RV) with abnormal septal motion and decreased left ventricle (LV) size ratio (i.e. sign of right heart strain) as highly suspicious of pulmonary embolus. In two young patients with Coronavirus disease 2019 (COVID-19), using FUSIC we identified severe LV dysfunction which was subsequentially diagnosed as myocarditis and Angiotensin-converting enzyme (ACE) inhibitors therapy was commenced within 24 hours. Further diagnosis included cardiac tamponade (n = 2) requiring pericardiocentesis and pneumothorax (n =1). In all cases, the use of ultrasound helped in promptly referring patients to the specialist team (i.e. respiratory or cardiology) and to the ICU consultant. Conclusions: In our critical care outreach practice, FUSIC is considered an indispensable tool for safe and accurate management of acutely ill and deteriorating patients on the wards.
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Background: Enpatoran is a selective and potent dual toll-like receptor (TLR) 7/8 inhibitor in development for the treatment of cutaneous and systemic lupus erythematosus (CLE/SLE). Enpatoran inhibits TLR7/8 activation in vitro and suppresses disease activity in lupus mouse models.1 Enpatoran was well tolerated and had linear pharmacokinetic (PK) parameters in healthy volunteers.2 As TLR7/8 mediate immune responses to single-stranded RNA viruses, including SARS-CoV-2, it was postulated that enpatoran may prevent hyperinfammation and cytokine storm in COVID-19. Objectives: In response to the COVID-19 pandemic, we conducted an exploratory Phase II trial to assess safety and determine whether enpatoran prevents clinical deterioration in patients (pts) hospitalized with COVID-19 pneumonia. PK and pharmacodynamics (PD) of enpatoran were also evaluated. Methods: ANEMONE was a randomized, double-blind, placebo (PBO)-con-trolled study conducted in Brazil, the Philippines, and the USA (NCT04448756). Pts aged 18-75 years, hospitalized with COVID-19 pneumonia (WHO 9-point scale score =4) but not mechanically ventilated, with SpO2 <94% and PaO2/FiO2 ≥150 (FiO2 maximum 0.4) were eligible. Those with a history of uncontrolled illness, active/unstable cardiovascular disease and SARS-CoV-2 vaccination were excluded. Pts received PBO or enpatoran (50 or 100 mg twice daily [BID]) for 14 days, with monitoring to Day 28 and safety follow-up to Day 60. Primary outcomes were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (time to clinical status >4, WHO 9-point scale) was a secondary outcome. Exploratory endpoints were enpatoran and biomarker concentrations (cytokines, C-reactive protein [CRP], D-dimer and interferon gene signature [IFN-GS] scores) assessed over time. Results: 149 pts received either PBO (n=49), or enpatoran 50 mg (n=54) or 100 mg (n=46) BID;88% completed treatment and 86% received concomitant steroids. Median age was 50 years (77% <60 years old), 66% were male, and 50% had ≥1 comorbidity (40% hypertension, 24% diabetes). Overall, 59% pts reported a treatment-emergent adverse event (TEAE) with three non-treatment-related deaths;11% reported a treatment-related TEAE. The proportion of pts in the enpatoran group reporting serious TEAEs was low (50 mg BID 9%;100 mg BID 2%) vs PBO (18%). Gastrointestinal disorders were most common (PBO 8%;50 mg BID 28%;100 mg BID 9%). The primary outcome of time to recovery with enpatoran vs PBO was not met;medians were 3.4-3.9 days. A positive signal in time to clinical deterioration from Day 1 through Day 28 was observed;hazard ratios [95% CI] for enpatoran vs PBO were 0.39 [0.13, 1.15] (50 mg BID) and 0.30 [0.08, 1.08] (100 mg BID). Mean enpatoran exposure was dose-proportional, and PK properties were within expectations. The median (quartile [Q]1-Q3) interleukin 6 (IL-6), CRP and D-dimer baseline concentration across the groups were 5.7 (4.0-13.5) pg/mL, 30.04 (11.40-98.02) and 0.62 (0.39-1.01) mg/L, respectively. Baseline IFN-GS scores were similar across groups. Conclusion: The ANEMONE trial was the frst to evaluate the safety and efficacy of a TLR7/8 inhibitor in an infectious disease for preventing cytokine storm. Enpa-toran up to 100 mg BID for 14 days was well tolerated by patients acutely ill with COVID-19 pneumonia. Time to recovery was not improved with enpatoran, perhaps due to the younger age of patients who had fewer comorbidities compared to those in similar COVID-19 trials. However, there was less likelihood for clinical deterioration with enpatoran than placebo. This trial provides important safety, tolerability, PK and PD data supporting continued development of enpatoran in SLE and CLE (NCT04647708, NCT05162586).
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Background: Millions of children in low- and middle-income countries (LMICs) die each year from preventable illness. Evidence-based guidelines (EBGs) from the World Health Organization reduce this amenable burden of disease, but utilization among healthcare workers is variable. Existing inperson training strategies like Emergency Triage Assessment and Treatment (ETAT) improve provider knowledge, adherence to EBG, and patient outcomes but are limited by labor intensity and implementation costs. Leveraging increasing mobile internet access in LMICs could speed dissemination of EBG to medical providers in a way that overcomes the limitations of in-person training. Adaptive electronic learning (AEL), which uses digital algorithms to deliver custom activities to individual learners, is shown to outperform traditional training among healthcare workers in high-income countries but is yet to be evaluated in LMICs. We propose to address the existing gap in LMIC healthcare worker training through a mixed-methods feasibility trial of an AEL curriculum designed to deliver EBG training to medical providers in Tanzania. Methods: Curriculum development: We sought to create a multi-module AEL course addressing context-specific gaps in healthcare worker training. A review of leading regional causes of pediatric mortality was performed to identify priority content areas. Source material was. selected to reflect EBG use at our study site. Training modules were created by pediatricians with expertise in both AEL and EBG. Module approval occurred through an iterative process of review by local stakeholders and international EBG experts. Mixed-methods feasibility trial: We are undertaking a parallelgroup, double-blinded randomized trial to evaluate our AEL curriculum (Figure 1). 30 medical interns will be randomized to either an adaptive or a non-adaptive electronic learning curriculum. The primary outcome is knowledge acquisition, defined by standard mean difference in pre- and postknowledge assessments scores between groups. Qualitative evaluation of the implementation process will be based on normalization process theory. All aspects of recruitment, quantitative, and qualitative data collection will be done remotely in accordance with local social distancing standards and international travel restrictions. Results: Curriculum publication: Our process of content identification, topic selection, and module development yielded an 11-module AEL curriculum. Priority content areas include the triage of acutely-ill children as well as the assessment, diagnosis, and management of pediatric pneumonia and hypovolemic shock based on current World Health Organization and Tanzanian guidelines (Figure 2). Mixed-methods feasibility trial: At present, we have enrolled 17 medical interns. Pre-knowledge assessment scores range from 6-60%. One intern has completed the curriculum to date and experienced a 30% increase in knowledge. Conclusion: We expect to complete this feasibility trial by August of 2021. Findings will inform the design of a large-scale implementation trial that will support the development of innovative solutions and low-cost implementation strategies for improving the care of seriously-ill children worldwide.
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Rationale: The relationship between disability and outcomes after COVID-19 hospitalization remains largely unexplored. We hypothesized that patients with pre-COVID disability would have poorer hospital outcomes, and that COVID-19 hospitalization would be associated with increased disability at hospital discharge. Methods: Between August 2020 and July 2021, NHLBI PETAL Network hospitals prospectively enrolled patients hospitalized with symptomatic SARS-CoV2 infection (fever and/or respiratory signs or symptoms) confirmed by molecular testing. Patients or their surrogates reported pre-COVID ability to perform activities of daily living (ADL) and degree of frailty using standardized surveys at study entry (Katz's ADLs and Rockwood's Clinical Frailty Scale (CFS)). Study staff collected detailed clinical data throughout hospitalization. We examined bivariate and multivariable associations between pre-COVID disability and hospital outcomes and reported risk factors for increased disability at hospital discharge among patients surviving to hospital discharge. In analyses exploring factors associated with returning home to living independently or walking at discharge, we excluded patients not living independently or walking prior to COVID admission, respectively. Results: We enrolled 1369 patients across 44 US hospitals. Demographics are presented in the table, along with clinical management and outcomes. Most patients lived at home without help prior to hospitalization (n=1130, 84%), while 14% were dependent in 1-3 ADLs and 14% were dependent in 4 or more. Before hospitalization, 15% of patients were frail (CFS>4) and 15% were vulnerable (CFS=4). Most patients did not receive critical care (“acute illness”);389 patients (28%) were cared for in ICUs (“critical illness”), and 192 (14%) received mechanical ventilation. Overall, 100 (7%) patients died during their COVID-19 hospitalization. Median hospital length of stay was 6 days (IQR 4-8) for acutely ill patients, 14 days (IQR 9-24 days) for critically ill patients. Pre-COVID frailty was independently associated with hospital mortality (OR 3.5, 95% CI 1.9-6.5), adjusting for age and critical illness. Many patients experienced inability to walk and/or return home independently at hospital discharge, which were associated with baseline disability (OR 2.1, 95% CI 1.1-4.1 for inability to walk, OR 1.9, 95% 1.1-3.4 for inability to return home), adjusting for age and critical illness. Conclusion: Disability and frailty are common among patients hospitalized with SARS-CoV2 infection and associated with poorer outcomes. Additionally, COVID hospitalization is associated with increased disability and loss of independence, especially among critically ill patients. Improving recovery and patient centered outcomes after severe SARS-CoV2 hospitalization will likely require careful discharge planning, post-hospital follow-up, and additional research.
ABSTRACT
Rationale -For the aging and comorbid veteran population, COVID-19 has made “ventilator” a household word. With the excessive cost and low quality of life associated with aggressive end of life (EOL) care, the need for effective goals of care (GOC) conversations prior to development of acute illness has never been higher. Physicians are often reluctant to initiate these conversations, but patients could be prompted to broach the topic using standardized media delivered in the waiting room. Methods -We conducted a randomized controlled trial evaluating educational media in the outpatient setting. Veterans in the waiting room who were over 65 were randomized to one of two interventions or control. The interventions were a VHA produced brochure on GOC or a 7-minute video on GOC featuring a mock code. Participants were given a survey, and had a follow up phone interview to assess if they had brought up EOL care at their office visit. At 30 days, chart review assessed documentation of GOC. Primary endpoint was whether the patient initiated an EOL discussion at their office visit. Secondary endpoints included code status, GOC documentation, and evaluation of emotional response. Results -Despite hundreds of eligible patients, <10% opted to discuss enrollment, and <5% enrolled in this study. Needed sample size was 153, with only 30 enrolled at study conclusion. There was low rates of all endpoints. Only one participant initiated EOL discussions, but this discussion was not documented. Three filed new GOC documents (including one who died while CMO). Two found the material upsetting (including one in the control). None indicated that they would not trust their physician to make EOL decisions for them, though several were unsure. All participants thought that their material should be shown to other veterans. Due to underpowering, there was no statistical difference in any outcome (Table 1). Conclusion -EOL discussions remain an important job of the outpatient physician, though many patients do not discuss EOL care until they are acutely ill. A standardized patient centered format delivered in the clinic waiting room remains a promising option to facilitate these discussions, though there are still physician level barriers in documenting these conversations. Larger studies are required to demonstrate that this type of intervention is effective. Our study shows that patients have low rates of negative emotional responses to this type of material, and would universally recommend this material to other veterans.
ABSTRACT
RATIONALE: Long-term quality of life is a significant concern for survivors of sepsis and acute respiratory failure (ARF). Financial burdens await as many patients never return to work. Notably, the duration of the ICU stay significantly correlates with the severity of physical impairment and up to 25% of skeletal muscle is lost within one week in the ICU. The recent pandemic due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) is likely to exacerbate these issues. We have previously reported that metabolites related to mitochondrial bioenergetics status can predict acute patient outcomes. Here, we propose that these same metabolomic and mitochondrial biomarkers of mortality also predict physical function in survivors. METHODS: To test this hypothesis, we performed a retrospective analysis of metabolomic changes in ARF survivors using ultrahigh performance liquid chromatography mass spectrometry. Six months after ICU admission, physical function was determined by the short physical performance battery (SPPB), an objective physical function measurement assessing gait speed, balance and lower extremity strength. A total of 70 consecutively enrolled patients were selected, of which 35 had good physical function (SPPB ≥ 7) and 35 had poor physical function (SPPB ≤6). The patients were matched for age, race and sex. Metabolomic analysis of patient's serum was measured at ICU admittance (n=70), 5d-post admittance (n=20) and discharge (n=20). RESULTS: More than 1250 named compounds were identified. There were only 19 metabolites that were significantly different at admittance (ANOVA;p < 0.05), of which seven were bile acids. However at discharge, despite less patient samples tested, 151 metabolites were significantly different (ANOVA;p < 0.05). Specifically, we found that 10 lysophospholipids, eight bile acids, three TCA cycle metabolites, eight kynurenine-related metabolites and nine urea cycle metabolites were significantly different. Many of these pathways have previously been shown to be altered in nonsurvivors of sepsis and ARF. CONCLUSIONS: Findings suggest that bioenergetic abnormalities arising during the acute phase of recovery may be persistent and predict longer-term decrements of physical function in survivors of ARF. Larger retrospective and prospective studies are needed to confirm these preliminary findings;however, predicting poor physical function in survivors as well as identifying the affected metabolic pathways may lead to improved therapies and long-term patient outcomes.
ABSTRACT
Introduction: Before the covid pandemic we provided community respiratory nursing support for patients with chronic lung diseases especially COPD, pulmonary rehabilitation (PR) and a home oxygen service supporting/assessing patients needing oxygen in the community. The pandemic has led to refocussing our services and staff, helping to keep patients out of hospital. Group pulmonary rehabilitation classes were no longer possible. Methods: We have refocussed our service to provide covid-safe services with PPE and early staff immunisation. Some staff were seconded to a rapid response unit for those acutely ill. Others carried out a care homes initiative to review all patients with respiratory disease in care homes. The oxygen team picked up patients discharged post covid from hospital requiring oxygen at home. We identified high risk patients for regular telephone contact. Results: Referrals after admission for non-covid respiratory infections fell as patients stayed at home and reduced contacts. 1.1-1.4 2020v 2021: 236 v 79;GP referrals also fell 1.1-1.4 2020-2021;87 v 35. Both have increased post lockdown. Referrals for PR fell. Total 1.1-1.4. 2020 v 2021, 373 v 107, GP referrals 226 v 54. Post lockdown 1.7.21-1.10.21 there has been an increase, total 139:GP 81. Group PR is starting up again. Oxygen referrals after covid admissions up to 1.10.20 were only 8 from the first wave of disease, but 119 from 15.10.20-10.5.21, and 18 from 9.8.21-1.11.21 (11 ambulatory alone): all patients discharged after covid requiring oxygen at home are contacted by telephone and visited at home. We identified 380 patients who were rated as high risk, either having <3 admissions in 12 months, recent oxygen required at home or PCO2 <7.5Kpa. These were contacted weekly as they sheltered at home. Our staff reviewed 163 patients in nursing homes, 116 with respiratory disease, 31/116 already known to the service. 75% of patients needed a new reliever inhaler or spacer. 58% did not have a rescue pack of antibiotics and steroids, 85% required a salbutamol inhaler. Conclusion: Identification of “high risk patients allowed us to provide telephone support to keep them safe at home. Reviewing all residents in care homes identified unmet needs for therapy and support. Prompt review of patients requiring oxygen after admission for covid helps them once discharged. Admissions for non covid exacerbations fell as patients remained at home with limited contacts, but on re-entering the outside world, admissions for COPD have risen again.