Evusheld prophylaxis increases social interactions and improves anxiety, depression, agoraphobia and quality of life scores

Evusheld is a combination injection of tixagevimab/cilgavimab for pre-exposure COVID-19 prophylaxis and was made available to UK private clinics from October 2022. NICE review is ongoing. Whilst efficacy analysis of Evusheld has focused on the risk-reduction of contracting COVID-19, anecdotal reports suggest additional psychological benefits from Evusheld, although supportive objective data are lacking. In this study, we used 4 well-established psychological health questionnaires to assess different psychological parameters (EQ5D-3 L quality of life (QoL) score, DSM5 Agoraphobia score, Duke's Social Support Index (DSSI) and the hospital anxiety and depression score (HADS)) in blood cancer patients treated with Evusheld at the Genesis Care (GC) Clinic, Cambridge. Patient data (pre-and post-Evusheld) were compared with a control group of GC blood cancer patients who had not received Evusheld. The study was approved by GC and all patients had consented to email contact. Questionnaire replies were anonymised and free-text comments were invited. Questionnaires were completed by 29/40 Evusheld and 54/100 control patients. With EQ5D, Evusheld did not impact mobility, self-care and pain/discomfort scores and patient/ control groups scored at similar levels. EQ5D scores for 'usual activities' and 'anxiety/depression' improved post-Evusheld (patients reporting 'normal activities' increased from 52% to 76% (control = 78%);patients reporting 'no anxiety/ depression' increased from 45% to 66% (control = 65%)). The mean global EQ5D QoL score improved post-Evusheld [69.4% to 72.9% (control = 75.7%)]. With the DSM5 agoraphobia score, Evusheld treatment improved agoraphobia parameters, reducing the mean score from 15.7 to 5.1 (control = 3.7;max = 40) with certain striking changes;72% of pretreatment patients avoided crowded situations all of/most of the time, reducing to 14% post-Evusheld (control = 11%). The DSSI score assessed social/work interactions with external household contacts and post-Evusheld the mean number of interactions over 3 weeks increased from 1.48 to 3.37 (control = 3.77). Pre-Evusheld, 52% of patients had no interactions outside their household, dropping to 20% in the 3 weeks post-Evusheld (control = 17%). Using the HADS 14-point analysis of depression and anxiety revealed on average that each parameter was 25.3% 'significantly improved' and 25.4% 'a little improved' post-Evusheld. Accepting limitations of a small study and potential biases associated with a self-funding patient cohort, Evusheld treatment broadly improved all psychological scores assessed. Free-text comments clearly indicate that Evusheld had a major positive impact on QoL/social mobility for specific patients. The Evusheld patients had higher baseline scores for social isolation, anxiety, depression and agoraphobia compared with control patients, yet Evusheld treatment appeared to improve these parameters to a level similar to control patients.

Combining information technology and human research efforts to lessen personnel burden and costs One success story

Objectives: Develop a coding system to extract EHR data and establish research validity to lessen need for manual data extraction Methods: As part of a data collection project for COVID + patients requiring ICU care, we established data elements able to be extracted from the Epic electronic health record (EHR). Collaboration between Information Technology (IT), research and clinical personnel established where data elements were located within the EHR and what data could be extracted with minimal manual assistance and uploaded to a research database. Coding was developed using Structured Query Language (SQL) with best practices (includes indexes, execution plans, optimized range keys, avoiding large reads inside read-write transactions as instructed by the Epic consultant). Accuracy of extracted data was evaluated by manual validation of data against Epic records via random selection of patient data within the cohort. Result(s): From July-December 2022, coding was developed which extracted over 130 fields of data from 3093 COVID patients across 5 INOVA ICU sites (demographic, physiologic, lab, interventions, outcome). Prior efforts at data extraction of these elements from research personnel (ZS) who previously performed this task noted an average of 4 hours/patient to complete coded fields. Coded data was also noted to be more accurate when accessed by the same personnel to manually extracted fields. Assuming 4 hrs/pt, manual extraction would require 12,372 hours, which equates to over 6 full time human research personnel. Data coding required 446 hours. Coded data extraction can be almost immediate once fields requested are established, decreasing personnel costs and effort significantly. Conclusion(s): Reduction in need for manual data collection using automated coding extraction can reduce costs, personnel time and enhance research efforts. Sharing coding mapping to other EPIC sites or use of similar methods may improve timeliness of ongoing data extraction and will be useful to develop earlywarning and patient-centered care algorithms to improve care.

Examining the Association of Air Quality on Covid-19 Patient Outcomes Using Area Level Data from the Electronic Health Record

Background: Within the coronavirus 2019 (COVID-19) pandemic, literature has found worsened patient outcomes and increased virus transmissibility associated with reduced air quality. This factor, a structural social determinant of health (SDOH), has shown great promise as a link between air quality and patient outcomes during the COVID-19 pandemic. Researching SDOH within our patient populations is often difficult and limited by poor documentation or extensive questionnaires or surveys. The use of demographic data derived from the electronic health record (EHR) to more accurately represent SDOH holds great promise. The use of area-level determinants of health outcomes has been shown to serve as a good surrogate for individual exposures. We posit that an area level measure of air quality, the county-level Air Quality Index (AQI), will be associated with disease worsening in intensive care unit (ICU) patients being treated for COVID-19. Method(s): We will calculate AQI using a combination of open-source records available via the United States Environmental Protection Agency (EPA) and manual calculations using geospatial informatics systems (GIS) methods. Subjects will be identified as adult (> 18 years) patients admitted to Vanderbilt University Medical Center's ICUs between January 1, 2020, and March 31, 2022 with a positive SARS-CoV-2 laboratory analysis result. We will exclude patients without a home address listed. Patient demographic and hospital data from ICU admission to 28 days following admission will include: age, sex, home address, race, insurance type, primary language, employment status, highest level of education, and hospital course data. Together these will be collated to produce our primary outcome variable of WHO Clinical Progression Scale score. These validated scores range from 0 (uninfected) to 10 (dead) to track clinically meaningful progression of COVID-19 infected patients. Our AQI variable will be obtained from the EPA available county-level monitoring station spatial data combined with open-source state/county center point spatial data. These data contain historic cataloguing to determine air quality at both specific time points and averages over time. Where a county's average yearly AQI is not available due to lack of a monitoring station, we will use spatial data tools to calculate an average based on data from nearby stations. We will utilize yearly averages of AQI in the year prior to COVID-19 diagnosis to describe overall impact of air quality on patients' respiratory outcomes as opposed to single day exposures. Linkage of patient data to AQI database will be performed using patient addresses. Discussion(s): By combining area level data with electronic health record (EHR) data, we will be positioned to understand the contribution of environmental and social determinants of health on patient outcomes. Our long-term goal is to elucidate which social and environmental determinants of health are associated with worse outcomes from COVID-19 and other respiratory viruses, using data extracted from the EHR.

Evaluating the Use of Patient Reported Outcome Measures to Assess Intra-Pandemic Psoriatic Arthritis Disease Activity and Comparing Them with Pre-Pandemic Clinical Assessments

Background/Aims In our department, patient reported outcome measures (PROMs), including RAPID-3 and PSAID12, were employed during the COVID-19 pandemic in asynchronous consultations for patients with psoriatic arthritis (PsA). We compared pre-pandemic DAS28-CRP with intrapandemic PROMs to assess changes in disease activity since the pandemic. Whilst previous studies have primarily compared PsA PROMs with clinician-assessed scores (e.g. PASDAS), we compare PsA PROMs with clinicians' overall assessment of disease activity;this judgement considers PROMs, serology studies and individual patient feedback. Finally, we assess whether patients with PROMs indicating active disease were followed up appropriately. Methods Clinician-assessed scores were collected between 01/01/2019-01/03/ 2020 (''pre-pandemic''). Between 01/12/2020-31/03/2022 (''intrapandemic''), patient data from electronic surveys were analysed in a secure database for calculation of PROMs. These data, alongside blood results and patient comments, informed clinicians' triage decisions. Clinical outcome data were collected from electronic patient records;>=3 months follow-up appointment allocation was the target for patients with active disease (moderate/high disease activity). Data analysis was performed using r (version 4.2.2). Results In our pre-pandemic cohort (n=393), 79.8% of patients were in remission (per DAS28-CRP). Conversely, the intra-pandemic cohort (n=231) showed remission rates of 14.3% (per PSAID12) and 0% (RAPID-3). Indeed, 33.7% (based on PSAID12) vs 75.8% (RAPID-3) had moderate/ high disease activity. These results were validated in a paired cohort (n=38, score recorded in both windows). Disease activity worsened during the pandemic for 63.2% (PSAID12) and 97.4% (RAPID-3) of patients. PSAID-12 correlated positively with RAPID-3 (r=0.52, p<0.001), especially when RAPID-3 >=6.5 (r=0.75, p<0.001). When comparing PROMs with clinicians' assessment of PsA activity in our paired cohort, PSAID12 and RAPID-3 accurately reflected disease status in 70.6% and 58.8% of patients respectively. 3/9 and 9/27 patients with active disease, based on PSAID12 and RAPID-3 respectively, were seen within three months. Conversely, 7/10 patients who clinicians had deemed to have active disease were seen within three months. Conclusion Despite approximately 80% of patients being in pre-pandemic remission, the majority reported active intra-pandemic PsA. Whilst RAPID-3 skewed patients towards active disease, PSAID12 skewed patients towards remission/low disease activity. PSAID-12 and RAPID- 3 have been previously correlated;however, here we suggest that they could be used interchangeably in patients with high disease activity. PSAID-12 was a better predictor of clinicians' assessment of disease activity, although neither PROM correlated well with >=3 months followup appointment allocation. Although RAPID-3 and PSAID12 helped inform clinicians' decisions, neither alone sufficiently reflects patients' disease states. Remote management is practicable, but future studies should validate these findings across a larger cohort and assess the utility of different PROMs across PsA disease activity categories. Furthermore, multivariate analysis is warranted to ascertain which (combination of) variable(s) (e.g., PROMs, serology results, tender/ swollen joint count) best correlates with clinician judgement.

Evaluation of Homologous and Heterologous Vaccine against Sars-Cov-2 in Systemic Lupus Erythematosus Patients: Data from Safer Study

Objectives: To evaluate the immunogenicity of ChAdOx1, Coronavac and BNT162B2 vaccines in SLE patients, including homologous and heterologous immunizations. Method(s): The 'Safety and efficacy on COVID-19 Vaccine in Rheumatic Disease-SAFER study' is a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 Vaccine in immune-mediated rheumatic diseases (IMRD) in real life, started on May 2021. SLE patients (according to the 2012 SLICC classification criteria), older than 18 years of age were recruited after 2 or 3 doses of vaccine against COVID-19 (ChAdOx1, BNT162b2 and CoronaVac) and were evaluated at baseline and on the 28th day after each dose. Homologous immunization was considered if they received three doses of the same vaccine and heterologous if a different one was applied. IgG antibody against SARS-CoV-2 spike receptor-binding domain were measured by chemiluminescence (SARS-CoV-2-IgG-II Quant assay, Abbott-Laboratories) at baseline and 28 days after the first, 2nd and 3rd doses (Seropositivity IgGSpike>= 7.1BAU/mL). Statistical analysis: ANOVA and pairwise comparisons tests Results: 316 SLE patients were included (255 heterologous and 61 homologous immunization), 89.2% were female and the mean age was 37.6 +/- 11.2 years. The two groups were homogeneous regarding demographical data, disease activity and immunosuppressive treatment. 49.7% used corticosteroids (alpha 5 mg/day in 52.3%), 83.5% antimalarials, 22.8% azathioprine and 20.3% mycophenolate mofetil. 207 patients received the first two doses with CoronaVac, 128 ChadOx-1 and 32 BNT162b2. Regarding the first two doses of the same vaccine, there was no difference in IgG titers over time between CoronaVac or ChadOx-1 (p = 0.313). IgG titers increased in all vaccine groups, with difference only after 2nd dose: 4.96 +/- 1.71BAU/mL CoronaVac vs. 6.00 +/- 1.99BAU/mL ChadOx-1 vs. 7.31 +/- 1.49BAU/mL BNT162b2 (p alpha 0.001). There was no difference in IgG titers over time between homologous or heterologous vaccine schedule (p = 0.872). IgG titers also increased in all groups, with difference only after 2nd dose: 5.49 +/- 1.96BAU/mL heterologous vs. 6.30 +/- 2.10BAU/mL homologous (p = 0.009). Conclusion(s): Induction of immunogenicity occurred in different vaccine regimens in SLE patients. Future research to explore different heterologous schemes in IMRD must be performed.

Real-time, leukocyte-related, four times validated, patient data partitioning

Introduction: Indicators that assess relationships among leukocytes may inform more and/or earlier than those measured in isolation. Method(s): Blood leukocyte differential counts collected from 101 Mayo Clinic COVID-19 patients were related to later outcomes following two approaches: (i) as unstructured data (e.g., lymphocyte percentages) and (ii) as data structures that assess intercellular interactions. Analyzing the same primary data, it was asked whether information contents differed among methods and/or when two sets of structured indicators are used. Result(s): While unstructured data did not distinguish survivors from non-survivors (Fig. 1, rectangle A), one data structure (here identified with letters expressed in italics) exhibited one perpendicular inflection that differentiated two patient groups (B). Two survivor-related observations were also distinguished from the remaining data points (B). A second data structure also revealed a single line of observations and a perpendicular data inflection (C), while more (four) patient groups were identified (D). Four validations were conducted: (i) increasing mortality levels among contiguous data subsets (0, 7.1, 16.2, or 44.4%) suggested construct validity (D);(ii) internal validity was indicated because 22 of the 45 survivors detected by the first data structure were also captured by the second one;(iii) the analysis of patients that differed in address, co-morbidities and other aspects supported external validity;and (iv) quasi non-overlapping data intervals predicted statistical validity (E, F). The structured approach also uncovered new and/ or dissimilar information: different leukocyte-related ratios explained the clusters identified in these analyses (E, F). Conclusion(s): Structured data may yield more information than methods that do not assess multicellular interactions. Possible applications include daily, longitudinal, and personalized analysis of hospital data.

Risk factors for nosocomial infections in COVID-19 ICU population

Introduction: The aim of this study is to identify the factors associated with an increased risk of developing nosocomial infections (NI) in COVID-19 patients admitted with pulmonary involvement in the ICU. NI in COVID-19 ICU population are an important cause of morbidity and mortality worldwide and its prompt identification might lead to its prevention and better outcomes. Method(s): This is a retrospective observational study of patients admitted with COVID-19 pneumonia in the ICU of a tertiary center in Portugal, between March 2020 and December 2021. We considered NI as any infection acquired > 48 h post ICU admission. Clinical, analytical and baseline patient data were evaluated. Logistic regression analysis was performed to correlate patient related variables with the development of NI. Result(s): A total of 338 patients were enrolled, from which 167 (47.9%) presented with NI. Baseline characteristics are described in Table 1. In the logistic regression analysis, older age (OR 1.13;95% CI 1.03-1.25;p = 0.013), coronary artery disease (CAD) (OR 28.7;95% CI 1.92-429;p = 0.02), obesity (OR 3.14;95% CI 0.86-11.42;p = 0.008), chronic liver disease (CLD) (OR 104.33;95% CI 1,.04-1008.49;p = 0.04), use of dexamethasone (OR 21.89;95% CI 3.04-157.85;p = 0.002) and days in RASS < 3 (OR 1.4;95% CI 1.05-1.86;p = 0.02) were associated with an increased risk of developing NI in the ICU. Surprisingly, SOFA at admission, days of invasive mechanical ventilation, days of sedation and PaO2/ FiO2 ratio at admission, although statistically significantly different between groups, did not correlate with the risk of infection. Conclusion(s): We identified prolonged deep sedation, corticosteroid use, and patient characteristics (CAD, obesity, CLD, older age) as independent risk factors for NI development in COVID-19 critically ill patients. It is also noteworthy to point out for the presence of confounding variables, including the excessive workload in the ICU during this period, leading to an increase in NI numbers.

Outcomes of renal replacement therapy in critically ill COVID-19 patients

Introduction: Our goal is to describe outcomes of critically ill COVID-19 patients submitted to renal replacement therapy (RRT), in particular the association of RRT with mortality. Multi-system organ failure or direct kidney injury caused by SARS-CoV-2 is associated with the development of acute kidney injury (AKI) which subsequently increases the need for RRT and may affect the outcomes. Method(s): This is a retrospective observational study of 338 critically ill patients admitted with COVID-19 pneumonia in the ICU of a tertiary center in Portugal, between March 2020 and December 2021. Clinical, analytical and baseline patient characteristics were evaluated. Logistic regression analysis was performed to correlate patient data with the need for RRT and ICU mortality. Result(s): From a total of 338 patients, 5% required RRT (n = 16), 25% of which received intermittent hemodialysis (n = 4) and 87,5% continuous veno-venous hemofiltration (n = 14). Baseline characteristics are described in Table 1. In our sample, 61 patients (18%) presented with acute AKI, from whom 14 (23%) were submitted to RRT. From all the patients receiving RRT, 10 (62.5%) did not have pre-existing chronic kidney disease. In the logistic regression analysis, AKI (OR 45.4;95% CI 7.7-269.5;p < 0.001), higher SOFA (OR 1.24;95% CI 103-1.51;p = 0,03), creatinine (OR 2.01;95% CI 1.4-3.0;p < 0.001) and C-reactive protein (OR 1.09;95% CI 1.02-1.16;p = 0,01) on admission were associated with the need for RRT. Additionally, ICU mortality associated with RRT was 75% compared to 28.3% in the group not submitted to RRT (OR 7.6;2.4-24.2;p = 0.001). Conclusion(s): The need for RRT in critically ill COVID-19 patients is associated with an increased mortality rate in our study. We were also able to identify AKI, higher SOFA, creatinine and C-reactive protein at admission as risk factors for RRT. However, due to the retrospective nature of our analysis and our small sample size, more studies on this topic are needed to confirm these results.

Derivation and validation of clinical phenotypes and associated treatment responses in critically ill COVID-19 patients

Introduction: Due to variability in the host response, a uniform treatment strategy for severe COVID-19 may be inadequate. We applied unsupervised clustering methods to large cohorts of COVID-19 ICU patients to derive and validate clinical phenotypes, and to explore treatment responses in these phenotypes. Method(s): Phenotypes were derived in 13.279 critically ill COVID-19 patients admitted to 82 Dutch ICUs from September 2020 to February 2022. Twenty-one features were selected from clinical characteristics measured within 24 h after ICU admission. Phenotypes were assigned using consensus k means clustering. External validation was performed in 6225 critically ill COVID-19 patients admitted to 55 Spanish ICUs from February 2020 to December 2021. Individual patient data on corticosteroids therapy enabled us to investigate phenotype-specific responses in this cohort. Result(s): Three distinct clinical phenotypes were derived (Fig. 1A). Patients with phenotype 1 (43%) were younger, had lower APACHE IV scores, higher BMI as well as a lower P/F ratio and 90-day in-hospital mortality (18%, Fig. 1A). Phenotype 2 patients (37%) were older and had slightly higher APACHE IV scores compared with phenotype 1, a lower BMI, and higher mortality compared to phenotype 1 (24%, p = 2.95e-07). Phenotype 3 (20%) included the oldest patients with the most comorbidities and highest APACHE IV scores, severe renal and metabolic impairment, and the worst outcome (47% mortality, p = 6.6e-16 and p = 6.6e-16 versus phenotypes 1 and 2, respectively). Phenotype distribution and outcome were very similar in the validation cohort (Fig. 1B). This cohort also revealed that corticosteroid therapy only benefited phenotype 3 (65% vs. 54% mortality, p = 2.5e-03, Fig. 1C). Conclusion(s): COVID-19 ICU phenotypes based on clinical data are related to outcome and treatment responses. This can inform treatment decisions as well as randomized trials employing precision medicine approaches.

Remdesivir in Hospitalized Covid-19 Patients: Individual Patient Data Meta-Analysis

Background: The interpretation of the evidence from randomized clinical trials (RCTs) on remdesivir for hospitalized patients with coronavirus disease 2019 (COVID-19) is conflicting. We conducted a systematic review and individual patient data meta-analysis (IPDMA) of RCTs to assess the benefit and harm of remdesivir compared to placebo or usual care in hospitalized patients and whether treatment effects differed between prespecified subgroups. Method(s): We systematically searched electronic databases and registries through April 11th 2022 and contacted authors of eligible trials to share individual patient data. The primary outcome was all-cause mortality at day 28. We used multivariable hierarchical regression adjusting for respiratory support, age, and enrollment period to investigate effect modifiers. The study was registered in PROSPERO (CRD42021257134). Result(s): Out of nine eligible RCTs, eight provided individual data for 10480 hospitalized COVID-19 patients (99% of global IPD) recruited between February 2020 and April 2021. Within 28 days of randomization, 662 of 5317 patients (12.5%) assigned to remdesivir and 706 of 5005 (14.1%) assigned to no remdesivir died (adjusted odds ratio [aOR] 0.88;95% confidence interval [CI], 0.78-1.00;p=0.045). We found evidence for a credible subgroup effect according to respiratory support at baseline (interaction p=0.019). Of those ventilated including high-flow oxygen, 253/844 (30.0%) assigned to remdesivir died versus 241/846 (28.5%) assigned to no remdesivir (aOR 1.10 [0.88-1.38];low certainty evidence). Of those receiving no or low flow oxygen, 409/4473 (9.1%) assigned to remdesivir died versus 465/4159 (11.2%) assigned to no remdesivir (aOR 0.80 [0.70-0.93];high certainty evidence). There was no credible subgroup effect with respect to time to start of remdesivir after symptom onset, age, presence of comorbidities, enrollment period or corticosteroid use. Remdesivir did not increase the frequency of severe or serious adverse events. Table 1 summarizes the findings according to GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Conclusion(s): This IPDMA, summarizing the evidence of 99% patients ever randomized on the topic, demonstrated that remdesivir reduced mortality in hospitalized COVID-19 patients requiring no or conventional oxygen support, but patients requiring more respiratory support may not benefit. These findings may inform clinical guidelines, especially due to increasing resistance to current monoclonal antibodies.

Investigating monotherapy and combination therapy trends in newly diagnosed patients with pulmonary arterial hypertension among EU3 & UK physicians over the COVID-19 pandemic

Background: Pulmonary Arterial Hypertension (PAH) is a form of pulmonary hypertension, where the narrowing of arteries in the lungs restricts blood flow and so increases pressure in the vessels. Studies have demonstrated that initial combination therapies are optimal for PAH management. However, prescription of monotherapy treatment is still prevalent as a first line therapy. Purpose(s): The purpose of this research was to investigate prescribing trends of physicians for first line patients with PAH in the UK, Germany, Italy and Spain. We investigated the proportions of newly diagnosed patients and the prescription trends for monotherapy and combination therapy prior to and during the COVID-19 pandemic. Method(s): A multi-country, multi-centre online medical chart review study of patients with PAH was conducted between April - June of 2019, 2020 and 2021 respectively. Recruited from a large access panel, 178 treating cardiologists, pulmonologists & rheumatologists in the UK (n=16), Germany (n=55), Italy (n=55) and Spain (n=52) were screened for duration of practice in their speciality and caseload (>=5 PAH patients in the last 3 months), and provided data on 694 PAH patients (UK = 71, Germany = 206, Italy = 208, Spain = 209). Reported patient data pertained to medical chart information reflecting the prior year, i.e., Q2 2021 data reflected the 2020 period (advent of the COVID-19 pandemic). Result(s): In this dataset, there has been a consistent decrease in the proportion of newly diagnosed (i.e. diagnosed within 12 months of being reported) patients reported from 2019 to 2020 and 2021. In 2019, 49% of the reported patients were diagnosed within the last 12 months. However, the newly diagnosed patient population dropped to 37% in 2020 and continued to drop to 27% in 2021. Despite this, there has been an increase in reported first line patients within the newly diagnosed segment from 74% in 2019, to 75% in 2020, then at 87% in 2021. This increase can be seen to coincide with the ongoing COVID-19 pandemic. In 2019, 58% of reported newly diagnosed patients were recorded as receiving monotherapy. This did drop to 33% in 2020;however, in 2021 monotherapy uptake increased to 47%. Of note, the usage of the endothelin receptor antagonist (ERA) drug class increased from 67% in 2019 to 83% in 2020 but dropped to 69% in 2021. Conclusion(s): This data set suggests a decreasing trend in newly diagnosed patients and a gradual shift in treatment type to first line monotherapy prescription, which coincided with the height of the COVID-19 pandemic. More newly diagnosed patients (those diagnosed within 12 months of being reported) are receiving monotherapy treatment at the expense of combination therapy, and this has also coincided with the pandemic. Further investigation using comparator cohort is warranted to assess whether the challenges physicians faced during the pandemic has had a causal effect on the prescribing habits for PAH therapies.

Patient Factors Associated with Death of COVID-19 Patients in an Urban Emergency Department

Objectives: We aim to identify demographics, chief complaints, and comorbidities among patients who tested positive for COVID-19 in the University Medical Center New Orleans (UMCNO) ED and to identify which variables are associated with death. Background(s): On March 9, 2020, the novel coronavirus (COVID-19) breached Louisiana state lines, spreading to all 64 parishes within a month with New Orleans as the epicenter. Louisiana Department of Health data reveal that Black and elderly patients are disproportionately affected by the virus. Despite these findings, it is still largely unknown what other patient characteristics are associated with COVID-19 outcomes in the Louisiana population. Method(s): A retrospective chart review of the first 500 patients >/= 18 years old testing positive for COVID-19 at UMCNO-ED was conducted. We queried for patient characteristics, clinical care practices, and hospital courses. Data was stored in RedCap. Descriptive and multivariate analyses were conducted using de-identified patient data in Microsoft Excel and SAS 9.4. Logistic regression was used for associations with death. Reported odds ratios are unadjusted as no confounding variables were identified. Result(s): The 500-patient sample was predominantly female (56%) and Black (88%). The leading range for BMI was >35 (35%) and for age was 50-59 years (25%, mean=49). Of the 23 patients who died, 83% were black, and the leading age range was 60-69 (36%, mean=63). Pre-existing health conditions in descending order of frequency included: obesity, hypertension, and diabetes for the entire cohort (n=500), and diabetes, hypertension, and obesity for patients who expired (n=23). Common chief complaints in descending order of frequency were fever, flu-like symptoms, and cough for the entire cohort, and shortness of breath, fever, and cough for those who expired. The following patient characteristics were found to be associated with death: age > 65 (OR, 4.9;95% CI, 2.1;p=0.0002), shortness of breath (OR, 2.9;95% CI, 1.2;p=0.02), and history of diabetes (OR, 6.2;95% CI, 2.5;p=0.0001). Conclusion(s): Our study described the predominant demographics, pre-existing health conditions, and chief complaints of the first 500 patients to test positive for COVID-19 at UMCNO-ED. The factors associated with a higher likelihood of COVID-19-related death were identified. Further investigation into the health disparities experienced between patient populations is warranted, as they may be associated with higher incidences of COVID-19 infection and mortality.Copyright © 2023

Real-World Experience on the Use of COVID-19 Vaccination in Multiple Sclerosis Patients Treated with Cladribine Tablets Participating in the ADVEVA Patient Support Program within the Gulf and Latin American Regions

Background: National Multiple Sclerosis Society and other international guidelines suggest that full COVID-19 vaccination status should be completed two to four weeks before starting Year 2 of treatment with cladribine tablets (CladT). CladT is administered twice over two years, Year 1 and Year 2. There is a special interest in real-world evidence on whether vaccination status may affect initiation of CladT treatment in Year 2. The objective of this analysis was to describe the proportion of patients treated with CladT who received COVID-19 vaccination, and whether this influenced the timing of initiating treatment with CladT in Year 2. Material(s) and Method(s): A vaccination questionnaire-based survey was sent to patients treated with CladT who were enrolled in the ADVEVA patient support program (PSP), upon their consent. The survey was carried out in the Gulf region (GULF) from Jun 2021 to Sept 2021, and in the Latin American region (LATAM) from Jan 2022 to Mar 2022. Demographics, COVID-19 vaccination status, type of vaccine(s), number of doses received, and dates of vaccination were collected. In each region, patient data from the survey were linked to data routinely collected by the PSP, with cut-off dates as mentioned. Fully vaccinated status was defined as having received 2 doses of mRNA vaccine, 1 dose of Johnson & Johnson vaccine or other vaccines approved by the World Health Organization, plus 14 days. Descriptive analyses were performed and time to Year 2 treatment initiation among those with at least 18 months' follow-up was estimated by vaccination status. Result(s): The survey participation rate in GULF was 87% (91 out of 105) and 19% in LATAM (152 out of 789). In total, 62 (68%) patients in GULF and 144 (95%) in LATAM were fully vaccinated against COVID-19. In both regions, among those with at least 18 months' follow-up (GULF, n=59;LATAM, n=81), all patients initiated Year 2 of treatment with CladT, regardless of vaccination status. In GULF, the mean (standard deviation) time to treatment initiation in Year 2 was 13.8(1.6) months among fully vaccinated patients (44%) and 13.3(3.5) months among those not fully vaccinated (21%). In LATAM, the mean time was 12.8(1.4) months among those fully vaccinated (52%) and 12.4(0.02) months among those not fully vaccinated (1.3%). In each region, only 1 patient initiated Year 2 treatment after at least 18 months from the start of Year 1. Conclusion(s): Most patients were fully vaccinated against COVID-19 in GULF and in LATAM, which was consistent with vaccination coverage and guidelines in both regions. In LATAM, low participation rates might lead to selection bias which limits interpretation of results. In these regions, with limited data, COVID-19 vaccination status did not appear to alter the time of treatment initiation with CladT in Year 2. Almost all patients followed the label recommendations in terms of timing of Year 2 treatment initiation.Copyright © 2022

Severe COVID-19 infection predisposes patients to greater burden of hair loss

There is a growing body of evidence suggesting a link between COVID-19 infection and certain forms of hair loss, such as telogen effluvium. The present study aims to determine the prevalence of hair loss following COVID-19 infection and ascertain the role of COVID-19 severity as a risk factor for its development. A retrospective study was conducted using patient data from the Northwestern Medicine Enterprise Data Warehouse with institutional review board approval from Northwestern University. Patients aged >= 18 years with COVID-19 diagnoses between January 2020-June 2022 and >= 1 encounter with dermatology providers within 180 days post-infection were included in the study. History of COVID-19 and documented hair loss diagnoses were recorded along with demographic data. COVID-19 severity was classified based on whether the patient was given outpatient or inpatient/emergency care for COVID-19. Time-to-alopecia onset was calculated relative to the nearest preceding COVID-19 diagnosis. Pearson's chi-squared and Kaplan-Meier analysis were performed to evaluate differences in incidence and time-to-alopecia onset by severity of COVID-19 infection. Analyses were conducted using R 4.2.1. In total, 10,861 patients met the inclusion criteria for the study. Patients were more commonly female (N = 6,974, 64.2%) and White (N = 8,301, 76.4%) with a mean age of 48 years at COVID-19 diagnosis. Overall, 6.5% of COVID-19 patients treated in inpatient/emergency settings developed hair loss compared to 4.7% in outpatient settings (P = 0.009). Patients with outpatient care had a median time to alopecia diagnosis of 73 days, compared to 99 days for patients with inpatient/emergency care (P = 0.019). Our findings demonstrate hair loss following COVID-19 infection as a notable sequela of infection. Clinicians should closely monitor patients following hospitalization for COVID-19, as they may be predisposed to hair loss following infection due to psychological or physiological stress. Future studies should aim to validate our findings and explore this relationship on a larger scale.Copyright © 2023

Immunogenicity, safety and efficacy in the CVID patients -Data from the 6-month prospective study

Background: A single-stranded mRNA virus SARS-CoV- 2 is associated with severe acute respiratory syndrome in the predisposed individuals such as elderly, obese, chronic cardiovascular or pulmonary diseases. Higher risk for severe course was also reported in inborn errors of immunity (IEI). While restriction measures play important role from the short-term perspective, vaccination may provide long-term protection. However, only limited data are available on safety and efficacy in immunocompromised patients with IEI such as Common variable immunodeficiency (CVID). Method(s): We assessed humoral and cellular responses, safety and efficacy in a cohort of 20 CVID patients after 2 doses of anti-SARS- CoV- 2 vaccine BNT162b. The humoral reponse was evaluated using ELISA and western blot methods, the T cell response measured by IFNg secretion functional assay. Adverse events were reported by Patient Clinical Questionnaire. Blood count, biochemical, coagulation and immunological parameters were checked before and after vaccination. The patients were followed for 6 months. Result(s): Despite severely impaired antibody production hunoral response was detected in 48% (n = 10/21) of patients at month 1. However, the response persisted in only 33% (n = 6/18) at month 3 and further decreaed to 13% (n = 2/15) at month 6. The T cell response was measurable in 5 patients (28%) at month 1. In total, 4 out of 20 (20%) patients got infected within the study period. None of them required oxygenotherapy or hospital admission. We did not observe any severe adverse effects beyond local pain, fatigue, headche, fever, arthralgia and myalgia. Conclusion(s): Vaccination with mRNA vaccine BNT162b provides safe and effective protection for a subgroup of CVID patients. However, the immunogenicity is lower compared to the general population.

Determining Typical Patient Effective Dose Levels Using a Dose Monitoring System for Optimization Studies: Application to Dental Cone Beam Ct Imaging

Purpose: To use a dose monitoring system for determining typical patient effective dose levels for optimization studies of x-ray exposures, with a focus on dental cone beam CT (CBCT) imaging. Material(s) and Method(s): A dose monitoring system (DOSE, Qaelum NV, Belgium) was used to collect radiation exposure data (i.e. the recorded Dose Area Product (DAP) value in dGy.cm2, Field Of View (FOV) selection in cm2, and the system operation mode), as well as the patient age for 5163 dental CBCT examinations performed in the university hospital of Leuven from January to December 2019, just prior to the Covid-19 pandemic. Examinations were performed on a 3D Accuitomo 170 (Morita, Japan) and a VGi EVO (NewTom, Italy) CBCT system. The extracted DAP values were corrected with an experimentally determined correction factor obtained during annual quality control tests. For each CBCT system, effective dose conversion factors (CFs) as a function of DAP and patient age were calculated and implemented in DOSE. CFs were determined for the following age groups: 4-6y, 7-11y, 12-14y, and >=15y. For the effective dose calculations, patient data was, for each system, further classified based on the selected FOV and operation mode. The FOV size was categorized into small (<=40 cm2), medium (>40 cm2 and <=100 cm2), or large (>100 cm2). Result(s): For the standard operation mode, average effective doses on the 3D Accuitomo 170 system as a function of age group were, from young to old: 77.7-300, 54.4-210, 39.9-154, 35.1-136 Sv, and for the VGi EVO system: 60.5-117, 12.1-97, 9.54-69.9, 9.26-61.5 Sv. For both systems, a decreasing trend in the effective dose with increasing age was observed. For each age group, the doses increased with increasing FOV size. The selected operation mode also influenced the dose to the patient (e.g. for the high-resolution mode on the VGi EVO system, 1.5-4 times higher effective doses were observed compared to the standard mode). The effective dose levels on the NewTom VGi evo system were significantly lower than on the 3D Accuitomo 170. For the VGi EVO system, the most frequently used system in clinical practice, the total radiation burden from the examinations was 0.22 manSv. Conclusion(s): This was one of the first studies providing a complete 1 year overview of dental CBCT effective doses in a university hospital dental department. The results could be used for optimization studies and/or to situate the exposures in comparison to multislice CT or panoramic examinations.Copyright © 2023 Southern Society for Clinical Investigation.

Universal Genetic Counseling for Breast Cancer Patients Mitigates Social Determinants of Health and Improves Genetic Testing Rates Across All Races

INTRODUCTION: While available since 1996, genetic testing for breast cancer patients has been limited by stigma, cost, and poor access. Many patients were not captured by traditional NCCN criteria, particularly those with healthcare barriers. Previously, genetic testing was used in high-risk screening and determining prophylactic utility, but with recent targeted therapies, has allowed personalized therapeutic benefit for patients. We expanded genetic testing counseling at a three-hospital Midwestern community hospital system from only NCCN high-risk patients to all patients diagnosed with breast cancer. METHOD(S): The implementation of universal genetic counseling to all newly diagnosed breast cancer patients began at our system in 2020. Under IRB approval, all new breast cancer patients were retrospectively reviewed from January 2019 through December 2019 (genetics based on NCCN guidelines group) and January 2021 through December 2021 (genetics offered to all group). Patient data regarding completion of genetic testing, pathologic mutations identified, stage, race/ethnicity, insurance type, primary language, and age was included in the analysis. Categorical variables were compared using Pearson's chi-square or Fisher's exact test;age was analyzed using ANOVA. RESULT(S): We reviewed a total of 973 patients, 439 diagnosed in 2019 and 534 in 2021. Demographic differences between 2019 and 2021 were similar including age, race/ethnicity, insurance, primary language. Despite the SARS CoV-2 pandemic, the stage of diagnosis between 2019 and 2021 was also similar (p=0.194). Completion of genetic testing increased significantly from 204 (48.6%) in 2019 to 338 (63.3%) (p=0.000) in 2021 with the universal access group. Across all demographic groups, genetic testing increased with significant findings in Medicare patients (p=0.005) and older patients (p=0.041) and near significant findings in non-white populations (0.059).[Table] Overall number of pathological mutations increased, 32 (7.29% of all patients) in 2019 to 39 (7.30%) in 2021, with the most common being BRCA2 (n=11), CFTR (n=9), CHEK2 (n=8), and BRCA1 (n=6). CONCLUSION(S): Implementation of universal access to breast cancer genetic counseling allowed for a significant expansion in genetic testing completion and overall increase in pathological mutations found. We saw an increase within sub-populations that may have not been targeted by NCCN guidelines previously including older patients, minority groups, and varying insurance types. (Table Presented).

Interplay between lymphocyte subpopulation, inflammatory cytokines and their correlation with oxidative stress parameters in COVID-19

Our objective was to investigate the inflammatory and oxidative stress markers in patients with moderate and severe form of coronavirus disease 2019 (COVID-19). In addition, we show the correlation between changes in lymphocyte subsets and markers of oxidative stress as a tool for patient classification. Interleukin-6 (IL-6) and VEGF were analyzed by utilizing a High Sensitivity Evidence InvestigatorTM Biochip Array technology. The total antioxidant capacity (PAT) and the free radical concentrations (d-ROM) were measured in serum utilizing analytical photometric system FRAS5. Peripheral blood was used to determine CD45 + mononuclear, B, T, and NK cells using a multi-parameter flow cytometric immunophenotypic test. Statistionly cally significant differences in IL-6 and VEGF levels were observed between the two patient groups. Decreased values of the absolute number of lymphocytes and their CD4 + and CD8 + positive T cells, NK cells, and CD8 were obtained. In the moderate group, good correlations were found between IL-6 and VEGF and NK cells (r=0.6973, P<0.05;for IL-6 and r=0.6498, P<0, for VEGF. 05). Cytokines were correlated with CD45+ (r=0.5610, P<0.05;for IL-6 and r=0.5462, P<0.05 for VEGF). The oxidative stress index can be used as a cheaper alternative and as a triage tool between severe and moderate illnesses, after showing good correlation with more expensive patient classification analysis.Copyright © the Author(s), 2022 Licensee PAGEPress, Italy.

Results of an Automatic Alert System from Microbiology to Link Diagnosis to Treatment in Patients with Chronic Hepatitis C

Introduction and Objectives: Strategies to simplify the care circuit for patients with the hepatitis C virus (HCV) are vital to achieving its eradication. To achieve this aim, we introduced an electronic system of HCV serology detection to link diagnosis with specialized assistance in order to minimize the loss of patients. Material(s) and Method(s): A retrospective single-center study of HCV patients developed by Microbiology Department from February 15th, 2020, to December 15th, 2021. In the event of a positive HCV antibody, the anti-HCV core was directly measured by the electronic system. If positive, an encrypted e-mail with the patient data was automatically sent to HCV specialized physicians, who, after evaluating the benefits of antiviral therapy in each patient, contacted them by phone for an appointment. In the first face-to-face consultation FibroScan, HCV genotype and viral load measurement were performed, and antiviral therapy was prescribed. Patient diagnosis origin and public health characteristics were recorded. We analyzed the association between antiviral therapy prescription and these variables. Statistical significance was set at p<0.005. Result(s): Of 171 patients identified, with a mean age of 59.6 +/- 15.9, 61.5 % of males and 81.2% of Spanish nationals. HCV origin from out-of-hospital settings predominated (50.9%, 87/171), particularly primary care (28.7%), penitentiary (11.6%) and addiction units (8.2%). In all, 43.3% (74/171) were aware of their diagnosis, but 64.9% (48/74) hadn't previously received antiviral therapy. Genotype 1 predominated. We recorded 19.4% (20/103) of patients F3 fibrosis and 27.2% (26/103) F4. Finally, 58.5% (100/171) attended a physician consultation. They were all treated with pangenotypic interferon-free therapy. A 100% rate of sustained viral response was achieved. The main reasons for not being treated were high comorbidity (43.7%,31/71), not located (23.9%, 17/71), patient refusal to treatment (23.9%,17/71) and death (8.5%,6/71). The sole association found between antiviral therapy and patient variables was that of comorbidities with being untreated (OR=7.14, p<0.001). Conclusion(s): Our alert system is simple and easily reproducible. It allows for minimizing the loss of HCV patients, even considering it was performed during the COVID-19 pandemic.Copyright © 2023

The use of an online teledermatology platform with patient-submitted history and images for waiting list recovery in dermatology

While teledermatology has been a feature of some dermatology services for some time, the COVID-19 pandemic has led to both a deterioration in waiting lists for routine patients, and the use of distance consultation as a means of providing and improving access for such patients. The majority of teledermatology platforms rely on general practitioner (GP)-submitted information and images, and most data suggest that these systems result in around 50% of patients avoiding hospital attendance through the implementation of management plans suggested by hospital-based consultants (Mehrtens SH, Shall L, Halpern SM. A 14 year review of a UK teledermatology service: experience of over 40,000 teleconsultations. Clin Exp Dermatol 2019;44: 874-81). We now report the use of an online platform (Virtual LucyTM) using patient-provided information via a structured questionnaire, and patient images uploaded following clear online guidance, reinforced by call centre interaction. The data are derived from funded National Health Service (NHS) work: there was no specific funding for its generation. In total, 3500 patients from two hospital trusts with routine waiting list pressures were invited to use the system as an alternative to eventual hospital attendance. After secure registration, they completed dermatology and general health questionnaires based on conventional medical history taking, as well as a Dermatology Life Quality Index and then uploaded one or more images as appropriate. The patient data were reviewed by a consultant and a self-populated report provided to the patient, GP and trust within 72 h. Forty-eight per cent of patients were discharged to their GP with reassurance or a management plan. Patients requiring hospital attendance were signposted to appropriate clinics (e.g. isotretinoin, phototherapy, patch testing) or to surgical clinics for biopsy or excision. Hospital trust-based consultants were able to access the platform to view images prior to any surgery. Of patients directed to hospital clinics, 32% were reclassified as being urgent - waiting list duration was the main determinant of the need for reclassification. Of all images, 0.5% were unsatisfactory, and those patients were contacted through the platform to ask for a replacement image with specific advice. One per cent of patients were contacted by clinical staff by telephone or video to clarify or expand on the information given, and approximately 1% of patients used the platform to ask for additional treatment details. There were no patient complaints, and GP and hospital staff issues related to logistics were increasingly uncommon as iterative development of the system and support processes occurred. Teledermatology using patient-derived information and images gives similar outcomes to those seen in published conventional teledermatology, puts fewer demands on clinical staff, is popular with patients and has a significant benefit to the NHS.