The Association of Inflammatory Marker Levels on Severity of Infection and in-Hospital Mortality among Covid-19 Confirmed Patients

Intro: COVID-19 is a respiratory and systemic disease with varying severity, caused by SARS-CoV-2 virus. The pathophysiology of COVID-19 has been postulated to be due to a release of pro-inflammatory cytokines causing cytokine storm. Several inflammatory markers have been studied to prognosticate the course of the disease but with varying results. Baseline inflammatory marker levels may be helpful in early recognition of disease severity which may translate to early aggressive treatment and better outcomes. The objective of this study is to determine the association of the initial levels of procalcitonin, CRP, LDH, Ferritin and D-Dimer on severity of infection and in-hospital outcomes among COVID-19 confirmed patients admitted at Our Lady of Lourdes Hospital Methods: A total of 238 subjects admitted from March 2020-June 2021 were included. Chart review was done and demographic and laboratory data were obtained. Subjects were categorized by disease severity and outcome. SASTM On Demand was used for data analysis: ordinal logistic regression to determine the association of initial inflammatory marker levels on the severity, while Binomial logistic regression to determined the association on the in-hospital outcome. Null hypothesis was rejected at 0.05-alpha level of significance. Finding(s): The study showed a significant association between LDH and severity of infection (p-value 0.014, Risk ratio 1.002), as well as on mortality (p-value 0.004, Risk ratio 1.003). There was no significant association between procalcitonin and severity of infection but there was significant association between procalcitonin and mortality. No significant association was noted between CRP, Ferritin and D-Dimer with severity of infection nor mortality. Conclusion(s): Patients with higher LDH levels were more at risk of severe and/or critical COVID-19 and in-hospital mortality. There was also significant association in the PCT levels and mortality but not with disease severity. There was no significant association between ferritin, D-DimeCopyright © 2023

Tele-Psychiatry during COVID-19 at HMC Peshawar

OBJECTIVE: The main objectives of the current study were to find out the frequencies of Psychiatric disorders in the general population during COVID-19 and to compare the gender-based association between newly diagnosed patients during COVID-19 with already existing psychiatric patients in Peshawar to provide patient care on priority bases. METHODOLOGY: This Cross-sectional design study was carried out in the Department of Psychiatry and Behavioral Sciences, HMC/MTI, from May to August 2020. Those patients who approached psychiatry OPD through video/audio online calls and could understand and respond to suggestions were included. The bio-data was collected, and DSM-5 criteria were used for diagnosis. Descriptive statistics were used for statistical significance, and the statistical package of social sciences (SPSS-21) was used for analysis and results. RESULTS: The results findings of the current study revealed that 59.3% of the patients approached for telepsychiatry consultation were from the district of Peshawar. Among them, 54% were female, and most patients were young married females (50.7%) with no job outside the home. The finding further revealed that most of the sample affected by psychiatric illness were uneducated (31.3%) and unemployed (28%). Furthermore, in the present findings, 46% of patients were diagnosed with depression, and 12% had Dissociative disorders. CONCLUSION: It is concluded from the present study that in the Covid-19 Pandemic, primarily females who were married with no job description are more vulnerable to psychiatric illness. Furthermore, during Covid-19 mostly cases were reported with depression and dissociative disorders. © 2023, Liaquat University of Medical and Health Sciences.

An Adaptive-to-Model Test for Parametric Functional Single-Index Model

Model checking methods based on non-parametric estimation are widely used because of their tractable limiting null distributions and being sensitive to high-frequency oscillation alternative models. However, this kind of test suffers from the curse of dimensionality, resulting in slow convergence, especially for functional data with infinite dimensional features. In this paper, we propose an adaptive-to-model test for a parametric functional single-index model by using the orthogonality of residual and its conditional expectation. The test achieves model adaptation by sufficient dimension reduction which utilizes functional sliced inverse regression. This test procedure can be easily extended to other non-parametric test methods. Under certain conditions, we prove the asymptotic properties of the test statistic under the null hypothesis, fixed alternative hypothesis and local alternative hypothesis. Simulations show that our test has better performance than the method that does not use functional sufficient dimension reduction. An analysis of COVID-19 data verifies our conclusion.

Evaluation of pulmonary function in post-COVID-19patients

Introduction: Changes in the lungs caused by COVID-19 can lead to impaired lung function. Recentrecommendations suggest that only patients with severe COVID-19 should be referred for pulmonary functionevaluation (PFT) 12 weeks after completion of treatment. The aim of this study was to evaluate PFT in bothmoderate and severe COVID-19 patients in the recommended period. Method(s): PFT was performed in 66 patients with no prior respiratory disease 3 months after COVID-19, analyzingthe forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, and thediffusing capacity for carbon monoxide (DLCO). Statistical analysis was done with the null hypothesis tested atp<0.05. Result(s): The study included 66 patients (45 males, 21 females) of mean age 56.1+/-11 years (30-75 years), with 28patients (42.4%) after severe COVID-19. The average values of PFT parameters are: FVC% 85.6+/-17.1 (52.1-124.9),FEV1% 88.2+/-17.6 (48.4-121.7), FEV1/FEV% 83.3+/-6.8 (64.3-97.3), DLCO% 72.6+/-19.1 (37-122). Reduced FVC was found in 13 patients (19.7%), while 3 patients (4.5%) had reduced FEV1/FVC values. DLCO was reduced in 25 patients (37.9%), but did not differ statistically significantly in relation to the severity of the disease (p>0.05). Conclusion(s): A significant number of patients had reduced diffusion capacity for carbon monoxide, although without statistically significant difference in relation to the disease severity. We conclude that the evaluation of pulmonary function is also important in patients after moderate COVID-19.

Anastrozole dose escalation for optimal estrogen suppression in postmenopausal early stage breast cancer: A prospective trial

Introduction: We performed matched case-control studies utilizing cohorts of postmenopausal women with ER+ breast cancer receiving adjuvant aromatase inhibitors (AI) on MA.27 [anastrozole, exemestane] or PreFace [letrozole] to assess the association between estrogen suppression after 6 months of treatment and an early breast cancer (EBC) event within 5 years of AI initiation (Clin Cancer Res 2020;26:2986-98). We found a significant 3.0-fold increase in risk of an EBC event for those taking anastrozole with levels of estrone (E1) >=1.3 pg/mL and estradiol (E2) >=0.5 pg/mL, but not for exemestane or letrozole. Given these findings we designed a prospective pharmacodynamic (PD) study to evaluate the impact of anastrozole (1 mg/day: ANA1) on E1 and E2 levels, and among those with inadequate estrogen suppression (IES: E1 >=1.3 pg/mL and E2 >=0.5 pg/mL), to evaluate the safety and PD efficacy of high-dose anastrozole (10 mg/day: ANA10), which has been found to be safe in prior clinical trials (Cancer 1998;83:1142-52). Method(s): Post-menopausal women with stage I-III, ER >=1% positive/HER2-negative breast cancer who were candidates for anastrozole were eligible after completion of locoregional therapy and chemotherapy, as clinically indicated. Women who were pre-menopausal at diagnosis were not eligible. All patients received 8-10 weeks of ANA1, after which those with adequate estrogen suppression (AES: E1< 1.3 pg/mL or E2< 0.5 pg/mL) came off study. Those with IES went on to receive ANA10 for 8-10 weeks, followed by letrozole (2.5 mg/day: LET) for 8-10 weeks. All patients were managed at their treating oncologist's discretion following study discontinuation. E1 and E2 blood levels were measured pre-treatment and after completion of each treatment cycle by a CLIA-approved liquid chromatography with tandem mass spectrometry in the Immunochemical Core Laboratory at Mayo Clinic. With a sample size of 29 patients with IES after ANA1, a one-sided binomial test of proportions with a significance level of 0.05 will have an 87% chance of rejecting the proportion with AES after ANA10 is at most 25% (Ho) when the true proportion is at least 50%. Specifically, the null hypothesis is rejected if the number of women with AES after ANA10 is 12 or more. Data lock was July 6, 2022. Result(s): Of the 161 women enrolled from April 2020 through May 2022, 3 withdrew consent prior to start of ANA1 and 2 were ineligible;thus, 156 women comprised the study cohort. Median patient age was 64 years (range 44-86), 10% of patients were of Hispanic ethnicity and/or non-white race, and 15% received chemotherapy. Six patients remain on ANA1, and 10 discontinued ANA1 due to refusal (7), adverse event (AE) (2), or COVID-19 (1). Forty-one of the remaining 140 patients (29.3% 95%CI: 21.9- 37.6%) had IES with ANA1. Nine of these 41 patients did not go on to ANA10 due to refusal (6) or AE (3). Of the 32 patients who started ANA10, 8 remain on treatment, 5 discontinued due to refusal (3) or AE (1-grade 2 urinary tract infection;1-grade 1 palpitations), and 19 had a blood draw 45 days or more after starting ANA10. No grade 3-5 AEs or grade 2 hot flashes or arthralgias were reported. Of these 19 patients, 14 achieved AES with ANA10 (73.7% 95%CI: 48.8-90.9%). All 19 patients switched to LET of which 3 remain on treatment, 1 is missing E1/E2 data, and 15 had a blood draw 45 days or more after starting LET. Of these 15 patients, 10 maintained AES, 2 acquired AES with LET, and 3 no longer had AES. Anastrozole and letrozole drug levels will be reported at the meeting. Conclusion(s): Approximately 29% of postmenopausal women with ER+/HER2- BC receiving adjuvant anastrozole 1 mg/daily had IES. A majority of these patients achieved AES with dose escalation to ANA10 without tolerability issues. E1 and E2 levels are logical biomarkers given the mechanism of action of anastrozole, and further study utilizing them to determine the optimal dose of anastrozole for a given patient should be performed.

Intravesical administration of durvalumab to patients with high risk non muscle invasive bladder cancer after BCG failure. A phase II trial by the Hellenic GU Cancer Group

Introduction & Objectives: Patients with high risk non muscle invasive bladder cancer (NMIBC) who experience BCG failure have limited bladder preserving treatment options as radical cystectomy currently represents the standard therapeutical approach. Systematic immunotherapy (IO) has changed the landscape in advanced bladder cancer and is currently being investigated in NMIBC. Based on the hypothesis that intravesical administration will not be related with severe adverse events, we evaluated the role of intravesically administered durvalumab in NMIBC patients after BCG failure. Material(s) and Method(s): An open label, single-arm, multi-center, phase II clinical trial was conducted. A run-in phase had the objective to determine the maximum tolerated dose (MTD) of durvalumab and to exclude a detrimental effect on disease relapse by this strategy. Durvalumab was administered for a total of 6 instillations per patient at consecutive levels of 500, 750 and 1000 mg. Phase II has as primary end point the 1-year high-grade-relapse-free (HGRF)-rate. Secondary endpoints included toxicity, and high-grade progression-free rat at 1, 3 and 6 months after treatment. Result(s): Thirty patients were enrolled (run in phase: 9, phase II: 21). One patient withdrew consent prior to receiving study treatment, so 29 patients were included in efficacy and toxicity analyses. Mean age was 66.5 years. MTD of durvalumab was set at 1000 mg as no dose related toxicities (DLTs) occurred at any level studied. Three of 9 patients included in the run-in phase (33.3%) were tumor free one month after the last durvalumab instillation, therefore, the null hypothesis was rejected by the futility analysis. Western blot showed that durvalumab remained stable in urine during instillation. One patient died from Covid-19, 3 months after the last durvalumab administration. All patients concluded at least 1 year follow up. One-year HGRF rate was 34.6%. HGRF rates at 1, 3 and 6 months was 73%, 65.3% and 50% respectively. Five patients (17%) experienced a T2 or above disease relapse. Five out of the six patients who received 500mg or 750mg of durvalumab relapsed within 1 year. When efficacy analyses were restricted to patients receiving 1000mg of durvalumab, 1-year HGRF rate was 35%. Interestingly, 2 out of 2 patients with only CIS disease at baseline experienced a tumor complete response, which was durable and was maintained at least for a year. No severe adverse events were noted. The most common adverse event was Grade 1 hematuria. Conclusion(s): Intravesical IO using durvalumab was proved to be feasible with an excellent safety profile. Oncological results seem to be promising and comparable with other bladder preserving strategies in BCG failure with the advantage of a better safety profile. Further study of intravesical IO in high-risk patients with NMIBC after BCG failure is warranted.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

CRP, ferritin,IL-6 and D-dimer: how significant they are in prediction of disease severity in COVID-19 - A retrospective study

Introduction: The evaluation of inflammatory response degree can be used in predicting disease severity in COVID19. Aims and objectives: We aimed to examine the significance of C-reactive protein, ferritin, IL-6 and D-dimer levels as predictors of disease severity in COVID-19 patients. Method(s): The study included 100 hospitalized patients (58 males, 42 females) divided into two groups: presenting with moderate (53) and severe disease (47). The C-reactive protein, ferritin, and D-dimer levels were retrospectively evaluated on day one, seven and fourteen, and IL-6 levels on day one of hospitalization. Data were statistically processed and the null hypothesis was tested with a significance threshold of p<0.05. Result(s): The mean age of patients is 62.03+/-13.72 years (30-96 years). CRP levels decrease statistically significantly during the follow-up period (p<0.001). D-dimer levels change statistically significantly over a period of 14 days (p=0.003), decreasing after the seventh day (p=0.006). Ferritin and D-dimer levels after day seven are statistically significantly higher in patients with severe disease (p=0.004 and p=0.001, respectively) and could be considered predictors of disease severity (OR 1.001;p=0.007 and p=0.005, respectively). Initial IL-6 levels are statistically significantly higher in patients with severe disease (p=0.014) so that values above 40.75 pg/ml predict severe disease with sensitivity of 61.8% and specificity of 50% (OR 1.010, p=0.024). Conclusion(s): Ferritin and D-dimer levels in the second week of hospitalization and initial IL-6 above 40.75 pg/ml could be used as predictors of disease severity in COVID-19 patients.

Back to basics: complete blood count parameters and the neutrophil-to-lymphocyte ratio as prognostic factors in hospitalized patients with COVID-19

Introduction: COVID-19 being widespread imposes a need for available and convenient prognostic markers that provide insight into the systemic inflammatory response degree. Our study aims to evaluate whether the complete blood count (CBC) parameters and the neutrophil-to-lymphocyte ratio (NLR) can be used as prognostic factors in hospitalized patients with COVID-19. Method(s): This retrospective study included 100 patients (58 men, 42 women) divided into two groups, moderate (53) and severe disease (47), treated for COVID-19 at the University Clinical Center Nis. CBC was monitored with NLR calculated on days one, seven, and fourteen of hospitalization. Statistical analysis was done with the null hypothesis tested at p<0.05. Result(s): The leukocyte count increased on day seven (p<0.001), with neutrophils increasing (p=0.021), lymphocytes decreasing (p=0.006), resulting in a higher NLR on day seven (p=0.002), compared to day one. The leukocyte and neutrophil counts were higher (p=0.029, p=0.020, respectively), the lymphocyte count lower (p=0.006), with NLR statistically significantly higher (p<0.001) in patients with severe disease on day seven. Leukocytes>12.25x10/L, neutrophils>87.80%, lymphocytes<11.05%, and NLR>7.08 on day seven are predictors of disease severity (OR 1.094, p=0.036;OR 1.052, p=0.026;OR 0.918, p=0.010;OR 1.080, p=0.003, respectively). Conclusion(s): Monitoring the course of COVID-19 can be done using the NLR, leukocyte, neutrophil, and lymphocyte counts, and on day seven of hospitalization they can be considered predictors of disease severity, with cut-off values of 12.05x10L, 87.80%, 11.05%, and 7.08, respectively.

COVID-19 and Digitizing Accounting Education: Theory and Literature Review

This article critically analyzes previously published literature and discusses the lessons learned in detail. Learning gleaned from the theories has been used to create a conceptual framework. Using data from the published sources, a null hypothesis is developed to suit the current case. The results highlight the importance of digitalization in education in general and the accounting field in particular. This paper also reveals the impact of COVID-19 on education and addresses the main challenges faced by education and the accounting sector after the pandemic. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Disparities in the uptake of telemedicine and implications for clinical trial enrollment in breast cancer patients

Purpose/Objectives: Since the COVID-19 pandemic, telemedicine has become an attractive alternative to office visits in routine radiation oncology practice. The purpose of this study was to identify factors associated with patient preference for an initial consult telemedicine visit and correlation with clinical trial enrollment. Materials/Methods: We evaluated breast cancer patients seen during the open enrollment of a prospective randomized controlled non inferiority trial evaluating radiation fibrosis with five versus three fractions from 07/13/2020 to 05/13/2021. Univariate and multivariate logistic regression models were used to identify factors associated with virtual vs inperson initial consultation and enrolled vs not enrolled patients. All statistical tests were two-sided and the null hypothesis was rejected for p< 0.05. Result(s): We identified 476 patient consultations with 259 office visits and 217 telemedicine visits. On multivariate analysis, increased age, unemployment, chemotherapy receipt and radiation at NYU were associated with decreased usage of telemedicine for consultation visit. Out of 217 patients who underwent a telemedicine initial consultation, 10% were eligible to enroll on the trial and of those eligible, 76% enrolled. Out of 259 patients who underwent office visit initial consultation, 14% were eligible to enroll on the trial and of those eligible, 53% enrolled. Among eligible patients, there was no statistically significant difference in clinical trial enrollment between telemedicine and office visits. There was no statistically significant difference in patient characteristics between enrolled vs not enrolled patients. Conclusion(s): Though patient and disease characteristics remained similar between patients undergoing telemedicine and office visits consultations, increased age, unemployment and receipt of chemotherapy were associated with lower usage of telemedicine. Those who underwent in person initial consultation were also more likely to subsequently receive their radiation at our clinic. Further studies are needed to better define underlying reasons for patient selection and impact on care and trial enrollment in order to ensure equal access and benefit from telemedicine, especially in already vulnerable patient populations.

Comparison of the prehospital altered respiratory parameters over the first two COVID-19 periods in Brussels: a retrospective cohort study

This retrospective cohort study analyses the impact of the COVID-19 pandemic on the prehospital pathology in 1 emergency response unit of Brussels. Three months of prehospital data with in total 1,030 interventions were analysed: 1 month in the first and second COVID-19 outbreak (April and November 2020 respectively) and 1 in the intermediate period (June 2020). The subtracted data contained altered respiratory signs as primary outcome parameter. Secondary outcome parameters were mean age, time from call to arrival of the intervention team, oxygen administration, medication administration, artificial ventilation and prehospital death. Statistical analyses are performed using SPSS, the cross table, the Chi-squared test and the Kruskal-Wallis test. Altered respiratory signs appeared in 31.9, 24.6 and 32.9% of the cases in April, June and November respectively (p-value: 0.039). Mean age was 59, 57 and 60 years (null hypothesis retained). Time from call to arrival of the intervention team was 11 minutes in all 3 periods (null hypothesis retained). Oxygen was administrated in 31.4, 27.4 and 32.6% of the cases (p-value: 0.315). Medication was given in 41.1, 39.7 and 41.2% (p-value: 0.908). Artificial ventilation was necessary in 2.8, 5.5 and 5.8% of the interventions (p-value: 0.115). Prehospital death was declared in 6.1, 4.9 and 6.9% of the cases. The COVID-19 pandemic had a significant impact on the prevalence of prehospital altered respiratory signs. Furthermore, no significant difference has been observed in the secondary outcome parameters. Copyright © 2022 The authors.

Analysis on the Impact of Education and Its Environment Issues in Covid 19 Period in India

The effects of COVID-19 on the educational system are extraordinary. There have been widespread effects on children of all socioeconomic backgrounds, races, and sexes. As a result of the digital gap, many students are being forced to drop out of school as a direct result of the widespread closure of schools and the choice to move traditional classrooms to digital platforms. Kids' health and nutrition would suffer irreparably if they didn't have the chance to go to school. Six primary aspects of the educational setting are examined here: (1) online education;(2) in-class instruction;(3) scholastic performance;(4) institutional support;(5) co-curricular offerings;and (6) instructors. Approximately 347 college students from coastal Karnataka participated in this descriptive study. With the help of a literature study, a working hypothesis has been constructed and will be put to the test using analysis of variance and a t-test for independence in service of the overarching goal. Path analysis is used to investigate the associations between students' attitudes toward their college's learning environment, the quality of that environment, and the outcomes for those students' academic careers. According to the findings, college students have a generally good view of online education (M=3.14), online teaching and learning (M=3.704), online evaluation (M=3.38), college and administration (M=3.83), extracurricular activities (M=3.87), and teachers (M=3.63). Students' views on different aspects of the higher education system did not change much, contrary to what was predicted by the null hypothesis. Copyright © 2022, Anka Publishers. All rights reserved.

The Impact of the COVID-19 Pandemic on Spontaneous Reporting of Adverse Drug Reactions in the Central Region of Portugal: An International Journal of Medical Toxicology and Drug Experience

Introduction: The COVID-19 pandemic has had an impact on several sectors of the society. Whether it has disrupted drug safety monitoring is yet to be determined. Objective: To investigate whether the COVID-19 pandemic has had an impact on the proportions of spontaneous reports (SRs) of serious and unexpected adverse drug reactions (ADRs). Methods: SRs received by the Coimbra Pharmacovigilance Unit (UFC) between January 2017 and December 2021 were included, except for those containing COVID-19 vaccines as suspected medicines. The SRs were categorized into two groups: pre-pandemic (2017-2019);and post-pandemic (2020-2021). The SRs were classified as serious or non-serious, and expected or unexpected, depending on the seriousness and expectedness of the suspected ADRs, according to the WHO criteria and the Summary of Product Characteristics [SmPC] of each suspected medicine, respectively [1,2]. To study the impact of the COVID-19 pandemic on the patterns of spontaneous reporting of suspected ADRs, two null hypotheses were proposed to test whether (i) the seriousness, and (ii) the expectedness were independent of the pandemic (i.e., if the pandemic has had no impact, then the proportions of SRs containing (i) serious and (ii) unexpected ADRs were expected to be the same in both periods). The qui-square test was used to test the hypotheses;p-values < 0.001 were considered statistically significant. Microsoft Excel® was used for the statistical analyses. Results: A total of 1,311 and 657 SRs were received in the prepandemic and post-pandemic periods, respectively. Of the 1,311 SRs received in the three pre-pandemic years, 1,012 (77%) were serious and 657 (13%) contained unexpected ADRs;of the 657 SR received during the two post-pandemic years, 434 (66%) were serious and 133 (20%) contained unexpected ADRs. The changes from pre- to postpandemic on both proportions of SRs containing serious (an absolute decrease of 11%;p = 0.01) or unexpected ADRs (an absolute increase of 7%;p = 0.01) were not statistically significant. Conclusion: The COVID-19 pandemic has had not a significant impact on the proportions of SRs of serious or unexpected ADRs in the Central Region of Portugal. Further research should be carried out in other pharmacovigilance databases to understand if the present conclusions are applicable to other geographic regions.

A Phase II Study of Metformin with Pemetrexed/Carboplatin in Patients with Metastatic Non-Squamous Non-Small Cell Lung Cancer

Introduction: There is a subset of NSCLC patients ineligible for benefit from TKIs/Immunotherapy (e.g. STK11 mutation conferring resistance to Immunotherapy). Besides, many patients cannot afford these therapies. Metformin has anticancer properties acting both on glycolytic metabolism and tumor microenvironment. In vitro studies suggest synergism between metformin and pemetrexed. STK11 deficient cell lines are more sensitive to metformin. Clinical studies combining metformin with chemotherapy are limited by small sample size. We conducted an exploratory phase-2 clinical trial of metformin with pemetrexed/carboplatin in advanced non-squamous NSCLC. Methods: This was a single center, open label, single arm phase 2 clinical trial with a Simon’s two stage design. The null hypothesis was that the combination would not improve the 6-month PFS rate by 15%, from 50%. Treatment-naive, non-diabetic patients aged 18-75 years with NSCLC (adenocarcinoma/not-otherwise-specified) with stage IV disease having ECOG PS 0-2 with unmutated EGFR/ALK and without brain metastasis or with asymptomatic brain metastases were treated with pemetrexed-carboplatin chemotherapy and metformin for six months. The primary outcome was 6-month progression free survival (PFS) rate. Secondary outcomes were safety, overall survival (OS), overall response rate (ORR), proportion of STK 11 mutation and effect of STK 11 mutation on 6-month PFS rate. PFS and OS were estimated using the Kaplan-Meier method. Targeted sequencing was attempted for available tissue specimens. Results: The first interim analysis was performed after enrollment of 26 patients for the first stage (before the target accrual of first stage was reached) due to slow accrual, in view of COVID pandemic. The study was terminated after first stage for futility. The median age of patients in the study was 52 years (range, 30 to 68) and 18 patients (69.0%) were males. Half of the patients had ECOG-PS 2. Brain metastases were present in eight (31%) patients and among these four (50%) were symptomatic at presentation. The median follow-up time was 25 months. The median PFS was four months. 6-month PFS rate was 28% (95% CI - 0.12 to 0.46). Of the 25 evaluable patients, five (20%) had a partial response, and eight (32%) had stable disease;13 (52%) of the patients had disease control. The median OS was 16 months. During combined therapy, 14 (54%) and 3 (11%) patients had any grade and grade 3 anemia respectively. One patient had grade 3 neutropenia. Among non-hematological toxicities, gastrointestinal toxicities (nausea, vomiting and diarrhea) were the most common. No grade 4 toxicities were reported. There were no treatment discontinuations, however treatment delay due to grade three toxicities was present in two patients. Dose modification for Metformin was required in four patients. Targeted Sequencing was possible in nine cases. Two of these patients had STK11 mutation and an associated bad outcome (PFS < 2 months). Conclusions: We could not demonstrate the benefit of combination of Metformin with pemetrexed-carboplatin in terms of improvement in 6-month PFS rate. The addition of metformin to pemetrexed-carboplatin has an acceptable safety profile. Future trials should test metformin in specific subsets (STK11 mutated) and in combination with immunotherapy and TKIs. Keywords: Metformin, NSCLC, STK11

A phase 2 clinical trial of axitinib and avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (ACC)

Background: ACC is a heterogeneous neoplasm and there is no standard treatment for patients (pts) with recurrent/metastatic (R/M) disease. Vascular endothelial growth factor receptor inhibitors (VEGFRi) are frequently used to treat R/M ACC rendering mostly disease stabilization. ACC is resistant to PD-1/PD-L1 inhibitors (PD-L1i), consistent with its low mutational burden and uninflamed immune microenvironment. We hypothesized that the immunomodulatory role of VEGFRi (axitinib) would enhance PD-L1i (Avelumab) activity and be a more effective therapy for R/M ACC. Methods: Eligible pts had R/M ACC with radiological or clinical progression within 6 months (mos) of enrollment. Treatment consisted of axitinib 5 mg PO bid and avelumab 10 mg/Kg IV every 2 weeks. Primary endpoint was objective response rate (ORR) per RECIST 1.1;secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Simon 2-stage design was applied to test the null hypothesis of ORR ≤ 5% versus the alternative ORR ≥ 20%;≥ 4 responses out of 29 pts was required to reject the null hypothesis. Results: 41 pts enrolled from 07/24/19 to 06/29/ 21;28 were evaluable for the primary endpoint (7 screen failures, 6 evaluable for safety only due to loss of insurance/logistics issues related to COVID-19 pandemic);16 pts were treated in first-line. Mutation data was available for 23 of 28 evaluable pts;7 had NOTCH1 activating mutations. The ORR was 17.9% (5/28, 95%CI: 6.1-36.9%). One response was unconfirmed (pt progressed in non-target lesions 2 mos after achieving a PR), for a confirmed ORR of 14.3% (95%CI: 4-32.7%). The median follow-up time for the 15 alive pts was 11.6 mos (min-max: 7.7-29.2 mos). Median PFS was 7.2 mos (95%CI: 3.7-11.7 mos) with a 6-mos PFS rate of 57% (95%CI: 41-79%). Median OS was 17.4 mos (95%CI: 13-NA). 5 pts remain on therapy, 2/5 with a PR. The median DOR for the 5 responders was 5.2 mos (95% CI: 3.7-NA mos). The most common treatment-related adverse events (TRAEs) were fatigue (62%), hypertension (32%), diarrhea (29%), and stomatitis (29%). Serious TRAEs occurred in 8 (24%) pts, all grade 3 and manageable. 4 (15%) pts discontinued avelumab and 9 (32%) underwent axitinib dose reduction due to toxicity. Conclusions: The study reached its primary endpoint with ≥ 4 responses out of 28 evaluable pts (ORR of 17.8%;confirmed ORR of 14.3%). The ORR and 6- mos PFS rate of 57% with axitinib and avelumab compares favorably with single agent axitinib and warrants further study of the combination.

CHANGES in PATIENT-REPORTED OUTCOME SCORES during COVID-19 PANDEMIC: DATA from the ARTHRITISPOWER REGISTRY

Background: The COVID-19 pandemic causes concern among patients with autoimmune and rheumatic disease (ARD) due to increased risk of infection and heightened isolation from social distancing.1 Objectives: Examine how mean patient-reported outcome (PRO) scores for mental, social and physical health fuctuated after COVID-19 vaccine availability was widespread in US. Methods: We conducted and reported on2 an initial analysis of January 2020-April 2021 where US participants (pts) of the ArthritisPower (AP) registry completed PROMIS measures of physical health (Physical Function, Pain Interference, Fatigue, Sleep Disturbance), mental health (Anger, Anxiety, Depression) and social health (Social Isolation, Emotional Support). Follow-up analysis was conducted May-December 2021. Only pts from initial analysis were included in follow-up. Null hypothesis was no change in monthly average scores across 23-month pandemic period. Analysis of means compared monthly assessment mean scores to overall mean score for each measure during study period. Pts with < 2 assessment time points and osteoarthritis with no ARD were excluded from analysis. Results: Total of 49,940 PRO scores were contributed by 2,266 pts during 23-month period, with 8,393 of the scores contributed from May-December 2021. Mean (standard deviation, SD) number of observations per pt was 5.6 (12.5). Pts were 87.6% female, 86.7% white, mean age of 52.1 (12.7) years. Rheumatoid arthritis (n=1,131, 49.9%) was the most common condition. Most commonly reported measures were Pain Interference, Fatigue, Sleep Disturbance and Physical Function, each with >11,000 total results (Table 1). Pts' mental and social health assessment scores improved then worsened during last 8 months of 2021 (Figure 1). Overall mean scores were: Anxiety 62.4 (12.5), Social Isolation 61.9 (10.5), and Anger 61.5 (12.8). From July-August, Social Isolation decreased by 1 SD. Compared to overall assessment mean, Anger declined by > / SD (53.3 [19.4]) in August and Anxiety declined by / SD (57.7 [11.3]) in September. By December, Anger rose by > / SD (68.6 [5.0]) of assessment mean. Pain Interference (mean: 63.3 [7.8]), Fatigue (62.6 [9.5]), and Sleep Disturbance (58.1 [9.0]) scores were signifcantly lower in May, June, July and August compared to the assessment mean, though none decreased by > / SD. Conclusion: ARD members of AP had mental, social and physical health scores improve during summer of 2021, corresponding with widespread availability of vaccines. However mental and social health scores worsened by December as US faced new variants of the virus.

Atypical Clinical Presentations of Pulmonary Thromboembolism to the Emergency Department: High Index of Suspicion and Application of Diagnostic Approach

Aim and background: Acute pulmonary thromboembolism is the most serious clinical presentation of venous thrombo-embolism with fatal pulmonary thromboembolism (PTE) being a common cause of sudden death. In yesteryears of practicing clinical medicine, PTE was the most common cause of unexplained sudden deaths in hospitalized patients. However, our understanding of the disease has improved with time and the growth of clinical scores, laboratory evidence, and radiographic scans. In few of the patients, the diagnosis is still missed and these are the nightmarish cases for the emergency physician. Especially after the second wave of the COVID pandemic, many patients presented to the emergency department (ED) even without any risk factors for pulmonary thromboembolism. Diagnosing patients without risk factors for PTE is quite challenging and suspicion of PTE should be kept in the differential diagnosis if patients are presenting with uncommon clinical history and examination. Objective: To decrease the incidence of missed diagnosis of PTE in ED. Materials and methods: The study was conducted using ED records of patients who had a confirmed diagnosis of PTE on CT pulmonary angiography (CTPA) between March and September 2021. COVID-19 infection was ruled out at the time of presentation to ED using a rapid antigen test and subsequently with RT PCR within the next 24 hours. The presenting complaints, past history of COVID-19 infection and COVID vaccination, WELLS score, ECG, CXR, ABG, D dimers, bedside echocardiography, and results of CTPA were collected and tabulated. The symptoms were divided into 2 groups-typical and atypical. Group I with typical symptoms studied patients who presented with acute onset of dyspnea, chest pain, and cough without expectoration. Group II with atypical symptoms included patients who presented with hemoptysis, wheeze, cerebrovascular accident, syncope, arrhythmias, and acute onset of delirium. The null hypothesis was that atypical symptoms of PTE make the diagnosis difficult (late) and have a poorer prognosis. Results: The comparative analysis with descriptive statistics will be presented at the conference. In Group II patients, three parameters were clinically significant enough to early diagnosis of PTE. These were sinus tachycardia on ECG, raised D dimers, and a low TAPSE on echocardiography. TAPSE or tricuspid annular plane systolic excursion with a cutoff <1.7 cm was found to be highly specific in our study. Conclusion: Acute pulmonary embolism can be a complex interplay between several different symptoms and between different organs that can lead to a potentially life-threatening cardiovascular condition that may be difficult to diagnose. The differential diagnosis of PTE should be kept in mind if a patient presents with rare clinical findings. Detailed physical examination, Wells-scoring, D dimers, and point of care ultrasonography (POCUS) examination are very crucial in diagnosing the patient. Working in this approach will decrease the incidence of missed diagnoses.

MONITORING OF COVID-19 VACCINATION IN PREGNANT WOMEN OF SIBERIA AND THE RUSSIAN FAR EAST

Objective: To evaluate the dynamics of vaccination against the new coronavirus infection COVID-19 in pregnant women in the Far Eastern and Siberian Federal Districts from October 29, 2021 to December 24, 2021. Materials and methods: A total of 127787 pregnant women were monitored for vaccination from October 29, 2021 to December 24, 2021 in 11 regions of the Far Eastern Federal District and 10 regions of the Siberian Federal District. The findings were presented by the chief obstetricians-gynecologists of the regions. Statistical processing of the obtained data was carried out using the software package Microsoft Excel 2007. The level of null hypothesis testing was considered to be statistically significant at p<0.05. Results: According to the presented data, 126897 pregnant women were registered in the regions of the Far East and Siberia as of October 29, 2021, and 127787 women as of December 24, 2021. The results of the study showed an extremely low percentage of preconception specific prevention in pregnant women in the Far East and Siberia as of October 29, 2021. This indicator increased within two months by more than 2.26 times, namely from 4.2% to 9.5%. During monitoring, the proportion of vaccinated women before 22 weeks gestation increased by 2.1 times, from 0.7 to 1.5%;after 22 weeks gestation, it increased by 3.7 times, from 1.5 to 5.5%. The proportion of pregnant women who were ill with COVID-19 or vaccinated in the regions of the Far Eastern and Siberian Federal Districts increased from 13.0% to 26.3% during the monitoring period (p<0.001). There were no serious adverse events during COVID-19 vaccination with the Gam-COVID-Vac vaccine (Sputnik V) in 9667 pregnant women. Conclusion: Despite the absence of serious adverse events during COVID-19 vaccination with the Gam-COVID-Vac (Sputnik V) vaccine in pregnant women, it is necessary to conduct further detailed studies of the safety of vaccination during pregnancy, and also to develop a set of organizational measures aimed at increasing compliance with vaccination against COVID-19 at the period of pregnancy planning.

DOES UNCONSCIOUS SOCIOECONOMIC BIAS INFLUENCE TELE-EVALUATION OF OBSTRUCTIVE SLEEP APNEA? A TELE-EQUITY EXPLORATORY ANALYSIS

Introduction: Telemedicine, once of limited scope, has become common and widespread due to the present and ongoing SARSCoV- 2 pandemic. Center to home delivery, the most common model, allows for convenient and efficient care. Concurrent with this groundshift, there is increasing attention to disparities in medical services, and how these disparities may impact patient outcomes. Telemedicine could be used to help bridge barriers to timely quality care, however, patient access and longstanding institutional biases may limit the potential. Healthcare providers must actively develop systems to ensure that telemedicine is optimized for people across the income spectrum. This exploratory analysis examined how economic disparities in patients being evaluated for obstructive sleep apnea may be associated with providers clinical impressions. The objective was to study the inter-method reliability of pre-test probability of obstructive sleep apnea assessed via telemedicine and in-person evaluations, and to compare that reliability between income classes. Methods: This is a secondary analysis of a pre-pandemic interrater reliability study, conducted between March 2017 and January 2019. Our researchers completed a randomized, blinded study comparing the pre-test probability of obstructive sleep apnea between an in-person physician and a separate physician seeing the same patient via televideo conferencing. Patients referred to the University of Rochester (UR) Sleep Center were eligible for the study. Women and men 30-70 years old were invited to participate. The patients were not necessarily referred to the center for evaluation of sleep disordered breathing. Patients with dementia, hearing or visual loss, severe psychiatric or developmental illness, or not fluent in English were excluded. Patients had adequate computer literacy, access to high speed internet, and a computing device with appropriate video camera and microphone.The primary objective of the original study was to assess the interrater reliability between the in-person and telemedicine raters for pre-test probability of sleep apnea (high, moderate, or low). Providers used clinical judgement from the history and examination to determine pre-test probabilityFor this present analysis, we assessed the inter-method reliability separately for strata defined by reported annual income level: low income (< $50,000), middle income ($50,000-$100,000), and high income (> $100,000). Reliability was quantified for each stratum using weighted kappa statistics given the ordinal nature of the outcome variable, pre-test probability of obstructive sleep apnea (high, moderate, or low). Weighted kappa statistics were compared between the income strata (high vs. middle, high vs. low, middle vs. low). The operant statistic assumed an approximate standard normal distribution under the null hypothesis of equal kappa values in the two income strata. The Bonferroni method was used to adjust the p-values for the three pairwise comparisons performed among the three income strata. Results: Data from 53 patients were avaiable for this analysis. 11 of these patients were in the low income group, 22 in the middle income, and 16 were in the high income group. 9 patients did not include their income bracket, and were not included in the analysis. Inter-method reliabilities, assessed using weighted kappa, were 0.83 (low income), 0.24 (middle income), and 0.66 (high income). When comparing between the strata, the kappa statistics were significantly different (p=0.005) between the low and moderate income groups. There was a trend between the high and moderate income groups that did not meet statistical significance (p=0.07). Conclusion: The intermethod reliability was substantial in the low income stratum, moderate in the high income stratum, and slight in the middle income group based on the kappa statistic. There was a significant difference in the reliability values of telemedicine versus in-person assessments between the low and middle income brackets, and there was a trend between the high and mo er te groups. Since the raters were unaware of the patients income levels, this association might suggest possible unconscious bias in evaluating for OSA. It may also suggest that beyond access to telemedicine technology, the quality of the care may also be influenced by socioeconomic factors. With telemedicine in its early stages, it is important to develop this technology that will minimize biases that could result from patients economic fortunes.

Factor Related the Use of Respiratory Supports among COVID-19 Patients in Sardjito Hospital Yogyakarta: A Cross-sectional Study

BACKGROUND: In patients with coronavirus disease-19 (COVID-19), respiratory failure is a serious condition that requires immediate respiratory supports. Various clinical conditions can be determinant factors to the need for used of ventilators. AIM: The aim of the study was to determine factor related to the used of ventilators among COVID-19 patients transferred to intensive care unit Sardjito Hospital. METHODS: Using a cross-sectional design, a total of 171 of 300 medical records selected in accordance to the inclusion criteria. Association of each clinical characteristics and outcome variable used contingency coefficient and Spearman rank tests, while multivariate logistic regression model was performed for hypothesis testing. The area under curve (AUC) was test to determine model fit of the logistic approach. RESULTS: There was a significant correlation between age (p = 0.004), blood sugar levels (p < 0.001), and oxygen saturation (p < 0.001), and the used of ventilator. Patients with hypoxia and severe hypoxia had odds of using ventilation supports 5 times and 114 times (OR = 5.623) and (OR = 114.3). The AUC test indicated that null hypothesis was rejected. CONCLUSION: The clinical characteristics were associated with age, blood sugar levels, and oxygen saturation. Patients with COVID-19 who admitted to hospital with hypoxia and severe hypoxia increased the odds of the use ventilators.