Virtual Reality Simulation for the Acquisition and Retention of Electrocardiogram Interpretation Skills: A Randomized Controlled Trial Among Undergraduate Medical Students.

Introduction The electrocardiogram (ECG) is one of the most important tools in diagnosing cardiac abnormalities, particularly arrhythmias and myocardial infarction. It is one of the certifiable competencies for final-year medical undergraduate students. We determined virtual reality's effectiveness in acquiring and retaining ECG interpretation skills among medical students compared to traditional teaching. Methods One hundred and forty students were randomized into two groups. Seventy-one students (immersion group) were trained using virtual reality simulation to acquire and retain interpretation skills of normal and abnormal ECG. Sixty-nine students (traditional group) were trained in the classroom using chalk and board. The primary outcome of change in acquiring knowledge of the interpretation of ECG was determined by comparing pre and post-test scores. The secondary outcome of retention of knowledge was determined by comparing pre-test and second post-test scores conducted after eight weeks of intervention. The p-value of <0.05 was considered significant. Results Out of 140 students, 50 (35.7%) were males and 90 (64.3%) were female. The mean age of the students was 22.1 (SD 1.1), with 69.3% of them between the ages of 21 and 22 years. Mean pre-test scores for the interpretation of normal ECG among immersion and traditional groups were 9.8 (SD 8.4) and 8.3 (SD 7.5), respectively, and post-test scores for the acquisition of knowledge were 24.3 (SD 5.5) and 24.8 (SD 6.3), respectively. The post-test scores for retention skills were 25.3 (SD 5.6) and 20.7 (SD 6.9) respectively (p<0.001). The mean pre-test scores for the interpretation of abnormal ECG of both groups were 7.0 (SD 6) and 8.3 (SD 6.6), respectively. Mean post-test scores for acquiring knowledge to interpret abnormal ECG were 23.5 (SD 6.2) and 17.7 (SD 9), respectively (p<0.001), and mean post-test scores for retention of interpretation skills of abnormal ECG were 19.2 (SD - 6.9) and 13.3 (SD 10.2) respectively (p=0.001). The pairwise comparison of the immersion group indicates that all the combinations that changed in score from the pre to post-intervention time points, from pre-to-retention time, and from the post-to-retention time were significant (p<0.001). Conclusion Virtual reality teaching had a better impact on acquiring and retaining the skill for interpreting normal and abnormal electrocardiograms.

Factors associated with severity of COVID-19 disease in a multicenter cohort of people with HIV in the United States, March-December 2020

BackgroundUnderstanding the spectrum of SARS-CoV-2 infection and COVID-19 disease in people with HIV (PWH) is critical to provide clinical guidance and implement risk-reduction strategies. ObjectiveTo characterize COVID-19 in PWH in the United States and identify predictors of disease severity. DesignObservational cohort study. SettingGeographically diverse clinical sites in the CFAR Network of Integrated Clinical Systems (CNICS) ParticipantsAdults receiving HIV care through December 31, 2020. MeasurementsCOVID-19 cases and severity (hospitalization, intensive care, death). ResultsOf 16,056 PWH in care, 649 were diagnosed with COVID-19 between March-December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized and 12 died. PWH with current CD4 count <350 cells/mm3 (aRR 2.68; 95%CI 1.93-3.71; P<.001) or lowest recorded CD4 count <200 (aRR 1.67; 95%CI 1.18-2.36; P<.005) had greater risk of hospitalization. HIV viral load suppression and antiretroviral therapy (ART) status were not associated with hospitalization, although the majority of PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared to other racial/ethnic groups (aRR 1.51; 95%CI 1.04-2.19, P=.03). Chronic kidney disease (CKD), chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher risk of hospitalization. PWH who were older, not on ART, with current CD4 <350, diabetes, and CKD were overrepresented amongst PWH who required intubation or died. LimitationsUnable to compare directly to persons without HIV; underestimate of total COVID-19 cases. ConclusionsPWH with CD4 <350 cells/mm3, low CD4/CD8 ratio, and history of CD4 <200, have a clear excess risk of severe COVID-19, after accounting for comorbidities also associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination, early treatment, and monitored closely for worsening illness.

Production of Trimeric SARS-CoV-2 Spike Protein by CHO Cells for Serological COVID-19 Testing

We describe scalable and cost-efficient production of full length, His-tagged SARS-CoV-2 spike glycoprotein trimer by CHO cells that can be used to detect SARS-CoV-2 antibodies in patient sera at high specificity and sensitivity. Transient production of spike in both HEK and CHO cells mediated by PEI was increased significantly (up to 10.9-fold) by a reduction in culture temperature to 32{degrees}C to permit extended duration cultures. Based on these data GS-CHO pools stably producing spike trimer under the control of a strong synthetic promoter were cultured in hypothermic conditions with combinations of bioactive small molecules to increase yield of purified spike product 4.9-fold to 53 mg/L. Purification of recombinant spike by Nichelate affinity chromatography initially yielded a variety of co-eluting protein impurities identified as host cell derived by mass spectrometry, which were separated from spike trimer using a modified imidazole gradient elution. Purified CHO spike trimer antigen was used in ELISA format to detect IgG antibodies against SARS-CoV-2 in sera from patient cohorts previously tested for viral infection by PCR, including those who had displayed COVID-19 symptoms. The antibody assay, validated to ISO 15189 Medical Laboratories standards, exhibited a specificity of 100% and sensitivity of 92.3%. Our data show that CHO cells are a suitable host for the production of larger quantities of recombinant SARS-CoV-2 trimer which can be used as antigen for mass serological testing.

Purification of recombinant SARS-CoV-2 spike, its receptor binding domain, and CR3022 mAb for serological assay

Serology testing for COVID-19 is highly attractive because of the relatively short diagnosis time and the ability to test for an active immune response against the SARS-CoV-2. In many types of serology tests, the sensitivity and the specificity are directly influenced by the quality of the antigens manufactured. Protein purification of these recombinantly expressed viral antigens [e.g., spike and its receptor binding domain (RBD)] is an important step in the manufacturing process. Simple and high-capacity protein purification schemes for spike, RBD, and CR3022 mAb, recombinantly expressed in CHO and HEK293 cells, are reported in this article. The schemes consist of an affinity chromatography step and a desalting step. Purified proteins were validated in ELISA-based serological tests. Interestingly, extracellular matrix proteins [most notably heparan sulfate proteoglycan (HSPG)] were co-purified from spike-expressing CHO culture with a long cultivation time. HSPG-spike interaction could play a functional role in the pathology and the pathogenesis of SARS-CoV-2 and other coronaviruses.

Influence of renal and hepatic impairment on the pharmacokinetics of anacetrapib.

Two open-label, parallel-group studies evaluated the influence of renal and hepatic insufficiency on the pharmacokinetics of a single-dose anacetrapib 100 mg. Eligible participants included adult men and women with moderate hepatic impairment (assessed by Child-Pugh criteria) or severe renal impairment (CrCl <30 mL/min/1.73 m(2)). In both studies, patients were matched (race, age, sex, BMI) with healthy control subjects. Twenty-four subjects were randomized in each study (12 with either moderate hepatic or severe renal impairment and 12 matched healthy controls). In the hepatic insufficiency study, the geometric mean ratio (GMR; mean value for the group with moderate hepatic insufficiency/mean value for the healthy controls) and 90% CIs for the area under the concentration-time curve from time zero to infinity (AUC(0-∞)) and the maximum concentration of drug in plasma (C(max)) were 1.16 (0.84, 1.60) and 1.02 (0.71, 1.49), respectively. In the renal insufficiency study, the GMRs (mean value for the group with severe renal insufficiency/mean value for the healthy controls) and 90% CIs for AUC(0-∞) and Cmax were 1.14 (0.80, 1.63) and 1.31 (0.93, 1.83), respectively. Anacetrapib was generally well tolerated and there was no clinically meaningful effect of moderate hepatic or severe renal insufficiency on the pharmacokinetics of anacetrapib.