Trends Affecting Biopharmaceutical Manufacturing

The landscape for bioprocessing continues to evolve, driven by many externally imposed trends that have been combined with ongoing technological changes and internal progress in bioprocessing. [...]most ongoing bioprocessing-related trends are not new and are reported after they become evident or familiar, making it difficult to cite when a specific trend starts and ends. The Top 1000+ Global Biopharmaceutical Facilities Index currently tracks over 1900 facilities worldwide with total estimated bioreactor capacity now over 17.3 million litres, including >720 facilities with an >2000 L capacity (2). * More biosimilars, biobetters, and biogenerics, with continued expansion in developed markets and capturing growing market shares in developing countries, due to an increase in prices of the originals. * Single-use bioprocessing systems will continue to rapidly displace commercialscale stainless steel-based manufacturing, both at commercial manufacturing and clinical scales. * Expansion of second-source bioprocessing facilities to combat supply chain issues due to the COVID-19 pandemic. * Flexible manufacturing facilities, including modulation, further aided by the increased adoption of single-use bioprocessing systems. [...]of this build-up and investment, non-pandemic projects continue to be shifted out to contract manufacturing organizations (CMOs).

Neurorecovery after Critical COVID-19 Illness.

With the hundreds of millions of people worldwide who have been, and continue to be, affected by pandemic coronavirus disease (COVID-19) and its chronic sequelae, strategies to improve recovery and rehabilitation from COVID-19 are critical global public health priorities. Neurologic complications have been associated with acute COVID-19 infection, usually in the setting of critical COVID-19 illness. Neurologic complications are also a core feature of the symptom constellation of long COVID and portend poor outcomes. In this article, we review neurologic complications and their mechanisms in critical COVID-19 illness and long COVID. We focus on parallels with neurologic disease associated with non-COVID critical systemic illness. We conclude with a discussion of how recent findings can guide both neurologists working in post-acute neurologic rehabilitation facilities and policy makers who influence neurologic resource allocation.

Scalable workflow for characterization of cell-cell communication in COVID-19 patients.

COVID-19 patients display a wide range of disease severity, ranging from asymptomatic to critical symptoms with high mortality risk. Our ability to understand the interaction of SARS-CoV-2 infected cells within the lung, and of protective or dysfunctional immune responses to the virus, is critical to effectively treat these patients. Currently, our understanding of cell-cell interactions across different disease states, and how such interactions may drive pathogenic outcomes, is incomplete. Here, we developed a generalizable and scalable workflow for identifying cells that are differentially interacting across COVID-19 patients with distinct disease outcomes and use this to examine eight public single-cell RNA-seq datasets (six from peripheral blood mononuclear cells, one from bronchoalveolar lavage and one from nasopharyngeal), with a total of 211 individual samples. By characterizing the cell-cell interaction patterns across epithelial and immune cells in lung tissues for patients with varying disease severity, we illustrate diverse communication patterns across individuals, and discover heterogeneous communication patterns among moderate and severe patients. We further illustrate patterns derived from cell-cell interactions are potential signatures for discriminating between moderate and severe patients. Overall, this workflow can be generalized and scaled to combine multiple scRNA-seq datasets to uncover cell-cell interactions.

The Impact of COVID-19 on Laboratory Test Utilization at a Pediatric Medical Center.

BACKGROUND: The epidemiology and clinical manifestation of coronavirus disease 2019 (COVID-19) in the pediatric population is different from the adult population. The purpose of this study is to identify effects of the COVID-19 pandemic on laboratory test utilization in a pediatric hospital. METHODS: We performed retrospective analysis on test utilization data from Ann & Robert H. Lurie Children's Hospital of Chicago, an academic pediatric medical center. Data between two 100-day periods prior to (prepandemic) and during the pandemic (mid-pandemic) were analyzed to evaluate changes in test volume, lab utilization, and test positivity rate. We also evaluated these metrics based on in- vs outpatient testing and performed modeling to determine what variables significantly impact the test positivity rate. RESULTS: During the pandemic period, there was an expected surge in COVID-19 testing, while over 84% of lab tests studied decreased in ordering volume. The average number of tests ordered per patient was not significantly different during the pandemic for any of the laboratories (adjusted P value > 0.05). Thirty-three studied tests showed significant change in positivity rate during the pandemic. Linear modeling revealed test volume and inpatient status as the key variables associated with change in test positivity rate. CONCLUSIONS: Excluding severe acute respiratory syndrome coronavirus 2 tests, the COVID-19 pandemic has generally led to decreased test ordering volume and laboratory utilization. However, at this pediatric hospital, the average number of tests performed per patient and test positivity rates were comparable between pre- and mid-pandemic periods. These results suggest that, overall, clinical test utilization at this site remained consistent during the pandemic.

FINANCES OF THE NATION

For almost 60 years, the Canadian Tax Foundation published an annual monograph, Finances of the Nation, and its predecessor, The National Finances. In a change of format, the 2014 Canadian Tax Journal introduced a new "Finances of the Nation" feature, which presents annual surveys of provincial and territorial budgets and topical articles on taxation and public expenditures in Canada. This article surveys the 2021-22 provincial and territorial budgets. The underlying data for the Finances of the Nation monographs and for the articles in this journal will be published online in the near future.

Impact of the COVID-19 pandemic on the management of open fractures in a major trauma centre.

INTRODUCTION: The Coronavrius-19 (COVID-19) pandemic has presented the biggest challenge that the National Health Service (NHS) has ever seen. As one of the worst affected regions, Orthopaedic service provision and delivery in London, changed dramatically. Our hypothesis is that these restrictions adversely impacted the care of open fractures in our major trauma unit in London. METHODS: This is a prospective case control study comparing the management of patients presenting pre-COVID, to those presenting during the height of the COVID pandemic in London. The pre-COVID, control cohort presented between the 1st October and the November 30, 2019. The COVID cohort presented between the April 1, 2020 and the May 31, 2020. Data was collected that related to the 11 clinical domains of the British Orthopaedic Association Standards of Trauma (BOAST) 4 guidance, as well as early complications. RESULTS: Of the 11 domains, 100 % compliance was achieved in 6 components, across both groups where applicable. During pre-COVID times, the timing to initial debridement was within 12 h for High energy trauma in 16/28 (57.1 %), dropping to 7/22 (31.8 %) during COVID, (p = 0.004). Definitive soft tissue closure within 72 h If not achievable at initial debridement dropped from 9/10 (90.0%) to 4/6 (66.7 %), (p = 0.006). There was no significant difference in early complication rates. CONCLUSION: Coronavirus has changed the landscape of healthcare worldwide and impacted open fracture care by increasing time to theatre. This had no effect on early complication rate but longer term effects remain to be seen.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).

COVID-19 and cardiac arrhythmias.

BACKGROUND: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. OBJECTIVES: The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. METHODS: We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia. RESULTS: Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality. CONCLUSION: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.