Cxbladder Monitor testing to reduce cystoscopy frequency in patients with bladder cancer.

PURPOSE: Bladder cancer surveillance is associated with high costs and patient burden. CxMonitor (CxM), a home urine test, allows patients to skip their scheduled surveillance cystoscopy if CxM-negative indicating a low probability of cancer presence. We present outcomes from a prospective multi-institutional study of CxM to reduce surveillance frequency during the coronavirus pandemic. MATERIALS AND METHODS: Eligible patients due for cystoscopy from March-June 2020 were offered CxM and skipped their scheduled cystoscopy if CxM-negative. CxM-positive patients came for immediate cystoscopy. The primary outcome was safety of CxM-based management, assessed by frequency of skipped cystoscopies and detection of cancer at immediate or next cystoscopy. Patients were surveyed on satisfaction and costs. RESULTS: During the study period, 92 patients received CxM and did not differ in demographics nor history of smoking/radiation between sites. 9 of 24 (37.5%) CxM-positive patients had 1 T0, 2 Ta, 2 Tis, 2 T2, and 1 Upper tract urothelial carcinoma (UTUC) on immediate cystoscopy and subsequent evaluation. 66 CxM-negative patients skipped cystoscopy, and none had findings on follow-up cystoscopy requiring biopsy. Six of these patients did not attend follow-up, 4 elected to undergo additional CxM instead of cystoscopy, 2 stopped surveillance, and 2 died of unrelated causes. CxM-negative and positive patients did not differ in demographics, cancer history, initial tumor grade/stage, AUA risk group, or number of prior recurrences. Median satisfaction (5/5, IQR 4-5) and costs (26/33, 78.8% no out-of-pocket costs) were favorable. CONCLUSIONS: CxM safely reduces frequency of surveillance cystoscopy in real-world settings and appears acceptable to patients as an at-home test.

Telehealth for Preoperative Evaluation of Patients With Breast Cancer During the COVID-19 Pandemic.

Introduction The COVID-19 pandemic drove rapid, widespread adoption of telehealth (TH). We evaluated surgical telehealth utilization and outcomes for newly diagnosed breast cancer patients during the initial pandemic period. Methods We identified patients with breast cancer diagnosed March 17, 2020 through May 17, 2020 who underwent surgery as the initial treatment. Clinicodemographic characteristics were collected. Initial consultation types (office, telephone, or video) were categorized. Outcomes included time to consultation, surgeon touchpoints, time to surgery, surgery types, and reexcision rates. Continuous variables were compared using Mann-Whitney tests or t-tests, and categorical variables were compared using χ2 or Fisher's exact tests. Results Of 158 patients, 56% had initial telehealth consultations (21% telephone, 35% video) and 42% did not have a preoperative physical examination. Age, race/ethnicity, and stage distributions were similar between initial visit types. Median time to consultation was lower in the initial telehealth group than the office group (6 days vs 9 days, p = 0.01). Other outcomes (surgeon touchpoints, time to surgery, surgery type, reconstruction) were similar between visit types. We observed higher reexcision rates in patients with initial telehealth visits (20% telehealth vs 4% office, p = 0.01), but evaluation was limited by small numbers. The reexcision rate was 13% for patients with telehealth visits and no preoperative physical exam. Discussion During the initial pandemic period, the majority of new breast cancer patients had an initial telehealth surgical consultation. Office and telehealth consultation visits had comparable numbers of postconsultation surgeon touchpoints and most outcomes. Our findings suggest that telehealth consultations may be feasible for preoperative breast cancer consultations.

Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review.

OBJECTIVES: The COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment. DESIGN: Rapid scoping review DATA SOURCES: Medline, Embase and biorxiv/medrxiv from inception to 15 May 2021. SETTING: Hospital and community care. PARTICIPANTS: COVID-19 patients of all ages. INTERVENTIONS: COVID-19 treatment. RESULTS: The literature search identified 616 relevant primary studies of which 188 were randomised controlled trials and 299 relevant evidence syntheses. The studies and evidence syntheses were conducted in 51 and 39 countries, respectively.Most studies enrolled patients admitted to acute care hospitals (84%), included on average 169 participants, with an average age of 60 years, study duration of 28 days, number of effect outcomes of four and number of harm outcomes of one. The most common primary outcome was death (32%).The included studies evaluated 214 treatment options. The most common treatments were tocilizumab (11%), hydroxychloroquine (9%) and convalescent plasma (7%). The most common therapeutic categories were non-steroidal immunosuppressants (18%), steroids (15%) and antivirals (14%). The most common therapeutic categories involving multiple drugs were antimalarials/antibiotics (16%), steroids/non-steroidal immunosuppressants (9%) and antimalarials/antivirals/antivirals (7%). The most common treatments evaluated in systematic reviews were hydroxychloroquine (11%), remdesivir (8%), tocilizumab (7%) and steroids (7%).The evaluated treatment was in favour 50% and 36% of the evaluations, according to the conclusion of the authors of primary studies and evidence syntheses, respectively. CONCLUSIONS: This rapid scoping review characterised a growing body of comparative-effectiveness primary studies and evidence syntheses. The results suggest future studies should focus on children, elderly ≥65 years of age, patients with mild symptoms, outpatient treatment, multimechanism therapies, harms and active comparators. The results also suggest that future living evidence synthesis and network meta-analysis would provide additional information for decision-makers on managing COVID-19.

Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review

Objectives The COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment. Design Rapid scoping review Data sources Medline, Embase and biorxiv/medrxiv from inception to 15 May 2021. Setting Hospital and community care. Participants COVID-19 patients of all ages. Interventions COVID-19 treatment. Results The literature search identified 616 relevant primary studies of which 188 were randomised controlled trials and 299 relevant evidence syntheses. The studies and evidence syntheses were conducted in 51 and 39 countries, respectively. Most studies enrolled patients admitted to acute care hospitals (84%), included on average 169 participants, with an average age of 60 years, study duration of 28 days, number of effect outcomes of four and number of harm outcomes of one. The most common primary outcome was death (32%). The included studies evaluated 214 treatment options. The most common treatments were tocilizumab (11%), hydroxychloroquine (9%) and convalescent plasma (7%). The most common therapeutic categories were non-steroidal immunosuppressants (18%), steroids (15%) and antivirals (14%). The most common therapeutic categories involving multiple drugs were antimalarials/antibiotics (16%), steroids/non-steroidal immunosuppressants (9%) and antimalarials/antivirals/antivirals (7%). The most common treatments evaluated in systematic reviews were hydroxychloroquine (11%), remdesivir (8%), tocilizumab (7%) and steroids (7%). The evaluated treatment was in favour 50% and 36% of the evaluations, according to the conclusion of the authors of primary studies and evidence syntheses, respectively. Conclusions This rapid scoping review characterised a growing body of comparative-effectiveness primary studies and evidence syntheses. The results suggest future studies should focus on children, elderly ≥65 years of age, patients with mild symptoms, outpatient treatment, multimechanism therapies, harms and active comparators. The results also suggest that future living evidence synthesis and network meta-analysis would provide additional information for decision-makers on managing COVID-19.

Pilot Projects as Catalysts for Research Initiatives

OBJECTIVES/GOALS: Pilot grants are small financial investments given out by CTSA hubs to facilitate new clinical and translational research projects. The New Jersey Alliance of Clinical and Translational Science (NJ ACTS) is one of 65 CTSA hubs. The goal of this project was to evaluate and improve the NJ ACTS program by learning from pilot programs across the consortium. METHODS/STUDY POPULATION: The initial research on pilot programs was conducted using the CTSA Search Solutions tool, a tool developed at NJ ACTS which provides links to individual pages by topic in all the hub websites. Using the tool, public information was accessed, including common award amounts, significant dates, and preferred categories of research. Then, a survey created in REDCap was distributed to colleagues at all CTSA hubs to gather additional information and thoughts on pilot programs. The data were compiled in an excel database to observe and analyze trends. These trends were graphically presented in figures developed from the data to see how NJ ACTS compares to other CTSA hubs in how they focus and operate their pilot programs. RESULTS/ANTICIPATED RESULTS: There are both similarities and differences between NJ ACTS and other hubs. NJ ACTS utilizes a REDCap form for its application, as do 14 other CTSA hubs. Surveys also show that NJ ACTS follows similar processes for: letter of intent and application due dates;having a standing review committee;and the categories of awards. Award categories for Clinical/Translational Innovation, Methodology/Infrastructure, and Partnership/Collaboration are shared with 47, 25, and 41 institutions, respectively. NJ ACTS requires collaboration between its multiple institutions, as do 28 other hubs. It does not, however, have a public notification of award date, and notifications tend to go out relatively late. NJ ACTS funded multiple proposals pertaining to COVID-19, something 11 other CTSA hubs did as well. DISCUSSION/SIGNIFICANCE: Although a new CTSA hub, NJ ACTSs Pilot Program operates comparably to more mature CTSA hubs. Using the survey data, NJ ACTS can implement modest changes, better serving its scientific community. CTSA Search Solutions has proven an excellent tool and can be used by any hub to understand how they compare and implement changes to improve their programs.

Care in the time of COVID-19: impact on the diagnosis and treatment of breast cancer in a large, integrated health care system.

PURPOSES: To delineate operational changes in Kaiser Permanente Northern California breast care and evaluate the impact of these changes during the initial COVID-19 Shelter-in-Place period (SiP, 3/17/20-5/17/20). METHODS: By extracting data from institutional databases and reviewing electronic medical charts, we compared clinical and treatment characteristics of breast cancer patients diagnosed 3/17/20-5/17/20 to those diagnosed 3/17/19-5/17/2019. Outcomes included time from biopsy to consultation and treatment. Comparisons were made using Chi-square or Wilcoxon rank-sum tests. RESULTS: Fewer new breast cancers were diagnosed in 2020 during the SiP period than during a similar period in 2019 (n = 247 vs n = 703). A higher percentage presented with symptomatic disease in 2020 than 2019 (78% vs 37%, p < 0.001). Higher percentages of 2020 patients presented with grade 3 (37% vs 25%, p = 0.004) and triple-negative tumors (16% vs 10%, p = 0.04). A smaller percentage underwent surgery first in 2020 (71% vs 83%, p < 0.001) and a larger percentage had neoadjuvant chemotherapy (16% vs 11%, p < 0.001). Telehealth utilization increased from 0.8% in 2019 to 70.0% in 2020. Times to surgery and neoadjuvant chemotherapy were shorter in 2020 than 2019 (19 vs 26 days, p < 0.001, and 23 vs 28 days, p = 0.03, respectively). CONCLUSIONS: During SiP, fewer breast cancers were diagnosed than during a similar period in 2019, and a higher proportion presented with symptomatic disease. Early-stage breast cancer diagnoses decreased, while metastatic cancer diagnoses remained similar. Telehealth increased significantly, and times to treatment were shorter in 2020 than 2019. Our system continued to provide timely breast cancer treatment despite significant pandemic-driven disruption.

A spatiotemporally resolved infection risk model for airborne transmission of COVID-19 variants in indoor spaces.

The classic Wells-Riley model is widely used for estimation of the transmission risk of airborne pathogens in indoor spaces. However, the predictive capability of this zero-dimensional model is limited as it does not resolve the highly heterogeneous spatiotemporal distribution of airborne pathogens, and the infection risk is poorly quantified for many pathogens. In this study we address these shortcomings by developing a novel spatiotemporally resolved Wells-Riley model for prediction of the transmission risk of different COVID-19 variants in indoor environments. This modelling framework properly accounts for airborne infection risk by incorporating the latest clinical data regarding viral shedding by COVID-19 patients and SARS-CoV-2 infecting human cells. The spatiotemporal distribution of airborne pathogens is determined via computational fluid dynamics (CFD) simulations of airflow and aerosol transport, leading to an integrated model of infection risk associated with the exposure to SARS-CoV-2, which can produce quantitative 3D infection risk map for a specific SARS-CoV-2 variant in a given indoor space. Application of this model to airborne COVID-19 transmission within a hospital ward demonstrates the impact of different virus variants and respiratory PPE upon transmission risk. With the emergence of highly contagious SARS-CoV-2 variants such as the Delta and Omicron strains, respiratory PPE alone may not provide effective protection. These findings suggest a combination of optimal ventilation and respiratory PPE must be developed to effectively control the transmission of COVID-19 in healthcare settings and indoor spaces in general. This generalised risk estimation framework has the flexibility to incorporate further clinical data as such becomes available, and can be readily applied to consider a wide range of factors that impact transmission risk, including location and movement of infectious persons, virus variant and stage of infection, level of PPE and vaccination of infectious and susceptible individuals, impacts of coughing, sneezing, talking and breathing, and natural and mechanised ventilation and filtration.

Finding Druggable Sites in Proteins Using TACTICS.

Structure-based drug discovery efforts require knowledge of where drug-binding sites are located on target proteins. To address the challenge of finding druggable sites, we developed a machine-learning algorithm called TACTICS (trajectory-based analysis of conformations to identify cryptic sites), which uses an ensemble of molecular structures (such as molecular dynamics simulation data) as input. First, TACTICS uses k-means clustering to select a small number of conformations that represent the overall conformational heterogeneity of the data. Then, TACTICS uses a random forest model to identify potentially bindable residues in each selected conformation, based on protein motion and geometry. Lastly, residues in possible binding pockets are scored using fragment docking. As proof-of-principle, TACTICS was applied to the analysis of simulations of the SARS-CoV-2 main protease and methyltransferase and the Yersinia pestis aryl carrier protein. Our approach recapitulates known small-molecule binding sites and predicts the locations of sites not previously observed in experimentally determined structures. The TACTICS code is available at https://github.com/Albert-Lau-Lab/tactics_protein_analysis.