OPTIMA, a prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer

Background: Multi-parameter tumor gene expression assays (MPAs) are used to estimate individual patient risk and guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in postmenopausal node-positive breast cancer has been provided by the RxPONDER trial interim analysis but this relies on the absence of superiority in an analysis where >50% of events were unrelated to breast cancer. There is much uncertainty about MPA use for premenopausal patients. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomized controlled trial designed to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Method(s): OPTIMA is a partially blinded study with an adaptive two-stage design. The trial recruits women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumor Score (ROR-PT) >60 receive standard management whilst those with a low score (<=60) tumor are treated with endocrine therapy alone. Endocrine therapy for premenopausal women includes ovarian suppression for all participants unless they experience a chemotherapy-induced menopause. Adjuvant abemaciclib is permitted. The trial will be analyzed for (1) non-inferiority of recurrence according to randomization and (2) cost-effectiveness. The key secondary outcome is non-inferiority of recurrence for patients with low ROR-PT score tumors. The efficacy analyses will be performed Per Protocol using Invasive Breast Cancer Free Survival (IBCFS) as the primary outcome measure to limit the risk of a false non-inferiority conclusion. Recruitment of 4500 patients over 8 years will permit demonstration of up to 3% non-inferiority of test-directed treatment with at least 83% power, assuming 5-year IBCFS is 87% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success. OPTIMA is strongly supported by a patient group which has helped design all patient documents and which is represented on the TMG. Result(s): The OPTIMA main trial opened in January 2017 and has continued to recruit throughout the COVID-19 pandemic. Overall recruitment as of 1 July 2022 was 2814 (2593 from UK, 221 from Norway). Patient characteristics are well balanced between the trial arms. Currently 95% of randomized participants are eligible for inclusion in the PP analysis. 66% of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is < 1%. Conclusion(s): OPTIMA will provide robust unbiased evidence on test-directed chemotherapy safety for both postmenopausal and premenopausal women with 1-3 involved nodes as well as for patients with 4-9 involved nodes and for patients treated with abemaciclib.

Impact of COVID-19 on the Belfast Bike Sharing Scheme

The COVID-19 pandemic brought the connectivity and mobility of Northern Irish residents to a halt forcing the bike hiring service Belfast Bikes to cease operations. After reintroducing the service in Summer 2020, the usage of the bike hiring service was severely impacted. This paper investigates the usage of Belfast Bikes pre-pandemic and during the pandemic. Research includes how consumer trends for Belfast Bikes customers changed due to the pandemic and predictive modelling is used to predict whether customers hire a Belfast Bike for direct travel from stations or for an indirect, leisurely trip. We will conclude how the connectivity and mobility of Belfast residents have changed due to the pandemic and provide recommendations for Belfast Bikes and Belfast City to recover after the pandemic. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Examining Effects of a Physical Activity Intervention on Exercise Capacity and Cardiovascular Function Among Patients With Lymphoma and Breast Cancer Undergoing Treatment

Introduction. Patients receiving serial outpatient infusion treatment for lymphoma or breast cancer (BC) with potentially cardio-toxic chemotherapeutic regimens may experience declines in left ventricular ejection fraction (LVEF) and exercise capacity. This study sought to determine if a physical activity intervention (PAI) administered during cancer treatment could attenuate deterioration of exercise capacity and LVEF. Methods. Across two NCI funded cancer centers, we randomized (2:1) 34 participants to a homebased PAI or healthy living education intervention (HLI) within 6 weeks of initiating curative therapies for stage I-IV Hodgkin's, non-Hodgkin's lymphoma, or stage I-III BC (NCT01719562). Training programs were tailored by treatment and functional status and adapted for remote delivery during COVID-19. Exercise capacity was determined via cardiopulmonary exercise test (peak VO2 [ml/kg/min]) and LVEF (%) was determined by magnetic resonance imaging at baseline, 3, and 6 months. Separate linear mixed-effects regression models controlling for baseline values examined changes in peak VO and LVEF by time and treatment group. Results. Demographics were similar between the two arms (PAI vs. HLI, 52.4 [16.3] vs. 56.8 [12.7] years of age [SD];69% vs. 75% white;and 57.7% vs. 50% female). Peak VO 2increased at 3 (+1.15 ml/kg/min [CI: -1.46 - 3.77]) and 6 months (+3.88 ml/kg/min [CI: 0.79 - 6.96]) in the PAI arm, while the HLI arm increased slightly at 3- (+0.67 ml/kg/min [CI: -5.14 - 6.48]) but not 6 months (-0.83 ml/kg/min [CI: -5.99 - 4.33]). LVEF declined slightly at 3 months in the PAI (-2.29% [CI: -4.83 - 0.25]) but not HLI arm (3.05.% [CI: -2.49 - 8.60]), while at 6 months, the PAI arm had returned to baseline LVEF (-0.58% [CI: -4.30 - 3.14]) and the HLI arm declined slightly (-1.76% [CI: -7.23 - 3.71]). Conclusions. This pilot RCT suggests the importance and utility of home-based physical activity during cancer treatment in protecting against expected declines in exercise capacity and LVEF. These results highlight the need for larger randomized trials that examine the effects of lifestyle interventions administered during treatment to improve quality of life and to support long term cardiovascular health in cancer survivors.

How Much Do Paediatricians Know About Poverty within the Paediatric Population?

Aims Poverty is an ever increasing problem with 4.2 million children living in poverty in the UK in 2019, an increase of 600,000 from 2011(1). This has been particularly exacerbated by the COVID pandemic with an estimated 200,000 more children living in poverty in the UK since the pandemic(1). Poverty can affect multiple aspects of children's health and wellbeing, putting additional strain on already stretched NHS recourses. We wanted to assess paediatricians' knowledge about poverty, particularly around prevalence, risk factors, the effect on children's health and wellbeing and how to help families if there are concerns of poverty. From this we hoped to highlight areas where more education and support is required. Methods We designed an online survey with 11 questions including a mixture of multiple choice and free text answers. The questionnaire was distributed to all doctors working in paediatrics at a tertiary paediatric hospital, over a 4 week period. Results There were 29 respondents in total, with grades ranging from FY1 to consultant. Nearly two-thirds of respondents underestimated the prevalence of poverty in the UK and 38% underestimated the prevalence by half or more. Over 80% of respondents underestimated the percentage of children living in poverty locally. All respondents recognised parental disability and unemployment as risk factors for poverty and 90% recognised child disability or serious illness as a risk factor. Only one person suggested parental drug and alcohol use as a risk factor. The respondents were able to list a wide range of health implications of poverty, the most common answers being failure to thrive/poor nutrition, obesity, tooth decay and poor mental health. Two-thirds of respondents admitted not feeling at all comfortable about asking parents about poverty and 40% felt that they never screen for poverty when assessing patients. To assess for poverty 34% would ask about employment, 24% about housing and 41% about benefits and additional supports. All respondents would like further education and support around poverty. Conclusion Overall there was good understanding of the health implications associated with poverty and the risk factors for poverty, but an under-appreciation of the scale of the problem. The majority of doctors do not feel comfortable asking patients and families about poverty, and do not regularly ask about poverty when assessing patients. In order to identify children living in poverty and be able to signpost families to resources that could be beneficial to them, we need to equip paediatricians with the knowledge and skills to assess for poverty and what resources are available for families in the local area. To aid this we have produced a poster to be used to in the local Emergency Department and outpatients to remind doctors about poverty, advice on how to approach the topic and resources available in the hospital and in the local area that be used to sign post families.

Impact of COVID-19 on the Belfast Bike Sharing Scheme

The COVID-19 pandemic brought the connectivity and mobility of Northern Irish residents to a halt forcing the bike hiring service Belfast Bikes to cease operations. After reintroducing the service in Summer 2020, the usage of the bike hiring service was severely impacted. This paper investigates the usage of Belfast Bikes pre-pandemic and during the pandemic. Research includes how consumer trends for Belfast Bikes customers changed due to the pandemic and predictive modelling is used to predict whether customers hire a Belfast Bike for direct travel from stations or for an indirect, leisurely trip. We will conclude how the connectivity and mobility of Belfast residents have changed due to the pandemic and provide recommendations for Belfast Bikes and Belfast City to recover after the pandemic. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Negative Impacts of Pandemic Induced At-Home Remote Learning Can Be Mitigated by Parental Involvement

Format changes in U.S. schooling in response to the COVID-19 pandemic varied by month and by school district, ranging from exclusively home-based to full in-person learning. The impact of these changes on adolescent schooling experiences, and the factors that mitigate such impact, have been challenging to quantify. To address these challenges we employed bi-monthly repeated surveys of youths (N = 6, 546, aged 13–14 years) in a longitudinal study, starting before the pandemic peak (October 2020) and continuing through one year after the pandemic was declared (March 2021). We investigated how school format (in-person vs. remote) impacted objective time spent on academic activities and the subjective experience of school, and how these were influenced by parental engagement. Periods of exclusive at-home remote schooling were pervasive—reported by more than 60% of youths—and linked to a reduction in school enjoyment and time spent on reading, math, and science. In contrast, such periods were linked to more time with parents or guardians helping with school activities, and the frequency of such parental involvement was associated with reductions in negative feelings about school. Results point to potential pathways to mitigate the negative consequences of future school disruptions. Copyright © 2022 Guillaume, Toomarian, Van Rinsveld, Baskin-Sommers, Dick, Dowling, Gonzalez, Hasak, Lisdahl, Marshall, Nguyen, Pelham, Pillai, Sheth, Wang, Tapert and McCandliss.

UNderstanding EQUity in Crisis Standards of Care (the UNEQUAL Crisis Study)

Study Objectives: High volumes of critically ill patients amidst the COVID19 pandemic prompted the development of crisis standards of care (CSC) to guide resource allocation should demand exceed supply. Racial equity in CSC has been discussed widely. This study explores the utility and racial equity implications of CSC when prioritizing critically ill patients for scarce resources across a major metropolitan area. Methods: This multi-site retrospective cohort study included patients admitted to an intensive care unit (ICU) within 20 miles of Boston at the height of the first COVID19 surge (April 18-21, 2020). A priority score (1-8) was calculated for each newly admitted patient based on state CSC using the Sequential Organ Failure Assessment (SOFA) or modified SOFA, as well as predicted 1- or 5-year mortality. Attending emergency physicians reviewed charts to determine likely near-term mortality and reported their confidence (0-100) in this decision. Descriptive statistics were used to characterize the study cohort. Fixed effects linear regression was used to model the effect of race on priority score. Results: Eight hospitals each contributed between 15 and 54 patients for a total cohort size of 257, of whom 130 (50.6%) were white, 52 (20.2%) Black, and 43 (16.7%) Hispanic. Nearly half (47.1%) had a priority score of 1 and 19.8% scored 2, such that 66.9% were in the top priority category for resource allocation. 9.4% had comorbidities indicating likely 5-year mortality, while 14.8% had conditions thought to predict death within 1 year. Reviewers were uncertain about these determinations, with an average confidence of only 48.2-68.0% depending upon the comorbidity. In the fixed effects model, Hispanics had an average priority score 0.81 points lower than whites (95% CI -1.20,-0.45);no difference was found between Black patients (0.3, 95%CI -0.20,0.80) and white patients. Conclusion: In this diverse, region-wide cohort of critically ill patients, few meaningful racial differences were identified in the prioritization of patients under existing crisis standards of care. Hispanic patients may score slightly better than whites, though this may have little real-world significance. Importantly, physicians who would make CSC-based resource allocation decisions had poor confidence in predicting near-term mortality. This raises concern both for clinician moral injury and the fairness of considering comorbid conditions in CSC. [Formula presented]

The Mid Atlantic Appalachian Orogen Traverse: a comparison of virtual and on-location field-based capstone experiences

The Stratigraphy, Structure, Tectonics (SST) course at James Madison University incorporates a capstone project that traverses the Mid Atlantic region of the Appalachian Orogen and includes several all-day field trips. In the Fall 2020 semester, the SST field trips transitioned to a virtual format, due to restrictions from the COVID pandemic. The virtual field trip projects were developed in web-based Google Earth and incorporated other supplemental Power-Point and PDF files. In order to evaluate the effectiveness of the virtual field experiences in comparison with traditional on-location field trips, an online survey was sent to SST students that took the course virtually in Fall 2020 and to students that took the course in person in previous years. Instructors and students alike recognized that some aspects of on-location field learning, especially those with a tactile component, were not possible or effective in virtual field experiences. However, students recognized the value of virtual field experiences for reviewing and revisiting outcrops as well as noting the improved access to virtual outcrops for students with disabilities and the generally more inclusive experience of virtual field trips. Students highlighted the potential benefits for hybrid field experiences that incorporate both on-location outcrop investigations and virtual field trips, which is the preferred model for SST field experiences in Fall 2021 and into the future.

The Bioinformatics Virtual Coordination Network: An Open-Source and Interactive Learning Environment

Lockdowns and “stay-at-home” orders, starting in March 2020, shuttered bench and field dependent research across the world as a consequence of the global COVID-19 pandemic. The pandemic continues to have an impact on research progress and career development, especially for graduate students and early career researchers, as strict social distance limitations stifle ongoing research and impede in-person educational programs. The goal of the Bioinformatics Virtual Coordination Network (BVCN) was to reduce some of these impacts by helping research biologists learn new skills and initiate computational projects as alternative ways to carry out their research. The BVCN was founded in April 2020, at the peak of initial shutdowns, by an international group of early-career microbiology researchers with expertise in bioinformatics and computational biology. The BVCN instructors identified several foundational bioinformatic topics and organized hands-on tutorials through cloud-based platforms that had minimal hardware requirements (in order to maximize accessibility) such as RStudio Cloud and MyBinder. The major topics included the Unix terminal interface, R and Python programming languages, amplicon analysis, metagenomics, functional protein annotation, transcriptome analysis, network science, and population genetics and comparative genomics. The BVCN was structured as an open-access resource with a central hub providing access to all lesson content and hands-on tutorials (https://biovcnet.github.io/). As laboratories reopened and participants returned to previous commitments, the BVCN evolved: while the platform continues to enable “a la carte” lessons for learning computational skills, new and ongoing collaborative projects were initiated among instructors and participants, including a virtual, open-access bioinformatics conference in June 2021. In this manuscript we discuss the history, successes, and challenges of the BVCN initiative, highlighting how the lessons learned and strategies implemented may be applicable to the development and planning of future courses, workshops, and training programs. © Copyright © 2021 Tully, Buongiorno, Cohen, Cram, Garber, Hu, Krinos, Leftwich, Marshall, Sieradzki, Speth, Suter, Trivedi, Valentin-Alvarado and Weissman.

Knowledge Discovery of the Delays Experienced in Reporting COVID-19 Confirmed Positive Cases Using Time to Event Models

Survival analysis techniques model the time to an event where the event of interest traditionally is recovery or death from a disease. The distribution of survival data is generally highly skewed in nature and characteristically can include patients in the study who never experience the event of interest. Such censored patients can be accommodated in survival analysis approaches. During the COVID-19 pandemic, the rapid reporting of positive cases is critical in providing insight to understand the level of infection while also informing policy. In this research, we introduce the very novel application of survival models to the time that suspected COVID-19 patients wait to receive their positive diagnosis. In fact, this paper not only considers the application of survival techniques for the time period from symptom onset to notification of the positive result but also demonstrates the application of survival analysis for multiple time points in the diagnosis pathway. The approach is illustrated using publicly available data for Ontario, Canada for one year of the pandemic beginning in March 2020. © 2021, Springer Nature Switzerland AG.

Pediatric tonsillectomy in England 2014-2019: An analysis of administrative data

Introduction: Efficiency in health care delivery is increasingly important as health care services look to recover from the COVID-19 pandemic. Day-case elective surgery can help keep hospital beds free and reduce the risk of nosocomial infection. We aimed to investigate outcomes for day-case and overnight stay elective pediatric tonsillectomy in England. Method: Data on tonsillectomies in patients aged ≤18 years were extracted from the Hospital Episodes Statistics (HES) data set from April 1, 2014, to March 31, 2019. HES contains data for all National Health Service-funded hospital admissions in England. Data were categorized as those seen as day cases and those that involved an overnight stay. Primary outcome was readmission within 30 days of discharge. Multilevel logistic regression modeling was used to explore the relationship between tonsillectomy, day-case surgery, and 30-day readmission. Covariates included age, sex, year, indication for operation, additional procedures (eg, adenoidectomy), and surgical technique (coblation). Results: A data set of 156,942 tonsillectomy procedures across 133 hospital trusts (centers) was identified over a 5-year period. Of these procedures, 88,354 (56.3%) were daycase procedures. Patients who were seen for day-case surgery were significantly older, with 39.8% of 0- to 4-year-olds seen as a day case compared with 73.1% of 15- to 18-year-olds. Patients with hypertrophy, obstructive sleep apnea, or adenoid involvement were much less likely to have day-case surgery than those without (70.8% vs 46.6%, respectively). The lowest rates of readmission were in patients aged 5 to 7 years and patients with hypertrophy, adenoid involvement, or obstructive sleep apnea. Centers that had higher day-case rates have lower 30-day readmission for infection. Conclusion: Our study provides further evidence of the safety of day-case tonsillectomy surgery for the majority of paediatric patients.

Planned surgery in the COVID-19 pandemic: a prospective cohort study from Nottingham.

PURPOSE: Globally planned surgical procedures have been deferred during the current COVID-19 pandemic. The study aimed to report the outcomes of planned urgent and cancer cases during the current pandemic using a multi-disciplinary prioritisation group. METHODS: A prospective cohort study of patients having urgent or cancer surgery at a NHS Trust from 1st March to 30th April 2020 who had been prioritised by a multi-disciplinary COVID Surgery group. Rates of post-operative PCR positive and suspected COVID-19 infections within 30 days, 30-day mortality and any death related to COVID-19 are reported. RESULTS: Overall 597 patients underwent surgery with a median age of 65 years (interquartile range (IQR) 54-74 years). Of these, 86.1% (514/597) had a current cancer diagnosis. During the period, 60.8% (363/597) of patients had surgery at the NHS Trust whilst 39.2% (234/597) had surgery at Independent Sector hospitals. The incidence of COVID-19 in the East Midlands was 193.7 per 100,000 population during the study period. In the 30 days following surgery, 1.3% (8/597) of patients tested positive for COVID-19 with all cases at the NHS site. Overall 30-day mortality was 0.7% (4/597). Following a PCR positive COVID-19 diagnosis, mortality was 25.0% (2/8). Including both PCR positive and suspected cases, 3.0% (18/597) developed COVID-19 infection with 1.3% at the independent site compared to 4.1% at the NHS Trust (p=0.047). CONCLUSIONS: Rates of COVID-19 infection in the post-operative period were low especially in the Independent Sector site. Mortality following a post-operative diagnosis of COVID-19 was high.

Implementation of a fetal ultrasound telemedicine service: women's views and family costs.

BACKGROUND: The complexity of fetal medicine (FM) referrals that can be managed within obstetric units is dependent on the availability of specialist ultrasound expertise. Telemedicine can effectively transfer real-time ultrasound images via video-conferencing. We report the successful introduction of a fetal ultrasound telemedicine service linking a specialist fetal medicine (FM) centre and a remote obstetric unit. METHODS: Over a four-year period from October 2015, all women referred for FM consultation from the obstetric unit were seen via telemedicine, excluding cases where invasive testing, intrauterine therapy or cardiac anomalies were anticipated. The outcomes measured included the indication for FM referral; scan duration and image and sound quality during the consultation. Women's perceptions of the telemedicine consultation and estimated costs to attend the FM centre were measured by a structured questionnaire completed following the first telemedicine appointment during the Phase 1 of the project. RESULTS: Overall, 297 women had a telemedicine consultation during Phase 1 (pilot and evaluation) and Phase 2 (embedding and adoption) of the project, which covered a 4 year period 34 women completed questionnaires during the Phase 1 of the study. Travel to the telemedicine consultation took a median (range) time of 20 min (4150), in comparison to an estimated journey of 230 min (120,450) to the FM centre. On average, women would have spent approximately £28 to travel to the FM centre per visit. The overall costs for the woman and her partner/ friend to attend the FM centre was estimated to be £439. Women were generally satisfied with the service and valued the opportunity to have a FM consultation locally. CONCLUSIONS: We have demonstrated that a fetal ultrasound telemedicine service can be successfully introduced to provide FM ultrasound of sufficient quality to allow fetal diagnosis and specialist consultation with parents. Furthermore, the service is acceptable to parents, has shown a reduction in family costs and journey times.