Advances in Adherence Reporting of Resistance Training in a Clinical Trial during Adjuvant Chemotherapy for Colon Cancer.

PURPOSE: Detailed reporting of individually tailored exercise prescriptions (ExR x ) used in clinical trials is essential to describe feasibility, tolerability, and efficacy of the intervention and to inform translation to clinical care. This article outlines the methodology used to develop a resistance training (RT) ExR x for people with colon cancer receiving chemotherapy and reports adherence to the randomized controlled trial testing the impact of RT on relative dose intensity of chemotherapy and patient-reported toxicities. METHODS: Participants randomized to the exercise arm ( n = 90) were included. To promote muscle hypertrophy, the ExR x was twice-weekly, moderate to heavy loads (65%-85% one-repetition maximum), high sets (3-5), and intermediate repetitions (6-10) of five large multijoint movements with adjustable dumbbells. Attendance (achieved frequency) and adherence (achieved volume) were calculated. Group-based trajectory modeling was used to identify clusters of individuals with similar adherence patterns and compared baseline characteristics across adherence groups. RESULTS: The median attendance was 69.1%. Adherence was 60.6% but higher for those receiving 3 versus 6 months of chemotherapy (80.4 vs 47.4%; P < 0.05 ). Participants engaged in a median of 1.4 d of RT each week, lifting 62% of the one-repetition maximum load, for 3.0 sets and 7.5 repetitions per set. Three distinct adherence groups were identified: 13% "nonstarter," 37% "tapered off," and 50% "consistent exercisers." Females were more likely to be in the nonstarter and tapered-off groups. CONCLUSIONS: This article outlines suggested methods for reporting ExR x of RT in oncology clinical trials and provides insight into the tolerance of ExR x of RT during chemotherapy treatment for colon cancer. These findings aim to foster constructive dialogue and offer a premise for designing future research to elucidate the benefits of exercise during chemotherapy.

Capturing heart valve development with Gene Ontology.

Introduction: The normal development of all heart valves requires highly coordinated signaling pathways and downstream mediators. While genomic variants can be responsible for congenital valve disease, environmental factors can also play a role. Later in life valve calcification is a leading cause of aortic valve stenosis, a progressive disease that may lead to heart failure. Current research into the causes of both congenital valve diseases and valve calcification is using a variety of high-throughput methodologies, including transcriptomics, proteomics and genomics. High quality genetic data from biological knowledge bases are essential to facilitate analyses and interpretation of these high-throughput datasets. The Gene Ontology (GO, http://geneontology.org/) is a major bioinformatics resource used to interpret these datasets, as it provides structured, computable knowledge describing the role of gene products across all organisms. The UCL Functional Gene Annotation team focuses on GO annotation of human gene products. Having identified that the GO annotations included in transcriptomic, proteomic and genomic data did not provide sufficient descriptive information about heart valve development, we initiated a focused project to address this issue. Methods: This project prioritized 138 proteins for GO annotation, which led to the curation of 100 peer-reviewed articles and the creation of 400 heart valve development-relevant GO annotations. Results: While the focus of this project was heart valve development, around 600 of the 1000 annotations created described the broader cellular role of these proteins, including those describing aortic valve morphogenesis, BMP signaling and endocardial cushion development. Our functional enrichment analysis of the 28 proteins known to have a role in bicuspid aortic valve disease confirmed that this annotation project has led to an improved interpretation of a heart valve genetic dataset. Discussion: To address the needs of the heart valve research community this project has provided GO annotations to describe the specific roles of key proteins involved in heart valve development. The breadth of GO annotations created by this project will benefit many of those seeking to interpret a wide range of cardiovascular genomic, transcriptomic, proteomic and metabolomic datasets.

Thinking beyond 'outbreak': The contentious politics of the science of early warning and overdose epidemic.

This Commentary on the article, "Early warnings and slow deaths: A sociology of outbreak and overdose" by Tim Rhodes and Kari Lancaster, reflects upon rapid response reflexes invoked in societal responses to 'emergency,' 'epidemic,' 'crisis,' and disasters, all of  which require immediate action with no time to think. Epidemiology has given us machines for producing 'fact' about the 'opioid overdose epidemic' that promote the forgetting of the ways in which apparatuses of social control enact the production of facticity. While facts are supposed to be epistemologically reliable and worthy, the work of Rhodes and Lancaster invites us to de-subscribe to these beliefs and re-member our way towards developing slower, more thorough, and more thoughtful ways of seeing a wider array of "indicators, signals, evidence, and narratives of an ecological kind" (Rhodes and Lancaster 2023; this issue). This Commentary focuses on the practices of 'early warning' in social, political, and economic context.

Physical activity in older adults with metastatic gastrointestinal cancer: a pilot and feasibility study.

Objectives: This study determined the feasibility of delivering a 12-week structured physical activity programme during chemotherapy to older adults recently diagnosed with metastatic gastrointestinal (GI) cancer. Methods: This study used a single-cohort design. Older adults (aged ≥65 years) diagnosed with metastatic oesophageal, gastric, pancreatic or colorectal cancer who planned to initiate chemotherapy were enrolled. The physical activity programme included a combination of aerobic, flexibility, strength and balance modalities delivered by a certified cancer exercise trainer during chemotherapy infusion appointments, then translated and sustained at home by participants. The co-primary endpoints included: (1) accrual of 20 participants in 12 months and (2) physical activity adherence of ≥50%. Results: Between March and October 2018, 29 participants were screened, and 20 were enrolled within 12 months (recruitment rate: 69% (90% CI: 55% to 83%); p<0.001), meeting the first co-primary endpoint. The median age of participants was 73.3 years (IQR: 69.3-77.2). At week 12, 67% (90% CI: 48% to 85%) of participants adhered to ≥50% of the prescribed physical activity (p=0.079 (statistically significant)), meeting the second co-primary endpoint. From baseline to week 12, accelerometer-measured light-intensity and moderate-intensity to vigorous-intensity physical activity increased by 307.4 (95% CI: 152.6 to 462.2; p<0.001) and 25.0 min per week (95% CI: 9.9 to 40.1; p=0.001), respectively. There were no serious or unexpected adverse events. The median overall survival was 16.2 months (8.4-22.4). Conclusion: These results establish the feasibility of a larger scale randomised controlled trial that enrols older adults with metastatic GI cancer and delivers a structured physical activity programme during chemotherapy. Trial registration number: NCT03331406.

The COVID-19 High-Performance Computing Consortium.

In March of 2020, recognizing the potential of High Performance Computing (HPC) to accelerate understanding and the pace of scientific discovery in the fight to stop COVID-19, the HPC community assembled the largest collection of worldwide HPC resources to enable COVID-19 researchers worldwide to advance their critical efforts. Amazingly, the COVID-19 HPC Consortium was formed within one week through the joint effort of the Office of Science and Technology Policy (OSTP), the U.S. Department of Energy (DOE), the National Science Foundation (NSF), and IBM to create a unique public-private partnership between government, industry, and academic leaders. This article is the Consortium's story-how the Consortium was created, its founding members, what it provides, how it works, and its accomplishments. We will reflect on the lessons learned from the creation and operation of the Consortium and describe how the features of the Consortium could be sustained as a National Strategic Computing Reserve to ensure the nation is prepared for future crises.

Vaping Prevention in a Middle School Population Using CATCH My Breath.

INTRODUCTION: The number of teens using electronic cigarettes in the United States has reached epidemic proportions. One in 20 middle school youth currently vapes regularly (Wang et al., 2020), supporting the need for e-cigarette education and prevention programs in this vulnerable population. METHOD: The evidence-based youth vaping prevention program, CATCH My Breath, was implemented and evaluated in a small, private, parochial middle school using a quasi-experimental, within-subjects, longitudinal design. RESULTS: Students' e-cigarette knowledge significantly improved postintervention (p < .001) and was sustained at 3 months follow-up. Attitudes about vaping remained stable after postintervention and at 3 months follow-up (p > .05). Susceptibility toward vaping increased or remained consistent despite increased knowledge (p = .096). DISCUSSION: CATCH My Breath is an effective school-based resource to educate middle school youth about the dangers of vaping. Additional research is needed to evaluate the intervention's impact on e-cigarette attitudes and the measurement of susceptibility in teens.

Improving laboratory quality and capacity through leadership and management training: Lessons from Zambia 2016-2018.

BACKGROUND: Competent leadership and management are imperative for delivering quality laboratory services; however, few laboratory managers receive job-specific training in organisational management and leadership. OBJECTIVE: To develop and evaluate participants' competencies in organisational leadership and management as measured through learner and laboratory quality improvement assessments. METHODS: This professional development programme employed a mentored, blended learning approach, utilising in-person didactic and online training, with the practical application of a capstone project in the laboratories. Programme impact was evaluated through a series of pre- and post-laboartory assessments using the Stepwise Laboratory Improvement Process Towards Accreditation checklist, as well as learner-competency assessments through online quizzes and discussions. RESULTS: From 2016 to 2018, 31 managers and quality officers from 16 individual laboratories graduated from the programme having completed capstone projects addressing areas in the entire laboratory testing process. Laboratories increased their compliance with the International Organization for Standardization 15189 standard and all but two laboratories significantly increased their accreditation scores. Two laboratories gained three stars, two laboratories gained two stars, and five laboratories gained one star. Five laboratories subsequently achieved International Organization for Standardization 15189 accreditation in 2019. CONCLUSION: This programme taught leadership theory to laboratory managers and allowed them to implement leadership and management practices in the laboratory setting. Programmes such as this complement existing laboratory quality management training programmes such as Strengthening Laboratory Management Toward Accreditation.

Paediatric lateral condyle fracture with a posterolateral elbow dislocation: an atypical injury in a preadolescent.

Paediatric lateral condyle fractures of the distal humerus are common but a concomitant elbow dislocation is rare. Typically, paediatric orthopaedic surgeons will treat lateral condyle fractures with pin or metaphyseal single-screw fixation and supplementary immobilisation for several weeks. These techniques sacrifice the early stability and mobilisation necessary to avoid stiffness after a complex elbow fracture-dislocation. We present an 11-year-old boy who sustained a traumatic posterolateral elbow dislocation with lateral condyle and coronoid fractures. Due to advanced skeletal age, both paediatric and adult treatment principles were applied to this rare injury. After initial closed reduction, open reduction and internal fixation of the distal humerus lateral condyle with divergent partially threaded compression screws was performed. Motion was initiated in 2 weeks and the patient regained almost full motion by 3 months. At 1.5-year follow-up, the affected limb carrying angle was unaffected and the patient had no functional limitations.

International Nursing Collaboration to Establish the Philippine Quit Line: Using a Conceptual Model for Partnership and Sustainability in Global Health.

ABSTRACT: Tobacco use remains the single most preventable cause of death and disability worldwide. In the Philippines, 28.3% of the people are current tobacco smokers, which is one of the highest smoking rates in Asia. The World Health Organization estimates that 10 Filipinos die every day from cancer, stroke, and lung and heart disease caused by cigarette smoke and approximately 24 million Filipinos are exposed to secondhand smoke in the home. Although there are quit lines in all 50 U.S. states and territories, there was no access to this smoking cessation program in the Philippines before the initiation of the international collaboration described in this article. In 2012, a Filipino-American nurse with extensive quit line expertise initiated collaboration between the United States and Philippine smoking cessation experts to plan the creation of a quit line at the Lung Center of the Philippines. The Conceptual Model for Partnership and Sustainability in Global Health was used as a foundation for the planning, implementation, and evaluation of the Philippine Quit Line project, which was funded in 2017 by the World Health Organization and the Philippine Department of Health. This funding and other outcomes related to nursing education about tobacco addictions in the Philippines suggest that the Partnership and Sustainability in Global Health Model can provide a blueprint for international collaboration on health projects that are rooted in real collaborative and sustainable partnerships.

Evaluating Emergency Department Utilization for Mobile Mental Health Patients: A Correlational Retrospective Analysis.

BACKGROUND: Patients who have barriers to attending traditional mental health clinics are at risk for psychiatric decompensation, which can lead to inappropriate utilization of emergency departments (EDs). Mobile health clinics have the potential to reduce avoidable ED visits by providing easily accessible care. AIMS: To determine whether psychiatric patients have a significant reduction in ED visits after admission to the mobile mental health clinic (MMHC). METHOD: This study is a replication of a pilot study on the first 43 patients admitted to the MMHC that was conducted soon after the opening. Results of that study were promising. In the current study, health records from a sample of 265 patients from the MMHC were reviewed retrospectively to determine the number of ED visits post admission to the MMHC. ED visits were examined 8 months prior to admission to the MMHC and 8 months after. Descriptive statistics and paired t-tests were used to analyze demographics and determine differences in ED visits pre- and post admission to the MMHC. RESULTS: Findings demonstrated that patients admitted to the MMHC had a significant reduction (p < .05) in ED utilization. There was also a decrease in mean ED visits in patients who received combined treatment, which included medication management and counseling. CONCLUSION: The MMHC is an effective initiative to reduce ED overutilization, thereby decreasing Medicaid costs. Psychiatric care provided directly in the home can promote health and prevent destabilization.

Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial.

Observational studies report that physical activity and metformin are associated with improved clinical outcome in patients with cancer. Inflammation is one biological mechanism hypothesized to mediate these associations. In this phase II, multicenter, 2 × 2 factorial trial, 139 patients with breast and colorectal cancer who completed standard therapy were randomized to one of four treatment groups for 12 weeks: exercise alone, metformin alone, exercise and metformin, or control. Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), soluble tumor necrosis factor alpha receptor two (sTNFαR2), and IL6. The primary modeling strategy evaluated the trial product estimand that was quantified using a generalized linear mixed model. Compared with control, exercise alone reduced hs-CRP [-30.2%; 95% confidence interval (CI), -50.3, -1.0] and IL6 (-30.9%; 95% CI, -47.3, -9.5) but did not change sTNFαR2 (1.0%; 95% CI, -10.4, 13.9). Compared with control, metformin alone did not change hs-CRP (-13.9%; 95% CI, -40.0, 23.4), sTNFαR2 (-10.4%; 95% CI, -21.3, 2.0), or IL6 (-22.9%; 95% CI, -42.3, 2.0). Compared with control, exercise and metformin reduced sTNFαR2 (-13.1%; 95% CI, -22.9, -1.0) and IL6 (-38.7%; 95% CI, -52.3, -18.9) but did not change hs-CRP (-20.5%; 95% CI, -44.0, 12.7). The combination of exercise and metformin was not synergistic for hs-CRP, sTNFαR2, or IL6. In survivors of breast and colorectal cancer with low baseline physical activity and without type 2 diabetes, exercise and metformin reduced measures of inflammation that are associated with cancer recurrence and mortality.

Addressing Health Inequities Exacerbated by COVID-19 Among Youth With HIV: Expanding Our Toolkit.

Adolescents and young adults, aged 13-24 years, are disproportionately affected by HIV in the United States. Youth with HIV (YHIV) face many psychosocial and structural challenges resulting in poor clinical outcomes including lower rates of medication adherence and higher rates of uncontrolled HIV. The Johns Hopkins Intensive Primary Care clinic, a longstanding HIV care program in Baltimore, Maryland, cares for 76 YHIV (aged 13-24 years). The multidisciplinary team provides accessible, evidenced-based, culturally sensitive, coordinated and comprehensive patient and family-centered HIV primary care. However, the ability to provide these intensive, in-person services was abruptly disrupted by the necessary institutional, state, and national coronavirus disease 2019 (COVID-19) mitigation strategies. As most of our YHIV are from marginalized communities (racial/ethnic, sexual, and gender minorities) with existing health and social inequities that impede successful clinical outcomes and increase HIV disparities, there was heightened concern that COVID-19 would exacerbate these inequities and amplify the known HIV disparities. We chronicle the structural and logistic approaches that our team has taken to proactively address the social determinants of health that will be negatively impacted by the COVID-19 pandemic, while supporting YHIV to maintain medication adherence and viral suppression.

Randomized Phase II Trial of Exercise, Metformin, or Both on Metabolic Biomarkers in Colorectal and Breast Cancer Survivors.

BACKGROUND: Observational data support inverse relationships between exercise or metformin use and disease outcomes in colorectal and breast cancer survivors, although the mechanisms underlying these associations are not well understood. METHODS: In a phase II trial, stage I-III colorectal and breast cancer survivors who completed standard therapy were randomly assigned to structured exercise or metformin or both or neither for 12 weeks. The primary outcome was change in fasting insulin levels; secondary outcomes included changes in other blood-based energetic biomarkers and anthropometric measurements. Analyses used linear mixed models. RESULTS: In total, 139 patients were randomly assigned; 91 (65%) completed follow-up assessments. Fasting insulin levels statistically significantly decreased in all three intervention arms (-2.47 µU/mL combination arm, -0.08 µU/mL exercise only, -1.16 µU/mL metformin only, + 2.79 µU/mL control arm). Compared with the control arm, all groups experienced statistically significant weight loss between baseline and 12 weeks (-1.8% combination arm, -0.22% exercise only, -1.0% metformin only, +1.55% control). The combination arm also experienced statistically significant improvements in the homeostatic model assessment for insulin resistance (-30.6% combination arm, +61.2% control) and leptin (-42.2% combination arm, -0.8% control), compared with the control arm. The interventions did not change insulin-like growth factor-1 or insulin-like growth factor binding protein-3 measurements as compared with the control arm. Tolerance to metformin limited compliance (approximately 50% of the participants took at least 75% of the planned dosages in both treatment arms). CONCLUSIONS: The combination of exercise and metformin statistically significantly improved insulin and associated metabolic markers, as compared to the control arm, with potential greater effect than either exercise or metformin alone though power limited formal synergy testing. Larger efforts are warranted to determine if such a combined modality intervention can improve outcomes in colorectal and breast cancer survivors.

Impact of a Pre-Operative Exercise Intervention on Breast Cancer Proliferation and Gene Expression: Results from the Pre-Operative Health and Body (PreHAB) Study.

PURPOSE: Exercise after breast cancer diagnosis is associated with lower cancer-specific mortality, but the biological mechanisms through which exercise impacts breast cancer are not fully understood. The Pre-Operative Health and Body (PreHAB) Study was a randomized window-of-opportunity trial designed to test the impact of exercise on Ki-67, gene expression, and other biomarkers in women with breast cancer. EXPERIMENTAL DESIGN: Inactive women with newly diagnosed breast cancer were randomized to an exercise intervention or mind-body control group, and participated in the study between enrollment and surgery (mean 29.3 days). Tumor and serum were collected at baseline and surgery. RESULTS: Forty-nine women were randomized (27 exercise, 22 control). At baseline, mean age was 52.6, body mass index was 30.2 kg/m2, and exercise was 49 minutes/week. Exercise participants significantly increased exercise versus controls (203 vs. 23 minutes/week, P < 0.0001). There were no differences in changes of expression of Ki-67, insulin receptor, and cleaved caspase-3 in exercise participants versus controls. KEGG pathway analysis demonstrated significant upregulation of 18 unique pathways between the baseline biopsy and surgical excision in exercise participants and none in control participants (q < 0.1). Top-ranked pathways included several implicated in immunity and inflammation. Exploratory analysis of tumor immune infiltrates demonstrated a trend toward a decrease in FOXP3+ cells in exercise versus control participants over the intervention period (P = 0.08). CONCLUSIONS: A window-of-opportunity exercise intervention did not impact proliferation but led to alterations in gene expression in breast tumors, suggesting that exercise may have a direct effect on breast cancer.See related commentary by Koelwyn and Jones, p. 5179.

A System-Level Approach to Improve HIV Screening in an Urban Pediatric Primary Care Setting.

BACKGROUND AND OBJECTIVES: Less than 50% of youth living with HIV know their status. The Centers for Disease Control and Prevention and the United States Preventive Services Task Force recommend universal HIV screening in adolescence. Pediatric primary care settings are still lacking in testing youth who are at risk for HIV. Our objective was to determine whether implementing rapid HIV screening improved HIV screening rates and result receipt in 13- to 25-year-old pediatric primary patients. METHODS: From March 2014 to June 2015, a 4-cycle plan-do-study-act quality improvement model was used. A total of 4433 patients aged 13 to 25 years were eligible for HIV screening on the basis of Centers for Disease Control and Prevention criteria. Logistic regression with random effects was used to estimate the odds of HIV screening and screening with a rapid test compared with each previous cycle. Statistical process control charts using standard interpretation rules assessed the effect of patients receiving rapid HIV screening. RESULTS: Baseline HIV screening rate was 29.6%; it increased to 82.7% in cycle 4. The odds of HIV screening increased 31% between cycle 1 and baseline (odds ratio 1.31 [95% confidence interval: 1.01-1.69]) to a 1272% increase between cycle 4 and baseline (odds ratio 12.72 [95% confidence interval: 10.45-15.48]), with most (90.4%) via rapid screening. Rapid screening yielded higher same-day result receipt . Five patients were identified with HIV and immediately linked to on-site care. CONCLUSIONS: Rapid HIV screening and system-level modifications significantly increased screening rates and result receipt, revealing this to be an effective method to deliver HIV services to youth.