The effects of aerobic exercise and heat stress on the unbound fraction of caffeine.

Introduction: The fraction of drug circulating in the blood that is not bound to plasma proteins ( ) is considered pharmacologically active since it readily binds to its receptor. evidence suggests that changes in temperature and pH affect the affinity of drug binding to plasma proteins, resulting in changes in . In light of the well-established effects of exercise on body temperature and blood pH, we investigated whether an increase in blood temperature and decrease in pH facilitated through passive heating and exercise translated to a change in the of caffeine.

Current and anticipated future state of cachexia care in patients with cancer.

We assessed care in cancer patients with cachexia across leading health systems (LHSs). Qualitative interviews and quantitative surveys were conducted with LHSs executives and frontline health care personnel, representing 46 total respondents and 42 unique LHSs and including oncology service line leaders, supportive care services, dietitians and surgical oncologists. Cachexia was not considered a top priority, and formal diagnoses were rare.

Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.

Background: Cancer cachexia is a multifactorial metabolic wasting syndrome characterized by anorexia, unintentional loss of weight involving both skeletal muscle and adipose tissues, progressive functional impairment and reduced survival. Therapeutic strategies for this serious condition are very limited. Growth differentiation factor 15 (GDF-15) is a cytokine that is implicated in cancer cachexia and may represent both a biomarker of cancer cachexia and a potential therapeutic target.

A mixed-methods landscape assessment of supportive care for heart failure.

Understanding factors that shape leading health systems' (LHS) perspectives around heart failure (HF) treatment. First of its kind study using a cross-sectional, descriptive, mixed-method design (from executives and frontline healthcare providers) with quantitative survey (n = 35) and qualitative interview (n = 12) data from 47 participants (41 different LHS). 97% of LHS had dedicated HF programs, but variations in maturity highlights opportunities for care standardization.

Arterial desaturation rate does not influence self-selected knee extension force but alters ventilatory response to progressive hypoxia: A pilot study.

The absolute magnitude and rate of arterial desaturation each independently impair whole-body aerobic exercise. This study examined potential mechanisms underlying the rate-dependent relationship. Utilizing an exercise protocol involving unilateral, intermittent, isometric knee extensions (UIIKE), we provided sufficient reperfusion time between contractions to reduce the accumulation of intramuscular metabolic by-products that typically stimulate muscle afferents.

Indirect Calorimetry to Measure Metabolic Rate and Energy Expenditure in Psychiatric Populations: A Systematic Review.

Psychiatric and metabolic disorders are highly comorbid and the relationship between these disorders is bidirectional. The mechanisms underlying the association between psychiatric and metabolic disorders are presently unclear, which warrants investigation into the dynamics of the interplay between metabolism, substrate utilization, and energy expenditure in psychiatric populations, and how these constructs compare to those in healthy controls. Indirect calorimetry (IC) methods are a reliable, minimally invasive means for assessing metabolic rate and substrate utilization in humans.

Potential physiological responses contributing to the ergogenic effects of acute ischemic preconditioning during exercise: A narrative review.

Ischemic preconditioning (IPC) has been reported to augment exercise performance, but there is considerable heterogeneity in the magnitude and frequency of performance improvements. Despite a burgeoning interest in IPC as an ergogenic aid, much is still unknown about the physiological mechanisms that mediate the observed performance enhancing effects. This narrative review collates those physiological responses to IPC reported in the IPC literature and discusses how these responses may contribute to the ergogenic effects of IPC.

Accelerating Virtual Health Implementation Following the COVID-19 Pandemic: Questionnaire Study.

Background: The COVID-19 pandemic accelerated drivers for virtual health adoption and triggered the US federal government to implement regulatory changes to reduce barriers to virtual health implementation. Consequently, virtual health solutions have been increasingly adopted, and health systems in the United States have been reorganizing their care delivery process with unprecedented speed.

Objective: This study aimed to assess and make recommendations on the strategy, business model, implementation, and future considerations for scaling and sustaining virtual health solutions based on the views of executives from the largest health systems in the United States.

Application of Real-World Data to External Control Groups in Oncology Clinical Trial Drug Development.

Randomized controlled trials (RCTs) that assess overall survival are considered the "gold standard" when evaluating the efficacy and safety of a new oncology intervention. However, single-arm trials that use surrogate endpoints (e.g.

Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration.

Background: Sasanlimab is a monoclonal antibody that binds to the programmed cell death receptor 1 (PD-1). Anti-PD-1 monoclonal antibodies have improved patient clinical outcomes; however, not all treated patients derive clinical benefit. Further insights on potential biomarkers beyond PD-L1 expression levels would help to identify the patients most likely to respond to treatment.

Navigating the Regulatory Landscape to Develop Pediatric Oncology Drugs: Expert Opinion Recommendations.

Regulatory changes have been enacted in the United States (US) and European Union (EU) to encourage the development of new treatments for pediatric cancer. Here, we review some of the factors that have hampered the development of pediatric cancer treatments and provide a comparison of the US and EU regulations implemented to address this clinical need. We then provide some recommendations for each stage of the oncology drug development pathway to help researchers maximize their chance of successful drug development while complying with regulations.

Dietary Intakes From Ad Libitum Consumption of Canadian Armed Forces Field Rations Compared With Usual Home Dietary Intakes and Military Dietary Reference Intakes.

Introduction: Diet has an impact on weight status, health, and physical performance. Assessing the usual at-home dietary intakes of military personnel can help ascertain their nutritional status before field training or operations. Preference for foods consumed on a routine basis can also impact the military's preference for and consumption of field rations.

Race and ethnicity representation in clinical trials: findings from a literature review of Phase I oncology trials.

To provide an assessment of published literature on the demographic representation in Phase I trials of biopharmaceutical oncology agents. We conducted a rapid evidence assessment to identify demographic representation reported in Phase I clinical trials for biopharmaceutical oncology agents published in 2019. Globally, the population was predominantly White/Caucasian (62.

The Effects of L-Citrulline on Blood-Lactate Removal Kinetics Following Maximal-Effort Exercise.

The accumulation of lactate in muscle and blood during high-intensity exercise is negatively correlated with the duration exercise can be sustained. Removal of lactate is a key component of acute recovery between consecutive bouts of such exercise. Low-intensity exercise enhances recovery by accelerating lactate turnover in metabolically active tissues, largely mediated by blood flow to these tissues.

Methodological Variations Contributing to Heterogenous Ergogenic Responses to Ischemic Preconditioning.

Ischemic preconditioning (IPC) has been repeatedly reported to augment maximal exercise performance over a range of exercise durations and modalities. However, an examination of the relevant literature indicates that the reproducibility and robustness of ergogenic responses to this technique are variable, confounding expectations about the magnitude of its effects. Considerable variability among study methodologies may contribute to the equivocal responses to IPC.

The Use of Patient-Reported Outcome Measures in Phase I Oncology Clinical Trials.

Objective: To investigate patient-reported outcome (PRO) usage in phase I oncology clinical trials, including types of PRO measures and changes over time.

Methods: We analyzed ClinicalTrials.gov records of phase I oncology clinical trials completed by December 2019.

Menthol Mouth Rinsing and Cycling Performance in Females Under Heat Stress.

Purpose: The effects of menthol (MEN) mouth rinse (MR) on performance, physiological, and perceptual variables in female cyclists during a 30-km independent time trial (ITT) were tested.

Methods: The participants (n = 9) cycled for 30 km in hot conditions (30°C [0.6°C], 70% [1%] relative humidity, 12 [1] km/h wind speed) on 2 test occasions: with a placebo MR and with MEN MR.

Addressing resistance to immune checkpoint inhibitor therapy: an urgent unmet need.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various cancers by reversing the immunosuppressive mechanisms employed by tumors to restore anticancer immunity. Although ICIs have demonstrated substantial clinical efficacy, patient response can vary in depth and duration, and many do not respond at all or eventually develop resistance. ICI resistance mechanisms can be tumor-intrinsic, related to the tumor microenvironment or patient-specific factors.

Ovarian cancer: new strategies and emerging targets for the treatment of patients with advanced disease.

Recently approved therapies have contributed to a significant progress in the management of ovarian cancer; yet, more options are needed to further improve outcomes in patients with advanced disease. Here we review the rationale and ongoing clinical trials of novel combination strategies involving chemotherapy, poly ADP ribose polymerase, programmed death 1 (PD-1)/PD-ligand 1 immune checkpoint and/or vascular endothelial growth factor receptor inhibitors. Further, we discuss novel agents aimed at targets associated with ovarian cancer growth or progression that are emerging as potential new treatment approaches.

Humanistic and Economic Burden of Non-Muscle Invasive Bladder Cancer: Results of Two Systematic Literature Reviews.

Purpose: Non-muscle invasive bladder cancer (NMIBC) is a malignancy restricted to the inner lining of the bladder. Intravesical Bacillus Calmette-Guerin (BCG) following transurethral resection of the bladder tumor is the mainstay first-line treatment for high-risk NMIBC patients. Two systematic literature reviews (SLRs) were conducted to further assess the current evidence on BCG use in NMIBC and the humanistic and economic burden of disease.

Paediatric Strategy Forum for medicinal product development of epigenetic modifiers for children: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

The fifth multistakeholder Paediatric Strategy Forum focussed on epigenetic modifier therapies for children and adolescents with cancer. As most mutations in paediatric malignancies influence chromatin-associated proteins or transcription and paediatric cancers are driven by developmental gene expression programs, targeting epigenetic mechanisms is predicted to be a very important therapeutic approach in paediatric cancer. The Research to Accelerate Cures and Equity (RACE) for Children Act FDARA amendments to section 505B of the FD&C Act was implemented in August 2020, and as there are many epigenetic targets on the FDA Paediatric Molecular Targets List, clinical evaluation of epigenetic modifiers in paediatric cancers should be considered early in drug development.

Energy Balance of Canadian Armed Forces Personnel during an Arctic-Like Field Training Exercise.

Operating in temperature extremes frequently leads to a discrepancy in energy balance. Investigating the effects of operating in extreme cold temperatures on metabolic requirements has not been well described in Canadian Armed Forces (CAF) personnel. The objective was to accurately assess energy deficits using the "gold standard" methodology for measuring energy intake (EI) and energy expenditure (EE).

The Promise for Histone Methyltransferase Inhibitors for Epigenetic Therapy in Clinical Oncology: A Narrative Review.

Epigenetic processes are essential for normal development and the maintenance of tissue-specific gene expression in mammals. Changes in gene expression and malignant cellular transformation can result from disruption of epigenetic mechanisms, and global disruption in the epigenetic landscape is a key feature of cancer. The study of epigenetics in cancer has revealed that human cancer cells harbor both genetic alterations and epigenetic abnormalities that interplay at all stages of cancer development.

Peripheral immune-based biomarkers in cancer immunotherapy: can we realize their predictive potential?

The immunologic landscape of the host and tumor play key roles in determining how patients will benefit from immunotherapy, and a better understanding of these factors could help inform how well a tumor responds to treatment. Recent advances in immunotherapy and in our understanding of the immune system have revolutionized the treatment landscape for many advanced cancers. Notably, the use of immune checkpoint inhibitors has demonstrated durable responses in various malignancies.

Comparison of dietary intakes of Canadian Armed Forces personnel consuming field rations in acute hot, cold, and temperate conditions with standardized infantry activities.

Background: Dietary Reference Intakes are used to guide the energy intake of the Canadian Armed Forces (CAF) field rations provided to military personnel deployed for training or operations. However, the high energy expenditures likely to occur under harsh environmental/metabolically challenging deployment conditions may not be adequately considered. This study examined the Ad libitum energy and nutrient intakes of CAF personnel (n = 18) consuming field rations in a resting thermoneutral environment and during a day of standardized strenuous infantry activities at varying environmental temperatures.