PURPOSEThe purpose of this study was to provide a rationale for “chemotherapy-periodized” exercise by characterizing cyclical variations in fatigue and exercise response across a chemotherapy cycle ...and comparing exercise adherence during chemotherapy between a prescription that is periodized according to chemotherapy cycle length and a standard linearly progressed prescription.
METHODSWomen with breast cancer who were prescribed taxane-based chemotherapy were randomly assigned to a supervised aerobic and resistance exercise program after a chemotherapy-periodized exercise prescription (n = 12) or to usual care during chemotherapy (n = 15). Fatigue and steady state exercise responses were assessed in both groups before the first taxane treatment and across the third treatment (i.e., 0–3 d prior and 3–5 d after the third treatment, and 0–3 d before the fourth treatment) to assess cyclical variations. Adherence to the chemotherapy-periodized exercise prescription was compared with adherence to a standard linear prescription from a prior study in a similar population (n = 51).
RESULTSFatigue increased from baseline (marginal mean ± standard error3.2 ± 0.4) to before the third treatment (4.1 ± 0.4, P = 0.025), then peaked at 3 to 5 d after the third treatment (5.1 ± 0.4, P = 0.001), before recovering before the fourth treatment (4.3 ± 0.5, P = 0.021). The peak in fatigue at 3 to 5 d post–third treatment corresponded to a decrease in steady state exercise oxygen consumption (V˙O2) (P = 0.013). Compared with a standard linear exercise prescription during chemotherapy, a chemotherapy-periodized exercise prescription resulted in higher attendance during the week after chemotherapy (57% ± 30% vs 77% ± 28%, P = 0.04) and overall attendance (63% + 25% vs 78% ± 23%, P = 0.05).
CONCLUSIONSFatigue and exercise V˙O2 vary across a chemotherapy cycle. A chemotherapy-periodized exercise prescription that accommodates cyclical variations in fatigue may increase adherence to supervised exercise.
A primary objective stated at the Cancer Rehabilitation Symposium at the National Institutes of Health was to improve outcome measurement. The purpose of this project was for the Cancer ...Rehabilitation Medicine Metrics Consortium (CRMMC) to develop an assessment tool to evaluate function in cancer patients via a data-driven and methodologically sound process. There is no agreed-upon measure of physical and cognitive function for cancer patients, making it difficult to demonstrate the value of rehabilitation interventions. Cancer patients are a particularly challenging population, with many tumor- and treatment-related variables impacting function.
Investigators from nine different cancer rehabilitation programs participated in a modified-Delphi process to delineate necessary aspects of an ideal patient assessment tool, including instrument type, domains evaluated, applicability across a range of patient traits, clinical feasibility, and item response characteristics. This involved numerous meetings, data review, and analysis of items involved in patient assessment.
The CRMMC developed a 21-item patient-reported outcome measure based on item response theory. The process by which the short form was developed was documented and provides a framework for other clinicians to follow.
This document provides a framework for rehabilitation providers to follow when developing an assessment tool. This process is described in a stepwise fashion for reproducibility even in different, non-cancer populations.
ABSTRACT The oldest stars in the Milky Way (born in the first few billion years) are expected to have a high density in the inner few kpc, spatially overlapping with the Galactic bulge. We use ...spectroscopic data from the Pristine Inner Galaxy Survey (PIGS) to study the dynamical properties of ancient, metal-poor inner Galaxy stars. We compute distances using starhorse, and orbital properties in a barred Galactic potential. With this paper, we release the spectroscopic AAT/PIGS catalogue (13 235 stars). We find that most PIGS stars have orbits typical for a pressure-supported population. The fraction of stars confined to the inner Galaxy decreases with decreasing metallicity, but many very metal-poor stars (VMP; Fe/H <−2.0) stay confined ($\sim 60~{{\ \rm per \, cent}}$ stay within 5 kpc). The azimuthal velocity vϕ also decreases between Fe/H = −1.0 and −2.0, but is constant for VMP stars (at ∼+40 km s−1). The carbon-enhanced metal-poor (CEMP) stars in PIGS appear to have similar orbital properties compared to normal VMP stars. Our results suggest a possible transition between two spheroidal components – a more metal-rich, more concentrated, faster rotating component, and a more metal-poor, more extended and slower/non-rotating component. We propose that the former may be connected to pre-disc in-situ stars (or those born in large building blocks), whereas the latter may be dominated by contributions from smaller galaxies. This is an exciting era where large metal-poor samples, such as in this work (as well as upcoming surveys, e.g. 4MOST), shed light on the earliest evolution of our Galaxy.
Despite research explicating the benefits of cancer rehabilitation interventions to optimize physical, social, emotional, and vocational functioning, many reports document low rates of referral to ...and uptake of rehabilitation in oncology. Cancer rehabilitation clinicians, researchers, and policy makers could learn from the multidisciplinary specialty of palliative care, which has benefited from a growth strategy and has garnered national recognition as an important and necessary aspect of oncology care. The purpose of this article is to explore the actions that have increased the uptake and integration of palliative care to yield insights and multimodal strategies for the development and growth of cancer rehabilitation. After examining the history of palliative care and its growth, the authors highlight 5 key strategies that may benefit the field of cancer rehabilitation: 1) stimulating the science in specific gap areas; 2) creating clinical practice guidelines; 3) building clinical capacity; 4) ascertaining and responding to public opinion; and 5) advocating for public policy change. Coordinated and simultaneous advances on these 5 strategies may catalyze the growth, utilization, and effectiveness of patient screening, timely referrals, and delivery of appropriate cancer rehabilitation care that reduces disability and improves quality of life for cancer survivors who need these services.
A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to ...validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of the Framingham Offspring Cohort.
Using available baseline measurements of serum levels of IL-18, GDF (growth and differentiation factor)-15, soluble form of receptor for advanced glycation end products, myeloperoxidase, and MCP-1 (monocyte chemoattractant protein-1) from Exam 7 of the Framingham Offspring Cohort (1998-2001), we constructed a population-normalized, equally weighted log-transformed mean
-score value representing the average level of each serum analyte to create an inflammatory composite score (ICS5). Multivariable regression models were used to determine the association of ICS5 with incident stroke, brain magnetic resonance imaging features, and cognitive testing performance.
We found a significant association between ICS5 score and increased risk for incident all-cause stroke (hazard ratio, 1.48 95% CI, 1.05-2.08;
=0.024) and ischemic stroke (hazard ratio, 1.51 95% CI, 1.03-2.21;
=0.033) in the Exam 7 cohort of 2201 subjects (mean age 62±9 years; 54% female) aged 45+ years with an all-cause incident stroke rate of 6.1% (135/2201) and ischemic stroke rate of 4.9% (108/2201). ICS5 and its component serum markers are all associated with the Framingham Stroke Risk Profile score (β±SE, 0.19±0.02;
<0.0001). In addition, we found a significant inverse association of ICS5 with a global cognitive score, derived from a principal components analysis of the neuropsychological battery used in the Framingham cohort (-0.08±0.03;
=0.019). No association of ICS5 with magnetic resonance imaging metrics of cerebral small vessel disease was observed.
Circulating serum levels of inflammatory biomarkers centered on IL-18 are associated with an increased risk of stroke and cognitive impairment in the Framingham Offspring Cohort. Linking specific inflammatory pathways to cerebral small vessel disease may enhance individualized quantitative risk assessment for future stroke and vascular cognitive impairment.
Evidence supporting physical activity, diet, and weight management for cancer survivors has grown, leading to the development of guidelines and interventions. The next step is to identify necessary ...practice and policy changes and to develop a research agenda to inform how interventions can be delivered to survivors most effectively and efficiently in health care settings and by community‐based organizations. Here, an agenda is proposed for research, practice, and policy that incorporates recommendations for a range of programming options, a patient‐centered, tailored screening and referral approach, and training needs for survivorship care providers and providers of exercise, nutrition, and weight management services. Research needs to focus on sustainability, dissemination, and implementation. Needed policy changes are presented, as well as opportunities to leverage current health care policies.
Renal medullary carcinoma (RMC) is a highly aggressive disease associated with sickle hemoglobinopathies and universal loss of the tumor suppressor gene
SMARCB1
. RMC has a relatively low rate of ...incidence compared with other renal cell carcinomas (RCCs) that has hitherto made molecular profiling difficult. To probe this rare disease in detail we performed an in-depth characterization of the RMC tumor microenvironment using a combination of genomic, metabolic and single-cell RNA-sequencing experiments on tissue from a representative untreated RMC patient, complemented by retrospective analyses of archival tissue and existing published data. Our study of the tumor identifies a heterogenous population of malignant cell states originating from the thick ascending limb of the Loop of Henle within the renal medulla. Transformed RMC cells displayed the hallmarks of increased resistance to cell death by ferroptosis and proteotoxic stress driven by
MYC
-induced proliferative signals. Specifically, genomic characterization of RMC tumors provides substantiating evidence for the recently proposed dependence of
SMARCB1
-difficient cancers on proteostasis modulated by an intact
CDKN2A
-p53 pathway. We also provide evidence that increased cystine-mTORC-
GPX4
signaling plays a role in protecting transformed RMC cells against ferroptosis. We further propose that RMC has an immune landscape comparable to that of untreated RCCs, including heterogenous expression of the immune ligand
CD70
within a sub-population of tumor cells. The latter could provide an immune-modulatory role that serves as a viable candidate for therapeutic targeting.
Purpose: To build consensus around an optimal patient-reported outcome measure of cancer symptoms and patient needs to facilitate patient-provider communication and trigger referrals to supportive ...services.
Methods and materials: The Grid-Enabled Measures platform was used to crowdsource and facilitate collaboration to achieve consensus. Respondents were invited to nominate and independently rate the usefulness of measures that: (1) have been actively used at a healthcare institution, (2) have a multiple choice or yes/no type format, (3) are applicable to adults with cancer, (4) are patient-reported, and 5) have psychometric data if possible. Discussion boards within the GEM workspace allowed respondents to identify barriers to implementing patient assessment and referral systems.
Results: 166 individuals from various disciplines from 25 organizations participated. Six instruments were nominated, and 553 rating surveys were submitted. The three most highly-rated overall instruments were the Distress Thermometer, the James Supportive Case Screening, and the Functional Assessment of Cancer Therapy-General. Participants noted that wide-scale implementation of this process requires both identifying problems and providing clinicians with algorithms to facilitate appropriate referrals.
Conclusions: Consensus reported three most highly-related measures as optimal for comprehensive screening and identification for referral by assessing multiple domains of functioning and quality of life.
Implications for Rehabilitation
Gaining consensus on the best patient reported outcome measures is an important step towards improving access to cancer rehabilitation services.
A consensus agreed on several measures to use for cancer rehabilitation screening. Functional Assessment of Cancer Therapy-General, National Comprehensive Cancer. Network Distress Thermometer and the James Instrument.
The selected measures do not put undue burden on clinicians and patients.
We evaluate the cost‐effectiveness of two early childhood interventions that use instructional coaching and parent coaching as levers for improvement. The study design allows us to compare the ...individual effects of each intervention as well as their combined effect on student outcomes. We find that teachers receiving instructional coaching improve their use of evidence‐based instructional practices, while families receiving parent coaching show increases in numerous responsive parenting behaviors associated with positive child outcomes. Both interventions demonstrate positive impacts on students, but only parent coaching shows statistically significant effects across a range of student outcomes. Instructional coaching alone is substantially less costly and may therefore be the most cost‐effective of the three treatment conditions; however, small sample sizes limit our ability to reach definitive conclusions. Policy simulations suggest that implementing these interventions could raise the overall cost‐effectiveness of Head Start by at least 16 percent.
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