Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer.

Multiple organizations around the world have issued evidence-based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health-related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home-based or community-based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Assessment of fatigue and its impact in chronic liver disease.

Patient-reported outcomes (PROs), such as health-related quality of life (HRQL), are important outcome measures for patients with chronic liver diseases (CLDs). Presence of cirrhosis and advanced liver disease have been associated with worsened HRQL and fatigue. On the other hand, some patients with earlier stages of CLD also experience fatigue, causing PRO impairment. Treatment for some CLDs may improve HRQL and, sometimes, levels of fatigue. We aimed to provide an in-depth expert review of concepts related to fatigue and HRQL in patients with primary biliary cholangitis, hepatitis C virus and MASLD (metabolic dysfunction-associated steatotic liver disease). A panel of experts in fatigue and CLD reviewed and discussed the literature and collaborated to provide this expert review of fatigue in CLD. Herein, we review and report on the complexity of fatigue, highlighting that it is comprised of peripheral (neuromuscular failure, often in conjunction with submaximal cardiorespiratory function) and central (central nervous system dysfunction) causes. Fatigue and HRQL are measured using validated self-report instruments. Additionally, fatigue can be measured through objective tests (e.g. grip strength). Fatigue has deleterious effects on HRQL and one's ability to be physically active and socially engaged but does not always correlate with CLD severity. Treatments for hepatitis C virus and MASLD can improve levels of fatigue and HRQL, but current treatments for primary biliary cholangitis do not seem to affect levels of fatigue. We conclude that obtaining PRO data, including on HRQL and fatigue, is essential for determining the comprehensive burden of CLD and its potential treatments.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

Risk factors for reduced function in women with a history of breast cancer.

PURPOSE: People with a history of breast cancer are at risk of losing function during and after treatment. Unfortunately, little is known about the individual and additive effects of specific treatment, disease-related, and demographic factors that may contribute to functional decline. This manuscript reports the results of a multi-center study to evaluate the effects of these factors on function. METHODS: In this cross-sectional study, women with a history of breast cancer referred to physical medicine and rehabilitation cancer rehabilitation clinics were administered the PROMIS® Cancer Function Brief 3D Profile to evaluate function in the domains of physical function, fatigue, and social participation. Clinical and demographic information, including treatment history and disease status, was recorded by clinicians. Patients were analyzed in two groups: those with active disease on antineoplastic treatment, and those with no evidence of disease (NED). A multivariable model was constructed to detect associations between clinical and demographic factors. RESULTS: In patients with NED, the presence of chemotherapy-induced peripheral neuropathy (CIPN) was strongly associated with reduced function in all three domains. In those with active disease, having brain metastases was significantly associated with reduced function in all domains and CIPN with reduced physical function. Radiation was associated with improved function in both cohorts. CONCLUSIONS: Among women seeking rehabilitative care, CIPN and the presence of brain metastases were most strongly associated with a decline in function. The effects of radiation on function were unexpected and may be partially explained by the treatment's role in symptom management. Clinicians who treat breast cancer should consider a patient's functional status when providing supportive care.

Evidence for an association of serum microanalytes and myofascial pain syndrome.

BACKGROUND: Myofascial Pain Syndrome (MPS) is a common pain disorder. Diagnostic criteria include physical findings which are often unreliable or not universally accepted. A precise biosignature may improve diagnosis and treatment effectiveness. The purpose of this study was to assess whether microanalytic assays significantly correlate with characteristic clinical findings in people with MPS. METHODS: This descriptive, prospective study included 38 participants (25 women) with greater than 3 months of myofascial pain in the upper trapezius. Assessments were performed at a university laboratory. The main outcome measures were the Beighton Index, shoulder range of motion, strength asymmetries and microanalytes: DHEA, Kynurenine, VEGF, interleukins (IL-1b, IL-2, IL-4, IL-5, IL-7, IL-8, IL-13), growth factors (IGF-1, IGF2, G-CSF, GM-CSF), MCP-1, MIP-1b, BDNF, Dopamine, Noradrenaline, NPY, and Acetylcholine. Mann-Whitney test and Spearman's multivariate correlation were applied for all variables. The Spearman's analysis results were used to generate a standard correlation matrix and heat map matrix. RESULTS: Mean age of participants was 32 years (20-61). Eight (21%) had widespread pain (Widespread Pain Index ≥ 7). Thirteen (34%) had MPS for 1-3 years, 14 (37%) 3-10 years, and 11 (29%) for > 10 years. The following showed strong correlations: IL1b,2,4,5,7,8; GM-CSF and IL 2,4,5,7; between DHEA and BDNF and between BDNF and Kynurenine, NPY and acetylcholine. The heat map analysis demonstrated strong correlations between the Beighton Index and IL 5,7, GM-CSF, DHEA. Asymmetries of shoulder and cervical spine motion and strength associated with select microanalytes. CONCLUSION: Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS.

Neutralizing Monoclonal Antibody Treatment Reduces Hospitalization for Mild and Moderate Coronavirus Disease 2019 (COVID-19): A Real-World Experience.

BACKGROUND: Neutralizing monoclonal antibody (NmAb) treatments have received Emergency Use Authorization to treat patients with mild or moderate COVID-19 infection. To date, no real- world data on the efficacy of NmAbs have been reported from clinical practice. We assessed the impact of NmAb treatment given in the outpatient clinical practice setting on hospital utilization. METHODS: Electronic medical records were used to identify adult COVID-19 patients who received NmAbs (bamlanivimab [BAM] or casirivimab and imdevimab [REGN-COV2]) and historic COVID-19 controls. Post-index hospitalization rates were compared. RESULTS: 707 confirmed COVID-19 patients received NmAbs and 1709 historic COVID-19 controls were included; 553 (78%) received BAM, 154 (22%) received REGN-COV2. Patients receiving NmAb infusion had significantly lower hospitalization rates (5.8% vs 11.4%, P < .0001), shorter length of stay if hospitalized (mean, 5.2 vs 7.4 days; P = .02), and fewer ED visits within 30 days post-index (8.1% vs 12.3%, P = .003) than controls. Hospitalization-free survival was significantly longer in NmAb patients compared with controls (P < .0001). There was a trend towards a lower hospitalization rate among patients who received NmAbs within 2-4 days after symptom onset. In multivariate analysis, having received an NmAb transfusion was independently associated with a lower risk of hospitalization after adjustment for age, sex, race, BMI, and referral source (adjusted HR [95% CI], .54 [0.38-0.79]; P = .0012). Overall mortality was not different between the 2 groups. CONCLUSIONS: NmAb treatment reduced hospital utilization, especially when received within a few days of symptom onset. Further study is needed to validate these findings.

Responsiveness and interpretation of the PROMIS Cancer Function Brief 3D Profile.

BACKGROUND: Measuring function with valid and responsive tools in patients with cancer is essential for driving clinical decision-making and for the end points of clinical trials. Current patient-reported outcome measurements of function fall short for many reasons. This study evaluates the responsiveness of the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile, a novel measure of function across multiple domains. METHODS: Two hundred nine participants across five geographically distinct tertiary care centers completed the assessment and pain rating at two outpatient cancer rehabilitation clinic visits. Patients and providers completed a global rating of change measure at the second visit to indicate whether the patient was improving or worsening in function. Multiple response indices and linear models measured whether the measure was responsive to self-reported and clinician-rated changes over time. Correlations between changes in function and changes in anchors (pain rating and performance status) were also calculated. RESULTS: Function as measured by the PROMIS Cancer Function Brief 3D Profile changed appropriately as both patients and clinicians rated change. Small to moderate effect sizes supported the tool's responsiveness. Function was moderately correlated with pain and more strongly correlated with performance status, and changes in function corresponded with changes in anchor variables. No floor/ceiling effect was found. CONCLUSIONS: The PROMIS Cancer Function Brief 3D Profile is sensitive to changes over time in patients with cancer. The measure may be useful in clinical practice and as an end point in clinical trials. LAY SUMMARY: We gave patients a questionnaire by which they told their physicians how well they were functioning, including how fatigued they were. This study tested that questionnaire to see whether the scores would change if patients got better or worse.

The impact of variants and vaccination on the mortality and resource utilization of hospitalized patients with COVID-19.

BACKGROUND: COVID-19 outcomes among hospitalized patients may have changed due to new variants, therapies and vaccine availability. We assessed outcomes of adults hospitalized with COVID-19 from March 2020-February 2022. METHODS: Data were retrieved from electronic health medical records of adult COVID-19 patients hospitalized in a large community health system. Duration was split into March 2020-June 2021 (pre-Delta period), July-November 2021 (Delta period), and December 2021-February 2022 (Omicron period). RESULTS: Of included patients (n = 9582), 75% were admitted during pre-Delta, 9% during Delta, 16% during Omicron period. The COVID-positive inpatients were oldest during Omicron period but had lowest rates of COVID pneumonia and resource utilization (p < 0.0001); 46% were vaccinated during Delta and 61% during Omicron period (p < 0.0001). After adjustment for demographics and comorbidities, vaccination was associated with lower inpatient mortality (OR = 0.47 (0.34-0.65), p < 0.0001). The Omicron period was independently associated with lower risk of inpatient mortality (OR = 0.61 (0.45-0.82), p = 0.0010). Vaccination and Omicron period admission were also independently associated with lower healthcare resource utilization (p < 0.05). Magnitudes of associations varied between age groups with strongest protective effects seen in younger patients. CONCLUSION: Outcomes of COVID-19 inpatients were evolving throughout the pandemic and were affected by changing demographics, virus variants, and vaccination. KEY POINT: In this observational study of almost 10,000 patients hospitalized from March 2020-February 2022 with COVID-19, age and having multiple comorbidities remained consistent risk factors for mortality regardless of the variant. Vaccination was high in our hospitalized patients. Vaccination conveyed less severe illness and was associated with lower inpatient mortality.

Psychometric Characteristics and Validity of the PROMIS Cancer Function Brief 3D Profile.

OBJECTIVE: To develop an item response theory (IRT)-calibrated, patient-reported outcome measure (the PROMIS Cancer Function Brief 3D Profile) of physical function, including associations with fatigue and social participation, in cancer rehabilitation patients. DESIGN: Large-scale field testing, graded response model IRT analyses, and multivariate regression analysis. SETTING: Six cancer rehabilitation clinics associated with cancer centers across the United States. PARTICIPANTS: Adults (N=616) treated in outpatient cancer rehabilitation medicine clinics. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The PROMIS(r) Cancer Function 3D Profile (including existing items from PROMIS(r) item banks). RESULTS: A total of 616 patients completed 21 items in the initial item pool. Nine items were removed because of comparatively lower information that they provide according to the IRT item calibrations, low item-total correlations, or bimodal distributions. The remaining items generated a 12-item short form. Regression analyses determined that the items were responsive to and representative of the patient population across trait ranges and multiple domains and subdomains of function. CONCLUSIONS: This psychometric investigation supports the use of the PROMIS Cancer Function Brief 3D Profile for evaluating function in outpatient cancer rehabilitation patients.

Systematic Review of Functional Outcomes in Cancer Rehabilitation.

OBJECTIVE: To systematically review the evidence regarding rehabilitation interventions targeting optimal physical or cognitive function in adults with a history of cancer and describe the breadth of evidence as well as strengths and limitations across a range of functional domains. DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Plus, Scopus, Web of Science, and Embase. The time scope was January 2008 to April 2019. STUDY SELECTION: Prospective, controlled trials including single- and multiarm cohorts investigating rehabilitative interventions for cancer survivors at any point in the continuum of care were included, if studies included a primary functional outcome measure. Secondary data analyses and pilot/feasibility studies were excluded. Full-text review identified 362 studies for inclusion. DATA EXTRACTION: Extraction was performed by coauthor teams and quality and bias assessed using the American Academy of Neurology (AAN) Classification of Evidence Scheme (class I-IV). DATA SYNTHESIS: Studies for which the functional primary endpoint achieved significance were categorized into 9 functional areas foundational to cancer rehabilitation: (1) quality of life (109 studies), (2) activities of daily living (61 studies), (3) fatigue (59 studies), (4) functional mobility (55 studies), (5) exercise behavior (37 studies), (6) cognition (20 studies), (7) communication (10 studies), (8) sexual function (6 studies), and (9) return to work (5 studies). Most studies were categorized as class III in quality/bias. Averaging results found within each of the functional domains, 71% of studies reported statistically significant results after cancer rehabilitation intervention(s) for at least 1 functional outcome. CONCLUSIONS: These findings provide evidence supporting the efficacy of rehabilitative interventions for individuals with a cancer history. The findings should be balanced with the understanding that many studies had moderate risk of bias and/or limitations in study quality by AAN criteria. These results may provide a foundation for future work to establish clinical practice guidelines for rehabilitative interventions across cancer disease types.

Continuous interscalene versus phrenic nerve-sparing high-thoracic erector spinae plane block for total shoulder arthroplasty: a randomized controlled trial.

PURPOSE: The high-thoracic erector spinae plane block (HT-ESPB) has been reported as an effective analgesic modality for the shoulder region without phrenic nerve palsy. The goal of this study was to compare the HT-ESPB as a phrenic nerve-sparing alternative to an interscalene block for total shoulder arthroplasty. METHODS: Thirty patients undergoing total shoulder arthroplasty at Stanford Health Care (Palo Alto, CA, USA) were enrolled in a double-blind randomized controlled trial. We randomized 28 patients to receive either an interscalene or HT-ESPB perineural catheter preoperatively; 26 patients were included in the final analysis. The study was powered for the primary outcome of incidence of hemidiaphragmatic paralysis in the postanesthesia care unit (PACU). Other outcome measures included incentive spirometry volume, brachial plexus motor and sensory exams, adverse events, pain scores, and opioid consumption. RESULTS: The incidence of hemidiaphragmatic paralysis in the HT-ESPB catheter group was significantly lower than in the interscalene catheter group (0/12, 0% vs 14/14, 100%; P < 0.001). No statistically significant differences were found in pain scores and opioid consumption (in oral morphine equivalents) between the interscalene and HT-ESPB groups through postoperative day (POD) 2. Nevertheless, the mean (standard deviation) point estimates for opioid consumption for the HT-ESPB group were higher than for the interscalene group in the PACU (HT-ESPB: 24.8 [26.7] mg; interscalene: 10.7 [21.7] mg) and for POD 0 (HT-ESPB: 20.5 [25.0] mg; interscalene: 6.7 [12.0] mg). In addition, cumulative postoperative opioid consumption was significantly higher at POD 0 (PACU through POD 0) in the HT-ESPB group (45.3 [39.9] mg) than in the interscalene group (16.6 [21.9] mg; P = 0.04). CONCLUSIONS: This study suggests that continuous HT-ESPB can be a phrenic nerve-sparing alternative to continuous interscalene brachial plexus blockade, although the latter provided superior opioid-sparing in the immediate postoperative period. This was a small sample size study, and further investigations powered to detect differences in analgesic and quality of recovery score endpoints are needed. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03807505); registered 17 January 2019.

RéSUMé: OBJECTIF: Le bloc des muscles érecteurs du rachis du haut thorax (BMER-HT) a été rapporté comme une modalité analgésique efficace pour la région de l'épaule et ce, sans paralysie du nerf phrénique. L'objectif de cette étude était de comparer ce bloc en tant qu'alternative épargnant le nerf phrénique à un bloc interscalénique pour l'arthroplastie totale de l'épaule. MéTHODE: Trente patients bénéficiant d'une arthroplastie totale de l'épaule au centre de soins Stanford Health Care (Palo Alto, CA, États-Unis) ont été recrutés dans une étude randomisée contrôlée à double insu. Nous avons randomisé 28 patients à recevoir un cathéter périneural interscalénique ou un BMER-HT en préopératoire; 26 patients ont été inclus dans l'analyse finale. Le calcul de puissance de l'étude a été effectué pour répondre au critère d'évaluation principal, qui était l'incidence de paralysie hémidiaphragmatique en salle de réveil. Les autres issues mesurées comprenaient les volumes de spirométrie, les examens moteurs et sensoriels du plexus brachial, les événements indésirables, les scores de douleur et la consommation d'opioïdes. RéSULTATS: L'incidence de paralysie hémidiaphragmatique dans le groupe cathéter BMER-HT était significativement plus faible que dans le groupe cathéter interscalénique (0/12, 0 % vs 14/14, 100 %; P < 0,001). Aucune différence statistiquement significative n'a été observée dans les scores de douleur et la consommation d'opioïdes (en équivalents morphine par voie orale) entre les groupes interscalénique et BMER-HT jusqu'au jour postopératoire (JPO) 2. Néanmoins, en salle de réveil, les estimations ponctuelles moyennes (écart type) de la consommation d'opioïdes pour le groupe BMER-HT étaient plus élevées que pour le groupe interscalénique (BMER-HT : 24,8 [26,7] mg; interscalénique : 10,7 [21,7] mg), ainsi qu'au JPO 0 (BMER-HT : 20,5 [25,0] mg; interscalénique: 6,7 [12,0] mg). De plus, la consommation cumulative d'opioïdes postopératoires était significativement plus élevée au JPO 0 (salle de réveil jusqu'au JPO 0) dans le groupe BMER-HT (45,3 [39,9] mg) que dans le groupe interscalénique (16,6 [21,9] mg; P = 0,04). CONCLUSION: Cette étude suggère que le BMER-HT continu peut être une alternative au bloc interscalénique continu du plexus brachial pour épargner le nerf phrénique, bien que le bloc interscalénique ait fourni une épargne d'opioïdes supérieure en période postopératoire immédiate. Il s'agissait d'une étude de petite taille d'échantillon, et d'autres études visant à détecter les différences dans les scores des critères d'évaluation en matière d'analgésie et de qualité de la récupération sont nécessaires. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03807505); enregistrée le 17 janvier 2019.

Patient-reported outcomes in patients with non-alcoholic fatty liver disease: A narrative review of Chronic Liver Disease Questionnaire-non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the leading causes of hepatocellular carcinoma and liver transplantation. Moreover, patients with NAFLD frequently complain of non-specific symptoms including fatigue, abdominal discomfort, as well as anxiety, and NAFLD is reported to affect patient-reported outcomes (PROs). Thus, for clarifying the total burden of NAFLD, it is crucial to assess all associated outcomes, including not only clinical and economic outcomes but also PROs. PROs are thought to reflect what is happening in one's daily life and is an important way patients and health-care professionals communicate. There are various instruments for the assessment of PROs. Recently, a NAFLD/non-alcoholic steatohepatitis (NASH)-specific instrument called "Chronic Liver Disease Questionnaire (CLDQ)-NAFLD/NASH" has been developed. CLDQ-NAFLD/NASH comprises six domains: (i) abdominal symptoms, (ii) activity/energy, (iii) emotional health, (iv) fatigue, (v) systemic symptoms, and (vi) worry. CLDQ-NAFLD/NASH has demonstrated excellent internal consistency, face validity, content validity, and test-retest reliability. It has been sufficiently validated in two international phase 3 clinical trials. In this review, we summarize features of various instruments for assessing PROs by focusing on CLDQ-NAFLD/NASH. We also examine the validity of CLDQ-NAFLD/NASH in Japanese patients and alterations in CLDQ-NAFLD/NASH score in Japanese patients with significant hepatic fibrosis. Moreover, we discuss the utility of CLDQ-NAFLD/NASH in phase 3 clinical trials and in a real-world clinical setting.

Cytokine balance is restored as patient-reported outcomes improve in patients recovering from chronic hepatitis C.

BACKGROUND & AIMS: Chronic hepatitis C (CHC) has a negative impact on patient-reported outcomes (PROs). Although most CHC patients who achieve sustained virologic response (SVR) show an improvement in PRO scores, some continue to experience impairment in PROs. The aim was to investigate if serum biomarkers (selected neurotransmitters and cytokines) are associated with changes in PROs in CHC patients who achieve SVR. METHODS: Data were utilized from a prospective clinical trial of ledipasvir/sofosbuvir fixed-dose combination. Chronic genotype 1 HCV subjects without cirrhosis (N = 40, age: 45.3 ± 11.5, 48% male, 90% white) were treated for 12 weeks open label with 97% achieving SVR24. PRO questionnaires included Short Form-36 (SF-36), Fatigue Severity Scale (FSS), Beck Depression Inventory-II (BDI-II), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Sera were used for measurement of selected neurotransmitters and cytokines. Data were collected at baseline and follow-up week 24. RESULTS: Changes in physical health correlated with changes in several biomarkers. BDNF negatively correlated with SF-36 physical health summary score (rho = -0.34, P < 0.05), SF-36 physical functioning (rho = -0.34, P < 0.05), SF-36 bodily pain (rho = -0.39, P < 0.05) and FACIT-F physical well-being (rho = -0.54, P < 0.001). Changes in emotional well-being (FACIT-F) were positively associated with changes in serotonin (rho = 0.34, P < 0.05), but negatively associated with changes in GABA and BDNF (rho = -0.4, P = 0.01, and rho = -0.35, P < 0.05 respectively). CONCLUSIONS: These data indicate relationships between PROs and serum biomarkers pre- and post-SVR in CHC. These concomitant changes may have important clinical relevance.

Identifying Gaps in Research on Rehabilitation for Patients With Head and Neck Cancer: A Scoping Review.

OBJECTIVES: Examine the amount and nature of research activity in head and neck cancer (HNC) rehabilitation; highlight publication trends, including information about the authors, settings, and study designs; and identify gaps in the existing literature. DATA SOURCES: Eligible studies were identified using PubMed, Embase, and CINAHL databases. STUDY SELECTION: Inclusion criteria included human subjects, English language, publication between 1/1/1990 and 4/30/2017, HNC patients at any timepoint in disease, and evaluation of rehabilitation outcomes as described by the International Classification of Functioning, Disability and Health (ICF) framework. Exclusion criteria included intervention or outcome not specific to rehabilitation or the HNC population, and protocols or abstracts without corresponding full manuscripts. DATA EXTRACTION: An established 6-step scoping review framework was utilized to develop the review protocol. A 3-level review was then performed. Data on eligible studies were collected using a Research Electronic Data Capture (REDCap) tool. DATA SYNTHESIS: Among 2201 publications, 258 met inclusion criteria. Publication rate increased by 390% over the study timeframe. Most studies were observational (n=150). Few were interventional (n=35). The most common interventions focused on chewing or swallowing (n=14), followed by exercise (n=10). Most primary outcome measures fit the ICF definition of impairment; fewer fit the definitions of activity limitation or participation restriction. CONCLUSIONS: Although research volume in HNC rehabilitation is increasing, the literature is dominated by small (≤100 patients), outpatient-based observational studies involving chewing or swallowing-related impairments. More prospective studies in multidisciplinary domains across the cancer care continuum are needed. There is particular need for interventional studies and prospective observational studies. Future studies should evaluate clinically-relevant activity limitations and participation restrictions. Rehabilitation professionals have an important role in the design of future HNC rehabilitation research.

Cognitive Performance in Individuals With Non-Alcoholic Fatty Liver Disease and/or Type 2 Diabetes Mellitus.

BACKGROUND: Individuals with nonalcoholic fatty liver disease (NAFLD) share some common pathophysiological features with individuals with type 2 diabetes mellitus (T2DM). There is a well-established association between T2DM and cognitive decline, but no corollary data of people with NAFLD and without T2DM or whether combination of the 2 disorders is associated with additive deficits in cognitive performance. OBJECTIVES: The purpose of this investigation is to compare measures of cognitive performance for individuals with NAFLD, individuals with T2DM, individuals with both or neither. METHODS: Using NHANES data from 2011-2014, 1102 individuals were identified who had completed cognitive assessments. RESULTS: After controlling for demographics, comorbidities, and metabolic components, individuals with both NAFLD and T2DM scored significantly lower on a task that combines processing speed, sustained attention, and working memory (Beta = -3.44, 95% CI: -6.75 to -0.12) than individuals with neither. Individuals with T2DM without NAFLD scored significantly lower on verbal fluency (Beta = -1.47, 95% CI: -2.7 to -0.23) than individuals with neither. CONCLUSIONS: Data from this study suggests that individuals with T2DM and individuals with both NAFLD and T2DM have lower cognitive performance on various tasks. These data support an approach that aims to apply preventive strategies to optimize management of T2DM in patients with NAFLD.

Demonstration of two types of fatigue in subjects with chronic liver disease using factor analysis.

PURPOSE: The purpose of this investigation was to determine if it was possible to separate fatigue self-reports into two distinct types of fatigue symptom clusters in research subjects with chronic liver disease (CLD). It was hypothesized that when items from the Medical Outcomes Study Short-Form (SF-36v2) are combined with items from the Fatigue Severity Scale (FSS), these distinct factors will emerge. METHODS: Confirmatory and exploratory factor analyses from data collected in a prospective, natural history study of CLD patients were conducted. Items were selected from the SF-36v2 and the FSS for entry into the factor analyses. In order to establish convergent and discriminant validity, derived factor scores were correlated with subscale scores of the Human Activity Profile (HAP), Mental Component Score (MCS) from the SF-36v2, and the Emotional Functioning Subscale of the Chronic Liver Disease Questionnaire (CLDQ-EF). RESULTS: 106 participants with CLD were included (50% female; age: 51 ± 10). Two factors were identified. The factors included one that clustered around questions addressing fatigue related to physical activity (peripheral fatigue) and the other to the questions addressing generalized fatigue that did not require physical tasks to produce the fatigue (central fatigue). The standardized factor loadings of all items were greater than 0.6 on their underlying constructs. Moreover, all factor loadings are significant at p < 0.01. Peripheral fatigue was related to HAP (r = 0.26, r = 0.24, p < 0.01), as was central fatigue (r = -0.34, r = -0.33, p < 0.01). Central fatigue was related to MCS and CLDQ-EF (r = -0.60; r = -0.63, p < 0.01), whereas peripheral fatigue was not (r = 0.07, p > 0.40). We then tested the original scales to determine if the newly created factors correlated better with the validity measures. The full FSS did not correlate as well as the newly created central fatigue scale, while the original peripheral fatigue scale (the SF-36v2 physical functioning) was more related to HAP than the newly created scale. CONCLUSIONS: In individuals with CLD, two separate factors pertaining to fatigue were identified. This recognition of the multifaceted nature of fatigue may help increase the specificity of self-reports of fatigue and lead to treatments that can specifically address the underlying factors contributing to fatigue.

Effects of Viral Eradication With Ledipasvir and Sofosbuvir, With or Without Ribavirin, on Measures of Fatigue in Patients With Chronic Hepatitis C Virus Infection.

BACKGROUND & AIMS: Fatigue is a disturbing symptom of chronic hepatitis C virus (HCV) infection. We assessed the effects of sustained virologic response 12 weeks after the end of therapy (SVR12) on fatigue. METHODS: We performed a retrospective analysis of 100 patients with chronic HCV infection who achieved an SVR12 after treatment with ledipasvir and sofosbuvir, with or without ribavirin. Data were collected on fatigue-related patient-reported outcomes (PROs) and assessed by using the Functional Assessment of Cancer Therapy-Fatigue scoring system and the Vitality subscale of Short Form 36. We measured levels of cytokines and growth factors in frozen serum samples collected at baseline, week 12 of treatment, and 4 weeks after treatment. Central fatigue and peripheral or muscle fatigue (PF) were determined by using items from PROs. Serum levels of cytokines, growth factors, serotonin, alanine aminotransferase, and aspartate aminotransferase were measured by using the Bio-Plex, enzyme-linked immunosorbent, and enzymatic assays. RESULTS: Compared with baseline, 4 weeks after the end of treatment, all fatigue-associated PROs improved significantly. Baseline PROs correlated inversely with serum level of interferon-γ; level of platelet-derived growth factor correlated with PF, central fatigue, and total fatigue score. Only PF correlated with serum level of serotonin. At baseline, high PF scores correlated with high serum levels of serotonin and low levels of interleukin-10 and tumor necrosis factor-α. In multivariate analysis, serum level of interleukin-8 was associated with greater fatigue (P < .02). Reductions in levels of chemokine (C-C motif) ligand 2 (also called monocyte chemotactic protein 1) were associated with fatigue after treatment (P = .0165). CONCLUSIONS: In an analysis of data from patients with chronic HCV infection participating in a clinical trial of ledipasvir and sofosbuvir, SVR12 was associated with reduced fatigue, compared with baseline. High baseline serum levels of interferon-γ were associated with fatigue. Reductions in levels of chemokine (C-C motif) ligand 2 were associated with persistent fatigue after SVR12. Central and peripheral fatigue each associated with different biomarkers, suggesting different pathogenic pathways.

Toward a National Initiative in Cancer Rehabilitation: Recommendations From a Subject Matter Expert Group.

The health care delivery system in the United States is challenged to meet the needs of a growing population of cancer survivors. A pressing need is to optimize overall function and reduce disability in these individuals. Functional impairments and disability affect most patients during and after disease treatment. Rehabilitation health care providers can diagnose and treat patients' physical, psychological, and cognitive impairments in an effort to maintain or restore function, reduce symptom burden, maximize independence and improve quality of life in this medically complex population. However, few care delivery models integrate comprehensive cancer rehabilitation services into the oncology care continuum. The Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health with support from the National Cancer Institute and the National Center for Medical Rehabilitation Research convened a subject matter expert group to review current literature and practice patterns, identify opportunities and gaps regarding cancer rehabilitation and its support of oncology care, and make recommendations for future efforts that promote quality cancer rehabilitation care. The recommendations suggest stronger efforts toward integrating cancer rehabilitation care models into oncology care from the point of diagnosis, incorporating evidence-based rehabilitation clinical assessment tools, and including rehabilitation professionals in shared decision-making in order to provide comprehensive cancer care and maximize the functional capabilities of cancer survivors. These recommendations aim to enable future collaborations among a variety of stakeholders to improve the delivery of high-quality cancer care.