Screening and Assessment of Cancer-Related Fatigue: A Clinical Practice Guideline for Health Care Providers

Cancer-related fatigue (CRF) is the most common side effect of cancer treatment. Regular surveillance is recommended, but few clinical practice guidelines transparently assess study bias, quality, and clinical utility in deriving recommendations of screening and assessment methods. The purpose of this clinical practice guideline (CPG) is to provide recommendations for the screening and assessment of CRF for health care professions treating individuals with cancer. Following best practices for development of a CPG using the Appraisal of Guidelines for Research and Evaluation (AGREE) Statement and Emergency Care Research Institute (ECRI) Guidelines Trust Scorecard, this CPG included a systematic search of the literature, quality assessment of included evidence, and stakeholder input from diverse health care fields to derive the final CPG. Ten screening and 15 assessment tools supported by 114 articles were reviewed. One screen (European Organisation for Research and Treatment of Cancer–Quality of Life Questionnaire–30 Core Questionnaire) and 3 assessments (Piper Fatigue Scale–Revised, Functional Assessment of Chronic Illness Therapy–Fatigue, and Patient Reported Outcome Measurement Information System [PROMIS] Fatigue-SF) received an A recommendation (“should be used in clinical practice”), and 1 screen and 5 assessments received a B recommendation (“may be used in clinical practice”). Health care providers have choice in determining appropriate screening and assessment tools to be used across the survivorship care continuum. The large number of tools available to screen for or assess CRF may result in a lack of comprehensive research evidence, leaving gaps in the body of evidence for measurement tools. More research into the responsiveness of these tools is needed in order to adopt their use as outcome measures. Impact: Health care providers should screen for and assess CRF using one of the tools recommended by this CPG

Screening and Assessment of Cancer-Related Fatigue: An Executive Summary and Road Map for Clinical Implementation

Background: Cancer-related fatigue (CRF) prevalence is reported as high as 90%. Cancer-related fatigue is multidimensional and associated with lower health-related quality of life. Effective screening and assessment are dependent upon use of valid, reliable, and clinically feasible measures. This Executive Summary of the Screening and Assessment of Cancer-related Fatigue Clinical Practice Guideline provides recommendations for best measures to screen and assess for CRF based on the quality and level of evidence, psychometric strength of the tools, and clinical utility. Methods: After a systematic review of the literature, studies evaluating CRF measurement tools were assessed for quality; data extraction included psychometrics and clinical utility. Measurement tools were categorized as either screens or assessments. Results: Four screens are recommended: European Organization of Research and Treatment of Cancer Quality of Life Questionnaire, the MD Anderson Symptom Inventory, the Distress Thermometer, and the One-Item Fatigue Scale. Eight assessments are recommended: Functional Assessment of Chronic Illness Therapy—Fatigue, Piper Fatigue Scale—Revised, Brief Fatigue Inventory, Cancer Fatigue Scale, Fatigue Symptom Inventory, Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form and CAT, and Multidimensional Fatigue Inventory-20. Discussion: This Executive Summary is a synopsis of and road map for implementation of the Clinical Practice Guideline for Screening and Assessment of CRF. Review of the full Clinical Practice Guideline is recommended. Additional research focused on responsiveness of instruments is needed in order to consider them for use as outcome measures. Screening and assessing CRF will result in opportunities to improve the quality of life of individuals with cancer

Relationship between intact HIV-1 proviruses in circulating CD4+ T cells and rebound viruses emerging during treatment interruption.

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4+ T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound

Conducting a Supportive Oncology Clinical Trial During the COVID-19 Pandemic: Challenges and Strategies

The coronavirus disease 2019 (COVID-19) pandemic resulted in severe interruptions to clinical research worldwide. This global public health crisis required investigators and researchers to rapidly develop and implement new strategies and solutions to mitigate its negative impact on the progress of clinical trials. In this paper, we describe the challenges, strategies, and lessons learned regarding the continuation of a supportive oncology clinical trial during the pandemic. We hope to provide insight into the implementation of clinical trials during a public health emergency to be better prepared for future instances. Trial registration: ClinicalTrials.gov, a service of the US National Institute of Health (NCT03030859). Registered on 22 January 2017

Defining the effect and mediators of two knowledge translation strategies designed to alter knowledge, intent and clinical utilization of rehabilitation outcome measures: a study protocol [NCT00298727]

BACKGROUND: A substantial number of valid outcome measures have been developed to measure health in adult musculoskeletal and childhood disability. Regrettably, national initiatives have merely resulted in changes in attitude, while utilization remains unacceptably low. This study will compare the effectiveness and mediators of two different knowledge transfer (KT) interventions in terms of their impact on changing knowledge and behavior (utilization and clinical reasoning) related to health outcome measures. METHOD/DESIGN: Physical and occupational therapists (n = 144) will be recruited in partnership with the national professional associations to evaluate two different KT interventions with the same curriculum: 1) Stakeholder-Hosted Interactive Problem-Based Seminar (SHIPS), and 2) Online Problem-Based course (e-PBL). SHIPS will consist of face-to-face problem-based learning (PBL) for 2 1/2 days with outcome measure developers as facilitators, using six problems generated in consultation with participants. The e-PBL will consist of a 6-week web-based course with six generic problems developed by content experts. SHIPS will be conducted in three urban centers in Canada. Participants will be block-allocated by a minimization procedure to either of the two interventions to minimize any prognostic differences. Trained evaluators at each site will conduct chart audits and chart-stimulated recall. Trained interviewers will conduct semi-structured interviews focused on identifying critical elements in KT and implementing practice changes. Interviews will be transcribed verbatim. Baseline predictors including demographics, knowledge, attitudes/barriers regarding outcome measures, and Readiness to Change will be assessed by self-report. Immediately post-intervention and 6 months later, these will be re-administered. Primary qualitative and quantitative evaluations will be conducted 6-months post-intervention to assess the relative effectiveness of KT interventions and to identify elements that contribute to changing clinical behavior. Chart audits will determine the utilization of outcome measures (counts). Incorporation of outcome measures into clinical reasoning will be assessed using an innovative technique: chart-stimulated recall. DISCUSSION: A strategy for optimal transfer of health outcome measures into practice will be developed and shared with multiple disciplines involved in primary and specialty management of musculoskeletal and childhood disability

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Knowledge Regarding Cancer-Related Fatigue: A Survey of Physical Therapists and Individuals Diagnosed with Cancer

Background: Cancer-related fatigue (CRF) is a common side effect and remains under-diagnosed. Screening of CRF by physical therapists (PTs) and patient perspectives of their experiences has not been comprehensively examined. Purpose: To survey PTs to understand the frequency of CRF screening, and to assess the knowledge and experiences of survivors as it relates to CRF. Methods: Two separate electronic surveys developed by the authors were distributed. One targeted oncology PTs, the other for adult survivors of cancer. Results: Of the 199 PT respondents, 36% reported screening for CRF at every encounter. Screening included interviews (46%) and/or standardized questionnaires (37%). The most common barriers to receiving treatment for CRF was lack of physician referrals and time constraints. Of patient responses (n = 61), 84% reported CRF as an important ongoing issue; 77% reported that they initiated the discussion about CRF with their provider, and 23% reported being told there were treatment options for CRF. Conclusion: CRF is common among cancer survivors. However, consistent screening by PTs is lacking. Patients with CRF frequently initiated the conversation with their providers because of symptoms and many patients were not told of treatment options. These findings represent a substantial gap in clinical practice regarding CRF screening and management

A Clinical Practice Guideline for the Screening and Assessment of Cancer-related Fatigue

Cancer-related fatigue (CRF) impacts nearly all individuals diagnosed with cancer at some point along the care continuum, with prevalence rates reported as high as 90%. CRF differs from typical fatigue in that it is a sense of physical, emotional, cognitive tiredness that is not associated with activity nor relieved by rest. CRF is associated with lower levels of health-related quality of life. This debilitating condition must be recognized and treated so that individuals with cancer can fully participate in life activities. Screening for referral and comprehensive assessment is dependent upon valid, reliable, and clinically feasible measures. The speakers will present a clinical practice guideline with evidence-based recommendations for use of the best measures to screen and assess for CRF

Photobiomodulation Therapy in Head and Neck Cancer-Related Lymphedema: A Pilot Feasibility Study.

PURPOSE: Lymphedema is a common debilitating late effect among patients post-head and neck cancer (HNC) treatment. Head and neck lymphedema was associated with symptom burden, functional impairment, and decreased quality of life. The objective of this study was to determine the feasibility and potential efficacy of the use of photobiomodulation (PBM) therapy for head and neck lymphedema, symptom burden, and neck range of motion among HNC survivors. METHODS: This was a single-arm, pre- and post-design clinical trial. Eligible patients included those with lymphedema after completion of complete decongestive therapy (CDT) and 3 to 18 months after completion of cancer therapy. The intervention included PBM therapy 2 times a week for 6 weeks for a total of 12 treatments. Lymphedema, symptom burden, and neck range of motion were measured at baseline, end-of-intervention, and 4-week post-intervention. RESULTS: Of the 12 patients enrolled in the study, 91.7% (n = 11) completed the study intervention and assessment visits, and no adverse events were reported. When comparing the baseline to 4-week post-intervention, we found statistically significant improvements in the severity of external lymphedema, symptom burden, and neck range of motion (all P \u3c .05). CONCLUSION: PBM therapy was feasible and potentially effective for the treatment of head and neck lymphedema. Future randomized controlled trials are warranted to examine the efficacy of PBM therapy for HNC-related lymphedema. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov Identifier: NCT03738332; date of registration: November 13, 2018

Relationship between intact HIV-1 proviruses in circulating CD4(+) T cells and rebound viruses emerging during treatment interruption

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4(+) T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound