Determining patient needs to enhance exercise program implementation and uptake in rural settings for women after a cancer diagnosis.

PURPOSE: To qualitatively explore exercise barriers and facilitators experienced by rural female cancer survivors from the program interventionist and recipient perspective for the purpose of enhancing exercise program implementation and uptake in rural settings. METHODS: A descriptive qualitative study design was utilized. Focus groups were conducted prior to implementation of an evidence-based exercise program by a rural non-research cancer clinical site. Nineteen rural female cancer survivors (mean age = 61.7 ± 10.9 years) and 11 potential interventionists (mean age = 42.3 ± 15.3 years) completed focus groups (stratified by participant role). Focus groups were audio recorded, transcribed, coded, and analyzed using inductive thematic analysis with NVivo 11. RESULTS: Cancer survivors identified 12 barrier themes (cancer specific adverse effects, lack of support, lack of knowledge, perceived negative aspects of exercise, cost, lack of resources, motivation, inconvenience, lack of program flexibility, time, weather, safety) and eight facilitator themes (knowledge, ease of access, resources, awareness, cost, options, organized, fun) related to exercise. Interventionists identified seven barrier themes (cost, transportation, lack of cancer survivor and interventionist knowledge, fear, motivation, lack of support, lack of resources) and four facilitator themes (resources, support, knowledge, motivation). Narratives revealed differing role-specific perspectives on shared themes between survivors and interventionists as well as potential implementation strategies for enhancing exercise participation and exercise program uptake among rural female cancer survivors. CONCLUSION: Exploring multi-level stakeholder perspectives on cancer survivors' exercise needs and related strategies yields important information for organizations to consider when implementing exercise programs in rural contexts.

Patterns of monoclonal immunoglobulins and serum free light chains are significantly different in black compared to white monoclonal gammopathy of undetermined significance (MGUS) patients.

Monoclonal gammopathy of undetermined significance (MGUS), the precursor to multiple myeloma, is more common in blacks than whites. The serum free light chain (sFLC) assay is an important prognostic test in MGUS, but no study has evaluated sFLC levels and ratios in black MGUS patients. One-hundred and twenty-five black MGUS patients at two urban centers were compared to the white population of the Mayo Clinic. The median age for blacks was 73 years [41-94] and 75% were male. The M-protein isotype in blacks was 81% IgG, 13% IgA, 2% IgM, and 4% biclonal compared to 70%, 12%, 16%, and 2%, respectively, in whites, (P < 0.0005). The median M-protein concentration for blacks was 0.44 gm/dL (trace-2.33) compared to 1.2 gm/dl in whites. An abnormal sFLC ratio was present in 45% of black compared to 33% of white (P = 0.01) patients. Using the Mayo Clinic risk model, black patients had a significantly lower proportion of higher risk MGUS compared to whites: low 43%, low-intermediate 45%, high-intermediate 10%, and high 2% (P = 0.014). Black patients with MGUS have significantly different laboratory findings compared to whites. The biologic basis for these disparities and their effect on prognostic assessment is unknown. Prognostic models based on these biomarkers should be used cautiously in nonwhite populations.

Promoting Physical Activity in Rural Settings: Effectiveness and Potential Strategies.

PURPOSE: Implementing efficacious physical activity interventions in real-world rural settings is needed because rural cancer survivors are more physically inactive and experience poorer health. To address this gap, this study evaluated effectiveness of an evidenced-based physical activity program (Better Exercise Adherence after Treatment for Cancer [BEAT Cancer]) for rural women cancer survivors when implemented by community-based, non-research staff. METHODS: 16 rural women cancer survivors received BEAT Cancer implemented by a rural, community organization and non-research staff; physical activity, patient-reported outcomes, and social cognitive constructs were measured at baseline and post-program. Cancer survivors and interventionists completed program evaluations post-program. RESULTS: Cancer survivor mean age was 58±12 years; 62% were White. Mean months since diagnosis was 54±72; 69% had breast cancer. Significant improvements from pre- to post-program occurred for self-report weekly minutes of moderate-to-vigorous physical activity (mean change [M] = 146±186, p = 0.009), anxiety (M = -1.3±1.8, p = 0.016), depression (M = -2.1±2.0, p = 0.001), self-efficacy (M = 20.9±30.5, p = 0.019), barriers interference (M = -15.0±14.1, p = 0.001), and social support (M = 5.0±7.4, p = 0.02). Cancer survivors ranked the program highly, identified strategies that were helpful (e.g., group activities, personalized exercise plan, etc.), and suggested additional implementation strategies (e.g., guide for home-based phase, etc.). Interventionists identified strategies (e.g., logistics, staff training and certification, cost, etc.) for enhancing organizational readiness for program delivery. CONCLUSION: Evidence-based physical activity programs can be effective when implemented by non-research staff in rural settings. Further research testing strategies that improve implementation is needed. PRACTICAL IMPLICATIONS: Effectiveness and identified strategies supporting delivery when implemented by a rural organization can improve physical activity promotion for rural, at-risk populations.

Beyond efficacy: a qualitative organizational perspective on key implementation science constructs important to physical activity intervention translation to rural community cancer care sites.

PURPOSE: To identify constructs relevant to implementation of evidence-based physical activity (PA) behavior change interventions for rural women cancer survivors from an organizational perspective. METHODS: During the development of a PA intervention implementation toolkit, 11 potential interventionists and 19 community and organizational stakeholders completed focus groups stratified by role. Narratives were audio recorded, transcribed, and coded for Consolidated Framework for Implementation Research (CFIR) constructs. RESULTS: Multiple CFIR constructs were identified: Implementation Process (i.e., Engaging, Reflecting and Evaluating), Intervention Characteristics (i.e., Design Quality and Packaging, Cost, Evidence Strength and Quality, Adaptability, Complexity), Inner Setting (i.e., Implementation Readiness, Implementation Climate, Structural Characteristics), Outer Setting (i.e., Patient Needs and Resources, Cosmopolitanism), and Characteristics of Individuals (i.e., Knowledge and Beliefs, Stage of Change). Narratives identified rural implementation barriers (e.g., transportation) and facilitators (e.g., community-oriented). Unique needs of the cancer survivor (e.g., coping during cancer treatment and long-term effects on physical abilities) were emphasized as important barriers potentially addressed through Adaptability and Readiness implementation strategies. Narratives identified multi-level (i.e., individual-, organizational-, and community-level) strategies for targeting the identified constructs. CONCLUSIONS: Fourteen CFIR constructs emerged as potentially important for organizations to consider when implementing PA interventions. Constructs were integrated into our implementation toolkit and research testing their potential mechanisms of action when implementing PA interventions in rural settings is warranted. IMPLICATIONS: Strategies that target the identified constructs may enhance the implementation of PA programs for rural cancer survivors. Cancer survivors can facilitate these efforts by partnering with their health care providers and community organizations. IMPLICATIONS FOR CANCER SURVIVORS: Organizations promoting physical activity programs for cancer survivors must overcome implementation barriers including but not limited to cost, necessary expertise, and lack of awareness. Cancer survivors can facilitate these efforts by partnering with their health care providers, cancer center, and local community organizations to raise awareness and champion these efforts. It will "take a village", with cancer survivors being their own best advocate, to bring physical activity promotion to a broad range of cancer survivors.

Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging.

The incidence and importance of bone marrow involvement and/or early bone lesions in multiple myeloma (MM) precursor diseases is largely unknown. This study prospectively compared the sensitivity of several imaging modalities in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM. Thirty patients (10 each with MGUS, SMM and MM) were evaluated with skeletal survey, [18F]FDG-PET/CT, [18F]NaF-PET/CT and morphologic dynamic contrast enhanced (DCE)-MRI. An additional 16 SMM patients had skeletal surveys and FDG-PET/CT. Among MGUS patients, DCE-MRI found only one focal marrow abnormality; other evaluations were negative. Among 26 SMM patients, five (19%) were re-classified as MM based on lytic bone lesions on CT and six had unifocal or diffuse marrow abnormality. Among MM, marrow abnormalities were observed on FDG-PET/CT in 8/10 patients and on DCE-MRI in nine evaluable patients. Abnormal NaF uptake was observed only in MM patients with lytic lesions on CT, providing no additional clinical information.

Unusual Late Presentation of Hemophilia A in an Active Duty U.S. Marine Following Open Shoulder Surgery.

Hemophilia A is clotting disorder affecting 8:100,000 males in the United States. It is an X-linked recessive genetic disorder, although about one-third of cases occur spontaneously without known family history. Because of the risk of uncontrolled hemorrhage on the battlefield, hemophilia and other bleeding disorders exclude individuals from service in the U.S. military. We report a case of an active duty U.S. Marine whose underlying diagnosis of Hemophilia A was discovered and treated by a multidisciplinary team of orthopedic surgeons and hematologists following recurrent hematomas after open rotator cuff surgery. The patient gave informed consent for publication.

Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management.

The manifestations of bone involvement in patients with multiple myeloma (MM) can have devastating clinical effects and increase mortality. Recent studies demonstrate that patients with the precursor conditions smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS) show evidence of bone disease and increased risk of fractures. The understanding of the pathogenesis of bone disease in MM has expanded in recent years. The traditional skeletal survey will probably be replaced by newer and more sensitive imaging techniques, which may have a prognostic impact and change our definition of MGUS and SMM. Bisphosphonates are recommended to prevent skeletal events in patients with MM, and have also been studied in SMM and MGUS. This article summarizes the current knowledge of bone disease in plasma cell disorders, and discusses the current standard and future role of novel imaging techniques, as well as the evidence and current guidelines for bisphosphonates in MM, SMM and MGUS.

The ubiquitin+proteasome protein degradation pathway as a therapeutic strategy in the treatment of solid tumor malignancies.

A concept that currently steers the development of cancer therapies has been that agents directed against specific proteins that facilitate tumorigenesis or maintain a malignant phenotype will have greater efficacy, less toxicity and a more sustained response relative to traditional cytotoxic chemotherapeutic agents. The clinical success of the targeted agent Imatinib mesylate as an inhibitor of the tyrosine kinase associated with the breakpoint cluster region-Abelson oncogene locus (BCR-ABL) in the treatment of Philadelphia-positive chronic myelogenous leukemia (CML) has served as a paradigm. While intellectually gratifying, the selective targeting of a single driver event by a small molecule, e.g., kinase inhibitor, to dampen a tumor-promoting pathway in the treatment of solid tumors is limited by many factors. Focus can alternatively be placed on targeting fundamental cellular processes that regulate multiple events, e.g., protein degradation, through the Ubiquitin (Ub)+Proteasome System (UPS). The UPS plays a critical role in modulating numerous cellular proteins to regulate cellular processes such as signal transduction, growth, proliferation, differentiation and apoptosis. Clinical success with the proteasome inhibitor bortezomib revolutionized treatment of B-cell lineage malignancies such as Multiple Myeloma (MM). However, many patients harbor primary resistance and do not respond to bortezomib and those that do respond inevitably develop resistance (secondary resistance). The lack of clinical efficacy of proteasome inhibitors in the treatment of solid tumors may be linked mechanistically to the resistance detected during treatment of hematologic malignancies. Potential mechanisms of resistance and means to improve the response to proteasome inhibitors in solid tumors are discussed.

Bone disease from monoclonal gammopathy of undetermined significance to multiple myeloma: pathogenesis, interventions, and future opportunities.

Manifestations of bone disease-osteopenia, osteolytic lesions, and fractures-are the hallmark of multiple myeloma (MM) and occur clinically in the vast majority of patients. These abnormalities can have devastating clinical effects by increasing both the morbidity and mortality of patients. Bone disease is usually found when patients are diagnosed with active MM; however, recent data suggest that it is present in early myelomagenesis, including patients with myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS). The primary mechanisms of abnormal bone remodeling are increased osteoclastic activity, which occurs in close proximity to active myeloma cells, and decreased activity of the surrounding osteoblasts. Better understanding of the pathogenesis of bone disease in MM will allow us to enhance our current therapeutic options in the treatment of bone disease. In patients with active MM and at least one lytic lesion, intravenous bisphosphonates have been shown to decrease skeletal-related events and pain, improve performance status, and maintain quality of life. Emerging evidence suggests that intervention at earlier stages of disease may prevent skeletal-related events at time of progression, but there is no evidence that bisphosphonates in this setting change the natural history of the disease.