Levels of secretory leukocyte protease inhibitor expression in acute wounds.

OBJECTIVE: Even with our best practices, we are frequently unable to prevent slow and stalled wound healing-particularly in people with impaired circulation and conditions such as diabetes. As a result, greater insight into the nature of wound healing and alternative treatment approaches is needed. An avenue that may be of particular promise is increasing understanding of the role of secretory leukocyte protease inhibitor (SLPI) as there is evidence that it enhances wound healing, its expression increases in response to inflammation and infection, and it exhibits anti-protease, anti-inflammatory, antiviral antibacterial and antifungal activities. METHOD: The response of SLPI levels to wounding and skin injury was assessed by taking punch skin biopsies from healthy volunteers and assessing the levels of SLPI at the site of injury at the time of wounding (baseline) as well as one, two, three, four, seven, nine and 12 weeks later. RESULTS: A total of 35 volunteers took part in the study. Significant elevations were found: levels of SLPI were greatly increased, 12 times that at baseline, and remained elevated at three weeks despite re-epithelialisation having occurred. CONCLUSION: These findings not only suggest that levels of SLPI rise rapidly following wounding, but that these elevations are sustained, and continue to increase even when re-epithelialisation has occurred. These results suggest that the role and potential benefits of this protease inhibitor deserve further exploration.

Improving the Delivery of Function-Directed Care During Acute Hospitalizations: Methods to Develop and Validate the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT).

OBJECTIVE: To (1) develop a patient-reported, multidomain functional assessment tool focused on medically ill patients in acute care settings; (2) characterize the measure's psychometric performance; and (3) establish clinically actionable score strata that link to easily implemented mobility preservation plans. DESIGN: This article describes the approach that our team pursued to develop and characterize this tool, the Functional Assessment in Acute Care Multidimensional Computer Adaptive Test (FAMCAT). Development involved a multistep process that included (1) expanding and refining existing item banks to optimize their salience for hospitalized patients; (2) administering candidate items to a calibration cohort; (3) estimating multidimensional item response theory models; (4) calibrating the item banks; (5) evaluating potential multidimensional computerized adaptive testing (MCAT) enhancements; (6) parameterizing the MCAT; (7) administering it to patients in a validation cohort; and (8) estimating its predictive and psychometric characteristics. SETTING: A large (2000-bed) Midwestern Medical Center. PARTICIPANTS: The overall sample included 4495 adults (2341 in a calibration cohort, 2154 in a validation cohort) who were admitted either to medical services with at least 1 chronic condition or to surgical/medical services if they required readmission after a hospitalization for surgery (N=4495). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: The FAMCAT is an instrument designed to permit the efficient, precise, low-burden, multidomain functional assessment of hospitalized patients. We tried to optimize the FAMCAT's efficiency and precision, as well as its ability to perform multiple assessments during a hospital stay, by applying cutting edge methods such as the adaptive measure of change (AMC), differential item functioning computerized adaptive testing, and integration of collateral test-taking information, particularly item response times. Evaluation of these candidate methods suggested that all may enhance MCAT performance, but none were integrated into initial MCAT parameterization. CONCLUSIONS: The FAMCAT has the potential to address a longstanding need for structured, frequent, and accurate functional assessment among patients hospitalized with medical diagnoses and complications of surgery.

Rehabilitation Medicine Approaches to Pain Management.

Rehabilitation medicine offers strategies that reduce musculoskeletal pain, targeted approaches to alleviate movement-related pain, and interventions to optimize patients' function despite the persistence of pain. These approaches fall into four categories: modulating nociception, stabilizing and unloading painful structures, influencing pain perception, and alleviating soft tissue musculotendinous pain. Incorporating these interventions into individualized, comprehensive pain management programs offers the potential to empower patients and limit pain associated with mobility and required daily activities. Rehabilitative approach may be particularly helpful for patients with refractory movement-associated pain and functional vulnerability, and for those who do not wish for, or cannot, tolerate pharmacoanalgesia.

The rationale, design, and methods of a randomized, controlled trial to evaluate the effectiveness of collaborative telecare in preserving function among patients with late stage cancer and hematologic conditions.

Disablement affects over 40% of patients with advanced stage cancer, devastates their quality of life (QoL), and increases their healthcare costs. Proactively treating the causes of disablement; physical impairments, pain, and immobility, can prolong functional independence, improve QoL and, potentially, reduce utilization. However rehabilitation service delivery models are reactive in nature and focus on catastrophic rather than incipient disability. A validated collaborative approach, the Three Component Model (TCM), optimizes important clinical outcomes and may provide an ideal framework to overcome barriers to proactively integrating rehabilitation into cancer care. A novel expansion of the TCM that targets disablement by engaging local physical therapists to address physical impairments and immobility, the TCM-Rehabilitation Services (TCM-RS), benefits and is well received by patients. However, its effectiveness has not been rigorously assessed. The 3-arm randomized COllaborative Care to Preserve PErformance in Cancer (COPE) Trial compared: 1) enhanced usual care, 2) rehabilitation services targeting physical impairments and immobility via the TCM-RS, and 3) TCM-RS plus conventional TCM pain management TCM-RS+Pain. Of the 516 participants, those randomized to arms 2 and 3 underwent an initial 4-week intervention period and were then followed for 6months with remote monitoring and monthly telephone calls. The trial's primary outcome, functional status, and secondary outcomes were assessed at baseline, 3, and 6months. Utilization was abstracted from clinical records. By estimating the effectiveness and cost-utility implications of the TCM-RS and TCM-RS+Pain, COPE will inform future delivery research, practice and policy in the means to reduce disablement in chronically diseased populations.

Integrating Function-Directed Treatments into Palliative Care.

The growing acceptance of palliative care has created opportunities to increase the use of rehabilitation services among populations with advanced disease, particularly those with cancer. Broader delivery has been impeded by the lack of a shared definition for palliative rehabilitation and a mismatch between patient needs and established rehabilitation service delivery models. We propose the definition that, in the advanced cancer population, palliative rehabilitation is function-directed care delivered in partnership with other clinical disciplines and aligned with the values of patients who have serious and often incurable illnesses in contexts marked by intense and dynamic symptoms, psychological stress, and medical morbidity to realize potentially time-limited goals. Although palliative rehabilitation is most often delivered by inpatient physical medicine and rehabilitation consultation/liaison services and by physical therapists in skilled nursing facilities, outcomes in these settings have received little scrutiny. In contrast, outpatient cancer rehabilitation programs have gained robust evidentiary support attesting to their benefits across diverse settings. Advancing palliative rehabilitation will require attention to historical barriers to the uptake of cancer rehabilitation services, which include the following: patient and referring physicians' expectation that effective cancer treatment will reverse disablement; breakdown of linear models of disablement due to presence of concurrent symptoms and psychological distress; tension between reflexive palliation and impairment-directed treatment; palliative clinicians' limited familiarity with manual interventions and rehabilitation services; and challenges in identifying receptive patients with the capacity to benefit from rehabilitation services. The effort to address these admittedly complex issues is warranted, as consideration of function in efforts to control symptoms and mood is vital to optimize patients' autonomy and quality of life. In addition, manual rehabilitation modalities are effective and drug sparing in the alleviation of adverse symptoms but are markedly underused. Realizing the potential synergism of integrating rehabilitation services in palliative care will require intensification of interdisciplinary dialogue.

Nested Cohort Study to Identify Characteristics That Predict Near-Term Disablement From Lung Cancer Brain Metastases.

OBJECTIVE: To test whether the presence of patient- and imaging-level characteristics (1) are associated with clinically meaningful changes in mobility among patients with late-stage cancer with metastatic brain involvement, and (2) can predict their risk of near-term functional decline. DESIGN: Prospective nested cohort study. SETTING: Quaternary academic medical center. PARTICIPANTS: The study population consisted of a nested cohort of the patients with imaging-confirmed brain metastases (n=66) among a larger cohort of patients with late-stage lung cancer (N=311). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional evaluations with the Activity Measure for Post-Acute Care Computer Adaptive Test (AM-PAC-CAT) and symptom intensity ratings were collected at monthly intervals for up to 2 years. RESULTS: In exploratory univariate models, whole brain radiation therapy (WBRT) and imaging findings of cerebellar or brainstem involvement were associated with large AM-PAC-CAT score declines reflecting worsening mobility (-4.55, SE 1.12; -2.87, SE, 1.0; and -3.14, SE 1.47, respectively). Also in univariate models, participants with new neurologic signs or symptoms at imaging (-2.48; SE .99), new brain metastases (-2.14, SE .99), or new and expanding metastases (-2.64, SE 1.14) declined significantly. Multivariate exploratory mixed logistic models, including WBRT, cerebellar/brainstem location, presence of new and expanding metastases, and worst pain intensity, had excellent predictive capabilities for AM-PAC-CAT score declines of 7.5 and 10 points (C statistics ≥0.8). CONCLUSIONS: Among patients with lung cancer and brain metastases, cerebellar/brainstem location, new and expanding metastases, and treatment with WBRT may predict severe, near-term mobility losses and indicate a need to consider rehabilitation services.

How Receptive Are Patients With Late Stage Cancer to Rehabilitation Services and What Are the Sources of Their Resistance?

OBJECTIVE: To describe the proportion and characteristics of patients with late stage cancer that are and are not receptive to receiving rehabilitation services, and the rationale for their level of interest. DESIGN: Prospective mixed-methods study. SETTING: Comprehensive cancer center in a quaternary medical center. PARTICIPANTS: Adults with stage IIIC or IV non-small cell or extensive stage small cell lung cancer (N=311). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Telephone-acquired responses to the administration of (1) the Activity Measure for Post Acute Care Computer Adaptive Test (AM-PAC-CAT); (2) numerical rating scales for pain, dyspnea, fatigue, general emotional distress, and distress associated with functional limitations; (3) a query regarding receptivity to receipt of rehabilitation services, and (4) a query about rationale for nonreceptivity. RESULTS: Overall, 99 (31.8%) of the study's 311 participants expressed interest in receiving rehabilitation services: 38 at the time of enrollment and an additional 61 during at least 1 subsequent contact. Participants expressing interest were more likely to have a child as primary caregiver (18.18% vs 9.91%, P=.04) and a musculoskeletal comorbidity (42.4% vs 31.6%, P=.05). Function-related distress was highly associated with receptivity, as were lower AM-PAC-CAT scores. Reasons provided for lack of interest in receiving services included a perception of their limited benefit, being too busy, and prioritization below more pressing tasks/concerns. CONCLUSIONS: One-third of patients with late stage lung cancer are likely to be interested in receiving rehabilitation services despite high levels of disability and related distress. These findings suggest that patient misperception of the role of rehabilitation services may be a barrier to improved function and quality of life. Efforts to educate patients on the benefits of rehabilitation and to more formally integrate rehabilitation as part of comprehensive care may curb these missed opportunities.

Scrambler Therapy for the management of chronic pain.

PURPOSE: Chronic pain is a widespread and debilitating condition, encountered by physicians in a variety of practice settings. Although many pharmacologic and behavioral strategies exist for the management of this condition, treatment is often unsatisfactory. Scrambler Therapy is a novel, non-invasive pain modifying technique that utilizes trans-cutaneous electrical stimulation of pain fibers with the intent of re-organizing maladaptive signaling pathways. This review was conducted to further evaluate what is known regarding the mechanisms and mechanics of Scrambler Therapy and to investigate the preliminary data pertaining to the efficacy of this treatment modality. METHODS: The PubMed/Medline, SCOPUS, EMBASE, and Google Scholar databases were searched for all articles published on Scrambler Therapy prior to November 2015. All case studies and clinical trials were evaluated and reported in a descriptive manner. RESULTS: To date, 20 reports, of varying scientific quality, have been published regarding this device; all but one small study, published only as an abstract, provided results that appear positive. CONCLUSION: The positive findings from preliminary studies with Scrambler Therapy support that this device provides benefit for patients with refractory pain syndromes. Larger, randomized studies are required to further evaluate the efficacy of this approach.

Imaging and Clinical Characteristics Predict Near-Term Disablement From Bone Metastases: Implications for Rehabilitation.

OBJECTIVE: To distinguish which patients with bone metastases are at risk for near-term disablement in order to assist clinicians in assessing the appropriateness of referrals for rehabilitation services. DESIGN: Prospective cohort study. SETTING: National Cancer Institute-designated comprehensive cancer center imbedded in a tertiary medical center. PARTICIPANTS: Data were collected from members (n=78) of a patient cohort (N=311) with stage IIIB or IV non-small-cell lung cancer or extensive-stage small-cell lung cancer who developed new or progressive imaging-confirmed bone metastases during the 2-year course of the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional capabilities were assessed at 3- to 4-week intervals over the study's 2-year duration with the Activity Measure for Post-Acute Care Computer Adaptive Testing. RESULTS: Seventy-eight participants developed new or progressive bone metastases during the study. Most were men, and 83% had non-small-cell lung cancer. Metastases were most frequently located in the ribs (n=62), pelvis (n=49), or the thoracic (n=60) and lumbar spine (n=44). While neither the number of bone metastases nor their specific location was associated with near-term changes in patient mobility, their association with pain or a focal neurologic deficit was strongly associated with large declines in mobility. Similarly, patients whose imaging studies revealed new metastases and the expansion of established metastases were more likely to lose mobility. CONCLUSIONS: The total burden, specific locations, and overall distribution of bone metastases did not predict disablement. Patients with lung cancer-associated bone metastases are at markedly increased risk for declining mobility when their metastases are expanding in size and increasing in number, or are associated with pain or with new neurologic deficits.

Improving Adherence to Cancer Treatment by Addressing Quality of Life in Patients With Advanced Gastrointestinal Cancers.

CONTEXT: Many patients with potentially curable cancer do not complete their prescribed treatment regimens because of the toxicity. There is evidence that the common endpoints of many of these toxicities are amenable to quality of life (QOL)-directed interventions. OBJECTIVES: This study was conducted to determine the effect of a multidisciplinary QOL-directed intervention on patients' adherence to planned chemoradiation (CR) regimens. METHODS: The results of two randomized controlled trials that used the same QOL intervention were pooled to form a cohort of 61 patients with advanced localized gastrointestinal cancer. Of these 61 subjects, 29 participated in six to eight bi- to triweekly sessions that included exercise, education, and relaxation, and 32 received usual medical care. The primary endpoint was completion of their prescribed CR regimens. Secondary outcomes included hospitalization during CR, rates of adverse postoperative events, and complete pathological response in those undergoing neoadjuvant therapy. RESULTS: Significantly, more members of the intervention than the control group completed their planned CR regimens (77.8 vs. 38.2%, P = 0.003). More participants in the control (n = 14) than the intervention (n = 5) group (P = 0.063) required hospitalization. Among those undergoing neoadjuvant CR, those in the intervention group were significantly more likely to complete CR as planned (81.0% vs. 37.5%, P = 0.005) and less likely to be hospitalized (14.3% vs. 50.0%, P = 0.011). CONCLUSION: A structured multidisciplinary QOL-directed intervention delivered to patients undergoing CR may increase the proportion of patients who complete CR as planned and reduce unplanned hospitalizations. Utilization is an important outcome in QOL-directed intervention trials.

Age, sex, and symptom intensity influence test taking parameters on functional patient-reported outcomes.

OBJECTIVE: Item response theory-based patient-reported outcomes such as the Activity Measure for Post Acute Care Computerized Adaptive Test are gaining use because of their flexibility and ease of administration. Their psychometric properties are being explored, but little is known about how respondent characteristics may impact precision. The goal of this study was, therefore, to assess the effects of age, sex, and symptom intensity on respondents' test taking behaviors and scores. DESIGN: Three hundred eleven adults with late-stage lung cancer were consecutively enrolled between April 2008 and April 2009. Demographics and comorbidities were abstracted from their electronic medical records. The participants were followed on a 3- to 4-wk basis by telephonic interviews that involved administration of the Activity Measure for Post Acute Care Computerized Adaptive Test, followed by numerical rating scales scoring of their pain, fatigue, and dyspnea. RESULTS: In more than 2538 computerized adaptive test (CAT) sessions, three findings were prominent. First, the women and the older patients took longer to complete CAT sessions, were more likely to skip items, and produced scores with larger standard errors. Second, the respondents with higher levels of dyspnea and fatigue, but not pain, completed their CAT sessions more rapidly and were less likely to skip items. Third, fatigue and dyspnea interact with age but not sex to influence CAT duration and skip count. CONCLUSIONS: The findings of this study suggest that certain common clinical populations, for example, women, geriatric patients, and patients with intense symptoms, differ systematically in the time they are willing to devote to testing and the precision of their responses. The latter finding, unstable precision, is unlikely to be CAT specific and has implications for the interpretation of the scores of the Activity Measure for Post Acute Care Computerized Adaptive Test and other patient-reported outcomes.

Role of rehabilitation medicine and physical agents in the treatment of cancer-associated pain.

PURPOSE: To provide an overview of rehabilitation medicine- and physical modality-based approaches to cancer pain management, and to highlight the fact that these approaches are generally used in conjunction and that a majority are focused on minimizing pain during periods of mobility and the performance of activities of daily living. METHODS: We performed a nonsystematic literature review and provide a description of the current standard of care. RESULTS: Rehabilitative and physical modalities used to manage pain can be grouped into four categories: those that modulate nociception, stabilize or unload painful structures, influence physiological processes that indirectly influence nociception, or alleviate pain arising from the overloading of muscles and connective tissues that often occurs after surgery or with sarcopenia in late-stage cancer. Most modalities have been pragmatically refined over the years, and many have an evidence base, although few have been explicitly validated in the oncologic setting. With few exceptions, they are patient controlled and free of adverse effects. CONCLUSION: Physical modalities and rehabilitation medicine offer a range of pain management approaches that may serve as beneficial adjuncts to the conventional systemic and interventional analgesic strategies used to control cancer-related pain. These approaches may be particularly beneficial to patients with movement-associated pain and those who are ambivalent regarding pharmacoanalgesia.

Appropriateness of the treatment of fatigued patients with stage IV cancer.

BACKGROUND: Fatigue among patients with cancer is prevalent, disabling, and treatable. While fatigue management guidelines have been in place for a decade, their use remains unclear. METHODS: We surveyed 160 patients with stage IV lung (40), breast (40), colon (40), and prostate (40) cancer who reported moderate to severe fatigue (i.e., >5 of 10 on an 11-point numerical rating scale). Participants were queried about receipt of treatments in fatigue management domains emphasized in the National Comprehensive Cancer Network guidelines: general management strategies, activity enhancement, psychosocial strategies, and pharmaceuticals. RESULTS: The cohort was half male, had a mean age of 67, and reported an average fatigue rating of 6.4. Participants reported treatment or receipt of specific guidance in the fatigue management domains as follows: general management strategies 16.8 %, activity enhancement 11.9 %, psychosocial strategies 9.9 %, and pharmaceuticals 37.3 %. Fatigue >7 of 10 increased the likelihood of instruction in activity enhancement but no other domain. CONCLUSION: The low rates of guideline-congruent treatment reported here are concerning, particularly as better validated behavioral treatments were the least prescribed.

A home-based exercise program to improve function, fatigue, and sleep quality in patients with Stage IV lung and colorectal cancer: a randomized controlled trial.

CONTEXT: Exercise benefits patients with cancer, but studies of home-based approaches, particularly among those with Stage IV disease, remain small and exploratory. OBJECTIVES: To conduct an adequately powered trial of a home-based exercise intervention that can be facilely integrated into established delivery and reimbursement structures. METHODS: Sixty-six adults with Stage IV lung or colorectal cancer were randomized, in an eight-week trial, to usual care or incremental walking and home-based strength training. The exercising participants were instructed during a single physiotherapy visit and subsequently exercised four days or more per week; training and step-count goals were advanced during bimonthly telephone calls. The primary outcome measure was mobility assessed with the Ambulatory Post Acute Care Basic Mobility Short Form. Secondary outcomes included ratings of pain and sleep quality as well as the ability to perform daily activities (Ambulatory Post Acute Care Daily Activities Short Form), quality of life (Functional Assessment of Cancer Therapy-General), and fatigue (Functional Assessment of Cancer Therapy-Fatigue). RESULTS: Three participants dropped out and seven died (five in the intervention and two in the control group, P=0.28). At Week 8, the intervention group reported improved mobility (P=0.01), fatigue (P=0.02), and sleep quality (P=0.05) compared with the usual care group, but did not differ on the other measures. CONCLUSION: A home-based exercise program seems capable of improving the mobility, fatigue, and sleep quality of patients with Stage IV lung and colorectal cancer.

Insights into the reluctance of patients with late-stage cancer to adopt exercise as a means to reduce their symptoms and improve their function.

CONTEXT: Exercise reduces cancer-related disablement and adverse symptoms, yet patients' attitudes toward exercise remain largely unexamined. OBJECTIVES: This qualitative study sought to characterize the beliefs of patients with late-stage disease regarding exercise, its relationship to their symptoms, and their clinicians' roles in providing related counseling. METHODS: Semistructured interviews with 20 adults (half male and half aged 65 years or older) with Stage IIIB or IV nonsmall cell lung cancer were qualitatively analyzed. Participants were questioned about their levels of activity, the influence of their symptoms on their activities, perceived barriers and facilitators for exercise, and exercise-related instructions received from their professional caregivers. RESULTS: Participants overwhelmingly cited usual daily activities as their source of "exercise." Symptoms, particularly treatment-related, discouraged participation, with fear of harm being a significant concern only among younger women. Exercise was recognized as important for physical and mental well-being but seldom as a means to mitigate symptoms. Weather, recalled levels of premorbid fitness, and exercise participation modulated current exercise behaviors. Although respondents preferred to receive guidance from their oncologist, none reported receiving more than general encouragement to "stay active." A lack of direction was typically accepted as a sanction of their current activity levels. Participants appeared less receptive to guidance from ancillary health professionals. CONCLUSION: Effective use of exercise and activity modification to ameliorate cancer-related symptoms appears to require a linkage to a patient's usual and past activities, proactive negotiation of potential barriers, education regarding symptoms and exercise, and the positive support of their oncologist.

Cost considerations regarding the prospective surveillance model for breast cancer survivors.

For this article, the authors examined the cost implications of the prospective surveillance model (PSM) for breast cancer (BC) survivors, a comprehensive framework designed to preemptively reduce the incidence and virulence of common impairments. The model clearly has the potential of providing significant benefits. However, its accompanying costs and resource requirements remain unclear and may be substantial. Thus, it is critical to examine which BC survivors may benefit from the PSM, how much they will benefit, and the costs of this benefit before its implementation. Because the PSM is not rigidly prescriptive, its examination must allow for different scenarios with emphasis on 4 critical determinants of cost--whether all or only high-risk BC survivors participate, assessment frequencies and locations, the credentials of the assessors, and requirements for supportive equipment. Another issue is the distribution of its cost: hypothetical implementation strategies vary widely in their distribution of fiscal burden across key stakeholders--survivors, providers, and payers--whose financial responsibilities will be an important factor in whether and how rapidly they adopt the PSM. Accurate valuation of the PSM will require capture of direct and indirect cost savings and benefits. Currently, a lack of data regarding these parameters, as well as outcomes that can be reliably attributed to the PSM, impedes cost-effectiveness analyses. Because the PSM may enhance many health state characteristics, assessments that integrate overall composite measures with evaluations of common, discrete impairments may be required to comprehensively assess its benefits.

An examination of the causes for the underutilization of rehabilitation services among people with advanced cancer.

To outline the potential reasons for the persistent underutilization of rehabilitation services in the care of patients with advanced cancer, a literature review and post hoc analysis of data collected from 163 patients with stage IV breast cancer are used to examine the role of accumulated physical impairments and adverse symptoms in cancer-related disablement. Univariate and multivariate regression analyses were used to estimate the variance in functional outcomes (as measured by the Physical Function-10, Functional Independence Measure, and the Older Americans Resource Study subscales) explained by the presence and interaction of physical impairments, pain (Brief Pain Inventory scores), and exertional limitations (6-min walk test performance). A majority of patients had more than three impairments. Potentially catastrophic impairments, for example, paraparesis and hemiparesis, occurred in only 15% of patients. Although most specific impairments explained less than 5% of the variance in functional outcomes, a participant's total number of impairments was strongly correlated with his/her performance status and explained between 36% and 52% of the variance in functional outcomes. Brief Pain Inventory scores and exertional intolerance explained a greater proportion of the variance in functional outcomes than did the presence of impairments. Multivariate models using total number of impairments, Brief Pain Inventory scores, exertional intolerance, and their interactions accounted for up to 65% of the variance in functional outcomes. The disablement process in metastatic breast cancer is driven by the accrual of multiple physical impairments, adverse symptoms, and their interactions rather than by discrete and functionally catastrophic impairments. Without systematic disability screening, the detection of functional decline may remain challenging.

The value of a symptom cluster of fatigue, dyspnea, and cough in predicting clinical outcomes in lung cancer survivors.

CONTEXT: Aggregates of concurrent symptoms, known as symptom clusters (SxCls), are reported to have prognostic capabilities beyond that of single symptom alone. A SxCl of fatigue, dyspnea, and cough has been delineated in a number of lung cancer cohorts. OBJECTIVES: The objective of this study was to characterize this SxCl's predictive value for important clinical outcomes relative to that of its component symptoms. METHODS: Analysis of an eight-year prospective cohort study that assessed 2405 patients with LC for self-reported symptom burden, employment status, and physical activity with the Baecke questionnaire, and overall quality of life (QoL) was undertaken using nested Cox and generalized linear multilevel mixed models. Models were adjusted for longitudinally assessed demographics, cancer progression and tobacco use, and cancer progression. RESULTS: The SxCl, as well as its individual symptoms and symptom pairs, were all negatively associated with survival in Cox models of Years 1-3 after diagnosis. Only in Year 3 did the SxCl prognosticate survival (and then marginally) better than single symptoms or symptom pairs; fatigue was strongly associated (P≤0.0005) with survival at all time points. The SxCl was not predictive of participants' employment status, physical activity, or QoL, whereas the presence of fatigue, dyspnea, or their combination was strongly associated with these outcomes. CONCLUSION: Fatigue and dyspnea are strongly associated with poor clinical outcomes in LC survivors; however, a SxCl that includes fatigue, dyspnea, and cough as part as its components does not appear to significantly improve their predictive capability.

Fatigue, dyspnea, and cough comprise a persistent symptom cluster up to five years after diagnosis with lung cancer.

CONTEXT: Aggregates of concurrent symptoms, known as symptom clusters (SxCls), have been described in predominantly cross-sectional samples of lung cancer (LC) patients undergoing treatment. OBJECTIVES: The objective of this study was to delineate SxCls in LC survivors up to five years after diagnosis, investigate their stability over time, and identify determinants of SxCl development and resolution. METHODS: A sensitivity approach involving multiple exploratory and confirmatory analyses was applied to an eight-year prospective cohort study that annually assessed 2405 patients with LC for symptom burden with the Lung Cancer Symptom Scale and Linear Analogue Self-Assessment. RESULTS: A single robust SxCl of fatigue, cough, and dyspnea was identified in 14.6%, 12.9%, 14.1%, 14.6%, and 15.4% of participants at Years 1-5 after diagnosis, respectively. Participants with the SxCl (SxCl (+)) were more likely to die than those without it; but this tendency diminished over time. SxCl persistence varied, with ≥40% of surviving patients annually transitioning to or from the SxCl(+) state until Year 4, after which the SxCl became increasingly stable. The SxCl was more likely to develop among male survivors who underwent surgery, received radiation, and were current smokers. CONCLUSION: A single SxCl comprising dyspnea, fatigue, and cough has a stable prevalence among LC survivors up to five years after diagnosis but is not stable among individuals. Initially, after diagnosis, the SxCl is associated with a greater risk of death; however, after Year 2, the SxCl becomes increasingly stable and provides a marker for parenchymal lung injury.

A prospective cohort study defining utilities using time trade-offs and the Euroqol-5D to assess the impact of cancer-related lymphedema.

BACKGROUND: The devastating impact of lymphedema on cancer survivors' quality of life has prompted consideration of several changes in medical and surgical care. Unfortunately, our understanding of the benefits gained from these approaches relative to their cost remains limited. This study was designed to estimate utilities for lymphedema and characterize how utilities differ between subgroups defined by lymphedema etiology and distribution. METHODS: A consecutive sample of 236 subjects with lymphedema seen at a lymphedema clinic completed both a time trade-off (TTO) exercise and the Euroqol 5D. Responses were adjusted in multivariate regression models for demographic factors, comorbidities, and lymphedema severity/location. RESULTS: Most participants (167 of 236, 71%) had lymphedema as a consequence of cancer treatment; 123 with breast cancer and upper extremity involvement. Mean TTO utility estimates were consistently higher than Euroqol 5D estimates. Unadjusted TTO (0.85; standard deviation [SD], 0.21) and Euroqol 5D (0.76; SD, 0.18) scores diminished with increasing lymphedema stage and patient body mass index (BMI). Adjusted utility scores were lowest in patients with cancer-related lower extremity lymphedema (TTO=0.82; SD, 0.04 and Euroqol 5D=0.80; SD, 0.03). Breast cancer patients also had lower adjusted Euroqol 5D scores (0.80; SD, 0.02). CONCLUSIONS: Lymphedema-associated utilities are in the range of 0.80. Lower utilities are observed for patients with higher lymphedema stages, elevated BMI, and cancer-related lymphedema. Greater expenditures for the prevention and treatment of cancer-related lymphedema are warranted.