The psychometric properties of cancer multisymptom assessment instruments: a clinical review.

PURPOSE: Various instruments are used to assess both individual and multiple cancer symptoms. We evaluated the psychometric properties of cancer multisymptom assessment instruments. METHODS: An Ovid MEDLINE search was done. All searches were limited to adults and in English. All instruments published from 2005 to 2014 (and with at least one validity test) were included. We excluded those who only reported content validity. Instruments were categorized by the three major types of symptom measurement scales employed as follows: visual analogue (VAS), verbal rating (VRS), and numerical rating (NRS) scales. They were then examined in two areas: (1) psychometric thoroughness (number of tests) and (2) psychometric strength of evidence (validity, reliability, generalizability). We also assigned an empirical global psychometric quality score (which combined the concepts of thoroughness and strength of evidence) to rank the instruments. RESULTS: We analyzed 57 instruments (17 original, 40 modifications). They varied in types of scales used, symptom dimensions measured, and time frames evaluated. Of the 57, 10 used VAS, 28 VRS, and 19 NRS. The Edmonton Symptom Assessment System (ESAS), ESAS-Spanish, Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Symptom Distress Scale (SDS), M.D. Anderson Symptom Inventory (MDASI)-Russian, and MDASI-Taiwanese were the most comprehensively tested for validity and reliability. The ESAS, ESAS-Spanish, ASDS-2, Memorial Symptom Assessment Scale (MSAS)-SF, POMS, SDS, MDASI (and some translations), and MDASI-Heart Failure all showed good validity and reliability. CONCLUSIONS: The MDASI appeared to be the best overall from a psychometric perspective. This was followed by the ESAS, ESAS-Spanish, POMS, SDS, and some MDASI translations. VRS-based instruments were most common. There was a wide range of psychometric rigor in validation. Consequently, meta-analysis was not possible. Most cancer multisymptom assessment instruments need further extensive validation to establish the excellent reliability and validity required for clinical utility and meaningful research.

Symptom severity and distress in advanced cancer.

We determined the relationship between symptom severity and distress for multiple cancer symptoms, and examined patient demographic influences on severity and distress in advanced cancer. A Cochran-Armitage trend test determined whether symptom distress increased with severity. Chi-square, Fisher's exact test and logistic regression analysis examined moderate/severe ('clinically important') and distressful symptoms by age (65), gender, primary site group, and ECOG performance status. Forty-six symptoms were analyzed in 181 individuals. More than 50% of individuals with clinically important symptoms rated them as distressful. The median percentage of individuals with mild but still distressful symptoms was 25%, with a range of 0% (bad dreams) to 73% (sore mouth). In both univariate and multivariate analysis, younger (

Components of the anorexia-cachexia syndrome: gastrointestinal symptom correlates of cancer anorexia.

INTRODUCTION: Cancer-related anorexia is traditionally considered part of a complex but ill-defined anorexia-cachexia syndrome in which anorexia is intimately associated with other gastrointestinal (GI) symptoms and weight loss. We surveyed cancer patients with anorexia to learn more about the relationship between anorexia and these symptoms. MATERIALS AND METHODS: A 22-item GI questionnaire assessed the severity of anorexia and the prevalence of concurrent GI symptoms, including taste changes, food aversions, altered sense of smell, and diurnal food intake changes. The relationship between anorexia severity and anticancer therapy and prior menstrual or pregnancy-related appetite changes was also assessed. RESULTS: Ninety-five of 101 patients with anorexia surveyed had complete data. Seventy-eight percent of them had moderate or severe anorexia. Abnormal diurnal appetite variation, taste changes, and food aversions were present in over 50% of all those with anorexia. Judged by the numerical rating scale, the worse the anorexia, the more prevalent were early satiety, constipation, vomiting, and food aversions. Those with more severe anorexia had greater weight loss, and worse performance status. Anorexia severity did not correlate with that during prior menses/pregnancy or antitumor therapy. CONCLUSIONS: Evaluation of multiple other GI symptoms is important in understanding the total experience of cancer anorexia. Early satiety, taste changes, food aversions, and altered sense of smell are important accompanying GI symptoms. Most validated anorexia tools do not assess these commonly associated GI symptoms. Future research should develop a comprehensive anorexia symptom questionnaire.

The pitfalls of a systematic MEDLINE review in palliative medicine: symptom assessment instruments.

The Medical Literature Analysis and Retrieval System Online (MEDLINE) database provides many references for reviews, but many relevant articles are missed, especially when the topic is complex. Reported here is the detailed methodology of a PubMed search of MEDLINE augmented by a related articles link search. Of 1181 citations identified, through a PubMed search, 10 articles met the inclusion criteria. Fifty-one were identified through the related articles link; of which 43 were not detected by standard searches using medical subject heading terms. More than 50% were identified using the related articles link. Only 14% of relevant articles were identified using the standard PubMed MEDLINE search. The related articles link is not included in methodologic recommendations for systematic literature reviews but this experience suggests that it is a useful tool in PubMed for reviewing complex evidence. Related links searches are proposed in any systematic PubMed MEDLINE literature review in palliative medicine.

Deep vein thrombosis (DVT) in advanced cancer patients with lower extremity edema referred for assessment.

Lower extremity edema is a common complication in advanced cancer patients, and deep vein thrombosis (DVT) is one among many causes. Clinical signs and symptoms are known to be unreliable, and radiographic investigations are often required in diagnosing DVT. A retrospective chart review was conducted on 46 advanced cancer patients with lower extremity edema. Researchers analyzed 52 venous duplex scans to determine the radiographic incidence of DVT the reliability of other clinical signs and symptoms in diagnosing DVT, apart from leg edema, and to assess other potential causes of lower extremity edema and their correlation to DVT. Twenty-three (44 percent) of 52 scans were positive for DVT. The most common presentation of edema in the patients with positive scans was bilateral asymmetric edema (11/23, 48 percent). There was limited documentation of other clinical signs and symptoms suggesting DVT. Other variables such as serum albumin (p = 0.46) and creatinine (p = 0.11) were not statistically different in patients who had positive and negative scans. Of other potential causes of lower extremity edema, such as previous surgery, radiotherapy, tumor, or lymph node compression, a number of patients had a coexisting DVT with bilateral asymmetric edema as the most common presentation. The results of this study suggest that advanced cancer patients with bilateral asymmetric lower extremity edema of potentially multifactorial origin have a high incidence of DVT.

Thrombosis and anticoagulation in palliative care: an evolving clinical challenge.

There is a clear recognition of the relationship between thrombosis and neoplastic diseases. In recent years, there have been a few reports dealing with some of the features of clinical progression and management of venous thromboembolism (VTE) in palliative care patients. In this report, we present four cases that describe some of the diverse aspects of this clinically challenging area to illustrate the symptom and quality of life issues for patients, and the management challenge for palliative care clinicians. Perhaps the most important issue in the palliative care setting is the need to balance the inconvenience of the various diagnostic and therapeutic options, particularly in settings where progression has resulted in a deteriorated physical and cognitive condition. We need to recognize that VTE does cause significant problems for some of our patients. We will always need to balance issues of life expectancy, comfort and quality of life, and risk and benefits of anticoagulation, and align these problems with the individual patient, and the family dynamics and desires we encounter.

Symptom prevalence in advanced cancer: age, gender, and performance status interactions.

Age, gender, and performance status (PS) are important patient characteristics which might influence to cancer symptom profile. We conducted a secondary analysis of a symptom database to examine any interaction of these factors on symptom prevalence. 38 symptoms were assessed in 1000 consecutive patients with advanced cancer. The association of the three demographic factors with each symptom was examined using logistic regression analysis. Eight symptoms were associated with more than one of the three factors. Model-based estimates of symptom prevalence were calculated for 30 groups based on combinations of age, gender, and ECOG PS (0-4). Prevalence differences between various groups >10% were empirically classified as clinically relevant. The frequency of all eight symptoms (pain, constipation, sleep problems, nausea, anxiety, vomiting, sedation, and blackouts) was associated with more than one of the demographic characteristics of age, gender, and PS level. The prevalence of all eight decreased with older age. Females had more nausea, anxiety, and vomiting than males; males greater sleep problems. The prevalence of constipation, sedation, and blackouts was higher with worse PS, whereas pain and anxiety became less common with worse PS. Age, gender, and PS appeared to be associated with variations in the prevalence of eight gastrointestinal and neuropsychological symptoms in cancer patients. They should be included as important variables in clinical practice symptom research data.

Cancer symptom clusters: clinical and research methodology.

INTRODUCTION: Patients with cancer experience multiple symptoms that frequently appear in groups or clusters. We conducted a comprehensive clinical review of cancer symptom cluster studies to identify common symptom clusters (SC), explore their clinical relevance, and examine their research importance. METHODS: Published studies and review articles on cancer SC were obtained through a literature search. We identified 65 reports. These varied in assessment instruments, outcomes, design, population characteristics, and study methods. RESULTS: Two main approaches to symptom cluster identification were found: clinical and statistical. Clinically determined SC were based upon observations of symptom co-occurrence, associations, or interrelations. These included fatigue-pain, fatigue-insomnia, fatigue-insomnia-pain, depression-fatigue, and depression-pain. They were analyzed by multivariate analysis. They had low to moderate statistical correlations. Disease- or treatment-related SC were influenced by primary cancer site, disease stage, or antitumor treatment. SC determined by statistical analysis were identified by factor and cluster analysis through nonrandom symptom distribution. Nausea-vomiting, anxiety-depression, fatigue-drowsiness, and pain-constipation consistently clustered by either or both of these statistical methods. The individual symptoms of pain, insomnia, and fatigue often appeared in different clusters. A consensus about standard criteria and methodological techniques for cluster analysis should be established. CONCLUSIONS: Several important cancer SC have been identified. Nausea-vomiting, anxiety-depression, and dyspnea-cough clusters were consistently reported. The techniques of symptom cluster identification remain a research tool, but one with considerable potential clinical importance. Further research should validate our analytical techniques, and expand our knowledge about SC and their clinical importance.

The relationship between symptom prevalence and severity and cancer primary site in 796 patients with advanced cancer.

Knowledge of differences in symptom experience between cancer sites may help better understand symptom pathophysiology. A total of 38 symptoms in 796 consecutive patients with advanced cancer were retrospectively analyzed. Symptom prevalence and severity were compared among the 12 primary site groups (PSGs) by the chi-square test. Pairwise comparisons determined which sites differed. Pain, fatigue, weakness, lack of energy, and anorexia had the highest overall prevalence but did not differ among PSGs. The 3 most common neuropsychological symptoms (insomnia, depression, and anxiety) also did not vary among PSGs. Nineteen (50%) symptoms varied significantly between PSGs, in prevalence (17), severity (14), or both (12). Nine of 17, 6 of 14, and 6 of 12 were gastrointestinal symptoms. Symptoms which varied by PSGs can be included in cancer site-specific symptom assessment instruments.

Cancer symptom clusters: old concept but new data.

Individuals with cancer have multiple symptoms, which frequently co-occur. A nonrandom distribution of symptoms suggests a common mechanism. Symptom clusters (SCs) were considered part of various syndromes in the early years of medicine. The SC concept in clinical medicine is old. Symptom clusters were commonly described in the psychology/psychiatry and neurology literature. Symptom cluster may be defined either clinically or statistically. Statistically derived clusters can differ from clinically defined clusters. The clinical importance of statistically derived clusters is unclear. Pain-insomnia-fatigue and pain-depression-fatigue are commonly recognized clinical clusters. Nausea-vomiting and anxiety-depression are also statistically observed clusters. The longitudinal stability of clusters is unknown. Certain SCs, appear to have a greater adverse influence on outcomes (such as performance status and survival) than others. Comorbidities probably influence symptoms at different levels, but their effect on cancer clusters is unknown. Comprehensive symptom assessment is crucial to cluster identification. The potential use of the cluster concept to abbreviate symptom assessment tools needs validation. Symptom cluster can be disease and/or treatment related and may change as individuals undergo antitumor therapies. Polypharmacy in symptom management is frequent but could be minimized if 1 drug could be used to treat cluster symptoms. Symptom cluster appears to vary with the assessment tool, disease stage, symptom domain used to cluster, cluster methodology, and number of symptoms assessed. The validity and reliability of SCs need universally accepted statistical methods, assessment tools, and symptom domains. For now, nausea-vomiting is recognized as a consistent cluster across multiple studies. Pain-depression-fatigue and pain-insomnia-fatigue are also well recognized. Symptom clusters may help in cancer diagnosis, symptom management, and prognostication. However, the cluster method, reliability, and validity need to be established before assessment or treatment guidelines are established. Symptom clusters require further research before becoming part of routine medical symptom assessment and management.

Symptom assessment in palliative medicine: complexities and challenges.

Symptoms are important patient-reported outcomes (PRO), which help to evaluate the impact of diseases and treatments and assess quality of care. Thorough symptom assessment is a challenge, as patients in palliative settings are often polysymptomatic and easily fatigued. There is no consensus about standardization of symptom assessment in palliative medicine. The available research provides some methodological guidance, but the psychometric properties of structured multisymptom assessments are largely understudied. New approaches may improve the efficacy of clinical assessment and create instruments with greater clinical utility. In this article, we discuss current methodological concepts of symptom assessment in clinical practice, specifically with reference to symptom questionnaires appropriate for palliative medicine.

Consistency of symptom clusters in advanced cancer.

BACKGROUND: The reproducibility of symptom clusters (SCs) in different populations would support the validity of the cluster concept. Ideal approaches to cluster identification are unknown. The presence of a sentinel (most prevalent) symptom may reduce the number of symptoms in a comprehensive symptom assessment tool. The primary purpose was to assess consistency of SCs between 2 independent data sets. A secondary aim was to evaluate whether use of a sentinel symptom might abbreviate assessment but retain acceptable accuracy. METHODS: An agglomerative hierarchical cluster analysis in 922 patients with advanced cancer identified 7 SCs. We conducted the same analysis on an additional 181 cancer patients to assess cluster consistency. The most prevalent symptom within each cluster was defined as the ''sentinel'' symptom. Positive predictive value (PPV) and negative predictive value (NPV) were calculated to assess ability of the sentinel symptom to predict other symptoms in the cluster. RESULTS: Similar clusters were identified in both data sets, which included nausea/vomiting, neuropsychologic, and aerodigestive clusters. When the sentinel symptom was present, >50% nonsentinel symptoms in a cluster were present; when absent, <50% nonsentinel symptoms were identified. However, the range for PPV and NPV of the sentinel symptom to identify other symptoms in the cluster was 19% to 72% and 41% to 95%, respectively. CONCLUSIONS: Consistent SCs were found in 2 separate data sets with the same assessment tool and statistical analysis. These findings support the statistical and clinical validity of the cluster concept through consistency between different populations. The nausea/vomiting, neuropsychologic, and aerodigestive clusters may be reliable for use in assessment. The presence or absence of a sentinel symptom in each cluster did not predict the presence or absence of other symptoms in the cluster. Sentinel symptoms are inadequate to assess symptom burden.

Validation of a simplified anorexia questionnaire.

CONTEXT: Anorexia is a common symptom in cancer and is usually assessed by multiple questions and multidimensional questionnaires. A simplified questionnaire would be less burdensome to patients and abbreviate the process. OBJECTIVES: We compared the reliability at one point in time, sensitivity to change over time, and prognostic accuracy of a two-item questionnaire with the Functional Assessment of Anorexia and Cachexia Therapy shortened 12-question version (A/CS-12). METHODS: Individuals with cancer, who were cognitively intact and verbally agreed to participate, completed a two-item questionnaire and A/CS-12 in random order and again seven days later. We compared the direction of response to the summated two-item questionnaire to the validated A/CS-12 score at a single point in time, then intra-patient changes over a seven-day period of time. Scores of both questionnaires were divided into poor, moderate and good appetite and compared to survival using Kaplan-Meyer curves. Bootstrapping was used to construct confidence intervals for estimated probability agreement. Survival analysis also used hazard ratios from a Cox Proportional Hazards model. RESULTS: One hundred seventeen individuals from a single institution participated, who were either admitted to an inpatient palliative unit or seen in an outpatient/palliative medicine unit. Median age was 58.8 (range 10.7-87.1 years). Agreement at one point in time was 0.64 (95% confidence interval [CI] 0.63 - 0.66). Agreement over time was 0.53 (CI 0.41 - 0.64). The A/CS-12 predicted survival based on scores on Days 1 and 7 (P<0.001), (P=0.003) (HR 0.97 day 1, HR 0.95 day 7), whereas the simplified questionnaire failed to predict survival. CONCLUSIONS: A simplified questionnaire has moderate correlation with the A/CS-12 at one point in time but loses sensitivity over time, and lacks the ability to predict survival. A change in the questionnaire may improve reliability. Changing question 2 of the simplified questionnaire to a neutral form (better, same or worse appetite) may improve sensitivity and prognostic capability.

Bioelectrical impedance phase angle changes during hydration and prognosis in advanced cancer.

INTRODUCTION: We wished to determine bioelectrical impedance (BIA) correlates before hydration or changes during hydration and determine if these changes were prognostically important. METHODS AND MATERIALS: Fifty eligible patients underwent BIA measurements 3 consecutive days. Laboratory studies (electrolytes, creatinine, and hemoglobin) on day 1; weights and vital signs were recorded. Kaplan-Meier survival estimates were made at 30 and 60 days. Hazard ratios (HRs) based on Cox proportional hazards model were calculated. RESULTS: Weight loss was associated with shorter survival. A higher phase angle (PA) on day 1 predicted longer survival. Increased PA during hydration predicted shorter survival: increased weight during hydration predicted longer survival. DISCUSSION: Higher phase angle before hydration predicts poorer survival and, paradoxically, an increase in phase angle during hydration predicted poorer survival and preexisting intracellular dehydration, cachexia, or poor membrane function. CONCLUSIONS: Phase angle and weight during hydration predict survival in cancer.

Cancer-related fatigue: central or peripheral?

To evaluate cancer-related fatigue (CRF) by objective measurements to determine if CRF is a more centrally or peripherally mediated disorder, cancer patients and matched noncancer controls completed a Brief Fatigue Inventory (BFI) and underwent neuromuscular testing. Cancer patients had fatigue measured by the BFI, were off chemotherapy and radiation (for more than four weeks), had a hemoglobin level higher than 10 g/dL, and were neither receiving antidepressants nor were depressed on a screening question. The controls were screened for depression and matched by age, gender, and body mass index. Neuromuscular testing involved a sustained submaximal elbow flexion contraction (SC) at 30% maximal level (30% maximum elbow flexion force). Endurance time (ET) was measured from the beginning of the SC to the time when participants could not maintain the SC. Evoked twitch force (TF), a measure of muscle fatigue, and compound action potential (M-wave), an assessment of neuromuscular-junction transmission were performed during the SC. Compared with controls, the CRF group had a higher BFI score (P<0.001), a shorter ET (P<0.001), and a greater TF with the SC (CRF>controls, P<0.05). This indicated less muscle fatigue. There was a greater TF (P<0.05) at the end of the SC, indicating greater central fatigue, in the CRF group, which failed to recruit muscle (to continue the SC), as well as the controls. M-Wave amplitude was lower in the CRF group than in the controls (P<0.01), indicating impaired neuromuscular junction conduction with CRF unrelated to central fatigue (M-wave amplitude did not change with SC). These data demonstrate that CRF patients exhibited greater central fatigue, indicated by shorter ET and less voluntary muscle recruitment during an SC relative to controls.

Combining objective and subjective outcomes in cancer-related fatigue: illustrations from a single case report.

Neurophysiologic measurements were made on a patient with multiple lung cancers and severe cancer-related fatigue (CRF) who responded to 5 mg methylphenidate twice daily, titrated to 10 mg twice daily after 2 weeks. She remained at 10 mg twice daily for 8 months. Improvement in severe CRF (Brief Fatigue Inventory score) was associated with normalization of neurophysiologic tests.

Cancer symptom assessment instruments: a systematic review.

PURPOSE: A variety of assessment instruments have been created to identify cancer symptoms. We reviewed systematically cancer symptom assessment instruments published in English. METHODS: A systematic search of the MEDLINE database, Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and EMBASE was performed. Non-peer-reviewed articles were identified through BIOSIS. Articles were accessed through the related article links in PubMed and references were searched by hand. Studies were included if the instrument had symptom assessment as the primary outcome. Quality-of-life instruments were excluded. RESULTS: We identified 21 instruments; some had undergone modification or validation. An additional 28 studies examined symptom prevalence and interrelations; many involved symptom checklists. Studies varied in design, patient characteristics, symptoms, and outcome. Meta-analysis was not possible due to heterogeneity in design, study outcomes, and validation. Seventy-six articles and two conference abstracts (derived from MEDLINE, Cochrane, CINAHL, EMBASE, BIOSIS, related articles link in PubMed, and search by hand) met inclusion/exclusion criteria. The electronic search (without related links) yielded only 26% of those articles and conference abstracts that met inclusion criteria. Searches by hand of related articles identified 59% of studies. CONCLUSION: Twenty-one instruments were identified as appropriate for clinical use. The instruments vary in symptom content and extent of psychometric validation. Both comprehensive and shorter instruments have been developed, and some instruments are intended for specific symptom assessment or symptoms related to treatment. There is no ideal instrument, and the wide variety of instruments reflects the different settings for symptom assessment. Additional research is necessary.