Katherine Hauser

Fatigue in Advanced Cancer: A Prospective Study

Fatigue is a common advanced cancer symptom. Clinical features are not well known. The authors surveyed consecutive patients admitted to a palliative medicine program to identify clinical correlates of fatigue. Data collected included age, sex, performance status, primary site, prior chemotherapy/radiation therapy, and blood transfusions. Visual analogue scales assessed fatigue, quality of life, and ability to perform daily activities. Weight change was estimated. Laboratory results including lactate dehydrogenase and hemoglobin were recorded. Fatigue severity was associated with brain metastases, poor performance status, poor quality of life, and reduced ability to perform activities. Prior radiation therapy was associated with less severe fatigue. Age, sex, and hemoglobin level were not associated with fatigue. Fatigue was universal on referral. Brain metastases and poor quality of life independently predicted severity. Hemoglobin level did not predict fatigue. Further studies are necessary to define the clinical features and relationships of fatigue.

Palliative sedation: welcome guidance on a controversial issue:

Palliative sedation (PS) is the use of medications to reduce consciousness for the relief of intolerable and refractory symptoms, in patients with limited life expectancy. The ethical justification of palliative sedation is based upon the principles of double effect, autonomy and proportionality. Double effect is predicated upon the primary intent being to relieve suffering, despite potential foreseeable, but unintended, adverse effects. Proportionality is based upon the use of PS in the face of intolerable distress as a ‘therapy of last resort’, when all other potentially less harmful options have been expended or are inappropriate. PS is neither slow euthanasia nor physician-assisted suicide. Both of these practices involve the specific intent to end life, the deliberate use of lethal doses of sedation drugs, or non-therapeutic escalation of doses disproportionate to symptom distress. PS does not shorten life overall (when implemented in specialist palliative care units), despite the expected risk of individual complications (e.g. respiratory or hemodynamic compromise, aspiration, or venous thromboembolism). Sedative drugs first appeared in modern medicine in the 19th century, with bromide and chloral hydrate. Barbiturates were introduced in 1903, and benzodiazepines in 1959. The first descriptions of sedation for symptom control in advanced disease were published in 1990–1991. The early literature described a wide range in prevalence, indications and clinical practices. The prevalence in these reports ranged from 16% to over 50%. Indications included agitation and restlessness, pain, delirium, respiratory distress, myoclonus, and psychological symptoms. Drugs used for sedation included benzodiazepines, antipsychotics and barbiturates. Despite a number of prospective studies and published guidelines, evidence upon which to base practice has remained limited and controversial issues persist. These include almost every aspect of PS; the definition and terminology (palliative versus terminal), the types of sedation included under this term (intermittent versus continuous, light versus deep), the indications (physical or existential distress), the use of artificial hydration and nutrition, and the ethical basis and differentiation from euthanasia. Decisions about palliative sedation are complex and can have significant implications for the patient and lasting impact on family and staff. Staff need to develop awareness of their own preferences about care of the dying, and the potential role of frustration, sense of failure and burnout in decision making. Individual physician personal and professional factors may influence the practice of PS, including prevalence, determination of refractoriness, level of sedation used, and drugs employed. Families and staff need extensive support to understand the decision-making process, and be clear about the goals and expected outcomes. Identifying a family spokesperson (preferably one chosen by the patient) may help communication, especially for large, geographically scattered or conflicted families. Without effective communication families may be left with feelings of profound confusion, guilt or remorse, which complicate their subsequent bereavement. For these reasons evaluation and decision making by a multidisciplinary team skilled in palliative care is essential prior to initiating PS. Initiating PS without palliative medicine involvement is potentially hazardous. Palliative medicine consultation has been demonstrated to elicit previously undocumented diagnoses (especially delirium), and suggest multiple management strategies in advanced cancer, even within tertiary cancer centers. A dilemma in decision making arises where there is a lack of access to, or awareness of, specialized interventions including palliative medicine, psychiatry, interventional pain management, and spiritual care. Non-palliative medicine physicians need to have insight into their own therapeutic limitations, whilst palliative medicine physicians should be available to provide support via telephone or videoconference to isolated clinicians.

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.

Symptom Variability During Repeated Measurement Among Hospice Patients With Advanced Cancer

Aim: In this prospective study, we explored symptom variability in patients with cancer during repeated measurements. Methods: Patients with cancer admitted to an inpatient hospice completed a daily questionnaire throughout their admission. The questionnaire consisted of 5 visual analogue scales (VAS) for anxiety, depression, nausea, pain, and sedation and 3 verbal rating scales (VRS) for depression, pain, and vomiting. Data from those who completed 5 consecutive days were used for the primary analysis. We used all available data points to compare VAS and VRS. An index was developed to assess for daily symptom variability. Results/Discussion: A total of 125 hospice inpatients were enrolled; 46 (38%) completed 3 consecutive daily questionnaires and 30 (24%), 5 days. We found (1) a statistically significant decrease in severity of symptoms present on admission, (2) new symptoms developed, (3) consequently overall symptom prevalence on days 1 and 5 appeared unchanged, (4) high daily symptom variability as demonstrated by the variability index and also changing daily symptom interrelationships, (5) demographic characteristics influenced symptom patterns on admission and subsequently, (6) severe pain predicted more frequent and severe symptom burden only on admission, (7) severe depression predicted more frequent and severe symptom burden on admission and thereafter, (8) VAS scores for depression and pain did not correspond with discrete VRS categories (mild, moderate, severe). Conclusions: (1) Symptom studies in advanced disease while difficult to conduct yield valuable information, (2) symptom relationships changed daily; strict timing of data collection is crucial for data analysis, (3) symptom monitoring following admission is an overlooked measure of risk assessment, (4) symptom prevalence studies alone for treatment follow-up may be misleading, (5) depression is an important predictor of symptoms and need to be more aggressively assessed and treated, (6) demographic characteristics may help identify symptom patterns and better direct treatment, (7) VRS rather than VAS was more reliable for assessing symptoms in hospice cancer patients.

What’s in a Name? Word descriptors of cancer-related fatigue

Many different words are used to describe fatigue. It is unclear whether these word descriptors represent the same cancer symptom or dimension. The objective of this study was to identify clinical associations of three fatigue word descriptors (FWDs): ‘easy fatigue’, ‘weakness’, and ‘lack of energy’ (LOE). One thousand consecutive palliative medicine patients completed a 38-item symptom checklist. The prevalence of the three FWDs alone and in combination was calculated. Spearman correlations assessed associations between FWDs. Logistic regression analysis identified univariable and multivariable predictors for each FWD. Survival was estimated using the Kaplan—Meier method, individually and for 0—1 versus 2—3 FWDs, and compared using log-rank tests. The prevalence of easy fatigue was 69%, weakness 66%, and LOE 61%. Correlations between the FWDs were high (0.65—0.79). In multivariable models, clinical associations (particularly neuro-psychiatric symptoms and performance status) of the FWDs were variable. Weakness was associated with performance status, but not anxiety or depression. LOE was associated with anxiety and depression, but not performance status. Fatigue was associated with depression, but not anxiety or performance status. All FWDs were associated with dry mouth, early satiety, sleep problems, and weight loss. The worst survival was associated with two or three reported FWDs compared with none or one (P < 0.001). Weakness and LOE had distinct clinical associations that differed from fatigue. Evaluation of fatigue should use multiple descriptors (particularly weakness), as they are not synonymous. Further research is necessary to identify biological associations for discrete FWDs.

Communication in Palliative Medicine: A Clinical Review of Family Conferences

AIM Family conferences are an important forum for communication, particularly for those with serious illnesses. DESIGN The strength of evidence was assessed by patient, intervention, comparator, and outcome (PICO). DATA SOURCE We searched electronic databases (MEDLINE, CINAHL, PsycINFO, Embase, PubMed), published articles, and multidisciplinary resource textbooks. RESULTS Four areas investigated family conferences: acute care, family medicine/geriatrics, intensive care units (ICU), and oncology/palliative medicine. A unifying theme was the importance of improved communication. A single randomized controlled ICU study demonstrated that family conferences positively influenced bereavement outcomes. A prospective (but single-arm) ICU study and several family medicine/geriatrics cohort studies, found that family conferences reduced hospital length of stay and/or decreased resource utilization. Other articles proposed guidelines or methods for the practical conduct of family conferences. CONCLUSIONS ICU studies supported the benefit of a family conference to the family, health care team, and hospital administration. The family conference in other clinical areas was not supported by a strong evidence base. Well-designed prospective studies are needed in multiple medical settings to assess the proposed and observed patient and financial benefits of the family conference, and determine their generalizability.

Should we cluster patients or symptoms? The myth of symptom clusters based on ‘depression, insomnia, pain’ and ‘depression, fatigue, pain’

Context ‘Depression, fatigue, pain’ (DFP) and ‘depression, insomnia, pain’ (DIP) symptom clusters (SCs) have been proposed in cancer. These symptoms are common and co-occur, that is, they constitute clusters of patients rather than symptoms. Objectives The following research questions were addressed: (1) What is the frequency of co-occurrence of two symptom groups (DFP and DIP) in advanced cancer? (2) What is the degree of symptom item association within each symptom group? (3) Were either of these symptom trios associated with prognosis? Methods We reanalysed a symptom data set of 1000 patients with advanced cancer. We identified the frequency of co-occurrence of two symptom groups: DFP and DIP, using both prevalence and severity data. The symptom associations were tested by χ2 and Spearman correlations. We also determined whether either of these symptom trios were associated with a major biological outcome, that is, survival by time-to-event analyses. Results (1) Although DFP and DIP co-occured in about a quarter of the population, they were not SCs, but rather patient clusters. (2) Many persons had only one symptom from any symptom pair, and correlation coefficients were low for all symptom pairs. (3) Neither DFP nor DIP were associated with survival. Conclusions Neither DFP nor DIP symptom item combinations constituted a specific cancer SC contrary to prior reports. DFP co-occurred in 27% and DIP in only 20%. Additionally, these symptom combinations were not associated with a biological outcome, that is, poor prognosis. Patient subgroups identified by shared symptom experiences alone do not identify SCs.

Serum C-reactive protein is an important and powerful prognostic biomarker in most adult solid tumors

Introduction Prognostication in cancer is challenging and inaccurate. C-Reactive Protein (CRP), a cheap and sensitive marker of inflammation may help. This study investigated the relationship between CRP and prognosis in a large cohort of solid tumors with mixed cancer diagnoses and stages. Methods Electronic medical records of 4931 adults with solid tumors who attended the Taussig Cancer Institute from 2006–2012 were reviewed. Demographic and clinical characteristics were recorded. Maximum CRP (mCRP) was identified for each individual. CRP was analysed as a time-dependent, continuous and categorical variable for association with survival. Results Two thirds of patients had a high mCRP. This was consistently associated with shorter survival, even after correction for time from diagnosis, and when analysed as a continuous or a categorical variable. When mCRP values above 10 mg/L were subcategorized, a higher mCRP was always worse. Even among those with normal values, statistically and clinically significant shorter survival was noted at mCRP levels >5 mg/L. Conclusions In a large representative cohort of consecutive solid tumor patients the risk of death was clinically and statistically significantly greater with a high mCRP. This was independent of other variables and regardless of statistical method from both dates of diagnosis and test. CRP appeared to be underutilized. Our results support the routine use of CRP as a universal cost-effective independent prognostic indicator in most solid tumors.