Clinical characteristics of patients having single versus multiple patient encounters within a palliative care programme.

OBJECTIVE: The objective of this study was to describe the clinical characteristics of patient initial presentations, and to explore associations between patients' clinical characteristics at initial presentation and number of encounters (single vs multiple) to an integrated palliative care programme. METHODS: This was a retrospective study of a decedent cohort of 2922 patient initial presentations to the Edmonton Zone Palliative Care Program (EZPCP). Data included age, gender, setting of encounter, diagnosis, Edmonton Symptom Assessment System, CAGE, Mini-Mental Status Examination, Palliative Performance Status, Edmonton Classification System for Cancer Pain and time to death. RESULTS: On initial presentation to the EZPCP, the mean age was 73 (SD 14 years), with 1358 (46%) being female, and the majority having a cancer diagnosis (n=2376, 81%), the most common of which was gastrointestinal primary (n=681, 29%). In univariate analyses, patients with younger age (<60), higher palliative performance status (>40%), a malignant diagnosis, gastrointestinal primary or unimpaired cognition at initial presentation were significantly associated with multiple encounters with an integrated palliative care programme (p<0.05). In a multivariate regression analysis, a malignant diagnosis, longer survival, higher performance status and initial entry through acute care sites were independently associated with multiple encounters in the programme (p<0.001). CONCLUSIONS: Larger prospective studies are warranted to further elucidate the complex relationships between patient clinical characteristics, initial presentations and subsequent encounters to an integrated palliative care programme.

Clinical prediction survival of advanced cancer patients by palliative care: a multi-site study.

AIMS: This study examined (1) accuracy of clinician prediction of survival (CPS) by palliative practitioners on first assessment with the use of standardised palliative tools, (2) factors affecting accuracy, (3) potential impact on clinical care. METHODS: A multi-site prospective study (n=1530) was used. CPS was divided into four time periods (<=2wks, >2 to 6wks, >6 to 12wks and >12wks). Multivariate analysis was assessed on six predictor variables. RESULTS: Overall, median survival of the sample was only 5 weeks. CPS category was accurate only 38.6% of the time, with 44.6% patients dying before the predicted time period. Of six candidate variables, on multivariate analysis only (i) the clinical time periods themselves and (ii) Palliative Performance Scale <=50 predicted for prognostic accuracy. CONCLUSION: CPS, even by palliative practitioners, remains overly optimistic with the existence of the horizon effect. This raises the question in that these individuals may have been potentially overtreated.

Efferent connections of the parvalbumin-positive (PV1) nucleus in the lateral hypothalamus of rodents.

A solitary cluster of parvalbumin-positive neurons--the PV1 nucleus--has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the PV1 nucleus using nonspecific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1 nucleus was found to project mainly to the periaqueductal grey matter (PAG), predominantly ipsilaterally. Indirectly in rats and directly in mice, a discrete, longitudinally oriented cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF is particularly dense in the rostral portion, which is located in the supraoculomotor nucleus (Su3). It is spatially interrupted over a short stretch at the level of the trochlear nucleus and abuts caudally on a second parvalbumin-positive (PV2) nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings, which stem from neurons scattered throughout the PV1 nucleus. Topographically, the longitudinal orientation of the PV1-CTF accords with that of the likewise longitudinally oriented functional modules of the PAG, but overlaps none of them. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger-Westphal, the lateral habenular, and the laterodorsal tegmental nuclei. So far, no obvious functions have been attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1 nucleus.

Conversion of Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG) to Palliative Performance Scale (PPS), and the interchangeability of PPS and KPS in prognostic tools.

AIM: The aim of our study was to assess whether the Karnofsky Performance Status (KPS), the Eastern Cooperative Oncology Group (ECOG) Performance Status, and the Palliative Performance Scale (PPS) are interchangeable individually or within two prognostic tools: the Palliative Prognostic Score (PaP) and the Palliative Prognostic Index (PPI). METHODS: We performed a subset analysis of a prospective comparative study of functional and prognostic tools and clinician prediction of survival. We studied 955 patients with advanced life-limiting illnesses (cancer and noncancer) in the acute care and community settings. We used a descriptive statistical model and Spearman's rank correlation to assess these interchangeabilities. RESULTS: There is a direct positive linear relationship between the KPS and the PPS, and a direct negative linear relationship between these tools and the ECOG. Exchange of the KPS and the PPS was possible within the PaP and the PPI. CONCLUSION: The PPS and the KPS can be used interchangeably as functional tools and within prognostic tools. The ECOG is interchangeable with the PPS and the KPS, but this interchangeability is population-specific.

Impact of infections on the survival of hospitalized advanced cancer patients.

CONTEXT: Advanced cancer patients remain highly susceptible to infections, leading to significant morbidity and mortality. A lack of consensus on the management of infections in this population stems from the heterogeneity of the patient group, divergent goals of care, and unknown prognosis with antibiotic treatment. OBJECTIVES: This prospective single cohort study examined the impact of infection and its treatment on the survival of hospitalized advanced cancer patients compared with a similar cohort without infection. METHODS: A total of 441 patients were referred to the palliative care (PC) consult service in a tertiary hospital over a 12-month period. The occurrence of sepsis, organ-related infection, and antibiotic use were recorded on initial PC consult. Survival was calculated from the point of PC consult to the date of death. RESULTS: Of these patients, 16.6% suffered a recent episode of sepsis (with or without an identifiable organ-related infection) and 23.4% had a recent episode of organ-related infection without clinically evident sepsis. Among the patients with sepsis, organ-related infection, or both, 89.7% received antibiotics (intravenous, oral, or both). Median survival of septic and nonseptic patients was 15 and 42 days, respectively. Septic patients who responded poorly to treatment (nonresponders) had a median survival of five days vs. 142 days in good responders. This equates with a hazard ratio of 9.74 for death in antibiotic nonresponders (P<0.05). Median survival for patients with an untreated organ-related infection (no sepsis) was 27 days compared with 48 days in a similar cohort receiving antibiotic therapy. Among patients on IV antibiotics, nonresponders had a median survival of six days vs. 108 days in responders. For patients on oral antibiotics, nonresponders had a median survival of six days vs. 70 days in responders. CONCLUSION: These findings suggest that a recent episode of sepsis and/or organ-related infection significantly reduces overall patient survival. Favorable antibiotic response is associated with an increase in median survival. These findings suggest that antibiotic treatment may prolong survival, and a time-limited trial may be indicated contingent on goals of care.

Evaluation of the Palliative Prognostic Score (PaP) and routinely collected clinical data in prognostication of survival for patients referred to a palliative care consultation service in an acute care hospital.

CONTEXT: Patients, caregivers, and clinicians require high levels of information regarding prognosis when conditions are incurable. OBJECTIVES: 1) To validate the Palliative Prognostic Score (PaP) and 2) to evaluate prognostic capacity of used clinical tools and the diagnosis of delirium, in a population referred to a palliative care consultation service at a Canadian acute care hospital. METHODS: This was a prospective observational cohort study on survival prediction based on the PaP and routinely collected clinical data, including the Palliative Performance Scale (PPS) and the Folstein Mini-Mental State Examination (MMSE). Kaplan-Meier survival curves, log-rank tests for significant differences between survival curves, and the Cox proportional hazards model were used to identify the relationship between the hazard ratio for death and the above variables. RESULTS: Nine hundred fifty-eight cases underwent final analysis, of which 181 (19%) had a noncancer diagnosis. Median and mean survival were 35 and 131 days, respectively. The three groups, divided based on different ranges of PaP, had significantly different survival curves, with 30-day-survival rates of 78%, 55%, and 11%. Age, PPS, and PaP remained significantly associated with survival, whereas diagnosis group, MMSE, and delirium became insignificant, despite lower hazard of death for cancer vs. noncancer and higher hazard for abnormal vs. normal MMSE and presence vs. absence of delirium. CONCLUSION: The PaP was successfully validated in a population with characteristics that extend beyond those of the population in which it was originally developed. This is the largest sample in which the PaP has been validated to date.

A patient-completed and optically read data acquisition system for clinical trials.

Data collection and management within multicentre clinical trials can be challenging. We describe an adaptation of Teleform® technology to enable data recording by patients and their families on teleforms faxed and optically read directly into an electronic database, eliminating the need for case report forms. Preliminary results from a modest study sample size support the use of optically read forms for data collection by patients and their families, requiring only a pen, paper, and fax machine at participating sites.

Prognostic factors in patients with advanced cancer: use of the patient-generated subjective global assessment in survival prediction.

PURPOSE: To determine whether elements of a standard nutritional screening assessment are independently prognostic of survival in patients with advanced cancer. PATIENTS AND METHODS: A prospective nested cohort of patients with metastatic cancer were accrued from different units of a Regional Palliative Care Program. Patients completed a nutritional screen on admission. Data included age, sex, cancer site, height, weight history, dietary intake, 13 nutrition impact symptoms, and patient- and physician-reported performance status (PS). Univariate and multivariate survival analyses were conducted. Concordance statistics (c-statistics) were used to test the predictive accuracy of models based on training and validation sets; a c-statistic of 0.5 indicates the model predicts the outcome as well as chance; perfect prediction has a c-statistic of 1.0. RESULTS: A training set of patients in palliative home care (n = 1,164) was used to identify prognostic variables. Primary disease site, PS, short-term weight change (either gain or loss), dietary intake, and dysphagia predicted survival in multivariate analysis (P < .05). A model including only patients separated by disease site and PS with high c-statistics between predicted and observed responses for survival in the training set (0.90) and validation set (0.88; n = 603). The addition of weight change, dietary intake, and dysphagia did not further improve the c-statistic of the model. The c-statistic was also not altered by substituting physician-rated palliative PS for patient-reported PS. CONCLUSION: We demonstrate a high probability of concordance between predicted and observed survival for patients in distinct palliative care settings (home care, tertiary inpatient, ambulatory outpatient) based on patient-reported information.

A method for encoding clinical datasets with SNOMED CT.

BACKGROUND: Over the past decade there has been a growing body of literature on how the Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) can be implemented and used in different clinical settings. Yet, for those charged with incorporating SNOMED CT into their organisation's clinical applications and vocabulary systems, there are few detailed encoding instructions and examples available to show how this can be done and the issues involved. This paper describes a heuristic method that can be used to encode clinical terms in SNOMED CT and an illustration of how it was applied to encode an existing palliative care dataset. METHODS: The encoding process involves: identifying input data items; cleaning the data items; encoding the cleaned data items; and exporting the encoded terms as output term sets. Four outputs are produced: the SNOMED CT reference set; interface terminology set; SNOMED CT extension set and unencodeable term set. RESULTS: The original palliative care database contained 211 data elements, 145 coded values and 37,248 free text values. We were able to encode ~84% of the terms, another ~8% require further encoding and verification while terms that had a frequency of fewer than five were not encoded (~7%). CONCLUSIONS: From the pilot, it would seem our SNOMED CT encoding method has the potential to become a general purpose terminology encoding approach that can be used in different clinical systems.

Temporal changes in the causal foundations of palliative care symptoms.

PURPOSE: We use longitudinal data to test and extend a structural equation model documenting changes in the causal connections among symptoms experienced in the final weeks of life. Our central thesis is that the relief of suffering and the promotion of quality end of life care require tailoring interventions to reflect the shifting causal foundations of symptoms. METHODS: Symptom information on pain, anxiety, nausea, shortness of breath, drowsiness, loss of appetite, tiredness, depression, and well-being was extracted from a palliative care database. For each of the 82 study participants, symptom scores measured at 4 full weeks and 1 full week prior to death were used to test a structural equation model of the causal structures underlying symptom clusters. RESULTS: This investigation confirms the reasonableness of our previously developed model. Tiredness, depression, and well-being were sufficiently labile that the observations at one week before death were not significantly dependent on the corresponding observations 3 weeks earlier. Patients' assessments of pain, anxiety, nausea, shortness of breath, drowsiness, and appetite were only moderately stable over this same period. CONCLUSIONS: The stability in some, and instability in other, symptoms meshed convincingly with the changes in symptom causal structures previously derived from cross-sectional data. Investigations assessing temporal shifts in palliative symptom coordination over longer periods of time and for specific medical conditions and social contexts seem warranted.

The changing causal foundations of cancer-related symptom clustering during the final month of palliative care: a longitudinal study.

BACKGROUND: Symptoms tend to occur in what have been called symptom clusters. Early symptom cluster research was imprecise regarding the causal foundations of the coordinations between specific symptoms, and was silent on whether the relationships between symptoms remained stable over time. This study develops a causal model of the relationships between symptoms in cancer palliative care patients as they approach death, and investigates the changing associations among the symptoms and between those symptoms and well-being. METHODS: Complete symptom assessment scores were obtained for 82 individuals from an existing palliative care database. The data included assessments of pain, anxiety, nausea, shortness of breath, drowsiness, loss of appetite, tiredness, depression and well-being, all collected using the Edmonton Symptom Assessment System (ESAS). Relationships between the symptoms and well-being were investigated using a structural equation model. RESULTS: The model fit acceptably and explained between 26% and 83% of the variation in appetite, tiredness, depression, and well-being. Drowsiness displayed consistent effects on appetite, tiredness and well-being. In contrast, anxiety's effect on well-being shifted importantly, with a direct effect and an indirect effect through tiredness at one month, being replaced by an effect working exclusively through depression at one week. CONCLUSION: Some of the causal forces explaining the variations in, and relationships among, palliative care patients' symptoms changed over the final month of life. This illustrates how investigating the causal foundations of symptom correlation or clustering can provide more detailed understandings that may contribute to improved control of patient comfort, quality of life, and quality of death.

The role of antibiotics in the management of infection-related symptoms in advanced cancer patients.

UNLABELLED: We prospectively evaluated the effect of antibiotic treatment on infection-related symptoms in patients with advanced cancer, in addition to assessing infection characteristics. METHODS: A questionnaire was completed for enrolled patients using a personal digital assistant. Pre-antibiotic and post-antibiotic treatment Edmonton Symptom Assessment Scale (ESAS) scores were evaluated. Patient and the patient's physician identified infection-related symptoms experienced by the patient, which were documented under the "other" category on the ESAS. Pre-antibiotic and post-antibiotic scores of the patient and physician for the identified infection-related symptoms were evaluated. RESULTS: Twenty-six patients on a tertiary palliative care unit with 31 episodes of infection were included for analysis. Patients' pre- and post-antibiotic ESAS scores revealed a small improvement in all variables except anxiety. Patient assessment of symptoms related to infection showed a small improvement in all symptoms, with dsyuria being statistically significant. Physician assessment revealed a slight improvement for all the symptoms, although only cough was statistically significant. A general comparative physician assessment of patient outcome following antibiotic treatment suggested symptom improvement in 48.4% of patients. However, 50% of patients died within a week of antibiotic discontinuation. CONCLUSIONS: Antibiotic treatment appears to offer a mild improvement in infection-related symptoms. Patients reported the greatest improvement in dysuria, and physicians, in cough. Despite this symptomatic improvement, one quarter of the patients died within one week of antibiotic administration. Further comparative studies to evaluate symptomatic benefit, patient burden, and cost/benefit of antibiotic therapy in the treatment of infections in advanced cancer patients are required.

Effect of contaminant hydrophobicity on hydrogen peroxide dosage requirements in the Fenton-like treatment of soils.

A homologous series of n-alcohols was used as model contaminants to investigate the effect of hydrophobicity on the hydrogen peroxide concentration necessary in Fenton-like treatment for near-complete (>99%) destruction of compounds sorbed to soil. These probe compounds were selected because they exhibit equal reactivities with hydroxyl radicals, but have varied hydrophobicities. The standard Fenton reaction was first used to confirm equal hydroxyl radical reactivity for the n-alcohols. Central composite rotatable design experiments were then used to determine the conditions in an iron(III)-hydrogen peroxide system that resulted in 99% degradation of each of the probe compounds when sorbed to soil. The hydrogen peroxide concentrations required for 99% destruction of the sorbed compounds increased with probe compound hydrophobicity. Furthermore, hydrogen peroxide concentration requirements were directly proportional to the log octanol-water partition coefficients (logK(OW)) of each probe compound. This quantitative relationship may not be directly applicable to other organic contaminants, but a strong correlation between logK(OW) and hydrogen peroxide requirements for other contaminants will likely be found. These results confirm that hydrogen peroxide requirements for soil treatment increase as a function of contaminant hydrophobicity and provide a basis for the development of an algorithm for hydrogen peroxide requirements when modified Fenton's reagent is used for in situ chemical oxidation (ISCO).

Safety of subcutaneous clodronate and efficacy in hypercalcemia of malignancy: a novel route of administration.

Bisphosphonates have become standard treatment in management of malignancy-induced hypercalcemia and malignant bone pain. One obstacle to the routine use of bisphosphonates in palliative patients is that oral bisphosphonates have low bioavailability and a degree of gastrointestinal toxicity that may explain poor compliance. Intravenous administration can be cumbersome in patients admitted to long-term care settings or at home. We have developed and tested a new way of administering clodronate via subcutaneous infusion. This retrospective cohort study evaluated 150 patients admitted to a tertiary palliative care unit from May 1996 to May 2000 who received 254 subcutaneous infusions of clodronate for hypercalcemia or bony complications. Data were collected by chart review and specifically evaluated site toxicity and biochemistry. There was minimal local toxicity and only 2 infusions needed to be discontinued because of pain at the subcutaneous site. Clodronate showed efficacy in normalizing the serum calcium within 5 days post-infusion in 32 of 43 infusions given for hypercalcemia. This study shows that subcutaneous clodronate is safe and can lower serum calcium levels in malignant hypercalcemia.