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1.  Characteristics and associations of pain intensity in patients referred to a specialist cancer pain clinic 
Uncontrolled cancer pain (CP) has the ability to impair quality of life and interfere with daily activities. Poor CP management is consistently attributed to inadequate assessment and clarification of pain. The authors of this study identified the need to understand the nature of CP and inform evidence-based strategies for its assessment and management. The study aimed to describe the characteristics of CP and to determine predictors of pain intensity with patients referred to a CP clinic in Portugal.
Uncontrolled cancer pain (CP) may impair quality of life. Given the multidimensional nature of CP, its poor control is often attributed to poor assessment and classification.
To determine the characteristics and associations of pain intensity in a specialist CP clinic.
Consecutive patients referred to the CP clinic of the Portuguese Cancer Institute (Lisbon, Portugal) had standardized initial assessments and status documentation of the following: Brief Pain Inventory ratings for ‘pain now’ as the outcome variable; initial pain intensity (iPI) on a 0 to 10 scale; pain mechanism (using the Douleur Neuropathique 4 tool to assess neuropathic pain); episodic pain; Eastern Cooperative Oncology Group rating; oral morphine equivalent daily dose (MEDD); Hospital Anxiety Depression Scale and Emotional Thermometer scores; and cancer diagnosis, metastases, treatment and pain duration. Univariable analyses were conducted to test the association of independent variables with iPI. Variables with P<0.1 were entered into a multivariable regression model, using backward elimination and a cut-point of P=0.2 for final model selection.
Of 371 participants, 285 (77%) had moderate (4 to 6) or severe (7 to 10) iPI. The initial median MEDD was relatively low (30 mg [range 20 mg to 60 mg]). In the multivariable model, higher income, Eastern Cooperative Oncology Group rating 3 to 4, cancer diagnosis (head and neck, genitourinary and gastrointestinal), adjuvant use and initial MEDD were associated with iPI (P<0.05). The model’s R2 was 18.6, which explained only 19% of iPI variance.
The diversity of factors associated with pain intensity and their limited explanation of its variance underscore the biopsychosocial complexity of CP. Adequacy of CP management warrants further exploration.
PMCID: PMC4596632  PMID: 26291125
Assessment; Cancer pain; Opioids; Pain characteristics; Pain intensity; Pain mechanisms
2.  Delirium 
PMCID: PMC4312154  PMID: 25487667
3.  An Analytical Framework for Delirium Research in Palliative Care Settings: Integrated Epidemiologic, Clinician-Researcher, and Knowledge User Perspectives 
Delirium often presents difficult management challenges in the context of goals of care in palliative care settings.
The aim was to formulate an analytical framework for further research on delirium in palliative care settings, prioritize the associated research questions, discuss the inherent methodological challenges associated with relevant studies, and outline the next steps in a program of delirium research.
We combined multidisciplinary input from delirium researchers and knowledge users at an international delirium study planning meeting, relevant literature searches, focused input of epidemiologic expertise, and a meeting participant and coauthor survey to formulate a conceptual research framework and prioritize research questions.
Our proposed framework incorporates three main groups of research questions: the first was predominantly epidemiologic, such as delirium occurrence rates, risk factor evaluation, screening, and diagnosis; the second covers pragmatic management questions; and the third relates to the development of predictive models for delirium outcomes. Based on aggregated survey responses to each research question or domain, the combined modal ratings of “very” or “extremely” important confirmed their priority.
Using an analytical framework to represent the full clinical care pathway of delirium in palliative care settings, we identified multiple knowledge gaps in relation to the occurrence rates, assessment, management, and outcome prediction of delirium in this population. The knowledge synthesis generated from adequately powered, multicenter studies to answer the framework’s research questions will inform decision making and policy development regarding delirium detection and management and thus help to achieve better outcomes for patients in palliative care settings.
PMCID: PMC4128755  PMID: 24726762
Delirium; palliative care; risk factors; decision making; hospice; research framework; assessment; treatment; predictive model
4.  Treating an Established Episode of Delirium in Palliative Care: Expert Opinion and Review of the Current Evidence Base With Recommendations for Future Development 
Delirium is a highly prevalent complication in patients in palliative care settings, especially in the end-of-life context.
To review the current evidence base for treating episodes of delirium in palliative care settings and propose a framework for future development.
We combined multidisciplinary input from delirium researchers and other purposely selected stakeholders at an international delirium study planning meeting. This was supplemented by a literature search of multiple databases and relevant reference lists to identify studies regarding therapeutic interventions for delirium.
The context of delirium management in palliative care is highly variable. The standard management of a delirium episode includes the investigation of precipitating and aggravating factors followed by symptomatic treatment with drug therapy. However, the intensity of this management depends on illness trajectory and goals of care in addition to the local availability of both investigative modalities and therapeutic interventions. Pharmacologically, haloperidol remains the practice standard by consensus for symptomatic control. Dosing schedules are derived from expert opinion and various clinical practice guidelines as evidence-based data from palliative care settings are limited. The commonly used pharmacologic interventions for delirium in this population warrant evaluation in clinical trials to examine dosing and titration regimens, different routes of administration, and safety and efficacy compared with placebo.
Delirium treatment is multidimensional and includes the identification of precipitating and aggravating factors. For symptomatic management, haloperidol remains the practice standard. Further high-quality collaborative research investigating the appropriate treatment of this complex syndrome is needed.
PMCID: PMC4081457  PMID: 24480529
Delirium; palliative care; evidence-based medicine; therapeutics; decision making; hospices
5.  Ethical Challenges and Solutions Regarding Delirium Studies in Palliative Care 
Delirium occurs commonly in settings of palliative care (PC), in which patient vulnerability in the unique context of end-of-life care and delirium-associated impairment of decision-making capacity may together present many ethical challenges.
Based on deliberations at the Studies to Understand Delirium in Palliative Care Settings (SUNDIPS) meeting and an associated literature review, this article discusses ethical issues central to the conduct of research on delirious PC patients.
Together with an analysis of the ethical deliberations at the SUNDIPS meeting, we conducted a narrative literature review by key words searching of relevant databases and a subsequent hand search of initially identified articles. We also reviewed statements of relevance to delirium research in major national and international ethics guidelines.
Key issues identified include the inclusion of PC patients in delirium research, capacity determination, and the mandate to respect patient autonomy and ensure maintenance of patient dignity. Proposed solutions include designing informed consent statements that are clear, concise, and free of complex phraseology; use of concise, yet accurate, capacity assessment instruments with a minimally burdensome schedule; and use of PC friendly consent models, such as facilitated, deferred, experienced, advance, and proxy models.
Delirium research in PC patients must meet the common standards for such research in any setting. Certain features unique to PC establish a need for extra diligence in meeting these standards and the employment of assessments, consent procedures, and patient-family interactions that are clearly grounded on the tenets of PC.
PMCID: PMC4082407  PMID: 24388124
Ethics; palliative care; delirium; research
6.  Clinical Practice Guidelines for Delirium Management: Potential Application in Palliative Care 
Delirium occurs in patients across a wide array of health care settings. The extent to which formal management guidelines exist or are adaptable to palliative care is unclear.
This review aims to 1) source published delirium management guidelines with potential relevance to palliative care settings, 2) discuss the process of guideline development, 3) appraise their clinical utility, and 4) outline the processes of their implementation and evaluation and make recommendations for future guideline development.
We searched PubMed (1990–2013), Scopus, U.S. National Guideline Clearinghouse, Google, and relevant reference lists to identify published guidelines for the management of delirium. This was supplemented with multidisciplinary input from delirium researchers and other relevant stakeholders at an international delirium study planning meeting.
There is a paucity of high-level evidence for pharmacological and non-pharmacological interventions in the management of delirium in palliative care. However, multiple delirium guidelines for clinical practice have been developed, with recommendations derived from “expert opinion” for areas where research evidence is lacking. In addition to their potential benefits, limitations of clinical guidelines warrant consideration. Guidelines should be appraised and then adapted for use in a particular setting before implementation. Further research is needed on the evaluation of guidelines, as disseminated and implemented in a clinical setting, focusing on measurable outcomes in addition to their impact on quality of care.
Delirium clinical guidelines are available but the level of evidence is limited. More robust evidence is required for future guideline development.
PMCID: PMC4128754  PMID: 24766743
Delirium; palliative care; practice guidelines
8.  Autonomic dysfunction in patients with advanced cancer; prevalence, clinical correlates and challenges in assessment 
BMC Palliative Care  2012;11:3.
The results of a small number of studies of autonomic function in patients with advanced cancer suggest that autonomic dysfunction (AD) is common. In other disease-specific groups this is associated with decreased survival, falls and symptoms such as postural hypotension, nausea, early satiety and fatigue. The contribution of AD to symptoms in advanced cancer is unknown.
We conducted a prospective cohort study designed to identify the risk factors for falls in patients with advanced cancer. Ambulant adult patients admitted consecutively to palliative care services were invited to participate. Participants underwent an assessment at baseline which included standard clinical tests of autonomic function, assessment of symptom severity, muscle strength, anthropometric measurements, walking speed, medication use, comorbidities and demographics. Information regarding survival was recorded ten months following cessation of recruitment. The clinical correlates of AD, defined as definite or severe dysfunction using Ewing's classification, were examined by univariate and multivariate logistic regression analysis. Survival analysis was conducted using Kaplan-Meier plots and the log rank test.
Of 185 patients recruited, 45% were unable to complete all of the clinical tests of autonomic function. Non-completion was associated with scoring high on clinical indicators of frailty. It was possible to accurately classify 138/185 (74.6%) of participants as having either definite or severe versus normal, early or atypical AD: 110 (80%) had definite/severe AD. In logistic regression analysis, age (OR = 1.07 [95% CI; 1.03-1.1] P = 0.001) and increased severity of fatigue (OR = 1.26 [95% CI; 1.05-1.5] p = 0.016) were associated with having definite/severe AD. In analysis adjusted for age, median survival of participants with definite/severe AD was shorter than in those with normal/early/atypical classification (χ2 = 4.3, p = 0.038).
Autonomic dysfunction is highly prevalent in patients with advanced cancer and is associated with increased severity of fatigue and reduced survival. Due to frailty, up to 45% of participants were unable to complete standard clinical tests of autonomic function. In order to further investigate the impact of AD and the therapeutic potential of treatment of AD in patients with advanced cancer, the validity of alternative novel methods of assessing autonomic function must be appraised.
PMCID: PMC3314561  PMID: 22379978
9.  Delirium diagnosis, screening and management 
Purpose of review
Our review focuses on recent developments across many settings regarding the diagnosis, screening and management of delirium, so as to inform these aspects in the context of palliative and supportive care.
Recent findings
Delirium diagnostic criteria have been updated in the long-awaited Diagnostic Statistical Manual of Mental Disorders, fifth edition. Studies suggest that poor recognition of delirium relates to its clinical characteristics, inadequate interprofessional communication and lack of systematic screening. Validation studies are published for cognitive and observational tools to screen for delirium. Formal guidelines for delirium screening and management have been rigorously developed for intensive care, and may serve as a model for other settings. Given that palliative sedation is often required for the management of refractory delirium at the end of life, a version of the Richmond Agitation-Sedation Scale, modified for palliative care, has undergone preliminary validation.
Although formal systematic delirium screening with brief but sensitive tools is strongly advocated for patients in palliative and supportive care, it requires critical evaluation in terms of clinical outcomes, including patient comfort. Randomized controlled trials are needed to inform the development of guidelines for the management of delirium in this setting.
PMCID: PMC4162328  PMID: 25004177
assessment; delirium; management; palliative care; screening

Results 1-11 (11)