Palliative Care Clinical Studies Collaborative (PaCCSC) - Collected Works

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Browsing Palliative Care Clinical Studies Collaborative (PaCCSC) - Collected Works by Author "Abernethy, Amy Pickar"
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    Adverse events in hospice and palliative care: a pilot study to determine feasibility of collection and baseline rates
    (Mary Ann Liebert, Inc., 2011-01-19) Currow, David Christopher ; Agar, Meera Ruth ; To, Timothy H M ; Rowett, Debra Sharon ; Greene, Aine ; Abernethy, Amy Pickar
    Background: Continuous quality improvement is fundamental in all health care, including hospice and palliative care. Identifying and systematically reducing symptomatic adverse events is limited in hospice and palliative care because these events are mostly attributed to disease progression. Objectives: The aim of this study was to assess the feasibility of symptomatic adverse events in hospice and palliative care and assessing their incidence. Methods: A retrospective, consecutive cohort of notes from a specialist palliative care inpatient service was surveyed by a clinical nurse consultant for symptomatic adverse events: falls, confusion, decreased consciousness, hypo- and hyperglycaemia, urinary retention, and hypotension. Demographic and clinical factors were explored for people at higher risk. Results: Data were available on the most recent admissions of 65 people, generating >900 inpatient days. Fifty people (78%) had events precipitating admission, of whom 31 (62%) had at least one further event during admission. Eleven of 15 people who were admitted without an event experienced at least one during their admissions. Only 4 did not have an adverse event. During their stay, there were 0.13 (standard deviation [SD] = 0.19) events per patient per day. No drug-drug or drug-host events were noted. No clinical or demographic factors predicted groups at higher risk. Conclusions: This pilot highlights the feasibility of collecting, and ubiquity of, symptomatic adverse events, and forms a baseline against which future interventions to decrease the frequency or intensity can be measured. Given the frailty of hospice and palliative patients, any adverse event is likely to accelerate irreversibly their systemic decline.
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    Anti-cholinergic load, health care utilization, and survival in people with advanced cancer: a pilot study
    (Mary Ann Liebert, Inc., 2010-07-02) Agar, Meera Ruth ; To, Timothy H M ; Plummer, John Lewis ; Abernethy, Amy Pickar ; Currow, David Christopher
    Introduction: Anti-cholinergic medications have been associated with increased risks of cognitive impairment, premature mortality and increased risk of hospitalisation. Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer, yet little is known about associated adverse outcomes in this setting. Methods: A substudy of 112 participants in a randomised control trial who had cancer and an Australia modified Karnofsky Performance Scale (AKPS) score (AKPS) of 60 or above, explored survival and health service utilisation; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale (modified version) longitudinally to death. A standardised starting point for prospectively calculating survival was an AKPS of 60 or above. Results: Baseline entry to the sub-study was a mean 62 ± 81 days (median 37, range 1–588) days before death (survival), with mean of 4.8 (median 3, SD 4.18, range 1 – 24) study assessments in this time period. Participants spent 22% of time as an inpatient. There was no significant association between anti-cholinergic score and time spent as an inpatient (adjusted for survival time) (p = 0.94); or survival time. Discussion: No association between anti-cholinergic load and survival or time spent as an inpatient was seen. Future studies need to include cognitively impaired populations where the risks of symptomatic deterioration may be more substantial.
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    Creating a research culture in a palliative care service environment: A qualitative study of the evolution of staff attitudes to research during a large longitudinal controlled trial (ISRCTN81117481)
    (Centre de Recherche Institut Universitaire de Gériatrie de Montreal, 2008) Fazekas, Belinda Susan ; Currow, David Christopher ; Grbich, Carol Frances ; Abernethy, Amy Pickar ; Shelby-James, Tania Maree
    This study investigated the impact of a three-year randomized control trial of different models of service provision on palliative care staff associated with the hospice where the trial was being conducted. Eleven open access de-identified qualitative focus groups were held over a period of three years: three months into the trial, one year after its inception, and at the end of the trial. Four staff groups were involved: inpatient hospice nurses, palliative care outreach nurses, medical palliative specialists, and administrative staff and social workers. Initially the impact of the trial produced high levels of staff stress which largely diminished over time, to be replaced by enthusiasm for the changes achieved and sadness that post trial the perceived benefits gained would be lost. When attempting to change a clinical culture to incorporate research, and in particular where increased staff workload is involved, highly interactive levels of communication and valuing of staff input are required to minimize the stress and burden of this imposition.
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    The evidence base for oxygen for chronic refractory breathlessness: issues, gaps, and a future work plan
    (Elsevier, 2012-09-26) Johnson, Miriam J ; Abernethy, Amy Pickar ; Currow, David Christopher
    Breathlessness or “shortness of breath”, medically termed dyspnoea, remains a devastating problem for many people and those who care for them. As a treatment intervention, administration of opioids to relieve breathlessness is an area where progress has been made with the development of an evidence base. As evidence in support of opioids has accumulated, so has our collective understanding about trial methodology, research collaboration and infrastructure that is crucial to generate reliable research results for palliative care clinical settings. Analysis of achievements to date and what it takes to accomplish these studies provides important insights into knowledge gaps needing further research as well as practical insight into design of pharmacological and non-pharmacological intervention trials in breathlessness and palliative care. This paper presents current understanding of opioids for treating breathlessness, what is still unknown as priorities for future research and highlights methodological issues for consideration in planned studies.
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    How should we conduct and interpret phase III clinical trials in palliative care?
    (Elsevier, 2010-01) Abernethy, Amy Pickar ; Clark, Katherine ; Currow, David Christopher
    The article by Wildiers et al.1 raises some challenges in terms of ethical approaches to phase III end-of-life studies and their interpretation. Although the authors should be commended for undertaking a large, multisite, randomized, controlled trial in palliative care, there are fundamental questions that do need to be addressed before the first steps can be taken to adopt the study's findings into practice.
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    An international initiative to create a collaborative for pharmacovigilance in hospice and palliative care clinical practice
    (Mary Ann Liebert, Inc., 2012-02-21) Currow, David Christopher ; Rowett, Debra Sharon ; Doogue, Matthew ; To, Timothy H M ; Abernethy, Amy Pickar
    Background: Medication registration currently requires evidence of safety and efficacy from adequately powered phase 3 studies. Pharmacovigilance (phase 4 studies, postmarketing data, adverse drug reaction reporting) provide data on more widespread and longer term use. Historically, voluntary reporting systems for pharmacovigilance have had low reporting rates, relying on ad hoc reporting and retrospective chart reviews, or prospective registries have often been limited to specific drugs or clinical conditions. Furthermore, these data are often irrelevant in hospice and palliative care due to the timeliness of which such data become available and the unique characteristics of our population and prescribing: compounding comorbidities, progressive organ failure, accumulation of symptom-specific medications, tendency to attribute toxicity to disease progression, use of old, off-patent medications, and incorporation of evolving evidence. There is a need for prospective, systematic pharmacovigilance in hospice and palliative care. Method: Here we describe an international, Web-based, 128-bit secure initiative to collect pharmacovigilance data documenting net clinical benefit and safety of common medications. The intention is for a diverse and large group of clinical units to record data prospectively on a small deidentified consecutive cohort of patients started on the medication of interest. A new medication would be studied every 3 months. Three key time points (different for each medication) will be assessed for each patient, collecting easily codefiable data at baseline, a point at which clinical benefit should be experienced, and a point at which short- to medium-term toxicities may occur. Toxicities can additionally be recorded at any time they occur. Data collection will take a maximum of 10 minutes per patient. Conclusion: The intention is to create an efficient, relevant system to improve hospice and palliative care with maximally generalizable results.
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    The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea
    (Mary Ann Liebert, Inc., 2013-07-22) Currow, David Christopher ; Quinn, Stephen ; Greene, Aine ; Bull, Janet ; Johnson, Miriam J ; Abernethy, Amy Pickar
    Background: While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern. Methods: This secondary analysis used breathlessness intensity scores (100mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved < 10% improvement over their own baseline at one week (10 mg) were titrated to 20mg and if no response, another week later to 30mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling. Results: Of the 83 participants, 17/52 responders required > 10 mg: 13 participants (20 mg) and 4 (30 mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3mm/ day ( p = 0.16); the average improvement in the first 24 hours of response was 10.9mm (7.0 to 14.7; p < 0.0001), with continued improvement of 2.2 mm/day ( p < 0.001) for six more days. Conclusion: When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered.
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    Off-label prescribing in palliative care – a cross-sectional national survey of Palliative Medicine doctors
    (SAGE Publications, 2012-11-05) To, Timothy H M ; Agar, Meera Ruth ; Shelby-James, Tania Maree ; Abernethy, Amy Pickar ; Doogue, Matthew ; Rowett, Debra Sharon ; Ko, Danielle N ; Currow, David Christopher
    Background: Regulatory bodies including the European Medicines Agency register medications (formulation, route of administration) for specific clinical indications. Once registered, prescription is at clinicians’ discretion. Off-label use is beyond the registered use. While off-label prescribing may, at times, be appropriate, efficacy and toxicity data are often lacking. Aim: The aim of this study was to document off-label use policies (including disclosure and consent) in Australian palliative care units and current practices by palliative care clinicians. Design: A national, cross-sectional survey was conducted online following an invitation letter. The survey asked clinicians their most frequent off-label medication/indication dyads and unit policies. Dyads were classified into unregistered, off-label and on-label, and for the latter, whether medications were nationally subsidised. Setting/participants: All Australian palliative medicine Fellows and advanced trainees. Results: Overall, 105 clinicians responded (53% response rate). The majority did not have policies on off-label medications, and documented consent rarely. In all, 236 medication/indication dyads for 36 medications were noted: 45 dyads (19%) were for two unregistered medications, 118 dyads (50%) were for 26 off-label medications and 73 dyads (31%) were for 12 on-label medications. Conclusions: Off-label prescribing with its clinical, legal and ethical implications is common yet poorly recognised by clinicians. A distinction needs to be made between where quality evidence exists but registration has not been updated by the pharmaceutical sponsor and the evidence has not been generated. Further research is required to quantify any iatrogenic harm from off-label prescribing in palliative care.
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    Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study
    (Elsevier, 2011-04-04) Currow, David Christopher ; McDonald, Christine ; Oaten, Sheila ; Kenny, Bernadette ; Allcroft, Peter ; Frith, Peter Anthony ; Briffa, Michael ; Johnson, Miriam J ; Abernethy, Amy Pickar
    Context Randomised controlled trials (RCTs) can answer questions of efficacy, but rarely generate a complete safety profile. Long term pharmacovigilance studies complement RCTs. Objectives Level I evidence supports short term efficacy of opioids in reducing refractory dyspnoea. This study aims to determine: the minimum effective daily dose of sustained release morphine to reduce refractory breathlessness; and whether net clinical benefits are sustained safely. Methods In a phase II dose increment study, 10mg sustained release morphine was administered daily, and increased by 10mg daily each week to a maximum of 30mg daily. The participant was withdrawn if there were unacceptable side-effects or no response to maximum dose. If participants had a 10% improvement in dyspnoea over their own baseline, they joined a long-term phase IV effectiveness/safety study at that dose. Complying with STROBE guidelines for reporting observational studies, response and side-effects are described, with demographic and clinical characteristics of responders. Results Eighty five participants (65 males, mean age 74, 59% with chronic obstructive pulmonary disease (COPD) provided >30 patient-years of data. Fifty three participants derived ≥10% benefit (35.4% improvement over baseline) giving a response rate of 62% (number needed to treat of 1.6); for 70%, this dose was 10mg/24hours. Benefit was maintained at three months for 28 (33%) people. Breathlessness was reduced significantly (p<0.001) but constipation increased (p<0.001) despite aperients. There were no severe adverse events including no respiratory depression nor hospitalisations. Conclusion Ten mg of sustained release oral morphine daily is safe in this population, and effective for most people.
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    Promoting patient centred palliative care through case conferencing
    (Royal Australian College of General Practitioners, 2007-11) Shelby-James, Tania Maree ; Currow, David Christopher ; Phillips, Paddy Andrew ; Williams, Helena ; Abernethy, Amy Pickar
    BACKGROUND What are the characteristics of case conferences between general practitioners and specialised palliative care services (SPCS)? METHODS Study participants were adults (N=461) with pain in the preceding 3 months who were referred to a SPCS and their GPs (N=230). Patients were randomised to case conferences or routine care by SPCS. RESULTS One hundred and sixty-seven conferences were held; 46 patients withdrew and 142 died before the conference could be conducted. Medicare payment was requested for 72 (43%) conferences. Median time from randomisation to case conference was 52 days (SD: 55), and from case conference to death/end of study was 79 days (SD: 166). Twenty-five percent of conferences had over three health professionals participant; patients and/or their caregivers participated in 91%. Average conference duration was 39 minutes (SD: 13). Mean conference length did not increase when more health professionals were present (3 vs. >3, 39 [SD: 14] vs. 42 [SD 11] minutes, p=0.274), nor when patients/caregivers were present (present vs. absent, 39 [SD: 13] vs. 44 [SD: 14] minutes, p=0.159). DISCUSSION Case conferencing involving SPCS, the GP, other health professionals and the patient can be an efficient part of routine care.
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    The role of benzodiazepines in breathlessness: a single site, open label pilot of sustained release morphine together with clonazepam
    (Mary Ann Liebert, Inc., 2013-04-18) Allcroft, Peter ; Margitanovic, Vera ; Greene, Aine ; Agar, Meera Ruth ; Clark, Katherine ; Abernethy, Amy Pickar ; Currow, David Christopher
    Background: Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid. Methods: This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to KapanolR 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale ≥2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity. Results: Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity. Conclusion: This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.
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    A strategy to advance the evidence base in palliative medicine: formation of a palliative care research cooperative group
    (Mary Ann Liebert, Inc., 2010-11-24) Abernethy, Amy Pickar ; Aziz, Noreen M ; Basch, Ethan ; Bull, Janet ; Cleeland, Charles S ; Currow, David Christopher ; Fairclough, Diane ; Hanson, Laura ; Hauser, Joshua ; Ko, Danielle N ; Lloyd, Linda ; Morrison, R Sean ; Otis-Green, Shirley ; Pantilat, Steve ; Portenoy, Russell K ; Ritchie, Christine ; Rocker, Graeme ; Wheeler, Jane L ; Zafar, S Yousuf ; Kutner, Jean S
    Background: Palliative medicine has made rapid progress in establishing its scientific and clinical legitimacy, yet the evidence base to support clinical practice remains deficient in both the quantity and quality of published studies. Historically, the conduct of research in palliative care populations has been impeded by multiple barriers including health care system fragmentation, small number and size of potential sites for recruitment, vulnerability of the population, perceptions of inappropriateness, ethical concerns, and gate-keeping. Methods: A group of experienced investigators with backgrounds in palliative care research convened to consider developing a research cooperative group as a mechanism for generating high-quality evidence on prioritized, clinically relevant topics in palliative care. Results: The resulting Palliative Care Research Cooperative (PCRC) agreed on a set of core principles: active, interdisciplinary membership; commitment to shared research purposes; heterogeneity of participating sites; development of research capacity in participating sites; standardization of methodologies, such as consenting and data collection/management; agile response to research requests from government, industry, and investigators; focus on translation; education and training of future palliative care researchers; actionable results that can inform clinical practice and policy. Consensus was achieved on a first collaborative study, a randomized clinical trial of statin discontinuation versus continuation in patients with a prognosis of less than 6 months who are taking statins for primary or secondary prevention. This article describes the formation of the PCRC, highlighting processes and decisions taken to optimize the cooperative group's success.