End-of-life research: do we need to build proxy consent into all clinical trial protocols studying the terminal phase?

Research into symptoms that occur at the end of life is paramount for ensuring we provide the best possible care for patients in the terminal phase, yet obtaining informed consent from the study participant is not possible at the time these symptoms occur. Importantly, these questions cannot be answered in any clinical population and defining the net clinical effect of medications used, for example, for noisy respiratory secretions is crucial if the quality of care is to be further improved

Progressing an evidence-base beyond case series

High-quality randomized trials in hospice and palliative care are achievable to provide quality evidence to guide our practice especially if several sites work together to conduct the trial. Palliative medicine is a specialty that is contributing more and more to the care of patients with life limiting disease. It is time we based this practice on highquality evidence and that can only come with high-quality research

A collateral benefit of research in palliative care

A collateral benefit of being in a research-active clinical unit is that there is evidence that better care is delivered. The most dramatic data to date demonstrate that in cardiology, research- active cardiology departments in community and university hospitals deliver better survival than those units that do not enroll people in clinical trials

Informed consent in palliative care clinical trials: challenging but possible

Obtaining informed consent is a key protection that should be afforded universally to people using health services and the basis around which any participation in clinical trials is built. Randomized controlled effectiveness studies are necessary to answer key questions in hospice and palliative care, in order to help systematically improve the quality of care. In order to be properly generalizable, such trials need to have broad inclusion criteria to reflect the population most likely to be affected by the condition. The inclusion of patients who are seriously ill, and therefore potentially vulnerable, requires careful exploration of ethical and legal principles that underpin informed consent. Specific challenges in obtaining informed consent for randomised clinical trials (RCTs) in clinically unstable populations such as hospice and palliative care include higher rates of people with impaired cognitive capacity as well as interventional studies in clinical situations which may present as a sudden change in condition. None of these challenges is unique to hospice and palliative care research, but the combination and frequency with which they are encountered require systematic and considered solutions. This article outlines five different ethically valid consent approaches and discusses their applicability to hospice and palliative care research trials. These include: consent by the patient (at the time of enrolment, in advance of the study, or delayed until after the study has commenced); a proxy (or legally authorised representative); or a consent waiver. Increased use of the less traditional modes of informed consent may lead to greater participation rates in hospice and palliative care trials, thereby improving the evidence base more rapidly in part by better reflecting the population served and hence improving generalizability

Anti-cholinergic load, health care utilization, and survival in people with advanced cancer: a pilot study

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

Pindaan AUKU Bukan Kosmetik - Pelajar IPT tetap digalak aktif kegiatan sihat: Mohamed Khaled

Menteri Pengajian Tinggi, Datuk Seri Mohamed Khaled Nordin menafikan dakwaan pindaan Akta Universiti 1971 (AUKU) hanya sekadar kosmetik dan masih mengongkong kebebasan pelajar

Off-label prescribing in palliative care – a cross-sectional national survey of Palliative Medicine doctors

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

The preventative role of exogenous melatonin administration to patients with advanced cancer who are at risk of delirium: study protocol for a randomized controlled trial

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Delirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer. The aim of this article is to describe the design of a feasibility study that is being conducted to inform a larger randomized, placebo-controlled, double-blind trial (RCT) to evaluate the role of exogenously administered melatonin in preventing delirium in patients with advanced cancer. Methods/Design Adult patients with a cancer diagnosis who are admitted to the palliative care unit will be randomized into a treatment or placebo group. The pharmacological intervention consists of a single daily dose of immediate-release melatonin (3 mg) at 21:00 ± 1 h, from day 1 to day 28 of admission. The primary objective of this initial study is to assess the feasibility of conducting the proposed RCT by testing recruitment and retention rates, appropriateness of study outcome measures, acceptability of study procedures and effectiveness of the blinding process. The primary outcome measure of the proposed larger RCT is time to first inpatient incident episode of delirium. We also plan to collect data on incident rates of delirium and patient-days of delirium, adjusting for length of admission. Discussion The outcomes of this feasibility study will provide information on recruitment and retention rates, protocol violation frequency, effectiveness of the blinding process, acceptability of the study procedures, and safety of the proposed intervention. This will inform the design of a fully powered randomized controlled trial to evaluate the preventative role of melatonin administration in patients with advanced cancer. Trial registration Registered with ClinicalTrials.gov: NCT02200172 Registered on 21 July 2014. Health Canada protocol number: BRI-MELAT-2013 (Final approved protocol version (Version 3): 18 June 2014) (Notice of Amended Authorization (NOA) received 14 November 2014). Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1525-8) contains supplementary material, which is available to authorized users

The Prospective Evaluation of the Net Effect of Red Blood Cell Transfusions in Routine Provision of Palliative Care.

"Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/jpm.2017.0072” This author accepted manuscript is made available following 12 month embargo from date of publication (June 2017) in accordance with the publisher’s archiving policyBackground Red Blood Cell (RBC) transfusions are commonly used in palliative care. RBCs are a finite resource, transfusions carry risks, and the net effect (benefits and harms) is poorly defined for people with life-limiting illnesses. Aim The aim of this study was to examine the indications and the effects of RBC transfusion in palliative care patients. Design This international, multisite, prospective consecutive cohort study assessed target symptoms (fatigue, breathlessness, generalised weakness, or dizziness) prior to transfusion and at day 7 by treating clinicians, using National Cancer Institute Common Terminology Criteria for Adverse Events. Assessment of harms was made at day 2. Setting/participants One-hundred and one transfusions with day 7 followup were collected. Median age was 72·0 (IQR 61·5-83·0) years, 58% male, and mean Australian-modified Karnofsky Performance Status of 48 (SD 17). Results A mean 2·1 (SD 0·6) units was transfused. The target symptom was fatigue (61%), breathlessness (16%), generalized weakness (12%), dizziness (6%) or other (5%). Forty-nine percent of transfusions improved the primary target symptom, and 78% of transfusions improved at least one of the target symptoms. Harms were infrequent and mild. An AKPS of 40-50% was associated with higher chances of symptomatic benefit in the target symptom, however no other predictors of response were identified. Conclusions In the largest prospective consecutive case series to date, clinicians generally reported benefit, with minimal harms. Ongoing work is required to define the optimal patient- and clinician-reported haematological and functional outcome measures to optimise the use of donor blood and minimise transfusion-associated risk

Evidence-based occupational therapy for people with dementia and their families: What clinical practice guidelines tell us and implications for practice

This author accepted manuscript (post print) is made available following a 12 month embargo from date of publication (3 October 2016) in accordance with the publisher copyright policy.Background: The first evidence based Clinical Practice Guidelines and Principles of Care for People with Dementia in Australia have been released. The Guidelines detail a number of important evidence based recommendations for occupational therapists. Aim: The aim of this paper is (1) to provide an overview of Guideline development, and (2) to describe the evidence supporting a recommendation for occupational therapy. Common characteristics of effective occupational therapy programs for people with dementia are described. Methods: Guideline development involved adaptation of existing high quality guidelines developed overseas and 17 systematic reviews to ensure that the most recent high quality evidence was included. One of the systematic reviews involved examining the evidence for interventions to promote independence in people with dementia. Specifically, we looked at the evidence for occupational therapy and its effect on activities of daily living, quality of life and carer impact. Results: A total of 109 recommendations are included in the Guidelines. Occupational therapy was found to significantly increase independence in activities of daily living and improve quality of life. Effective occupational therapy programs involve: environmental assessment, problem solving strategies, carer education and interactive carer skills training. Conclusion: Occupational therapists working with people with dementia in community settings should ensure that their time is spent on those aspects of intervention that are shown to be effective