".the author has packaged an excellent and modern set of topics around the development and use of quantitative models... If you need to learn about resampling, this book would be a good place to ...start."
-Technometrics (Review of the Second Edition)
This thoroughly revised and expanded third edition is a practical guide to data analysis using the bootstrap, cross-validation, and permutation tests. Only requiring minimal mathematics beyond algebra, the book provides a table-free introduction to data analysis utilizing numerous exercises, practical data sets, and freely available statistical shareware.
Topics and Features
* Practical presentation covers both the bootstrap and permutations along with the program code necessary to put them to work.
* Includes a systematic guide to selecting the correct procedure for a particular application.
* Detailed coverage of classification, estimation, experimental design, hypothesis testing, and modeling.
* Suitable for both classroom use and individual self-study.
New to the Third Edition
* Procedures are grouped by application; a prefatory chapter guides readers to the appropriate reading matter.
* Program listings and screen shots now accompany each resampling procedure: Whether one programs in C++, CART, Blossom, Box Sampler (an Excel add-in), EViews, MATLAB, R, Resampling Stats, SAS macros, S-PLUS, Stata, or StatXact, readers will find the program listings and screen shots needed to put each resampling procedure into practice.
* To simplify programming, code for readers to download and apply is posted at http://www.springeronline.com/0-8176-4386-9.
* Notation has been simplified and, where possible, eliminated.
* A glossary and answers to selected exercises are included.
With its accessible style and intuitive topic development, the book is an excellent basic resource for the power, simplicity, and versatility of resampling methods. It is an essential resource for statisticians, biostatisticians, statistical consultants, students, and research professionals in the biological, physical, and social sciences, engineering, and technology.
Background: Clinical trials rarely explore the patient's lived experience. Qualitative research bridges the gap between evidence-based medicine and the patient's journey.
Objective: The aim of this ...article is to explore key aspects of the lived experience of patients with end-stage heart failure (ESHF). This will allow clinicians to better engage with patients and carers faced with this condition.
Discussion: Psychological and spiritual distress are common in ESHF. Patients with ESHF often feel socially isolated. Inadequate communication from clinical staff is a common negative experience for patients to which they frequently resign themselves. The ambiguous illness trajectory in advanced heart failure makes both general practitioners and cardiologists uncomfortable initiating advance care planning and less sure of their roles in these discussions. Patients have spiritual concerns that they reportedly feel awkward raising during consultation. Attention to these concerns will help build rapport and provide more personalised care for patients with ESHF.
Background
Many palliative care patients have a reduced oral intake during their illness. The management of this can include the provision of medically assisted nutrition with the aim of prolonging ...the length of life of a patient, improving their quality of life, or both. This is an updated version of the original Cochrane review published in Issue 4, 2008.
Objectives
To determine the effect of medically assisted nutrition on the quality and length of life of palliative care patients.
Search methods
We identified studies from searching Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, CANCERLIT, Caresearch, Dissertation s, SCIENCE CITATION INDEX and the reference lists of all eligible trials, key textbooks and previous systematic reviews. The date of the latest search was 26 March 2014.
Selection criteria
All relevant randomised controlled trials (RCTs) or prospective controlled trials (if no RCTs were found).
Data collection and analysis
We found no RCTs or prospectively controlled trials that met the inclusion criteria.
Main results
The original review identified four prospective non‐controlled trials and the updated search in 2014 identified one more (plus an updated version of a Cochrane review on enteral feeding in motor neuron disease). There were five prospective non‐controlled trials (including one qualitative study) that studied medically assisted nutrition in palliative care participants, and one Cochrane systematic review (on motor neuron disease that found no RCTs), but no RCTs or prospective controlled studies.
Authors' conclusions
Since the last version of this review, we found no new studies. There are insufficient good‐quality trials to make any recommendations for practice with regards to the use of medically assisted nutrition in palliative care patients.
Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids but little ...high-quality evidence to guide clinicians. This study aims to define the role of a 1:1 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.
One hundred fifty participants will be recruited from five sites within the Queensland Palliative Care Research Group (QPCRG) and randomly assigned to an active treatment or placebo group. This study is a pragmatic multicentre, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:1 THC/CBD cannabinoid preparation. It will compare efficacy and safety outcomes of a titrated dose (10 mg/10 mg/mL oral solution formulation, dose range 2.5 mg/2.5 mg-30 mg/30 mg/day) against placebo. There is a 2-week patient-determined titration phase, using escalating doses of 1:1 THC/CBD or placebo, to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians. The primary objective is to assess the effect of escalating doses of a 1:1 THC/CBD cannabinoid preparation against placebo on change in total symptom score, with secondary objectives including establishing a patient-determined effective dose, the change in total physical and emotional sores, global impression of change, anxiety and depression, opioid use, quality of life and adverse effects.
This will be the first placebo-controlled clinical trial to rigorously evaluate the efficacy, safety and acceptability of 1:1 THC/CBD for symptom relief in advanced cancer patients. This study will allow the medical community to have some evidence to present to patients wishing to access cannabis for their symptoms caused by advanced malignancy.
ACTRN, ACTRN12619000037101 . Registered on 14 January 2019. Trial Sponsor: Mater Misericordiae Limited (MML) and Mater Medical Research Institute Limited (MMRI)-Raymond Terrace, South Brisbane, Brisbane, QLD, Australia.
Background
Dyspnoea is a common symptom in advanced cancer, with a prevalence of up to 70% among patients at end of life. The cause of dyspnoea is often multifactorial, and may cause considerable ...psychological distress and suffering. Dyspnoea is often undertreated and good symptom control is less frequently achieved in people with dyspnoea than in people with other symptoms of advanced cancer, such as pain and nausea. The exact mechanism of action of corticosteroids in managing dyspnoea is unclear, yet corticosteroids are commonly used in palliative care for a variety of non‐specific indications, including pain, nausea, anorexia, fatigue and low mood, despite being associated with a wide range of adverse effects. In view of their widespread use, it is important to seek evidence of the effects of corticosteroids for the management of cancer‐related dyspnoea.
Objectives
To assess the effects of systemic corticosteroids for the management of cancer‐related breathlessness (dyspnoea) in adults.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index Web of Science, Latin America and Caribbean Health Sciences (LILACS) and clinical trial registries, from inception to 25 January 2018.
Selection criteria
We included randomised controlled trials that included adults aged 18 years and above. We included participants with cancer‐related dyspnoea when randomised to systemic corticosteroids (at any dose) administered for the relief of cancer‐related dyspnoea or any other indication, compared to placebo, standard or alternative treatment.
Data collection and analysis
Five review authors independently assessed trial quality and three extracted data. We used means and standard deviations for each outcome to report the mean difference (MD) with 95% confidence interval (CI). We assessed the risk of bias and quality of evidence using GRADE. We extracted primary outcomes of sensory‐perceptual experience of dyspnoea (intensity of dyspnoea), affective distress (quality of dyspnoea) and symptom impact (burden of dyspnoea or impact on function) and secondary outcomes of serious adverse events, participant satisfaction with treatment and participant withdrawal from trial.
Main results
Two studies met the inclusion criteria, enrolling 157 participants (37 participants in one study and 120 in the other study), of whom 114 were included in the analyses. The studies compared oral dexamethasone to placebo, followed by an open‐label phase in one study. One study lasted seven days, and the duration of the other study was 15 days.
We were unable to conduct many of our predetermined analyses due to different agents, dosages, comparators and outcome measures, routes of drug delivery, measurement scales and time points. Subgroup analysis according to type of cancer was not possible.
Primary outcomes
We included two studies (114 participants) with data at one week in the meta‐analysis for change in dyspnoea intensity/dyspnoea relief from baseline. Corticosteroid therapy with dexamethasone resulted in an MD of lower dyspnoea intensity compared to placebo at one week (MD –0.85 lower dyspnoea (scale 0–10; lower score = less breathlessness), 95% CI ‐1.73 to 0.03; very low‐quality evidence), although we were uncertain as to whether corticosteroids had an important effect on dyspnoea as results were imprecise. We downgraded the quality of evidence by three levels from high to very low due to very serious study limitations and imprecision.
One study measured affective distress (quality of dyspnoea) and results were similar between groups (29 participants; very low‐quality evidence). We downgraded the quality of the evidence three times for imprecision, inconsistency, and serious study limitations.
Both studies assessed symptom impact (burden of dyspnoea or impact on function) (113 participants; very low‐quality evidence). In one study, it was unclear whether dexamethasone had an effect on dyspnoea as results were imprecise. The second study showed more improvement for physical well‐being scores at days eight and 15 in the dexamethasone group compared with the control group, but there was no evidence of a difference for FACIT social/family, emotional or functional scales. We downgraded the quality of the evidence three times for imprecision, inconsistency, and serious study limitations.
Secondary outcomes
Due to the lack of homogenous outcome measures and inconsistency in reporting, we could not perform quantitative analysis for any secondary outcomes. In both studies, the frequency of adverse events was similar between groups, and corticosteroids were generally well tolerated. The withdrawal rates for the two studies were 15% and 36%. Reasons for withdrawal included lost to follow‐up, participant or carer (or both) refusal, and death due to disease progression. We downgraded the quality of evidence for these secondary outcomes by three levels from high to very low due to serious study limitations, inconsistency and imprecision.
Neither study examined participant satisfaction with treatment.
Authors' conclusions
There are few studies assessing the effects of systemic corticosteroids on cancer‐related dyspnoea in adults with cancer. We judged the evidence to be of very low quality that neither supported nor refuted corticosteroid use in this population. Further high‐quality studies are needed to determine if corticosteroids are efficacious in this setting.
This research explores the implementation of a child-centred, co-designed, community-embedded program called 'Young Doctors for Life' (YDFL). YDFL is designed to improve health and wellbeing outcomes ...for Aboriginal children in the middle childhood years. Focus is given in this paper to the processes of program adaptation of the YDFL to ensure local cultural relevance, drawing on the experiences and perspectives of children, parents, schoolteachers, and the implementation team.
Two focus groups with program stakeholders were convened. The first group consisted of three members from the local Aboriginal implementation team, and the second group comprised two members of the program design team. Children (
= 22) and schoolteachers (
= 2) participated in semi-structured interviews. Parent survey data (
= 16) were also collected and included. The data was analysed, guided by the five elements of implementation as outlined in the Hexagon Implementation framework (Capacity; Fit; Need; Usability; Support; and Evidence), which served as
themes.
YDFL provides a promising example of how programs can be adapted with and for Aboriginal communities to support child health. Successful adaptation and implementation of this program required a co-design approach engaging program designers and the local implementation team. Community collaboration was also essential to identifying and addressing local community goals and aligning new programs with local service and cultural contexts.
Health programs to support positive child outcomes are more likely to be successful when they share their focus between the risks and challenges within a community, and the positive, protective factors that can be leveraged to support children to flourish. Stakeholder engagement and community leadership are necessary to achieve meaningful program adaptation and implementation in Aboriginal communities.
The end of life represents a therapeutic context that acutely raises cultural and linguistic specificities, yet there is very little evidence illustrating the importance of such dynamics in shaping ...choices, trajectories and care practices. Culture and language interplay to offer considerable potential challenges to both patient and provider, with further work needed to explore patient and caregiver perspectives across cultures and linguistic groups, and provider perspectives. The objective of this study was to develop a critical, evidence-based understanding of the experiences of people from Culturally and Linguistically Diverse (CALD) backgrounds, and their caregivers, in a palliative care setting.
A qualitative study, using semi-structured interviews to explore key experiences and perspectives of CALD patients and caregivers currently undergoing treatment under oncology or palliative care specialists in two Australian hospitals. Interviews were digitally audio recorded and transcribed in full. A thematic analysis was conducted utilising the framework approach.
Sixteen patients and fourteen caregivers from a range of CALD backgrounds participated in semi-structured interviews. The research identified four prevalent themes among participants: (1) Terminology in the transition to palliative care; (2) Communication, culture and pain management; (3) (Not) Talking about death and dying; and, (4) Religious faith as a coping strategy: challenging the terminal diagnosis.
CALD patients and caregivers' experiences are multifaceted, particularly in negotiating linguistic difficulties, beliefs about treatment, and issues related to death and dying. Greater attention is needed to develop effective communication skills, recognise CALD patients' particular cultural, linguistic and spiritual values and needs, and acknowledge the unique nature of each doctor-patient interaction.
Cancer pain is the most feared symptom at end of life. Methadone has advantages over other opioids but is associated with significant variability in clinical response, making dosing challenging in ...practice. OPRM1 is the most studied pharmacogene associated with the pharmacodynamics of opioids, however reports on the association of the A118G polymorphism on opioid dose requirements are conflicting, with no reports including methadone as the primary intervention. This association study on OPRM1 A118G and response to methadone for pain management, includes a review of this genetic factor's role in inter-patient variability. Fifty-four adult patients with advanced cancer were recruited in a prospective, multi-centre, open label dose individualization study. Patient characteristics were not shown to influence methadone response, and no significant associations were observed for methadone dose or pain score. The findings of our review of association studies for OPRM1 A118G in advanced cancer pain demonstrate the importance of taking ancestry into account. While our sample size was small, our results were consistent with European populations, but in contrast to studies in Chinese patients, where carriers of the A118G polymorphism were associated with higher opioid dose requirements. Pharmacogenetic studies in palliative care are challenging, continued contribution will support future genotype-based drug dosing guidelines.
Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is ...little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.
This study is a multicentre, randomised, placebo controlled, two arm, parallel trial of escalating doses of oral CBD. It will compare efficacy and safety outcomes of a titrated dose of CBD (100 mg/mL formulation, dose range 50 mg to 600 mg per day) against placebo. There is a 2-week patient determined titration phase, using escalating doses of CBD or placebo to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians.
A major strength of this study is that it will target symptom burden as a whole, rather than just individual symptoms, in an attempt to describe the general improvement in wellbeing previously reported by some patients in open label, non controlled trials of medicinal cannabis. Randomisation with placebo is essential because of the well-documented over reporting of benefit in uncontrolled trials and high placebo response rates in cancer pain trials. This will be the first placebo controlled clinical trial to evaluate rigorously the efficacy, safety and acceptability of CBD for symptom relief in advanced cancer patients. This study will provide the medical community with evidence to present to patients wishing to access medicinal cannabis for their cancer related symptoms.
ALCTRN12618001220257 Registered 20/07/2018.
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