General practitioners' engagement in end-of-life care: a semi-structured interview study.

BACKGROUND: Early identification of approaching end-of-life and care planning improve outcomes at the end of life. Nevertheless, the majority of people who die are not identified in time to enable appropriate care planning. We aimed to describe the challenges general practitioners (GPs) found in providing end-of-life care; what prompted GPs to identify and discuss approaching end of life with their patient and how their practice changed. METHODS: We conducted a qualitative study of 15 Australian GPs using semi-structured interviews, examining end-of-life care of one of their randomly selected, deceased patients. Interviews were analysed using a general inductive approach. RESULTS: When a life-limiting prognosis was articulated, GPs integrated end-of-life care into their clinical care directly. Care often included a care plan developed in consultation with the patient. Even when death was not articulated, GPs were aware of approaching end of life and changed their focus to comfort of the patient. GPs generally had an informal care plan in mind, but this developed gradually and without discussing these plans with the patient. How GPs provided end-of-life care depended primarily on patient traits (eg, willingness to discuss physical decline) and the GP's characteristics (eg, experience, training and consulting style). CONCLUSIONS: GPs were aware of their patients' approaching end of life and care was adjusted accordingly. However, under certain circumstances this was not explicitly articulated and discussed. It is not clear if implicit but unarticulated end-of-life care is sufficient to meet patients' needs. Future studies should investigate this.

Systematic review of the effectiveness, barriers and facilitators to general practitioner engagement with specialist secondary services in integrated palliative care.

The general practitioner (GP) has a critical role in an integrated model of palliative care as they often know the patient and carer well, are experts in generalist care and have knowledge of health and social services in the community. Specialist palliative services have insufficient capacity to meet demand and those with non-cancer terminal conditions and those from rural and remote areas are underserved. Research has focused on improving access to palliative care by engaging the GP with specialist secondary services in integrated palliative care. OBJECTIVES: (1) Evaluate the effectiveness of interventions designed to engage GPs and specialist secondary services in integrated palliative care; and (2) identify the personal, system and structural barriers and facilitators to integrated palliative care. METHOD: MEDLINE, EMBASE and CINAHL were searched. Any study of a service that engaged the GP with specialist secondary services in the provision of palliative care was included. GP engagement was defined as any organised cooperation between the GP and specialist secondary services in the care of the patient including shared consultations, case conferences that involved at least both the GP and the specialist clinician and/or other secondary services, and/or any formal shared care arrangements between the GP and specialist services. The specialist secondary service is either a specialist palliative service or a service providing specialist care to a palliative population. A narrative framework was used to describe the findings. RESULTS: 17 studies were included. There is some evidence that integrated palliative care can reduce hospitalisations and maintain functional status. There are substantial barriers to providing integrated care. Principles and facilitators of the provision of integrated palliative care are discussed. CONCLUSIONS: This is an emerging field and further research is required assessing the effectiveness of different models of integrated palliative care.

A series of n-of-1 trials of stimulants in brain injured children.

BACKGROUND: There is controversy about whether central nervous system stimulant (CNS) medication is an effective method of treating acquired attention deficits in children with acquired brain injury (ABI). OBJECTIVE: The primary objective was to determine the effectiveness of stimulants on attention, concentration and executive function in children with ABI. METHODS: Randomised, double-blind, placebo-controlled, multi-centre n-of-1 trials of stimulants assessing effect on attention, concentration and executive function in 53 children and adolescents with ABI who were outpatients of three tertiary hospitals in Australia. Trials consisted of 3 two-week cycles, each cycle consisting of stimulant medication at doses titrated by physician (1 week) and placebo (1 week) in random order. The effect on parent and teacher Conners' 3 and Behaviour Rating Inventory of Executive Function (BRIEF) was analysed using hierarchical Bayesian methods. RESULTS: Overall, Teacher Conners' Hyperactivity/Impulsivity and Teacher BRIEF Global Executive scales showed important improvement (T-score mean change 2.6; 95% credible interval (CI): 0.4, 4.9; posterior probability of mean change >0 : 0.99; T-score mean change 3.1; 95% CI: -0.1, 6.4; posterior probability of mean change >0 : 0.97). There were no important improvements in parent/guardian-reported primary outcomes. There was heterogeneity in response identified through individual results of the N-of-1 trials. CONCLUSIONS: N-of-1 trials have a clear role in identifying those children/adolescents with ABI and secondary Attention Deficit Hyperactivity Disorder (ADHD) who have important improvements, or worsening on stimulants. The results can only be generalized to children/adolescents who have an apparent pre-trial clinical effect from stimulants.

Testing pilocarpine drops for dry mouth in advanced cancer using n-of-1 trials: A feasibility study.

BACKGROUND: Dry mouth is a common and troublesome symptom in palliative care. Pilocarpine is a cholinergic agent that promotes salivation. AIM: This study aimed to test the feasibility of using n-of-1 trials to test pilocarpine drops compared to placebo, for patients of palliative care units with advanced cancer, who experienced dry mouth. DESIGN: This was an N-of-1 study, in which each participant was offered three cycles of pilocarpine drops 4% (6 mg tds) (3 days) and placebo drops (3 days) in random order. SETTING/PARTICIPANTS: Participants were patients of specialist palliative care services with advanced cancer assessed as having a dry mouth, defined as having a score of ⩾ 3 on an 11-point self-rated xerostomia numerical rating scale, from any cause. Patients self-completed a diary using validated symptom and quality-of-life scores. The randomisation order was unmasked at the end of each person's trial by a clinician independent of the trial to allow a treatment decisions for individual patients to be made. RESULTS: Nine patients completed at least 1 cycle; 33 cycles of data were completed in total, comprising 438 doses of pilocarpine. Four patients completed the trial: two responded and two did not. Most withdrawals related to deteriorating condition, unacceptable toxicity, non-compliance with study procedures or withdrawal of consent. Many issues contributed to slow recruitment and high withdrawal rate. CONCLUSION: The formulation of pilocarpine drops proved unacceptable to most participants. More work is required to determine an appropriate formulation, dose and method of delivery and then a retest of pilocarpine drops for this symptom.

The Effect of Methylphenidate on Fatigue in Advanced Cancer: An Aggregated N-of-1 Trial.

CONTEXT: Fatigue is common in life-limiting cancer. Methylphenidate (MPH), a psychostimulant, may be a useful therapy. Gathering evidence in patients with advanced cancer can be challenging. OBJECTIVES: To determine if MPH improves cancer-related fatigue in people with advanced cancer. METHODS: N-of-1 trials are multicycle, double-blind, randomized, controlled crossover trials using standardized measures of effect in individuals. They are normally used to assess treatment effects in individuals. Aggregated N-of-1 trials from participants with end-stage cancer suffering fatigue were used to assess the group effect of MPH, producing an estimate of equivalent power to a parallel-group randomized controlled trial (RCT) but requiring less than half of the sample size. Up to three cycles of MPH 5 mg twice daily (three days) vs. identical placebo (three days) capsules were offered to participants. Primary outcome was improvement in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale and the Wu Cancer Fatigue Scale. Analysis used Bayesian statistical methods using intention-to-treat principles. RESULTS: Forty-three participants completed 84 cycles of MPH and placebo in random order, exceeding sample size estimates. Overall, MPH did not improve fatigue (mean difference 3.2; 95% credible interval -2.0, 9.0; posterior probability of favorable effect 0.890). Eight participants showed important improvement, and one participant showed important worsening of fatigue on MPH. There were no features that distinguished participants whose fatigue responded to MPH compared with those who did not. CONCLUSION: MPH does not improve fatigue in the population of patients with end-stage cancer. Aggregated N-of-1 trial methodology is feasible and produces population-based sample estimates with less than half the sample size required for the equivalent parallel-group RCT. It also identified individuals who did and did not respond to MPH, which is a feature difficult to achieve in a standard RCT. The study was registered with the Australian Clinical Trials Registry (12609000794202).

Aggregated n-of-1 trials of central nervous system stimulants versus placebo for paediatric traumatic brain injury--a pilot study.

BACKGROUND: In 2006 there were 432,700 people in Australia who had acquired brain injury (ABI) with some limitation of activities; 90% of these were traumatic brain injuries (TBIs) and nearly a third sustained injury below age 15 years. One to four years post injury, 20% to 46% of children with traumatic brain injury (TBI) have clinically significant disorders of attention. There is controversy as to whether central nervous system (CNS) stimulants can be an effective method of treating these.Objectives were to determine the efficacy of CNS stimulants for children with TBI, and to calculate the sample size for a larger trial using the Conners' 3 Parent Rating Scales Score as the primary endpoint. METHODS: Pilot series of aggregated prospective randomised, double-blind, n-of-1 trials of stimulant versus placebo within individual patients. SETTING: tertiary children's public hospital. PARTICIPANTS: ten children aged 6 to 16 years more than 12 months post TBI with attention, concentration and behavioral difficulties on stimulants. INTERVENTIONS: Three cycles of methylphenidate or dexamphetamine orally at doses titrated by physician compared to placebo. MAIN OUTCOME MEASURES: Conners 3 Parent (Conners 3-P) and Teacher (Conners 3-T) Rating Scales (Global Index), Behaviour Rating Inventory of Executive Function (BRIEF) and Eyberg Child Behaviour Inventory (ECBI). RESULTS: Five of ten patients completed the study. Data from 18 completed cycles from seven patients were analysed. The posterior mean difference between stimulant and placebo scores for the Conners 3-PS (Global Index) was 2.3 (SD 6.2; 95% credible region -1.0 to 6.1; posterior probability that this mean difference was greater than zero was 0.92), and for the Conners 3-T (Global Index) the posterior mean difference was 5.9 (SD 4.5; 95% credible region -3.1 to 14.9; posterior probability 0.93). Posterior mean differences suggest improvement in behaviour and executive function and a decrease in number and intensity of child behaviour problems when taking stimulants compared to placebo. Taken together these data are suggestive of a small benefit at group level. CONCLUSIONS: In this pilot study, there was sufficient evidence that stimulants may be useful in management of behavioral and cognitive sequelae following TBI, to warrant a larger trial. TRIAL REGISTRATION: he trial was registered with the Australian and New Zealand Clinical Trials Registry: registration number ACTRN12609000873224.

Do pilocarpine drops help dry mouth in palliative care patients: a protocol for an aggregated series of n-of-1 trials.

BACKGROUND: It is estimated that 39,000 Australians die from malignant disease yearly. Of these, 60% to 88% of advanced cancer patients suffer xerostomia, the subjective feeling of mouth dryness. Xerostomia has significant physical, social and psychological consequences which compromise function and quality of life. Pilocarpine is one treatment for xerostomia. Most studies have shown some variation in individual response to pilocarpine, in terms of dose used, and timing and extent of response.We will determine a population estimate of the efficacy of pilocarpine drops (6 mg) three times daily compared to placebo in relieving dry mouth in palliative care (PC) patients. A secondary aim is to assess individual patients' response to pilocarpine and provide reports detailing individual response to patients and their treating clinician. METHODS/DESIGN: Aggregated n-of-1 trials (3 cycle, double blind, placebo-controlled crossover trials using standardized measures of effect). Individual trials will identify which patients respond to the medication. To produce a population estimate of a treatment effect, the results of all cycles will be aggregated. DISCUSSION: Managing dry mouth with treatment supported by the best possible evidence will improve functional status of patients, and improve quality of life for patients and carers. Using n-of-1 trials will accelerate the rate of accumulation of high-grade evidence to support clinical therapies used in PC. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry Number: 12610000840088.

Central nervous system stimulants for secondary attention deficit-hyperactivity disorder after paediatric traumatic brain injury: a rationale and protocol for single patient (n-of-1) multiple cross-over trials.

BACKGROUND: It is estimated that 22,800 children were living with an Acquired Brain Injury (ABI) (0.6% of children aged under 15 years) in Australia during 2003. Many children after a traumatic brain injury will experience difficulties with attention and concentration; a condition termed secondary Attention Deficit-Hyperactivity Disorder. There is conflicting evidence on whether treatment with stimulant therapy with medications such as methylphenidate or dexamphetamine will improve the attention and behavior of children with this condition. METHODS/DESIGN: Single patient trials (n-of-1s or SPTs) evaluate the effect of titrated doses of psychostimulants methylphenidate or dexamphetamine compared to placebo on attention and behavior, in children with TBI and secondary ADHD. The aggregation of multiple SPTs will produce a population estimate of the benefit. Forty-two children will be registered into the trial through rehabilitation services at three large children's hospitals in Australia. Patients will complete up to 3 cycles of treatment. Each cycle is 2 weeks long comprising seven days each of treatment and placebo, with the first two days of each cycle considered a washout period and the data not analysed. The order of treatment and placebo is randomly allocated for each cycle. The Conners' Parent Rating Scales long forms will be employed to measure change in attention-deficit/hyperactivity and related problems of the child, and the primary outcome measure is the Conners' Global Index Parent Version. Secondary outcomes include the teacher and child (if aged > 12 years) Conners' Rating Scales, the Behaviour Rating Inventory of Executive Function among other measures. This study will provide high-level evidence using a novel methodological approach to inform clinicians about the most appropriate treatment for individual children. Through aggregation of individual trials, a population estimate of treatment effect will be provided to guide clinical practice in the treatment of children with secondary ADHD after a traumatic brain injury. DISCUSSION: This study employs an innovative methodological approach on the effectiveness of CNS stimulants for secondary ADHD from a brain injury. The findings will both guide clinicians on treatment recommendations, and inform the concept and acceptance of SPTs in paediatric research. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12609000873224.

Using aggregated single patient (N-of-1) trials to determine the effectiveness of psychostimulants to reduce fatigue in advanced cancer patients: a rationale and protocol.

BACKGROUND: It is estimated that 29% of deaths in Australia are caused by malignant disease each year and can be expected to increase with population ageing. In advanced cancer, the prevalence of fatigue is high at 70-90%, and can be related to the disease and/or the treatment. The negative impact of fatigue on function (physical, mental, social and spiritual) and quality of life is substantial for many palliative patients as well as their families/carers. METHOD/DESIGN: This paper describes the design of single patient trials (n-of-1 s or SPTs) of a psychostimulant, methylphenidate hydrochloride (MPH) (5 mg bd), compared to placebo as a treatment for fatigue, with a population estimate of the benefit by the aggregation of multiple SPTs. Forty patients who have advanced cancer will be enrolled through specialist palliative care services in Australia. Patients will complete up to 3 cycles of treatment. Each cycle is 6 days long and has 3 days treatment and 3 days placebo. The order of treatment and placebo is randomly allocated for each cycle. The primary outcome is a reduction in fatigue severity as measured by the Functional Assessment of Cancer Therapy-fatigue subscale (FACIT-F). Secondary outcomes include adverse events, quality of life, additional fatigue assessments, depression and Australian Karnovsky Performance Scale. DISCUSSION: This study will provide high-level evidence using a novel methodological approach about the effectiveness of psychostimulants for cancer-related fatigue. If effective, the findings will guide clinical practice in reducing this prevalent condition to improve function and quality of life. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000794202.

Pilot study to determine the optimal dose of methylphenidate for an n-of-1 trial for fatigue in patients with cancer.

PURPOSE: In advanced cancer, the prevalence of fatigue is high and can be related to treatment or disease. Methylphenidate hydrochloride (MPH) is a central nervous system stimulant that has been used to palliate fatigue. There is no standard dose for MPH when used for this indication; recommended doses range from 5­20 + mg/d. METHOD: To identify a dose to test formally in a subsequent n-of-1 trial of fatigue, we recruited patients with advanced cancer and a fatigue score of 4 or more on a 10-point scale. Following a 3-day baseline assessment, each patient titrated MPH at doses ranging from 5 mg/d to 15 mg twice daily at 3-day intervals. In a daily diary, patients recorded measures of fatigue, depression, toxicity, and symptom control. RESULTS: Ten patients provided consent, 9 completed 8 days and 5 received maximum dose at day 15. Three patients were unwilling to increase the dose to maximum levels as they were satisfied with the response at a lower dose. Across all patients, there was a pattern of rapidly improving fatigue and depression scores to day 9 (5 mg twice daily), with minimal improvement thereafter. CONCLUSION: The results indicate a dose of 5 mg twice daily for the definitive study. There was little correlation between performance status and maximum tolerated dose. No patient withdrew because of toxicity.

Can technology and the media help reduce dysfunctional parenting and increase engagement with preventative parenting interventions?

In an evaluation of the television series "Driving Mum and Dad Mad," 723 families participated and were randomly assigned to either a standard or technology enhanced viewing condition (included additional Web-support). Parents in both conditions reported significant improvements from pre- to postintervention in their child's behavior, dysfunctional parenting, parental anger, depression, and self-efficacy. Short-term improvements were maintained at 6-months follow-up. Regressions identified predictors of program outcomes and level of involvement. Parents who watched the entire series had more severe problems at preintervention and high sociodemographic risk than parents who did not watch the entire series. Few sociodemographic, child, or parent variables assessed at preintervention predicted program outcomes or program engagement, suggesting that a wide range of parents from diverse socioeconomic status benefited from the program. Media interventions depicting evidence-based parenting programs may be a useful means of reaching hard to engage families in population-level child maltreatment prevention programs.

Does self-directed and web-based support for parents enhance the effects of viewing a reality television series based on the Triple P-Positive Parenting Programme?

BACKGROUND: This study investigated whether providing self-directed and web-based support for parents enhanced the effects of viewing a reality television series based on the Triple P - Positive Parenting Programme. METHOD: Parents with a child aged 2 to 9 (N = 454) were randomly assigned to either a standard or enhanced intervention condition. In the standard television alone viewing condition, parents watched the six-episode weekly television series, 'Driving Mum and Dad Mad'. Parents in the enhanced television viewing condition received a self-help workbook, extra web support involving downloadable parenting tip sheets, audio and video streaming of positive parenting messages and email support, in addition to viewing the television series. RESULTS: Parents in both conditions reported significant improvements in their child's disruptive behaviour and improvements in dysfunctional parenting practices. Effects were greater for the enhanced condition as seen on the ECBI, two of the three parenting indicators and overall programme satisfaction. However, no significant differences were seen on other measures, including parent affect indicators. The level of improvement was related to number of episodes watched, with greatest changes occurring in families who watched each episode. Improvements achieved at post-intervention by parents in both groups were maintained at six-month follow-up. Online tip sheets were frequently accessed; uptake of web-based resources was highest early in the series. CONCLUSIONS: The value of combining self-help approaches, technology and media as part of a comprehensive public health approach to providing parenting support is discussed.

The needs of cancer patients and their families from rural and remote areas of Queensland.

This study examines the impact of travelling for treatment on cancer patients and their families. Twenty-eight consecutive cancer patients, who were receiving radiation therapy treatment and 19 family carers, completed a structured needs assessment questionnaire and an in-depth interview. Both patients and carers reported moderate to high levels of unmet psychological need. Carers were found to have higher levels of anxiety than patients, although both groups had higher anxiety levels than the general population. Taking more responsibility for household tasks and organising new living arrangements for the family were the most frequently identified demands of a dual burden of caring. Nearly 40% of carers reported some disruption to their schedule and half reported experiencing financial difficulties. The qualitative interviews highlight the disruption that parents and children experience under the present system, particularly in relation to the demands of family life and the need to maintain some level of continuity and security for children.