Explore the vast range of titles available.

Background Although a five level version of the widely-used EuroQol 5 dimensions (EQ-5D) instrument has been developed, population norms are not yet available for Australia to inform the future valuation of health in economic evaluations. The aim of this study was to estimate HrQOL normative values for the EQ-5D-5L preference-based measure in a large, randomly selected, community sample in South Australia. Methods The EQ-5D-5L instrument was included in the 2013 South Australian Health Omnibus Survey, an interviewer-administered, face-to-face, cross-sectional survey. Respondents rated their level of impairment across dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and global health rating on a visual analogue scale (EQ-VAS). Utility scores were derived using the newly-developed UK general population-based algorithm and relationships between utility and EQ-VAS scores and socio-demographic factors were also explored using multivariate regression analyses. Results Ultimately, 2,908 adults participated in the survey (63.4 % participation rate). The mean utility and EQ-VAS scores were 0.91 (95 CI 0.90, 0.91) and 78.55 (95 % CI 77.95, 79.15), respectively. Almost half of respondents reported no problems across all dimensions (42.8 %), whereas only 7.2 % rated their health >90 on the EQ-VAS (100 = the best health you can imagine). Younger age, male gender, longer duration of education, higher annual household income, employment and marriage/de facto relationships were all independent, statistically significant predictors of better health status ( p  < 0.01) measured with the EQ-VAS. Only age and employment status were associated with higher utility scores, indicating fundamental differences between these measures of health status. Conclusions This is the first Australian study to apply the EQ-5D-5L in a large, community sample. Overall, findings are consistent with EQ-5D-5L utility and VAS scores reported for other countries and indicate that the majority of South Australian adults report themselves in full health. When valuing health in Australian economic evaluations, the utility population norms can be used to estimate HrQOL. More generally, the EQ-VAS score may be a better measure of population health given the smaller ceiling effect and broader coverage of HrQOL dimensions. Further research is recommended to update EQ-5D-5L population norms using the Australian general population specific scoring algorithm once this becomes publically available.

Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia. ROMANA 1 and ROMANA 2 were randomised, double-blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 6 months or body-mass index <20 kg/m2) were randomly assigned 2:1 to anamorelin 100 mg orally once daily or placebo, with a computer-generated randomisation algorithm stratified by geographical region, cancer treatment status, and weight loss over the previous 6 months. Co-primary efficacy endpoints were the median change in lean body mass and handgrip strength over 12 weeks and were measured in all study participants (intention-to-treat population). Both trials are now completed and are registered with ClinicalTrials.gov, numbers NCT01387269 and NCT01387282. From July 8, 2011, to Jan 28, 2014, 484 patients were enrolled in ROMANA 1 (323 to anamorelin, 161 to placebo), and from July 14, 2011, to Oct 31, 2013, 495 patients were enrolled in ROMANA 2 (330 to anamorelin, 165 to placebo). Over 12 weeks, lean body mass increased in patients assigned to anamorelin compared with those assigned to placebo in ROMANA 1 (median increase 0·99 kg [95% CI 0·61 to 1·36] vs −0·47 kg [–1·00 to 0·21], p<0·0001) and ROMANA 2 (0·65 kg [0·38 to 0·91] vs −0·98 kg [–1·49 to −0·41], p<0·0001). We noted no difference in handgrip strength in ROMANA 1 (−1·10 kg [–1·69 to −0·40] vs −1·58 kg [–2·99 to −1·14], p=0·15) or ROMANA 2 (−1·49 kg [–2·06 to −0·58] vs −0·95 kg [–1·56 to 0·04], p=0·65). There were no differences in grade 3–4 treatment-related adverse events between study groups; the most common grade 3–4 adverse event was hyperglycaemia, occurring in one (<1%) of 320 patients given anamorelin in ROMANA 1 and in four (1%) of 330 patients given anamorelin in ROMANA 2. Anamorelin significantly increased lean body mass, but not handgrip, strength in patients with advanced non-small-cell lung cancer. Considering the unmet medical need for safe and effective treatments for cachexia, anamorelin might be a treatment option for patients with cancer anorexia and cachexia. Helsinn Therapeutics.

Very few measures are used successfully as part of routine care within national palliative care outcome programs. Only a handful of studies examine these measures. The aim of this study is to evaluate the validity of a measure used in a national outcomes program: the Palliative Care Outcomes Collaboration Symptom Assessment Scale (PCOC SAS). A retrospective multi-site cohort study with secondary analysis of routinely collected patient-level data to assess PCOC SAS's internal consistency, construct validity, reliability, interpretability, acceptability and sensitivity. The analyses used two sets, with data collected by inpatient and community palliative care services registered with the Australian national PCOC. Dataset one included 1,117 patients receiving palliative care from 21 services. Dataset two included 5,294 patients receiving palliative care from 119 PCOC services. PCOC SAS demonstrated the ability to detect and discriminate distress by palliative care phase, functional status and diagnosis. Excellent and good convergent and discriminant validity were demonstrated. Fair through to substantial inter-rater and intra-rater reliability levels were evidenced. Sufficient interpretability resulted along with necessary levels of acceptability and sensitivity. PCOC SAS is a valid and reliable patient-reported outcome measure suitable for use in routine clinical care with patients requiring palliative and or end-of-life care, including in national outcomes programs.

This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0–10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group ( p  = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms. Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314).

Background Cancer cachexia presents a significant challenge, but the ghrelin agonist anamorelin shows promise as a potential treatment. This study examined whether the baseline systemic inflammatory response (SIR) (measured by the modified Glasgow Prognostic Score [mGPS]), low BMI or greater weight loss, was associated with a differential treatment effect of anamorelin in people with cachexia and non–small‐cell lung cancer (NSCLC). Methods ROMANA 1 and ROMANA 2 were double‐blind, placebo‐controlled, randomised Phase 3 trials that enrolled people with inoperable stage III/IV NSCLC with cachexia (≥ 5% weight loss within 6 months or body mass index [BMI] < 20 kg/m2). Patients were randomised 2:1 to anamorelin 100 mg once daily or placebo, for 12 weeks. This is a post hoc analysis of efficacy endpoints (body weight and body composition: lean body mass [LBM] and fat mass [FM]), stratified by baseline mGPS, BMI and weight loss and measured in the modified intent‐to‐treat pooled population. Results Seven hundred ninety‐five patients had available data. Anamorelin improved body weight (p < 0.001) and body composition parameters (LBM and FM, p < 0.01) in all mGPS groups. In patients with mGPS = 2, anamorelin increased weight > 5% and improved hand grip strength (HGS) and the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). In patients with BMI < 20 kg/m2 at baseline or weight loss ≥ 10% in the prior 6 months, anamorelin led to significant increases in body weight from baseline (p < 0.001) versus placebo. Patients with weight loss ≥ 10% in the prior 6 months showed the highest improvements in LBM (p < 0.001). Patients with BMI < 20 kg/m2 at baseline showed the highest improvements in FM (p < 0.001). Conclusion Anamorelin improved body composition parameters in all patients, as well as physical function and symptom burden, particularly in patients with systemic inflammation, BMI < 20 kg/m2 and weight loss ≥ 10%. These results highlight that the anabolic mechanisms of anamorelin are more effective in high‐risk groups. Trial Registration NCT identifiers: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.

Abstract Rationale Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from breathlessness, deconditioning, and reduced health-related quality of life (HRQL) despite best medical management. Opioids may relieve breathlessness at rest and on exertion in COPD. Objectives We aimed to estimate the efficacy and safety of opioids on refractory breathlessness, exercise capacity, and HRQL in COPD. Methods This was a systematic review and metaanalysis using Cochrane methodology. We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase up to 8 September, 2014 for randomized, double-blind, placebo-controlled trials of any opioid for breathlessness, exercise capacity, or HRQL that included at least one participant with COPD. Effects were analyzed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random effect models. Measurements and Main Results A total of 16 studies (15 crossover trials and 1 parallel-group study, 271 participants, 95% with severe COPD) were included. There were no serious adverse effects. Breathlessness was reduced by opioids overall: SMD, −0.35 (95% CI, −0.53 to −0.17; I  2, 48.9%), by systemic opioids (eight studies, 118 participants): SMD, −0.34 (95% CI, −0.58 to −0.10; I  2, 0%), and less consistently by nebulized opioids (four studies, 82 participants): SMD, −0.39 (95% CI, −0.71 to −0.07; I  2, 78.9%). The quality of evidence was moderate for systemic opioids and low for nebulized opioids on breathlessness. Opioids did not affect exercise capacity (13 studies, 149 participants): SMD, 0.06 (95% CI, −0.15 to 0.28; I  2, 70.7%). HRQL could not be analyzed. Findings were robust in sensitivity analyses. Risk of study bias was low or unclear. Conclusions Opioids improved breathlessness but not exercise capacity in severe COPD.

Background Breathlessness that persists despite treatment of causal disease(s) is disabling, associated with high therapy-related costs and poor socioeconomic outcomes. Low resource countries bear a disproportionate burden of respiratory problems, often characterised by disabling breathlessness. Low-cost self-management breathlessness-targeted interventions are effective and deliverable in community settings but have been developed in high-income countries. We aim to understand how breathlessness self-management works in 'real life' populations and cultural contexts, to develop programme theory and co-design a prototype intervention to improve persistent breathlessness management in India. Methods and analysis Using a Realist approach, Intervention Mapping and the Medical Research Council Complex Intervention Framework we will undertake two phases of work supported by our Expert Group (of respiratory, primary, palliative care physicians) and key stakeholder groups (opinion leader clinicians, community health workers and people with lived experiences of breathlessness). 1) Realist review and evaluation to identify and refine evidence and theory for breathlessness self-management, producing intervention and implementation programme theory. We will identify literature through our Expert Group, scoping searches and systematic searches (Medline, Ebscohost, CINAHL, Scopus, Psychinfo). We will map intervention components to 'what works, for whom, and where.' 2) Intervention development using Intervention Mapping to map intervention and implementation programme theory to intervention components, develop materials to support intervention delivery, and co-design a prototype educational intervention ready for early acceptability and delivery-feasibility testing and evaluation planning in India. Use of stakeholder groups is to allow people with experience of breathlessness and/or its management to contribute their views on content developed by our team based upon review of secondary data sources. Experts and Stakeholders are therefore not research subjects but are included as extended members of the study team and will not follow informed consent procedures. Experts and stakeholders will be acknowledge in outputs arising from our project if they wish to be. Our review conduct will be consistent with RAMESES quality standards. Discussion At the conclusion of our study, we will have co-designed a breathlessness intervention for use in the community setting in India ready for further evaluation of: effectiveness, socioeconomic outcomes, acceptability and transferability to other low resource settings.

Background Ketamine at subanaesthetic dosages ([less than or equal to]0.5mg/kg) exhibits rapid onset (over hours to days) antidepressant effects against major depressive disorder in people who are otherwise well. However, its safety, tolerability and efficacy are not known for major depressive disorder in people with advanced life-limiting illnesses. Objective To determine the feasibility, safety, tolerability, acceptability and any antidepressant signal/activity to justify and inform a fully powered study of subcutaneous ketamine infusions for major depressive disorder in the palliative setting. Methods This was a single arm, open-label, phase II feasibility study (Australian New Zealand Clinical Trial Registry Number-ACTRN12618001586202). We recruited adults ([greater than or equal to] 18-years-old) with advanced life-limiting illnesses referred to four palliative care services in Sydney, Australia, diagnosed with major depressive disorder from any care setting. Participants received weekly subcutaneous ketamine infusion (0.1-0.4mg/kg) over two hours using individual dose-titration design. Outcomes assessed were feasibility, safety, tolerability and antidepressant activity. Results Out of ninety-nine referrals, ten participants received ketamine and were analysed for responses. Accrual rate was 0.54 participants/month across sites with 50% of treated participants achieving [greater than or equal to] 50% reduction in baseline Montgomery-Åsberg Depression Rating Scale, meeting feasibility criteria set a priori. There were no clinically relevant harms encountered. Conclusions A future definitive trial exploring the effectiveness of subcutaneous infusion of ketamine for major depressive disorder in the palliative care setting may be feasible by addressing identified study barriers. Individual dose-titration of subcutaneous ketamine infusions over two hours from 0.1mg/kg can be well-tolerated and appears to produce transient antidepressant signals over hours to days.

The routine measurement of patient-reported outcomes in cancer clinical care using electronic patient-reported outcome measures (ePROMs) is gaining momentum worldwide. However, a deep understanding of the mechanisms underpinning ePROM interventions that could inform their optimal design to improve health outcomes is needed. This study aims to identify the implicit mechanisms that underpin the effectiveness of ePROM interventions and develop program theories about how and when ePROM interventions improve health outcomes. A realist synthesis of the literature about ePROM interventions in cancer clinical care was performed. A conceptual framework of ePROM interventions was constructed to define the scope of the review and frame the initial program theories. Literature searches of Ovid MEDLINE, Ovid Embase, Scopus, and CINAHL, supplemented by citation tracking, were performed to identify relevant literature to develop, refine, and test program theories. Quality appraisal of relevant studies was performed using the Mixed Methods Appraisal Tool. Overall, 61 studies were included in the realist synthesis: 15 (25%) mixed methods studies, 9 (15%) qualitative studies, 13 (21%) descriptive studies, 21 (34%) randomized controlled trials, and 3 (5%) quasi-experimental studies. In total, 3 initial program theories were developed regarding the salient components of ePROM interventions-remote self-reporting, real-time feedback to clinicians, and clinician-patient telecommunication. The refined theories posit that remote self-reporting enables patients to recognize and report symptoms accurately and empowers them to communicate these to clinicians, real-time feedback prompts clinicians to manage symptoms proactively, and clinician-patient telephone interactions and e-interactions between clinic encounters improve symptom management by reshaping how clinicians and patients communicate. However, the intervention may not achieve the intended benefit if ePROMs become a reminder to patients of their illness and are not meaningful to them and when real-time feedback to clinicians lacks relevance and increases the workload. The key to improving health outcomes through ePROM interventions is enabling better symptom reporting and communication through remote symptom self-reporting, promoting proactive management of symptoms through real-time clinician feedback, and facilitating clinician-patient interactions. Patient engagement with self-reporting and clinician engagement in responding to feedback are vital and may reinforce each other in improving outcomes. Effective ePROM interventions might fundamentally alter how clinicians and patients interact between clinic encounters.

Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD).Design Population based longitudinal consecutive cohort study.Setting Centres prescribing long term oxygen therapy in Sweden.Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register.Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs.Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia.Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.