Breathlessness that persists despite treatment for the underlying conditions is debilitating. Identifying this discrete entity as a clinical syndrome should raise awareness amongst patients, ...clinicians, service providers, researchers and research funders.Using the Delphi method, questions and statements were generated
expert group consultations and one-to-one interviews (n=17). These were subsequently circulated in three survey rounds (n=34, n=25, n=31) to an extended international group from various settings (clinical and laboratory; hospital, hospice and community) and working within the basic sciences and clinical specialties. The
target agreement for each question was 70%. Findings were discussed at a multinational workshop.The agreed term, chronic breathlessness syndrome, was defined as breathlessness that persists despite optimal treatment of the underlying pathophysiology and that results in disability. A stated duration was not needed for "chronic". Key terms for French and German translation were also discussed and the need for further consensus recognised, especially with regard to cultural and linguistic interpretation.We propose criteria for chronic breathlessness syndrome. Recognition is an important first step to address the therapeutic nihilism that has pervaded this neglected symptom and could empower patients and caregivers, improve clinical care, focus research, and encourage wider uptake of available and emerging evidence-based interventions.
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.
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.
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.
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.
Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding Helsinn Therapeutics.
Full integration of oncology and palliative care relies on the specific knowledge and skills of two modes of care: the tumour-directed approach, the main focus of which is on treating the disease; ...and the host-directed approach, which focuses on the patient with the disease. This Commission addresses how to combine these two paradigms to achieve the best outcome of patient care. Randomised clinical trials on integration of oncology and palliative care point to health gains: improved survival and symptom control, less anxiety and depression, reduced use of futile chemotherapy at the end of life, improved family satisfaction and quality of life, and improved use of health-care resources. Early delivery of patient-directed care by specialist palliative care teams alongside tumour-directed treatment promotes patient-centred care. Systematic assessment and use of patient-reported outcomes and active patient involvement in the decisions about cancer care result in better symptom control, improved physical and mental health, and better use of health-care resources. The absence of international agreements on the content and standards of the organisation, education, and research of palliative care in oncology are major barriers to successful integration. Other barriers include the common misconception that palliative care is end-of-life care only, stigmatisation of death and dying, and insufficient infrastructure and funding. The absence of established priorities might also hinder integration more widely. This Commission proposes the use of standardised care pathways and multidisciplinary teams to promote integration of oncology and palliative care, and calls for changes at the system level to coordinate the activities of professionals, and for the development and implementation of new and improved education programmes, with the overall goal of improving patient care. Integration raises new research questions, all of which contribute to improved clinical care. When and how should palliative care be delivered? What is the optimal model for integrated care? What is the biological and clinical effect of living with advanced cancer for years after diagnosis? Successful integration must challenge the dualistic perspective of either the tumour or the host, and instead focus on a merged approach that places the patient's perspective at the centre. To succeed, integration must be anchored by management and policy makers at all levels of health care, followed by adequate resource allocation, a willingness to prioritise goals and needs, and sustained enthusiasm to help generate support for better integration. This integrated model must be reflected in international and national cancer plans, and be followed by developments of new care models, education and research programmes, all of which should be adapted to the specific cultural contexts within which they are situated. Patient-centred care should be an integrated part of oncology care independent of patient prognosis and treatment intention. To achieve this goal it must be based on changes in professional cultures and priorities in health care.
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).
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.
Globally, the number of people affected by coronavirus disease 2019 (COVID-19) is rapidly increasing. In most (>80%), the illness is relatively mild and can be self-managed out of hospital. However, ...in about 20% the illness causes respiratory compromise severe enough to require hospital admission 1. Patients with severe and critical disease need full active treatment. This may include oxygen for hypoxaemia and ventilatory support, along with optimal management of complications,
e.g.
super-imposed bacterial infection, and any underlying co-morbidities,
e.g.
chronic obstructive pulmonary disease, congestive heart failure. To date, no antiviral agent has shown to be effective in treating the disease 2.
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.
We aimed to estimate the efficacy and safety of opioids on refractory breathlessness, exercise capacity, and HRQL in COPD.
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.
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.
Opioids improved breathlessness but not exercise capacity in severe COPD.
To provide guidance on the clinical management of dyspnea in adult patients with advanced cancer.
ASCO convened an Expert Panel to review the evidence and formulate recommendations. An Agency for ...Healthcare Research and Quality (AHRQ) systematic review provided the evidence base for nonpharmacologic and pharmacologic interventions to alleviate dyspnea. The review included randomized controlled trials (RCTs) and observational studies with a concurrent comparison group published through early May 2020. The ASCO Expert Panel also wished to address dyspnea assessment, management of underlying conditions, and palliative care referrals, and for these questions, an additional systematic review identified RCTs, systematic reviews, and guidelines published through July 2020.
The AHRQ systematic review included 48 RCTs and two retrospective cohort studies. Lung cancer and mesothelioma were the most commonly addressed types of cancer. Nonpharmacologic interventions such as fans provided some relief from breathlessness. Support for pharmacologic interventions was limited. A meta-analysis of specialty breathlessness services reported improvements in distress because of dyspnea.
A hierarchical approach to dyspnea management is recommended, beginning with dyspnea assessment, ascertainment and management of potentially reversible causes, and referral to an interdisciplinary palliative care team. Nonpharmacologic interventions that may be offered to relieve dyspnea include airflow interventions (eg, a fan directed at the cheek), standard supplemental oxygen for patients with hypoxemia, and other psychoeducational, self-management, or complementary approaches. For patients who derive inadequate relief from nonpharmacologic interventions, systemic opioids should be offered. Other pharmacologic interventions, such as corticosteroids and benzodiazepines, are also discussed.Additional information is available at www.asco.org/supportive-care-guidelines.
The anesthetic ketamine is widely used for pain related to cancer, but the evidence to support its use in this setting is weak. This study aimed to determine whether ketamine is more effective than ...placebo when used in conjunction with opioids and standard adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity.
In this multisite, dose-escalation, double-blind, randomized, placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously over 3 to 5 days.
In all, 185 participants were included in the primary analysis. There was no significant difference between the proportion of positive outcomes (0.04; 95% CI, -0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% 25 of 92 and 31% 29 of 93). Pain type (nociceptive v neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P < .001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four to 13).
Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard coanalgesics in cancer pain.
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