Miriam Johnson

Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study

CONTEXT Randomized controlled trials can answer questions of efficacy, but long-term pharmacovigilance studies generate complementary safety data. OBJECTIVES Level I evidence supports short-term efficacy of opioids in reducing chronic refractory dyspnea. This study aimed to determine the minimum effective once-daily dose of sustained-release morphine, and whether net clinical benefits are sustained safely. METHODS In a Phase II dose increment study, 10mg daily of sustained-release morphine was administered, and increased in nonresponders by 10mg daily each week to a maximum of 30 mg daily. The participant was withdrawn if there were unacceptable side effects or no response to maximum dose. If participants had a 10% improvement in dyspnea over their own baseline, they joined a long-term Phase IV effectiveness/safety study at that dose. Complying with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, response and side effects are described, with demographic and clinical characteristics of responders. RESULTS Eighty-three participants (53 males, mean age 75 years, 54% with chronic obstructive pulmonary disease) provided more than 30 patient-years of data. Fifty-two participants derived ≥ 10% benefit (on average 35% improvement over baseline), giving a response rate of 62% (number needed to treat of 1.6: number needed to harm 4.6); for 70%, this dose was 10mg/24h. Benefit was maintained at three months for 28 (33%) people. Ranking of breathlessness was reduced significantly (P<0.001), but constipation increased (P<0.001) despite laxatives. There were no episodes of respiratory depression or hospitalizations as a result of the sustained-release morphine. Overall, one in three people continued to derive benefit at three months. CONCLUSION Ten milligrams of sustained-release oral morphine once daily is safe and effective for most people who respond.

Management of venous thromboembolism in patients with advanced cancer: a systematic review and meta-analysis

Venous thromboembolism is common in patients with cancer. However, no management guidelines exist for venous thromboembolism specific to patients with advanced progressive cancer. To help develop recommendations for practice, we have done a comprehensive review of anticoagulation treatment in patients with cancer, with particular focus on studies that included patients with advanced disease. Data from 19 publications, including randomised, prospective, and retrospective studies suggest that: long-term full-dose low-molecular-weight heparin (LMWH) is more effective than warfarin in the secondary prophylaxis of venous thromboembolism in patients with cancer of any stage, performance status, or prognosis; warfarin should not be used in patients with advancing progressive disease; and in patients at high risk of bleeding, full-dose LMWH for 7 days followed by a long-term decreased fixed dose long term can be considered. The optimum treatment duration is unclear, but because the prothrombotic tendency will persist in patients with advanced cancer, indefinite treatment is generally recommended. For patients with contraindications to anticoagulation, inferior-vena-caval filters can be considered, but their use needs careful patient selection. Ultimately, the decision to initiate, continue, and stop anticoagulation will need to be made on an individual basis, guided by the available evidence, the patients circumstances, and their informed preferences.

Researching breathlessness in palliative care: consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup.

Breathlessness is common in advanced disease and can have a devastating impact on patients and carers. Research on the management of breathlessness is challenging. There are relatively few studies, and many studies are limited by inadequate power or design. This paper represents a consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup. The aims of this paper are to facilitate the design of adequately powered multi-centre interventional studies in breathlessness, to suggest a standardised, rational approach to breathlessness research and to aid future ‘between study’ comparisons. Discussion of the physiology of breathlessness is included.

Short‐term opioids for breathlessness in stable chronic heart failure: a randomized controlled trial

To assess the effect of oral opioids vs. placebo on breathlessness in patients with chronic heart failure (CHF).

Measurement of breathlessness in clinical trials in patients with chronic heart failure: the need for a standardized approach: a systematic review

Chronic breathlessness is a major symptom for patients with compensated chronic heart failure (CHF) and its impact is different to the breathlessness resulting from pulmonary oedema. This systematic review aims to establish which tools have been used for research into the subjective severity of breathlessness in patients with compensated CHF and to discuss recommendations for the future.

Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness

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 via 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 a priori 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. Chronic breathlessness syndrome: breathlessness and disability despite an optimally treated underlying pathophysiology http://ow.ly/V0g2309z4tF

Opioids for chronic refractory breathlessness: patient predictors of beneficial response

Chronic refractory breathlessness is common and distressing in advanced disease. Despite level I evidence to support the use of opioids for this symptom, not all patients benefit. This study aimed to discover which patient characteristics predict those most likely to gain improvement in breathlessness. This is an international, multicentre, retrospective analysis of 213 individual pooled datasets from four clinical trials of an opioid for chronic refractory breathlessness. “Response to opioid” was defined as 1) an absolute value of ≥10 mm improvement on the visual analogue scale (VAS) and 2) a relative value of ≥10% improvement from baseline VAS. We investigated baseline predictors using logistic regression. In the final model, higher baseline breathlessness intensity scores strongly predicted absolute and relative response (p<0.001). Younger age also predicted relative response (p = 0.025); functional status and dominant cause of breathlessness did not. Some evidence supported the descriptor “not enough air”, but was not statistically significant (p = 0.052). A therapeutic trial of opioids is appropriate, irrespective of the cause of the breathlessness or functional status. Younger people or those with worse breathlessness are more likely to benefit. Opioids have a role in the management of chronic refractory breathlessness, but net benefit for individuals must be optimised. A role for opioids in the management of chronic refractory breathlessness; net benefit for individuals must be optimised http://ow.ly/kRf22

Management of end stage cardiac failure

Optimum heart failure medication and an increasing array of interventions have had an enormous effect on morbidity and mortality over the past 10 years. However, patients with end stage disease can still be highly symptomatic. Moreover, such patients are disadvantaged compared with patients with malignant disease. They are less likely to have an understanding of their illness or have access to supportive care. They are also less likely to have the opportunity to plan for care with regard to death and dying. There is increasing demand that the multi-professional clinical team gain good communication and supportive care skills, and that appropriate access to specialist palliative care services is available.

Palliative care among heart failure patients in primary care: a comparison to cancer patients using English family practice data.

Introduction Patients with heart failure have a significant symptom burden and other palliative care needs often over a longer period than patients with cancer. It is acknowledged that this need may be unmet but by how much has not been quantified in primary care data at the population level. Methods This was the first use of Clinical Practice Research Datalink, the worlds largest primary care database to explore recognition of the need for palliative care. Heart failure and cancer patients who had died in 2009 aged 18 or over and had at least one year of primary care records were identified. A palliative approach to care among patients with heart failure was compared to that among patients with cancer using entry onto a palliative care register as a marker for a palliative approach to care. Results Among patients with heart failure, 7% (234/3 122) were entered on the palliative care register compared to 48% (3 669/7 608) of cancer patients. Of heart failure patients on the palliative care register, 29% (69/234) were entered onto the register within a week of their death. Conclusions This confirms that the stark inequity in recognition of palliative care needs for people with heart failure in a large primary care dataset. We recommend a move away from prognosis based criteria for palliative care towards a patient centred approach, with assessment of and attention to palliative needs including advance care planning throughout the disease trajectory.

Is there a role for subcutaneous furosemide in the community and hospice management of end-stage heart failure?

Patients with advanced chronic heart failure (CHF) can experience ‘revolving door’ admissions, often for parenteral diuretics, when time at home is precious. Home intravenous diuretic services are patchy. This retrospective review describes 43 consecutive episodes of continuous subcutaneous infusion of furosemide (CSCI-F) in 32 advanced CHF patients; 28 episodes aiming to correct fluid balance and prevent hospital admission and 15 aiming to prevent symptoms in the dying. Overall, 26/28 (93%) avoided hospital admission. Weight loss occurred in 20/28 (70%): a median loss of 5.6 kg [interquartile range (IQR) 0.1–8.9]). The daily dose of furosemide ranged from 40 to 250 mg. The median number of days on CSCI-F was 10.5 (range 2–48; IQR 6–13.8). Site reactions occurred in 10/43 (23%); all of which were mild except two, one of which required oral antibiotics. Symptoms were controlled in all 15 dying patients. CSCI-F for patients with advanced CHF is effective in terms of weight loss and prevention of hospital admission with the heart failure nurse specialist playing a key overall management role in selection and monitoring. As the majority of community and hospice nurses have access to and are familiar with CSCI pumps, this practice should be nationally transferable. The role in the dying patient requires further assessment.