Advance care planning in patients with advanced cancer: A 6-country, cluster-randomised clinical trial.

BACKGROUND: Advance care planning (ACP) supports individuals to define, discuss, and record goals and preferences for future medical treatment and care. Despite being internationally recommended, randomised clinical trials of ACP in patients with advanced cancer are scarce. METHODS AND FINDINGS: To test the implementation of ACP in patients with advanced cancer, we conducted a cluster-randomised trial in 23 hospitals across Belgium, Denmark, Italy, Netherlands, Slovenia, and United Kingdom in 2015-2018. Patients with advanced lung (stage III/IV) or colorectal (stage IV) cancer, WHO performance status 0-3, and at least 3 months life expectancy were eligible. The ACTION Respecting Choices ACP intervention as offered to patients in the intervention arm included scripted ACP conversations between patients, family members, and certified facilitators; standardised leaflets; and standardised advance directives. Control patients received care as usual. Main outcome measures were quality of life (operationalised as European Organisation for Research and Treatment of Cancer [EORTC] emotional functioning) and symptoms. Secondary outcomes were coping, patient satisfaction, shared decision-making, patient involvement in decision-making, inclusion of advance directives (ADs) in hospital files, and use of hospital care. In all, 1,117 patients were included (442 intervention; 675 control), and 809 (72%) completed the 12-week questionnaire. Patients' age ranged from 18 to 91 years, with a mean of 66; 39% were female. The mean number of ACP conversations per patient was 1.3. Fidelity was 86%. Sixteen percent of patients found ACP conversations distressing. Mean change in patients' quality of life did not differ between intervention and control groups (T-score -1.8 versus -0.8, p = 0.59), nor did changes in symptoms, coping, patient satisfaction, and shared decision-making. Specialist palliative care (37% versus 27%, p = 0.002) and AD inclusion in hospital files (10% versus 3%, p < 0.001) were more likely in the intervention group. A key limitation of the study is that recruitment rates were lower in intervention than in control hospitals. CONCLUSIONS: Our results show that quality of life effects were not different between patients who had ACP conversations and those who received usual care. The increased use of specialist palliative care and AD inclusion in hospital files of intervention patients is meaningful and requires further study. Our findings suggest that alternative approaches to support patient-centred end-of-life care in this population are needed. TRIAL REGISTRATION: ISRCTN registry ISRCTN63110516.

WITHDRAWN: Antibiotics / anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs.

BACKGROUND: Lymphoedema is a chronic, progressive condition and one area of debate is the optimum management for infective/inflammatory episodes (AIE's). OBJECTIVES: To determine whether antibiotic/anti-inflammatory drugs given prophylactically reduce the number and severity of AIE's in patients with lymphoedema. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register in September 2003, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and the International Society of Lymphology congress proceedings. SELECTION CRITERIA: Randomised controlled trials testing an antibiotic or anti-inflammatory drug against placebo (with or without physical therapies) were included. DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers. The papers were screened independently using a checklist of criteria relating to quality. Both reviewers extracted data from the eligible studies using a data extraction form. MAIN RESULTS: Four studies (364 randomised patients) were included. Two studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE's, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the trial period in the treated group but one case of infection in the two placebo groups respectively. Seven additional cases of infection in trial one and 14 cases in trial two required treatment in the three month follow up period.One anti-filarial trial reported 127 ADL episodes for all groups during the treatment year (compared with 684 episodes during the pre-treatment year). There were 228 ADL episodes during the trial follow-up year but no findings were significant. No link was found between the grade of oedema and the frequency of ADL episodes. There was a significant link between increased episodes and the rainy season. Penicillin reduced the mean number of inflammatory episodes from 4.6 to 0.5 after treatment, which increased to 1.9 at the end of follow-up. AUTHORS' CONCLUSIONS: The effectiveness of selenium in preventing AIE in lymphoedema remains inconclusive in the absence of properly conducted randomised-controlled trials. Anti-filarials do not appear to reduce ADL episodes in filarial lymphoedema. Penicillin appears to contribute to a significant reduction in ADL when combined with foot-care. The importance of foot-care should be recommended, which may also apply to care of the arm following breast cancer treatment. Properly conducted trials are needed to demonstrate any efficacy of these interventions.