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Breathlessness frequently becomes severe among people with respiratory disease. Mirtazapine, a widely used antidepressant, has shown promise in the modulation of respiratory sensation and the response to it, as well as reducing feelings of panic, which often accompanies breathlessness. We aimed to determine the effectiveness of mirtazapine to alleviate severe persisting breathlessness. This international, multicentre, phase 3, parallel-group, double-blind, randomised, placebo-controlled trial across 16 centres in seven countries (Australia, Germany, Ireland, Italy, New Zealand, Poland, and the UK), recruited adults with chronic obstructive pulmonary disease (COPD), interstitial lung diseases, or both, and grade 3 or 4 of the modified Medical Research Council breathlessness scale. Consenting participants were randomly assigned (1:1) to receive oral mirtazapine or matching placebo for 56 days. Randomisation was by minimisation. The initial mirtazapine dose was 15 mg, escalating to a maximum of 45 mg per day, tapered at treatment end. Participants, caregivers, assessors, and investigators were masked to group assignment. The primary outcome was worst breathlessness in the preceding 24 h measured on a 0–10 numerical rating scale (NRS), at 56 days post-treatment start, with follow-up to 180 days. The primary analysis was performed in the modified intention-to-treat population using multivariable multi-level repeated measures model. This trial was registered with ISRCTN (ISRCTN10487976 and ISRCTN15751764 [Australia and New Zealand]) and EudraCT (2019–002001–21) and is complete. Between Feb 4, 2021 and March 28, 2023, we enrolled 225 eligible participants (148 men and 77 women, 113 to the mirtazapine group and 112 to the placebo group). The median age was 74 years (IQR 67–78). No evidence of a difference was found in worst breathlessness at day 56 between mirtazapine and placebo (difference in adjusted mean NRS score was 0·105 [95% CI –0·407 to 0·618]; p=0·69). Although the study was underpowered, the primary endpoint effect did not reach the pre-specified treatment effect of 0·55 for worst breathlessness score reduction that the study was powered to detect for the primary analysis. There were 215 adverse reactions in 72 (64%) of 113 participants in the mirtazapine group versus 116 in 44 (40%) of 110 participants in the placebo group; 11 serious adverse events in six (5%) participants in the mirtazapine group versus eight in seven (6%) participants in the placebo group; and one (1%) suspected unexpected serious adverse reaction in the mirtazapine group. At day 56, there were three deaths in the mirtazapine group and two deaths in the placebo group. At day 180, there were seven deaths in the mirtazapine group and 11 deaths in the placebo group. Our findings suggested that mirtazapine of doses 15 to 45 mg daily over 56 days does not improve severe breathlessness among patients with COPD or interstitial lung diseases and might cause adverse reactions. Based on these findings, we do not recommend mirtazapine as a treatment to alleviate severe breathlessness. EU Horizon 2020 (grant agreement No. 825319); Cicely Saunders International Breathlessness Programme; National Institute for Health and Care Research Applied Research Collaboration South London; Australian National Health and Medical Research Council—EU (application ID: APP1170731). [ABSTRACT FROM AUTHOR]

Objectives: Congruence between the preferred and actual place of death is recognised as an important quality indicator in end-of-life care. However, there may be complexities about preferences that are ignored in summary congruence measures. This article examined factors associated with preferred place of death, actual place of death, and congruence for a sample of patients who had received specialist palliative care in the last three months of life in Ireland. Methods: This article analysed merged data from two previously published mortality follow-back surveys: Economic Evaluation of Palliative Care in Ireland (EEPCI); Irish component of International Access, Rights and Empowerment (IARE I). Logistic regression models examined factors associated with (a) preferences for home death versus institutional setting, (b) home death versus hospital death, and (c) congruent versus non-congruent death. Setting: Four regions with differing levels of specialist palliative care development in Ireland. Participants: Mean age 77, 50% female/male, 19% living alone, 64% main diagnosis cancer. Data collected 2011-2015, regression model sample sizes: n = 342-351. Results: Congruence between preferred and actual place of death in the raw merged dataset was 51%. Patients living alone were significantly less likely to prefer home versus institution death (OR 0.389, 95%CI 0.157-0.961), less likely to die at home (OR 0.383, 95%CI 0.274-0.536), but had no significant association with congruence. Conclusions: The findings highlight the value in examining place of death preferences as well as congruence, because preferences may be influenced by what is feasible rather than what patients would like. The analyses also underline the importance of well-resourced community-based supports, including homecare, facilitating hospital discharge, and management of complex (eg, non-cancer) conditions, to facilitate patients to die in their preferred place. [ABSTRACT FROM AUTHOR]

Background: People approaching end of life account disproportionately for health care costs, and the majority of these costs accrue in hospitals. The economic evidence base to improve value of care to this population is thin. Natural experiment methods may be helpful in bridging evidence gaps with credible causal estimates from routine data, but these methods have seldom been applied in this field. This study aimed to evaluate the association between timely palliative care consultation and length of stay for adults with serious illness admitted to acute hospital in Ireland., Methods: In primary analysis we evaluated if timely palliative care receipt following emergency hospital inpatient admission impacted length of stay (LOS); in secondary analysis we verified if palliative medicine service (PMS) implementation co-occurred with any changes in in-hospital mortality, and we estimated cost differences associated with any change in LOS. This was a secondary analysis on routinely collected data for acute admissions to public hospitals in Ireland. We used difference-in-differences analysis to exploit the staggered implementation of PMS teams at acute public hospitals in Ireland between 2010 and 2015. We identified palliative care receipt following PMS implementation using ICD-10 codes, and we matched admissions involving a palliative care interaction to admissions in years prior to PMS implementation using propensity score weights., Results: Our primary analytic sample included 4,314 observations, of whom 608 (14%) received timely palliative care. We estimated that the intervention reduced LOS by nearly two days, with an estimated associated saving per admission of €1,820. These analyses were robust to multiple sensitivity analyses on regression specification, weighting strategy and site selection. Proportion of admissions ending in death did not change following PMS implementation., Conclusions: Prompt interaction between suitable patients and palliative care can improve the quality and efficiency of care to this population. Many patients receive palliative care later in the hospital stay, which does not yield cost-savings. Future studies can extend and strengthen our approach with better data, as well as using different methods to understand how to trigger palliative care early in a hospital admission and realise available gains.