The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea

Background: While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern. Methods: This secondary analysis used breathlessness intensity scores (100mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved < 10% improvement over their own baseline at one week (10 mg) were titrated to 20mg and if no response, another week later to 30mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling. Results: Of the 83 participants, 17/52 responders required > 10 mg: 13 participants (20 mg) and 4 (30 mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3mm/ day ( p = 0.16); the average improvement in the first 24 hours of response was 10.9mm (7.0 to 14.7; p < 0.0001), with continued improvement of 2.2 mm/day ( p < 0.001) for six more days. Conclusion: When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study proto

© Article author(s). Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended-release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-Arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Application and Evaluation of Modified Atmosphere Packaging in Selected Minimally Processed Vegetables

The central aim of this study was to optimise the processing and storage of selected vegetable within the parameters of extended shelf life, time/temperature relationships and sensory quality. The vegetables were selected on the basis of the results of a survey of the Irish vegetable industry. The current literature in the field of modified atmosphere packaging (MAP) and the Irish vegetable industry was reviewed. The current state and future requirements of the Irish vegetable industry was investigated through the use of a questionnaire. This established the views of Irish vegetable purchasers (food service, fast food and retail outlets), in relation to vegetables currently purchased. It emerged that retail outlets are ultimately governed by consumer purchasing trends. Retailers purchase the widest selection of vegetables of all sectors in a variety of packaging formats. The purchasing patterns of food service outlets are strongly governed by seasonality and quality. These outlets continue to perform processing operations on site, as opposed to purchasing ready prepared samples. While retailers are interested in prolonged vegetable shelf life at an extra cost, food service outlets are constrained by budgets within their business. The questionnaire highlighted that the packaged vegetables most frequently purchased by retailers and food service outlets were broccoli, carrots, lettuce, onions, peppers and potatoes. These vegetables that were selected for modified atmosphere packaging and sensory analysis were carrot, pepper, broccoli and cauliflower. The second phase of this research involved MA packaging of these selected vegetable to generate the ideal packaging conditions to prolong their shelf life. Storage temperatures and gas atmosphere were varied for each vegetable packaged. Changes occurring in product quality over time were investigated for both raw and cooked vegetable products and analysed by a trained taste panel. Products were scored for individual quality attributes (surface moisture, colour, flavour and texture). It was concluded that higher temperatures accelerated the deterioration of sensory attributes in carrot and celery. Extended shelf life of 10 days for carrots and peppers and 7 days for celery is achievable through strict temperature control combined with passive packaging. Superior quality was observed for pepper, and mixes involving pepper in packages store at 8°C for up to 10 days. Storage temperature was found to have a greater influence on quality of carrot, celery and pepper than storage atmosphere. It was apparent that broccoli and cauliflower require an active atmosphere to optimise quality attributes for up to 7 days at either 4 or 8°C. It was found that deterioration of several sensory attributes that were detected in the raw product were not detected in the corresponding cooked product. This reveals that passive packaging would be sufficient to reduce quality deterioration of these vegetables for use as part of a cooked dish. Further research in the area of MAP is recommended to focus on the requirements of food service outlets and in outlining the benefits of use of MA packaged vegetables in increasing productivity and reducing costs within the food service business. A microbiological profile of the packaged vegetables over time is also recommended to identify the point at which it is unsafe to consume MA packaged vegetables due to microbiological risk

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Background: Continuous quality improvement is fundamental in all health care, including hospice and palliative care. Identifying and systematically reducing symptomatic adverse events is limited in hospice and palliative care because these events are mostly attributed to disease progression