Digoxin–Itraconazole Interaction: Possible Mechanisms

Objective To document a case in which the administration of itraconazole was associated with an apparent decrease in digoxin clearance, resulting in an increase in the serum digoxin concentration. Case Summary A man receiving digoxin for atrial fibrillation was concurrently treated with itraconazole 200 mg/d for esophageal candidiasis. The estimated urinary digoxin clearance was decreased during this combination therapy. Discussion Digoxin is primarily cleared by the kidneys, and the mechanism of renal clearance involves both glomerular filtration and tubular secretion. We postulate that itraconazole or a metabolite of this compound may have resulted in decreased tubular secretion of digoxin, accounting for decreased urinary digoxin clearance. Conclusions Monitoring of serum digoxin concentrations should be performed if patients taking digoxin are treated with itraconazole. Further investigation is necessary to elucidate the nature of the interaction between digoxin and itraconazole. </jats:sec

A case series of suprascapular nerve block (with an historical comparator) for shoulder pain in motor neurone disease

Background: Shoulder pain is a distressing but under-reported and poorly managed symptom in people with motor neurone disease. Objectives: This study aimed to assess the efficacy of suprascapular nerve block for the management of shoulder pain in patients with motor neurone disease. Methods: A total of 27 patients with motor neurone disease and shoulder pain were offered a suprascapular nerve block. Ten of these patients had bilateral shoulder pain and both were injected, making a total of 37 shoulders. The patients were followed up for a total of 3 months, or until death. Shoulder pain was measured using the pain scale (out of 100) of the shoulder pain and disability index and compared with baseline scores and a placebo control group from an earlier study using the same methodology (ACTRN12619000353190). Results: Following the nerve block there was a significant improvement of pain scores from baseline (58.4) at week 1 (20.8, p &lt; 0.000), week 6 (17.6, p &lt; 0.000) and week 12 (30.4, p = 0.001) and a significant improvement compared with the control group across each time interval. Conclusion: Suprascapular nerve block is a safe, effective therapy for patients with chronic shoulder pain. </jats:sec

Elements of effective palliative care interventions in advanced heart failure: A narrative review

Abstract People with advanced heart failure experience significant biopsychosocial needs and have a poor prognosis. International guidelines have called for integrating palliative care in heart failure management. This review explores the elements of effective palliative care interventions in advanced heart failure. PubMed, Embase, CINAHL and Cochrane Reviews were searched following an a priori review protocol for clinical trials of advanced heart failure and palliative care. The risk of bias was assessed using Risk of Bias 2 (RoB2). A qualitative, emergent approach was used to synthesize context + mechanism = outcome. Twenty‐one papers from 18 studies were the data source. The efficacy of palliative care in advanced heart failure was mixed. Five studies reported significant improvement in health outcomes compared with the usual care control group. Timing may be necessary in accounting for improvement in quality of life (occurring on or about 3 months) and functional and symptomatic improvements (occurring on or about 6 months or longer). Effective models of secondary palliative care in advanced heart failure include interdisciplinary teams comprising primary care, cardiology and palliative care, routine check‐ins, personalized care plans that explore goals, evidence‐based symptom management and counselling. Integrating palliative care with heart failure management could improve patient outcomes. Future research and policy development may wish to consider when, how and what palliative care modalities are to be incorporated into the care of patients with advanced heart failure

Assessment and Management of Sleep Disturbance in Palliative Care Settings

Background: Sleep disturbances, including insomnia, sleep-disordered breathing, and circadian rhythm disorders with potential consequences including excessive daytime somnolence and worsening fatigue, are prevalent yet largely under-measured and therefore under-managed problems in people receiving palliative care. This has the potential to negatively affect the person\u27s functioning and quality of life. Objectives: We aimed to review the current practice of assessment and management of sleep disturbances in people with life-limiting illnesses in Australian and New Zealand palliative care settings, and to define areas for improvement in assessment and management of sleep disturbances and further research. Design: A cross-sectional, online survey was conducted with palliative care health professionals (PCHPs) to explore current approaches to routine assessment of sleep disturbances and PCHPs\u27 awareness of, and perceived access to, evidence-based resources for assessing and managing sleep disturbances in their local settings. Results: Fifty-four PCHPs responded to the survey, including allied health professionals (44%), palliative care nurses (26%), and physicians (19%). Over 70% of PCHPs endorsed routine verbal screening of sleep symptoms, and \u3e90% recommended management with basic behavioral strategies. However, none of PCHPs used validated patient-reported outcome measures for sleep, and \u3c10% of PCHPs demonstrated awareness or use of sleep-specific interventions (including medications). Only 40% reported they had access to sleep specialist services for patients. Conclusion: Our findings provide a useful snapshot of current approaches to managing sleep disturbances in palliative care. Gaps in current practice are highlighted, including the lack of structured, clinical assessment, referral pathways, and PCHPs\u27 perceived lack of access to targeted interventions for sleep disturbances

Isolating peripheral effects of endogenous opioids in modulating exertional breathlessness in people with moderate or severe COPD: a randomised controlled trial

Question addressed by the studyEndogenous opioids (endorphins) have been reported to modulate exercise-induced breathlessness, but the relative contribution of peripheral opioid receptors has not been tested.Materials, participants and methodsThis was a double-blind, randomised, three-arm, cross-over trial in outpatients with spirometry-verified moderate to severe chronic obstructive pulmonary disease. Participants undertook an incremental symptom-limited treadmill test followed by five endurance treadmill tests at 75% of their maximal work rate; two tests for familiarisation and three tests 30 min after intravenous injection of either methylnaltrexone 0.3 mg·kg−1 (blocking peripheral opioid receptors only) or naloxone 0.1 mg·kg−1 (blocking both central and peripheral opioid receptors) or normal saline, in randomised order. The primary end-point was the regression slope between breathlessness intensity (0–10 numerical rating scale) and oxygen consumption (V′O2) during the walk tests, comparing methylnaltrexone and placebo using a paired t-test.Results17 participants completed the trial: median (range) 66 (55–82) years; 15 males; mean±sd forced expiratory volume (FEV1) 53.8±17.6% predicted; FEV1/forced vital capacity ratio 0.55±15.9. There was no statistically or clinically significant difference in the primary end-point (regression slope of breathlessness intensity and V′O2) for methylnaltrexone (p=0.498) or naloxone (p=0.804), compared to placebo. Secondary outcomes were similar between the three treatment groups, including peak and mean breathlessness intensity and unpleasantness, exercise capacity, endurance time and leg fatigue.Answer to the questionBlocking peripheral opioid receptors (methylnaltrexone) or peripheral and central opioid receptors (naloxone) did not appear to modulate breathlessness intensity nor exercise capacity when compared with placebo (no blockade).</jats:sec

Health-related quality of life in patients with inoperable malignant bowel obstruction: secondary outcome from a double-blind, parallel, placebo-controlled randomised trial of octreotide

Abstract Background This analysis aims to evaluate health-related quality of life (HrQoL) (primary outcome for this analysis), nausea and vomiting, and pain in patients with inoperable malignant bowel obstruction (IMBO) due to cancer or its treatments randomised to standardised therapies plus octreotide or placebo over a maximum of 72 h in a double-blind clinical trial. Methods Adults with IMBO and vomiting recruited through 12 services spanning inpatient, consultative and community settings in Australia were randomised to subcutaneous octreotide infusion or saline. HrQoL was measured at baseline and treatment cessation (EORTC QLQ-C15-PAL). Mean within-group paired differences between baseline and post-treatment scores were analysed using Wilcoxon Signed Rank test and between group differences estimated using linear mixed models, adjusted for baseline score, sex, age, time, and study arm. Results One hundred six of the 112 randomised participants were included in the analysis (n = 52 octreotide, n = 54 placebo); 6 participants were excluded due to major protocol violations. Mean baseline HrQoL scores were low (octreotide 22.1, 95% CI 14.3, 29.9; placebo 31.5, 95% CI 22.3, 40.7). There was no statistically significant within-group improvement in the mean HrQoL scores in the octreotide (p = 0.21) or placebo groups (p = 0.78), although both groups reported reductions in mean nausea and vomiting (octreotide p &lt; 0.01; placebo p = 0.02) and pain scores (octreotide p &lt; 0.01; placebo p = 0.03). Although no statistically significant difference in changes in HrQoL scores between octreotide and placebo were seen, an adequately powered study is required to fully assess any differences in HrQoL scores. Conclusion The HrQoL of patients with IMBO and vomiting is poor. Further research to formally evaluate the effects of standard therapies for IMBO is therefore warranted. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12608000211369 (date registered 18/04/2008) </jats:sec