Cannabis in Palliative Care: A Systematic Review of Current Evidence.

CONTEXT: Palliative care aims to improve the quality of life in patients with incurable illness. Medicinal cannabis (MC) has been used in the palliative care setting to address multiple symptoms in patients. OBJECTIVES: To evaluate the full scope of available literature investigating the effects and potential harms of MC on symptom management and quality of life in palliative care. METHODS: PubMed, Embase, The Cochrane Library and clinicaltrials.gov were searched for eligible articles, published between 1960 and September 9, 2021. Quality of the evidence was assessed in accordance with Grading of Recommendations, Assessment, Development and Evaluations. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized trials. RESULTS: Fifty-two studies (20 randomised; 32 non-randomised) with 4786 participants diagnosed with cancer (n = 4491), dementia (n = 43), AIDS (n = 235), spasticity (n = 16), NORSE syndrome (n = 1) were included. The quality of evidence was 'very low' or 'low' for all studies, and low for only two randomised controlled trials. Positive treatment effects (statistical significance with P < 0.05) were seen for some MC products in pain, nausea and vomiting, appetite, sleep, fatigue, chemosensory perception and paraneoplastic night sweats in patients with cancer, appetite and agitation in patients with dementia and appetite, nausea and vomiting in patients with AIDS. Meta-analysis was unable to be performed due to the wide range of cannabis products used and the heterogeneity of the study outcomes. CONCLUSION: While positive treatment effects have been reported for some MC products in the palliative care setting, further high quality evidence is needed to support recommendations for its use in clinical practice.

Rhinothermy delivered by nasal high flow therapy in the treatment of the common cold: a randomised controlled trial.

BACKGROUND: The common cold is the most common infectious disease affecting humans and has a substantial economic impact on society. Human rhinoviruses, which cause almost two-thirds of colds, have demonstrated temperature-dependent replication which is optimal between 33°C and 35°C. METHODS: This randomised, single-blind, parallel-group trial completed at a single-centre in New Zealand, recruited 170 participants aged 18-75 years (mean age 27.5 years) who were within 48 hours of common cold symptom onset and had a symptom score (the Modified Jackson Score (MJS)) ≥7 and a negative point-of-care test for influenza. Participants were blinded to the intervention and randomised (1:1) to 5 days of either nasal high flow rhinothermy (rNHF) (100% humidified air delivered at 35 L/min and 41°C for 2 hours daily) (n=85) or 'sham' rhinothermy (100% humidified air delivered at 10 L/min and 31°C for 10 min daily) (n=85) and completed daily symptom diaries, which included the MJS, for 14 days, to investigate whether rNHF reduced common cold symptom severity and duration compared with 'sham' rhinothermy. RESULTS: An intention-to-treat superiority analysis included all randomised participants and showed no difference between treatment groups for the primary outcome, the day 4 MJS analysed by analysis of covariance: mean (SD) 6.33 (3.97) for rNHF vs 5.8 (3.15) for 'sham'; estimated difference (95% CI) 0.37 (-0.69 to 1.42), p=0.49. There was no difference in time until resolution of symptoms: mean (SD) 5.96 (4.47) days for rNHF vs 6.42 (4.09) days for 'sham'; estimated difference (95% CI) 1.02 (0.75 to 1.38), p=0.91. There were no serious adverse events related to the study treatments. CONCLUSIONS: This well-powered, single-blind randomised controlled trial does not provide evidence that 5 days of rNHF (100% humidified air heated to 41°C delivered at 35 L/min for 2 hours daily) reduces common cold symptom severity or duration. However, investigation of rNHF in the treatment of influenza is warranted. TRIAL REGISTRATION NUMBER: ACTRN12617001340325.

Closed-Loop Oxygen Control Using a Novel Nasal High-Flow Device: A Randomized Crossover Trial.

BACKGROUND: Oxygen administration is recommended for patients with hypoxemia to achieve a target [Formula: see text] range. Strategies to achieve this in clinical practice are suboptimal. We investigated automatic oxygen titration using a novel nasal high-flow device with closed-loop oxygen control. The objective of this proof-of-concept study was to determine whether closed-loop control was able to respond to desaturation and subsequent recovery in a controlled laboratory-based environment. METHODS: We conducted a single-blind randomized crossover trial in adults with chronic respiratory disease who had a resting [Formula: see text] ≥ 92% and desaturated to < 90% during a 6-min walk test (6MWT). Nasal high-flow was administered during a 6MWT and a subsequent 10-min rest period with either room air, a fixed concentration of 28% oxygen, or oxygen titrated automatically using closed-loop control. RESULTS: The study involved 42 subjects. Closed-loop control maintained [Formula: see text] within the target range of 92-96% for a mean (SD) duration of 54.4 ± 30.1% of the 6MWT and 67.3 ± 26.8% of the recovery period. The proportion of time spent with an [Formula: see text] in the target range during the 6MWT was significantly greater for closed-loop control compared to room air, with a difference of 26.0% (95% CI 17.7-34.2, P < .001); this proportion of time was not significantly different compared to the fixed concentration of 28% oxygen, with a difference of -8.2% (95% CI -16.5 to 0.1, P = .052). The proportion of time spent in the target range during the rest period was significantly greater compared to 28% oxygen, with a difference of 19.3% (95% CI 8.9-29.7, P < .001); this proportion of time was not significantly different compared to room air, with a difference of -9.3% (95% CI -19.7 to 1.0, P = .08). CONCLUSIONS: This study provides proof-of-concept evidence that the novel nasal high-flow device with closed-loop control can respond to changes in [Formula: see text] outside a target saturation range using a model of exercise-induced desaturation and subsequent recovery.

Knowledge and perspectives about the use of cannabis as a medicine: a mixed methods observational study in a cohort of New Zealand general practice patients.

AIM: To determine what patients presenting to general practice (GP) understand about the use of cannabis as a medicine, beliefs of how this may impact their medical conditions and interactions with doctors. METHOD: An in-person survey of 134 GP patients from four GP practices throughout the North Island of New Zealand undertaken from November 2018 to October 2019. RESULTS: Fifty-five percent of the sample were female, with 40% of all participants aged 60 years plus. Ninety-one percent of participants indicated they would use a prescribed medicinal cannabis product while 45% reported they believed it may be of some benefit to their medical condition. Of those who believed it beneficial, 71% indicated they thought it useful for pain relief. Participants indicated comfort discussing medicinal cannabis use with GPs and specialists (92% respectively); however, less than 10% had done this. CONCLUSIONS: Just under half of patients surveyed believe that medicinal cannabis products may be helpful to their condition, and while the majority report willingness, few have discussed this with their GP or specialist. There is need for accessible, accurate information regarding the use of cannabis-based medicine for patients and doctors alike to guide the patient-doctor consultation and decrease barriers to open discussion.

Inhaled Corticosteroids in Acute Asthma: A Systemic Review and Meta-Analysis.

BACKGROUND: Asthma exacerbations are a common and important cause of attendance at emergency departments (ED) and subsequent hospital admissions. Despite previous reviews reporting that in acute settings the risk of hospital admission is reduced with the use of high doses of inhaled corticosteroids (ICS), this evidence has not changed clinical practice. OBJECTIVE: To estimate the efficacy of ICS in the treatment of acute asthma in ED. METHODS: Randomized controlled trials were identified using PubMed, The Cochrane Library, and EMBASE. The primary outcome was hospital admission rates. The primary comparison was between administration of ICS in addition to systemic corticosteroids (SCS) and to SCS alone. Secondary comparisons were ICS alone compared with SCS alone and ICS compared with placebo. RESULTS: There were 25 studies involving 2733 participants. For the primary comparison, ICS in addition to SCS reduced the risk of hospital admission compared with SCS; fixed-effects odds ratio (95% confidence interval) 0.73 (0.57-0.94). Lung function was poorly reported. There was moderate evidence of an improvement in clinical scores and vital signs with ICS in addition to SCS. Relatively few studies reported adverse events. CONCLUSION: There is moderate evidence that high doses of ICS, in addition to SCS, reduce the risk of hospital admission in ED treatment of moderate-to-severe asthma exacerbations. Further research is required to determine their optimal role in both ED and outpatient settings.

Oral steroid-sparing effect of high-dose inhaled corticosteroids in asthma.

BACKGROUND: The proportion of the efficacy of high-dose inhaled corticosteroids (ICS) in oral corticosteroid-dependent asthma that is due to systemic effects is uncertain. This study aimed to estimate the ICS dose-response relationship for oral corticosteroid-sparing effects in oral corticosteroid-dependent asthma, and to determine the proportion of oral corticosteroid-sparing effects due to their systemic effects, based on the comparative dose-response relationship of ICS versus oral corticosteroids on adrenal suppression. METHODS: Systematic review and meta-analysis of randomised controlled trials reporting oral corticosteroid-sparing effects of high-dose ICS in oral corticosteroid-dependent asthma. In addition, reports of oral corticosteroid to ICS dose-equivalence in terms of adrenal suppression were retrieved. The primary outcome was the proportion of the oral corticosteroid-sparing effect of ICS that could be attributed to systemic absorption, per 1000 µg increase of ICS, expressed as a ratio. This ratio estimates the oral corticosteroid sparing effect of ICS due to systemic effects. RESULTS: 11 studies including 1283 participants reporting oral corticosteroid-sparing effects of ICS were identified. The prednisone dose decrease per 1000 µg increase in ICS varied from 2.1 mg to 4.9 mg, depending on the type of ICS. The ratio of the prednisone-sparing effect due to the systemic effects per 1000 µg of fluticasone propionate was 1.02 (95% CI 0.68-2.08) and for budesonide was 0.93 (95% CI 0.63-1.89). CONCLUSION: In patients with oral corticosteroid-dependent asthma, the limited available evidence suggests that the majority of the oral corticosteroid-sparing effect of high-dose ICS is likely to be due to systemic effects.

Inhaled Corticosteroid Therapy in Adult Asthma. Time for a New Therapeutic Dose Terminology.

The Global Initiative for Asthma guidelines use the traditional terminology of "low," "medium," and "high" doses of inhaled corticosteroids (ICS) to define daily maintenance doses of 100 to 250 µg, >250 to 500 µg, and >500 µg, respectively, of fluticasone propionate or equivalent for adults with asthma. This concise clinical review proposes that this terminology is not evidence based and that prescribing practice based on this terminology may lead to the use of inappropriately excessive doses of ICS. Specifically, the ICS dose that achieves 80-90% of the maximum obtainable benefit is currently classified as a low dose, with the description of two higher dose levels of medium and high, which are associated with significant risk of systemic adverse effects. Asthma guidelines and clinician prescribing practice need to be modified in accordance with the currently available evidence of the dose-response relationship of ICS in adult asthma. We propose a reclassification of ICS doses based on a "standard daily dose," which is defined as 200-250 µg of fluticasone propionate or equivalent, representing the dose at which approximately 80-90% of the maximum achievable therapeutic benefit of ICS is obtained in adult asthma across the spectrum of severity. It is recommended that ICS treatment be started at these standard doses, which then represent the doses at which maintenance ICS are prescribed at step 2 and within ICS/long-acting ß-agonist combination therapy at step 3. The opportunity is available to prescribe higher doses within ICS/long-acting ß-agonist maintenance therapy in accordance with the stepwise approach to asthma treatment at step 4.

Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands.

BACKGROUND AND AIMS: Epidemiological data on autoimmune hepatitis (AIH) are scarce. In this study, we determined the clinical and epidemiological characteristics of AIH patients in the Netherlands (16.7 million inhabitants). METHODS: Clinical characteristics were collected from 1313 AIH patients (78% females) from 31 centers, including all eight academic centers in the Netherlands. Additional data on ethnicity, family history and symptoms were obtained by the use of a questionnaire. RESULTS: The prevalence of AIH was 18.3 (95% confidential interval [CI]: 17.3-19.4) per 100,000 with an annual incidence of 1.1 (95% CI: 0.5-2) in adults. An incidence peak was found in middle-aged women. At diagnosis, 56% of patients had fibrosis and 12% cirrhosis in liver biopsy. Overall, 1% of patients developed HCC and 3% of patients underwent liver transplantation. Overlap with primary biliary cirrhosis and primary sclerosing cholangitis was found in 9% and 6%, respectively. The clinical course did not differ between Caucasian and non-Caucasian patients. Other autoimmune diseases were found in 26% of patients. Half of the patients reported persistent AIH-related symptoms despite treatment with a median treatment period of 8 years (range 1-44 years). Familial occurrence was reported in three cases. CONCLUSION: This is the largest epidemiological study of AIH in a geographically defined region and demonstrates that the prevalence of AIH in the Netherlands is uncommon. Although familial occurrence of AIH is extremely rare, our twin data may point towards a genetic predisposition. The high percentage of patients with cirrhosis or fibrosis at diagnosis urges the need of more awareness for AIH.