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Background: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting β 2 -agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed., Objective: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma., Methods: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned., Conclusion: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting β-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children., Competing Interests: Conflict of interest: L. Fleming reports consulting fees from AstraZeneca, Sanofi Regeneron and GSK, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for AstraZeneca, Novartis and Sanofi Regeneron, outside the submitted work. Conflict of interest: C.A. Byrnes reports grants or contracts from the National Health and Medical Research Council Australia, Fisher & Paykel, the Buddle Findlay & Paul Stevenson Memorial Fund and FluLab, outside the submitted work; participation on a Clinical Advisory Panel for Cystic Fibrosis New Zealand and as a Bronchiectasis Foundation Trustee, outside the submitted work; and is a group for Chair, Respiratory Network, Paediatric Society of New Zealand, and a member of the Royal Australasian College of Physicians Paediatric Research Committee, outside the submitted work. Conflict of interest: D. McNamara reports participation on a data safety monitoring board or advisory board for PRECARE study primary outcome arbitration committee, outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group for Co-Chair NZ Paediatric Respiratory and Sleep Clinical Network Reference Group, and Member Scientific Advisory Board, Asthma and Respiratory Foundation of NZ, outside the submitted work. Conflict of interest: S.R. Dalziel reports grants or contracts from Cure Kids New Zealand, Health Research Council New Zealand and Starship Foundation, outside the submitted work. Conflict of interest: R. Beasley reports receiving support for the present manuscript from AstraZeneca; grants or contracts from AstraZeneca, Genentech, HRC (NZ) and Cure Kids NZ, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Avillion, Cipla, Teva and CSL Seqirus, outside the submitted work; support for attending meetings and/or travel from AstraZeneca, Avillion, Cipla, Teva and CSL Seqirus, outside the submitted work; NZ asthma guidelines chair, and GOLD board member, disclosures made outside the submitted work; and receipt of equipment, materials, drugs, medical writing, gifts or other services from AstraZeneca, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Drawing has played a key role in the development and dissemination of Medicine and Surgery, such as to share anatomy, pathology, and techniques for clinical interventions. While many of the visuals used in medicine today are created by medical illustration professionals, and by imaging techniques such as photography and radiography; many doctors continue to draw routinely in their clinical practice. This is known to be valued by patients, for example when making informed decisions about care. We surveyed doctors in New Zealand online regarding their use of drawing to explore the prevalence of this practice. 472 complete responses were obtained over 3 months. There were very high rates of drawing among responding doctors practicing in both medical and surgical specialties. Reasons for drawing are explored and included professional, collegial, and patient communication, supporting informed consent, clinical documentation, and for planning procedures. Widespread use of drawing in clinical practice, almost non-existent training or support for this in digital workflows, and high interest in resources to develop clinical drawing skills, suggest unmet training needs for this practical clinical communication tool.

Background: In randomised controlled trials, as-needed inhaled corticosteroid (ICS)-formoterol reliever therapy reduces severe exacerbation risk compared with maintenance ICS plus short-acting beta 2 -agonist (SABA) reliever in adolescent and adult asthma, but results in slightly worse control of asthma symptoms, as measured by mean Asthma Control Questionnaire-5 (ACQ-5) score., Objective: To assess the levels and changes in asthma control for as-needed budesonide-formoterol versus maintenance budesonide plus SABA in post hoc analyses from the Novel START and PRACTICAL clinical trials., Methods: The number and proportion of participants at study end in each ACQ-5 category ('well-controlled', 'partly controlled' or 'inadequately controlled' symptoms), and in each responder category based on the minimal clinically important difference for ACQ-5 of 0.5 (improved, no change and worse) with as-needed budesonide-formoterol and maintenance budesonide plus SABA treatment were calculated., Results: With last observation carried forwards, 189/214 (88.3%) and 354/434 (81.6%) of patients in the budesonide-formoterol group had 'well-controlled' or 'partly controlled' symptoms at the end of the study, vs 183/214 (85.5%) and 358/431 (83.1%) in the budesonide maintenance group, for Novel START and PRACTICAL, respectively. The proportion of patients whose symptom control was either improved or unchanged from baseline was 190/214 (88.8%) and 368/434 (84.8%) for budesonide-formoterol, vs 185/214 (86.4%) and 376/431 (87.2%) for maintenance budesonide, in Novel START and PRACTICAL respectively., Conclusions: There were no clinically important differences in the proportions of patients with 'well-controlled' or 'partly controlled' asthma symptoms, or proportions who improved or maintained their level of control, with as-needed budesonide-formoterol versus maintenance budesonide plus SABA., Competing Interests: Competing interests: LH, PB, CH, AE, RH, IB, MW, KO and MH have nothing to declare. IP reports speak fees from Aerocrine AB; speaker and consultant fees from Almirall and Novartis; speaker fees, payments for organisation of educational events, consultant fees, international scientific meeting sponsorship from AstraZeneca; speaker fees, consultant fees, international scientific meeting sponsorship from Boehringer Ingelheim; speaker fees, consultant fees, international scientific meeting sponsorship, research grant from Chiesi; speaker fees, payments for organisation of educational events, consultant fees, international scientific meeting sponsorship from GlaxoSmithKline, Regeneron Pharmaceuticals Inc, Sanofi, and Teva; consultant fees from Circassia, Dey Pharma, Genetech, Knopp Biosciences, Merk, MSD, RespiVert, and Schering-Plough; consultant fees and international scientific meeting sponsorship from Napp Pharmaceuticals. HKR reports support for the present manuscript from AstraZeneca (for Novel START) and the Health Research Council of New Zealand (for PRACTICAL); research grants from AstraZeneca, GlaxoSmithKline, Novartis; consulting fees from AstraZeneca and Novartis; independent medical education fees from AstraZeneca, GlaxoSmithKline, Teva, Boehringer-Ingelheim, Sanofi and Chiesi; participation on Advisory Boards for AstraZeneca, GlaxoSmithKline, Novartis, Chiesi and Sanofi; unpaid board roles for the Global Initiative for Asthma and the National Asthma Council (Australia). AP reports research grants from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Teva, and Sanofi; consulting fees from Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, IQVIA, Avillion, Elpen Pharmaceuticals, MSD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Menarini, Novartis, Zambon, Mundipharma, Teva, Sanofi, Edmond Pharma, IQIVA; Participation on a Data Safety Monitoring Board or Advisory Board for Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, IQVIA, Avillion, Elpen Pharmaceuticals, MSD. RB reports support for the present manuscript from AstraZeneca (for Novel START) and the Health Research Council of New Zealand (for PRACTICAL); research grants from AstraZeneca, Genentech, the Health Research Council of New Zealand and Cure Kids NZ; fees and support from AstraZeneca, Cipla, Avillion, and the Asthma and Respiratory Foundation NZ for presentations, AdBoards, attending meetings and travel, participation on advisory boards., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Janus Kinases (JAKs) mediate activity of many asthma-relevant cytokines. GDC-0214, an inhaled small molecule JAK1 inhibitor, has previously been shown to reduce fractional exhaled nitric oxide (FeNO) in patients with mild asthma, but required an excessive number of inhalations., Aim: To assess whether GDC-4379, a new inhaled JAK inhibitor, reduces FeNO and peripheral biomarkers of inflammation., Methods: This study assessed the activity of GDC-4379 in a double-blind, randomized, placebo-controlled, Phase 1 study in patients with mild asthma. Participants included adults (18-65y) with a diagnosis of asthma for ≥6 months, forced expiratory volume in 1 s (FEV 1 )> 70% predicted, FeNO >40 ppb, using as-needed short-acting beta-agonist medication only. Four sequential, 14-day, ascending-dose cohorts (10 mg QD, 30 mg QD, 40 mg BID, and 80 mg QD) of 12 participants each were randomized 2:1 to GDC-4379 or placebo. The primary activity outcome was percent change from baseline (CFB) in FeNO to Day 14 compared to the pooled placebo group. Safety, tolerability, pharmacokinetics, and pharmacodynamic biomarkers, including blood eosinophils, serum CCL17, and serum CCL18, were also assessed., Results: Of 48 enrolled participants, the mean age was 25 years and 54% were female. Median (range) FeNO at baseline was 79 (41-222) ppb. GDC-4379 treatment led to dose-dependent reductions in FeNO. Compared to placebo, mean (95% CI) percent CFB in FeNO to Day 14 was: -6 (-43, 32) at 10 mg QD, -26 (-53, 2) at 30 mg QD, -55 (-78, -32) at 40 mg BID and -52 (-72, -32) at 80 mg QD. Dose-dependent reductions in blood eosinophils and serum CCL17 were also observed. Higher plasma drug concentrations corresponded with greater FeNO reductions. No serious AEs occurred. The majority of AEs were mild to moderate. The most common AEs were headache and oropharyngeal pain. Minor changes in neutrophils were noted at 80 mg QD, but were not considered clinically meaningful., Conclusions: In patients with mild asthma, 14-day treatment with GDC-4379 reduced FeNO levels and peripheral biomarkers of inflammation. Treatment was well tolerated without any major safety concerns., Australian New Zealand Clinical Trials Registry: ACTRN12619000227190., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To describe the characteristics of offenders found not guilty on the grounds of mental illness (NGMI) in New South Wales and rates of NGMI and other homicide verdicts., Method: Demographic, legal and clinical data after referral to the NSW Mental Health Review Tribunal following an NGMI verdict for homicide matched with results from the National Homicide Monitoring Program., Results: Between 1993 and 2016, a total of 2159 homicide offenders were dealt with by the NSW courts, including 169 (7.8%) who were found NGMI. Over this period, the rate of non-NGMI homicide convictions fell from 1.83 per 100,000 per annum to 0.65 per 100,000 per annum (Kendall's tau = -0.79, p  ⩽ 0.001) while the rate of NGMI homicide fluctuated, with an average annual rate of about 0.1 per 100,000 per annum (Kendall's tau = 0.17, p  = 0.23). There was no association between the annual rates of NGMI and non-NGMI homicides (Pearson r  = -0.3, p  = 0.16) but falling rate of non-NGMI homicide meant that the proportion of NGMI offences doubled from 5.5% in the first 12 years to 11% in the second 12 years. Nearly all (88.7%) of those found NGMI had a schizophrenia-related psychosis. However, there were high rates of psychiatric comorbidity including substance use disorder (60.7%) and a history of a prior head injury (41.1%). Most (83.4%) of the NGMI offenders had previous contact with mental health services, but only half of these had received treatment with antipsychotic medication., Conclusion: The fall in conviction for homicide offences in the last 24 years has not been matched by a reduction in NGMI homicide verdicts. More assertive treatment of emerging psychosis and comorbid substance use disorders, and improved continuity of care of chronic psychosis might prevent some homicides.

Purpose of Study: To explore the experiences, patient interactions and knowledge regarding the use of cannabis as a medicine in New Zealand doctors in an oncology setting., Study Design: An observational cross-sectional survey undertaken between November 2019 and January 2020 across four secondary-care hospital oncology departments within New Zealand (Auckland, Wellington, Christchurch and Dunedin). Participants were a convenience sample of doctors; consultants, registrars, medical officers of special status and house surgeons working in oncology departments. Of 53 individuals approached, 45 participated (85% Response Rate). The primary outcome was reporteddoctor-patient interactions. Secondary outcomes included knowledge of cannabis-based products, their efficacy, prescribing regulations and educational access., Results: Of 44 doctors, 37 (84%, 95% CI: 70 to 93) reported patient requests to prescribe cannabis-based products and 43 (98%, 95% CI: 88 to 100) reported patients using illicit cannabis for medical symptoms. Primary request reasons were pain, nausea/vomiting and cancer treatment. 33/45 (73%, 95% CI: 58 to 85) cited knowledge of at least one cannabis-based product and 27/45 (60%, 95% CI: 44 to 74) indicated at least one condition that had evidence of efficacy. 36/44 (82%, 95% CI: 67 to 92) expressed future prescribing concerns but all were willing to use a cannabis-based product developed with traditional medical provenance., Conclusion: In the oncology setting, patients are asking doctors about symptomatic and curative treatment with cannabis-based products. Doctors are not biased against the use of products showing medical provenance; however, NZ-specific clinical and regulatory guidelines are essential to support patient discussions and appropriate prescribing., Competing Interests: Competing interests: KO declares that she has received funding through a Clinical Research Training Fellowship from the Health Research Council of New Zealand (HRC). IB, AS and KO are members of the Medical Cannabis Research Collaborative (NZ), an impartial collaboration of academics and regulatory experts with an interest in research into the use of cannabis as a medicine. AE, JT-S and RB have no competing interests to declare. The Medical Research Institute of New Zealand is funded by the HRC by way of an Independent Research Organisation (IRO) grant. The Medical Research Institute of New Zealand has undertaken unrelated consultant work for Helius Therapeutics, Whakaora Pharma, RuaBio and ZHM., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Recurrence is a well-established complication of spontaneous coronary artery dissection (SCAD). However, the exact incidence and correlates of recurrence are unknown. We, therefore, performed a systematic review and meta-analysis to determine and consolidate the evidence on the global incidence of SCAD recurrence., Methods: A comprehensive search of the four major databases (EMBASE, OVID Medline, PubMed and Google Scholar) was performed from their inception to 17 January 2019. We included original research studies, recruiting ≥10 participants, with ≥12 months follow-up that reported data on recurrence in patients with SCAD., Results: Out of 556 studies searched, 19 cohorts (1538 SCAD patients) were included in the analysis. There were 153 cases of de novo recurrence over a mean follow-up period of 31.2 months (95% confidence interval, 25-41 months). Type 1, 2 and 3 SCAD was noted in 33.2, 73.2 and 5.3%, respectively. The involved coronary artery was LMCA, LAD, RCA, LCx and multi-vessel CAD respectively in 3.5%, 53.4%, 19.8%, 20.4% and 12.6% of cases. The overall SCAD de novo recurrence was 7% (ES 0.07, 95% confidence interval, 0.04-0.10, I2 = 65.3%). On meta-regression, we found discharge medications at index admission, including β-blockers, ACE inhibitors, statins, as well as baseline cardiac risk factors, did not correlate with recurrence., Conclusion: SCAD recurrence is common, occurring in 7% of patients over medium-term follow up. No specific medications at discharge were found to reduce recurrence. Further long-term and prospective data are required., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Regulatory approvals for Epidiolex (purified cannabidiol) in the treatment of childhood drug resistant epilepsy have set a precedent for the use of cannabinoids as a prescribed medicine. Two common reasons cited for the use and prescription of cannabis-based products are pain and insomnia. Unlike drug resistant epilepsy, the level of evidence of efficacy in pain is poorly developed. The lowest quality trials with the greatest methodological shortcomings suggest some benefit, a level of evidence that is inconsistent with widespread prescribing. The evidence in insomnia is scant. Ongoing trial development and critical review of the literature should not be overshadowed by increasing permissiveness towards cannabis use and anecdotal reports of efficacy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To review the literature regarding label accuracy and contamination of medical cannabinoid-based products., Methods: A systematic review with meta-analysis following PRISMA guidelines. This study is registered with PROSPERO (CRD42019131565)., Results: Five studies reported label accuracy data ranging between 17% and 86%. Four studies reported contaminants, including pesticides, solvents and AB-FUBINACA. Meta-analysis was limited to the proportion of pesticide-contaminated samples found in two studies (0.25 (95% CI [0.10, 0.40])) and displayed significant heterogeneity., Conclusions: Label inaccuracies and contaminants are found across a spectrum of cannabinoid-based products. The review highlights the paucity and heterogeneity of research relating to cannabinoid-based products in light of changing global legislation. Further robust research is required to support ongoing pharmacovigilance and patient safety.

Immune checkpoint inhibitors (ICIs) are increasingly used to treat certain malignancies due to their higher efficacy compared with conventional chemotherapy. As familiarity with these agents increases, it is becoming apparent that a significant number of patients treated with ICIs experience adverse events. With time, more immune-related adverse events (IRAEs) are being recognised. It is important to be vigilant for IRAEs and recognise that a patient may have multiple IRAEs affecting multiple organ systems. Common cardiovascular adverse events associated with ICIs include myocarditis, arrhythmias and pericarditis. This case report identifies a patient presenting with takotsubo syndrome followed by ketoacidosis (associated with sodium-glucose transport protein 2 (SGLT2) inhibitor) in the setting of combination ipilimumab and nivolumab therapy for metastatic melanoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Insomnia is associated with significant comorbidity, disability and impact on quality of life and, despite advances in pharmacotherapy and psychotherapy, remains a significant burden to society. Cannabinoids are gaining acceptance for use as medicines in the treatment of insomnia disorder., Objective: We conducted a systematic review and meta-analysis to evaluate the efficacy of cannabinoids in the treatment of insomnia disorder., Methods: We performed a systematic review of the PubMed, Cochrane Library, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature Complete databases from inception to 5 December 2019, and again prior to data abstraction, for studies of cannabis-based products for the treatment of insomnia disorder in adults. Inclusion criteria were (1) clinical studies, (2) participants aged ≥ 18 years, (3) insomnia disorder either formally diagnosed against contemporaneous diagnostic criteria or quantified with validated instruments and (4) compared cannabis-based products with the standard of care, placebo or a sedative. No language restrictions were imposed. Non-primary research, animal studies and studies of cannabis-induced insomnia were excluded. Risk of bias was assessed using the RoB 2 tool for randomised controlled trials (RCTs) and Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) tool for non-randomized trials. Heterogeneity was assessed with the I 2 statistic., Results: A total of five studies (two RCTs and three non-randomised studies) with 219 study participants were included, of which three could be combined. The three non-randomised studies contributed data on the Pittsburgh Sleep Quality Index Questionnaire score, showing a favourable effect of cannabinoids at ≤ 4 weeks of follow-up (mean difference - 1.89 [95% confidence interval {CI} - 2.68 to - 1.10]; n = 176) and at 8 weeks of follow-up (mean difference - 2.41 [95% CI - 3.36 to - 1.46]; n = 166). One double-blind crossover RCT (n = 32) reported that, compared with amitriptyline, nabilone-a synthetic analogue to tetrahydrocannabinol (THC)-improved Insomnia Severity Index scores after 2 weeks of treatment (adjusted difference - 3.25 [95% CI - 5.26 to - 1.24]) and resulted in a more restful sleep as a sub-measure of the Leeds Sleep Evaluation Questionnaire (LSEQ) (difference 0.48 [95% CI 0.01-0.95]) but with no effect on overall sleep quality as measured by the LSEQ. In a single ascending-dose RCT (n = 9), THC reduced sleep-onset latency compared with placebo at 10 mg, 20 mg and 30 mg doses (mean difference - 43.00 min [95% CI - 82.76 to - 3.24], - 62.00 [95% CI - 103.60 to - 20.40] and - 54.00 [95% CI - 103.93 to - 4.07], respectively). All the included studies were assessed as poor quality, mainly due to small sample sizes, short treatment periods, uncertain clinical significance and high risk of bias., Conclusions: Few studies have examined the efficacy of cannabinoids in the treatment of insomnia disorder. Despite some possible signals for efficacy, the heterogeneity of participants, interventions, efficacy outcomes and results, and the high risk of bias across included trials, do not reliably inform evidence-based practice. This review highlights shortcomings in the existing literature, including lack of diagnostic clarity, poorly defined participant groups, non-standardised interventions and studies of inappropriate design, duration and power to detect clinically meaningful outcomes. Further research in the form of high-quality RCTs are required before drawing any conclusions about the efficacy of cannabinoids in the treatment of insomnia disorder., Trial Registration: PROSPERO registration number, CRD42020161043.

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., Competing Interests: Karen Oldfield declares that she has received funding through a Clinical Research Training Fellowship from the Health Research Council of New Zealand (HRC). Irene Braithwaite, Alex Semprini and Karen Oldfield are members of the Medical Cannabis Research Collaborative (NZ), an impartial collaboration of academics and regulatory experts with an interest in research into the use of cannabis as a medicine. Ingrid Maijers, Allie Eathorne and Richard Beasley have no competing interests to declare. The Medical Research Institute of New Zealand has undertaken unrelated consultant work for RuaBio, Zealand Health Manufacturing, Whakaora Pharma and Helius Therapeutics.

Background: Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. In this prespecified subgroup analysis of a previously published open-label clinical trial, we aimed to assess associations between blood eosinophil counts and FeNO with outcomes and response to asthma treatment., Methods: In the previously reported 52-week, open-label, randomised controlled trial, people with mild asthma receiving only β agonist reliever inhalers were enrolled at one of 16 clinical trials units in New Zealand, the UK, Italy, or Australia. Eligible participants were randomly assigned (1:1:1, stratified by country), to receive inhalers to take as-needed salbutamol (two inhalations of 100 μg in a pressurised metered dose inhaler), maintenance budesonide (200 μg twice per day by inhaler) plus as-needed salbutamol (two inhalations of 100 μg), or as-needed budesonide-formoterol (one inhalation of 200 μg budesonide and 6μg formoterol by inhaler). The primary outcome was the annual rates of asthma exacerbations per patient, and in this prespecified subgroup analysis, we assessed whether annual exacerbation rates in each treatment group were significantly different depending on levels of blood eosinophil count, FeNO, or a composite score of both. Analyses were done for patients with available biomarker measurements The study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000999538., Findings: 675 participants were enrolled between March 17, 2016, and Aug 29, 2017, of whom 656 had results for blood eosinophil analysis and 668 had results for FeNO. Of the patients who received as-needed salbutamol, the proportion of patients having a severe exacerbation increased progressively with increasing blood eosinophil count (two [4%] of 49 participants with <0·15 × 10 9 /L, six [6%] of 93 with 0·15 to <0·3 × 10 9 /L, and 15 [19%] of 77 with ≥0·3 × 10 9 /L; p=0·014). There were no significant interactions between blood eosinophil count or FeNO level and the effect of as-needed budesonide-formoterol compared with as-needed salbutamol for either exacerbations or severe exacerbations. However, there were significant interactions between blood eosinophil count subgroups and the effect of maintenance budesonide plus as-needed salbutamol compared with as-needed salbutamol, both for exacerbations (p=0·0006) and severe exacerbations (p=0·0007). Maintenance budesonide plus as-needed salbutamol was more effective than as-needed salbutamol in patients with blood eosinophil counts of 0·3 × 10 9 /L or more, both for exacerbations (rate ratio 0·13 [95% CI 0·05-0·33]) and severe exacerbations (risk odds ratio 0·11 [0·03-0·45]). This difference was not seen for blood eosinophil counts of less than 0·15 × 10 9 /L (1·15 [0·51-1·28] for exacerbations and 5·72 [0·97-33·60] for severe exacerbations). There was no consistent interaction between treatment response and FeNO or the composite score., Interpretation: In patients with mild asthma, the effects of as-needed budesonide-formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts than in patients with low counts., Funding: AstraZeneca, Health Research Council of New Zealand., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: The changing medicolegal climate regarding the medicinal use of cannabinoids in New Zealand will increase the likelihood of patients consulting general practitioners (GPs) about these products. Arthritis is a common medical condition for which cannabis-based products are promoted and used; however, doctors' knowledge about the efficacy and safety of these products in the setting of arthritis may be limited., Methods: We undertook a rapid review of the medical literature on cannabis-based medicinal products in arthritis., Results: Animal studies have identified endocannabinoid pathways in arthritis that are potentially amenable to interventions. One randomised placebo-controlled trial of Sativex® in adults with rheumatoid arthritis has shown some improvements in pain but not in comparison with a standardised pharmacological treatment regimen. Systematic reviews of cannabis-based products in arthritis have determined that there is currently insufficient evidence to recommend cannabis-based medicines for routine clinical use. There were five ongoing registered clinical trials of cannabis-based products in arthritis, the results of which are yet to be reported., Conclusions: While animal models have identified possible endocannabinoid pathways in arthritis, there is no clear evidence of benefit in humans or comparative efficacy with current treatments. At this stage, there is little evidence to support GPs prescribing cannabis-based medicinal products for arthritis., Competing Interests: Prof Michelle Glass and Drs Karen Oldfield, Alex Semprini and Irene Braithwaite are members of the Medical Cannabis Research Collaborative, an impartial collaboration of academics and regulatory experts in the field of cannabis-based medicine development. The Medical Research Institute of New Zealand has undertaken research activity Helius Therapuetics, Hikurangi Enterprises and Whakaora Pharma, all of which are New Zealand-based medicinal cannabis companies. There are no other conflicts of interest to declare. The Medical Research Institute receives Independent Research Organisation funding from the Health Research Council of New Zealand.

Aim: To investigate GP knowledge of the use of cannabis as a medicine and its regulation in New Zealand., Method: A convenience sample of GPs completed a questionnaire during continuing medical education sessions. Key domains investigated were: patient interactions around use of cannabis as a medicine; prescription facilitation and impediments; knowledge of evidence for and against the use of cannabis as a medicine; knowledge of the New Zealand regulatory processes and knowledge of pharmaceutical grade products. Questionnaires were administered between June and October 2018., Results: There were 42/76 (55%) GPs who stated at least one patient had asked for a cannabis prescription for medical use in the last 12 months and 43/76 (57%) were aware of pharmaceutical grade preparations, the majority Sativex. There were 59/75 (79%) who expressed concerns about future prescribing; however, 63/75 (84%) indicated they would be 'somewhat' or 'very' likely to prescribe a PHARMAC-funded product with good evidence in specific conditions., Conclusion: Some GPs have concerns about prescribing medicinal cannabis. Due to regulatory restrictions, including no currently funded products, and uncertain scientific evidence of efficacy and safety, education programmes will be required to inform the medico-legal, evidential and practical elements of prescribing cannabis as a medicine., Competing Interests: Karen Oldfield, Irene Braithwaite, Giles Newton-Howes and Alex Semprini are members of the Medical Cannabis Research Collaborative (NZ), an impartial collaboration of academics and regulatory experts with an interest in research into the use of cannabis as a medicine. The Medical Research Institute of New Zealand has undertaken research activity that is unrelated to this article for Helius and Whakaora Pharma, both of which are New Zealand-based medicinal cannabis companies. There are no other conflicts of interest to declare.

With rapidly changing legislation designed to improve access to cannabis-based medicinal products, we assess the obligations of the law and professional bodies on the proposed prescribers of these products. We argue that the current legal and professional obligations may limit prescribing practices despite legislative change, and that without the usual licensing processes of Medsafe being applied to these products, prescribers and their professional bodies must engage in the process of change to ensure short- and long-term patient safety and to maintain professional standards., Competing Interests: All authors are members of the Medical Marijuana Research Collaborative, an impartial collaboration of academics and regulatory experts in the field of cannabis-based medicine development. The Medical Research Institute of New Zealand has undertaken research activity unrelated to this article for Helius, and Whakaora Pharma, both of which are New Zealand-based medicinal cannabis companies. There are no other conflicts of interest to declare.