Sympathetic activation is the hallmark of cardiac disease, driving disease progression and triggering ventricular arrhythmia (VA). Despite optimal medical therapy, many patients experience recurrent VAs refractory to medical therapy, leading to repetitive implantable cardioverter defibrillator (ICD) therapy, worse quality of life and adverse outcomes. Cardiac sympathetic denervation (CSD) through surgical removal of the stellate ganglia is an effective treatment for refractory VAs but carries a high complication rate. We hypothesise that high precision image guided radiotherapy can be used to target the stellate ganglia to achieve CSD non-invasively.

RADIO-STAR (hypofractionated radiotherapy to the stellate ganglia for ventricular arrhythmia) is a first-in-human, phase 1 safety and dose finding study of radiotherapy to the stellate ganglia in patients with recurrent VAs. Patients with structural heart disease requiring recurrent ICD therapy for VAs are invited to undergo radiotherapy bilaterally to their stellate ganglia with a predetermined sample size of n=13. Radiotherapy dose will be determined by a prespecified dose escalation protocol. The primary outcome is safety defined as any treatment-related grade 3–5 toxicity occurring within 6 months of radiotherapy treatment, as defined by the Common Terminology Criteria for Adverse Events or any treatment-related side effects detected on patient symptom questionnaires and clinical examination during study visits. Secondary outcome measures to evaluate feasibility and efficacy include ability to safely deliver radiotherapy and consequent changes in circulating catecholamines and neuropeptide-Y, heart rate variability, structural changes in the stellate ganglia on MRI imaging and ICD therapy burden.

This study has received ethical approval by the South Central—Oxford B Research Ethics Committee (REC/SC/0005). Study findings will be submitted for publication in peer-reviewed scientific journals and presented at national and/or international scientific conferences.

ISRCTN49861434.

To detail the development of the Canadian National Questionnaire on Overdose Monitoring (CNQOM), a questionnaire aimed at assessing the perspectives of key stakeholders towards elements of overdose prevention interventions—supervised consumption sites (SCSs) and overdose hotlines and applications (ORHAs).

Cross-sectional survey.

Canadian health system.

English or French speaking adults from four key informant groups: people who use substances (PWUS), health professionals, emergency responders and the general public.

Test–retest reliability of CNQOM items.

A novel questionnaire was developed. Item development followed a standard approach, with face validity verified by representatives from the four informant groups. Input from experts in harm reduction and addiction medicine enhanced content and face validity of the questionnaire. A rigorous response validation approach was undertaken to ensure respondents were human and from Canada. Test–retest reliability items were assessed using Spearman’s rank correlation, Wilcoxon rank-sum test and Cohen’s kappa.

After data cleaning and response validation, 4445 valid responses were obtained from the four key informant groups. Respondents represented a range of sociodemographic backgrounds and housing scenarios from all provinces and territories in Canada. Test–retest reliability was assessed using a small subsample of 142 participants (primarily from general public informants). Questionnaire items demonstrated slight to substantial stability in responses (kappa coefficients: 0.15–0.58; Spearman’s r: 0.08–0.66).

The CNQOM is the first online questionnaire in Canada designed to capture perspectives and attitudes towards specific elements of SCSs and ORHAs among diverse key informant groups. Our questionnaire was administered to a large, geographically diverse sample and designed to capture the perspectives of four key informant groups. Lower than expected test–retest reliability may be explained by lack of participant familiarity with SCS and especially ORHAs and the impersonal nature of the instrument content among some respondents. Future work will elucidate key informant perspectives on these services based on the data.