ABSTRACT
OBJECTIVES: (1) Assess the distribution of skin-to-deltoid-muscle distance (SDMD) at the deltoid intramuscular (IM) injection site; (2) its relationship with demographic and anthropometric variables and (3) Consider the findings in relation to clinical guidance on IM injection, such as COVID-19 vaccines. DESIGN: Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL and SCOPUS between June and July 2021 with no publication date limit. ELIGIBILITY CRITERIA: Studies reporting measurements of the SDMD in living adults aged 16 years and older, at the deltoid IM injection site, published in English were considered. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers performed each stage of screening, data extraction and quality assessments using the Joanna Briggs Institute Critical Appraisal Checklist for analytical cross sectional studies. RESULTS: 16 105 papers were identified, of which 11 studies were suitable for review, representing 1414 participants. Heterogeneity in the definition of the deltoid IM injection site, locations measured and methods of measurement precluded meta-analysis. Evidence from ultrasound SDMD measurements demonstrated some patients in all but 'underweight' body mass index (BMI) categories, may require needles longer than 25 mm for successful IM injection. Calliper measurements overestimated SDMD compared with ultrasound. Female sex, higher BMI categories and greater weight in women were associated with greater SDMD. CONCLUSIONS: The reviewed evidence was insufficient to inform definitive needle length 'cut points' for IM injection based on demographic or anthropomorphic variables. Contemporary clinical guidance currently based on this evidence, including the site of injection and choice of needle length, may result in subcutaneous administration in a small proportion of recipients, particularly if obese or of female sex. PROSPERO REGISTRATION NUMBER: CRD42021264625.
Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , Female , Injections, Intramuscular/methods , Cross-Sectional Studies , NeedlesABSTRACT
OBJECTIVE: To compare bronchodilator response after to salbutamol and budesonide/formoterol in adults with stable asthma. METHODS: A double-blind, cross-over, single-centre, placebo-controlled, non-inferiority trial. Adults with stable asthma were randomised to different orders of two treatment regimens: two actuations of placebo via MDI and one actuation of budesonide/formoterol 200/6 µg via turbuhaler; and one actuation of placebo turbuhaler and two actuations of salbutamol 100 µg via MDI. The primary outcome measure was FEV1 after 2 min. Secondary outcome measures included FEV1, mBorg Dyspnoea Scale score and visual analogue score for breathlessness over 30 min. RESULTS: Forty-nine of 50 potential participants were randomised. One participant withdrew following the first intervention visit and another could not be randomised due to COVID-19 restrictions. The mean (SD) change from baseline FEV1 2 min after treatment administration for budesonide/formoterol and salbutamol was 0.08 (0.14) L, n=49, and 0.17 (0.18) L, n=48, respectively, mean (95% CI) paired difference of -0.097 L (-0.147 to -0.047), p=0.07, against a non-inferiority bound of -0.06 L. In the secondary analysis, FEV1 over 30 min was lower for budesonide/formoterol compared with salbutamol, difference (95% CI): -0.10 (-0.12 to -0.08) L, p<0.001. There were no differences in Visual Analogue Scale score or mBorg Dyspnoea Scale score between treatments. CONCLUSION: The results do not support the primary hypothesis of non-inferiority at the boundary of -0.06 L for the difference between budesonide/formoterol 200/6 µg compared with salbutamol 200 µg for FEV1 at 2 min, and could be consistent with inferiority with a p value of 0.07. For the secondary analysis of FEV1 measurements over time, the FEV1 was higher with salbutamol. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ACTRN 12619001387112).
ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) has exposed the disproportionate effects of pandemics on frontline workers and the ethical imperative to provide effective prophylaxis. We present a model for a pragmatic randomised controlled trial (RCT) that utilises Bayesian methods to rapidly determine the efficacy or futility of a prophylactic agent. METHODS: We initially planned to undertake a multicentre, phase III, parallel-group, open-label RCT, to determine if hydroxychloroquine (HCQ) taken once a week was effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in healthcare workers (HCW) aged ≥ 18 years in New Zealand (NZ) and Ireland. Participants were to be randomised 2:1 to either HCQ (800 mg stat then 400 mg weekly) or no prophylaxis. The primary endpoint was time to Nucleic Acid Amplification Test-proven SARS-CoV-2 infection. Secondary outcome variables included mortality, hospitalisation, intensive care unit admissions and length of mechanical ventilation. The trial had no fixed sample size or duration of intervention. Bayesian adaptive analyses were planned to occur fortnightly, commencing with a weakly informative prior for the no prophylaxis group hazard rate and a moderately informative prior on the intervention log hazard ratio centred on 'no effect'. Stopping for expected success would be executed if the intervention had a greater than 0.975 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Final success would be declared if, after completion of 8 weeks of follow-up (reflecting the long half-life of HCQ), the prophylaxis had at least a 0.95 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Futility would be declared if HCQ was shown to have less than a 0.10 posterior probability of reducing acquisition of SARS-CoV-2 infection by more than 20%. DISCUSSION: This study did not begin recruitment due to the marked reduction in COVID-19 cases in NZ and concerns regarding the efficacy and risks of HCQ treatment in COVID-19. Nonetheless, the model presented can be easily adapted for other potential prophylactic agents and pathogens, and pre-established collaborative models like this should be shared and incorporated into future pandemic preparedness planning. TRIAL REGISTRATION: The decision not to proceed with the study was made before trial registration occurred.