Efficacy of a topical herbal and mineral formulation (Dynamiclear) for the treatment of herpes simplex labialis in the community setting : study protocol for a randomised, double-blind placebo-controlled trial

Introduction Herpes simplex labialis (HSL) is a common infection that can cause painful lesions on the oral mucosa, commonly referred to as cold sores. Current biomedical treatments include topical aciclovir, which reduces the episode duration by an average of 0.5 days. This study will examine the efficacy and tolerability of an over-the- counter topical treatment, Dynamiclear in reducing duration and severity of HSL episodes. Methods and analysis This prospective, randomised, double-blind, placebo-controlled, multi-centre trial will recruit a minimum of 292 adult participants across Australia and New Zealand who present with a cold sore within 48 hours of onset. They will be randomly allocated in a 2:1 ratio to receive either topical Dynamiclear (active) or placebo. Dynamiclear’s active ingredients are Hypericum perforatum, Calendula Officinalis and copper sulfate. A single topical treatment of active or placebo will be applied by a pharmacy-based investigator, and participants will be provided with a viral swab kit to confirm presence of herpes virus 1 or 2 from ulcerated lesions. Participants will receive reminders by email and/ or SMS to complete an online daily diary assessing their cold sore lesion using a visual guide, and recording other symptoms on numeric scales until healed. The primary outcome variable is median duration of HSL episode in days (participant evaluated) from presentation to return to normal skin. Secondary outcomes include severity of lesion pain, itching, burning and tingling during the symptomatic phase and proportion of lesions progressing to ulceration

Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis : a randomised controlled trial

Objective To compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis. Design Prospective parallel randomised controlled open-label superiority trial. Setting 76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017. Participants 952 adults randomised within the first 72 hours of a herpes simplex labialis episode. Interventions Random assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily. Outcome measures The primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability. Results Primary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported. Conclusion There was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis

Cohort feasibility study of an intermittent pneumatic compression device within a below-knee cast for the prevention of venous thromboembolism

OBJECTIVES: To determine the likely enrolment rate of eligible participants into a randomised controlled trial (RCT) in which a within-cast intermittent pneumatic compression device using Jet Impulse Technology (IPC/JIT) is 1 of 3 possible interventions in a RCT for the prevention of venous thromboembolism (VTE) in the clinical setting of isolated lower limb cast immobilisation. DESIGN: A prospective, open-label feasibility study of the IPC/JIT device placed within a lower limb cast. SETTING: Wellington Regional Hospital Fracture Clinic.PARTICIPANTS: Individuals aged 18-70 who presented with a lower limb injury requiring a minimum of 4 weeks below-knee cast immobilisation. INTERVENTION: Placement of an IPC/JIT device within lower limb cast. OUTCOME MEASURES: The main outcome measure was the proportion of eligible participants who participated in the feasibility study. Secondary outcome measures included adherence to device usage throughout the study, ease of application of the device and adverse events potentially associated with its use. RESULTS: The proportion of potentially eligible participants for the IPC/JIT device was only 7/142 (5%), 95% CI 2 to 9.9. Devices were used for a mean (range) of 4.1 (1.9 to 10.2) hours per day and none of 7 participants had adequate adherence to the device. 3 of the 7 participants suffered an adverse event, including 1 deep vein thrombosis, 2 dorsal foot ulcer and 1 skin maceration. CONCLUSIONS: A within-cast IPC/JIT device is unlikely to be a feasible randomisation arm for a RCT assessing possible interventions for the reduction of VTE risk in the clinical setting of lower limb injury requiring below knee cast immobilisation for a minimum of 4 weeks

Cohort feasibility study of an intermittent pneumatic compression device within a below-knee cast for the prevention of venous thromboembolism

OBJECTIVES: To determine the likely enrolment rate of eligible participants into a randomised controlled trial (RCT) in which a within-cast intermittent pneumatic compression device using Jet Impulse Technology (IPC/JIT) is 1 of 3 possible interventions in a RCT for the prevention of venous thromboembolism (VTE) in the clinical setting of isolated lower limb cast immobilisation. DESIGN: A prospective, open-label feasibility study of the IPC/JIT device placed within a lower limb cast. SETTING: Wellington Regional Hospital Fracture Clinic.PARTICIPANTS: Individuals aged 18-70 who presented with a lower limb injury requiring a minimum of 4 weeks below-knee cast immobilisation. INTERVENTION: Placement of an IPC/JIT device within lower limb cast. OUTCOME MEASURES: The main outcome measure was the proportion of eligible participants who participated in the feasibility study. Secondary outcome measures included adherence to device usage throughout the study, ease of application of the device and adverse events potentially associated with its use. RESULTS: The proportion of potentially eligible participants for the IPC/JIT device was only 7/142 (5%), 95% CI 2 to 9.9. Devices were used for a mean (range) of 4.1 (1.9 to 10.2) hours per day and none of 7 participants had adequate adherence to the device. 3 of the 7 participants suffered an adverse event, including 1 deep vein thrombosis, 2 dorsal foot ulcer and 1 skin maceration. CONCLUSIONS: A within-cast IPC/JIT device is unlikely to be a feasible randomisation arm for a RCT assessing possible interventions for the reduction of VTE risk in the clinical setting of lower limb injury requiring below knee cast immobilisation for a minimum of 4 weeks

How big is your bubble? : characteristics of self-isolating household units ('bubbles') during the COVID-19 Alert Level 4 period in New Zealand : a cross-sectional survey

Objective To characterise the self-isolating household units (bubbles) during the COVID-19 Alert Level 4 lockdown in New Zealand. Design, setting and participants In this cross-sectional study, an online survey was distributed to a convenience sample via Facebook advertising and the Medical Research Institute of New Zealand's social media platforms and mailing list. Respondents were able to share a link to the survey via their own social media platforms and by email. Results were collected over 6 days during Alert Level 4 from respondents living in New Zealand, aged 16 years and over. Main outcomes measures The primary outcome was the mean size of a self-isolating household unit or bubble. Secondary outcomes included the mean number of households in each bubble, the proportion of bubbles containing essential workers and/or vulnerable people, and the mean number of times the home was left each week. Results 14 876 surveys were included in the analysis. The mean (SD) bubble size was 3.58 (4.63) people, with mean (SD) number of households 1.26 (0.77). The proportion of bubbles containing one or more essential workers, or one or more vulnerable persons was 45.3% and 42.1%, respectively. The mean number of times individual bubble members left their home in the previous week was 12.9 (12.4). Bubbles that contained at least one vulnerable individual had fewer outings over the previous week compared with bubbles that did not contain a vulnerable person. The bubble sizes were similar by respondent ethnicity. Conclusion In this New Zealand convenience sample, bubble sizes were small, mostly limited to one household, and a high proportion contained essential workers and/or vulnerable people. Understanding these characteristics from a country which achieved a low COVID-19 infection rate may help inform public health interventions during this and future pandemics

RCT of the effect of berryfruit polyphenolic cultivar extract in mild steroid-naive asthma : a cross-over, placebo-controlled study

Objective: There is preclinical evidence that consumption of berryfruit extract may reduce chronic airways inflammation and modify airway remodelling in allergen-induced models of lung inflammation. We investigated the effect of berryfruit extract on the fractional expired nitric oxide (FeNO), a biomarker of eosinophilic airways inflammation, in adults with steroid-naïve asthma. Design: Randomised placebo-controlled cross-over double-blind trial. Setting: Single-centre community-based trial. Participants: 28 steroid-naïve mild asthmatics with FeNO >40 ppb, of whom 25 completed both study interventions. Interventions: Participants were randomised to receive, according to the cross-over design, 100 mg berryfruit polyphenolic extract (BFPE) or placebo for 4 weeks, with a 4-week washout period between the interventions. Primary outcome measure: The primary outcome variable was FeNO at 4 weeks, analysed by a mixed linear model, with a random effect for participant and baseline FeNo as a covariate. Results: The mean (SD) natural logarithm transformed (ln) FeNO after 4 weeks of treatment for the BFPE and placebo groups was 4.28 (0.47) and 4.22 (0.47), respectively. The paired change from baseline mean (SD) BFPE minus placebo ln FeNO was -0.03 (0.39), N=25. The mixed linear model estimate, with baseline covariate adjustment, difference in ln FeNO, was -0.002 (95% CI -0.15 to 0.14), p=0.98. This is equivalent to a ratio of geometric mean FeNO of 1.0 (95% CI 0.86 to 1.15). Conclusions: In steroid-naïve participants with mild asthma and elevated FeNO, there was no effect of BFPE on FeNO, a biomarker of eosinophilic airways inflammation. Caution is required in the extrapolation of apparent benefit in murine models of lung eosinophilia to clinical efficacy in patients with asthma

Randomised controlled trial of paracetamol or ibuprofen, as required for fever and pain in the first year of life, for prevention of asthma at age 6 years : paracetamol or ibuprofen in the primary prevention of asthma in Tamariki (PIPPA Tamariki) protocol

Introduction Asthma is one of the most common diseases in the world and is a global public health burden. There is an urgent need for research that leads to evidenced-based primary prevention strategies to reduce the prevalence of asthma. One novel risk factor that might have a role in the pathogenesis of asthma is the use of paracetamol in early life. This trial aims to determine if paracetamol, compared with ibuprofen use, as required for fever and pain in the first year of life, increases the risk of asthma at age 6 years. Methods and analysis The Paracetamol and Ibuprofen in Primary Prevention of Asthma in Tamariki trial is a multicentre, open-label, two-Arm parallel randomised controlled trial. 3922 infants born at ≥32 weeks' gestation will be randomly allocated to receive only paracetamol or only ibuprofen for treatment of fever and pain, if required in the first year of life. The primary outcome is asthma at 6 years of age, defined as the presence of wheeze in the preceding 12 months. Secondary outcomes include hospital admissions for bronchiolitis, wheeze or asthma in the first year of life, and within the first 6 years of life; wheeze at 3 years of age; eczema within the first year and at 3 and 6 years of age; atopy at 3 and 6 years of age. Ethics and dissemination The trial has been approved by the Northern A Health and Disability Ethics Committee of New Zealand (17/NTA/233). Dissemination plans include publication in international peer-reviewed journals, and presentation at national and international scientific meetings, assimilation into national and international guidelines, and presentation of findings to lay audiences through established media links. Trial registration number ACTRN12618000303246; Pre-results

Efficacy of a 3% kānuka oil cream for the treatment of moderate-to-severe eczema : a single blind randomised vehicle-controlled trial

Background: Māori, the indigenous people of New Zealand, have traditionally used the kānuka tree as part of their healing system, Rongoā Māori, and the oil from the kānuka tree has demonstratable anti-inflammatory and anti-bacterial properties. This trial investigated the efficacy and safety of a 3% kānuka oil (KO) cream compared to vehicle control (VC) for the topical treatment of eczema. The trial was conducted through a nationwide community pharmacy research network. Methods: This single-blind, parallel-group, randomised, vehicle-controlled trial was undertaken in 11 research trained community pharmacies across New Zealand. Eighty adult participants with self-reported moderate-to-severe eczema, assessed by Patient Orientated Eczema Measure (POEM) were randomised by blinded investigators to apply 3% KO cream or VC topically, twice daily, for six weeks. Randomisation was stratified by site and eczema severity, moderate versus severe. Primary outcome was difference in POEM scores at week six between groups by intention to treat. The study is registered on the Australian New Zealand Clinical Trial Registry (ANZCTR) reference number, ACTRN12618001754235. Findings: Eighty participants were recruited between 17 May 2019 and 10 May 2021 (41 KO group, 39 VC group). Mean POEM score (standard deviation) improved between baseline and week six for KO group, 18·4 (4·4) to 6·8 (5·5), and VC group, 18·7 (4·5) to 9·8 (6·5); mean difference between groups (95% confidence interval) was -3·1 (-6·0 to -0·2), p = 0·036. There were three adverse events reported in the KO group related to the intervention and two in the control group. Interpretation: The KO group had a significant improvement in POEM score compared to VC. Rates of adverse events and withdrawals were similar between groups with no serious adverse events reported. Treatment acceptability was high for both groups across all domains. Our results suggest that in adults with moderate-to-severe eczema, the addition of KO to a daily emollient regimen led to a reduction in POEM score compared to VC. KO may represent an effective, safe, and well tolerated treatment for moderate-to-severe eczema in adults

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

Medical cannabis : knowledge and expectations in a cohort of North Island New Zealand general practitioners

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