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

Dose-response relationship of ICS/fast-onset LABA as reliever therapy in asthma

The dose-response relationship of inhaled corticosteroid (ICS)/fast-onset long acting beta agonist (LABA) reliever therapy has not been formally addressed. The objective of this retrospective analysis is to ascertain from the available evidence whether ICS/fast-onset LABA administered as reliever therapy has a different dose-response relationship than maintenance fixed dose ICS/fast-onset LABA therapy in reducing risk of severe exacerbations

ICS-formoterol reliever therapy stepwise treatment algorithm for adult asthma

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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

An Aotearoa New Zealand survey of the impact and diagnostic delay for endometriosis and chronic pelvic pain

Chronic pelvic pain (CPP) causes important negative effects on quality of life. Endometriosis is the most common cause of CPP in females, and diagnostic delay is over six years internationally. Data remain scarce for CPP impact or diagnostic delay in Aotearoa New Zealand. This study used an online survey to explore the impact of CPP on various life domains for those aged over 18. Additionally, for those with an endometriosis diagnosis, diagnostic delay and factors affecting this over time were explored. There were 800 respondent (620 with self-reported endometriosis). CPP symptoms, irrespective of final diagnosis, started prior to age 20 and negatively impacted multiple life domains including employment, education, and relationships. Mean diagnostic delay for those with endometriosis was 8.7 years, including 2.9 years between symptom onset and first presentation and 5.8 years between first presentation and diagnosis. Five doctors on average were seen prior to diagnosis. However, there was a reduction in the interval between first presentation and diagnosis over time, from 8.4 years for those presenting before 2005, to two years for those presenting after 2012. While diagnostic delay is decreasing, CPP, irrespective of aetiology, continues to have a significant negative impact on the lives of those affected

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