Manuka oil based ECMT-154 versus vehicle control for the topical treatment of eczema: study protocol for a randomised controlled trial in community pharmacies in Aotearoa New Zealand.

BACKGROUND: Eczema is a chronic, relapsing skin condition commonly managed by emollients and topical corticosteroids. Prevalence of use and demand for effective botanical therapies for eczema is high worldwide, however, clinical evidence of benefit is limited for many currently available botanical treatment options. Robustly-designed and adequately powered randomised controlled trials (RCTs) are essential to determine evidence of clinical benefit. This protocol describes an RCT that aims to investigate whether a manuka oil based emollient cream, containing 2% ECMT-154, is a safe and effective topical treatment for moderate to severe eczema. METHODS: This multicentre, single-blind, parallel-group, randomised controlled trial aims to recruit 118 participants from community pharmacies in Aotearoa New Zealand. Participants will be randomised 1:1 to receive topical cream with 2% ECMT-154 or vehicle control, and will apply assigned treatment twice daily to affected areas for six weeks. The primary outcome is improvement in subjective symptoms, assessed by change in POEM score. Secondary outcomes include change in objective symptoms assessed by SCORAD (part B), PO-SCORAD, DLQI, and treatment acceptability assessed by TSQM II and NRS. DISCUSSION: Recruitment through community pharmacies commenced in January 2022 and follow up will be completed by mid-2023. This study aims to collect acceptability and efficacy data of manuka oil based ECMT-154 for the treatment of eczema. If efficacy is demonstrated, this topical may provide an option for a novel emollient treatment. The community-based design of the trial is anticipated to provide a generalisable result. ETHICS AND DISSEMINATION: Ethics approval was obtained from Central Health and Disability Ethics Committee (reference: 2021 EXP 11490). Findings of the study will be disseminated to study participants, published in peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001096842. Registered on August 18, 2021 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382412&isReview=true ). PROTOCOL VERSION: 2.1 (Dated 18/05/2022).

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

Background: Maori, the indigenous people of New Zealand, have traditionally used the kanuka tree as part of their healing system, Rongoa Maori, and the oil from the kanuka tree has demonstratable anti-inflammatory and anti-bacterial properties. This trial investigated the efficacy and safety of a 3% kanuka 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. Funding: Hikurangi Bioactives (Ruatoria, New Zealand) and HoneyLab (Tauranga, New Zealand), supported by a grant from Callaghan Innovation.

Automatic versus manual oxygen titration using a novel nasal high-flow device in medical inpatients with an acute illness: a randomised controlled trial.

BACKGROUND: Guideline recommendations state oxygen should be administered to acutely unwell patients to achieve a target oxygen saturation (SpO2) range. The current practice of manual oxygen titration frequently results in SpO2 outside of a prescribed range. The aim of this study was to assess the efficacy of automatic oxygen titration using a closed-loop feedback system to achieve SpO2 within a prescribed target range METHODS: An open-label randomised parallel group trial was undertaken comparing automatic oxygen titration using a novel nasal high-flow device to manual oxygen titration using nasal high flow. Medical inpatients requiring oxygen therapy in Wellington Regional Hospital, New Zealand with a prescribed target SpO2 range of 88%-92% or 92%-96% were recruited and randomised equally between the interventions for a period of 24 hours. The primary outcome was the proportion of time spent with SpO2 within the prescribed range. RESULTS: 20 patients were included in the analysis. Automatic oxygen titration resulted in a median (IQR) 96.2% (95.2-97.8) of time within the target range compared with 71% (59.4-88.3) with manual titration; difference (95% CI) 24.2% (7.9% to 35%), p<0.001. There was a reduction in the time spent with SpO2 ≥2% above and ≥2% below range in the automatic titration group, although the point estimate for the differences were small; -1% (-8.2% to -0.04%), p=0.017 and -2.4% (-11.5% to 0.3%), p=0.05 respectively. CONCLUSIONS: Nasal high-flow with automatic oxygen titration resulted in a greater proportion of time spent with SpO2 in target range compared with manual titration. TRIAL REGISTRATION: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619000901101).

Closed-Loop Oxygen Control Using a Novel Nasal High-Flow Device: A Randomized Crossover Trial.

BACKGROUND: Oxygen administration is recommended for patients with hypoxemia to achieve a target [Formula: see text] range. Strategies to achieve this in clinical practice are suboptimal. We investigated automatic oxygen titration using a novel nasal high-flow device with closed-loop oxygen control. The objective of this proof-of-concept study was to determine whether closed-loop control was able to respond to desaturation and subsequent recovery in a controlled laboratory-based environment. METHODS: We conducted a single-blind randomized crossover trial in adults with chronic respiratory disease who had a resting [Formula: see text] ≥ 92% and desaturated to < 90% during a 6-min walk test (6MWT). Nasal high-flow was administered during a 6MWT and a subsequent 10-min rest period with either room air, a fixed concentration of 28% oxygen, or oxygen titrated automatically using closed-loop control. RESULTS: The study involved 42 subjects. Closed-loop control maintained [Formula: see text] within the target range of 92-96% for a mean (SD) duration of 54.4 ± 30.1% of the 6MWT and 67.3 ± 26.8% of the recovery period. The proportion of time spent with an [Formula: see text] in the target range during the 6MWT was significantly greater for closed-loop control compared to room air, with a difference of 26.0% (95% CI 17.7-34.2, P < .001); this proportion of time was not significantly different compared to the fixed concentration of 28% oxygen, with a difference of -8.2% (95% CI -16.5 to 0.1, P = .052). The proportion of time spent in the target range during the rest period was significantly greater compared to 28% oxygen, with a difference of 19.3% (95% CI 8.9-29.7, P < .001); this proportion of time was not significantly different compared to room air, with a difference of -9.3% (95% CI -19.7 to 1.0, P = .08). CONCLUSIONS: This study provides proof-of-concept evidence that the novel nasal high-flow device with closed-loop control can respond to changes in [Formula: see text] outside a target saturation range using a model of exercise-induced desaturation and subsequent recovery.

Protocol for a randomised controlled trial of 90% kanuka honey versus 5% aciclovir for the treatment of herpes simplex labialis in the community setting.

INTRODUCTION: Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as 'cold sores', which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban). METHODS AND ANALYSIS: This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution. ETHICS AND DISSEMINATION: New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results.SCOTT Registration: 15/SCOTT/14 PROTOCOL VERSION: 4.0 (12 June 2017).

Dorsomedial fracture dislocation of the first ray and medial cuneiform: a case report.

Isolated dislocation of the medial cuneiform is a rare injury. A favorable outcome relies on an accurate and stable reduction. Evidence of residual instability can be subtle. We present 1 such injury whose true extent was not fully appreciated at presentation, despite multiple plain films. Occult fracture of the medial cuneiform contributed to residual instability of the first ray and persistent and progressive symptoms and ultimately necessitated operative stabilization of the medial arch. We recommend the use of computed tomography as an adjunct to plain radiography for all midfoot dislocations to more accurately define the extent of the injury.

Outcomes following pantalar arthrodesis in rheumatoid arthritis.

BACKGROUND: We report a consecutive series of pantalar arthrodeses in patients with rheumatoid arthritis, using a single laterally based incision and autologous bone graft. MATERIALS AND METHODS: All operations were performed by a single surgeon and were assessed preoperatively and at 6 and 12 months postoperatively. The levels of patient satisfaction, functional improvement and pain scores of the foot following surgery were recorded along with radiological parameters. Seventeen patients (two male and 15 female) underwent 18 hindfoot surgeries and were assessed preoperatively using the SF-12 General Health survey questionnaire, Manchester-Oxford Foot Survey and pain scores. RESULTS: We found a significant improvement in pain levels and SF-12 scores. In addition the patients reported a high level of satisfaction with the outcome of surgery and improvement in function. CONCLUSION: The results show that pantalar arthrodesis is a very effective operative treatment for severe ankle and concomitant hindfoot disease. The treatment period is prolonged and patients should be counselled appropriately. LEVEL OF EVIDENCE: IV, Retrospective Case Series

Bizarre parosteal osteochondromatous proliferation of the metatarsal: a pediatric case report and archival review.

UNLABELLED: Bizarre parosteal osteochondromatous proliferations (BPOP), also known as Nora's lesions, are rare tumors occurring most commonly in the hands and feet. They are benign and rarely exhibit radiological evidence of cortical invasion. We report a case of BPOP showing atypical magnetic resonance imaging features that are inconsistent with BPOP and having a novel chromosomal aberration. We also review the BPOP cases in our regional benign bone tumor database. LEVEL OF CLINICAL EVIDENCE: 4.

An age- and sex-matched comparative study on both-bone diaphyseal paediatric forearm fracture.

PURPOSE: Intramedullary (IM) nailing and plating are recognised fixation methods for both-bone midshaft forearm fractures. Although both methods are effective, IM nailing has recently been the accepted operative treatment for the paediatric population. The aim of the study was to compare the differences in the radiographic and functional outcomes of an age- and sex-matched cohort of children following treatment by IM fixation or plate fixation with screws for an unstable both-bone diaphyseal fracture. METHODS: A retrospective study was conducted and 17 age- and sex-matched pairs of patients returned for a research review clinic. The average age of our patients was 11.6 years at follow up, with 11 boys and six girls in each group. The mean follow up was similar in both groups (IM 31.5 months, plating 31.8 months). RESULTS: Plating and IM nailing result in good or excellent functional and radiological outcomes. Radiographs at the review clinic showed complete healing in the plating group, with reconstitution of the radial bow. Three patients in the IM group did not regain the natural radial bow radiographically. There were no significant differences between both groups for maximum radial bow and its location (P > 0.05). However, the maximum radial bow was significantly different from normative values in both groups (P = 0.003 plate, P = 0.005 IM). No non-union or malunion was observed. There were no significant differences in the loss of forearm motion and grip strength between both groups. There was no difference in the Pediatric Orthopaedic Society of North America (POSNA) scores between both groups. The plating group had a significantly worse Manchester scar score than the IM group (P = 0.012). One major complication was observed in each group: osteomyelitis for IM fixation and ulnar never palsy for plating. CONCLUSION: Our study suggests that functional outcome is likely to be equivalent, regardless of which method of internal fixation is used.

The use of a nerve stimulator to allow safe placement of Ilizarov wires.

OBJECTIVE: Avoidance of potential iatrogenic nerve injury during insertion of Ilizarov fine wires into areas of high anatomic risk by using a modified nerve stimulation technique. INDICATIONS: Application of the Ilizarov ring fixator to areas of high anatomic hazard, in situations where anatomic topography may be distorted by previous surgery, trauma, or congenital anomalies. CONTRAINDICATIONS: Use of systemic muscle relaxants. Caution in patient with cardiac pacemaker. SURGICAL TECHNIQUE: Preliminary experiments showed that a standard nerve-stimulating device can deliver a negatively charged, monophasic square pulse of current through Ilizarov wires. During the application of an Ilizarov frame to potentially hazardous anatomic regions, providing no systemic muscle relaxants are used, a voltage field sufficient to cause nerves in close proximity to the Ilizarov wire to depolarize is produced. Identification of a distal muscle twitch provoked by the stimulation may indicate a potential for iatrogenic nerve injury. RESULTS: Results show that with the nerve stimulator set at 2.5 mA (pulsed at a frequency of 2 Hz), peripheral nerves are stimulated if they lie within 5 mm of the wires. Should a distal muscle twitch occur, wires should be repositioned so that equivalent stimulation produces no twitch. The technique was used during Ilizarov frame application in ten patients, with only a single occurrence of distal muscle twitches in a lower-leg frame. Following repositioning of the Ilizarov wire in this case, no further twitches were observed, indicating that no Ilizarov wire was inserted close to peripheral nerves. No neurologic impairment was present postoperatively.

Predicting the loss of knee flexion during limb lengthening using inherent muscle length.

Limb lengthening procedures can be associated with loss of range of knee movement, although the amount of knee flexion lost varies markedly between patients. The exact aetiology of this problem is not fully understood. This study investigates whether the amount of joint range that is lost during limb lengthening might be affected by the inherent passive compliance and length of the patients' soft tissues determined preoperatively. A simple mathematical model has been developed to calculate the inherent length and 'spare' length of the hamstring and quadriceps muscle groups in 28 patients undergoing limb lengthening procedures. The range of knee motion was recorded preoperatively and loss of movement recorded during follow-up. The results show a strong correlation between predicted 'spare' length of quadriceps and loss of knee flexion. An association was noted between loss of knee extension and the straight leg raise and correlation of knee extension and the spare length of the hamstrings. The straight leg raise test, and calculation of spare quadriceps length using our formula, as part of the preoperative assessment, can help predict which patient is at risk of a reduced range of motion of the knee.

Mortality after low-energy fractures in patients aged at least 45 years old.

BACKGROUND: Fractures sustained in low-energy injuries are recognized as a major public health issue, although, with the exception of proximal femoral fractures, little is known about the subsequent mortality rates. The aim of this study was to compare the survival rates of a population of individuals who sustained 3 types of low-energy fractures with age-matched cohorts from within the same population. METHODS: Between January 1988 and December 1999, data were prospectively gathered from all inpatient and outpatient fracture cases at a single trauma unit. During this time, 18,019 patients sustained low-energy fractures of the proximal femur, proximal humerus, or wrist. Survival analysis using the life table method was performed and hazard ratios calculated for risk of mortality when compared to general population controls within the first year postinjury, between the second and fifth years postinjury, and between the sixth and tenth years postinjury. The effects of various social, physical, and mental health parameters on survival were also analyzed using a Cox proportional hazards model. RESULTS: The patients who sustained proximal femoral fractures were older and significantly more physically and mentally impaired than the patients who sustained wrist fractures. The demographic features of the proximal humeral fracture cohort were intermediate between these 2 groups. The mortality was high in all age groups following proximal femoral and proximal humeral fractures, though the relative risk of death, when compared to age-matched population controls, decreased with increasing age at fracture. The risk of death in these groups was greatest in younger individuals and in the first year postinjury. The wrist fracture population had similar or enhanced survival when compared to age-matched population controls. The mortality after fracture was independently predicted by age at fracture, male gender, and use of walking aids, for all 3 fracture groups (P < 0.05), and additionally by level of social dependence in the proximal femoral fracture group (P < 0.05). LEVEL OF EVIDENCE: level one, prospective cohort study. CONCLUSIONS: There is prolonged risk of premature mortality seen in both proximal femoral and proximal humeral fracture groups in the younger age cohorts, possibly as a result of concomitant medical comorbidities contributing to their premature deaths. Elderly patients sustaining proximal femoral fractures, despite high risk of mortality in the first year after injury, have survival approaching those of the general population in the longer term. Elderly patients who sustain wrist fractures have consistently better survival rates than the general population. This group of patients may be physiologically more robust than their age-matched peers in the general population.