Impact of venous leg ulceration on health-related quality of life: A synthesis of data from randomized controlled trials compared to population norms.

Venous insufficiency is the most common cause of leg ulceration, but the impact of venous leg ulceration on health-related quality of life has not been adequately assessed. This study compared data from randomized controlled trials to population norms obtained from a large national population survey. We combined the baseline Short Form-36 (SF-36) version 1 data from two New Zealand randomized controlled trials that recruited participants with VLU and compared the pooled data to the population scores obtained from the New Zealand Health Survey using general linear regression to adjust for age, sex, and ethnicity differences between the cohorts. Baseline SF-36 scores obtained from 618 trial participants were compared to the SF-36 scores obtained from the 12,529 participants in the New Zealand Health Survey. Participants with VLU had significantly lower crude SF-36 scores across all eight SF-36 domains, but there was interaction between age and group. Adjusted mean differences for participants aged 65 years or younger were -25.8, -32.1, -21.2, -9.6, -7.6, -23.9, -21.5, and -9.3, respectively, for Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health whereas the adjusted mean differences for older participants were -15.7, -23.8, -13.8, -0.3 (nonsignificant), -4.6, -15.3, -21.2, and -6.6. This study is the first to compare a VLU population to norms from a general population survey and the first to show VLU interacts with age creating stronger impact in younger patients compared their age cohort. Younger patients may have need of more pastoral care as a consequence.

Evaluation of MyTeen - a SMS-based mobile intervention for parents of adolescents: a randomised controlled trial protocol.

BACKGROUND: Parents play an important role in the lives of adolescents and efforts aimed at strengthening parenting skills and increasing knowledge on adolescent development hold much promise to prevent and mitigate adolescent mental health problems. Innovative interventions that make use of technology-based platforms might be an effective and efficient way to deliver such support to parents. This protocol presents the design of a randomised controlled trial to investigate the effectiveness of a SMS-based mobile intervention (MyTeen) for parents of adolescents on promoting parental competence and mental health literacy. METHODS: A parallel two-arm randomised controlled trial will be conducted in New Zealand, aiming to recruit 214 parents or primary caregivers of adolescents aged 10-15 years via community outreach and social media. Eligible participants will be allocated 1:1 into the control or the intervention group, stratified by ethnicity. The intervention group will receive a tailored programme of text messages aimed at improving their parental competence and mental health literacy, over 4 weeks. The control group (care-as-usual) will receive no intervention from the research team, but can access alternative services if they wish, and will be offered the intervention programme upon completion of a 3-month post-randomisation follow-up assessment. Data will be obtained at baseline, post intervention (1-month), and 3-month follow up. The primary outcome is parental competence assessed by the Parental Sense of Competence Scale at 1-month follow up. Secondary outcomes include: mental health literacy; knowledge of help-seeking; parental distress; parent-adolescent communication; and programme satisfaction. DISCUSSION: To our knowledge this is the first randomised controlled trial on the effectiveness of delivering a parenting support intervention for parents of adolescents solely via a SMS-based mobile intervention. If effective, it could have great potential to reach and support parents of adolescents. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ( ACTRN12618000117213 ) Registered on 29/01/2018.

Optical treatment of amblyopia in older children and adults is essential prior to enrolment in a clinical trial.

PURPOSE: Optical treatment alone can improve visual acuity (VA) in children with amblyopia, thus clinical trials investigating additional amblyopia therapies (such as patching or videogames) for children require a preceding optical treatment phase. Emerging therapies for adult patients are entering clinical trials. It is unknown whether optical treatment is effective for adults with amblyopia and whether an optical correction phase is required for trials involving adults. METHODS: We examined participants who underwent optical treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO) clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in three age groups (7 to 12, 13 to 17, or ≥18 years), and had unilateral amblyopia due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30-1.00 logMAR (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on cycloplegic refraction to fully correct any anisometropia. VA was assessed using the electronic visual acuity testing algorithm (e-ETDRS) test and near stereoacuity was assessed using the Randot Preschool Test. Participants were assessed every four weeks up to 16 weeks, until either VA was stable or until amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant ineligible for the trial. RESULTS: Eighty participants (mean age 24.6 years, range 7.6-55.5 years) completed four to 16 weeks of optical treatment. A small but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR was observed (S.D. 0.08 logMAR; paired t-test p < 0.0001). Twenty-five participants (31%) improved by ≥1 logMAR line and of these, seven (9%) improved by ≥2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual improvements were not associated with age, presence of strabismus, or prior occlusion treatment. Two adult participants withdrew due to intolerance to anisometropic correction. Sixteen out of 80 participants (20%) achieved better than 0.30 logMAR VA in the amblyopic eye after optical treatment. Nine of these participants attended additional follow-up and four (44%) showed further VA improvements. CONCLUSIONS: Improvements from optical treatment resulted in one-fifth of participants becoming ineligible for the main clinical trial. Studies investigating additional amblyopia therapies must include an appropriate optical treatment only phase and/or parallel treatment group regardless of patient age. Optical treatment of amblyopia in adult patients warrants further investigation.

Low-dose aspirin as an adjuvant treatment for venous leg ulceration: study protocol for a randomized controlled trial (Aspirin4VLU).

AIM: The aim of this study was to determine the effect of low-dose aspirin on venous leg ulcer healing when used in addition to compression. BACKGROUND: The mainstay of treatment for venous leg ulcers is compression therapy and there are few adjuvant treatments to accelerate healing. DESIGN: Pragmatic, community-based, double-blind, randomized trial. METHODS: Participants with venous leg ulcers will receive either 150 mg aspirin or placebo daily for up to 24 weeks. Participants will receive background treatment with compression therapy (system of choice guided by participant and/or clinical preference) delivered through district nursing services. The primary outcome will be time-to-healing. Secondary outcomes will include proportion healed at 24 weeks, change in ulcer area, change in health-related quality of life, adherence, efficacy of blinding and adverse events. The trial was funded in June 2014. DISCUSSION: The trial commenced in March 2015 and is successfully recruiting. The trial is one of three trials that will contribute to an individual participant data meta-analysis to be undertaken at the York Trials Centre. TRIAL REGISTRATION: Registered 5 June 2014 ClinicalTrials.gov NCT02158806. Protocol version 1·1, 14 April 2015.

Recruiting equal numbers of indigenous and non-indigenous participants to a 'polypill' randomized trial.

INTRODUCTION: Maori are disproportionately affected by cardiovascular disease (CVD), which is the main reason for the eight year difference in life expectancy between Maori and non-Maori. The primary care-based IMPACT (IMProving Adherence using Combination Therapy) trial evaluates whether fixed dose combination therapy (a "polypill") improves adherence to guideline-based therapy compared with current care among people at high risk of CVD. Interventions shown in trials to be effective do not necessarily reduce ethnic disparities, and may in fact widen them. Indigenous populations with poorer health outcomes are often under-represented in trials so the effect of interventions cannot be assessed for them, specifically. Therefore, the IMPACT trial aimed to recruit as many Maori as non-Maori to assess the consistency of the effect of the polypill. This paper describes the methods and results of the recruitment strategy used to achieve this. METHODS: Experienced Maori researchers were involved in trial governance throughout trial development and conduct. The trial Steering Committee included leading Maori researchers and was committed to equal recruitment of Maori and non-Maori. Additional funding and Maori research nurses were sought to allow home-based assessment, establishment of the relationship between research nurse and participant, more family involvement prior to enrollment, continuity of the research nurse-participant relationship, and acknowledgement of other Maori culturally important procedures, interactions, language and manners. Primary care practices with high enrollment of Maori were targeted, with over-sampling of potentially eligible Maori patients, lower thresholds for screening of Maori and 6 months continued Maori recruitment after non-Maori recruitment had finished. RESULTS: A total of 257 Maori and 256 non-Maori participants were randomized. Four Maori and eight non-Maori participants were randomized per research nurse per month. Potentially eligible Maori were more likely than non-Maori to proceed to subsequent stages of recruitment. Differences between randomized Maori and non-Maori were evident (e.g. Maori were less likely to have established coronary artery disease). CONCLUSIONS: Recruitment of equal numbers of indigenous and non-indigenous participants is possible if it is prioritised, adequately resourced and self-determination is supported. TRIAL REGISTRATION: The trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN12606000067572.

Recruitment and Retention of Parents of Adolescents in a Text Messaging Trial (MyTeen): Secondary Analysis From a Randomized Controlled Trial.

BACKGROUND: Parenting programs are well established as an effective strategy for enhancing both parenting skills and the well-being of the child. However, recruitment for family programs in clinical and nonclinical settings remains low. OBJECTIVE: This study aims to describe the recruitment and retention methods used in a text messaging program (MyTeen) trial for parents of adolescents (10-15 years) and identify key lessons learned. We aim to provide insights and direction for researchers who seek to recruit parents and build on the limited literature on recruitment and retention strategies for parenting program trials. METHODS: A recruitment plan was developed, monitored, and modified as needed throughout the course of the project. Strategies to facilitate recruitment were identified (eg, program content and recruitment material, staff characteristics, and study procedures). Traditional and web-based recruitment strategies were used. RESULTS: Over a 5-month period, 319 parents or caregivers expressed interest in our study, of which 221 agreed to participate in the study, exceeding our recruitment target of 214 participants. Attrition was low at the 1-month (4.5% overall; intervention group: n=5, 4.6%; control group: n=5, 4.5%) and 3-month follow-ups (9% overall; intervention group: n=10, 9.2%; control group: n=10, 8.9%). CONCLUSIONS: The use of web-based recruitment strategies appeared to be most effective for recruiting and retaining parents in a text-messaging program trial. However, we encountered recruitment challenges (ie, underrepresentation of ethnic minority groups and fathers) similar to those reported in the literature. Therefore, efforts to engage ethnic minorities and fathers are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000117213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374307.

See How They Grow: Testing the feasibility of a mobile app to support parents' understanding of child growth charts.

BACKGROUND: Mobile devices provide new opportunities for the prevention of overweight and obesity in children. We aimed to co-create and test an app that offered comprehensible feedback to parents on their child's growth and delivered a suite of age-specific information about nutrition and activity. METHODS: A two-phased approach was used to co-create the digital growth tool-See How They Grow-and test its feasibility. Phase one used focus groups (parents and professionals such as paediatricians and midwives) and a national on-line survey to gather requirements and build the app. Phase two involved testing the app over 12-weeks, with parents or carers of children aged ≤ 2-years. All research activities were undertaken exclusively through the app, and participants were recruited using social media and hard copy materials given to patents at a child health visit. FINDINGS: Four focus groups and 101 responses to the national survey informed the features and functions to include in the final app. Two hundred and twenty-five participants downloaded the app, resulting in 208 eligible participants. Non-Maori/Non-Pacific (78%) and Maori (14%) had the highest downloads. Fifty-four per cent of participants were parents of children under 6-months. These participants were more likely to regularly use the app than those with children older than 6-months (64% vs 36%, P = 0.011). Over half of the participants entered three measures (n = 101, 48%). Of those that completed the follow-up survey (n = 101, 48%), 72 reported that the app helped them better understand how to interpret growth charts. CONCLUSION: The app was acceptable and with minor modifications, has the potential to be an effective tool to support parents understanding of growth trajectories for their children. A larger trial is needed to evaluate if the app can have a measurable impact on increasing knowledge and behaviour, and therefore on preventing childhood overweight and obesity.

Prescribed exercise regimen versus usual care and hypochlorous acid wound solution versus placebo for treating venous leg ulcers: study protocol for a randomised controlled trial (Factorial4VLU).

INTRODUCTION: Compression is the mainstay of treatment for venous leg ulcers (VLUs) and there are few effective adjuvant treatments. There is only observational evidence supporting the use of hypochlorous acid (HOCl) as a topical wound solution on VLU and some limited randomised evidence for the effect of a prescribed regimen of exercise. METHODS AND ANALYSIS: The Factorial4VLU trial is a pragmatic, blinded, factorial randomised controlled trial, with 380 participants receiving either a prescribed exercise regimen compared with usual care and either active HOCl wound solution or placebo wound solution at each dressing change for up to 24 weeks. All participants will receive compression therapy. The primary outcome is the proportion of participants with healed VLU at 12 weeks after randomisation as adjudicated by blinded review of ulcer photographs. Secondary outcomes are proportion healed at 24 weeks, time to healing, estimated change in ulcer area, change in 2-Minute Walk Test, change in health-related quality of life, incidence of infection and incidence of all-cause adverse events. If either of the interventions shows a statistically significant positive difference on healing outcomes, cost-effectiveness will be modelled using a health service perspective. ETHICS AND DISSEMINATION: The Factorial4VLU trial received ethical approval from the Northern B Health and Disability Ethics Committee. We plan to publish the results within 1 year of trial completion and will include the results on the trial registration page. TRIAL REGISTRATION NUMBERS: Australia and New Zealand Clinical Trials Register (http://www.anzctr.org.au) (ACTRN12620000116921); Universal Trial Number (WHO) (U1111-1236-2997).

Adherence to home-based videogame treatment for amblyopia in children and adults.

Clinical relevance: Home-based videogame treatments are increasingly popular for amblyopia treatment. However, at-home treatments tend to be done in short sessions and with frequent disruptions, which may reduce the effectiveness of binocular visual stimulation. These treatment adherence patterns need to be accounted for when considering dose-response relationships and treatment effectiveness.Background: Home-based videogame treatments are increasingly being used for various sensory conditions, including amblyopia ('lazy eye'), but treatment adherence continues to limit success. To examine detailed behavioural patterns associated with home-based videogame treatment, we analysed in detail the videogame adherence data from the Binocular tReatment of Amblyopia with VideOgames (BRAVO) clinical trial (ACTRN12613001004752).Methods: Children (7-12 years), teenagers (13-17 years) and adults (≥ 18 years) with unilateral amblyopia were loaned iPod Touch devices with either an active treatment or placebo videogame and instructed to play for a total of 1-2 hours/day for six weeks at home. Objectively-recorded adherence data from device software were used to analyse adherence patterns such as session length, daily distribution of gameplay, use of the pause function, and differences between age groups. Objectively-recorded adherence was also compared to subjectively-reported adherence from paper-based diaries.Results: One hundred and five of the 115 randomised participants completed six weeks of videogame training. Average adherence was 65% (SD 37%) of the minimum hours prescribed. Game training was generally performed in short sessions (mean 21.5, SD 11.2 minutes), mostly in the evening, with frequent pauses (median every 4.1 minutes, IQR 6.1). Children played in significantly shorter sessions and paused more frequently than older age groups (p < 0.0001). Participants tended to over-report adherence in subjective diaries compared to objectively-recorded gameplay time.Conclusion: Adherence to home-based videogame treatment was characterised by short sessions interspersed with frequent pauses, suggesting regular disengagement. This complicates dose-response calculations and may interfere with the effectiveness of treatments like binocular treatments for amblyopia, which require sustained visual stimulation.

Wool-derived keratin dressings versus usual care dressings for treatment of slow healing venous leg ulceration: a randomised controlled trial (Keratin4VLU).

OBJECTIVE: To determine the effect of a keratin dressing for treating slow-to-heal venous leg ulcers (VLU) on VLU healing. DESIGN: Pragmatic parallel group randomised controlled trial. SETTING: Community-dwelling participants. PARTICIPANTS: People aged 18 or more years with VLU (either present for more than 26 weeks or ulcer area larger than 5 cm2 or both). INTERVENTION: Wool-derived keratin dressing or usual care formulary of non-medicated dressings, on a background treatment with compression. PRIMARY AND SECONDARY OUTCOME MEASURES: Healing at 24 weeks based on blinded assessment of ulcer photographs. Other outcomes included time to complete healing, change in ulcer area to 24 weeks, change in health-related quality of life and incidence of adverse events. RESULTS: We screened 1068 patients with VLU and randomised 143 participants (51.1% of target recruitment), 71 to the keratin dressing group and 72 to the usual care group.The mean age was 66.1 years (SD 15.9) and 53 participants (37.1%) were women. There were no significant differences between the groups on the primary outcome (risk difference -6.4%, 95% CI -22.5% to 9.7%), change in ulcer area (-1.9 cm2, 95% CI -16.5 to 12.8 cm2), time to complete healing (HR 0.80, 95% CI 0.52 to 1.23) or the incidence of adverse events (incidence rate ratio 1.19, 95% CI 0.89 to 1.59) in the intention-to-treat analyses. However, the direction of effect on the primary outcome was reversed in a per protocol analysis specified a priori (risk difference 6.2%, 95% CI -12.4% to 24.9%). CONCLUSION: The effect of adding a keratin dressing to the treatment regimen for prognostically slow-to-heal VLU remains unclear. TRIAL REGISTRATION NUMBER: NCT02896725.

Development of MyTeen Text Messaging Program to Support Parents of Adolescents: Qualitative Study.

BACKGROUND: Parents play an important role in the lives of adolescents, and supporting and addressing the needs of families continue to be the focus of many researchers and policy makers. Mobile health interventions have great potential for supporting parents at a population level because of their broad reach and convenience. However, limited evidence exists for such interventions for parents of adolescents. This study reports on the formative work conducted with parents and/or primary caregivers to identify their needs and preferences for the development of MyTeen-an SMS text messaging program on promoting parental competence and mental health literacy for parents of adolescents (aged 10-15 years). OBJECTIVE: The aim of this qualitative study was to explore parents and/or primary caregivers' perspectives around youth well-being, parenting, and parenting support and their input on the development of MyTeen SMS text messaging parenting intervention. METHODS: A total of 5 focus groups (n=45) were conducted with parents or primary caregivers of adolescents aged 10 to 15 years between October and December 2017 in New Zealand. A semistructured interview guideline and prompts were used. Data were audiotaped, transcribed, and analyzed using inductive thematic analysis. RESULTS: Participants were concerned about youth mental health (ie, stigma and increasing demand on adolescents), and a number of parenting challenges (ie, social expectations, time, impact of technology, changes in family communication pattern, and recognizing and talking about mental health issues) were noted. Importantly, participants reported the lack of services and support available for families, and many were not aware of services for parents themselves. A number of recommendations were given on the style, content, and frequency of developing the text messaging program. CONCLUSIONS: Findings from this qualitative work informed the development of MyTeen, an SMS text messaging program designed to increase parental competence and improve mental health literacy for parents of adolescents.

Effect of MyTeen SMS-Based Mobile Intervention for Parents of Adolescents: A Randomized Clinical Trial.

Importance: There is global pressure to respond to the burden posed by adolescent mental health problems. The National Mental Health Commission has made a call for investment in mobile health services directed at prevention and early intervention to relieve the demand on targeted mental health services that are costly to provide. Parents and primary caregivers play a significant role in the lives of adolescents and are important targets for such efforts. Currently, there is no evidence for the effectiveness of programs delivered solely via text message for parents of adolescents. Objective: To evaluate the effects of a text-messaging program (MyTeen) on promoting parental competence and mental health literacy for parents of adolescents. Design, Setting, and Participants: A parallel 2-group randomized clinical trial was conducted in New Zealand. A total of 221 parents and primary caregivers of adolescents aged 10 to 15 years were recruited from March 19 to August 17, 2018, via community outreach and social media and were randomly allocated 1:1 into the control or the intervention group. Statistical analysis was performed on the principle of intention to treat with adjustment for baseline factors and ethnicity. Intervention: A text-messaging program for parents of adolescents (age 10-15 years) to promote parental competence and mental health literacy. Participants received 1 daily text message over 4 weeks. Main Outcomes and Measures: Parental competence, assessed at 1 month after randomization by the Parenting Sense of Competence Scale. Results: In total, 221 participants (214 [96.8%] female) were randomized, 109 to the intervention group and 112 to the control group; 201 participants (91%) completed the trial at 3 months. Significant group difference was observed on the primary outcome at the end of 1 month of intervention, with participants reporting a higher level of parental competence than those in the control group (estimated mean difference, 3.33 points; 95% CI, 1.37-5.29 points; P = .002). Except for knowledge about mental health, all secondary outcomes were significant, including continued improvement in parental competence at 3 months (estimated mean difference, 4.08 points; 95% CI, 1.96-6.20 points; P < .001), knowledge of help seeking (estimated mean difference, 0.99 points; 95% CI, 0.49-1.50 points; P < .001), parental distress (estimated mean difference, -2.39 points; 95% CI, -4.37 to -0.40 points; P = .02), and parent-adolescent communication (estimated mean difference, 2.21 points; 95% CI, 0.48-3.95 points; P = .01), with participants in the intervention group reporting better parenting-related outcomes than the control group at 1 and 3 months after the intervention. Conclusions and Relevance: This text-messaging program for parents of adolescents appears to be an effective and feasible way to facilitate the implementation and delivery of evidence-based information to populations that are not easily reached with other intervention modalities. The program can be easily scaled up for delivery as an early preventive intervention and may represent a less expensive option for service delivery. Trial Registration: anzctr.org.au Identifier: ACTRN12618000117213.

Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials.

OBJECTIVE: The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. METHODS: We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. RESULTS: Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. CONCLUSIONS: Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.

Wool-derived keratin dressings versus usual care dressings for treatment of slow-healing venous leg ulceration: study protocol for a randomised controlled trial (Keratin4VLU).

INTRODUCTION: Keratins, filament-forming proteins found in vertebrate epithelium, are downregulated in slow-healing venous leg ulcers (VLU) compared with normal-healing VLU. Laboratory and animal model research has suggested exogenous keratins increase expression of endogenous keratins. A non-randomised controlled trial of an exogenous keratin dressing reported increased healing in slow-healing VLU. To date, no randomised controlled trial has been done to verify these promising findings. METHODS AND ANALYSIS: The Keratin4VLU trial is a single-blind, pragmatic, parallel group, randomised controlled trial of keratin dressings compared with usual care non-medicated dressings in patients with VLU where either (1) the ulcer area is greater than 5 cm2, (2) the ulcer has been present for more than 26 weeks or (3) both. All patients will receive compression therapy. The primary outcome is the proportion of patients with healed VLU at 24 weeks after randomisation as adjudicated by blinded review of an ulcer photograph. Secondary outcomes are time to healing, estimated change in ulcer area, change in health-related quality of life, agreement between blinded and unblinded assessors and adverse events. The analysis will be intention-to-treat on the primary and secondary outcomes (excepting health-related quality of life). ETHICS AND DISSEMINATION: The Keratin4VLU trial received ethical approval from the Northern A Health and Disability Ethics Committee. We plan to publish the results within 1 year of trial completion and will include the results on the trial registration page. TRIAL REGISTRATION NUMBER: NCT02896725; Pre-results.

Effectiveness of a Binocular Video Game vs Placebo Video Game for Improving Visual Functions in Older Children, Teenagers, and Adults With Amblyopia: A Randomized Clinical Trial.

Importance: Binocular amblyopia treatment using contrast-rebalanced stimuli showed promise in laboratory studies and requires clinical trial investigation in a home-based setting. Objective: To compare the effectiveness of a binocular video game with a placebo video game for improving visual functions in older children and adults. Design, Setting, and Participants: The Binocular Treatment of Amblyopia Using Videogames clinical trial was a multicenter, double-masked, randomized clinical trial. Between March 2014 and June 2016, 115 participants 7 years and older with unilateral amblyopia (amblyopic eye visual acuity, 0.30-1.00 logMAR; Snellen equivalent, 20/40-20/200) due to anisometropia, strabismus, or both were recruited. Eligible participants were allocated with equal chance to receive either the active or the placebo video game, with minimization stratified by age group (child, age 7 to 12 years; teenager, age 13 to 17 years; and adult, 18 years and older). Interventions: Falling-blocks video games played at home on an iPod Touch for 1 hour per day for 6 weeks. The active video game had game elements split between eyes with a dichoptic contrast offset (mean [SD] initial fellow eye contrast, 0.23 [0.14]). The placebo video game presented identical images to both eyes. Main Outcomes and Measures: Change in amblyopic eye visual acuity at 6 weeks. Secondary outcomes included compliance, stereoacuity, and interocular suppression. Participants and clinicians who measured outcomes were masked to treatment allocation. Results: Of the 115 included participants, 65 (56.5%) were male and 83 (72.2%) were white, and the mean (SD) age at randomization was 21.5 (13.6) years. There were 89 participants (77.4%) who had prior occlusion. The mean (SD) amblyopic eye visual acuity improved 0.06 (0.12) logMAR from baseline in the active group (n = 56) and 0.07 (0.10) logMAR in the placebo group (n = 59). The mean treatment difference between groups, adjusted for baseline visual acuity and age group, was -0.02 logMAR (95% CI, -0.06 to 0.02; P = .25). Compliance with more than 25% of prescribed game play was achieved by 36 participants (64%) in the active group and by 49 (83%) in the placebo group. At 6 weeks, 36 participants (64%) in the active group achieved fellow eye contrast greater than 0.9 in the binocular video game. No group differences were observed for any secondary outcomes. Adverse effects included 3 reports of transient asthenopia. Conclusions and Relevance: The specific home-based binocular falling-blocks video game used in this clinical trial did not improve visual outcomes more than the placebo video game despite increases in fellow eye contrast during game play. More engaging video games with considerations for compliance may improve effectiveness. Trial Registration: anzctr.org.au Identifier: ACTRN12613001004752.

Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU).

Objective To determine the effect of low dose aspirin on ulcer healing in patients with venous leg ulcers.Design Pragmatic, community based, parallel group, double blind, randomised controlled trial.Setting Five community nursing centres in New Zealand.Participants 251 adults with venous leg ulcers who could safely be treated with aspirin or placebo: 125 were randomised to aspirin and 126 to placebo.Interventions 150 mg oral aspirin daily or matching placebo for up to 24 weeks treatment, with compression therapy as standard background treatment.Main outcome measures The primary outcome was time to complete healing of the reference ulcer (largest ulcer if more than one ulcer was present). Secondary outcomes included proportion of participants healed, change in ulcer area, change in health related quality of life, and adverse events. Analysis was by intention to treat.Results The median number of days to healing of the reference ulcer was 77 in the aspirin group and 69 in the placebo group (hazard ratio 0.85, 95% confidence interval 0.64 to 1.13, P=0.25). The number of participants healed at the endpoint was 88 (70%) in the aspirin group and 101 (80%) in the placebo group (risk difference -9.8%, 95% confidence interval -20.4% to 0.9%, P=0.07). Estimated change in ulcer area was 4.1 cm2 in the aspirin group and 4.8 cm2 in the placebo group (mean difference -0.7 cm2, 95% confidence interval -1.9 to 0.5 cm2, P=0.25). 40 adverse events occurred among 29 participants in the aspirin group and 37 adverse events among 27 participants in the placebo group (incidence rate ratio 1.1, 95% confidence interval 0.7 to 1.7, P=0.71).Conclusion Our findings do not support the use of low dose aspirin as adjuvant treatment for venous leg ulcers.Trial registration ClinicalTrials.gov NCT02158806.

The impact of a point-of-care testing device on CVD risk assessment completion in New Zealand primary-care practice: A cluster randomised controlled trial and qualitative investigation.

OBJECTIVES: To assess the effect of a point of care (POC) device for testing lipids and HbA1c in addition to testing by community laboratory facilities (usual practice) on the completion of cardiovascular disease (CVD) risk assessments in general practice. METHODS: We conducted a pragmatic, cluster randomised controlled trial in 20 New Zealand general practices stratified by size and rurality and randomised to POC device plus usual practice or usual practice alone (controls). Patients aged 35-79 years were eligible if they met national guideline criteria for CVD risk assessment. Data on CVD risk assessments were aggregated using a web-based decision support programme common to each practice. Data entered into the on-line CVD risk assessment form could be saved pending blood test results. The primary outcome was the proportion of completed CVD risk assessments. Qualitative data on practice processes for CVD risk assessment and feasibility of POC testing were collected at the end of the study by interviews and questionnaire. The POC testing was supported by a comprehensive quality assurance programme. RESULTS: A CVD risk assessment entry was recorded for 7421 patients in 10 POC practices and 6217 patients in 10 control practices; 99.5% of CVD risk assessments had complete data in both groups (adjusted odds ratio 1.02 [95%CI 0.61-1.69]). There were major external influences that affected the trial: including a national performance target for CVD risk assessment and changes to CVD guidelines. All practices had invested in systems and dedicated staff time to identify and follow up patients to completion. However, the POC device was viewed by most as an additional tool rather than as an opportunity to review practice work flow and leverage the immediate test results for patient education and CVD risk management discussions. Shortly after commencement, the trial was halted due to a change in the HbA1c test assay performance. The trial restarted after the manufacturing issue was rectified but this affected the end use of the device. CONCLUSIONS: Performance incentives and external influences were more powerful modifiers of practice behaviours than the POC device in relation to CVD risk assessment completion. The promise of combining risk assessment, communication and management within one consultation was not realised. With shifts in policy focus, the utility of POC devices for patient engagement in CVD preventive care may be demonstrated if fully integrated into the clinical setting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000607774.

Polypill-based therapy likely to reduce ethnic inequities in use of cardiovascular preventive medications: Findings from a pragmatic randomised controlled trial.

OBJECTIVE: The purpose of this study was to investigate the consistency of the proportional effect of fixed-dose combination therapy (the 'polypill') on the use of recommended cardiovascular preventative medications among indigenous Maori and non-indigenous adults in New Zealand. METHODS: We randomised Maori and non-Maori primary care patients at high risk of cardiovascular disease (either because of a prior event or with an estimated 5-year risk of a first event of at least 15%) to a polypill (containing aspirin, statin and two antihypertensives) or usual care for a minimum of 12 months. All patients had indications for all polypill components according to their general practitioner, and all medications (including the polypill) were prescribed by the patient's general practitioner and dispensed at community pharmacies. The main outcome for this study was the use of all recommended medications (antiplatelet, statin and two antihypertensives) at 12 months. Heterogeneity in the effect of polypill-based care compared with usual care on this outcome by ethnicity was assessed by logistic regression. RESULTS: Baseline use of recommended medications was 36% (93/257) among Maori and 51% (130/156) among non-Maori participants. Polypill-based care was associated with an increase in the use of recommended medications among Maori (relative risk [RR]: 1.87; 95% confidence interval [CI]: 1.50-2.34) and non-Maori (RR: 1.66; 95% CI: 1.37-2.00) when compared with usual care at 12 months, and there was no statistically significant heterogeneity in this outcome by ethnicity (p = 0.92). CONCLUSION: Polypill-based care is likely to reduce absolute inequities between Maori and non-Maori in the use of recommended cardiovascular preventative medications given baseline absolute differences and the consistency of the proportional effect of this intervention by ethnicity in this pragmatic trial in primary care.

Do polypills lead to neglect of lifestyle risk factors? Findings from an individual participant data meta-analysis among 3140 patients at high risk of cardiovascular disease.

AIM: The aim of this study was to investigate whether polypill-based care for the prevention of cardiovascular disease (CVD) is associated with a change in lifestyle risk factors when compared with usual care, among patients with CVD or high calculated cardiovascular risk. METHODS: We conducted an individual participant data meta-analysis of three trials including patients from Australia, England, India, Ireland, the Netherlands and New Zealand that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior CVD event or who were at high risk of their first event. Analyses investigated any differential effect on anthropometric measures and self-reported lifestyle behaviours. RESULTS: Among 3140 patients (75% male, mean age 62 years and 76% with a prior CVD event) there was no difference in lifestyle risk factors in those randomised to polypill-based care compared with usual care over a median of 15 months, either across all participants combined, or in a range of subgroups. Furthermore, narrow confidence intervals (CIs) excluded any major effect; for example differences between the groups in body mass index was -0.1 (95% CI -0.2 to 0.1) kg/m(2), in weekly duration of moderate intensity physical activity was -2 (-26 to 23) minutes and the proportion of smokers was 16% vs 17% (RR 0.98, 0.84 to 1.15) at the end of trial. DISCUSSION: This analysis allays concern that polypill-based care may lead to neglect of lifestyle risk factors, at least among high-risk patients. Maximally effective preventive approaches should address lifestyle factors alongside pharmaceutical interventions, as recommended by major international guidelines.

Effectiveness of fixed dose combination medication ('polypills') compared with usual care in patients with cardiovascular disease or at high risk: A prospective, individual patient data meta-analysis of 3140 patients in six countries.

AIMS: To conduct a prospective, individual participant data (IPD) meta-analysis of randomised controlled trials comparing a polypill-based approach with usual care in high risk individuals. METHODS AND RESULTS: Three trials comparing polypill-based care with usual care in individuals with CVD or high calculated cardiovascular risk contributed IPD. Primary outcomes were self-reported adherence to combination therapy (anti-platelet, statin and ≥ two blood pressure (BP) lowering agents), and difference in mean systolic BP (SBP) and LDL-cholesterol at 12 months. Analyses used random effects models. Among 3140 patients from Australia, England, India, Ireland, New Zealand and The Netherlands (75% male, mean age 62 years), median follow-up was 15 months. At baseline, 84%, 87% and 61% respectively were taking a statin, anti-platelet agent and at least two BP lowering agents. At 12 months, compared to usual care, participants in the polypill arm had higher adherence to combination therapy (80% vs. 50%, RR 1.58; 95% CI, 1.32 to 1.90; p < 0.001), lower SBP (-2.5 mmHg; 95% CI, -4.5 to -0.4; p = 0.02) and lower LDL-cholesterol (-0.1 mmol/L; 95% CI, -0.2 to 0.0; p = 0.04). Baseline treatment levels were a major effect modifier for adherence and SBP (p-homog < 0.0001 and 0.02 respectively) with greatest improvements seen among those under-treated at baseline. CONCLUSIONS: Polypill therapy significantly improved adherence, SBP and LDL-cholesterol in high risk patients compared with usual care, especially among those who were under-treated at baseline.