A randomised controlled trial of amniotic membrane in the treatment of a standardised burn injury in the merino lamb

Burn injury is associated with disabling scar formation which impacts on many aspects of the patient's life. Previously we have shown that the fetus heals a deep dermal burn in a scarless fashion. Amniotic membrane (AM) is the outermost fetal tisue and has beeen used as a dressing in thermal injuries, though there is little data to support this use. To assess the efficacy of AM in scar minimisation after deep dermal burn wound, we conducted a randomised controlled study in the 1-month lamb. Lambs were delivered by caesarian section and the amniotic membranes stored after which lambs were returned to their mothers post-operatively. At 1 month, a standardised deep dermal burn was created under general anaesthesia on both flanks of the lamb. One flank was covered with unmatched AM, the other with paraffin gauze. Animals were sequentially euthanased from Day 3-60 after injury and tissue analysed for histopathology and immunohistochemically for alpha-smooth muscle actin (alphaSMA) content. AM resulted in reduced scar tissue as assessed histopathologically and reduced alphaSMA content. This study provides the first laboratory evidence that AM may reduce scar formation after burn injury.

Comparison of three different dressings for partial thickness burns in children : study protocol for a randomised controlled trial

BACKGROUND: In the paediatric population, pain and distress associated with burn injuries during wound care procedures remain a constant challenge. Although silver dressings are the gold standard for burn care in Australasia, very few high-level trials have been conducted that compare silver dressings to determine which will provide the best level of care clinically. Therefore, for paediatric patients in particular, identifying silver dressings that are associated with lower levels of pain and rapid wound re-epithelialisation is imperative. This study will determine whether there is a difference in time to re-epithelialisation and pain and distress experienced during wound care procedures among Acticoat, Acticoat combined with Mepitel and Mepilex Ag dressings for acute, paediatric partial thickness burns. METHODS/DESIGN: Children aged 0 to 15 years with an acute partial thickness (superficial partial to deep partial thickness inclusive) burn injury and a burn total body surface area of trial. Patients will be randomised to one of the three dressing groups: (1) Acticoat or (2) Acticoat combined with Mepitel or (3) Mepilex Ag. A minimum of 28 participants will be recruited for each treatment group. Primary measures of pain, distress and healing will be repeated at each dressing change until complete wound re-epithelialisation occurs or skin grafting is required. Additional data collected will include infection status at each dressing change, physical function, scar outcome and scar management requirements, cost effectiveness of each dressing and staff perspectives of the dressings. DISCUSSION: The results of this study will determine the effects of three commonly used silver and silicone burn dressing combinations on the rate of wound re-epithelialisation and pain experienced during dressing procedures in acute, paediatric partial thickness burn injuries. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000105741.

Perioperative medication management: expanding the role of the preadmission clinic pharmacist in a single centre, randomised controlled trial of collaborative prescribing

Objectives Current evidence to support non-medical prescribing is predominantly qualitative, with little evaluation of accuracy, safety and appropriateness. Our aim was to evaluate a new model of service for the Australia healthcare system, of inpatient medication prescribing by a pharmacist in an elective surgery preadmission clinic (PAC) against usual care, using an endorsed performance framework. Design Single centre, randomised controlled, two-arm trial. Setting Elective surgery PAC in a Brisbane-based tertiary hospital. Participants 400 adults scheduled for elective surgery were randomised to intervention or control. Intervention A pharmacist generated the inpatient medication chart to reflect the patient's regular medication, made a plan for medication perioperatively and prescribed venous thromboembolism (VTE) prophylaxis. In the control arm, the medication chart was generated by the Resident Medical Officers. Outcome measures Primary outcome was frequency of omissions and prescribing errors when compared against the medication history. The clinical significance of omissions was also analysed. Secondary outcome was appropriateness of VTE prophylaxis prescribing. Results There were significantly less unintended omissions of medications: 11 of 887 (1.2%) intervention orders compared with 383 of 1217 (31.5%) control (p<0.001). There were significantly less prescribing errors involving selection of drug, dose or frequency: 2 in 857 (0.2%) intervention orders compared with 51 in 807 (6.3%) control (p<0.001). Orders with at least one component of the prescription missing, incorrect or unclear occurred in 208 of 904 (23%) intervention orders and 445 of 1034 (43%) controls (p<0.001). VTE prophylaxis on admission to the ward was appropriate in 93% of intervention patients and 90% controls (p=0.29). Conclusions Medication charts in the intervention arm contained fewer clinically significant omissions, and prescribing errors, when compared with controls. There was no difference in appropriateness of VTE prophylaxis on admission between the two groups.

A randomized controlled trial of a correspondence-based intervention for carers of relatives with psychosis

Background Family members play a crucial role in supporting the recovery of loved ones with psychosis. The journey of recovery is not only traversed by the person experiencing the mental illness but also by their family. Interventions to support these families have traditionally either focused on psychoeducation or addressed problematic interactions or expressed emotion. Family programmes have far less frequently emphasized supporting family members' adjustment to the challenges posed by their relative's disorder or their recovery from associated distress. The study compared a control condition that received only a psychoeducational booklet (Information) and a condition also receiving a correspondence-based interactive recovery-oriented intervention (Connections). The Connections group was expected to show greater improvements in recovery knowledge, well-being, experiences of caregiving, hopefulness and distress. Method A randomized controlled trial was conducted to evaluate the effectiveness of two correspondence-based family interventions delivered to 81 carers of relatives with psychosis. Results Intent-to-treat analyses showed no differential outcomes between conditions, but an analysis of participants who substantially completed their allocated treatment showed that carers receiving Connections had significantly more improvements in well-being, positive experiences of caregiving and distress. Conclusions Correspondence interventions that support carer's recovery may result in more positive mental health for those who complete key elements of the programme compared with information alone. However, many carers do not complete a correspondence programme and this may limit its impact.

Randomized controlled trial of MICBT for co-existing alcohol misuse and depression : outcomes to 36-months

Integrated psychological treatment addressing co-existing alcohol misuse and depression has not been compared with single-focused treatment. This trial evaluates changes over 36 months following randomization of 284 outpatients to one of four motivational interviewing and cognitive-behavior therapy (MICBT) based interventions: (1) brief integrated intervention (BI); or BI plus 9 further sessions with (2) an integrated-, (3) alcohol-, or (4) depression-focus. Outcome measures included changes in alcohol consumption, depression (BDI-II: Beck Depression Inventory) and functioning (GAF: Global Assessment of Functioning), with average improvements from baseline of 21.8 drinks per week, 12.6 BDI-II units and 8.2 GAF units. Longer interventions tended to be more effective in reducing depression and improving functioning in the long-term, and in improving alcohol consumption in the short-term. Integrated treatment was at least as good as single-focused MICBT. Alcohol-focused treatment was as effective as depression-focused treatment at reducing depression and more effective in reducing alcohol misuse. The best approach seems to be an initial focus on both conditions followed by additional integrated- or alcohol-focused sessions.

Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

Effect of ramipril on walking times and quality of life among patients with peripheral artery disease and intermittent claudication : a randomized controlled trial

Importance Approximately one-third of patients with peripheral artery disease experience intermittent claudication, with consequent loss of quality of life. Objective To determine the efficacy of ramipril for improving walking ability, patient-perceived walking performance, and quality of life in patients with claudication. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial conducted among 212 patients with peripheral artery disease (mean age, 65.5 [SD, 6.2] years), initiated in May 2008 and completed in August 2011 and conducted at 3 hospitals in Australia. Intervention Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks. Main Outcome Measures Maximum and pain-free walking times were recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively. Results At 6 months, relative to placebo, ramipril was associated with a 75-second (95% CI, 60-89 seconds) increase in mean pain-free walking time (P < .001) and a 255-second (95% CI, 215-295 seconds) increase in maximum walking time (P < .001). Relative to placebo, ramipril improved the WIQ median distance score by 13.8 (Hodges-Lehmann 95% CI, 12.2-15.5), speed score by 13.3 (95% CI, 11.9-15.2), and stair climbing score by 25.2 (95% CI, 25.1-29.4) (P < .001 for all). The overall SF-36 median Physical Component Summary score improved by 8.2 (Hodges-Lehmann 95% CI, 3.6-11.4; P = .02) in the ramipril group relative to placebo. Ramipril did not affect the overall SF-36 median Mental Component Summary score. Conclusions and Relevance Among patients with intermittent claudication, 24-week treatment with ramipril resulted in significant increases in pain-free and maximum treadmill walking times compared with placebo. This was associated with a significant increase in the physical functioning component of the SF-36 score. Trial Registration clinicaltrials.gov Identifier: NCT00681226

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

A randomized controlled trial of a 10 percent CPP-ACP cream to reduce mutans streptococci colonization

Purpose The purpose of this study was to investigate the effectiveness of a 10 percent casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) cream to reduce mutans streptococci (MS) colonization and prevent early childhood caries. Methods The cohort was randomized at mean age of 11 days old to receive once-daily CPP-ACP cream (n=102) or no product (comparison group; n=89) from the time of first tooth eruption. All mothers were contacted by telephone at six, 12, and 18 months and advised to brush their children's teeth twice daily with low-dose fluoride toothpaste. At 24 months, all children were examined at a community clinic. Results At 24 months old, one out of 65 (2 percent) children in the CPP-ACP group had caries vs. four out of 58 (seven percent) in the comparison group (difference not statistically significant). There were fewer MS-positive children in the CPP-ACP group (26 percent) vs. the comparison group (47 percent; P=.02). A dose-response effect of CPP-ACP usage on MS was observed, where MS was present in eight percent of regular CPP-ACP users, 28 percent of irregular users, and 47 percent of non-users (P<.02). Conclusions CPP-ACP reduced the percentages of mutans streptococci-positive 24-month-old children, although it did not reduce caries prevalence.

A randomized controlled trial of self-management programme improves health-related outcomes of older people with heart failure

Aims This paper is a report on the effectiveness of a self-management programme based on the self-efficacy construct, in older people with heart failure. Background Heart failure is a major health problem worldwide, with high mortality and morbidity, making it a leading cause of hospitalization. Heart failure is associated with a complex set of symptoms that arise from problems in fluid and sodium retention. Hence, managing salt and fluid intake is important and can be enhanced by improving patients' self-efficacy in changing their behaviour. Design Randomized controlled trial. Methods Heart failure patients attending cardiac clinics in northern Taiwan from October 2006–May 2007 were randomly assigned to two groups: control (n = 46) and intervention (n = 47). The intervention group received a 12-week self-management programme that emphasized self-monitoring of salt/fluid intake and heart failure-related symptoms. Data were collected at baseline as well as 4 and 12 weeks later. Data analysis to test the hypotheses used repeated-measures anova models. Results Participants who received the intervention programme had significantly better self-efficacy for salt and fluid control, self-management behaviour and their heart failure-related symptoms were significantly lower than participants in the control group. However, the two groups did not differ significantly in health service use. Conclusion The self-management programme improved self-efficacy for salt and fluid control, self-management behaviours, and decreased heart failure-related symptoms in older Taiwanese outpatients with heart failure. Nursing interventions to improve health-related outcomes for patients with heart failure should emphasize self-efficacy in the self-management of their disease.

Study protocol : a randomised controlled trial of a theory-based online intervention to improve sun safety among Australian adults

Background The effects of exposure to ultraviolet radiation are a significant concern in Australia which has one of the highest incidences of skin cancer in the world. Despite most skin cancers being preventable by encouraging consistent adoption of sun-protective behaviours, incidence rates are not decreasing. There is a dearth of research examining the factors involved in engaging in sun-protective behaviours. Further, online multi-behavioural theory-based interventions have yet to be explored fully as a medium for improving sun-protective behaviour in adults. This paper presents the study protocol of a randomised controlled trial of an online intervention based on the Theory of Planned Behaviour (TPB) that aims to improve sun safety among Australian adults. Methods/Design Approximately 420 adults aged 18 and over and predominantly from Queensland, Australia, will be recruited and randomised to the intervention (n = 200), information only (n = 200) or the control group (n = 20). The intervention focuses on encouraging supportive attitudes and beliefs toward sun-protective behaviour, fostering perceptions of normative support for sun protection, and increasing perceptions of control/self-efficacy over sun protection. The intervention will be delivered online over a single session. Data will be collected immediately prior to the intervention (Time 1), immediately following the intervention (Time 1b), and one week (Time 2) and one month (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun-protective behaviour. Secondary outcomes are the participants’ attitudes toward sun protection, perceptions of normative support for sun protection (i.e. subjective norms, group norms, personal norms and image norms) and perceptions of control/self-efficacy toward sun protection. Discussion The study will contribute to an understanding of the effectiveness of a TPB-based online intervention to improve Australian adults’ sun-protective behaviour. Trials registry Australian and New Zealand Trials Registry number ACTRN12613000470796

A pilot randomised trial of Medilixir cream shows some promising results, but control treatment may have been inappropriate

Aim To test the efficacy of Medilixir [cream] against the standard treatment of aqueous cream in the provision of relief from the symptoms of postburn itch. Design RCT with two parallel arms. Setting Professor Stuart Pegg Adult Burns Centre, Royal Brisbane and Women's Hospital, Brisbane, Australia. Participants Fifty-two patients aged between 18 and 80 years, admitted directly to the burns centre between 10 March and 22 July 2008, were able to provide informed consent, and had shown no allergic reaction to a patch test with the study medication, were randomised. Patients admitted from intensive care or high dependency were excluded. Main results Effect estimates and confidence intervals were not reported for any of the outcomes; only group means/proportions and P-values from hypothesis testing were provided. More patients in the intervention group reported itch reduction compared to comparison treatment (91 vs. 82%, P=0.001). Itch recurrence after cream application occurred later in the intervention group compared to the control group (P<0.001). Use of antipruritic medication was significantly greater in the control group (P=0.023). There was no difference in sleep disturbance between groups (not quantified). On average, Medilixir took longer to apply than aqueous cream (157s for Medilixir vs. 139s for aqueous cream; mean difference 17s), but authors noted that the groups did not differ significantly (CI for mean difference and P-values were not reported).

Non-response bias in randomized control experiments in criminology : putting the Queensland Community Engagement Trial (QCET) under a microscope

Objectives The goal of this article is to examine whether or not the results of the Queensland Community Engagement Trial (QCET)-a randomized controlled trial that tested the impact of procedural justice policing on citizen attitudes toward police-were affected by different types of nonresponse bias. Method We use two methods (Cochrane and Elffers methods) to explore nonresponse bias: First, we assess the impact of the low response rate by examining the effects of nonresponse group differences between the experimental and control conditions and pooled variance under different scenarios. Second, we assess the degree to which item response rates are influenced by the control and experimental conditions. Results Our analysis of the QCET data suggests that our substantive findings are not influenced by the low response rate in the trial. The results are robust even under extreme conditions, and statistical significance of the results would only be compromised in cases where the pooled variance was much larger for the nonresponse group and the difference between experimental and control conditions was greatly diminished. We also find that there were no biases in the item response rates across the experimental and control conditions. Conclusion RCTs that involve field survey responses-like QCET-are potentially compromised by low response rates and how item response rates might be influenced by the control or experimental conditions. Our results show that the QCET results were not sensitive to the overall low response rate across the experimental and control conditions and the item response rates were not significantly different across the experimental and control groups. Overall, our analysis suggests that the results of QCET are robust and any biases in the survey responses do not significantly influence the main experimental findings.

Optimising the length of Random Breath Tests : results from the Queensland Community Engagement Trial

Research suggests that the length and quality of police-citizen encounters affect policing outcomes. The Koper Curve, for example, shows that the optimal length for police presence in hot spots is between 14 and 15 minutes, with diminishing returns observed thereafter. Our study, using data from the Queensland Community Engagement Trial (QCET), examines the impact of encounter length on citizen perceptions of police performance. QCET involved a randomised field trial, where 60 random breath test (RBT) traffic stop operations were randomly allocated to an experimental condition involving a procedurally just encounter or a business-as-usual control condition. Our results show that the optimal length of time for procedurally just encounters during RBT traffic stops is just less than 2 minutes. We show, therefore, that it is important to encourage and facilitate positive police–citizen encounters during RBTat traffic stops, while ensuring that the length of these interactions does not pass a point of diminishing returns.