Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial

Aims: To identify risk factors for major Adverse Events (AEs) and to develop a nomogram to predict the probability of such AEs in individual patients who have surgery for apparent early stage endometrial cancer. Methods: We used data from 753 patients who were randomized to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analyzed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6 weeks of surgery and the nomogram was internally validated. Results: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson’s medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline ECOG score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. Conclusions: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimize the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer : results from a randomised controlled trial

AIM: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

Randomised controlled trial of an automated, interactive telephone intervention (TLC Diabetes) to improve type 2 diabetes management : Baseline findings and six-month outcomes

Background: Effective self-management of diabetes is essential for the reduction of diabetes-related complications, as global rates of diabetes escalate. Methods: Randomised controlled trial. Adults with type 2 diabetes (n = 120), with HbA1c greater than or equal to 7.5 %, were randomly allocated (4 × 4 block randomised block design) to receive an automated, interactive telephone-delivered management intervention or usual routine care. Baseline sociodemographic, behavioural and medical history data were collected by self-administered questionnaires and biological data were obtained during hospital appointments. Health-related quality of life (HRQL) was measured using the SF-36. Results: The mean age of participants was 57.4 (SD 8.3), 63 % of whom were male. There were no differences in demographic, socioeconomic and behavioural variables between the study arms at baseline. Over the six-month period from baseline, participants receiving the Australian TLC (Telephone-Linked Care) Diabetes program showed a 0.8 % decrease in geometric mean HbA1c from 8.7 % to 7.9 %, compared with a 0.2 % HbA1c reduction (8.9 % to 8.7 %) in the usual care arm (p = 0.002). There was also a significant improvement in mental HRQL, with a mean increase of 1.9 in the intervention arm, while the usual care arm decreased by 0.8 (p = 0.007). No significant improvements in physical HRQL were observed. Conclusions: These analyses indicate the efficacy of the Australian TLC Diabetes program with clinically significant post-intervention improvements in both glycaemic control and mental HRQL. These observed improvements, if supported and maintained by an ongoing program such as this, could significantly reduce diabetes-related complications in the longer term. Given the accessibility and feasibility of this kind of program, it has strong potential for providing effective, ongoing support to many individuals with diabetes in the future.

Study protocol : Screening and treatment of alcohol-related trauma (START): a randomised controlled trial

Background: The incidence of mandibular fractures in the Northern Territory of Australia is very high, especially among Indigenous people. Alcohol intoxication is implicated in the majority of facial injuries, and substance use is therefore an important target for secondary prevention. The current study tests the efficacy of a brief therapy, Motivational Care Planning, in improving wellbeing and substance misuse in youth and adults hospitalised with alcohol-related facial trauma. Methods and design: The study is a randomised controlled trial with 6 months of follow-up, to examine the effectiveness of a brief and culturally adapted intervention in improving outcomes for trauma patients with at-risk drinking admitted to the Royal Darwin Hospital maxillofacial surgery unit. Potential participants are identified using AUDIT-C questionnaire. Eligible participants are randomised to either Motivational Care Planning (MCP) or Treatment as Usual (TAU). The outcome measures will include quantity and frequency of alcohol and other substance use by Timeline Followback. The recruitment target is 154 participants, which with 20% dropout, is hoped to provide 124 people receiving treatment and follow-up. Discussion: This project introduces screening and brief interventions for high-risk drinkers admitted to the hospital with facial trauma. It introduces a practical approach to integrating brief interventions in the hospital setting, and has potential to demonstrate significant benefits for at-risk drinkers with facial trauma.

Recruiting and engaging new mothers in nutrition research studies : lessons from the Australian NOURISH randomised controlled trial

Background: Despite important implications for the budgets, statistical power and generalisability of research findings, detailed reports of recruitment and retention in randomised controlled trials (RCTs) are rare. The NOURISH RCT evaluated a community-based intervention for first-time mothers that promoted protective infant feeding practices as a primary prevention strategy for childhood obesity. The aim of this paper is to provide a detailed description and evaluation of the recruitment and retention strategies used. Methods: A two stage recruitment process designed to provide a consecutive sampling framework was used. First time mothers delivering healthy term infants were initially approached in postnatal wards of the major maternity services in two Australian cities for consent to later contact (Stage 1). When infants were about four months old mothers were re-contacted by mail for enrolment (Stage 2), baseline measurements (Time 1) and subsequent random allocation to the intervention or control condition. Outcomes were assessed at infant ages 14 months (Time 2) and 24 months (Time 3). Results: At Stage 1, 86% of eligible mothers were approached and of these women, 76% consented to later contact. At Stage 2, 3% had become ineligible and 76% could be recontacted. Of the latter, 44% consented to full enrolment and were allocated. This represented 21% of mothers screened as eligible at Stage 1. Retention at Time 3 was 78%. Mothers who did not consent or discontinued the study were younger and less likely to have a university education. Conclusions: The consent and retention rates of our sample of first time mothers are comparable with or better than other similar studies. The recruitment strategy used allowed for detailed information from non-consenters to be collected; thus selection bias could be estimated. Recommendations for future studies include being able to contact participants via mobile phone (particular text messaging), offering home visits to reduce participant burden and considering the use of financial incentives to support participant retention.

Impact of a novel nurse-led prechemotherapy education intervention (ChemoEd) on patient distress, symptom burden, and treatment-related information and support needs : results from a randomised, controlled trial

Background: High levels of distress and need for self-care information by patients commencing chemotherapy suggest that current prechemotherapy education is suboptimal. We conducted a randomised, controlled trial of a prechemotherapy education intervention (ChemoEd) to assess impact on patient distress, treatment-related concerns, and the prevalence and severity of and bother caused by six chemotherapy side-effects. Patients and methods: One hundred and ninety-two breast, gastrointestinal, and haematologic cancer patients were recruited before the trial closing prematurely (original target 352). ChemoEd patients received a DVD, question-prompt list, self-care information, an education consultation ≥24 h before first treatment (intervention 1), telephone follow-up 48 h after first treatment (intervention 2), and a face-to-face review immediately before second treatment (intervention 3). Patient outcomes were measured at baseline (T1: pre-education) and immediately preceding treatment cycles 1 (T2) and 3 (T3). Results: ChemoEd did not significantly reduce patient distress. However, a significant decrease in sensory/psychological (P = 0.027) and procedural (P = 0.03) concerns, as well as prevalence and severity of and bother due to vomiting (all P = 0.001), were observed at T3. In addition, subgroup analysis of patients with elevated distress at T1 indicated a significant decrease (P = 0.035) at T2 but not at T3 (P = 0.055) in ChemoEd patients. Conclusions: ChemoEd holds promise to improve patient treatment-related concerns and some physical/psychological outcomes; however, further research is required on more diverse patient populations to ensure generalisability.

School-based first aid training and the implications for traffic injury prevention : a randomised controlled trial

Adolescent injury remains a significant public health concern and is often the result of at-risk transport related behaviours. When a person is injured actions taken by bystanders are of crucial importance and timely first aid appears to reduce the severity of some injuries (Hussain & Redmond, 1994). Accordingly, researchers have suggested that first aid training should be more widely available as a potential strategy to reduce injury (Lynch et al., 2006). Further research has identified schools as an ideal setting for learning first aid skills as a means of injury prevention (Maitra, 1997). The current research examines the implications of school based first aid training for young adolescents on injury prevention, particularly relating to transport injuries. First aid training was integrated with peer protection and school connectedness within the Skills for Preventing Injury in Youth (SPIY) program (Buckley & Sheehan, 2009) and evaluated to determine if there was a reduction in the likelihood of transport related injuries at six months post-intervention. In Queensland, Australia, 35 high schools were recruited and randomly assigned to intervention and control conditions in early April 2012. A total of 2,000 Year nine students (mean age 13.5 years, 39% male) completed surveys six months post-intervention in November 2012. Analyses will compare the intervention students with control group students who self-reported i) first aid training with a teacher, professional or other adult and ii) no first aid in the preceding six months. Using the Extended Adolescent Injury Checklist (E-AIC) (Chapman, Buckley & Sheehan, 2011) the transport related injury experiences included being injured while “riding as a passenger in a car”, “driving a car off road” and “riding a bicycle”. It is expected that students taught first aid within SPIY will report significantly fewer transport related injuries in the previous three months, compared to the control groups described above. Analyses will be conducted separately for sex and socio-economic class of schools. Findings from this study will provide insight into the value of first aid in adolescent injury prevention and provide evidence as to whether teaching first aid skills within a school based health education curriculum has traffic safety implications.

Randomised, double blind, placebo-controlled trial of Echinacea supplementation in air travellers

Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (

A randomised, controlled clinical trial comparing chlorhexidine gel and low-dose fluoride toothpaste to prevent early childhood caries

Objectives This randomised, controlled trial compared the effectiveness of 0.12% chlorhexidine (CHX) gel and 304% fluoride toothpaste to prevent early childhood caries (ECC) in a birth cohort by 24 months. Methods The participants were randomised to receive either (i) twice daily toothbrushing with toothpaste and once daily 0.12% CHX gel (n = 110) or (ii) twice daily toothbrushing with toothpaste only (study controls) (n = 89). The primary outcome measured was caries incidence and the secondary outcome was percentage of children with mutans streptococci (MS). All mothers were contacted by telephone at 6, 12, and 18 months. At 24 months, all children were examined at a community dental clinic. Results At 24 months, the caries prevalence was 5% (3/61) in the CHX and 7% (4/58) in the controls (P = 0.7). There were no differences in percentages of MS-positive children between the CHX and control groups (54%vs 53%). Only 20% applied the CHX gel once daily and 80% less than once daily. Conclusions Toothbrushing using 304% fluoride toothpaste with or without the application of chlorhexidine gel (0.12%) reduces ECC from 23% found in the general community to 5–7%. The lack of effect with chlorhexidine is likely to be due to low compliance.

The benefits of thermal clothing during winter in patients with heart failure : a pilot randomised controlled trial

Background Many Australian cities experience large winter increases in deaths and hospitalisations. Flu outbreaks are only part of the problem and inadequate protection from cold weather is a key independent risk factor. Better home insulation has been shown to improve health during winter, but no study has examined whether better personal insulation improves health. Data and Methods We ran a randomised controlled trial of thermal clothing versus usual care. Subjects with heart failure (a group vulnerable to cold) were recruited from a public hospital in Brisbane in winter and followed-up at the end of winter. Those randomised to the intervention received two thermal hats and tops and a digital thermometer. The primary outcome was the number of days in hospital, with secondary outcomes of General Practitioner (GP) visits and self-rated health. Results The mean number of days in hospital per 100 winter days was 2.5 in the intervention group and 1.8 in the usual care group, with a mean difference of 0.7 (95% CI: –1.5, 5.4). The intervention group had 0.2 fewer GP visits on average (95% CI: –0.8, 0.3), and a higher self-rated health, mean improvement –0.3 (95% CI: –0.9, 0.3). The thermal tops were generally well used, but even in cold temperatures the hats were only worn by 30% of subjects. Conclusions Thermal clothes are a cheap and simple intervention, but further work needs to be done on increasing compliance and confirming the health and economic benefits of providing thermals to at-risk groups.

Does a functional activity programme improve function, quality of life, and falls for residents in long term care? Cluster randomised controlled trial

Objective To assess the effectiveness of an activity programme in improving function, quality of life, and falls in older people in residential care. Design Cluster randomised controlled trial with one year follow-up. Setting 41low level dependency residential carehomes in New Zealand. Participants 682 people aged 65 years or over. Interventions 330 residents were offered a goal setting and individualised activities of daily living activity programme by a gerontology nurse, reinforced by usual healthcare assistants; 352 residents received social visits. Main outcome measures Function (late life function and disability instruments, elderly mobility scale, FICSIT-4

Promoting independence in residential care : successful recruitment for a randomised controlled trial

OBJECTIVES: To describe the recruitment strategy and association between facility and staff characteristics and success of resident recruitment for the Promoting Independence in Residential Care (PIRC) trial. DESIGN: Cross-sectional study of staff and facility characteristics and recruitment rates within facilities with calculation of cluster effects of multiple measures. SETTING AND PARTICIPANTS: Staff of low-level dependency residential care facilities and residents able to engage in a physical activity program in 2 cities in New Zealand. MEASURES: A global impression of staff willingness to facilitate research was gauged by research nurses, facility characteristics were measured by staff interview. Relevant outcomes were measured by resident interview and included the following: (1) Function: Late Life FDI scale, timed-up-and-go, FICSIT balance scale and the Elderly Mobility Scale; (2) Quality of Life: EuroQol quality of life scale, Life Satisfaction Index; and (3) falls were assessed by audit of the medical record. Correlation between recruitment rates, facility characteristics and global impression of staff willingness to participate were investigated. Design effects were calculated on outcomes. RESULTS: Forty-one (85%) facilities and 682 (83%) residents participated, median age was 85 years (range 65-101), and 74% were women. Participants had complex health problems. Recruitment rates were associated (but did not increase linearly) with the perceived willingness of staff, and were not associated with facility size. Design effects from the cluster recruitment differed according to outcome. CONCLUSIONS: The recruitment strategy was successful in recruiting a large sample of people with complex comorbidities and high levels of functional disability despite perceptions of staff reluctance. Staff willingness was related to recruitment success.

Cryotherapy for docetaxel-induced hand and nail toxicity: Randomised control trial

Purpose This study investigated the efficacy and safety of cryotherapy, in the form of frozen gel gloves, in relation to docetaxel-induced hand and fingernail toxicities. Patients and methods After piloting with 21 patients, a consecutive series sample of patients (n=53) prescribed docetaxel every three weeks, for a minimum of three cycles, was enrolled in this randomised control trial. Participants acted as their own control, with the frozen gel glove worn on one randomised hand for 15 minutes prior to infusion, for the duration of the infusion, and for 15 minutes of after completion of treatment. Hand and nail toxicities were evaluated by two blinded assessors according to CTCAE.v4 criteria. To assess the potential for cross-infection of multi-use gloves, microbial culture and sensitivity swabs were taken of each glove at every tenth use. Results Of the 53 participants enrolled in the main study, 21 provided evaluable data. There was a 60% withdrawal rate due to patient discomfort with the intervention. The mean incidence and severity of toxicities in all evaluable cycles in control and intervention hands respectively were erythroderma Grade 1 (5%/5%); nail discolouration Grade 1 (81%/67%); nail loss Grade 1 (19%/19%) and nail ridging Grade 1 (57%/57%). No significant differences were determined between hand conditions in terms of time to event, nor in terms of toxicity in gloved and non-gloved hands. Conclusion While cryotherapy in the form of frozen gloves for the cutaneous toxicities associated with docetaxel is safe, its limited efficacy, patient discomfort and some logistical issues preclude its use in our clinical setting.

Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel.