Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial.

Background
Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the eff ect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.

Methods
We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks’ and 22 weeks’ gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive1000 mg vitamin C and 400 IU vitamin E (a-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratifi ed by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defi ned as gestational hypertension with proteinuria. Analysis was by modifi ed intention to treat. This study is registered, ISRCTN27214045.

Findings
Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70)groups (risk ratio 0·81, 95% CI 0·59–1·12). No adverse maternal or neonatal outcomes were reported.

Interpretation
Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be benefi cial in women with a low antioxidant status at baseline needs further testing.

Optimal glycaemic control, pre-eclampsia and gestational hypertension in women with type 1 diabetes in the Diabetes and Pre-Eclampsia Intervention Trial

OBJECTIVE
To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes.

RESEARCH DESIGN AND METHODS
Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1–6.9%), moderate (7.0–7.9%), and poor (=8.0%) glycemic control, respectively.

RESULTS
Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C =8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values =6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values =7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension.

CONCLUSIONS
Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.

Concord Grape Juice, cognitive function and driving performance: a 12 week, placebo controlled, randomised, crossover trial in mothers of pre-teen children

Background: Daily consumption of Concord grape juice (CGJ) over three to four months has been shown to improve memory function in adults with mild cognitive impairment, and reduce blood pressure in hypertensive adults. These benefits are likely due to the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus we examined the potential beneficial effect of CGJ in individuals experiencing somewhat stressful demanding lifestyles. Objective: To examine the effects of twelve weeks’ daily consumption of CGJ on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. Design: Twenty five healthy mothers of pre-teen children, aged 40-50 years, who were employed for > 30 hours/week consumed 12oz (355ml) CGJ (containing 777mg total polyphenols) or an energy, taste and appearance matched placebo daily for twelve weeks according to a randomised, crossover design with a four week washout. Verbal and spatial memory, executive function, attention, blood pressure and mood were assessed at baseline, six weeks and twelve weeks. Immediately following the cognitive battery, a subsample of seventeen females completed a driving performance assessment in the University of Leeds Driving Simulator. The twenty five minute driving task required participants to match the speed and direction of a lead vehicle. Results: Significant improvements in immediate spatial memory and driving performance were observed following CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. Conclusions: Cognitive benefits associated with chronic consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond cessation of flavonoid consumption and future studies should carefully consider the length of washout within crossover designs.

Prevention of hypertension in patients with pre-hypertension: Protocol for the PREVER-prevention trial

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial Registration: Clinical Trials NCT00970931. © 2011 Fuchs et al; licensee BioMed Central Ltd.

Does a Pre-Treatment Diagnostic Interview Affect the Outcome of Internet-Based Self-Help for Social Anxiety Disorder? A Randomized Controlled Trial

BACKGROUND: Numerous studies suggest that Internet-based self-help treatments are effective in treating anxiety disorders. Trials evaluating such interventions differ in their screening procedures and in the amount of clinician contact in the diagnostic assessment phase. The present study evaluates the impact of a pre-treatment diagnostic interview on the outcome of an Internet-based treatment for Social Anxiety Disorder (SAD). METHOD: One hundred and nine participants seeking treatment for SAD were randomized to either an interview-group (IG, N = 53) or to a non-interview group (NIG, N = 56). All participants took part in the same 10-week cognitive-behavioural unguided self-help programme. Before receiving access to the programme, participants of the IG underwent a structured diagnostic interview. Participants of the NIG started directly with the programme. RESULTS: Participants in both groups showed significant and substantial improvement on social anxiety measures from pre- to post-assessment (d IG = 1.30-1.63; d NIG = 1.00-1.28) and from pre- to 4-month follow-up assessment (d IG = 1.38-1.87; d NIG = 1.10-1.21). Significant between-groups effects in favour of the IG were found on secondary outcome measures of depression and general distress (d = 0.18-0.42). CONCLUSIONS: These findings suggest that Internet-based self-help is effective in treating SAD, whether or not a diagnostic interview is involved. However, the pre-treatment interview seems to facilitate change on secondary outcomes such as depression and general distress.

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

AIMS: Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. METHODS: 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. RESULTS: Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: Results from the Metocard-CNIC trial (Effect of Metoprolol in Cardioprotection during an Acute Myocardial Infarction)

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions.

The efficacy of an augmented virtual reality system to alleviate pain in children undergoing burns dressing changes : a randomised controlled trial

In children, the pain and anxiety associated with acute burn dressing changes can be severe, with drug treatment alone frequently proving to be inadequate. Virtual reality (VR) systems have been successfully trialled in limited numbers of adult and paediatric burn patients. Augmented reality (AR) differs from VR in that it overlays virtual images onto the physical world, instead of creating a complete virtual world. This prospective randomised controlled trial investigated the use of AR as an adjunct to analgesia and sedation in children with acute burns. Forty-two children (30 male and 12 female), with an age range of 3–14 years (median age 9 years) and a total burn surface area ranging from 1 to 16% were randomised into a treatment (AR) arm and a control (basic cognitive therapy) arm after administration of analgesia and/or sedation. Pain scores, pulse rates (PR), respiratory rates (RR) and oxygen saturations (SaO2) were recorded pre-procedurally, at 10 min intervals and post-procedurally. Parents were also asked to grade their child's overall pain score for the dressing change. Mean pain scores were significantly lower (p = 0.0060) in the AR group compared to the control group, as were parental pain assessment scores (p = 0.015). Respiratory and pulse rates showed significant changes over time within groups, however, these were not significantly different between the two study groups. Oxygen saturation did not differ significantly over time or between the two study groups. This trial shows that augmented reality is a useful adjunct to pharmacological analgesia.

Use of face masks by non-scrubbed operating room staff : a randomized controlled trial.

Background: Ambiguity remains about the effectiveness of wearing surgical face masks. The purpose of this study was to assess the impact on surgical site infections when non-scrubbed operating room staff did not wear surgical face masks. Design: Randomised controlled trial. Participants: Patients undergoing elective or emergency obstetric, gynecological, general, orthopaedic, breast or urological surgery in an Australian tertiary hospital. Intervention: 827 participants were enrolled and complete follow-up data was available for 811 (98.1%) patients. Operating room lists were randomly allocated to a ‘Mask roup’ (all non-scrubbed staff wore a mask) or ‘No Mask group’ (none of the non-scrubbed staff wore masks). Primary end point: Surgical site infection (identified using in-patient surveillance; post discharge follow-up and chart reviews). The patient was followed for up to six weeks. Results: Overall, 83 (10.2%) surgical site infections were recorded; 46/401 (11.5%) in the Masked group and 37/410 (9.0%) in the No Mask group; odds ratio (OR) 0.77 (95% confidence interval (CI) 0.49 to 1.21), p = 0.151. Independent risk factors for surgical site infection included: any pre-operative stay (adjusted odds ratio [aOR], 0.43 (95% CI, 0.20; 0.95), high BMI aOR, 0.38 (95% CI, 0.17; 0.87), and any previous surgical site infection aOR, 0.40 (95% CI, 0.17; 0.89). Conclusion: Surgical site infection rates did not increase when non-scrubbed operating room personnel did not wear a face mask.

Case management educational intervention with public health nurses : cluster randomized controlled trial

Aim: This paper is a report of a study conducted to determine the effectiveness of a community case management collaborative education intervention in terms of satisfaction, learning and performance among public health nurses. Background: Previous evaluation studies of case management continuing professional education often failed to demonstrate effectiveness across a range of outcomes and had methodological weaknesses such as small convenience samples and lack of control groups. Method: A cluster randomised controlled trial was conducted between September 2005 and February 2006. Ten health centre clusters (5 control, 5 intervention) recruited 163 public health nurses in Taiwan to the trial. After pre-tests for baseline measurements, public health nurses in intervention centres received an educational intervention of four half-day workshops. Post-tests for both groups were conducted after the intervention. Two-way repeated measures analysis of variance was performed to evaluate the effect of the intervention on target outcomes. Results: A total of 161 participants completed the pre- and post-intervention measurements. This was almost a 99% response rate. Results revealed that 97% of those in the experimental group were satisfied with the programme. There were statistically significant differences between the two groups in knowledge (p = 0.001), confidence in case management skills (p = 0.001), preparedness for case manager role activities (p = 0.001), self-reported frequency in using skills (p = 0.001), and role activities (p = 0.004). Conclusion: Collaboration between academic and clinical nurses is an effective strategy to prepare nurses for rapidly-changing roles.

Design and implementation of the Exercise for Health trial – a pragmatic exercise intervention for women with breast cancer

Background Exercise for Health was a pragmatic, randomised, controlled trial comparing the effect of an eight-month exercise intervention on function, treatment-related side effects and quality of life following breast cancer, compared with usual care. The intervention commenced six weeks post-surgery, and two modes of delivering the same intervention was compared with usual care. The purpose of this paper is to describe the study design, along with outcomes related to recruitment, retention and representativeness, and intervention participation. Methods: Women newly diagnosed with breast cancer and residing in a major metropolitan city of Queensland, Australia, were eligible to participate. Consenting women were randomised to a face-to-face-delivered exercise group (FtF, n=67), telephone-delivered exercise group (Tel, n=67) or usual care group (UC, n=60) and were assessed pre-intervention (5-weeks post-surgery), mid-intervention (6 months post-surgery) and 10 weeks post-intervention (12 months post-surgery). Each intervention arm entailed 16 sessions with an Exercise Physiologist. Results: Of 318 potentially eligible women, 63% (n=200) agreed to participate, with a 12-month retention rate of 93%. Participants were similar to the Queensland breast cancer population with respect to disease characteristics, and the randomisation procedure was mostly successful at attaining group balance, with the few minor imbalances observed unlikely to influence intervention effects given balance in other related characteristics. Median participation was 14 (min, max: 0, 16) and 13 (min, max: 3, 16) intervention sessions for the FtF and Tel, respectively, with 68% of those in Tel and 82% in FtF participating in at least 75% of sessions. Discussion: Participation in both intervention arms during and following treatment for breast cancer was feasible and acceptable to women. Future work, designed to inform translation into practice, will evaluate the quality of life, clinical, psychosocial and behavioural outcomes associated with each mode of delivery.

Physical activity and nutrition program for seniors (PANS) : protocol of a randomized controlled trial

Background Along with reduced levels of physical activity, older Australian's mean energy consumption has increased. Now over 60% of older Australians are considered overweight or obese. This study aims to confirm if a low-cost, accessible physical activity and nutrition program can improve levels of physical activity and diet of insufficiently active 60-70 year-olds. Methods/Design This 12-month home-based randomised controlled trial (RCT) will consist of a nutrition and physical activity intervention for insufficiently active people aged 60 to 70 years from low to medium socio-economic areas. Six-hundred participants will be recruited from the Australian Federal Electoral Role and randomly assigned to the intervention (n = 300) and control (n = 300) groups. The study is based on the Social Cognitive Theory and Precede-Proceed Model, incorporating voluntary cooperation and self-efficacy. The intervention includes a specially designed booklet that provides participants with information and encourages dietary and physical activity goal setting. The booklet will be supported by an exercise chart, calendar, bi-monthly newsletters, resistance bands and pedometers, along with phone and email contact. Data will be collected over three time points: pre-intervention, immediately post-intervention and 6-months post-study. Discussion This trial will provide valuable information for community-based strategies to improve older adults' physical activity and dietary intake. The project will provide guidelines for appropriate sample recruitment, and the development, implementation and evaluation of a minimal intervention program, as well as information on minimising barriers to participation in similar programs.

Associations between parenting behaviours and feeding beliefs of first-time Australian mothers in the NOURISH obesity prevention trial

Purpose: Parenting style and early feeding practices have been linked to child intake, eating behaviour and weight status. The purpose of this study was to examine associations between general maternal parenting behaviours and feeding beliefs in Australian mothers of 11-17 month-old children. Methods: This cross-sectional analysis included 223 first-time mothers and their children (49% male, mean age 14 [sd 1] months) enrolled in the control group of the NOURISH trial. Mothers self-reported their feeding beliefs and parenting behaviours (overprotection, irritability, warmth, autonomy-encouraging) using modified questions from the Infant Feeding Questionnaire (Baughcum, 2001) and the Longitudinal Study of Australian Children. Multiple regression analyses were conducted, using feeding beliefs (four factors) as dependent and parenting behaviours as independent variables while adjusting for child gender, age, weight-for-age z-score and maternal age, education level, feeding mode (breast vs. non-breast), and perception of own pre-pregnancy and child weight status. Results/Findings: Two of four parenting behaviours were significantly associated with feeding beliefs. Maternal warmth was inversely associated with concerns that the child would become underweight (β=-0.156, p=0.022) and positively associated with mothers’ awareness of child’s hunger/satiety cues (β=0.303, p<0.001). Mothers’ overprotection was positively associated with concerns that the child would become underweight (β=0.213, p=0.001); become overweight (β=0.174, p=0.005); and mother’s responsive feeding (β=0.135, p=0.057). Weight-for-age z-score, mothers’ perception of their child and own weight status, education, feeding mode, and child’s age were significant covariates. Conclusions: Feeding occurs within the broader parenting context. Improving early feeding beliefs and practices may require addressing mother’s approaches to parenting, especially warmth and overprotection.