Medulloblastoma Down Under 2013 : a report from the third annual meeting of the International Medulloblastoma Working Group.

Medulloblastoma is curable in approximately 70% of patients. Over the past decade, progress in improving survival using conventional therapies has stalled, resulting in reduced quality of life due to treatment-related side effects, which are a major concern in survivors. The vast amount of genomic and molecular data generated over the last 5-10 years encourages optimism that improved risk stratification and new molecular targets will improve outcomes. It is now clear that medulloblastoma is not a single-disease entity, but instead consists of at least four distinct molecular subgroups: WNT/Wingless, Sonic Hedgehog, Group 3, and Group 4. The Medulloblastoma Down Under 2013 meeting, which convened at Bunker Bay, Australia, brought together 50 leading clinicians and scientists. The 2-day agenda included focused sessions on pathology and molecular stratification, genomics and mouse models, high-throughput drug screening, and clinical trial design. The meeting established a global action plan to translate novel biologic insights and drug targeting into treatment regimens to improve outcomes. A consensus was reached in several key areas, with the most important being that a novel classification scheme for medulloblastoma based on the four molecular subgroups, as well as histopathologic features, should be presented for consideration in the upcoming fifth edition of the World Health Organization's classification of tumours of the central nervous system. Three other notable areas of agreement were as follows: (1) to establish a central repository of annotated mouse models that are readily accessible and freely available to the international research community; (2) to institute common eligibility criteria between the Children's Oncology Group and the International Society of Paediatric Oncology Europe and initiate joint or parallel clinical trials; (3) to share preliminary high-throughput screening data across discovery labs to hasten the development of novel therapeutics. Medulloblastoma Down Under 2013 was an effective forum for meaningful discussion, which resulted in enhancing international collaborative clinical and translational research of this rare disease. This template could be applied to other fields to devise global action plans addressing all aspects of a disease, from improved disease classification, treatment stratification, and drug targeting to superior treatment regimens to be assessed in cooperative international clinical trials.

Management of lipids in rural Australia : are the guidelines being followed?

Background: Hypercholesterolaemia is ranked seventh among the major factors contributing to the overall burden of disease in Australia. Guidelines for evidence-based lipid management were released in 2001 and updated in 2005, however little population level data has been published on the current gap between recommended management and actual practice in Australia.

Method: Three population stratified surveys were undertaken in the Greater Green Triangle. Three thousand three hundred and twenty adults aged 25–74 years were randomly selected, stratified by gender and 10-year age groups. Anthropometric, clinical and self-administered questionnaire data relating to cardiovascular disease risk were collected in accordance with the WHO MONICA protocol. Blood samples were collected for lipid profile analysis. Participants were divided into four groups—Group 1: treated, high CVD risk; Group 2: treated, primary prevention; Group 3: untreated, high CVD risk; Group 4: untreated, low CVD risk. For each of these groups we compared cholesterol, HDL cholesterol, triglyceride and LDL cholesterol with targets recommended by the National Heart Foundation's 2005 guidelines.

Results: All lipids were at target in 39.4% of the study population with marked differences between groups: Group 1, 11.2%; Group 2, 38.5%; Group 3, 1.8%; Group 4, 47.6%.

Only 50.8% of the untreated high CVD risk group reported having blood cholesterol measured within the last 12 months.

Conclusion: Current rates of detection and treatment practices in rural Australia are suboptimal. Although one-third of the study population age 25–74 years are at sufficiently high risk to warrant consideration of lipid lowering medication only just over half of these were on treatment at the time of the study. These results suggest that an intensive implementation plan is required for the management of hyperlipidaemia in rural Australia.

Weight loss and attrition in overweight and obese young women during a 36- week internet-based lifestyle intervention

Background: Young women are at high risk of weight gain yet few studies have examined the long-term effectiveness of weight loss programs in this group. This study aimed to investigate the effects of a self-directed internet-based lifestyle program on body weight in young women.

Methods: Overweight or obese young women (BMI 33.4 ± 0.3 kg/m2, age 27.8 ± 0.3 years) were initially randomized to General lifestyle advice (G) or Structured lifestyle advice (S) via in-person and website support for 12 weeks (Phase I). After Phase I, all participants were supported through a self-directed internet-based program for 36 weeks (Phase II). The internet-based program included a structured hypocaloric diet, physical activity program, self-monitoring tools, peer group forum and monthly emails. Body weight, energy intake and physical activity were measured at week 0, week 12, week 24 and week 48. Adherence to self-regulatory behaviors was measured at week 48. Mixed model analyses were conducted to determine changes in body weight, energy intake and physical activity.

Results: A total of 203 overweight or obese young women commenced Phase I and 130 commenced Phase II. In Phase I, S group had significantly greater weight loss than G group (4.2 ± 0.6 kg vs 0.6 ± 0.3 kg, P<0.001). In Phase II, both groups had significant weight loss over time without significant group differences (-0.8 ± 1.1kg vs -0.8 ± 0.6, P>0.05). Forty-one percent (53/130) of the participants who commenced Phase II completed the internet-based intervention. Dropouts had a higher baseline BMI, were more likely to be married or in a de facto relationship, and more likely to have at least one child.

Conclusions: A self-directed internet-based program could be effective in providing support in maintaining weight loss on a structured lifestyle program in young women over 36 weeks. Further research is required to maintain engagement in young women who were married/in a de facto relationship or have children.

Midazolam for sedation before procedures

BACKGROUND: Midazolam is used for sedation before diagnostic and therapeutic medical procedures. It is an imidazole benzodiazepine that has depressant effects on the central nervous system (CNS) with rapid onset of action and few adverse effects. The drug can be administered by several routes including oral, intravenous, intranasal and intramuscular. OBJECTIVES: To determine the evidence on the effectiveness of midazolam for sedation when administered before a procedure (diagnostic or therapeutic). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL to January 2016), MEDLINE in Ovid (1966 to January 2016) and Ovid EMBASE (1980 to January 2016). We imposed no language restrictions. SELECTION CRITERIA: Randomized controlled trials in which midazolam, administered to participants of any age, by any route, at any dose or any time before any procedure (apart from dental procedures), was compared with placebo or other medications including sedatives and analgesics. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed risk of bias for each included study. We performed a separate analysis for each different drug comparison. MAIN RESULTS: We included 30 trials (2319 participants) of midazolam for gastrointestinal endoscopy (16 trials), bronchoscopy (3), diagnostic imaging (5), cardioversion (1), minor plastic surgery (1), lumbar puncture (1), suturing (2) and Kirschner wire removal (1). Comparisons were: intravenous diazepam (14), placebo (5) etomidate (1) fentanyl (1), flunitrazepam (1) and propofol (1); oral chloral hydrate (4), diazepam (2), diazepam and clonidine (1); ketamine (1) and placebo (3); and intranasal placebo (2). There was a high risk of bias due to inadequate reporting about randomization (75% of trials). Effect estimates were imprecise due to small sample sizes. None of the trials reported on allergic or anaphylactoid reactions. Intravenous midazolam versus diazepam (14 trials; 1069 participants)There was no difference in anxiety (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.39 to 1.62; 175 participants; 2 trials) or discomfort/pain (RR 0.60, 95% CI 0.24 to 1.49; 415 participants; 5 trials; I² = 67%). Midazolam produced greater anterograde amnesia (RR 0.45; 95% CI 0.30 to 0.66; 587 participants; 9 trials; low-quality evidence). Intravenous midazolam versus placebo (5 trials; 493 participants)One trial reported that fewer participants who received midazolam were anxious (3/47 versus 15/35; low-quality evidence). There was no difference in discomfort/pain identified in a further trial (3/85 in midazolam group; 4/82 in placebo group; P = 0.876; very low-quality evidence). Oral midazolam versus chloral hydrate (4 trials; 268 participants)Midazolam increased the risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; moderate-quality evidence). Oral midazolam versus placebo (3 trials; 176 participants)Midazolam reduced pain (midazolam mean 2.56 (standard deviation (SD) 0.49); placebo mean 4.62 (SD 1.49); P < 0.005) and anxiety (midazolam mean 1.52 (SD 0.3); placebo mean 3.97 (SD 0.44); P < 0.0001) in one trial with 99 participants. Two other trials did not find a difference in numerical rating of anxiety (mean 1.7 (SD 2.4) for 20 participants randomized to midazolam; mean 2.6 (SD 2.9) for 22 participants randomized to placebo; P = 0.216; mean Spielberger's Trait Anxiety Inventory score 47.56 (SD 11.68) in the midazolam group; mean 52.78 (SD 9.61) in placebo group; P > 0.05). Intranasal midazolam versus placebo (2 trials; 149 participants)Midazolam induced sedation (midazolam mean 3.15 (SD 0.36); placebo mean 2.56 (SD 0.64); P < 0.001) and reduced the numerical rating of anxiety in one trial with 54 participants (midazolam mean 17.3 (SD 18.58); placebo mean 49.3 (SD 29.46); P < 0.001). There was no difference in meta-analysis of results from both trials for risk of incomplete procedures (RR 0.14, 95% CI 0.02 to 1.12; downgraded to low-quality evidence). AUTHORS' CONCLUSIONS: We found no high-quality evidence to determine if midazolam, when administered as the sole sedative agent prior to a procedure, produces more or less effective sedation than placebo or other medications. There is low-quality evidence that intravenous midazolam reduced anxiety when compared with placebo. There is inconsistent evidence that oral midazolam decreased anxiety during procedures compared with placebo. Intranasal midazolam did not reduce the risk of incomplete procedures, although anxiolysis and sedation were observed. There is moderate-quality evidence suggesting that oral midazolam produces less effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures.