A novel, multidomain, primary care nurse-led and mHealth-assisted intervention for dementia risk reduction in middle-aged adults (HAPPI MIND): study protocol for a cluster randomised controlled trial.

INTRODUCTION: Middle-aged multidomain risk reduction interventions targeting modifiable risk factors for dementia may delay or prevent a third of dementia cases in later life. We describe the protocol of a cluster randomised controlled trial (cRCT), HAPPI MIND (Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia). HAPPI MIND will evaluate the efficacy of a multidomain, nurse-led, mHealth supported intervention for assessing dementia risk and reducing associated risk factors in middle-aged adults in the Australian primary care setting. METHODS AND ANALYSIS: General practice clinics (n≥26) across Victoria and New South Wales, Australia, will be recruited and randomised. Practice nurses will be trained to implement the HAPPI MIND intervention or a brief intervention. Patients of participating practices aged 45-65 years with ≥2 potential dementia risk factors will be identified and recruited (approximately 15 patients/clinic). Brief intervention participants receive a personalised report outlining their risk factors for dementia based on Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) scores, education booklet and referral to their general practitioner as appropriate. HAPPI MIND participants receive the brief intervention as well as six individualised dementia risk reduction sessions with a nurse trained in motivational interviewing and principles of behaviour change, a personalised risk reduction action plan and access to the purpose-built HAPPI MIND smartphone app for risk factor self-management. Follow-up data collection will occur at 12, 24 and 36 months. Primary outcome is ANU-ADRI score change at 12 months from baseline. Secondary outcomes include change in cognition, quality of life and individual risk factors of dementia. ETHICS AND DISSEMINATION: Project approved by Monash University Human Research Ethics Committee (ID: 28273). Results will be disseminated in peer-reviewed journals and at healthcare conferences. If effective in reducing dementia risk, the HAPPI MIND intervention could be integrated into primary care, scaled up nationally and sustained over time. TRIAL REGISTRATION NUMBER: ACTRN12621001168842.

mTOR Inhibitors for the Treatment of Severe Congenital Hyperinsulinism: Perspectives on Limited Therapeutic Success.

CONTEXT: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in neonates and infants. In medically unresponsive CHI, subtotal pancreatectomy is performed to achieve euglycemia with consequent diabetes in later life. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been reported to obviate the need for pancreatectomy, but experience is limited. OBJECTIVE: We have investigated the efficacy and adverse effect profile of mTOR inhibitors in the treatment of severe CHI. DESIGN, SETTING, AND PATIENTS: This was an observational review of 10 severe CHI patients treated with mTOR inhibitors, in France and the United Kingdom, with the intention of achieving glycemic control without pancreatectomy. Safety information was recorded. MAIN OUTCOME MEASURE(S): We examined whether mTOR inhibitors achieved glycemic control, fasting tolerance, and weaning of supportive medical therapy. RESULTS: mTOR inhibition achieved euglycemia, fasting tolerance, and reduced medical therapy in only three patients (30%). Triglyceride levels were elevated in five patients (50%). One child required a blood transfusion for anemia, four had stomatitis, two had sepsis, one developed varicella zoster, and two patients developed gut dysmotility in association with exocrine pancreatic insufficiency. In silico analysis of transcriptome arrays from CHI patients revealed no significant association between mTOR signaling and disease. Pancreatic tissue from two patients who did not respond to sirolimus showed no reduction in cell proliferation, further suggesting that mTOR signaling did not down-regulate proliferation in the CHI pancreas. CONCLUSION: mTOR inhibitor treatment is associated with very limited success and must be used with caution in children with severe CHI.

Invasive pneumococcal disease among children in Victoria.

This study analysed notification data from the first year of enhanced surveillance of invasive pneumococcal disease (IPD) in Victoria (1 July 2001 - 30 June 2002), with a focus on risk factors for infection and vaccination status among children under five years of age. Overall, there were 397 notifications (8.2 per 100,000 population), 131 (33%) were children under five years of age. The highest notification rates were among those aged less than two years (72.6 per 100,000 population). Among children aged less than five years: bacteraemia without a primary focus of infection was the most common clinical presentation (64%); 89 per cent were hospitalised with the median length of stay being three days; four children (3%) died. There were 107 cases of a known serotype, 92% (n = 98) were either in or closely related to those included in the 7-valent conjugate pneumococcal vaccine (7vPCV). Most cases (98%) were not eligible for free 7vPCV under the currently funded program in Victoria. Only one child had been vaccinated. The results from the first year of enhanced IPD surveillance in Victoria suggest consideration should be given to extending the publicly funded program to include all children under two years of age.