Evaluation of dose-dependent treatment effects after mid-trial dose escalation in biomarker, clinical, and cognitive outcomes for gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Introduction: While the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) was ongoing, external data suggested higher doses were needed to achieve targeted effects; therefore, doses of gantenerumab were increased 5-fold, and solanezumab was increased 4-fold. We evaluated to what extent mid-trial dose increases produced a dose-dependent treatment effect.

Methods: Using generalized linear mixed effects (LME) models, we estimated the annual low- and high-dose treatment effects in clinical, cognitive, and biomarker outcomes.

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years.

Intercountry Consensus Building: Lessons From Developing a Chronic-Conditions Self-Management Support Framework.

Self-management support initiatives that aim to improve the self-care of chronic conditions are considered a key part of a health promotion strategy for addressing the impacts of long-term illness. Given the growth of these activities and still evolving evidence base, thoughtful intercountry collaborations with subject matter experts can be an effective way to expedite building self-management support capacity, promoting the advancement of evidence, and developing effective policies and programs. The challenge is to find an effective consensus building process that promotes linkages between researchers and health promotion decisions makers across vast geographical boundaries and limited resources.

Toward consensus on self-management support: the international chronic condition self-management support framework.

Self-management support (SMS) initiatives have been hampered by insufficient attention to underserved and disadvantaged populations, a lack of integration between health, personal and social domains, over emphasis on individual responsibility and insufficient attention to ethical issues. This paper describes a SMS framework that provides guidance in developing comprehensive and coordinated approaches to SMS that may address these gaps and provides direction for decision makers in developing and implementing SMS initiatives in key areas at local levels. The framework was developed by researchers, policy-makers, practitioners and consumers from 5 English-speaking countries and reviewed by 203 individuals in 16 countries using an e-survey process.

Using Concept Mapping to Develop a Strategy for Self-Management Support for Underserved Populations Living With Chronic Conditions, British Columbia, August 2013-June 2014.

Introduction: Self-management support (SMS) is an essential component of public health approaches to chronic conditions. Given increasing concerns about health equity, the needs of diverse populations must be considered. This study examined potential solutions for addressing the gaps in self-management support initiatives for underserved populations.

Understanding how self-management interventions work for disadvantaged populations living with chronic conditions: protocol for a realist synthesis.

Introduction: Self-management programmes are complex interventions aimed at improving the way individuals self-manage chronic conditions, but there are questions about the overall impact of these programmes on disadvantaged populations, in terms of their capacity to engage with and receive the benefits from these initiatives. Given the increased resources being directed towards self-management initiatives, clinicians and policy makers need knowledge on how self-management interventions work for these populations. Most systematic reviews of self-management interventions do not consider the complex interactions between implementation contexts, intervention strategies, and mechanisms that influence how self-management interventions work in real life for disadvantaged groups.

Dominantly Inherited Alzheimer Network: facilitating research and clinical trials.

The Dominantly Inherited Alzheimer Network (DIAN) is an international registry of individuals at risk for developing autosomal dominant Alzheimer's disease (AD). Its primary aims are to investigate the temporal ordering of AD pathophysiological changes that occur in asymptomatic mutation carriers and to identify those markers that herald the transition from cognitive normality to symptomatic AD. DIAN participants undergo longitudinal evaluations, including clinical and cognitive assessments and measurements of molecular and imaging AD biomarkers.

The spectral composition of evening light and individual differences in the suppression of melatonin and delay of sleep in humans.

The effect of light on circadian rhythms and sleep is mediated by a multi-component photoreceptive system of rods, cones and melanopsin-expressing intrinsically photosensitive retinal ganglion cells. The intensity and spectral sensitivity characteristics of this system are to be fully determined. Whether the intensity and spectral composition of light exposure at home in the evening is such that it delays circadian rhythms and sleep also remains to be established.

Central effects of cinnarizine: restricted use in aircrew.

Hypothesis: Our aim was to establish the effects of cinnarizine, a drug used for the treatment of motion sickness, on daytime sleepiness and performance.

Methods: The effects of cinnarizine (15, 30, and 45 mg) were assessed on digit symbol substitution, tracking, vigilance, and on subjective and objective (daytime sleep latencies) sleepiness in six healthy volunteers between the ages of 20 and 34 yr (mean 27 yr) from 1.0 h prior to ingestion to 8.