Improving Data Sharing in Research with Contect-free Encoded Missing Data

Lack of attention to missing data in research may result in biased results, loss of power and reduced generalizability. Registering reasons for missing values at the time of data collection, or — in the case of sharing existing data — before making data available to other teams, can save time and efforts, improve scientific value and help to prevent erroneous assumptions and biased results. To ensure that encoding of missing data is sufficient to understand the reason why data are missing, it should ideally be context-free. Therefore, 11 context-free codes of missing data were carefully designed based on three completed randomized controlled clinical trials and tested in a new randomized controlled clinical trial by an international team consisting of clinical researchers and epidemiologists with extended experience in designing and conducting trials and an Information System expert. These codes can be divided into missing due to participant and/or participation characteristics (n=6), missing by design (n=4), and due a procedural error (n=1). Broad implementation of context-free missing data encoding may enhance the possibilities of data sharing and pooling, thus allowing more powerful analyses using existing data. Keywords: missing data; data pooling; data sharing; context free encodingHATICE (www.hatice.eu) is a collaborative project co-funded by the European Union’s Seventh Framework Program (FP7, 2007-2013), under grant agreement No 305374. The research leading to these results has also been funded by the “Multimodal preventive trials for Alzheimer´s Disease: towards multinational strategies-programme: MIND-AD”, Academy of Finland (291803) and VTR, Kuopio University Hospital (5772815)

The Effect of Multidomain Interventions on Global Cognition, Symptoms of Depression and Apathy - A Pooled Analysis of Two Randomized Controlled Trials.

BACKGROUND: Cardiovascular risk factors and lifestyle factors are associated with an increased risk of cognitive decline and dementia in observational studies, and have been targeted by multidomain interventions. OBJECTIVES: We pooled individual participant data from two multi-domain intervention trials on cognitive function and symptoms of depression to increase power and facilitate subgroup analyses. DESIGN: Pooled analysis of individual participant data. SETTING: Prevention of Dementia by Intensive Vascular Care trial (preDIVA) and Multidomain Alzheimer Preventive Trial (MAPT). PARTICIPANTS: Community-dwelling individuals, free from dementia at baseline. INTERVENTION: Multidomain interventions focused on cardiovascular and lifestyle related risk factors. MEASUREMENTS: Data on cognitive functioning, depressive symptoms and apathy were collected at baseline, 2 years and 3-4 years of follow-up as available per study. We analyzed crude scores with linear mixed models for overall cognitive function (Mini Mental State Examination [MMSE]), and symptoms of depression and apathy (15-item Geriatric Depression Scale). Prespecified subgroup analyses were performed for sex, educational level, baseline MMSE <26, history of hypertension, and history of stroke, myocardial infarction and/or diabetes mellitus. RESULTS: We included 4162 individuals (median age 74 years, IQR 72, 76) with a median follow-up duration of 3.7 years (IQR 3.0 to 4.1 years). No differences between intervention and control groups were observed on change in cognitive functioning scores and symptoms of depression and apathy scores in the pooled study population. The MMSE declined less in the intervention groups in those with MMSE <26 at baseline (N=250; MD: 0.84; 95%CI: 0.15 to 1.54; p<0.001). CONCLUSIONS: We found no conclusive evidence that multidomain interventions reduce the risk of global cognitive decline, symptoms of depression or apathy in a mixed older population. Our results suggest that these interventions may be more effective in those with lower baseline cognitive functioning. Extended follow-up for dementia occurrence is important to inform on the potential long-term effects of multidomain interventions

Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis.

An estimated one-third of the world population is latently infected with Mycobacterium tuberculosis. These nonreplicating, dormant bacilli are tolerant to conventional anti-tuberculosis drugs, such as isoniazid. We recently identified diarylquinoline R207910 (also called TMC207) as an inhibitor of ATP synthase with a remarkable activity against replicating mycobacteria. In the present study, we show that R207910 kills dormant bacilli as effectively as aerobically grown bacilli with the same target specificity. Despite a transcriptional down-regulation of the ATP synthase operon and significantly lower cellular ATP levels, we show that dormant mycobacteria do possess residual ATP synthase enzymatic activity. This activity is blocked by nanomolar concentrations of R207910, thereby further reducing ATP levels and causing a pronounced bactericidal effect. We conclude that this residual ATP synthase activity is indispensable for the survival of dormant mycobacteria, making it a promising drug target to tackle dormant infections. The unique dual bactericidal activity of diarylquinolines on dormant as well as replicating bacterial subpopulations distinguishes them entirely from the current anti-tuberculosis drugs and underlines the potential of R207910 to shorten tuberculosis treatment. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

BMC Public Health

BACKGROUND: In 2009, the World Health Organization's Commission on Social Determinants of Health set out its recommendations for action, which included establishing equity from early childhood onwards by enabling all children and their mothers to benefit from a comprehensive package of quality programmes. In order to address social inequalities in health, it is recommended that action be taken from early childhood, and actions providing support for parenting are an effective lever in this respect. The aim of this review of systematic reviews is to analyse, on the one hand, the components and characteristics of effective interventions in parenting support and, on the other, the extent to which the reviews took into account social inequalities in health. METHODS: A total of 796 reviews were selected from peer-reviewed journals published between 2009 and 2016 in French or English. Of these, 21 reviews responding to the AMSTAR and selected ROBIS criteria were retained. These were analysed in relation to the consideration they gave to social inequalities in health according to PRISMA-equity. RESULTS: The reviews confirmed that parenting support programmes improved infants' sleep, increased mothers' self-esteem and reduced mothers' anger, anxiety and stress levels. The mainly authors noted that the contexts in which the interventions had taken place were described either scantly or not at all, making it difficult to evaluate them. Only half of the reviews had addressed the question of social inequalities in health. In particular, there had been little research conducted on the relational aspect and the social link. CONCLUSION: In terms of addressing social inequalities in perinatal health, the approach remains both modest and reductive. Understanding how, for whom and in what conditions interventions operate is one way of optimising their results. Further research is needed to study the interactions between the interventions and their contexts

Absolute configuration and structural features of R207910, a novel anti-tuberculosis agent

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