Statistical analysis plan for the COMPARE trial: a 3-arm randomised controlled trial comparing the effectiveness of Constraint-induced Aphasia Therapy Plus and Multi-modality Aphasia Therapy to usual care in chronic post-stroke aphasia (COMPARE)

BackgroundWhile high-quality meta-analyses have confirmed the effectiveness of aphasia therapy after stroke, there is limited evidence for the comparative effectiveness of different aphasia interventions. Two commonly used interventions, Constraint-induced Aphasia Therapy Plus (CIAT Plus) and Multi-modality Aphasia Therapy (M-MAT), are hypothesised to rely on diverse underlying neural mechanisms for recovery and may be differentially responsive to aphasia severity. COMPARE is a prospective randomised open-blinded end-point trial designed to determine whether, in people with chronic post-stroke aphasia living in the community, CIAT Plus and M-MAT provide greater therapeutic benefit compared to usual care, are differentially effective according to aphasia severity, and are cost-effective. This paper details the statistical analysis plan for the COMPARE trial developed prior to data analysis.MethodsParticipants (n = 216) are randomised to one of three arms, CIAT Plus, M-MAT or usual care, and undertake therapy with a study trained speech pathologist in groups of three participants stratified by aphasia severity. Therapy occurs for 3 h blocks per day for 10 days across 2 weeks. The primary clinical outcome is aphasia severity as measured by the Western Aphasia Battery-Revised Aphasia Quotient (WAB-R-AQ) immediately post intervention. Secondary outcomes include WAB-R-AQ at 12-week follow-up, and functional communication, discourse efficiency, multimodal communication, and health-related quality of life immediately post intervention and at 12-week follow-up.ResultsLinear mixed models (LMMs) will be used to analyse differences between M-MAT and UC, and CIAT-Plus and UC on each outcome measure immediately and at 12 weeks post-intervention. The LMM for WAB-R-AQ will assess the differences in efficacy between M-MAT and CIAT-Plus. All analyses will control for baseline aphasia severity (fixed effect) and for the clustering effect of treatment groups (random effect).DiscussionThis trial will provide relative effectiveness data for two common interventions for people with chronic post-stroke aphasia, and highlight possible differential effects based on aphasia severity. Together with the health economic analysis data, the results will enable more informed personalised prescription for aphasia therapy after stroke.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN 12615000618550 . Registered on 15 June 2016

Prevalence of depression and anxiety among participants with glaucoma in a population-based cohort study : the Gutenberg Health Study

Background To investigate the prevalence of depression and anxiety among subjects with self-reported glaucoma and the association between self-reported glaucoma and depression respectively anxiety in a European cohort. Methods A study sample of 14,657 participants aged 35 to 74 years was investigated in a population-based cohort study. All participants reported presence or absence of glaucoma. Ophthalmological examinations were carried out in all participants and demographic and disease related information were obtained by interview. Depression was assessed with the Patient Health Questionnaire (PHQ-9), and generalized anxiety with the two screening items (GAD-2) of the short form of the GAD-7 (Generalized Anxiety Disorder-7 Scale). Prevalence of depression and generalized anxiety were investigated for subjects with and without self-reported glaucoma. Logistic regression analyses with depression, respectively anxiety as dependent variable and self-reported glaucoma as independent variable were conducted and adjusted for socio-demographic factors, systemic comorbidities (arterial hypertension, myocardial infarction, stroke, diabetes mellitus, chronic obstructive pulmonary disease, cancer), ocular diseases (cataract, macular degeneration, corneal diseases, diabetic retinopathy), visual acuity, intraocular pressure, antiglaucoma eye drops (sympathomimetics, parasympathomimetics, carbonic anhydrase inhibitors, beta-blockers, prostaglandins) and general health status. Results 293 participants (49.5% female) reported having glaucoma. Prevalence of depression among participants with and without self-reported glaucoma was 6.6% (95%-CI 4.1–10.3) respectively 7.7% (95%-CI 7.3–8.2), and for anxiety 5.3% (95%-CI 3.1–8.7) respectively 6.6% (95%-CI 6.2–7.1). Glaucoma was not associated with depression (Odds ratio 1.10, 95%-CI 0.50–2.38, p = 0.80) or anxiety (1.48, 95%-CI 0.63–3.30, p = 0.35) after adjustment for socio-demographic factors, ocular/systemic diseases, ocular parameters, antiglaucoma drugs and general health status. A restriction to self-reported glaucoma cases either taking topical antiglaucoma medications or having a history of glaucoma surgery did not alter the result. Conclusions This is the first study analyzing both depression and anxiety among glaucoma patients in a European cohort. Subjects with and without self-reported glaucoma had a similar prevalence of depression and anxiety in our population-based sample. Self-reported glaucoma was not associated with depression or anxiety. A lack of a burden of depressive symptoms may result from recruitment from a population-based sample as compared to previous study groups predominantly recruited from tertiary care hospitals

No evidence for an association of plasma homocysteine levels and refractive error - Results from the population-based Gutenberg Health Study (GHS)

Purpose There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007-2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. We used linear regression models to evaluate the potential association between Hcy and refraction at baseline, and between Hcy and change in refraction between baseline and 5-year-follow-up examination. We used generalized estimating equation models to account for the correlation between fellow eyes. Results We included 13,749 participants, categorized as having no myopia (spherical equivalent > -0.75 D, 65.2%), low myopia (-0.75 D-2.75 D, 21.5%), moderate myopia (-3.00 D- 5.75 D, 9.8%) and high myopia (≤ -6

Municipal water quantities and health in Nunavut households: an exploratory case study in Coral Harbour, Nunavut, Canada

Background: Access to adequate quantities of water has a protective effect on human health and well-being. Despite this, public health research and interventions are frequently focused solely on water quality, and international standards for domestic water supply minimums are often overlooked or unspecified. This trend is evident in Inuit and other Arctic communities even though numerous transmissible diseases and bacterium infections associated with inadequate domestic water quantities are prevalent. Objectives: Our objective was to explore the pathways by which the trucked water distribution systems being used in remote northern communities are impacting health at the household level, with consideration given to the underlying social and environmental determinants shaping health in the region. Methods: Using a qualitative case study design, we conducted 37 interviews (28 residents, 9 key informants) and a review of government water documents to investigate water usage practices and perspectives. These data were thematically analysed to understand potential health risks in Arctic communities and households. Results: Each resident receives an average of 110 litres of municipal water per day. Fifteen of 28 households reported experiencing water shortages at least once per month. Of those 15, most were larger households (5 people or more) with standard sized water storage tanks. Water shortages and service interruptions limit the ability of some households to adhere to public health advice. The households most resilient, or able to cope with domestic water supply shortages, were those capable of retrieving their own drinking water directly from lake and river sources. Residents with extended family and neighbours, whom they can rely on during shortages, were also less vulnerable to municipal water delays. Conclusions: The relatively low in-home water quantities observed in Coral Harbour, Nunavut, appear adequate for some families. Those living in overcrowded households, however, are accessing water in quantities more typically seen in water insecure developing countries. We recommend several practical interventions and revisions to municipal water supply systems

Progress On Compare: A Randomised Controlled Trial Comparing Constraint-Induced And Multi-Modal Aphasia Therapy To Usual Care In People With Chronic Aphasia

Background/Aims: Chronic post-stroke aphasia impacts 30% of stroke survivors. The aim of this trial is to determine whether two contrasting, intensive treatments, Constraint Induced Aphasia Therapy (CIAT) and Multi-Modal Aphasia Therapy (M-MAT), are superior and cost-effective than usual care (UC). The variable response to these therapies may be accounted for by aphasia severity and co-occurring cognitive problems. Methods: 3-arm prospective, single-blinded, randomised controlled trial. Primary end point at 3 months post-treatment. Participants (n = 198) are randomised to CIAT, M-MAT or UC. CIAT and M-MAT both focus on intensive speech practice (30 hours over 2 weeks) using interactive game formats. However, while M-MAT involves gesture, writing, and drawing cues, CIAT focuses on speech alone. UC is usual health service-based aphasia therapy. Primary outcome immediately post treatment is the Aphasia Quotient of the Western Aphasia Battery. Secondary outcomes at 3-month follow-up include measures of connected speech, multi-modal communication, and quality of life. Participant cognitive and linguistic predictors of treatment response are identified. Re-randomised UC participants will undertake a less intense schedule (30 hours over 5 weeks) in a nested sub-study exploring the impact of treatment intensity on outcomes. A full cost-effectiveness analysis will be undertaken. Results: The trial is underway: ethics approval, trial registration, and database are established. Recruitment from five Australian states has commenced. Conclusions: This trial will determine if there is a significant therapeutic effect of, and variable response to treatment types in chronic aphasia. Essential economic evaluation information for service delivery standards for aphasia rehabilitation will be described.1 page(s

Priming Picture Naming with a Semantic Task: An fMRI Investigation

Prior semantic processing can enhance subsequent picture naming performance, yet the neurocognitive mechanisms underlying this effect and its longevity are unknown. This functional magnetic resonance imaging study examined whether different neurological mechanisms underlie short-term (within minutes) and long-term (within days) facilitation effects from a semantic task in healthy older adults. Both short- and long-term facilitated items were named significantly faster than unfacilitated items, with short-term items significantly faster than long-term items. Region of interest results identified decreased activity for long-term facilitated items compared to unfacilitated and short-term facilitated items in the mid-portion of the middle temporal gyrus, indicating lexical-semantic priming. Additionally, in the whole brain results, increased activity for short-term facilitated items was identified in regions previously linked to episodic memory and object recognition, including the right lingual gyrus (extending to the precuneus region) and the left inferior occipital gyrus (extending to the left fusiform region). These findings suggest that distinct neurocognitive mechanisms underlie short- and long-term facilitation of picture naming by a semantic task, with long-term effects driven by lexical-semantic priming and short-term effects by episodic memory and visual object recognition mechanisms

The impact of pseudophakia on vision-related quality of life in the general population - The Gutenberg Health Study.

Cataract surgery is the most frequently performed surgical procedure worldwide. We aim to determine the prevalence of having implanted an artificial lens (pseudophakia) and of no lens (aphakia) and to compare visual function.As part of the Gutenberg Health study, a population-based cross-sectional study was conducted in Germany. An ophthalmological examination including slit-lamp examination was conducted. Prevalence including 95% confidential intervals were calculated and analyses were conducted for systemic and ocular associated factors with pseudophakia using multivariable logistic regression models. Vision-related quality of life was assessed using a standardized questionnaire and Rasch transformation.14,696 people were included. Of these, 1.55% [1.36%-1.77%] had unilateral pseudophakia and 3.08% [2.81%-3.37%] had bilateral pseudophakia. Unilateral aphakia was present in 21 people and bilateral aphakia in 2 people. Pseudophakia was independently associated with age, higher body weight and lower body height, diabetes and smoking. Vision-related quality of life values were similar for those with bilateral phakia and pseudophakia but were lower for those with unilateral pseudophakia.The pseudophakia status is related to several cardiovascular risk factors, indicating a relationship to an aging effect that causes premature lens opacification. Bilateral pseudophakia can almost imitate the physiological condition of phakia except for the need to use glasses

A shifting enemy: analysing the BBC’s representations of “al-Qaeda” in the aftermath of the September 11th 2001 attacks

This article seeks to explore how the BBC made sense of the al-Qaeda phenomenon in its flagship “News at Ten” bulletin during the aftermath of the September 11th 2001 attacks. Using Critical Multimodal Discourse Analysis, it shows how the BBC’s representations function as a dynamic and continually shifting site upon which a range of fears, identities, discourses and forms of knowledge and power struggle and contend, and through which a number of different “al-Qaedas” manifest themselves. In particular, three shifting modes of visual and verbal representation are identified within the BBC’s coverage which each correspond to a separate understanding of al-Qaeda: the “Islamic” mode, the “Personalised” mode and the “Elusive” mode. These representations both draw upon and challenge the dominant discourses surrounding Islam, non-state terrorism and the identities of terrorist suspects, providing audiences with a variety of often conflicting ways of seeing and speaking about this entity. As such, the article provides insight into the complex nature of the BBC’s representations of al-Qaeda during its coverage of the September 11th 2001 attacks, and shows how such complexity serves, albeit inadvertently, to legitimise the far-reaching counterterrorism policies that were enacted in the aftermath of these attacks

The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141801/1/epi13937_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141801/2/epi13937.pd

Impaired serine metabolism complements LRRK2-G2019S pathogenicity in PD patients

Parkinson's disease (PD) is a multifactorial disorder with complex etiology. The most prevalent PD associated mutation, LRRK2-G2019S is linked to familial and sporadic cases. Based on the multitude of genetic predispositions in PD and the incomplete penetrance of LRRK2-G2019S, we hypothesize that modifiers in the patients' genetic background act as susceptibility factors for developing PD. To assess LRRK2-G2019S modifiers, we used human induced pluripotent stem cell-derived neuroepithelial stem cells (NESCs). Isogenic controls distinguish between LRRK2-G2019S dependent and independent cellular phenotypes. LRRK2-G2019S patient and healthy mutagenized lines showed altered NESC self-renewal and viability, as well as impaired serine metabolism. In patient cells, phenotypes were only partly LRRK2-G2019S dependent, suggesting a significant contribution of the genetic background. In this context we identified the gene serine racemase (SRR) as a novel patient-specific, developmental, genetic modifier contributing to the aberrant phenotypes. Its enzymatic product, n-serine, rescued altered cellular phenotypes. Susceptibility factors in the genetic background, such as SRR, could be new targets for early PD diagnosis and treatment.Analytical BioScience