Duration of disease does not equally influence all aspects of quality of life in Parkinson’s disease

Health related quality of life (HRQoL) is negatively impacted in patients suffering from Parkinsons disease (PD). For the specific components that comprise HRQoL, the relationship between clinical variables, such as disease duration, is not fully characterized. In this cross-sectional study (n=302), self-reported HRQoL on the Parkinsons Disease Questionnaire (PDQ-39) was evaluated as a global construct as well as individual subscale scores. HRQoL was compared in three groups: those within 5years of diagnosis, those within 6-10years of diagnosis, and those greater than 11years since diagnosis. Non-parametric analyses revealed lower HRQoL with increasing disease duration when assessed as a global construct. However, when subscales were evaluated, difficulties with bodily discomfort and cognitive complaints were comparable in individuals in the 1-5years and 6-10year duration groups. Exploratory regression analyses suggested disease duration does explain unique variance in some subscales, even after controlling for Hoehn and Yahr stage and neuropsychiatric features. Our findings show that HRQoL domains in PD patients are affected differentially across the duration of the disease. Clinicians and researchers may need to tailor interventions intended to improve HRQoL at different domains as the disease progresses

Additive scales in degenerative disease - calculation of effect sizes and clinical judgment

<p>Abstract</p> <p>Background</p> <p>The therapeutic efficacy of an intervention is often assessed in clinical trials by scales measuring multiple diverse activities that are added to produce a cumulative global score. Medical communities and health care systems subsequently use these data to calculate pooled effect sizes to compare treatments. This is done because major doubt has been cast over the clinical relevance of statistically significant findings relying on <it>p </it>values with the potential to report chance findings. Hence in an aim to overcome this pooling the results of clinical studies into a meta-analyses with a statistical calculus has been assumed to be a more definitive way of deciding of efficacy.</p> <p>Methods</p> <p>We simulate the therapeutic effects as measured with additive scales in patient cohorts with different disease severity and assess the limitations of an effect size calculation of additive scales which are proven mathematically.</p> <p>Results</p> <p>We demonstrate that the major problem, which cannot be overcome by current numerical methods, is the complex nature and neurobiological foundation of clinical psychiatric endpoints in particular and additive scales in general. This is particularly relevant for endpoints used in dementia research. 'Cognition' is composed of functions such as memory, attention, orientation and many more. These individual functions decline in varied and non-linear ways. Here we demonstrate that with progressive diseases cumulative values from multidimensional scales are subject to distortion by the limitations of the additive scale. The non-linearity of the decline of function impedes the calculation of effect sizes based on cumulative values from these multidimensional scales.</p> <p>Conclusions</p> <p>Statistical analysis needs to be guided by boundaries of the biological condition. Alternatively, we suggest a different approach avoiding the error imposed by over-analysis of cumulative global scores from additive scales.</p

Single left coronary artery with separate origins of proximal and distal right coronary arteries from left anterior descending and circumflex arteries – a previously undescribed coronary circulation

A single left coronary artery with right coronary artery arising from either left main stem (LMS) or left anterior descending artery (LAD) or circumflex artery (Cx) is an extremely rare coronary anomaly. This is the first report of separate origins of proximal and distal RCA from LAD and circumflex arteries respectively in a patient with a single left coronary artery. This 57 year old patient presented with unstable angina and severe stenotic disease of LAD and Cx arteries and underwent urgent successful quadruple coronary artery bypass grafting. The anomalies of right coronary artery in terms of their origin, number and distribution are reviewed

Hyperdominant left anterior descending artery continuing across left ventricular apex as posterior descending artery coexistent with aortic stenosis

We describe, in a 61 year old man, with coexistent aortic stenosis, the anomalous origin of posterior descending artery (PDA) from a stenotic left anterior descending (LAD) artery, as its continuation across the left ventricular apex, in the presence of a normally arising and atretic proximal right coronary artery. The patient underwent mechanical aortic valve replacement and triple coronary artery bypass grafting and made an uneventful recovery. To the best of our knowledge, origin of PDA as a continuation of LAD across the left ventricular apex in the presence of a normally arising but atretic proximal right coronary artery has never been described in literature before. There is one previous case report of continuation of LAD as PDA across the left ventricular apex in a patient with single left coronary coronary artery with an absent right coronary ostium. As the blood supply to the entire interventricular septum is derived from this "hyperdominant" LAD system, stenosis of LAD can be catastrophic. A review of literature of the anomalies of right coronary artery and, in particular, of its anomalous origin from LAD and its coexistence with aortic stenosis, is presented

Cement degradation in CO2 storage sites: a review on potential applications of nanomaterials

© 2018 The Author(s) Carbon capture and sequestration (CCS) has been employed to reduce global warming, which is one of the critical environmental issues gained the attention of scientific and industrial communities worldwide. Once implemented successfully, CCS can store at least 5 billion tons of CO2per year as an effective and technologically safe method. However, there have been a few issues raised in recent years, indicating the potential leakages paths created during and after injection. One of the major issues might be the chemical interaction of supercritical CO2with the cement, which may lead to the partial or total loss of the cement sheath. There have been many approaches presented to improve the physical and mechanical properties of the cement against CO2attack such as changing the water-to-cement ratio, employing pozzolanic materials, and considering non-Portland cements. However, a limited success has been reported to the application of these approaches once implemented in a real-field condition. To date, only a few studies reported the application of nanoparticles as sophisticated additives which can reinforce oil well cements. This paper provides a review on the possible application of nanomaterials in the cement industry where physical and mechanical characteristics of the cement can be modified to have a better resistance against corrosive environments such as CO2storage sites. The results obtained indicated that adding 0.5 wt% of Carbon NanoTubes (CNTs) and NanoGlass Flakes (NGFs) can reinforce the thermal stability and coating characteristics of the cement which are required to increase the chance of survival in a CO2sequestrated site. Nanosilica can also be a good choice and added to the cement by as much as 3.0 wt% to improve pozzolanic reactivity and thermal stability as per the reports of recent studies

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington\u27s Disease Patients-A Randomized Phase 2 Clinical Trial.

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood-brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple-ascending dose clinical trials. The present study was a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12-week, dose escalation study of SRX246 in early symptomatic Huntington\u27s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington\u27s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty-two out of 106 subjects randomized completed the trial on their assigned dose of drug. One-sided exact-method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression

Item response theory analysis of cognitive tests in people with dementia:a systematic review

BACKGROUND: Performance on psychometric tests is key to diagnosis and monitoring treatment of dementia. Results are often reported as a total score, but there is additional information in individual items of tests which vary in their difficulty and discriminatory value. Item difficulty refers to an ability level at which the probability of responding correctly is 50%. Discrimination is an index of how well an item can differentiate between patients of varying levels of severity. Item response theory (IRT) analysis can use this information to examine and refine measures of cognitive functioning. This systematic review aimed to identify all published literature which had applied IRT to instruments assessing global cognitive function in people with dementia. METHODS: A systematic review was carried out across Medline, Embase, PsychInfo and CINHAL articles. Search terms relating to IRT and dementia were combined to find all IRT analyses of global functioning scales of dementia. RESULTS: Of 384 articles identified four studies met inclusion criteria including a total of 2,920 people with dementia from six centers in two countries. These studies used three cognitive tests (MMSE, ADAS-Cog, BIMCT) and three IRT methods (Item Characteristic Curve analysis, Samejima’s graded response model, the 2-Parameter Model). Memory items were most difficult. Naming the date in the MMSE and memory items, specifically word recall, of the ADAS-cog were most discriminatory. CONCLUSIONS: Four published studies were identified which used IRT on global cognitive tests in people with dementia. This technique increased the interpretative power of the cognitive scales, and could be used to provide clinicians with key items from a larger test battery which would have high predictive value. There is need for further studies using IRT in a wider range of tests involving people with dementia of different etiology and severity