British Neurotoxin Network recommendations for managing cervical dystonia in patients with a poor response to botulinum toxin

Botulinum toxin (BoNT) injections are an effective treatment for cervical dystonia. Approximately 20% of patients eventually stop BoNT treatment, mostly because of treatment failure. These recommendations review the different therapeutic interventions for optimising the treatment in secondary poor responder patients. Immunoresistance has become less common over the years, but the diagnosis has to be addressed with a frontalis test or an Extensor Digitorum Brevis test. In case of immunoresistance to BoNTA, we discuss the place the different therapeutic options (BoNT-A holidays, BoNT-B injections, alternative BoNT-A injections, deep brain stimulation). When poor responders are not immunoresistant, they benefit from reviewing (1) injections technique with electromyography or ultrasound guidance, (2) muscles selection and (3) dose of BoNT. In addition, in both scenarios, a holistic approach including drug treatment, retraining and psychological support is valuable in the management of these complex and severe cervical dystonia

Yawning, fatigue and cortisol: expanding the Thompson Cortisol Hypothesis.

Yawning and its involvement in neurological disorders has become the new scientific conundrum. Cortisol levels are known to rise during stress and fatigue; yawning may occur when we are under stress or tired. However, the link between yawning, fatigue, and cortisol has not been fully understood. Expansion of the Thompson Cortisol Hypothesis proposes that the stress hormone, cortisol, is responsible for yawning and fatigue especially in people with incomplete innervation such as multiple sclerosis. This informs our understanding of the functional importance of the brain stem region of the brain in regulating stress and fatigue

Phenotype execution and modeling architecture to support disease surveillance and real-world evidence studies: English sentinel network evaluation

Objective To evaluate Phenotype Execution and Modelling Architecture (PhEMA), to express sharable phenotypes using Clinical Quality Language (CQL) and intensional Systematised Nomenclature of Medicine (SNOMED) Clinical Terms (CT) Fast Healthcare Interoperability Resources (FHIR) valuesets, for exemplar chronic disease, sociodemographic risk factor, and surveillance phenotypes. Method We curated 3 phenotypes: Type 2 diabetes mellitus (T2DM), excessive alcohol use, and incident influenza-like illness (ILI) using CQL to define clinical and administrative logic. We defined our phenotypes with valuesets, using SNOMED’s hierarchy and expression constraint language, and CQL, combining valuesets and adding temporal elements where needed. We compared the count of cases found using PhEMA with our existing approach using convenience datasets. We assessed our new approach against published desiderata for phenotypes. Results The T2DM phenotype could be defined as 2 intensionally defined SNOMED valuesets and a CQL script. It increased the prevalence from 7.2% to 7.3%. Excess alcohol phenotype was defined by valuesets that added qualitative clinical terms to the quantitative conceptual definitions we currently use; this change increased prevalence by 58%, from 1.2% to 1.9%. We created an ILI valueset with SNOMED concepts, adding a temporal element using CQL to differentiate new episodes. This increased the weekly incidence in our convenience sample (weeks 26-38) from 0.95 cases to 1.11 cases per 100 000 people. Conclusions Phenotypes for surveillance and research can be described fully and comprehensibly using CQL and intensional FHIR valuesets. Our use case phenotypes identified a greater number of cases, whilst anticipated from excessive alcohol this was not for our other variable. This may have been due to our use of SNOMED CT hierarchy. Our new process fulfilled a greater number of phenotype desiderata than the one that we had used previously, mostly in the modeling domain. More work is needed to implement that sharing and warehousing domains

Evaluation of surveillance case definition in the diagnosis of leptospirosis, using the Microscopic Agglutination Test: a validation study

<p>Abstract</p> <p>Background</p> <p>Leptospirosis is endemic in both urban and rural areas of Sri Lanka and there had been many out breaks in the recent past. This study was aimed at validating the leptospirosis surveillance case definition, using the Microscopic Agglutination Test (MAT).</p> <p>Methods</p> <p>The study population consisted of patients with undiagnosed acute febrile illness who were admitted to the medical wards of the Teaching Hospital Kandy, from 1^stJuly 2007 to 31^stJuly 2008. The subjects were screened to diagnose leptospirosis according to the leptospirosis case definition. MAT was performed on blood samples taken from each patient on the 7^thday of fever. Leptospirosis case definition was evaluated in regard to sensitivity, specificity and predictive values, using a MAT titre ≥ 1:800 for confirming leptospirosis.</p> <p>Results</p> <p>A total of 123 patients were initially recruited of which 73 had clinical features compatible with the surveillance case definition. Out of the 73 only 57 had a positive MAT result (true positives) leaving 16 as false positives. Out of the 50 who didn't have clinical features compatible with the case definition 45 had a negative MAT as well (true negatives), therefore 5 were false negatives. Total number of MAT positives was 62 out of 123. According to these results the test sensitivity was 91.94%, specificity 73.77%, positive predictive value and negative predictive values were 78.08% and 90% respectively. Diagnostic accuracy of the test was 82.93%.</p> <p>Conclusion</p> <p>This study confirms that the surveillance case definition has a very high sensitivity and negative predictive value with an average specificity in diagnosing leptospirosis, based on a MAT titre of ≥ 1: 800.</p

Reduction in membrane component of diffusing capacity is associated with the extent of acute pulmonary embolism

Acute pulmonary embolism (PE) often decreases pulmonary diffusing capacity for carbon monoxide (DL,CO), but data on the mechanisms involved are inconsistent. We wanted to investigate whether reduction in diffusing capacity of alveolo-capillary membrane (DM) and pulmonary capillary blood volume (Vc) is associated with the extent of PE or the presence and severity of right ventricular dysfunction (RVD) induced by PE and how the possible changes are corrected after 7-month follow-up. Forty-seven patients with acute non-massive PE in spiral computed tomography (CT) were included. The extent of PE was assessed by scoring mass of embolism. DL,CO, Vc, DM and alveolar volume (VA) were measured by using a single breath method with carbon monoxide and oxygen both at the acute phase and 7 months later. RVD was evaluated with transthoracic echocardiography and electrocardiogram. Fifteen healthy subjects were included as controls. DL,CO, DL, CO/VA, DM, vital capacity (VC) and VA were significantly lower in the patients with acute PE than in healthy controls (P<0·001). DM/Vc relation was significantly lower in patients with RVD than in healthy controls (P = 0·004). DM correlated inversely with central mass of embolism (r = −0·312; P = 0·047) whereas Vc did not. DM, DL,CO, VC and VA improved significantly within 7 months. In all patients (P = 0·001, P = 0·001) and persistent RVD (P = 0·020, P = 0·012), DM and DL,CO remained significantly lower than in healthy controls in the follow-up. DM was inversely related to central mass of embolism. Reduction in DM mainly explains the sustained decrease in DL,CO in PE after 7 months despite modern treatment of PE

Sizing and economic analysis of stand-alone hybrid photovoltaic-wind system for rural electrification: A case study Lundu, Sarawak

Energy Consumption has been increasing at an alarming rate due to the growing energy need. More and more non-renewable sources are harvested to fulfill the energy demand resulting in and rising environmental health issues. However, harvesting Solar and Wind energy is considered as the best alternative in generating energy as these resources are renewable. Hybrid Renewable Energy System (HRES) has been grabbed the attention recently, as it involves with renewable, environmentally friendly sources to generate energy. The limitation of single Renewable Energy (RE) system is overcome by systems such as HRES. Even though it has been introduced different sizing and optimization techniques, due to the lack of system function, it had posed issues in calculating the optimized cost of a hybrid system considering the solar, wind resources and load demand as the optimization of the system cannot be predicted accurately. The aim of this research was to obtain optimization of a Hybrid PV-wind system in term of sizing and cost over the 20 years of the period of interest. The simulation of the PV-Wind Hybrid system using MATLAB for the verification purpose. This work includes detailed calculation using the Life Cycle Cost method for identifying all possible combinations. The combination of eleven Solar Panels, one Wind Turbine and nine Batteries was identified as the optimal Combination with LCC of RM 221,329.97 and has been verified using simulation results. Lastly, a sensitivity test was carried out using the exiting results of verified by the simulation to identify the most deterministic system in affecting LCC of the Hybrid system. Further, total Cost distribution for the Optimized hybrid PV-Wind system was conducted and identified that 50% of system cost was contributed by the Wind turbine. Determination of LCC, was done as a combination of Component and Operation costs. It was identified that Replacement cost contributed the highest while Wind turbine showed the highest Operation cost from the system cost. Thus, this work was included with the sensitivity test assuming 10% price increment for each component and it was concluded that price changes in Wind turbine results the greatest difference in LCC while further verified with the results of the simulation

Comprehensive review on the feasibility of developing wave energy as a renewable energy resource in Australia

The facts are that increasing energy demand, depletion of fossil fuel, and greenhouse gas emissions have increased the world's interest in renewable energy. Out of all RE options, Wave Energy (WE) is the least harnessed one despite the availability of WE Resource (WERs) in many countries and with the potential to cover a significant proportion of the world's energy needs. Australia, mainly in the southern part of the country, has plenty of this resource. Although recently, the Australian Government has started to focus on WERs as a Renewable Energy Source (RES) to cope with the energy crisis, research suggests that the country's progress in the WE generation to meet the energy demand is well below the potential generation capacity. However, insufficient research and studies address the issues and technologies in detail. This study examines the viability of further developing WE as a renewable energy source in Australia by evaluating the current constraints and challenges to achieving a satisfactory level of WE generation in the country. As a result, this study emphasizes the trustworthiness of WE in terms of several criteria. The availability of WERs within Australia and the status of producing WE are reviewed in this study. It also highlighted certain Australian technologies and devices that are now being tested or deployed in real-time. Moreover, this review is expanded by comparing the key developers in the WE sector to Australia to uncover some of the contributing elements in other countries that may have contributed to the growth of the WE generation in other nations. Finally, some of the barriers identified are lack of high-resolution data and social & environmental challenges. Some recommendations are given in the latter part of the review to accelerate WE production in Australia

Predictors of the development of myocarditis or acute renal failure in patients with leptospirosis: An observational study

<p>Abstract</p> <p>Background</p> <p>Leptospirosis has a varied clinical presentation with complications like myocarditis and acute renal failure. There are many predictors of severity and mortality including clinical and laboratory parameters. Early detection and treatment can reduce complications. Therefore recognizing the early predictors of the complications of leptospirosis is important in patient management. This study was aimed at determining the clinical and laboratory predictors of myocarditis or acute renal failure.</p> <p>Methods</p> <p>This was a prospective descriptive study carried out in the Teaching Hospital, Kandy, from 1st July 2007 to 31st July 2008. Patients with clinical features compatible with leptospirosis case definition were confirmed using the Microscopic Agglutination Test (MAT). Clinical features and laboratory measures done on admission were recorded. Patients were observed for the development of acute renal failure or myocarditis. Chi-square statistics, Fisher's exact test and Mann-Whitney <it>U </it>test were used to compare patients with and without complications. A logistic regression model was used to select final predictor variables.</p> <p>Results</p> <p>Sixty two confirmed leptospirosis patients were included in the study. Seven patients (11.3%) developed acute renal failure and five (8.1%) developed myocarditis while three (4.8%) had both acute renal failure and myocarditis. Conjunctival suffusion - 40 (64.5%), muscle tenderness - 28 (45.1%), oliguria - 20 (32.2%), jaundice - 12 (19.3%), hepatomegaly - 10 (16.1%), arrhythmias (irregular radial pulse) - 8 (12.9%), chest pain - 6 (9.7%), bleeding - 5 (8.1%), and shortness of breath (SOB) 4 (6.4%) were the common clinical features present among the patients. Out of these, only oliguria {odds ratio (OR) = 4.14 and 95% confidence interval (CI) 1.003-17.261}, jaundice (OR = 5.13 and 95% CI 1.149-28.003), and arrhythmias (OR = 5.774 and 95% CI 1.001-34.692), were predictors of myocarditis or acute renal failure and none of the laboratory measures could predict the two complications.</p> <p>Conclusions</p> <p>This study shows that out of clinical and laboratory variables, only oliguria, jaundice and arrhythmia are strong predictors of development of acute renal failure or myocarditis in patients with leptospirosis presented to Teaching Hospital of Kandy, Sri Lanka.</p

Yawning and cortisol levels in multiple sclerosis: Potential new diagnostic tool.

Yawning is a significant behavioural response and, together with cortisol, is potentially a new diagnostic marker of neurological diseases. Evidence of an association between yawning and cortisol was found which supports the Thompson Cortisol Hypothesis and thermoregulation hypotheses, indication that brain cooling occurs when yawning. 117 volunteers aged 18-69 years were randomly allocated to experimentally controlled conditions to provoke yawning. Thirty-three had been diagnosed with multiple sclerosis. Saliva cortisol samples were collected before and after yawning or after stimuli presentation in the absence of yawning. Hospital Anxiety and Depression Scale, General Health Questionnaire, demographic and health details were collected. Comparisons were made of yawners and non-yawners, healthy volunteers and MS participants. EXCLUSION CRITERIA: chronic fatigue, diabetes, fibromyalgia, heart condition, high blood pressure, hormone replacement therapy, stroke. Yawners had significant differences between saliva cortisol sample 1 and 2 among healthy participants (p < .007) and MS participants (p < .003). There was significant difference between the healthy versus MS non-yawners (P < .042) but not between yawners (p < .862). These results support the Thompson Cortisol Hypothesis suggesting that cortisol levels are elevated during yawning. Furthermore, this evidence suggests cortisol levels in the MS participants (non-yawners) are significantly different to those of healthy participants. Changes in cortisol levels may be similar in healthy and MS participants but when associated with observations of excessive yawning may become a new diagnostic tool in the early diagnosis of neurological symptoms. DRYAD DOI: https://doi.org/10.5061/dryad.r09m1

Multiway Array Decomposition Analysis of EEGs in Alzheimer’s Disease

Methods for the extraction of features from physiological datasets are growing needs as clinical investigations of Alzheimer’s disease (AD) in large and heterogeneous population increase. General tools allowing diagnostic regardless of recording sites, such as different hospitals, are essential and if combined to inexpensive non-invasive methods could critically improve mass screening of subjects with AD. In this study, we applied three state of the art multiway array decomposition (MAD) methods to extract features from electroencephalograms (EEGs) of AD patients obtained from multiple sites. In comparison to MAD, spectral-spatial average filter (SSFs) of control and AD subjects were used as well as a common blind source separation method, algorithm for multiple unknown signal extraction (AMUSE). We trained a feed-forward multilayer perceptron (MLP) to validate and optimize AD classification from two independent databases. Using a third EEG dataset, we demonstrated that features extracted from MAD outperformed features obtained from SSFs AMUSE in terms of root mean squared error (RMSE) and reaching up to 100% of accuracy in test condition. We propose that MAD maybe a useful tool to extract features for AD diagnosis offering great generalization across multi-site databases and opening doors to the discovery of new characterization of the disease