The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2 : a systematic review of cost-effectiveness studies

Tese de mestrado, Epidemiologia, Universidade de Lisboa, Faculdade de Medicina, 2015

A randomized trial of nebulized 3% hypertonic saline with salbutamol in the treatment of acute bronchiolitis in hospitalized infants

OBJECTIVE: Acute bronchiolitis is a common disorder of infants that often results in hospitalization. Apart from supportive care, no therapy has been shown to influence the course of the disease, except for a possible effect of nebulized hypertonic saline (HS). To determine whether this does have beneficial effects on length of stay in hospital or on severity scores, we undertook a double-blind, randomized, controlled trial in a pediatric department of a Portuguese hospital. METHODS: Previously healthy infants, younger than 12 months, hospitalized with mild-to-moderate acute viral bronchiolitis were randomized to receive either nebulized 3% (hypertonic, HS) or 0.9% (normal, NS) saline during their entire hospital stay. Primary endpoints were: length of hospital stay and severity scores on each day of hospitalization. Need for supplemental oxygen, further add-on medications and adverse effects were also analyzed. RESULTS: Sixty-eight patients completed the study (HS: 33; NS: 35). The median length of hospital stay did not differ between groups: HS: 5.6 ± 2.3 days; NS: 5.4 ± 2.1 days (P = 0.747). We found no difference between groups in severity scores from day 1 to day 4. There were no differences in need for supplemental oxygen or add-on medications. Patients in HS group had significantly more cough (46% vs. 20%, P = 0.025) and rhinorrhoe (58% vs. 31%, P = 0.30). CONCLUSION: This study does not support the use of nebulized HS over NS in therapy of hospitalized children with mild-to-moderate acute viral bronchiolitis

SubCM: A tool for improved visibility of software change in an industrial setting

Software Configuration Management is the discipline of managing large collections of software development artefacts from which software products are built. Software configuration management tools typically deal with artefacts at fine levels of granularity - such as individual source code files - and assist with coordination of changes to such artefacts. This paper describes a lightweight tool, designed to be used on top of a traditional file-based configuration management system. The add-on tool support enables users to flexibly define new hierarchical views of product structure, independent of the underlying artefact-repository structure. The tool extracts configuration and change data with respect to the user-defined hierarchy, leading to improved visibility of how individual subsystems have changed. The approach yields a range of new capabilities for build managers, and verification and validation teams. The paper includes a description of our experience using the tool in an organization that builds large embedded software systems.

SGLT2 inhibitors:glucuretic treatment for type 2 diabetes

Sodium glucose co-transporter-2 (SGLT2) inhibitors offer a novel approach to treat diabetes by reducing hyperglycaemia via increased glucosuria. This approach reduces renal glucose reabsorption in the proximal renal tubules providing an insulin-independent mechanism to lower blood glucose. The glucuretics are advanced in clinical development and dapagliflozin has received most extensive study. Once daily dapaglifolozin as monotherapy or as add-on to metformin for 12-24 weeks in type 2 diabetic patients (baseline HbA 8-9%) reduced HbA by about 0.5-1%, accompanied by weight loss (2-3 kg) and without significant risk of hypoglycaemia. Dapagliflozin has reduced insulin requirement and improved glycaemic control without weight gain in insulin-treated patients. A mild osmotic diuresis associated with glucuretic therapy may account for a small increase in haematocrit (1-2%) and reduced blood pressure (2-5 mmHg). Dehydration and altered electrolyte balance have not been encountered. Urinary tract and genital infections increased in most studies with dapagliflozin, but were typically mild - resolving with selfmedication or standard intervention. Thus glucuretics provide a novel insulin-independent approach for control of hyperglycaemia which does not incur hypoglycaemia, promotes weight loss, may reduce blood pressure and offers compatibility with other glucose-lowering agents. © 2010 The Author(s).

Pronounced reduction of postprandial glucagon by lixisenatide:a meta-analysis of randomized clinical trials

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. Methods: Six randomized, placebo-controlled studies of lixisenatide 20μg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. Results: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9mmol/l, p<0.001) and glucose excursion (LS mean difference vs. placebo: -4.5mmol/l, p<0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0ng/l, p<0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p<0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. Conclusions: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion. © 2014 John Wiley and Sons Ltd.

Dynamic joint sentiment-topic model

Social media data are produced continuously by a large and uncontrolled number of users. The dynamic nature of such data requires the sentiment and topic analysis model to be also dynamically updated, capturing the most recent language use of sentiments and topics in text. We propose a dynamic Joint Sentiment-Topic model (dJST) which allows the detection and tracking of views of current and recurrent interests and shifts in topic and sentiment. Both topic and sentiment dynamics are captured by assuming that the current sentiment-topic-specific word distributions are generated according to the word distributions at previous epochs. We study three different ways of accounting for such dependency information: (1) Sliding window where the current sentiment-topic word distributions are dependent on the previous sentiment-topic-specific word distributions in the last S epochs; (2) skip model where history sentiment topic word distributions are considered by skipping some epochs in between; and (3) multiscale model where previous long- and shorttimescale distributions are taken into consideration. We derive efficient online inference procedures to sequentially update the model with newly arrived data and show the effectiveness of our proposed model on the Mozilla add-on reviews crawled between 2007 and 2011. © 2013 ACM 2157-6904/2013/12-ART5 $ 15.00.

Pharmacotherapies to manage diabesity:an update

Several pharmacotherapies have recently become available for addition to lifestyle measures to assist the management of coexistent type 2 diabetes and obesity. These are mostly administered as add-on to metformin or as alternative therapies if metformin is not appropriate. The sodium–glucose cotransporter 2 inhibitors (dapagliflozin, canagliflozin and empagliflozin) act by eliminating excess glucose in the urine. These agents provide a non-insulin-dependent mechanism to reduce hyperglycaemia and facilitate weight loss without causing frank hypoglycaemia. Their efficacy requires the individual to have adequate renal function. The glucagon-like peptide-1 (GLP-1) receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide and albiglutide [the last at the pre-launch stage at the time of writing]) are injected subcutaneously. Different members of the class offer different time courses for their onset and duration of action. Each potentiates insulin secretion and reduces glucagon secretion in a glucose-dependent manner to address prandial glycaemic excursions while avoiding interprandial hypoglycaemia. A satiety effect of these agents assists weight reduction, but delayed gastric emptying can cause initial nausea. The dipeptidyl peptidase-4 inhibitor class now comprises sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin. These agents offer similar glucose-lowering efficacy without weight gain or hypoglycaemia by boosting the half-life of endogenous incretins, particularly GLP-1. A fixed-ratio injected combination of insulin degludec with liraglutide (IDegLira) has recently been launched and further agents to address hyperglycaemia and assist weight loss are advancing in development.

Discovering biomarkers for antidepressant response:protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

Character education in a Muslim school: A case study of a comprehensive Muslim school's curricula

Deteriorating social behavior, negative media influence and violence among adolescents have given cause to pause and assess character development for the youth of this country. The purpose of this case study was to examine how a Muslim school’s curricula implemented character education. This study used a qualitative single-case methodology to examine character education as it was experienced by the participants in a private Muslim school. Data were collected from participant interviews, document analysis, and observations of classrooms, daily activities and special events. Data were analyzed to determine how character education was defined by the school, the method of delivery for the character education initiatives and the implementation of character education in this Muslim school. Analysis was based on Character Education Partnership’s (CEP) Eleven Principles of Effective Character Education (2007). The results of the study revealed: (a) participants defined character education using varied traits, processes, and expected behaviors. (b) The school delivers its character education curriculum primarily through the Islamic studies division; an add-on delivery method. Still, there was evidence of partial integration of character education in the core courses and (c) based on CEP’s Eleven Principles four were present and five were partially present in the school’s character education initiatives. Findings also revealed that the school’s emphasis on values, morality and spirituality was instrumental in their teaching character. Findings suggest that if participants in the school community work together they might formulate a definition of character education based on common process and expected behavior and create a collaborative working relationship to implement a character education program. Finally, addressing the absent and partially absent elements of the eleven principles could enhance the school’s character education initiatives. The study provides a process by which religious schools could examine their character education programs. The criteria used to measure the use of character education elements are transferable to other settings; however, this method of study does not allow generalization of findings.

Self-directed Learning in the Technological Age

Concerns arising out of technology often being used as an add-on to self-directed learning practices in the workplace and factors affecting such learning were investigated through a literature analysis. What is needed is an exploration of new possibilities of computational media on how self-directed learners think, create and learn.

Development of effective approaches to the large-scale aerodynamic testing of low-rise buildings

Low-rise buildings are often subjected to high wind loads during hurricanes that lead to severe damage and cause water intrusion. It is therefore important to estimate accurate wind pressures for design purposes to reduce losses. Wind loads on low-rise buildings can differ significantly depending upon the laboratory in which they were measured. The differences are due in large part to inadequate simulations of the low-frequency content of atmospheric velocity fluctuations in the laboratory and to the small scale of the models used for the measurements. A new partial turbulence simulation methodology was developed for simulating the effect of low-frequency flow fluctuations on low-rise buildings more effectively from the point of view of testing accuracy and repeatability than is currently the case. The methodology was validated by comparing aerodynamic pressure data for building models obtained in the open-jet 12-Fan Wall of Wind (WOW) facility against their counterparts in a boundary-layer wind tunnel. Field measurements of pressures on Texas Tech University building and Silsoe building were also used for validation purposes. The tests in partial simulation are freed of integral length scale constraints, meaning that model length scales in such testing are only limited by blockage considerations. Thus the partial simulation methodology can be used to produce aerodynamic data for low-rise buildings by using large-scale models in wind tunnels and WOW-like facilities. This is a major advantage, because large-scale models allow for accurate modeling of architectural details, testing at higher Reynolds number, using greater spatial resolution of the pressure taps in high pressure zones, and assessing the performance of aerodynamic devices to reduce wind effects. The technique eliminates a major cause of discrepancies among measurements conducted in different laboratories and can help to standardize flow simulations for testing residential homes as well as significantly improving testing accuracy and repeatability. Partial turbulence simulation was used in the WOW to determine the performance of discontinuous perforated parapets in mitigating roof pressures. The comparisons of pressures with and without parapets showed significant reductions in pressure coefficients in the zones with high suctions. This demonstrated the potential of such aerodynamic add-on devices to reduce uplift forces.

Software Components for Serious Game Development

The large upfront investments required for game development pose a severe barrier for the wider uptake of serious games in education and training. Also, there is a lack of well-established methods and tools that support game developers at preserving and enhancing the games’ pedagogical effectiveness. The RAGE project, which is a Horizon 2020 funded research project on serious games, addresses these issues by making available reusable software components that aim to support the pedagogical qualities of serious games. In order to easily deploy and integrate these game components in a multitude of game engines, platforms and programming languages, RAGE has developed and validated a hybrid component-based software architecture that preserves component portability and interoperability. While a first set of software components is being developed, this paper presents selected examples to explain the overall system’s concept and its practical benefits. First, the Emotion Detection component uses the learners’ webcams for capturing their emotional states from facial expressions. Second, the Performance Statistics component is an add-on for learning analytics data processing, which allows instructors to track and inspect learners’ progress without bothering about the required statistics computations. Third, a set of language processing components accommodate the analysis of textual inputs of learners, facilitating comprehension assessment and prediction. Fourth, the Shared Data Storage component provides a technical solution for data storage - e.g. for player data or game world data - across multiple software components. The presented components are exemplary for the anticipated RAGE library, which will include up to forty reusable software components for serious gaming, addressing diverse pedagogical dimensions.

VirRAD: A New Paradigm for Technology Enhanced Learning

In most e-learning scenarios, communication and on-line collaboration is seen as an add-on feature to resource based learning. This paper will endeavour to present a pedagogical framework for inverting this view and putting communities of practice as the basic paradigm for e-learning. It will present an approach currently being used in the development of a virtual Radiopharmacy community, called VirRAD, and will discuss how theory can lead to an instructional design approach to support technologically enhanced learning.(DIPF/Orig.)

Supplemental Coverage Option Expanding as Part of the Farm Safety Net

The 2014 Farm Bill created Supplemental Coverage Option (SCO), a new add-on crop insurance option which provides supplemental coverage on a producer’s underlying crop insurance policy. SCO operates by mimicking a producer’s individual crop insurance coverage and covering a portion of the deductible based on county-level yield or revenue. SCO is available in select Maryland counties for apples, barley, corn, grain sorghum, green peas, oats, peaches, processing beans, soybeans, sweet corn, and winter wheat, as of the 2017 crop year. USDA’s Risk Management Agency (RMA) continues to expand covered counties and crops covered, and begin distinguishing by practices (such as irrigated compared to non-irrigated).

Four-channel reconfigurable optical add-drop multiplexer based on photonic wire waveguide

We designed and fabricated a four-channel reconfigurable optical add-drop multiplexer based on silicon photonic wire waveguide controlled through thermo-optic effect. The effective footprint of the device is about 1000 x 500 mu m(2). The minimum insertion loss is about 10.7 dB and the tuning bandwidth about 17 nm. The average tuning power efficiency is about 6.187 mW/nm and the tuning speed about 24.4 kHz. The thermo-optic polarization-rotation effect is firstly reported in this paper. (C) 2009 Optical Society of America