Health and economic impact of combining metformin with nateglinide to achieve glycemic control: Comparison of the lifetime costs of complications in the U.K

BACKGROUND: To reduce the likelihood of complications in persons with type 2 diabetes, it is critical to control hyperglycaemia. Monotherapy with metformin or insulin secretagogues may fail to sustain control after an initial reduction in glycemic levels. Thus, combining metformin with other agents is frequently necessary. These analyses model the potential long-term economic and health impact of using combination therapy to improve glycemic control. METHODS: An existing model that simulates the long-term course of type 2 diabetes in relation to glycosylated haemoglobin (HbA(1c)) and post-prandial glucose (PPG) was used to compare the combination of nateglinide with metformin to monotherapy with metformin. Complication rates were estimated for major diabetes-related complications (macrovascular and microvascular) based on existing epidemiologic studies and clinical trial data. Utilities and costs were estimated using data collected in the United Kingdom Prospective Diabetes Study (UKPDS). Survival, life years gained (LYG), quality-adjusted life years (QALY), complication rates and associated costs were estimated. Costs were discounted at 6% and benefits at 1.5% per year. RESULTS: Combination therapy was predicted to reduce complication rates and associated costs compared with metformin. Survival increased by 0.39 (0.32 discounted) and QALY by 0.46 years (0.37 discounted) implying costs of £6,772 per discounted LYG and £5,609 per discounted QALY. Sensitivity analyses showed the results to be consistent over broad ranges. CONCLUSION: Although drug treatment costs are increased by combination therapy, this cost is expected to be partially offset by a reduction in the costs of treating long-term diabetes complications

A Pilot Study to Determine MBSE Utility for Process Modeling of Complex Interfaces

Modeling a full system or a complete interface between systems in a MBSE environment is a very large task and not all organizations will benefit enough from using MBSE to offset the effort that is required to do this. Completely modeling a system or interface is not necessary to evaluate the utility of MBSE for a specific application or organization. A small pilot can be executed over a short period of time that only models small portions of a system or interface and, if structured properly, this pilot can successfully demonstrate the utility of MBSE for an organization before having to invest a larger amount of resources to fully implement and deploy MBSE. This paper documents one such pilot that was conducted for NASAs Launch Services Program

A Pilot Study to Determine MBSE Utility for Process Modeling of Complex Interfaces

Modeling a full system or a complete interface between systems in a MBSE environment is a very large task and not all organizations will benefit enough from using MBSE to offset the effort that is required to do this. Completely modeling a system or interface is not necessary to evaluate the utility of MBSE for a specific application or organization. A small pilot can be executed over a short period of time that only models small portions of a system or interface and, if structured properly, this pilot can successfully demonstrate the utility of MBSE for an organization before having to invest a larger amount of resources to fully implement and deploy MBSE. This paper documents one such pilot that was conducted for NASA's Launch Services Program

Expanding our Roles: Embedded in Curriculum Design

Objectives To describe how librarians became involved in helping to design curriculum for Problem- Based Learning (PBL) Course for first- and second-year medical students. Librarians became part of a team collaborating with medical faculty to revise the PBL curriculum, incorporating innovative teaching techniques and creating effective simulated patient case scenarios. Methods In August 2010, the PBL Director contacted the Library to help revise 10 cases for second-year problem-based learning course. Two librarians joined the PBL multi-disciplinary curriculum team meeting bi-weekly to create and revise medical tutor and student guides, and case modules. The cases successfully evolved from paper handouts to interactive PowerPoint modules with embedded videos. In the fall of 2011, the team continued revising the cases for second-year and expanded the process to revamp the first-year PBL curriculum. In the spring of 2012, four cases added standardized patients to enrich the experience of students\u27 patient interactions and apply psychosocial learning objectives including EBM informatics. Spring 2012 semester the team collaborated in conducting an IRB-approved research study evaluating the effectiveness and learning outcomes for students participating in the PBL curriculum case on abortion and sexual reproduction. Results The librarians’ met regularly with the PBL Program Director, and collaborated with Medical Faculty and Standardized Patient department to revise PBL cases. The librarians’ key contributions focused on revising and editing PBL Tutor Guides, providing technical expertise, Blackboard support, navigating copyright and updating medical literature. As the PBL cases evolved, a core team developed the research study, resulting in opportunities for qualitative and quantitative research as well as subsequent publishing. Conclusions Working within a multi-disciplinary collaborative team on curriculum development allows for librarians to move beyond the traditional role of instruction. The embedded role highlights the additional contributions librarians can make to the team in the areas of technology and research

A Pilot Study to Determine MBSE Utility for Process Modeling of Complex Interfaces

Modeling a full system or a complete interface between systems in a MBSE environment is a very large task and not all organizations will benefit enough from using MBSE to offset the effort that is required to do this. Completely modeling a system or interface is not necessary to evaluate the utility of MBSE for a specific application or organization. A small pilot can be executed over a short period of time that only models small portions of a system or interface and, if structured properly, this pilot can successfully demonstrate the utility of MBSE for an organization before having to invest a larger amount of resources to fully implement and deploy MBSE. This paper documents one such pilot that was conducted for NASA's Launch Services Program

An exploratory study into the effects of a 20 minute crushed ice application on knee joint position sense during a small knee bend.

Objectives The effect of cryotherapy on joint positioning presents conflicting debates as to whether individuals are at an increased risk of injury when returning to play or activity immediately following cryotherapy application at the knee. The aim of this study was to investigate whether a 20 minute application of crushed ice at the knee immediately affects knee joint position sense during a small knee bend. Design Pre and post-intervention. Setting University movement analysis laboratory. Participants Eleven healthy male participants. Main Outcome Measures Kinematics of the knee were measured during a weight bearing functional task pre and post cryotherapy intervention using three-dimensional motion analysis (Qualisys Medical AB Gothenburg, Sweden). Tissue cooling was measured via a digital thermometer at the knee. Results Results demonstrated significant reductions in the ability to accurately replicate knee joint positioning in both sagittal (P=.035) and coronal (P=.011) planes during the descent phase of a small knee bend following cryotherapy. Conclusion In conclusion a twenty minute application of crushed ice to the knee has an adverse effect on knee joint repositioning. Team doctors, clinicians, therapists and athletes should consider these findings when deciding to return an athlete to functional weight bearing tasks immediately following ice application at the knee, due to the potential increase risk of injury

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube.

INTRODUCTION: Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. MATERIALS AND METHODS: We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. RESULTS: Agitation and storage of blood samples at 37 degrees C for 1hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. CONCLUSIONS: We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses

A pragmatic randomised controlled trial and economic evaluation of family therapy versus treatment as usual for young people seen after second or subsequent episodes of self-harm: the Self-Harm Intervention - Family Therapy (SHIFT) trial

Background: Self-harm in adolescents is common and repetition rates high. There is limited evidence of the effectiveness of interventions to reduce self-harm. Objectives: To assess the clinical effectiveness and cost-effectiveness of family therapy (FT) compared with treatment as usual (TAU). Design: A pragmatic, multicentre, individually randomised controlled trial of FT compared with TAU. Participants and therapists were aware of treatment allocation; researchers were blind to allocation. Setting: Child and Adolescent Mental Health Services (CAMHS) across three English regions. Participants: Young people aged 11–17 years who had self-harmed at least twice presenting to CAMHS following self-harm. Interventions: Eight hundred and thirty-two participants were randomised to manualised FT delivered by trained and supervised family therapists (n = 415) or to usual care offered by local CAMHS following self-harm (n = 417). Main outcome measures: Rates of repetition of self-harm leading to hospital attendance 18 months after randomisation. Results: Out of 832 young people, 212 (26.6%) experienced a primary outcome event: 118 out of 415 (28.4%) randomised to FT and 103 out of 417 (24.7%) randomised to TAU. There was no evidence of a statistically significant difference in repetition rates between groups (the hazard ratio for FT compared with TAU was 1.14, 95% confidence interval 0.87 to 1.49; p = 0.3349). FT was not found to be cost-effective when compared with TAU in the base case and most sensitivity analyses. FT was dominated (less effective and more expensive) in the complete case. However, when young people’s and caregivers’ quality-adjusted life-year gains were combined, FT incurred higher costs and resulted in better health outcomes than TAU within the National Institute for Health and Care Excellence cost-effectiveness range. Significant interactions with treatment, indicating moderation, were detected for the unemotional subscale on the young person-reported Inventory of Callous–Unemotional Traits (p = 0.0104) and the affective involvement subscale on the caregiver-reported McMaster Family Assessment Device (p = 0.0338). Caregivers and young people in the FT arm reported a range of significantly better outcomes on the Strengths and Difficulties Questionnaire. Self-reported suicidal ideation was significantly lower in the FT arm at 12 months but the same in both groups at 18 months. No significant unexpected adverse events or side effects were reported, with similar rates of expected adverse events across trial arms. Conclusions: For adolescents referred to CAMHS after self-harm, who have self-harmed at least once before, FT confers no benefits over TAU in reducing self-harm repetition rates. There is some evidence to support the effectiveness of FT in reducing self-harm when caregivers reported poor family functioning. When the young person themselves reported difficulty expressing emotion, FT did not seem as effective as TAU. There was no evidence that FT is cost-effective when only the health benefits to participants were considered but there was a suggestion that FT may be cost-effective if health benefits to caregivers are taken into account. FT had a significant, positive impact on general emotional and behavioural problems at 12 and 18 months. Limitations: There was significant loss to follow-up for secondary outcomes and health economic analyses; the primary outcome misses those who do not attend hospital following self-harm; and the numbers receiving formal FT in the TAU arm were higher than expected. Future work: Evaluation of interventions targeted at subgroups of those who self-harm, longer-term follow-up and methods for evaluating health benefits for family groups rather than for individuals

Evaluation of inter-observer variation for computed tomography identification of childhood interstitial lung disease

Computed tomography; Childhood; Interstitial lung diseaseTomografía computarizada; Infancia; Enfermedad pulmonar intersticialTomografia assistida per ordinador; Infància; Malaltia pulmonar intersticialMaking chILD diagnoses on CT is poorly reproducible, even amongst sub-specialists. CT might best improve diagnostic confidence in a multidisciplinary team setting when augmented with clinical, functional and haematological results.Joseph Jacob was supported by Wellcome Trust Clinical Research Career Development Fellowship 209553/Z/17/Z. Andrew Bush is an Emeritus NIHR Senior Investigator and is supported by chILD-EU (FP7, No: 305653) and the European Cooperation in Science and Technology COST A16125. Andre Altmann holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship. This work was supported by the Medical Research Council (grant number MR/L016311/1). Funding information for this article has been deposited with the Crossref Funder Registry