Development of oedema is associated with an improved glycaemic response in patients initiating thiazolidinediones: a MASTERMIND study

Abstracts of the 51st EASD Annual Meeting, Stockholm, Sweden, 14–18 September 2015This is the author accepted manuscript. The final version is available from Springer VerlagBackground and aims: Oedema is a common and serious side effect of thiazolidinedione therapy. A stratified medicines approach would aim to give thiazolidinediones to patients likely to have a good glycaemic response but to not develop oedema. We investigated whether oedema was associated with glycaemic response to thiazolidinedione therapy. Materials and methods: We retrospectively studied 11,459 patients initiating a thiazolidinedione from UK primary care data (Clinical Practice Research Datalink), and identified medical records of new oedema in the subsequent twelve months. Response was defined as change in HbA1c at twelve months and was adjusted for baseline HbA1c, baseline BMI, gender and compliance (medication possession ratio). In secondary analyses we restricted oedema classification to patients with concomitant weight gain. As a comparison the same analysis was performed in 13,089 patients initiating a sulfonylurea. Results: The 5% of patients with recorded oedema on thiazolidinediones had a mean (CI) 2.2 (1.1-3.2)mmol/mol greater fall in HbA1c (p3 kg (p< 0.001) and a 3.6 (1.8-5.4)mmol/mol greater fall when weight gain >5 kg (p3 kg (p=0.19). Conclusion: Patients with Type 2 diabetes who develop oedema on initiating thiazolidinediones have an improved glycaemic response, and more severe oedema may be associated with greater reductions in HbA1c. An association between oedema and glycaemic response was not observed in patients initiating sulfonylureas. This supports glycaemic lowering and fluid retention being mediated by a common pathway of thiazolidinedione drug action.Supported by: MRC grant MR-K005707-

Capitals and commitment. The case of a local learning and employment network.

This article draws on research undertaken with a Local Learning and Employment Network (LLEN) in the state of Victoria, Australia. LLEN are networks that were implemented by the state government in 2001 to undertake community capacity building through which the outcomes of young people aged 15-19 in education, training and employment would be enhanced. In 2008, in the context of an enhanced federal commitment to social inclusion through ‘joining-up’, the Victorian experience provides insights on the implications of such policy initiatives. Drawing on Bourdieu’s discussion of the forms of capital and Granovetter’s notion of the strength of weak ties, I argue that stores of economic, cultural and social capital as outlined by Bourdieu were necessary, but insufficient, for LLEN to achieve the objectives with which they were charged given the failure of government to follow through on the implications of its policies. I argue for a commitment on the part of all stakeholders to realise the potential of ‘joining-up’

The dynamics of organizational autonomy: Oscillations at Automobili Lamborghini

Through a 21-year longitudinal study of the relationship between Italian supercar manufacturer Automobili Lamborghini and its parent, German carmaker Audi AG, we examine how a unit’s degree of organizational autonomy is renegotiated over long periods of time. Using detailed empirical data, we develop a process model of the dynamics of organizational autonomy in a unit–parent relationship. This process model shows an ongoing dialectical tension between parent managers’ autonomy-reduction efforts and unit managers’ autonomy-extension efforts, and it reveals oscillations in the unit managers’ discretion over resource-orchestration decisions. Driving this dialectic are parent managers’ appraisal respect for the unit, their search for firm-wide strategic integration, and unit managers’ organizational identity and concern for distinctiveness. Our process model captures concurrent feedback loops that endogenously produce these oscillations between lower and higher autonomy. We then conceptualize a harmonic domain in the unit–parent relationship, in which these oscillations persist without deviating toward amalgamation or separation. Finally, we develop a theory of change in autonomy by identifying a theoretical link between resource orchestration and specific dimensions of organizational identity. Our study highlights the dialectical, dynamic, and ongoing nature of organizational autonomy

Does merger & acquisition (M&A) strategy matter? A contingency perspective

This paper takes a contingency approach to investigate whether there are market performance variations for different types of M&A. Eight different types of M&A are identified in a typology based upon the conjunction of three contextual dimensions: external environmental, acquiring firm level strategy and CEO motivation. Drawing upon a sample of 1,926 domestic UK deals we evaluate the typology to determine whether the financial markets distinguish between different types of M&A. Results indicate significant market and risk-adjusted performance differences by M&A type. These confirm that a contingency approach to M&A performance has merit. We suggest that the proposed integrated typology, that recognizes the importance of multiple aspects of strategic fit to M&A performance, addresses the paradox that M&A practitioners continue to pursue deals despite widespread acceptance that they result in high failure rates

TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea - a MASTERMIND study protocol

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordINTRODUCTION: Pharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents. METHODS AND ANALYSIS: TriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA1c) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase-4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA1c after 4 months of therapy (allowing a range of 12-18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects. ETHICAL APPROVAL: This study was approved by National Health Service Health Research Authority Research Ethics Committee South Central-Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants. TRIAL REGISTRATION NUMBERS: 12039221; 2015-002790-38 and NCT02653209.Medical Research Council (MRC)National Institute for Health Research (NIHR)Wellcome TrustBritish Heart Foundatio

Algorithms as folding:Reframing the analytical focus

This article proposes an analytical approach to algorithms that stresses operations of folding. The aim of this approach is to broaden the common analytical focus on algorithms as biased and opaque black boxes, and to instead highlight the many relations that algorithms are interwoven with. Our proposed approach thus highlights how algorithms fold heterogeneous things: data, methods and objects with multiple ethical and political effects. We exemplify the utility of our approach by proposing three specific operations of folding-proximation, universalisation and normalisation. The article develops these three operations through four empirical vignettes, drawn from different settings that deal with algorithms in relation to AIDS, Zika and stock markets. In proposing this analytical approach, we wish to highlight the many different attachments and relations that algorithms enfold. The approach thus aims to produce accounts that highlight how algorithms dynamically combine and reconfigure different social and material heterogeneities as well as the ethical, normative and political consequences of these reconfigurations

Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation

Introduction: To identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i). Research design and methods: We assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation. Results: Genital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; &lt;1 year before initiation (HR 4.38; 3.73 to 5.13), 1–5 years (HR 3.04; 2.64 to 3.51), and &gt;5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07). Conclusions: Female sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i

Automatic radiographic quantification of hand osteoarthritis; accuracy and sensitivity to change in joint space width in a phantom and cadaver study

This is the final version of the article. Available from Springer Verlag via the DOI in this record.OBJECTIVE: To validate a newly developed quantification method that automatically detects and quantifies the joint space width (JSW) in hand radiographs. Repeatability, accuracy and sensitivity to changes in JSW were determined. The influence of joint location and joint shape on the measurements was tested. METHODS: A mechanical micrometer set-up was developed to define and adjust the true JSW in an acrylic phantom joint and in human cadaver-derived phalangeal joints. Radiographic measurements of the JSW were compared to the true JSW. Repeatability, systematic error (accuracy) and sensitivity (defined as the smallest detectable difference (SDD)) were determined. The influence of joint position on the JSW measurement was assessed by varying the location of the acrylic phantom on the X-ray detector with respect to the X-ray beam and the influence of joint shape was determined by using morphologically different human cadaver joints. RESULTS: The mean systematic error was 0.052 mm in the phantom joint and 0.210 mm in the cadaver experiment. In the phantom experiments, the repeatability was high (SDD = 0.028 mm), but differed slightly between joint locations (p = 0.046), and a change in JSW of 0.037 mm could be detected. Dependent of the joint shape in the cadaver hand, a change in JSW between 0.018 and 0.047 mm could be detected. CONCLUSIONS: The automatic quantification method is sensitive to small changes in JSW. Considering the published data of JSW decline in the normal and osteoarthritic population, the first signs of OA progression with this method can be detected within 1 or 2 years.This work was funded by the Dutch Arthritis Association (Reumafonds). The study sponsor had no involvement in study design, data collection, data analysis, or interpretation of the results

Crowdsourcing the Perception of Machine Teaching

Teachable interfaces can empower end-users to attune machine learning systems to their idiosyncratic characteristics and environment by explicitly providing pertinent training examples. While facilitating control, their effectiveness can be hindered by the lack of expertise or misconceptions. We investigate how users may conceptualize, experience, and reflect on their engagement in machine teaching by deploying a mobile teachable testbed in Amazon Mechanical Turk. Using a performance-based payment scheme, Mechanical Turkers (N = 100) are called to train, test, and re-train a robust recognition model in real-time with a few snapshots taken in their environment. We find that participants incorporate diversity in their examples drawing from parallels to how humans recognize objects independent of size, viewpoint, location, and illumination. Many of their misconceptions relate to consistency and model capabilities for reasoning. With limited variation and edge cases in testing, the majority of them do not change strategies on a second training attempt.Comment: 10 pages, 8 figures, 5 tables, CHI2020 conferenc