Glatiramer acetate as a clinically and cost-effective treatment of relapsing multiple sclerosis over 10 years of use within the National Health Service: Final results from the UK Risk Sharing Scheme.

Background: The UK Risk Sharing Scheme (RSS) provided information on the effect of first-line multiple sclerosis (MS) disease-modifying treatments on long-term disability. Objective: The aim is to provide results specific to glatiramer acetate (GA; Copaxone®) from the final 10-year analysis of the RSS. Methods: A Markov model was used to assess clinical effectiveness measured as Expanded Disability Status Scale (EDSS) progression and utility loss. Untreated patients from the British Columbia MS cohort (1980-1995) were used as a 'virtual comparator' group. A separate Markov model assessed cost-effectiveness, based on a 50-year time horizon (with a 50% treatment waning effect imposed at 10 years) and using NHS list price (£513.95 per 28 days). Results were expressed in quality-adjusted life years (QALYs). Results: In total, 755 patients with relapsing-remitting MS (RRMS) received GA, with a mean follow-up of 7.1 (standard deviation 1.3) years. EDSS progression was reduced by 23% (progression ratio 76.7, 95% confidence interval [CI] 69.0-84.3) and utility loss by 39% (progression ratio 61.0, 95% CI 52.7-69.3) compared with no treatment. There was no persistent waning in GA treatment effect over time (EDSS: p = 0.093; utilities: p = 0.119). The cost per QALY was £17,841. Conclusion: GA had a beneficial effect on long-term disability and was a cost-effective treatment for RRMS

Augmenting the 6-3-5 method with design information

This paper describes a comparative study between the 6-3-5 Method and the ICR Grid. The ICR Grid is an evolved variant of 6-3-5 intended to better integrate information into the concept generation process. Unlike a conventional 6-3-5 process where participants continually sketch concepts, using the ICR Grid (the name derived from its Inform, Create, Reflect activities and structured, grid-like output) participants are additionally required to undertake information search tasks, use specific information items for concept development, and reflect on the merit of concepts as the session progresses. The results indicate that although the quantity of concepts was lower, the use of information had a positive effect in a number of areas, principally the quality and variety of output. Although grounded in the area of product development, this research is applicable to any organisation undertaking idea generation and problem solving. As well as providing insights on the transference of information to concepts, it holds additional interest for studies on the composition and use of digital libraries

Institutional strategies for capturing socio-economic impact of academic research

Evaluation of socio-economic impact is an emerging theme for publicly-funded academic research. Within this context the paper suggests that the concept of institutional research capital be expanded to include the capture and evaluation of socio-economic impact. Furthermore, it argues that understanding the typology of impacts and the tracking from research to impact will assist the formulation of institutional strategies for capturing socio-economic impact. A three-stage approach is proposed for capturing and planning activities to enhance the generation of high-quality impact. Stage one outlines the critical role of user engagement that facilitates the tracking of such impact. Stage two employs an analytical framework based on the criteria of ‘depth’ and ‘spread’ to evaluate impacts that have been identified. Stage three utilizes the outcomes of the framework to devise strategies, consisting of either further research (to increase depth) or more engagement (to increase spread) that will improve the generation of higher quality impact

Dilated Cardiomyopathy: Phosphorus 31 MR Spectroscopy at 7 T

Purpose To test whether the increased signal-to-noise ratio of phosphorus 31 (31P) magnetic resonance (MR) spectroscopy at 7 T improves precision in cardiac metabolite quantification in patients with dilated cardiomyopathy (DCM) compared with that at 3 T. Materials and Methods Ethical approval was obtained, and participants provided written informe consent. In a prospective study, 31P MR spectroscopy was performed at 3 T and 7 T in 25 patients with DCM. Ten healthy matched control subjects underwent 31P MR spectroscopy at 7 T. Paired Student t tests were performed to compare results between the 3-T and 7-T studies. Results The phosphocreatine (PCr) signal-to-noise ratio increased 2.5 times at 7 T compared with that at 3 T. The PCr to adenosine triphosphate (ATP) concentration ratio (PCr/ATP) was similar at both field strengths (mean ± standard deviation, 1.48 ± 0.44 at 3 T vs 1.54 ± 0.39 at 7 T, P = .49), as expected. The Cramér-Rao lower bounds in PCr concentration (a measure of uncertainty in the measured ratio) were 45% lower at 7 T than at 3 T, reflecting the higher quality of 7-T 31P spectra. Patients with dilated cardioyopathy had a significantly lower PCr/ATP than did healthy control subjects at 7 T (1.54 ± 0.39 vs 1.95 ± 0.25, P = .005), which is consistent with previous findings. Conclusion 7-T cardiac 31P MR spectroscopy is feasible in patients with DCM and gives higher signal-to-noise ratios and more precise quantification of the PCr/ATP than that at 3 T. PCr/ATP was significantly lower in patients with DCM than in control subjects at 7 T, which is consistent with previous findings at lower field strengths

Continuous glucose monitoring demonstrates low risk of clinically significant hypoglycemia associated with sulphonylurea treatment in an African type 2 diabetes population: results from the OPTIMAL observational multicenter study

This is the final version. Available from BMJ Publishing via the DOI in this record. Data availability statement: Data are available on reasonable request. Data analyzed in this study are available to researchers on reasonable request from the corresponding author.INTRODUCTION: People living with diabetes in low-resource settings may be at increased hypoglycemia risk due to food insecurity and limited access to glucose monitoring. We aimed to assess hypoglycemia risk associated with sulphonylurea (SU) and insulin therapy in people living with type 2 diabetes in a low-resource sub-Saharan African setting. RESEARCH DESIGN AND METHODS: This study was conducted in the outpatients' diabetes clinics of two hospitals (one rural and one urban) in Uganda. We used blinded continuous glucose monitoring (CGM) and self-report to compare hypoglycemia rates and duration in 179 type 2 diabetes patients treated with sulphonylureas (n=100) and insulin (n=51) in comparison with those treated with metformin only (n=28). CGM-assessed hypoglycemia was defined as minutes per week below 3mmol/L (54mg/dL) and number of hypoglycemic events below 3.0 mmol/L (54 mg/dL) for at least 15 minutes. RESULTS: CGM recorded hypoglycemia was infrequent in SU-treated participants and did not differ from metformin: median minutes/week of glucose <3 mmol/L were 39.2, 17.0 and 127.5 for metformin, sulphonylurea and insulin, respectively (metformin vs sulphonylurea, p=0.6). Hypoglycemia risk was strongly related to glycated haemoglobin (HbA1c) and fasting glucose, with most episodes occurring in those with tight glycemic control. After adjusting for HbA1c, time <3 mmol/L was 2.1 (95% CI 0.9 to 4.7) and 5.5 (95% CI 2.4 to 12.6) times greater with sulphonylurea and insulin, respectively, than metformin alone. CONCLUSIONS: In a low-resource sub-Saharan African setting, hypoglycemia is infrequent among people with type 2 diabetes receiving sulphonylurea treatment, and the modest excess occurs predominantly in those with tight glycemic control.National Institute for Health Research (NIHR

Using Routinely Collected Administrative Data in Public Health Research: Geocoding Alcohol Outlet Data

We describe our process of geocoding alcohol outlets to create a national longitudinal exposure dataset for Wales, United Kingdom from 2006 to 2011. We investigated variation in the availability of data items and the quality of alcohol outlet addresses held within unitary authorities. We used a standard geocoding method augmented with a manual matching procedure to achieve a fully spatially referenced dataset. We found higher quality addresses are held for outlets based in urban areas, resulting in the automatic geocoding of 68 % of urban outlets, compared to 48 % in rural areas. Missing postcodes and a lack of address structure contributed to a lower geocoding proportion. An urban rural bias was removed with the development of a manual matching procedure. Only one-half of the unitary authorities provided data on on/off sales and opening times, which are important availability factors. The resulting outlet dataset is suitable for contributing to the evidence-base of alcohol availability and alcohol-related harm. Local government should be encouraged to use standardised data fields, including addresses, to enable accurate geocoding of alcohol outlets and facilitate research that aims to prevent alcohol-related harm. Standardising data collection would enable efficient secondary data reuse using record linkage techniques, allowing the retrospective creation and evaluation of population-based natural experiments to provide evidence for policy and practice

HbA1c performs well in monitoring glucose control even in populations with high prevalence of medical conditions that may alter its reliability: The OPTIMAL observational multicenter study

This is the final version. Available from BMJ Publishing via the DOI in this record.Data availability statement: Data are available upon reasonable request.Introduction: The utility of HbA1c (glycosylated hemoglobin) to estimate glycemic control in populations of African and other low-resource countries has been questioned because of high prevalence of other medical conditions that may affect its reliability. Using continuous glucose monitoring (CGM), we aimed to determine the comparative performance of HbA1c, fasting plasma glucose (FPG) (within 5 hours of a meal) and random non-fasting glucose (RPG) in assessing glycemic burden. Research design and methods: We assessed the performance of HbA1c, FPG and RPG in comparison to CGM mean glucose in 192 Ugandan participants with type 2 diabetes. Analysis was undertaken in all participants, and in subgroups with and without medical conditions reported to affect HbA1c reliability. We then assessed the performance of FPG and RPG, and optimal thresholds, in comparison to HbA1c in participants without medical conditions thought to alter HbA1c reliability. Results: 32.8% (63/192) of participants had medical conditions that may affect HbA1c reliability: anemia 9.4% (18/192), sickle cell trait and/or hemoglobin C (HbC) 22.4% (43/192), or renal impairment 6.3% (12/192). Despite high prevalence of medical conditions thought to affect HbA1c reliability, HbA1c had the strongest correlation with CGM measured glucose in day-to-day living (0.88, 95% CI 0.84 to 0.91), followed by FPG (0.82, 95% CI 0.76 to 0.86) and RPG (0.76, 95% CI 0.69 to 0.81). Among participants without conditions thought to affect HbA1c reliability, FPG and RPG had a similar diagnostic performance in identifying poor glycemic control defined by a range of HbA1c thresholds. FPG of ≥7.1 mmol/L and RPG of ≥10.5 mmol/L correctly identified 78.2% and 78.8%, respectively, of patients with an HbA1c of ≥7.0%. Conclusions: HbA1c is the optimal test for monitoring glucose control even in low-income and middle-income countries where medical conditions that may alter its reliability are prevalent; FPG and RPG are valuable alternatives where HbA1c is not available.National Institute for Health Research (NIHR

Dilated Thin-Walled Blood and Lymphatic Vessels in Human Endometrium: A Potential Role for VEGF-D in Progestin-Induced Break-Through Bleeding

Progestins provide safe, effective and cheap options for contraception as well as the treatment of a variety of gynaecological disorders. Episodes of irregular endometrial bleeding or breakthrough bleeding (BTB) are a major unwanted side effect of progestin treatment, such that BTB is the leading cause for discontinued use of an otherwise effective and popular medication. The cellular mechanisms leading to BTB are poorly understood. In this study, we make the novel finding that the large, dilated, thin walled vessels characteristic of human progestin-treated endometrium include both blood and lymphatic vessels. Increased blood and lymphatic vessel diameter are features of VEGF-D action in other tissues and we show by immunolocalisation and Western blotting that stromal cell decidualisation results in a significant increase in VEGF-D protein production, particularly of the proteolytically processed 21 kD form. Using a NOD/scid mouse model with xenografted human endometrium we were able to show that progestin treatment causes decidualisation, VEGF-D production and endometrial vessel dilation. Our results lead to a novel hypothesis to explain BTB, with stromal cell decidualisation rather than progestin treatment per se being the proposed causative event, and VEGF-D being the proposed effector agent

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Implementation of a Family Intervention for Individuals with Schizophrenia

Families are rarely included in clinical care despite research showing that family involvement has a positive effect on individuals with schizophrenia by reducing relapse, improving work functioning, and social adjustment. The VA QUERI study, EQUIP (Enhancing QUality of care In Psychosis), implemented family services for this population. At two VA medical centers, veterans with schizophrenia and their clinicians were interviewed separately at baseline and 15 months. A family intervention was implemented, and a process evaluation of the implementation was conducted. Veterans with schizophrenia (n = 173) and their clinicians (n = 29). Consent to contact family was obtained, mailers to engage families were sent, families were prioritized as high need for family services, and staff volunteers were trained in a brief three-session family intervention. Of those enrolled, 100 provided consent for family involvement. Seventy-three of the 100 were sent a mailer to engage them in care; none became involved. Clinicians were provided assessment data on their patients and notified of 50 patients needing family services. Of those 50, 6 families were already involved, 34 were never contacted, and 10 were contacted; 7 new families became involved in care. No families were referred to the family psychoeducational program. Uptake of the family intervention failed due to barriers from all stakeholders. Families did not respond to the mailer, patients were concerned about privacy and burdening family, clinicians had misperceptions of family-patient contact, and organizations did not free up time or offer incentives to provide the service. If a full partnership with patients and families is to be achieved, these barriers will need to be addressed, and a family-friendly environment will need to be supported by clinicians and their organizations. Applicability to family involvement in other disorders is discussed