Towards the standardisation of adult person-reported outcome domains in diabetes research: A Consensus Statement development panel.

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data.

Upscale fermenter design for lactic acid production from cheese whey permeate focusing on impeller selection and energy optimization.

This study focusses on the design and scale-up of industrial lactic acid production by fermentation of dairy cheese whey permeate based on standard methodological parameters. The aim was to address the shortcomings of standard scale-up methodologies and provide a framework for fermenter scale-up that enables the accurate estimation of energy consumption by suitable selection of turbine and speed for industrial deployment. Moreover, life cycle assessment (LCA) was carried out to identify the potential impacts and possibilities to reduce the operation associated emissions at an early stage. The findings showed that a 3000 times scale-up strategy assuming constant geometric dimensions and specific energy consumption (P/V w ) resulted in lower impeller speed and energy demand. The Rushton turbine blade (RTB) and LightninA315 four-blade hydrofoil (LA315) were found to have the highest and lowest torque output, respectively, at a similar P/V w of 2.8 kWm-3, with agitation speeds of 1.33 and 2.5 s-1, respectively. RTB demonstrating lower shear damage towards cells (up to 1.33 s-1) was selected because it permits high torque, low-power and acceptable turbulence. The LCA results showed a strong relation between the number of impellers installed and associated emissions suggesting a trade-off between mixing performance and environmental impacts. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-021-05239-6.

Health Care Professional Experiences and Opinions on Depression and Suicide in People With Diabetes.

OBJECTIVE: People with diabetes have an increased risk of depression, intentional self-injury and self-harm (ISI), and suicide compared with the general population. This study aimed to explore experiences and awareness of health care professionals (HCPs) regarding depression, ISI, and suicide, and understand resource use and needs among HCPs who care for persons with diabetes (PWD). METHODS: Health care professionals who see children and/or adults with type 1 diabetes or type 2 diabetes anonymously completed an online survey about their experiences, opinions, barriers, and needs surrounding identification and care of PWD with depression, ISI, and suicide. RESULTS: One hundred twenty-nine HCPs participated. The majority were medical doctors (MDs) or advanced practice providers (APPs). Only a quarter of MDs and APPs felt very comfortable asking about ISI or suicidal ideation (SI), whereas 20% felt they had received appropriate training to support those with ISI or SI. The primary needs reported include more training on how to ask, respond, and support those expressing ISI and SI. Health care professionals reported wanting better access to resources for PWD. DISCUSSION: The HCPs tend to underestimate SI in the diabetes population and rates of training were low. Areas to address include providing education and training to HCPs to improve identification and management of ISI and suicide risk. These data can inform the development of mechanisms to improve discussions of depression and suicide and of resources to help HCPs support PWD.

Early Outcomes From the English National Health Service Diabetes Prevention Programme.

OBJECTIVE: To assess weight and HbA1c changes in the Healthier You: National Health Service Diabetes Prevention Programme (NHS DPP), the largest DPP globally to achieve universal population coverage. RESEARCH DESIGN AND METHODS: A service evaluation assessed intervention effectiveness for adults with nondiabetic hyperglycemia (HbA1c 42-47 mmol/mol [6.0-6.4%] or fasting plasma glucose 5.5-6.9 mmol/L) between program launch in June 2016 and December 2018, using prospectively collected, national service-level data in England. RESULTS: By December 2018, 324,699 people had been referred, 152,294 had attended the initial assessment, and 96,442 had attended at least 1 of 13 group-based intervention sessions. Allowing sufficient time to elapse, 53% attended an initial assessment, 36% attended at least one group-based session, and 19% completed the intervention (attended >60% of sessions). Of the 32,665 who attended at least one intervention session and had sufficient time to finish, 17,252 (53%) completed: intention-to-treat analyses demonstrated a mean weight loss of 2.3 kg (95% CI 2.2, 2.3) and an HbA1c reduction of 1.26 mmol/mol (1.20, 1.31) (0.12% [0.11, 0.12]); completer analysis demonstrated a mean weight loss of 3.3 kg (3.2, 3.4) and an HbA1c reduction of 2.04 mmol/mol (1.96, 2.12) (0.19% [0.18, 0.19]). Younger age, female sex, Asian and black ethnicity, lower socioeconomic status, and normal baseline BMI were associated with less weight loss. Older age, female sex, black ethnicity, lower socioeconomic status, and baseline overweight and obesity were associated with a smaller HbA1c reduction. CONCLUSIONS: Reductions in weight and HbA1c compare favorably with those reported in recent meta-analyses of pragmatic studies and suggest likely future reductions in participant type 2 diabetes incidence.

Experience of point-of-care HbA1c testing in the English National Health Service Diabetes Prevention Programme: an observational study.

INTRODUCTION: To report the observations of point-of-care (POC) glycated hemoglobin (HbA1c) testing in people with non-diabetic hyperglycemia (NDH; HbA1c 42-47 mmol/mol (6.0%-6.4%)), applied in community settings, within the English National Health Service Diabetes Prevention Programme (NHS DPP). RESEARCH DESIGN AND METHODS: A service evaluation assessing prospectively collected national service-level data from the NHS DPP, using data from the first referral received in June 2016-October 2018. Individuals were referred to the NHS DPP with a laboratory-measured HbA1c in the NDH range and had a repeat HbA1c measured at first attendance of the program using one of three POC devices: DCA Vantage, Afinion or A1C Now+. Differences between the referral and POC HbA1c and the SD of the POC HbA1c were calculated. The factors associated with the difference in HbA1c and the association between POC HbA1c result and subsequent attendance of the NHS DPP were also evaluated. RESULTS: Data from 73 703 participants demonstrated a significant mean difference between the referral and POC HbA1c of -2.48 mmol/mol (-0.23%) (t=157, p<0.001) with significant differences in the mean difference between devices (F(2, 73 700)=738, p<0.001). The SD of POC HbA1c was 4.46 mmol/mol (0.41%) with significant differences in SDs between devices (F(2, 73 700)=1542, p<0.001). Participants who were older, from more deprived areas and from Asian, black and mixed ethnic groups were associated with smaller HbA1c differences. Normoglycemic POC HbA1c versus NDH POC HbA1c values were associated with lower subsequent attendance at behavioral interventions (58% vs 67%, p<0.001). CONCLUSION: POC HbA1c testing in community settings was associated with significantly lower HbA1c values when compared with laboratory-measured referrals. Acknowledging effects of regression to the mean, we found that these differences were also associated with POC method, location, individual patient factors and time between measurements. Compared with POC HbA1c values in the NDH range, normoglycemic POC HbA1c values were associated with lower subsequent intervention attendance.

Maximising engagement, motivation and long term change in a Structured Intensive Education Programme in Diabetes for children, young people and their families: Child and Adolescent Structured Competencies Approach to Diabetes Education (CASCADE).

BACKGROUND: This trial aims to evaluate effective delivery and cost effectiveness of an innovative structured psycho-educational programme (CASCADE) for young people and their families living with diabetes. The increase in numbers of people being diagnosed with diabetes is posing a challenge for both the UK and the rest of the world. The peak age for diagnosis is between 10 and 14 years of age. There is clear evidence that improved diabetes control from diagnosis in childhood can reduce the incidence and progression of long-term complications. However, despite the development of improved insulin regimens and delivery methods, the overall metabolic control in children and adolescents has improved little in the UK in the past decade. Therefore there is a need for novel interventions and health delivery mechanisms aimed at young people and their families to help improve control and reduce complications, illness burden and costs to the NHS. METHODS/DESIGN: The CASCADE trial is a multi-centre randomised control trial with 26 clinics randomised to control or intervention groups, with 572 children and young people involved in the study. The intervention will be delivered in 4 group sessions, over a 4 month period. A developmentally appropriate curriculum will be delivered to groups of 3 - 4 families, focusing on achievement of increasing competency in self-management of diabetes. The control group will receive standard care from their clinical team, usually consisting of regular 3-monthly clinic visits and telephone contact as required with the clinical nurse specialist and consultant. The primary outcomes of the trial will be change in HbA1c between baseline and 12 months and 24 months post recruitment. Secondary outcomes will include measures related to the economic evaluation, psychosocial outcomes, outcomes related to management of diabetes outcomes, and adherence to the intervention. DISCUSSION: The trial will be run by independent research and service delivery teams and supervised by a trial steering committee. A data monitoring and ethics committee has been put in place to monitor the trial and recommend stopping/continuation according to a Peto-Haybittle rule. The trial will be conducted according to the principles of MRC Good Clinical Practice (GCP) Guidelines and CTRU Phase III Trial Standard Operating procedures. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52537669.

Structured, intensive education maximising engagement, motivation and long-term change for children and young people with diabetes: a cluster randomised controlled trial with integral process and economic evaluation - the CASCADE study.

BACKGROUND: Type 1 diabetes (T1D) in children and young people is increasing worldwide with a particular increase in children under the age of 5 years. Fewer than one in six children and young people achieve glycosylated fraction of haemoglobin (HbA1c) values in the range identified as providing best future outcomes. There is an urgent need for clinic-based pragmatic, feasible and effective interventions that improve both glycaemic control and quality of life (QoL). The intervention offers both structured education, to ensure young people know what they need to know, and a delivery model designed to motivate self-management. OBJECTIVE: To assess the feasibility of providing a clinic-based structured educational group programme incorporating psychological approaches to improve long-term glycaemic control, QoL and psychosocial functioning in a diverse range of young people. DESIGN: The study was a pragmatic, cluster randomised control trial with integral process and economic evaluation. SETTING: Twenty-eight paediatric diabetes services across London, south-east England and the Midlands. RANDOMISATION: Minimised by clinic size, age (paediatric or adolescent) and specialisation (district general hospital clinic or teaching hospital/tertiary clinic). ALLOCATION: Half of the sites were randomised to the intervention arm and half to the control arm. Allocation was concealed until after clinics had consented and the first participant was recruited. Where possible, families were blind to allocation until recruitment finished. PARTICIPANTS: Forty-three health-care practitioners (14 teams) were trained in the intervention. The study recruited 362 children aged 8-16 years, diagnosed with T1D for > 12 months, with a mean 12-month HbA1c level of ≥ 8.5%. INTERVENTION: Two 1-day workshops taught intervention delivery. A detailed manual and resources were provided. The intervention consists of four group education sessions led by a paediatric diabetes specialist nurse with another team member. OUTCOMES: The primary outcome was glycaemic control, assessed at the individual level using venous HbA1c values, measured at baseline, 12 and 24 months. Secondary outcomes were directly and indirectly related to diabetes management, including hypoglycaemic episodes, hospital admissions, diabetes regimen, knowledge, skills and responsibility for diabetes management, intervention compliance, clinic utilisation, emotional and behavioural adjustment, and general and diabetes-specific QoL. PROCESS EVALUATION: Questionnaires, semistructured interviews, informal discussion following observation sessions, fieldwork notes and case note review were used to collect qualitative and quantitative data from key stakeholder groups at specific time points in the trial. STATISTICAL ANALYSES: Primary and secondary analyses were intention-to-treat comparisons of outcomes at 12 and 24 months, using analysis of covariance with a random effect for clinic. Prespecified subgroup analyses based on age, gender, initial HbA1c value and socioeconomic status were estimated from models that included an interaction term. The economic analysis compared long-term costs and predicted quality-adjusted life-years (QALYs). RESULTS: The intervention did not improve HbA1c at 12 months [intervention effect 0.11; 95% confidence interval (CI) -0.28 to 0.50; p = 0.584] or 24 months (intervention effect 0.03; 95% CI -0.36 to 0.41; p = 0.891). A total of 298/362 patients (82.3%) provided blood samples at 12-month follow-up, and 284/362 (78.5%) provided blood samples at 24-month follow-up. Follow-up questionnaires were completed by 307 patients (85.3%) at 12 months and by 295 patients (81.5%) at 24 months. Intervention group parents at 12 months (95% CI 0.74; 0.03 to 1.52) and young people at 24 months (0.85; 95% CI 0.03 to 1.61) had higher scores on the diabetes family responsibility questionnaire. Young people reported reduced happiness with body weight at 12 months (-0.56; 95% CI -1.03 to -0.06). Only 68% of groups were run. Of the 180 families recruited, 96 (53%) attended at least one module. Reasons for low uptake included difficulties organising groups, and work and school commitments. Young people with higher HbA1c levels were less likely to attend. Parents and young people who attended groups described improved family relationships, improved knowledge and understanding, greater confidence and increased motivation to manage diabetes. Twenty-four months after the intervention, nearly half of the young people reported that the groups had made them want to try harder and that they had carried on trying. A high-quality, complex, pragmatic trial of structured education can be delivered alongside standard care in NHS diabetes clinics. Health-care providers benefited from behaviour change skill training and can deliver pragmatic aspects of a National Institute for Health and Care Excellence (NICE)-compliant structured education programme after relatively brief training. The process evaluation provides insight into aspects of the model, and highlights strengths and aspects that may have contributed to the failure to influence primary and secondary outcomes. Current NHS practice dominates CASCADE (Child and Adolescent Structured Competencies Approach to Diabetes Education) in that it achieves the same number of QALYs at a lower cost. The mean cost of providing the intervention was £5098 per site or £683 per child. Members of paediatric diabetes services trained to deliver the CASCADE structured education package using behaviour change techniques did not improve glycaemic control in patients compared with control subjects 1 and 2 years after the intervention. The training workshops for practitioners were well evaluated; however, more intensive training was needed. The intervention cost £683 per patient but was not cost-effective because it did not improve metabolic control. CONCLUSIONS: A high-quality, complex, pragmatic trial of structured education can be successfully conducted alongside standard care in NHS diabetes clinics. Pragmatic components of a NICE-compliant structured education programme can be successfully delivered following a relatively brief 2-day training while paediatric health-care professionals benefit from training in behaviour change skills. The study provides invaluable information on barriers and opportunities regarding future, similar interventions. A low dropout rate and good attendance for the subgroup that attended the intervention suggests there might be improved uptake if offered to young people with lower HbA1c. Testing whether this approach can be more successful with a robust ongoing supervisory element should be a target of further research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52537669. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 20. See the NIHR Journals Library website for further project information.