Impact of glycaemic technologies on quality of life and related outcomes in adults with type 1 diabetes: A narrative review.

AIMS: To explore the association between the use of glycaemic technologies and person-reported outcomes (PROs) in adults with type 1 diabetes (T1D). METHODS: We included T1D and technology publications reporting on PROs since 2014. Only randomised controlled trials and cohort studies that used validated PRO measures (PROMs) were considered. RESULTS: T1D studies reported on a broad range of validated PROMs, mainly as secondary outcome measures. Most studies examined continuous glucose monitoring (CGM), intermittently scanned CGM (isCGM), and the role of continuous subcutaneous insulin infusion (CSII), including sensor-augmented CSII and closed loop systems. Generally, studies demonstrated a positive impact of technology on hypoglycaemia-specific and diabetes-specific PROs, including reduced fear of hypoglycaemia and diabetes distress, and greater satisfaction with diabetes treatment. In contrast, generic PROMs (including measures of health/functional status, emotional well-being, depressive symptoms, and sleep quality) were less likely to demonstrate improvements associated with the use of glycaemic technologies. Several studies showed contradictory findings, which may relate to study design, population and length of follow-up. Differences in PRO findings were apparent between randomised controlled trials and cohort studies, which may be due to different populations studied and/or disparity between trial and real-world conditions. CONCLUSIONS: PROs are usually assessed as secondary outcomes in glycaemic technology studies. Hypoglycaemia-specific and diabetes-specific, but not generic, PROs show the benefits of glycaemic technologies, and deserve a more central role in future studies as well as routine clinical care.

Characteristics of repeat non-attenders at Diabetes Eye Screening Wales, a national community-based diabetes-related retinopathy screening service, during 2003-2018.

AIMS: To understand factors associated with repeat non-attendance at screening for diabetes-related retinopathy. METHODS: Retrospective observational study using anonymised data from Diabetic Eye Screening Wales for people with a full history of screening invitations and attendances was linked with primary and secondary care records held in the Secure Anonymised Information Linkage Databank. Repeat non-attendance was defined as no record of attendance during any 36-month period despite three cycles of annual screening invitations. The associations between repeat non-attendance and potential risk factors were examined using multivariable logistic regression analysis, stratified according to type 1 and type 2 diabetes. RESULTS: A total of 18% with type 1 diabetes (1146/6513) and 8% with type 2 diabetes (12,475/156,525) were repeat non-attenders. Participants attending their very first appointment were least likely to become repeat non-attenders [odds ratio (95% confidence interval)]: type 1 diabetes: 0.12 (0.09, 0.17) and type 2 diabetes: 0.08 (0.07, 0.09). For both types of diabetes, those of a younger age, living in areas of higher deprivation and subject to multiple house moves were at greater risk of becoming repeat non-attenders. CONCLUSION/INTERPRETATION: A more tailored approach is needed for the younger population, those living in areas of higher deprivation and/or undergoing multiple residential relocation and to ensure attendance at their initial appointment to minimise future repeat non-attendance.

Unexpected finding of uniparental disomy mosaicism in term placentas: Is it a common feature in trisomic placentas?

OBJECTIVE: Non-invasive prenatal testing (NIPT) detects placental chromosome aberrations. When amniocentesis reveals a normal karyotype, confined placental mosaicism (CPM) may be assumed. In order to confirm this, placental cytogenetic studies were performed. METHOD: NIPT was conducted in the course of the Dutch TRIDENT study. Placentas of 10 cases with NIPT results indicating an autosomal trisomy and showing a normal (N = 9) or low mosaic karyotype (N = 1) in amniotic fluid (AF) were investigated. The cytotrophoblast as well as the mesenchymal core of two to four placental chorionic villi biopsies were studied with single nucleotide polymorphism (SNP) array. Clinical outcome data were collected. RESULTS: In 10/10 cases, CPM was proven. In 3/10 cases trisomy/uniparental disomy (UPD)/biparental disomy (BPD) mosaicism was discovered. In 2/3 cases, all three cell lines were present in the placenta, whereas BPD was found in AF. In 1/3 cases trisomy 22/UPD22 was present in AF while trisomy 22/BPD22 mosaicism was found in the placenta. Five of 10 pregnancies were affected with pre-eclampsia, low birth weight, preterm delivery, and/or congenital malformations. CONCLUSION: The presence of trisomy/UPD/BPD mosaicism in 3/10 cases that we investigated proves that trisomic zygote rescue may involve multiple rescue events during early embryogenesis. UPD mosaicism, when present in crucial fetal tissues, may explain the abnormal phenotype in undiagnosed cases.

Development and validation of the Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ).

BACKGROUND AND STUDY AIMS: Patient satisfaction is a key indicator of the quality of gastrointestinal (GI) endoscopy. The aim of this study was to develop and validate a specific patient satisfaction questionnaire for patients undergoing GI endoscopy--the Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ). PATIENTS AND METHODS: We developed and validated the GESQ within the context of a national multi-institution nurse endoscopy trial, based in secondary care, in three stages: (1) item generation with a panel of patients and professionals following a detailed literature review to identify the most relevant items from existing scales; (2) development and piloting of a draft questionnaire on a sample of patients referred for GI endoscopy; and (3) testing of the questionnaire within a large multicenter pragmatic randomized trial. We undertook psychometric analysis of the questionnaire to identify the underlying dimensions and assessed the questionnaire for reliability and validity. RESULTS: The final version of the GESQ contains 21 items. Principal components analysis revealed four subscales with high internal consistency: skills and hospital (seven items; Cronbach's alpha 0.83), pain and discomfort during and after endoscopy (four items; Cronbach's alpha 0.84), information before endoscopy (five items; Cronbach's alpha 0.80), and information after endoscopy (five items; Cronbach's alpha 0.76). CONCLUSIONS: The four identified subscales are clinically relevant and correspond to domains of patient satisfaction identified in previous studies. Our development and validation of the GESQ confirmed that it is a valid, reliable, interpretable, and acceptable tool to measure satisfaction in patients who have undergone a GI endoscopy.

Economic evaluation of policy initiatives in the organisation and delivery of healthcare: a case study of gastroenterology endoscopy services.

BACKGROUND: Complex clinical interventions are increasingly subject to evaluation by randomised trial linked to economic evaluation. However evaluations of policy initiatives tend to eschew experimental designs in favour of interpretative perspectives which rarely allow the economic evaluation methods used in clinical trials. As evidence of the cost effectiveness of such initiatives is critical in informing policy, it is important to explore whether conventional economic evaluation methods apply to experimental evaluations of policy initiatives. METHODS: We used mixed methods based on a quasi-experimental design to evaluate a policy initiative whose aim was to expedite the modernisation of gastroenterology endoscopy services in England. We compared 10 sites which had received funding and support to modernise their endoscopy services with 10 controls. We collected data from five waves of patients undergoing endoscopy. The economic component of the study compared sites by levels of investment in modernisation and patients' use of health service resources, time off work and health related quality of life. RESULTS: We found no statistically significant difference between intervention and control sites in investment in modernisation or any patient outcome including health. CONCLUSIONS: This study highlights difficulties in applying the rigour of a randomised trial and associated technique of economic evaluation to a policy initiative. It nevertheless demonstrates the feasibility of using this approach although further work is needed to demonstrate its generalisability in other applications. The present application shows that the small incentives offered to intervention sites did not enhance modernisation of gastroenterology endoscopy services or improve patient outcomes.

Brief lifestyle interventions for prediabetes in primary care: a service evaluation.

BACKGROUND: The increasing number of cases of prediabetes in the UK is concerning, particularly in Wales where there is no standard programme of support. The aim of the current service evaluation was to examine the effectiveness of brief lifestyle interventions on glucose tolerance in people at risk of developing type 2 diabetes. METHODS: In this pragmatic service evaluation clinical data on people deemed at risk of developing type 2 diabetes were evaluated from two GP clusters. Patients (n = 1207) received a single 15 to 30-min, face-to-face, consultation with a health care practitioner. Interventions were assessed by changes in HbA1c and distribution across the HbA1c ranges 12 months following intervention. Statistical significance of reversion to normoglycaemia and development of diabetes were assessed through comparison with expected rates without intervention. RESULTS: Between baseline and 12-month follow-up HbA1c fell from 43.85 ± 1.57 mmol/mol (6.16 ± 0.14%) to 41.63 ± 3.84 mmol/mol (5.96 ± 0.35%), a decrease of 2.22 mmol/mol (0.20%) (95% CI 2.01 (0.18%), 2.42 (0.22%); p < 0.0001). The proportion of people with normal glucose tolerance at 12 months (0.50 95%CI 0.47, 0.52) was significantly larger than the lower (0.06 (p < 0.0001) and the upper (0.19 (p < 0.0001)) estimates based on no intervention. CONCLUSION: Results indicate significant improvement in glucose tolerance across GP clusters. The brief intervention has the potential to offer a robust and effective option to support people at risk of developing type 2 diabetes. Further research in the form of a randomised trial is needed to confirm this and identify those likely to benefit most from this intervention.

Differences in healthcare service utilisation in elderly, registered in eight districts of five European countries.

AIMS: The aim of the study was to compare and analyse the differences in self-reported frequencies of visits paid to physicians and hospitalisation rates, as well as their association with socio-demographic factors and health status self-rated by elderly. METHODS: A cross-sectional study was performed in eight districts of five European countries (Finland, Sweden, Ireland, Croatia, and Greece). A total of 3540 persons aged 70 or more were interviewed by trained interviewers. Healthcare service utilisation and its association with demographic characteristics and self-rated health were analysed using descriptive statistical methods, chi-square test, and logistic regression. RESULTS: Almost 90% of elderly visited a physician in the past year; 50% visited a specialist, while 24% were hospitalised. A visit to a specialist was paid by 70% of the Greek, 50% to 60% of the Croatian, and around 40% of the Irish, the Finnish, and the Swedish elderly. The highest proportion of hospitalisations (32%) was encountered in Greece and the lowest one (20%) in Sweden. Self-rated poor health appears to be the only common denominator associated with increased healthcare utilisation. Younger age stood out as a statistically significant predictor of the likelihood of specialist consults, while older age, male gender, and the synergy of male gender and current single life were disclosed as the predictors of hospitalisation frequency. CONCLUSIONS: Healthcare service utilisation exercised by the elderly across European districts was found to be highly variable and showed a clear distinction between north-western and south-eastern Europe; this is in line with differences in self-rated health.

Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol.

INTRODUCTION: Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%-20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals. We propose to test ustekinumab (STELARA), a targeted and well-tolerated therapy that may halt T-cell and cytokine-mediated destruction of beta-cells in the pancreas at the time of diagnosis. METHODS AND ANALYSIS: This is a double-blind phase II study to assess the safety and efficacy of ustekinumab in 72 children and adolescents aged 12-18 with new-onset T1D.Participants should have evidence of residual functioning beta-cells (serum C-peptide level >0.2nmol/L in the mixed-meal tolerance test (MMTT) and be positive for at least one islet autoantibody (GAD, IA-2, ZnT8) to be eligible.Participants will be given ustekinumab/placebo subcutaneously at weeks 0, 4 and 12, 20, 28, 36 and 44 in a dose depending on the body weight and will be followed for 12 months after dose 1.MMTTs will be used to measure the efficacy of ustekinumab for preserving C-peptide area under the curve at week 52 compared with placebo. Secondary objectives include further investigations into the efficacy and safety of ustekinumab, patient and parent questionnaires, alternative methods for measuring insulin production and exploratory mechanistic work. ETHICS AND DISSEMINATION: This trial received research ethics approval from the Wales Research Ethics Committee 3 in September 2018 and began recruiting in December 2018.The results will be disseminated using highly accessed, peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN14274380.

Evaluating innovations in the delivery and organization of endoscopy services in England and Wales.

This article presents four focus groups conducted with health professionals, part of a mixed-method evaluation of modernization of endoscopy services in England catalyzed by the UK National Health Service Modernisation Agency. Transcripts were analyzed adapting van Manen's "sententious" or "wholistic" approach to thematic analysis. Seven analysts worked to distil lengthy transcripts into summative paragraphs to capture the essentiality of text. Five major themes emerged: lack of senior management understanding and appropriate management systems, inadequate resources, loss of personal autonomy and erosion of professionalism, barriers and facilitators to change, and differences between English and Welsh units-the Welsh perspective. Achieving long-lasting, positive effects of modernization within complex systems demands senior management to actively support innovations, consider staff morale, and provide appropriate levels of funding. However, although professional morale was low, ambition to improve services was strong. The methodological framework offered a comprehensive and applicable approach to data analysis, and our analysis approach was inclusive and collaborative, with far-reaching possibilities for experimental studies and large-scale, mixed-method studies, including trials.

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial.

BACKGROUND: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology--hand-held computers with computerised clinical decision support (CCDS) software--to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. METHODS/DESIGN: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial.Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders.The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. DISCUSSION: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services.In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen. TRIAL REGISTRATION: ISRCTN10538608.

Cost-effectiveness of biennial screening for diabetes related retinopathy in people with type 1 and type 2 diabetes compared to annual screening.

OBJECTIVE: Examine the health and economic impact of extending screening intervals in people with Type 2 diabetes (T2DM) and Type 1 diabetes (T1DM) without diabetes-related retinopathy (DR). SETTING: Diabetic Eye Screening Wales (DESW). STUDY DESIGN: Retrospective observational study with cost-utility analysis (CUA) and Decremental Cost-Effectiveness Ratios (DCER) study. INTERVENTION: Biennial screening versus usual care (annual screening). INPUTS: Anonymised data from DESW were linked to primary care data for people with two prior screening events with no DR. Transition probabilities for progression to DR were estimated based on a subset of 26,812 and 1232 people with T2DM and T1DM, respectively. DCER above £20,000 per QALY was considered cost-effective. RESULTS: The base case analysis DCER results of £71,243 and £23,446 per QALY for T2DM and T1DM respectively at a 3.5% discount rate and £56,822 and £14,221 respectively when discounted at 1.5%. Diabetes management represented by the mean HbA1c was 7.5% for those with T2DM and 8.7% for T1DM. SENSITIVITY ANALYSIS: Extending screening to biennial based on HbA1c, being the strongest predictor of progression of DR, at three levels of HbA1c 6.5%, 8.0% and 9.5% lost one QALY saving the NHS £106,075; £58,653 and £31,626 respectively for T2DM and £94,696, £37,646 and £11,089 respectively for T1DM. In addition, extending screening to biennial based on the duration of diabetes > 6 years for T2DM per QALY lost, saving the NHS £54,106 and for 6-12 and > 12 years for T1DM saving £83,856, £23,446 and £13,340 respectively. CONCLUSIONS: Base case and sensitivity analyses indicate biennial screening to be cost-effective for T2DM irrespective of HbA1c and duration of diabetes. However, the uncertainty around the DCER indicates that annual screening should be maintained for those with T1DM especially when the HbA1c exceeds 80 mmol/mol (9.5%) and duration of diabetes is greater than 12 years.

An evaluation of the appropriateness of advice and healthcare contacts made following calls to NHS Direct Wales.

BACKGROUND: An evaluation of NHS Direct Wales (NHSDW), a national telephone-based healthcare advice and information service, was undertaken. A key objective was to describe the actions of callers and assess the appropriateness of advice and healthcare contacts made following calls, results of which are reported here. METHODS: Postal questionnaires were sent to consecutive callers to NHSDW in May 2002 and February 2004 to determine 1) callers' actions following calls and 2) their views about the appropriateness of: advice given; and when to seek further care. An independent clinical panel agreed and applied a set of rules about healthcare sites where examinations, investigations, treatments and referrals could be obtained. The rules were then applied to the subsequent contacts to healthcare services reported by respondents and actions were classified in terms of whether they had been necessary and sufficient for the care received. RESULTS: Response rates were similar in each survey: 1033/1897 (54.5%); 606/1204 (50.3%), with 75% reporting contacting NHSDW. In both surveys, nearly half of all callers reported making no further healthcare contact after their call to NHSDW. The most frequent subsequent contacts made were with GPs.More than four fifths of callers rated the advice given - concerning any further care needed and when to seek it - as appropriate (further care needed: survey 1: 673/729, 82.3%; survey 2: 389/421, 92.4%; when to seek further care - survey 1: 462/555, 83.2%; survey 2: n = 295/346, 85.3%). A similar proportion of cases was also rated through the rule set and backed up by the clinical panel as having taken necessary and sufficient actions following their calls to NHSDW (survey 1: 624/729, 80.6%; survey 2: 362/421, 84.4%), with more unnecessary than insufficient actions identified at each survey (survey 1: unnecessary 132/729, 17.1% versus insufficient 11/729, 1.4%; survey 2: unnecessary 47/421, 11.0% versus insufficient 14/421, 3.3%). CONCLUSION: Based on NHSDW caller surveys responses and applying a transparent rule set to caller actions a large majority of subsequent actions were assessed as appropriate, with insufficient contacts particularly infrequent. The challenge for NHSDW is to reduce the number of unnecessary contacts made following calls to the service, whilst maintaining safety.

Development of a parent version of the Manchester-Minneapolis quality of life survey for use by parents and carers of UK children: MMQL-UK (PF).

BACKGROUND: Although it is now widely endorsed that children should as far as possible rate their own health related quality of life (HRQL), there are situations where proxy information on child HRQL may be useful, especially where a child is too ill or young to provide their own HRQL assessment. There is limited availability of generic HRQL scales that have a parallel child and parent version and that are reliable, valid, brief, comprehensible and suitable for use in UK populations. The aims of this study were therefore to develop and validate a parent version of the anglicised Manchester-Minneapolis Quality of Life child form (MMQL-UK (CF)) and to determine the level of association between the child and parent versions of this form. METHODS: This study was undertaken concurrently with the anglicisation and validation of the MMQL, a measure of HRQL developed for use with children in North America. At that time, no parent version existed, so the MMQL form for children (MMQL-UK (CF)) was used as the basis for the development of the MMQL-UK parent form (PF). The sample included a control group of healthy children and their parents and five exemplar groups; children diagnosed with asthma, diabetes or inflammatory bowel disease and their parents, children in remission from cancer and their parents and children in public care and their carers. Consistency of the MMQL-UK (PF) components were assessed by calculating Cronbach's alpha. Validation of the parent questionnaire was undertaken by comparing MMQL-UK (PF) component scores with comparable components on the proxy PedsQLtrade mark quality of life scales, comparing MMQL-UK (PF) component scores between parents of healthy and chronic disease children and by comparison of component scores from children and their parents or carers. Reproducibility and responsiveness were assessed by retesting parents by follow-up questionnaires. RESULTS: A total of 874 children (completing MMQL-UK (CF)) and 572 parents or carers (completing MMQL-UK (PF)) took part in the study. The internal consistency of all the MMQL-UK (PF) components exceeding the accepted criterion of 0.70 and the construct validity was good with moderate correlations being evident between comparable components of the MMQL-UK (PF) and the proxy PedsQLtrade mark. Discriminant validity was demonstrated with significant differences being identified between parents of healthy children and those with chronic conditions. Intra-class correlations exceeded 0.65 for all MMQL-UK (PF) components demonstrating good reproducibility. Weak to moderate levels of responsiveness were demonstrated for all but social functioning. The MMQL-UK (PF) showed moderate parent-child correlation with the MMQL-UK (CF) for all components. The best correlations were seen for those components measuring the same construct (Pearson's r ranged from 0.31 to 0.61, p < 0.01 for equivalent components). CONCLUSION: The MMQL-UK (PF) showed moderate to good correlations with the MMQL-UK (CF) component scores. The MMQL-UK (PF) will be of use when comparing child and parent/carer perception of the impact of a child's condition on their HRQL or where the child is too ill or young to provide their own report.

Chorionic gonadotropin can enhance innate immunity by stimulating macrophage function.

Human chorionic gonadotropin (hCG) is a placental glycoprotein, mainly secreted by trophoblasts during pregnancy. Its function in endocrine regulation has been well documented, but its immunological role is still largely unclear. For a successful pregnancy, an effective innate immunity is needed to protect the mother and fetus against infection, while maintaining tolerance against the paternal antigens of the fetus. The aim of this study was to investigate the effect of hCG on the function of macrophages (Mvarphi), which are major players in the innate response. hCG treatment of IFN-gamma-primed Mvarphi resulted in increased production of NO, reactive oxygen species, IL-6 and IL-12p40, and enhanced phagocytosis of apoptotic cells. hCG treatment did not affect the induction of allogeneic T cell proliferation by IFN-gamma-primed Mvarphi. The observed effects were receptor-mediated and involved the protein kinase A signaling pathway, as indicated by blocking studies using specific inhibitors. In vivo thioglycollate-elicited Mvarphi also exhibited increased phagocytic ability upon IFN-gamma activation and hCG treatment. In conclusion, hCG enhances Mvarphi functions involved in innate immunity, while the capacity to stimulate allogeneic T cells remains unchanged.

Real nursing? The development of telenursing.

AIM: This paper is a report of a study to understand the impact of telenursing from the perspective of nurses involved in its provision, and in more traditional roles. BACKGROUND: Nurse-led telephone helplines have recently been introduced across the United Kingdom, a major step in the development of nursing practice. METHOD: A structured questionnaire was sent to all nurses working in the NHS Direct (National Health Service Direct) Wales telephone service (n = 111). Ninety-two completed questionnaires were returned (response rate 83 per cent). Two focus groups were conducted: one with telephone service nurses (n = 8) and one with other nurses (n = 5). The data were collected in 2002. FINDINGS: Respondents represented a highly educated workforce from a range of healthcare specialties. They reported that they joined the telephone service for improved salary and flexible working. Two-thirds reported improved job satisfaction. All focus group participants reported that the development of nursing skills was affected by the use of decision support software and the remote nature of the consultation. Participants reported opportunities for skill development, although the role could be stressful. All agreed that the service was popular with callers, but the nurses from outside raised concerns about whether telenursing was 'real' nursing and about the evidence base for the service and access by disadvantaged groups. CONCLUSION: Differences between the groups reflect policy tensions between the need to develop new nursing skills, including the use of technology, to improve efficiency and recognition of the worth of hands-on nursing. These tensions must be addressed for the telephone service to function as part of an integrated healthcare system.

Proinsulin in the identification and risk stratification of gestational diabetes mellitus: study protocol for a prospective, longitudinal cohort study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common metabolic disorder occurring in up to 10% of pregnancies in the western world. Most women with GDM are asymptomatic; therefore, it is important to screen, diagnose and manage the condition as it is associated with an increased risk of maternal and perinatal complications. Diagnosis of GDM is made in the late second trimester or early third trimester because accurate diagnosis or risk stratification in the first trimester is still lacking. An increase in serum proinsulin may be seen earlier in pregnancy and before a change in glycaemic control can be identified. This study will aim to establish if fasting proinsulin concentrations at 16-18 weeks gestation will help to identify or risk stratify high-risk pregnant women with GDM. METHODS AND ANALYSIS: This is a prospective, longitudinal cohort study. Two oral glucose tolerance tests will be carried out at 16-18 and 24-28 weeks gestation in 200 pregnant women with at least one risk factor for GDM (body mass index>30 kg/m2, previous macrosomic baby (>4.5 kg), previous gestational diabetes, first degree relative with type 2 diabetes mellitus) recruited from antenatal clinics. Blood samples will be taken fasting and at 30 min, 1 and 2 hours following the 75 g glucose load. In addition, a fasting blood sample will be taken 6-weeks post delivery. All samples will be analysed for glucose, insulin, C peptide and proinsulin. Recruitment began in November 2017. Optimal cut-off points for proinsulin to diagnose gestational diabetes according to National Institute for Health and Care Excellence (2015) criteria will be established by the receiver operating characteristic plot and sensitivity and specificity will be calculated to assess the diagnostic accuracy of proinsulin at 16-18 weeks gestation. ETHICS AND DISSEMINATION: This study received ethical approval from the Wales Research Ethics Committee (Panel 6) (Ref. 17/WA/0194). Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN16416602; Pre-results.

Successful development and testing of a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS).

OBJECTIVES: To develop a tool for the accurate reporting and aggregation of findings from each of the multiple methods used in a complex evaluation in an unbiased way. STUDY DESIGN AND SETTING: We developed a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS) within a gastroenterology study [Evaluating New Innovations in (the delivery and organisation of) Gastrointestinal (GI) endoscopy services by the NHS Modernisation Agency (ENIGMA)]. We subsequently tested it on a different gastroenterology trial [Multi-Institutional Nurse Endoscopy Trial (MINuET)]. We created three layers to define the effects, methods, and findings from ENIGMA. We assigned numbers to each effect in layer 1 and letters to each method in layer 2. We used an alphanumeric code based on layers 1 and 2 to every finding in layer 3 to link the aims, methods, and findings. We illustrated analogous findings by assigning more than one alphanumeric code to a finding. We also showed that more than one effect or method could report the same finding. We presented contradictory findings by listing them in adjacent rows of the MATRICS. RESULTS: MATRICS was useful for the effective synthesis and presentation of findings of the multiple methods from ENIGMA. We subsequently successfully tested it by applying it to the MINuET trial. CONCLUSION: MATRICS is effective for synthesizing the findings of complex, multiple-method studies.

Psychometric development of the Gastrointestinal Symptom Rating Questionnaire (GSRQ) demonstrated good validity.

OBJECTIVES: To develop and validate a gastrointestinal (GI) symptom rating questionnaire for patients with luminal GI symptoms including where no diagnosis has been made. STUDY DESIGN AND SETTING: We developed and validated the Gastrointestinal Symptom Rating Questionnaire (GSRQ) in three stages: (1) item generation to identify the relevant items for scale inclusion; (2) development and piloting on patients with a known GI disorder; and (3) testing in a sample of trial patients. We examined the underlying dimensions of the scale, internal consistency, validity, reproducibility, and responsiveness. RESULTS: We identified four interpretable factors on the GSRQ. The GSRQ had good internal consistency (corrected item-subscale correlations between 0.4 and 0.8) and Cronbach's alpha greater than 0.7 for each subscale. Construct validity was demonstrated by modest but significant correlations with the Short Form 36 and the EQ5D index value. We demonstrated good reproducibility with intraclass correlations for test-retest scores between 0.71 and 0.77, and significant responsiveness ratios for all subscales in patients who had improved, and in two of the subscales in patients who had deteriorated. CONCLUSION: The GSRQ could be a useful tool to monitor quality of life in various luminal GI conditions and where a formal diagnosis has not been made.

Development of a short questionnaire to assess the quality of life in Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS: Most of the disease-specific quality of life (QoL) measures for inflammatory bowel disease (IBD) are lengthy and time consuming. None have been established for routine use in clinical practice. We designed this study to develop a short QoL measure in IBD. METHODS: A 32-item questionnaire, the Crohn's and ulcerative colitis questionnaire (CUCQ)-32 was developed by reviewing the literature of the previously validated questionnaires and by consultation with patients and experts. Construct validity was carried out using the Short Form 12 and the EuroQol 5 dimensions questionnaires and two disease severity measures (the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw Index). Test-retest analysis was done by asking patients to complete the CUCQ questionnaire twice within a period of two weeks. RESULTS: Data were obtained from 205 patients with IBD who completed the CUCQ-32. Psychometric analysis showed that Cronbach's α was 0.88, item-total correlations were good, and there were no ceiling or flooring effects. Stepwise regression identified eight items that accounted for >95% of the variance in the CUCQ-32. The resulting CUCQ-8 demonstrated good internal consistency (Cronbach's α = 0.84), had good reproducibility (intraclass correlation coefficient = 0.94), was well correlated with the EuroQol 5 dimensions questionnaire (r = 0.58) and the Short Form-12 (r = 0.65 for physical component and r = 0.63 for mental component), and was responsive to change (responsiveness ratio was 0.64, p-value < 0.05). CONCLUSIONS: CUCQ-8 is a short questionnaire that has the potential to be an efficient tool for assessing the QoL of all patients with IBD in clinical practice.