Population Health Management in Diabetes Care: Combining Clinical Audit, Risk Stratification, and Multidisciplinary Virtual Clinics in a Community Setting to Improve Diabetes Care in a Geographically Defined Population. An Integrated Diabetes Care Pilot in the North East Locality, Oxfordshire, UK.

BACKGROUND: Disparities in diabetes care are prevalent, with significant inequalities observed in access to, and outcomes of, healthcare. A population health approach offers a solution to improve the quality of care for all with systematic ways of assessing whole population requirements and treating and monitoring sub-groups in need of additional attention. DESCRIPTION OF THE CARE PRACTICE: Collaborative working between primary, secondary and community care was introduced in seven primary care practices in one locality in England, UK, caring for 3560 patients with diabetes and sharing the same community and secondary specialist diabetes care providers. Three elements of the intervention included 1) clinical audit, 2) risk stratification, and 3) the multi-disciplinary virtual clinics in the community. METHODS: This paper evaluates the acceptability, feasibility and short-term impact on primary care of implementing a population approach intervention using direct observations of the clinics and surveys of participating clinicians. RESULTS AND DISCUSSION: Eighteen virtual clinics across seven teams took place over six months between March and July 2017 with organisation, resources, policies, education and approximately 150 individuals discussed. The feedback from primary care was positive with growing knowledge and confidence managing people with complex diabetes in primary care. CONCLUSION: Taking a population health approach helped to identify groups of people in need of additional diabetes care and deliver a collaborative health intervention across traditional organisational boundaries.

Menu engineering to encourage sustainable food choices when dining out: An online trial of priced-based decoys.

Menu-based 'nudges' hold promise as effective ways to encourage a shift away from ruminant meat and towards more environmentally friendly plant-based food when dining out. One example of a menu-based nudge is including an inferior 'decoy' option to existing items on menus. Decoys have been shown to influence decision-making in other domains (e.g. Lichters, Bengart, Sarstedt, & Vogt, 2017), but have yet to be used to promote sustainable food choices. Two online randomized controlled trials tested whether the addition of higher priced 'decoy' vegetarian options on menus influenced the number of diners choosing a 'target' vegetarian option. Adjusted Generalized Estimating Equations on data from four menu conditions showed no main effect of the intervention in study 1 (decoy absent vs. decoy present; Odds Ratio (OR) 1.08 95% Confidence Interval (CI) 0.45 to 2.57). Replicating the trial in study 2 across seven menu conditions and testing a more expensive decoy also showed no main effect of the intervention decoy absent vs. decoy present; OR 0.68 (95% CI 0.41 to 1.12). Further analyses revealed that our price-based decoy strategy (a 30% price increase) did not significantly influence the number of people choosing the inferior decoy dish, possibly because dish choices were purely hypothetical. Further research is needed to clarify which attributes of a dish (e.g. taste, portion size, signature ingredients etc.) are optimal candidates for use as decoys and testing these in real world choice contexts.

A Modified AUGIS Delphi Process to Establish Future Research Priorities in Benign Upper Gastrointestinal Surgery.

BACKGROUND: The aim of our study was to use a modified Delphi process to determine the research priorities amongst benign upper gastrointestinal (UGI) surgeons in the United Kingdom. METHODS: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland were invited to submit individual research questions via an online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high-priority research questions. RESULTS: Four hundred and twenty-seven questions were submitted in phase I, and 51 with a benign UGI focus were taken forward for prioritisation in phase II. Twenty-eight questions were ranked in phase III. A final list of 11 high-priority questions had an emphasis on acute pancreatitis, Barrett's oesophagus and benign biliary disease. CONCLUSION: A modified Delphi process has produced a list of 11 high-priority research questions in benign UGI surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research.

[EndoStim® treatment-a new minimally invasive technology in antireflux surgery]. / EndoStim®-Therapie ­ eine neue minimal-invasive Technologie in der Antirefluxchirurgie.

BACKGROUND: The symptoms of gastroesophageal reflux disease (GERD) are very common. Despite the fact that 40% of patients continue to suffer under conservative treatment, only approximately 1% of affected patients are operated on in Germany. Until recently, antireflux surgery was performed nearly exclusively in the form of a Nissen fundoplication or a Toupet hemifundoplication. These methods are still considered the gold standard. A new surgical minimally invasive procedure is described which treats reflux symptoms through electrical neuromodulation of the lower esophageal sphincter (LES). METHOD: An electrical neuromodulator for the LES (EndoStim®, EndoStim BV, Nijmegen, The Netherlands) is implanted into the abdominal wall as a pulse generator (IPG) and connected via an electrode cable to a pair of electrodes on the lower esophageal sphincter. In our own setting, patients are selected for this procedure after extensive functional diagnostics in the context of an interdisciplinary expert conference. The patient selection, patient education, required surgical training, surgical technique, postoperative phase as well as the results, complications and side effects are described. CONCLUSION: Electrical neuromodulation is a technique that successfully provides patients with GERD with control of their reflux symptoms. The technique requires interdisciplinary patient selection, comprehensive patient education, and comprehensive surgical training. The method is not free of postoperative problems. The electrical neuromodulation of the LES should therefore be used especially in centers with high expertise in reflux therapy.

UK guidelines on oesophageal dilatation in clinical practice

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques-including stents-will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.

The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.

BACKGROUND: Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. METHODS: In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. RESULTS: A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. CONCLUSIONS: Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.

Reasons for non-participation in a primary care-based physical activity trial: a qualitative study.

OBJECTIVES: To explore reasons for non-participation in a primary care-based physical activity trial and understand how these may contribute to recruitment of non-representative research samples. We also aimed to elicit non-participants' own recommendations for enhancing trial uptake in primary care. DESIGN: Semistructured telephone interviews with non-participants to a randomised controlled trial of a very brief intervention for promoting physical activity conducted in primary care (the Very Brief Interventions trial), with thematic analysis of interview transcripts. SETTING: 5 general practice (GP) surgeries in the East of England, UK. PARTICIPANTS: Interviews were completed with 10 female and 6 male non-participants of white ethnicity and aged between 40 and 71 years. 13 of the 16 interviewees were either active or moderately active according to the GP Physical Activity Questionnaire (GPPAQ). RESULTS: Interviewees discussed a range of reasons for non-participation. These included beliefs surrounding the personal relevance of the trial based on preconceptions of intervention content. Many interviewees considered themselves either sufficiently active or too functionally limited to increase activity levels further, so rendering participation pointless in their view. Other identified barriers included a lack of free time, for trial participation and for increasing physical activity, and dissatisfaction with appointment scheduling systems in place at GP surgeries. Interviewees questioned the appropriateness of primary care as a context for delivering interventions to promote physical activity. In general, interviewees were positively disposed towards the idea of trial participation, especially if personal benefits are made salient, but suggested that interventions could be delivered in a different setting such as the internet. CONCLUSIONS: To increase participation in physical activity promotion trials conducted in primary care, the content of invitation materials and procedures for contacting potential participants require reconsideration. Specific recommendations include streamlining intervention materials and enhancing their relevance to the health concerns of invitees. TRIAL REGISTRATION NUMBER: ISRCTN72691150; Pre-results.

Exploring equity in primary-care-based physical activity interventions using PROGRESS-Plus: a systematic review and evidence synthesis.

BACKGROUND: Little is known about equity effects in primary care based physical activity interventions. This review explored whether differences in intervention effects are evident across indicators of social disadvantage, specified under the acronym PROGRESS-Plus (place of residence, race/ethnicity, occupation, gender, religion, education, social capital, socioeconomic status, plus age, disability and sexual orientation). METHODS: Six bibliographic databases were systematically searched for randomised controlled trials (RCTs) of physical activity interventions conducted in primary care. Harvest plots were used to synthesize findings from RCTs reporting subgroup or interaction analyses examining differences in intervention effects across levels of at least one PROGRESS-Plus factor. RESULTS: The search yielded 9052 articles, from which 173 eligible RCTs were identified. Despite PROGRESS-Plus factors being commonly measured (N = 171 RCTs), differential effect analyses were infrequently reported (N = 24 RCTs). Where reported, results of equity analyses suggest no differences in effect across levels or categories of place of residence (N = 1RCT), race (N = 4 RCTs), education (N = 3 RCTs), socioeconomic status (N = 3 RCTs), age (N = 16 RCTs) or disability (N = 2 RCTs). Mixed findings were observed for gender (N = 22 RCTs), with some interventions showing greater effect in men than women and others vice versa. Three RCTs examined indicators of social capital, with larger post-intervention differences in physical activity levels between trial arms found in those with higher baseline social support for exercise in one trial only. No RCTs examined differential effects by participant occupation, religion or sexual orientation. CONCLUSION: The majority of RCTs of physical activity interventions in primary care record sufficient information on PROGRESS-Plus factors to allow differential effects to be studied. However, very few actually report details of relevant analyses to determine which population subgroups may stand to benefit or be further disadvantaged by intervention efforts.

Laparoscopic alternatives to fundoplication for gastroesophageal reflux: the role of magnetic augmentation and electrical stimulation of the lower esophageal sphincter.

Reflux symptoms are very common, and despite modern medication they are a major cause of disease burden and loss of quality of life worldwide. Laparoscopic anti-reflux surgery is the only current effective alternative but suffers from the risks of long-term side effects. Surgery also suffers variation in standards and outcomes. Magnetic augmentation and electrical stimulation of the lower esophageal sphincter represent promising innovative procedures in the field.

Exploring equity in uptake of the NHS Health Check and a nested physical activity intervention trial.

BACKGROUND: Socio-demographic factors characterizing disadvantage may influence uptake of preventative health interventions such as the NHS Health Check and research trials informing their content. METHODS: A cross-sectional study examining socio-demographic characteristics of participants and non-participants to the NHS Health Check and a nested trial of very brief physical activity interventions within this context. Age, gender, Index of Multiple Deprivation (IMD) and ethnicity were extracted from patient records of four General Practices (GP) in England. RESULTS: In multivariate analyses controlling for GP surgery, the odds of participation in the Health Check were higher for older patients (OR 1.05, 95% CI 1.04-1.07) and lower from areas of greater deprivation (IMD Quintiles 4 versus 1, OR 0.37, 95% CI 0.18-0.76, 5 versus 1 OR 0.42, 95% CI 0.20-0.88). Older patients were more likely to participate in the physical activity trial (OR 1.04, 95% CI 1.02-1.06). CONCLUSIONS: Younger patients and those living in areas of greater deprivation may be at risk of non-participation in the NHS Health Check, while younger age also predicted non-participation in a nested research trial. The role that GP-surgery-specific factors play in influencing participation across different socio-demographic groups requires further exploration.

Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies.

BACKGROUND: Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety. AIM: To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies. METHODS: Safety data were collected from patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and changes in laboratory variables were analysed. RESULTS: Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12 , folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the first year. CONCLUSION: No major safety concerns arose during 5-12 years of continuous PPI therapy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

Comparison of three competing dynamic force spectroscopy models to study binding forces of amyloid-ß (1-42).

We performed single molecule dynamic force spectroscopy experiments to study the dimerization of two amyloid-ß (1-42) peptides and compared three different theoretical models used to fit experimental data: Bell-Evans, Dudko-Hummer-Szabo, and Friddle-De Yoreo. Using these models we extracted values of the dissociation rate at zero force, k0, and height and the width of the energy barrier, ΔG and xß. We show the importance of including the effect of the linker molecule. All three models corrected for the linker effect give comparable results for xß and show more discrepancy for k0 and ΔG values, ΔG parameter correlates well between Dudko-Hummer-Szabo and Friddle-De Yoreo models but differs for the Bell-Evans model.

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography (COGNATE): report of pragmatic randomised trial.

BACKGROUND: Endoscopic ultrasonography is recommended for staging gastro-oesophageal cancers, but has never been evaluated. OBJECTIVE: COGNATE (Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography) therefore aimed to evaluate whether adding 'endoscopic ultrasound' (EUS) to the usual staging algorithm changes treatment, improves (quality-adjusted) survival, and uses resources cost-effectively. DESIGN: Pragmatic parallel-group trial. Patients with gastro-oesophageal cancer received standard staging algorithms. Multidisciplinary teams chose provisional management plans from endoscopic mucosal resection, immediate surgery, surgery after chemotherapy, or chemotherapy and radiotherapy. We used dynamic randomisation to allocate consenting patients remotely by telephone in equal proportions between EUS and not. Thereafter we recorded changes in management plan, use of health-care resources, and three aspects of participant-reported quality of life: generic [measured by European Quality of Life - 5 Dimensions (EQ-5D)], cancer related [Functional Assessment of Cancer Therapy - General scale (FACT-G)] and condition-specific [FACT - Additional Concerns scale (FACT-AC)]. We followed participants regularly until death or the end of the trial - for between 1 and 4.5 years. We devised a quality assurance programme to maintain standards of endosonographic reporting. SETTING: Eight British hospitals, of which two - one Scottish teaching hospital and one English district general hospital - contributed 80% of participants; we combined the other six for analysis. PARTICIPANTS: Patients were eligible if they had a diagnosis of gastro-oesophageal cancer, had not started treatment, were free of metastatic disease, were fit for surgery (even if not planned) and had American Society of Anesthesiologists and World Health Organization grades of less than 3. INTERVENTIONS: Intervention group: standard staging algorithm plus EUS; control group: standard staging algorithm. MAIN OUTCOME MEASURES: Primary: quality-adjusted survival. Secondary: survival; health-related quality of life (EQ-5D, FACT-G and FACT-AC scales); changes in management plan; and complete resection rate. Although blinding participants was neither possible nor desirable, those responsible for analysis remained blind until the Trial Steering Committee had reviewed the definitive analysis. RESULTS: We randomised 223 patients, of whom 213 yielded enough data for primary analysis. EUS improved survival adjusted for generic quality of life with a hazard ratio of 0.705 [95% confidence interval (CI) 0.499 to 0.995], and crude survival with a hazard ratio of 0.706 (95% CI 0.501 to 0.996). The benefits of EUS were significantly greater for those with poor initial quality of life, but did not differ between centres. EUS reduced net use of health-care resources by £2860 (95% 'bootstrapped' CI from -£2200 to £8000). Combining benefits and savings shows that EUS is likely to be cost-effective, with 96% probability of achieving the National Institute for Health and Care Excellence criterion of costing of < £20,000 to gain a QALY. There were no serious adverse reactions attributable to EUS. EUS enhanced the management plan for many participants, increased the proportion of tumours completely resected from 80% (44 out of 55) to 91% (48 out of 53), and improved the survival of those who changed plan; although underpinning the significant differences in outcome, none of these process differences was itself significant. CONCLUSION: Endoscopic ultrasound significantly improves (quality-adjusted) survival, has the potential to reduce health-care resource use (not statistically significant) and is probably cost-effective (with 96% probability). We recommend research into the best time to evaluate new technologies. TRIAL REGISTRATION: ISRCTN1444215. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 39. See the HTA programme website for further project information.

Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy: results of a 5-year follow-up in the LOTUS trial.

BACKGROUND: Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals. AIMS: To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266). METHODS: Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy. RESULTS: Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P < 0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P < 0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P < 0.05), accompanied by a marginal decrease in gastrin and chromogranin. CONCLUSIONS: Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.

Outcome of patients in laparoscopic training courses compared to standard patients.

BACKGROUND & AIM: Current Laparoscopic simulators have limited usefulness and patients have been used for training since the dawn of surgery. NUGITS (Northumbrian Upper Gastro Intestinal Team of Surgeons) Laparoscopic Skills courses utilise hands-on experience with simulators moving to live operating on volunteer patients. It is vital to know that the volunteer patient is not disadvantaged by greater surgical risk. METHODS: This was a case-controlled prospective comparison of patients undergoing both Laparoscopic Cholecystectomy (LC) [n=51] and Laparoscopic Inguinal Hernia (LIH) [n=62] during NUGITS training courses. They are compared with a matched (age, sex and ASA grade) control group LC (n=51) and LIH (n=62) operated on by consultants. The outcome measures were surgical peri-and post-operative complications, post-operative hospital stay, readmission and early recurrence of inguinal hernia (<6 months). RESULTS: In the LC cohort, there was no significant difference in the length of hospital stay (p=0.07) or readmission (p=0.16) in both the groups. The mean operating time was higher in the trainee compared to the control group (p=0.001). There was no difference in the post-operative morbidity or mortality in either group. In LIH cohort, the mean operating time was higher in the trainee compared with the control group. There was no significant difference in post-operative complications (p>0.05) and early post-operative recurrence of hernia (p>0.05). CONCLUSION: The post-operative outcomes of patients undergoing laparoscopic surgery during laparoscopic training courses are similar to consultant-operated patients. Thus, it is acceptable and safe to encourage patients to volunteer for laparoscopic training courses.