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.

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.

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.

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.

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.

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.

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.

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.

Is informed choice in prenatal testing universally valued? A population-based survey in Europe and Asia.

OBJECTIVE: Informed choice has become an integral part of healthcare provision. We investigated the extent to which informed choice in the context of prenatal testing is universally valued. DESIGN: The value attached to parental choice in prenatal testing and the perceived importance of significant others' views when making test decisions were assessed in a cross-sectional, descriptive study. SAMPLE AND SETTING: Male and female participants from general population samples in six countries: the UK (n = 210), the Netherlands (n = 197), Italy (n = 200), Greece (n = 200), China (n = 200) and India (n = 199). METHODS: The questionnaires assessed values attached to parental involvement and the perceived importance of the views of significant others when making prenatal test decisions. MAIN OUTCOME MEASURES: Attitudes towards parental choice and attitudes towards the importance of others' views were analysed by age, gender and education using Chi-squared tests, Analysis of Variances and multiple logistic regression. RESULTS: The majority of respondents from Northern European countries believed that undergoing prenatal tests should reflect parental choice. Conversely, only a minority of respondents from Southern European and Asian countries advocated parental choice, with most expressing the belief that all pregnant women should have the procedure. The perceived importance of significant others' views when making test decisions also varied across countries: those in favour of parental choice perceived others' views as less important in the test decision. A preference for prenatal testing decisions to reflect an informed choice was predicted by (i) country and (ii) the perceived importance of significant others' views. Education, age and gender did not predict decisions. CONCLUSION: The implications of these findings for policy and practice depend upon whether placing a low value on parental choice, but a high value on the others' views regarding prenatal testing is considered an informed choice. Further research is needed to determine whether cultural variation in values remains significant in a multicultural society.

Day-case laparoscopic Nissen fundoplication.

INTRODUCTION: Nissen fundoplication has been performed laparoscopically for over 15 years, being associated with shorter hospital stay and fewer complications than conventional open surgery with good long-term outcomes. Day-case laparoscopic Nissen fundoplication (LNF) is rarely performed in the UK and most series in the literature report length of stay >2 days. METHODS: The objective of this study was to examine the safety and efficacy of day-case LNF. The clinical records of all patients undergoing LNF under the care of three surgeons in a district general hospital (DGH) during a 5-year period (January 2003 to December 2007) were reviewed to examine length of stay, complications, length of procedure, grade of operating surgeon and symptoms on follow-up. RESULTS: One hundred thirteen day-case LNFs were recorded in this series. Day-case LNF patients had median age of 45 years (range 20-68 years, 65% (64.6%) male) and 98% were American Society of Anesthesiologists (ASA) grade I or II. Twenty-one cases (19%) were performed by higher surgical trainees. Median operative time was 54 minutes (range 25-120 min). Only one perioperative complication (port-site bleed) occurred, treated without prolonging length of stay. The proportion of all LNF performed as day cases increased from 8% to 52% during the study period. Median operative time has significantly reduced from the first 20 consecutive LNF cases to the latest 20 cases [65 min (range 40-120 min) versus 48 min (range 25-72 min); p = 0.037]. At follow-up (median 7 weeks, range 2-31 weeks) 82% of patients had improvement in all presenting symptoms. Eight patients had postoperative complications [wound infection (n = 2), persistent regurgitation requiring laparoscopic division of a gastric band adhesion (n = 1), dysphagia (n = 5 with two patients requiring redo partial fundoplication and one patient requiring dilatation) and there were no conversions to open surgery. CONCLUSION: Day-case LNF is safe and effective for treating selected patients with gastroesophageal reflux disease (GERD) in a DGH. The proportion of day-case LNFs is increasing in our unit. Half of the LNFs in a DGH can be done as day cases. Experience is associated with a significant reduction in operative time.

Is the etiology of eosinophilic esophagitis in adults a response to allergy or reflux injury? Study of cellular proliferation markers.

Recent research suggests that allergy may be the key factor in the etiology of eosinophilic esophagitis (EE); however, historically, the condition was hypothesized as related to reflux injury to the esophageal mucosa. We studied this hypothesis by comparing markers of inflammation and cellular proliferation in EE and reflux esophagitis. Lower esophageal biopsies of adult patients with EE (n = 10), reflux esophagitis (n = 8), and normal controls (n = 13) were assessed quantitatively for the expression of the cyclooxygenase-2 (COX-2) enzyme, cellular proliferation, and oncogenic resistance to apoptosis using monoclonal antibodies for COX-2, Ki-67, and Bcl-2, respectively. Normal esophageal epithelium demonstrated weak diffuse uptake of COX-2 stain in the basal layer. No COX-2 expression was demonstrated in the EE group, significantly less than the control and reflux groups (P < 0.01 and P < 0.001, respectively). Cellular proliferation measured by Ki-67 expression was higher in EE and reflux compared with control (P < 0.001 and P < 0.01). Ki-67 expression, and thus degree of hyperplasia, appeared greater in EE than reflux, but was not statistically significant (P = 0.228). The degree of apoptosis was similar in all study groups. EE and reflux esophagitis are proliferative conditions expressing Ki-67 in higher concentrations than control. Mucosal proliferation in reflux esophagitis is COX-2 dependent. This novel research in EE has demonstrated downregulation of COX-2 expression compared with reflux esophagitis and control. We hypothesize that the allergy-related cytokine IL-13 known to inhibit COX-2 expression and found in high concentrations in EE as responsible for this. The pathogenesis of EE is likely dependent on allergy rather than reflux injury to the esophagus.

Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: a 3-year interim analysis of the LOTUS trial.

BACKGROUND: With the introduction of laparoscopic antireflux surgery (LARS) for gastro-oesophageal reflux disease (GORD) along with the increasing efficacy of modern medical treatment, a direct comparison is warranted. The 3-year interim results of a randomised study comparing both the efficacy and safety of LARS and esomeprazole (ESO) are reported. METHODS: LOTUS is an open, parallel-group multicentre, randomised and controlled trial conducted in dedicated centres in 11 European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg once daily, which could be increased stepwise to 40 mg once daily and then 20 mg twice daily in the case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan-Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol. RESULTS: 554 patients were randomised, of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the intention to treat population, p = 0.25 (90% vs 95% per protocol). No major unexpected postoperative complications were experienced and ESO was well tolerated. However, postfundoplication complaints remain a problem after LARS. CONCLUSIONS: Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous ESO treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD.

Day case emergency laparoscopic appendectomy.

BACKGROUND: Laparoscopic appendectomy (LA) is associated with a shorter hospital stay and fewer complications than conventional open appendectomy (OA). This study aimed to examine the safety and efficacy of day case emergency LA. METHODS: The records of patients undergoing emergency LA under the care of two laparoscopic surgeons over a 3-year period (Februrary 2003 to February 2006) were reviewed to examine hospital length of stay (LOS), complications, histology, grade of the operating surgeon, and time required to perform the procedure. RESULTS: A total of 104 patients (median age, 25 years; range, 11-72 years; 58 men) underwent LA, with 9 and 66 patients discharged in 8 and 24 hours, respectively (median LOS 22 hours: range 6-170 hours). One patient underwent conversion to OA. Histologically, 86 patients had appendicitis and 18 had normal appendices with another pathology present. The median operative time was 35 min (range, 20-80 min). The complications included three wound infections and two pelvic abscesses not requiring further operative intervention. CONCLUSION: Day case emergency LA is safe and effective for treating selected patients.

[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.

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.

A taxonomic re-appraisal of Sarcocystis nesbitti (Protozoa: Sarcocystidae) from the monkey Macaca fascicularis in Yunnan, PR China.

The first detection of Sarcocystis nesbitti Mandour, 1969 in the Chinese mainland is reported and the morphology of the sarcocyst is described in detail. The parasite was detected in the monkey, Macaca fascicularis, maintained on a monkey farm in Yunnan Province; the infection may have occurred via faecal contamination from local rats, mice and/or birds. S. nesbitti was characterized as follows: a macroscopic sarcocyst, length of the cyst up to 2 mm; cyst wall smooth, thin and no perpendicular protrusion is seen under the light microscope; border of cyst wall wavy, primary cyst wall thin (38-65 nm) and invaginated; ground substance about 0.5-0.76 microm thick with electron-dense granules and concentric spherical bodies. The cyst wall is described as type 1 by electron microscopy. It is suspected that S. nesbitti may utilize Macaca mulatta, M. fascicularis, Cercocebus atys, and Papio papionis, as well as human as intermediate hosts. The taxonomy of S. nesbitti is re-appraised in the light of a consideration of possible experimental artefacts and examination of the past literature. Evidence is presented that S. nesbitti may be one of the species infecting humans in South Asia and that the monkey may be a potential reservoir host.

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).