Systematic review and meta-analysis: the incidence and prevalence of paediatric coeliac disease across Europe.

BACKGROUND: Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. AIM: To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. METHODS: Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. RESULTS: The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages <5 years. CONCLUSIONS: Paediatric coeliac disease incidence and prevalence have risen across Europe and appear highest in Scandinavia, Finland and Spain. The most recent evidence shows large increases in incidence in most regions, but stabilisation in some (notably Sweden and Finland). Sharp increases in the age at diagnosis may reflect increases in milder and asymptomatic cases diagnosed since reliable serology testing became widely used, through endomysial antibodies after 1990 and tissue transglutaminase antibodies around 2000.

Protocol for a multicentre randomised feasibility trial evaluating early Surgery Alone In LOw Rectal cancer (SAILOR).

INTRODUCTION: There are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence. Advances in MRI-guided prediction of resection margin status and improvements in abdominoperineal excision of the rectum (APER) technique supports a reassessment of the contribution of preoperative RT. A more selective approach to RT may be appropriate given the associated toxicity. METHODS AND ANALYSIS: This trial will explore the feasibility of a definitive trial evaluating the omission of RT in resectable low rectal cancer requiring APER. It will test the feasibility of randomising patients to (1) standard care (neoadjuvant long course RT±chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy over 5 weeks as current standard, with restaging and surgery after 8-12 weeks. Recruitment will be for 24 months with a minimum 12-month follow-up. OBJECTIVES: Objectives include testing the ability to recruit, consent and retain patients, to quantify the number of patients eligible for a definitive trial and to test feasibility of outcomes measures. These include locoregional recurrence rates, distance to circumferential resection margin, toxicity and surgical complications including perineal wound healing, quality of life and economic analysis. The quality of MRI staging, RT delivery and surgical specimen quality will be closely monitored. ETHICS AND DISSEMINATION: The trial is approved by the Regional Ethics Committee and Health Research Authority (HRA) or equivalent. Written informed consent will be obtained. Serious adverse events will be reported to Swansea Trials Unit (STU), the ethics committee and trial sites. Trial results will be submitted for peer review publication and to trial participants. TRIAL REGISTRATION NUMBER: ISRCTN02406823.

Colectomy rates in patients with ulcerative colitis following treatment with infliximab or ciclosporin: a systematic literature review.

This review aimed to compile all available published data on colectomy rates following treatment using infliximab or ciclosporin in adult ulcerative colitis patients and to analyse colectomy rates, timing to colectomy and postcolectomy mortality for each treatment. We systematically reviewed the literature after 1990 reporting colectomy rates in ulcerative colitis patients treated with infliximab or ciclosporin, excluding articles on paediatric patients, patients with indeterminate colitis or Crohn's disease and bowel surgery not related to ulcerative colitis. We presented weighted mean colectomy rates and mortality rates. Cox's regression was used to assess time to colectomy adjusting for colitis severity, patient age and sex. We tabulated 78 studies reporting on ciclosporin and/or infliximab and colectomy rates or postcolectomy mortality rates. Not all studies reported data in a standardized manner. Infliximab had a significantly lower colectomy rate than ciclosporin at 36 months when analysing all studies, studies directly comparing infliximab and ciclosporin and studies using severe colitis patients, but not at 3, 12 or 24 months. Severity and age were key indicators in the likelihood of undergoing colectomy after treatment. Postcolectomy mortality rates were less than 1.5% for both drugs. This review indicates that long-term colectomy rates following infliximab are significantly lower than ciclosporin in the longer term, and that postcolectomy mortality following infliximab and ciclosporin is very low. However, many key data items were missing from research articles, reducing our ability to establish with more confidence the actual impact of these two drugs on colectomy rates and postcolectomy mortality rates.

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.

The impact of social deprivation on mortality following acute myocardial infarction, stroke or subarachnoid haemorrhage: a record linkage study.

BACKGROUND: The impact of social deprivation on mortality following acute myocardial infarction (AMI), stroke and subarachnoid haemorrhage (SAH) is unclear. Our objectives were, firstly, to determine, for each condition, whether there was higher mortality following admission according to social deprivation and secondly, to determine how any higher mortality for deprived groups may be correlated with factors including patient demographics, timing of admission and hospital size. METHODS: Routinely collected, linked hospital inpatient, mortality and primary care data were analysed for patients admitted as an emergency to hospitals in Wales between 2004 and 2011 with AMI (n = 30,663), stroke (37,888) and SAH (1753). Logistic regression with Bonferroni correction was used to examine, firstly, any significant increases in mortality with social deprivation quintile and, secondly, the influence of patient demographics, timing of admission and hospital characteristics on any higher mortality among the most socially deprived groups. RESULTS: Mortality was 14.3 % at 30 days for AMI, 21.4 % for stroke and 35.6 % for SAH. Social deprivation was significantly associated with higher mortality for AMI (25 %; 95 % CI = 12 %, 40 %) higher for quintile V compared with I), stroke (24 %; 14 %, 34 %), and non-significantly for SAH (32 %; -7 %, 87 %). The higher mortality at 30 days with increased social deprivation varied significantly according to patient age for AMI patients and time period for SAH. It was also highest for both AMI and stroke patients, although not significantly for female patients, for admissions on weekdays and during autumn months. CONCLUSIONS: We have demonstrated a positive association between social deprivation and higher mortality following emergency admissions for both AMI and stroke. The study findings also suggest that the influence of patient demographics, timing of admission and hospital size on social inequalities in mortality are quite similar for AMI and stroke.

Mortality following Stroke, the Weekend Effect and Related Factors: Record Linkage Study.

BACKGROUND: Increased mortality following hospitalisation for stroke has been reported from many but not all studies that have investigated a 'weekend effect' for stroke. However, it is not known whether the weekend effect is affected by factors including hospital size, season and patient distance from hospital. OBJECTIVE: To assess changes over time in mortality following hospitalisation for stroke and how any increased mortality for admissions on weekends is related to factors including the size of the hospital, seasonal factors and distance from hospital. METHODS: A population study using person linked inpatient, mortality and primary care data for stroke from 2004 to 2012. The outcome measures were, firstly, mortality at seven days and secondly, mortality at 30 days and one year. RESULTS: Overall mortality for 37 888 people hospitalised following stroke was 11.6% at seven days, 21.4% at 30 days and 37.7% at one year. Mortality at seven and 30 days fell significantly by 1.7% and 3.1% per annum respectively from 2004 to 2012. When compared with week days, mortality at seven days was increased significantly by 19% for admissions on weekends, although the admission rate was 21% lower on weekends. Although not significant, there were indications of increased mortality at seven days for weekend admissions during winter months (31%), in community (81%) rather than large hospitals (8%) and for patients resident furthest from hospital (32% for distances of >20 kilometres). The weekend effect was significantly increased (by 39%) for strokes of 'unspecified' subtype. CONCLUSIONS: Mortality following stroke has fallen over time. Mortality was increased for admissions at weekends, when compared with normal week days, but may be influenced by a higher stroke severity threshold for admission on weekends. Other than for unspecified strokes, we found no significant variation in the weekend effect for hospital size, season and distance from hospital.

Mortality following acute pancreatitis: social deprivation, hospital size and time of admission: record linkage study.

BACKGROUND: Very little is known about whether mortality following acute pancreatitis may be influenced by the following five factors: social deprivation, week day of admission, recruitment of junior doctors in August each year, European Working Time Directives (EWTDs) for junior doctors' working hours and hospital size. The aim of this study was to establish how mortality following acute pancreatitis may be influenced by these five factors in a large cohort study. METHODS: Systematic record linkage of inpatient, mortality and primary care data for 10 589 cases of acute pancreatitis in Wales, UK (population 3.0 million), from 1999 to 2010. The main study outcome measure was mortality at 60 days following the date of admission. RESULTS: Mortality was 6.4% at 60 days. There was no significant variation in mortality according to social deprivation or the week day of admission. There was also no significant variation according to calendar month for acute pancreatitis overall or for gallstone aetiology, but for alcoholic acute pancreatitis, mortality was increased significantly by 93% for admissions during the months of August and September and 102% from August to October when compared with all other calendar months. Mortality was increased significantly for alcoholic aetiology in August 2004, the official month that the first EWTD was implemented, but there were no other increases following the first or second EWTDs. There were also indications of increased mortality in large hospitals when compared with small hospitals, for acute pancreatitis overall and for gallstone aetiology but not for alcoholic acute pancreatitis, although these increases in mortality were of quite marginal significance. CONCLUSIONS: Although we found some evidence of increased mortality for patients admitted with alcoholic acute pancreatitis during August to October, in August 2004, and in large hospitals for acute pancreatitis overall and for gallstone aetiology, the study factors had limited impact on mortality following acute pancreatitis and no significant impact when adjusted for multiple comparisons.

Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT).

INTRODUCTION: Many patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC. METHODS AND ANALYSIS: Between May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants' scores, analysed by Cox regression. Secondary outcome measures include: the CCQ-an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures-EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants' views on therapies for acute severe UC and healthcare professionals' views on the two drugs and their administration. ETHICS AND DISSEMINATION: The Research Ethics Committee for Wales has given ethical approval (Ref. 08/MRE09/42); each participating Trust or Health Board has given NHS Reseach & Development approval. We plan to present trial findings at international and national conferences and publish in high-impact peer-reviewed journals. TRIAL REGISTRATION NUMBER ISRCTN: 22663589; EudraCT number: 2008-001968-36.

An independent evaluation of the modernization of NHS endoscopy services in England: data poverty and no improvement.

RATIONALE, AIMS AND OBJECTIVES: The Modernising Endoscopy Services (MES) programme introduced a focussed modernization drive and data collection regime to English NHS endoscopy services. We independently evaluated the MES programme by comparing routinely collected, service-related endoscopy data from sites that participated in the MES programme and sites that did not. METHODS: A random selection of 10 endoscopy units who had participated in the MES programme (intervention sites) were compared with a random selection of 10 endoscopy units who redesigned their services independently (control sites). Data on demand, numbers waiting, activity and cancellations were collected for eight time points between January 2003 and April 2006. Data were aggregated into intervention and control groups for statistical analysis using a two-way analysis of variance. Activity data were validated using an equivalent Hospital Episode Statistics dataset. RESULTS: Data were not routinely collected by 11 of 19 endoscopy units. Trust-held datasets were subsequently included to address problems with data availability. The accuracy of the Activity data was successfully validated. Statistical analysis of the data showed that neither the intervention group nor the control group were able to significantly improve their services over time. There was also no significant difference between the intervention group and the control group in the improvement of their endoscopy services at any point time. CONCLUSIONS: Based on the data collected, the intervention programme did not significantly improve NHS endoscopy services in England over and above what could have been achieved independently with only the intention to redesign.

Unmeasured improvement work: the lack of routinely collected, service-related data in NHS endoscopy units in England involved in "modernisation".

BACKGROUND: The availability of routinely collected service-related endoscopy data from NHS endoscopy units has never been quantified. METHODS: This retrospective observational study asked 19 endoscopy units to submit copies of all in-house, service-related endoscopy data that had been routinely collected by the unit - Referral numbers, Activity, Number of patients waiting and Number of lost slots. Nine of the endoscopy units had previously participated in the Modernising Endoscopy Services (MES) project during 2003 to redesign their endoscopy services. These MES sites had access to additional funding and data collection software. The other ten (Control sites) had modernised independently. All data was requested in two phases and corresponded to eight specific time points between January 2003 and April 2006. RESULTS: Only eight of 19 endoscopy units submitted routinely collected, service-related data. Another site's data was collected specifically for the study. A further two units claimed to routinely collect service-related data but did not submit any to the study. The remaining eight did not collect any service-related endoscopy data routinely and liaised with their Trust for data. Of the eight sites submitting service-related data, only three were MES project sites. Of these three, the data variables collected were limited and none collected the complete set of endoscopy data variables requested. Of the other five sites, two collected all four endoscopy data types. Data for the three MES project sites went back as far as January 2003, whilst the five Control sites were only able to submit data from December 2003 onwards. CONCLUSION: There was a lack of service-related endoscopy data routinely collected by the study sites, especially those who had participated in the MES project. Without this data, NHS endoscopy services cannot have a true understanding of their services, cannot identify problems and cannot measure the impact of any changes. With the increasing pressures placed on NHS endoscopy services, the need to effectively inform redesign plans is paramount. We recommend the compulsory collection of service-related endoscopy data by all NHS endoscopy units using a standardised format with rigorous guidelines.

The effects of the Two-Week Rule on NHS colorectal cancer diagnostic services: a systematic literature review.

BACKGROUND: The Two-Week Rule (TWR) was introduced to ensure that all patients with a suspected colorectal cancer (CRC) saw a hospital specialist within 14 days of an urgent GP referral. Guidelines were available to GPs to facilitate the appropriate TWR referral of patients exhibiting high-risk CRC symptoms. METHODS: We aimed to evaluate the TWR and its CRC detection rate on NHS CRC diagnostic services by performing a literature search and critically appraising the peer-reviewed studies. Only 12 studies were eligible for inclusion. Data was collected and overall results were given as weighted averages. RESULTS: The studies identified indicated that only 10.3% of patients referred by the TWR were eventually diagnosed with CRC. When examining the referral origin of all CRC patients diagnosed during the time of the studies, 24% had been referred using the TWR, 24.1% were referred as emergency cases, and 52.4% were referred using alternative routes. No evidence was found to indicate that the TWR had resulted in identifying CRC patients at an earlier, more treatable stage of their disease. CONCLUSION: The TWR referral system needs to be improved to increase the number of CRC patients referred using this fast track method as they present to their GP. The TWR and new NICE Guidelines for the referral of patients with suspected cancer should be independently evaluated.