International trends in oesophageal cancer survival by histological subtype between 1995 and 2014.

INTRODUCTION: Survival from oesophageal cancer remains poor, even across high-income countries. Ongoing changes in the epidemiology of the disease highlight the need for survival assessments by its two main histological subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC). METHODS: The ICBP SURVMARK-2 project, a platform for international comparisons of cancer survival, collected cases of oesophageal cancer diagnosed 1995 to 2014, followed until 31st December 2015, from cancer registries covering seven participating countries with similar access to healthcare (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK). 1-year and 3-year age-standardised net survival alongside incidence rates were calculated by country, subtype, sex, age group and period of diagnosis. RESULTS: 111 894 cases of AC and 73 408 cases of SCC were included in the analysis. Marked improvements in survival were observed over the 20-year period in each country, particularly for AC, younger age groups and 1 year after diagnosis. Survival was consistently higher for both subtypes in Australia and Ireland followed by Norway, Denmark, New Zealand, the UK and Canada. During 2010 to 2014, survival was higher for AC compared with SCC, with 1-year survival ranging from 46.9% (Canada) to 54.4% (Ireland) for AC and 39.6% (Denmark) to 53.1% (Australia) for SCC. CONCLUSION: Marked improvements in both oesophageal AC and SCC survival suggest advances in treatment. Less marked improvements 3 years after diagnosis, among older age groups and patients with SCC, highlight the need for further advances in early detection and treatment of oesophageal cancer alongside primary prevention to reduce the overall burden from the disease.

Is 3D faster and safer than 4K laparoscopic cholecystectomy? A randomised-controlled trial.

BACKGROUND: Laparoscopic surgery has well-established benefits for patients; however, laparoscopic procedures have a long and difficult learning curve, in large part due to the lack of stereoscopic depth perception. Developments in high-definition and stereoscopic imaging have attempted to overcome this. Three-dimensional high-definition (3D HD) systems are thought to improve operating times compared to two-dimensional high-definition systems. However their performance against new, ultra-high-definition ('4K') systems is not known. METHODS: Patients undergoing laparoscopic cholecystectomy were randomised to 3D HD or 4K laparoscopy. Operative videos were recorded, and the time from gallbladder exposure to separation from the liver (minus on table cholangiogram) was calculated. Blinded video assessment was performed to calculate intraoperative error scores. RESULTS: One hundred and twenty patients were randomised, of which 109 were analysed (3D HD n = 54; 4K n = 55). No reduction in operative time was detected with 3D HD compared to 4K laparoscopy (median [IQR]; 23.41 min [17.00-37.98] vs 20.90 min [17.67-33.03]; p = 0.91); nor was there any decrease observed in error scores (60 [56-62] vs 58 [56-60]; p = 0.27), complications or reattendance. Stone spillage occurred more frequently with 3D HD, but there were no other differences in individual error rates. Gallbladder grade and operating surgeon had significant effects on time to complete the operation. Gallbladder grade also had a significant effect on the error score. CONCLUSIONS: A 3D HD laparoscopic system did not reduce operative time or error scores during laparoscopic cholecystectomy compared with a new 4K imaging system.

Laparoscopic versus open subtotal gastrectomy for adenocarcinoma of the stomach in a Western population: peri-operative and 5-year oncological outcomes.

BACKGROUND: This study compares the peri-operative and long-term oncological outcomes for laparoscopic subtotal gastrectomy (LSG) versus open subtotal gastrectomy (OSG) for adenocarcinoma of the stomach in a Western population. METHODS: A retrospective, intention-to-treat analysis study was conducted for consecutive patients undergoing gastrectomy with curative intent for adenocarcinoma of the stomach between November 2006 and October 2016. Univariate analysis was used to compare peri-operative outcomes between LSG and OSG. Logistic regression with bootstrapping validation was used to identify independent risk factors for predicting 2-year overall survival. RESULTS: The final analysis included 79 patients. When comparing LSG (n = 30) to OSG (n = 49), there was no difference in the number of resected lymph nodes (36 (IQR 24.3-44) vs. 42 (IQR 28-59), p = 0.165), a reduction in intra-operative blood loss (150 ml (IQR 100-250) vs. 553 ml (IQR 338-1075), p < 0.001) and an increase incidence of post-operative bleeding (3 patients vs. 0, p = 0.024), respectively. Five-year overall survival for LSG (n = 22) versus OSG (n = 20) was 63.6% and 50% (p = 0.372), respectively. The number of positive lymph nodes [OR 0.64 (CI 0.47-0.88), p = 0.006] was the only significant independent risk factor for 2-year overall survival. Pre-operative ASA grading and operative approach did not influence survival outcomes at 2 years. CONCLUSION: This study suggests that LSG is comparable to OSG in Western patients with respect to oncological quality and peri-operative morbidity. Two-year overall survival is predicted by the number of positive lymph nodes and not the operative access employed for resection.

Toward More Efficient Surveillance of Barrett's Esophagus: Identification and Exclusion of Patients at Low Risk of Cancer.

BACKGROUND: Endoscopic surveillance of Barrett's esophagus (BE) is probably not cost-effective. A sub-population with BE at increased risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) who could be targeted for cost-effective surveillance was sought. METHODS: The outcome for BE surveillance from 2003 to 2012 in a structured program was reviewed. Incidence rates and incidence rate ratios for developing HGD or EAC were calculated. Risk stratification identified individuals who could be considered for exclusion from surveillance. A health-state transition Markov cohort model evaluated the cost-effectiveness of focusing on higher-risk individuals. RESULTS: During 2067 person-years of follow-up of 640 patients, 17 individuals progressed to HGD or EAC (annual IR 0.8%). Individuals with columnar-lined esophagus (CLE) ≥2 cm had an annual IR of 1.2% and >8-fold increased relative risk of HGD or EAC, compared to CLE <2 cm [IR-0.14% (IRR 8.6, 95% CIs 4.5-12.8)]. Limiting the surveillance cohort after the first endoscopy to individuals with CLE ≥2 cm, or dysplasia, followed by a further restriction after the second endoscopy-exclusion of patients without intestinal metaplasia-removed 296 (46%) patients, and 767 (37%) person-years from surveillance. Limiting surveillance to the remaining individuals reduced the incremental cost-effectiveness ratio from US$60,858 to US$33,807 per quality-adjusted life year (QALY). Further restrictions were tested but failed to improve cost-effectiveness. CONCLUSIONS: Based on stratification of risk, the number of patients requiring surveillance can be reduced by at least a third. At a willingness-to-pay threshold of US$50,000 per QALY, surveillance of higher-risk individuals becomes cost-effective.

Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.

BACKGROUND: Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records. OBJECTIVE: We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates. METHODS: We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs. RESULTS: In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001). CONCLUSIONS: The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.

Developing a Long COVID Phenotype for Postacute COVID-19 in a National Primary Care Sentinel Cohort: Observational Retrospective Database Analysis.

BACKGROUND: Following COVID-19, up to 40% of people have ongoing health problems, referred to as postacute COVID-19 or long COVID (LC). LC varies from a single persisting symptom to a complex multisystem disease. Research has flagged that this condition is underrecorded in primary care records, and seeks to better define its clinical characteristics and management. Phenotypes provide a standard method for case definition and identification from routine data and are usually machine-processable. An LC phenotype can underpin research into this condition. OBJECTIVE: This study aims to develop a phenotype for LC to inform the epidemiology and future research into this condition. We compared clinical symptoms in people with LC before and after their index infection, recorded from March 1, 2020, to April 1, 2021. We also compared people recorded as having acute infection with those with LC who were hospitalized and those who were not. METHODS: We used data from the Primary Care Sentinel Cohort (PCSC) of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. This network was recruited to be nationally representative of the English population. We developed an LC phenotype using our established 3-step ontological method: (1) ontological step (defining the reasoning process underpinning the phenotype, (2) coding step (exploring what clinical terms are available, and (3) logical extract model (testing performance). We created a version of this phenotype using Protégé in the ontology web language for BioPortal and using PhenoFlow. Next, we used the phenotype to compare people with LC (1) with regard to their symptoms in the year prior to acquiring COVID-19 and (2) with people with acute COVID-19. We also compared hospitalized people with LC with those not hospitalized. We compared sociodemographic details, comorbidities, and Office of National Statistics-defined LC symptoms between groups. We used descriptive statistics and logistic regression. RESULTS: The long-COVID phenotype differentiated people hospitalized with LC from people who were not and where no index infection was identified. The PCSC (N=7.4 million) includes 428,479 patients with acute COVID-19 diagnosis confirmed by a laboratory test and 10,772 patients with clinically diagnosed COVID-19. A total of 7471 (1.74%, 95% CI 1.70-1.78) people were coded as having LC, 1009 (13.5%, 95% CI 12.7-14.3) had a hospital admission related to acute COVID-19, and 6462 (86.5%, 95% CI 85.7-87.3) were not hospitalized, of whom 2728 (42.2%) had no COVID-19 index date recorded. In addition, 1009 (13.5%, 95% CI 12.73-14.28) people with LC were hospitalized compared to 17,993 (4.5%, 95% CI 4.48-4.61; P<.001) with uncomplicated COVID-19. CONCLUSIONS: Our LC phenotype enables the identification of individuals with the condition in routine data sets, facilitating their comparison with unaffected people through retrospective research. This phenotype and study protocol to explore its face validity contributes to a better understanding of LC.

Splenectomy for non-haematological metastatic malignant disease.

PURPOSE: Multiple cases and small series of patients who have undergone splenectomy for metastatic malignant disease have been reported. This study examines the outcome of patients with metastatic malignant disease to the spleen treated by splenectomy at a tertiary oncology centre and a review of cases published in the last 10 years. METHODS: The hospital histopathology database was searched over a 25-year period up to 2004 for patients who had undergone splenectomy for non-haematological malignancy. Medical records of these patients were reviewed and clinical course was examined. The literature review was undertaken using a search of PubMed for the terms "splenectomy" and "metastasis" from 2000 to 2010. RESULTS: Twenty-one cases at our institution were identified. The most common primary site of malignancy was ovary (nine cases), followed by malignant melanoma (three) and pancreas (three). There were two cases of metastatic disease from colonic primary and one each from renal, breast, nasopharyngeal and unknown primary disease. There were two cases of long-term disease-free survival (both primary ovarian tumours) and four cases of patients who survived more than 4 years but had disease recurrence (ovarian and colonic primaries). The literature review provided a further 115 cases. CONCLUSIONS: More favorable outcomes were seen in patients with metachronous disease. There was a trend to improved outcome in ovarian and colorectal primaries over malignant melanoma. It is postulated that improved outcome may be seen in patients for whom there were effective adjuvant chemotherapeutic options, low probability of other metastatic disease and less aggressive tumour biology. However, frequently the presentation is indicative of aggressive widespread disease with a poor prognosis.

Diabetic retinopathy in newly diagnosed Type 2 diabetes mellitus: Prevalence and predictors of progression; a national primary network study.

AIMS: To determine, inreal-world primary care settings, the prevalence of, and risk factors for, retinopathy atType 2 diabetes mellitus diagnosis and report cumulative incidence and progression of retinopathy seven years after diabetes diagnosis. METHODS: Retrospective cohort analysis of people with newly diagnosed Type 2 diabetesrecorded bythe Royal College of General Practitioners Research and Surveillance Centre(between 2005 and 2009, n=11,399).Outcomes included; retinopathy prevalence atdiabetesdiagnosis (baseline) and cumulative incidence or progression of retinopathy at seven years. Retinopathy prevalence was compared with the United Kingdom Prospective Diabetes Study (UKPDS-1998). Factors influencing retinopathy incidence and progression were analysed using logistic regression. RESULTS: Baseline retinopathy prevalencewas 18% (n=2,048) versus 37% in UKPDS. At seven years, 11.6% (n=237) of those with baseline retinopathyhad progression of retinopathy. In those without baseline retinopathy, 46.4% (n=4,337/9,351) developed retinopathy by seven years. Retinopathy development (OR: 1.05 [95%CI: 1.02-1.07] per mmol/mol increase) and progression (OR: 1.05 [1.04-1.06]) at seven years was associated with higher HbA1catdiabetesdiagnosis. Obesity (OR: 0.88 [0.79-0.98]) and high socioeconomic status (OR: 0.63 [0.53-0.74]) were negatively associated with retinopathy development at seven years. CONCLUSIONS: Baseline retinopathy prevalence has declined since UKPDS. Additionally, HbA1c at diabetes diagnosis remains important for retinopathy development and progression.

Using Primary Care Data to Report Real-World Pancreatic Cancer Survival and Symptomatology.

Pancreatic cancer is the 10th most common cancer diagnosed; despite recent advances in many areas of oncology, survival remains poor, in part owing to late diagnosis. Whilst primary care data are used widely for epidemiology and pharmacovigilance, they are less used for observing survival. In this study we extracted a pancreatic cancer cohort from a nationally representative English primary care database of electronic health records (EHRs) and reported on their symptom and mortality data. A total of 11, 649 cases were identified within the Oxford Royal College of General Practitioners (RCGP) Clinical Informatics Digital Hub network. All-cause mortality data was recorded for 4623 (39.69%). Mean age at recording of cancer diagnosis was 71.4 years (SD 12.0 years). 1-year and 5-year survival was 22.06% and 3.27% respectively. Within a multivariate model, age had a significant impact on survival; those diagnosed under the age of 60 had the longest survival, as compared to those age 60 - 79 (HR: 1.36, 95% CI: 1.20 - 1.54, p < 0.001) and 80+ (HR: 2.13, 95% CI: 1.86 - 2.44, p < 0.01). Symptomatology was examined; at any time point abdominal pain was the most commonly reported symptom present in 5271 cases (45.2%), but within the 12 months preceding diagnosis jaundice was the most common feature, present in 2587 patients (22.2%). Future studies clarifying other contributing factors on survival outcomes and patterns of symptomatology are needed; primary care EHRs provide an opportunity to evaluate real-world cancer patient cohort data.

Adverse events of interest vary by influenza vaccine type and brand: Sentinel network study of eight seasons (2010-2018).

BACKGROUND: Influenza contributes significantly to the burden of disease worldwide; the United Kingdom has a policy of vaccination across all ages. Influenza vaccinations are known to be associated with common minor adverse events of interest (AEIs). The European Medicines Agency (EMA) recommends ongoing surveillance of AEIs following influenza vaccination to monitor common and detect infrequent but important AEIs. METHODS: A retrospective cohort study using computerised medical record data from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network database 2010-2018 (N = 848,375). We extracted data about vaccine exposure (n = 3,121,334) and consultations for AEIs within seven days of receiving vaccinations specified by the EMA (1,488,870 consultations by 430,029 unique individuals). We used a self-case series design which employs a likelihood estimation method using conditioning of observed adverse events. Such a model assumes non-homogenous Poisson intensity processes for each exposure period and age interval. We compared AEI between QIV and TIV reporting relative incidence (RI) of AEIs. A RI < 1 signified lower AEI rate compared to TIV. RESULTS: QIV was associated with a RI of AEIs of 1.14 (95%CI, 1.10-1.18, p < 0.01), though the number of years exposure was limited. By way of contrast, LAIV had a lower rate 0.60 (95%CI 0.63-0.68, p < 0.001). Cellular manufacture was also associated with a lower rate 0.78 (95%CI 0.61-0.99, p = 0.04). AEIs varied by season: Rash and musculoskeletal conditions are particularly pronounced in the 2014/15 season and respiratory conditions in 2016/17. In an analysis of all seasons, we found an elevated relative incidence of AEIs of 1.78 (95%CI, 1.62-1.95) in pregnant women and 1.76 (95%CI, 1.56 - 1.99) in children under 5 years. CONCLUSION: Routine sentinel network data can be used to contrast AEIs between vaccine types and may provide a consistent method of observation of vaccine benefit-risk over time.

Routinely diagnosed low-grade dysplasia in Barrett's oesophagus: a population-based study of natural history.

AIMS: To examine the natural history of columnar-lined oesophagus with routinely diagnosed low-grade dysplasia and ascertain the risk of oesophageal adenocarcinoma development. METHODS AND RESULTS: A multicentre retrospective cohort study of 283 patients with low-grade dysplasia. Follow-up data were obtained from examination of hospital records. One hundred and forty-four patients had biopsies prior to low-grade dysplasia diagnosis and 217 had follow-up biopsies after index low-grade dysplasia diagnosis. In these patients the incidence of high-grade dysplasia and adenocarcinoma combined was 4.6% per annum and of adenocarcinoma alone was 2.7% per annum. At most recent follow-up, 43 (19.8%) had persistent low-grade dysplasia, 37 (17.1%) had changes indefinite for dysplasia and 108 (49.8%) had non-dysplastic columnar-lined oesophagus. When prevalent cases were excluded (those occurring within 1 year of index low-grade dysplasia diagnosis), the annual incidence of high-grade dysplasia and adenocarcinoma combined was 2.2% and of adenocarcinoma alone was 1.4%. The relative risk for adenocarcinoma development in low-grade dysplasia compared with non-dysplastic columnar-lined oesophagus was 2.871 (P = 0.002). CONCLUSIONS: Low-grade dysplasia has a threefold increased risk of progression to cancer compared with non-dysplastic epithelium, but in the majority of patients dysplasia is not subsequently detected.

Treatment modality and risk of development of dysplasia and adenocarcinoma in columnar-lined esophagus.

Columnar metaplasia is the precursor lesion for esophageal adenocarcinoma, resulting from prolonged gastroesophageal reflux. The influence of the efficacy of reflux control on the development of neoplastic change in columnar-lined esophagus is not established. This study compares the rate of development of dysplasia and adenocarcinoma in patients with columnar metaplasia of the esophagus between patients treated pharmacologically and those treated with antireflux surgery. This study is a retrospective review of a cohort of patients enrolled in a multicenter national registry involving 738 patients from seven UK centers. Forty-one were treated with antireflux surgery, 42 with H2 receptor antagonist, 532 with proton pump inhibitor, and 114 with a combination of these medications. Nine had none of these medications or surgery. Total follow-up was 3697 years. Mean age and follow-up for patients treated medically were 61.6 and 4.96 years and surgically were 50.5 and 6.19 years, respectively. No patient in the surgical group developed high-grade dysplasia (HGD) or adenocarcinoma. Twenty patients treated medically developed adenocarcinoma and 10 developed HGD. Hazards ratio comparing pharmacological to surgical therapy for development of all grades of dysplasia and adenocarcinoma 1.77 (P = 0.272). Log rank test comparing antireflux surgery to pharmacological therapy for development of HGD or adenocarcinoma P = 0.1287 and for adenocarcinoma P = 0.2125. Although there was a trend towards greater efficacy of antireflux surgery over pharmacological therapy in reducing the development of dysplasia and adenocarcinoma, this did not reach statistical significance.

The impact of therapy on the risk of asthma in type 2 diabetes.

BACKGROUND AND OBJECTIVES: There are limited data about the risk of asthma in people with diabetes. We examined the incidence of asthma in subjects with type 2 diabetes (T2DM) compared to controls, and the association with metformin, sulphonylureas and insulin therapy. MATERIALS AND METHODS: We conducted a retrospective cohort study using a representative UK primary care database (N = 894 646 adults). We used 1:1 propensity score matching (age, gender, socio-economic deprivation, body mass index and smoking status) to match 29 217 pairs of T2DM cases and controls. We used Cox proportional hazard regression to compare the incidence of asthma in both groups over 8 years of follow-up. In those with T2DM, we used Cox proportional hazard regression to assess for any impact of antidiabetic medications on asthma incidence. RESULTS: Individuals with T2DM were less likely to develop asthma than matched controls (hazard ratio [HR] 0.85, 95% CI 0.77-0.93). Insulin increased the risk of incident asthma (HR 1.25, 95% CI 1.01-1.56), whilst metformin and sulphonylureas were associated with reduced risk (HR 0.80, 95% CI 0.69-0.93 and HR 0.76, 95% CI 0.60-0.97, respectively). There was no association with diabetes duration, complications or glycaemic control. CONCLUSIONS: T2DM may have a protective effect against asthma development. Insulin use was associated with an increased risk of asthma, while metformin and sulphonylureas reduced the risk in those with T2DM.

Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus.

OBJECTIVE: In the USA, detection of intestinal metaplasia is a requirement for enrollment in surveillance programmes for dysplasia or adenocarcinoma in columnar-lined oesophagus. In the UK, it is believed that failure to detect intestinal metaplasia at index endoscopy does not imply its absence within the columnarized segment or that the tissue is not at risk of neoplastic transformation. The aim of this study was to investigate the factors predicting the probability of detection of intestinal metaplasia in the columnarized segment. MATERIAL AND METHODS: Demonstration of intestinal metaplasia was analysed in 3568 biopsies of non-dysplastic columnar-lined oesophagus from 1751 patients from 7 centres in the UK. Development of dysplasia and adenocarcinoma was analysed in 322 patients without intestinal metaplasia and compared with that in 612 patients with intestinal metaplasia. RESULTS: Intestinal metaplasia was more commonly detected in males than in females (odds ratio 1.244), longer segment length (10.3% increase per centimetre) and increasing number of biopsies taken (24% increase per unit increase). After 5 years of follow-up, 54.8% of patients without intestinal metaplasia at index endoscopy demonstrated intestinal metaplasia, and 90.8% after 10 years. There was no significant difference in the rate of development of dysplasia or adenocarcinoma between patients with or without intestinal metaplasia detection at index endoscopy. CONCLUSIONS: Detection of intestinal metaplasia is subject to significant sampling error. It increases with segment length and number of biopsies taken. In the majority of patients, if sufficient biopsies are taken over time, intestinal metaplasia will be demonstrated. The decision to offer surveillance should not be based upon the presence or absence of intestinal metaplasia at index endoscopy as the risk of dysplasia and adenocarcinoma is similar in both groups.

Type 2 diabetes: A protective factor for COPD?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2DM) are common comorbidities. COPD is a known risk factor for incident T2DM, however few studies have examined the relationship in reverse. The primary aim of this study was to compare the incidence of COPD in people with and without T2DM. MATERIALS AND METHODS: We conducted a retrospective case-control study using a long-established English general practice network database (n=894,646). We matched 29,217 cases of T2DM with controls, adjusting for age, gender, smoking status, BMI and social deprivation, to achieve 1:1 propensity matching and compared the rate of incident COPD over eight years of follow-up. We performed a secondary analysis to investigate the effect of insulin, metformin and sulphonylureas on COPD incidence. RESULTS: People with T2DM had a reduced risk of COPD compared to matched controls over the follow-up period (HR 0.89, 95%CI 0.79-0.93). 48.5% of those with T2DM were ex-smokers compared with 27.3% of those without T2DM. Active smoking rates were 20.4% and 23.7% respectively. Insulin, metformin and sulphonylureas were not associated with incident COPD. CONCLUSIONS: People with T2DM are less likely to be diagnosed with COPD than matched controls. This may be due to positive lifestyle changes, such as smoking cessation in those with T2DM.

Ischaemic stroke, haemorrhage, and mortality in older patients with chronic kidney disease newly started on anticoagulation for atrial fibrillation: a population based study from UK primary care.

OBJECTIVE: To assess the association between anticoagulation, ischaemic stroke, gastrointestinal and cerebral haemorrhage, and all cause mortality in older people with atrial fibrillation and chronic kidney disease. DESIGN: Propensity matched, population based, retrospective cohort analysis from January 2006 through December 2016. SETTING: The Royal College of General Practitioners Research and Surveillance Centre database population of almost 2.73 million patients from 110 general practices across England and Wales. PARTICIPANTS: Patients aged 65 years and over with a new diagnosis of atrial fibrillation and estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73m2, calculated using the chronic kidney disease epidemiology collaboration creatinine equation. Patients with a previous diagnosis of atrial fibrillation or receiving anticoagulation in the preceding 120 days were excluded, as were patients requiring dialysis and recipients of renal transplants. INTERVENTION: Receipt of an anticoagulant prescription within 60 days of atrial fibrillation diagnosis. MAIN OUTCOME MEASURES: Ischaemic stroke, cerebral or gastrointestinal haemorrhage, and all cause mortality. RESULTS: 6977 patients with chronic kidney disease and newly diagnosed atrial fibrillation were identified, of whom 2434 were on anticoagulants within 60 days of diagnosis and 4543 were not. 2434 pairs were matched using propensity scores by exposure to anticoagulant or none and followed for a median of 506 days. The crude rates for ischaemic stroke and haemorrhage were 4.6 and 1.2 after taking anticoagulants and 1.5 and 0.4 in patients who were not taking anticoagulant per 100 person years, respectively. The hazard ratios for ischaemic stroke, haemorrhage, and all cause mortality for those on anticoagulants were 2.60 (95% confidence interval 2.00 to 3.38), 2.42 (1.44 to 4.05), and 0.82 (0.74 to 0.91) compared with those who received no anticoagulation. CONCLUSION: Giving anticoagulants to older people with concomitant atrial fibrillation and chronic kidney disease was associated with an increased rate of ischaemic stroke and haemorrhage but a paradoxical lowered rate of all cause mortality. Careful consideration should be given before starting anticoagulants in older people with chronic kidney disease who develop atrial fibrillation. There remains an urgent need for adequately powered randomised trials in this population to explore these findings and to provide clarity on correct clinical management.

Short segment columnar-lined oesophagus: an underestimated cancer risk? A large cohort study of the relationship between Barrett's columnar-lined oesophagus segment length and adenocarcinoma risk.

OBJECTIVE: Longer columnar-lined oesophagus (CLO) segments have been associated with higher cancer risk, but few studies have demonstrated a significant difference in neoplastic risk stratified by CLO segment length. This study establishes adenocarcinoma risk in CLO by segment length. METHODS: This is a multicentre retrospective observational study. Medical records of 1000 patients registered from six centres were examined and data extracted on demographic factors, endoscopic features and histopathology of oesophageal biopsies. Adenocarcinoma incidence was evaluated for patients stratified by their diagnostic segment length. RESULTS: Seven hundred and eighty-one patients had biopsy-proven CLO and a segment length recorded. Four hundred and ninety patients had at least 1 year of follow-up, providing 2620 patient-years of follow-up for incidence analysis. The overall annual adenocarcinoma incidence was 0.62%/year (95% confidence interval: 0.36-1.01). The annual incidence in the segment length groups was 0.59% (0.19-1.37) in short segment (3 6 9 cm; P=0.004. CONCLUSION: This study demonstrates that the neoplastic risk of CLO varies according to segment length, and that overall, the risk of adenocarcinoma development is similar in short-segment and long-segment (>3 cm) CLO. The highest adenocarcinoma risk was found in the longest CLO segments and lowest risk in segments >3

Tension enterothorax and hepatothorax due to a diaphragmatic hernia: successful emergency repair of a life-threatening condition.

A 70-year-old female patient presented with acute severe respiratory distress at a district general hospital. Medical history included type 2 diabetes, recurrent pulmonary embolisms and pre-existing diaphragmatic hernia containing part of the liver. Despite initial treatment with steroid inhalers, her clinical picture rapidly deteriorated requiring emergency intubation and positive pressure ventilation. Imaging investigations revealed tension enterothorax and hepatothorax with tracheal deviation. The patient was transferred and underwent an emergency laparotomy at the Regional Oesophagogastric Unit. A large diaphragmatic hernia (central tendon defect) which contained the duodenum, porta hepatis, right lobe of liver, gallbladder and right colon was reduced and successfully repaired. Her postoperative course was uneventful with no signs of recurrence at 2 months follow-up.This case describes an extremely rare and life-threatening condition of tension enterothorax and hepatothorax, which should be considered in the differential diagnosis of acute respiratory distress with tracheal deviation.

Barrett's oesophagus: Current controversies.

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.