Venous Thromboembolism Following Discharge from Hospital in Patients Admitted for Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Patients admitted to hospital with inflammatory bowel disease[IBD] are at increased risk of venous thromboembolism[VTE]. This study aims to identify IBD patients at increased VTE risk on hospital discharge and to develop a risk scoring system to recognise them. METHODS: Hospital episode statistics data were used to identify all patients admitted with IBD as an emergency or electively for surgery. All patients with VTE within 90 days of hospital discharge were identified. A multilevel logistic regression model was used to identify patient- and admission-level factors associated with VTE. A scoring system to identify patients at higher risk for VTE was constructed. RESULTS: A total of 201 779 admissions in 101 966 patients were included. The rate of VTE within 90 days was 17.2 per 1000 patient-years at risk and was highest in patients admitted as an emergency who underwent surgery[36.9]. VTE was associated with: female sex (odds ratio 0.65 [95% confidence interval 0.53-0.80], p <0.001); increasing age [49-60 years] (4.67 [3.36-6.49], p <0.001); increasing length of hospital stay [>10 days] (3.80 [2.80-5.15], p <0.001); more than two hospital admissions in previous 3 months (2.23 [1.60-3.10], p <0.001); ulcerative colitis (1.48 [1.21-1.82], p <0.001); and emergency admission including surgery (1.59 [1.12-2.27], p = 0.010); or emergency admission not including surgery (1.59 [1.08-2.35], p = 0.019) compared with elective surgery. A score >12 in the VTE scoring system gave a positive predictive value [PPV] of VTE of 1%. The area under the curve [AUC] was 0.714 [95% CI 0.70-0.73]. CONCLUSION: IBD patients admitted to hospital with a prolonged length of stay, increasing age, male sex, or as an emergency were at increased risk of VTE following discharge. Higher-risk patients were identifiable by a VTE risk scoring system.

The association between physician staff numbers and mortality in English hospitals.

BACKGROUND: Physician medical specialties place specific demands on medical staff. Often patients have multiple co-morbidities, frailty is common, and mortality rates are higher than other specialties such as surgery. The key intervention for patients admitted under physician subspecialties is the care provided on the ward. The current evidence base to inform staffing in physician medical specialty wards is limited. The aim of this analysis is to investigate the association between medical staffing levels within physician medical specialties and mortality. METHODS: This study is a cross-sectional analysis of national data, which is aggregated at provider level. Medical beds per senior, middle grade and junior physicians employed in physician medical specialties were calculated from national employment records for acute hospitals in England, in 2017. Outcome measures included unadjusted mortality rate and Summary Hospital-level Mortality Indicator (SHMI) in physician medical specialties. Both Raw mortality and SHMI include deaths during admission or within 30 days following discharge. Linear regression models were constructed for each medical staffing grade for unadjusted mortality, SHMI and SHMI adjusted for local provider factors. FINDINGS: The mean number of medical beds per senior, middle grade and junior physicians were 7.3(SD 2.5), 19.7(11.5), 10.1(3.1) respectively. Lower bed numbers per medical staff grade were associated with lower than expected mortality by SHMI; senior(Coefficient 0.012(95%CI:0.005-0.018),p = 0.001), middle grade(0.002(0.0002-0.005),p = 0.032) and junior(0.008(0.002-0.015),p = 0.014). Hospital providers were more likely to achieve a better than expected mortality (SHMI<1) if  beds per physician were lower than; 5.3, 14.6 and 9.0 for senior, middle grade and junior doctors respectively. INTERPRETATION: Acute hospital providers with fewer beds per medical staff of all grades are associated with lower than expected mortality. FUNDING: No external funding is associated with this analysis.

The association between low birth weight, childhood recollections of parental response to illness, and irritable bowel syndrome: a twin study.

BACKGROUND: The aetiology of irritable bowel syndrome (IBS) is multifactorial, including genetic and environmental factors. Previous studies have suggested that low birth weight and family environment during childhood are associated with developing IBS. METHODS: A survey was sent to all individuals in a UK twin registry. Questions included IBS diagnosed by the Rome IV criteria and if a doctor had previously diagnosed them with IBS. Subjects were categorized as having IBS by Rome IV criteria, a medical diagnosis of IBS or no IBS. Further questions included subjects' recollections of their parents' responses to illness in both the respondent as a child and in the parents themselves. Information regarding birth weight and gestational age have been collected previously. KEY RESULTS: 4258 subjects responded to the questionnaire (51.7%), mean age of 52 (SD 14) years, of whom 98.5% were white and 89.6% female. The mean birth weight was 2.4  (0.6) kg. 5.1% satisfied the Rome IV IBS criteria, the same prevalence as the UK population. However, 14.1% had a previous medical diagnosis of IBS. There was no association found between birth weight and IBS or a medical diagnosis of IBS. On multivariable regression analysis, including parental responses to illness, subjects recalling a parent responding to the parent's bowel symptoms by excusing themselves from household chores were associated with a Rome IV diagnosis of IBS (OR 2.19 (95% CI 1.17-4.10), P = .013). CONCLUSIONS AND INFERENCES: There was no association between birth weight and IBS. However, observing their parents excuse themselves from household chores when they had bowel symptoms was associated with IBS in later life.

Higher volume providers are associated with improved outcomes following ERCP for the palliation of malignant biliary obstruction.

BACKGROUND: Relieving malignant biliary obstruction improves quality of life and permits chemotherapy. Outcomes of endoscopic retrograde cholangio-pancratography(ERCP) in inoperable malignant biliary obstruction have been examined in a national cohort to establish factors associated with poor outcomes. METHODS: Hospital Episode Statistics include diagnostic and procedural data for all NHS hospital attendances in England. Patients from 2006 to 2017 with a Hepaticopancreaticobiliary (HPB) malignancy who had undergone ERCP were studied. Patients undergoing a potentially curative operation were excluded. Associations between demographics, co-morbidities, unit ERCP volume and mortality were examined by logistic regression. FINDINGS: 39,702 patients were included; 49.4% were male; median age was 75 (IQR 66-88)years. Pancreatic cancer was the most common tumour (63.9%). Mortality was 4.1%, 9.7% and 19.1% for 7-day, in hospital and 30-day respectively. On multivariable analysis: men (OR 1.20(95%CI 1.14-1.26), p < 0.001); increasing age quintile 78-83(1.73(1.59-1.89), p < 0.001), >83(2.70(2.48-2.94),p < 0.001); most deprived quintile (1.21(1.11-1.32), p < 0.001); increasing co-morbidity score >20(3.36(2.94-3.84),p < 0.001); small bowel malignancy (1.45(1.22-1.72), p < 0.001), intrahepatic biliary malignancy(1.10(1.03-1.17), p = 0.005) and year of ERCP 2006/07 (1.37(1.22-1.55), p < 0.001) were associated with increased 30-day mortality. Extrahepatic biliary tree cancers (0.67(0.61-0.73), p<0.001), high volume providers of ERCP (>318 annually, 0.91(0.84-0.98), p = 0.01) and high volume of ERCP for malignant obstruction (>40 annually (0.91(0.85-0.98), p = 0.014) were negatively associated with 30-day mortality. Patients were less likely to require a second ERCP in high volume providers (>318, 8.0%) compared to low volume ((<204, 13.4%), p<0.001). INTERPRETATION: Short term mortality in patients with malignant biliary obstruction following ERCP was high. 30-day mortality was positively associated with increasing age and co-morbidity, men, deprivation, and earlier year of ERCP and negatively with extrahepatic biliary tree cancer and high volume ERCP providers. FUNDING: Internal funding only.

Outcomes following feeding gastrostomy (FG) insertion in patients with learning disability: a retrospective cohort study using the health improvement network (THIN) database.

OBJECTIVES: To measure the rates of lower respiratory tract infection (LRTI) and mortality following feeding gastrostomy (FG) placement in patients with learning disability (LD). Following this to compare these rates between those having LRTI prior to FG placement and those with no recent LRTI. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: The study population included patients with LD undergoing FG placement in the 'The Health Improvement Network' database. Patients with LRTI in the year prior (LYP) to their FG placement were compared with patients without a history of LRTI in the year prior (non-LYP) to FG placement. FG placement and LD were identified using Read codes previously developed by an expert panel. MAIN OUTCOME MEASURES: Incidence rate ratio (IRR) of developing LRTI and mortality following FG, comparing patients with LRTI in the year prior to FG placement to patients without a history of LRTI. RESULTS: 214 patients with LD had a FG inserted including 743.4 person years follow-up. 53.7% were males and the median age was 27.6 (IQR 19.6 to 38.6) years. 27.1% were in the LYP patients. 18.7% had a LRTI in the year following FG, with an estimated incidence rate of 254 per 1000-person years. Over the study period the incidence rate of LRTI in LYP patients was 369 per 1000-person years, in non-LYP patients this was 91 per 1000-person years (adjusted IRR 4.21 (95% CI 2.68 to 6.63) p<0.001). 27.1% of patients died during study follow-up. Incidence rate of death was 80 and 45 per 1000-person year for LYP and non-LYP patients, respectively (adjusted IRR 1.80 (1.00 to 3.23) p=0.05). CONCLUSION: In LD patients, no clinically meaningful reduction in LRTI incidence was observed following FG placement. Mortality and LRTI were higher in patients with at least one LRTI in the year preceding FG placement, compared with those without a preceding LRTI.

Outcomes of colorectal stents when used as a bridge to curative resection in obstruction secondary to colorectal cancer.

BACKGROUND: Up to 25% of colorectal cancers present with bowel obstruction. Metal stents (MS) can provide a bridge to surgery by relieving obstruction and allowing the subject's condition to improve pre-operatively. METHODS: Hospital Episode Statistics (HES) is a database of all NHS funded secondary care episodes in England. Subjects admitted with bowel obstruction secondary to colorectal cancer without metastases were identified and subdivided into two groups: MS insertion prior to surgery and surgery only. Due to demographic differences between the groups, propensity score matching was used to analyse procedural outcomes, mortality and readmission within 30 days in left-sided cancers based upon age, sex and Charlson co-morbidity score. RESULTS: Over 10 years, 4571 subjects were identified; 401 received a MS and 4170 underwent surgery only. Median age of MS subjects was 71 (IQR 62-79) years; 226 (56.4%) were male. Median age of surgery-only subjects was 73 (64-81); 2165 (51.9%) were male. Following propensity matching 375 MS and 375 surgery-only subjects remained; MS had fewer readmissions within 30 days (28 (7.5%) versus 44 (11.7%), p = 0.047), fewer respiratory complications (< 6 (< 1.5%) versus 28 (7.5%), p < 0.001), lower stoma rates (49 (13.1%) versus 159 (42.4%), p < 0.001) and higher rates of laparoscopic surgery (154 (41.1%) versus 25 (6.7%), p < 0.001). Mortality was lower in the MS group at 30 days (7 (1.9%) versus 33 (8.8%), p < 0.001) and 1 year (37 (9.9%) versus 71 (19.0%), p < 0.001). CONCLUSIONS: In subjects presenting with obstructing colorectal cancer outcomes including respiratory complications, readmission and mortality appear to be better in subjects undergoing MS as a bridge to surgery compared to surgery alone.

Outcomes of pneumatic dilatation and Heller's myotomy for achalasia in England between 2005 and 2016.

INTRODUCTION: Achalasia is a disorder characterised by failed relaxation of the lower oesophageal sphincter. The aim of this study was to examine, at a national level, the long-term outcomes of achalasia therapies. METHODS: Hospital Episode Statistics include diagnostic and procedural data for all English National Health Service-funded hospital admissions. Subjects with a code for achalasia who had their initial treatment between January 2006 and December 2015 were grouped by treatment; pneumatic dilatation (PD) or surgical Heller's myotomy (HM). Procedural failure was defined as time to a further episode of the same therapy or a change to a different therapy. Up to three PDs were permitted without being considered a therapy failure. RESULTS: 6938 subjects were included; 3619 (52.2%) were men and median age at diagnosis was 59 (IQR 43-75) years. 4748 (68.4%) initially received PD and 2190 (31.6%) HM. The perforation rate following PD was 1.6%. Mortality at 30 days was 0.0% for HM and 1.9% for PD, and <8% after perforation following PD. Factors associated with increased mortality after PD included age quintile 66-77 (OR 4.55 (95% CI 2.00 to 10.38), p<0.001), >77 (9.78 (4.33 to 22.06), p<0.001); Charlson comorbidity score >4 (2.87 (2.08 to 3.95), p<0.001); previous HM (2.47 (1.33 to 4.62), p<0.001); and repeat PD 1-3 (1.58 (1.15 to 2.16), p=0.005), >3 (1.97 (1.21 to 3.19), p=0.006). Durability of up to 3 PD and HM over 10 years of follow-up was 86.2% and 81.9%, respectively (p<0.001). DISCUSSION: The efficacy of PD for achalasia appears to be greater than HM over 10 years. There was no mortality associated with HM, but 1.9% of subjects died within 30 days of PD. Mortality was associated with increasing age, comorbidity, previous HM and repeat PD.

Incidence, morbidity and mortality of patients with achalasia in England: findings from a study of nationwide hospital and primary care data.

BACKGROUND: Achalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited. METHODS: Hospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality. RESULTS: There were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), p<0.001), aspiration pneumonia (13.38 (1.66 to 107.79), p=0.015), lower respiratory tract infection (1.33 (1.05 to 1.70), p=0.02) and mortality (1.33 (1.17 to 1.51), p<0.001). The median time from achalasia diagnosis to oesophageal cancer diagnosis was 15.5 (IQR 20.4) years. CONCLUSION: The incidence of achalasia is 1.99 per 100 000 population in secondary care data and 1.53 per 100 000 person-years in primary care data. Subjects with achalasia have an increased incidence of oesophageal cancer, aspiration pneumonia, lower respiratory tract infections and higher mortality. Clinicians treating patients with achalasia should be made aware of these associated morbidities and its increased mortality.

The Risk of Inflammatory Bowel Disease in Subjects Presenting With Perianal Abscess: Findings From the THIN Database.

BACKGROUND: Perianal abscess [PA] is associated with inflammatory bowel disease [IBD]. The incidence of IBD after a diagnosis of PA and potential predictors of a future diagnosis of IBD are unknown. METHODS: The Health Improvement Network [THIN] is a primary care database representative of the UK population. Incident cases of PA were identified between 1995 and 2017. Subjects with PA were matched to controls within the same general practice. The primary outcome was a subsequent diagnosis of Crohn's Disease [CD] or ulcerative colitis [UC]. A Cox regression model was used to assess potential predictors of a new diagnosis of CD or UC following PA. RESULTS: The risk of CD was higher in the PA cohort compared with controls; adjusted hazard ratio [HR] 7.51 (95% confidence interval [CI] 4.86-11.62), p < 0.0001. The risk of UC was also higher in the PA cohort compared with controls; adjusted HR 2.03 [1.38-2.99], p < 0.0001. Anaemia in men (HR 2.82 [1.34-5.92], p = 0.002), and use of antidiarrhoeal medications (HR 2.70 [1.71-4.25], p < 0.0001) were associated with an increased risk of CD following PA. Anaemia in men (HR 2.58 [1.09-6.07], p = 0.03), diarrhoea (HR 2.18 [1.23-3.85], p = 0.007), and use of anti-diarrhoeal medication (HR 2.27 [1.19-4.30], p = 0.012) were associated with an increased risk of UC following PA. CONCLUSION: Subjects with PA are at an increased risk of subsequent diagnosis of CD and UC. Clinicians should strongly consider investigation for IBD in young patients presenting with diarrhoea and anaemia [in males] following PA. Future research should discern appropriate screening strategies for this high-risk cohort.

Managing a patient with globus pharyngeus.

A woman aged 47 years reported the feeling of a lump in her throat for the past year. The sensation was present intermittently and usually improved when she ate. She noted it was worse with dry swallows when she felt like a tablet was stuck in her throat. The sensation had become more persistent in recent weeks leading her to worry that she had cancer. She had no cough, sore throat or hoarseness. There were no precipitating factors and no symptoms of weight loss, dysphagia, odynophagia or change in her voice. She had smoked previously and rarely had heartburn. She had no other anxieties and was not under any unusual stress. She was initially assessed by an ear, nose and throat surgeon, who found no abnormalities on examination of her neck, throat and oral cavity. Nasolaryngoscopy was normal. An upper gastrointestinal endoscopy was organised and reported a hiatus hernia, but a 3-month trial of a proton pump inhibitor did not have any impact on her symptoms. The benign nature of her symptoms was discussed at her gastroenterology follow-up appointment. She was discharged back to primary care with a final diagnosis of 'globus'. A trial of speech therapy, cognitive behavioural therapy or amitriptyline would be recommended if her symptoms became more troublesome in future.

B-cell targeted therapies in systemic lupus erythematosus: successes and challenges.

Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the formation of autoantibodies that target a variety of self antigens. B cells are fundamental to the development of these antibodies and are a target for intervention in the disease. This review discusses four therapies that target B cells by inducing B-cell depletion, reduction in B-cell proliferation and differentiation, or modulation of B-cell function. Rituximab is an anti-CD20 chimeric monoclonal antibody that depletes B cells but not plasma cells. Systematic reviews of open label studies, particularly in lupus patients refractory to conventional therapy, have suggested that rituximab can be an effective treatment for non-renal lupus and lupus nephritis. However, randomized, double-blind, controlled trials comparing rituximab with placebo in addition to standard of care therapy for non-renal lupus and lupus nephritis over 12 months failed to demonstrate efficacy using the planned primary endpoints, although there were some post-hoc analyses suggesting that rituximab may have beneficial effects that would be worthy of further study as no significant toxicity has been demonstrated. Treatment with belimumab, a humanized monoclonal antibody targeted against B lymphocyte stimulator (BLys), was more efficacious than placebo and had no significant increase in adverse events in two non-renal, phase III lupus trials when given in addition to standard of care therapy for 52 weeks. Belimumab is licensed for the management of lupus in the US and in Europe. Atacicept is a humanized fusion protein that binds BLys and APRIL (a proliferation-inducing ligand) that might be more effective than belimumab in the management of lupus. Unfortunately a phase II/III trial of atacicept in lupus nephritis had to be stopped due to the development of low immunoglobulin levels and pneumonias in some patients. However, in retrospect these complications may have been due to concomitant treatment with mycophenolate mofetil and results of a 52-week, non-renal, phase III trial with atacicept are awaited. Epratuzumab is a humanized monoclonal antibody that targets CD22 on B cells and results in modulation of B-cell function and migration, as CD22 regulates adhesion and inhibits B-cell receptor (BCR) signalling. Epratuzumab at a cumulative dose of 2,400 mg over 4 weeks has been shown to improve lupus disease activity compared with placebo 12 weeks after initiation of therapy in a phase II study, and a 12-month phase III study is on-going. B-cell targeted therapies are an attractive prospect for treating lupus disease and the results of current phase III trials are eagerly awaited. Finding the most appropriate trial design to demonstrate efficacy in lupus trials has been a challenge. The SRI (SLE response index) used in the belimumab studies and the BICLA (British Isles Lupus Assessment Group-based Composite Lupus Assessment) used in the epratuzumab studies are currently the promising trial designs for non-renal studies. For lupus nephritis it is important that trials are of adequate duration to be able to demonstrate benefit of new therapies over conventional therapy.

Is an average of routine postdialysis blood pressure a good indicator of blood pressure control and cardiovascular risk?

INTRODUCTION: Hypertension is associated with left ventricular hypertrophy (LVH), a predictor of cardiovascular mortality in haemodialysis (HD) patients. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) blood pressure (BP) targets are pre-HD <140/90 mm Hg, post-HD <130/80 mm Hg. This study aims to assess 3-month mean in-unit BP, pre- and post-HD, for correlations with left ventricular mass index (LVMI), a measure of long-term BP control. METHODS: Of 648 HD patients, including those on HD >6 months, 262 had echocardiograms. Those with significant coronary artery disease, reduced ejection fraction or valvular disease were excluded, as were those without appropriate echocardiogram, leaving 100 patients. Data on BP and confounding factors for LVH were collected covering 3 months prior to echocardiogram. RESULTS: Mean BP pre-HD was 147/77 ± 19/13 mm Hg, and post-HD, 133/71 ± 20/11 mm Hg; <50% of patients achieved NKF targets. Mean LVMI was 203.7 ± 74 g/m(2); 88% of patients had LVH. On univariate analysis, mean pre- and post-HD systolic BP, mean arterial blood pressure (MAP) and post-HD diastolic and pulse pressure correlated with LVMI. On stepwise multiple regression analysis only post-HD MAP correlated with LVMI (p=0.000047, r=0.395). CONCLUSIONS: We conclude that long-term averages of in-unit post-HD BP measurements are useful in assessing BP control and cardiovascular risk, especially in the absence of routine ambulatory or home BP monitoring.