Ethnicity and socio-economic status affects the incidence and survival of hepatosplenic T-cell lymphoma.

To address the lack of contemporary population-based epidemiological studies of hepatosplenic T-cell lymphoma (HSTCL), we undertook a population-based study of ICD-O-3-coded HSTCL in England. We used the National Cancer Registration Dataset and linked datasets on hospital admissions, Systemic Anti-Cancer Therapy, socio-demographics, comorbidities and death, identifying cases from 1 January 2013 to 31 December 2019 with survival data up to 5 January 2021. Crude and directly age-standardised incidence rates per million persons per year were calculated. Crude and adjusted incidence rate ratios compared incidence between groups using Poisson regression. A Cox proportional hazards model estimated mortality risks adjusted for age, sex, ethnicity, deprivation and allogenic stem cell transplant (allo-SCT; time varying). We identified 44 patients, mean age 42 years. Median survival was 11 months, and 1 and 5 year survivals were 48% (95% CI 29%-43%) and 22% (95% CI 12%-42%) respectively. The age-standardised incidence was 0.1 per million/year. Incidence was higher in areas with greater deprivation (0.15 per million/year), and more cases than expected were in non-White patients (39%). Non-Whites had a twofold increased risk of death (adjusted hazard ratio 2.21 [95% CI 1.03-4.78]) even after adjusting for deprivation, younger age and allo-SCT. In conclusion, ethnicity and socio-economic status affect both the incidence and survival of HSTCL.

Is Vaccination Against COVID-19 Associated With Inflammatory Bowel Disease Flare? Self-Controlled Case Series Analysis Using the UK CPRD.

INTRODUCTION: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) flare. METHODS: Patients with IBD vaccinated against COVID-19 who consulted for disease flare between December 1, 2020, and December 31, 2021, were ascertained from the Clinical Practice Research Datalink. IBD flares were identified using consultation and corticosteroid prescription records. Vaccinations were identified using product codes and vaccination dates. The study period was partitioned into vaccine-exposed (vaccination date and 21 days immediately after), prevaccination (7 days immediately before vaccination), and the remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and IBD flares. Season-adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) were calculated using self-controlled case series analysis. RESULTS: Data for 1911 cases with IBD were included; 52% of them were female, and their mean age was 49 years. Approximately 63% of participants had ulcerative colitis (UC). COVID-19 vaccination was not associated with increased IBD flares in the vaccine-exposed period when all vaccinations were considered (aIRR [95% CI] 0.89 [0.77-1.02], 0.79 [0.66-0.95], and 1.00 [0.79-1.27] in IBD overall, UC, and Crohn's disease, respectively). Analyses stratified to include only first, second, or third COVID-19 vaccinations found no significant association between vaccination and IBD flares in the vaccine-exposed period (aIRR [95% CI] 0.87 [0.71-1.06], 0.93 [0.75-1.15], and 0.86 [0.63-1.17], respectively). Similarly, stratification by COVID-19 before vaccination and by vaccination with vectored DNA or messenger RNA vaccine did not reveal an increased risk of flare in any of these subgroups. DISCUSSION: Vaccination against COVID-19 was not associated with IBD flares regardless of prior COVID-19 infection and whether messenger RNA or DNA vaccines were used.

Predicting Need for Escalation of Care or Death From Repeated Daily Clinical Observations and Laboratory Results in Patients With Severe Acute Respiratory Syndrome Coronavirus 2.

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n = 1,141; C statistic: C = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission.

Obesity Is the Most Common Risk Factor for Chronic Liver Disease: Results From a Risk Stratification Pathway Using Transient Elastography.

INTRODUCTION: Obesity has been associated with liver fibrosis, yet guidelines do not emphasize it as an independent risk factor in which to have a high index of suspicion of advanced disease. We aimed to elucidate the effect of a raised body mass index on the risk of liver disease using data from a community risk stratification pathway. METHODS: We prospectively recruited patients from a primary care practice with hazardous alcohol use and/or type 2 diabetes and/or obesity. Subjects were invited for a transient elastography reading. A threshold of ≥8.0 kPa defined an elevated reading consistent with clinically significant liver disease. RESULTS: Five hundred seventy-six patients participated in the pathway; of which, 533 patients had a reliable reading and 66 (12.4%) had an elevated reading. Thirty-one percent of patients with an elevated reading had obesity as their only risk factor. The proportion of patients with an elevated reading was similar among those with obesity (8.9%) to patients with more recognized solitary risk factors (type 2 diabetes 10.8%; hazardous alcohol use 4.8%). Obesity in combination with other risk factors further increased the proportion of patients with an elevated reading. In multivariate logistic regression, increasing body mass index and type 2 diabetes were significantly associated with an elevated reading. DISCUSSION: Obesity as a single or additive risk factor for chronic liver disease is significant. Future case-finding strategies using a risk factor approach should incorporate obesity within proposed algorithms.

All-cause and cause-specific mortality rates of patients treated for alcohol use disorders: A meta-analysis.

BACKGROUND: Although alcohol use disorders (AUDs) are known to increase the relative risk of all-cause and some cause-specific mortality, the absolute mortality rates of the AUD population are unknown. Such knowledge would benefit planners of the provision of services for this population, including in prioritizing the identification and/or treatment of diseases likely to cause their death. METHODS: We conducted a systematic review of studies in English, reporting the cause-specific mortality rates among people treated for AUDs. Number of deaths by cause and total person-years of follow-up were extracted. All-cause and cause-specific mortality rates per 1000 person-years were meta-analyzed assuming random effects. RESULTS: Thirty-one studies were included. Participants were mainly middle-aged males. The quality of studies was generally good. A total of 6768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients) were recorded, and the pooled all-cause mortality rate was 27.67/1000 person-years (py) (95% confidence interval [CI]: 23.9, 32.04). The most common cause of death in the AUD population was cardiovascular disease (CVD) (6.9/1000 py; 95% CI: 5.61, 8.49), followed by gastrointestinal deaths (5.63/1000 py; 95% CI: 4.1, 7.74), unnatural deaths (4.95/1000 py; 95% CI: 4.01, 6.09)), neoplasms, respiratory diseases, and substance use disorders. CONCLUSIONS: Patients with AUDs have increased rates of all-cause and cause-specific mortality compared with the general population. Like the general population, they are most likely to die of CVD. In contrast to the general population, gastrointestinal and unnatural deaths are the next most common causes of death. We believe these facts should be considered when planning health care services for patients with AUDs.

Proton pump inhibitor prescribing patterns in the UK: a primary care database study.

PURPOSE: To determine the prevalence and pattern of proton pump inhibitor (PPI) prescription and the practices employed to reduce PPI use in the UK general population. METHODS: The UK's Clinical Practice Research Database was used to identify individuals who were issued with ≥1 PPI prescription during the period 1990-2014. Point and period prevalence of PPI use were estimated annually. Additionally, new users of PPI therapy who had 5 years of follow-up data were included in a cohort analysis to describe patterns of cessation and duration of PPI use. RESULTS: Both the period and point prevalence of PPI use increased between 1990 and 2014 (period prevalence increased from 0.2 to 15.0% and point from 0.03 to 7.7%). A total of 596 334 new users of PPI therapy in the cohort study received 8 784 272 prescriptions. Of these, 26.7% used PPI therapy long term (≥1 year continuously), while 3.9% remained on PPI therapy for 5 years. Clear attempts to step down dose were identified in 39.9% of long-term users, while this was 47% in patients whose initial indication did not mandate long-term use. CONCLUSION: A considerable increase in PPI use was observed in UK general practice. Of long-term PPI users, 60% did not have an attempt to discontinue or step down. Considerable opportunities may therefore exist to reduce the cost and side effects of PPI use through improving adherence to recommended withdrawal strategies. Copyright © 2016 John Wiley & Sons, Ltd.

Extra-Gastrointestinal Manifestations of Inflammatory Bowel Disease May Be Less Common Than Previously Reported.

BACKGROUND AND AIMS: Extra-intestinal manifestations are well recognized in inflammatory bowel disease (IBD). To what extent the commonly recognized extra-intestinal manifestations seen in IBD patients are attributable to IBD is, however, not clear due to the limited number of controlled studies published. METHODS: We have conducted a study of these manifestations using electronic primary care records. We have identified extra-intestinal manifestations in IBD and non-IBD patients and derived odds ratios (ORs) using conditional logistic regression. RESULTS: A total of 56,097 IBD patients (32.5 % Crohn's disease, 48.3 % ulcerative colitis (UC) and 19.2 % not classified) were matched to 280,382 non-IBD controls. We found records of pyoderma gangrenosum (OR = 29.24), erythema nodosum (OR = 5.95), primary sclerosing cholangitis (OR = 188.25), uveitis (OR = 2.81), ankylosing spondylitis (OR = 7.07), sacroiliitis (OR = 2.79) and non-rheumatoid inflammatory arthritides (OR = 2.66) to be associated with IBD. One or more of these was recorded in 8.1 % of IBD patients and 2.3 % of controls. Non-specific arthritides were present in many more patients, affecting 30 % of IBD patients and 23.8 % of controls overall. We also found weaker associations with a number of conditions not generally considered to be extra-intestinal manifestations including psoriasis, ischemic heart disease, multiple sclerosis and hay fever. CONCLUSION: Although "classical" extra-intestinal manifestations are strongly associated with IBD, most IBD patients remain unaffected. Arthropathies, perceived to be the commonest extra-intestinal manifestation, are not strongly associated with IBD, and the proportion of arthropathies attributable to IBD is likely to be small.

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology.

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.

Cause-specific mortality of people with Barrett's esophagus compared with the general population: a population-based cohort study.

BACKGROUND & AIMS: Understanding the causes of death in people with Barrett's esophagus (BE) could guide evidence-based practice in the follow-up of these patients. METHODS: We identified individuals diagnosed with BE in the UK's Clinical Practice Research Datalink and linked their information with that from England's Hospital Episode Statistics database. Eligible patients (N = 8448) were matched with individuals without BE for age, sex, and general practice (controls, N = 155,212). Causes of death were obtained from the UK's Office for National Statistics. Cox proportional hazard regression, excluding data from the first year of follow-up, was used to estimate hazard ratios and cumulative mortality. Absolute excess risks were calculated by subtracting cause-specific mortality values of controls from those of patients with BE. RESULTS: Compared with the control population, patients with BE had increased risks of death from neoplasms and from respiratory and digestive causes but not from circulatory disorders. The annual mortality rate from esophageal cancer among patients with BE was 0.14%; 4.5% of deaths among these patients resulted from this cancer, leading to a cumulative 10-year risk of almost 2%. Nonetheless, the largest single cause of death among patients with BE was ischemic heart disease (5.6 per 1000 patients); 168 patients with BE died of this cause, nearly 4-fold the number that died of esophageal cancer. CONCLUSIONS: Among patients with BE, approximately 2% will die of esophageal cancer within 10 years. However, patients with BE died more frequently of other causes, such as ischemic heart disease. Evidence-based strategies are available to prevent this disease and might be more cost-effective for reducing mortality among patients with BE.

Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study.

OBJECTIVES: Few studies have quantified the incidence and prevalence of celiac disease (CD) and dermatitis herpetiformis (DH) nationally and regionally by time and age groups. Understanding this epidemiology is crucial for hypothesizing about causes and quantifying the burden of disease. METHODS: Patients with CD or DH were identified in the Clinical Practice Research Datalink between 1990 and 2011. Incidence rates and prevalence were calculated by age, sex, year, and region of residence. Incidence rate ratios (IRR) adjusted for age, sex, and region were calculated with Poisson regression. RESULTS: A total of 9,087 incident cases of CD and 809 incident cases of DH were identified. Between 1990 and 2011, the incidence rate of CD increased from 5.2 per 100,000 (95% confidence interval (CI), 3.8-6.8) to 19.1 per 100,000 person-years (95% CI, 17.8-20.5; IRR, 3.6; 95% CI, 2.7-4.8). The incidence of DH decreased over the same time period from 1.8 per 100,000 to 0.8 per 100,000 person-years (average annual IRR, 0.96; 95% CI, 0.94-0.97). The absolute incidence of CD per 100,000 person-years ranged from 22.3 in Northern Ireland to 10 in London. There were large regional variations in prevalence for CD but not DH. CONCLUSIONS: We found a fourfold increase in the incidence of CD in the United Kingdom over 22 years, with large regional variations in prevalence. This contrasted with a 4% annual decrease in the incidence of DH, with minimal regional variations in prevalence. These contrasts could reflect differences in diagnosis between CD (serological diagnosis and case finding) and DH (symptomatic presentation) or the possibility that diagnosing and treating CD prevents the development of DH.

Smoking is a Risk Factor for Autoimmune Hepatitis: An English Registry-Based Case-Control Study.

Purpose: Smoking is a risk factor for some autoimmune diseases, but its association with autoimmune hepatitis remains unknown. We conducted a population-based matched case-control study to examine the association between tobacco smoking and the risk of autoimmune hepatitis in England. Patients and Methods: From the Clinical Practice Research Datalink and linked Hospital Episode Statistics, 2005-2017, we included 987 cases diagnosed with autoimmune hepatitis after age 18 years and up to 10 frequency-matched population controls per case. We used multiple logistic regression to estimate the odds ratio of autoimmune hepatitis in ever-smokers vs never-smokers, adjusting for sex, age, general practice, calendar time of registration with the general practice, and socioeconomic status. Results: The autoimmune hepatitis cases were more likely to be ever-smokers than the controls (44% vs 37%). The ever-smokers had an increased risk of autoimmune hepatitis compared with the never-smokers (adjusted odds ratio = 1.20, 95% confidence interval 1.03-1.39). Conclusion: Smoking was associated with an increased risk of autoimmune hepatitis.

Primary biliary cirrhosis does not increase the risk of UTIs following diagnosis compared to other chronic liver diseases?

BACKGROUND: Urinary Tract Infections (UTIs) occur more frequently in patients with Primary Biliary Cirrhosis (PBC). Previous studies have compared UTI occurrence in PBC and general population controls, however, it remains unclear if UTI is a feature of all chronic liver diseases (CLD)s, or is specific to PBC, or if this is a cause or consequence of PBC. AIMS: We aimed to determine if UTIs are more common after a diagnosis of PBC compared to general population and CLD controls. METHODS: A cohort study was conducted using the General Practice Research Database. We selected all cases of PBC plus 10 age- and sex-matched general population controls, and an unmatched group with other CLDs. We formed a Cox-proportional hazard model of time to first UTI following diagnosis. RESULTS: Two hundred and forty-eight (24.6%) of PBC cases had a UTI event compared with 2127 (21.1%) of matched and 2131 (11.7%) of the unmatched CLD controls. Comparing PBC with matched controls showed an approximately 30% increased risk of UTI [hazard ratio (HR) 1.33 confidence interval (CI) 1.17-1.52]. Adjusting for diabetes, smoking and previous UTI reduced this (HR 1.25 CI 1.09-1.42). The Hazard Ratio comparing PBC with unmatched CLD controls was 2.00 (CI 1.76-2.28), but this became non-significant when adjusting for age, sex, diabetes, smoking and previous UTI 0.98 (0.86-1.12). CONCLUSIONS: There is increased risk of UTI in PBC patients compared to general population controls, but not compared to CLD controls suggesting that this association is not specific to PBC after diagnosis.

An excess of prior irritable bowel syndrome diagnoses or treatments in Celiac disease: evidence of diagnostic delay.

OBJECTIVE: It is recognized that celiac disease can present with symptoms characteristic of irritable bowel syndrome (IBS) and that a substantial proportion of patients referred to gastroenterologists with these symptoms may have celiac disease. The authors set out to discover how commonly those suffering with celiac disease are misdiagnosed as suffering from IBS and whether such misdiagnosis delays the correct diagnosis. MATERIALS AND METHODS: A case control study using computerized records from the General Practice Research Database was conducted. The authors compared the proportion of patients with celiac disease who had a diagnosis of or had undergone treatment for IBS over a variety of time periods before the diagnosis of celiac disease with the proportion of a matched group without celiac disease who were similarly diagnosed or treated. RESULTS: It was found that 16% of celiac patients had such a prior diagnosis compared to 4.9% of controls (a threefold increased risk of prior IBS; OR = 3.8, 95% CI: 3.6-4.2), and that if one looked at typical treatment for IBS rather than diagnostic codes, 28% of celiac patients appeared to have been treated compared to 9% of controls. Many of the diagnoses of IBS occurred within the last year before diagnosis of celiac disease, but there was a clear excess of IBS even 10 years earlier. CONCLUSIONS: In contemporary UK practice, it is likely that at least some patients with celiac disease spend many years being treated as having IBS. Following guidelines to test serologically for celiac disease will minimize this problem.

Respiratory rate responses to both hypercapnia and acidaemia are modified by age in patients with acidosis.

OBJECTIVE: To explore the associations between arterial pO2, pCO2 and pH and how these are modified by age. METHODS: An analysis of 2598 patients admitted with a diagnosis of Covid-19 infection to a large UK teaching hospital. RESULTS: There were inverse associations for arterial pO2, pCO2 and pH with respiratory rate. The effects of pCO2 and pH on respiratory rate were modified by age; older patients had higher respiratory rates at higher pCO2 (p = 0.004) and lower pH (p = 0.007) values. CONCLUSIONS: This suggests that ageing is associated with complex changes in the physiological feedback loops that control respiratory rate. As well as having clinical relevance, this may also impact on the use of respiratory rate in early warning scores across the age range.

Anaemia of acute inflammation: a higher acute systemic inflammatory response is associated with a larger decrease in blood haemoglobin levels in patients with COVID-19 infection.

AIMS: The study tests the hypothesis that a higher acute systemic inflammatory response was associated with a larger decrease in blood hemoglobin levels in patients with Coronavirus 2019 (COVID-19) infection. METHODS: All patients with either suspected or confirmed COVID-19 infection admitted to a busy UK hospital from February 2020 to December 2021 provided data for analysis. The exposure of interest was maximal serum C-reactive protein (CRP) level after COVID-19 during the same admission. RESULTS: A maximal serum CRP >175mg/L was associated with a decrease in blood haemoglobin (-5.0 g/L, 95% confidence interval: -5.9 to -4.2) after adjustment for covariates, including the number of times blood was drawn for analysis.Clinically, for a 55-year-old male patient with a maximum haemoglobin of 150 g/L who was admitted for a 28-day admission, a peak CRP >175 mg/L would be associated with an 11 g/L decrease in blood haemoglobin, compared with only 6 g/L if the maximal CRP was <4 mg/L. CONCLUSIONS: A higher acute systemic inflammatory response is associated with larger decreases in blood haemoglobin levels in patients with COVID-19. This represents an example of anaemia of acute inflammation, and a potential mechanism by which severe disease can increase morbidity and mortality.