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.

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.

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.

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.

Age modifies both the maximal temperature and inflammatory response in patients with SARS-CoV-2 infection.

OBJECTIVE: To determine the maximal response of the temperature and inflammatory response to SARS-CoV-2 infection and how these are modified by age. METHODS: Participants were patients admitted to hospital with SARS-CoV-2 infection. For each participant, the maximal temperature and serum C-reactive protein (CRP) were identified and stratified by age. In a secondary analysis, these were compared in patients treated before and after dexamethasone. RESULTS: Mean maximal temperature varied by age (p<0.001; ANOVA) with the highest mean maximal temperature of 37.3°C observed in patients aged 30-49 years and decreasing maximal mean temperatures in the older age groups, with the lowest measure of 36.8°C observed in individuals aged 90-99 years. The mean maximal serum CRP also varied across age groups (p<0.001; ANOVA) and increased with age across all age categories from 34.5 mg/dL (95% confidence interval (CI) 22.0-47.0) for individuals aged 20-29 years to 77.6 mg/dL (95% CI 72.0-83.2) in those aged 80-89 years. After dexamethasone became standard treatment for COVID-19 pneumonia, mean maximal CRP decreased by 17 mg/dL (95% CI -22 to -11). CONCLUSION: Age modifies both maximal temperature and systemic inflammatory response in patients with SARS-CoV-2 infection.

The risk of unexpected hospital admissions and primary care visits after an elective day-case gastroscopy: a cohort study within England.

AIM: To determine the excess of acute medical contacts following a day-case diagnostic gastroscopy. METHODS: Cohort study using English linked primary, secondary care and death registry electronic health data. We included 277,535 diagnostic day-case gastroscopies in 225,304 people between 1998 and 2016 and followed up for 30 days. 1,383,535 30-day periods without a gastroscopy within 991,249 people frequency matched on year, gender and decade of birth. Non-cancer deaths, emergency non-cancer admissions and cardio, vascular or respiratory (CVR) primary care consultations were identified and adjusted for each other as competing risks. Outcomes related to possible indications for gastroscopy were censored. RESULTS: 5.1% of day-case diagnostic gastroscopies were followed by emergency hospital admission, 0.4% for a CVR diagnosis. Adjusted for age, sex, morbidity, time trends, indications and competing risks, there was a 0.1% excess of CVR-related hospital admissions compared to controls. This reduced to 0.05% (95% confidence interval 0.04-0.06%) in people under 40 years without morbidity and increased to 1.1% (0.6%-1.6%) in people over 90 years with high comorbidity. Similarly, by 30 days, 3.8% had a primary care consultation for a CVR problem, with an excess after adjustment ranging from 0.13% (0.11%-0.16%) to 0.31% (0.14%-0.50%). Overall numbers needed to harm ranged from 1 in 294 gastroscopies to 1 in 67 gastroscopies. CONCLUSIONS: There was an excess of vascular and respiratory events associated with a diagnostic gastroscopy. In younger patients, this risk manifested as an increase in primary care consultations while in older patients there was an increase in emergency hospital admissions.

Disease Activity in Inflammatory Bowel Disease Is Associated With Arterial Vascular Disease.

BACKGROUND AND AIMS: There is evidence that several inflammatory diseases are associated with increased cardiovascular risk. Whether this is true for inflammatory bowel diseases remains controversial. We aimed to assess this risk, corrected for the effects of conventional vascular risk factors and IBD disease activity. METHODS: We conducted a cohort study in British general practice and hospital records from the Clinical Practice Research Datalink. We extracted the records of subjects with IBD and matched controls from 1997 to 2017. We conducted Cox proportional hazards and self-controlled case series analyses to examine the associations of IBD, disease activity, and hospitalization with the risk of myocardial infarction, stroke, and cardiovascular death in a manner attempting to remove the effect of likely confounders. RESULTS: We identified 31,175 IBD patients (16,779 UC, 10,721 Crohn's disease, and 3675 unclassifiable cases) and 154,412 matched controls. Five hundred thirty-two myocardial infarctions, 555 strokes, and 469 cardiovascular deaths were observed in IBD cases. Our Cox regression models, adjusted for potential confounders, showed no significant excess of vascular events for IBD patients overall. There was, however, an increased hazard of myocardial infarction in ambulatory patients for acute disease (hazard ratio, 1.83 [1.28-2.62]) and chronic activity (hazard ratio, 1.69 [1.24-2.30]). This effect of disease activity was confirmed in our case series analysis. CONCLUSIONS: Though we have found no evidence of an overall excess of vascular events in IBD patients, our findings of increased risk with more active disease suggest the potential for anti-inflammatory therapies to reduce cardiovascular risk in this patient group.

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.

Mortality in people with coeliac disease: Long-term follow-up from a Scottish cohort.

Background: Few studies have determined the very long-term mortality risks in adult and childhood-diagnosed coeliac disease. Objective: We quantified mortality risks in coeliac disease and determined whether age at diagnosis, or time following diagnosis, modified these risks. Methods: Standardised mortality ratios were determined using data from a cohort of 602 coeliac patients assembled between 1979-1983 from Lothian, Scotland, and followed up from 1970-2016. Results: All-cause mortality was 43% higher than in the general population. Excess deaths were primarily from haematological malignancies (standardised mortality ratio, 4.77) and external causes (standardised mortality ratio, 2.62) in adult and childhood-diagnosed cases respectively. Mortality risks declined steadily with time in adult-diagnosed cases (standardised mortality ratio, 4.85 in first year compared to 0.97, 25 years post-diagnosis). Beyond 15 years, this group had a significantly reduced risk of any malignancy (standardised mortality ratio, 0.57 (95% confidence interval: 0.33-0.92)). In contrast, for childhood-diagnosed cases an increased risk existed beyond 25 years (standardised mortality ratio, 2.24). Conclusions: Adult-diagnosed coeliac patients have a temporarily increased mortality risk mainly from malignant lymphomas and a decreased risk of any malignancy beyond 15 years post-diagnosis. In contrast, childhood-diagnosed cases are at an increased risk of mortality mainly from external causes, and have long-term mortality risks that requires further investigation.

The XL probe: A luxury or a necessity? Risk stratification in an obese community cohort using transient elastography.

BACKGROUND: Transient elastography is a non-invasive tool which can stratify patients at risk of chronic liver disease. However, a raised body mass index has been independently associated with a failed or unreliable examination. OBJECTIVE: The purpose of this study was to analyse the performance of two probes (M/XL) on a portable transient elastography device within an obese community population. METHOD: The method involved a prospective study with recruitment from a primary care practice. Patients identified with a risk factor for chronic liver disease were invited to a community-based risk stratification pathway for transient elastography readings with both probes. A threshold of ≥8.0 kPa defined elevated liver stiffness. RESULTS: A total of 477 patients attended the pathway. Of the patients, 21% had no valid measurements with the M probe. There was a significant difference between the probes in the proportion achieving ≥10 valid readings (M versus XL probe: 66.2% versus 90.2%; p ≤ 0.001) and in their reliability (M versus XL probe: 77.4% versus 98.5%; p = 0.028). Unreliable readings with the M probe increased as the body mass index increased. The XL probe re-stratified 5.2% of patients to have a normal reading. CONCLUSION: The XL probe on a portable device significantly improves the applicability of transient elastography within a community-based risk stratification pathway.

The risk of venous thromboembolism during and after hospitalisation in patients with inflammatory bowel disease activity.

BACKGROUND: Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism. AIMS: To determine when patients are at high risk of thromboembolic events, including after major surgery, and to guide timing of thromboprophylaxis. METHODS: Each IBD patient from Clinical Practice Research Datalink, linked with Hospital Episode Statistics, was matched to up to five non-IBD patients in this cohort study. We examined their risk of thromboembolism in hospital and within 6 weeks after leaving hospital, with or without undergoing major surgery, and while ambulant. Hazard ratios were estimated using Cox regression, with adjustment for age, sex, body mass index, smoking and history of malignancy or thromboembolism. RESULTS: Overall 23 046 IBD patients had a thromboembolic risk 1.74-times (95% CI = 1.55-1.96) higher than 106 795 non-IBD patients. Among ambulant patients, the thromboembolic risk was raised during acute (hazard ratio = 3.94, 2.79-5.57) or chronic disease activity (3.97, 2.90-5.45) but their absolute risk remained below 5/1000 person-years. The hazard ratio for thromboembolism among in-patients not undergoing major surgery was 1.13 (0.63-2.02), compared to 2.43 (1.20-4.92) among surgical patients, with a near doubling of absolute risk associated with surgery (59.5/1000 person-years, compared with 31.1 without surgery). The absolute risk remained elevated within 6 weeks after leaving hospital (18.6/1000 person-years in IBD patients after surgery). CONCLUSIONS: IBD patients are at an increased risk of venous thromboembolism. Absolute risks are raised during active disease, when in hospital, and after leaving hospital following major surgery.

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.