Population-Based Study of Alcohol-Related Liver Disease in England in 2001-2018: Influence of Socioeconomic Position.

INTRODUCTION: England has seen an increase in deaths due to alcohol-related liver disease (ALD) since 2001. We studied the influence of socioeconomic position on the incidence of ALD and the mortality after ALD diagnosis in England in 2001-2018. METHODS: This was an observational cohort study based on health records contained within the UK Clinical Practice Research Datalink covering primary care, secondary care, cause of death registration, and deprivation of neighborhood areas in 18.8 million residents. We estimated incidence rate and incidence rate ratios of ALD and hazard ratios of mortality. RESULTS: ALD was diagnosed in 57,784 individuals with a median age of 54 years and of whom 43% had cirrhosis. The ALD incidence rate increased by 65% between 2001 and 2018 in England to reach 56.1 per 100,000 person-years in 2018. The ALD incidence was 3-fold higher in those from the most deprived quintile vs those from the least deprived quintile (incidence rate ratio 3.30, 95% confidence interval 3.21-3.38), with reducing inequality at older than at younger ages. For 55- to 74-year-olds, there was a notable increase in the incidence rate between 2001 and 2018, from 96.1 to 158 per 100,000 person-years in the most deprived quintile and from 32.5 to 70.0 in the least deprived quintile. After ALD diagnosis, the mortality risk was higher for patients from the most deprived quintile vs those from the least deprived quintile (hazard ratio 1.22, 95% confidence interval 1.18-1.27), and this ratio did not change during 2001-2018. DISCUSSION: The increasing ALD incidence in England is a greater burden on individuals of low economic position compared with that on those of high socioeconomic position. This finding highlights ALD as a contributor to inequality in health.

Uptake and safety of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide observational study.

OBJECTIVE: The uptake and safety of pneumococcal vaccination in people with immune mediated inflammatory diseases (IMIDs) is poorly understood. We investigated the UK wide pneumococcal vaccine uptake in adults with IMIDs and explored the association between vaccination and IMID flare. METHODS: Adults with IMIDs diagnosed on or before 01/09/2018, prescribed steroid-sparing drugs within the last 12 months and contributing data to the Clinical Practice Research Datalink Gold were included. Vaccine uptake was assessed using a cross-sectional study design. Self-controlled case series (SCCS) analysis investigated the association between pneumococcal vaccination and IMID flare. The SCCS observation period was up-to six-month before and after pneumococcal vaccination. This was partitioned into a 14-day pre-vaccination induction, 90-days post-vaccination exposed, and the remaining unexposed periods. RESULTS: We included 32 277 patients, 14 151 with RA, 13 631 with IBD, 3,804 with axial spondyloarthritis and 691 with SLE. Overall, 57% were vaccinated against pneumococcus. Vaccine uptake was lower in those younger than 45 years (32%), with IBD (42%), and without additional indication(s) for vaccination (46%). In the vaccine-safety study, data for 1,067, 935, and 451vaccinated patients with primary-care consultations for joint pain, AIRD flare and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with primary-care consultations for joint pain, AIRD flare and IBD flare in the exposed period with incidence rate ratios (95% Confidence Interval) 0.95 (0.83-1.09), 1.05 (0.92-1.19), and 0.83 (0.65-1.06) respectively. CONCLUSION: Uptake of pneumococcal vaccination in UK patients with IMIDs was suboptimal. Vaccination against pneumococcal disease was not associated with IMID flare.

Patient and health professional views on risk-stratified monitoring of immune-suppressing treatment in adults with inflammatory diseases.

OBJECTIVE: To explore the acceptability of an individualised risk-stratified approach to monitoring for target-organ toxicity in adult patients with immune-mediated inflammatory diseases established on immune-suppressing treatment(s). METHODS: Adults (≥18 years) taking immune-suppressing treatment(s) for at-least six months, and healthcare professionals (HCPs) with experience of either prescribing and/or monitoring immune-suppressing drugs were invited to participate in a single, remote, one-to-one, semi-structured interview. Interviews were conducted by a trained qualitative researcher and explored their views and experiences of current monitoring and acceptability of a proposed risk-stratified monitoring plan. Interviews were transcribed verbatim and inductively analysed using thematic analysis in NVivo. RESULTS: Eighteen patients and 13 HCPs were interviewed. While participants found monitoring of immune-suppressing drugs with frequent blood-tests reassuring, the current frequency of these was considered burdensome by patients and HCPs alike, and to be a superfluous use of healthcare resources. Given abnormalities rarely arose during long-term treatment, most felt that monitoring blood-tests were not needed as often. Patients and HCPs found it acceptable to increase the interval between monitoring blood-tests from three-monthly to six-monthly or annually depending on the patients' risk profiles. Conditions of accepting such a change included: allowing for clinician and patient autonomy in determining an individuals' frequency of monitoring blood-tests, the flexibility to change monitoring frequency if someone's risk profile changed, and endorsement from specialist societies and healthcare providers such as the National Health Service. CONCLUSION: A risk-stratified approach to monitoring was acceptable to patients and HCPs. Guideline groups should consider these findings when recommending blood-test monitoring intervals.

Discontinuation of anti-tumour necrosis factor alpha treatment owing to blood test abnormalities, and cost-effectiveness of alternate blood monitoring strategies.

BACKGROUND: There is no evidence base to support the use of 6-monthly monitoring blood tests for the early detection of liver, blood and renal toxicity during established anti-tumour necrosis factor alpha (TNFα) treatment. OBJECTIVES: To evaluate the incidence and risk factors of anti-TNFα treatment cessation owing to liver, blood and renal side-effects, and to estimate the cost-effectiveness of alternate intervals between monitoring blood tests. METHODS: A secondary care-based retrospective cohort study was performed. Data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) were used. Patients with at least moderate psoriasis prescribed their first anti-TNFα treatment were included. Treatment discontinuation due to a monitoring blood test abnormality was the primary outcome. Patients were followed-up from start of treatment to the outcome of interest, drug discontinuation, death, 31 July 2021 or up to 5 years, whichever came first. The incidence rate (IR) and 95% confidence intervals (CIs) of anti-TNFα discontinuation with monitoring blood test abnormality was calculated. Multivariate Cox regression was used to examine the association between risk factors and outcome. A mathematical model evaluated costs and quality-adjusted life years (QALYs) associated with increasing the length of time between monitoring blood tests during anti-TNFα treatment. RESULTS: The cohort included 8819 participants [3710 (42.1%) female, mean (SD) age 44.76 (13.20) years] that contributed 25 058 person-years (PY) of follow-up and experienced 125 treatment discontinuations owing to a monitoring blood test abnormality at an IR of 5.85 (95% CI 4.91-6.97)/1000 PY. Of these, 64 and 61 discontinuations occurred within the first year and after the first year of treatment start, at IRs of 8.62 (95% CI 6.74-11.01) and 3.44 (95% CI 2.67-4.42)/1000 PY, respectively. Increasing age (in years), diabetes and liver disease were associated with anti-TNFα discontinuation after a monitoring blood test abnormality [adjusted hazard ratios of 1.02 (95% CI 1.01-1.04), 1.68 (95% CI 1.00-2.81) and 2.27 (95% CI 1.26-4.07), respectively]. Assuming a threshold of £20 000 per QALY gained, no monitoring was most cost-effective, but all extended periods were cost-effective vs. 3- or 6-monthly monitoring. CONCLUSIONS: Anti-TNFα drugs were uncommonly discontinued owing to abnormal monitoring blood tests after the first year of treatment. Extending the duration between monitoring blood tests was cost-effective. Our results produce evidence for specialist society guidance to reduce patient monitoring burden and healthcare costs.

Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity.

BACKGROUND AND AIMS: It is thought that alcohol intake and body mass index (BMI) interact supra-additively to modulate the risk of cirrhosis, but evidence for this phenomenon is limited. We investigated the interrelationship between alcohol and BMI on the incidence of cirrhosis morbidity for participants of the United Kingdom Biobank (UKB) study. APPROACH AND RESULTS: The primary outcome was the cumulative incidence of cirrhosis morbidity, defined as a first-time hospital admission for cirrhosis (with noncirrhosis mortality incorporated as a competing risk). All UKB participants without a previous hospital admission for cirrhosis were included in the analysis. We determined the ratio of the 10-year cumulative incidence in harmful drinkers versus safe drinkers according to BMI. We also calculated the excess cumulative incidence at 10 years for individuals with obesity and/or harmful alcohol compared to safe drinkers with a healthy BMI of 20-25.0 kg/m2 . A total of 489,285 UK Biobank participants were included, with mean of 10.7 person-years' follow-up. A total of 2070 participants developed the primary outcome, equating to a crude cumulative incidence of 0.36% at 10 years (95% CI:0.34-0.38). The 10-year cumulative incidence was 8.6 times higher for harmful (1.38%) versus safe drinkers (0.16%) if BMI was healthy. Conversely, it was only 3.6 times higher for obese participants (1.99% vs. 0.56%). Excess cumulative incidence was 1.22% (95% CI:0.89-1.55) for harmful drinkers with a healthy BMI, 0.40% (95% CI:0.34-0.46) for obese individuals drinking at safe levels, and 1.83% (95% CI:1.46-2.20) for obese harmful drinkers (all compared to safe drinkers with a healthy BMI). CONCLUSIONS: Alcohol intake and obesity are independent risk factors for cirrhosis morbidity, but they do not interact supra-additively to modulate the cumulative incidence of this outcome.

Is vaccination against COVID-19 associated with autoimmune rheumatic disease flare? A self-controlled case series analysis.

OBJECTIVES: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and autoimmune rheumatic disease (AIRD) flare. MATERIAL AND METHODS: Patients with AIRDs vaccinated against COVID-19 who consulted for disease flare between 1 December 2020 and 31 December 2021 were ascertained in Clinical Practice Research Datalink (Aurum). AIRD flare was defined as consultation for AIRD with CS prescription on the same day or the next day. Vaccination was defined using date of vaccination and product code. The observation period was partitioned into vaccine-exposed (21 days after vaccination), pre-vaccination (7 days before vaccination) and remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and outcomes. Season adjusted incidence rate ratios (aIRR) and 95% CI were calculated using self-controlled case series analysis. RESULTS: Data for 3554 AIRD cases, 72% female, mean age 65 years and 68.3% with RA, were included. COVID-19 vaccination was associated with significantly fewer AIRD flares in the 21-day vaccine-exposed period when all vaccinations were considered [aIRR (95% CI) 0.89 (0.80, 0.98)]. Using dose-stratified analyses there was a statistically significant negative association in the 21 days after first COVID-19 vaccination but no association after the second or third COVID-19 vaccinations [aIRR (95% CI) 0.76 (0.66, 0.89), 0.94 (0.79, 1.11) and 1.01 (0.85, 1.20), respectively]. On AIRD-type stratified analyses, vaccination was not associated with disease flares. Vaccination without or after severe acute respiratory syndrome coronavirus 2 infection, and with vectored DNA or mRNA vaccines, associated with comparable reduced risk of AIRD flares in the vaccine-exposed period after first COVID-19 vaccination. CONCLUSIONS: Vaccination against COVID-19 was not associated with increased AIRD flares regardless of prior COVID-19, AIRD type, and whether mRNA or DNA vaccination technology were used.

Inverse association between blood pressure and pulse oximetry accuracy: an observational study in patients with suspected or confirmed COVID-19 infection.

BACKGROUND: Pulse oximeters are a standard non-invasive tool to measure blood oxygen levels, and are used in multiple healthcare settings. It is important to understand the factors affecting their accuracy to be able to use them optimally and safely. This analysis aimed to explore the association of the measurement error of pulse oximeters with systolic BP, diastolic BP and heart rate (HR) within ranges of values commonly observed in clinical practice. METHODS: The study design was a retrospective observational study of all patients admitted to a large teaching hospital with suspected or confirmed COVID-19 infection from February 2020 to December 2021. Data on systolic and diastolic BPs and HR levels were available from the same time period as the pulse oximetry measurements. RESULTS: Data were available for 3420 patients with 5927 observations of blood oxygen saturations as measured by pulse oximetry and ABG sampling within 30 min. The difference in oxygen saturation using the paired pulse oximetry and arterial oxygen saturation difference measurements was inversely associated with systolic BP, increasing by 0.02% with each mm Hg decrease in systolic BP (95% CI 0.00% to 0.03%) over a range of 80-180 mm Hg. Inverse associations were also observed between the error for oxygen saturation as measured by pulse oximetry and with both diastolic BP (+0.03%; 95% CI 0.00% to 0.05%) and HR (+0.04%; 95% CI 0.02% to 0.06% for each unit decrease in the HR). CONCLUSIONS: Care needs to be taken in interpreting pulse oximetry measurements in patients with lower systolic and diastolic BPs, and HRs, as oxygen saturation is overestimated as BP and HR decrease. Confirmation of the oxygen saturation with an ABG may be appropriate in some clinical scenarios.

Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.

Incidence and survival of haemophagocytic lymphohistiocytosis: A population-based cohort study from England.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory condition with poor outcomes. OBJECTIVES: Few population-based estimates of the incidence and survival in adults exist. We aimed to provide these data for England. METHODS: We used population-based linked data from primary care, secondary care, cancer registries and mortality databases in England to identify people diagnosed with HLH between 1 January 2000 and 31 December 2016. We calculated annual incidence rates by age and sex, modelled change in incidence over time with Poisson regression, calculated overall 1-year survival using Kaplan-Meier methods and estimated adjusted hazard ratios (HRs) of death using a Cox proportional hazards model. RESULTS: We identified 214 patients with HLH. The reported age and sex-adjusted incidence increased twofold over the period, from around one to around two per million. Incidence was highest in those below 1 year (14.6 per million) and ≥75 years (2.2 per million), and lowest in those aged 15-44 years (0.8 per million). One-year survival varied by age and sex from 77% (95% confidence interval [CI] 63%-86%) in those <15 years to 30% (95% CI 14%-49%) in those ≥75. In patients with haematological cancer, the adjusted HR for death was 2.60 (95% CI 1.45-4.66) compared to patients with no malignant or rheumatological disease. CONCLUSION: The incidence of HLH diagnosis in England has increased between 2000 and 2016 and occurs in all ages with varying underlying diseases. One-year survival varies substantially, being particularly poor in those aged over 75 years and those with haematological malignancy.

Development and validation of a prognostic model for leflunomide discontinuation with abnormal blood tests during long-term treatment: cohort study using data from the Clinical Practice Research Datalink Gold and Aurum.

OBJECTIVE: To develop and validate a prognostic model for LEF discontinuation with abnormal blood test results. METHODS: Data from the Clinical Practice Research Datalink Gold and Aurum were used for model development and external validation, respectively. Participants prescribed LEF between 1 January 2007 and 31 December 2019 were followed up from 6 months after the first general practitioner prescription to the earliest of date of outcome, death, 5 year follow-up or 31 December 2019. Candidate prognostic factors were ascertained using theory and data-driven approaches. Penalized Cox regression was performed to develop the risk equation, followed by internal validation using 500 bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination. RESULTS: Data for 1487 and 2329 participants contributing 3140 and 5246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy and either cytopenia or elevated liver enzymes during the first 6 months of shared-care LEF prescription were strong predictors of drug discontinuation with a hazard ratio of 4.39 (95% CI 1.74, 11.06) and 3.06 (2.15, 4.35), respectively. The unadjusted and optimism-adjusted calibration slope in development data was 1.00 (95% CI 0.75, 1.25) and 0.72 (95% CI 0.47, 0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74, 1.07). The model showed prognostic separation with an optimism-adjusted Royston D statistic of 0.73 (95% CI 0.44, 1.02). CONCLUSION: We have developed and externally validated an easy-to-use prognostic model that may be used to risk stratify monitoring for LEF toxicity and to make informed choices about risks when choosing treatments.

A validation study of the identification of haemophagocytic lymphohistiocytosis in England using population-based health data.

We assessed the validity of coded healthcare data to identify cases of haemophagocytic lymphohistiocytosis (HLH). Hospital Episode Statistics (HES) identified 127 cases within five hospital Trusts 2013-2018 using ICD-10 codes D76.1, D76.2 and D76.3. Hospital records were reviewed to validate diagnoses. Out of 74 patients, 73 were coded D76.1 or D76.2 (positive predictive value 89·0% [95% Confidence Interval {CI} 80·2-94·9%]) with confirmed/probable HLH. For cases considered not HLH, 44/53 were coded D76.3 (negative predictive value 97·8% [95% CI 88·2-99·9%]). D76.1 or D76.2 had 68% sensitivity in detecting HLH compared to an established active case-finding HLH register in Sheffield. Office for National Statistics (ONS) mortality data (2003-2018) identified 698 patients coded D76.1, D76.2 and D76.3 on death certificates. Five hundred and forty-one were coded D76.1 or D76.2 of whom 524 (96·9%) had HLH in the free-text cause of death. Of 157 coded D76.3, 66 (42·0%) had HLH in free text. D76.1 and D76.2 codes reliably identify HLH cases, and provide a lower bound on incidence. Non-concordance between D76.3 and HLH excludes D76.3 as an ascertainment source from HES. Our results suggest electronic healthcare data in England can enable population-wide registration and analysis of HLH for future research.

What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline?

OBJECTIVES: To examine incidence of treatment changes due to abnormal blood-test results and, to explore rates of treatment changes due to liver, kidney and haematological blood-test abnormalities in autoimmune rheumatic diseases (AIRD) treated with low-dose MTX or LEF. METHODS: Data for people with AIRDs prescribed MTX or LEF were extracted from the Clinical Practice Research Datalink. Participants were followed-up from first prescription of MTX or LEF in primary care. Primary outcome of interest was drug discontinuation, defined as a prescription gap of ≥90 days following an abnormal (or severely abnormal) blood-test result. Dose reduction was examined between consecutive prescriptions. Incidence rates per 1000 person-years were calculated. RESULTS: 15, 670 and 2,689 participants contributing 46, 571 and 4,558 person-years follow-up were included in MTX and LEF cohorts, respectively. The incidence of MTX and LEF discontinuation with abnormal (severely abnormal) blood-test was 42.24 (6.16) and 106.53 (9.42)/1000 person-years in year 1, and 22.44 (2.84) and 31.69 (4.40)/1000 person years, respectively, thereafter. The cumulative incidence of MTX and LEF discontinuation with abnormal (severely abnormal) blood tests was 1 in 24 (1 in 169), 1 in 9 (1 in 106) at 1 year; and 1 in 45 (1 in 352), 1 in 32 (1 in 227) per-year, respectively, thereafter. Raised liver enzymes were the commonest abnormality associated with drug discontinuation. MTX and LEF dose reduction incidence were comparable in year 1, however, thereafter MTX dose was reduced more often than LEF [16.60 (95% CI 13.05, 21.13) vs 8.10 (95% CI 4.97, 13.20)/1000 person-years]. CONCLUSION: MTX and LEF were discontinued for blood-test abnormalities after year 1 of treatment, however, discontinuations for severely abnormal results were uncommon.

Diagnosis of Barrett's esophagus and esophageal varices using a magnetically assisted capsule endoscopy system.

BACKGROUND AND AIMS: Magnetically assisted capsule endoscopy (MACE) potentially offers a comfortable, patient friendly, and community-based alternative to gastroscopy (EGD). This pilot study aims to explore whether this approach can be used to accurately diagnose Barrett's esophagus (BE) and esophageal varices. METHOD: The MiroCam Navi capsule system was used to examine the upper GI tract in patients due to undergo a clinically indicated EGD. A total of 50 participants were enrolled: 34 had known pathology (17 BE, 17 esophageal varices [EV]) and 16 controls. Patients underwent the MACE procedure with the operator blinded to the indication and any previous endoscopic diagnoses. The subsequent EGD was performed by an endoscopist blinded to the MACE findings. Diagnostic yield, comfort, and patient preference between the 2 modalities were compared. RESULTS: The mean age of the participants was 61 years, the male/female ratio was 2.1:1, the mean body mass index was 29.5 kg/m2, and the average chest measurement was 105.3 cm. Forty-seven patients underwent both procedures; 3 patients were unable to swallow the capsule. With the use of the magnet, it was possible to hold the capsule within the esophagus for a mean duration of 190 seconds and up to a maximum of 634 seconds. A correct real-time MACE diagnosis was made in 11 of 15 patients with EV (sensitivity 73.3% [95% confidence interval (CI), 44.9%-92.2%] and specificity 100% [95% CI, 89.1%-100%]) and 15 of 16 patients with BE (sensitivity 93.8% [95% CI, 69.8%-99.8%] and specificity of 100% [95% CI, 88.8%-100%]). MACE was considered more comfortable than conventional endoscopy (P < .0001); the mean score was 9.2 for MACE compared with 6.7 for EGD when assessed on a 10-point scale. No MACE- or EGD-related adverse events occurred. CONCLUSION: This pilot study demonstrates that MACE is both safe and well tolerated by patients. Accuracy for the diagnosis of BE was high, and therefore MACE may have a role in screening for this condition. (Clinical trial registration number: NCT02852161.).

Use of rapid reading software to reduce capsule endoscopy reading times while maintaining accuracy.

BACKGROUNDS AND AIMS: A typical capsule endoscopy (CE) case generates tens of thousands of images, with abnormalities often confined to a just few frames. Omni Mode is a novel EndoCapsule software algorithm (Olympus, Tokyo, Japan) that proposes to intelligently remove duplicate images while maintaining accuracy in lesion detection. METHODS: This prospective multicenter study took place across 9 European centers. Consecutive, unselected CE cases were read conventionally in normal mode, with every captured frame reviewed. Cases were subsequently anonymized and randomly allocated to another center where they were read using Omni Mode. Detected lesions and reading times were recorded, with findings compared between both viewing modes. The clinical significance of lesions was described according to the P classification (P0, P1, and P2). Where a discrepancy in lesion detection in either mode was found, expert blinded review at a consensus meeting was undertaken. RESULTS: The patient population undergoing CE had a mean age of 49.5 years (range, 18-91), with the investigation of anemia or GI bleeding accounting for 71.8% of cases. The average small-bowel transit time was 4 hours, 26 minutes. The mean reading time in normal mode was 42.5 minutes. The use of Omni Mode was significantly faster (P < .0001), with an average time saving of 24.6 minutes (95% confidence interval, 22.8-26.9). The 2127 lesions were identified and classified according to the P classification as P0 (1234), P1 (656), and P2 (237). Lesions were identified using both reading modes in 40% (n = 936), and 1186 lesions were identified by either normal or Omni Mode alone. Normal mode interpretation was associated with 647 lesions being missed, giving an accuracy of .70. Omni Mode interpretation led to 539 lesions being missed, with an accuracy of .75. There was no significant difference in clinical conclusions made between either reading mode. CONCLUSIONS: This study shows that CE reading times can be reduced by an average of 40%, without any reduction in clinical accuracy.

Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data.

BACKGROUND & AIMS: Cirrhosis, the prevalence of which is increasing, is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. METHODS: We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients vs. controls, adjusted for age, sex and comorbidity. RESULTS: The five-year hip fracture risk was raised both in England (2.9% vs. 0.8% for controls) and Denmark (4.6% vs. 0.9% for controls). With confounder adjustment, patients with cirrhosis had fivefold (adjusted HR 5.5; 95% CI 4.3-6.9), and 8.5-fold (adjusted HR 8.5; 95% CI 7.8-9.3) increased rates of hip fracture, in England and Denmark, respectively. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p <0.001), being stronger in younger age groups (under 45 years, HR 17.9 and 16.6 for English and Danish patients, respectively) than in patients over 75 years (HR 2.1 and 2.9, respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. CONCLUSIONS: Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population. These findings support the need for more effort towards fracture prevention in this population, to benefit individuals and reduce the societal burden. LAY SUMMARY: Alcoholic cirrhosis creates a large public health burden and is a risk factor for bone fractures. Based on data from England and Denmark, we found that hip fractures occur more than five times more frequently in people with alcoholic cirrhosis than in people without the disease. Additionally, the aftermath of the hip fracture is severe, such that up to 11% of patients with alcoholic cirrhosis die within 30 days after their hip fracture. These results suggest that efforts directed towards fracture prevention in people with alcoholic cirrhosis could be beneficial.

When are breast cancer patients at highest risk of venous thromboembolism? A cohort study using English health care data.

Patients with breast cancer are at increased risk of venous thromboembolism (VTE), particularly in the peridiagnosis period. However, no previous epidemiologic studies have investigated the relative impact of breast cancer treatments in a time-dependent manner. We aimed to determine the impact of breast cancer stage, biology, and treatment on the absolute and relative risks of VTE by using several recently linked data sources from England. Our cohort comprised 13,202 patients with breast cancer from the Clinical Practice Research Datalink (linked to Hospital Episode Statistics and Cancer Registry data) diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, treatment-related, and biological factors independently affected VTE risk. Women had an annual VTE incidence of 6% while receiving chemotherapy which was 10.8-fold higher (95% confidence interval [CI], 8.2-14.4; absolute rate [AR], 59.6 per 1000 person-years) than that in women who did not receive chemotherapy. After surgery, the risk was significantly increased in the first month (hazard ratio [HR], 2.2; 95% CI, 1.4-3.4; AR, 23.5; reference group, no surgery), but the risk was not increased after the first month. Risk of VTE was noticeably higher in the 3 months after initiation of tamoxifen compared with the risk before therapy (HR, 5.5; 95% CI, 2.3-12.7; AR, 24.1); however, initiating therapy with aromatase inhibitors was not associated with VTE (HR, 0.8; 95% CI, 0.5-1.4; AR, 28.3). In conclusion, women receiving chemotherapy for breast cancer have a clinically important risk of VTE, whereas an increased risk of VTE immediately after endocrine therapy is restricted to tamoxifen.

Venous thromboembolism and mortality in breast cancer: cohort study with systematic review and meta-analysis.

BACKGROUND: Breast cancer patients are at an increased risk of venous thromboembolism (VTE). However, current evidence as to whether VTE increases the risk of mortality in breast cancer patients is conflicting. We present data from a large cohort of patients from the UK and pool these with previous data from a systematic review. METHODS: Using the Clinical Practice Research Datalink (CPRD) dataset, we identified a cohort of 13,202 breast cancer patients, of whom 611 were diagnosed with VTE between 1997 and 2006 and 12,591 did not develop VTE. Hazard ratios (HR) were used to compare mortality between the two groups. These were then pooled with existing data on this topic identified via a search of the MEDLINE and EMBASE databases (until January 2015) using a random-effects meta-analysis. RESULTS: Within the CPRD, VTE was associated with increased mortality when treated as a time-varying covariate (HR = 2.42; 95% CI, 2.13-2.75), however, when patients were permanently classed as having VTE based on presence of a VTE event within 6 months of cancer diagnosis, no increased risk was observed (HR = 1.22; 0.93-1.60). The pooled HR from seven studies using the second approach was 1.69 (1.12-2.55), with no effect seen when restricted to studies which adjusted for key covariates. CONCLUSION: A large HR for VTE in the time-varying covariate analysis reflects the known short-term mortality following a VTE. When breast cancer patients are fortunate to survive the initial VTE, the influence on longer-term mortality is less certain.