Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review.

BACKGROUND: Immune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood. PURPOSE: To ascertain prognostic factors associated with liver, blood or kidney adverse-events in people receiving immune-suppressing drugs. DATA SOURCES: MEDLINE, Web of Science, EMBASE and the Cochrane library (01 January 1995 to 05 January 2023), and supplementary sources. DATA EXTRACTION AND SYNTHESIS: Data were extracted by one reviewer using a modified CHARMS-PF checklist and validated by another. Two independent reviewers assessed risk of bias using Quality in Prognostic factor Studies tool and assessed the quality of evidence using a Grading of Recommendations Assessment, Development and Evaluation-informed framework. RESULTS: Fifty-six studies from 58 papers were included. High-quality evidence of the following associations was identified: elevated liver enzymes (6 studies) and folate non-supplementation (3 studies) are prognostic factors for hepatotoxicity in those treated with methotrexate; that mercaptopurine (vs azathioprine) (3 studies) was a prognostic factor for hepatotoxicity in those treated with thiopurines; that mercaptopurine (vs azathioprine) (3 studies) and poor-metaboliser status (4 studies) were prognostic factors for cytopenia in those treated with thiopurines; and that baseline elevated liver enzymes (3 studies) are a prognostic factor for hepatotoxicity in those treated with anti-tumour necrosis factors. Moderate and low quality evidence for several other demographic, lifestyle, comorbidities, baseline bloods/serologic or treatment-related prognostic factors were also identified. LIMITATIONS: Studies published before 1995, those with less than 200 participants and not published in English were excluded. Heterogeneity between studies included different cut-offs for prognostic factors, use of different outcome definitions and different adjustment factors. CONCLUSIONS: Prognostic factors for target-organ damage were identified which may be further investigated for their potential role in targeted (risk-stratified) monitoring. PROSPERO REGISTRATION NUMBER: CRD42020208049.

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.

1-year survival in haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018.

Haemophagocytic lymphohistiocytosis (HLH) is a lethal syndrome of excessive immune activation. We undertook a nationwide study in England of all cases of HLH diagnosed between 2003 and 2018, using linked electronic health data from hospital admissions and death certification. We modelled interactions between demographics and comorbidities and estimated one-year survival by calendar year, age group, gender and comorbidity (haematological malignancy, auto-immune, other malignancy) using Cox regression. There were 1628 people with HLH identified. Overall, crude one-year survival was 50% (95% Confidence interval 48-53%) which varied substantially with age (0-4: 61%; 5-14: 76%; 15-54: 61%; > 55: 24% p < 0.01), sex (males, 46%, worse than females, 55% p < 0.01) and associated comorbidity (auto-immune, 69%, haematological malignancy 28%, any other malignancy, 37% p < 0.01). Those aged < 54 years had a threefold increased risk of death at 1-year amongst HLH associated with malignancy compared to auto-immune. However, predicted 1-year survival decreased markedly with age in those with auto-immune (age 0-14, 84%; 15-54, 73%; > 55, 27%) such that among those > 55 years, survival was as poor as for patients with haematological malignancy. One-year survival following a diagnosis of HLH varies considerably by age, gender and associated comorbidity. Survival was better in those with auto-immune diseases among the young and middle age groups compared to those with an underlying malignancy, whereas in older age groups survival was uniformly poor regardless of the underlying disease process.

Temporal Trends in the Incidence of Hemophagocytic Lymphohistiocytosis: A Nationwide Cohort Study From England 2003-2018.

Hemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality, and is increasingly being diagnosed. We aimed to quantify the incidence of diagnosed HLH and examine temporal trends in relation to age and associated diseases. Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between January 1, 2003, and December 31, 2018. We calculated incidence rates of diagnosed HLH per million population by calendar year, age group, sex, and associated comorbidity (hematological malignancy, inflammatory rheumatological or bowel diseases [IBD]). We modeled trends in incidence and the interactions between calendar year, age, and associated comorbidity using Poisson regression. There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (incidence rate ratio [IRR] 2018 compared to 2003: 3.88, 95% confidence interval [CI] 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11, 95% CI 1.09 to 1.12). There was a transition across age groups with greater increases in those aged 5-14 years of HLH associated with rheumatological disease/IBD compared with hematological malignancy, with similar increases in HLH associated with both comorbidities for those 15-54, and greater increases in HLH associated with hematological malignancies for those 55 years and older. The incidence of HLH in England has quadrupled between 2003 and 2018. Substantial variation in the incidence occurred with inflammatory rheumatological diseases/IBD-associated HLH increasing more among the younger age groups, whereas in older age groups, the largest increase was seen with hematological malignancy-associated HLH.

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.

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.

The impact of reader fatigue on the accuracy of capsule endoscopy interpretation.

BACKGROUND AND AIMS: Capsule endoscopy (CE) interpretation requires the review of many thousands of images, with lesions often limited to just a few frames. In this study we aim to determine whether lesion detection declines according to the number of capsule videos read. METHODS: 32 participants, 16 of which were novices (NR) and 16 experienced (ER) capsule readers took part in this prospective evaluation study. Participants read six capsule cases with a variety of lesions, in a randomly assigned order during a single sitting. Psychomotor Vigilance Tests and Fatigue Scores were recorded prior to commencing and then after every two capsules read. Changes in lesion detection and measures of fatigue were assessed across the duration of the study. RESULTS: Mean agreement with the predefined lesions was 48.3% (SD:16.1), and 21.3% (SD:15.1) for the experienced and novice readers respectively. Lesion detection declined amongst experienced reader after the first study (p = 0.01), but remained stable after subsequent capsules read, while NR accuracy was unaffected by capsule numbers read. Objective measures of fatigue did not correlate with reading accuracy. CONCLUSION: This study demonstrates that reader accuracy declines after reading just one capsule study. Subjective and objective measures of fatigue were not sufficient to predict the onset of the effects of fatigue.

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.).

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.

Risk of venous thromboembolism in hospitalised cancer patients in England-a cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognised and life-threatening complication in patients with cancer. However, the precise risk of VTE in hospitalised cancer patients in England has not been previously reported. METHODS: We conducted a cohort study using linked Hospital Episodes Statistics and Office for National Statistics mortality data. We determined the risk of VTE separately for 24 cancer sites following first hospitalisation for cancer (index date) and how this varied by age, proximity from hospital admission, administration of chemotherapy and calendar time. RESULTS: Between 1998 and 2012, 3,558,660 patients were hospitalised for cancer. The cancer sites with the highest risk of VTE during initial hospitalisation for cancer were pancreatic (4.9 %), ovarian (4 %) and liver (3.8 %). The three cancer sites with the highest risk of first VTE event within 6 months from discharge were pancreatic (3.7 %), oesophagus (3 %) and stomach (2.8 %). For most cancers, the risk of VTE within 6 months from discharge was higher amongst patients who underwent chemotherapy compared to those who did not. The impact of age on risk of VTE varied considerably between cancer sites. CONCLUSIONS: The risk of VTE amongst patients hospitalised for cancer varies greatly by cancer site, age, proximity from hospital admission, and chemotherapy administration.

Risk of venous thromboembolism in people with lung cancer: a cohort study using linked UK healthcare data.

BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable cause of death in people with lung cancer. Identification of those most at risk and high-risk periods may provide the opportunity for better targeted intervention. METHODS: We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics and Cancer Registry data. Our cohort comprises 10 598 people with lung cancer diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, tumour and treatment-related factors (time-varying effects of chemotherapy and surgery) independently affected VTE risk. We also determined the effect of a VTE diagnosis on the survival of people with lung cancer. RESULTS: People with lung cancer had an overall VTE incidence of 39.2 per 1000 person-years (95% confidence interval (CI), 35.4-43.5), though rates varied depending on the patient group and treatment course. Independent factors associated with increased VTE risk were metastatic disease (hazard ratio (HR)=1.9, CI 1.2-3.0 vs local disease); adenocarcinoma subtype (HR=2.0, CI 1.5-2.7, vs squamous cell; chemotherapy administration (HR=2.1, CI 1.4-3.0 vs outside chemotherapy courses); and diagnosis via emergency hospital admission (HR=1.7, CI 1.2-2.3 vs other routes to diagnosis). Patients with VTE had an approximately 50% higher risk of mortality than those without VTE. CONCLUSIONS: People with lung cancer have especially high risk of VTE if they have advanced disease, adenocarcinoma or are undergoing chemotherapy. The presence of VTE is an independent risk factor for death.

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.

Support for patients with celiac disease: A literature review.

BACKGROUND: Celiac disease (CD) is a lifelong disorder. Patients are at increased risk of complications and comorbidity. OBJECTIVES: We conducted a review of the literature on patient support and information in CD and aim to issue recommendations about patient information with regards to CD. DATA SOURCE: We searched PubMed for English-language articles published between 1900 and June 2014, containing terms related to costs, economics of CD, or education and CD. STUDY SELECTION: Papers deemed relevant by any of the participating authors were included in the study. DATA SYNTHESIS: No quantitative synthesis of data was performed. Instead we formulated a consensus view of the information that should be offered to all patients with CD. RESULTS: There are few randomized clinical trials examining the effect of patient support in CD. Patients and their families receive information from many sources. It is important that health care personnel guide the patient through the plethora of facts and comments on the Internet. An understanding of CD is likely to improve dietary adherence. Patients should be educated about current knowledge about risk factors for CD, as well as the increased risk of complications. Patients should also be advised to avoid other health hazards, such as smoking. Many patients are eager to learn about future non-dietary treatments of CD. This review also comments on novel therapies but it is important to stress that no such treatment is available at present. CONCLUSION: Based on mostly observational data, we suggest that patient support and information should be an integral part of the management of CD, and is likely to affect the outcome of CD.

Causes of death in people with coeliac disease in England compared with the general population: a competing risk analysis.

INTRODUCTION: Quantifying excess cause-specific mortality among people with coeliac disease (CD) compared with the general population accounting for competing risks will allow accurate information to be given on risk of death from specific causes. METHOD: We identified from the Clinical Practice Research Datalink all patients with CD linked to Office for National Statistics between 1998 and 2012. We selected controls by frequency matching from the registered general practice population within 10-year age bands. We calculated the adjusted cumulative incidence (including adjustment for competing risks) and excess cumulative incidence for different causes of death up to 10 years from diagnosis. RESULTS: Of the 10 825 patients with CD, 773 died within the study period. The overall mortality rate among patients with CD was 128/10 000 person years compared with 153/10 000 in controls (HR=0.94 95% CI 0.84 to 1.01). We found no overall difference in the cumulative incidence of respiratory disease, digestive disease or cancer related death among cases and controls. The adjusted cumulative incidence of death from cardiovascular deaths was slightly lower compared with those without CD diagnosis (CD 0.32% vs controls 0.41%) with a corresponding excess cumulative incidence of -0.08% (95% CI -0.13 to -0.04). However, patients with CD had 0.15% excess risk (95% CI 0.03 to 0.27) of deaths from non-Hodgkin's lymphoma from the general population baseline risk. CONCLUSIONS: Overall, people with CD have no major excess risk of cancer, digestive disease or respiratory disease related or cardiovascular mortality compared with the general population. These findings should be reassuring to patients with CD and clinicians managing their care.

The association of exposure to hepatitis B and C viruses with lung function and respiratory disease: a population based study from the NHANES III database.

BACKGROUND: Globally, 500 million people are chronically infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV). While these viruses are notorious for their detrimental effect on the liver they are also known to affect multiple organs in the body including the lungs. AIM: To investigate if exposure to HBV and HCV is associated with lung function and respiratory diseases. METHODS: Data from the Third National Health and Nutrition Examination Survey (NHANES III) was analysed using multiple linear regressions to investigate the association between exposure to HBV and HCV with the various measures of lung function, while multiple logistic regressions were used to evaluate the association with the respiratory diseases asthma and chronic obstructive pulmonary disease (COPD). RESULTS: Exposure to HCV was significantly associated with an increase in Forced Expiratory Volume in 1 s, FEV1 (Coef: 97.94 ml, 95% CI: 38.87 to 157.01) and Full Vital Capacity, FVC (Coef: 90 ml, 95% CI: 14.50 to 166.24). Individuals who had been exposed to both HBV and HCV also had a significantly higher FEV1 (Coef: 145.82, CI: 60.68 to 230.94) and FVC (Coef: 195.09, CI: 78.91 to 311.26). There was also a significant association between exposure to HBV and asthma (OR: 1.28, 95% CI: 1.05 to 1.58). These associations were no longer significant after additionally adjusting for cocaine and marijuana use as well as poverty income ratio. CONCLUSION: Our research implies that hepatotropic viruses may affect the respiratory system, but more work at a population level is needed to further explore these associations.

Venous thromboembolism in children with cancer - a population-based cohort study.

INTRODUCTION: Cancer is a known risk factor for venous thromboembolism (VTE) in adults, but population-based data in children are scarce. MATERIALS AND METHODS: We conducted a cohort study utilising linkage of the Clinical Practice Research Database (primary care), Hospital Episodes Statistics (secondary care), UK Cancer Registry data and Office for National Statistics cause of death data. From these databases, we selected 498 children with cancer diagnosed between 1997 and 2006 and 20,810 controls without cancer. We calculated VTE incidence rates in children with cancer vs. controls, and hazard ratios (HRs) using Cox regression. RESULTS: We identified four VTE events in children with cancer compared with four events in the larger control population corresponding to absolute risks of 1.52 and 0.06 per 1000 person-years respectively. The four children with VTE and cancer were diagnosed with hematological, bone or non-specified cancer. Childhood cancer was hence associated with a highly increased risk of VTE (HR adjusted for age and sex: 28.3; 95%CI=7.0-114.5). CONCLUSIONS: Children with cancer are at increased relative risk of VTE compared to those without cancer. Physicians could consider thromboprophylaxis in children with cancer to reduce their excess risk of VTE however the absolute risk is extremely small and the benefit gained therefore would need to be balanced against the risk invoked of implementing such a strategy. NOVELTY & IMPACT STATEMENTS: While there is a reasonable level of knowledge about the risk of VTE in adult populations, it is not well known whether this risk is reflected in paediatric patients. We found a substantial increase in risk of VTE in children with cancer compared to a child population without cancer. While this finding is important, the absolute risk of VTE is still low and must be balanced with the risks of anticoagulation.

Antibiotic exposure and the development of coeliac disease: a nationwide case-control study.

BACKGROUND: The intestinal microbiota has been proposed to play a pathogenic role in coeliac disease (CD). Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce. METHODS: In this population-based case-control study we linked nationwide histopathology data on 2,933 individuals with CD (Marsh stage 3; villous atrophy) to the Swedish Prescribed Drug Register to examine the association between use of systemic antibiotics and subsequent CD. We also examined the association between antibiotic use in 2,118 individuals with inflammation (Marsh 1-2) and in 620 individuals with normal mucosa (Marsh 0) but positive CD serology. All individuals undergoing biopsy were matched for age and sex with 28,262 controls from the population. RESULTS: Antibiotic use was associated with CD (Odds ratio [OR] = 1.40; 95% confidence interval [CI] = 1.27-1.53), inflammation (OR = 1.90; 95% CI = 1.72-2.10) and normal mucosa with positive CD serology (OR = 1.58; 95% CI = 1.30-1.92). ORs for prior antibiotic use in CD were similar when we excluded antibiotic use in the last year (OR = 1.30; 95% CI = 1.08-1.56) or restricted to individuals without comorbidity (OR = 1.30; 95% CI = 1.16 - 1.46). CONCLUSIONS: The positive association between antibiotic use and subsequent CD but also with lesions that may represent early CD suggests that intestinal dysbiosis may play a role in the pathogenesis of CD. However, non-causal explanations for this positive association cannot be excluded.