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.</p

All-cause mortality in people with cirrhosis compared with the general population: a population-based cohort study

Background: Mortality due to cirrhosis has tripled over the last 30 years in the UK. However, we lack adequate, contemporary, population-based estimates of the excess mortality patients who are at risk compared with the general population. Aim: To determine the overall survival in patients with cirrhosis compared with the general population taking into account the effects of severity and aetiology of disease and comorbidity. Methods: In a cohort study, we identified 4537 people with cirrhosis and a control cohort of 44 403 patients, matched by age, sex and general practice from the UK General Practice Research Database between June 1987 and April 2002. Results: Patients with compensated cirrhosis had a nearly five-fold [hazard ratio (HR) 4.7, 95% confidence interval (CI) 4.4–5.0] increased risk of death, while those with decompensated cirrhosis had a near 10-fold (HR 9.7, 95% CI 8.9–10.6) increased risk compared with the general population. Alcoholic cirrhosis conferred a worse prognosis than non-alcohol-related cirrhosis both in the first year following diagnosis and subsequently. Conclusion: Having a diagnosis of cirrhosis confers a substantial increased mortality risk compared with the general population, even for those with compensated disease, with 5-year survival between that seen for breast and colorectal cancer

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

Temporal trends in the incidence of haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018

Background Haemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality and is increasingly being diagnosed. Little is known about what is driving the apparent rise in the incidence of this disease.Methods Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between 1/1/2003 and 31/12/2018 were identified using a previously validated approach. We calculated incidence rates of diagnosed HLH per million population using mid-year population estimates by calendar year, age group, sex and associated comorbidity (haematological malignancy, inflammatory rheumatological or bowel diseases (IBD)) associated with the diagnosis of HLH. We modelled trends in incidence and the interactions between calendar year, age and associated comorbidity using Poisson regression.Findings 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 rising trend in all age groups except those aged less than 5 years. There was a transition across the age groups with greater increases in those aged 5 to 14 years of HLH associated with rheumatological disease/IBD compared to HLH associated with haematological malignancy, with similar increases in HLH associated with both co-morbidities for those 15-54, and greater increases in associated haematological malignancies for those 55 years and older.Interpretation The incidence of HLH in England has quadrupled between 2003 and 2018, increasing 11% annually. Substantial variation in the incidence occurred by age group and by HLH associated comorbidities with inflammatory rheumatological diseases or IBD associated HLH increasing more among the young and middle age groups, whereas in older age groups the largest increase was seen with haematological malignancy-associated HLH.Evidence before this study There is a paucity of population-based data on the epidemiology of HLH worldwide. The available evidence relies mostly upon a collection of cases series published in The Lancet in 2014 which described 2197 cases of HLH in adults reported in the literature to that point. Almost all of these were from tertiary referral specialist centres and/or described in small case series. The incidence of HLH has only been described in a few reports – and mainly this has focused on children with primary HLH. No previous studies have been large enough to examine trends in incidence by age, sex, underlying risk factors and calendar time.Added value of this study This study quantifies the incidence of diagnosed HLH for the first time in a nationwide manner for all age groups. It reports on 1674 patients with HLH from England and shows that there is substantial variation in the incidence by age group, associated disease and calendar time. The results imply reasons for the increase in HLH could be related to the increasing occurrence of haematological cancer, inflammatory rheumatological or bowel diseases and the treatments given for these conditions. This study has been carried out in partnership with the National Congenital Anomalies and Rare Diseases Registration Service and the methodology described can in future be applied to many rare diseases that as yet lack a way of quantifying crucial epidemiological metrics.Implications of all the available evidence The incidence of HLH is rising rapidly in people older than 5 years of age. This could be due to an increase in the biologic, immunomodulation or immunosuppressive therapy being used in people with haematological cancer and inflammatory rheumatological and bowel diseases. Further work should focus on how to minimise the risk of HLH occurring, or to improve treatment of this often fatal disease among those who need treatment for an associated comorbidity

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

Background: Venous thromboembolism 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 comprised 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 sub-type (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. 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 healthcare data

Breast cancer patients are at increased risk of VTE, particularly in the peri-diagnosis period. However, no previous epidemiological 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, using several recently linked data sources from England. Our cohort comprised 13,202 breast cancer patients 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% whilst receiving chemotherapy which was 10.8-fold higher (95% CI, 8.2 to 14.4; absolute risk (AR) =59.6 per 1000 person-years) than women who did not receive chemotherapy. Following surgery the risk was significantly raised in the first month (HR=2.2; 95% CI 1.4 to 3.4; AR=23.5; reference group, no surgery), but it was not raised subsequent to this. Risk of VTE was noticeably higher in the 3-months following initiation of Tamoxifen compared with the risk before therapy (HR=5.5; 95% CI 2.3 to 12.7; AR=24.1), however commencement of aromatase inhibitors was not associated with VTE (HR=0.8; 95% CI 0.5 to 1.4; AR=28.3). In conclusion, women receiving chemotherapy for breast cancer have a clinically important risk of VTE, whilst an increased risk of VTE immediately following endocrine therapy is restricted to Tamoxifen

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

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