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.

How Do Biological Characteristics of Primary Intracranial Tumors Affect Their Clinical Presentation in Children and Young Adults?

We demonstrated the pattern in presentation of primary intracranial tumors in a population-based cohort of patients aged 0-24 years identified from the National Cancer Registry for England, using linked medical records from primary care and hospitals. We used generalized additive models to estimate temporal changes in presentation rates. Borderline and malignant tumors presented at a similar rate in primary care (6.4 and 6.6 consultations per 100 patients each month) and in hospital (3.4 and 3.6). Benign tumors presented earlier but less frequently (rate = 4.4 and rate ratio = 0.75, 95% CI = 0.60-0.93, in primary care; rate = 2.6 and rate ratio = 0.83, 95% CI = 0.77-0.89, in hospital). Many tumors began presenting shortly before their diagnosis, but less aggressive tumors were likely to present earlier in primary care. Earlier detection of less aggressive tumors in primary care may reduce the risk of complications and morbidity among survivors.

The Pattern of Underlying Cause of Death in Patients with Inflammatory Bowel Disease in England: A Record Linkage Study.

BACKGROUND AND AIMS: Numerous studies have established that mortality risk in inflammatory bowel disease [IBD] patients is higher than in the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD. METHODS: A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records. We described the distribution of causes of death among IBD patients by age at death and time since IBD diagnosis. We estimated age-specific mortality rates and hazard ratios of death in multivariable Cox proportional hazards models. RESULTS: 20293 IBD patients were matched to 83261 non IBD patients. The mortality rate was 40% higher in IBD patients [2005 deaths] than in non IBD patients [6024 deaths] (adjusted overall hazard ratio: = 1.4, 95% confidence interval [CI]: = 1.4-1.5], with greater risk of death in Crohn's disease [hazard ratio: = 1.6, 1.5-1.7] than in ulcerative colitis [1.3, 1.3-1.4]. Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis and 8.3% in Crohn's disease. Among IBD patients, death was less likely to be due to circulatory, respiratory or neoplastic diseases than among non IBD patients. In both IBD and non IBD patients all these causes became more clinically important with advancing age, with the commonest neoplastic cause of death being lung cancer rather than gastrointestinal cancers. CONCLUSIONS: IBD patients have an additional risk of death. Most IBD patients die of circulatory or respiratory causes, and the contribution to mortality from long-term complications of IBD is clinically less important.

Where are the opportunities for an earlier diagnosis of primary intracranial tumours in children and young adults?

BACKGROUND: Childhood brain tumours have some of the longest time to diagnosis. A timely diagnosis may have a role in reducing anxiety in waiting for a diagnosis and subsequent morbidity and mortality. We investigated where the opportunities for an earlier diagnosis were, and for which anatomical locations this strategy will most likely to be effective. METHODS: A record-linkage cohort study of patients diagnosed aged 0-24 years with a primary intracranial tumour between 1989 and 2006 in England, using records from the National Cancer Registry linked to hospital admission records from Hospital Episode Statistics (HES, 1997-2006) and primary care consultation records from Clinical Practice Research Datalink (CPRD, 1989-2006). Relevant neurological presentations were extracted from HES and CPRD. Temporal changes in presentation rates were estimated in generalised additive models. RESULTS: Frequency of presentation began to increase six months before diagnosis in primary care and three months before diagnosis in hospital. Supratentorial and midline tumours had the longest presentation history before diagnosis. Peri-ventricular tumours presented frequently in hospital (rate ratio = 1.29 vs supratentorial tumours; 95% CI = 1.12-1.48) or as an emergency (1.24; 1.01-1.51), and in primary care (1.12; 0.62-1.85). CONCLUSIONS: Opportunities for an earlier diagnosis are greater in supratentorial, midline or cranial nerve tumours, which have a longer presentation history than peri-ventricular, cerebellar or brainstem tumours. Common features before diagnosis include headache, convulsions, and growth or endocrine disorders. Focal neurological deficits are uncommon and emerge late in the pre-diagnosis period.

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

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

Pattern of symptoms and signs of primary intracranial tumours in children and young adults: a record linkage study.

OBJECTIVE: To describe the age pattern and temporal evolution of symptoms and signs of intracranial tumours in children and young adults before diagnosis. DESIGN AND SETTING: A record linkage study using population-based data from the National Cancer Registry, linked to Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). PATIENT COHORT: Patients aged 0-24 years when diagnosed with a primary intracranial tumour between 1989 and 2006 in England. METHODS: Linked records of relevant symptoms and signs in primary care and hospitals were extracted from CPRD (1989-2006, 181 patients) and HES (1997-2006, 3959 patients). Temporal and age-specific changes in presentation rates before diagnosis of an intracranial tumour, for each of eight symptom groups, were estimated in generalised additive models. RESULTS: All symptoms presented with increasing frequency until eventual diagnosis. The frequency of presentation of raised intracranial pressure (ICP) to hospitals rose rapidly to 36.4 per 100 person-months (95% CI 34.6 to 38.4) in the final month before diagnosis in the entire cohort. Clinical features in primary care were less specific: the main features were visual disturbance (rate: 0.49 per 100 person-months; 95% CI 0.33 to 0.72) in newborns to 4-year-olds, headache in 5-year-olds to 11-year-olds (0.64; 0.47 to 0.88), 12-year-olds to 18-year-olds (1.59; 1.21 to 2.08) and 19-year-olds to 24-year-olds (2.44; 1.71 to 3.49). The predominant features at hospital admission were those of raised ICP: between 1.17 per 100 person-months (95% CI 1.08 to 1.26) in newborns to 4-year-olds and 0.77 (0.67 to 0.88) in 19-year-olds to 24-year-olds. CONCLUSIONS: Non-localising symptoms and signs were more than twice as common as focal neurological signs. An intracranial tumour should be considered in patients with relevant symptoms that do not resolve or that progress rapidly.