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.

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.

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.

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.

Upper gastrointestinal haemorrhage and deprivation: a nationwide cohort study of health inequality in hospital admissions.

OBJECTIVE: Inequalities in health are well recognized in cardiovascular disease and cancer, but in comparison, we have minimal understanding for upper gastrointestinal bleeding. Since furthering our understanding of such inequality signposts preventable disease, we investigated in detail the association between upper gastrointestinal bleeding and socioeconomic status. DESIGN: Population-based cohort study. SETTING: All English National Health Service hospitals. POPULATION: English adult population, 1 January 2001 to 31 December 2007. EXPOSURE MEASURES: Deprivation scores defined according to quintiles of neighbourhood areas ranked by the Indices of Multiple Deprivation for England 2007. OUTCOME MEASURES: Rates of all adult admissions coded with a primary diagnosis of upper gastrointestinal bleed were analysed by deprivation quintile and adjusted for age, sex, region and year using Poisson regression. RESULTS: The annual hospitalization rate for non-variceal haemorrhage was 84.6 per 100,000 population (95% CI 83.5 to 84.1; n=237,145), and for variceal haemorrhage, it was 2.83 per 100,000 population (95% CI 2.87 to 2.99; n=8291). There was a twofold increase in the hospitalization rate ratio for non-variceal haemorrhage from the most deprived areas compared to the least deprived (2.00, 95% CI 1.98 to 2.03). The ratio for variceal haemorrhage was even more pronounced (2.49, 95% CI 2.32 to 2.67). Inequality increased over the study period (non-variceal p<0.0001, variceal p=0.0068), and adjusting for age and sex increased the disparity between deprived and affluent areas. Case fatality did not have a similar socioeconomic gradient. CONCLUSION: Both variceal and non-variceal haemorrhage hospitalization rates increased with deprivation, and there was a similar gradient in all areas of the country and in all age bands. The existence of such a steep gradient suggests that there are opportunities to reduce hospitalizations down to the low rates seen in the most affluent, and thus, there is the potential to prevent almost 10,000 admissions and over 1000 deaths a year.

Survival of glioma and colorectal cancer patients using tricyclic antidepressants post-diagnosis.

BACKGROUND: Tricyclic antidepressants have been demonstrated in the laboratory to have anticancer properties. A recent study by our group also suggested a protective effect against development of colorectal cancer and glioma. This study aims to determine whether the anticancer action of tricyclics translates to improved survival in these cancers post-diagnosis. METHODS: A study using the General Practice Research Database examined whether tricyclic antidepressant exposure in the months following diagnosis of glioma or colorectal cancer would affect longer term all-cause mortality. Cox proportional hazards modelling adjusted for age, gender, smoking, body mass index, comorbidity, and diagnosed depression. RESULTS: A cohort of 1,364 glioma and 16,519 colorectal cancer patients were identified. There was a non-significant reduction in the hazard for glioma patients treated with tricyclics (HR = 0.83, CI = 0.53-1.30). This was mainly found in patients who were not previously exposed to tricyclics (HR = 0.56, CI = 0.26-1.18). In contrast, a significant increase in hazard was found for colorectal cancer (HR = 1.37, CI = 1.21-1.54). This was mostly in patients prescribed low-dose tricyclics (HR = 1.57, CI = 1.33-1.86). CONCLUSIONS: We have shown no significant mortality reduction in colorectal cancer or glioma patients treated with tricyclics. An apparent detrimental effect observed in colorectal cancer may be related to prescription of low-dose tricyclics in the management of pain related to disseminated cancer. We cannot rule out small effects or an effect that occurs exclusively at higher doses. Blinded clinical studies may therefore be the only method of determining efficacy in glioma patients.

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.

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.

Angiotensin converting enzyme inhibitors and hepatocellular carcinoma incidence in the General Practice Research Database.

OBJECTIVE: Laboratory findings demonstrate anticancer effects of angiotensin converting enzyme (ACE) inhibitors, including anti-angiogenic activity and inhibition of liver cancer growth in rodent models. Small studies in humans indicate potential for therapeutic anticancer effects and warrant further larger studies. METHODS: A case-control study using the General Practice Research Database examined whether prior ACE inhibitor usage was associated with a reduction in incidence of hepatocellular carcinoma (HCC). RESULTS: Two hundred twenty-four HCC cases were identified, each matched to up to 10 controls by age, sex, and general practice. The data show that HCC is associated with a small, nonsignificant increase in prior use of ACE inhibitors (OR = 1.16, CI = 0.67-2.00). ACE inhibitor use was 7.1% (of 224) in cases and 5.9% (of 2,313) in controls. No significant effects were found when investigating the effect of dose and exposure duration. CONCLUSIONS: We found no clear protective effect of ever or long term use of ACE inhibitors against the development of HCC. Our study suggests that it is unlikely that this class of drugs will be a clinically useful cancer chemoprevention therapy.

The Use of a Bayesian Hierarchy to Develop and Validate a Co-Morbidity Score to Predict Mortality for Linked Primary and Secondary Care Data from the NHS in England.

BACKGROUND: We have assessed whether the linkage between routine primary and secondary care records provided an opportunity to develop an improved population based co-morbidity score with the combined information on co-morbidities from both health care settings. METHODS: We extracted all people older than 20 years at the start of 2005 within the linkage between the Hospital Episodes Statistics, Clinical Practice Research Datalink, and Office for National Statistics death register in England. A random 50% sample was used to identify relevant diagnostic codes using a Bayesian hierarchy to share information between similar Read and ICD 10 code groupings. Internal validation of the score was performed in the remaining 50% and discrimination was assessed using Harrell's C statistic. Comparisons were made over time, age, and consultation rate with the Charlson and Elixhauser indexes. RESULTS: 657,264 people were followed up from the 1st January 2005. 98 groupings of codes were derived from the Bayesian hierarchy, and 37 had an adjusted weighting of greater than zero in the Cox proportional hazards model. 11 of these groupings had a different weighting dependent on whether they were coded from hospital or primary care. The C statistic reduced from 0.88 (95% confidence interval 0.88-0.88) in the first year of follow up, to 0.85 (0.85-0.85) including all 5 years. When we stratified the linked score by consultation rate the association with mortality remained consistent, but there was a significant interaction with age, with improved discrimination and fit in those under 50 years old (C = 0.85, 0.83-0.87) compared to the Charlson (C = 0.79, 0.77-0.82) or Elixhauser index (C = 0.81, 0.79-0.83). CONCLUSIONS: The use of linked population based primary and secondary care data developed a co-morbidity score that had improved discrimination, particularly in younger age groups, and had a greater effect when adjusting for co-morbidity than existing scores.

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.

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.

Incidence of venous thromboembolism in patients with cancer - a cohort study using linked United Kingdom databases.

BACKGROUND: Accurate population-based data are needed on the incidence of venous thromboembolism (VTE) in patients with different cancers in order to inform guidelines on which hospitalised and ambulatory cancer patients should receive VTE prophylaxis. METHODS: We conducted a cohort study using data from the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data and Office for National Statistics cause of death data. We determined the incidence rates (cases per 1000 person-years) of VTE separately for 24 cancer sites. To determine relative risk, incidence rates were compared to frequency-matched controls (by age) with no record of cancer. FINDINGS: We identified 83,203 cancer patients and 577,207 controls. New cases of VTE were diagnosed in 3352 cancer patients, and 6353 controls. The absolute rate of VTE in all cancers was 13.9 per 1000 person-years (95% confidence interval [CI] 13.4-14.4), corresponding to an age, sex and calendar year adjusted hazard-ratio of 4.7 (CI 4.5-4.9) between cancer patients and the general population. Rates varied greatly by cancer site (range; 98 (CI 80-119) in pancreatic cancer to 3.1 (CI 1.5-6.5) in thyroid cancer), age (range; 16.9 for patients over 80 years to 4.9 for those under 30 years) and time from diagnosis (range; 75 in the first three months to 8.4, >1 year after diagnosis). INTERPRETATION: VTE is strongly linked to cancer, but the annual rate varies greatly by cancer site, proximity to diagnosis and age. Prophylaxis guidelines should take account of cancer site and such intervention should also be targeted towards the three months following diagnosis.

Incidence, mortality, and disease associations of pyoderma gangrenosum in the United Kingdom: a retrospective cohort study.

Pyoderma gangrenosum (PG) is an important disease with significant complications. The objectives of this study were to determine incidence and mortality of PG and strength of reported associations. A retrospective cohort study was completed using computerized medical records from the General Practice Research Database, a large representative UK database. Patients with PG and three groups of age-, sex-, and practice-matched controls--general population, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) controls--were included in the study. Incidence and mortality were determined and validation undertaken to inform diagnostic accuracy. In all there were 313 people with the median age of 59 (interquartile range 41-72) years, and of them 185 (59%) were female. The adjusted incidence rate standardized to European standard population was 0.63 (95% confidence interval (CI) 0.57-0.71) per 100,000 person-years. The risk of death was three times higher than that for general controls (adjusted hazard ratio=3.03, 95% CI 1.84-4.73, P<0.001), 72% higher than that for IBD controls (adjusted hazard ratio=1.72, 95% CI 1.17-2.59, P=0.013), with a borderline increase compared with RA controls (adjusted hazard ratio=1.55, 95% CI 1.01-2.37, P=0.045). Disease associations were present in 110 (33%) participants: IBD, n=67 (20.2%); RA, n=39 (11.8%); and hematological disorders, n=13 (3.9%). To our knowledge, there are no previous population-based studies of the epidemiology of PG, an important disease with significantly increased mortality.

Incidence and mortality of primary sclerosing cholangitis in the UK: a population-based cohort study.

BACKGROUND/AIMS: Little is known about the occurrence of Primary Sclerosing Cholangitis (PSC) in the population of the United Kingdom or its associated risks of mortality and malignancy. We aimed to fill these gaps in knowledge. METHODS: We identified 223 people with PSC and 2217 control subjects from the General Practice Research Database in the UK. We calculated incidence rates (1991-2001) and mortality rates and used Poisson and Cox regression to make comparisons between populations. RESULTS: There were 149 incident cases giving a rate of 0.41 per 100,000 person years (95% CI 0.34-0.48) and a prevalence in 2001 of 3.85 per 100,000 (95% CI 3.04 to 4.80). The incidence of PSC increased about 50% over the period studied and was higher in men compared with women. There was a three-fold mortality rate increase (Hazard ratio 2.92 (95% CI 2.16-3.94) in people with PSC compared to the general population, a two-fold increase in risk of any malignancy and a 40-fold increase in the risk of primary liver cancer (HR 2.23 and 37.44, respectively). CONCLUSIONS: We believe this paper provides the most reliable estimates of the occurrence of PSC and of its risk in terms of death and malignancy in the UK available to date.

Influence of ursodeoxycholic acid on the mortality and malignancy associated with primary biliary cirrhosis: a population-based cohort study.

UNLABELLED: There is debate over the mortality and malignancy risk in people with primary biliary cirrhosis (PBC) and whether this risk is reduced by use of ursodeoxycholic acid. To investigate this issue, we identified 930 people with PBC and 9,202 control subjects from the General Practice Research Database in the United Kingdom. We categorized regular ursodeoxycholic acid as treatment with 6 or more prescriptions and nonregular treatment as less than 6. We found a 2.7-fold increase in mortality for the PBC cohort compared with the general population [adjusted hazard ratio (HR), 2.69; 95% CI, 2.35-3.09]. In those having regular ursodeoxycholic acid (43%), the mortality increase was 2.2-fold (HR, 2.19; 95% CI, 1.66-2.87) and in those not treated 2.7-fold (HR, 2.69; 95% CI, 2.18-3.33). This apparent reduction in mortality was not explained by less severe disease in the ursodeoxycholic acid-treated group. The increased risk of primary liver cancer in ursodeoxycholic acid-treated patients was 3-fold (HR, 3.17; 95% CI, 0.64-15.62), in contrast to an 8-fold increase in those not treated (HR, 7.77; 95% CI, 1.30-46.65). CONCLUSION: We found that people with PBC had a 3-fold mortality increase when compared with the general population, which was somewhat reduced by regular treatment with ursodeoxycholic acid. However, the observed effect of ursodeoxycholic acid was not statistically significant.