Colorectal cancer risk reduction following macrogol exposure: a cohort and nested case control study in the UK.

BACKGROUND AND AIMS: Animal studies have demonstrated macrogol laxatives may reduce colorectal cancer (CRC) risk. This study aimed to investigate the association between macrogol prescribing and CRC risk. METHODS: A case-control study nested within a cohort of laxative users was conducted using data from the UK General Practice Research Database. Six controls per case were identified and to account for the lead time of CRC, additional control sets were selected on the index date backdated by 1 to 5 years. Exposure to macrogols and covariate status before each of the backdated index dates was established. Conditional logistic regression was used to calculate the risk of CRC following macrogol prescribing adjusted for potential confounders. RESULTS: 4734 incident CRC cases were identified; 2722, 2195, 1789, 1481 and 1214 had received a laxative prescription before the index dates backdated by 1 to 5 years. A suggestion of a non-significant reduction in CRC risk associated with 'macrogol after other laxative' prescribing was observed when the index date was backdated by 1 and 2 years, ORadj = 0.87 (CI950.74-1.03) and ORadj = 0.80 (CI950.65-1.00) compared to non-macrogol laxative exposure. The odds ratios reduced further and were significant when backdated by 3, 4 and 5 years, ORadj = 0.68 (CI950.50-0.92), ORadj = 0.60 (CI950.40-0.90) and ORadj = 0.30 (CI950.14-0.64) respectively. This reduction in risk was not observed, however, for 'macrogol only' and 'macrogol before other laxative' exposure categories. CONCLUSIONS: In this study we observed a reduced CRC risk associated with macrogol prescribing after accounting for the lead time for CRC. Further studies are required to determine whether the association is causal and whether it can partly be explained by selective prescribing.

Smoking and delay to diagnosis are associated with poorer functional outcome in psoriatic arthritis.

OBJECTIVE: To identify predictors of poorer physical function in established psoriatic arthritis (PsA). METHODS: PsA patients with disease duration of ≥10 years were identified from the Bath longitudinal cohort. Physical function was assessed using the Stanford Health Assessment Questionnaire (HAQ). Sex, age at diagnosis, duration of symptoms prior to diagnosis, smoking, treatment and year of diagnosis were included in a multivariable regression analysis to identify associations with HAQ. RESULTS: 267 patients were identified for inclusion. The median age was 56 years (IQR 45-63), median disease duration was 13 years (IQR 10-18) and median HAQ score was 0.63 (IQR 0.13-1.25). The model predicted significant increases in HAQ related to smoking (0.23, 95% CI 0.04 to 0.42), age >50 years at diagnosis (0.27, 95% CI 0.03 to 0.51), symptom duration of ≥1 year before diagnosis (0.22, 95% CI 0.02 to 0.42), female sex (0.39, 95% CI 0.20 to 0.57) and history of treatment with an anti-TNF agent (0.63, 95% CI 0.32 to 0.93) at follow-up. CONCLUSIONS: Smoking, delay to diagnosis, older age at diagnosis, female sex and a history of anti-TNF treatment are associated with worse physical function in established PsA.

The incidence of primary glomerulonephritis worldwide: a systematic review of the literature.

BACKGROUND: Little is known about the worldwide variation in incidence of primary glomerulonephritis (GN). The objective of this review was to critically appraise studies of incidence published in 1980-2010 so that an overall view of trends of these diseases can be found. This would provide important information for determining changes in rates and understanding variations between countries. METHODS: All relevant papers found through searches of Medline, Embase and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data. RESULTS: This review includes 40 studies of incidence of primary GN from Europe, North and South America, Canada, Australasia and the Middle East. Rates for the individual types of disease were found to be in adults, 0.2/100,000/year for membrano-proliferative GN, 0.2/100,000/year for mesangio-proliferative GN, 0.6/100,000/year for minimal change disease, 0.8/100,000/year for focal segmental glomerulosclerosis, 1.2/100,000/year for membranous nephropathy and 2.5/100,000/year for IgA nephropathy. Rates were lower in children at around 0.1/100,000/year with the exception of minimal change disease where incidence was reported to be 2.0/100,000/year in Caucasian children with higher rates in Arabian children (9.2/100,000/year) and Asian children (6.2-15.6/100,000/year). CONCLUSIONS: This study found that incidence rates of primary GN vary between 0.2/100,000/year and 2.5/100,000/year. The incidence of IgA nephropathy is at least 2.5/100,000/year in adults; this disease can exist subclinically and is therefore only detected by chance in some patients. In addition, referral policies for diagnostic biopsy vary between countries. This will affect the incidence rates found.

The incidence of myasthenia gravis: a systematic literature review.

BACKGROUND: A systematic review of literature published between 1980 and 2007, on the incidence of myasthenia gravis, was undertaken. METHODS: All relevant papers found through searches of Medline, Embase and Science Direct were critically appraised and an assessment was made of the reliability of the reported incidence data. RESULTS: Thirty-one studies were included in the review, the majority of which investigated populations in Europe. The incidence rates reported were between 3.0 and 30.0/1,000,000/year. However, it is thought that the rates at the upper end of this range, reported by the prospective studies, provided the most accurate estimates. Overall, incidence rates have increased over time owing to a greater awareness of the disease and improved methods of diagnosis. CONCLUSIONS: The most accurate estimate of incidence of myasthenia gravis was around 30/ 1,000,000/year. The incidence in children and adolescents aged 0-19 years was found to be between 1.0 and 5.0/ 1,000,000/year. The rates presented in this review are likely to be an underestimate of the true incidence rates, as mild cases will have been missed and cases in the elderly will have been misdiagnosed.

Venous thromboembolism and cyproterone acetate in men with prostate cancer: a study using the General Practice Research Database.

OBJECTIVE: To evaluate the risk of venous thromboembolism (VTE) associated with the use of cyproterone acetate (CPA) amongst men with prostate cancer. PATIENTS AND METHODS: Using data from the General Practice Research Database, cases of VTE were identified amongst men with prostate cancer. Four controls with no evidence of a VTE were selected for each case. The time from diagnosis of prostate cancer to first hormonal treatment, and from first hormonal treatment to VTE, was compared for different treatments. Adjusted risk estimates for VTE were derived from further analysis using a nested case-control study design amongst all men with advanced prostate cancer, qualified by evidence of hormonal treatment. RESULTS: The time between diagnosis and first treatment was significantly shorter for men first treated with CPA than for men first treated with a luteinizing hormone releasing hormone (LHRH) analogue (adjusted hazard ratio 1.33, 95% confidence interval, CI, 1.06-1.67). When the first treatment was CPA, the treatment-free period after diagnosis was significantly shorter for men who later had a VTE than for those who did not. The case-control study yielded an adjusted risk estimate for VTE amongst CPA users that was significantly higher than amongst men who were prescribed an LHRH analogue or who had had an orchidectomy (adjusted odds ratio 5.23, 95% CI 3.12-8.79). CONCLUSION: There was a greater risk of VTE associated with CPA, which might be due to differences in disease severity between users of different products. The clinical significance of this finding is unclear.

Tibolone and endometrial cancer: a cohort and nested case-control study in the UK.

OBJECTIVE: Case series and spontaneous reports of endometrial cancer have raised the question as to whether the use of tibolone (introduced into the UK in 1991) is associated with an increased risk of endometrial cancer. This study set out to evaluate whether tibolone use is associated with an increased risk of endometrial cancer. METHODS: Age-adjusted incidence rate ratios (IRRs) of endometrial cancer were calculated for tibolone use compared with the use of other hormone replacement therapy (HRT). Separate sets of controls, matched for age and general practice, were compared with cases, all nested within a cohort of HRT users identified from the UK General Practice Research Database (GPRD). Conditional logistic regression analysis, adjusted for potential confounders, was used to study the association between tibolone use and the risk of endometrial cancer. RESULTS: 4995 women used tibolone as their first HRT product; 10 783 (4.3%) of the users of combined HRT had changed to tibolone at some time during the study period. Amongst women whose HRT began with tibolone, the age-adjusted IRR relative to those who started with combined sequential HRT was 1.83 (95% CI 1.19, 2.82). The nested case-control study comprised 162 cases, each matched to two sets of 972 controls. There were 43 tibolone-exposed subjects, 28 of whom had used other HRT before or after tibolone. The adjusted odds ratio of the risk of endometrial cancer in women who had ever used tibolone, compared with users of combined sequential HRT, was 1.54 (95% CI 1.03, 2.32) in the age-matched set and 1.58 (95% CI 1.01, 2.47) in the practice-matched set. Sensitivity analyses did not decrease the risk estimates found. DISCUSSION: Tibolone may be associated with an increased risk of endometrial cancer compared with conventional forms of HRT, but our data are fragile. Residual bias and uncontrolled confounding cannot be excluded, and follow-up time is insufficient to draw any firm conclusions with respect to the endometrial safety of tibolone.