FIT for the future: a case for risk-based colorectal cancer screening using the faecal immunochemical test.

Worldwide, the guaiac faecal occult blood test (gFOBT) is being replaced with the more accurate faecal immunochemical test (FIT) for colorectal cancer (CRC) screening. From January 2016, the National Screening Committee in the UK has recommended a change from the gFOBT to the FIT following a successful Bowel Cancer Screening Programme pilot study with over 40 000 participants. Although the test has shown improved uptake and the ability to detect significantly more colorectal cancers and advanced adenomas, the higher uptake and test positivity will challenge the capacity of colonoscopy services. One of the main advantages of the FIT is that it provides a quantitative haemoglobin concentration which has been shown to relate to the risk of CRC. Risk scoring systems which combine the FIT concentration with risk factor assessment have been shown to improve the sensitivity of the test. This individualized approach to screening could enable those at greatest risk to be referred for colonoscopy, optimizing resource use and ultimately patient outcomes.

Endometriosis and its coexistence with irritable bowel syndrome and pelvic inflammatory disease: findings from a national case-control study--Part 2.

OBJECTIVE: To investigate whether the increased chances of having a diagnosis of irritable bowel syndrome (IBS) and pelvic inflammatory disease (PID) in women with endometriosis is due to misdiagnosis or co-morbidity. DESIGN: A case-control study of women aged 15-55 years with endometriosis and matched controls. SETTING: Data from the UK's General Practice Research Database for the years 1992-2001. SAMPLE: A total of 5540 women aged 15-55 years, diagnosed with endometriosis, each matched to four controls without endometriosis. The index date was defined as the date of diagnosis. METHODS: Data were analysed to determine whether women with endometriosis were more likely to receive a diagnosis of PIDor IBS than women without endometriosis. Odds ratios were calculated for endometriosis associated with IBS and PID before and after the index date. MAIN OUTCOME MEASURES: Diagnosis of IBS or PID before and after the index date. RESULTS: Compared with the controls, women with endometriosis were 3.5 times more likely to have received a diagnosis of IBS (OR 3.5 [95% CI: 3.1-3.9]). Even after women had been diagnosed with endometriosis, they were still two and a half times more likely to receive a new diagnosis of IBS when compared with the controls (OR 2.5 [95% CI: 2.2-2.8]). Similarly, women with endometriosis were more likely than those without endometriosis to have been treated for PID both before (OR 5.9 [95% CI: 5.1-6.9]) and after (OR 3.8 [95% CI: 3.1-4.6]) being diagnosed with endometriosis. CONCLUSIONS: Women with endometriosis are more likely to be diagnosed with IBS and PID than controls, even after a definitive diagnosis of endometriosis has been reached.

Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study--Part 1.

OBJECTIVE: To determine the value of patient-reported symptoms in diagnosing endometriosis. DESIGN: A national case-control study. SETTING: Data from the UK General Practice Research Database for years 1992-2001. SAMPLE: A total of 5540 women aged 15-55 years, diagnosed with endometriosis, each matched to four controls without endometriosis. METHODS: Data were analysed to determine whether specific symptoms were highly indicative of endometriosis. Odds ratios for these symptoms were derived by conditional logistic regression analysis. MAIN OUTCOME MEASURES: Symptoms associated with endometriosis. RESULTS: The prevalence of diagnosed endometriosis was 1.5%. A greater proportion of women with endometriosis had abdominopelvic pain, dysmenorrhoea or menorrhagia (73%) compared with controls (20%). Compared with controls, women with endometriosis had increased risks of abdominopelvic pain (OR 5.2 [95% CI: 4.7-5.7]), dysmenorrhoea (OR 8.1 [95% CI: 7.2-9.3]), menorrhagia (OR 4.0 [95% CI: 3.5-4.5]), subfertility (OR 8.2 [95% CI: 6.9-9.9]), dyspareunia and/or postcoital bleeding (OR 6.8 [95% CI: 5.7-8.2]), and ovarian cysts (OR 7.3 [95% CI: 5.7-9.4]), and of being diagnosed with irritable bowel syndrome (IBS) (OR 1.6 [95% CI: 1.3-1.8]) or pelvic inflammatory disease (OR 3.0 [95% CI: 2.5-3.6]). Women with endometriosis were also found to consult the doctor more frequently than the controls and were twice as likely to have time off work. CONCLUSIONS: Specific symptoms and frequent medical consultation are associated with endometriosis and appear useful in the diagnosis. Endometriosis may coexist with or be misdiagnosed as pelvic inflammatory disease or IBS.

Risk of myocardial infarction in men and women with type 2 diabetes in the UK: a cohort study using the General Practice Research Database.

AIMS/HYPOTHESIS: Our primary aim was to establish reliable and generalisable estimates of the risk of myocardial infarction (MI) for men and women with type 2 diabetes in the UK compared with people without diabetes. Our secondary aim was to investigate how the MI risk associated with diabetes differs between men and women. METHODS: A cohort study using the General Practice Research Database (1992-1999) was carried out, selecting 40,727 patients with type 2 diabetes and 194,913 age and sex-matched patients without diabetes. Rates of MI in men and women with and without diabetes were derived, as were hazard ratios for MI adjusted for known risk factors. RESULTS: The rate of MI in men with type 2 diabetes was 19.74 (95% CI 18.83-20.69) per 1,000 person-years compared with 16.18 (95% CI 15.33-17.08) per 1,000 person-years in women with type 2 diabetes. The overall adjusted relative risk of MI in diabetes versus no diabetes was 2.13 (95% CI 2.01-2.26) in men and 2.95 (95% CI 2.75-3.17) in women and decreased with age in both sexes. Women with type 2 diabetes aged 35 to 54 years were at almost five times the risk of MI compared with women of the same age without diabetes (HR 4.86 [95% CI 2.78-8.51]). CONCLUSIONS/INTERPRETATION: This study has demonstrated that women with type 2 diabetes are at a much greater relative risk of MI than men even when adjusted for risk factors.

Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database.

AIMS/HYPOTHESIS: Risk estimates for stroke in patients with diabetes vary. We sought to obtain reliable risk estimates for stroke and the association with diabetes, comorbidity and lifestyle in a large cohort of type 2 diabetic patients in the UK. MATERIALS AND METHODS: Using the General Practice Research Database, we identified all patients who had type 2 diabetes and were aged 35 to 89 years on 1 January 1992. We also identified five comparison subjects without diabetes and of the same age and sex. Hazard ratios (HRs) for stroke between January 1992 and October 1999 were calculated, and the association with age, sex, body mass index, smoking, hypertension, atrial fibrillation and duration of diabetes was investigated. RESULTS: The absolute rate of stroke was 11.91 per 1,000 person-years (95% CI 11.41-12.43) in people with diabetes (n = 41,799) and 5.55 per 1,000 person-years (95% CI 5.40-5.70) in the comparison group (n = 202,733). The age-adjusted HR for stroke in type 2 diabetic compared with non-diabetic subjects was 2.19 (95% CI 2.09-2.32) overall, 2.08 (95% CI 1.94-2.24) in men and 2.32 (95% CI 2.16-2.49) in women. The increase in risk attributable to diabetes was highest among young women (HR 8.18; 95% CI 4.31-15.51) and decreased with age. No investigated comorbidity or lifestyle characteristic emerged as a major contributor to risk of stroke. CONCLUSIONS/INTERPRETATION: This study provides risk estimates for stroke for an unselected population from UK general practice. Patients with type 2 diabetes were at an increased risk of stroke, which decreased with age and was higher in women. Additional risk factors for stroke in type 2 diabetic patients included duration of diabetes, smoking, obesity, atrial fibrillation and hypertension.

Mortality in people with type 2 diabetes in the UK.

AIMS: Under-reporting of diabetes on death certificates contributes to the unreliable estimates of mortality as a result of diabetes. The influence of obesity on mortality in Type 2 diabetes is not well documented. We aimed to study mortality from diabetes and the influence of obesity on mortality in Type 2 diabetes in a large cohort selected from the General Practice Research Database (GPRD). Methods A cohort of 44 230 patients aged 35-89 years in 1992 with Type 2 diabetes was identified. A comparison group matched by year of birth and sex with no record of diabetes at any time was identified (219 797). Hazards ratios (HRs) for all-cause mortality during the period January 1992 to October 1999 were calculated using the Cox Proportional Hazards Model. The effects of body mass index (BMI), smoking and duration of diabetes on all-cause mortality amongst people with diabetes was assessed (n = 28 725). Results The HR for all-cause mortality in Type 2 diabetes compared with no diabetes was 1.93 (95% CI 1.89-1.97), in men 1.77 (1.72-1.83) and in women 2.13 (2.06-2.20). The HR decreased with increasing age. In the multivariate analysis in diabetes only, the HR for all-cause mortality amongst smokers was 1.50 (1.41-1.61). Using BMI 20-24 kg/m(2) as the reference range, for those with a BMI 35-54 kg/m(2) the HR was 1.43 (1.28-1.59) and for those with a BMI 15-19 kg/m(2) the HR was 1.38 (1.18-1.61). CONCLUSIONS: Patients with Type 2 diabetes have almost double the mortality rate compared with those without. The relative risk decreases with age. In people with Type 2 diabetes, obesity and smoking both contribute to the risk of all-cause mortality, supporting doctrines to stop smoking and lose weight.

Venous thromboembolism associated with cyproterone acetate in combination with ethinyloestradiol (Dianette): observational studies using the UK General Practice Research Database.

PURPOSE: To derive risk estimates for venous thromboembolism (VTE) in women prescribed cyproterone acetate combined with ethinyloestradiol (CPA/EE), a drug licensed in the UK for the treatment of women with acne or hirsutism. CPA/EE provides a treatment option for women with polycystic ovary syndrome (PCOS). CPA/EE has been associated with an increased risk of VTE. METHODS: Using the General Practice Research Database, we conducted cohort and case-control analyses in all women aged 15-39 and then nested in a population of women of the same age with acne, hirsutism or PCOS. RESULTS: The incidence rate ratio (IRR) for VTE in women exposed to CPA/EE versus conventional combined oral contraceptives (COCs) was significantly raised (all women: 1.92; 95% CI: 1.22,2.88; nested: 2.51; 95% CI: 1.07,5.75). Using exposure to conventional COCs as the reference, the adjusted odds ratio (ORadj) for VTE associated with CPA/EE was 1.45 (95% CI: 0.80,2.64) in all women and 1.71 (95% CI: 0.31,9.49) in women with acne, hirsutism or PCOS. CONCLUSIONS: The risk of VTE associated with CPA/EE use does not differ significantly from that associated with the use of conventional COCs. These data are reassuring and together with knowledge of the risks associated with other treatments for acne, in particular, should influence prescribing practice.

The risk of liver disorders in women prescribed cyproterone acetate in combination with ethinyloestradiol (Dianette): a nested case-control study using the GPRD.

PURPOSE: To explore the risk of liver disorders associated with cyproterone acetate combined with ethinyloestradiol (CPA/EE). CPA/EE is licensed in the UK for the treatment of women with acne and hirsutism and is a treatment option for polycystic ovary syndrome (PCOS). It acts as a contraceptive also. METHODS: Using the General Practice Research Database, we conducted a cohort analysis and case-control study in women aged 15-39 with acne, hirsutism or PCOS to estimate the risk of liver disorders associated with CPA/EE. RESULTS: Compared with cases exposed to conventional combined oral contraceptives (COCs), the age-adjusted incidence rate ratio for liver disorders in women using CPA/EE was 1.7 (95% CI: 0.9, 3.4) and compared with no use it was 1.5 (95% CI: 0.8, 2.8). In the case-control study, the adjusted odds ratio (OR) for liver disorders in women exposed to CPA/EE was 1.6 (95% CI: 0.7, 3.5) and 0.8 (95% CI: 0.5, 1.3) for exposure to conventional COCs, compared with no use. The risk of liver disorders in women prescribed CPA/EE was not significantly greater than that in women prescribed conventional COCs (OR: 2.1 [95% CI: 0.9, 4.8]). CONCLUSION: Our results do not indicate an increased risk for liver disorders associated with CPA/EE use in women with acne, hirsutism or PCOS after adjusting for potential confounding. This may be due to lack of statistical power.

Differences in the use of combined oral contraceptives amongst women with and without acne.

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) provides a treatment option for women with acne, hirsutism or polycystic ovary syndrome (PCOS). CPA/EE may be prescribed as an oral contraceptive (OC), but is not licensed as such in the UK. The use of CPA/EE steadily increased after its introduction to the UK market in 1987, but there was a marked increase in its share of the OC market after 1995. METHODS: Using the General Practice Research Database, utilization patterns of CPA/EE and conventional oral contraceptives were compared in women aged 15-39 years, with or without acne or PCOS. RESULTS: Between 1994 and 1998, CPA/EE accounted for an increasing proportion of all OC use. The proportion of CPA/EE prescribed to women with acne declined between 1994 and 1998, whereas that prescribed to women with PCOS remained constant. The age-specific use of CPA/EE by women with acne or PCOS almost doubled. After 1995, there was a marked increase in the use of products containing levonorgestrel by women with acne or PCOS. CONCLUSIONS: A large proportion of CPA/EE is prescribed to women with acne and/or PCOS, although this proportion decreased between 1992 and 1998. This has important implications in CPA/EE risk assessment studies.

The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.

The risk of liver damage associated with minocycline: a comparative study.

Using the General Practice Research Database, the authors performed (1) a cohort analysis comparing the incidence of liver dysfunction in new users of minocycline with new users of oxytetracycline/tetracycline and (2) a case control study assessing antibiotic exposure in new cases of liver dysfunction and controls without liver dysfunction. In new users, the incidence of liver dysfunction in those exposed to minocycline was 1.04 cases/10,000 exposed person months (EPM) and 0.69 cases/10,000 EPM in those exposed to oxytetracycline/tetracycline (relative risk 1.51 [CI95: 0.63, 3.65]). The risk in both groups was greatest in the first month of use. The adjusted odds ratio (ORadj) of liver dysfunction associated with exposure to minocycline compared with nonuse was 2.10 (CI95: 1.30, 3.40); for oxytetracycline/tetracycline, the ORadj was 1.46 (CI95: 0.81, 2.64); and for exposure to erythromycin, the ORadj was 1.64 (CI95: 0.71, 3.80). The authors thus support a weak association between the use of oral antibiotics and liver dysfunction in patients with acne. The risk associated with exposure to minocycline appears to be very small. The cohort analysis demonstrated that any risk associated with minocycline was not significantly greater than that associated with oxytetracycline/tetracycline exposure.

Liver damage associated with minocycline use in acne: a systematic review of the published literature and pharmacovigilance data.

OBJECTIVE: Minocycline is an antibacterial drug used in the treatment of acne. Concern has been expressed over the possibility of severe adverse reactions to minocycline, including hepatitis. This study set out to identify and characterise reported cases of hepatotoxicity associated with the use of minocycline. METHODS: A systematic review of the literature including a search of computerised databases and analysis of data from the Uppsala Monitoring Centre (WHO Collaborating Centre for International Drug Monitoring) was conducted. The review involved a search for original case reports involving liver damage in people using minocycline. Patients taking minocycline for reasons other than acne or those given intravenous minocycline were excluded. The search strategy involved an enquiry of computerised databases and a search for secondary references. Cases were then classified appropriately. RESULTS: 65 reported cases of hepatitis or liver damage in association with minocycline from either case reports or case series were identified from the literature review. 58% of cases occurred in females and 94% were aged under 40 years. For 20 case reports there was insufficient information to classify the type of event, but for the remaining 45, 2 types of hepatic reaction were recognised: autoimmune hepatitis associated with lupus-like symptoms occurring after a median duration of exposure to minocycline of 365 days in females (n = 20) and 730 days in males (n = 9), hypersensitivity reaction associated with eosinophilia and exfoliative dermatitis occurring within 35 days of therapy (n = 16). Reports to the WHO of hepatic adverse drug reactions associated with minocycline accounted for 6% (493) of all minocycline-related adverse drug reactions (8025). The pattern of distribution in relation to exposure demonstrated 2 groups, similar to that described by the case reports. CONCLUSIONS: Severe cases of minocycline-associated hepatotoxicity appear to be a hypersensitivity reaction and occur within a few weeks of commencing therapy. An autoimmune hepatitis usually presents after exposure to minocycline of a year or more, is more common in women and is sometimes associated with lupus-like symptoms.