Masoud Solaymani-Dodaran

Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux

Background and aims: While patients with Barrett’s oesophagus develop oesophageal adenocarcinoma more frequently than the general population, it has controversially been suggested that gastro-oesophageal reflux (GORD) itself is a more important determinant of risk. In order to assess the validity of this suggestion, we examined the risk of oesophageal cancer in patients with Barrett’s and with GORD compared with the general population in a community based cohort study. Methods: Cohorts of patients with Barrett’s (n = 1677), oesophagitis (n = 6392), and simple reflux (n = 6328), and a reference cohort (n = 13416) were selected from the General Practice Research Database. The last three cohorts were matched to the Barrett’s cohort by general practitioner practice, age, and sex. Cox’s regression analysis was used to calculate relative risks for oesophageal cancer. Standardised incidence ratio methodology was used to estimate the relative risks for oesophageal adenocarcinoma. Results: A total of 137 oesophageal cancers were identified, of which 94 prevalent cases were excluded. The hazard ratios for oesophageal cancer were 10.6 (5.1–22.0), 2.2 (0.9–5.2), and 1.7 (0.7–4.5) in the Barrett’s, oesophagitis, and reflux cohorts compared with the reference cohort, respectively. The corresponding relative risks for oesophageal adenocarcinoma were 29.8 (9.6–106), 4.5 (1.04–19.6), and 3.1 (0.6–14.2). Conclusion: Barrett’s oesophagus increases the risk of oesophageal cancer approximately 10 times and oesophageal adenocarcinoma approximately 30 times compared with the general population. There is only a modestly increased risk of oesophageal cancer in patients with reflux who have no record of Barrett’s oesophagus. Our findings therefore do not support the suggestion that gastro-oesophageal reflux disease itself predisposes to cancer.

Incidence and prevalence of cirrhosis in the United Kingdom, 1992-2001 : A general population-based study

BACKGROUND/AIMS To determine the incidence and prevalence of cirrhosis in the United Kingdom. METHODS We identified patients aged 25 or over with cirrhosis, oesophageal varices or portal hypertension from the UK General Practice Research Database between 1992 and 2001. We measured incidence rates by sex, year and aetiology, incidence rate ratios and estimated prevalence figures. RESULTS Three thousand three hundred and sixty cases of cirrhosis were identified. Crude incidence was 14.55 per 100,000 person years increasing from 12.05 to 16.99 per 100,000 person years from 1992 to 2001. Incidence was over 50% higher in men compared with women (adjusted incidence rate ratio 1.52 (95%CI [1.42-1.63])). A statistically significant increase in incidence of both alcoholic cirrhosis and non-alcohol-related cirrhosis was seen in men and women. Prevalence of cirrhosis was an estimated 76.3 per 100,000 population aged over 25 in mid-2001. CONCLUSIONS There was a 45% increase in the incidence of cirrhosis during the decade 1992-2001 in the UK and a 68% increase in prevalence. Cirrhosis occurred more commonly and at younger ages in men than women. Cirrhosis represents a growing burden of morbidity and mortality in the UK, with an estimated 30,000 people living with cirrhosis and at least 7000 new cases being diagnosed each year.

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.

Modeling Age at Menopause Using Serum Concentration of Anti-Mullerian Hormone

CONTEXT Anti-Mullerian hormone (AMH) has already been used for prediction of age at menopause with promising results. OBJECTIVE We aimed to improve our previous prediction of age at menopause in a population-based cohort by including all eligible subjects and additional follow-up time. DESIGN AND SETTING All reproductive-aged women who met our eligibility criteria were selected from the Tehran Lipid and Glucose Study. The serum concentration of AMH was measured at the time of recruitment, and participants date of menopause was recorded over a 10-year follow-up. SUBJECTS A total of 1015 women, aged 20 to 50 years, with regular and predictable menstrual cycles at the initiation of the study were recruited. MAIN OUTCOME MEASURE The actual ages at menopause were compared with the predicted ones obtained from accelerated failure time model. RESULTS We observed 277 occurrences of menopause. Median menopausal age was 50 years (range 30.1-58.2 years). The median (SD) of differences between the actual menopausal age and those predicted by our model was 0.5 (2.5) years. Model adequacy (measured by C-statistics) for correct prediction of age at menopause was 92%. The estimated ages at menopause and their 95% confidence intervals for a range of values of AMH and age were calculated and summarized in a table. CONCLUSIONS Using a model built on age and AMH, we can predict age at menopause many years earlier. This could provide opportunities for interventions in those who are at risk of early or late menopause.

Predicting age at menopause from serum antimüllerian hormone concentration.

Objective: We aimed to estimate age at menopause using serum antimüllerian hormone (AMH) concentration. Methods: We randomly selected 266 study participants from a pool of 1,265 eligible women in the Tehran Lipid and Glucose Study cohort. We measured AMH levels three times at about 3-year intervals. There were 63 occurrences of menopause in our participants over an average of 6-year follow-up. We built an accelerated failure time model using serum AMH level at the start of follow-up to estimate age at menopause. The goodness of fit for the model was tested using Cox-Snell residuals and the Bland-Altman plot. Results: We estimated ages at menopause for different levels of serum AMH concentration among women aged 20 to 49 years. For those who reached menopause, serum AMH concentrations about 6 years before the event provided fairly accurate estimates of the age at menopause. The Bland-Altman plot showed an acceptable agreement between predicted and observed values. Conclusions: Serum AMH concentrations can reasonably forecast the age at menopause for individual women.

Mortality Associated with Barrett's Esophagus and Gastroesophageal Reflux Disease Diagnoses—A Population-Based Cohort Study

INTRODUCTION:Patients with Barretts esophagus have a much increased risk of esophageal adenocarcinoma but recent evidence suggests no increase in overall mortality. We have reexamined this surprising finding in a large, prospectively population-based cohort study.METHODS:Cohorts of patients having Barretts esophagus (n = 1,677), esophagitis (n = 6,392), simple reflux (n = 6,328), and a standard reference cohort representing the general population in the United Kingdom (n = 13,416) were selected from General Practice Research Database. The last three cohorts were matched to the Barretts cohort by general practice, age, and sex. Mortality rates and hazard ratios with their 95% confidence intervals were calculated for deaths due to all causes and deaths due to all causes except esophageal cancer occurring beyond the first year of the follow-up.RESULTS:A total of 1,725 deaths were analyzed including 49 deaths in subjects having esophageal cancer. Of 111 deaths in the Barretts cohort, 13 (12%) were in subjects with esophageal cancer. Compared with the reference cohort, hazard ratios for all causes of death were 1.37 (1.12–1.66) for the Barretts, 1.16 (1.02–1.32) for the esophagitis, and 1.16 (1.01–1.33) for the reflux cohorts. The corresponding figures for deaths due to all causes except esophageal cancer were 1.23 (1.00–1.51), 1.13 (0.99–1.30), and 1.15 (1.00–1.31). Of the excess mortality rates in the Barretts, esophagitis, and reflux cohorts, at the most 45%, 20%, and 13%, respectively, could be attributed to esophageal cancer.CONCLUSION:People with Barretts esophagus and gastroesophageal reflux disease have higher mortality rates than the general population, and an increase in esophageal cancer risk accounts for less than half the excess mortality in Barretts.

Is polycystic ovary syndrome an exception for reproductive aging

BACKGROUND Anti-Mullerian hormone (AMH) is increased in women with polycystic ovary syndrome (PCOS), suggesting a delay in ovarian aging. We examined AMH levels in PCOS and normo-ovulatory women in a population-based cohort over a period of 10 years and used this information to estimate their menopausal age. METHODS Of a subset of 1002 non-menopausal women randomly selected from the Tehran Lipid and Glucose Study, 85 cases of PCOS were diagnosed. We frequency-matched our control subjects with PCOS cases based on age and BMI. AMH levels were assessed at the time of recruitment (T1) and twice after that (T2 and T3). AMH levels were then plotted against age of the individual at the time of the measurement and the most appropriate model was selected. Menopause was calculated based on AMH levels below 0.2 ng/ml. RESULTS AMH levels were significantly higher in PCOS cases compared with controls at the beginning of the study (5.58 +/- 3.64 versus 4.35 +/- 2.90 ng/ml, P = 0.03), but the difference diminished considerably in subsequent assessments. The rate of AMH decline in PCOS cases decreased in the second compared with the first interval; however, no apparent change in the rate of decline was observed in controls. Estimated ages at menopause were 51 [95% confidence interval (CI), 34-81] and 49 (95% CI, 38-63) years in PCOS cases and controls, respectively. CONCLUSIONS The reproductive lifespan of PCOS women extends on average 2 years beyond that of normo-ovulatory women.

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

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. (HEPATOLOGY 2007.)

The long‐term risk of malignancy following a diagnosis of coeliac disease or dermatitis herpetiformis: a cohort study

People with coeliac disease are known to be at increased risk of malignancy; however, long‐term risks of malignancy beyond 10–15 years are largely unstudied.

Long-term mortality in people with celiac disease diagnosed in childhood compared with adulthood: a population-based cohort study.

INTRODUCTION: To explore whether the excess mortality in celiac disease is related directly to the disease and duration of gluten exposure before diagnosis we have examined the long-term mortality experience of people with celiac disease diagnosed as children and as adults.METHODS:Two hundred eighty-five children and 340 adults diagnosed with celiac disease were followed until death, loss to follow-up, or December 31, 2004. We calculated standardized mortality ratios (SMRs).RESULTS:All-cause mortality more than 5 yr after diagnosis was increased threefold in children (SMR 3.32, 95% CI 2.05–5.07) compared with only a 38% increase in adults (SMR 1.38, 95% CI 1.16–1.63). This excess mortality in children was primarily because of an increased risk of death from accidents, suicide, and violence (seven deaths, SMR 3.22, 95% CI 1.29–6.63), cancer (five deaths, SMR 3.72, 95% CI 1.21–8.67), and cerebrovascular disease (two deaths, SMR 10.03, 95% CI 1.21–36.00).CONCLUSIONS:Children diagnosed with celiac disease had a threefold increased risk of long-term mortality. This is in marked contrast to the experience of adult celiac disease where the long-term increase of mortality was modest. The increased mortality in children from external causes may reflect behavioral change associated with coping with a chronic disease and its treatment.