Coeliac disease and risk of tuberculosis: A population-based cohort study.
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Celiac Disease↗
Biomedical subjects
J West
Publications and source records attributed to J West.
Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension.
Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC) proliferation. Changes in the ECM can modulate vasoreactivity and SMC contraction. Galectin-1 (Gal-1) is a hypoxia-inducible beta-galactoside-binding lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1 regulates SMC differentiation, proliferation, and apoptosis via interactions with the ECM, as well as immune system function, and, therefore, likely plays a role in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to chronic hypoxia in vivo. By constructing and screening a subtractive library, we found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after 6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by quantitative Western analysis. Gal-1 knockout (Gal-1(-/-)) mice showed a decreased PH response, as measured by right ventricular pressure and the ratio of right ventricular to left ventricular + septum wet weight compared with their WT counterparts. However, the number and degree of muscularized vessels increased similarly in WT and Gal-1(-/-) mice. In response to chronic hypoxia, the decrease in factor 8-positive microvessel density was similar in both groups. Vasoreactivity of WT and Gal-1(-/-) mice was tested in vivo and with use of isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a significant increase in RV pressure in wild-type and Gal-1(-/-) mice; however, the response of the Gal-1(-/-) mice was greater. These results suggest that Gal-1 influences the contractile response to hypoxia and subsequent remodeling during hypoxia-induced PH, which influences disease progression.
Animals↗
Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK.
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and sarcoidosis are common diagnoses in patients attending chest clinics, but little is known about the epidemiology of these diseases. We used data from a general practice database to provide information on the current incidence of IPF and sarcoidosis in the UK. METHODS: Data were extracted for all patients with a diagnosis of IPF or sarcoidosis between 1991 and 2003. The whole population of the database was used to calculate disease incidence stratified by age, sex, region, and time period. Poisson regression was used to compare the incidence between populations and Cox regression was used to compare survival between populations. RESULTS: 920 cases of IPF (mean age 71 years, 62% male) and 1019 cases of sarcoidosis (mean age 47 years, 47% male) were identified. The overall incidence rate per 100 000 person-years was 4.6 for IPF and 5.0 for sarcoidosis. The incidence of IPF increased progressively between 1991 and 2003 (p<0.00001), and was highest in Northern England and Scotland (p<0.0001). The survival of patients with IPF was stable over time. In contrast, the incidence of sarcoidosis was highest in London, West Midlands and Northern Ireland and remained stable over time. CONCLUSIONS: The incidence of IPF has more than doubled between 1990 and 2003; this is not due to the ageing of the UK population or an increased ascertainment of milder cases. The incidence of sarcoidosis has not changed during this time period. Our findings suggest that more than 4000 new cases of IPF and 3000 new cases of sarcoidosis are currently diagnosed each year in the UK.
Adult↗
Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971-2001.
In the last two decades, mortality from primary liver cancer has increased in the UK. We aimed to determine whether the incidence trends for these cancers were similar and in particular if the increasing occurrence of cholangiocarcinoma has continued. We calculated directly age-standardised incidence rates (using the European standard population) by subsite and histological type for all cancers of the liver, gallbladder and biliary tract in England and Wales from 1971 to 2001, using cancer registry data. The incidence of cancers of the liver, gallbladder and biliary tract increased, with the greatest rise, around 12-fold, in intrahepatic bile duct cancers. The rate of liver cell cancer increased by around 45% in males, but by <10% in females. There were marked reductions in the incidence of gallbladder and extrahepatic bile duct cancer. Cholangiocarcinoma increased around 16-fold and became the most common type of primary liver cancer in females, while hepatocellular carcinoma remained the commonest type in males. The age-specific incidence rates showed that intrahepatic bile duct cancer continued to increase throughout the 1990s in those aged 75 and over, while liver cell cancer decreased in the older age groups. In conclusion, there were increases in the incidence of primary liver cancer, which have been particularly dramatic for intrahepatic bile duct cancer, over the last three decades of the 20th century in England and Wales. There has been a halving in the incidence of gallbladder cancer and a reduction of a third in extrahepatic bile duct cancer.
Adult↗
Current opinion on treatment of asymptomatic retinal detachments.
AIMS: To determine the current opinion of vitreoretinal consultants in the UK on the treatment of asymptomatic retinal detachments. METHODS: A questionnaire survey of UK and Eire vitreoretinal consultants on recommended therapy for eight different case scenarios of asymptomatic retinal detachment. RESULTS: A questionnaire was sent to 115 consultants in UK and Eire. Fifty-four per cent were returned. The majority of surgeons favoured active intervention for most types of asymptomatic retinal detachment, with surgery being the most popular. Laser demarcation of the detached retina was the second most favoured approach followed by observation alone. Discharge with advice to seek attention if symptoms appeared was the least frequently recommended. Recommended management varied considerably for each scenario. The presence or absence of a demarcation line had the greatest influence on the management of each case. Age of patient had a much smaller effect, and degree of myopia had very little effect. CONCLUSIONS: Surgery remains the most common recommended management for an asymptomatic retinal detachment. The striking outcome of the survey is the variability in responses for any given scenario, ranging from surgical intervention to the patient being discharged with advice. This reflects the absence of hard clinical evidence to support any particular management option in such cases. As patient involvement in decision making over management is essential, the opinions expressed in this survey may not be a true reflection of actual practice, although it does highlight the need for further research in this field to provide guidance for treatment of this important condition.
Adolescent↗
Oral and inhaled corticosteroids and adrenal insufficiency: a case-control study.
BACKGROUND: Adrenal insufficiency, a well recognised complication of treatment with oral corticosteroids, has been described in association with inhaled corticosteroid use in over 60 case reports. The risk of adrenal insufficiency in people prescribed an oral or inhaled corticosteroid in the general population is not known. A study was undertaken to quantify the association between adrenal insufficiency and oral and inhaled corticosteroid exposure. METHODS: A case-control study was performed using computerised general practice data from The Health Improvement Network. RESULTS: From a cohort of 2.4 million people, 154 cases of adrenal insufficiency and 870 controls were identified. There was a dose related increased risk of adrenal insufficiency in people prescribed an oral corticosteroid with an odds ratio of 2.0 (95% CI 1.6 to 2.5) per course of treatment per year. Adrenal insufficiency was associated with a prescription for an inhaled corticosteroid during the 90 day period before the diagnosis with an odds ratio of 3.4 (95% CI 1.9 to 5.9) and this effect was dose related (p for trend <0.001). After adjusting for oral corticosteroid exposure, this odds ratio was reduced to 1.6 (95% CI 0.8 to 3.2) although the dose relation remained (p for trend 0.036). CONCLUSION: People prescribed an oral or inhaled corticosteroid are at a dose related increased risk of adrenal insufficiency although the absolute risk is small. This analysis suggests that the increased risk in people prescribed an inhaled corticosteroid is largely due to oral corticosteroid exposure, but inhaled corticosteroids may have an effect when they are taken at higher doses.
Administration, Inhalation↗
Risk of schizophrenia in people with coeliac disease, ulcerative colitis and Crohn's disease: a general population-based study.
BACKGROUND: Recently, interest has been revived in whether people with coeliac disease, in contrast to other inflammatory gastrointestinal diseases, have an increased risk of schizophrenia. AIM: To compare the risk of schizophrenia in people diagnosed with coeliac disease, ulcerative colitis and Crohn's disease with the general population. METHODS: We used data from the UK General Practice Research Database. People with coeliac disease, Crohn's disease and ulcerative colitis were matched individually with five age-, sex- and general practice-matched controls. The prevalence of schizophrenia was calculated and compared between disease groups and their respective controls. We calculated odds ratios for schizophrenia using conditional logistic regression adjusting for smoking status. RESULTS: In people with coeliac disease, Crohn's disease and ulcerative colitis the prevalence of schizophrenia was 0.25%, 0.27% and 0.24%, respectively, compared with a general population prevalence of 0.37%. The adjusted odds ratios showed no association between schizophrenia and gastrointestinal disease (coeliac disease vs. controls 0.76, 95% CI: 0.41-1.4; Crohn's disease vs. controls 0.74, 95% CI: 0.44-1.3; ulcerative colitis 0.71, 95% CI: 0.44-1.1). CONCLUSIONS: Contrary to recent findings we found no evidence of an increased risk of schizophrenia in people with coeliac disease compared with the general population.
Celiac Disease↗
Elevated serum alanine transaminase in patients with type 1 or type 2 diabetes mellitus.
BACKGROUND: The risk of chronic liver disease is higher in diabetics, and serum alanine transaminase (ALT) is a sensitive predictor of mortality from liver disease. AIM: To estimate the prevalence of elevated ALT in type 1 and type 2 diabetes, and identify possible risk factors. METHODS: We identified all patients (n = 2077) attending review between September 2002 and August 2003. We excluded those with no ALT measurement (n = 73); those whose alcohol consumption was >14 units/week (women) (n = 276) or >21 units/week (men) (n = 324); and those with a diagnosis of Maturity Onset Diabetes of the Young, secondary diabetes, gestational diabetes or uncertain type of diabetes (n = 51). We calculated the prevalences of elevated ALT in both type 1 and type 2 diabetes patients, and compared the demographic, microvascular risk factors and current drug use between each group using multivariate logistic regression. RESULTS: Of 1353 patients included, 836 (61.9%) had type 2 diabetes. Elevated ALT was found in 9.5% (95%CI 7.1-12.3%) of patients with type 1 diabetes, and 12.1% (95%CI 9.9-14.5%) of those with type 2 diabetes. The risk of elevated ALT in patients with type 2 diabetes increased with increasing body mass index (p(trend) = 0.04), and was lower in those taking insulin (OR 0.38, 95%CI 0.22-0.65). DISCUSSION: The prevalence of elevated ALT is 3-4 times higher in patients with either type 1 or type 2 diabetes than in the general population. Further studies investigating the aetiology and mechanisms of this elevation may suggest appropriate early interventions.
Adolescent↗
Recent advances in coeliac disease.
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Celiac Disease↗
Is an internal comparison better than using national data when estimating mortality in longitudinal studies?
BACKGROUND: Discrepancies between the results of different studies looking at mortality in similar disease cohorts led us to consider the impact of methodology upon outcome. METHODS: Cohort studies were carried out using age, sex, practice, and calendar time matched control groups in the general practice research database. Data were used on all subjects with inflammatory bowel disease, coeliac disease, or Barrett's oesophagus. Mortality data for the population of England and Wales were obtained from the UK Office for National Statistics. The study compared hazard ratios (HR) for mortality using the matched controls to those found when an indirect standardisation to the mortality experience of England and Wales was carried out. RESULTS: For all three conditions the mortality risk was slightly lower when the national population data were used compared with the internal comparison group (coeliac disease HR 1.33 v standardised mortality ratios (SMR) 1.25, Barrett's oesophagus HR 1.32 v SMR 1.32, inflammatory bowel disease HR 1.50 v SMR 1.34). CONCLUSIONS: A bias was found towards underestimating mortality risk when cohort studies use national population death rates as a comparator. Estimates obtained when an internal comparison group has been used are probably more appropriate.
Adult↗
Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?
BACKGROUND: A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people. AIM: To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently. METHODS: We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis. RESULTS: Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants. CONCLUSIONS: Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.
Adult↗
Bupropion and the risk of sudden death: a self-controlled case-series analysis using The Health Improvement Network.
BACKGROUND: Bupropion is an effective smoking cessation therapy but its use in the UK has been limited by concerns that it may increase the risk of sudden death. METHODS: Data for all patients prescribed bupropion within The Health Improvement Network (a computerised general practice database) were extracted and the self-controlled case-series method was used to estimate the relative incidence of death during the first 28 days of treatment. The incidence of seizures, a recognised adverse effect of bupropion, was also investigated during this period. RESULTS: A total of 9329 individuals had been prescribed bupropion (mean age 44 years, 48% male). The total person-time after the first prescription for bupropion was 17,586 years, and during this time 121 people died. Two people died within the first 28 days of treatment, which was less than expected in comparison with the remaining observation period by an incidence ratio of 0.50 (95% confidence interval (CI) 0.12 to 2.05). Twenty eight people were recorded as having a total of 45 seizures (23 before starting bupropion, two in the first 28 days of treatment, and 20 at a later point). The relative incidence of seizures during the first 28 days of treatment was 3.62 (95% CI 0.87 to 15.09), equivalent to one additional seizure per 6219 first time bupropion users. CONCLUSIONS: Bupropion use is probably associated with an increased risk of seizures, but no evidence was found to suggest that the drug is associated with an increased risk of sudden death.
Antidepressive Agents, Second-Generation↗
Autoimmune cholestatic liver disease in people with coeliac disease: a population-based study of their association.
BACKGROUND: Population data supporting an association between the autoimmune cholestatic liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis and coeliac disease, is limited and at times contradictory. AIM: To explore the relationship between coeliac disease and both primary biliary cirrhosis and primary sclerosing cholangitis within the General Practice Research Database, a UK-based longitudinal primary care database. METHODS: We identified 4732 people with diagnosed coeliac disease and 23 620 age- and sex-matched controls within the General Practice Research Database. We calculated the prevalence of primary biliary cirrhosis and primary sclerosing cholangitis for both the coeliac disease and control group. RESULTS: There was a higher prevalence of primary biliary cirrhosis in adults with coeliac disease, compared with controls [0.17% vs. 0.05%, odds ratio 3.63 (95% confidence interval: 1.46-9.04)]. Primary sclerosing cholangitis was also more common in the coeliac disease group [0.04% vs. 0%, fishers exact test (P = 0.03)]. CONCLUSIONS: There was a threefold or greater increase in risk of both primary biliary cirrhosis and primary sclerosing cholangitis in people with coeliac disease compared with the general population. The association with primary biliary cirrhosis was weaker than in some reports and it is difficult on the basis of this study to justify screening patients with coeliac disease for either primary biliary cirrhosis or primary sclerosing cholangitis.
Adult↗
Screening for visual impairment in elderly patients with hip fracture: validating a simple bedside test.
AIMS: 1. To assess the prevalence of visual impairment in those patients who sustain proximal hip fracture after a simple fall. 2. To test the validity of a simple screening test to identify patients with visual impairment. METHODS: Patients on the orthopaedic rehabilitation ward recuperating from proximal hip fracture were recruited. The nurse screener and examining Ophthalmologist independently assessed the patients' distance visual acuity and visual field to confrontation. In addition, the nurse screener assessed for the presence of cataract in the red reflex and the examining Ophthalmologist performed a dilated slit-lamp examination. On completion of the examination, the Ophthalmologist documented the cause(s) of any visual impairment found. RESULTS: A total of 89 patients were assessed. In all, 29 patients (33%) could be classified as visually impaired using the United States criteria and 52 patients (58%) had a distance visual acuity of 6/18 or worse in at least one eye. The test reliably identified those patients with visual impairment (sensitivity 94% (+/-5%), specificity 92% (+/-6%)), but was less reliable at identifying those patients with potentially remedial visual impairment (sensitivity 70% (+/-10%), specificity 92% (+/-6%)). CONCLUSION: The level of visual impairment in this group of patients is high and screening for visual impairment in the elderly with a history of falls is justified. We have demonstrated that a suitably trained member of the rehabilitation team can identify over 94% of those patients with impaired vision. We believe this simple test should now be incorporated into the assessment of all patients requiring rehabilitation after a proximal hip fracture.
Aged↗
Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study.
BACKGROUND & AIMS: Previous studies have raised concern about reduced fertility and increased adverse pregnancy-related events in women with celiac disease, but none has estimated overall fertility compared with the general female population. METHODS: We compared computerized primary care data for 1521 women with celiac disease with data for 7732 age- and practice-matched women without celiac disease. We estimated population-based rates of fertility and adverse pregnancy outcomes. RESULTS: Crude fertility rates were 48.2 and 47.7 live births per 1000 person-years for women with and without celiac disease, respectively (rate ratio, 1.01; 95% confidence interval, 0.90-1.14). Age-specific fertility rates showed that women with celiac disease had lower fertility when younger but higher fertility when older compared with women without celiac disease. This increase in relative fertility with increasing age held whether women had treated or untreated celiac disease. Risks of cesarean section (odds ratio, 1.33; 95% confidence interval, 1.03-1.70) and miscarriage (rate ratio, 1.31; 95% confidence interval, 1.06-1.61) were moderately higher in women with celiac disease, but risks of assisted birth, breech birth, preeclampsia, postpartum hemorrhage, ectopic pregnancy, stillbirth, and termination were similar. CONCLUSIONS: Overall, women with celiac disease have fertility similar to that of the general female population, but they have their babies at an older age. Although our findings may reflect a disease effect, the age shift in fertility rates and the increase in cesarean section risk is consistent with socioeconomic or educational advantages of women with celiac disease.
Abortion, Spontaneous↗
General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction.
OBJECTIVE: To investigate the impact of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) on the risk of first acute myocardial infarction (MI). DESIGN: Case-control analysis and a self controlled case series. SETTING: 644 general practices throughout England, Scotland, Wales, and Northern Ireland. PATIENTS: Over 60,000 cases of MI and 360,000 age, sex, and practice matched controls randomly selected from the UK General Practice Research Database. MAIN OUTCOME MEASURES: Matched odds ratios and incidence rate ratios estimating whether there is an acute or prolonged increased risk of MI after exposure to TCA and SSRI drugs and individual drugs within these families. RESULTS: Case-control analysis found an initial increased risk of MI after TCA exposure (for example, at 1-7 days after the first dothiepin prescription: odds ratio (OR) 1.90, 95% confidence interval (CI) 1.15 to 3.14) or SSRI exposure (for example, at 1-7 days after first fluoxetine prescription: OR 2.59, 95% CI 1.44 to 4.66). In the self controlled analysis the equivalent risk estimates were an incidence rate ratio of 1.43, 95% CI 0.92 to 2.22 for dothiepin and an incidence rate ratio of 1.66, 95% CI 1.01 to 2.71 for fluoxetine. CONCLUSIONS: Antidepressant prescriptions are associated with an increased risk of MI. The size of these effects is similar for TCA and SSRI exposures; however, the lack of specificity between types of antidepressants and the lower risks found in the self controlled analysis suggest that these associations are more likely due to factors relating to underlying depression and health services utilisation than to specific adverse drug effects.
Adult↗
Do clinical trials improve quality of care? A comparison of clinical processes and outcomes in patients in a clinical trial and similar patients outside a trial where both groups are managed according to a strict protocol.
BACKGROUND: The conventional view that participants in randomised controlled trials sacrifice themselves for the good of future patients is challenged by increasing evidence to suggest that individual patients benefit from participation in trials. OBJECTIVE: To test the hypothesis that trial participants receive higher quality care and, as a consequence, have better outcomes than patients receiving guideline driven routine care. METHODS: Retrospective comparative study of 408 women with pre-eclampsia all managed according to a strict protocol. Trial participants were 86 women who participated in a multicentre randomised controlled trial of magnesium sulphate for the treatment of pre-eclampsia (Magpie Trial); 322 non-participants formed the control group. Indicators of the process of care and clinical outcomes were compared between the two groups. RESULTS: Trial participants were significantly more likely to have received daily blood tests (odds ratio (OR) 6.82, 95% CI 1.62 to 28.72) and had their respiration rate measured hourly (OR 3.42, 95% CI 1.69 to 6.92) than control patients. There were no significant differences in other markers of clinical process and no significant difference in clinical outcomes. CONCLUSION: This study shows minor differences in process markers and no difference in clinical outcomes between patients in a clinical trial and patients receiving protocol driven care. The benefits of improved clinical care that have previously been associated with being in a trial may be explained by the use of clear clinical protocols. In routine practice, patients may be well advised to insist on treatment as part of a protocol.
Clinical Protocols↗
The low-voltage-activated calcium channel CAV3.1 controls proliferation of human pulmonary artery myocytes.
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Calcium Channels, T-Type↗