The association between coeliac disease and cardiovascular disease

Background  Coeliac disease is more prevalent than was previously thought. The association between coeliac disease and cardiovascular outcome is not clear.
Aim  To investigate whether coeliac disease patients have an increased risk of cardiovascular events.
Methods  A community-based cohort study using a record-linkage database. Three hundred and sixty-seven coeliac patients identified by a positive antiendomysial antibody test or a diagnosis with small bowel biopsy, and 5537 subjects who were tested and had a negative coeliac immunology, were included in the study.
Results  The crude rates of cardiovascular events were 9.5 per 1000 person-years (95% CI: 4.4–14.6) in the coeliac cohort and 8.9 per 1000 person-years (95% CI: 7.6–10.3) in the antiendomysial antibody-negative cohort. Compared with the antiendomysial antibody-negative cohort, the adjusted relative risk of cardiovascular events for coeliac cohort was 1.9 (95% CI: 1.00–3.60). When we excluded patients who had previous hospitalization for cardiovascular disease, the adjusted relative risk was 2.5 (95% CI: 1.22–5.01). The use of any cardiovascular drugs prior to and after entry to the study were 36% and 29% for the coeliac cohort ( P  = 0.05), and 34% and 26% for the antiendomysial antibody-negative cohort ( P  < 0.01).
Conclusion  Our findings suggest that coeliac disease seems to be associated with an increased risk of cardiovascular outcome.     

Epidemiological study of gastro-oesophageal reflux disease: reflux in spouse as a risk factor

Background  Gastro-oesophageal reflux disease (GERD) is a growing health-care problem with variable distribution.
Aim  To assess GERD prevalence and risk factors and their possible correlation with pathophysiology in a population-based study.
Methods  Individuals aged 18–65 years were enrolled through random cluster sampling in Tehran. Previously validated self-administered questionnaires were used.
Results  Of the 2500 questionnaires, 2057 were analysed (mean age: 34.8 ± 13.0 years, 55.1% female). Frequent GERD was seen in 18.2%. Minor symptoms increased prevalence. Female gender (OR: 1.55, 95% CI: 1.01–2.41), BMI >30 kg/m² (OR: 1.79, 95% CI: 1.03–3.12), less education (OR: 1.52, 95% CI: 1.02–2.27), smoking (OR: 1.83, 95% CI: 1.12–2.99), NSAID use (OR: 4.23, 95% CI: 1.66–10.74) and GERD in spouse (OR: 1.82, 95% CI: 1.18–2.82) were associated with frequent GERD on multivariable analysis. GERD in first-degree relatives (OR: 1.73, 95% CI: 1.23–2.43) and asthma (OR: 4.09, 95% CI: 1.27–13.15) correlated with infrequent GERD. Minor symptoms correlated with GERD history in first-degree relatives, coffee consumption and NSAID use. Prevalence in the past 3 months was similar to that in the past 12 months ( P  < 0.05).
Conclusions  Gastro-oesophageal reflux disease is common in Tehran. The association of 'infrequent symptoms' with GERD history in first-degree relatives and 'frequent symptoms' with GERD history in spouse may point to the presence of yet unknown precipitating environmental factors inducing GERD in a genetically susceptible host. Minor GERD symptoms seem to have independent contribution to GERD. Assessing GERD in the past 3 months predicts prevalence in the past year.     

Use of dexfenfluramine, fenfluramine and phentermine and the risk of stroke

AIMS: To estimate the incidence of newly diagnosed idiopathic stroke among users of fenfluramine, dexfenfluramine and phentermine compared to obese nonusers. METHODS: We conducted a cohort study with nested case-control analysis utilizing data from the General Practice Research Database in the UK. Eight thousand four hundred and twenty-three subjects aged 69 years or less at the start of follow-up were exposed to at least one of the three study drugs and 17 225 similarly obese subjects were not exposed to any of the study drugs. RESULTS: We identified 45 incident cases of idiopathic CVA in this cohort of subjects. The incidence of CVA among all current users of a diet drug was 1.3/1000 person-years (95% CI 0.5, 3.5). The incidence for current fenfluramine users (n=2) was 2.6/1000 person-years (95% CI 0.7, 9.6), for current dexfenfluramine users (n=1) 1.1/1000 person-years (95% CI 0.3, 3.8), and for current phentermine users 0/1000 person-years (95% CI 0.0, 12.9). The incidence in obese nonusers was 0.6/1000 person-years (95% CI 0.4, 0. 9). The adjusted matched odds ratio (OR) for thrombotic stroke from the case-control analysis comparing current use of a diet drug to nonuse was 2.4 (95% CI 0.6, 9.1). There was only one exposed subject among seven who had haemorrhagic stroke. CONCLUSIONS: The incidence of CVA in generally young obese subjects during use of fenfluramine, dexfenfluramine or phentermine is low. Although we found an OR of 2. 4 comparing users of any of the anorexiants with nonusers, this is based on only three exposed cases and the confidence limits are wide. We conclude that our study does not support a substantial increased risk of stroke attributable to the use of fenfluramine, dexfenfluramine or phentermine.     

No increase in risk of fracture, malignancy or mortality in dermatitis herpetiformis: a cohort study

Background  Dermatitis herpetiformis forms part of the same spectrum of gluten-sensitive disorders as coeliac disease yet may have different risks of morbidity and mortality.
Aims  To quantify the risks of fracture, malignancy and mortality in people with dermatitis herpetiformis compared with the general population.
Methods  Using the General Practice Research Database, we identified 846 people with dermatitis herpetiformis and 4225 age-, gender- and practice-matched controls. We used Cox regression to estimate hazard ratios.
Results  Comparing people with dermatitis herpetiformis to the general population, the overall hazard ratio for any fracture was 1.1 (95% CI: 0.77–1.52). The overall hazard ratio for any malignancy was 1.0 (95% CI: 0.73–1.49); there was no increased risk of gastrointestinal (HR: 1.6; 95% CI: 0.67–3.67) or lymphoproliferative cancers (HR: 1.6; 95% CI: 0.44–6.06). A reduction in risk of breast cancer was not statistically significant (HR: 0.19; 95% CI: 0.03–1.39). The hazard ratio for all-cause mortality was 0.93 (95% CI: 0.70–1.23).
Conclusions  Unlike the fivefold increase in risk seen in coeliac disease, we found no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy or mortality in people with dermatitis herpetiformis compared with the general population. It is not clear whether differences in degree of intestinal inflammation or other reasons account for this. Like coeliac disease, dermatitis herpetiformis may protect against breast cancer.     

Prognostic Factors Related to Recovery from Diarrhea among U.S. Students with Diarrhea in Mexico

Background: Medical charts of subjects treated with placebo from five double-blinded placebo-controlled clinical trials were reviewed to determine pre-enrollment prognostic factors related to later recovery from diarrhea.
Method: Recovery or time from initiation of a placebo until passage of the last unformed stool after being declared well was calculated for each subject.
Results: A longer duration of diarrhea was associated with presence of fever (rate ratio = 0.34; 95% CI = 0.2–0.9), presence of an invasive pathogen in the stool (rate ratio = 0.35; 95% CI = 0.2–0.7) or a noninvasive pathogen in stool (rate ratio = 0.7; 95% CI = 0.6–1.0), severe abdominal pain or cramps (rate ratio = 0.5; 95% CI = 0.3–0.9), passage of more than five watery stools per 24 hours (rate ratio = 0.58; 95% CI = 0.4–0.8). Severe vomiting predicted a shorter duration of post-enrollment diarrhea (rate ratio = 2.43; 95% CI = 1.1–5.6).
Conclusion: A number of clinical and microbiologic factors found in travelers with diarrhea in the present study predicted duration of untreated diarrhea. The authors suggest the use of antimicrobial therapy in travelers with predictors of a long duration of diarrhea. Data developed in the present study may be used to create a historical control for clinical trials of antidiarrheal compounds using the same study criteria.     

Over 1200 drugs-related deaths and 190,000 opiate-user-years of follow-up: Relative risks by sex and age group

Heroin users/injectors’ risk of drugs-related death by sex and current age is weakly estimated both in individual cohorts of under 1000 clients, 5000 person-years or 50 drugs-related deaths and when using cross-sectional data. A workshop in Cambridge analysed six cohorts who were recruited according to a common European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) protocol from drug treatment agencies in Barcelona, Denmark, Dublin, Lisbon, Rome and Vienna in the 1990s; and, as external reference, opiate-user arrestees in France and Hepatitis C diagnosed ever-injectors in Scotland in 1993–2001, both followed by database linkage to December 2001. EMCDDA cohorts recorded approximately equal numbers of drugs-related deaths (864) and deaths from other non-HIV causes (865) during 106,152 person-years of follow-up. External cohorts contributed 376 drugs-related deaths (Scotland 195, France 181) and 418 deaths from non-HIV causes (Scotland 221, France 197) during 86,417 person-years of follow-up (Scotland 22, 670, France 63, 747).

EMCDDA cohorts reported 707 drugs-related deaths in 81,367 man-years (8.7 per 1000 person-years, 95% CI: 8.1–9.4) but only 157 in 24,785 person-years for females (6.3 per 1000 person-years, 95% CI: 5.4–7.4).

Except in external cohorts, relative risks by current age group were not particularly strong, and more modest in Poisson regression than in cross-sectional analyses: relative risk was 1.2 (95% CI: 1.0–1.4) for 35–44 year olds compared to 15–24 year olds, but 1.4 for males (95% CI: 1.2–1.6), and dramatically lower at 0.44 after the first year of follow-up (95% CI: 0.37–0.52).     

All-cause and cause-specific mortality rates of patients treated for alcohol use disorders: A meta-analysis

Background: Although alcohol use disorders (AUDs) are known to increase the relative risk of all-cause and some cause-specific mortality, the absolute mortality rates of the AUD population are unknown. Such knowledge would benefit planners of the provision of services for this population, including in prioritizing the identification and/or treatment of diseases likely to cause their death. Methods: We conducted a systematic review of studies in English, reporting the cause-specific mortality rates among people treated for AUDs. Number of deaths by cause and total person-years of follow-up were extracted. All-cause and cause-specific mortality rates per 1000 person-years were meta-analyzed assuming random effects. Results: Thirty-one studies were included. Participants were mainly middle-aged males. The quality of studies was generally good. A total of 6768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients) were recorded, and the pooled all-cause mortality rate was 27.67/1000 person-years (py) (95% confidence interval [CI]: 23.9, 32.04). The most common cause of death in the AUD population was cardiovascular disease (CVD) (6.9/1000 py; 95% CI: 5.61, 8.49), followed by gastrointestinal deaths (5.63/1000 py; 95% CI: 4.1, 7.74), unnatural deaths (4.95/1000 py; 95% CI: 4.01, 6.09)), neoplasms, respiratory diseases, and substance use disorders. Conclusions: Patients with AUDs have increased rates of all-cause and cause-specific mortality compared with the general population. Like the general population, they are most likely to die of CVD. In contrast to the general population, gastrointestinal and unnatural deaths are the next most common causes of death. We believe these facts should be considered when planning health care services for patients with AUDs.     

Blood pressure categories and mortality during a thirty-six-year follow-up

Background

The aim of this study was to assess the mortality rate and risk of death in relation to the blood pressure (BP) categories during 36 years of follow-up period.

Methods

265 healthy middle-aged participants were included in the follow up for 36 years; 136 deaths occurred during this time. Causes of death (myocardial infarction (MI), stroke and other causes) were obtained from the death certificates. Participants were divided into four groups according to their blood pressure measurements (normal blood pressure, prehypertension, stage I and stage II hypertension). Hazard ratios (HR) for mortality from all investigated causes of death were calculated using measurements of normal BP as a reference. Kaplan-Meier method was used to calculate probability of survival for each BP category.

Results

Participants with prehypertension and stage I hypertension have shared similar all-cause mortality rates (15 deaths per 1000 person-years), and MI mortality rates (7 per 1000 person-years). Participants with stage II hypertension had the highest risk of all-cause mortality (HR 2.78, 95% confidence interval 1.16 to 6.66).

Conclusion

Prehypertension and stage I hypertension induced similar rates of mortality due to myocardial infarction or all-causes. The survival probabilities were lower for participants with hypertension and prehypertension in comparison with those who had normal blood pressure. Participants with stage II hypertension had the highest mortality rates and the lowest probability of survival during a 36-year follow-up period.     

Predictors of mortality in atypical antipsychotic-treated community-dwelling elderly patients with behavioural and psychological symptoms of dementia: a prospective population-based cohort study from Italy

Purpose

To evaluate the effect of a broad range of covariates on the survival of a real-life long-term follow-up cohort of community-dwelling patients with behavioural and psychological symptoms of dementia who were new users of atypical antipsychotic medications (APMs).

Methods

This was a prospective cohort study of 1,618 subjects aged ≥65 years with dementia and BPSD (“behavioural and psychological symptoms of dementia”) who were new users of atypical APMs and registered in a Dementia Evaluation Unit of Campania Region (Italy) from September 2006 to March 2010. The potential of baseline features to predict mortality was assessed with the Cox proportional hazards model.

Results

The average follow-up was 309 days. Of the 1,618 new users of atypical antipsychotics, 9.3 % experienced at least one adverse event, including death (5.1 %), drug therapeutic failure (3.0 %), extrapyramidal symptoms (0.5 %) and stroke (0.2 %). The crude all-cause mortality rate was 6.0 per 100 person-years [95 % confidence interval (CI) 4.8–7.4]; the rate was higher in patients aged >85 years (9.0 per 100 person-years, 95 % CI 6.4–12.7) and among male patients (7.5 per 100 person-years, 95% CI 5.3–10.6). In the multivariate analysis, only age was associated to all-cause mortality [hazard ratio (HR) 1.1; 95 % CI 1.0–1.1 and HR 1.4; 95 % CI: 0.9–2.2, respectively). In contrast, hallucination (HR 0.4; 95 % CI 0.2–0.6) and dosage change (HR 0.4; 95 % CI 0.2–0.78) were significantly associated with a lower risk of all-cause mortality.

Conclusions

Among our patient cohort, the mortality rate of patients with BPSD receiving long-term treatment with atypical APMs was lower than that reported in other studies, and only age was found to be significant predictor factor of mortality.     

Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk.

BACKGROUND AND OBJECTIVE: The search for NSAIDs with less gastrointestinal toxicity led to the introduction of the selective cyclo-oxygenase-2 (COX-2) inhibitors. However, following their introduction into the market, concerns have developed regarding their safety, particularly their cardiovascular safety. The purpose of this study was to assess the cardiovascular risk (events included were myocardial infarction, stroke and myocardial infarction-related deaths) associated with long-term (>180 days of exposure) and short-term (or=35 years of age who received celecoxib, rofecoxib, ibuprofen, etodolac and naproxen from 1 January 1999 through 31 December 2001, were included. Multivariate Cox proportional hazard models were used to analyse the relationship between cardiovascular risk and NSAID use, including selective COX-2 inhibitor use, while adjusting for various risk factors. RESULTS: We identified 12 188 exposure periods (11 930 persons) and 146 cardiovascular events over the entire study period. Compared with long-term ibuprofen use, long-term use of celecoxib (adjusted hazard ratio [HR] 3.64; 95% CI 1.36, 9.70) and rofecoxib (adjusted HR 6.64; 95% CI 2.17, 20.28) was associated with a significant increase in cardiovascular risk. When restricted to patients >or=65 years of age, the cardiovascular risks associated with long-term celecoxib (adjusted HR 7.36; 95% CI 1.62, 33.48) and rofecoxib (adjusted HR 13.24; 95% CI 2.59, 67.68) use increased. Short-term use of celecoxib (adjusted HR 0.75; 95% CI 0.42, 1.35) and rofecoxib (adjusted HR 0.85; 95% CI 0.39, 1.86) was not associated with any significant change in cardiovascular risk when compared with short-term ibuprofen use. Neither long- nor short-term exposure to naproxen and etodolac was associated with cardionegative or cardioprotective effects when compared with ibuprofen use. CONCLUSIONS: The findings of this observational study, along with recent clinical trial results, suggest that prolonged exposure to selective COX-2 inhibitors may be associated with an increased risk of adverse cardiovascular outcomes.     

Emergency admissions for upper gastrointestinal disease and their relation to NSAID use

Background: There are considerable variations in estimates of the number of emergency upper gastrointestinal admissions per annum which are attributable to nonsteroidal anti-inflammatory drug (NSAID) use.
Aim : To obtain a more accurate estimate of the number of these emergency admissions per annum in UK.
Methods : A retrospective survey of the case notes of all emergency admissions for upper gastrointestinal disease ('Cases') to two English District General Hospitals with a combined catchment population of 550000. Records of all community deaths attributed to upper gastrointestinal diagnoses (with the same ICD codes) were also surveyed. Matched controls were identified from emergency admissions not caused by upper gastrointestinal diagnoses. The proportions of patients taking NSAIDs on admission to hospital (or at the time of death at home) and the outcome following admission to hospital were analysed.
Results : 620 emergency upper gastrointestinal admissions were identified and matched with 460 controls. Cases were more likely to be NSAID users than Controls (31% vs. 16%, OR 2.4, 95% CI: 1.8, 3.3; P <0.001). Case NSAID use was higher in females and with increasing age. As severity of mode of presentation worsened, the probability of NSAID use increased (e.g. OR relative to controls for peptic pain 1.9, for perforation 5.9). Blood transfusion requirements were significantly higher ( P <0.0001) in Cases taking NSAIDs, although NSAID use did not influence mortality. Extrapolation from these data indicate that there are 65000 emergency upper gastrointestinal admissions per annum in UK; 12000 of these admissions (including 2230 deaths) are attributable to NSAID use. A further 330 attributable deaths occur in the community.
Conclusions : There is a strong association between NSAID use and propensity for upper gastrointestinal emergency admission; NSAID use is associated with significant morbidity and mortality each year in UK.     

Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study

Background  Between 3% and 40% of patients surviving an episode of upper gastrointestinal bleeding (UGIB) experience a recurrence within 1 year.
Aim  To characterize further the recurrence rate of UGIB and to investigate the role of long-term acid suppressive therapy in its secondary prevention.
Methods  Recurrent cases of UGIB were identified among patients registered in The Health Improvement Network in the UK. A nested case–control analysis provided relative risk (RR) estimates of factors associated with recurrence.
Results  Of 1287 patients included, 67 (5.2%) were identified with a recurrent UGIB episode, corresponding to a recurrence rate of 17.5 per 1000 person-years during a mean follow-up of 3 years. The greatest risk of recurrence was in patients prescribed the oral anticoagulant warfarin (RR: 5.38; 95% confidence interval: 2.02–14.36). Use of a single proton pump inhibitor (PPIs) was associated with a reduced risk of recurrence (RR: 0.51; 95% confidence interval: 0.26–0.99), even in patients taking warfarin, while current use of H₂-receptor antagonists was not. After the first episode of UGIB, use of nonsteroidal anti-inflammatory drugs and aspirin was greatly reduced, preventing estimation of the risk associated with these drugs.
Conclusion  Long-term PPI therapy reduces the risk of UGIB recurrence.     

Vaccination Strategies Against Hepatitis A in Travelers Older Than 40 Years: An Economic Evaluation

Background.  In recent years, the number of travelers aged >40 years who acquire hepatitis A while traveling has increased. Therefore, there is a need to review hepatitis A vaccination protocols in travelers. The aims of the study were to assess immunity levels to hepatitis A virus (HAV) in international travelers >40 years and to determine the least costly immunization strategy.
Methods.  A serological examination of HAV antibodies in 427 international travelers aged >40 years traveling endemic zones was carried out. The prevalence of antibodies in each age group was assessed. The costs of two preventive strategies, direct vaccination of all subjects (independent of the immune status) or screening and subsequent vaccination of susceptible subjects were compared. The critical value of prevalence (CVP) (the value at which the costs for the two strategies are equal) was calculated.
Results.  Total prevalence of HAV antibodies was 78.9% [95% confidence interval (CI): 74.8–82.5] and was 80.0% (95% CI: 73.8–85.2) in men and 77.9% (95% CI: 71.9–83.2) in women. There was a positive association with age. In the 40 to 49, 50 to 59, 60 to 69, and 70 to 95 years age groups, the prevalence rates were 62.6 (95% CI: 53.8–71.5), 76.8 (95% CI: 70.0–82.7), 91.7 (95% CI: 85.2–95.6), and 97.5% (95% CI: 87.4–99.6), respectively. The CVP was 58.4% using two doses of vaccine.
Conclusions.  The CVP was lower than the prevalence rate found in our international travelers. Therefore, we recommend systematic screening for HAV antibodies before selective vaccination of international travelers aged >40 years traveling to hepatitis A endemic zones.