Utilization and safety of proton-pump inhibitors and histamine-2 receptor antagonists in children and adolescents: an observational cohort study.

BACKGROUND: Little is known about the use of acid-suppressing treatments and related safety events in children. OBJECTIVE: This study compared patient characteristics and safety outcomes among children prescribed acid-suppressing drugs for the first time. METHODS: The Health Improvement Network was used to determine the characteristics of children prescribed a proton pump inhibitor (PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H2RA) by UK primary care physicians between October 2009 and September 2012. Pre-defined safety outcomes were compared among the treatment groups in up to 18 months of follow-up. RESULTS: The cohorts comprised 8,172 patients on PPIs (including 24 patients on esomeprazole) and 7,905 on H2RAs. The baseline characteristics were similar between cohorts, although the children in the PPI cohorts tended to be older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n = 36; 39.1%). In the H2RAs cohort, 193 safety outcomes occurred, most commonly gastroenteritis (n = 62; 32.1%). The incidence of most safety outcomes was higher in the H2RAs cohort than in the other-PPIs cohort, including failure to thrive (3.11 [95% confidence interval (CI) = 2.25-4.28] vs 0.49 per 1,000 person-years [95% CI = 0.22-1.07]) and gastroenteritis (5.27 [95% CI = 4.11-6.75] vs 3.04 per 1,000 person-years [95% CI = 2.20-4.20]). CONCLUSION: Esomeprazole is rarely prescribed to children when they first require acid-suppressing medication, compared with other PPIs/H2RAs. Overall, more safety outcomes occurred in the H2RAs cohort than in the PPI cohorts.

Fascitis eosinofílica: causa infrecuente de edemas / Eosinophilic Fasciitis: An Uncommon Cause of Edema

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Ascertainment of acute liver injury in two European primary care databases.

PURPOSE: The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI. METHODS: The Clinical Practice Research Datalink (CPRD) in UK and the Spanish "Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria" (BIFAP) were used. Both are primary care databases from which we selected individuals of all ages registered between January 2004 and December 2009. We developed two case definitions of idiopathic ALI using computer algorithms: (i) restrictive definition (definite cases) and (ii) broad definition (definite and probable cases). Patients presenting prior liver conditions were excluded. Manual review of potential cases was performed to confirm diagnosis, in a sample in CPRD (21%) and all potential cases in BIFAP. Incidence rates of ALI by age, sex and calendar year were calculated. RESULTS: In BIFAP, all cases considered definite after manual review had been detected with the computer algorithm as potential cases, and none came from the non-cases group. The restrictive definition of ALI had a low sensitivity but a very high specificity (95% in BIFAP) and showed higher rates of agreement between computer search and manual review compared to the broad definition. Higher incidence rates of definite ALI in 2008 were observed in BIFAP (3.01 (95% confidence interval (CI) 2.13-4.25) per 100,000 person-years than CPRD (1.35 (95% CI 1.03-1.78)). CONCLUSIONS: This study shows that it is feasible to identify ALI cases if restrictive selection criteria are used and the possibility to review additional information to rule out differential diagnoses. Our results confirm that idiopathic ALI is a very rare disease in the general population. Finally, the construction of a standard definition with predefined criteria facilitates the timely comparison across databases.

Incidence rates and trends of hip/femur fractures in five European countries: comparison using e-healthcare records databases.

Hip fractures represent a major public health challenge worldwide. Multinational studies using a common methodology are scarce. We aimed to estimate the incidence rates (IRs) and trends of hip/femur fractures over the period 2003-2009 in five European countries. The study was performed using seven electronic health-care records databases (DBs) from Denmark, The Netherlands, Germany, Spain, and the United Kingdom, based on the same protocol. Yearly IRs of hip/femur fractures were calculated for the general population and for those aged ≥50 years. Trends over time were evaluated using linear regression analysis for both crude and standardized IRs. Sex- and age-standardized IRs for the UK, Netherlands, and Spanish DBs varied from 9 to 11 per 10,000 person-years for the general population and from 22 to 26 for those ≥50 years old; the German DB showed slightly higher IRs (about 13 and 30, respectively), whereas the Danish DB yielded IRs twofold higher (19 and 52, respectively). IRs increased exponentially with age in both sexes. The ratio of females to males was ≥2 for patients aged ≥70-79 years in most DBs. Statistically significant trends over time were only shown for the UK DB (CPRD) (+0.7% per year, P < 0.01) and the Danish DB (-1.4% per year, P < 0.01). IRs of hip/femur fractures varied greatly across European countries. With the exception of Denmark, no decreasing trend was observed over the study period.

Depression and treatment with antidepressants are associated with the development of gastro-oesophageal reflux disease.

BACKGROUND: The roles of depression and antidepressants in triggering reflux symptoms remain unclear. AIM: To compare the incidence of gastro-oesophageal reflux disease (GERD) in individuals with and without a depression diagnosis and to evaluate risk factors for a GERD diagnosis. The relationship between antidepressant treatment and GERD was also assessed. METHODS: The Health Improvement Network UK primary care database was used to identify patients with incident depression and an age- and sex-matched control cohort with no depression diagnosis. Incident GERD diagnoses were identified during a mean follow-up of 3.3 years. Furthermore, we performed nested case-control analyses where odds ratios (OR) with 95% confidence intervals (CI) were estimated by unconditional logistic regression in multivariable models. RESULTS: The incidence of GERD was 14.2 per 1000 person-years in the depression cohort and 8.3 per 1000 person-years in the control cohort. The hazard ratio of GERD in patients with depression compared with controls was 1.72 (95% CI: 1.60-1.85). Among patients with depression, tricyclic antidepressant use was associated with an increased risk of GERD (OR: 1.71; 95% CI: 1.34-2.20), while selective serotonin reuptake inhibitors were not associated with GERD. CONCLUSIONS: A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants.

Rheumatoid arthritis in UK primary care: incidence and prior morbidity.

OBJECTIVES: To estimate the incidence of rheumatoid arthritis (RA) in primary care and to investigate associations with consultation behaviour, risk factors, and comorbidities, using the UK General Practice Research Database (GPRD). METHODS: Subjects with a first-ever diagnosis of RA between 1 January 1996 and 31 December 1997 (n = 579) were identified from a cohort of 1 206 918 subjects aged 20-79 years without cancer. Controls from the same cohort were frequency-matched to the RA group by age, sex, and calendar year (n = 4234). Odds ratios (ORs) and 95% confidence intervals (CIs) of being diagnosed with RA in association with a range of factors were estimated using logistic regression analysis. RESULTS: RA incidence was 0.15 per 1000 person-years, was higher in women than in men, and increased with age in both sexes. Consultations and use of non-steroidal anti-inflammatory drugs (NSAIDs) prior to diagnosis were increased in subjects with RA. An increased risk of RA was observed in association with anaemia in the previous year (OR 2.63, 95% CI 1.54-4.48) and with smoking (1.33, 1.07-1.67). A decreased risk of RA was observed in association with infectious diseases (0.68, 0.50-0.94) and pregnancy in the previous year (0.22, 0.06-0.77), diabetes (0.45, 0.26-0.78), and hypertension (0.74, 0.57-0.94). We found no association with alcohol intake, obesity, or use of low-dose aspirin, oral contraceptives, or hormone replacement therapy (HRT). CONCLUSIONS: Smoking was identified as the only significant lifestyle-related risk factor for RA. Infection in the previous year was associated with a reduced likelihood of RA.

Endoscopic findings in a cohort of newly diagnosed gastroesophageal reflux disease patients registered in a UK primary care database.

Gastroesophageal reflux disease (GERD) may be accompanied by erosive complications that are diagnosed by endoscopy. This study aimed to describe the characteristics of patients newly diagnosed with GERD who are referred for endoscopy, and the factors associated with esophageal endoscopic findings. This study included patients aged 2-79 years with a first recorded diagnosis of GERD in 1996, as identified in a previous cohort study in the UK General Practice Research Database. The rate and results of endoscopy were recorded. Unconditional logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals for the relationship between a range of factors and endoscopy and its findings. Of the 7159 patients with a new GERD diagnosis, 805 (11%) underwent endoscopy close to the time of first consultation for GERD. Endoscopic findings indicative of esophageal damage were recorded in 73% of these patients. Esophageal endoscopic findings were significantly more likely in males, older patients, and individuals with a history of peptic ulcer disease or gastrointestinal bleeding. Use of acid-suppressive drugs, particularly proton pump inhibitors, was inversely associated with erosive endoscopic findings. Patients with erosive endoscopic findings were more likely to start a new course of treatment with a proton pump inhibitor. In conclusion, relatively few patients are referred for endoscopy close to the first consultation for GERD, and the majority of these individuals have esophageal findings. Male gender, increasing age and a history of bleeding were risk factors for esophageal complications.

Endoscopic findings in a cohort of newly diagnosed gastroesophageal reflux disease patients registered in a UK primary care database.

Gastroesophageal reflux disease (GERD) may be accompanied by erosive complications that are diagnosed by endoscopy. This study aimed to describe the characteristics of patients newly diagnosed with GERD who are referred for endoscopy, and the factors associated with esophageal endoscopic findings. The study included patients aged 2-79 years with a first recorded diagnosis of GERD in 1996, as identified in a previous cohort study in the UK General Practice Research database. The rate and results of endoscopy were recorded. Unconditional logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals for the relationship between a range of factors and endoscopy and its findings. Of the 7159 patients with a new GERD diagnosis, 805 (11%) underwent endoscopy close to the time of first consultation for GERD. Endoscopic findings indicative of esophageal damage were recorded in 73% of these patients. Esophageal endoscopic findings were significantly more likely in males, older patients, and individuals with a history of peptic ulcer disease or gastrointestinal bleeding. Use of acid-suppressive drugs, particularly proton pump inhibitors, was inversely associated with erosive endoscopic findings. Patients with erosive endoscopic findings were more likely to start a new course of treatment with a proton pump inhibitor. In conclusion, relatively few patients are referred for endoscopy close to the first consultation for GERD and the majority of these individuals have esophageal findings. Male gender, increasing age and a history of bleeding were risk factors for esophageal complications.

Unspecified abdominal pain in primary care: the role of gastrointestinal morbidity.

BACKGROUND: Many patients with abdominal pain have no obvious cause for their symptoms and receive a diagnosis of unspecified abdominal pain. AIM: The objective of this study was to ascertain risk factors and consequences of a diagnosis of unspecified abdominal pain in primary care. METHODS: A population-based, case-control study was conducted using the UK General Practice Research Database. We identified 29,299 patients with a new diagnosis of abdominal pain, and 30,000 age- and sex-matched controls. Only diagnostic codes that did not specify the type or location of abdominal pain were included. RESULTS AND DISCUSSION: The incidence of newly diagnosed unspecified abdominal pain was 22.3 per 1000 person-years. The incidence was higher in females than in males, and 29% of patients were below 20 years of age. Prior gastrointestinal morbidity was associated with abdominal pain, but high body mass index, smoking and alcohol intake were not. Patients newly diagnosed with abdominal pain were 16 to 27 times more likely than controls to receive a subsequent new diagnosis of gallbladder disease, diverticular disease, pancreatitis or appendicitis in the year after the diagnosis of abdominal pain. The likelihood of receiving other gastrointestinal diagnoses such as peptic ulcer disease, hiatus hernia, gastro-oesophageal reflux disease (GERD), irritable bowel syndrome (IBS) or dyspepsia was increased three- to 14-fold among patients consulting for abdominal pain. CONCLUSION: When managing abdominal pain in primary care, morbidities such as GERD and IBS should be considered as diagnoses once potentially life-threatening problems have been excluded.

Diagnóstico y manejo de un bloqueo espinal alto durante la realización de una analgesia epidural obstétrica / Diagnosis and management of a high spinal block during obstetric epidural analgesia

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Natural history of gastro-oesophageal reflux disease diagnosed in general practice.

BACKGROUND: Cross-sectional studies indicate that gastro-oesophageal reflux disease symptoms have a prevalence of 10-20% in Western countries and are associated with obesity, smoking, oesophagitis, chest pain and respiratory disease. AIM: To determine the natural history of gastro-oesophageal reflux disease presenting in primary care in the UK. METHODS: Patients with a first diagnosis of gastro-oesophageal reflux disease during 1996 were identified in the UK General Practice Research Database and compared with age- and sex-matched controls. We investigated the incidence of gastro-oesophageal reflux disease, potential risk factors and comorbidities, and relative risk for subsequent oesophageal complications and mortality. RESULTS: The incidence of a gastro-oesophageal reflux disease diagnosis was 4.5 per 1000 person-years (95% confidence interval: 4.4-4.7). Prior use of non-steroidal anti-inflammatory drugs, smoking, excess body weight and gastrointestinal and cardiac conditions were associated with an increased risk of gastro-oesophageal reflux disease diagnosis. Subjects with gastro-oesophageal reflux disease had an increased risk of respiratory problems, chest pain and angina in the year after diagnosis, and had a relative risk of 11.5 (95% confidence interval: 5.9-22.3) of being diagnosed with an oesophageal complication. There was an increase in mortality in the gastro-oesophageal reflux disease cohort only in the year following the diagnosis. CONCLUSIONS: Gastro-oesophageal reflux disease is a disease associated with a range of potentially serious oesophageal complications and extra-oesophageal diseases.

Is there any association between myocardial infarction, gastro-oesophageal reflux disease and acid-suppressing drugs?

BACKGROUND: A link between gastro-oesophageal reflux disease and coronary heart disease has been suggested. AIM: To estimate the incidence of myocardial infarction in patients with newly diagnosed gastro-oesophageal reflux disease in comparison with that in the general population. METHODS: A population-based cohort study was performed in the UK. Patients aged 18-79 years with a first diagnosis of gastro-oesophageal reflux disease (n = 7084) were identified and a group of 10,000 patients free of gastro-oesophageal reflux disease were sampled. A nested case-control analysis was performed to assess the risk factors for myocardial infarction. RESULTS: The incidence of myocardial infarction in the general population was 4.0 per 1,000 person-years [95% confidence interval (CI), 3.2-4.9] and 5.1 per 1,000 person-years (95% CI, 4.1-6.4) in patients with gastro-oesophageal reflux disease. The relative risk of myocardial infarction in patients with gastro-oesophageal reflux disease was 1.4 (95% CI, 1.0-1.9). The increased risk of myocardial infarction was limited to the immediate days after the diagnosis of gastro-oesophageal reflux disease. Previous chest pain was an important predictor of myocardial infarction in patients free of gastro-oesophageal reflux disease. No association was found between the use of acid-suppressing drugs and the risk of myocardial infarction. CONCLUSION: Our results suggest that gastro-oesophageal reflux disease is not an independent predictor of myocardial infarction. Rather, the increased risk of myocardial infarction in patients with gastro-oesophageal reflux disease in the immediate days after diagnosis indicates that prodromal ischaemic symptoms were misinterpreted as reflux symptoms.

[Guidelines of the Spanish Society of Cardiology for car driving, airplane flying,and underwater activities in subjects with heart disease]. / Guías de práctica clínica de la Sociedad Española de Cardiología sobre conducción de vehículos, pilotaje de aviones y actividades subacuáticas en cardiópatas.

Car driving, airplane piloting and underwater activities by subjects with heart disease may cause sudden incapacitation leading to the loss of the safety margins necessary to avoid accidents. In the case of car driving and airplane piloting the risk affects, not only the driver or pilot, but also passengers and/or bystanders within an accident zone. In the case of diving the risk resides basically in the loss of control of the vital support mechanisms necessary in a very hostile medium. This document reviews the possible causes of unexpected incapacitation, with or without loss of consciousness, in the light of the pathophysiologic consequences of fatigue, hypoxia, stress or barotrauma posed by each activity. Detailed recommendations are made for limiting driving, piloting and diving, based on official Spanish and European regulations and the addresses of specialized centers are provided for consultation. Moreover, recommendations for airplane travel for patients with heart disease are indicated.

Incidence of newly diagnosed heart failure in UK general practice.

AIM: To estimate the incidence rate of heart failure in the general population and to assess risk factors associated with the occurrence of newly diagnosed heart failure. METHODS: From the source population that was derived from the UK General Practice Research Database, we identified patients aged 40--84 years newly diagnosed with heart failure in 1996, and estimated incidence rates. We sent questionnaires to a random sample of heart failure patients (N=1200) and performed a nested case-control analysis to assess risk factors for heart failure. RESULTS: The overall incidence rate for heart failure was 4.4 per 1000 person-years in men and 3.9 per 1000 person-years in women. The incidence increased steeply with age in both sexes. The relative risk of heart failure was 2.1 (95% C.I.: 1.7--2.6) among men compared with women less than 65 years old and 1.3 (95% C.I.: 1.2--1.4) above the age of 65. Slightly more than half of the cases were categorized in NYHA III--IV at the time of the first diagnosis. Within one month of initial diagnosis 62% of the men and 50% of the women were referred to specialists and/or hospitalized for heart failure. Smoking, hypertension, diabetes, obesity were independently associated with heart failure as well as history of distant dyspnoea. Coronary heart disease was the most common cause of heart failure with a greater relative prevalence in men than women. CONCLUSION: Incident heart failure cases mainly comprised elderly men and women frequently burdened with several diseases in general practice. Women had a lower incidence of heart failure than men. However, traditional risk factors such as smoking, hypertension, obesity, diabetes and dyspnoea appeared to confer the same relative increase in heart failure risk among women and men.

Gender and drug treatment as determinants of mortality in a cohort of heart failure patients.

AIM: We assessed gender differences in the risk of mortality in heart failure (HF) patients and evaluated the association between HF drug treatment and mortality. METHODS AND RESULTS: We identified a cohort of 820 patients with newly diagnosed HF in 1996 in UK general practices. The diagnosis of HF was confirmed by the general practitioner. Fifty per cent were females and 27% were less than 70 years old. During a mean follow-up of 2 years, 172 patients died. We used computerized records to assess risk factors and drugs prescribed as treatment. The information on severity was assessed through a questionnaire. We performed a nested case-control analysis, and observed that men had twice the risk of dying than females, however the effect of age on mortality was stronger in females than males. We found a similar interaction between HF severity and sex. Data on use of some cardiovascular drugs such as diuretics, beta-blockers ACE-inhibitors and calcium channel blockers were suggestive of a reduced mortality risk. Current use of nitrates and glycosides carried an increased risk. CONCLUSION: Older age, male sex and severity of HF were the main predictors of mortality among HF patients. Long-term use of beta-blockers was associated with a significantly reduced risk of mortality.

Are schizophrenia or antipsychotic drugs a risk factor for cataracts?

Lens changes and ocular disturbances have been reported in conjunction with the use of antipsychotic drugs. We estimated the incidence rate of a clinical diagnosis of cataract in patients with a psychotic disorder, schizophrenia, and compared it with the rate in the general population. Among the schizophrenic patients, we also examined the role of dose and duration of antipsychotic drugs on the risk of cataract development. We followed up two cohorts of patients 30-85 years of age who were included in the United Kingdom General Practice Research Database. Patients in one group had a diagnosis of schizophrenia (N = 4,209). The other group was an age- and sex-matched cohort of 10,000 patients sampled from the source population. The incidence of cataracts was 4.5 per 1,000 person-years among the general population and 3.5 in the schizophrenia population. Overall, antipsychotic drug use was not associated with the occurrence of cataracts. Nevertheless, among long-term users of chlorpromazine at daily doses of 300 mg or greater, and among users of prochlorperazine, the relative risks were 8.8 (95% confidence interval = 3.1-25.1) and 4.0 (95% confidence interval = 0.8-20.7), respectively. There is no indication that schizophrenia per se is associated with an increased risk of developing cataracts.

Detection of colorectal tumor and inflammatory bowel disease during follow-up of patients with initial diagnosis of irritable bowel syndrome.

BACKGROUND: We wanted to estimate the incidence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the general population, and the detection of colorectal tumor (CRT) and inflammatory bowel disease (IBD) after the diagnosis of IBS and FD. METHODS: Patients aged 20-79 years newly diagnosed with IBS (N = 2956) or FD (N = 9900), together with a comparison cohort randomly sampled from the general source population, were followed-up during a mean time of 3 years. RESULTS: We found an overall incidence of 10.3 per 1000 person-years for FD and 2.6 per 1000 person-years for IBS. There was a greater prevalence of depression, stress, fatigue, and pain disorders among IBS and FD patients than in the general population. During the 1st year after a diagnosis of IBS the cumulative risk of detecting CRT was close to 1% in IBS patients. After the 1st year the risk of CRT in IBS patients was close to that in the general population. We found a significantly increased risk of detecting IBD among patients initially diagnosed as having IBS (relative risk (RR), 16.3; 95% confidence interval (CI), 6.6-40.7), which was constant during all the follow-up period. No association was found between dyspepsia and CRT, or IBD. CONCLUSION: IBS and FD shared some comorbidity features, yet demographics and incidence rates were different. Unlike the detection of colorectal tumor, the excess risk of IBD after an initial diagnosis of IBS was cumulatively increased during all the follow-up period. The continuously increased risk of IBD detection in IBS patients favors a true association between IBS and IBD.

Overall mortality among patients surviving an episode of peptic ulcer bleeding.

STUDY OBJECTIVE: The authors investigated whether patients who have survived an acute episode of peptic ulcer bleeding (PUB) have an excess long term all cause mortality compared with the general population free of PUB. DESIGN: Follow up study of previously identified cohort of patients with a PUB episode and a general population cohort. SETTING: The source population included all people aged 30 to 89 years, registered with general practitioners in the United Kingdom. PATIENTS: All patients alive one month after the PUB episode constituted the cohort of PUB patients (n = 978). A control group of 5000 people was randomly sampled from the source population. The same eligibility criteria as for patients with PUB were applied to the control series. Also, controls had to be free of PUB before start date. MAIN RESULTS: Relative risk of mortality among PUB patients was 2.1, 95% CI: 1.7, 2.6) compared with the general population. This increased mortality risk occurred mainly in the patients less than 60 years old. No difference was observed between men and women. The excess mortality was not only circumscribed to deaths attributable to recurrent gastrointestinal bleed, but also cardiovascular, cancer and other causes. CONCLUSIONS: People who have survived an acute episode of PUB have a reduced long term survival compared with the general population. This reduction was stronger among middle age patients than in the elderly.