Validation of venous thromboembolism diagnoses in patients receiving rivaroxaban or warfarin in The Health Improvement Network.

PURPOSE: To describe the effect that validation of venous thromboembolism (VTE) coded entries in the health improvement network (THIN) has on incidence rates of VTE among a cohort of rivaroxaban/warfarin users. METHODS: Among 36 701 individuals with a first prescription for rivaroxaban/warfarin between 2012 and 2015, we performed a two-step VTE case identification process followed by a two-step case validation process involving manual review of patient records. A valid case required a coded entry for VTE at some point after their first rivaroxaban/warfarin prescription with evidence of referral/hospitalization either as a coded entry or entered as free text. Positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated using validated cases as the gold standard. Incidence rates were calculated per 1000 person-years with 95% CIs. RESULTS: We identified 2166 patients with a coded entry of VTE after their initial rivaroxaban/warfarin prescription; incidence rate of 45.31 per 1000 person-years (95% CI: 43.49-47.22). After manual review of patient records including the free text, there were 712 incident VTE cases; incidence rate of 14.90 per 1000 person-years (95% CI: 13.85-16.02). The PPV for coded entries of VTE alone was 32.9%, and the PPV for coded entries of VTE with a coded entry of referral/hospitalization was 39.8%; this increased to 69.6% after manual review of coded clinical entries in patient records. CONCLUSIONS: Among rivaroxaban/warfarin users in THIN, valid VTE case identification requires manual review of patient records including the free text to prevent outcome misclassification and substantial overestimation of VTE incidence rates.

Use of non-vitamin K antagonist oral anticoagulants in Colombia: A descriptive study using a national administrative healthcare database.

PURPOSE: We aimed to describe time-trends in the use of NOACs among a group of ambulatory patients with nonvalvular atrial fibrillation (NVAF) in Colombia and to describe treatment patterns and user characteristics. METHODS: Using the Audifarma S.A administrative healthcare database in Colombia, we identified 10 528 patients with NVAF aged at least 18 years between July 2009 and June 2017 with a first prescription (index date) for apixaban, dabigatran or rivaroxaban (index NOAC) and followed them for at least year (max, 8.0 years, mean 2.2 years). We described patient characteristics, NOAC use over time, and the dose of the first NOAC prescription. RESULTS: A total of 2153 (20.5%) patients started on apixaban, 3089 (29.3%) on dabigatran and 5286 (50.2%) on rivaroxaban. The incidence of new users of apixaban and rivaroxaban increased over study years while for dabigatran it decreased. Mean age at the index date was: 78.5 years (apixaban), 76.5 years (dabigatran), 76.0 years (rivaroxaban). The percentage of patients started NOAC therapy on the standard dose was: apixaban 38.0%, dabigatran 30.9%, rivaroxaban 56.9%. The percentage still prescribed their index NOAC at 6 months was apixaban 44.6%, dabigatran 51.4%, rivaroxaban 52.7%. Hypertension was the most common comorbidity (>80% in each NOAC cohort). CONCLUSION: During the last decade, the incidence of NOAC use in patients with NVAF affiliated with a private healthcare regime in Colombia has markedly increased. Future studies should evaluate whether the large number of patients with NVAF starting NOAC treatment on a reduced dose are done so appropriately.

Ascertainment and validation of major bleeding events in a primary care database.

PURPOSE: The purpose of the study is to evaluate the impact of validation on the identification of major bleeding events in The Health Improvement Network (THIN) database in patients receiving anticoagulant therapy. METHODS: Patients aged 2 to 89 years with a first prescription for an anticoagulant (rivaroxaban or warfarin) between 2012 and 2015 were identified in THIN. Major bleeding events, defined as bleeding events necessitating hospitalization or referral to accident and emergency services or a specialist clinic, were identified using a 2-step ascertainment process based on read codes only, and then validated using a 2-step process requiring manual review of patients' records. RESULTS: The positive predictive value for the ascertainment of major intracranial (IC) bleeds using only read codes was 96.9%, compared with 70.4% for gastrointestinal (GI) bleeds and 64.1% for urogenital (UG) bleeds. The incidence rate of major IC bleeding events was therefore similar when it was calculated before and after validation (0.32 per 100 person-years and 0.31 per 100 person-years, respectively). The incidence rate of major GI bleeds identified using read codes alone was reduced following validation from 2.05 to 0.94 per 100 person-years, and that of major UG bleeds decreased from 2.45 to 1.11 per 100 person-years. CONCLUSIONS: Major GI and UG bleeding events ascertained from THIN using read codes require validation using additional information to prevent outcome misclassification. The absence of validation may lead to overestimated incidence rates of major bleeding for GI and UG bleeds.

The risk of acute liver injury among users of antibiotic medications: a comparison of case-only studies.

PURPOSE: The aims of this study were two-fold: (i) to investigate the effect of exposure to antibiotic agents on the risk of acute liver injury using a self-controlled case series and case-crossover study and (ii) to compare the results between the case-only studies. METHODS: For the self-controlled case series study relative incidence ratios (IRR) were calculated by dividing the rate of acute liver injury experienced during patients' periods of exposure to antibiotics to patients' rate of events during non-exposed time using conditional Poisson regression. For the case-crossover analysis we calculated Odds Ratios (OR) using conditional logistic regression by comparing exposure during 14- and 30-day risk windows with exposure during control moments. RESULTS: Using the self-controlled case series approach, the IRR was highest during the first 7 days after receipt of a prescription (10.01, 95% CI 6.59-15.18). Omitting post-exposure washout periods lowered the IRR to 7.2. The highest estimate in the case-crossover analysis was found when two 30-day control periods 1 year prior to the 30-day ALI risk period were retained in the analysis: OR = 6.5 (95% CI, 3.95-10.71). The lowest estimate was found when exposure in the 14-day risk period was compared to exposure in four consecutive 14-day control periods immediately prior to the risk period (OR = 3.05, 95% CI, 2.06-4.53). CONCLUSION: An increased relative risk of acute liver injury was consistently observed using both self-controlled case series and case-crossover designs. Case-only designs can be used as a viable alternative study design to study the risk of acute liver injury, albeit with some limitations.

Risk of acute liver injury associated with use of antibiotics. Comparative cohort and nested case-control studies using two primary care databases in Europe.

PURPOSE: To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use. METHODS: The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression. RESULTS: The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP. CONCLUSION: Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP.

Prevalence of antibiotic use: a comparison across various European health care data sources.

PURPOSE: There is widespread concern about increases in antibiotic use, but comparative data from different European countries on rates of use are lacking. This study was designed to measure and understand the variation in antibiotic utilization across five European countries. METHODS: Seven European healthcare databases with access to primary care data from Denmark, Germany, the Netherlands, Spain and the UK were used to measure and compare the point and 1-year-period prevalence of antibiotic use between 2004 and 2009. Descriptive analyses were stratified by gender, age and type of antibiotic. Separate analyses were performed to measure the most common underlying indications leading to the prescription of an antibiotic. RESULTS: The average yearly period prevalence of antibiotic use varied from 15 (Netherlands) to 30 (Spain) users per 100 patients. A higher prevalence of antibiotic use by female patients, the very young (0-9 years) and old (80+ years), was observed in all databases. The lowest point prevalence was recorded in June and September and ranged from 0.51 (Netherlands) to 1.47 (UK) per 100 patients per day. Twelve percent (Netherlands) to forty-nine (Spain) percent of all users were diagnosed with a respiratory tract infection, and the most common type of antibiotic prescribed were penicillin. CONCLUSION: Using identical methodology in seven EU databases to assess antibiotic use allowed us to compare drug usage patterns across Europe. Our results contribute quantitatively to the true understanding of similarities and differences in the use of antibiotic agents in different EU countries.

Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project.

PURPOSE: Studies on drug utilization usually do not allow direct cross-national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases. METHODS: Crude and standardized prevalence rates of drug prescribing from 2001-2009 were calculated in databases from Spain, United Kingdon (UK), The Netherlands, Germany and Denmark. Prevalence was stratified by age, sex, BZD type [(using ATC codes), i.e. BZD-anxiolytics BZD-hypnotics, BZD-related drugs and clomethiazole], indication and number of prescription. RESULTS: Crude prevalence rates of BZDs prescribing ranged from 570 to 1700 per 10,000 person-years over the study period. Standardization by age and sex did not substantially change the differences. Standardized prevalence rates increased in the Spanish (+13%) and UK databases (+2% and +8%) over the study period, while they decreased in the Dutch databases (-4% and -22%), the German (-12%) and Danish (-26%) database. Prevalence of anxiolytics outweighed that of hypnotics in the Spanish, Dutch and Bavarian databases, but the reverse was shown in the UK and Danish databases. Prevalence rates consistently increased with age and were two-fold higher in women than in men in all databases. A median of 18% of users received 10 or more prescriptions in 2008. CONCLUSION: Although similar methods were applied, the prevalence of BZD prescribing varied considerably across different populations. Clinical factors related to BZDs and characteristics of the databases may explain these differences.

Impact of hyperkalaemia definition on incidence assessment: implications for epidemiological research based on a large cohort study in newly diagnosed heart failure patients in primary care.

BACKGROUND: Various definitions of hyperkalaemia have been used in clinical research, and data from routine clinical practice on its incidence are sparse. We aimed to establish the incidence of hyperkalaemia in patients with newly diagnosed heart failure in the UK general population using different definitions for the condition. METHODS: We conducted a large retrospective cohort study using data from The Health Improvement Network primary care database. Patients with newly diagnosed heart failure (N = 19,194) were identified and followed until the first occurrence of hyperkalaemia. Different serum potassium (K(+)) thresholds were evaluated as possible definitions for hyperkalaemia, and incidence rates (IRs) calculated using a final operational definition both overall and among patient sub-groups. RESULTS: IRs of hyperkalaemia ranged from 0.92-7.93 per 100 person-years according to the definition. Based on considerable differences in the serum K(+) normal range used between practices, 2176 (11.3 %) individuals were identified with a record of hyperkalaemia using our operational definition of a proportional increase of ≥10 % above the upper bound of the normal range: IR 2.90 per 100 person-years (95 % CI 2.78-3.02) over a mean follow-up of 3.91 years. Incidence rates were higher in older patients, and in those with diabetes or renal impairment. CONCLUSIONS: Hyperkalaemia is a common finding in heart failure patients in primary care, but its incidence can vary nearly ten-fold depending on its definition. Since assessment of hyperkalaemia risk is essential for therapeutic decision making in heart failure patients, this finding warrants consideration in future epidemiological studies.

Risk of uncomplicated peptic ulcer disease in a cohort of new users of low-dose acetylsalicylic acid for secondary prevention of cardiovascular events.

BACKGROUND: The aim of this study was to analyse the risk of uncomplicated peptic ulcer disease (PUD) in a cohort of new users of low-dose acetylsalicylic acid (ASA) for secondary prevention of cardiovascular events in a UK primary care setting. METHODS: New users of low-dose ASA for secondary prevention of cardiovascular events, aged 50-84 years in 2000-2007, were identified from The Health Improvement Network. Among those 38,975 individuals, 309 patients were considered to be incident cases of uncomplicated PUD. Incidence of uncomplicated PUD was calculated and a nested case-control analysis adjusted for potential confounding factors was performed to calculate the odds ratios (ORs) for the association of potential risk factors with uncomplicated PUD. RESULTS: The crude incidence of uncomplicated PUD was 1.41 per 1000 person-years (95% confidence interval [CI], 1.26-1.58). Individuals with a history of PUD were more likely to develop uncomplicated PUD than those without such a history (hazard ratio [HR], 2.22, 95% CI, 1.60-3.09). In nested case-control analyses, the risk of uncomplicated PUD was associated with current use of non-steroidal anti-inflammatory drugs, oral steroids or acid suppressants. Other risk factors for developing uncomplicated PUD included smoking, stress, depression, anaemia and social deprivation. CONCLUSION: Our results indicate that several risk factors significantly increase the risk of development of uncomplicated PUD in new users of low-dose ASA. Therefore, physicians should monitor ASA users for gastrointestinal symptoms and signs of ulcer, particularly if they have additional risk factors.

Safety profile of rivaroxaban in first-time users treated for venous thromboembolism in four European countries.

BACKGROUND: The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice. METHODS: Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed. RESULTS: Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9-63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes. CONCLUSIONS: This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.

Challenges and lessons learned from a long-term postauthorisation safety study programme of rivaroxaban in Europe.

OBJECTIVES: To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements. DESIGN: PASS programme of rivaroxaban carried out as part of the regulatory postapproval commitment to the European Medicines Agency. SETTING: Clinical practice in Germany, the Netherlands, Sweden and the UK (electronic health records)-undertaken by pharmacoepidemiology research teams using country-specific databases with different coding structures. PARTICIPANTS: 355 152 patients prescribed rivaroxaban and 338 199 patients prescribed vitamin K antagonists. RESULTS: Two major challenges that were encountered throughout the lengthy PASS programme were related to: (1) finalising country-tailored study designs before the extent of rivaroxaban uptake was known, and (2) new research questions that arose during the programme (eg, those relating to an evolving prescribing landscape). RECOMMENDATIONS: We advocate the following strategies to help address these major challenges (should they arise in any future PASS): conducting studies based on a common data model that enable the same analytical tools to be applied when using different databases; maintaining early, clear, continuous communication with the regulator (including discussing the potential benefit of studying drug use as a precursor to planning a safety study); consideration of adaptive designs whenever uncertainty exists and following an initial period of data collection; and setting milestones for the review of study objectives.

Safety and effectiveness of rivaroxaban for prevention of stroke in patients with nonvalvular atrial fibrillation: analysis of routine clinical data from four countries.

BACKGROUND: The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. RESEARCH DESIGN AND METHODS: Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and SOC with NVAF; outcomes were analyzed using cohort (rivaroxaban or SOC use) and nested case-control designs (current vs nonuse). Statistical analyses comparing rivaroxaban and SOC cohorts were not performed. RESULTS: Overall, 162,919 rivaroxaban users and 177,758 SOC users were identified. In the cohort analysis, incidence ranges for rivaroxaban users were 0.25-0.63 events per 100 person-years for intracranial bleeding, 0.49-1.72 for gastrointestinal bleeding, and 0.27-0.54 for urogenital bleeding. Corresponding ranges for SOC users were 0.30-0.80, 0.30-1.42, and 0.24-0.42, respectively. In the nested case-control analysis, current SOC use generally presented a greater risk of bleeding outcomes than nonuse. Rivaroxaban use (vs nonuse) was associated with a higher risk of gastrointestinal bleeding, but a similar risk of intracranial or urogenital bleeding, in most countries. Ischemic stroke incidence ranged from 0.31 to 1.52 events per 100 person-years for rivaroxaban users. CONCLUSIONS: Incidences of intracranial bleeding were generally lower with rivaroxaban than with SOC, whereas incidences of gastrointestinal and urogenital bleeding were generally higher. The safety profile of rivaroxaban for NVAF in routine practice is consistent with findings from randomized controlled trials and other studies.

Gastroesophageal reflux disease in primary care: using changes in proton pump inhibitor therapy as an indicator of partial response.

OBJECTIVE: Up to one-third of patients with gastroesophageal reflux disease (GERD) in primary care have residual symptoms despite proton pump inhibitor (PPI) therapy. We aimed to characterize partial response to PPIs among adult patients in UK primary care. MATERIAL AND METHODS: Newly diagnosed GERD patients aged 20-79 years who were prescribed PPI for treatment of GERD were identified in The Health Improvement Network. Those with a treatment change suggesting partial response to PPIs (new treatment added to PPI, increased PPI dose, or switching PPI) during the subsequent 6 months were identified as potential cases and confirmed after manual review of each patient's complete computer medical record including free-text comments. Patients without these treatment changes were study controls. A nested case-control analysis was conducted using logistic regression. RESULTS: The proportion of newly diagnosed GERD patients with partial response to PPI therapy was 18.6% (1201/6453). Partial response was associated with female gender (odds ratio [OR]: 1.20; 95% confidence interval [CI]: 1.05-1.37), anxiety or depression (OR: 1.15; 95% CI: 1.00-1.31), and prescription of ≥ 6 drugs in the month before GERD diagnosis (OR: 1.42; 95% CI: 1.14-1.78). Among new PPI users (n = 2907), partial response was associated with esophageal ulcer or Barrett's esophagus at initial diagnosis (OR: 3.14; 95% CI: 1.60-6.17). CONCLUSIONS: Approximately one in five newly diagnosed patients with GERD appear to have a partial response to PPI therapy. Female gender, polymedication, and a severe initial diagnosis may be associated with partial response.

Hospitalised ischaemic cerebrovascular accident and risk factors in a primary care database.

PURPOSE: Ischaemic cerebrovascular accident (ICVA) is a common cause of morbidity and mortality. Identification of risk factors can reduce its incidence. We aim to estimate the incidence rate (IR) of hospitalised ICVA in the general population by sex and quantify its risk associated with several factors. METHODS: We followed up 907, 001 individuals aged 40-84 years during a mean of 3.63 years to ascertain the first episode of hospitalised ICVA between 2000 and 2004 using a UK primary care database. We evaluated the risk factors for ICVA through unconditional logistic regression (OR) with a nested case-control analysis, using 2953 incident cases and 10, 000 random controls frequency-matched by age, sex and year. RESULTS: The IR of hospitalised ICVA was 1.94 (95%CI: 1.87-2.01) per 1000 person-years in men and 1.59 (95%CI: 1.53-1.65) in women. The IR ratio adjusted by age was 1.35 (95%CI: 1.28-1.43). Major risk factors for the first ICVA were atrial fibrillation (AF) (OR of 1.96 (95%CI: 1.59-2.42) for men and 3.54 (95%CI: 2.85-4.39) for women), smoking, epilepsy and hypertension. AF patients on anticoagulant therapy presented a reduced risk of ICVA (OR: 0.39; 95%CI: 0.27-0.56) in both sexes. Hypertensive women that discontinued the treatment had an increased risk (OR: 2.53; 95%CI: 1.63-3.91). CONCLUSIONS: Men had higher incidence of hospitalised ICVA than women. AF was the major risk factor for ICVA (more in women than men), followed by smoking. Among AF patients, those under anticoagulant therapy showed a significant reduced risk of first ICVA. Antihypertensive drug discontinuation increased the risk of ICVA among women.

Identification and Validation of Major Cardiovascular Events in the United Kingdom Data Sources Included in a Multi-database Post-authorization Safety Study of Prucalopride.

INTRODUCTION: A multinational post-authorization safety study assessed cardiovascular safety in initiators of prucalopride for chronic constipation compared with a matched cohort of polyethylene glycol 3350 initiators. The primary safety outcome was major adverse cardiovascular events (MACE), a composite of hospitalization for acute myocardial infarction, stroke, or in-hospital cardiovascular death. We report the validation process for MACE endpoints in United Kingdom (UK) data sources: Clinical Practice Research Datalink (CPRD GOLD), The Health Improvement Network (THIN), and the Information Services Division (ISD) Scotland. METHODS: Modified electronic algorithms from prior research identified potential MACE cases. Validation followed a common protocol, adapted for each database, with all information anonymized: (1) direct confirmation via linkage to hospital records (CPRD GOLD); (2) requests for additional clinical information through questionnaires (CPRD GOLD), free-text (THIN), or abstraction of hospital records (ISD); (3) manual review of electronic records of potential events retrieved by the algorithm (CPRD GOLD/THIN); and (4) event adjudication by three clinicians, blinded to exposure, for all remaining events. RESULTS: Electronic algorithms identified 260 potential MACE cases: 38 confirmed via linkage to hospital records (CPRD GOLD), 56 ruled out as non-cardiovascular death cases (THIN), and three unavailable for review (ISD), leaving 163 potential cases. After manual review with additional information (steps 2 and 3), 45 were considered noncases (CPRD GOLD/THIN). Upon final adjudication (step 4), remaining potential events were adjudicated as definite (n = 62), probable (n = 10), possible (n = 13), or noncases (n = 33). CONCLUSIONS: Given the limitations of relying solely on computer algorithms to identify cardiovascular outcomes, validation with clinical review is essential to guide interpretation.

Gastroesophageal reflux disease in children and adolescents in primary care.

OBJECTIVES: To determine the prevalence and incidence of a diagnosis of gastroesophageal reflux disease (GERD) in children and adolescents in UK primary care, and to assess comorbidities that are associated with a diagnosis of GERD. MATERIAL AND METHODS: Incident GERD cases during 2000-05 were identified from The Health Improvement Network (THIN) UK primary care database via a computer search for diagnostic codes for GERD, followed by manual review of the patient records. RESULTS: We identified 1700 children with a first diagnosis of GERD during 2000-05. The incidence of GERD was 0.84 per 1000 person-years. The incidence decreased with age from 1.48 per 1000 person-years among 1-year-old children until the age of 12 years, whereupon it increased to a maximum at 16-17 years of 2.26 per 1000 person-years for girls and 1.75 per 1000 person-years for boys. Pregnant adolescents were not included in the study. In addition to typical GERD symptoms (epigastric pain, heartburn, reflux, regurgitation), 21.2% of children reported nausea or vomiting. Children with neurological disorders were at increased risk of a GERD diagnosis. Hiatus hernia and congenital esophageal disorders were also associated with a diagnosis of GERD. Children and adolescents using antiepileptics, oral/inhaled steroids, beta-agonists and paracetamol had an increased risk of a GERD diagnosis. CONCLUSIONS: The incidence of a GERD diagnosis was age-dependent and was highest among very young children and older female adolescents. Children with neurological impairments and other comorbidities were at increased risk of a GERD diagnosis.

Follow-up of a cohort of children and adolescents with gastro-esophageal reflux disease who were free of reflux esophagitis at initial diagnosis.

OBJECTIVE: Few studies have examined the incidence of complications from gastro-esophageal reflux disease (GERD) in children and adolescents in primary care. Here we aimed to describe the natural history of GERD in a pediatric population with no reflux esophagitis at initial diagnosis, assessing diagnoses of new esophageal complications and extra-esophageal conditions. MATERIAL AND METHODS: We used The Health Improvement Network UK primary care database (which includes data on more than 2 million patients) to identify individuals aged 1-17 years with a first diagnosis of gastro-esophageal reflux or heartburn in the period 2000-2005, via a computerized search followed by a manual review of the patient records. This search identified 1242 individuals with an incident diagnosis of GERD but no record of esophagitis. This cohort was followed-up to detect new diagnoses of esophageal complications and extra-esophageal conditions. RESULTS: During a mean follow-up period of almost 4 years, 40 children and adolescents had a confirmed new diagnosis of reflux esophagitis (incidence: 10.9 per 1000 person-years). No cases of Barrett's esophagus, esophageal stricture or esophageal ulcer were reported. Individuals with GERD had double the risk of an extra-esophageal condition such as asthma, pneumonia, cough or chest pain compared with children and adolescents with no diagnosis of GERD. CONCLUSIONS: Children and adolescents with GERD may be at risk of developing reflux esophagitis and a range of other extra-esophageal conditions, but more severe esophageal complications are rare.

Validation of ischemic cerebrovascular diagnoses in the health improvement network (THIN).

PURPOSE: To evaluate the validity of recorded diagnoses of ischemic cerebrovascular events requiring hospitalization within The Health Improvement Network (THIN) UK primary care database. METHODS: We identified 15 397 individuals aged 40-84 years with a first recorded ischemic event in 2000-2004. Of these, 4239 had a code suggestive of a hospitalization within 2 weeks of the event. A three-step strategy was used to validate the records of these patients: manual review of computerized medical records excluding free-text comments; manual review including free-text comments (which include information gained from specialists, hospital discharge letters and results of diagnostic tests) of a random sample of possible cases (n = 300) and non-cases (n = 100); and review of full medical records of this random sample and a questionnaire completed by their primary care physician. The positive predictive value (PPV) of each step was calculated. The confirmation rate was used to estimate incidence in the general population. RESULTS: After step 1, 3447 individuals were classified as possible cases and 792 were excluded as non-cases. After step 2, 82% of possible cases were still classified as such. Step 3 showed that inclusion of free-text comments increased the PPV of a diagnosis from 76 to 86%. The weighted incidence of hospitalized ischemic cerebrovascular events was 1.73 per 1000 person-years (95% CI:1.68-1.77). CONCLUSIONS: THIN demonstrates a high validity for the study of ischemic cerebrovascular events when reviewing computer records with additional free-text comments. Accuracy of hospitalization status was not as well recorded.

Prevalence, incidence, morbidity and treatment patterns in a cohort of patients diagnosed with anxiety in UK primary care.

BACKGROUND: Anxiety disorders are common and can cause substantial quality of life impairment. OBJECTIVE: The aim of this study was to investigate the frequency of anxiety in UK primary care. Treatment patterns and factors associated with an anxiety diagnosis were also assessed. METHODS: The Health Improvement Network was used to identify all patients aged 10-79 years with a new diagnosis of anxiety in 2002-04 (n = 40 873) and age-, sex- and calendar-year-matched controls (n = 50 000). A nested case-control analysis was used to quantify potential risk factors for anxiety by multivariate logistic regression. RESULTS: The prevalence of anxiety was 7.2% and the incidence was 9.7 per 1000 person-years. Incidence and prevalence were highest in women and young adults (20-29 years). Anxiety was associated with heavy alcohol use, smoking and addiction problems as well as stress, sleep and depression disorders. Anxiety patients used health care services more frequently than controls. Among patients diagnosed with anxiety, 63% were treated pharmacologically. Antidepressants accounted for almost 80% of prescriptions. CONCLUSIONS: The prevalence and incidence of anxiety are high in UK primary care and are almost twice as high in women than in men. Anxiety is associated with other psychiatric morbidity as well as frequent health care use. Antidepressants are the most commonly used pharmacological treatment.

[Incidence rate of community acquired pneumonia in a population cohort registered in BIFAP]. / Incidencia de neumonía adquirida en la comunidad en la cohorte poblacional de la base de datos en atención primaria (BIFAP).

OBJECTIVE: To estimate the incidence rate (IR) of community acquired pneumonia (CAP) using the information in the Primary Healthcare database in Spain. DESIGN: Retrospective study (2003-2007) using the information registered in the Database for Pharmaco-Epidemiological Research in Primary Care (BIFAP). STUDY POPULATION: Subjects aged 20 to 79 years old, were followed up until the occurrence of a pneumonia episode, death, age of 80, or the end of the study, whichever came first. CASE SELECTION: A computerised search was performed to detect suggestive cases of pneumonia using ICPC codes (International Classification of Primary Care) and free text. The computerised histories were manually reviewed in order to identify those cases fulfilling the CAP's determined definition. ANALYSE: IR of pneumonia was computed by age, sex and season. The percentage of hospitalisation was estimated. These results were compared with the IR from the United Kingdom using THIN database (The Health Improvement Network). RESULTS: IR of CAP was 2.69 per 1000 persons-year (IR women=2.29; IR men=3.16) with BIFAP database, and 32 % of the CAP cases were hospitalised. In United Kingdom, IR was 1.07 per 1000 persons-year (IR women=0.93; IR men=1.22) and 17% of CAP were hospitalised. CONCLUSION: The BIFAP computerised Primary Care database is useful to estimate the incidence rate of CAP in Spain, as well as to compare the results with those obtained using other European computerised Primary Care databases.