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To evaluate the 9-year incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cumulative adherence to perform a next test in a cohort of women aged 40+ years with no cervical screening cytology within a window of 5 years (underscreened women), after baseline cervical cytology and HPV tests.In Catalonia, Spain, co-testing with cytology and HPV test has been recommended in the Public Health system since 2006 for underscreened women. In 2007, 1,594 women with underscreened criteria were identified and followed through medical records form Pathological Department. 9-year cumulative incidence of histologically confirmed CIN2+ and cumulative adherence to perform a next test were estimated using Kaplan-Meier statistics.Follow-up was available for 1,009 women (63.3%) resulting in 23 women with. CIN2+ (2.3%). Of them, 4 women (17%) had both tests negative at baseline (3CIN2 and 1CIN3) with cumulative incidence of CIN2+ of 0.4% (95% CI: 0.1-1.4) at 5-years and 1.3% (95% CI: 0.4-3.7) at 9-years. During the first year, the prevalence among women with both tests positive was 27.0% (95% CI: 13.0-50.6) for CIN2+. Lost to follow-up was higher among women with both tests negative compared to those with both positive tests (38.7% vs 4.2%, p-value <0.001). 40.5% of the women HPV-/cyto- had a re-screening test during the 4 years following the baseline, increasing until 53.5% during the 6 years of follow-up.HPV detection shows a high longitudinal predictive value at 9-year to identify women at risk to develop CIN2+. The data validate a safe extension of the 3-year screening intervals (current screening interval) to 5-year intervals in underscreened women that had negative HPV result at baseline. It is necessary to establish mechanisms to ensure screening participation

BACKGROUND: Atrial fibrillation (AF) is associated with subsequent cardiovascular events including ischemic stroke, transient ischemic events, and coronary events. This study aimed to evaluate the risk of ischemic cerebrovascular events (ICVE), coronary events (CE) or heart failure (HF) following a diagnosis of AF. METHODS: Patients were selected from the UK General Practice Research Database. The incidence of ICVE, CE and HF was determined during a 6-year follow-up period for patients with a first diagnosis of AF (n=831) and a control group without AF (n=8226). Relative risk of developing a cardiovascular event associated with prior AF and other potential risk factors was estimated using Cox regression analysis. RESULTS: A first diagnosis of ICVE, CE or HF was made in 261 patients in the AF group and 622 in the control group. The relative risks associated with AF were 2.1 for CE (95% CI: 1.6-2.9), 3.0 for ICVE (95% CI: 2.3-4.0) and 6.4 for HF (95% CI: 5.0-8.3). The risks of CE, HF and ICVE were higher in patients with chronic AF than paroxysmal AF (odds ratio: 1.5, 95% CI: 1.0-2.2) and in patients aged at least 60 years or with diabetes. Lifestyle factors did not significantly affect the risk of cardiovascular events in patients with AF. CONCLUSIONS: After a first episode of AF there is an increased risk of ICVE, CE and HF. Patients initially diagnosed with chronic AF have a higher risk than those with paroxysmal AF.

BACKGROUND: Venous thromboembolism (VTE) manifesting as deep vein thrombosis (DVT) and pulmonary embolism (PE) remains a common vascular disease with high mortality and morbidity. Our aim was to study the clinical spectrum of VTE, assess its incidence in the general population, and evaluate potential risk factors. METHODS: Prospective cohort study with nested case-control analysis using the General Practice Research Database (1994-2000). Venous thromboembolism was newly diagnosed in 6550 patients. Cases were compared with a random sample of 10,000 controls and frequency-matched by age, sex, and year. RESULTS: The incidence rate of VTE was 74.5 per 100,000 person-years. Overweight, varicose veins, inflammatory bowel disease, cancer, and oral corticosteroid use were associated with a greater risk of VTE. Ischemic heart disease, heart failure, and cerebrovascular diseases were associated with an increased risk of PE but not with DVT. Venous thromboembolism was strongly associated with fractures (odds ratio [OR], 21.3; 95% confidence interval [CI], 15.7-28.9) and surgery (OR, 25.0; 95% CI, 14.4-43.5). In women, the risk of VTE was 1.9 (95% CI, 1.5-2.3) among those receiving opposed hormone therapy (in which the woman takes estrogen throughout the month and progesterone for 10-14 days later in the month) and 1.9 (95% CI, 1.4-2.5) among those taking oral contraceptives. Cancer and cerebrovascular diseases presented a greater relative risk of fatal PE compared with nonfatal PE. CONCLUSIONS: Overweight, varicose veins, cancer, inflammatory bowel disease, fractures, surgery, and use of oral corticosteroids, oral contraceptives, and opposed hormone therapy were independent risk factors for both DVT and PE. The magnitude of the association with some risk factors varied between DVT and PE, as well as between fatal and nonfatal PE.

Background. Many individuals consulting their GP with upper abdominal symptoms are initially classified as having dyspepsia. Few studies have described the incidence of dyspepsia or the comorbidities, risk factors or prognosis associated with this diagnosis. Methods. We used the UK General Practice Research Database to find patients with a new diagnosis of dyspepsia in 1996 (n = 6913) and a control cohort (n = 11 036). We determined the incidence of dyspepsia, potential risk factors and comorbidity, and the risk of new onset morbidity in the year following the index date. Results. The incidence of dyspepsia was 15.3 per 1000 person-years. An increased probability of a dyspepsia diagnosis was associated with chest pain [odds ratio (OR): 2.4], general pain (OR: 1.8), sleep disorders (OR: 1.5), angina (OR: 1.5), osteoarthritis/rheumatoid arthritis (OR: 1.4) and smoking (OR: 1.2). There was only a borderline association with obesity (OR: 1.1). Patients with dyspepsia had an increased likelihood of a diagnosis of irritable bowel syndrome (IBS) (OR: 264), gastroesophageal reflux disease (GERD) (OR: 62.8) or peptic ulcer disease (PUD) (OR: 27.2) during the following year. Conclusions. The commonest diagnosis to emerge after an initial consultation for dyspepsia was IBS, followed by GERD and PUD.

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.

Objective: It is unclear how gastro-oesophageal reflux disease (GORD) is diagnosed in primary care. The aim of this study is to compare patients given a diagnosis of GORD with those diagnosed with heartburn. Research design and methods: Data from the UK General Practice Research Database were extracted for patients newly diagnosed with heartburn (n = 1841) or GORD (n = 5318) in 1996. Main outcome measures., Patient characteristics, morbidity, healthcare use and prescribed treatments were compared using unconditional logistic regression analysis. Results: GORD was diagnosed more frequently than heartburn (3.2 vs. 1.1 per 1000 patient-years). A diagnosis of GORD was less likely among females (odds ratio (OR): 0.8; confidence interval (Cl): 0.7-0.9), smokers (OR: 0.8; Cl: 0.7-0.9) and patients who consulted their physician frequently (OR: 0.8; Cl: 0.7-0.9). There was a wide distribution in the ratio of GORD-to-heartburn diagnoses between primary care practices (mean 2.9; range 0-infinity). GORD patients were more likely to receive proton pump inhibitors (OR: 2.9; Cl: 2.6-3.4), but 24% of GORD patients and 40% of heartburn patients received no acid-suppressive treatment in the month after diagnosis. Conclusions: Several factors influenced the diagnosis of gastro-oesophageal reflux symptoms by primary care physicians. Further research is needed to aid the diagnosis of GORD in primary care.

Background: Natural history of paroxysmal atrial fibrillation (AF) is not very well documented. Clinical experience suggests that paroxysmal AF could progress to chronic AF with estimates ranging between 15 and 30% over a period of 1–3 years. We performed an epidemiologic study to elucidate the natural history of paroxysmal AF, this study estimated its incidence in a general practice setting, identified associated factors and analyzed the progression into chronic AF as well as the mortality rate. Methods: Using the UK General Practice Research Database (GPRD), we identified patients aged 40–89 years with a first-recorded episode of paroxysmal AF during 1996. Risk factors were assessed using 525 incident paroxysmal AF cases confirmed by the general practitioner (GP) and a random sample of controls. We follow-up paroxysmal AF patients and estimated their mortality rate and progression to chronic AF. Results: The incidence of paroxysmal AF was 1.0 per 1,000 person-years. Major risk factors for paroxysmal AF were age and prior valvular heart disease, ischaemic heart disease, heart failure and hyperthyroidism. During a mean follow-up of 2.7 years, 70 of 418 paroxysmal AF patients with complete information progressed to chronic AF. Risk factors associated with progression were valvular heart disease (OR 2.7, 95% CI 1.2–6.0) and moderate to high alcohol consumption (OR 3.0, 95% CI 1.1–8.0). Paroxysmal AF patients did not carry an increased risk of mortality, compared to an age and sex matched sample of the general population. There was a suggestion of a small increased risk among patients progressing to chronic AF (RR 1.5, 96% CI 0.8–2.9). Conclusion: Paroxysmal AF is a common arrhythmia in the general practice setting, increasing with age and commonly associated with other heart diseases. It sometimes is the initial presentation and then progress to chronic AF. A history of valvular heart disease and alcohol consumption are associated with this progression.

BACKGROUND The aetiology of inflammatory bowel disease remains largely unknown. AIM We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease. METHODS We identified a cohort of patients 20-84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case-control analysis using all cases and a random sample of 10 000 frequency-matched controls. RESULTS Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89-6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14-1.00). CONCLUSIONS Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.

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.

BACKGROUND There has been some debate on the existence of an association between hypertension, antihypertensive medications and cancer risk. METHODS We performed a nested case-control study to assess the association between the risk of prostate cancer and the use of the angiotensin converting enzyme (ACE)-inhibitor captopril, and other antihypertensive drugs. We used data from the General Practice Research Database in UK. RESULTS We found an incidence rate of prostate cancer of 1.61 per 1,000 person-years among male patients aged 50–79 years old. Patients with a history of benign prostatic hyperplasia and/or prostatism carried a two-fold greater risk of prostate cancer than those without such antecedents. None of the other studied co-morbidities were associated with prostate cancer. We found that users of captopril had a relative risk of 0.7 (95% CI: 0.4–1.2) to develope prostate cancer. None of the other studied individual ACE-inhibitors shared a similar effect with the one observed for captopril. CONCLUSIONS No clear association was apparent between the use of antihypertensive drugs and prostate cancer. However, specific focus on users of captopril showed a lower risk of subsequent prostate cancer. Further research is needed to explore this association.

AIMS The objective of this study was to estimate the risk of acute liver injury associated with individual acid-suppressing drugs and assess the role of dose and duration of treatment. METHODS We used a nested case-control study design within a cohort of over 100,000 users of cimetidine, famotidine, omeprazole and ranitidine. The primary source of information was the General Practitioners Research Database. We identified 108,981 persons aged 20-74 years who received at least one prescription for cimetidine, famotidine, omeprazole, or ranitidine during 1990-93, and we ascertained the first occurrence of clinically acute liver injury referred to a specialist or admitted to a hospital. RESULTS After review of medical records, 33 patients were considered eligible cases of idiopathic acute liver injury with no fatal cases. The type of liver injury was hepatocellular in almost half of the cases, and 80% of all cases presented with jaundice. Twelve cases occurred among current users of cimetidine, five among ranitidine users and one in an omeprazole user. The absolute risk of acute liver injury associated with cimetidine was estimated to be slightly greater than one per 5000 users of cimetidine. The adjusted relative risk (RRs) and 95% CI of developing acute liver injury associated with current use of cimetidine compared to non-use was 5.5 (1.9-15.9), with omeprazole 2.1 (0.2-19.2) and with ranitidine 1.7 (0.5-5.8). In the absence of concomitant use of other hepatotoxic drugs, the RR with cimetidine was 14.4 (2.9-73.7). Among users of cimetidine, the risk was especially high in the first 2 months of starting therapy (RR: 11.3, 3.7-35.1) and at daily doses of 800 mg or greater (RR: 8.8, 3.0-26.0). CONCLUSIONS Cimetidine was the individual anti-ulcer drug with the highest risk of developing symptomatic acute liver disease. Further data are required to confirm this finding. Our study indicates that there is a dose relationship and a short latent period between cimetidine trea

No comparative epidemiological data can be found in the literature on the renal safety of acid-suppressing drugs. We followed-up a cohort of close to 180,000 persons during periods of treatment and non-treatment with five anti-ulcer drugs to evaluate the risk of idiopathic acute renal failure and/or nephrotic syndrome. After reviewing medical records, five patients were found to be cases. Two presented with acute renal failure and three had nephrotic syndrome. Three cases occurred during periods of non-exposure to anti-ulcer drugs. Two cases occurred during current use of ranitidine: one of acute renal failure and one of nephrotic syndrome. No case was encountered during treatment with cimetidine, famotidine, nizatidine or omeprazole. The incidence of idiopathic renal disease in the general population was 1 per 100,000 person-years. The relative risk associated with use of acid-suppressing drugs was 1.8 (95% CI, 0.3-10.7) compared to non-use. These results do not suggest a major increased risk for acute renal injury and/or nephrotic syndrome associated with use of anti-ulcer drugs.

1. Recently, some cases have been reported where intravenous use of omeprazole was followed by loss of vision. We followed up a cohort of close to 140,000 persons during periods of treatment and non-treatment with five anti-ulcer drugs. 2. The relative risk of vascular disorders of the eye during use of omeprazole compared with non-use was 1.8 (95% CI 0.5-6.0). Use of other anti-ulcer drugs was associated with a similar risk of vascular disorders. The relative risk associated with current use of any anti-ulcer drug was 1.9 (95% CI 1.1-3.4). We did not find a single case of optic inflammatory disorder during treatment with any of the five anti-ulcer drugs. 3. These results do not suggest a major increased risk for vascular or inflammatory disorders of the eye associated with use of omeprazole or other anti-ulcer drugs.