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Occupational activity and bone mineral density in postmenopausal women in England

Few studies have assessed the relationship between occupational activity and bone mineral density (BMD), although two case-control studies have reported a protective effect of occupational activity on hip fracture. In the present study 580 postmenopausal women aged 45-61 years completed a risk factor questionnaire including a detailed occupational history. For each job, hours spent sitting, standing, walking, lifting and carrying were recorded; these measures, evaluated at ages 20, 30, 40 years, in the current job and over the working lifetime, were used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and measurements at five sites were used in a multiple regression analysis adjusting for potential confounding variables. There was a significant negative association between sitting at age 20 years and BMD at the radius (p = 0.037), with negative relationships of borderline significance at the anteroposterior spine (p = 0.091) and whole body (p = 0.078). There were significant positive associations between standing at age 30 years and BMD at all five sites (p < 0.05), but no significant linear associations for standing at ages 20 and 40 years. No significant associations were found for lifetime or current occupational measures of sitting, standing, walking and lifting or carrying. The lack of consistency of these significant findings suggests that they may have occurred by chance, and that occupational activity has little if any effect on BMD in postmenopausal women.

Alendronate and estrogen-progestin in the long-term prevention of bone loss: Four-year results from the early postmenopausal intervention cohort study: A randomized, controlled trial

Background: Up to 3 years of treatment with alendronate, 5 mg/d, prevents postmenopausal bone loss. Objective: To determine whether the effect of alendronate is sustained at 4 years of treatment and persists after treatment is discontinued. Design: Randomized, controlled trial. Setting: United States and Europe. Participants: 1609 postmenopausal women 45 to 59 years of age. Intervention: Participants were randomly assigned to receive oral alendronate, 5 mg/d or 2.5 mg/d; placebo; or open-label estrogen- progestin. Women in the alendronate groups received alendronate for the first 2 years of the study. Treatment was then continued without change or replaced with placebo for the last 2 years of the study. Measurements: Annual measurement of bone mineral density. Results: By year 4, the bone mineral density of participants in the placebo group had decreased by 1% to 6% (P < 0.001). Four years of treatment with 5 mg of alendronate per day increased bone mineral density at the spine (mean change [±SE], 3.8% ± 0.3%), hip (mean, 2.9% ± 0.2%), and total body (mean, 0.9% ± 0.2%) (P < 0.001 overall). By year 4, bone mineral density at most skeletal sites was greater in participants who switched from alendronate to placebo than in those who continuously received placebo. In years 3 and 4, bone loss in participants who switched from alendronate to placebo was similar to that seen during years 1 and 2 in those who continuously received placebo. Compared with 5 mg of alendronate per day, estrogen-medroxyprogesterone acetate produced similar increases in bone mineral density and estradiol-norethisterone acetate produced increases that were substantially greater. Conclusions: Four years of treatment with alendronate or estrogen-progestin prevented postmenopausal bone loss. A residual effect was seen 2 years after alendronate therapy was stopped; however, continuous alendronate treatment was more effective in preventing postmenopausal bone loss than 2 years of alendronate followed by 2 years of placebo.

Risk factors for testicular germ cell tumours by histological tumour type

There are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology.

Association between a family history of fractures and bone mineral density in early postmenopausal women

The aim of this analysis was to measure the strength of the association between a family history of fractures and bone mineral density (BMD), and to determine what definition of family fracture history best predicts BMD. Five hundred and eighty postmenopausal women aged 45-59 at recruitment completed a risk factor questionnaire. Women were asked to recall details of fractures sustained by any female relative. BMD measurements taken at five sites were used. The data were analysed using linear regression, adjusting for age. Two hundred and ninety-seven (52.8%) women reported a family history of fractures, and they had a significantly lower BMD at two of the sites measured (p < 0.05). The associations with BMD were most significant when only counting fractures that occurred in the subject's mother or a sister as a result of low trauma, with no restrictions made on age at the time of fracture and site of fracture (p < 0.01 at three sites; 0.01 < p < 0.05 at two sites). Women with a family history according to this definition had a 4.6% reduction in BMD at the femoral neck. When T scores were used to categorize women as either osteopenic/osteoporotic (T < -1) or normal at the femoral neck, the sensitivity of using this definition was 39% and the specificity was 74%. The small group of women that reported a low-trauma hip fracture in a mother or sister (n = 23) had a mean femoral neck BMD which was 8.9% lower than that of the remainder of the sample, although this difference was less statistically significant than when low trauma fractures at any site were counted. Of these 23 women, 70% were osteopenic or osteoporotic, compared with 57% of those reporting a low-trauma fracture at any site and 47% of the sample as a whole. The sensitivity of this definition, however, was low (6%). From these analyses it can be concluded that the definition of family fracture history that best predicts BMD in postmenopausal women is a fracture at any age in a mother or sister resulting from low trauma, although the sensitivity and specificity of using a family history of fractures by itself to screen for low BMD were poor. Copyright (C) 1999 Elsevier Science Inc.

Trends in antidepressant prescriptions in children and young people in England, 1998-2017: Protocol of a cohort study using linked primary care and secondary care datasets

Introduction Increasing numbers of children and young people (CYP) are receiving prescriptions for antidepressants. This is the protocol of a study aiming to describe the trends and variation in antidepressant prescriptions in CYP in England, and to examine the indications for the prescriptions recorded and whether there was contact with secondary care specialists on or around the time of the first antidepressant prescription. Methods and analysis All eligible CYP aged between 5 and 17 years in 1998-2017 from the QResearch primary care database will be included. Incidence and prevalence rates of any antidepressant prescription in each year will be calculated. We will examine four different antidepressant classes: selective serotonin reuptake inhibitors, tricyclic and related antidepressants, serotonin and norepinephrine reuptake inhibitors and other antidepressants, as well as for individual drugs. Linked primary and secondary care data (hospital episode statistics) in the year before and up to 6 months after the first antidepressant prescription will be examined for CYP whose first antidepressant prescription was in 2006-2017. Whether there were records of indications and being seen by psychiatric or paediatric specialists will be identified. Trends over time and differences by region, deprivation and ethnicity will be examined using Poisson regression. Discussion This large, population-based study will give an up-to-date picture of antidepressant prescribing in CYP and identify any variation. Understanding what indications are recorded when CYP are being prescribed antidepressants, and whether this was done in partnership with secondary care specialists, will provide evidence of whether appropriate guidelines are being followed.

A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database

Symptoms and risk factors to identify people with suspected cancer in primary care.

Predicting risk of emergency admission to hospital using primary care data: Derivation and validation of QAdmissions score

Objective: To develop and externally validate a risk algorithm (QAdmissions) to estimate the risk of emergency hospital admission for patients aged 18-100 years in primary care. Design: Prospective open cohort study using routinely collected data from general practice linked to hospital episode data during the 2-year study period 1 January 2010 to 31 December 2011. Setting: 405 general practices in England contributing to the national QResearch database to develop the algorithm. Two validation cohorts to validate the algorithm (1) 202 different QResearch practices and (2) 343 practices in England contributing to the Clinical Practice Research DataLink (CPRD). All general practices had data linked to hospital episode statistics at the individual patient level. Participants: We studied 2 849 381 patients aged 18-100 years in the derivation cohort with over 4.6 million person-years of follow-up. 265 573 of these patients had one or more emergency admissions during follow-up. For the QResearch validation cohort, we identified 1 340 622 patients aged 18-100 years with over 2.2 million person-years of follow-up. Of these patients, 132 723 had one or more emergency admissions during follow-up. The CPRD cohort included 2 475 360 patients aged 18-100 years with over 3.8 million person-years of follow-up. 234 204 of these patients had one or more emergency admissions during follow-up. We excluded patients without a valid NHS number and a valid Townsend score. Endpoint: First (ie, incident) emergency admission to hospital in the next 2 years as recorded on the linked hospital episodes records. Risk factors: Candidate variables recorded on the general practitioner computer system including (1) demographic variables (age, sex, strategic health authority, Townsend deprivation score, ethnicity); (2) lifestyle variables (smoking, alcohol intake); (3) chronic diseases; (4) prescribed medication; (5) clinical values (body mass index, systolic blood pressure); (6) laboratory test results (haemoglobin, platelets, erythrocyte sedimentation rate, ratio of total serum cholesterol to high density lipoprotein cholesterol concentrations, liver function tests). We also included the number of emergency admissions in the preceding year based on information recorded on the linked hospital episodes records. Results: The final QAdmissions algorithm incorporated 30 variables. When applied to the QResearch validation cohort, it explained 41% of the variation in women and 43% of that in men. The D statistic for QAdmissions was 1.7 in women and 1.8 in men. The receiver operating curve statistic was 0.78 for men and 0.77 for women. QAdmissions had good performance on all measures of discrimination and calibration. The positive predictive value for emergency admissions for the top tenth of patients at highest risk was 42% and the sensitivity was 39%. The results for the CPRD validation cohort were similar.

Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: Open cohort study in primary care

ObjeCtive: To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones). Design: Open cohort study in primary care. setting: 1243 practices contributing data to the QResearch database in England. PartiCiPants: 469 688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015. exPOsures: Hypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination. Main OutCOMe Measures: First recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders. results: 21 308 (4.5%) and 32 533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confdence interval 0.57 to 0.89; rate 14.4 per 10 000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confdence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94). COnClusiOns: We have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs.

Identifying women with suspected ovarian cancer in primary care: Derivation and validation of algorithm

Objective: To derive and validate an algorithm to estimate the absolute risk of having ovarian cancer in women with and without symptoms. Design: Cohort study with data from 375 UK QResearch general practices for development and 189 for validation. Participants: Women aged 30-84 without a diagnosis of ovarian cancer at baseline and without appetite loss, weight loss, abdominal pain, abdominal distension, rectal bleeding, or postmenopausal bleeding recorded in previous 12 months. Main outcome: The primary outcome was incident diagnosis of ovarian cancer recorded in the next two years. Methods: Risk factors examined included age, family history of ovarian cancer, previous cancers other than ovarian, body mass index (BMI), smoking, alcohol, deprivation, loss of appetite, weight loss, abdominal pain, abdominal distension, rectal bleeding, postmenopausal bleeding, urinary frequency, diarrhoea, constipation, tiredness, and anaemia. Cox proportional hazards models were used to develop the risk equation. Measures of calibration and discrimination assessed performance in the validation cohort. Results: In the derivation cohort there were 976 incident cases of ovarian cancer from 2.03 million person years. Independent predictors were age, family history of ovarian cancer (9.8-fold higher risk), anaemia (2.3-fold higher), abdominal pain (sevenfold higher), abdominal distension (23-fold higher), rectal bleeding (twofold higher), postmenopausal bleeding (6.6-fold higher), appetite loss (5.2-fold higher), and weight loss (twofold higher). On validation, the algorithm explained 57.6% of the variation. The receiver operating characteristics curve (ROC) statistic was 0.84, and the D statistic was 2.38. The 10% of women with the highest predicted risks contained 63% of all ovarian cancers diagnosed over the next two years. Conclusion: The algorithm has good discrimination and calibration and, after independent validation in an external cohort, could potentially be used to identify those at highest risk of ovarian cancer to facilitate early referral and investigation. Further research is needed to assess how best to implement the algorithm, its cost effectiveness, and whether, on implementation, it has any impact on health outcomes.

Exposure to statins and risk of common cancers: A series of nested case-control studies

Background: Many studies and meta-analyses have investigated the effects of statins on cancer incidence but without showing consistent effects.Methods: A series of nested case-control studies was conducted covering 574 UK general practices within the QResearch database. Cases were patients with primary cancers diagnosed between 1998 and 2008. The associations between statin use and risk of ten site-specific cancers were estimated with conditional logistic regression adjusted for co-morbidities, smoking status, socio-economic status, and use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2 inhibitors and aspirin.Results: 88125 cases and 362254 matched controls were analysed. The adjusted odds ratio for any statin use and cancer at any site were 1.01 (95%CI 0.99 to 1.04). For haematological malignancies there was a significant reduced risk associated with any statin use (odds ratio 0.78, 95%CI 0.71 to 0.86). Prolonged (more than 4 years) use of statins was associated with a significantly increased risk of colorectal cancer (odds ratio 1.23, 95%CI 1.10 to 1.38), bladder cancer (odds ratio 1.29, 95%CI 1.08 to 1.54) and lung cancer (odds ratio 1.18, 95%CI 1.05 to 1.34). There were no significant associations with any other cancers.Conclusion: In this large population-based case-control study, prolonged use of statins was not associated with an increased risk of cancer at any of the most common sites except for colorectal cancer, bladder cancer and lung cancer, while there was a reduced risk of haematological malignancies. © 2011 Vinogradova et al; licensee BioMed Central Ltd.

Exposure to cyclooxygenase-2 inhibitors and risk of cancer: Nested case-control studies

Background: Selective cyclooxygenase-2 (COX2) inhibitors are widely used as analgesics and it is unclear whether its long-term use affects cancer risk.Methods:A series of nested case-control studies using the QResearch primary care database. Associations of COX2 inhibitor use with risk of all cancers and 10 common site-specific cancers were estimated using conditional logistic regression adjusted for comorbidities, smoking status, socioeconomic status, and use of non-steroidal anti-inflammatory drugs, aspirin and statins.Results:A total of 88 125 cancers, diagnosed between 1998 and 2008, matched with up to five controls, were analysed. Use of COX2 inhibitors for more than a year was associated with a significantly increased risk of breast cancer (odds ratio (OR) 1.24, 95% confidence interval (CI) 1.08-1.42) and haematological malignancies (OR 1.38, 95% CI 1.12-1.69) and a decreased risk of colorectal cancer (OR 0.76, 95% CI 0.63-0.92). There were no other significant associations. Conclusion: Prolonged use of COX2 inhibitors was associated with an increased risk of breast and haematological cancers and decreased risk of colorectal cancer. These findings need to be confirmed using other data sources. © 2011 Cancer Research UK All rights reserved.

Authors' reply to Zagarella

Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: Cohort study using primary care database

Objective To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression. Design Cohort study. Setting UK general practices contributing to the QResearch primary care database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs. Main outcome measures First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years' follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables. Results During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years' follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years' follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥40 mg/day). Conclusions This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine.

Development and validation of QDiabetes-2018 risk prediction algorithm to estimate future risk of type 2 diabetes: cohort study

Objectives To derive and validate updated QDiabetes-2018 prediction algorithms to estimate the 10 year risk of type 2 diabetes in men and women, taking account of potential new risk factors, and to compare their performance with current approaches.Design Prospective open cohort study.Setting Routinely collected data from 1457 general practices in England contributing to the QResearch database: 1094 were used to develop the scores and a separate set of 363 were used to validate the scores.Participants 11.5 million people aged 25-84 and free of diabetes at baseline: 8.87 million in the derivation cohort and 2.63 million in the validation cohort.Methods Cox proportional hazards models were used in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QDiabetes (age, ethnicity, deprivation, body mass index, smoking, family history of diabetes in a first degree relative, cardiovascular disease, treated hypertension, and regular use of corticosteroids) and new risk factors: atypical antipsychotics, statins, schizophrenia or bipolar affective disorder, learning disability, gestational diabetes, and polycystic ovary syndrome. Additional models included fasting blood glucose and glycated haemoglobin (HBA1c). Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status.Main outcome measure Incident type 2 diabetes recorded on the general practice record.Results In the derivation cohort, 178 314 incident cases of type 2 diabetes were identified during follow-up arising from 42.72 million person years of observation. In the validation cohort, 62 326 incident cases of type 2 diabetes were identified from 14.32 million person years of observation. All new risk factors considered met our model inclusion criteria. Model A included age, ethnicity, deprivation, body mass index, smoking, family history of diabetes in a first degree relative, cardiovascular disease, treated hypertension, and regular use of corticosteroids, and new risk factors: atypical antipsychotics, statins, schizophrenia or bipolar affective disorder, learning disability, and gestational diabetes and polycystic ovary syndrome in women. Model B included the same variables as model A plus fasting blood glucose. Model C included HBA1c instead of fasting blood glucose. All three models had good calibration and high levels of explained variation and discrimination. In women, model B explained 63.3% of the variation in time to diagnosis of type 2 diabetes (R2), the D statistic was 2.69 and the Harrell's C statistic value was 0.89. The corresponding values for men were 58.4%, 2.42, and 0.87. Model B also had the highest sensitivity compared with current recommended practice in the National Health Service based on bands of either fasting blood glucose or HBA1c. However, only 16% of patients had complete data for blood glucose measurements, smoking, and body mass index.Conclusions Three updated QDiabetes risk models to quantify the absolute risk of type 2 diabetes were developed and validated: model A does not require a blood test and can be used to identify patients for fasting blood glucose (model B) or HBA1c (model C) testing. Model B had the best performance for predicting 10 year risk of type 2 diabetes to identify those who need interventions and more intensive follow-up, improving on current approaches. Additional external validation of models B and C in datasets with more completely collected data on blood glucose would be valuable before the models are used in clinical practice.

Development and validation of QMortality risk prediction algorithm to estimate short term risk of death and assess frailty: cohort study

Objectives To derive and validate a risk prediction equation to estimate the short term risk of death, and to develop a classification method for frailty based on risk of death and risk of unplanned hospital admission.Design Prospective open cohort study.Participants Routinely collected data from 1436 general practices contributing data to QResearch in England between 2012 and 2016. 1079 practices were used to develop the scores and a separate set of 357 practices to validate the scores. 1.47 million patients aged 65-100 years were in the derivation cohort and 0.50 million patients in the validation cohort.Methods Cox proportional hazards models in the derivation cohort were used to derive separate risk equations in men and women for evaluation of the risk of death at one year. Risk factors considered were age, sex, ethnicity, deprivation, smoking status, alcohol intake, body mass index, medical conditions, specific drugs, social factors, and results of recent investigations. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for each age and ethnic group. The new mortality equation was used in conjunction with the existing QAdmissions equation (which predicts risk of unplanned hospital admission) to classify patients into frailty groups.Main outcome measure The primary outcome was all cause mortality.Results During follow-up 180 132 deaths were identified in the derivation cohort arising from 4.39 million person years of observation. The final model included terms for age, body mass index, Townsend score, ethnic group, smoking status, alcohol intake, unplanned hospital admissions in the past 12 months, atrial fibrillation, antipsychotics, cancer, asthma or chronic obstructive pulmonary disease, living in a care home, congestive heart failure, corticosteroids, cardiovascular disease, dementia, epilepsy, learning disability, leg ulcer, chronic liver disease or pancreatitis, Parkinson's disease, poor mobility, rheumatoid arthritis, chronic kidney disease, type 1 diabetes, type 2 diabetes, venous thromboembolism, anaemia, abnormal liver function test result, high platelet count, visited doctor in the past year with either appetite loss, unexpected weight loss, or breathlessness. The model had good calibration and high levels of explained variation and discrimination. In women, the equation explained 55.6% of the variation in time to death (R2), and had very good discrimination-the D statistic was 2.29, and Harrell's C statistic value was 0.85. The corresponding values for men were 53.1%, 2.18, and 0.84. By combining predicted risks of mortality and unplanned hospital admissions, 2.7% of patients (n=13 665) were classified as severely frail, 9.4% (n=46 770) as moderately frail, 43.1% (n=215 253) as mildly frail, and 44.8% (n=223 790) as fit.Conclusions We have developed new equations to predict the short term risk of death in men and women aged 65 or more, taking account of demographic, social, and clinical variables. The equations had good performance on a separate validation cohort. The QMortality equations can be used in conjunction with the QAdmissions equations, to classify patients into four frailty groups (known as QFrailty categories) to enable patients to be identified for further assessment or interventions.

Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: Prospective cohort study

Objectives: To derive and validate a new clinical risk prediction algorithm (QThrombosis, www.qthrombosis.org) to estimate individual patients'risk of venous thromboembolism. Design: Prospective open cohort study using routinely collected data from general practices. Cox proportional hazards models used in derivation cohort to derive risk equations evaluated at 1 and 5 years. Measures of calibration and discrimination undertaken in validation cohort. Setting: 564 general practices in England and Wales contributing to the QResearch database. Participants: Patients aged 25-84 years, with no record of pregnancy in the preceding 12 months or any previous venous thromboembolism, and not prescribed oral anticoagulation at baseline: 2 314 701 in derivation cohort and 1 240 602 in validation cohort. Outcomes: Incident cases of venous thromboembolism, either deep vein thrombosis or pulmonary embolism, recorded in primary care records or linked cause of death records. Results: The derivation cohort included 14 756 incident cases of venous thromboembolism from 10 095 199 person years of observation (rate of 14.6 per 10 000 person years). The validation cohort included 6913 incident cases from 4 632 694 person years of observation (14.9 per 10 000 person years). Independent predictors included in the final model for men and women were age, body mass index, smoking status, varicose veins, congestive cardiac failure, chronic renal disease, cancer, chronic obstructive pulmonary disease, inflammatory bowel disease, hospital admission in past six months, and current prescriptions for antipsychotic drugs. We also included oral contraceptives, tamoxifen, and hormone replacement therapy in the final model for women. The risk prediction equation explained 33% of the variation in women and 34% in men in the validation cohort evaluated at 5 years The D statistic was 1.43 for women and 1.45 for men. The receiver operating curve statistic was 0.75 for both sexes. The model was well calibrated. Conclusions: We have developed and validated a new risk prediction model that quantifies absolute risk of thrombosis at 1 and 5 years. It can help identify patients at high risk of venous thromboembolism for prevention. The algorithm is based on simple clinical variables which the patient is likely to know or which are routinely recorded in general practice records. The algorithm could be integrated into general practice clinical computer systems and used to risk assess patients before hospital admission or starting medication which might increase the risk of venous thromboembolism.

Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: Cohort study using a primary care database

Objective To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression. Design Cohort study. Setting Patients registered with UK general practices contributing data to the QResearch database. Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012. Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables. Main outcome measures Suicide and attempted suicide or self harm during follow-up. Results During follow-up, 87.7% (n=209 476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79-590 days). During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants (1.80, 1.61 to 2.00). The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine (1.85, 1.61 to 2.13), trazodone (1.73, 1.26 to 2.37), and mirtazapine (1.70, 1.44 to 2.02), and significantly reduced for amitriptyline (0.71, 0.59 to 0.85). The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment. Conclusion Rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants. Mirtazapine, venlafaxine, and trazodone were associated with the highest rates of suicide and attempted suicide or self harm, but the number of suicide events was small leading to imprecise estimates. As this is an observational study the findings may reflect indication biases and residual confounding from severity of depression and differing characteristics of patients prescribed these drugs. The increased rates in the first 28 days of starting and stopping antidepressants emphasise the need for careful monitoring of patients during these periods.

Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: Cohort study using a primary care database

Background: Epilepsy is a serious condition which can profoundly affect an individual's life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years. Methods: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox's proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables. Results: In the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166). Conclusions: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies.

Risk of pneumonia in patients taking statins: Population-based nested case-control study

Background: Community-acquired pneumonia is one of the most common causes of hospitalisation and death in older people. Recent research suggests that statins might improve the outcome of infectious diseases because of their anti-oxidative and anti-inflammatory properties. Aim: To estimate the association between current statin use and the risk of community-acquired pneumonia. Design and setting: Nested case-control study of 443 general practices in the UK within the QResearch®database. Method: Individuals with newly recorded pneumonia, diagnosed between 1996 and 2006 and aged 45 years and older, were matched with up to five controls by age, sex, general practice, and calendar year. Odds ratios for pneumonia associated with statin use were adjusted for smoking status, deprivation, comorbidities, use of acid-lowering drugs, influenza, and pneumococcal vaccines. Results: The analysis found a decreased risk of pneumonia in patients prescribed statins in the year prior to diagnosis (adjusted odds ratio = 0.78, 95% confidence interval [CI] = 0.74 to 0.83), particularly in patients with prescriptions in the last 28 days (adjusted odds ratio = 0.68, 95% CI = 0.63 to 0.73). Atorvastatin and simvastatin had similar associations with pneumonia risk. Analysis repeated on lobar and pneumococcal pneumonia cases showed comparable results. Conclusion: In this large population-based case-control study, current exposure to statins was associated with a reduced risk of pneumonia. The findings were similar to other observational population-based studies, but further randomised controlled trials are necessary before recommending statins to patients at high risk of pneumonia. ©British Journal of General Practice.