Lianne Parkin

Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database

Objective To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel. Design Nested case-control study. Setting UK General Practice Research Database. Participants Women aged 15-44 years without major risk factors for venous thromboembolism who started a new episode of use of an oral contraceptive containing 30 µg oestrogen in combination with either drospirenone or levonorgestrel between May 2002 and September 2009. Cases were women with a first diagnosis of venous thromboembolism; up to four controls, matched by age, duration of recorded information, and general practice, were randomly selected for each case. Main outcome measures Odds ratios and 95% confidence intervals estimated with conditional logistic regression; age adjusted incidence rate ratio estimated with Poisson regression. Results 61 cases of idiopathic venous thromboembolism and 215 matched controls were identified. In the case-control analysis, current use of the drospirenone contraceptive was associated with a threefold higher risk of non-fatal idiopathic venous thromboembolism compared with levonorgestrel use; the odds ratio adjusted for body mass index was 3.3 (95% confidence interval 1.4 to 7.6). Subanalyses suggested that referral, diagnostic, first time user, duration of use, and switching biases were unlikely explanations for this finding. The crude incidence rate was 23.0 (95% confidence interval 13.4 to 36.9) per 100 000 woman years in current users of drospirenone and 9.1 (6.6 to 12.2) per 100 000 woman years in current users of levonorgestrel oral contraceptives. The age adjusted incidence rate ratio was 2.7 (1.5 to 4.7). Conclusions These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel.

Oral contraceptives and fatal pulmonary embolism.

In a national case-control study of fatal pulmonary embolism in New Zealand women of childbearing age, we estimated that current users of combined oral contraceptives had a relative risk of 9.6 (95% CI 3.1-29.1). From national distribution data, the absolute risk of death from pulmonary embolism in current users was estimated to be 10.5 per million woman-years.

A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use

The magnitude of the suspected increase in risk of acute interstitial nephritis among proton pump inhibitor users is uncertain. Here, we conducted a nested case-control study using routinely collected national health and drug dispensing data in New Zealand to estimate the relative and absolute risks of acute interstitial nephritis resulting in hospitalization or death in users of proton pump inhibitors. The cohort included 572,661 patients without a history of interstitial nephritis or other renal diseases who started a new episode of proton pump inhibitor use between 2005 and 2009. Cases had a first diagnosis after cohort entry of acute interstitial nephritis confirmed by hospital discharge letter or death record, and renal histology (definite, 46 patients), or discharge letter or death record only (probable, 26 patients). Ten controls, matched by birth year and sex, were randomly selected for each case. In the case-control analysis based on definite cases and their controls, the unadjusted matched odds ratio (95% confidence interval) for current versus past use of proton pump inhibitors was 5.16 (2.21–12.05). The estimate was similar when all cases (definite and probable) and their corresponding controls were analyzed, and when potential confounders were added to the models. The crude incidence rates and confidence intervals per 100,000 person-years were 11.98 (9.11–15.47) and 1.68 (0.91–2.86) for current and past use, respectively. Thus, current use of a proton pump inhibitor was associated with a significantly increased risk of acute interstitial nephritis, relative to past use.

Body Mass Index, Surgery, and Risk of Venous Thromboembolism in Middle-Aged Women A Cohort Study

Background— Obesity and surgery are known risk factors for venous thromboembolism (VTE), but there is limited information about the independent effects of obesity on the incidence of postoperative VTE. We linked questionnaire data from the Million Women Study with hospital admission and death records to examine the risk of VTE in relation to body mass index (BMI) both in the absence of surgery and in the first 12 weeks following an operation. Methods and Results— Overall, 1 170 495 women (mean age, 56.1 years) recruited in 1996 to 2001 through the National Health Service Breast Screening Programme in England and Scotland were followed for an average of 6 years, during which time 6438 were admitted to hospital or died of VTE. The adjusted relative risks of VTE increased progressively with increasing BMI and women with a BMI ≥35 kg/m2 were 3–4 times as likely to develop VTE as those with a BMI 22.5 to 24.9 (relative risk 3.45 [95% CI 3.09–3.86]). Overweight and obese women were more likely than lean women to be admitted for surgery and also to develop postoperative VTE. During a 12-week period without surgery, the incidence rates of VTE per 1000 women with a BMI <25 and ≥25 were 0.10 (0.09–0.10) and 0.19 (0.18–0.20); the corresponding rates in the 12 weeks following day and inpatient surgery were, respectively, about 4 and 40 times higher. Conclusions— VTE risk increases with increasing BMI and the associated excess risk is much greater after surgery than without surgery.

Smoking, Surgery, and Venous Thromboembolism Risk in Women United Kingdom Cohort Study

Background— Evidence about the effect of smoking on venous thromboembolism risk, generally and in the postoperative period, is limited and inconsistent. We examined the incidence of venous thromboembolism in relation to smoking habits, both in the absence of surgery and in the first 12 postoperative weeks, in a large prospective study of women in the United Kingdom. Methods and Results— During 6 years’ follow-up of 1 162 718 women (mean age 56 years), 4630 were admitted to hospital for or died of venous thromboembolism. In the absence of surgery, current smokers had a significantly increased incidence of venous thromboembolism compared with never-smokers (adjusted relative risk 1.38, 95% confidence interval 1.28–1.48), with significantly greater risks in heavier than lighter smokers (relative risks 1.47 [95% confidence interval 1.34–1.62] and 1.29 [95% confidence interval 1.17–1.42] for ≥15 versus <15 cigarettes per day). Current smokers were also more likely to have surgery than never-smokers (relative risk 1.12, 95% confidence interval 1.12–1.13). Among women who had surgery, the incidence of venous thromboembolism in the first 12 postoperative weeks was significantly greater in current than never-smokers (relative risk 1.16, 95% confidence interval 1.02–1.30). Conclusions— Venous thromboembolism incidence was increased in current smokers, both in the absence of surgery and in the 12 weeks after surgery. Smoking is another factor to consider in the assessment of venous thromboembolism risk in patients undergoing surgery.

Comprehensive Comparison of Drug Prescribing in the United States and United Kingdom

Study Objective. To compare the frequency of outpatient drug prescribing in the United States and United Kingdom according to individual drugs and therapeutic categories during 2004–2006.

Antidepressants, Depression, and Venous Thromboembolism Risk: Large Prospective Study of UK Women

Background Some investigators have reported an excess risk of venous thromboembolism (VTE) associated with depression and with use of antidepressant drugs. We explored these associations in a large prospective study of UK women. Methods and Results The Million Women Study recruited 1.3 million women through the National Health Service Breast Screening Programme in England and Scotland. Three years after recruitment, women were sent a second questionnaire that enquired about depression and regular use of medications in the previous 4 weeks. The present analysis included those who responded and did not have prior VTE, cancer, or recent surgery. Follow‐up for VTE was through linkage to routinely collected National Health Service statistics. Cox regression analyses yielded adjusted hazard ratios and 95% CIs. A total of 734 092 women (mean age 59.9 years) were included in the analysis; 6.9% reported use of antidepressants, 2.7% reported use of other psychotropic drugs, and 1.8% reported being treated for depression or anxiety but not use of psychotropic drugs. During follow‐up for an average of 7.3 years, 3922 women were hospitalized for and/or died from VTE. Women who reported antidepressant use had a significantly higher risk of VTE than women who reported neither depression nor use of psychotropic drugs (hazard ratio, 1.39; 95% CI, 1.23–1.56). VTE risk was not significantly increased in women who reported being treated for depression or anxiety but no use of antidepressants or other psychotropic drugs (hazard ratio, 1.19; 95% CI, 0.95–1.49). Conclusions Use of antidepressants is common in UK women and is associated with an increased risk of VTE.

Incidence of stomach cancer in oman and the other gulf cooperation council countries.

OBJECTIVES Stomach cancer is the most common cancer among males in Oman and the second most frequent among females from 1997 to 2007. Reports have suggested the rate is higher in Oman than in the other GCC countries. This study aims to describe the epidemiology of stomach cancer in Oman and to explore the apparent differences in the incidence of stomach cancer between Oman and the other Gulf Cooperation Council (GCC) countries. METHODS Data were obtained from the Omani National Cancer Registry (1997 - 2007) and from Gulf Centre for Cancer Registration reports (1998 - 2004). RESULTS The annual average age-adjusted incidence rates for stomach cancer in Oman were 10.1 per 100,000 for males and 5.6 per 100,000 for females between 1997 and 2007. The age-adjusted incidence varied by region within Oman, and the incidence rate was higher in Oman than in most other GCC countries between 1998 and 2004. CONCLUSION Further investigation of the completeness and accuracy of cancer registration is essential for exploration of variations in stomach cancer rates in the GCC countries.

Simvastatin dose and risk of rhabdomyolysis: Nested case–control study based on national health and drug dispensing data

BACKGROUND Two randomised controlled trials have found a higher risk of rhabdomyolysis in users of 80 mg versus 20 mg simvastatin, but there is very limited information about the risk associated with other doses. We undertook a nested case-control study, using routinely collected national health and drug dispensing data, to estimate the relative and absolute risks of rhabdomyolysis resulting in hospital admission or death according to simvastatin dose. METHODS AND RESULTS The underlying study cohort comprised all patients (n=313,552) who initiated a new episode of simvastatin use in New Zealand between 1 May 2005 and 31 December 2009. Cases (n=29) were patients with a diagnosis of rhabdomyolysis after cohort entry, confirmed by hospital discharge letter or death records. Ten controls, matched by year of birth and sex, were randomly selected from the study cohort using risk set sampling. Current users of 40 mg simvastatin daily were about five times as likely to develop rhabdomyolysis as those taking 20mg; the adjusted odds ratio was 5.3 (95% CI 1.9-15.0). The absolute excess risk of rhabdomyolysis associated with the use of 40 mg versus 20mg was about 10 per 100,000 person-years; the crude incidence rates were 11.5 (95% CI 7.1-17.5) and 2.1 (95% CI 0.7-4.8) per 100,000 person-years respectively. CONCLUSIONS These findings provide reassurance that the absolute risk of rhabdomyolysis in a general population of simvastatin users is very low. Nonetheless, they also raise questions about the optimal simvastatin regimen to maximise cardiovascular benefits and minimise the risk of serious muscle injury.

A cluster of thyrotoxicosis associated with consumption of a soy milk product

Objective: To determine whether a New Zealand cluster of thyrotoxicosis with low uptake on scintiscan was associated with soy milk consumption.