Pseudotumor cerebri syndrome with different types of hormonal contraceptives in women of child-bearing age.

BACKGROUND AND PURPOSE: There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel. METHODS: We conducted a retrospective cohort study, with a case-control analysis of 4 871 504 women aged 15-45 years in the period 2008-2015, using IQVIA Ambulatory Electronic Medical Records data in the USA. Patients who used nine different contraceptive agents including intrauterine levonorgestrel, medroxyprogesterone injection, etonogestrel/ethinyl estradiol vaginal ring and combination oral contraceptives (COCs) that contained ethinyl estradiol and the progestins levonorgestrel, norgestimate, desogestrel, norethindrone and drospirenone, were included. Diagnosis of PTCS was defined using the first International Classification of Diseases, 9th or 10th revision, code for intracranial hypertension in patients who had also received an imaging code in the 30 days prior to the index date. RESULTS: A total of 3323 PTCS cases and 13 292 matched controls were identified. No increase in risk was found when analysing intrauterine levonorgestrel or COCs containing desogestrel, norethindrone, drospirenone, norgestimate or norgestrel versus COC levonorgestrel. The adjusted incidence rate ratio for etonogestrel/etonogestrel/ethinyl estradiol vaginal ring and medroxyprogesterone suspension compared with levonorgestrel COC was 4.45 [95% confidence interval (CI) 1.98-9.96] and 2.20 (95% CI 1.33-3.64), respectively. CONCLUSIONS: This study found an elevated risk for PTCS among users of etonogestrel vaginal ring and medroxyprogesterone suspension when compared with oral levonorgestrel. Future studies are needed to confirm these findings.

Correction to: Acetylcholinesterase inhibitors and the risk of osteoporotic fractures: nested case-control study.

Please find below the correction for the paragraph under the Heading "Materials and methods - Regulatory approval".

Acetylcholinesterase inhibitors and the risk of osteoporotic fractures: nested case-control study.

The objective of this study was to analyze the effect of acetylcholinesterase inhibitors (AChEIs) on the risk of osteoporotic fractures in Alzheimer patients. A nested case-control study was conducted on 1190 cases and 4760 controls. The use of AChEIs was found to decrease the risk of osteoporotic fractures in these patients. INTRODUCTION: The objective of this study is to estimate the extent to which the use of AChEIs is associated with a reduction in the risk of osteoporotic fractures. METHODS: A nested case-control study was conducted using data from the UK Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database (1998-2013). The study cohort consisted of Alzheimer's Disease (AD) patients aged ≥ 65 years with no previous history of osteoporotic fractures at cohort baseline. Cases were individuals who suffered an osteoporotic fracture during the study period, whereas controls were subject who did not experience any osteoporotic fractures during the same period. Controls were drawn from the population time at risk while being matched to the cases in respect to age, sex, up-to-standard follow-up in the CPRD, calendar time, and duration of AD (control-to-case ratio: 4-to-1). Information on the use of AChEIs and the relevant potential confounders was ascertained from the CPRD database for all the cases and controls. RESULTS: We identified 1190 cases and 4760 controls. Compared to non-users, any use of AChEIs prior to the fracture was associated with a reduction in the fracture risk [adjusted odds ratio (OR) 0.80 (confidence interval (CI) 95%, 0.70-0.91)]. The use of AChEIs corresponding to a proportion of days covered of 0.8-1.0 was associated with a lower osteoporotic fracture risk compared to non-use [adjusted OR 0.76 (CI 95%, 0.66-0.87)]. CONCLUSIONS: In this study using large primary care databases, the use and treatment adherence to AChEIs were associated with a decreased risk of osteoporotic fractures in elderly AD patients.

Effect of acetylcholinesterase inhibitors on post-surgical complications and mortality following a hip fracture: a cohort study.

There is increasing evidence suggesting that the use of acetylcholinesterase inhibitors may have beneficial effects on bone. Data on the potential post-surgical effects of these medications on orthopedic interventions are very limited. This study was designed to determine whether the use of acetylcholinesterase inhibitors is associated with a decrease in post-surgical mortality and complications in hip fracture patients with Alzheimer's disease. To accomplish this objective, a retrospective cohort study was performed using data from the Clinical Practice Research Database, UK. The study included 532 Alzheimer's disease patients of age 65 years and older, who sustained a hip fracture between 1998 and 2012. During the follow-up period, 34% of the patients died (n=182), 22% sustained a second hip fracture (n=118) and 5% (n=29) required reintervention. The users of acetylcholinesterase inhibitors had a 56% reduction in all-cause mortality (HR= 0.44, 95% CI 0.30-0.63) and a 41% reduction in second hip fracture incidence during a year of post-surgical follow-up (HR= 0.59, 95% CI 0.38-0.94) after adjusting for potential confounders. Our results show that acetylcholinesterase inhibitors may have the potential to reduce all-cause mortality and the risk of suffering a second hip fracture during the first year after surgery.

The influence of systemic glucocorticoid therapy upon the risk of non-serious infection in older patients with rheumatoid arthritis: a nested case-control study.

BACKGROUND: Glucocorticoid therapy is strongly associated with an elevated risk of serious infections in patients with rheumatoid arthritis (RA). The association between glucocorticoids and common non-serious infections (NSI) is not well studied. METHODS: A cohort of 16 207 patients with RA aged over 65 years was assembled using administrative data from Quebec. Glucocorticoid and disease-modifying antirheumatic drug (DMARD) therapy were identified from drug dispensing records. NSI cases were defined as first occurrence of a community physician billing code for infection or community-dispensed anti-infectives. A nested case-control analysis was performed considering drugs dispensed within 45 days of the index date, adjusting for age, sex, markers of disease severity, DMARD and comorbidity. RESULTS: For 13 634 subjects, a NSI occurred during 28 695 person-years of follow-up, generating an incidence rate of 47.5/100 person-years. The crude rate of NSI in glucocorticoid-exposed and unexposed person time was 52.4 and 38.8/100 person-years, respectively. Glucocorticoid therapy was associated with an adjusted RR of 1.20 (95% CI 1.15 to 1.25). A dose response was seen, the adjusted RR increasing from 1.10 (<5 mg prednisolone/day) to 1.85 for doses greater than 20 mg/day. All glucocorticoid risk estimates (including <5 mg/day) were higher than that seen for methotrexate (adjusted RR 1.00; 0.95 to 1.04). CONCLUSION: Glucocorticoid therapy is associated with an increased risk of NSI. The magnitude of risk increases with dose, and is higher than that seen with methotrexate, although residual confounding may exist. While the RR is low at 1.20, the absolute risk is high with one additional infection seen for every 13 patients treated with glucocorticoids for 1 year.

Long-term persistence with orlistat and sibutramine in a population-based cohort.

OBJECTIVE: Orlistat and sibutramine are widely prescribed antiobesity agents that are approved for 2 years of continuous use. Previous 1-4-year randomized, placebo-controlled trials of these drugs have reported average weight losses of <5 kg, significant adverse effects and attrition rates of up to 60%. The objective of this study was to determine the long-term persistence with orlistat and sibutramine therapy outside a clinical trial setting. DESIGN, SETTING AND PATIENTS: Population-based administrative data from British Columbia, Canada, were used to create an inception cohort of orlistat and sibutramine users and determine the 2-year persistence with therapy. MAIN OUTCOME MEASURE: Persistence with therapy at 2 years. Drug discontinuation was defined as the failure to refill a prescription within 120 days. Patients discontinuing therapy were censored at the 60-day mark. RESULTS: Nearly 17 000 users of orlistat and 3500 users of sibutramine were identified. For both orlistat and sibutramine, 1-year persistence rates were <10% and 2-year persistence rates were 2%. CONCLUSION: This population-based, retrospective cohort analysis demonstrated very poor long-term persistence rates with orlistat and sibutramine and discontinuation rates that were much higher than those reported in clinical trials.

ACE-inhibitor use and the long-term risk of renal failure in diabetes.

The incidence of end-stage renal disease (ESRD) owing to diabetes has continued to increase despite the extensive use of angiotensin-converting enzyme (ACE) inhibitors to prevent diabetic nephropathy, primarily from evidence of short-term effectiveness. We assessed the long-term effect of ACE inhibitors on the risk of ESRD. We formed a population-based cohort of all diabetic patients treated with antihypertensive drugs in the Province of Saskatchewan, Canada, between 1982 and 1986. The patients were followed up to the end of 1997 to identify cases of end-stage renal failure. A nested case-control analysis was used with the controls matched to each case on age, diabetes type, and duration of follow-up. The cohort comprised 6102 subjects, of which the 102 cases who developed end-stage renal failure were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of end-stage renal failure associated with the use of ACE inhibitors was 2.5 (95% confidence interval 1.3-4.7), whereas it was 0.8 (95% confidence interval 0.5-1.4) for beta-blockers and 0.7 (95% confidence interval 0.4-1.3) for calcium antagonists. The rate ratio of end-stage renal failure with the use of ACE inhibitors was 0.8 (95% confidence interval 0.3-2.5) during the first 3 years of follow-up, but increased to 4.2 (95% confidence interval 2.0-9.0) after 3 years. ACE-inhibitor use does not appear to decrease the long-term risk of end-stage renal failure in diabetes. Our data suggest instead that ACE inhibitors might actually increase this risk, which may possibly contribute to the continued increasing incidence of ESRD owing to diabetes.

Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma.

BACKGROUND: Inhaled corticosteroids are effective at preventing asthma morbidity and mortality. Most studies, however, have focused on short term effects, raising uncertainty about their effectiveness in the long term. METHODS: The Saskatchewan Health databases were used to form two population based cohorts of asthma patients aged 5-44 between 1975 and 1991. The first cohort included all subjects from the start of asthma treatment, while the second included subjects hospitalised for asthma from the date of discharge. Subjects were followed up, starting 1 year after cohort entry and continuing until 1997, 54 years of age, or death. The outcome was the first asthma hospital admission and readmission, respectively, to occur during follow up. A nested case-control design was used by which all cases were matched on calendar time and several markers of asthma severity to all available controls within the cohort. RESULTS: The full cohort included 30 569 asthmatic subjects of which 3894 were admitted to hospital for asthma and 1886 were readmitted. The overall rate of asthma hospitalisation was 42.4 per 1000 asthma patients per year. Regular use of inhaled corticosteroids was associated with reductions of 31% in the rate of hospital admissions for asthma (95% confidence interval (CI) 17 to 43) and 39% in the rate of readmission (95% CI 25 to 50). The rate reduction found during the first 4 years of follow up was sustained over the longer term. Regular use of inhaled corticosteroids can potentially prevent between five hospital admissions and 27 readmissions per 1000 asthma patients per year. CONCLUSION: Regular use of low dose inhaled corticosteroids prevents a large proportion of hospital admissions with asthma, both early and later on in the course of the disease.