Lisa J. McQuay

Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture.

OBJECTIVE: Depot medroxyprogesterone acetate (DMPA) reversibly reduces bone mineral density. To estimate the extent to which DMPA might increase fracture risk, we undertook a retrospective cohort study of fractures in DMPA users and users of non-DMPA contraceptives, using the General Practice Research Database. METHODS: Eligible women were aged younger than 50 years at the qualifying first contraceptive prescription. The DMPA users were classified by DMPA exposure (cumulative and time of last dose) based on prescription records. All incident fractures were included; fracture incidence and risk factors before starting contraceptive use (DMPA or other) also were estimated. RESULTS: We identified 11,822 fractures in 312,395 women during 1,722,356 person-years of follow-up. Before contraceptive use started, DMPA users had higher fracture risk than nonusers (incidence rate ratio 1.28, 95% confidence interval [CI] 1.07–1.53). After DMPA started, crude fracture incidence was 9.1 per 1,000 person-years for DMPA users and 7.3 for nonusers (crude incidence rate ratio 1.23, 95% CI 1.16–1.30). Fracture risk in DMPA users did not increase after starting DMPA (incidence rate ratio after or before 1.08, 95% CI 0.92–1.26). There was little confounding by age or other factors that could be measured. Fracture incidence was 9.4 per 1,000 person-years in low-exposure DMPA users, and 7.8 per 1,000 in high-exposure DMPA users. The DMPA users had higher fracture risk than nonusers at the start of contraceptive use, with no discernible induction period. CONCLUSION: Although DMPA users experienced more fractures than nonusers, this association may be the result of confounding by a pre-existing higher risk for fractures in women who chose DMPA for contraception. LEVEL OF EVIDENCE: II

Validation of Acute Liver Injury Cases in a Population-Based Cohort Study of Oral Antimicrobial Users

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.

Cancer Incidence after Initiation of Antimuscarinic Medications for Overactive Bladder in the United Kingdom: Evidence for Protopathic Bias

To estimate the incidence of 10 common cancers among patients treated with antimuscarinic medications for overactive bladder (AMOABs).

Validation of cancer cases using primary care, cancer registry, and hospitalization data in the UK:

Background: In the United Kingdom, hospital or cancer registry data can be linked to electronic medical records for a subset of general practices and years. Methods: We used Clinical Practice Research Datalink data (2004–2012) from patients treated for overactive bladder. We electronically identified provisional cases of 10 common cancers in General Practitioner Online Database data and validated them by medical profile review. In practices with linkage to Hospital Episodes Statistics and National Cancer Data Repository (2004–2010), we validated provisional cancer cases against these data sources. This linkage also let us identify additional cancer diagnoses in individuals without cancer diagnosis records in the General Practitioner Online Database. Results: Among 50,840 patients, 1,486 provisional cancer cases were identified in the General Practitioner Online Database for 2004–2012. Medical profile review confirmed 93% of 661 cases in nonlinked practices (range, 100% of non-Hodgkin lymphomas and uterine cancer to 77% of skin melanomas) and 96% of 825 cases in linked practices (100% of kidney and uterine cancers to 92% of melanomas). In the subset of linked practices, for 2004–2010, 720 cases were confirmed, of which 68% were identifiable in the General Practitioner Online Database (range, 90% of breast to 36% of kidney cancers). Conclusions: Most cases of cancer identified electronically in the General Practitioner Online Database were confirmed. A substantial proportion of cases, especially of cancer types not typically managed by general practitioners, would be missed without Hospital Episodes Statistics and National Cancer Data Repository data (and are likely missed in nonlinked practices). See video abstract at, http://links.lww.com/EDE/B315. Registration (before study conduct): European Union electronic Register of Post-Authorisation Studies (EU PAS Registry) number EUPAS5529, http://www.encepp.eu/encepp/viewResource.htm?id=11107.

Value of Free-Text Comments for Validating Cancer Cases Using Primary-Care Data in the UK:

© 2018 Wolters Kluwer Health, Inc. All rights reserved. www.epidem.com | e41 Reproducibility: The results of the study were generated by RTI Health Solutions (RTI-HS) using data obtained from CPRD. RTI-HS developed proprietary code to perform the analyses on the data. Researchers desiring access to the data would be required to obtain permission from the study sponsor, obtain data use agreement with CPRD, and develop their own code. This study was funded by Astellas Pharma Global Development, Inc. The contract provides the research team independent publication rights. A.M., J.F., J.K., B.C., M.R., E.P., L.M., S.P.-G., and A.A. are employees of RTI International, an independent, nonprofit research organization that does work for government agencies and pharmaceutical companies. W.J.A., B.F., and S.d.V. are employees of Astellas Pharma Global Development, the sponsors of this study. Value of Free-text Comments for Validating Cancer Cases Using Primarycare Data in the United Kingdom

The feasibility of using multiple databases to study rare outcomes: the potential effect of long-acting beta agonists with inhaled corticosteroid therapy on asthma mortality.

Long‐acting beta agonists (LABAs) when used without concomitant inhaled corticosteroids (ICS) increase the risk of asthma‐related deaths, but the effect on asthma‐related death of LABA used in combination with ICS therapy is unknown. To address this question, we explored the feasibility of conducting an observational study using multiple US health care data sources.

Comment on journal review of ‘Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture’

We thank Dr Curry for an accurate summary1 of our study entitled ‘Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture’.2 Nevertheless, we do not recommend more selective use of depot medroxyprogesterone acetate (DMPA) on account of fracture risk, as we believe that this recommendation would reduce access to an effective, safe contraceptive without actually reducing fracture risk. As we reported, in those subjects with at least 6 months of pre-DMPA medical history (176 pre-treatment fractures …