The Effect of Denosumab on Risk for Emergently Treated Hypocalcemia by Stage of Chronic Kidney Disease : A Target Trial Emulation.

Background: There is a paucity of data on treatment of osteoporosis in patients with advanced chronic kidney disease (CKD).

Objective: To assess the risk for emergently treated hypocalcemia with denosumab by stage of CKD and presence of CKD-mineral and bone disorder (CKD-MBD).

Design: Target trial emulation.

Severe Hypocalcemia With Denosumab Among Older Female Dialysis-Dependent Patients.

Importance: Dialysis-dependent patients experience high rates of morbidity from fractures, yet little evidence is available on optimal treatment strategies. Chronic kidney disease-mineral and bone disorder is nearly universal in dialysis-dependent patients, complicating diagnosis and treatment of skeletal fragility.

Objective: To examine the incidence and comparative risk of severe hypocalcemia with denosumab compared with oral bisphosphonates among dialysis-dependent patients treated for osteoporosis.

Validation of an ICD-9-Based Algorithm to Identify Stillbirth Episodes from Medicaid Claims Data.

Introduction: In administrative data, accurate timing of exposure relative to gestation is critical for determining the effect of potential teratogen exposure on pregnancy outcomes.

Objective: To develop an algorithm for identifying stillbirth episodes in the ICD-9-CM era using national Medicaid claims data (1999-2014).

Methods: Unique stillbirth episodes were identified from clusters of medical claims using a hierarchy that identified the encounter with the highest potential of including the actual stillbirth delivery and that delineated subsequent pregnancy episodes.

Utility of fertility procedures and prenatal tests to estimate gestational age for live-births and stillbirths in electronic health plan databases.

Purpose: Current algorithms to evaluate gestational age (GA) during pregnancy rely on hospital coding at delivery and are not applicable to non-live births. We developed an algorithm using fertility procedures and fertility tests, without relying on delivery coding, to develop a novel GA algorithm in live-births and stillbirths.

Methods: Three pregnancy cohorts were identified from 16 health-plans in the Sentinel System: 1) hospital admissions for live-birth, 2) hospital admissions for stillbirth, and 3) medical chart-confirmed stillbirths.

Validation of an ICD-10-based algorithm to identify stillbirth in the Sentinel System.

Purpose: To develop and validate an International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM)-based algorithm to identify cases of stillbirth using electronic healthcare data.

Methods: We conducted a retrospective study using claims data from three Data Partners (healthcare systems and insurers) in the Sentinel Distributed Database. Algorithms were developed using ICD-10-CM diagnosis codes to identify potential stillbirths among females aged 12-55 years between July 2016 and June 2018.

Idelalisib for Treatment of Relapsed Follicular Lymphoma and Chronic Lymphocytic Leukemia: A Comparison of Treatment Outcomes in Clinical Trial Participants vs Medicare Beneficiaries.

Importance: Idelalisib (IDEL) is approved as monotherapy in relapsed follicular lymphoma (FL) and with rituximab (IDEL+R) for relapsed chronic lymphocytic leukemia (CLL). Toxic effects can be severe and treatment-limiting. Outcomes in a real-world population are not yet characterized.

First-Trimester Exposure to Gadolinium-based Contrast Agents: A Utilization Study of 4.6 Million U.S. Pregnancies.

BackgroundThe safety of gadolinium-based contrast agent (GBCA) exposure during pregnancy has not been established, and the use of GBCAs during pregnancy is not recommended unless it is essential to the health of the woman or fetus.PurposeTo examine the prevalence of GBCA exposure in a large sample of pregnancies resulting in a live birth.Materials and MethodsThe Sentinel Distributed Database was used to retrospectively identify U.

Healthy User Bias in Comparative Safety Studies for Brand-Name vs. Generic Products: The Example of Warfarin.

Warfarin was selected as a case study to examine confounding when comparing a product across different manufacturers because it is a narrow therapeutic index drug with prevalent beliefs for brand-name superiority. Medicare beneficiaries aged ≥65 years with atrial fibrillation and an incident outpatient warfarin prescription from July 2006 through July 2015 were included in the study population (N = 746,098). Substantial imbalances were observed between brand-name warfarin and generics for (i) clinical comorbidity, (ii) socioeconomic status, (iii) prescriber specialty, (iv) recent ambulatory and emergent care, (v) drug adherence, (vi) pharmacy setting (e.

Effects of deferasirox dose and decreasing serum ferritin concentrations on kidney function in paediatric patients: an analysis of clinical laboratory data from pooled clinical studies.

Background: Serious and fatal deferasirox-induced kidney injury has been reported in paediatric patients. This study aimed to investigate the effects of deferasirox dose and serum ferritin concentrations on kidney function and the effect of impaired kidney function on dose-normalised deferasirox minimum plasma concentration (C).

Methods: We did a case-control analysis using pooled data from ten clinical studies.

Misclassification in Assessment of First Trimester In-utero Exposure to Drugs Used Proximally to Conception: the Example of Letrozole Utilization for Infertility Treatment.

Letrozole is an aromatase inhibitor that has an unapproved use for ovulation induction with infertility. Because of the proximity of this use to conception, we selected letrozole to study the effect of 3 different methods for identifying the pregnancy start date and their impact on exposure misclassification. Using electronic health data from the US Sentinel database (2001-2015), we identified live-birth pregnancies conceived through in-vitro fertilization or intrauterine insemination.

Entacapone and prostate cancer in Parkinson's disease patients: A large Veterans Affairs healthcare system study.

Background: An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting.

Utilization of drugs with pregnancy exposure registries during pregnancy.

Purpose: To describe the utilization of drugs with pregnancy exposure registries by trimester during pregnancy, in comparison with matched nonpregnant episodes and a pre-pregnancy period.

Methods: We identified live-born deliveries from women aged 10 to 54 years and matched the pregnancies 1:1 with nonpregnant episodes from a comparator cohort not delivering live-born infants, using data from 2001 to 2013 in the Sentinel Distributed Database. We evaluated the utilization of 34 drugs with pregnancy exposure registries, comparing utilization during pregnancy to the matched nonpregnant episodes, and to the 90 days before pregnancy.

Enrollment and Retention in 34 United States Pregnancy Registries Contrasted with the Manufacturer's Capture of Spontaneous Reports for Exposed Pregnancies.

Introduction: Pregnancy registries and spontaneous reports are essential pharmacovigilance tools to evaluate drug safety during pregnancy.

Objectives: The aim of this study was to evaluate postmarket capture of exposed pregnancies.

Methods: Pregnancy registries for drugs and biologics were identified in a systematic review.

Antiemetic use among pregnant women in the United States: the escalating use of ondansetron.

Purpose: To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births.

Methods: We assessed ondansetron and other antiemetic use among pregnant women delivering live births between 2001 and 2015 in 15 data partners contributing data to the Mini-Sentinel Distributed Database. We identified live birth pregnancies using a validated algorithm, and all forms of ondansetron and other available antiemetics were identified using National Drug Codes or procedure codes.

A systematic review of pregnancy exposure registries: examination of protocol-specified pregnancy outcomes, target sample size, and comparator selection.

Purpose: Our study sought to systematically evaluate protocol-specified study methodology in prospective pregnancy exposure registries including pre-specified pregnancy outcomes, power calculations for sample size, and comparator group selection.

Methods: U.S.

Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology.

Objective: To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia.

Design: Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology).

Setting: Healthcare claims data from the IMS Lifelink database in the United States.

Antihypertensive drug class interactions and risk for incident diabetes: a nested case-control study.

Background: We aimed to determine how single and combination antihypertensive therapy alters risk for diabetes mellitus (DM).Thiazide diuretics (TD), β blockers (BB), and renin-angiotensin system blockers (RASB) impact DM risk while calcium channel blockers (CCB) are neutral. DM risk associated with combinations is unclear.

Risk of acute kidney injury associated with the use of fluoroquinolones.

Background: Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers.

Methods: We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011.

Male breast cancer and 5α-reductase inhibitors finasteride and dutasteride.

Purpose: We examined the association between 5α-reductase inhibitors and male breast cancer.

Materials And Methods: Study participants were men 40 to 85 years old, with prescription and medical coverage, enrolled in the United States IMS LifeLink™ Health Plan claims database between 2001 and 2009. Cases required a primary breast cancer diagnosis (ICD-9-CM 175.

Polycystic ovary syndrome and combined oral contraceptive use: a comparison of clinical practice in the United States to treatment guidelines.

The October 2010 ESHRE/ASRM polycystic ovary syndrome (PCOS) workshop concluded: (1) all combined oral contraceptives (COC) appear to have equal efficacy for PCOS, (2) addition of antiandrogens (spironolactone) to COCs has little treatment benefit and (3) metformin does not improve the live-birth rate and should only be used with impaired glucose tolerance. We compared these guidelines to current practice in the United States IMS claims-database. Time-series analyses were conducted by calendar-year in women with PCOS to evaluate prescribing preferences for COCs, concomitant use of spironolactone, and utilization of metformin.