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.

Purpose: 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.

Methods: Retrospective cohort study to evaluate the likelihood of getting an upper 95% confidence limit ≤1.

Topiramate use during pregnancy and major congenital malformations in multiple populations.

Background: We measured birth prevalence of major congenital malformations (MCMs) after topiramate use during pregnancy to screen for a possible signal of increased risk.

Methods: Using four healthcare databases, we identified three cohorts of pregnant women: cohort 1, used topiramate during the first trimester; cohort 2, used topiramate or another antiepileptic drug previously but not during pregnancy; and cohort 3, were pregnant and did not use topiramate but had indications for use individually matched to those of users. Cohort 1 was compared with cohorts 2 and 3.

Advantages and problems with pregnancy registries: observations and surprises throughout the life of the International Lamotrigine Pregnancy Registry.

Purpose: The International Lamotrigine Pregnancy Registry monitored for a signal of a substantial increase in the frequency of major congenital malformations associated with lamotrigine exposures in pregnancy over an 18-year period. Key methodological lessons are discussed.

Methods: The strengths and weaknesses of the Registry were assessed using quantifiable methodological and operational parameters including enrollment, completeness of exposure and outcome data reporting, and lost to follow-up.

Topiramate use in pregnancy and the birth prevalence of oral clefts.

Purpose: First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants exposed to TPM in utero. We evaluated the association between TPM use in early pregnancy and the risk of OC.

A US postmarketing evaluation of the frequency and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years: 2009-2010 season.

The 2007 US approval for use of Ann Arbor strain live attenuated influenza vaccine (LAIV) in children aged 24 through 59 months included precautions against use in (1) children <24 months and children aged 24 through 59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. Results from the third season (2009-2010) of a 3-year study postmarketing commitment to monitor LAIV vaccination rates and frequency of hospitalizations or emergency department visits within 42 days after LAIV are reported here. As in the first 2 seasons, LAIV usage in cohorts 1, 2, and 4 were low relative to those in LAIV-recommended populations.

Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis.

Purpose: To quantify the incidence of osteonecrosis of the jaw (ONJ) by bisphosphonate exposure among two cohorts of patients.

Methods: In a retrospective cohort study, we identified cohort members via health insurance claim diagnosis codes and identified potential cases of ONJ that were confirmed with medical record review. One cohort included patients aged ≥40 years with breast or prostate cancer or multiple myeloma; the other cohort included men aged ≥60 years and women ≥50 years with osteoporosis.

Healthcare utilization and comorbidity burden among children and young adults in the United States with systemic lupus erythematosus or inflammatory bowel disease.

Objective: We sought to assess the feasibility of using a health insurance claims database to estimate the prevalence and health care utilization and costs among children diagnosed with systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD).

Study Design: This was a retrospective analysis of the LifeLink insurance claims database for the years 2000-2006. Children (0-15 years) and young adults (16-25 years) with ≥ 2 diagnosis claims for SLE or IBD were selected as the 2 cohorts of interest.

Maternal outcomes among pregnant women receiving live attenuated influenza vaccine.

Background: Although the live attenuated influenza vaccine (LAIV) prescribing information contains warnings/precautions against use during pregnancy, administration of LAIV to pregnant women does occur. Data regarding maternal outcomes after LAIV administration during pregnancy are limited.

Objectives: Maternal outcomes after LAIV vaccination during pregnancy were examined.

A postmarketing evaluation of the frequency of use and safety of live attenuated influenza vaccine use in nonrecommended children younger than 5 years.

The 2007 US approval for use of live attenuated influenza vaccine (LAIV) in children aged 24-59 months included precautions against use in (1) children <24 months and children aged 24-59 months with (2) asthma, (3) recurrent wheezing, and (4) altered immunocompetence. A postmarketing commitment was initiated to monitor LAIV use and the frequency of select safety outcomes in these cohorts. Vaccination rates and the frequency of hospitalizations or emergency department visits within 42 days after LAIV and trivalent inactivated influenza vaccine (TIV) administration were estimated from 2007 to 2009 claims data from a health insurance database.

Cancer risk in asthmatic populations.

Objective: To conduct a meta-analysis of epidemiologic studies to derive a pooled estimate of the association between asthma and cancer incidence and between allergy and cancer incidence.

Data Sources: Five cohort studies and 1 case-control study of cancer incidence in asthma, 4 studies of cancer mortality in asthma, and 3 studies of cancer incidence in allergy.

Study Selection: We searched the National Library of Medicine Gateway to identify observational studies of cancer incidence in asthma and included any case-control or cohort study of incident cancers or of cancer mortality that met the predefined inclusion criteria.

Lamotrigine and the risk of malformations in pregnancy.

Objective: To report the frequency of major malformations in lamotrigine-exposed pregnancies from September 1, 1992, through March 31, 2004, in the International Lamotrigine Pregnancy Registry.

Methods: Health care professionals throughout the world can voluntarily enroll lamotrigine-exposed pregnancies in this observational study. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis.

Preliminary results on pregnancy outcomes in women using lamotrigine.

Purpose: In 1992, the International Lamotrigine Pregnancy Registry was initiated to enroll prospectively and to monitor pregnancies exposed to lamotrigine (LTG) for the occurrence of major birth defects. This study presents results as of September 2001 on 168 outcomes exposed to LTG monotherapy and 166 outcomes after pregnancies exposed to LTG polytherapy during the first trimester.

Methods: LTG pregnancy exposures are voluntarily reported to the registry by health care providers before they are aware of each pregnancy outcome.