Characteristics of new adult users of mepolizumab with asthma in the USA.

BACKGROUND: In the USA, over 25 million people have asthma; 5%-10% of cases are severe. Mepolizumab (Nucala) is an interleukin-5 antagonist monoclonal antibody; it was approved by the FDA in 2015 as add-on maintenance treatment of severe asthma for patients aged ≥12 years with an eosinophilic phenotype. OBJECTIVES: (1) Describe baseline demographic and clinical characteristics of new US adult mepolizumab users 2015-2019, (2) describe asthma medication use in the 12 months preceding initiation of and concomitant with mepolizumab and (3) assess mepolizumab adherence, persistence and discontinuation patterns in 12 months postinitiation. METHODS: We conducted a new-user observational cohort study using data from Aetna, a CVS Health Company, HealthCore (Anthem), Harvard Pilgrim Healthcare, and IBM MarketScan Research Databases. Curated administrative claims data in the FDA Sentinel System common data model format and publicly available Sentinel analytical tools were used to query the databases. We included adults who initiated mepolizumab in 2015-2019 with an asthma diagnosis in the preceding 12 months and no evidence of cystic fibrosis. We examined age, sex, comorbid conditions, asthma medication use and severe asthma exacerbations. RESULTS: We identified 3496 adults (mean age 54.2 years, SD 12.5 years) who initiated mepolizumab. In the 12 months before mepolizumab initiation, 22% had received inhaled corticosteroids, 46% had inhaled corticosteroid/long-acting beta agonists, 72.6% had leukotriene antagonists, 38% had long-acting muscarinic antagonist, 18% had omalizumab,<1% had reslizumab, dupilumab or benralizumab. In the previous 12 months, 70% had a diagnosis of allergic rhinitis, 32% had chronic obstructive pulmonary disease, 17% eosinophilia and 3% eosinophilic granulomatosis with polyangiitis. Further, 56% had an asthma-related ambulatory visit, 73%≥1 course of oral corticosteroids lasting 3-27 days, 10% an asthma-related emergency department visit and 22% an asthma-related hospitalisation. In the 12 months following initiation, the mean proportion of days covered was 70%, and reductions in the average mean dispensings of rescue oral corticosteriods (35%) and omalizumab (61%) were observed. CONCLUSIONS: Adults with asthma treated with mepolizumab had varying levels of healthcare utilisation and we observed evidence of mepolizumab use in patients without severe asthma.

Validity of Privacy-Protecting Analytical Methods That Use Only Aggregate-Level Information to Conduct Multivariable-Adjusted Analysis in Distributed Data Networks.

Distributed data networks enable large-scale epidemiologic studies, but protecting privacy while adequately adjusting for a large number of covariates continues to pose methodological challenges. Using 2 empirical examples within a 3-site distributed data network, we tested combinations of 3 aggregate-level data-sharing approaches (risk-set, summary-table, and effect-estimate), 4 confounding adjustment methods (matching, stratification, inverse probability weighting, and matching weighting), and 2 summary scores (propensity score and disease risk score) for binary and time-to-event outcomes. We assessed the performance of combinations of these data-sharing and adjustment methods by comparing their results with results from the corresponding pooled individual-level data analysis (reference analysis). For both types of outcomes, the method combinations examined yielded results identical or comparable to the reference results in most scenarios. Within each data-sharing approach, comparability between aggregate- and individual-level data analysis depended on adjustment method; for example, risk-set data-sharing with matched or stratified analysis of summary scores produced identical results, while weighted analysis showed some discrepancies. Across the adjustment methods examined, risk-set data-sharing generally performed better, while summary-table and effect-estimate data-sharing more often produced discrepancies in settings with rare outcomes and small sample sizes. Valid multivariable-adjusted analysis can be performed in distributed data networks without sharing of individual-level data.

Stakeholders' views on data sharing in multicenter studies.

AIM: To understand stakeholders' views on data sharing in multicenter comparative effectiveness research studies and the value of privacy-protecting methods. MATERIALS & METHODS: Semistructured interviews with five US stakeholder groups. RESULTS: We completed 11 interviews, involving patients (n = 15), researchers (n = 10), Institutional Review Board and regulatory staff (n = 3), multicenter research governance experts (n = 2) and healthcare system leaders (n = 4). Perceptions of the benefits and value of research were the strongest influences toward data sharing; cost and security risks were primary influences against sharing. Privacy-protecting methods that share summary-level data were acknowledged as being appealing, but there were concerns about increased cost and potential loss of research validity. CONCLUSION: Stakeholders were open to data sharing in multicenter studies that offer value and minimize security risks.

Identification of Stevens-Johnson syndrome and toxic epidermal necrolysis in electronic health record databases.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) carry a high mortality risk. While identifying clinical and genetic risk factors for these conditions has been hindered by their rarity, large electronic health databases hold promise for identifying large numbers of cases for study, especially with the introduction in 2008 of ICD-9 codes more specific for these conditions. OBJECTIVE: The objective of this study is to estimate the validity of ICD-9 codes for ascertaining SJS/TEN in 12 collaborating research units in the USA, covering almost 60 million lives. METHODS: From the electronic databases at each site, we ascertained potential cases of SJS/TEN using ICD-9 codes. At five sites, a subset of medical records was abstracted and standardized criteria applied by board-certified dermatologists to adjudicate diagnoses. Multivariate logistic regression was used to identify factors independently associated with validated SJS/TEN cases. RESULTS: A total of 56 591 potential cases of SJS/TEN were identified. A subset of 276 charts was selected for adjudication and 39 (of the 276) were confirmed as SJS/TEN. Patients with the ICD-9 codes introduced after 2008 were more likely to be confirmed as cases (OR 3.32; 95%CI 0.82, 13.47) than those identified in earlier years. Likelihood of case status increased with length of hospitalization. Applying the probability of case status to the 56 591 potential cases, we estimated 475-875 to be valid SJS/TEN cases. CONCLUSION: Newer ICD-9 codes, along with length of hospitalization, identified patients with a high likelihood of SJS/TEN. This is important for identification of subjects for future pharmacogenomics studies.

Health behavior change in pregnant women: a two-phase study.

BACKGROUND: Maternal health behaviors during pregnancy/infancy can have a significant impact on maternal and child health. Many women engage in health risk behaviors during pregnancy. Multiple health behavior change (MHBC) interventions provide support to change health behaviors, but further information is needed on potential targets for such an intervention, as well as on the feasibility of technology use and e-health with this population. MATERIALS AND METHODS: Two studies were completed as part of this project. First, a survey to examine views regarding health behaviors, desires to change health behaviors, and use of technology was completed by 68 pregnant women presenting for routine care. Based on survey findings, a brief MHBC e-health educational intervention related to breastfeeding, healthy nutrition/lifestyle, and stress management, using iPad(®) (Apple, Cupertino, CA) and text-messaging media, was then developed and piloted in the home with five pregnant women. RESULTS: In the survey, the majority of participants reported interest in receiving help to improve health behaviors, including losing weight or eating a healthier diet, breastfeeding, smoking cessation, and help with depression. The majority of women reported access to a computer with Internet, a phone, and frequent use of text messaging. In the second phase, results suggest that the home-based intervention was feasible and that the technology was convenient and user-friendly. CONCLUSIONS: Pregnant women are interested in improving health behaviors and found a brief technology-based e-health intervention feasible, convenient, and user-friendly. In-home technology appears to be a feasible and convenient approach to addressing the multiple health behavior change needs of pregnant women.

Neonatal outcomes after antenatal influenza immunization during the 2009 H1N1 influenza pandemic: impact on preterm birth, birth weight, and small for gestational age birth.

BACKGROUND: Influenza infection during pregnancy is associated with adverse fetal outcomes such as preterm birth and small for gestational age (SGA). Maternal influenza immunization may prevent these adverse infant outcomes during periods of influenza circulation. METHODS: We conducted a retrospective cohort study of live births within Kaiser Permanente (KP) Georgia and Mid-Atlantic States (n = 3327) during the period of 2009 influenza A (H1N1) virus circulation. Primary outcomes were third-trimester preterm birth (27-36 weeks), birth weight, low birth weight (LBW, <2500 g), and SGA. RESULTS: There were 327 (9.8%) preterm, 236 (7.4%) LBW, and 267 (8.4%) SGA births. Among H1N1-vaccinated mothers (n = 1125), there were 86 (7.6%) preterm, 68 (6.4%) LBW, and 99 (9.3%) SGA births, and the mean birth weight was 3308.5 g (95% confidence interval [CI], 3276.6-3340.4). Among unvaccinated mothers (n = 1581), there were 191 (12.1%) preterm, 132 (8.8%) LBW, and 123 (8.2%) SGA births, and the mean birth weight was 3245.3 g (95% CI, 3216.5-3274.2). Infants of H1N1-vaccinated mothers had 37% lower odds of being born preterm than infants of unvaccinated mothers (adjusted odds ratio, 0.63 [95% CI, .47-.84]). The mean birth weight difference between infants of H1N1-vaccinated mothers and infants of unvaccinated mothers was 45.1 g (95% CI, 1.8-88.3). There was no significant association between maternal H1N1 influenza immunization and LBW or SGA. CONCLUSIONS: Pregnant women who received H1N1 influenza vaccine were less likely to give birth preterm, and gave birth to heavier infants. The findings support US vaccine policy choices to prioritize pregnant women during the 2009 influenza A (H1N1) pandemic.

A large, population-based study of 2009 pandemic Influenza A virus subtype H1N1 infection diagnosis during pregnancy and outcomes for mothers and neonates.

BACKGROUND: Pregnant women were at increased risk for serious outcomes of 2009 pandemic influenza A virus subtype H1N1 (influenza A[H1N1]pdm09) infection, but little is known about the overall impact of the pandemic on neonatal and maternal outcomes. METHODS: We identified live births that occurred from 1 July 2008 through 31 May 2010 in 5 Kaiser Permanente regions. Pregnant women were considered to have influenza if they had a positive result of a laboratory test for influenza virus or if they received a diagnosis of influenza during a period in which seasonal influenza virus or A(H1N1)pdm09 was the predominant circulating virus. RESULTS: There were 111 158 births from 109 015 pregnancies involving 107 889 mothers; 368 pregnant women (0.3%) received a diagnosis of influenza due to seasonal virus, and 959 (0.9%) received a diagnosis of influenza due to A(H1N1)pdm09; 107 688 did not receive an influenza diagnosis. Pregnant women with influenza due to A(H1N1)pdm09 were more likely than women with seasonal influenza infection to be hospitalized within 30 days of the diagnosis (27% vs 12%; odds ratio [OR], 2.84 [95% confidence interval {CI}, 2.01-4.02]). Pregnant women with A(H1N1)pdm09 who started antiviral treatment ≥2 days after the diagnosis were significantly more likely to be hospitalized than those who started antiviral treatment <2 days after diagnosis (OR, 3.43 [95% CI, 1.55-7.56]). Mothers with seasonal influenza virus infection had an increased risk for having a small-for-gestational-age infant (OR, 1.59 [95% CI, 1.15-2.20]). CONCLUSIONS: In this large, geographically diverse population, A(H1N1)pdm09 infection increased the risk for hospitalization during pregnancy. Late initiation of antiviral treatment was also associated with an increased risk for hospitalization.