Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder.

BACKGROUND: Many second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk. METHODS: Patients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013-February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions. RESULTS: Median follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG. CONCLUSIONS: In this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.

Multicenter randomized controlled trial and registry study to assess the safety and efficacy of the NanoKnife® system for the ablation of stage 3 pancreatic adenocarcinoma: overview of study protocols.

BACKGROUND: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. METHODS: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only. DISCUSSION: These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.

Characterizing Health Outcomes in Idiopathic Pulmonary Fibrosis using US Health Claims Data.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease (ILD). Characterizing health outcomes of IPF patients is challenging due to disease rarity. OBJECTIVE: This study aimed to identify the burden of disease in patients newly diagnosed with IPF. METHODS: Patients with ≥1 claim with an IPF diagnosis were identified from a United States healthcare insurer's database (2000-2013). Patients with other known causes of ILD or aged <40 years were excluded. Subgroups were compared based on the 2011 change in International Classification of Diseases, 9th Revision (ICD-9) definition of IPF and occurrence of IPF testing. The prevalence and incidence of preselected health conditions of clinical interest were estimated. RESULTS: Median age of newly diagnosed patients (n = 7,298) was 62 years (54.0% male). Restricting to patients with IPF diagnostic testing did not substantially affect cohort characteristics, nor did ICD-9 IPF coding change. Mean follow-up was 1.7 years; 16.8% of patients died; and a substantial proportion of patients were censored due to end of health plan enrollment (50.7%) and other causes of ILD (19.6%). The incidence of pulmonary hypertension, lung cancer, and claims-based algorithm proxy for acute respiratory worsening of unknown cause was 22.5, 17.6, and 12.6 per 1,000 person-years, respectively. CONCLUSIONS: Patients with IPF had a high disease burden with a variety of health outcomes observed, including a high rate of mortality. Database censoring due to changes in enrollment or other ILD diagnoses limited follow-up. Altering cohort entry definitions, including IPF testing or ICD-9 IPF coding change, had little impact on cohort baseline characteristics.

Liraglutide use and evaluation of pancreatic outcomes in a US commercially insured population.

AIMS: Both acute pancreatitis (AP) and pancreatic cancer (PC) have been areas of focus for studies of incretin drugs. This 5-year prospective cohort study aimed to quantify possible associations between liraglutide and risk of AP and PC as compared to other antidiabetic drugs (ADs). MATERIALS AND METHODS: Patients initiating liraglutide or other ADs who were enrolled in a US health plan (2010-2014) were included. Comparisons of AP and PC incidence rates were made between matched cohorts of liraglutide initiators and initiators of other ADs. Adjudicated AP cases and algorithm-based PC cases were identified. Propensity score-matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed using Poisson regression. A latency analysis was performed for PC. RESULTS: Median follow-up was 405 days for AP cohorts (9995 liraglutide, 1:1 matched to all comparators) and 503 days for PC cohorts (35 163 liraglutide, 1:1 matched to all comparators). In the primary AP analysis, "current" use of liraglutide was not significantly associated with elevated risk across comparators (all comparators relative risk [RR] = 1.2; 95% confidence interval [CI], 0.6-2.3). ITT results were similar where, in the primary analysis, no RRs were significantly associated with PC (all comparators RR = 0.7; 95% CI, 0.3-1.4); latency and TOD analyses did not alter findings. There was no evidence of a dose-response effect. CONCLUSIONS: Liraglutide was not associated with an increased risk of AP or PC, although risk estimates were more variable for AP, and numbers of cases for both outcomes were limited because of the rarity of outcomes.

Characterizing idiopathic pulmonary fibrosis patients using US Medicare-advantage health plan claims data.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare life-threating interstitial lung disease (ILD). This study characterizes demographics, health care utilization, and comorbidities among elderly IPF patients and estimates prevalence and incidence rates for selected outcomes. METHODS: Cohort study using a large US health insurance database (Optum's Medicare Advantage plan). INCLUSION CRITERIA: ≥ 1 diagnosis code for IPF (2008 - 2014), age ≥65 years, no diagnosis of IPF or other ILD in prior 12 months. Demographics, health care utilization, comorbidities and incidence rates for various outcomes were estimated. Follow-up continued until the earliest of: health plan disenrollment, death, a claim for another known cause of ILD, or end of the study period. RESULTS: 4,716 patients were eligible; 53.4% had IPF diagnostic testing. Median age was 77.5 years, 50.3% were male, median follow-up time was 0.8 years. Incidence rates ranged from 1.0/1,000 person-years (lung transplantation) to 374.3/1,000 person-years (arterial hypertension). Baseline characteristics and incidence rates were similar for cohorts of patients with and without IPF diagnostic testing. CONCLUSIONS: Elderly IPF patients experience a variety of comorbidities before and after IPF diagnosis. Therapies for IPF and for the associated comorbidities may reduce morbidity and associated health care utilization of these patients.

Exposure to traffic-related air pollution during pregnancy and term low birth weight: estimation of causal associations in a semiparametric model.

Traffic-related air pollution is recognized as an important contributor to health problems. Epidemiologic analyses suggest that prenatal exposure to traffic-related air pollutants may be associated with adverse birth outcomes; however, there is insufficient evidence to conclude that the relation is causal. The Study of Air Pollution, Genetics and Early Life Events comprises all births to women living in 4 counties in California's San Joaquin Valley during the years 2000-2006. The probability of low birth weight among full-term infants in the population was estimated using machine learning and targeted maximum likelihood estimation for each quartile of traffic exposure during pregnancy. If everyone lived near high-volume freeways (approximated as the fourth quartile of traffic density), the estimated probability of term low birth weight would be 2.27% (95% confidence interval: 2.16, 2.38) as compared with 2.02% (95% confidence interval: 1.90, 2.12) if everyone lived near smaller local roads (first quartile of traffic density). Assessment of potentially causal associations, in the absence of arbitrary model assumptions applied to the data, should result in relatively unbiased estimates. The current results support findings from previous studies that prenatal exposure to traffic-related air pollution may adversely affect birth weight among full-term infants.

Real-world evidence analysis of the impact of steroid-eluting implants on healthcare resource use among chronic rhinosinusitis patients undergoing sinus surgery.

OBJECTIVE: To compare healthcare resource use (HCRU) in patients undergoing sinus surgery with or without steroid-eluting sinus implants. METHODS: A retrospective, observational cohort study using real-world evidence data (OM1, Inc, Boston, MA, USA) was conducted on adult patients with chronic rhinosinusitis (CRS) with or without nasal polyps who underwent endoscopic sinus surgery between 2014 and 2019 and had at least 18 months of data both before and after surgery. Patients receiving implants ("implant cohort") were matched to patients who did not receive implants ("non-implant cohort") based on a propensity score developed using baseline characteristics. Chi-square for binary variables and analysis of variance tests for continuous variables were applied to compare HCRU measures. RESULTS: Comparison of the implant (N = 1983) and non-implant (N = 1983) cohorts during the 18-month follow-up period demonstrated significantly lower HCRU in those receiving implants, including all-cause outpatient visits (94.3% vs. 96.6%, p < .001), all-cause otolaryngologist visits (47.3% vs. 59.6%, p < .001) and all cause ER/urgent care visits (9.2% vs. 11.8%, p = .007), as well as sinus-related endoscopies (39.1% vs. 43.8%, p = .003). Although not statistically significant, fewer patients in the implant cohort had undergone repeat surgeries (4.6% vs. 5.3%, p = .273). CONCLUSION: Patients with steroid-eluting sinus implants had lower HCRU over a post-operative period of 18 months. These findings support the contention that reductions in HCRU may be achieved using steroid-eluting implants during sinus surgery.What is known on this topicChronic rhinosinusitis (CRS) causes severe symptoms that lead to poor quality of life.Endoscopic sinus surgery (ESS) is 76-98% effective in improving CRS patients' symptoms.Surgical outcomes can be compromised in the immediate post-operative period by scarring, adhesion formation, and early polyp recurrence.Oral and topical corticosteroid therapy has become integral to the maintenance of successful surgical outcomes, the management of post-operative scarring and edema, and the prevention of nasal polyp recurrence.Steroid-eluting sinus implants have been shown in clinical trials to improve postoperative outcomes after ESS by delivering localized, sustained release of corticosteroids directly onto inflamed sinus tissue.What this study addsThis observational study is one of the first to use real-world evidence to assess the effect of steroid-eluting sinus implants on healthcare resource use (HCRU) in patients with chronic rhinosinusitis who underwent sinus surgery with or without implants.Use of implants significantly reduced HCRU, including all-cause outpatient visits (94.3% vs 96.6%, p < .001), all-cause otolaryngologist visits (47.3% vs 59.6%, p < .001), and all-cause ER/urgent care visits (9.2% vs 11.8%, p = .007), as well as sinus endoscopy (39.1% vs 43.8%, p = .003).Use of implants had no significant effect on sinus procedures such as debridement and polypectomy, as well as sinus-related imaging such as CT, MRI, and x-ray.

Resources Required for Implementation of SARS-CoV-2 Screening in Massachusetts K-12 Public Schools in Winter/Spring 2021.

BACKGROUND: The financial costs and human resource requirements at the school and district level to implement a SARS-CoV-2 screening program are not well known. METHODS: A consortium of Massachusetts public K-12 schools was formed to implement and evaluate a range of SARS-CoV-2 screening approaches. Participating districts were surveyed weekly about their programs, including: type of assay used, individual vs. pooled screening, approaches to return of results and deconvolution of positive pools, number and type of personnel, and hours spent implementing the screening program, and hours spent on program implementation. RESULTS: In 21 participating districts, over 21 weeks from January to June 2021, the positivity rate was 0.0% to 0.21% among students and 0.0% to 0.13% among educators/staff. The average weekly cost to implement a screening program, including assay and personnel costs, was $17.00 per person tested; this was $46.68 for individual screenings and $15.61 for pooled screenings. The total weekly costs by district ranged from $1,644 to $93,486, and districts screened between 58 and 3675 people per week. CONCLUSIONS: Where screening is recommended for the 2021 to 2022 school year due to high COVID-19 incidence, understanding the human resources and finances required to implement screening will assist district policymakers in planning.

Implementation of G-computation on a simulated data set: demonstration of a causal inference technique.

The growing body of work in the epidemiology literature focused on G-computation includes theoretical explanations of the method but very few simulations or examples of application. The small number of G-computation analyses in the epidemiology literature relative to other causal inference approaches may be partially due to a lack of didactic explanations of the method targeted toward an epidemiology audience. The authors provide a step-by-step demonstration of G-computation that is intended to familiarize the reader with this procedure. The authors simulate a data set and then demonstrate both G-computation and traditional regression to draw connections and illustrate contrasts between their implementation and interpretation relative to the truth of the simulation protocol. A marginal structural model is used for effect estimation in the G-computation example. The authors conclude by answering a series of questions to emphasize the key characteristics of causal inference techniques and the G-computation procedure in particular.

Risk of Thyroid Cancer Associated with Use of Liraglutide and Other Antidiabetic Drugs in a US Commercially Insured Population.

BACKGROUND: Quantify association between the glucagon-like peptide-1 receptor agonist liraglutide and risk of thyroid cancer (TC) compared to other antidiabetics. PATIENTS AND METHODS: Initiators of liraglutide, exenatide, metformin, pioglitazone or groups of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US health plan (2010-2014) and followed for a median of 17 months. Thyroid cancer cases during follow-up were identified via a validated algorithm. Incidence rates of TC among liraglutide and comparators were assessed using relative risks estimated within propensity score-matched cohorts using intention to treat (ITT) and time on drug analyses. Latency effects and potential surveillance bias were evaluated. RESULTS: Relative risks from ITT analyses ranged from 1.00 (95% confidence interval (CI) 0.56-1.79) versus metformin to 1.70 (95% CI 1.03-2.81) versus all comparators excluding exenatide. Effect estimates from latency analyses were slightly attenuated. Time on drug analyses suggested no increased risk for either longer duration or higher cumulative dose of liraglutide. Medical record review found 85% were papillary or a follicular variant of papillary or both; 46% were microcarcinomas (≤10 millimeters), which were more prevalent in the liraglutide cohort (67% versus 43% in all comparators). CONCLUSION: Relative risks were elevated for several comparisons, which should be interpreted cautiously because of potential residual confounding and surveillance bias. Liraglutide cases had smaller thyroid nodules and shorter time-to-diagnosis, suggesting increased surveillance for TC among liraglutide initiators, especially shortly after the drug´s approval. After adjusting the primary analyses (ITT) for latency, no significant elevated risk of TC was observed among liraglutide initiators.

Outcomes by Race in Breast Cancer Screening With Digital Breast Tomosynthesis Versus Digital Mammography.

PURPOSE: Digital breast tomosynthesis (DBT) in conjunction with digital mammography (DM) is becoming the preferred imaging modality for breast cancer screening compared with DM alone, on the basis of improved recall rates (RR) and cancer detection rates (CDRs). The aim of this study was to investigate racial differences in the utilization and performance of screening modality. METHODS: Retrospective data from 63 US breast imaging facilities from 2015 to 2019 were reviewed. Screening outcomes were linked to cancer registries. RR, CDR per 1,000 examinations, and positive predictive value for recall (cancers/recalled patients) were compared. RESULTS: A total of 385,503 women contributed 542,945 DBT and 261,359 DM screens. A lower proportion of screenings for Black women were performed using DBT plus DM (referred to as DBT) (44% for Black, 48% for other, 63% for Asian, and 61% for White). Non-White women were less likely to undergo more than one mammographic examination. RRs were lower for DBT among all women (8.74 versus 10.06, P < .05) and lower across all races and within age categories. RRs were significantly higher for women with only one mammogram. CDRs were similar or higher in women undergoing DBT compared with DM, overall (4.73 versus 4.60, adjusted P = .0005) and by age and race. Positive predictive value for recall was greater for DBT overall (5.29 versus 4.45, adjusted P < .0001) and by age, race, and screening frequency. CONCLUSIONS: All racial groups had improved outcomes with DBT screening, but disparities were observed in DBT utilization. These data suggest that reducing inequities in DBT utilization may improve the effectiveness of breast cancer screening.

Altered pulmonary function in children with asthma associated with highway traffic near residence.

Cross-sectional analyses were conducted to evaluate the effects of exposure to highway traffic on pulmonary function in Fresno, California. Traffic and spirometry data were available for 214 children (enrollment ages six to 11 years). Multiple linear regression was used to evaluate the relations between pulmonary function and traffic parameters. Heavy-duty vehicle count was used as a surrogate measure for diesel-related exposures. Pulmonary function was non-significantly associated with longer distance-to-road and non-significantly associated with higher traffic intensity. Evaluation of effect modification by FEF(25-75)/FVC (a measure of intrinsic airway size) showed that all pulmonary function measures of flow were significantly inversely related to a traffic metric that incorporates traffic intensity and roadway proximity. The results indicate that residence proximity to highway traffic is associated with lower pulmonary function among children with asthma, and smaller airway size is an important modifier of the effect of traffic exposure on pulmonary function and a marker of increased susceptibility.

Air pollution and pulmonary function in asthmatic children: effects of prenatal and lifetime exposures.

BACKGROUND: Prenatal and early life periods represent critical windows for oxidant pollutant-induced lung remodeling. The objective of this study was to examine the association of prenatal and lifetime exposures to air pollutants with pulmonary function in a cohort of children with asthma. METHODS: Prenatal and lifetime exposure to several air pollutants was reconstructed for 232 children with asthma from the San Joaquin Valley of California, USA. Prenatal and lifetime residences were geocoded. We obtained data on monthly average ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter with a median aerodynamic diameter <10 microm (PM10) concentrations. Metrics were created for key developmental periods. Predictive models were developed for 8 pulmonary function measures. A newly-developed stepwise model selection procedure-the Deletion/Substitution/Addition algorithm-was implemented and results were compared with those obtained using traditional stepwise methods. RESULTS: Second-trimester exposure to NO2 negatively affected forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1), and first trimester exposure to PM10 negatively affected peak expiratory flow (PEF) rate. Exposure to CO in early years of life also had a negative effect on FEV1/FVC and forced expiratory flow between 25% and 75% of FVC (FEF25-75)/FVC. Second trimester exposure to PM10 and exposure to CO in the first 6 years of life had negative effects on forced expiratory flow at 25% of FVC. Prenatal, but not trimester-specific, exposure to CO was negatively associated with FEF25-75. Effects were limited to subgroups, such as children who were African American, those diagnosed with asthma before the age of 2 years, and those exposed to maternal smoking during pregnancy. CONCLUSION: Prenatal and early-life exposures to CO, PM10, and NO2 have a negative effect on pulmonary function in subgroups of asthmatic children.

Early-lifetime exposure to air pollution and allergic sensitization in children with asthma.

Observations on the association between exposure to common outdoor air pollutants and allergic sensitization have not been consistent. Little research has been done on the effects of prenatal exposure or the effect among asthmatics. The association between prenatal and early-life exposures and outdoor air pollutants with allergic sensitization was examined within a cohort of 170 children ages 6-11 years with asthma, living in the Central Valley of California. Allergic sensitization was ascertained by skin-prick tests to 14 allergens. Prenatal and early-life exposure to ozone (O(3)), nitrogen dioxide (NO(2)), carbon monoxide (CO) and particulate matter with a median aerodynamic diameter < 10 micro m (PM(10)) was reconstructed for each child. Models were developed for sensitized to (a) any allergen, (b) at least one outdoor allergen, and (c) at least one indoor allergen. In multivariable analyses, higher exposure to CO during pregnancy was associated with an increased risk of sensitization to at least one outdoor allergen. The largest effect was seen for the association between exposure to 8-hour daily maximum CO during pregnancy and sensitization to at least one outdoor allergen. (OR = 1.55 (95% CI: 1.01, 2.37)) per interquartile range (IQR) increase.) Similar effects estimates were seen for 2nd trimester exposure to CO, but these were less precisely estimated (OR = 1.45 (95%CI: 0.90, 2.35)). No significant associations with the pollutants were seen for sensitization to allergens in general or to at least one indoor allergen. Exposure to traffic-related pollutants during pregnancy may increase the risk of sensitization to outdoor allergens among asthmatic children.

Is there an association between liraglutide use and female breast cancer in a real-world setting?

BACKGROUND: Liraglutide is a human glucagon-like peptide-1 receptor agonist approved for treatment of adults with type 2 diabetes mellitus at a maximum dose of 1.8 mg/day (Victoza®) and more recently at 3.0 mg/day for weight management (Saxenda®). During the evaluation of liraglutide for approval in weight management, a minor imbalance in the numbers of reported breast neoplasms was observed, motivating the present study. Our objective was to quantify the association between liraglutide and incidence of breast cancer (BC) among women in a real-world setting. PATIENTS AND METHODS: Women initiating liraglutide or other antidiabetic therapies and who were enrolled in a large US health plan (2010-2014) were included. Comparisons of BC incidence rates were made between matched cohorts of initiators of liraglutide and cohorts of initiators of exenatide, metformin, pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors separately and as two "all comparators" groupings: with or without exenatide. Women with two or more claims with BC diagnosis codes within 61days of each other were identified as possible cases, with additional confirmation by clinician review of comprehensive claims listings. Propensity score matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed via Poisson regression. A latency analysis was performed. RESULTS: Relative risks for BC for liraglutide vs comparators from the ITT analyses ranged from 0.90 (95% CI: 0.67-1.22) for both the "all comparator" and "all comparator except exenatide" cohorts to 1.46 (95% CI: 0.96-2.22) relative to exenatide. Latency analyses excluding the first year of follow-up yielded slightly attenuated point estimates. The TOD analyses of cumulative use of liraglutide suggested no increased risk of BC. CONCLUSION: Neither the ITT (overall or latency analysis) nor cumulative TOD analyses suggested an elevated risk of BC among liraglutide initiators. Short length of follow-up and the potential for confounding by unmeasured factors limit the full assessment of long-term risk.

Population intervention models to estimate ambient NO2 health effects in children with asthma.

Health effects of ambient air pollution are most frequently expressed in individual studies as responses to a standardized unit of air pollution changes (e.g., an interquartile interval), which is thought to enable comparison of findings across studies. However, this approach does not necessarily convey health effects in terms of a real-world air pollution scenario. In the present study, we use population intervention modeling to estimate the effect of an air pollution intervention that makes explicit reference to the observed exposure data and is identifiable in those data. We calculate the association between ambient summertime nitrogen dioxide (NO2) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) in a cohort of children with asthma in Fresno, California. We scale the effect size to reflect NO2 abatement on a majority of summer days. The effect estimates were small, imprecise, and consistently indicated improved pulmonary function with decreased NO2. The effects ranged from -0.8% of mean FEF25-75 (95% confidence interval (CI): -3.4, 1.7) to -3.3% (95% CI: -7.5, 0.9). We conclude by discussing the nature and feasibility of the exposure change analyzed here given the observed air pollution profile, and we propose additional applications of population intervention models in environmental epidemiology.

Adherence to risk evaluation and mitigation strategies (REMS) requirements for monthly testing of liver function.

BACKGROUND: Risk evaluation and mitigation strategies (REMS), as mandated by the US Food and Drug Administration (FDA) for medications with the potential for harm, are increasingly incorporating rigid protocols for patient evaluation, but little is known about compliance with these programs. Despite the inherent limitations, data on administrative claims may provide an opportunity to investigate adherence to these programs. METHODS: We assessed adherence to liver function test (LFT) requirements included in the REMS program for bosentan through use of administrative claims. Patients observed in the Optum Research Database who were initiators of bosentan from November 20, 2001 to March 31, 2013 were included. Adherence to LFTs was calculated using pharmacy claims for bosentan dispensation and medical claims for laboratory services, and was assessed at the time of drug initiation and within specified time intervals throughout follow-up. RESULTS: Of 742 patients, 523 (70.5%) had ≥1 qualifying LFT. Among patients with ≥12 dispensations, claims for LFTs at individual dispensations were 53.2-64.0%. Median proportion of dispensations with ≥1 LFT was 0.8 among patients with ≥6 (interquartile range, 0.7-1.0) or ≥12 (0.7-0.9) dispensations. Adherence was 90-100% for 33.3% of all initiators, whereas 29.3% of initiators were non-adherent (defined as <50% of on-therapy LFTs). CONCLUSIONS: Analyses of administrative claims suggest that the REMS program for bosentan may not have adequately guaranteed adherence to the program's monthly monitoring of LFTs. Such investigations of existing REMS programs may provide insight on how to accomplish more successful evaluation of REMS.

Evaluating the use of a portable spirometer in a study of pediatric asthma.

STUDY OBJECTIVES: Laboratory-based spirometry is the "gold standard" for the assessment of lung function, both in clinical and research protocols. These spirometers, however, are neither practical nor affordable for home-based monitoring or studies that collect data in multiple locations. Traditionally, peak flowmeters have been used, but they have important limitations. DESIGN: Based on data from a cohort of 92 children with asthma, we evaluated the agreement between a portable spirometer and a office-based spirometer, using an in-line technique to evaluate measures from the same effort. We compared a range of pulmonary function parameters collected during office-based tests, and also evaluated whether adequate adherence and data quality could be achieved in a home-based study of children with asthma. RESULTS: The agreement between the devices for the actual values of peak expiratory flow, FEV(1), and forced expiratory flow at 25% of FVC was excellent. The portable device was programmed with customized software to grade each curve using revised American Thoracic Society acceptability and reproducibility criteria. For 74% of the curves, quality grade agreed with a grade assigned by physician review of the curve from the office-based spirometer. During 2 weeks of twice-daily monitoring at home, children completed an average of 23 of 28 possible sessions (83%). Of these, 84% had at least two acceptable and two reproducible curves. Although children >or= 8 years old were not more adherent, they were significantly more likely to achieve acceptable and reproducible curves. CONCLUSIONS: Portable spirometers can provide measurements that are highly comparable to those obtained from "gold standard" laboratory spirometers, and high-quality tracings can be achieved both at home and in the office setting. Visual inspection of the curves by experienced reviewers identified unacceptable curves that were not rejected by the quality control software. Portable spirometers are an important contribution to epidemiologic and clinical studies that require frequent measures of a more broad range of pulmonary function parameters than can be provided by peak flowmeters.

Traffic-related air pollution and risk of preterm birth in the San Joaquin Valley of California.

PURPOSE: To evaluate associations between traffic-related air pollution during pregnancy and preterm birth in births in four counties in California during years 2000 to 2006. METHODS: We used logistic regression to examine the association between the highest quartile of ambient air pollutants (carbon monoxide, nitrogen dioxide, particulate matter <10 and 2.5 µm) and traffic density during pregnancy and each of five levels of prematurity based on gestational age at birth (20-23, 24-27, 28-31, 32-33, and 34-36 weeks) versus term (37-42 weeks). We examined trimester averages and the last month and the last 6 weeks of pregnancy. Models were adjusted for birthweight, maternal age, race/ethnicity, education, prenatal care, and birth costs payment. Neighborhood socioeconomic status (SES) was evaluated as a potential effect modifier. RESULTS: There were increased odds ratios (ORs) for early preterm birth for those exposed to the highest quartile of each pollutant during the second trimester and the end of pregnancy (adjusted OR, 1.4-2.8). Associations were stronger among mothers living in low SES neighborhoods (adjusted OR, 2.1-4.3). We observed exposure-response associations for multiple pollutant exposures and early preterm birth. Inverse associations during the first trimester were observed. CONCLUSIONS: The results confirm associations between traffic-related air pollution and prematurity, particularly among very early preterm births and low SES neighborhoods.