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Purpose: Develop and test a flexible, scalable tool using interrupted time series (ITS) analysis to assess the impact of Food and Drug Administration (FDA) regulatory actions on drug use. Methods: We applied the tool in the Sentinel Distributed Database to assess the impact of FDA's 2010 drug safety communications (DSC) concerning the safety of long‐acting beta2‐agonists (LABA) in adult asthma patients. We evaluated changes in LABA use by measuring the initiation of LABA alone and concomitant use of LABA and asthma controller medications (ACM) after the DSCs. The tool generated ITS graphs and used segmented regression to estimate baseline slope, level change, slope change, and absolute and relative changes at up to two user‐specified time point (s) after the intervention. We tested the tool and compared our results against prior analyses that used similar measures. Results: Initiation of LABA alone declined among asthma patients aged 18–45 years before FDA DSCs (−0.10% per quarter; 95%CI: −0.11% to −0.09%) and the downward trend continued after. Concomitant use of LABA and ACM was stable before FDA DSCs. After FDA DSCs, there was a small trend decrease of 0.006% per quarter (95% CI, −0.008% to −0.003%). We found similar results among those aged 46–64 years and patients with poorly‐controlled asthma. Our results were consistent with previous studies, confirming the performance of the new tool. Conclusions: We developed and tested a reusable ITS tool in real‐world databases formatted to the Sentinel Common Data Model that can assess the impact of regulatory actions on drug use. [ABSTRACT FROM AUTHOR]

Process yield has been a standard metric for measuring the capability and performance of manufacturing processes. Process capability index Spk, a concise unit-less gauge with yield-sensitive functionality, communicates succinctly the genuine process yield for normally distributed processes. However, in frequentist statistics, the exact sampling distribution of Spk's natural estimator is intractable. Various frequentist approaches have attempted to address its wide-scale accuracy in statistical inference. Among them, the approach of generalized confidence interval (GCI) has been demonstrated superiority. In this paper, we incorporate Markov chain Monte Carlo (MCMC) algorithms to introduce a Bayesian-type approach. Extensive simulations in comparison of accuracy and precision performances between the Spk's frequentist and Bayesian inferences are conducted. Concerning coverage rates and average interval widths of the inferential criteria, Spk's Bayesian MCMC credibility intervals perform better than frequentist GCIs in most cases, particularly, the cases with only a few samples of information acquired from the manufacturing process. [ABSTRACT FROM AUTHOR]

The US Sentinel System and the Canadian Network for Observational Drug Effect Studies (CNODES) are two medical product safety surveillance networks. Using Sentinel's preprogrammed, parameterizable analytic tools, we reproduced two protocol‐based studies conducted by CNODES to assess the risks of acute pancreatitis and heart failure (HF) associated with the use of incretin‐based drugs, compared with use of ≥ 2 oral hypoglycemic agents. Results from the replication new‐user cohort analyses aligned with those from the CNODES nested case‐control studies. The adjusted hazard ratios were 0.95 (0.81–1.12; vs. 1.03 (0.87–1.22) in CNODES) for acute pancreatitis and 0.91 (0.84–1.00; vs. 0.82 (0.67–1.00) in CNODES) for HF among patients without HF history. The CNODES's common protocol approach allows studies tailored to specific safety questions, whereas the Sentinel's common data model plus pretested program approach enables more rapid analysis. Despite these differences, it is possible to obtain comparable results using both approaches. [ABSTRACT FROM AUTHOR]

Purpose The CHA2DS2‐VaSc and HAS‐BLED risk scores are commonly used in the studies of oral anticoagulants (OACs). The best ways to map these scores to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD‐10‐CM) codes is unclear, as is how they perform in various types of OAC users. We aimed to assess the distributions of CHA2DS2‐VaSc and HAS‐BLED scores and C‐statistics for outcome prediction in the ICD‐10‐CM era using different mapping strategies. Methods: We compared the distributions of CHA2DS2‐VaSc and HAS‐BLED scores from various mapping strategies in atrial fibrillation patients before, during, and after ICD‐10‐CM transition. We estimated the C‐statistics predicting the 90‐day risk of hospitalized stroke (for CHA2DS2‐VaSc) or hospitalized bleeding (for HAS‐BLED) in patients identified at least 6 months after the ICD‐10‐CM transition, overall and by anticoagulant type. Results: Forward‐backward mapping produced higher CHA2DS2‐VaSc and HAS‐BLED scores in the ICD‐10‐CM era compared to the ICD‐9‐CM era: the mean difference was 0.074 (95% confidence interval 0.064‐0.085) for CHA2DS2‐VaSc and 0.055 (0.048‐0.062) for HAS‐BLED. Both scores had higher C‐statistics in patients taking no OACs (0.697 [0.677‐0.717] for CHA2DS2‐VaSc; 0.719 [0.702‐0.737] for HAS‐BLED) or direct OACs (0.695 [0.654‐0.735] for CHA2DS2‐VaSc; 0.700 [0.673‐0.728] for HAS‐BLED) than those taking warfarin (0.655 [0.613‐0.697] for CHA2DS2‐VaSc; 0.663 [0.6320.695] for HAS‐BLED). Conclusions: Existing mapping strategies generally preserved the distributions of CHA2DS2‐VaSc and HAS‐BLED scores after ICD‐10‐CM transition. Both scores performed better in patients on no OACs or direct OACs than patients on warfarin. [ABSTRACT FROM AUTHOR]

Background: Epidemiological study reporting is improving but is not transparent enough for easy evaluation or replication. One barrier is insufficient details about design elements in published studies. Methods: Using a previously conducted drug safety evaluation in claims as a test case, we investigated the impact of small changes in five key design elements on risk estimation. These elements are index day of incident exposure's determination of look‐back or follow‐up periods, exposure duration algorithms, heparin exposure exclusion, propensity score model variables, and Cox proportional hazard model stratification. We covaried these elements using a fractional factorial design, resulting in 24 risk estimates for one outcome. We repeated eight of these combinations for two additional outcomes. We measured design effects on cohort sizes, follow‐up time, and risk estimates. Results: Small changes in specifications of index day and exposure algorithm affected the risk estimation process the most. They affected cohort size on average by 8 to 10%, follow‐up time by up to 31%, and magnitude of log hazard ratios by up to 0.22. Other elements affected cohort before matching or risk estimate's precision but not its magnitude. Any change in design substantially altered the matched control‐group subjects in 1:1 matching. Conclusions: Exposure‐related design elements require attention from investigators initiating, evaluating, or wishing to replicate a study or from analysts standardizing definitions. The methods we developed, using factorial design and mapping design effect on causal estimation process, are applicable to planning of sensitivity analyses in similar studies. [ABSTRACT FROM AUTHOR]

The effect of treating comorbid depression to achieve optimal management of chronic obstructive pulmonary disease (COPD) has not yet empirically tested. We examined the association between antidepressant treatment and use of and adherence to COPD maintenance medications among patients with new-onset COPD and comorbid depression.Methods: Using 2006-2012 Medicare data, this retrospective cohort study identified patients with newly diagnosed COPD and new-onset major depression. Two exposures-antidepressant use (versus non-use) and adherence measured by proportion of days covered (PDC) (PDC ≥0.8 versus <0.8)-were assessed quarterly. We used marginal structural models to estimate the effects of prior antidepressant use and adherence on subsequent COPD maintenance inhaler use and adherence outcomes, accounting for time-varying confounders.Results: A total of 25 458 COPD-depression patients, 82% with antidepressant treatment, were followed for a median of 2.5 years. Nearly half (48%) used at least 1 COPD maintenance inhaler in any given quarter; among users, 3 in 5 (61%) had a PDC of <0.8. Compared to patients with no antidepressant treatment, those with antidepressant use were more likely to use (relative ratio [RR] = 1.15, 95% confidence interval [CI] = 1.12- 1.17) and adhere to (RR = 1.08, 95% = 1.03-1.14) their COPD maintenance inhalers. Patients who adhered to antidepressant treatment were more likely to use and adhere to COPD maintenance inhalers.Conclusion: Regularly treated depression may increase use of and adherence to necessary maintenance medications for COPD. Antidepressant treatment may be a key determinant to improving medication-taking behaviors among COPD patients comorbid with depression. [ABSTRACT FROM AUTHOR]

Objective: This study examined the latent constructs of delirium symptoms among nursing home (NH) residents in the United States. Method: Cross-sectional NH assessment data (Minimum Data Set 2.0) from the 2009 Medicare Current Beneficiary Survey were used. Data from two independent, randomly selected subsamples of residents ≥65 years were analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Results: There were 367 and 366 individuals in the EFA and CFA, respectively. Assessment of multiple model fit statistics in CFA indicated that the two-factor structure provided better fit for the data than a one-factor solution. The two factors represented cognitive and behavioral latent constructs as suggested by the related literature. A correlation of .72 between these constructs suggested moderate discriminant validity. Conclusion: This finding emphasizes the importance of health care providers to be attentive to both cognitive and behavioral symptoms when diagnosing, treating, and managing delirium. [ABSTRACT FROM AUTHOR]

Objectives: Depression is a common comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with increased exacerbations, healthcare utilization, and mortality. Among Medicare beneficiaries newly diagnosed with COPD, the objectives of this study were to (1) estimate the rate of new episodes of depression and (2) identify factors associated with depression.Methods: We identified beneficiaries with a first diagnosis of COPD during 2006-2012 using a 5% random sample of Medicare administrative claims data by searching for ICD-9-CM codes 490, 491.x, 492.x, 494.x, or 496. We identified episodes of depression using ICD-9-CM codes 296.2x, 296.3x, and 311.xx. We calculated incidence rates and their 95% confidence intervals (95% CI) and used a discrete time analysis to identify factors associated with development of depression.Results: Between 2006 and 2012, 125,348 beneficiaries meeting inclusion criteria were newly diagnosed with COPD. Twenty-three percent developed depression following COPD diagnosis. The annualized incidence rate of depression per 100 beneficiaries following COPD diagnosis was 9.4 (95% CI 9.3, 9.5). Rates were highest in the first 2 months following COPD diagnosis. COPD diagnosis was associated with increased risk of depression (risk ratio 1.76; 95% CI 1.73, 1.79) as were COPD-related hospitalizations (risk ratio 4.59; 95% CI 4.09, 5.15), a measure of COPD severity.Conclusions: Diagnosis of COPD increases the risk of depression. This study will aid in the allocation of resources to monitor and provide support for individuals with COPD at high risk of developing depression. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a major pathogen in the initiation and progression of periodontal disease, which is recognized as a common complication of diabetes. ICAM-1 expression by human gingival fibroblasts ( HGFs) is crucial for regulating local inflammatory responses in inflamed periodontal tissues. However, the effect of P. gingivalis in a high-glucose situation in regulating HGF function is not understood. The P. gingivalis strain CCUG25226 was used to study the mechanisms underlying the modulation of HGF ICAM-1 expression by invasion of high-glucose-treated P. gingivalis ( HGPg). A high-glucose condition upregulated fimA mRNA expression in P. gingivalis and increased its invasion ability in HGFs. HGF invasion with HGPg induced increases in the expression of ICAM-1. By using specific inhibitors and short hairpin RNA ( shRNA), we have demonstrated that the activation of p38 MAPK and Akt pathways is critical for HGPg-induced ICAM-1 expression. Luciferase reporters and chromatin immunoprecipitation assays suggest that HGPg invasion increases NF-κ B- and Sp1- DNA-binding activities in HGFs. Inhibition of NF-κ B and Sp1 activations blocked the HGPg-induced ICAM-1 promoter activity and expression. The effect of HGPg on HGF signalling and ICAM-1 expression is mediated by CXC chemokine receptor 4 ( CXCR4). Our findings identify the molecular pathways underlying HGPg-dependent ICAM-1 expression in HGFs, providing insight into the effect of P. gingivalis invasion in HGFs. [ABSTRACT FROM AUTHOR]