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To provide recent population-based estimates of transthoracic needle biopsy (TTNB) complications and risk factors associated with these complications.This retrospective cohort analysis included adults from a nationally representative longitudinal insurance claims data set who underwent TTNB in 2017 or 2018. Complications that were evaluated included pneumothorax, hemorrhage, and air embolism. Separate logistic regression models estimated the association of pneumothorax or hemorrhage with the setting of care (ie, inpatient or outpatient) and selected baseline patient demographic and clinical characteristics including age, gender, history of chronic obstructive pulmonary disease, diagnosis of pleural effusion, tobacco use, use of oral anticoagulants and antiplatelet agents, prior lung cancer screening, previous bronchoscopy within 1 year, and Elixhauser comorbidity index.Among 16,971 patients who underwent TTNB, 25.8% experienced a complication within 3 days of the procedure (pneumothorax 23.3%, hemorrhage 3.6%, and air embolism 0.02%). Among patients who experienced pneumothorax, 31.9% required chest tube drainage. Among patients undergoing an outpatient TTNB (n = 12,443), 6.9% were hospitalized within 7 days. Biopsy in an inpatient setting, chronic obstructive pulmonary disease diagnosis, and prior bronchoscopy were associated with higher rates of both pneumothorax and hemorrhage. Prior lung cancer screening was associated with an increased risk of pneumothorax, and prior use of oral anticoagulants or antiplatelets was associated with higher rates of hemorrhage.This contemporary population-based cohort study demonstrated that approximately one-quarter of patients undergoing TTNB experienced a complication. Pneumothorax was the most frequent complication, and hemorrhage and air embolism were rare. Among outpatients, complications from TTNB are an important cause of hospitalization.

Drug-drug interactions (DDIs) with oral anticoagulants may lead to under-anticoagulation and increased risk of thromboembolism. Although warfarin is susceptible to numerous DDIs, few studies have examined DDIs resulting in thromboembolism or those involving direct-acting oral anticoagulants (DOACs). We aimed to identify medications that increase the rate of hospitalization for thromboembolic events when taken concomitantly with oral anticoagulants. We conducted a high-throughput pharmacoepidemiologic screening study using Optum Clinformatics Data Mart, 2000-2016. We performed self-controlled case series studies among adult users of oral anticoagulants (warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban) with at least one hospitalization for a thromboembolic event. Among eligible patients, we identified all oral medications frequently co-prescribed with oral anticoagulants as potential interacting precipitants. Conditional Poisson regression was used to estimate rate ratios comparing precipitant exposed vs. unexposed time for each anticoagulant-precipitant pair. To minimize within-person confounding by indication for the precipitant, we used pravastatin as a negative control object drug. Multiple estimation was adjusted using semi-Bayes shrinkage. We screened 1,622 oral anticoagulant-precipitant drug pairs and identified 226 (14%) drug pairs associated with statistically significantly elevated risk of thromboembolism. Using pravastatin as the negative control object drug, this list was reduced to 69 potential DDI signals for thromboembolism, 33 (48%) of which were not documented in the DDI knowledge databases Lexicomp and/or Micromedex. There were more DDI signals associated with warfarin than DOACs. This study reproduced several previously documented oral anticoagulant DDIs and identified potential DDI signals that deserve to be examined in future etiologic studies.

Acid rain has severely negatively impacted terrestrial ecosystems and biogeochemical cycles. However, the potential impacts of nitric acid rain (NAR) on soil nitrogen (N) fractions and fungal community diversity in northern subtropical forest soils remain largely unevaluated. In this study, treatments of NAR at pH = 4.5 (AR4.5), pH = 3.5 (AR3.5), and pH = 2.5 (AR2.5) were randomly sprayed in a typical Quercus acutissima Carruth. stand in northern subtropical China. The soil N fractions and soil fungal communities were analyzed after a 12-month experimental period. The results revealed that compared to the control, the soil total N (TN), microbial biomass N (MBN), hydrolysable ammonium N (HAN), amino-sugar N (ASN) and amino-acid N (AAN) contents decreased significantly by 19.61-13.07 %, 20.10-9.04 %, 60.41-28.87 %, 74.10-62.25 %, and 65.69-45.64 % under stronger acidity inputs (i.e., AR2.5 and AR3.5), respectively. Besides, the AR2.5 and AR3.5 treatments increased the α-diversity indices of soil fungal communities and altered the soil fungal community structure. Moreover, the NAR treatments represented an increase in the relative abundance of Ascomycota and Mortierellomycota and a decrease in that of Basidiomycota. Mortierella, Penicillium, and Tomentella can be used as indicator genera for changes in soil fungal community structures under NAR stress. Furthermore, AAN was the main environmental factor affecting soil fungal community at the phylum and genus levels. Cumulatively, findings from this research provide valuable insight into NAR's effects on N cycling and microbial communities in forest soils.

Few population-based studies have examined bleeding associated with clopidogrel drug-drug interactions (DDIs). We sought to identify precipitant drugs taken concomitantly with clopidogrel (an object drug) that increased serious bleeding rates. We screened 2000-2015 Optum commercial health insurance claims to identify DDI signals. We performed self-controlled case series studies for clopidogrel plus precipitant pairs, examining associations with gastrointestinal bleeding or intracranial hemorrhage. To distinguish native bleeding effects of a precipitant, we reexamined associations using pravastatin as a negative control object drug. Among 431 analyses, 28 clopidogrel plus precipitant pairs were statistically significantly positively associated with serious bleeding. Ratios of rate ratios ranged from 1.13-3.94. Among these pairs, 13 were expected given precipitant drugs alone increased and/or were harbingers of serious bleeding. The remaining 15 pairs constituted new DDI signals, none of which are currently listed in two major DDI knowledge bases.

In 2020, the European Commission up-classified pure cobalt metal to a Category 1B hazard, based primarily on data from rodent inhalation carcinogenicity studies of metallic cobalt. The European Commission review did not evaluate cobalt-containing alloys in medical devices, which have very different properties vs. pure cobalt metal and did not include a systematic epidemiologic review. We performed a systematic review and meta-analysis of published, peer-reviewed epidemiologic studies evaluating the association between overall cancer risk and exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings. Study-specific estimates were pooled using random-effects models. Analyses included 20 papers on orthopedic implants and 10 occupational cohort papers (~1 million individuals). The meta-analysis summary estimates (95% confidence intervals) for overall cancer risk were 1.00 (0.96–1.04) overall and 0.97 (0.94–1.00) among high-quality studies. Results were also similar in analyses stratified by type of exposure/data sources (occupational cohort, implant registry or database), comparators (general or implant population), cancer incidence or mortality, follow-up duration (latency period), and study precision. In conclusion, meta-analysis found no association between exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings and overall cancer risk, including an analysis of studies directly comparing metal-on-metal vs. non-metal-on-metal implants.

Sentinel is a program sponsored by the US Food and Drug Administration to monitor the safety of medical products. We conducted a cohort assessment to evaluate the ability of the Sentinel Propensity Score Matching Tool to reproduce in an expedited fashion the known association between glyburide (vs. glipizide) and serious hypoglycemia. Thirteen data partners who contribute to the Sentinel Distributed Database participated in this analysis. A pretested and customizable analytic program was run at each individual site. De-identified summary results from each data partner were returned and aggregated at the Sentinel Operations Center. We identified a total of 198,550 and 379,507 new users of glyburide and glipizide, respectively. The incidence of emergency department visits and hospital admissions for serious hypoglycemia was 19 per 1000 person-years (95% confidence interval = 17.9, 19.7) for glyburide users and 22 (21.6, 22.7) for glipizide users. In cohorts matched by propensity score based on predefined variables, the hazard ratio (HR) for glyburide was 1.36 (1.24, 1.49) versus glipizide. In cohorts matched on a high-dimensional propensity score based on empirically selected variables, for which the program ran to completion in five data partners, the HR was 1.49 (1.31, 1.70). In cohorts matched on propensity scores based on both predefined and empirically selected variables via the high-dimensional propensity score algorithm (the same five data partners), the HR was 1.51 (1.32, 1.71). These findings are consistent with the literature, and demonstrate the ability of the Sentinel Propensity Score Matching Tool to reproduce this known association in an expedited fashion.See video abstract at, http://links.lww.com/EDE/B275.

An important component of the Food and Drug Administration’s Sentinel Initiative is the active post-market risk identification and analysis (ARIA) system, which utilizes semi-automated, parameterized computer programs to implement propensity-score adjusted and self-controlled risk interval designs to conduct targeted surveillance of medical products in the Sentinel Distributed Database. In this manuscript, we review literature relevant to the development of these programs and describe their application within the Sentinel Initiative. These quality-checked and publicly available tools have been successfully used to conduct rapid, replicable, and targeted safety analyses of several medical products. In addition to speed and reproducibility, use of semi-automated tools allows investigators to focus on decisions regarding key methodological parameters. We also identified challenges associated with the use of these methods in distributed and prospective datasets like the Sentinel Distributed Database, namely uncertainty regarding the optimal approach to estimating propensity scores in dynamic data among data partners of heterogeneous size. Future research should focus on the methodological challenges raised by these applications as well as developing new modular programs for targeted surveillance of medical products.

Dabigatran is a direct thrombin inhibitor approved by the FDA in October 2010 for the treatment of nonvalvular atrial fibrillation. Little is known regarding patient adherence to this therapy.To examine adherence and persistence to dabigatran among adults with atrial fibrillation.We used IMS Health's LifeLink Health Plan Claims Database from 2010 to 2012 to identify patients with atrial fibrillation who were new users of dabigatran. We derived adherence and persistence for continuously enrolled patients at 6 months, 9 months, and 12 months of follow-up. We measured adherence using the medication possession ratio (MPR), defined as individuals with MPRs of 0.80 or greater as adherent, and examined persistence by identifying individuals with gaps in drug possession of 60 days or greater.Of 5,951 adults with atrial fibrillation who were new users of dabigatran, 49% had prevalent atrial fibrillation and at least 6 months of continuous follow-up. Of these, 89% used dabigatran as the only oral anticoagulant, whereas the remainder filled prescriptions for at least 1 other oral anticoagulant during the follow-up period. Among those using dabigatran alone (n = 2,713), the mean MPR was 0.73 (standard error = 0.30), 41% were nonadherent with therapy, and 32% had gaps of 60 days or greater. Among those observed for 9 (or 12) months who used dabigatran alone, rates of nonadherence were 47% (49%), whereas 48% (49%) discontinued therapy during follow-up. Rates of adherence and persistence were similar for patients with incident atrial fibrillation.Nonadherence to dabigatran was common among patients with atrial fibrillation. Future studies are needed to understand the reasons for nonadherence.

This article aims to evaluate the real world risk of gastrointestinal bleeding among users naïve to dabigatran. We adopted a self-controlled case series design. We sampled 1215 eligible adult participants who were continuous insured users between July 1, 2010 and March 31, 2012 with use of dabigatran and at least one gastrointestinal bleeding episode. We used a conditional Poisson regression to estimate incidence rate ratios. The population consisted of 64.69% of male and 60.25% patients equal to or greater than age 65 at start of observation. After adjustment for time-variant confounders, the incidence rate of gastrointestinal bleeding was similar during dabigatran risk period and non-exposed period (incidence rate ratio [IRR] = 1.01, 95% confidence interval [CI] 0.90, 1.15). There was no significant difference in GI incidence rate between periods of dabigatran and warfarin (IRR = 0.99, 95% CI 0.75–1.31). Among this database of young and healthy participants, dabigatran was not associated with increased incidence rate of GI bleeding compared with non-exposed period among naïve dabigatran users. We did not detect an increased risk of GI bleeding over dabigatran vs warfarin risk period. Along with other studies on safety and effectiveness, this study should help clinicians choose the appropriate anticoagulant for their patients.

Objectives To determine the real world safety of dabigatran or rivaroxaban compared with warfarin in terms of gastrointestinal bleeding. Design Retrospective cohort study. Setting Large administrative database of commercially insured people in United States from 1 October 2010 through 31 March 2012. Participants Enrollees with a prescription of warfarin, dabigatran, or rivaroxaban between 1 October 2010 and 31 March 2012, who were aged 18 years or older, had continuous enrollment and no oral anticoagulant use during the six months before the entry date, with known age and sex, and with no gastrointestinal bleeding for at least six months before the cohort entry date. The final study sample of 46 163 patients included 4907 using dabigatran, 1649 using rivaroxaban, and 39 607 using warfarin. Main outcome measure Time to gastrointestinal bleeding. Hazard ratios were derived from Cox proportional hazard models with propensity score weighting and robust estimates of errors. Results Dabigatran users tended to be older (dabigatran v rivaroxaban v warfarin: 62.0 v 57.6 v 57.4 years) and more likely to be male (69% v 49% v 53%). The rate of gastrointestinal bleeding was highest among dabigatran users and lowest among rivaroxaban users (dabigatran v rivaroxaban v warfarin: 9.01 v 3.41 v 7.02 cases per 100 person years). After adjustment for potentially confounding covariates, there was no evidence of a statistically significant difference in the risk of gastrointestinal bleeding between dabigatran and warfarin users (adjusted hazard ratio 1.21, 95% confidence interval 0.96 to 1.53) or between rivaroxaban and warfarin users (0.98, 0.36 to 2.69). Conclusions Although rates of gastrointestinal bleeding seem to be similar in this commercially insured sample of adults in the United States, we cannot rule out as much as a 50% increase in the risk of gastrointestinal bleeding with dabigatran compared with warfarin or a more than twofold higher risk of bleeding with rivaroxaban compared with warfarin.

ImportanceHypertension is common and costly. Over the past decade, new antihypertensive therapies have been developed, several have lost patent protection and additional evidence regarding the safety and effectiveness of these agents has accrued.ObjectiveTo examine trends in the use of antihypertensive therapies in the United States between 1997 and 2012.Design, setting and participantsWe used nationally representative audit data from the IMS Health National Disease and Therapeutic Index to examine the ambulatory pharmacologic treatment of hypertension.Outcome measuresOur primary unit of analysis was a visit where hypertension was a reported diagnosis and treated with a pharmacotherapy (treatment visit). We restricted analyses to the use of six therapeutic classes of antihypertensive medications among individuals 18 years or older.ResultsAnnual hypertension treatment visits increased from 56.9 million treatment visits (95% confidence intervals [CI], 53.9-59.8) in 1997 to 83.3 million visits (CI 79.2-87.3) in 2008, then declined steadily to 70.9 million visits (CI 66.7-75.0) by 2012. Angiotensin receptor blocker utilization increased substantially from 3% of treatment visits in 1997 to 18% by 2012, whereas calcium channel blocker use decreased from 27% to 18% of visits. Rates of diuretic and beta-blocker use remained stable and represented 24%-30% and 14-16% of visits, respectively. Use of direct renin inhibitor accounted for fewer than 2% of annual visits. The proportion of visits treated using fixed-dose combination therapies increased from 28% to 37% of visits.ConclusionsSeveral important changes have occurred in the landscape of antihypertensive treatment in the United States during the past decade. Despite their novel mechanism of action, the adoption rate of direct renin inhibitors remains low.

Briefly introduced the status of MAC protocol for underwater acoustic communication, By improving the existing TopDisc algorithms, described the network topology needed by this paper and Proposed a suitable MAC layer protocol F-MAC for underwater communication. This protocol doesn't require synchronization and use the wasted time caused by RTS/CTS's handshake. The Simulation results show that, this protocol has a certain applicability for a network topology organized by TopDisc algorithm, and can improve the throughout capacity of the whole network and reduce network latency.