Multispecialty Physician Online Survey Reveals That Burnout Related to Adverse Event Involvement May Be Mitigated by Peer Support.

OBJECTIVES: Involvement in adverse events can negatively impact physician well-being. Because burnout is increasingly recognized as a threat to patient safety, we examined the relationship between physician adverse event involvement and burnout as well as facilitators and barriers to support among physicians experiencing burnout. METHODS: We surveyed physicians in the United States who are members of the networking platform, Doximity. We conducted quantitative and qualitative analyses investigating experiences with adverse events, the impact of adverse events, the type of support the physician sought and received after the event, and burnout. RESULTS: Across specialties, involvement in an adverse event and burnout was common. Most respondents involved in an adverse event experienced emotional impact, but only a minority received support. Those reporting that the error resulted in emotional impact were more likely to experience burnout (adjusted odds ratio, 1.90; 95% confidence interval, 1.18-3.07); this association was mitigated by the most common form of support sought, peer support (adjusted odds ratio for burnout among those who received peer support versus those who did not, 0.65; 95% confidence interval, 0.52-0.82). Barriers to support after an adverse event include punitive culture and systems factors such as administrative bureaucracy. Facilitators that emerged include peer, professional, and spiritual support, mentorship, helping others, the learning environment, and improved/flexible working hours. CONCLUSIONS: Physicians who experienced emotional repercussions from adverse events were more likely to report burnout compared with those who did not. Respondents proposed barriers and facilitators to support that have not been widely implemented. Peer support may help mitigate physician burnout related to adverse events.

Application of Pteris vittata L. for phytoremediation of arsenic and biomonitoring of the process through cyto-genetic biomarkers of Trigonella foenum-graecum L.

The arsenic (As) contamination demands its remediation from the environment which is naturally possible by the application of Pteris vittata L. However, biomonitoring of phytoremediation potential of P. vittata at chromosomal and DNA level is still meager. The present study was designed to biomonitor the phytoremediation efficiency of P. vittata through phytotoxic and cyto-genotoxic biomarkers assessment using Trigonella foenum-graecum L. (Fenugreek; Methi) as test system. Study revealed hyperaccumulation potential of P. vittata which extracted arsenic in its tissues. Biomonitoring evaluation depicted that phytotoxic damage was reduced in Trigonella exposed to remediated soil, which was revealed through reduced electrolyte leakage, hydrogen peroxide and MDA content. Moreover, cyto-genetic endpoints like mitotic depression (44.03%), relative abnormality rate (16.6%) and chromosomal abnormality frequency (1.06%) were also lesser in test plants grown in remediated soil compared to those grown in non-remediated soil. Along with this various chromosomal aberrations like stickiness, breaks, laggards, bridges, fragmentations and micronuclei were also augmented in test plants exposed to non-remediated arsenic enriched soil. It was evident that arsenic enriched soil caused toxicity to plants in dose-dependent manner that was assessable through the analysis of biochemical parameters and cyto-genetic biomarkers. The cyto-genetic biomarkers are very efficient, simple and non-expensive tools to biomonitor arsenic toxicity at chromosomal as well as DNA level to assess the remediation potential of P. vittata in field conditions.

The Abrupt Expansion of Ambulatory Telemedicine: Implications for Patient Safety.

The exponential growth of telemedicine in ambulatory care triggered by the COVID-19 public health emergency has undoubtedly impacted the quality of care and patient safety. In particular, the increased adoption of remote care has impacted communication, care teams, and patient engagement, which are key factors that impact patient safety in ambulatory care. In this perspective, we draw on a scoping review of the literature, our own clinical experiences, and conversations with patient safety experts to describe how changes in communication, care teams, and patient engagement have impacted two high priority areas in ambulatory safety: diagnostic errors and medication safety. We then provide recommendations for research funders, researchers, healthcare systems, policy makers, and healthcare payors for how to improve patient safety in telemedicine based on what is currently known as well as next steps for how to advance understanding of the safety implications of telemedicine utilization.

Evaluation of Phytoremediation Potential of Pteris vittata L. on Arsenic Contaminated Soil Using Allium cepa Bioassay.

The present study assessed the utility of Allium cepa based cyto-genotoxicity bioassays in evaluating the arsenic toxicity and remediation potential of Pteris vittata on contaminated soil of Lakhimpur-Kheri district. Untreated and P. vittata treated soil extracts were used for cyto-genotoxicity tests in A. cepa. Results showed that P. vittata extracted high concentration of arsenic, which ranged from 220 to 1420 mgkg-1 in different soils. Cyto-genotoxic assessment of A. cepa showed that extract of P. vittata treated soil had lower cyto-genotoxic effects as compared to untreated soil. A higher mitotic index (10%) while lower mitotic depression (29%), relative abnormality rate (10%), chromosomal aberrations (1%) and micronuclei (2%) were detected in root meristematic cells of A. cepa exposed to remediated soil extract in comparison to untreated soil. The studies provide a simple, rapid and economic cyto-genotoxicity bioassay tool for evaluating toxicity of contaminated soils of contaminated soils as well as revealed the phytoremdiation property of P. vittata against arsenic toxicity.

Corrigendum to "Effectiveness and Safety of Oral Anticoagulants in Adults with Non-valvular Atrial Fibrillation Patients and Concomitant Coronary/Peripheral Artery Disease" American Journal of Medicine 131:09 (2018): 1074-1085.e4.

RESULTS: There were 33,269 apixaban-warfarin, 9,345 dabigatran-warfarin, and 42,156 rivaroxaban-warfarin matched pairs, with a median follow-up of 4-5 months. Compared with warfarin, apixaban was associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.52; 95% confidence interval [95% CI], 0.43-0.62), major bleeding (HR 0.60; 95% CI, 0.55-0.66) and stroke/myocardial infarction/all-cause mortality (HR 0.70; 95%CI, 0.66-0.74); dabigatran was associated with lower rates of major bleeding (HR: 0.73; 95% CI, 0.62-0.85); dabigatran and rivaroxaban were associated with lower rates of stroke/myocardial infarction/all-cause mortality (HR 0.77; 95% CI, 0.69-0.86 and HR 0.81; 95% CI, 0.77-0.85, respectively). Rivaroxaban was associated with a lower rate of stroke/systemic embolism (HR 0.61; 95% CI, 0.53-0.71) and a higher rate of major bleeding (HR 1.10; 95%CI, 1.03-1.18) versus warfarin.

Comparative efficacy and safety of current therapies for early rheumatoid arthritis: a systematic literature review and network meta-analysis.

OBJECTIVES: This systematic literature review (SLR) and network meta-analysis (NMA) was aimed at comparing the relative efficacy and safety of abatacept (ABA) with other currently recommended therapies for patients with early RA. METHODS: An SLR (January 1998 to June 2018) was conducted including MEDLINE®, Embase, and CENTRAL databases, and grey literature. Population was adults with active RA for ≤2 years treated with biologic DMARDs as monotherapy or in combination with conventional DMARDs. A Bayesian NMA was performed using randomised controlled trials (RCTs) and comparisons for ACR50, DAS28 remission, withdrawal due to adverse events and total withdrawal where reported. RESULTS: Ninety publications pertaining to 69 studies (43 RCTs and 26 observational studies) were identified. Twenty-eight RCTs were eligible to be included in the NMA. ABA as monotherapy was similar to the combination of ABA+methotrexate (MTX) for ACR50 (RR: 0.82 [95% CI 0.51-1.35]), and DAS28 remission (RR: 0.69 [95% CI 0.37-1.3]), as well as for withdrawal due to AEs (RR: 2.35 [95% CI 0.69-7.38]) and all-cause withdrawal (RR: 1.73 [95% CI 0.905-3.35]). ABA as monotherapy and ABA+MTX were both comparable to all other therapies for the main efficacy and safety outcomes. Observational study data reported was congruous with the RCT analysis. CONCLUSIONS: The results of this NMA show similar efficacy and safety between ABA (as monotherapy or in combination with MTX) and other biologics in early RA. Further comparison of different treatment options for early RA is warranted as growing research provides evidence for the application of new novel therapies for RA.

Correction: Photocatalytic antibacterial performance of TiO2 and Ag-doped TiO2 against S. aureus. P. aeruginosa and E. coli.

[This corrects the article DOI: 10.3762/bjnano.4.40.].

Toxicological impact of deltamethrin on growth and nitrogen content of a rice field cyanobacterium Calothrix sp. (GUEco 1002).

Cyanobacteria are an important component in the rice field ecosystem and are a well known source of natural biofertilizer. Pesticidal application for the control of pests in rice field soil has led to several environmental problems, and poses a great threat to these beneficial microorganisms. Studies on the impact of pesticides on the diazotrophic growth and survivability of these microorganisms have recently gained much attention. The present paper describes the effects of an iterated use of the insecticide deltamethrin (2.8% EC) on the growth and nitrogen fixation capacity of the filamentous cyanobacterium Calothrix sp. (strain GUEco 1002). This organism has shown a varying degree of sensitivity to the insecticide. For evaluating the deltamethrin toxicity, the test organism was subjected to varying concentrations of deltamethrin i.e. 17.5 ppm, 35 ppm, 70 ppm and 140 ppm based upon LC50 for 20 days. The data obtained in the laboratory revealed that the treatment of the test organism with deltamethrin (17.5-140 ppm) negatively affected its growth, pigments, protein and nitrogen content in a time dose dependent manner. In contrast, carbohydrate content significantly increased with increasing concentrations of deltamethrin, this effect being more prominent at 140 ppm treatment (38%). At this high level (140 ppm), the test organism showed a significant decrease in dry weight biomass (46%), chlorophyll-a (72%), carotenoids (57%), phycocyanin (67%), protein (69%) and nitrogen content (61%) over the control. A little, but insignificant, stimulatory effect on nitrogen content was recorded at 17.5 ppm of the insecticide which however, was the opposite in the case of growth, pigments, carbohydrate and protein content.

Phyto-genotoxicity of arsenic contaminated soil from Lakhimpur Kheri, India on Vicia faba L.

The present experiment was designed to evaluate physico-chemical characteristics and phyto-genotoxicity of arsenic (As) contaminated soil collected from different sites of Lakhimpur, Uttar Pradesh (UP), India by employing Vicia faba L. The analyses included various biochemical as well as cyto-genotoxicity assays. The results showed that soil pH was slightly acidic to neutral in nature. The bulk density (1.18-1.23 gcm-3), particle density (2.51-2.59 gcm-3) and porosity (44-53%) varied in different places. The level of available nutrients, nitrogen, phosphorus and potassium was found to vary as 124-165 mgkg-1, 173-186 mgkg-1 and 48-98 mgkg-1, respectively. The maximum As levels were found in soil of Fulvareya (27.13 mgkg-1) and Atareya (24.12 mgkg-1), the level of As in water samples of these sites were 0.19 mgl-1and 0.21 mgl-1, respectively. Phytotoxicity of the As present in soils was evident through significant increases in stress metabolites, hydrogen peroxide (H2O2), malondialdehyde (MDA) and carbonyl groups in root and shoot of V. faba. Cyto-genotoxic effects were also seen through reduced mitotic index (MI) and increased mitotic depression (MD), relative abnormality rate (RAR) as well as other chromosomal abnormalities along with micronuclei in root meristematic cells of V. faba. The phytotoxicity and cyto-genotoxicity assessment suggests the harmful soil properties that might affect biota.

Real-world outcomes among patients with early rapidly progressive rheumatoid arthritis.

OBJECTIVES: To characterize treatment patterns, healthcare resource utilization (HRU), and disease activity among patients with early rapidly progressive rheumatoid arthritis (eRPRA) in the United States when treated with a first-line biologic disease-modifying antirheumatic drug (bDMARD) tumor necrosis factor-α (TNF) inhibitor or first-line abatacept. STUDY DESIGN: Observational, multicenter, retrospective, longitudinal, medical records-based, cohort study. METHODS: Patients with eRPRA were identified by anti-citrullinated protein antibody positivity, 28-joint Disease Activity Score-C-reactive protein of 3.2 or greater, symptomatic synovitis in 2 or more joints for at least 8 weeks prior to the index date, and onset of symptoms within 2 years or less of the index date. Patients received abatacept or a TNF inhibitor as first-line treatment. Patient characteristics, treatment patterns, HRU, and disease activity following bDMARD initiation were compared across the 2 groups. Odds ratios (ORs) of HRU in the first 6 months of bDMARD treatment were estimated using multivariable logistic regression to adjust for patient mix. RESULTS: There were 60 patients treated with abatacept and 192 treated with a TNF inhibitor in the first line. Those treated with first-line abatacept had lower adjusted odds of hospitalization (OR, 0.42; 95% CI, 0.18-0.95), emergency department (ED) visits (OR, 0.39; 95% CI, 0.16-0.93), and magnetic resonance imaging (MRI) (OR, 0.45; 95% CI, 0.21-0.97) than those treated with a first-line TNF inhibitor (all P <.05). Adjusted odds of achieving low disease activity as measured by clinical disease activity index within 100 days of bDMARD initiation favored first-line abatacept versus a first-line TNF inhibitor (OR, 4.37; 95% CI, 1.34-13.94; P = .01). CONCLUSIONS: Adjusting for disease severity, patients with eRPRA who were treated with first-line abatacept were less likely to have hospitalizations, ED visits, and MRI use during the first 6 months of bDMARD treatment and more likely to achieve low disease activity within 100 days of bDMARD start compared with those who received a first-line TNF inhibitor.

Treatment patterns and economic outcomes in patients with juvenile idiopathic arthritis.

Purpose: To describe health care resource utilization (HCRU) and costs among patients with juvenile idiopathic arthritis (JIA) compared to patients without JIA and to describe treatment patterns among JIA patients who initiated biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). Patients and methods: The IBM MarketScan® Commercial Database was used to identify patients aged 2-17 years with a new JIA diagnosis (index date) and 12 months continuous enrollment pre- and post-diagnosis from 2008 to 2016. JIA patients were matched to non-JIA patients on age, gender, region, and health plan type. Patients with other rheumatic or autoimmune conditions were excluded. Receipt of a biologic and/or non-biologic was evaluated on or after the new JIA diagnosis. Results: A total of 3,815 JIA patients were matched to 11,535 non-JIA patients (mean age 10.0 [SD=4.5], 69% female). Average total costs were greater for JIA patients than non-JIA controls ($18,611 [SD=$42,104; median=$8,189] versus $2,203 [SD=$9,309; median=$649], p<0.001). Outpatient pharmacy costs were 33.6% of the total costs among JIA patients compared to 18.4% among non-JIA patients (p<0.001). The proportion of inpatient cost (11.4% versus 14.3%, p<0.001) and outpatient costs (55% versus 67.4%, p<0.001) of total costs was lower among JIA patients compared to non-JIA patients. Patients with 12 months of continuous enrollment post-treatment initiation (n=2,014) were classified as non-biologic only (n=734), biologic only (n=873), and both biologic and non-biologic (n=407) users. Among biologic and non-biologic users, 41.1% and 56.8% were persistent on their index medication for 12 months. Of patients treated with a biologic only, TNF inhibitors (TNFi) comprised 87.1% of the total treatment costs. Conclusion: JIA is associated with increased costs and utilization in every HCRU category compared to matched non-JIA patients. While JIA-related costs varied by treatment cohort, patients on biologic DMARDs had substantially higher costs than patients on non-biologic DMARDs and fewer than one-half were persistent at 12 months after biologic initiation.

Effectiveness and safety of direct oral anticoagulants compared to warfarin in treatment naïve non-valvular atrial fibrillation patients in the US Department of defense population.

BACKGROUND: Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are at least non-inferior to warfarin in reducing the risk of stroke/systemic embolism (SE) among patients with non-valvular atrial fibrillation (NVAF), but the comparative risk of major bleeding varies between DOACs and warfarin. Using US Department of Defense (DOD) data, this study compared the risk of stroke/SE and major bleeding for DOACs relative to warfarin. METHODS: Adult patients with ≥1 pharmacy claim for apixaban, dabigatran, rivaroxaban, or warfarin from 01 Jan 2013-30 Sep 2015 were selected. Patients were required to have ≥1 medical claim for atrial fibrillation during the 12-month baseline period. Patients with a warfarin or DOAC claim during the 12-month baseline period were excluded. Each DOAC cohort was matched to the warfarin cohort using propensity score matching (PSM). Cox proportional hazards models were conducted to evaluate the risk of stroke/SE and major bleeding of each DOAC vs warfarin. RESULTS: Of 41,001 identified patients, there were 3691 dabigatran-warfarin, 8226 rivaroxaban-warfarin, and 7607 apixaban-warfarin matched patient pairs. Apixaban was the only DOAC found to be associated with a significantly lower risk of stroke/SE (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.39, 0.77; p < 0.001) and major bleeding (HR: 0.65; 95% CI: 0.53, 0.80; p < 0.001) compared to warfarin. Dabigatran and rivaroxaban initiation were associated with similar risk of stroke/SE (dabigatran: HR: 0.68; 95% CI: 0.43, 1.07; p = 0.096; rivaroxaban: HR: 0.83; 95% CI: 0.64, 1.09; p = 0.187) and major bleeding (dabigatran: HR: 1.05; 95% CI: 0.79, 1.40; p = 0.730; rivaroxaban: HR: 1.07; 95% CI: 0.91, 1.27; p = 0.423) compared to warfarin. CONCLUSION: Among NVAF patients in the US DOD population, apixaban was associated with significantly lower risk of stroke/SE and major bleeding compared to warfarin. Dabigatran and rivaroxaban were associated with similar risk of stroke/SE and major bleeding compared to warfarin.

Decisions and repercussions of second victim experiences for mothers in medicine (SAVE DR MoM).

BACKGROUND: The second victim effect is defined as emotional distress experienced by providers involved in mistakes. This study characterises events contributing to the second victim effect among a diverse sample of physician mothers, describes the impact on both provider and patient and seeks to determine the association between experiencing a mistake and burnout. METHODS: In this mixed-methods study, an anonymous, cross-sectional survey was posted to an online network of over 65 000 physician mothers on 17 June 2016. Self-reported involvement in a mistake provided opportunity to describe the error and impact on both provider and patient. Free-text responses were qualitatively coded to identify error types. Hypothesising that making a mistake contributes to burnout, self-reported burnout was examined using a single question. We used logistic regression to estimate the association between involvement in a mistake and burnout, adjusting for practice years, setting and specialty. RESULTS: 5782 members completed the survey for an estimated response rate of 16.5% based on 34956 active users during the survey period. 2859 respondents reported involvement in a mistake (49%), which was associated with higher reported burnout (p<0.0001). 56% of those reporting a mistake provided descriptions. Qualitative analysis revealed that self-reported treatment errors were more common and diagnostic errors were most often reported to result in greater patient harm. Of those involved in a mistake, 82% reported feelings of guilt; 2.2% reported reducing clinical workload, taking leave or leaving the profession. CONCLUSIONS: Physician mothers involved in errors experience negative outcomes and may be at increased risk for burnout. Additional research should focus on strategies to mitigate burnout associated with the second victim effect, particularly among women physicians and those with family responsibilities.

One-step fabrication of recycled Ag nanoparticles/graphene aerogel with high mechanical property for disinfection and catalytic reduction of 4-nitrophonel.

Fabrication of smart composites with expected removal property and excellent recycle performance for micro-pollutants including microbes and organic contaminants without formation of second-pollutants is highly desired. In this work, Ag nanoparticles (Ag NPs) homogenously loaded on graphene aerogel (GA) as Ag NPs/GA was facilely fabricated by a one-step process and the composite was characterized in detail. The bactericidal performance of the composite towards escherichia coli (E. coli) was evaluated and the catalytic activity was probed for the reduction of 4-nitrophenol (4-NP). Results showed that the composite contains about 44.4 wt% of well-dispersed Ag NPs with diameters ranging from 10 to 100 nm. Compared with the bare Ag particles or GA, Ag NPs/GA exhibited an enhanced bactericidal performance for 8-lg of E. coli cells with 100% inactivation rate and catalytic activity for 4-NP with 96.6% degradation rate, respectively. Impressively, the 100% inactivation rates for 8-lg of E. coli remained after 7 recycles and the releasing silver was negligible compared with the loaded Ag NPs. Moreover, the used Ag NPs/GA for the catalytic reduction of 4-NP can be regenerated easily by calcination in inert atmosphere. Hence, Ag NPs/GA can be regarded as a promising and cost-efficient composite for environmental remediation.

Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients.

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Real-World Comparative Effectiveness, Safety, and Health Care Costs of Oral Anticoagulants in Nonvalvular Atrial Fibrillation Patients in the U.S. Department of Defense Population.

BACKGROUND: The ARISTOTLE trial demonstrated that apixaban had significantly lower rates of stroke/systemic embolism (SE) and major bleeding than warfarin; however, no direct clinical trials between apixaban and other direct oral anticoagulants (DOACs) are available. Few real-world studies comparing the effectiveness and safety between DOACs have been conducted. OBJECTIVE: To compare effectiveness, safety, and health care costs among oral anticoagulants (OACs) for nonvalvular atrial fibrillation (NVAF) patients in the U.S. Department of Defense (DoD) population. METHODS: Adult NVAF patients initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from U.S. DoD data from January 1, 2013, to September 30, 2015. The first OAC claim date was designated as the index date. Patients initiating another OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risk of stroke/SE and major bleeding for each OAC versus apixaban. Generalized linear and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE-related and major bleeding-related medical costs. RESULTS: Of the 41,001 eligible patients, 7,607 warfarin-apixaban, 4,129 dabigatran-apixaban, and 11,284 rivaroxaban-apixaban pairs were matched. Warfarin (HR = 1.84; 95% CI = 1.30-2.59; P < 0.001) and rivar-oxaban (HR = 1.46; 95% CI = 1.08-1.98; P = 0.015) were associated with a significantly higher risk of stroke/SE compared with apixaban. Dabigatran (HR = 1.17; 95% CI = 0.68-2.03; P = 0.573) was associated with a numerically higher risk of stroke/SE compared with apixaban. Warfarin (HR = 1.53; 95% CI = 1.24-1.89; P < 0.001), dabigatran (HR = 1.76; 95% CI = 1.27-2.43; P < 0.001), and rivaroxaban (HR = 1.59; 95% CI = 1.34-1.89; P < 0.001) were associated with higher risks of major bleeding compared with apixaban. Compared with apixaban, patients prescribed warfarin incurred numerically higher all-cause total health care costs per patient per month (PPPM) ($2,498 vs. $2,277; P = 0.148) and significantly higher stroke/SE-related ($118 vs. $46; P = 0.012) and major bleeding-related ($166 vs. $76; P = 0.003) medical costs. Dabigatran patients incurred numerically higher all-cause total health care PPPM costs ($2,372 vs. $2,143; P = 0.150) and stroke/SE-related medical costs ($61 vs. $32; P = 0.240) but significantly higher major bleeding-related costs ($114 vs. $58; P = 0.025). Rivaroxaban patients incurred significantly higher all-cause total health care costs ($2,546 vs. $2,200; P < 0.001) and major bleeding-related medical costs PPPM ($137 vs. $69; P < 0.001) but numerically higher stroke/SE-related medical costs PPPM ($58 vs. $38; P = 0.057). CONCLUSIONS: Among NVAF patients in the U.S. DoD population, warfarin and rivaroxaban were associated with a significantly higher risk of stroke/SE and major bleeding compared with apixaban. Dabigatran use was associated with a numerically higher risk of stroke/SE and a significantly higher risk of major bleeding compared with apixaban. Warfarin and dabigatran incurred numerically higher all-cause total health care costs compared with apixaban. Rivaroxaban was associated with significantly higher all-cause total health care costs compared with apixaban. DISCLOSURES This study was funded by Bristol-Myers Squibb and Pfizer, which were involved in the study design, as well as in the writing and revision of the manuscript. Keshishian and Zhang are paid employees of STATinMED Research, which was paid by Bristol-Myers Squibb and Pfizer to conduct this study and develop the manuscript. Gupta, Rosenblatt, Hede, and Nadkarni are paid employees of Bristol-Myers Squibb. Trocio, Dina, Mardekian, Liu, and Shank are paid employees of Pfizer.

Effectiveness and Safety of Anticoagulants in Adults with Non-valvular Atrial Fibrillation and Concomitant Coronary/Peripheral Artery Disease.

BACKGROUND: Direct oral anticoagulants (DOAC) are at least non-inferior to warfarin in efficacy and safety among patients with nonvalvular atrial fibrillation. Limited evidence is available regarding outcomes for nonvalvular atrial fibrillation patients with coronary/peripheral artery disease. METHODS: Non-valvular atrial fibrillation patients aged ≥65 years diagnosed with coronary/peripheral artery disease in the US Medicare population, newly initiating DOACs (apixaban, rivaroxaban, dabigatran) or warfarin were selected from January 1, 2013 to September 30, 2015. Propensity score matching was used to compare DOACs vs warfarin. Cox proportional hazards models were used to estimate the risk of stroke/systemic embolism, major bleeding, and composite of stroke/myocardial infarction/all-cause mortality. RESULTS: There were 15,527 apixaban-warfarin, 6,962 dabigatran-warfarin, and 25,903 rivaroxaban-warfarin-matched pairs, with a mean follow-up of 5-6 months. Compared with warfarin, apixaban was associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.37-0.62), major bleeding (HR 0.66; 95% CI, 0.58-0.75), and stroke/myocardial infarction/all-cause mortality (HR 0.63; 95% CI, 0.58-0.69); dabigatran and rivaroxaban were associated with lower rates of stroke/myocardial infarction/all-cause mortality (HR 0.79; 95% CI, 0.70-0.90 and HR 0.87; 95% CI, 0.81-0.92, respectively). Rivaroxaban was associated with a lower rate of stroke/systemic embolism (HR 0.72; 95% CI, 0.60-0.89) and a higher rate of major bleeding (HR 1.14; 95% CI, 1.05-1.23) vs warfarin. CONCLUSIONS: All DOACs were associated with lower stroke/myocardial infarction/all-cause mortality rates compared with warfarin; differences were observed in rates of stroke/systemic embolism and major bleeding. Findings from this observational analysis provide important insights about oral anticoagulation therapy among non-valvular atrial fibrillation patients with coronary/peripheral artery disease and may help physicians in the decision-making process when treating this high-risk group of patients.

Teratogenic Effects of Third-Generation Antiepileptic Drug, Pregabalin: An In vivo Study.

BACKGROUND: In the recent past, many third-generation antiepileptic drugs (AEDs) including Pregabalin (PGB) were launched for the treatment of diverse forms of epilepsy with better efficacy and safety profile than first-and-second-generation AEDs, but their teratogenic safety has not been established so far. OBJECTIVE: The present study has been undertaken to evaluate the reproductive and teratogenic potential (external and skeletal) of a novel and third generation AED, PGB in pregnant albino rats. METHODS: In this study, pregnant subjects were exposed to clinically relevant doses (41, 82 and 123 mg) of PGB from gestation days 6-20, and sacrificed on GD-21, and their fetuses were collected and examined to identify the birth defects and skeletal anomalies. RESULTS: This study revealed that prenatal exposure to PGB induced dose-dependent substantial fetal resorptions, litter size, fetal length and weight; and variety of minor external and internal malformations in fetuses predominant with limbs, tail, eyes, abdomen including hemorrhages, and poor skeletal ossification. CONCLUSION: Thus, PGB was found to be teratogenic in rats at equivalent therapeutic doses, hence precaution should be taken before prescribing PGB to pregnant women with epilepsy.