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Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26-1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27-1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17-1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban.

Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran, or rivaroxaban. This retrospective cohort study evaluated newly-anticoagulated NVAF patients in the MarketScan® data population from 01/01/2012 through 12/31/2014. Discontinuation was defined as a lack of subsequent prescription of the index drug within 30 days after the last supply day of the last prescription. A Cox model was used to estimate the hazard ratio (HR) of discontinuation, adjusted for age, sex, and comorbidities. Among 45,361 eligible NVAF patients, 15,461 (34.1%) initiated warfarin; 7,438 (16.4%) apixaban; 4,661 (10.3%) dabigatran; and 17,801 (39.2%) initiated rivaroxaban treatment. Compared to warfarin, patients who initiated dabigatran (adjusted HR [aHR]: 0.84, 95% confidence interval [CI]: 0.80-0.87, P<0.001), rivaroxaban (aHR: 0.70, 95% CI: 0.68-0.73, P<0.001), or apixaban (aHR: 0.57, 95% CI: 0.55-0.60, P<0.001) were 16%, 30%, and 43% less likely to discontinue treatment, respectively. When compared to apixaban, patients who initiated dabigatran (aHR: 1.46, 95% CI: 1.38-1.54, P<0.001) or rivaroxaban (aHR: 1.23, 95% CI: 1.17-1.28, P<0.001) were more likely to discontinue treatment. Among newly-anticoagulated NVAF patients in the real-world setting, initiation on rivaroxaban, dabigatran, or apixaban was associated with a significantly lower risk of discontinuation compared to warfarin. When compared to apixaban, patients who initiated treatment with warfarin, dabigatran, or rivaroxaban were more likely to discontinue treatment.

Summary Background Limited data are available about the real‐world safety of non‐vitamin K antagonist oral anticoagulants (NOACs). Objectives To compare the major bleeding risk among newly anticoagulated non‐valvular atrial fibrillation (NVAF) patients initiating apixaban, warfarin, dabigatran or rivaroxaban in the United States. Methods and results A retrospective cohort study was conducted to compare the major bleeding risk among newly anticoagulated NVAF patients initiating warfarin, apixaban, dabigatran or rivaroxaban. The study used the Truven MarketScan® Commercial & Medicare supplemental US database from 1 January 2013 through 31 December 2013. Major bleeding was defined as bleeding requiring hospitalisation. Cox model estimated hazard ratios (HRs) of major bleeding were adjusted for age, gender, baseline comorbidities and co‐medications. Among 29 338 newly anticoagulated NVAF patients, 2402 (8.19%) were on apixaban; 4173 (14.22%) on dabigatran; 10 050 (34.26%) on rivaroxaban; and 12 713 (43.33%) on warfarin. After adjusting for baseline characteristics, initiation on warfarin [adjusted HR (aHR): 1.93, 95% confidence interval (CI): 1.12–3.33, P=.018] or rivaroxaban (aHR: 2.19, 95% CI: 1.26–3.79, P=.005) had significantly greater risk of major bleeding vs apixaban. Dabigatran initiation (aHR: 1.71, 95% CI: 0.94–3.10, P=.079) had a non‐significant major bleeding risk vs apixaban. When compared with warfarin, apixaban (aHR: 0.52, 95% CI: 0.30–0.89, P=.018) had significantly lower major bleeding risk. Patients initiating rivaroxaban (aHR: 1.13, 95% CI: 0.91–1.41, P=.262) or dabigatran (aHR: 0.88, 95% CI: 0.64–1.21, P=.446) had a non‐significant major bleeding risk vs warfarin. Conclusion Among newly anticoagulated NVAF patients in the real‐world setting, initiation with rivaroxaban or warfarin was associated with a significantly greater risk of major bleeding compared with initiation on apixaban. When compared with warfarin, initiation with apixaban was associated with significantly lower risk of major bleeding. Additional observational studies are required to confirm these findings.

Abstract Introduction: KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). Methods: HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity. Results: The HRQoL population included patients randomly assigned to pembrolizumab (n = 298) and placebo (n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, −8.4; 95% CI: −11.7 to −5.1) versus pembrolizumab (−4.0; 95% CI: −6.4 to −1.6; difference vs. placebo: 4.4; 95% CI: 0.5–8.4; nominal p = 0.0142). Similarly, a greater decline in the EQ-5D-3L visual analog scale score was observed with placebo (−6.9; 95% CI: −9.4 to −4.5) versus pembrolizumab (−2.7; 95% CI: −4.5 to −1.0; difference vs. placebo: 4.2; 95% CI: 1.2–7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58–1.25; nominal p = 0.1993). Conclusion: Patients receiving placebo showed a greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.

Background: Previous studies have documented substantial differences by patient race/ethnicity and insurance in the use of highvolume surgical providers. The extent to which regional availability of surgical capabilities explains such differences has not been examined. Objectives: To examine the existence of racial/ ethnic and payer differences in using high-volume hospitals and surgeons for coronary artery bypass graft (CABG) in the state of Florida and to study the role of regional availability of high-volume providers in explaining the differences. Research Design: We conducted descriptive analysis of the distribution of CABG providers and patient populations by race/ethnicity and insurance across the 19 Hospital Referral Regions (HRRs) in Florida. We estimated logistic regressions of using a high- volume provider to derive estimates of overall group differences. We further estimated models with HRR fixed effects to derive within-HRR differences. We derived implications by comparing findings based on the 2 sets of models. Results: Non-Hispanic black patients were 58% as likely (95% CI: 52%, 65%), Hispanic patients were 84% as likely (95% CI:77%, 90%), to have received CABGs at a high-volume hospital, compared with non-Hispanic whites. Controlling for inter-HRR differences eliminated almost all racial/ethnic differences. Substantial differences in using high-volume providers existed between Medicaid/uninsured and privately insured patients and such differences persisted within HRRs. Conclusions: Unequal distribution of CABG capabilities coupled with racial/ethnic concentration in residence across Florida HRRs accounted for almost all racial/ethnic differences in using highvolume hospitals. Factors other than availability of surgical resources were responsible for differences between Medicaid/uninsured and privately insured patients.

This review of minority health describes the existing health disparities, the barriers to healthcare access and utilization, the role of three social determinants of health [i.e., (1) socioeconomic status, (2) education, and (3) stress and/or depression], the existing public-policies; and a health literacy strategy addressing social determinants of health to reduce disparities and improve outcomes in African-American women undergoing Percutaneous Coronary Intervention (PCI). Insurance, geography, facility-types, physician referral-bias, and cultural-differences pose as potential significant barriers to healthcare access and utilization. Likewise, lower socioeconomic-status, lack of education, and higher stress and/or depression is associated with adverse health-outcomes for this population. Although the elimination of health disparities is a national priority, comprehensive educational approaches focusing on cross-cultural communication, language barriers, cultural-sensitivity, and cultural-competence are needed.

Obesity and morbid obesity represent one of the major public health problems in the United States (U.S.) that affects nearly one-third of the adult American population. Gastric bypass (GB) is a complex operation, performed in a high-risk morbidly obese population, requiring well-trained surgeons and well-equipped hospital facilities to ensure optimal surgical outcomes. The volume-outcomes relationship is well-established for providers (both surgeons and hospitals) performing GB procedures. However, the findings of improved outcomes after GB for high volume providers have been attributed only to the high volume of GB and not the volume of other non-gastric bypass (non-GB) procedures. The studies in this dissertation were undertaken to examine the effect of provider's (general surgeon and hospital) non-GB complex (non-GB C) and non-complex (non-GBNC) volume on in-hospital complications and length of stay (LOS) for patients undergoing GB. The population-based studies used a combination of various existing retrospective data to address the research objectives. The datasets used include: a two-year (2003-2004) Florida hospital inpatient discharge data as the main analytic dataset, the 2003-2005 work Relative Value Units (RVU) data (available from the Physician Fee Schedule from the Centers of Medicare and Medicaid, to segment the provider's non-GB case load into non-GBC and non-GBNC procedures performed by a provider per year), 2005 Florida hospital characteristics file, 2005 Florida surgeon characteristics file, and 2004 Area Resource File data. Separate generalized estimating equation (GEE) regression models, adjusting standard errors for the non-nested surgeon and hospital cluster effect, were constructed for each outcome: composite complications (one or more complications), technical complications (including unexpected reoperations, splenic injury, hemorrhage, anastomotic leaks, small bowel obstructions, and wound), systemic complications (including pulmonary, cardiac, thromboembolic, genitourinary tract, and postoperative shock), and LOS. Covariates included were patient characteristics, year, surgeon GB volume, and hospital characteristics. In adjusted analyses, the gastric bypass patients operated by general surgeons with high non-GBNC volume (>142 procedures/year) had 70% and 88% higher likelihood of composite and systemic complications, respectively. In contrast, those operated at hospitals with high non-GBNC volume (>6,478 procedures/year) had 49% and 40% lower likelihood of composite and technical complications, respectively. There was no clear association between providers' high non-GBC volume and adverse outcomes. Furthermore, patients operated by general surgeons with high GB volume (>50 GBs/year) had 27% and 41% lower likelihood of composite and systemic complications, respectively. However, those operated at hospital's with high GB volume (>125 GBs/year) had 30% lower likelihood of technical complications. The study findings suggest that while provider GB volume matters for in-hospital complications, the complexity of overall surgical load also matters for general surgeons but the overall scale matters for hospitals to deliver better in-hospital outcomes for GB. In particular, the outcomes may improve if GB patients avoided general surgeons with a high volume of non-complex procedures and if GB patients avoided hospitals with low total volume.

Pseudomonas aeruginosa is an ESKAPE pathogen associated with difficult-to-treat burn wound and surgical-site infections. This study aimed to characterise an extensively drug resistant (XDR) P . aeruginosa isolate (designated PAW1) and to investigate the antibiofilm and antipersister effect of acetic acid on PAW1. PAW1 was identified using biotypic (VITEK) and genotypic (16S rDNA) analysis. Minimum inhibitory concentration (MIC) and disc susceptibility testing showed high level resistance against all antibiotics from classes including beta lactams, cephems, carbapenems and fluoroquinolones. It was therefore identified as extensively drug resistant (XDR), showing resistance to all antibiotics except for, aminoglycoside (gentamicin and netilmicin) and lipopeptides (polymyxin B). Time kill assays showed antibiotic tolerant, persister cell formation in presence of 100X MICs of gentamicin and polymyxin B. Other virulence traits such as ability to produce lipase, protease, haemolysin, and siderophores and to form biofilms were additional factors which may contribute to its pathogenicity. PAW1 showed promising susceptibility against acetic acid with MIC and minimum biofilm inhibitory concentration of 0.156% (v/v). Percent viability of PAW1 was dependent on dose and treatment time of acetic acid. 0.625% acetic acid treatment of 5 minutes was effective in killing >90% planktonic cells showing lesser toxicity to L929 cells (IC 50 = 0.625%). Biofilm disruption caused due to acetic acid was also dose dependent, showing 40.57% disruption after treatment with 0.625% acetic acid for 5 minutes. FESEM imaging and live dead staining of planktonic and biofilm forms of PAW1 confirmed that acetic acid treatment caused 19.04% of cell shrinkage and disruption of extracellular matrix resulting in killing of cells. Antipersister activity of acetic acid was demonstrated by showing complete killing of PAW1 at 4X MIC. Overall, this study characterised an XDR isolate P . aeruginosa showing resistance and tolerance to various antibiotics. Antipersister and antibiofilm effect of acetic acid demonstrates the importance of forgotten topical agents as an effective strategy to treat XDR pathogens.

The frequency of infections associated with multidrug resistant has risen substantially in India. The use of next-generation sequencing (NGS) techniques combined with comparative genomics has great potential for tracking, monitoring, and ultimately controlling the spread of this troublesome pathogen. Here, we investigated the whole genome sequences of 47 A from India. In brief, genomes were analyzed for the presence of antibiotic resistance genes (ARGs), virulence factors genes (VFGs), and mobile genetic elements (MGEs) using various in silico tools. The AbaR-type resistance islands (AbaRIs) were detected by examining the genetic environment of the chromosomal gene. Multilocus sequence types were determined using the Pasteur scheme. The eBURST and whole genome SNPs-based phylogenetic analysis were performed to analyze genetic diversity between genomes. A larger number of isolates belonging to the ST2 genotype was observed. The SNPs-based phylogenetic analysis showed a diversity between compared genomes. The predicted resistome showed the presence of intrinsic and acquired ARGs. The presence of plasmids, insertion sequences, and resistance islands carrying putative ARGs conferring resistance to antibiotics, quaternary ammonium compounds, and heavy metals was predicted in 43 (91%) genomes. The presence of putative VFGs related to adherence, biofilm formation and iron uptake was observed in the study. Overall, the comprehensive genome analysis in this study provides an essential insight into the resistome, virulome and mobilome of isolates from India.

[This corrects the article DOI: 10.3389/fcimb.2022.997897.].