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The latest variant of coronavirus is omicron. The World Health Organization (WHO) designated variation 'B.1.1.529' named omicron as a variant of concern (VOC) on 26 November 2021. By September 2020, it will have infected over 16 million patients and killed over 600,000 people over the world. This very infectious viral illness still poses a danger to world health; it has also become the greatest problem the world is facing and become the main area of research. The development of vaccines is insufficient to stop their spread and serious effects. Despite several reputable pharmaceutical firms claiming to have developed a cure for COVID-19. For that purpose, the field-based 3D-QSAR model has been used to analyze a series of anti-diabetic drugs to repurpose them against COVID-19. The LOO verified partial least square (PLS) model generates satisfactory q 2 (0.4) and r 2 (0.5) values. By using this model 10 compounds were screened out of 55 FDA approved anti-diabetic drugs (built-up library). Additionally, these substances were examined using molecular docking screening and ADMET. Finally, the drugs L8 , and L23 were discovered to be the lead drugs. Density functional theory at the B3LYP/6-311G* technique was used to examine structural geometries, electronic characteristics, and molecular electrostatic potential (MEP). This work will greatly assist in the detection and development of leads for early drug development to control COVID-19.Communicated by Ramaswamy H. Sarma.

Background: ST-segment myocardial infarction (STEMI) is typically associated with increased age, but there is an important group of patients who suffer from STEMI under the age of 50 who are not well characterized in studies., Methods and Results: We analysed results from Myocardial Ischemia National Audit Project (MINAP) from the United Kingdom (UK) between 2010 and 2017 and the National Inpatient Sample (NIS) from the United States of America (USA) between 2010 and 2018. After exclusion criteria, there were 32 719 STEMI patients aged ≤50 from MINAP, and 238 952 patients' ≤50 from the NIS. We analysed temporal trends in demographics, management, and mortality. The proportion of females increased, 15.6% (2010-2012) to 17.6% (2016-2017) (UK) and 22.8% (2010-2012) to 23.1% (2016-2018) (USA). The proportion of white patients decreased, from 86.7% (2010) to 79.1% (2017) (UK) and 72.1% (2010) to 67.1% (2017) (USA). Invasive coronary angiography (ICA) rates increased in UK (2010-2012: 89.0%, 2016-2017: 94.3%), while decreased in USA (2010-2012: 88.9%, 2016-2018: 86.2% (USA). After adjusting for baseline characteristics and management strategies, there was no difference in all-cause mortality in the UK in 2016-2017 compared to 2010-2012 (OR:1.21, 95% CI:0.60-2.40), but there was a decrease in the USA in 2016-2018 compared to 2010-2012 (OR: 0.84, 95% CI: 0.79-0.90)., Conclusion: The demographics of young STEMI patients have temporally changed in the UK and USA, with increased proportions of females and ethnic minorities. There was a significant increase in the frequency of diabetes mellitus over the respective time periods in both countries., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Obesity's effect on outcomes in heart failure (HF) patients with reduced versus maintained ejection fraction (HFrEF and HFpEF) remains debatable. We evaluated hospital outcomes and healthcare expenditures in these patients based on their Body Mass Index (BMI)., Methods: Using the USA National Inpatient Sample (NIS) database, patients >18 years admitted with a primary diagnosis of HFrEF or HFpEF between January 1, 2004, and August 31, 2015, were studied. Patients were stratified into the following BMI categories: underweight, normal weight, overweight, obese, and morbidly obese. Adjusted multivariable analyses using Poisson regression models were used to study the association between BMI and hospital outcomes and healthcare costs., Results: Overall, 1,699,494 patients were included. After full adjustment, obesity (OR=1.84; 95% CI: 1.22-2.76) and morbid obesity (OR=1.81; 95% CI: 1.22-2.70) increased the odds of in-hospital mortality compared with normal weight. When stratified per ejection fraction, underweight patients had higher odds of in-hospital mortality in HFrEF (OR=1.46; 95% CI: 1.06-2.01). Obese and morbidly obese patients had higher odds of in-hospital mortality in both HFrEF and HFpEF. Furthermore, obese and morbidly obese patients had a longer mean adjusted length of stay and higher health care expenses., Conclusions: Being underweight is associated with increased risk of in-hospital mortality in HFrEF patients. Obesity and morbid obesity increase the risk of in-hospital mortality and higher healthcare costs in both HFrEF and HFpEF. These findings have clinical significance for HF patients, and further research is needed to investigate the ideal weight for HF patients.

Introduction: Noninvasive cardiac diagnostic tests (NITs) for the diagnosis of coronary artery disease have been estimated to cost >$3 billion annually in the United States alone and have recently undergone scrutiny over concerns of overuse. Consequently, comparing costs of different NIT testing strategies is of urgent importance to health care planning., Methods: We utilized population-based administrative and clinical data from Ontario, Canada, to compare downstream costs between 4 available NIT testing strategies (graded exercise stress testing [GXT], stress echocardiography, cardiac computed tomography angiography [CCTA], and myocardial perfusion imaging [MPI] as well as no testing), among patients evaluated for chest pain. To compare costs among the tested (overall and by testing strategy) and nontested groups, we used a log-gamma generalized linear model to account for the skewed distribution of health care cost data, adjusting for relevant clinical covariates., Results: A total of 2,340,699 patients were included in our cohort, of whom 481,170 (21%) patients received 1 of the 4 NITs. Among patients who received a NIT, 254,492 (53%) received a GXT as their initial test, 154,137 (32%) received MPI, 69,160 (14%) received a stress echo, and 3,381 (<1%) received a CCTA. After adjustment for differences in baseline patient characteristics, receipt of any NIT was associated with an approximate 12% reduction in downstream 1-year mean costs (cost ratio = 0.88; 95% CI, 0.87, 0.89) compared with those without any testing. Comparing the different testing strategies with no testing, both GXT (cost ratio = 0.80; 95% CI, 0.79-0.81) and stress echocardiography (cost ratio = 0.82; 95% CI, 0.81-0.83) were associated with the lower downstream costs, while both MPI (cost ratio = 1.26; 95% CI, 1.25, 1.27) and CCTA (cost ratio = 1.29; 95% CI, 1.23, 1.35) were associated with higher downstream costs., Conclusions: In a large population-based cohort consisting of >2 million people evaluated for chest pain, we report that receipt of noninvasive testing was associated with a 12% reduction in downstream costs when compared with no testing. Graded exercise stress testing and stress echocardiography were associated with the least downstream costs, whereas CCTA and MPI were associated with higher costs when compared with no testing. These findings may help inform testing decisions in chest pain patients., Competing Interests: Conflicts of Interest None., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Data are limited on whether the causes of emergency department (ED) encounters for cardiovascular diseases (CVDs) and associated clinical outcomes vary by frailty status. Using the United States Nationwide ED Sample, selected CVD encounters (acute myocardial infarction [AMI], ischemic stroke, atrial fibrillation [AF], heart failure [HF], pulmonary embolism, cardiac arrest, and hemorrhagic stroke) were stratified by hospital frailty risk score (HFRS). Logistic regression was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of ED mortality among the different frailty groups. A total of 8,577,028 selected CVD ED encounters were included. A total of 5,120,843 (59.7%) had a low HFRS (<5), 3,041,699 (35.5%) had an intermediate HFRS (5 to 15), and 414,485 (4.8%) had a high HFRS (>15). Ischemic stroke was the most common reason for the encounter in the high HFRS group (66.9%), followed by hemorrhagic stroke (11.7%) and AMI (7.2%). For the low HFRS group, AF was the most common reason for the encounter (30.2%), followed by AMI (23.6%) and HF (16.8%). Compared with the low-risk group, high-risk patients had a decreased ED mortality and an increased overall mortality across most CVD encounters (p <0.001). The strongest association with overall mortality was observed among patients with a high HFRS admitted for AF (aOR 27.14, 95% CI 25.03 to 29.43) and HF (aOR 13.71, 95% CI 12.95 to 14.51) compared with their low-risk counterparts. In conclusion, patients presenting to the ED with acute CVD have a significant frailty burden, with different patterns of CVD according to frailty status. Frailty is associated with an increased all-cause mortality in patients for most CVD encounters., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Adverse childhood experiences (ACEs) such as abuse and neglect have an immediate impact on children and are associated with poorer health and behavioural outcomes in adulthood. This study examined the prevalence of ACEs and their association with socio-demographic factors, physical and mental health, morbidity and health-harming behaviours in adulthood among Americans., Method: Data for the study come from the 2019 Behavioral Risk Factor Surveillance System (BRFSS), covering a sample of 116 032 adult respondents from 22 states of the United States. Descriptive and inferential statistical techniques, including multiple logistic regression models, were employed to analyse the data., Results: At least one kind of ACE was found to be quite common among American adults, as 60% of adults had at least one kind of ACE, 22.5% had one ACE and 17% had four or more ACEs during 0-17 years of life. Of the total ACEs, 42.2% were due to abuse (physical, emotional or sexual), and 46% were due to any kind of household dysfunction. There is an increasing trend in ACEs in the United States. Adults with low socio-economic status, female, living in urban areas, gay or bisexual orientation, minority other than White and unemployed had a significantly higher prevalence of ACEs than their counterparts. ACEs were found to be significantly associated with poor physical and mental health; health-harming behaviours such as binge drinking, heavy drinking and smoking; and chronic morbidities., Conclusion: Programmes aimed at reducing ACEs and mitigating the harms of ACEs among those who have already experienced them should be strengthened to improve public health and quality of life and reduce health-harming behaviours., (© 2023 John Wiley & Sons Ltd.)

Background: The prevalence of multimorbidity in patients with acute myocardial infarction (AMI) is increasing. It is unclear whether comorbidities cluster into distinct phenogroups and whether are associated with clinical trajectories., Methods: Survey-weighted analysis of the United States Nationwide Inpatient Sample (NIS) for patients admitted with a primary diagnosis of AMI in 2018. In-hospital outcomes included mortality, stroke, bleeding, and coronary revascularisation. Latent class analysis of 21 chronic conditions was used to identify comorbidity classes. Multivariable logistic and linear regressions were fitted for associations between comorbidity classes and outcomes., Results: Among 416,655 AMI admissions included in the analysis, mean (±SD) age was 67 (±13) years, 38% were females, and 76% White ethnicity. Overall, hypertension, coronary heart disease (CHD), dyslipidaemia, and diabetes were common comorbidities, but each of the identified five classes (C) included ≥1 predominant comorbidities defining distinct phenogroups: cancer/coagulopathy/liver disease class (C1); least burdened (C2); CHD/dyslipidaemia (largest/referent group, (C3)); pulmonary/valvular/peripheral vascular disease (C4); diabetes/kidney disease/heart failure class (C5). Odds ratio (95% confidence interval [CI]) for mortality ranged between 2.11 (1.89-2.37) in C2 to 5.57 (4.99-6.21) in C1. For major bleeding, OR for C1 was 4.48 (3.78; 5.31); for acute stroke, ORs ranged between 0.75 (0.60; 0.94) in C2 to 2.76 (2.27; 3.35) in C1; for coronary revascularization, ORs ranged between 0.34 (0.32; 0.36) in C1 to 1.41 (1.30; 1.53) in C4., Conclusions: We identified distinct comorbidity phenogroups that predicted in-hospital outcomes in patients admitted with AMI. Some conditions overlapped across classes, driven by the high comorbidity burden. Our findings demonstrate the predictive value and potential clinical utility of identifying patients with AMI with specific comorbidity clustering., Competing Interests: SSZ, LYS, EK, MKR, DS, DMA MAM, MR declare no competing interests. SW is a currently an employee of GSK. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Zghebi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pericardiocentesis is undertaken in patients with cancer for diagnostic and therapeutic purposes. However, there are limited data on the frequency, characteristics and mortality of patients with different cancers undergoing pericardiocentesis., Methods: All hospitalisations of adult cancer patients (≥18 years) in the US National Inpatient Sample between January 2004 and December 2017 were included. The cohort was stratified by discharge code of pericardiocentesis and cancer, using the International Classification of Diseases. The prevalence of pericardiocentesis, patient characteristics, cancer types and in-hospital all-cause mortality were analysed between cancer patients undergoing pericardiocentesis versus not., Results: A total of 19,773,597 weighted cancer discharges were analysed, out of which 18,847 (0.1%) underwent pericardiocentesis. The most common cancer types amongst the patients receiving pericardiocentesis were lung (51.3%), haematological (15.9%), breast (5.4%), mediastinum/heart (3.2%), gastroesophageal (2.2%) and female genital cancer (1.8%), whilst 'other' cancer types were present in 20.2% patients. Patients undergoing pericardiocentesis had significantly higher mortality (15.6% vs. 4.2%, p < 0.001) compared to their counterparts. The presence of metastatic disease (aOR 2.67 95% CI 1.79-3.97), weight loss (aOR 1.48 95% CI 1.33-1.65) and coagulopathy (aOR 3.22 95% CI 1.63-6.37) were each independently associated with higher mortality in patients who underwent pericardiocentesis., Conclusion: Pericardiocentesis is an infrequent procedure in cancer patients and is most commonly performed in patients with lung, haematological and breast cancer. Cancer patients undergoing pericardiocentesis have increased mortality, irrespective of the underlying cancer type., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To investigate the utility of Charlson comorbidity index (CCI) as a measure of comorbidity burden to predict procedural outcomes after de novo cardiac implantable electronic device (CIED) implantation., Methods: All de novo CIED implantations in the United States National Inpatient Sample between 2015 and 2018 were retrospectively analyzed, stratified by CCI score (0=no comorbidity burden, 1=mild, 2=moderate, ≥3=severe). Multivariable logistic regression models were performed to examine the association between unit CCI score (scale) and in-hospital outcomes (major adverse cerebrovascular and cardiovascular events [MACCE]: composite of all-cause mortality, acute ischemic stroke, thoracic and cardiac complications, and device-related complications; and MACCE individual components)., Results: Of 474,475 CIED procedures, the distribution of CCI score was as follows: CCI=0 (17.7%), CCI=1 (21.8%), CCI=2 (18.7%), and CCI=3+ (41.8%). Charlson comorbidity index score was associated with increased odds ratios of MACCE (1.10; 95% CI, 1.09 to 1.11), all-cause mortality (1.23; 95% CI, 1.21 to 1.25), and acute stroke (1.45; 95% CI, 1.44 to 1.46). This finding was consistent across all CIED groups except the cardiac resynchronization therapy groups in which CCI was not associated with increased risk of mortality. A higher CCI score was not associated with increased odds of procedural (thoracic and cardiac) and device-related complications., Conclusion: In a nationwide cohort of CIED procedures, higher comorbidity burden as measured by CCI score was associated with an increased risk of in-hospital mortality and acute ischemic stroke, but not procedure-related (thoracic and cardiac) or device-related complications. Objective assessment of comorbidity burden is important to risk-stratify patients undergoing CIED implantation for better prognostication of their in-hospital survival., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To examine rates and predictors repeat revascularization strategies (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]) in patients with prior CABG., Methods: Using the National Inpatient Sample, patients with a history of CABG hospitalized for revascularization by PCI or CABG from January 2004 to September 2015 were included. Regression analyses were performed to examine predictors of receipt of either revascularization strategy as well as in-hospital outcomes., Results: The rate of redo CABG doubled between 2004 (5.3%) and 2015 (10.3%). Patients who underwent redo CABG were more comorbid and experienced significantly worse major adverse cardiovascular and cerebrovascular events (odds ratio [OR]: 5.36 95% CI 5.11-5.61), mortality (OR 2.84 95% CI 2.60,-3.11), bleeding (OR 5.97 95% CI 5.44-6.55) and stroke (OR 2.15 95% CI 1.92-2.41), but there was no difference in cardiac complications between groups. Thoracic complications were high in patients undergoing redo CABG (8%), especially in females. Factors favoring receipt of redo CABG compared to PCI included male sex, age < 80 years, and absence of diabetes and renal failure., Conclusion: Reoperation in patients with prior CABG has doubled in the United States over a 12-year period. Patients undergoing redo CABG are more complex and associated with worse clinical outcomes than those receiving PCI., (© 2020 Wiley Periodicals LLC.)

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals., Patients and Methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation., Results: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years., Conclusion: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD., Competing Interests: Hagit N. BarisConsulting or Advisory Role: Sanofi, Igentify LtdSpeakers' Bureau: Sanofi, Takeda, Pfizer Donald BaselHonoraria: BioMarinConsulting or Advisory Role: iQvia Deborah T. BlumenthalConsulting or Advisory Role: AstraZeneca, Novocure, Takeda Miriam BornhorstConsulting or Advisory Role: AstraZeneca/MedImmune Sara RhodeHonoraria: Myriad GeneticsSpeakers' Bureau: Myriad GeneticsTravel, Accommodations, Expenses: Myriad Genetics Roula FarahHonoraria: Novo NordiskConsulting or Advisory Role: Novo Nordisk William D. FoulkesResearch Funding: AstraZeneca David GassEmployment: X4 PharmaceuticalsHonoraria: X4 PharmaceuticalsSpeakers' Bureau: Precisionscientia Heather HampelStock and Other Ownership Interests: Genome MedicalConsulting or Advisory Role: InVitae, Genome Medical, Promega, 23andMe Jordan R. HansfordConsulting or Advisory Role: Bayer Craig HarlosTravel, Accommodations, Expenses: GlaxoSmithKline Nobuko HijiyaHonoraria: NovartisConsulting or Advisory Role: Novartis, IncyteResearch Funding: Pfizer Junne KamiharaStock and Other Ownership Interests: PanTher Therapeutics, ROME Therapeutics, TellBioHonoraria: Pfizer, NanoString Technologies, Third Rock Ventures, Foundation MedicineConsulting or Advisory Role: ROME Therapeutics, Third Rock VenturesResearch Funding: PureTech, Ribon Therapeutics, ACD BiotechnePatents, Royalties, Other Intellectual Property: Patent on drug delivery device licensed to PanTher Therapeutics, Patents on Repeat RNA biomarkers and therapeutics licensed to Rome Therapeutics, Patents on Circulating Tumor Cell Biomarkers Licensed to TellBio Inc Jeffrey KnipsteinEmployment: PRA Health SciencesConsulting or Advisory Role: Atheneum Alvaro LassalettaStock and Other Ownership Interests: Gilead SciencesConsulting or Advisory Role: Shire, Jazz Pharmaceuticals, Roche, ServierTravel, Accommodations, Expenses: Shire, Gilead Sciences Simon C. LingHonoraria: AbbvieResearch Funding: Abbvie, Gilead Sciences Michael P. LinkConsulting or Advisory Role: Incyte, ADC Therapeutics, Lilly, Steba Biotech, Mesoblast, GlaxoSmithKline, SyndaxResearch Funding: Seattle Genetics, Janssen Oncology Rebecca Loret de MolaEmployment: Huron Consulting Maura MassiminoConsulting or Advisory Role: Oncoscience, Novartis Gary MasonEmployment: Janssen Research & Development, MerckStock and Other Ownership Interests: Johnson & Johnson, MerckTravel, Accommodations, Expenses: Janssen Research & Development Kim E. NicholsStock and Other Ownership Interests: IncyteResearch Funding: Incyte/Novartis, Alpine Immune Sciences Enrico OpocherConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: AstraZeneca Michael OsbornTravel, Accommodations, Expenses: Amgen, Pfizer Benjamin OshrineHonoraria: Mesoblast Alyssa ReddyConsulting or Advisory Role: Novartis, AstraZeneca Lara ReichmanResearch Funding: Illumina Marc RemkeStock and Other Ownership Interests: Bayer, BB Biotech Ventures, BioNTech AG, InVitae, IDEXX Laboratories Kami Wolfe SchneiderOther Relationship: Journal of Genetic Counseling Duncan StearnsConsulting or Advisory Role: AstraZenecaOpen Payments Link: https://openpaymentsdata.cms.gov/physician/792397 Patrick TombocHonoraria: Unicare Health PlanConsulting or Advisory Role: UniCare Health Plan An Van DammeConsulting or Advisory Role: Octapharm, Pfizer, BayerResearch Funding: Johnson & JohnsonTravel, Accommodations, Expenses: Pfizer, Sobi, Shire, Roche Ira WinerResearch Funding: Oncoceutics David S. ZieglerConsulting or Advisory Role: Bayer, AmgenTravel, Accommodations, Expenses: Bayer Cynthia HawkinsConsulting or Advisory Role: BayerPatents, Royalties, Other Intellectual Property: IP for low-grade glioma and sarcoma fusion panels as well as medulloblastoma subgrouping panel David MalkinConsulting or Advisory Role: Bayer Eric BouffetConsulting or Advisory Role: NovartisResearch Funding: Roche, Bristol Myers SquibbNo other potential conflicts of interest were reported.

Outcomes of acute heart failure hospitalizations are worse during the winter than the rest of the year. Seasonality data are more limited for outcomes in chronic heart failure and the effect of environmental variables is unknown. In this population-level study, we merged 20-year data for 555,324 patients with heart failure from the national Veterans Administration database with data on climate from the National Oceanic and Atmospheric Administration and air pollutants by the Environmental Protection Agency. The outcome was the all-cause mortality rate, stratified by geographical location and each month. The impact of environmental factors was assessed through Pearson's correlation and multiple regression with a family-wise α = 0.05. The monthly all-cause mortality was 13.9% higher in the winter than the summer, regardless of gender, age group, and heart failure etiology. Winter season, lower temperatures, and higher concentrations of nitrogen dioxide were associated with a higher mortality rate in multivariate analysis of the overall population. Different environmental factors were associated in regions with similar patterns of temperature and precipitation. The only environmental factor associated with the mortality rate of patients dwelling in large urban centers was the air quality index. In conclusion, the mortality in chronic heart failure exhibits a seasonal pattern, regardless of latitude or climate. In this group of patients, particularly those of male gender, a higher mortality was associated with environmental factors and incorporating these factors in treatment plans and recommendations could have a favorable cost-benefit ratio., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study., (Copyright © 2021. Published by Elsevier Inc.)

The need for subspecialty-trained neurologists is growing in parallel with increasing disease burden. However, despite the immense burden of neurological diseases, like headache and neurodegenerative disorders, recruitment into these subspecialties remains insufficient in the United States. In this manuscript, a group of educators from the American Academy of Neurology's A.B. Baker Section on Neurological Education sought to review and discuss the current landscape of neurology fellowships in the United States, the factors driving fellowship recruitment and the educational barriers. Moreover, suggestions to potentially improve recruitment for under-selected fellowships, which can contribute towards an alignment between neurological education and neurological needs, and future educational scenarios are discussed.

Objective: To investigate the clinical and procedural characteristics in patients with a history of renal transplant (RT) and compare the outcomes with patients without RT in 2 national cohorts of patients undergoing percutaneous coronary intervention (PCI)., Patients and Methods: Data from the National Inpatient Sample (NIS) and British Cardiovascular Intervention Society (BCIS) were used to compare the clinical and procedural characteristics and outcomes of patients undergoing PCI who had RT with those who did not have RT. The primary outcome of interest was in-hospital mortality., Results: Of the PCI procedures performed in 2004-2014 (NIS) and 2007-2014 (BCIS), 12,529 of 6,601,526 (0.2%) and 1521 of 512,356 (0.3%), respectively, were undertaken in patients with a history of RT. Patients with RT were younger and had a higher prevalence of congestive cardiac failure, hypertension, and diabetes but similar use of drug-eluting stents, intracoronary imaging, and pressure wire studies compared with patients who did not have RT. In the adjusted analysis, patients with RT had increased odds of in-hospital mortality (NIS: odds ratio [OR], 1.90; 95% CI, 1.41-2.57; BCIS: OR, 1.60; 95% CI, 1.05-2.46) compared with patients who did not have RT but no difference in vascular or bleeding events. Meta-analysis of the 2 data sets suggested an increase in in-hospital mortality (OR, 1.79; 95% CI, 1.40-2.29) but no difference in vascular (OR, 1.24; 95% CI, 0.77-2.00) or bleeding (OR, 1.21; 95% CI, 0.86-1.68) events., Conclusion: This large collaborative analysis of 2 national databases revealed that patients with RT undergoing PCI are younger, have more comorbidities, and have increased mortality risk compared with the general population undergoing PCI., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: There is limited evidence on the influence of sex on the decision to implant a cardiac resynchronization therapy device with pacemaker (CRT-P) or defibrillator (CRT-D) and the existence of sex-dependent differences in complications that may affect this decision., Methods: All patients undergoing de novo CRT implantation (2004-2014) in the United States National Inpatient Sample were included and stratified by device type (CRT-P and CRT-D). Multivariable logistic regression models were conducted to assess the association of female sex with receipt of CRT-D and periprocedural complications., Results: Out of 400,823 weighted CRT procedural records, the overall percentages of women undergoing CRT-P and CRT-D implantations were 41.5% and 27.8%, respectively, and these percentages increased compared with men over the study period. Women were less likely to receive CRT-D (odds ratio 0.66, 95% confidence interval 0.64-0.67), and this trend remained stable throughout the study period (P = 0.06). Furthermore, compared with men, women were associated with increased odds of procedure-related complications (bleeding, thoracic, and cardiac) in the CRT-D group but not in the CRT-P group. Factors such as atrial fibrillation, malignancies, renal failure, advanced age (> 60 years), and admission to nonurban/small hospitals favoured the receipt of CRT-P over CRT-D, whereas history of ischemic heart disease, cardiac arrest ,or ventricular arrhythmias favoured the receipt of CRT-D over CRT-P., Conclusions: Women were associated with persistently reduced odds of receipt of CRT-D compared with men over an 11-year period. This study identifies important factors that predict the choice of CRT device offered to patients in the United States., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Although no tobacco products are safe, tobacco companies in the United States may request regulatory authorization to make certain "modified risk tobacco product" (MRTP) claims in their marketing. However, few qualitative studies have explored consumer perceptions and understanding of comparative risk messages and wordings. We examined consumer perceptions of statements indicating reduced risks and exposure to chemicals from snus and e-cigarettes relative to smoking. We conducted 12 focus groups with adult smokers (ages 21-66) and young adult (YA) non-smokers (ages 18-25) ( n = 57) in the USA in 2019. Participants shared reactions to modified risk and exposure messages and message variations. Participants largely understood claims, including language about "switching completely." However, participants expressed desire for more message specificity, evidence, risk reduction reasons, and statistics/quantitative information. Claim believability and acceptance was also limited by existing negative product beliefs and experiences, negative media reports, and skepticism about message source. YAs did not express product interest based on message exposure. Some YAs suggested the included "smoker" language made the messages less interesting/relevant. Given existing proposals for and use of MRTP messages, additional research on their wording, framing, delivery, and effects may help inform regulatory or organizational decisions about such messages, optimize potential benefits, and mitigate unintended consequences.

Aims: To compare and contrast the indications, clinical and procedural characteristics, and periprocedural outcomes of patients with cardiac transplant undergoing percutaneous coronary intervention (PCI) in the United States and United Kingdom., Methods and Results: The British Cardiovascular Intervention Society Registry (BCIS) (2007-2014) and the United States National Inpatient Sample (NIS) (2004-2014) data were utilized for this analysis. There were 466 PCIs (0.09%) and 1122 PCIs (0.02%) performed in cardiac transplant patients in the BCIS and NIS registries, respectively. The cardiac transplant PCI cohort was younger and mostly men, with an increased prevalence of chronic kidney disease, left main PCI, and multivessel disease, and with lower use of newer antiplatelets agents, antithrombotics, and radial artery access vs the non-cardiac transplant PCI cohort. In the BCIS registry, the cardiac transplant PCI cohort had similar in-hospital mortality (odds ratio [OR], 1.05; P=.91), 30-day mortality (OR, 1.38; P=.31), vascular complications (OR, 0.69; P=.46), and major adverse cardiovascular event (OR, 1.41; P=.26) vs the non-cardiac transplant PCI cohort. However, the cardiac transplant group had higher 1-year mortality (OR, 2.30; P<.001). The NIS data analysis revealed similar rates of in-hospital mortality (OR, 2.40; P=.14), cardiac complications (OR, 0.26; P=.17), major bleeding (OR, 0.36; P=.16), vascular complications (OR, 0.46; P=.45), and stroke (OR, 0.50; P=.40) in the cardiac transplant PCI cohort vs the non-cardiac transplant PCI cohort., Conclusions: PCI in cardiac transplant recipients was associated with similar short-term mortality and vascular complications compared with PCI in the general populace. However, a higher 1-year morality was observed in the BCIS cohort.

Objectives: To examine the association between current leukemia diagnosis and in-hospital clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) in the United States., Background: Leukemia is the most common hematological malignancy and is associated with an increased risk of thrombotic and bleeding complications in patients undergoing PCI. There are limited data around clinical outcomes of leukemia patients undergoing PCI., Methods: We used the National Inpatient Sample to investigate the outcomes of leukemia patients undergoing PCI between 2004 and 2014. Patients were then subdivided into diagnoses of acute myeloid leukemia (AML) or chronic myeloid leukemia and acute lymphoid leukemia or chronic lymphoid leukemia (CLL). Multiple logistic regressions were used to study the association of a leukemia diagnosis with in-hospital outcomes: mortality, bleeding, vascular and cardiac complications, and stroke., Results: There were 6,561,445 records of patients who underwent PCI during the study time, of which 15,789 patients had a diagnosis of leukemia. The most common leukemia subtype was CLL accounting for 75% of the cohort (n = 10,800). After multivariable adjustment, a leukemia diagnosis was associated with significantly increased odds of in-hospital mortality (odds ratio [OR]: 1.41; 95% confidence interval [CI]: [1.11-1.79]) and bleeding (OR: 1.87; 95% CI: [1.56-2.09]), whereas patients with AML had a fivefold increase of in-hospital mortality (OR: 5.38; 95% CI: [2.94-9.76])., Conclusions: Patients with current diagnosis of leukemia are at increased risk of procedure-related complications following PCI. A multidisciplinary approach is needed among interventional cardiologists, oncologists, and hematologists to minimize procedural complications and improve outcomes in this high-risk cohort., (© 2019 Wiley Periodicals, Inc.)

The art and the skill set of compounding fulfill the important need of tailor-made pharmaceuticals for use by both institutions and individual  patients. Over the last 20 years, there have been more than 200 adverse events involving compounded products; infections, poisonings, contaminations, and dosing inaccuracies have been problematic. The probability of a correlation between the lack of institutional training and number of serious events could be significant. This survey was an endeavor at fundamental cause analysis and proactive management in relation to the PharmD Curricula as a means of error prevention. A questionnaire was sent to the pharmacy school faculty (department chairs, dean/assistant deans, and pharmaceutical science faculty) across the country. The survey responses were received from 78 participants. The questionnaire evaluated the respondent's overall knowledge and approach toward the subject in their curriculum. The survey results show 38.9% faculty agree that their college's curricula lacks sufficient training in microbiological testing, and 16.7% faculty agree their college does not provide sufficient training in nonsterile and sterile compounding (as per United States Pharmacopeia Chapters <795> and <797>). A majority of faculty agree on the implementation of quality assurance in compounding courses (as per United States Pharmacopeia Chapter  <1163>) as either an elective (62.5%) or mandatory class (43.3%), and most of the participants (85.1%) think there is a need to teach quality assurance as continuing education to practicing pharmacists. The survey data suggest a general desire for enhancement of compounding course curriculum, which could reduce the number of adverse events related to compounding. The data also suggests a necessity for the implementation of continuing education programs for practicing pharmacists and academic faculty across the country., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Aims: The aim of this study is to evaluate temporal trends, treatment, and clinical outcomes of patients who present with an acute myocardial infarction (AMI) and have a current or historical diagnosis of cancer, according to cancer type and presence of metastases., Methods and Results: Data from 6 563 255 patients presenting with an AMI between 2004 and 2014 from the US National Inpatient Sample (NIS) database were analysed. A total of 5 966 955 had no cancer, 186 604 had current cancer, and 409 697 had a historical diagnosis of cancer. Prostate, breast, colon, and lung cancer were the four most common types of cancer. Patients with cancer were older with more comorbidities. Differences in invasive treatment were noted, 43.9% received percutaneous coronary intervention (PCI) in patients without cancer, whilst only 21.0% of patients with lung cancer received PCI. Lung cancer was associated with the highest in-hospital mortality [odds ratio (OR) 2.71, 95% confidence interval (CI) 2.62-2.80], major adverse cardiovascular and cerebrovascular complications (OR 2.38, 95% CI 2.31-2.45), and stroke (OR 1.91, 95% CI 1.80-2.02), while colon cancer was associated with highest risk of bleeding (OR 2.82, 95% CI 2.68-2.98). Irrespective of the type of cancer, presence of metastasis was associated with worse in-hospital outcomes, and historical cancer did not adversely impact on survival (OR 0.90, 95% CI 0.89-0.91)., Conclusion: A concomitant cancer diagnosis is associated with a conservative medical management strategy for AMI, and worse clinical outcomes, compared to patients without cancer. Survival and clinical outcomes in the context of AMI vary significantly according to the type of cancer and metastasis status. The management of this high-risk group is challenging and requires a multidisciplinary and patient-centred approach to improve their outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with leukaemia are at increased risk of cardiovascular events. There are limited outcomes data for patients with a history of leukaemia who present with an acute myocardial infarction (AMI)., Methods: We queried the Nationwide Inpatient Sample (2004-2014) for patients with a primary discharge diagnosis of AMI, and a concomitant diagnosis of leukaemia, and further stratified according to the subtype of leukaemia. Multivariable logistic regression was conducted to identify the association between leukaemia and major acute cardiovascular and cerebrovascular events (MACCE; composite of mortality, stroke and cardiac complications) and bleeding., Results: Out of 6 750 878 AMI admissions, a total of 21 694 patients had a leukaemia diagnosis. The leukaemia group experienced higher rates of MACCE (11.8% vs 7.8%), mortality (10.3% vs 5.8%) and bleeding (5.6% vs 5.3%). Following adjustments, leukaemia was independently associated with increased odds of MACCE (OR 1.26 [1.20, 1.31]) and mortality (OR 1.43 [1.37, 1.50]) without an increased risk of bleeding (OR 0.86 [0.81, 0.92]). Acute myeloid leukaemia (AML) was associated with approximately threefold risk of MACCE (OR 2.81 [2.51, 3.13]) and a fourfold risk of mortality (OR 3.75 [3.34, 4.22]). Patients with leukaemia were less likely to undergo coronary angiography (CA) (48.5% vs 64.5%) and percutaneous coronary intervention (PCI) (28.2% vs 42.9%) compared with those without leukaemia., Conclusion: Patients with leukaemia, especially those with AML, are associated with poor clinical outcomes after AMI, and are less likely to receive CA and PCI compared with those without leukaemia. A multi-disciplinary approach between cardiologists and haematology oncologists may improve the outcomes of patients with leukaemia after AMI., (© 2020 John Wiley & Sons Ltd.)

Background: While major complications associated with CIED lead extractions are uncommon, they carry a significant risk of morbidity and mortality in the absence of surgical intervention. However, there is limited data on the differences in outcomes of these procedures between centers with and without on-site CS support. The present study examined outcomes of transvenous cardiac implantable electronic device (CIED) lead extractions according to admitting hospitals' cardiac surgery (CS) facilities., Methods: We analyzed the National Inpatient Sample for CIED lead extraction procedures, stratified by hospitals' CS facilities into two groups; on-site and off-site CS. Logistic regression analyses were performed to estimate the adjusted odds (aOR) of procedure-related complications in off-site CS centers., Results: In 221,606 procedures over an 11-year-period, CIED lead extractions were increasingly undertaken in on-site as opposed to off-site CS centers (Onsite CS 2004 vs. 2014: 78.2% vs. 90.4%, p < 0.001) during the study period. In comparison to on-site CS group, patients admitted to off-site CS group were older, less comorbid, and experienced lower adjusted odds of major adverse cardiovascular events (0.72 [0.67, 0.77]), mortality (0.60 [0.52, 0.69]), procedure-related bleeding (0.48 [0.44, 0.54]) and complications (thoracic: 0.81 [0.75, 0.88]; cardiac: 0.45 [0.38, 0.54]) (p < 0.001 for all)., Conclusions: Our national analysis demonstrates that transvenous CIED lead extractions are being increasingly undertaken in centers with on-site CS surgery, in compliance with international guideline recommendations. Patients managed with lead extractions in on-site CS centers are more comorbid and critically ill compared to those admitted to off-site CS centers, and remain at a higher risk of procedure-related complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The disparity in outcomes of cardiac electronic device implantations between sexes has been previously demonstrated in device-specific cohorts (eg, implantable cardioverter-defibrillators [ICDs]). However, it is unclear whether sex differences are present with all types of cardiac implantable electronic devices (CIEDs) and, if so, what the trends of such differences have been in recent years., Methods: With the use of the National Inpatient Sample, all hospitalizations from 2004 to 2014 for de novo implantation of permanent pacemakers, cardiac resynchronization therapy with or without a defibrillator, and ICDs were analyzed to examine the association between sex and in-hospital acute complications of CIED implantation., Results: Out of 2,815,613 hospitalizations for de novo CIED implantation, 41.9% were performed on women. Women were associated with increased adjusted odds (95% confidence interval) of adverse procedural complications (major adverse cardiovascular complications: 1.17 [1.16-1.19]; bleeding: 1.13 [1.12-1.15],-thoracic: 1.42 [1.40-1.44]; cardiac: 1.44 [1.38-1.50]), whereas the adjusted odds of in-hospital all-cause mortality compared with men was 0.96 (0.94-1.00). The odds of adverse complications in the overall CIED cohort were persistently raised in women throughout the study period, whereas similar odds of all-cause mortality across the sexes were observed throughout the study period., Conclusion: In a national cohort of CIED implantations we demonstrate that women are at an overall higher risk of procedure-related adverse events compared with men, but not at increased risk of all-cause mortality. Further studies are required to identify procedural techniques that would improve outcomes among women undergoing such procedures., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the impact of frailty on length of stay (LOS), cost, and in-hospital procedural outcomes of cardiac implantable electronic device (CIED) implantation procedures., Methods: All de novo CIED implantations recorded in the United States (2004-2014) from a national database were stratified according to the Hospital Frailty Risk Score into low-risk (LRF; <5), intermediate-risk (IRF; 5-15), and high-risk (HRF; > 15) frailty groups. Regression analyses were performed to assess the association between frailty and procedural outcomes., Results: Of 2,902,721 implantations, LRF, IRF, and HRF were 77.6%, 21.2%, and 1.2%, respectively. Frailty increased from 2004 to 2014 (IRF: 14.3% to 32.5%, HRF: 0.2% to 3.3%). Complications were 2- to 3-fold higher in the IRF and HRF groups, whereas all-cause mortality was 4- to 9-fold higher in the IRF (2.9%) and HRF (5.3%) groups, depending on the type of CIED (P < 0.001 for all). Rates of complications increased over the study years and all-cause mortality declined, especially in the higher frailty risk groups (2004 vs 2014; mortality: IRF: 3.8% vs 2.2%, HRF: 9.9% vs 4.5%; bleeding: IRF: 3.7% vs 9.0%, HRF: 3.9% vs 12.2%; thoracic: IRF: 4.3% vs 6.0%, HRF: 2.9% vs 9.1%; cardiac: IRF: 0.5% vs 0.9%, HRF: 0.5% vs 0.9%). Rising frailty was associated with an increase in cost (P < 0.001) and LOS (median 3, 8, 11 days for LRF, IRF, HRF, respectively, P < 0.001). The cost for patients with HRF receiving a defibrillator was approximately a quarter million USD$ per patient., Conclusions: Frailty is associated with worse clinical outcomes, higher cost, and LOS independent of age or CIED type. Our findings emphasize the importance of frailty assessment., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

This study examines a national cohort of patients with a diagnosis of acute coronary syndrome (ACS) for the prevalence of frailty, temporal changes over time, and its association with treatments and clinical outcomes. The National Inpatient Sample database was used to identify US adults with a diagnosis of ACS between 2004 and 2014. Frailty risk was determined using a validated Hospital Frailty Risk Score based on ICD-9 codes using the cutoffs <5, 5 to 15, and >15 for low- (LRS), intermediate- (IRS), and high-risk (HRS) frailty scores, respectively. Logistic regression assessed associations of frailty with clinical outcomes, adjusted for patient co-morbidities and hospital characteristics. From 7,398,572 hospital admissions with ACS between 2004 and 2014, 86.5% of patients had LRS, 13.4% had an IRS, and 0.1% had an HRS. From 2004 to 2014, the prevalence of IRS and HRS patients increased from 8.1% to 18.2% and 0.03% to 0.18%, respectively (p <0.001 for both). The proportion of patients treated with percutaneous coronary intervention was greatest among patients with lowest frailty risk scores (LRS 42.9%, IRS 21.0%, and HRS 14.6%). Comparing HRS to LRS, there was a significant increase in bleeding complications (odds ratio [OR] 2.34, 95% confidence interval [CI] 2.03 to 2.69), vascular complications (OR 2.08, 95% CI 1.79 to 2.41), in-hospital stroke (OR 7.84, 95% CI 6.93 to 8.86), and in-hospital death (OR 2.57, 95% CI 2.18 to 3.04). Risk of frailty is common among patients with ACS, is increasing in prevalence, and is associated with differential management strategies, and outcomes during hospitalization. Increased awareness could facilitate frailty-tailored care to minimize the risk of adverse outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most common arrhythmia in patients presenting with acute coronary syndrome (ACS). The present study examined the rates and trends of clinical outcomes and management strategies of non-ST-elevation ACS (NSTE-ACS) related hospitalizations in the United States, in patients with concomitant AF compared with those in sinus rhythm (SR). We analyzed the "Nationwide Inpatient Sample" database (2004 to 2014) for patients with a primary discharge diagnosis of NSTE-ACS, and further stratified the cohort on the basis of diagnoses into SR and AF groups. Multivariate analysis was performed to examine the association between AF and major adverse cardiovascular and cerebrovascular events (composite of mortality, stroke, and cardiac complications) and its components. Of 4,668,737 NSTE-ACS hospitalizations, the proportions of SR and AF groups were 82.4% (3,848,202) and 17.6% (820,535), respectively. The incidence of AF increased significantly over time from 16.5% (2004) to 19.3% (2014). The AF group was at a greater risk of adverse outcomes with higher rates and adjusted relative risk (RR) of major adverse cardiovascular and cerebrovascular events (12.9% vs 5.3%; RR 1.74 [1.72, 1.75]), mortality (6.5% vs 3.3%; RR 1.12 [1.11, 1.13]), stroke (2.7% vs 1.5%; RR 1.32 [1.30, 1.34]), and bleeding (14.7% vs 8.8%; RR 1.42 [1.41, 1.43]). Furthermore, the AF group was less likely to receive coronary angiography (47.1% vs 58%) and percutaneous coronary intervention (18.7% vs 32.6%) in comparison to SR (p <0.001 for all outcomes). In conclusion, patients with concomitant AF and NSTE-ACS are less likely to be offered an invasive management strategy for their ACS and are associated with worse complications and higher mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Severe mental illness (SMI) is associated with increased cardiovascular mortality. We sought to examine the prevalence, clinical outcomes, and management strategy of patients with SMI presenting with acute myocardial infarction (AMI)., Methods: All AMI hospitalizations from the National Inpatient Sample were included, stratified by mental health status into 5 groups: no SMI, schizophrenia, other non-organic psychoses (ONOP), bipolar disorder, and major depression. Regression analyses were performed to assess the association (adjusted odds ratios [ORs], P ≤ 0.001 for all outcomes) between SMI subtypes and clinical outcomes., Results: Of 6,968,777 AMI hospitalizations between 2004 and 2014, 439,544 patients (6.5%) had an SMI diagnosis. Although patients with schizophrenia and ONOP experienced higher crude rates of in-hospital mortality and stroke compared with those without SMI, only schizophrenic patients were at increased odds of mortality (OR, 1.10; 95% confidence interval [CI], 1.04-1.16), whereas ONOP was the only group at increased odds of stroke (OR, 1.53; 95% CI, 1.42-1.65) after multivariate adjustment. Patients with ONOP were the only group associated with increased odds of in-hospital bleeding compared with those without SMI (OR, 1.11; 95% CI, 1.04-1.17). All those with SMI subtypes were less likely to receive coronary angiography and percutaneous coronary intervention, with the schizophrenia group being at least odds of either procedure (OR, 0.46; 95% CI, 0.45-0.48 and OR, 0.57; 95% CI, 0.55-0.59, respectively)., Conclusion: Schizophrenia and ONOP are the only SMI subtypes associated with adverse clinical outcomes after AMI. However, all patients with SMI were less likely to receive invasive management for AMI, with female gender and schizophrenia diagnosis being the strongest predictors of conservative management. A multidisciplinary approach between psychiatrists and cardiologists could improve the outcomes of this high-risk population., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: This study aims to examine the temporal trends and outcomes in patients who undergo percutaneous coronary intervention (PCI) with a previous or current diagnosis of cancer, according to cancer type and the presence of metastases., Methods and Results: Individuals undergoing PCI between 2004 and 2014 in the Nationwide Inpatient Sample were included in the study. Multivariable analyses were used to determine the association between cancer diagnosis and in-hospital mortality and complications. 6 571 034 PCI procedures were included and current and previous cancer rates were 1.8% and 5.8%, respectively. Both rates increased over time and the four most common cancers were prostate, breast, colon, and lung cancer. Patients with a current lung cancer had greater in-hospital mortality (odds ratio (OR) 2.81, 95% confidence interval (95% CI) 2.37-3.34) and any in-hospital complication (OR 1.21, 95% CI 1.10-1.36), while current colon cancer was associated with any complication (OR 2.17, 95% CI 1.90-2.48) and bleeding (OR 3.65, 95% CI 3.07-4.35) but not mortality (OR 1.39, 95% CI 0.99-1.95). A current diagnosis of breast was not significantly associated with either in-hospital mortality or any of the complications studied and prostate cancer was only associated with increased risk of bleeding (OR 1.41, 95% CI 1.20-1.65). A historical diagnosis of lung cancer was independently associated with an increased OR of in-hospital mortality (OR 1.65, 95% CI 1.32-2.05)., Conclusions: Cancer among patients receiving PCI is common and the prognostic impact of cancer is specific both for the type of cancer, presence of metastases and whether the diagnosis is historical or current. Treatment of patients with a cancer diagnosis should be individualized and involve a close collaboration between cardiologists and oncologists., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Objective: This study aims to investigate the temporal trends in utilization of invasive coronary angiography (CA) at different time points and changing profiles of patients undergoing CA following non-ST-elevation acute coronary syndrome (NSTEACS). We also describe the association between time to CA and in-hospital clinical outcomes., Patients and Methods: We queried the National Inpatient Sample to identify all admissions with a primary diagnosis of NSTEACS from 2004 to 2014. Patients were stratified into early (day 0, 1), intermediate (day 2) and late strategy (day≥3) according to time to CA. Multivariable logistic regression was used to investigate the association between time to CA and in-hospital mortality, major bleeding, stroke and Major Adverse Cardiac and Cerebrovascular Events., Results: A total of 4 380 827 records were identified with a diagnosis of NSTEACS, out of which 57.5% received CA. The proportion of patients undergoing early CA increased from 65.6 to 72.6%, whereas late CA commensurately declined from 19.6 to 13.5%. Patients receiving early CA were younger (age: 64 vs. 70 years), more likely to be male (63.7 vs. 55.3%) and of Caucasian ethnic background (68.7 vs. 64.7%) compared with late CA group. Similarly, Women, weekend admissions and African Americans remain less likely to receive early CA. In-hospital mortality was lowest in the intermediate group (odds ratio=0.30, 95% confidence interval: 0.28-0.33)., Conclusion: Use of early CA has increased in the management of NSTEACS; however, there remain significant disparities in utilization of an early invasive approach in women, African Americans, admission day and older patients in the USA.

Objectives: The aim of this study was to describe the rates and causes of unplanned readmissions at different time periods following percutaneous coronary intervention (PCI)., Background: The rates and causes of readmission at different time periods after PCI remain incompletely elucidated., Methods: Patients undergoing PCI between 2010 and 2014 in the U.S. Nationwide Readmission Database were evaluated for the rates, causes, predictors, and costs of unplanned readmission between 0 and 7 days, 8 and 30 days, 31 and 90 days, and 91 and 180 days after index discharge., Results: This analysis included 2,412,000 patients; 2.5% were readmitted between 0 and 7 days, 7.6% between 8 and 30 days, 8.9% between 31 and 90 days, and 8.0% between 91 and 180 days (cumulative rates 2.5%, 9.9%, 18.0%, and 24.8%, respectively). The majority of readmissions during each time period were due to noncardiac causes (53.1% to 59.6%). Nonspecific chest pain was the most common identifiable noncardiac cause for readmission during each time period (14.2% to 22.7% of noncardiac readmissions). Coronary artery disease including angina was the most common cardiac cause for readmission during each time period (37.4% to 39.3% of cardiac readmissions). The second most common cardiac cause for readmission was acute myocardial infarction between 0 and 7 days (27.6% of cardiac readmissions) and heart failure during all subsequent time periods (22.2% to 23.7% of cardiac readmissions)., Conclusions: Approximately 25% of patients following PCI have unplanned readmissions within 6 months. Causes of readmission depend on the timing at which they are assessed, with noncardiovascular causes becoming more important at longer time points., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary angiography (CA) is the basis of an invasive management strategy in non-ST elevation acute coronary syndromes (NSTEACS). There are limited contemporary data on national temporal trends in utilization of CA in different patient subgroups. We sought to investigate temporal trends, predictors and clinical outcomes associated with the use of CA in the US. Using the Nationwide Inpatient Sample (NIS) from 2004-2014, we identified all inpatient admissions, age ≥18, with a primary diagnosis of NSTEACS. Descriptive statistics and multivariable logistic regression models were used to investigate temporal trends, predictors and clinical outcomes associated with CA. From a total of 4,380,827 patients, 57.5% received CA during the study period and were more likely to be male, younger and less comorbid as defined per Charlson comorbidity index. The proportion of patients receiving CA increased from 48.5% to 68.5%, however, higher proportional increase was observed in males (53.9% to 69.4% P trend  < 0.001) and those age ≤60 years (59.0% to 77.9% P trend  < 0.001). Prior history of CABG (OR 0.33 95%CI 0.35-0.36), previous PCI (OR 0.84 95%CI 0.83-0.86) and previous AMI (OR 0.65 95%CI 0.64-0.67) were inversely related with receipt of CA. Receipt of CA was strongly associated with decreased odds of in-hospital mortality (OR 0.38 95%CI 0.36-0.40). In this national analysis, we observed a temporal increase in utilization of CA albeit slower adoption was noted in older, women and more comorbid patients. The risk-treatment paradox wherein patients who are most likely to benefit were less likely to receive CA persists even in contemporary practice.

Background: Prior studies have reported inconsistencies in the baseline risk profile, comorbidity burden and their association with clinical outcomes in women compared to men. More importantly, there is limited data around the sex differences and how these have changed over time in contemporary percutaneous coronary intervention (PCI) practice., Methods and Results: We used the Nationwide Inpatient Sample to identify all PCI procedures based on ICD-9 procedure codes in the United States between 2004-2014 in adult patients. Descriptive statistics were used to describe sex-based differences in baseline characteristics and comorbidity burden of patients. Multivariable logistic regressions were used to investigate the association between these differences and in-hospital mortality, complications, length of stay and total hospital charges. Among 6,601,526 patients, 66% were men and 33% were women. Women were more likely to be admitted with diagnosis of NSTEMI (non-ST elevation acute myocardial infarction), were on average 5 years older (median age 68 compared to 63) and had higher burden of comorbidity defined by Charlson score ≥3. Women also had higher in-hospital crude mortality (2.0% vs 1.4%) and any complications compared to men (11.1% vs 7.0%). These trends persisted in our adjusted analyses where women had a significant increase in the odds of in-hospital mortality men (OR 1.20 (95% CI 1.16,1.23) and major bleeding (OR 1.81 (95% CI 1.77,1.86)., Conclusion: In this national unselected contemporary PCI cohort, there are significant sex-based differences in presentation, baseline characteristics and comorbidity burden. These differences do not fully account for the higher in-hospital mortality and procedural complications observed in women., Competing Interests: The authors have declared that no competing interests exist.

This study aims to evaluate the impact of co-morbidity burden on outcomes in patients who undergo percutaneous coronary intervention (PCI). We used the Nationwide Inpatient Sample to identify all PCI procedures undertaken in the United States from 2004 to 2014. We then determined co-morbidity burden for each patient record based on the Charlson Co-morbidity Score. Multivariable logistic regression models were used to examine the association between co-morbidity burden and in-hospital mortality other in-hospital complications. A total of 6,601,526 PCI procedures were included in the analysis. Overall co-morbidity burden increased over time, with severe co-morbidity burden (defined as a CCI score ≥3) increasing from 5.3% in 2004 to 14.2% in 2014 (p <0.0001). After adjustment for confounding factors increasing co-morbidity burden was independently associated with increased odds of in-hospital mortality, complications, length of hospital stay, and total cost of hospitalization post PCI. A CCI score of 1 was independently associated with an increase in the odds of in hospital mortality (odds ratio [OR] 1.19 [95% confidence interval [CI] 1.15 to 1.25]), a score of 2 associated with an almost 1.5-fold increase (OR 1.41 [95% CI 1.34 to 1.48]) and a score of ≥3 a 2-fold increase (OR 1.96 [95% CI 1.86 to 2.07]) compared with no co-morbid burden (CCI score of 0). In conclusion, our results show that co-morbid burden is independently associated with increased risk of in-hospital mortality, in-hospital complications, length of stay, and healthcare costs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to evaluate discharge against medical advice (DAMA) in percutaneous coronary intervention (PCI) and how DAMA affects readmissions., Background: DAMA is infrequent but associated with poor patient outcomes. DAMA in the context of PCI has not been described in the published reports., Methods: The authors analyzed patients in the Nationwide Readmission Database between 2010 and 2014 with a PCI procedure who were either discharged home or against medical advice. The primary endpoint was all-cause 30-day readmissions and their causes. Descriptive statistics were used to compare DAMA with patients discharged home, and multiple logistic regressions were used to determine patient characteristics associated with DAMA and readmission., Results: Among the 2,021,104 patients in the analysis, the proportion of patients who DAMA was 0.5% (n = 10,049). The 30-day readmission rate for patients who were DAMA and those discharged home was 16.8% and 8.5%, respectively (p < 0.001). Important predictors of DAMA included diagnosis of acute myocardial infarction (odds ratio [OR]: 1.37; 95% confidence interval [CI]: 1.25 to 1.51; p < 0.001), smoking (OR: 1.71; 95% CI: 1.57 to 1.86; p < 0.001), drug abuse (OR: 1.82; 95% CI: 1.60 to 2.06; p < 0.001), and alcohol misuse (OR: 1.53; 95% CI: 1.32 to 1.78; p < 0.001). DAMA was the strongest predictor for readmission (OR: 1.89; 95% CI: 1.71 to 2.08; p < 0.001). DAMA patients were more likely to have neuropsychiatric reasons for noncardiac causes of readmission (8.3% vs. 2.4%) and acute myocardial infarction for cardiac causes of readmission (39.4% vs. 19.5%) compared with patients discharged home., Conclusions: DAMA occurs in approximately 0.5% of patients following PCI and is strongly associated with readmission within 30 days. Interventions should be developed to reduce DAMA in high-risk groups and initiate interventions to avoid complications and readmission when it occurs., (Copyright © 2018 American College of Cardiology Foundation. All rights reserved.)

It is unclear how age affects rates and causes of unplanned early readmissions after percutaneous coronary intervention (PCI). We analyzed patients in the Nationwide Readmission Database in the United States from 2010 to 2014 and examined the impact of age on readmissions after PCI. The primary outcomes were age-specific 30-day rates and causes of unplanned readmissions. A total of 2,294,345 procedures were analyzed with a 9.6% unplanned readmission rate within 30 days. Unplanned readmissions were 8.1%, 8.1%, 9.5%, and 12.6% for age groups <55, 55.0 to 64.9, 65.0-74.9, and ≥75 years, respectively. With increasing age, there was an increase in the rate of noncardiac causes for readmissions (for ages <55, 55.0 to 64.9, and ≥75 years, the rates were 54.1%, 54.8%, 56.6%, and 57.1%, respectively; p <0.001). Older age was associated with an increased prevalence of infections (13.9% ≥75 years vs 7.7% <55 years), gastrointestinal disease (11.5% ≥75 years vs 9.5% <55 years), and bleeding (7.4% ≥75 years vs 2.9% <55 years) as causes for noncardiac readmissions and a reduced prevalence of nonspecific chest pain (9.9% ≥75 years vs 31.4% <55 years). For cardiac causes, older age was associated with increased prevalence for readmissions due to heart failure (34.6% ≥75 years vs 11.9% <55 years) but a reduced prevalence of coronary artery disease, including angina (25.7% ≥75 years vs 51.3% <55 years). In conclusion, older patients have the highest rates of unplanned 30-day readmissions after PCI, with different causes for readmission compared with younger patients. Interventions designed to reduce readmissions after PCI should be age specific., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to examine the 30-day unplanned readmissions rate, predictors of readmission, causes of readmissions, and clinical impact of readmissions after percutaneous coronary intervention (PCI)., Background: Unplanned rehospitalizations following PCI carry significant burden to both patients and the local health care economy and are increasingly considered as an indicator of quality of care., Methods: Patients undergoing PCI between 2013 and 2014 in the U.S. Nationwide Readmission Database were included. Incidence, predictors, causes, and cost of 30-day unplanned readmissions were determined., Results: A total of 833,344 patients with PCI were included, of whom 77,982 (9.3%) had an unplanned readmission within 30 days. Length of stay for the index PCI was greater (4.7 vs. 3.9 days) and mean total hospital cost ($23,211 vs. $37,524) was higher for patients who were readmitted compared with those not readmitted. The factors strongly independently associated with readmissions were index hospitalization discharge against medical advice (odds ratio [OR]: 1.91; 95% confidence interval [CI]: 1.65 to 2.22), transfer to short-term hospital for inpatient care (OR: 1.62; 95% CI: 1.38 to 1.90), discharge to care home (OR: 1.57; 95% CI: 1.51 to 1.64), and chronic kidney disease (OR: 1.50; 95% CI: 1.44 to 1.55). Charlson Comorbidity Index score (OR: 1.28; 95% CI: 1.27 to 1.29) and number of comorbidities (OR: 1.18; 95% CI: 1.17 to 1.18) were independently associated with unplanned readmission. The majority of readmissions were due to noncardiac causes (56.1%)., Conclusions: Thirty-day readmissions after PCI are relatively common and relate to baseline comorbidities and place of discharge. More than one-half of the readmissions were due to noncardiac causes., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Women who undergo percutaneous coronary intervention (PCI) are at higher risk of adverse outcomes compared with men, but it is unknown whether gender affects early unplanned rehospitalization. We analyzed 832,753 patients who underwent PCI from 2013 to 2014 in the Nationwide Readmissions Database. We compared gender differences in incidences, predictors, causes, and cost of unplanned 30-day readmissions and examined the effect of co-morbidity. A total of 832,753 men and women who survived the index PCI and were not admitted for a planned readmission were included in the analysis. Overall, 9.4% of patients had an unplanned readmission within 30 days. Thirty-day readmission rates were higher in women compared with men (11.5% vs 8.4%, p <0.001) even after multivariate adjustment (odds ratio 1.19, 95% confidence interval 1.16 to 1.22, p <0.001), although women had significantly lower costs associated with the readmission ($11,927 vs $12,758, p <0.001). The cause of readmission for women and men were similar and the majority of the readmissions were due to noncardiac causes (58% vs 55%), the most common of which were nonspecific chest pain, gastrointestinal disease, and infections. In contrast, for cardiac readmissions, women are more likely to be readmitted for heart failure (29.64% vs 22.34%), whereas men are more likely to be readmitted for coronary artery disease, including angina (33.47% vs 28.54%). In conclusion, gender disparities exist in rates of unplanned rehospitalization after PCI, where more than 1 in 10 women who undergo PCI are readmitted within 30 days. Gender differences were not observed for causes of noncardiac readmissions, whereas important differences were observed for cardiovascular causes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In 2006, Critical Care Nursing Quarterly published a study of the physical design features of a set of best practice example adult intensive care units (ICUs). These adult ICUs were awarded between 1993 and 2003 by the Society of Critical Care Medicine (SCCM), the American Association of Critical-Care Nurses, and the American Institute of Architects/Academy of Architecture for Health for their efforts to promote the critical care unit environment through design. Since 2003, several more adult ICUs were awarded by the same organizations for similar efforts. This study includes these newer ICUs along with those of the previous study to cover a period of 2 decades from 1993 to 2012. Like the 2006 study, this study conducts a systematic content analysis of the materials submitted by the award-winning adult ICUs. On the basis of the analysis, the study compares the 1993-2002 and 2003-2012 adult ICUs in relation to construction type, unit specialty, unit layout, unit size, patient room size and design, support and service area layout, and family space design. The study also compares its findings with the 2010 Guidelines for Design and Construction of Health Care Facilities of the Facility Guidelines Institute and the 2012 Guidelines for Intensive Care Unit Design of the SCCM. The study indicates that the award-winning ICUs of both decades used several design features that were associated with positive outcomes in research studies. The study also indicates that the award-winning ICUs of the second decade used more evidence-based design features than those of the first decades. In most cases, these ICUs exceeded the requirements of the Facility Guidelines Institute Guidelines to meet those of the SCCM Guidelines. Yet, the award-winning ICUs of both decades also used several features that had very little or no supporting research evidence. Since they all were able to create an optimal critical care environment for which they were awarded, having knowledge of the physical design of these award-winning ICUs may help design better ICUs.

In the United States, unintended pregnancy is a serious health, social, and economic concern. However, the existing prevention policies have proven ineffective at decreasing the rate of unintended pregnancy at a national level. This lack of effective national prevention policy is better understood when viewed through the lens of a policy theory that incorporates an understanding of social construction and its effects on policy development. Through the application of one such policy theory, this article explores how the social construction of fertile women in the United States affects previous and recently enacted unintended pregnancy prevention policies.

Changing market demand, aging population, severity of illnesses, hospital acquired infection, clinical staff shortage, technological innovations, and environmental concerns-all are shaping the critical care practice in the United States today. However, how these will shape intensive care unit (ICU) design in the coming decade is anybody's guess. In a graduate architecture studio of a research university, students were asked to envision the ICU of the future while responding to the changing needs of the critical care practice through innovative technological means. This article reports the ICU design solutions proposed by these students.

This article reports a study of the physical design characteristics of a set of adult intensive care units (ICUs), built between 1993 and 2003. These ICUs were recognized as the best-practice examples by the Society of Critical Care Medicine, the American Association of Critical Care Nurses, and the American Institute of Architects. This study is based on a systematic analysis of the materials found on these ICUs in the booklet and videos jointly published by the above organizations in 2005. The study finds that most of these examples of best-practice adult ICUs have the following negative characteristics: (1) they are built as renovation projects with more health and safety hazards during construction; (2) most of them are mixed-service units with more safety and staffing problems; (3) the overall layout and the layout of staff work areas in these ICUs do not have any common design solutions for improved patient and staff outcomes; and (4) in these ICUs, family space is often located outside the unit, and family access to the patient room is restricted, even though family presence at the bedside may be important for improved patient outcomes. Some of these negative characteristics are offset by the following positive characteristics in most ICUs: (1) they have only private patient rooms for improved patient care, safety, privacy, and comfort; (2) most patient beds are freestanding for easy access to patients from all sides; (3) they have handwashing sinks and waste disposal facilities in the patient room for improved safety; and (4) most patient rooms have natural light to help patients with circadian rhythms. The article discusses, in detail, the implications of its findings, and the role of the ICU design community in a very complicated design context.

Background: Patients with cystic fibrosis (CF) are at risk of developing vitamin K deficiency because of pancreatic insufficiency, hepatobiliary disease, or both., Objective: Our objective was to determine the prevalence of vitamin K deficiency in unsupplemented patients with CF and to identify risk factors that might be associated with the deficiency., Design: Ninety-eight patients with CF-83 who were pancreatic insufficient (age: 15.2 +/- 10.7 y; range: 0.6-45.8 y), 15 who were pancreatic sufficient (age: 26.2 +/- 11.6 y; range: 6.5-45.3 y), and 62 healthy individuals (age: 16.2 +/- 12. 8 y; range: 1-45 y)-were studied prospectively. None had taken vitamin K supplements. Eight pancreatic-insufficient patients had advanced CF-associated liver disease. Plasma prothrombin in vitamin K absence (PIVKA-II) was measured by immunoassay. All control subjects had PIVKA-II concentrations <3 microg/L., Results: Seventy-eight percent of pancreatic-insufficient patients had PIVKA-II concentrations >/=3 microg/L (22.8 +/- 35.7 microg/L). All patients with CF-associated liver disease had abnormal PIVKA-II concentrations. The mean PIVKA-II concentration of pancreatic-insufficient patients with liver disease was greater than that of those without liver disease (46.6 +/- 65.3 compared with 15. 3 +/- 26.1 microg/L; P < 0.05). Five pancreatic-sufficient patients had mildly elevated PIVKA-II concentrations. Six (7%) pancreatic insufficient patients (3 with CF-associated liver disease) had mildly prolonged prothrombin time but no clinical bleeding. There was no correlation between PIVKA-II concentrations and severity of fat malabsorption or antibiotic use., Conclusions: Vitamin K deficiency is common in unsupplemented patients with CF and pancreatic insufficiency and routine supplementation should be considered in all of these patients.