Citations

Background The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm—the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. Results For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

Purpose: Studies have shown a modest association between pericardial fat volume (PFV) and coronary artery disease (CAD), potentially mediated by local inflammation. We aimed to investigate the association between a new biomarker of pericardial fat inflammation, named pericardial fat enhancement (PFE), and the severity of CAD on coronary computed tomography angiography (CCTA). Materials and Methods: We evaluated 114 patients referred for CCTA from 2007 to 2011. PFV, presence of obstructive CAD, and the burden of CAD were determined. PFE was measured in 10 mm2 regions of interest, adjusted to aortic enhancement (aPFE). The population was divided into those with greater than median (G-PFE) versus less than median pericardial fat enhancement (L-PFE). Stratified adjusted logistic regressions were performed. A P-value <0.05 was considered significant. The study was approved by our institutional review board. Results: Patients were 54.3±14.8 years of age, and 57/114 (50%) were male individuals, with body mass index of 27.3±6.3. There was an independent association between CAD severity and PFV. There was a significant independent association between PFV and obstructive CAD (odds ratio=1.26, P=0.005), and PFV and burden of CAD (odds ratio=1.25, P=0.05) in those with greater PFE. However, there was no significant association between obstructive CAD and CAD burden in either adjusted model for patients with less PFE. Conclusions: Our results suggest that PFE influences significantly the relationship between PFV and CAD, supporting the hypothesis of local pericardial fat inflammation as a mechanism for CAD development.

Objective Non-vitamin K oral anticoagulants (NOACs) require dose adjustment for renal function. We sought to investigate change in renal function over time in patients with atrial fibrillation (AF) and whether those on NOACs have appropriate dose adjustments according to its decline. Methods We included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry treated with oral anticoagulation. Worsening renal function (WRF) was defined as a decrease of >20% in creatinine clearance (CrCl) from baseline. The US Food and Drug Administration (FDA)-approved package inserts were used to define the reduction criteria of NOACs dosing. Results Among 6682 patients with AF from 220 sites (median age (25th, 75th): 72.0 years (65.0, 79.0); 57.1% male; median CrCl at baseline: 80.1 mL/min (57.4, 108.5)), 1543 patients (23.1%) experienced WRF with mean decline in CrCl during 2 year follow-up of −6.63 mL/min for NOACs and −6.16 mL/min for warfarin. Among 4120 patients on NOACs, 154 (3.7%) patients had a CrCl decline sufficient to warrant FDA-recommended dose reductions. Of these, NOACs dosing was appropriately reduced in only 31 (20.1%) patients. Compared with patients with appropriately reduced NOACs, those without were more likely to experience bleeding complications (major bleeding: 1.7% vs 0%; bleeding hospitalisation: 2.6% vs 0%) at 1 year. Conclusions In the US practice, about one-fourth of patients with AF had >20% decline in CrCl over time during 2 year follow-up. As a result, about 3.7% of those treated with NOACs met guideline criteria for dose reduction, but of these, only 20.1% actually had a reduction.

Background: Disparities in diversity, equity and inclusivity are endemic in American society, and in the United States (US) healthcare system. As US population diversity increases, physical therapists (PTs) must be able to provide equitable care for all people, regardless of their cultural or personal identity. Culturally-humble Hospice and palliative Care (HPC) PT practice, with vigilant awareness of cultural complexities and commitment to approaching cultural understanding with humility, is essential to provide optimal end of life care for all persons. Purpose: This Perspective paper will 1) provide an overview of the role of PT in HPC, 2) describe culturally-related disparities in HPC, and 3) suggest evidence-based strategies for cultural humility in HPC PT best practice. Specific challenges in the delivery of culturally-humble end of life care will be discussed, including advanced care planning, truth telling, and death beliefs/practices.

Abstract Background How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB). Methods The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (&gt;URL 6.5%), NT-proBNP (&gt;URL 125 ng/L) and eGFR (&lt;60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods. Results Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women. Conclusions Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.

ABSTRACTCoxsackievirus B3 (CVB3) infection induces myocardial inflammation and myocyte necrosis in some, but not all, strains of mice. C57BL/6 mice, which inherently lack major histocompatibility complex (MHC) class II IE antigen, develop minimal cardiac lesions despite high levels of virus in the heart. The present experiments evaluate the relative roles of class II IA and IE expression on myocarditis susceptibility in four transgenic C57BL/6 mouse strains differing in MHC class II antigen expression. Animals lacking MHC class II IE antigen (C57BL/6 [IA+IE−] and ABo[IA−IE−]) developed minimal cardiac lesions subsequent to infection despite high concentrations of virus in the heart. In contrast, strains expressing IE (ABoEα [IA−IE+] and Bl.Tg.Eα [IA+IE+]) had substantial cardiac injury. Myocarditis susceptibility correlated to a Th1 (gamma interferon-positive) cell response in the spleen, while disease resistance correlated to a preferential Th2 (interleukin-4-positive) phenotype. Vγ/Vδ analysis indicates that distinct subpopulations of γδ+T cells are activated after CVB3 infection of C57BL/6 and Bl.Tg.Eα mice. Depletion of γδ+T cells abrogated myocarditis susceptibility in IE+animals and resulted in a Th1→Th2 phenotype shift. These studies indicate that the MHC class II antigen haplotype controls myocarditis susceptibility, that this control is most likely mediated through the type of γδ T cells activated during CVB3 infection, and finally that different subpopulations of γδ+T cells may either promote or inhibit Th1 cell responses.

Objective. We explore the clinicopathologic features of Ewing sarcoma (ES) presenting in older adulthood. Methods. Cases of molecularly confirmed ES arising in patients aged ≥40 years were evaluated. Results. Fifty patients were identified (33 males/17 females; 41-86 years). The majority of tumors (41) arose at extraskeletal sites, while 9 were bone primaries. Twenty-eight cases showed nested architecture, while the remaining cases showed sheet-like growth. Tumor cytology was categorized as conventional (n = 39), crushed (n = 5), clear cell (n = 4), rhabdoid (n = 3), and epithelioid (n = 2). Fifty percent had necrosis, while rosettes were noted in 1 case. Immunostains performed ranged from 1 to 28 (median = 10). Follow-up (n = 43, 1-147 months) revealed 15 patients with metastasis. Conclusion. Although rare, ES should be considered in the differential diagnosis for round cell malignancies in older adult patients. In this cohort, ES is most often extraskeletal, and may show unusual morphologic features, closely simulating more common neoplasms in this age group.