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Background Longitudinal analyses of large, detailed adult critical care datasets provide insights into practice trends and generate useful outcome and process benchmarks. Methods Data representing 991,571 consecutive critical care visits to 160 US adult ICUs from 2009 to 2013 from the eICU Research Institute clinical practice database were used to quantitate patient characteristics, APACHE IV–based acuity predictions, treatments, and outcomes. Analyses for changes over time were performed for patient characteristics, entry and discharge locations, primary admission diagnosis, treatments, adherence to consensus ICU best practices, length of stay (LOS), and inpatient mortality. Results We detected significant trends for increasing age, BMI, and risk of mortality, higher frequency of admission from an ED and stepdown unit, and more frequent hospital discharge to substance abuse centers and skilled nursing facilities. Significantly more patients were admitted for sepsis, emphysema, coma, congestive heart failure, diabetic ketoacidosis, and fewer were admitted for asthma, unspecified chest pain, coronary artery bypass graft, and stroke care. The frequency of noninvasive mechanical ventilation and adherence to critical care best practices significantly increased, whereas the duration of renal replacement therapies, frequency of transfusions, antimicrobial use, critical care complications, LOS, and inpatient mortality decreased. Conclusions Analyses of patients, practices, and outcomes from a large geographically dispersed sample of adult ICUs revealed trends of increasing age and acuity, higher rates of adherence to best practice, use of noninvasive mechanical ventilation, and decreased use of antimicrobials, transfusions, and duration of renal replacement therapies. Acuity-adjusted LOS and in hospital mortality decreased.

OBJECTIVE To synthesize the existing literature on benefits and risks of anticoagulant use after traumatic brain injury (TBI). DESIGN Systematic review. A literature search was performed in MEDLINE, International Pharmaceutical Abstracts, Health Star, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) on October 11, 2012, and updated on September 2, 2013, using terms related to TBI and anticoagulants. MAIN MEASURES Human studies evaluating the effects of post-TBI anticoagulation on venous thromboembolism, hemorrhage, mortality, or coagulation parameters with original analyses were eligible for the review. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed throughout the conduct of the review. RESULTS Thirty-nine eligible studies were identified from the literature, of which 23 studies with complete information on post-TBI anticoagulant use and patient outcomes were summarized in this review. Meta-analysis was unwarranted because of varying methodological design and quality of the studies. Twenty-one studies focused on the effects of pharmacological thromboprophylaxis (PTP) post-TBI on venous thromboembolism and/or progression of intracranial hemorrhage, whereas 2 randomized controlled trials analyzed coagulation parameters as the result of anticoagulation. CONCLUSION Pharmacological thromboprophylaxis appears to be safe among TBI patients with stabilized hemorrhagic patterns. More evidence is needed regarding effectiveness of PTP in preventing venous thromboembolism as well as preferred agent, dose, and timing for PTP.

Should advanced age be a contraindication to the surgical management of head and neck cancer patients? A retrospective chart review was performed of patients aged ≥80 years treated surgically for a head and neck malignancy during the period 1996-2011 in a tertiary care cancer centre. The average follow-up was 32 months. Fifty-three patients were identified (mean age 85 years). Cardiovascular disease was the most prevalent co-morbidity (43%). Forty-five patients (85%) had oral cavity/oropharynx squamous cell carcinoma. Surgeries performed included 40 neck dissections and 12 microvascular free flaps. The average length of hospital stay (LOS) was 6.4 days. An increased LOS was significant in patients requiring free flap reconstruction (P0.01). There were no perioperative deaths or free flap failures. The most common postoperative complications were cardiovascular (n=8), infection (n=10), and delirium (n=6). Thirty-four patients were discharged directly home. Free flap reconstruction did not adversely affect discharge disposition (P0.05). More than 75% of patients did not report any major limitations to their activities of daily living. Major head and neck surgical procedures can be tolerated by patients of advanced age using careful patient selection. Age alone should not be a primary factor in the management of head and neck cancer patients.

This study examined warfarin usage for elderly Medicare beneficiaries with atrial fibrillation (AF) who suffered traumatic brain injury (TBI), hip fracture, or torso injuries. Using the 5% Chronic Condition Data Warehouse administrative claims data, this study included fee-for-service Medicare beneficiaries who had a single injury hospitalization (TBI, hip fracture, or major torso injury) between 1/1/2007 and 12/31/2009, with complete Medicare Parts A, B (no Medicare Advantage), and D coverage 6 months before injury, and who were aged 66 years or older and diagnosed with AF at least 1 year before injury. About 45% of the AF patients were using warfarin before TBI or torso injury, and 35% before hip fracture. After injury, there was a dramatic and persistent decrease in warfarin use in TBI and torso injury groups (30% for TBI and 37% for torso injury at 12 months after injury). Warfarin usage in hip fracture patients also dropped after injury but returned to pre-injury level within 4 months. TBI and torso injury lead to significant decreases in warfarin usage in elderly AF patients. Further research is needed to understand reasons for the pattern and to develop evidence-based management strategies in the post-acute setting.

Objectives: To assess the effectiveness of medications used in the management of Alzheimer's disease and related dementias (ADRD) on cognition and activity of daily living (ADL) trajectories and to determine whether sex modifies these effects. Design: Two-year (2007�2008) longitudinal study. Setting: Medicare enrollment and claims data linked to the Minimum Dataset 2.0. Participants: Older nursing home (NH) residents with newly diagnosed ADRD (n = 18,950). Measurements: Exposures included four medication classes: antidementia medications (ADMs), antipsychotics, antidepressants, and mood stabilizers. Outcomes included ADLs and cognition (Cognitive Performance Scale (CPS)). Marginal structural models were employed to account for time-dependent confounding. Results: The mean age was 83.6, and 76% of the sample was female. Baseline use of ADMs was 15%, antidepressants was 40%, antipsychotics was 13%, and mood stabilizers was 3%. Mean baseline ADL and CPS scores were 16.6 and 2.1, respectively. ADM use was not associated with change in ADLs over time but was associated with a slower CPS decline (slope difference: -0.09 points/year, 99% confidence interval (CI) = -0.14 to -0.03). Antidepressant use was associated with slower declines in ADL (slope difference: -0.36 points/year, 99% CI = -0.58 to -0.14) and CPS (slope difference: -0.12 points/year, 99% CI = -0.17 to -0.08). Sex modified the effect of both antipsychotic and mood stabilizer use on ADLs; female users declined most quickly. Antipsychotic use was associated with slower CPS decline (slope difference: -0.11 points/year, 99% CI = -0.17 to -0.06), whereas mood stabilizer use had no effect. Conclusion: Despite the observed statistically significantly slower declines in cognition with ADMs, antidepressants, and antipsychotics and the slower ADL decline found with antidepressants, it is unlikely that these benefits are of clinical significance.

© 2017 Nature America, Inc., part of Springer Nature. All rights reserved. Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10-8; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

The effect of the respiratory therapist (RT)/patient ratio and RT organizational factors on respiratory resource utilization is unknown. We describe the impact of a multi-component intervention that called for an increase in RT/patient ratio (1:14 to 1:10), improved RT orientation, and formation of a core staffing model on best practice, including spontaneous breathing trials (SBTs) and catheter and bronchoscopically directed lower respiratory tract cultures, or bronchoalveolar lavage (BAL), in both ventilated and non-ventilated patients in the ICU.We conducted a single center, quasi-experimental study comparing 651 patients with single and first admissions between April 19, 2005 and April 18, 2006 before the RT services reorganization with 1,073 patients with single and first admissions between September 16, 2007 and September 4, 2008. Baseline characteristics were compared, along with SBTs, BAL use, lower respiratory tract cultures, and chest physiotherapy.Patients in the 2 groups were similar in terms of age (52.9 ± 15.8 y vs 53.9 ± 16.4 y, P = .23), comorbidity as measured by Charlson score (2.8 ± 2.6 vs 2.8 ± 2.7, P = .56), and acuity of illness as measured by the Case Mix Index (3.2 ± 3.9 vs 3.3 ± 4.1, P = .47). Mechanically ventilated patients had similar prevalences of respiratory diseases (24.2% vs 25.1%, P = .61). There was an increase in SBTs (0.5% vs 73.1%, P.001), chest physiotherapy (7.4% vs 21.6%, P.001), BALs (24.0% vs 41.4%, P.001), and lower respiratory tract cultures (21.5% vs 38.0%, P.001) in mechanically ventilated patients post-intervention.A multi-component intervention, including an increase in RT/patient ratio, improved RT orientation, and establishment of a core staffing model, was associated with increased respiratory resource utilization and evidence-based practice, specifically BALs and SBTs.

Gingival squamous cell carcinoma (SCC) is relatively uncommon, and little is known about its metastatic pattern. We retrospectively reviewed 864 consecutive patients with oral SCC who were seen at the University of Maryland Department of Oral and Maxillofacial Surgery (1991-2005), and identified 111 cases of gingival SCC. Inclusion criteria were fulfilled in 72 patients (mean duration of follow up 49 (1-153) months). Mean (range) age was 72 (45-93) years; 41 patients were women and 31 men. Distribution was almost equal: mandible 35 and maxilla 37. Forty (56%) were in the early stages (pI/II) and 32 (44%) in the later stages (pIII/IV). Twenty-nine patients had primary neck dissections, of whom 7/21 had clear, and 6/8 invaded, cervical nodes. The total number of occult nodal metastases was 9/29 (31%) in the mandible and 14/35 in the maxilla (one patient with initially clear nodes had both invaded nodes at neck dissection and a recurrence in the neck). The number of early compared with late stage occult metastases was 4 of 20 patients (20% T1/T2) and 5 of 9 patients (55% T3/T4) in the mandible and 2 of 22 patients (9% T1/T2) and 2 of 13 patients (15% T3/T4) in the maxilla. Two of 9 patients developed occult nodes within T2 maxillary gingival SCC. Bony invasion was identified in 17 patients (24%) occurring in 8 of 19 patients (42%) with invaded nodes compared with 9 of 53 patients (17%) with clear nodes. Overall survival at 2 and 5 years was 53 of 72 patients (74%) and 27 of 72 patients (38%) respectively. Elective neck dissection is indicated for all stages of mandibular gingival tumours and T3/T4 carcinomas of the maxillary gingiva. T2 maxillary SCC should be considered for elective neck dissection. Overall disease-free survival was worse among those with cervical metastases (p=0.004) and those who had had marginal resections (p=0.04).

BACKGROUND: Clinical guidelines recommend a restrictive transfusion strategy in nonhemorrhaging critically ill patients. STUDY DESIGN AND METHODS: We conducted a retrospective observational study of 3533 single-admission patients, without evidence of acute coronary syndromes, hemorrhage, or hemoglobinopathy admitted to the medical intensive care unit (MICU) of a large, academic medical center. RESULTS: MICU admission hemoglobin (Hb) level did not change significantly over the study period. The proportion of transfused patients decreased from 31.0% in 1997 to 1998 to 18.0% in 2006 to 2007 (p

SummaryOvarian cancer is a leading cause of death from gynecologic malignancies. Treatment for advanced-stage disease remains limited and, to date, targeted therapies have been incompletely explored. By systematically suppressing each human tyrosine kinase in ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines. Perturbation of this circuit with ErbB3-directed RNAi decreased cell growth in three-dimensional culture and resulted in decreased disease progression and prolonged survival in a xenograft mouse model of ovarian cancer. Furthermore, a monoclonal ErbB3-directed antibody (MM-121) also significantly inhibited tumor growth in vivo. These findings identify ErbB3 as a potential therapeutic target in ovarian cancer.

Objectives The Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA 3 CT) is a Phase IIb randomized, placebo-controlled clinical trial, testing doxycycline (100 mg bid) for inhibition of growth in the greatest transverse, orthogonal diameter of small abdominal aortic aneurysms (AAA). Methods We will enroll 258 patients, ≥ 55 years of age who have AAA, men: 3.5–5.0 cm and women: 3.5–4.5 cm on CT scans confirmed centrally. The primary outcome is growth in maximal transverse, orthogonal diameter from baseline to 24-month follow-up. Secondary analyses address doxycycline effects on clinical events, aneurysm volume, and biomarkers. Primary analysis will be performed according to the principle of intention-to-treat accounting for death and ruptures by use of normal scores in analysis of covariance. At the time of the data file reported, 200 subjects have been randomized. We started enrollment in mid-2013 and will complete enrollment by mid-2016. Results Participant average age = 70.9 years, (SD = 7.6 years) and maximum transverse diameter = 4.3 cm for men (SD = 0.4) and 4.0 cm for women (SD = 0.3). Conclusion N-TA 3 CT is a critical experiment to determine whether doxycycline reduces growth of small AAA and systemic markers of inflammation previously seen in bench experiments and observational human studies to be associated with AAA growth. Our patient population baseline measurements agree with the design assumptions supporting our expectation of 90% power or greater to reject a null hypothesis in favor of an alternative hypothesis when growth is reduced by at least 40%. Registration: clinicaltrials.gov # NCT01756833 .

RESULTS Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0.72-0.96]).

Objective Following traumatic brain injury (TBI), older adults are at an increased risk of hemorrhagic and thromboembolic events, but it is unclear whether the increased risk continues after hospital discharge. We estimated incidence rates of hemorrhagic and ischemic stroke following hospital discharge for TBI among adults 65 years or older and compared them with pre-TBI rates. Participants A total of 16 936 Medicare beneficiaries 65 years or older with a diagnosis of TBI in any position on an inpatient claim between June 1, 2006, and December 31, 2009, who survived to hospital discharge. Design Retrospective analysis of a random 5% sample of Medicare claims data. Main measures Hemorrhagic stroke was defined as ICD-9 (International Classification of Diseases, Ninth Revision) codes 430.xx-432.xx. Ischemic stroke was defined as ICD-9 codes 433.xx-435.xx, 437.0x, and 437.1x. Results There was a 6-fold increase in the rate of hemorrhagic stroke following TBI compared with the pre-TBI period (adjusted rate ratio, 6.5; 95% confidence interval, 5.3-7.8), controlling for age and sex. A smaller increase in the rate of ischemic stroke was observed (adjusted rate ratio, 1.3; 95% CI, 1.2-1.4). Conclusion Future studies should investigate causes of increased stroke risk post-TBI as well as effective treatment options to reduce stroke risk and improve outcomes post-TBI among older adults.

The optimal approach for managing increased risk of VTE among critically ill adults is unknown.An observational study of 294,896 episodes of critical illness among adults was conducted in 271 geographically dispersed US adult ICUs. The primary outcomes were all-cause ICU and in-hospital mortality after adjustment for acuity and other factors among groups of patients assigned, based on clinical judgment, to prophylactic anticoagulation, mechanical devices, both, or neither. Outcomes of those managed with prophylactic anticoagulation or mechanical devices were compared in a separate paired, propensity-matched cohort.After adjustment for propensity to receive VTE prophylaxis, APACHE (Acute Physiology and Chronic Health Evaluation) IV scores, and management with mechanical ventilation, the group treated with prophylactic anticoagulation was the only one with significantly lower risk of dying than those not provided VTE prophylaxis (ICU, 0.81 [95% CI, 0.79-0.84]; hospital, 0.84 [95% CI, 0.82-0.86; P.0001). The mortality risk of those receiving mechanical device prophylaxis was not lower than that of patients without VTE prophylaxis. A study of 87,107 pairs of patients matched for propensity to receive VTE prophylaxis found that those managed with prophylactic anticoagulation therapy had significantly lower risk of death (ICU subhazard ratio, 0.82 [95% CI, 0.78-0.85]; hospital subhazard ratio, 0.82 [95% CI, 0.79-0.85]; P.001) than those receiving only mechanical device prophylaxis.These findings support a recommendation for prophylactic anticoagulation therapy in preference to mechanical device prophylaxis for critically ill adult patients who do not have a contraindication to anticoagulation.

Background and aimHypothesizing that intrathoracic fat might exert local effects on the coronary vasculature, we assessed the association of intrathoracic fat volume and its two subcomponents with coronary artery calcification (CAC) in 909 relatively healthy Amish adults.Methods and resultsIntrathoracic fat, which is comprised of fat between the surface of the heart and the visceral epicardium (epicardial fat) and fat around the heart but outside of the fibrous pericardium (pericardial fat), was measured from electron beam CT scans. We examined the association between intrathoracic fat volume and cardiovascular disease risk factors in multivariate regression model. Fat volume in the epicardial and pericardial compartments were highly correlated with each other and with body mass index. Neither CAC extent nor CAC presence (Agatston score > 0) was associated with increased intrathoracic fat volume in sex-stratified models adjusting for age (p > 0.10). Intrathoracic fat volume was significantly correlated with higher systolic/diastolic blood pressure, pulse pressure, fasting glucose, insulin, triglyceride and lower high-density lipoprotein cholesterol in sex-stratified models adjusting for age (p < 0.05). However, associations were attenuated after further adjustment for body mass index.ConclusionsThese data do not provide support for a significant role for intrathoracic fat in the development of CAC.

The objective of the present study was to summarize the treatment and outcomes of cT1N0M0 tongue cancer for which the management is less defined.A total of 65 consecutive cases of cT1 tongue cancer were retrospectively reviewed. The Fisher exact, χ(2), and Wilcoxon tests were used to statistically analyze the data.The tumor depth had a significant relation to the presence of neck metastasis (P.05). A 3-mm cutoff point provided better predictive value, with a sensitivity of 92.9% and specificity of 43.1%. The biopsy depth combined with palpation was accurate in determining the tumor depth preoperatively in 87.7%. On multivariate analysis, only the tumor site (ventral tongue) and the presence of erythroleukoplakia had any significant relation to disease-free survival (P = .010).Elective neck dissection should be considered for patients with cT1N0 oral tongue squamous carcinoma with a biopsy depth of 3 mm or greater. The biopsy depth, combined with the clinical examination findings, is a useful method to help determine the tumor depth preoperatively.

Purpose Squamous carcinoma of the buccal mucosa is relatively uncommon in the North American population. It is considered an aggressive cancer, with difficulty in obtaining negative surgical margins and poor locoregional control. This single-institution retrospective analysis attempted to identify prognostic variables, treatment outcomes, and survival patterns of patients with buccal carcinoma. Materials and Methods A retrospective chart review of all patients with buccal carcinoma treated in the Department of Oral and Maxillofacial Surgery, University of Maryland from 1992 through 2008 was conducted. Thirty newly diagnosed and previously untreated patients were reviewed and their outcomes data were analyzed. Results Thirteen female and 17 male patients were identified (mean age, 64 yr). Eighteen patients had early-stage disease (stages I to II). Fifteen patients (50%) developed recurrence, with 13 patients developing local recurrence despite 80% of patients achieving negative surgical margins. The overall nodal metastasis rate was 43%, with an occult nodal rate of 32%. Overall 2- and 5-year survival rates were 69% and 53%, respectively. Thirty-nine percent of patients not receiving adjuvant therapy developed recurrence. Early recurrence tended to occur more commonly and was a poor prognostic indicator of successful salvage. Conclusions Buccal carcinoma is an aggressive disease, with high rates of locoregional disease recurrence independent of surgical margin status. Elective neck dissection and adjuvant therapy should be considered for early-stage disease. Successful salvage is rare in cases of early recurrence.