PCOM Library / Archive for "Hot Topics in Research"

Category: Hot Topics in Research

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

pjgrier Cardiology, Hot Topics in Research

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack
BACKGROUND Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease.
METHODS In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.
RESULTS By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).
CONCLUSIONS In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.)
W.N. Kernan, C.M. Viscoli, K.L. Furie, L.H. Young, S.E. Inzucchi, M. Gorman, P.D. Guarino, A.M. Lovejoy, P.N. Peduzzi, R. Conwit, L.M. Brass,* G.G. Schwartz, H.P. Adams, Jr., L. Berger, A. Carolei, W. Clark, B. Coull, G.A. Ford, D. Kleindorfer, J.R. O’Leary, M.W. Parsons, P. Ringleb, S. Sen, J.D. Spence, D. Tanne, D. Wang, and T.R. Winder
N Engl J Med 2016;374:1321-31. DOI: 10.1056/NEJMoa1506930 Copyright © 2016 Massachusetts Medical Society

Defining Rates and Risk Factors for Readmissions Following Emergency General Surgery

pjgrier Hot Topics in Research

Defining Rates and Risk Factors for Readmissions Following Emergency General Surgery

Hospital readmission rates following surgery are increasingly being used as a marker of quality of care and are used in pay-for-performance metrics. To our knowledge, comprehensive data on readmissions to the initial hospital or a different hospital after emergency general surgery (EGS) procedures do not exist.
Objective  To define readmission rates and identify risk factors for readmission after common EGS procedures.
Design, Setting, and Participants  Patients undergoing EGS, as defined by the American Association for the Surgery of Trauma, were identified in the California State Inpatient Database (2007-2011) on January 15, 2015. Patients were 18 years and older. We identified the 5 most commonly performed EGS procedures in each of 11 EGS diagnosis groups. Patient demographics (sex, age, race/ethnicity, and insurance type) as well as Charlson Comorbidity Index score, length of stay, complications, and discharge disposition were collected. Factors associated with readmission were determined using multivariate logistic regression models analysis.
Main Outcomes and Measures  Thirty-day hospital readmission.
Results  Among 177 511 patients meeting inclusion criteria, 57.1% were white, 48.8% were privately insured, and most were 45 years and older (51.3%). Laparoscopic appendectomy (35.2%) and laparoscopic cholecystectomy (19.3%) were the most common procedures. The overall 30-day readmission rate was 5.91%. Readmission rates ranged from 4.1% (upper gastrointestinal) to 16.8% (cardiothoracic). Of readmitted patients, 16.8% were readmitted at a different hospital. Predictors of readmission included Charlson Comorbidity Index score of 2 or greater (adjusted odds ratio: 2.26 [95% CI, 2.14-2.39]), leaving against medical advice (adjusted odds ratio: 2.24 [95% CI, 1.89-2.66]), and public insurance (adusted odds ratio: 1.55 [95% CI, 1.47-1.64]). The most common reasons for readmission were surgical site infections (16.9%), gastrointestinal complications (11.3%), and pulmonary complications (3.6%).
Conclusions and Relevance  Readmission after EGS procedures is common and varies widely depending on patient factors and diagnosis categories. One in 5 readmitted patients will go to a different hospital, causing fragmentation of care and potentially obscuring the utility of readmission as a quality metric. Assisting socially vulnerable patients and reducing postoperative complications, including infections, are targets to reduce readmissions.

Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus Bloodstream Infection: A Propensity Score–Matched Cohort Study

pjgrier Cardiology, Hot Topics in Research

Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus Bloodstream Infection: A Propensity Score–Matched Cohort Study
Objectives: Staphylococcus aureus bloodstream infection is associated with considerable mortality. Experimental models suggest a direct antistaphylococcal effect of acetylsalicylic acid, but evidence from human studies is scarce. We aimed to estimate the effect of low-dose acetylsalicylic acid therapy on mortality in bloodstream infections caused by S. aureus compared with Escherichia coli.
Design: Retrospective cohort study based on observational data from 838 and 602 episodes of S. aureus and E. coli bloodstream infection, respectively. Setting: Swiss tertiary referral center. Patients: Adult patients with S. aureus and E. coli bloodstream infection, respectively, categorized according to low-dose acetylsalicylic acid therapy as outpatient or inpatient before bacteremia.
Interventions: None.
Measurements and Main Results: Thirty-day all-cause mortality was analyzed in a total of 314 propensity score-matched S. aureus bloodstream infection and in 268 E. coli bloodstream infection patients, respectively (1:1 match of low-dose acetylsalicylic acid users and nonusers). S. aureus bloodstream infection cases and controls were equally matched for relevant confounders except treatment with statins, which was strongly associated with a low-dose acetylsalicylic acid use (p < 0.001). At day 30, 12.1% of cases and 27.4% of controls had died (hazard ratio, 0.40; p < 0.001). Low-dose acetylsalicylic acid use was associated with a reduced 30-day all-cause mortality in multivariate analysis (hazard ratio, 0.38; 95% CI, 0.21-0.69; p = 0.001) of matched patients and also of the entire cohort (n = 689) after adjustment for the propensity score (hazard ratio, 0.58, 95% CI, 0.34-0.98; p = 0.04). In contrast, low-dose acetylsalicylic acid use was not associated with the primary endpoint in patients with E. coli bloodstream infection (hazard ratio, 0.78; 95% CI, 0.40-1.55; p = 0.8).
Conclusions: Low-dose acetylsalicylic acid at the time of bloodstream infection was strongly associated with a reduced short-term mortality in patients with S. aureus bloodstream infection. Future studies are required to investigate if early low-dose acetylsalicylic acid is a suitable treatment in patients with S. aureus bloodstream infection.
Osthoff, Michael MD; Sidler, Jan A. MD; Lakatos, Botond MD; Frei, Reno MD; Dangel, Marc MPH; Weisser, Maja MD; Battegay, Manuel MD; Widmer, Andreas F. MD, MS
Copyright (C) by 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Association of Child Poverty, Brain Development, and Academic Achievement

pjgrier Brain, Hot Topics in Research

Association of Child Poverty, Brain Development, and Academic Achievement

Importance  Children living in poverty generally perform poorly in school, with markedly lower standardized test scores and lower educational attainment. The longer children live in poverty, the greater their academic deficits. These patterns persist to adulthood, contributing to lifetime-reduced occupational attainment.
Objective  To determine whether atypical patterns of structural brain development mediate the relationship between household poverty and impaired academic performance.
Design, Setting, and Participants  Longitudinal cohort study analyzing 823 magnetic resonance imaging scans of 389 typically developing children and adolescents aged 4 to 22 years from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development with complete sociodemographic and neuroimaging data. Data collection began in November 2001 and ended in August 2007. Participants were screened for a variety of factors suspected to adversely affect brain development, recruited at 6 data collection sites across the United States, assessed at baseline, and followed up at 24-month intervals for a total of 3 periods. Each study center used community-based sampling to reflect regional and overall US demographics of income, race, and ethnicity based on the US Department of Housing and Urban Development definitions of area income. One-quarter of sample households reported the total family income below 200% of the federal poverty level. Repeated observations were available for 301 participants.
Exposure  Household poverty measured by family income and adjusted for family size as a percentage of the federal poverty level.
Main Outcomes and Measures  Children’s scores on cognitive and academic achievement assessments and brain tissue, including gray matter of the total brain, frontal lobe, temporal lobe, and hippocampus.
Results  Poverty is tied to structural differences in several areas of the brain associated with school readiness skills, with the largest influence observed among children from the poorest households. Regional gray matter volumes of children below 1.5 times the federal poverty level were 3 to 4 percentage points below the developmental norm (P < .05). A larger gap of 8 to 10 percentage points was observed for children below the federal poverty level (P < .05). These developmental differences had consequences for children’s academic achievement. On average, children from low-income households scored 4 to 7 points lower on standardized tests (P < .05). As much as 20% of the gap in test scores could be explained by maturational lags in the frontal and temporal lobes.
Conclusions and Relevance  The influence of poverty on children’s learning and achievement is mediated by structural brain development. To avoid long-term costs of impaired academic functioning, households below 150% of the federal poverty level should be targeted for additional resources aimed at remediating early childhood environments.
Nicole L. Hair, PhD; Jamie L. Hanson, PhD; Barbara L. Wolfe, PhD; Seth D. Pollak, PhD
JAMA Pediatr. 2015;169(9):822-829. doi:10.1001/jamapediatrics.2015.1475.

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer

pjgrier Hot Topics in Research, Oncology, Prostate

Association Between Treatment at a High-Volume Facility and Improved Survival for Radiation-Treated Men With High-Risk Prostate Cancer
Purpose: Although the association between higher hospital volume and improved outcomes has been well-documented in surgery, there is little data about whether this effect exists for radiation-treated patients. We investigated whether treatment at a radiation facility that treats a high volume of prostate cancer patients is associated with improved survival for men with high-risk prostate cancer. Methods and Materials: We used the National Cancer Database (NCDB) to identity patients diagnosed with prostate cancer from 2004 to 2006. The radiation case volume (RCV) of each hospital was based on its number of radiation-treated prostate cancer patients. We used propensity-score based analysis to compare the overall survival (OS) of high-risk prostate cancer patients in high versus low RCV hospitals. Primary endpoint is overall survival. Covariates adjusted for were tumor characteristics, sociodemographic factors, radiation type, and use of androgen deprivation therapy (ADT). Results: A total of 19,565 radiation-treated high-risk patients were identified. Median follow-up was 81.0 months (range: 1-108 months). When RCV was coded as a continuous variable, each increment of 100 radiation-managed patients was associated with improved OS (adjusted hazard ratio [AHR]: 0.97; 95% confidence interval [CI]: 0.95- 0.98; P<.0001) after adjusting for known confounders. For illustrative purposes, when RCV was dichotomized at the 80th percentile (43 patients/year), high RCV was associated with improved OS (7-year overall survival 76% vs 74%, log-rank test PZ.0005; AHR: 0.91, 95% CI: 0.86-0.96, PZ.0005). This association remained significant when RCV was dichotomized at 75th (37 patients/year), 90th (60 patients/year), and 95th (84 patients/year) percentiles but not the 50th (19 patients/year). Conclusions: Our results suggest that treatment at centers with higher prostate cancer radiation case volume is associated with improved OS for radiation-treated men with high-risk prostate cancer. 
Int J Radiation Oncol Biol Phys, Vol. 94, No. 4, pp. 683e690, 2016
Copyright: 2016 The Authors
Yu-Wei Chen, MD, MS, Brandon A. Mahal, MD, Vinayak Muralidhar, MSc, Michelle Nezolosky, BA, Clair J. Beard, MD, Robert B. Den, MD, Felix Y. Feng, MD,Karen E. Hoffman, MD, MPH, MHSc, Neil E. Martin, MD, MPH, Peter F. Orio, DO, MS, and Paul L. Nguyen, MD

Visualization of regional tau deposits using 3H-THK5117 in Alzheimer brain tissue

pjgrier Alzheimer Disease, Hot Topics in Research

Visualization of regional tau deposits using 3H-THK5117 in Alzheimer brain tissue


 The accumulation of neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein, starts spreading early in specific regions in the course of Alzheimer’s disease (AD), correlating with the progression of memory dysfunction. The non-invasive imaging of tau could therefore facilitate the early diagnosis of AD, differentiate it from other dementing disorders and allow evaluation of tau immunization therapy outcomes. In this study we characterized the in vitro binding properties of THK5117, a tentative radiotracer for positron emission tomography (PET) imaging of tau brain deposits.


Saturation and competition binding studies of 3H-THK5117 in post-mortem AD brain tissue showed the presence of multiple binding sites. THK5117 binding was significantly higher in hippocampal (p < 0.001) and temporal (p < 0.01) tissue homogenates in AD compared to controls. Autoradiography studies with 3H-THK5117 was performed on large frozen brain sections from three AD cases who had been followed clinically and earlier undergone in vivo 18F-FDG PET investigations. The three AD cases showed distinct differences in regional THK5117 binding that were also observed in tau immunohistopathology as well as in clinical presentation. A negative correlation between in vivo 18F-FDG PET and in vitro 3H-THK5117 autoradiography was observed in two of the three AD cases.


This study supports that new tau PET tracers will provide further understanding on the role of tau pathology in the diversity of the clinical presentation in AD.

Acta Neuropathologica Communications20153:40, DOI: 10.1186/s40478-015-0220-4; Lemoine et al. 2015; Received: 14 June 2015; Accepted: 15 June 2015; Published: 2 July 2015

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report

pjgrier Blood, Hot Topics in Research, Lung, Research Commentary

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report
BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.
METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.
RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).
CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.
CHEST 2016; 149(2):315-352
Clive Kearon, MD, PhD; Elie A. Akl, MD, MPH, PhD; Joseph Ornelas, PhD; Allen Blaivas, DO, FCCP; David Jimenez, MD, PhD, FCCP; Henri Bounameaux, MD; Menno Huisman, MD, PhD; Christopher S. King, MD, FCCP; Timothy A. Morris, MD, FCCP; Namita Sood, MD, FCCP; Scott M. Stevens, MD; Janine R. E. Vintch, MD, FCCP; Philip Wells, MD; Scott C. Woller, MD; and COL Lisa Moores, MD, FCCP

Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies

pjgrier Atrial Fibrillation, Cardiology, Hot Topics in Research

Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies

Objective To determine whether atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men.

Design Meta-analysis of cohort studies.

Data sources Studies published between January 1966 and March 2015, identified through a systematic search of Medline and Embase and review of references.

Eligibility for selecting studies Cohort studies with a minimum of 50 participants with and 50 without atrial fibrillation that reported sex specific associations between atrial fibrillation and all cause mortality, cardiovascular mortality, stroke, cardiac events (cardiac death and non-fatal myocardial infarction), and heart failure.

Data extraction Two independent reviewers extracted study characteristics and maximally adjusted sex specific relative risks. Inverse variance weighted random effects meta-analysis was used to pool sex specific relative risks and their ratio.

Results 30 studies with 4 371 714 participants were identified. Atrial fibrillation was associated with a higher risk of all cause mortality in women (ratio of relative risks for women compared with men 1.12, 95% confidence interval 1.07 to 1.17) and a significantly stronger risk of stroke (1.99, 1.46 to 2.71), cardiovascular mortality (1.93, 1.44 to 2.60), cardiac events (1.55, 1.15 to 2.08), and heart failure (1.16, 1.07 to 1.27). Results were broadly consistent in sensitivity analyses.

Conclusion Atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men, though further research would be needed to determine any causality.

Connor A Emdin, DPhil; Christopher X Wong; Allan J Hsiao; Douglas G Altman; Sanne AE Peters; Mark Woodward; Ayodele A Odutayo
BMJ 2016; 352 doi: http://dx.doi.org/10.1136/bmj.h7013 (Published 19 January 2016)